@article {pmid38638844, year = {2024}, author = {Zhou, H and Liu, D and Chen, L and Zhang, Y and Zhao, X and Ge, Y and Liu, M and Kong, T}, title = {Metastasis to the bladder from primary breast cancer: A case report and literature review.}, journal = {Oncology letters}, volume = {27}, number = {6}, pages = {249}, pmid = {38638844}, issn = {1792-1082}, abstract = {Breast cancer is the most prevalent malignant tumor affecting women and represents the leading cause of female cancer-related mortality worldwide. Although distant organ metastasis accounts for the majority of breast cancer-related deaths, reports on bladder metastasis are limited in the existing literature. The present study describes the case of a patient with bladder metastasis originating from breast cancer. In addition, the present study also provides a review of 54 cases of similar disease that have been documented in the currently available literature. The literature review aims to elucidate the clinicopathological characteristics and therapeutic approaches for such conditions. The median time from breast cancer diagnosis to bladder metastasis was found to be 5.6 years (range, 0-28 years). The origin of the bladder metastases was predominantly invasive ductal carcinoma (IDC) accounting for 52.3% of cases, followed by invasive lobular carcinoma, accounting for 40.9% of cases. The pathology in the primary tumor was the same as the pathology of the bladder metastases in all cases. There was an 88.9% concordance rate for estrogen receptor status, while the progesterone receptor status was 83.3% and the human epidermal growth factor receptor 2 expression status was 100%. The primary initial symptoms included urinary system manifestations, such as increased frequency, urgency, dysuria, urinary incontinence, nocturia and gross hematuria. For the cystoscopic examination, the predominant findings were bladder wall thickening or masses, along with ureteral orifice masses. Overall, the present study demonstrated that the occurrence of bladder metastasis often follows the metastasis of other organs, with IDC being the most prevalent subtype. The pathological characteristics between the primary tumor and bladder metastasis exhibit a high degree of concordance.}, }
@article {pmid37855288, year = {2024}, author = {Mohammed, BT and Uzodi, N and Gotimukul, A and Kokebie, R}, title = {Case Report of MPO+ ANCA Vasculitis with Pauci-immune GN Associated with Invasive Ductal Carcinoma of the Breast.}, journal = {Current rheumatology reviews}, volume = {20}, number = {2}, pages = {213-218}, doi = {10.2174/0115733971246438230924163114}, pmid = {37855288}, issn = {1875-6360}, mesh = {Female ; Humans ; Aged ; Antibodies, Antineutrophil Cytoplasmic ; *Glomerulonephritis ; Abscess ; *Breast Neoplasms/complications ; Mastectomy ; *Vasculitis ; Peroxidase ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast.<br><br>CASE PRESENTATION: A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion.<br><br>CONCLUSION: Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.}, }
@article {pmid38409747, year = {2024}, author = {Ruan, GJ and Zanwar, S and Ravindran, A and Schram, S and Abeykoon, JP and Hazim, A and Young, JR and Shah, MV and Bennani, NN and Jiang, L and Morlote, D and Rech, KL and Goyal, G and Go, RS and , }, title = {Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.}, journal = {American journal of hematology}, volume = {99}, number = {5}, pages = {871-879}, doi = {10.1002/ajh.27263}, pmid = {38409747}, issn = {1096-8652}, support = {P50 CA097274/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Histiocytic Sarcoma/genetics/therapy/pathology ; Macrophages/pathology ; Bone Marrow/pathology ; Prognosis ; Liver/pathology ; }, abstract = {Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.}, }
@article {pmid38578876, year = {2024}, author = {Rodriguez, GF and Shah, A and Maderal, AD}, title = {Telangiectasias induced by combination tucatinib and ado-trastuzumab emtansine in a patient with metastatic breast cancer.}, journal = {Breast disease}, volume = {43}, number = {1}, pages = {61-64}, doi = {10.3233/BD-230053}, pmid = {38578876}, issn = {1558-1551}, mesh = {Female ; Humans ; Aged ; Ado-Trastuzumab Emtansine/therapeutic use ; *Breast Neoplasms/pathology ; Trastuzumab/adverse effects ; Quinazolines/therapeutic use ; Receptor, ErbB-2/genetics/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Oxazoles ; *Pyridines ; }, abstract = {BACKGROUND: Tucatinib is a tyrosine kinase inhibitor currently used in salvage therapy for human epidermal growth factor receptor 2 (HER2)-positive breast and colorectal cancer. The use of tucatinib alone or in combination with ado-trastuzumab emtansine (T-DM1) in the treatment of advanced HER2-positive cancers is rapidly expanding.<br><br>OBJECTIVE/METHODS: We report the case of a 66-year-old female who presented to the dermatology clinic with a one-year history of widespread telangiectasias that began after initiation of combination chemotherapy with tucatinib and T-DM1 for metastatic HER2-positive invasive ductal carcinoma.<br><br>RESULTS: The patient's lesions regressed upon cessation of combination therapy and reappeared in the setting of tucatinib re-initiation, with gradual improvement over the following four months following electrocautery to the affected regions.<br><br>CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.}, }
@article {pmid38577141, year = {2024}, author = {Sukhija, S and Purohit, P and Pareek, P and Garg, PK and Vishnoi, JR and Elhence, PA and Varthya, SB and Sharma, P and Ambwani, S and Charan, J}, title = {Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.}, journal = {Indian journal of clinical biochemistry : IJCB}, volume = {39}, number = {2}, pages = {214-220}, pmid = {38577141}, issn = {0970-1915}, abstract = {Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m[2]), Cyclophosphamide (600 mg/m[2]) with or without Taxane (75-175 mg/m[2]) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.}, }
@article {pmid38576929, year = {2024}, author = {Jamal, O and Makhchoune, M and Laidi, A and Misbahi, T and Haouas, MY and Chellaoui, A and Bertal, A and Hilmani, S and Ibahiouine, K and Naja, A and Lakhder, A}, title = {Rupture of a dermoid cyst in the subarachnoid space: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {4}, pages = {2366-2369}, pmid = {38576929}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Intracranial dermoid cysts (IDC) are defined as rare, slow-growing cystic congenital neoplasms. Rupture of an intracranial dermoid cyst occurs rarely and most often spontaneously and results in potentially serious symptoms.<br><br>CASE PRESENTATION: A39-year-old female, with mechanical prosthetic heart valve presented with history of headache for 10 months and generalized tonicoclonic seizures. On the admission, the patient had a normal neurological and cranial nerve exam. The authors performed a computed tomography of the brain, The MRI could not be performed because of the presence of the prosthetic valve, revealed rupture of the dermoid cyst in the bilateral subarachnoid spaces. The patient underwent a large temporal craniotomy and the tumour was well exposed and completely removed without incident, the histopathological examination concludes to dermoid cyst, the patient recovered well from surgery.<br><br>CLINICAL DISCUSSION: Rupture is a very rare phenomenon. there are about 60 cases reported in the literature. the contents of the cyst disseminate into the subarachnoid and ventricular spaces in the event of rupture. A variety of clinical symptoms is usually caused. The mechanism of spontaneous rupture of the dermoid cyst is unclear. Among the proposed mechanisms is a rapid expansion of the cyst. Complete surgical resection of dermoid cysts is the only effective treatment for the prevention of recurrences and/or complications.<br><br>CONCLUSION: Rupture of an intracranial dermoid cyst is associated with significant morbidity and mortality, although it remains a rare phenomenon. Surgical excision should be considered as soon as the diagnosis is made in order to prevent more severe intracranial complication.}, }
@article {pmid38570490, year = {2024}, author = {Wang, J and Li, B and Luo, M and Huang, J and Zhang, K and Zheng, S and Zhang, S and Zhou, J}, title = {Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {83}, pmid = {38570490}, issn = {2059-3635}, support = {82172344//National Natural Science Foundation of China (National Science Foundation of China)/ ; LY21H160039//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LGF21H030010//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; *Breast Neoplasms/pathology ; Clinical Relevance ; Artificial Intelligence ; Gene Expression Profiling ; Tumor Microenvironment/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.}, }
@article {pmid38571894, year = {2024}, author = {Maiti, S and Nayak, S and Hebbar, KD and Pendem, S}, title = {Differentiation of invasive ductal and lobular carcinoma of the breast using MRI radiomic features: a pilot study.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {91}, pmid = {38571894}, issn = {2046-1402}, abstract = {BACKGROUND: Breast cancer (BC) is one of the main causes of cancer-related mortality among women. For clinical management to help patients survive longer and spend less time on treatment, early and precise cancer identification and differentiation of breast lesions are crucial. To investigate the accuracy of radiomic features (RF) extracted from dynamic contrast-enhanced Magnetic Resonance Imaging (DCE MRI) for differentiating invasive ductal carcinoma (IDC) from invasive lobular carcinoma (ILC).<br><br>METHODS: This is a retrospective study. The IDC of 30 and ILC of 28 patients from Dukes breast cancer MRI data set of The Cancer Imaging Archive (TCIA), were included. The RF categories such as shape based, Gray level dependence matrix (GLDM), Gray level co-occurrence matrix (GLCM), First order, Gray level run length matrix (GLRLM), Gray level size zone matrix (GLSZM), NGTDM (Neighbouring gray tone difference matrix) were extracted from the DCE-MRI sequence using a 3D slicer. The maximum relevance and minimum redundancy (mRMR) was applied using Google Colab for identifying the top fifteen relevant radiomic features. The Mann-Whitney U test was performed to identify significant RF for differentiating IDC and ILC. Receiver Operating Characteristic (ROC) curve analysis was performed to ascertain the accuracy of RF in distinguishing between IDC and ILC.<br><br>RESULTS: Ten DCE MRI-based RFs used in our study showed a significant difference (p <0.001) between IDC and ILC. We noticed that DCE RF, such as Gray level run length matrix (GLRLM) gray level variance (sensitivity (SN) 97.21%, specificity (SP) 96.2%, area under curve (AUC) 0.998), Gray level co-occurrence matrix (GLCM) difference average (SN 95.72%, SP 96.34%, AUC 0.983), GLCM interquartile range (SN 95.24%, SP 97.31%, AUC 0.968), had the strongest ability to differentiate IDC and ILC.<br><br>CONCLUSIONS: MRI-based RF derived from DCE sequences can be used in clinical settings to differentiate malignant lesions of the breast, such as IDC and ILC, without requiring intrusive procedures.}, }
@article {pmid38554305, year = {2024}, author = {Dogan, I and Khanmammadov, N and Ozkurt, S and Aydiner, A and Saip, P}, title = {Outcomes of the patients with metastatic male breast cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {1}, pages = {98-102}, doi = {10.4103/jcrt.jcrt_1829_22}, pmid = {38554305}, issn = {1998-4138}, mesh = {Humans ; Male ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Breast Neoplasms, Male/drug therapy ; Retrospective Studies ; Receptor, ErbB-2 ; Disease-Free Survival ; *Breast Neoplasms/pathology ; Trastuzumab/therapeutic use ; Prognosis ; *Brain Neoplasms/drug therapy/secondary ; Kaplan-Meier Estimate ; }, abstract = {BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC).<br><br>METHODS: A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables.<br><br>RESULTS: At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC.<br><br>CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.}, }
@article {pmid38553788, year = {2024}, author = {Dreindl, R and Bolsa-Ferruz, M and Fayos-Sola, R and Padilla Cabal, F and Scheuchenpflug, L and Elia, A and Amico, A and Carlino, A and Stock, M and Grevillot, L}, title = {Commissioning and clinical implementation of an independent dose calculation system for scanned proton beams.}, journal = {Journal of applied clinical medical physics}, volume = {}, number = {}, pages = {e14328}, doi = {10.1002/acm2.14328}, pmid = {38553788}, issn = {1526-9914}, abstract = {PURPOSE: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center.<br><br>METHODS: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined.<br><br>RESULTS: Beam model validation showed agreement of ranges within&#xa0;&#xb1;&#xa0;0.2&#xa0;mm, Bragg-Peak widths within&#xa0;&#xb1;&#xa0;0.1&#xa0;mm, and spot sizes at various air gaps within&#xa0;&#xb1;&#xa0;5% compared to physical measurements. Simulated dose in 2D reference fields deviated by&#xa0;-0.3%&#xa0;&#xb1;&#xa0;0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4&#xa0;&#xb1;&#xa0;0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2&#xa0;mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3&#xa0;mm. Root causes of GPR outliers, for example, implants were identified and evaluated.<br><br>CONCLUSION: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year.}, }
@article {pmid38539179, year = {2024}, author = {Esmat, E and Haidary, AM and Saadaat, R and Rizvi, SN and Aleena, S and Haidari, M and Hofiani, SMS and Hussaini, N and Hakimi, A and Khairy, A and Abdul-Ghafar, J}, title = {Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {388}, pmid = {38539179}, issn = {1471-2407}, abstract = {BACKGROUND: Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.<br><br>METHODOLOGY: A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.<br><br>RESULTS: One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58&#x2009;&#xb1;&#x2009;11.16&#xa0;years. Out of the total patients, 68 (56.7%) were above 40&#xa0;years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50&#xa0;years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.<br><br>CONCLUSION: In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.}, }
@article {pmid38523303, year = {2024}, author = {Yanase, Y and Bando, H and Sato, R and Matsuo, T and Ueda, A and Okazaki, M and Hashimoto, S and Iguchi-Manaka, A and Hara, H}, title = {Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {150}, pmid = {38523303}, issn = {1752-1947}, mesh = {Female ; Humans ; Adult ; Aged ; *Breast Neoplasms/drug therapy/pathology ; *Hypocalcemia/chemically induced ; Lapatinib/adverse effects ; Denosumab/adverse effects ; Calcium/therapeutic use ; *Bone Neoplasms/secondary ; }, abstract = {BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements.<br><br>CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole&#x2009;+&#x2009;lapatinib, trastuzumab emtansine, and lapatinib&#x2009;+&#x2009;capecitabine.<br><br>CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.}, }
@article {pmid38525191, year = {2024}, author = {Lopez-Vazquez, P and Fernandez-Caggiano, M and Barge-Caballero, E and Barge-Caballero, G and Couto-Mallon, D and Grille-Cancela, Z and Blanco-Canosa, P and Paniagua-Martin, MJ and Enriquez-Vazquez, D and Vazquez-Rodriguez, JM and Domenech, N and Crespo-Leiro, MG}, title = {Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1349417}, pmid = {38525191}, issn = {2297-055X}, abstract = {INTRODUCTION AND OBJECTIVES: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.<br><br>METHODS: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.<br><br>RESULTS: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.<br><br>CONCLUSION: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.}, }
@article {pmid38523415, year = {2024}, author = {Seth, A and Slama, EM}, title = {Delayed Diagnosis of Inflammatory Breast Cancer Presenting as Acute Mastitis in a Patient One Month Postpartum.}, journal = {The American surgeon}, volume = {}, number = {}, pages = {31348241241736}, doi = {10.1177/00031348241241736}, pmid = {38523415}, issn = {1555-9823}, abstract = {Inflammatory breast cancer (IBC) is a rare yet aggressive form of invasive ductal carcinoma, with a poor prognosis and decreased 5-year survival rates. Characteristic findings for IBC include rapid onset of breast edema, peau d'orange appearance, and involvement of the breast skin. Additionally, diagnosis is confirmed with a skin punch biopsy. With such nonspecific features, IBC can be mistaken for benign etiologies, causing delays in diagnosis and treatment. This patient is a 44-year-old woman presenting with left breast swelling while concurrently breastfeeding. Following antibiotic treatment but no symptom resolution, the patient was referred out for further follow-up. Despite multiple imaging studies, suggesting benign findings, clinical suspicion prompted continued evaluation and finally diagnosis of triple-negative inflammatory breast cancer with distant metastases. Further awareness of the presentation of IBC and its mimicking of other disease processes such as mastitis is paramount to earlier detection and improved outcomes in future patients.}, }
@article {pmid38417222, year = {2024}, author = {Hu, J and Chen, X and Sun, F and Liu, L and Liu, L and Yang, Z and Zhang, H and Yu, Z and Zhao, R and Wang, Y and Liu, H and Yang, X and Sun, F and Han, B}, title = {Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.}, journal = {Neoplasia (New York, N.Y.)}, volume = {50}, number = {}, pages = {100983}, pmid = {38417222}, issn = {1476-5586}, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating ; Proto-Oncogene Proteins B-raf/genetics ; Prostate/pathology ; Mutation ; *Prostatic Neoplasms/genetics/pathology ; China ; }, abstract = {While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAF[K601E] and BRAF[L597R] exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.}, }
@article {pmid38180699, year = {2024}, author = {Nakagawa, S and Miyashita, M and Maeda, I and Goda, A and Tada, H and Amari, M and Kojima, Y and Tsugawa, K and Ohi, Y and Sagara, Y and Sato, M and Ebata, A and Harada-Shoji, N and Suzuki, T and Nakanishi, M and Ohta, T and Ishida, T}, title = {Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.}, journal = {Breast cancer research and treatment}, volume = {204}, number = {3}, pages = {453-463}, pmid = {38180699}, issn = {1573-7217}, mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *Carcinoma, Lobular/pathology ; Selective Estrogen Receptor Modulators/therapeutic use ; *Carcinoma, Ductal, Breast/pathology ; Treatment Outcome ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC.<br><br>METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy.<br><br>RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P&#x2009;<&#x2009;0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P&#x2009;=&#x2009;0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P&#x2009;=&#x2009;0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P&#x2009;=&#x2009;0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis.<br><br>CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.}, }
@article {pmid37474400, year = {2024}, author = {Chappidi, MR and Sjöström, M and Greenland, NY and Cowan, JE and Baskin, AS and Shee, K and Simko, JP and Chan, E and Stohr, BA and Washington, SL and Nguyen, HG and Quigley, DA and Davicioni, E and Feng, FY and Carroll, PR and Cooperberg, MR}, title = {Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes.}, journal = {European urology oncology}, volume = {7}, number = {2}, pages = {222-230}, doi = {10.1016/j.euo.2023.06.007}, pmid = {37474400}, issn = {2588-9311}, mesh = {Male ; Humans ; *Prostate-Specific Antigen ; Retrospective Studies ; Transcriptome ; *Prostatic Neoplasms/genetics/surgery/pathology ; Gene Expression Profiling ; }, abstract = {BACKGROUND: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited.<br><br>OBJECTIVE: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival.<br><br>This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR.<br><br>Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival.<br><br>RESULTS AND LIMITATIONS: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity.<br><br>CONCLUSIONS: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments.<br><br>PATIENT SUMMARY: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.}, }
@article {pmid38485913, year = {2024}, author = {Heidari, N and Abbasi-Kenarsari, H and Niknam, B and Asadirad, A and Amani, D and Mirsanei, Z and Hashemi, SM}, title = {Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.}, journal = {Iranian journal of allergy, asthma, and immunology}, volume = {23}, number = {1}, pages = {97-106}, doi = {10.18502/ijaai.v23i1.14957}, pmid = {38485913}, issn = {1735-5249}, abstract = {Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat-shocked tumor cells (HS-TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS-TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS-TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that DCs treated with HS-TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS-TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS-TEXs could be used as a strategy to improve DC maturation and activation.}, }
@article {pmid38485644, year = {2024}, author = {Shi, Y and Wang, H and Golijanin, B and Amin, A and Lee, J and Sikov, M and Hyams, E and Pareek, G and Carneiro, BA and Mega, AE and Lagos, GG and Wang, L and Wang, Z and Cheng, L}, title = {Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.}, journal = {Urologic oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urolonc.2024.01.037}, pmid = {38485644}, issn = {1873-2496}, abstract = {Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.}, }
@article {pmid38233262, year = {2024}, author = {Wang, B and Fu, Y and Chen, M and Peng, S and Marra, G and Zhuang, J and Zhang, S and Guo, H and Qiu, X}, title = {The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy.}, journal = {Urologic oncology}, volume = {42}, number = {3}, pages = {67.e9-67.e15}, doi = {10.1016/j.urolonc.2023.11.018}, pmid = {38233262}, issn = {1873-2496}, mesh = {Male ; Humans ; Prostate/surgery/pathology ; *Prostatic Neoplasms/drug therapy/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Neoadjuvant Therapy ; Androgen Antagonists/therapeutic use ; Prospective Studies ; Prostatectomy ; Risk Factors ; }, abstract = {OBJECTIVE: To explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer.<br><br>METHODS: Eighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology.<br><br>RESULTS: IDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176-10.971, P&#x202f;=&#x202f;0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234-11.930, P&#x202f;=&#x202f;0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis.<br><br>CONCLUSION: IDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.}, }
@article {pmid38007354, year = {2024}, author = {Miyajima, K and Sato, S and Uchida, N and Suzuki, H and Iwatani, K and Imai, Y and Aikawa, K and Yanagisawa, T and Kimura, S and Tashiro, K and Tsuzuki, S and Honda, M and Koike, Y and Miki, J and Miki, K and Shimomura, T and Yuen, S and Yamada, Y and Aoki, M and Takahashi, H and Urabe, F and Kimura, T}, title = {Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.}, journal = {Clinical genitourinary cancer}, volume = {22}, number = {2}, pages = {149-156.e1}, doi = {10.1016/j.clgc.2023.10.005}, pmid = {38007354}, issn = {1938-0682}, mesh = {Male ; Humans ; *Brachytherapy/adverse effects ; Prostate/pathology ; Retrospective Studies ; *Carcinoma, Intraductal, Noninfiltrating/etiology ; Clinical Relevance ; *Prostatic Neoplasms/pathology ; }, abstract = {BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT).<br><br>METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P.<br><br>RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003).<br><br>CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.}, }
@article {pmid38461375, year = {2024}, author = {Turhan, &#x15e; and Sultan, DAO and Altuner, EM and Kurnaz, A and Bakır, TK and Altamemi, RAA}, title = {Determination of radon concentrations and physicochemical parameters of non-alcoholic carbonated beverages consumed in Türkiye and assessment of radiological health risk.}, journal = {International journal of environmental health research}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/09603123.2024.2327530}, pmid = {38461375}, issn = {1369-1619}, abstract = {The strategy for controlling the existence of radionuclides in drinking water depends upon an individual dose criterion (IDC) of 0.1 mSv/y, which represents a very low level of risk that is not expected to cause any identified adverse health effects. Radon gas, considered a carcinogenic radionuclide, can dissolve and accumulate in drinking water. Non-alcoholic carbonated beverages (NACBs), which mainly contain drinking water, phosphoric acid, citric acid, caffeine, and sugar, represent one of the most consumed groups worldwide and in Türkiye. In this study, the radon activity concentration and some physicochemical characteristics of 45 NACB samples from 24 most preferred commercial brands in Türkiye were determined to assess the radiological health risk associated with the ingestion of these samples. Radon activity concentrations measured in NACB samples using the AlphaGUARD radon analyzer ranged from 22.8 ± 0.7 to 54.9 ± 1.7 mBq/L. The pH, conductivity, total dissolved solids, and brix values in NACB samples ranged from 2.31 to 7.29, 401 to 3281 μSv/cm, 355 to 2453 mg/L, and 0.10 to 12.95%, respectively. Total (ingestion and inhalation) annual effective doses and the corresponding excess lifetime cancer risks estimated for adults to assess the radiological health risk are significantly below the IDC and advised safety limit (10[-3]), respectively.}, }
@article {pmid38451627, year = {2024}, author = {Saeed, U and Uppal, R and Khan, AA and Uppal, MR and Piracha, ZZ and Uppal, SR}, title = {Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e265550}, doi = {10.1590/1519-6984.265550}, pmid = {38451627}, issn = {1678-4375}, mesh = {Humans ; *COVID-19/diagnosis ; Cross-Sectional Studies ; Nasopharynx/virology ; Pakistan ; Pandemics ; *SARS-CoV-2/genetics ; *Reagent Kits, Diagnostic ; Sensitivity and Specificity ; }, abstract = {Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.}, }
@article {pmid38070191, year = {2024}, author = {Mouabbi, JA and Qaio, W and Shen, Y and Raghavendra, AS and Tripathy, D and Layman, RM}, title = {Efficacy of Single-Agent Chemotherapy in Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma.}, journal = {The oncologist}, volume = {29}, number = {3}, pages = {213-218}, pmid = {38070191}, issn = {1549-490X}, support = {MIRA RP170067//Cancer Prevention and Research Institute of Texas/ ; //NIH/ ; //NCI/ ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; Prospective Studies ; Receptor, ErbB-2/genetics/therapeutic use ; *Breast Neoplasms/pathology ; Capecitabine/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.<br><br>MATERIALS AND METHODS: Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients.<br><br>RESULTS: CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P&#x2005;<&#x2005;.001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P&#x2005;=&#x2005;.241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P&#x2005;=&#x2005;.001).<br><br>CONCLUSION: In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.}, }
@article {pmid38432595, year = {2024}, author = {Chuang, ML}, title = {Analyzing Key Elements of Breathing Patterns, Deriving Remaining Variables, and Identifying Cutoff Values in Individuals with Chronic Respiratory Disease and Healthy Subjects.}, journal = {Respiratory physiology &amp; neurobiology}, volume = {}, number = {}, pages = {104242}, doi = {10.1016/j.resp.2024.104242}, pmid = {38432595}, issn = {1878-1519}, abstract = {BACKGROUND: Pulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm.<br><br>METHODS: Screening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values.<br><br>RESULTS: Inspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V&#x307;E=Bf&#xd7;VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104L/min may differentiate ILD from control, while V&#x307;E of 54L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99s, and IDC of.45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84-0.91 versus 0.59-0.90).<br><br>CONCLUSION: The quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.}, }
@article {pmid38308423, year = {2024}, author = {Agaoglu, NB and Unal, B and Hayes, CP and Walker, M and Ng, OH and Doganay, L and Can, ND and Rana, HQ and Ghazani, AA}, title = {Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients.}, journal = {Cancer medicine}, volume = {13}, number = {3}, pages = {e6852}, pmid = {38308423}, issn = {2045-7634}, support = {Number YNY2016/144//The Istanbul Development Agency (ISTKA)/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; *Carcinoma, Lobular ; Genomics ; *Carcinoma, Ductal, Breast ; Oncogenes ; }, abstract = {OBJECTIVE: Turkish genome is underrepresented in large genomic databases. This study aims to evaluate the effect of allele frequency in the Turkish population in determining the clinical utility of germline findings in breast cancer, including invasive lobular carcinoma (ILC), mixed invasive ductal and lobular carcinoma (IDC-L), and ductal carcinoma (DC).<br><br>METHODS: Two clinic-based cohorts from the Umraniye Research and Training Hospital (URTH) were used in this study: a cohort consisting of 132 women with breast cancer and a non-cancer cohort consisting of 492 participants. The evaluation of the germline landscape was performed by analysis of 27 cancer genes. The frequency and type of variants in the breast cancer cohort were compared to those in the non-cancer cohort to investigate the effect of population genetics. The variant allele frequencies in Turkish Variome and gnomAD were statistically evaluated.<br><br>RESULTS: The genetic analysis identified 121 variants in the breast cancer cohort (actionable&#x2009;=&#x2009;32, VUS&#x2009;=&#x2009;89) and 223 variants in the non-cancer cohort (actionable&#x2009;=&#x2009;25, VUS&#x2009;=&#x2009;188). The occurrence of 21 variants in both suggested a possible genetic population effect. Evaluation of allele frequency of 121 variants from the breast cancer cohort showed 22% had a significantly higher value in Turkish Variome compared to gnomAD (p&#x2009;<&#x2009;0.0001, 95% CI) with a mean difference of 60 times (ranging from 1.37-354.4). After adjusting for variant allele frequency using the ancestry-appropriate database, 6.7% (5/75) of VUS was reclassified to likely benign.<br><br>CONCLUSION: To our knowledge, this is the first study of population genetic effects in breast cancer subtypes in Turkish women. Our findings underscore the need for a large genomic database representing Turkish population-specific variants. It further highlights the significance of the ancestry-appropriate population database for accurate variant assessment in clinical settings.}, }
@article {pmid38424901, year = {2020}, author = {Samreen, N and Moy, L and Lee, CS}, title = {Architectural Distortion on Digital Breast Tomosynthesis: Management Algorithm and Pathological Outcome.}, journal = {Journal of breast imaging}, volume = {2}, number = {5}, pages = {424-435}, doi = {10.1093/jbi/wbaa034}, pmid = {38424901}, issn = {2631-6129}, abstract = {Architectural distortion on digital breast tomosynthesis (DBT) can occur due to benign and malignant causes. With DBT, there is an increase in the detection of architectural distortion compared with 2D digital mammography, and the positive predictive value is high enough to justify tissue sampling when imaging findings are confirmed. Workup involves supplemental DBT views and ultrasound, with subsequent image-guided percutaneous biopsy using the modality on which it is best visualized. If architectural distortion is subtle and/or questionable on diagnostic imaging, MRI may be performed for problem solving, with subsequent biopsy of suspicious findings using MRI or DBT guidance, respectively. If no suspicious findings are noted on MRI, a six-month follow-up DBT may be performed. On pathology, malignant cases are noted in 6.8%-50.7% of the cases, most commonly due to invasive ductal carcinoma, followed by invasive lobular carcinoma. Radial scars are the most common benign cause, with stromal fibrosis and sclerosing adenosis being much less common. As there is an increase in the number of benign pathological outcomes for architectural distortion on DBT compared with 2D digital mammography, concordance should be based on the level of suspicion of imaging findings. As discordant cases have upgrade rates of up to 25%, surgical consultation is recommended for discordant radiologic-pathologic findings.}, }
@article {pmid38406950, year = {2023}, author = {Asad, S and Khan, SA and Khan, FA and Jalal-Ud-Din, M and Bhatti, G and Kamran, H}, title = {Pattern Of Breast Cancer: Experience At Ayub Teaching Hospital, Abbottabad.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {35}, number = {4}, pages = {629-632}, doi = {10.55519/JAMC-04-12089}, pmid = {38406950}, issn = {1819-2718}, abstract = {BACKGROUND: Breast cancer is the most common malignancy found in females all over the world and the second leading cause of cancer death in European countries. The purpose of this study was to find out the pattern of disease presentation in our region where a proper tumour registry system is lacking.<br><br>METHODS: This descriptive study was carried out in the Department of Surgery, Ayub Teaching Hospital Abbottabad, from July 2021 to June 2022. All female patients with biopsy-proven breast cancer were included in the study: benign lumps, refused to enrol, and those who were lost to follow-up were excluded.<br><br>RESULTS: A total of 87 patients with carcinoma breast were included: 92 % (n=80) had invasive ductal carcinoma. Axillary lymph nodes were involved in 88.5% (n=77), 75.8% of the tumours, (n=66), were Grade 2, 34.5% (n=30) were in the 40-49 years age group, and 30 % (n=27) of the disease was categorized as Stage III or IV. In 55 % (n=48), the tumour was on the right side and in 39% (n=34), the upper outer quadrant was involved. Most of the patients, 90.8% (n=79), were married and had used contraceptive measures. Only 19.5% of patients (n=17), had a history of nipple discharge and 56% (n=49) had a positive family history: 71% (n=62) had nipple retraction, and 54% (n=47), proved to be ER PR positive.<br><br>CONCLUSIONS: Our patients presented late: axilla was commonly involved and a third had advanced disease. Screening and community awareness programs may help in early detection. Hormone use for contraception needs to be weighed carefully. Better data collection may help in designing screening and care programs.}, }
@article {pmid38406898, year = {2023}, author = {,  and Haider, G and Shaikh, Z and Memon, P and Shahid, A and Rahul, R and Kumar, P and Beg, S and Parkash, J}, title = {Significance of ca15-3 in carcinoma of the breast with Visceral metastases.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {35(Suppl 1)}, number = {4}, pages = {S710-S714}, pmid = {38406898}, issn = {1819-2718}, abstract = {BACKGROUND: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi.<br><br>METHODS: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data.<br><br>RESULTS: A total of 139 females were included in the study. The mean age &amp; BMI of the patients were reported as 46.5 years &amp; 26.69 kg/m2. In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L).<br><br>CONCLUSION: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients.}, }
@article {pmid37925055, year = {2024}, author = {Derakhshan, F and Da Cruz Paula, A and Selenica, P and da Silva, EM and Grabenstetter, A and Jalali, S and Gazzo, AM and Dopeso, H and Marra, A and Brown, DN and Ross, DS and Mandelker, D and Razavi, P and Chandarlapaty, S and Wen, HY and Brogi, E and Zhang, H and Weigelt, B and Pareja, F and Reis-Filho, JS}, title = {Nonlobular Invasive Breast Carcinomas with Biallelic Pathogenic CDH1 Somatic Alterations: A Histologic, Immunophenotypic, and Genomic Characterization.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {37}, number = {2}, pages = {100375}, doi = {10.1016/j.modpat.2023.100375}, pmid = {37925055}, issn = {1530-0285}, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Cadherins/genetics ; Genomics ; Antigens, CD/genetics ; }, abstract = {CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, biallelic CDH1 alterations may be found in nonlobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 biallelic genetic alterations. Analysis of 5842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multigene panel was conducted to identify BCs with biallelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features. The genomic profiles of NL-BCs with CDH1 biallelic genetic alterations were compared with those of ILCs and invasive ductal carcinomas (IDCs), matched by clinicopathologic characteristics. Of the 896 CDH1-altered BCs, 889 samples were excluded based on the diagnosis of invasive mixed ductal/lobular carcinoma or ILC or the detection of monoallelic CDH1 alterations. Only 7 of the 5842 (0.11%) BCs harbored biallelic CDH1 alterations and lacked lobular features. Of these, 4/7 (57%) cases were ER-positive/HER2-negative, 1/7 (14%) was ER-positive/HER2-positive, and 2/7 (29%) were ER-negative/HER2-negative. In total, 5/7 (71%) were of Nottingham grade 2, and 2/7 (29%) were of grade 3. The NL-BCs with CDH1 biallelic genetic alterations included a mucinous carcinoma (n = 1), IDCs with focal nested growth (n = 2), IDC with solid papillary (n = 1) or apocrine (n = 2) features, and an IDC of no special type (NST; n = 1). E-cadherin expression, as detected by immunohistochemistry, was absent (3/5) or aberrant (discontinuous membranous/cytoplasmic/granular; 2/5). However, NL-BCs with CDH1 biallelic genetic alterations displayed recurrent genetic alterations, including TP53, PIK3CA (57%, 4/7; each), FGFR1, and NCOR1 (28%, 2/7, each) alterations. Compared with CDH1 wild-type IDC-NSTs, NL-BCs less frequently harbored GATA3 mutations (0% vs 47%, P = .03), but no significant differences were detected when compared with matched ILCs. Therefore, NL-BCs with CDH1 biallelic genetic alterations are vanishingly rare, predominantly comprise IDCs with special histologic features, and have genomic features akin to luminal B ER-positive BCs.}, }
@article {pmid38399000, year = {2024}, author = {Khan, MRR}, title = {Development of a Battery-Free, Chipless, and Highly Sensitive Radio Frequency Glucose Biosensor.}, journal = {Micromachines}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/mi15020272}, pmid = {38399000}, issn = {2072-666X}, abstract = {In our study, we designed and developed a glucose biosensor that operates without a battery or chip. This biosensor utilizes the principles of radio frequency (RF) to operate. For the construction of a glucose-sensitive interdigitated capacitor (IDC), a famous glucose-sensitive substance called phenylboronic acid (PBA) is combined with a polyvinyl chloride (PVC) and n,n-dimethylacetamide (DMAC) solution. According to the theory of radio frequency sensing, the resonance frequency shifts whenever there is a change in the capacitance of the glucose-sensitive IDC. This change is caused by the fluctuations in glucose concentrations. As far as we are aware, this is the first glucose sensor that employs the RF principle to detect changes in glucose solution concentrations using PBA as the principal glucose-sensitive material. The sensor can detect glucose levels with remarkable sensitivity, around 40.89 kHz/decade, and a broad dynamic range covering 10 μM to 1 M. Additionally, the designed biosensor has excellent linearity performance, with a value of around 0.988. The proposed glucose biosensor has several benefits: lightweight, inexpensive, easy to build, and an acceptable selectivity response. Our study concludes by comparing the proposed RF sensor's effectiveness to that of existing glucose sensors, which it outperforms.}, }
@article {pmid38396137, year = {2024}, author = {Matsumoto, T and Tanaka, G and Mori, S and Niki, M and Sato, S and Shiraki, T and Iso, Y and Nagashima, K and Irisawa, A and Nozawa, Y and Takada-Owada, A and Ishida, K and Aoki, T}, title = {A resected case of pancreatic head cancer developing 40 years after lateral pancreaticojejunostomy for chronic pancreatitis.}, journal = {Clinical journal of gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {38396137}, issn = {1865-7265}, abstract = {A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.}, }
@article {pmid38278448, year = {2024}, author = {Mahlow, J and Barry, M and Albertson, DJ and Jo, YJ and Balatico, M and Seasor, T and Gebrael, G and Kumar, SA and Sayegh, N and Tripathi, N and Agarwal, N and Swami, U and Sirohi, D}, title = {Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway.}, journal = {Human pathology}, volume = {144}, number = {}, pages = {28-33}, doi = {10.1016/j.humpath.2024.01.005}, pmid = {38278448}, issn = {1532-8392}, mesh = {Male ; Humans ; Recombinational DNA Repair ; BRCA1 Protein/genetics ; *Carcinoma, Lobular ; BRCA2 Protein/genetics ; Mutation ; *Breast Neoplasms ; *Prostatic Neoplasms/genetics ; }, abstract = {Somatic or germline homologous recombination repair (HRR) pathway gene mutations are commonly detected in prostate cancer, especially in advanced disease, and are associated with response to poly (ADP-ribose) polymerase (PARP) inhibitors. In this study, we evaluated whether histological patterns are predictive of HRR pathway gene mutations. The study population comprised 130 patients with advanced prostate carcinoma who underwent comprehensive genomic profiling (CGP) of tumor tissue at a CLIA-certified laboratory. HRR genes in the study included BRCA1, BRCA2, ATM, BARD1, BRIP, CHEK2, MRE11A, NBN, PALB2, RAD51C, RAD51D, EMSY, ATR, CHEK1, and FAM175A. Overall, 38 patients had mutations in BRCA1/2, 36 in other HRR genes, and 56 were negative for HRR mutations. All cases were re-reviewed and quantified by two genitourinary pathologists blinded to mutational status for the following histological patterns of prostate carcinoma: cribriform, ductal, intraductal carcinoma (IDC), small cell carcinoma, signet ring-like pattern, and lobular carcinoma-like pattern. Discordances were resolved by consensus review. Histologic patterns were analyzed for any correlation with mutations in HRR pathway genes (grouped as BRCA1/2 mutated or non-BRCA1/2 mutated) compared to tumors without mutations in HRR genes by Chi-square testing. Patterns with >20 % and >30 % of tumor volume were additionally evaluated for correlation with mutational status. We found no significant association between HRR pathway mutations and cribriform pattern, IDC, ductal carcinoma, small cell carcinoma, signet ring-like pattern, or lobular carcinoma-like patterns. Tumors with >20 % or >30 % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.}, }
@article {pmid38384043, year = {2023}, author = {Soman, PS and Hemalatha, A and Sreeramulu, PN}, title = {Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {Suppl 2}, pages = {S706-S711}, doi = {10.4103/jcrt.jcrt_639_22}, pmid = {38384043}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Immunohistochemistry ; Receptor, ErbB-2/genetics/metabolism ; Mastectomy ; *Carcinoma, Ductal, Breast/genetics/therapy/metabolism ; Biomarkers, Tumor/genetics/metabolism ; BRCA1 Protein/genetics ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established.<br><br>AIMS AND OBJECTIVES: To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression.<br><br>MATERIALS AND METHODS: This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant.<br><br>RESULTS: Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available.<br><br>CONCLUSION: Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.}, }
@article {pmid38379333, year = {2024}, author = {Zhu, S and Xu, N and Zeng, H}, title = {Molecular complexity of intraductal carcinoma of the prostate.}, journal = {Cancer medicine}, volume = {13}, number = {2}, pages = {e6939}, pmid = {38379333}, issn = {2045-7634}, support = {NSFC 82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; 2022-I2M-C&amp;T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; X-J-2020-016//Bethune Foundation, Oncology Basic Research Program/ ; ZYJC21020//West China Hospital, Sichuan University/ ; ZYGD22004//West China Hospital, Sichuan University/ ; mnzl202002//Bethune Foundation, Urological Oncology Special Research Fund/ ; mnzl202007//Bethune Foundation, Urological Oncology Special Research Fund/ ; }, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; Prognosis ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.}, }
@article {pmid38376291, year = {2023}, author = {Piracha, ZZ and Saeed, U}, title = {Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {7}, pages = {1870-1879}, pmid = {38376291}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; Leucine ; beta Catenin ; *Fibroadenoma/genetics ; Glycogen Synthase Kinase 3 ; Prognosis ; Proto-Oncogene Proteins c-akt ; Immunoglobulin Domains ; *Carcinoma, Ductal ; Membrane Glycoproteins ; }, abstract = {BACKGROUND: LRIG1 belongs to the family of transmembrane proteins containing leucine-rich repeats. LRIGs are considered as tumor suppressors as they negatively regulate receptor tyrosine kinases. The role of LRIG1 as an EGFR regulator makes it an important marker to be studied in various epithelial-derived cancers.<br><br>METHODS: LRIG1 expression was determined in Erbb2 + cell lines by western blotting, and cell motility was examined by cell migration assay. The AKT/GSK3-&#x3b2;/&#x3b2;-catenin pathway was determined in the presence of LRIG1 and Erbb2 by using western blotting.<br><br>RESULTS: So far, no study has reported the expression of LRIG1 in benign forms of tumor such as fibroadenoma. The current study aims to analyze LRIG1 expression in fibroadenoma and invasive ductal carcinoma (IDC) tissues. In this study, we compared the LRIG1 expression with different clinicopathological parameters of patients having IDC or fibroadenoma. LRIG1 expression was low in Erbb2+ cell lines, and more cell motility was observed. The AKT/GSK3-&#x3b2;/&#x3b2;-catenin pathway was activated when LRIG1 was downregulated; consequently, Erbb2 was upregulated. Our results indicated that LRIG1 expression can be significantly correlated with age, Nottingham index, and Her2/neu status of cancer. The expression of LRIG1 in IDC and fibroadenoma were found to be significantly different.<br><br>CONCLUSION: The fibroadenoma tissue sections were found to express LRIG1 more intensely as compared to the IDC sections, which are in line with the studies reporting reduced copy number of the gene either due to gene deletion or transcriptional inhibition. This further supports that the downregulation of LRIG1 may lead to malignant tumor acting as a tumor suppressor.}, }
@article {pmid38375814, year = {2023}, author = {Huang, T and Lu, C and Zhang, Y and Lin, BY and Zhang, ZJ and Zhu, D and Wang, L and Lu, Y}, title = {Effect of activating cancer-associated fibroblasts biomarker TNC on immune cell infiltration and prognosis in breast cancer.}, journal = {Annals of medicine}, volume = {55}, number = {2}, pages = {2250987}, doi = {10.1080/07853890.2023.2250987}, pmid = {38375814}, issn = {1365-2060}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Biomarkers/metabolism ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most important components of the tumor microenvironment (TME). CAFs are heterogeneous and involved in tumor tumorigenesis and drug resistance, contributing to TME remodeling and predicting clinical outcomes as prognostic factors. However, the effect of CAFs the TME and the prognosis of patients with breast cancer (BC) is not fully understood. This study investigated the correlation between CAFs-activating biomarkers immune cell infiltration and survival in patients with breast cancer.<br><br>METHODS: RNA sequencing data and survival information for patients with breast cancer were downloaded from The Cancer Genome Atlas (TCGA) using R software. We then analyzed the correlation between CAFs-expressing biomarkers and immune cells using the clusterProfiler package, and evaluated the prognostic role of appealing genes using the Survminer package. Immunohistochemical (IHC) staining was used to determine the expression levels of TNC in 160 breast cancer samples pathologically diagnosed as invasive ductal carcinoma that were not otherwise specified (IDC-NOS).<br><br>RESULTS: Data analysis showed that CAFs-expressing genes was higher than in normal tissues (p&#x2009;<&#x2009;0.05). Pathway enrichment revealed that the overexpression of CAFs-related genes was mainly enriched in the focal adhesion and phosphoinositol-3 kinase-serine/threonine kinase (PI3K-AKT) signaling pathways. Immune infiltration analysis suggested that high expression of CAFs-related genes was significantly positively correlated with the infiltration of naive B cells and resting dendritic cells and inversely correlated with macrophages cell infiltration. In addition, high TNC expression in tumor cells was associated with the most adverse clinicopathological features and reduced metastasis-free survival (MFS) (hazard ratio (HR) 0.574, 95% confidence interval (CI) 0.404-0.815, p&#x2009;=&#x2009;0.035).<br><br>CONCLUSIONS: This study found that CAFs may participate in immunosuppression and regulate tumor cell proliferation and invasion. High TNC expression is associated with several adverse clinicopathological features, and high TNC expression in tumor cells has been identified as an independent prognostic factor for IDC-NOS.}, }
@article {pmid38369589, year = {2024}, author = {Liu, XS and Chen, YX and Wan, HB and Wang, YL and Wang, YY and Gao, Y and Wu, LB and Pei, ZJ}, title = {TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4042}, pmid = {38369589}, issn = {2045-2322}, mesh = {Humans ; *Transcription Factors/metabolism ; LIM Domain Proteins/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Glycolysis ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; }, abstract = {Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.}, }
@article {pmid38368669, year = {2024}, author = {Gomez, D and Seneviratne, S}, title = {Invasive breast carcinoma with ipsilateral axillary squamous carcinoma of unknown primary: A case report.}, journal = {International journal of surgery case reports}, volume = {116}, number = {}, pages = {109397}, doi = {10.1016/j.ijscr.2024.109397}, pmid = {38368669}, issn = {2210-2612}, abstract = {INTRODUCTION &amp; IMPORTANCE: Invasive ductal carcinoma is the commonest primary breast carcinoma to metastasize to the axillary nodes. Squamous carcinoma (SCC) of the breast is seen rarely as a primary breast malignancy. Breast SCC with coexistent invasive ductal/lobular carcinoma as a 'collision tumour' is rare.<br><br>CASE PRESENTATION: A 52-year-old Sri Lankan female presented with a right sided breast lump and ipsilateral cystic axillary mass. She was diagnosed with locally advanced invasive breast carcinoma and underwent neoadjuvant chemotherapy followed by mastectomy and axillary clearance where tumour infiltration of the brachial plexus was observed. Histology revealed two separate carcinomas; an invasive carcinoma of the breast and squamous carcinoma in the axilla. A squamous primary was not found despite evaluation. The patient developed recurrent axillary ulceration due to residual tumour and was transferred for oncological care.<br><br>CLINICAL DISCUSSION: This patient had a biopsy-proven invasive breast carcinoma with a cystic axillary mass with lymphadenopathy. This was concluded as locally advanced breast cancer. Pathological examination of the specimen indicated the presence of two separate malignancies of the breast and axilla. No evidence of squamous metaplasia or carcinoma of the breast was seen on histology, neither was a squamous primary identified on imaging or endoscopy. Neoadjuvant therapy may have caused resolution of the squamous component.<br><br>CONCLUSION: The presence of two separate cancers of varied histology in the breast and ipsilateral axilla in close proximity to each other is a rare phenomenon. Clinicians must be cautious not to misinterpret it as evidence of lymphatic spread.}, }
@article {pmid38343885, year = {2023}, author = {Santos, MM and Baerga, CG and Lamsal, S and Engel, C and Ozdemir, S}, title = {Breast cancer in a Hispanic patient with Werner syndrome.}, journal = {Journal of radiology case reports}, volume = {17}, number = {10}, pages = {21-31}, pmid = {38343885}, issn = {1943-0922}, mesh = {Humans ; Female ; Adult ; *Werner Syndrome/complications/diagnostic imaging ; *Breast Neoplasms/diagnostic imaging ; Werner Syndrome Helicase/genetics ; Mastectomy ; Mutation ; Hispanic or Latino ; }, abstract = {Werner Syndrome is a rare autosomal recessive condition characterized by premature aging and increased risk of malignancies due to gene mutations associated with DNA stability. We present the first case report of a 29-year-old Hispanic female with WS diagnosed with breast cancer. Diagnostic mammography and ultrasound, breast MRI and PET examinations revealed two lesions biopsy proven as invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy and radical mastectomy. Recurrence occurred 10 months postoperatively with molecular analysis demonstrating TP53 mutations. The multifactorial assessment of breast cancer in this case study is crucial towards optimizing screening, diagnosis and management of this disease in patients with WS.}, }
@article {pmid38336663, year = {2024}, author = {Ye, C and Shi, M and Xie, D and Wu, H and Chen, Q and Yang, L}, title = {A rare case of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament in a child: a case report and literature review.}, journal = {BMC musculoskeletal disorders}, volume = {25}, number = {1}, pages = {118}, pmid = {38336663}, issn = {1471-2474}, support = {82372431//National Natural Science Foundation of China/ ; 2022LJ007//Shanghai Municipal Health Commission Health Leading Talents Program/ ; 22ZR1476700//the Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality/ ; 201409003200//the Science and Technology Innovation Action Plan of the Science and Technology Commission of Shanghai Municipality/ ; 0906//the Fifth Round Innovation Team of Shanghai Changning District, the Pyramid Talent Project of Shanghai Changzheng Hospital in 2020/ ; 2021X002//the Discipline Team Support Project of No. 905 Hospital of PLA Navy/ ; }, mesh = {Humans ; Child ; Longitudinal Ligaments/diagnostic imaging ; Osteogenesis ; *Intervertebral Disc Degeneration/complications/diagnostic imaging ; *Ossification of Posterior Longitudinal Ligament/complications/diagnostic imaging/therapy ; *Calcinosis/complications/diagnostic imaging/therapy ; *Chondrocalcinosis/complications ; Cervical Vertebrae/diagnostic imaging ; *Intervertebral Disc/diagnostic imaging ; }, abstract = {BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition.<br><br>CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion.<br><br>CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.}, }
@article {pmid38307851, year = {2024}, author = {Coria, LM and Rodriguez, JM and Demaria, A and Bruno, LA and Medrano, MR and Castro, CP and Castro, EF and Del Priore, SA and Hernando Insua, AC and Kaufmann, IG and Saposnik, LM and Stone, WB and Prado, L and Notaro, US and Amweg, AN and Diaz, PU and Avaro, M and Ortega, H and Ceballos, A and Krum, V and Zurvarra, FM and Sidabra, JE and Drehe, I and Baqué, JA and Li Causi, M and De Nichilo, AV and Payes, CJ and Southard, T and Vega, JC and Auguste, AJ and Álvarez, DE and Flo, JM and Pasquevich, KA and Cassataro, J}, title = {A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {997}, pmid = {38307851}, issn = {2041-1723}, support = {R01 AI153433/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Mice ; Humans ; *SARS-CoV-2 ; Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; *COVID-19/prevention &amp; control ; Vaccines, Subunit ; Adjuvants, Immunologic ; Epitopes, B-Lymphocyte ; Antibodies, Viral ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus/genetics ; }, abstract = {In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.}, }
@article {pmid38326829, year = {2024}, author = {Verma, VK and Beevi, SS and Nair, RA and Kumar, A and Kiran, R and Alexander, LE and Dinesh Kumar, L}, title = {MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways.}, journal = {Cell communication and signaling : CCS}, volume = {22}, number = {1}, pages = {100}, pmid = {38326829}, issn = {1478-811X}, mesh = {Animals ; Female ; Mice ; Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *MicroRNAs/genetics/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common form of breast cancer which accounts for 85% of all breast cancer diagnoses. Non-invasive and early stages have a better prognosis than late-stage invasive cancer that has spread to lymph nodes. The involvement of microRNAs (miRNAs) in the initiation and progression of breast cancer holds great promise for the development of molecular tools for early diagnosis and prognosis. Therefore, developing a cost effective, quick and robust early detection protocol using miRNAs for breast cancer diagnosis is an imminent need that could strengthen the health care system to tackle this disease around the world.<br><br>METHODS: We have analyzed putative miRNAs signatures in 100 breast cancer samples using two independent high fidelity array systems. Unique and common miRNA signatures from both array systems were validated using stringent double-blind individual TaqMan assays and their expression pattern was confirmed with tissue microarrays and northern analysis. In silico analysis were carried out to find miRNA targets and were validated with q-PCR and immunoblotting. In addition, functional validation using antibody arrays was also carried out to confirm the oncotargets and their networking in different pathways. Similar profiling was carried out in Brca2/p53 double knock out mice models using rodent miRNA microarrays that revealed common signatures with human arrays which could be used for future in vivo functional validation.<br><br>RESULTS: Expression profile revealed 85% downregulated and 15% upregulated microRNAs in the patient samples of IDC. Among them, 439 miRNAs were associated with breast cancer, out of which 107 miRNAs qualified to be potential biomarkers for the stratification of different types, grades and stages of IDC after stringent validation. Functional validation of their putative targets revealed extensive miRNA network in different oncogenic pathways thus contributing to epithelial-mesenchymal transition (EMT) and cellular plasticity.<br><br>CONCLUSION: This study revealed potential biomarkers for the robust classification as well as rapid, cost effective and early detection of IDC of breast cancer. It not only confirmed the role of these miRNAs in cancer development but also revealed the oncogenic pathways involved in different progressive grades and stages thus suggesting a role in EMT and cellular plasticity during breast tumorigenesis per se and IDC in particular. Thus, our findings have provided newer insights into the miRNA signatures for the classification and early detection of IDC.}, }
@article {pmid38281565, year = {2024}, author = {Dimitrov, G and Shousha, S and Troianova, P}, title = {CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.}, journal = {Experimental and molecular pathology}, volume = {135}, number = {}, pages = {104885}, doi = {10.1016/j.yexmp.2024.104885}, pmid = {38281565}, issn = {1096-0945}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; Anthracyclines/therapeutic use ; Retrospective Studies ; Receptor, ErbB-2/metabolism ; Neoadjuvant Therapy ; Antibiotics, Antineoplastic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown.<br><br>AIM: This retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy.<br><br>METHODS: We analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates.<br><br>RESULTS: Univariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762-20.1699); p&#xa0;=&#xa0;0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024-0.30); p&#xa0;<&#xa0;0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8-0.19); p&#xa0;=&#xa0;0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268-0.4503); p&#xa0;=&#xa0;0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270-0.3462); p&#xa0;=&#xa0;0.0003]. Concordance was observed between core biopsies and excised samples.<br><br>CONCLUSION: Positive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.}, }
@article {pmid38329829, year = {2024}, author = {Fang, L and Simman, R and Workman, L and Ayoub, S and Bratton, C}, title = {Malignant wound aetiology, diagnosis and management: a case series and literature review.}, journal = {Journal of wound care}, volume = {33}, number = {2}, pages = {102-117}, doi = {10.12968/jowc.2024.33.2.102}, pmid = {38329829}, issn = {0969-0700}, abstract = {OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy.<br><br>METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles.<br><br>RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC.<br><br>CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.}, }
@article {pmid38318566, year = {2024}, author = {Youh, J and Yamaguchi, Y and Hiraguchi, E}, title = {Centrifugally Spreading Annular Erythema as a Dermatological Indicator of Metastatic Breast Carcinoma.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51641}, doi = {10.7759/cureus.51641}, pmid = {38318566}, issn = {2168-8184}, abstract = {Breast cancer is the leading cause of skin metastasis in women with internal malignancies. This report highlights an atypical case of cutaneous metastasis of breast cancer (CMBC) in a 66-year-old woman. Starting four months before her dermatology consultation, the patient underwent a chemotherapy regimen comprising pertuzumab, trastuzumab, and vinorelbine for right breast cancer, right axillary lymph node enlargement, and bone metastases. After commencing chemotherapy, erythematous macules appeared around her right nipple. Subsequently, the cutaneous lesions developed into annular erythematous patches around her right nipple and began to coalesce and expand to the contralateral breast. A skin biopsy revealed dysplastic cells indicative of metastasis from invasive ductal carcinoma. In addition, lymphovascular tumor cell invasion was noted in the reticular dermis. Based on these clinical progressions and histopathologic findings, a diagnosis of CMBC was made, specifically considering the possibility of inflammatory breast cancer (IBC). The patient continued the same chemotherapy regimen for 17 cycles, which improved the skin lesions, but she succumbed to breast cancer two years later. This case emphasizes the importance of considering CMBC in breast cancer patients with expanding, treatment-resistant thoracic cutaneous lesions, especially in aggressive subtypes like IBC. The diverse presentations of CMBC require thorough histopathological evaluation.}, }
@article {pmid38305220, year = {2024}, author = {Tsilingiris, D and Schimpfle, L and Κender, Z and Sulaj, A and von Rauchhaupt, E and Herzig, S and Szendroedi, J and Kopf, S}, title = {Utility of bioelectrical phase angle for cardiovascular risk assessment among individuals with and without diabetes mellitus.}, journal = {Diabetes &amp; vascular disease research}, volume = {21}, number = {1}, pages = {14791641231223701}, pmid = {38305220}, issn = {1752-8984}, mesh = {Adult ; Humans ; Male ; Female ; *Cardiovascular Diseases/diagnosis/etiology ; Carotid Intima-Media Thickness ; Pulse Wave Analysis ; *Diabetes Mellitus, Type 1 ; Risk Factors ; Heart Disease Risk Factors ; *Diabetes Mellitus, Type 2 ; Natriuretic Peptide, Brain ; Peptide Fragments ; Biomarkers ; }, abstract = {PURPOSE: Low values of bioimpedance-derived phase angle (PA) have been associated with various adverse outcomes. We investigated the association of PA with cardiovascular markers in individuals with and without diabetes mellitus (DM).<br><br>METHODS: PA was measured in 452 adults (without DM n = 153, T1DM n = 67, T2DM n = 232). Carotid intima-media thickness (IMT), renal resistive index (RRI), ankle-brachial index (ABI) and carotid-femoral Pulse Wave Velocity (cfPWV) were estimated. Furthermore, the levels of high-sensitive Troponin-T [hsTnT], N-terminal brain natriuretic peptide [NT-pro-BNP]) were measured.<br><br>RESULTS: PA values were lower in DM independently of age, gender, and BMI (estimated marginal means 6.21, 5.83, 5.95 for controls, T1DM, T2DM p < .05), a finding which persisted after propensity score matching. PA correlated negatively with IMT (r = -0.181), RRI (r = -0.374), cfPWV (r = -0.358), hsTnT (r = -0.238) and NT-pro-BNP (r = -0.318) (all p < .001). In multivariable analysis, the associations with RRI, cfPWV, hsTnT and NT-pro-BNP remained unchanged. PA values 6.0-6.5&#xb0; for males and 5.2-5.8&#xb0; for females were predictive of commonly used cutoffs. The combination of &#x391;CC/AHA ASCVD Score with PA outperformed either factor in predicting cfPWV, RRI for males and hsTnT, BNP for both genders.<br><br>CONCLUSIONS: PA exhibits independent correlations with various parameters pertinent to cardiovascular risk and may be useful for cardiovascular assessment.}, }
@article {pmid38303308, year = {2023}, author = {Aoyagi, T and Namura, M and Sakata, H and Tamanuki, T and Iwai, M and Iwata, K and Takahashi, H and Matsuzaki, H}, title = {[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {50}, number = {13}, pages = {1462-1464}, pmid = {38303308}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; Middle Aged ; *Breast Neoplasms/drug therapy/genetics/surgery ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Mastectomy ; Neoplasm Recurrence, Local/drug therapy/surgery ; *Antineoplastic Agents/therapeutic use ; BRCA1 Protein/genetics ; }, abstract = {The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.}, }
@article {pmid38303174, year = {2023}, author = {Takeda, Y and Ohmura, Y and Katsura, Y and Shinke, G and Kinoshita, M and Aoyama, S and Kihara, Y and Yanagisawa, K and Katsuyama, S and Ikeshima, R and Hiraki, M and Sugimura, K and Masuzawa, T and Hata, T and Murata, K}, title = {[Robotic and Laparoscopic Pancreaticoduodenectomy for the Elderly Patients-A Single Institutional Experience].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {50}, number = {13}, pages = {1688-1690}, pmid = {38303174}, issn = {0385-0684}, mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; Pancreaticoduodenectomy/adverse effects ; *Pancreatic Neoplasms/surgery/complications ; Pancreatic Fistula/etiology ; *Robotic Surgical Procedures/adverse effects ; Retrospective Studies ; *Laparoscopy/adverse effects ; Postoperative Complications/epidemiology/etiology ; Length of Stay ; *Carcinoma, Ductal/complications ; }, abstract = {INTRODUCTION: Laparoscopic pancreaticoduodenectomy(LPD)has been covered by insurance since 2016 in Japan. Advance LPD and robotic pancreaticoduodenectomy(RPD)has been also covered by insurance since 2020 in Japan. The aim of this study was to analyze the perioperative results and outcomes of RPD and LPD for the elderly patients and to compare to the non-elderly patients.<br><br>PATIENTS AND METHOD: Between July 2020 and April 2023, 67 patients underwent RPD and between May 2012 and February 2021, 63 patients underwent LPD at Kansai Rosai Hospital. Sixty-seven RPD and 62 LPD patients without extended resection were divided into 2 groups those who were over 75 years old(R/LPD E)(n=55)and under 74 years old(R/LPD non-E)(n=74). Control patients who received open pancreaticoduodenectomy(OPD)without extended resection between April 2010 and April 2023 were also divided into 2 groups those who were over 75 years old(OPD E)(n =60)and under 74 years old(OPD non-E)(n=78). The patient age was 79.0 and 60.5 years, the male to female ratio was 35/20 and 45/29, disease ratio(invasive ductal carcinoma or not)was 7/48 and 9/65 in R/LPD E and R/LPD non-E groups, respectively. The patient age was 79.0 and 79.5 years, the male to female ratio was 35/20 and 31/29, disease ratio (invasive ductal carcinoma or not)was 7/48 and 30/30(p<0.0001)in R/LPD E and OPD E groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2001019).<br><br>RESULTS: The average operation time was 644.6 and 675.2 minutes, an estimated blood loss was 220.8 and 134.4 g, postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 28/25/21/0, delayed gastric emptying(ISGPS 2007, [-]/Grade A/B/C)was 48/0/4/3 and 61/2/6/5 and postoperative hospital stay was 27.9 and 25.9 and in R/LPD E and R/LPD non-E groups, respectively. No significant differences were noted between the groups, However, postoperative complication over &#x2162;a Clavien-Dindo classification was 8(15.7%)and 3(4.4%)cases(p=0.0319)in R/LPD E and R/ LPD non-E groups. The average operation time was 644.6 and 492.1 minutes(p<0.0001), an estimated blood loss was 220.8 and 534.8 g(p=0.0004), postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 27/8/24/1(p=0.0442), postoperative hospital stay was 27.9 and 42.0(p=0.0490)in R/LPD E and OPD E groups, respectively.<br><br>CONCLUSION: The R/LPD was undergone in safety, even for the over 75 years old patients.}, }
@article {pmid38285770, year = {2024}, author = {Younas, H and Shahid, M and Khan, Z and Fatima, K and Tasadduq, R}, title = {Investigating the association of Angiotensin II Type I Receptor A1166C Polymorphism with Breast Cancer Risk in the Pakistani Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {25}, number = {1}, pages = {79-85}, doi = {10.31557/APJCP.2024.25.1.79}, pmid = {38285770}, issn = {2476-762X}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; Angiotensin II/genetics ; Pakistan/epidemiology ; Polymorphism, Genetic ; Renin-Angiotensin System/genetics ; Genotype ; Genetic Predisposition to Disease ; }, abstract = {The polymorphisms of the Renin-Angiotensin System are related to many disorders like diabetes, cardiovascular disease, and different types of cancer. Among all the polymorphisms related to AGTR1, A1166C has been associated with several disorders, including cardiovascular diseases and breast cancer. This study was conducted to discover the association of AGTR1 polymorphism (A1166C) Renin-Angiotensin and its effect on the development and progression of breast cancer in the Pakistani population. One hundred forty participants, including seventy diagnosed breast cancer patients and seventy healthy individuals, were included in this study and genotyped with an allele-specific polymerase chain reaction. The most frequent genotype in healthy participants and breast cancer patients was CC. An insignificant (p value>0.05) risk of breast cancer was found with A1166C polymorphism in codominant (CC vs. AA OR=1.200 [0.256-5.631] and AC vs. AA 0.941 [OR=0.223-3.976]), dominant (OR=1.00 [0.240-4.167]), recessive (OR=1.230 [0.593-2.552]) and additive models (OR=1.028 [0.533-1.983]) of general population genotypes. Nonetheless, when the AA genotype was considered a reference group, a significant association was found between AC and CC genotypes and invasive ductal and ductal carcinoma development in breast cancer patients. In conclusion, this study demonstrated no significant association between AGTR1 (A1166C) polymorphism and breast cancer risk.}, }
@article {pmid38049608, year = {2024}, author = {Maggi, G and Giacobbe, C and Vitale, C and Amboni, M and Obeso, I and Santangelo, G}, title = {Theory of mind in mild cognitive impairment and Parkinson's disease: The role of memory impairment.}, journal = {Cognitive, affective &amp; behavioral neuroscience}, volume = {24}, number = {1}, pages = {156-170}, pmid = {38049608}, issn = {1531-135X}, mesh = {Humans ; *Parkinson Disease/complications/psychology ; *Theory of Mind ; *Cognitive Dysfunction/etiology/psychology ; Executive Function ; *Cognition Disorders ; Memory Disorders ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Social cognition is impaired in Parkinson's disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI).<br><br>METHODS: Fifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses.<br><br>RESULTS: Memory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests.<br><br>CONCLUSIONS: Our findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.}, }
@article {pmid38273267, year = {2024}, author = {Yang, ZJ and Xin, F and Chen, ZJ and Yu, Y and Wang, X and Cao, XC}, title = {Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {134}, pmid = {38273267}, issn = {1471-2407}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/metabolism ; Neoadjuvant Therapy ; Treatment Outcome ; Receptor, ErbB-2/metabolism ; Ki-67 Antigen ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Neoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy.<br><br>METHODS: This retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR.<br><br>RESULTS: The breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68-0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER&#x2009;+&#x2009;PR&#x2009;+&#x2009;HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2&#x2009;+&#x2009;, Ki67 index&#x2009;<&#x2009;30% population. However, for ER-PR-HER2-positive patients, the neoadjuvant chemotherapy regimen has a great influence on the pCR rates.<br><br>CONCLUSIONS: Patients with ER-negative, PR-negative, HER2 3&#x2009;+&#x2009;and high KI-67 index were more likely to achieve pCR. THP may be used as an alternative to AC-THP or TCbHP in selected HER2-positive patients.}, }
@article {pmid38273260, year = {2024}, author = {Saad, HA and Baz, A and Riad, M and Eraky, ME and El-Taher, A and Farid, MI and Sharaf, K and Said, HEM and Ibrahim, LA}, title = {Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.}, journal = {BMC immunology}, volume = {25}, number = {1}, pages = {9}, pmid = {38273260}, issn = {1471-2172}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; Mastectomy ; Vimentin/therapeutic use ; *Carcinoma, Ductal, Breast/pathology/secondary/surgery ; Tumor Microenvironment ; Matrix Metalloproteinase 1/therapeutic use ; *Carcinoma, Lobular/pathology/secondary/surgery ; }, abstract = {BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences.<br><br>METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, &#x3b1;-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated.<br><br>RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p&#x2009;=&#x2009;0.000 and 0.021), PDGF (p&#x2009;=&#x2009;0.000 and 0.002), and CD95 (p&#x2009;=&#x2009;0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p&#x2009;=&#x2009;0.000) and &#x3b1;-SMA (p&#x2009;=&#x2009;0.000). &#x3b1;-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form.<br><br>CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.}, }
@article {pmid37919558, year = {2024}, author = {Avatefi, M and HadavandSiri, F and Nazari, SSH and Akbari, ME}, title = {Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {7}, number = {1}, pages = {e1927}, pmid = {37919558}, issn = {2573-8348}, mesh = {Female ; Humans ; *Breast Neoplasms/diagnosis/epidemiology/therapy ; Retrospective Studies ; *Neoplasms, Second Primary/diagnosis/epidemiology/etiology ; Risk Factors ; Proportional Hazards Models ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem.<br><br>AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors.<br><br>METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6&#x2009;months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92&#x2009;years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60&#x2009;years and older were negatively associated with CBC.<br><br>CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.}, }
@article {pmid38272241, year = {2024}, author = {Failayev, H and Ganoth, A and Tsfadia, Y}, title = {Molecular insights on the coronavirus MERS-CoV interaction with the CD26 receptor.}, journal = {Virus research}, volume = {}, number = {}, pages = {199330}, doi = {10.1016/j.virusres.2024.199330}, pmid = {38272241}, issn = {1872-7492}, abstract = {The Middle East respiratory syndrome (MERS) is a severe respiratory disease with high fatality rates, caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus initiates infection by binding to the CD26 receptor (also known as dipeptidyl peptidase 4 or DPP4) via its spike protein. Although the receptor-binding domain (RBD) of the viral spike protein and the complex between RBD and the extracellular domain of CD26 have been studied using X-ray crystallography, conflicting studies exist regarding the importance of certain amino acids outside the resolved RBD-CD26 complex interaction interface. To gain atomic-level knowledge of the RBD-CD26 complex, we employed computational simulations to study the complex's dynamic behavior as it evolves from its crystal structure to a conformation stable in solution. Our study revealed previously unidentified interaction regions and interacting amino acids within the complex, determined a novel comprehensive RBD-binding domain of CD26, and by that expanded the current understanding of its structure. Additionally, we examined the impact of a single amino acid substitution, E513A, on the complex's stability. We discovered that this substitution disrupts the complex through an allosteric domino-like mechanism that affects other residues. Since MERS-CoV is a zoonotic virus, we evaluated its potential risk of human infection via animals, and suggest a low likelihood for possible infection by cats or dogs. The molecular structural information gleaned from our insights into the RBD-CD26 complex pre-dissociative states may be proved useful not only from a mechanistic view but also in assessing inter-species transmission and in developing anti-MERS-CoV antiviral therapeutics.}, }
@article {pmid38265547, year = {2024}, author = {Dai, Q and Feng, K and Liu, G and Cheng, H and Tong, X and Wang, X and Feng, L and Wang, Y}, title = {Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China.}, journal = {Targeted oncology}, volume = {}, number = {}, pages = {}, pmid = {38265547}, issn = {1776-260X}, support = {CIFMS//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: 2021-I2M-1-014//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: LC2022A02//Beijing Hope Run Special Fund of Cancer Foundation of China/ ; }, abstract = {BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status.<br><br>OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups.<br><br>PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months.<br><br>RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models.<br><br>CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.}, }
@article {pmid38091153, year = {2024}, author = {Schwartz, CJ and Khorsandi, N and Blanco, A and Mukhtar, RA and Chen, YY and Krings, G}, title = {Clinicopathologic and genetic analysis of invasive breast carcinomas in women with germline CHEK2 variants.}, journal = {Breast cancer research and treatment}, volume = {204}, number = {1}, pages = {171-179}, pmid = {38091153}, issn = {1573-7217}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; *Breast Neoplasms/genetics/pathology ; Checkpoint Kinase 2/genetics ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Germ Cells ; Carrier Proteins/genetics ; }, abstract = {PURPOSE: Germline pathogenic variants in checkpoint kinase 2 (CHEK2) are associated with a moderately increased risk of breast cancer (BC). The spectrum of clinicopathologic features and genetics of these tumors has not been fully established.<br><br>METHODS: We characterized the histopathologic and clinicopathologic features of 44 CHEK2-associated BCs from 35 women, and assessed responses to neoadjuvant chemotherapy. A subset of cases (n&#x2009;=&#x2009;23) was additionally analyzed using targeted next-generation DNA sequencing (NGS).<br><br>RESULTS: Most (94%, 33/35) patients were heterozygous carriers for germline CHEK2 variants, and 40% had the c.1100delC allele. Two patients were homozygous, and five had additional germline pathogenic variants in ATM (2), PALB2 (1), RAD50 (1), or MUTYH (1). CHEK2-associated BCs occurred in younger women (median age 45&#xa0;years, range 25-75) and were often multifocal (20%) or bilateral (11%). Most (86%, 38/44) were invasive ductal carcinomas of no special type (IDC-NST). Almost all (95%, 41/43) BCs were ER&#x2009;+&#x2009;(79% ER&#x2009;+&#x2009;HER2-, 16% ER&#x2009;+&#x2009;HER2&#x2009;+&#x2009;, 5% ER-HER2&#x2009;+), and most (69%) were luminal B. Nottingham grade, proliferation index, and results of multiparametric molecular testing were heterogeneous. Biallelic CHEK2 alteration with loss of heterozygosity was identified in most BCs (57%, 13/23) by NGS. Additional recurrent alterations included GATA3 (26%), PIK3CA (226%), CCND1 (22%), FGFR1 (22%), ERBB2 (17%), ZNF703 (17%), TP53 (9%), and PPM1D (9%), among others. Responses to neoadjuvant chemotherapy were variable, but few patients (21%, 3/14) achieved pathologic complete response. Most patients (85%) were without evidence of disease at time of study (n&#x2009;=&#x2009;34). Five patients (15%) developed distant metastasis, and one (3%) died (mean follow-up 50&#xa0;months).<br><br>CONCLUSION: Almost all CHEK2-associated BCs were ER&#x2009;+&#x2009;IDC-NST, with most classified as luminal B with or without HER2 overexpression. NGS supported the luminal-like phenotype and confirmed CHEK2 as an oncogenic driver in the majority of cases. Responses to neoadjuvant chemotherapy were variable but mostly incomplete.}, }
@article {pmid37897648, year = {2024}, author = {Zhao, YY and Ge, HJ and Yang, WT and Shao, ZM and Hao, S}, title = {Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.}, journal = {Breast cancer research and treatment}, volume = {203}, number = {3}, pages = {543-551}, pmid = {37897648}, issn = {1573-7217}, support = {82203789//National Natural Science Foundation of China/ ; 82102683//National Natural Science Foundation of China/ ; }, mesh = {Male ; Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma, Ductal, Breast/pathology ; In Situ Hybridization, Fluorescence ; China ; Prognosis ; *Triple Negative Breast Neoplasms/pathology ; *Carcinoma ; }, abstract = {PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method.<br><br>RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46&#xa0;years (mean, 48.1&#xa0;years; range, 10-80&#xa0;years). The tumor sizes ranged from 0.3 to 6.8&#xa0;cm, with a mean of 3.5&#xa0;cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients.<br><br>CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve&#xa0;diagnosis and management in this unique subtype of breast cancer.}, }
@article {pmid38170222, year = {2024}, author = {Li, QY and Guo, Q and Luo, WM and Luo, XY and Ji, YM and Xu, LQ and Guo, JL and Shi, RS and Li, F and Lin, CY and Zhang, J and Ke, D}, title = {Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.}, journal = {Aging}, volume = {16}, number = {1}, pages = {66-88}, doi = {10.18632/aging.205338}, pmid = {38170222}, issn = {1945-4589}, mesh = {Humans ; Cisplatin/pharmacology/therapeutic use ; *Lung Neoplasms/drug therapy/genetics/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; *Adenocarcinoma of Lung/drug therapy/genetics/pathology ; Drug Resistance, Neoplasm/genetics ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Tumor Microenvironment/genetics ; }, abstract = {OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis.<br><br>METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting.<br><br>RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC.<br><br>CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.}, }
@article {pmid38250443, year = {2023}, author = {Wang, Y and Zhang, X and Yan, Y and Niu, T and Zhang, M and Fan, C and Liang, W and Shu, Y and Guo, C and Guo, D and Bi, Y}, title = {GmABCG5, an ATP-binding cassette G transporter gene, is involved in the iron deficiency response in soybean.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1289801}, pmid = {38250443}, issn = {1664-462X}, abstract = {Iron deficiency is a major nutritional problem causing iron deficiency chlorosis (IDC) and yield reduction in soybean, one of the most important crops. The ATP-binding cassette G subfamily plays a crucial role in substance transportation in plants. In this study, we cloned the GmABCG5 gene from soybean and verified its role in Fe homeostasis. Analysis showed that GmABCG5 belongs to the ABCG subfamily and is subcellularly localized at the cell membrane. From high to low, GmABCG5 expression was found in the stem, root, and leaf of young soybean seedlings, and the order of expression was flower, pod, seed stem, root, and leaf in mature soybean plants. The GUS assay and qRT-PCR results showed that the GmABCG5 expression was significantly induced by iron deficiency in the leaf. We obtained the GmABCG5 overexpressed and inhibitory expressed soybean hairy root complexes. Overexpression of GmABCG5 promoted, and inhibition of GmABCG5 retarded the growth of soybean hairy roots, independent of nutrient iron conditions, confirming the growth-promotion function of GmABCG5. Iron deficiency has a negative effect on the growth of soybean complexes, which was more obvious in the GmABCG5 inhibition complexes. The chlorophyll content was increased in the GmABCG5 overexpression complexes and decreased in the GmABCG5 inhibition complexes. Iron deficiency treatment widened the gap in the chlorophyll contents. FCR activity was induced by iron deficiency and showed an extraordinary increase in the GmABCG5 overexpression complexes, accompanied by the greatest Fe accumulation. Antioxidant capacity was enhanced when GmABCG5 was overexpressed and reduced when GmABCG5 was inhibited under iron deficiency. These results showed that the response mechanism to iron deficiency is more actively mobilized in GmABCG5 overexpression seedlings. Our results indicated that GmABCG5 could improve the plant's tolerance to iron deficiency, suggesting that GmABCG5 might have the function of Fe mobilization, redistribution, and/or secretion of Fe substances in plants. The findings provide new insights into the ABCG subfamily genes in the regulation of iron homeostasis in plants.}, }
@article {pmid38229073, year = {2024}, author = {Ido, M and Fujii, K and Mishima, H and Kubo, A and Saito, M and Banno, H and Ito, Y and Goto, M and Ando, T and Mouri, Y and Kousaka, J and Imai, T and Nakano, S}, title = {Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {85}, pmid = {38229073}, issn = {1471-2407}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Phosphatidylinositol 3-Kinases/genetics ; Neoplasm Recurrence, Local/drug therapy/genetics ; Genomics ; Mutation ; *Carcinoma ; High-Throughput Nucleotide Sequencing ; }, abstract = {AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease.<br><br>PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n&#x2009;=&#x2009;19) and inoperable de novo stage IV breast cancer (n&#x2009;=&#x2009;3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient.<br><br>RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n&#x2009;=&#x2009;19), invasive lobular carcinoma (n&#x2009;=&#x2009;2), and invasive micropapillary carcinoma (n&#x2009;=&#x2009;1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n&#x2009;=&#x2009;9), followed by TP53 (n&#x2009;=&#x2009;7), MYC (n&#x2009;=&#x2009;4), PTEN (n&#x2009;=&#x2009;3), and CDH1 (n&#x2009;=&#x2009;3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment.<br><br>CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.}, }
@article {pmid32239879, year = {2023}, author = {Zheng, X and Yin, J}, title = {Efficacy of texture analysis in determining the gene amplification status of HER2 2+ for invasive ductal carcinoma cases.}, journal = {Minerva medica}, volume = {114}, number = {6}, pages = {832-838}, doi = {10.23736/S0026-4806.20.06536-2}, pmid = {32239879}, issn = {1827-1669}, mesh = {Humans ; Female ; Gene Amplification ; Magnetic Resonance Imaging/methods ; In Situ Hybridization, Fluorescence ; Contrast Media ; *Carcinoma, Ductal/genetics ; *Breast Neoplasms/diagnostic imaging/genetics ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {BACKGROUND: Gene amplification of human epidermal growth factor receptor2 (HER2) 2+ is essential to be determined for treatment planning. A search of the PubMed database indicates that the correlation between texture features from dynamic contrast enhanced (DCE)-MRI and HER2 2+ status has not been investigated extensively in invasive ductal carcinoma cases.<br><br>METHODS: Seventy-one DCE-MRI cases of HER2 2+ status verified using fluorescence in-situ hybridization (FISH) were selected, including 36 positive and 35 negative cases. Overall, 279 texture features were derived from lesion regions of interest manually drawn onto the subtraction images between pre- and post-contrast agent. Fisher coefficient, mutual information, minimization of both classification error probability and average correlation coefficients as well as a combination of all three methods (MPF) were independently used to reduce the dimensionality of texture parameters. A popular machine learning algorithm, the Support Vector Machine, was further applied to determine HER2 2+ status. Receiver operating characteristic (ROC) analysis was conducted to evaluate the classification performance.<br><br>RESULTS: Diagnostic accuracy was optimal when the most significant discriminatory features were selected using MPF. The area under ROC curve reached 0.863 with corresponding accuracy, sensitivity and specificity rates of 81.80%, 85.71% and 77.78%, respectively.<br><br>CONCLUSIONS: Texture analysis based on breast MRI delivered consistently high performance with FISH detection and may serve as a useful supplementary tool for determining the gene amplification status of HER2 2+ for cases with invasive ductal carcinoma.}, }
@article {pmid38193247, year = {2024}, author = {Okano, K and Miyai, K and Mikoshi, A and Edo, H and Ito, K and Tsuda, H and Shinmoto, H}, title = {Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {}, number = {}, pages = {}, doi = {10.1111/iju.15385}, pmid = {38193247}, issn = {1442-2042}, abstract = {OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer.<br><br>METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups.<br><br>RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p&#x2009;<&#x2009;0.0001), anterior location (p&#x2009;=&#x2009;0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p&#x2009;=&#x2009;0.026), and high stromal periostin expression (p&#x2009;<&#x2009;0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup.<br><br>CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.}, }
@article {pmid37847513, year = {2024}, author = {Zhao, J and Xu, N and Zhu, S and Nie, L and Zhang, M and Zheng, L and Cai, D and Sun, X and Chen, J and Dai, J and Ni, Y and Wang, Z and Zhang, X and Liang, J and Chen, Y and Hu, X and Pan, X and Yin, X and Liu, H and Zhao, F and Zhang, B and Chen, H and Miao, J and Qin, C and Zhao, X and Yao, J and Liu, Z and Liao, B and Wei, Q and Li, X and Liu, J and Gao, AC and Huang, H and Shen, P and Chen, N and Zeng, H and Sun, G}, title = {Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.}, journal = {Cancer research}, volume = {84}, number = {1}, pages = {154-167}, doi = {10.1158/0008-5472.CAN-23-1176}, pmid = {37847513}, issn = {1538-7445}, support = {82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; ZYJC21020//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; 2022-12M-C&amp;T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Mediccal Sciences/ ; mnzl202002//Beijing Bethune Charitable Foundation/ ; mnzl202007//Beijing Bethune Charitable Foundation/ ; 2023HXBH024//Postdoctoral Research and Development Fund of West China Hospital of Sichuan University/ ; }, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Prostate/pathology ; *Adenocarcinoma/genetics/pathology ; *Prostatic Neoplasms/pathology ; Genomics ; Neoplasm Grading ; }, abstract = {UNLABELLED: Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.<br><br>SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.}, }
@article {pmid38157332, year = {2023}, author = {Shinohara, T and Asoda, T and Nakano, Y and Yamada, H and Fujimori, Y}, title = {Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e942208}, doi = {10.12659/AJCR.942208}, pmid = {38157332}, issn = {1941-5923}, abstract = {BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.}, }
@article {pmid38131316, year = {2023}, author = {Özden, A and Dalgıç, B and Demir, M and Hazırolan, G and Uzun, &#xd6; and Metan, G}, title = {Impact of a hospital sepsis management protocol on the selection of empirical antibiotics in infectious disease consultations.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/1120009X.2023.2296146}, pmid = {38131316}, issn = {1973-9478}, abstract = {It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=0.33). However, the rate of susceptibility to piperacillin-tazobactam was statistically higher in the pre-protocol period (82.6% vs 46.2%, p=0.016) when 39.7% of the patients received piperacillin-tazobactam as the empirical treatment. This study highlights the significance of using a structured protocol to attain appropriate empirical treatment for patients suspected of sepsis, even in a setting where IDC is readily available.}, }
@article {pmid37769530, year = {2023}, author = {Siregar, KB and Al Anas, M}, title = {Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia's tertiary referral hospital.}, journal = {Cancer treatment and research communications}, volume = {37}, number = {}, pages = {100764}, doi = {10.1016/j.ctarc.2023.100764}, pmid = {37769530}, issn = {2468-2942}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/secondary ; *Carcinoma, Ductal, Breast/secondary ; Retrospective Studies ; Indonesia/epidemiology ; Tertiary Care Centers ; *Bone Neoplasms ; }, abstract = {INTRODUCTION: The histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each.<br><br>METHODS: The cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories.<br><br>RESULTS: The average age was 44.28&#xb1;9.80 years (25-62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively).<br><br>CONCLUSION: There is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.}, }
@article {pmid38104283, year = {2023}, author = {Maman, A and Senol, O}, title = {Evaluating Alterations in Breast Cancer Patients after Recovery Via A PET/CT-Assisted Metabolomics Approach.}, journal = {Puerto Rico health sciences journal}, volume = {42}, number = {4}, pages = {276-282}, pmid = {38104283}, issn = {2373-6011}, abstract = {OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery.<br><br>MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm.<br><br>RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient.<br><br>CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.}, }
@article {pmid38090235, year = {2023}, author = {Adedokun, KA and Oluogun, WA and Oyenike, MA and Imodoye, SO and Yunus, LA and Lasisi, SA and Bello, IO and Kamorudeen, RT and Adekola, SA}, title = {Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients.}, journal = {Sultan Qaboos University medical journal}, volume = {23}, number = {4}, pages = {526-533}, pmid = {38090235}, issn = {2075-0528}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53 ; Receptor, ErbB-2/genetics/metabolism ; Hormones ; }, abstract = {OBJECTIVES: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade.<br><br>METHODS: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53.<br><br>RESULTS: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed.<br><br>CONCLUSION: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.}, }
@article {pmid38076287, year = {2023}, author = {Tractenberg, RE and Groah, SL and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH}, title = {Urinary Symptoms Among People With Neurogenic Lower Urinary Tract Dysfunction (NLUTD) Vary by Bladder Management.}, journal = {Topics in spinal cord injury rehabilitation}, volume = {29}, number = {3}, pages = {31-43}, pmid = {38076287}, issn = {1945-5763}, mesh = {Humans ; Urinary Bladder ; *Urinary Bladder, Neurogenic/therapy/diagnosis ; *Spinal Cord Injuries/complications ; Catheters, Indwelling ; Pain/complications ; }, abstract = {OBJECTIVES: To determine whether assessment and decision-making around urinary symptoms in people with neurogenic lower urinary tract dysfunction (NLUTD) should depend on bladder management.<br><br>METHODS: Three surveys of urinary symptoms associated with NLUTD (USQNBs) were designed specific to bladder management method for those who manage their bladders with indwelling catheter (IDC), intermittent catheter (IC), or voiding (V). Each was deployed one time to a national sample. Subject matter experts qualitatively assessed the wording of validated items to identify potential duplicates. Clustering by unsupervised structural learning was used to analyze duplicates. Each item was classified into mutually exclusive and exhaustive categories: clinically actionable ("fever"), bladder-specific ("suprapubic pain"), urine quality ("cloudy urine"), or constitutional ("leg pain").<br><br>RESULTS: A core of 10 "NLUTD urinary symptoms" contains three clinically actionable, bladder-specific, and urine quality items plus one constitutional item. There are 9 (IDC), 11 (IC), and 8 (V) items unique to these instruments. One decision-making protocol applies to all instruments.<br><br>CONCLUSION: Ten urinary symptoms in NLUTD are independent of bladder management, whereas a similar number depend on bladder management. We conclude that assessment of urinary symptoms for persons with NLUTD should be specific to bladder management method, like the USQNBs are.}, }
@article {pmid37792368, year = {2023}, author = {Martelli, G and Barretta, F and Vernieri, C and Folli, S and Pruneri, G and Segattini, S and Trapani, A and Carolla, C and Spatti, G and Miceli, R and Ferraris, C}, title = {Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection.}, journal = {JAMA surgery}, volume = {158}, number = {12}, pages = {1275-1284}, pmid = {37792368}, issn = {2168-6262}, mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/genetics/prevention &amp; control/surgery ; Salpingo-oophorectomy ; BRCA1 Protein/genetics ; Mastectomy ; Retrospective Studies ; BRCA2 Protein/genetics ; Genes, BRCA1 ; Neoplasm Recurrence, Local/genetics ; Ovariectomy ; *Ovarian Neoplasms/genetics/prevention &amp; control ; Mutation ; }, abstract = {IMPORTANCE: Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death.<br><br>OBJECTIVE: To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer.<br><br>This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023.<br><br>EXPOSURE: Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not.<br><br>MAIN OUTCOMES AND MEASURES: The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality.<br><br>RESULTS: Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P&#x2009;<&#x2009;.001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P&#x2009;=&#x2009;.001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P&#x2009;=&#x2009;.002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P&#x2009;=&#x2009;.008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality.<br><br>CONCLUSIONS: The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.}, }
@article {pmid38067216, year = {2023}, author = {Bernhardt, M and Kristiansen, G}, title = {Molecular Alterations in Intraductal Carcinoma of the Prostate.}, journal = {Cancers}, volume = {15}, number = {23}, pages = {}, doi = {10.3390/cancers15235512}, pmid = {38067216}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69-84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.}, }
@article {pmid36420590, year = {2023}, author = {Roberts, AC and Lunt, LG and Coogan, AC and Madrigrano, A}, title = {The Role of Radiation Therapy in Locally Advanced Breast Cancer in a Patient With Li-Fraumeni Syndrome.}, journal = {The American surgeon}, volume = {89}, number = {11}, pages = {4958-4960}, doi = {10.1177/00031348221135780}, pmid = {36420590}, issn = {1555-9823}, mesh = {Female ; Humans ; Adult ; *Li-Fraumeni Syndrome/complications/surgery ; *Breast Neoplasms/radiotherapy/surgery/pathology ; *Neoplasms, Radiation-Induced/etiology/surgery ; Mastectomy/adverse effects ; }, abstract = {Li-Fraumeni syndrome (LFS) is associated with many different cancers, including early onset breast cancer. Due to an increased risk of radiation-induced malignancy, radiation therapy is often avoided in this patient population. This case study evaluates a 38-year-old female with a history of juvenile granulosa cell tumor of the ovary and malignant phyllodes tumor of right breast, who subsequently developed bilateral invasive ductal carcinoma and was treated with bilateral mastectomies. Studies show that in a high-risk patient, post-mastectomy radiation therapy (PMRT) should not be ruled out due to a history of LFS, as the benefit of PMRT may outweigh the risk of a radiation-induced malignancy.}, }
@article {pmid38047107, year = {2023}, author = {Zhang, W and Nowotny, H and Theodoropoulou, M and Simon, J and Hemmer, CM and Bidlingmaier, M and Auer, MK and Reincke, M and Uhlenhaut, H and Reisch, N}, title = {E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1249863}, pmid = {38047107}, issn = {1664-2392}, mesh = {Humans ; Female ; Animals ; Mice ; *Glucocorticoids/pharmacology ; Prospective Studies ; Lipid Metabolism/genetics ; Adrenocorticotropic Hormone/metabolism ; Hydrocortisone ; *Cushing Syndrome ; Dexamethasone/pharmacology ; Cholesterol ; RNA, Messenger/metabolism ; }, abstract = {PURPOSE: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism.<br><br>METHODS: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47.<br><br>RESULTS: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30&#xa0;min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission.<br><br>CONCLUSION: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as&#xa0;dyslipidemia.}, }
@article {pmid38046902, year = {2023}, author = {Naeimzadeh, Y and Ilbeigi, S and Dastsooz, H and Rafiee Monjezi, M and Mansoori, Y and Tabei, SMB}, title = {Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers.}, journal = {BioMed research international}, volume = {2023}, number = {}, pages = {8236853}, pmid = {38046902}, issn = {2314-6141}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/pathology ; Breast/pathology ; GTPase-Activating Proteins/genetics/metabolism ; }, abstract = {Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully defined. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR). Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their significant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDC pathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC.}, }
@article {pmid37890687, year = {2024}, author = {Liao, H and Wang, H and Zheng, R and Yu, Y and Zhang, Y and Lv, L and Zhang, B and Chen, J}, title = {LncRNA CARMN suppresses EMT through inhibiting transcription of MMP2 activated by DHX9 in breast cancer.}, journal = {Cellular signalling}, volume = {113}, number = {}, pages = {110943}, doi = {10.1016/j.cellsig.2023.110943}, pmid = {37890687}, issn = {1873-3913}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *RNA, Long Noncoding/genetics/metabolism ; Matrix Metalloproteinase 2/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Epithelial Cells/metabolism ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; *MicroRNAs/genetics ; Neoplasm Proteins/genetics/metabolism ; DEAD-box RNA Helicases/genetics/metabolism ; }, abstract = {Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.}, }
@article {pmid38026906, year = {2023}, author = {Günay, S and Gökçek, B and Kandemir, &#xd6; and Akan, A and Yalçın, O}, title = {Long-term results of breast cancer patients who received IOERT as boost during BCS: A single-institution retrospective analysis.}, journal = {Turkish journal of surgery}, volume = {39}, number = {2}, pages = {115-120}, doi = {10.47717/turkjsurg.2023.5978}, pmid = {38026906}, issn = {2564-6850}, abstract = {OBJECTIVES: Intraoperative electron radiotherapy (IOERT) applied as boost to the tumor bed during breast conserving surgery is advantageous in terms of local recurrence in breast cancer patients. In addition, it has other advantages over the adjuvant boost RT such as no risk of tumor bed change, ease of sequencing radiotherapy chemotherapy, and reduced workload of the radiotherapy clinic. This study aimed to evaluate the long-term results of our patients who were treated with this method in our institution and are still being followed up.<br><br>MATERIAL AND METHODS: One hundred and three patients enrolled in this study received IOERT equivalent to 10 Gy as boost during BCS and were subsequently given adjuvant WBI according to the biological subtype of the tumor systemic therapy. These patients were analyzed using their files and hospital records. Patients were evaluated for overall survival, local recurrence, distant metastasis, and cosmetic outcome (using LENT-SOMA scale).<br><br>RESULTS: Median age was 53,5 (27-74), mean follow-up time was 75 (48-106) months. Mean pathological tumor size was 18 mm (4-30), 90 of the patients had invasive ductal carcinoma, eight of them were lobular and five of them had mixed histological structure. Ninety-three of the patients presented histological grade II, 15 grade III; 74 patients were luminal A-like, 15 luminal B-like, eight HER2 positive and six triple negative breast cancer. According to the LENT-SOMA scale, 35 had grade 0, 42 each had grade I, 23 had grade II, and two had grade III. All patients underwent whole breast irradiation after surgery, 81 received chemotherapy and 90 endocrine therapy. There was one local recurrence, distant recurrence was seen in four patients and one patient died of non-breast cancer causes. Overall survival was %99, and event free survival %96.<br><br>CONCLUSION: IOERT for breast cancer treatment during BCS is a safe option with low chronic toxicity and the cosmetic outcome gets better over time.}, }
@article {pmid38024052, year = {2023}, author = {Prabhu, SD and Rai, HS and Nayak, R and Naik, R and Jayasheelan, S}, title = {Study of the Immunohistochemical Expression of p63 in Benign Lesions and Carcinoma of the Breast at a Tertiary Hospital in South India.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e48557}, doi = {10.7759/cureus.48557}, pmid = {38024052}, issn = {2168-8184}, abstract = {BACKGROUND: Invasive breast carcinoma is among the most common female cancers worldwide, causing high morbidity and mortality. Considerable disagreement in the interpretation of diagnostically challenging breast lesions based on histology alone has been documented. One of the essential histopathological findings that help distinguish benign from malignant lesions is the presence of the myoepithelial cell layer. Myoepithelial markers such as tumor protein 63 (p63) help distinguish invasive carcinoma from benign proliferations. p63 antibody is superior to other myoepithelial markers as it selectively stains the nuclei and is negative in stromal cells.<br><br>OBJECTIVE: To study the expression of p63 in various histological subtypes and grades of breast carcinomas.<br><br>METHODS: After routine hematoxylin and eosin stain, 65 cases of breast lesions were subjected to immunohistochemistry for p63 antigen using Novacastra ready-to-use monoclonal antibody p6. All cases were analyzed for p63 expression, and its staining arrangement was interpreted.<br><br>RESULTS: In all benign lesions, immunoreactivity was noted in the myoepithelial cells, forming a continuous layer surrounding the luminal epithelial cells. The benign papillary lesions showed p63 staining in the fibrovascular core of the papillary fronds and at the periphery. A few single myoepithelial cells stained by p63 were also seen scattered discontinuously in ductal carcinoma in situ (DCIS). All invasive carcinomas and encapsulated papillary carcinomas were completely devoid of peripheral p63 staining of myoepithelial cells.<br><br>CONCLUSION: p63 is a specific nuclear marker of myoepithelial cells in the breast and can, therefore, aid in distinguishing invasive ductal carcinoma from DCIS or rare questionable hyperplastic lesions. They also play a significant role in distinguishing various papillary lesions of the breast and, hence, can be incorporated into routine reporting for definitive diagnosis and accurate treatment.}, }
@article {pmid38022397, year = {2023}, author = {Zhu, XD and Yu, JH and Ai, FL and Wang, Y and Lv, W and Yu, GL and Cao, XK and Lin, J}, title = {Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.}, journal = {World journal of oncology}, volume = {14}, number = {6}, pages = {476-487}, doi = {10.14740/wjon1553}, pmid = {38022397}, issn = {1920-454X}, abstract = {BACKGROUND: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma.<br><br>METHODS: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram.<br><br>RESULTS: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis.<br><br>CONCLUSIONS: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.}, }
@article {pmid38012767, year = {2023}, author = {Deguchi, S and Iwakami, A and Tujigiwa, M and Otake, H and Mano, Y and Yamamoto, N and Nakazawa, Y and Misra, M and Nagai, N}, title = {Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone.}, journal = {Journal of pharmaceutical health care and sciences}, volume = {9}, number = {1}, pages = {44}, pmid = {38012767}, issn = {2055-0294}, abstract = {BACKGROUND: Gastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).<br><br>METHODS: Gastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.<br><br>RESULTS: On day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.<br><br>CONCLUSIONS: These results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.}, }
@article {pmid38008819, year = {2023}, author = {Jalilian, E and Abolhasani-Zadeh, F and Afgar, A and Samoudi, A and Zeinalynezhad, H and Langroudi, L}, title = {Neutralizing tumor-related inflammation and reprogramming of cancer-associated fibroblasts by Curcumin in breast cancer therapy.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20770}, pmid = {38008819}, issn = {2045-2322}, support = {IR.KMU.REC.1398.326//Kerman University of Medical Sciences/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer-Associated Fibroblasts/metabolism ; *Curcumin/pharmacology/therapeutic use/metabolism ; Cyclooxygenase 2/metabolism ; Dinoprostone/metabolism ; Fibroblasts/metabolism ; Inflammation/pathology ; Cell Line, Tumor ; Tumor Microenvironment ; }, abstract = {Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.}, }
@article {pmid37978324, year = {2023}, author = {Stead, Z and Capuano, R and Di Natale, C and Pain, A}, title = {The volatilome signatures of Plasmodium falciparum parasites during the intraerythrocytic development cycle in vitro under exposure to artemisinin drug.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20167}, pmid = {37978324}, issn = {2045-2322}, support = {BAS/1/1020-01-01//KAUST faculty baseline fund/ ; BAS/1/1020-01-01//KAUST faculty baseline fund/ ; Giunta Regionale n. G10795//Regione Lazio/ ; Giunta Regionale n. G10795//Regione Lazio/ ; }, mesh = {Humans ; Animals ; Plasmodium falciparum ; *Parasites ; *Antimalarials/pharmacology/therapeutic use ; *Volatile Organic Compounds/pharmacology ; Drug Resistance ; *Artemisinins/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; *Malaria/drug therapy ; Protozoan Proteins/pharmacology ; }, abstract = {Volatile organic compounds (VOCs) comprise a diverse range of metabolites with high vapour pressure and low boiling points. Although they have received attention, they are a largely unexplored part of the metabolome. Previous studies have shown that malaria infections produce characteristic, definitive, and detectable volatile signatures. Many transcriptional and metabolic differences are observed at different stages of the parasite Intraerythrocytic Developmental Cycle (IDC) as well as when artemisinin-resistant parasites are put under drug pressure. This prompted our research to characterize whether these responses are reflected at a volatile level in malaria during the IDC stages using gas chromatography-mass spectrometry. We investigated whether the resistant P. falciparum parasites would produce their own characteristic volatilome profile compared to near-isogenic wild-type parasite in vitro; firstly at three different stages of the IDC and secondly in the presence or absence of artemisinin drug treatment. Finally, we explored the VOC profiles from two media environments (Human serum and Albumax) of recently lab-adapted field parasite isolates, from Southeast Asia and West/East Africa, compared to long-term lab-adapted parasites. Recognizable differences were observed between IDC stages, with schizonts having the largest difference between wild type and resistant parasites, and with cyclohexanol and 2,5,5-trimethylheptane only present for resistant schizonts. Artemisinin treatment had little effect on the resistant parasite VOC profile, whilst for the wild type parasites compounds ethylbenzene and nonanal were greatly affected. Lastly, differing culturing conditions had an observable impact on parasite VOC profile and clustering patterns of parasites were specific to geographic origin. The results presented here provide the foundation for future studies on VOC based characterization of P. falciparum strains differing in abilities to tolerate artemisinin.}, }
@article {pmid37993256, year = {2023}, author = {Wang, H and Ma, X and Li, S and Ni, X}, title = {SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.}, journal = {Aging}, volume = {15}, number = {}, pages = {}, doi = {10.18632/aging.205227}, pmid = {37993256}, issn = {1945-4589}, abstract = {BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear.<br><br>METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting.<br><br>RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more.<br><br>CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.}, }
@article {pmid37705411, year = {2023}, author = {McMurtry, V and Cleary, AS and Ruano, AL and Lomo, L and Gulbahce, HE}, title = {Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.}, journal = {American journal of clinical oncology}, volume = {46}, number = {12}, pages = {559-566}, doi = {10.1097/COC.0000000000001041}, pmid = {37705411}, issn = {1537-453X}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/genetics ; *Breast Neoplasms/genetics/epidemiology ; Proportional Hazards Models ; SEER Program ; Registries ; Prognosis ; }, abstract = {OBJECTIVES: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC.<br><br>METHODS: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. &#x3c7; 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD).<br><br>RESULTS: Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2&#xa0;cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC.<br><br>CONCLUSIONS: All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.}, }
@article {pmid37652705, year = {2023}, author = {Li, X and Stitt, D and Lanzino, G and Giannini, C and Dubey, D and Carabenciov, ID}, title = {Teaching NeuroImage: Pachymeningitis and Aortitis as the Initial Presentation of Granulomatosis With Polyangiitis.}, journal = {Neurology}, volume = {101}, number = {21}, pages = {979-980}, pmid = {37652705}, issn = {1526-632X}, mesh = {Humans ; *Aortitis/complications/diagnostic imaging ; *Granulomatosis with Polyangiitis/complications/diagnostic imaging ; *Meningitis/complications/diagnostic imaging ; }, }
@article {pmid37608749, year = {2023}, author = {Ito, T and Takahara, T and Taniguchi, N and Yamamoto, Y and Satou, A and Ohashi, A and Takahashi, E and Sassa, N and Tsuzuki, T}, title = {PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients.}, journal = {Pathology international}, volume = {73}, number = {11}, pages = {542-548}, doi = {10.1111/pin.13369}, pmid = {37608749}, issn = {1440-1827}, support = {21K06933//Japan Society for the Promotion of Science/ ; 21K15392//Japan Society for the Promotion of Science/ ; }, mesh = {Male ; Humans ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Incidence ; East Asian People ; *Prostatic Neoplasms/pathology ; PTEN Phosphohydrolase/genetics/metabolism ; }, abstract = {Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.}, }
@article {pmid37922498, year = {2023}, author = {Maggi, G and Giacobbe, C and Iannotta, F and Santangelo, G and Vitale, C}, title = {Prevalence and clinical aspects of obstructive sleep apnea in Parkinson disease: A meta-analysis.}, journal = {European journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ene.16109}, pmid = {37922498}, issn = {1468-1331}, abstract = {BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) frequently occurs in Parkinson Disease (PD), probably caused by upper airway dysfunctions or shared pathogenetic mechanisms. OSA may precede PD diagnosis or worsen throughout its course, but its relationship with clinical features and dopaminergic medication remains unclear. This meta-analysis aimed to provide a reliable estimate of OSA prevalence in the PD population (PD-OSA) and to clarify its clinical associated factors to help clinicians in understanding the underlying pathophysiological mechanisms.<br><br>METHODS: A systematic literature search was performed up to April 2023 using the PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with and without OSA. Pooled prevalence for PD-OSA was calculated using the proportions of PD participants diagnosed with OSA. Demographic and clinical features associated with PD-OSA were explored by comparing PD patients with and without OSA.<br><br>RESULTS: Seventeen studies were included in the meta-analysis. Pooled OSA prevalence was 45% of a total sample of 1448 PD patients and was associated with older age, male sex, higher body mass index (BMI), more severe motor disturbances and periodic limb movements, reduced risk of rapid eye movement sleep behavior disorder, intake of dopamine agonists, and worse excessive daytime sleepiness. No relationship emerged with cognitive functioning and neuropsychiatric manifestations.<br><br>CONCLUSIONS: OSA affects nearly half of PD patients as a secondary outcome of predisposing factors such as older age and higher BMI in addition to PD-related motor impairment. Future studies should focus on determining the impact of both clinical features and dopaminergic medication on the development of PD-OSA.}, }
@article {pmid37921670, year = {2023}, author = {Kalra, R and Lim, B and Ellis, MJ and Kavuri, SM}, title = {The uncharted role of HER2 mutant alleles in breast cancer.}, journal = {Oncotarget}, volume = {14}, number = {}, pages = {904-907}, pmid = {37921670}, issn = {1949-2553}, support = {P50 CA186784/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/genetics ; Alleles ; Receptor, ErbB-2/genetics ; }, abstract = {Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.}, }
@article {pmid37914605, year = {2023}, author = {Shuman, E and Goldenberg, A and Saguy, T and Halperin, E and van Zomeren, M}, title = {When Are Social Protests Effective?.}, journal = {Trends in cognitive sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tics.2023.10.003}, pmid = {37914605}, issn = {1879-307X}, abstract = {Around the world, people engage in social protests aimed at addressing major societal problems. Certain protests have led to significant progress, yet other protests have resulted in little demonstrable change. We introduce a framework for evaluating the effectiveness of social protest made up of three components: (i) what types of action are being considered; (ii) what target audience is being affected; and (iii) what outcomes are being evaluated? We then review relevant research to suggest how the framework can help synthesize conflicting findings in the literature. This synthesis points to two key conclusions: that nonviolent protests are effective at mobilizing sympathizers to support the cause, whereas more disruptive protests can motivate support for policy change among resistant individuals.}, }
@article {pmid37910521, year = {2023}, author = {Imamichi, T and Chen, Q and Sowrirajan, B and Yang, J and Laverdure, S and Marquez, M and Mele, AR and Watkins, C and Adelsberger, JW and Higgins, J and Sui, H}, title = {Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0287829}, pmid = {37910521}, issn = {1932-6203}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Interleukin-27 ; *HIV Infections ; Virus Internalization ; *HIV-1 ; Interleukins/metabolism ; Monocytes ; Autophagy/genetics ; DNA/metabolism ; Dendritic Cells/metabolism ; Virus Replication ; Spectrin/metabolism ; }, abstract = {Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3% without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.}, }
@article {pmid37879875, year = {2023}, author = {Wang, HY and Li, SJ and Zhang, AL and Ni, XC}, title = {[Identification of lymph node metastasis related genes in prostate cancer using weighted gene co-expression network analysis].}, journal = {Zhonghua yi xue za zhi}, volume = {103}, number = {40}, pages = {3204-3210}, doi = {10.3760/cma.j.cn112137-20230531-00902}, pmid = {37879875}, issn = {0376-2491}, mesh = {Male ; Humans ; Lymphatic Metastasis ; *Nomograms ; *Prostatic Neoplasms/genetics/pathology ; Neoplasm Grading ; Risk Factors ; }, abstract = {Objective: To explore the molecular markers related to lymph node metastasis of prostate cancer (PCa) based on bioinformatics technology and carry out clinical verification. Methods: The differentially expressed genes of PCa with lymph node metastasis were screened from geo data, and the hub genes of the gene co expression network were constructed. The hub genes were incorporated into the support vector machine model to evaluate its prediction efficiency. The hub genes were verified in the TCGA data set and analyzed for immune infiltration. The clinical data of 80 patients with prostate cancer in the Fourth Hospital of Hebei Medical University from January 2019 to December 2022 were collected. The logistic risk model was used to evaluate the prediction efficiency of hub gene metastasis. Results: Five hub genes (GSK3B, TP53, PSMC6, SUMO1, PIK3CA) were identified, and the support vector machine model constructed by them had good diagnostic value (the accuracy rate was 83.87%). TCGA validation results showed that only PSMC6 was significantly differentially expressed in PCa tissues with lymph node metastasis (P<0.001). The results of immune infiltration analysis showed that the expression of PSMC6 was significantly correlated with 9 kinds of immune cells (B cells, DC, IDC, etc.). Clinical information analysis showed that the expression of PSMC6 was significantly correlated with lymph node metastasis, PSA value, T stage and Gleason score (P<0.01). Univariate logistic results showed that T stage (OR=3.230, 95%CI:1.192-8.757, P=0.021), Gleason score (OR=4.627, 95%CI:2.212-9.677, P<0.001), PSMC6 (OR=25.235, 95%CI:5.326-119.560, P<0.001) could be used as predictors of lymph node metastasis. Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. Conclusion: PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.}, }
@article {pmid37874803, year = {2023}, author = {Coskunpinar, E and Tiryakioglu, DZ and Abaci, N and Tukenmez, M and Pence, S}, title = {Investigation of the miR-637 and miR-523-5p as candidate biomarkers in breast cancer.}, journal = {Bratislavske lekarske listy}, volume = {124}, number = {11}, pages = {814-820}, doi = {10.4149/BLL_2023_125}, pmid = {37874803}, issn = {0006-9248}, mesh = {Humans ; Female ; *Fibroadenoma/diagnosis/genetics ; *Breast Neoplasms/diagnosis/genetics/pathology ; *MicroRNAs/metabolism ; Biomarkers ; *Carcinoma, Ductal ; Biomarkers, Tumor/genetics ; Gene Expression Profiling ; }, abstract = {OBJECTIVES: The distinction of benign lesions from malign tumors is crucial for the diagnosis and treatment of breast cancers.<br><br>BACKGROUND: The aim of this study was to investigate the use of miRNAs as plasma biomarkers for the discrimination of malign and benign breast tumors.<br><br>METHODS: Whole blood samples obtained from 40 individuals in 3 groups designated as invasive ductal carcinoma group, fibroadenoma group and healthy controls were included in this study. The expression levels of 372 miRNAs were determined using RT-PCR. &#xa0;Results: The comparison of fibroadenoma group with healthy controls revealed an upregulation of thirty miRNAs and downregulation of twenty-nine miRNAs. The comparison of invasive ductal carcinoma (IDC) group with controls has shown that eight miRNAs were upregulated while eleven miRNAs were downregulated. When comparing IDC and fibroadenoma groups, 15 miRNAs were found to be upregulated, while 10 miRNAs were downregulated. Further analysis of these miRNAs aimed to determine their power in distinguishing&#xa0; IDCs from fibroadenomas. Among the miRNAs analyzed, seven miRNAs have shown sufficient discriminative power, of which three miRNAs, namely miR-637, miR-523-5p and miR-490-3p, have shown a significantly high discriminative power.<br><br>CONCLUSIONS: Circulating miR-637 and miR-523-5p combination maybe used to discriminate between invasive ductal carcinomas and fibroadenomas. (Tab. 9, Fig. 4, Ref. 30).}, }
@article {pmid37873952, year = {2023}, author = {Patel, K and Rao, DM and Sundersingh, S and Velusami, S and Rajkumar, T and Nair, B and Pandey, A and Chatterjee, A and Mani, S and Gowda, H}, title = {MicroRNA Expression Profile in Early-Stage Breast Cancers.}, journal = {MicroRNA (Shariqah, United Arab Emirates)}, volume = {}, number = {}, pages = {}, doi = {10.2174/0122115366256479231003064842}, pmid = {37873952}, issn = {2211-5374}, abstract = {BACKGROUND: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples. We identified 76 miRNAs that were differentially expressed in DCIS and IDC.<br><br>METHODS: Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in early-stage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples.<br><br>RESULTS: Higher expression of miR-301a-3p is associated with poor overall survival in The Can-cer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation.<br><br>CONCLUSION: We also analyzed competing endogenous networks associated with differentially expressed miRNAs and identified LRRC75A-AS1 and MAGI2-AS3 as lncRNAs that potentially play an important role in early-stage breast cancers.}, }
@article {pmid37835856, year = {2023}, author = {Khalid, A and Mehmood, A and Alabrah, A and Alkhamees, BF and Amin, F and AlSalman, H and Choi, GS}, title = {Breast Cancer Detection and Prevention Using Machine Learning.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {19}, pages = {}, pmid = {37835856}, issn = {2075-4418}, abstract = {Breast cancer is a common cause of female mortality in developing countries. Early detection and treatment are crucial for successful outcomes. Breast cancer develops from breast cells and is considered a leading cause of death in women. This disease is classified into two subtypes: invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The advancements in artificial intelligence (AI) and machine learning (ML) techniques have made it possible to develop more accurate and reliable models for diagnosing and treating this disease. From the literature, it is evident that the incorporation of MRI and convolutional neural networks (CNNs) is helpful in breast cancer detection and prevention. In addition, the detection strategies have shown promise in identifying cancerous cells. The CNN Improvements for Breast Cancer Classification (CNNI-BCC) model helps doctors spot breast cancer using a trained deep learning neural network system to categorize breast cancer subtypes. However, they require significant computing power for imaging methods and preprocessing. Therefore, in this research, we proposed an efficient deep learning model that is capable of recognizing breast cancer in computerized mammograms of varying densities. Our research relied on three distinct modules for feature selection: the removal of low-variance features, univariate feature selection, and recursive feature elimination. The craniocaudally and medial-lateral views of mammograms are incorporated. We tested it with a large dataset of 3002 merged pictures gathered from 1501 individuals who had digital mammography performed between February 2007 and May 2015. In this paper, we applied six different categorization models for the diagnosis of breast cancer, including the random forest (RF), decision tree (DT), k-nearest neighbors (KNN), logistic regression (LR), support vector classifier (SVC), and linear support vector classifier (linear SVC). The simulation results prove that our proposed model is highly efficient, as it requires less computational power and is highly accurate.}, }
@article {pmid37828835, year = {2023}, author = {Yang, SY and Zhang, J and Yang, ZQ and Duan, JJ and Zhang, Y and Li, MK and Wang, L and Ye, CM and Nie, JY}, title = {Advanced hormone receptor-positive/human epidermal growth factor receptor 2-positive invasive ductal carcinoma with cecal metastasis: A case report.}, journal = {Science progress}, volume = {106}, number = {4}, pages = {368504231201043}, pmid = {37828835}, issn = {2047-7163}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; *Breast Neoplasms/metabolism ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {The incidence of gastrointestinal metastases from breast cancer (BC) is low. We report a special case of Luminal B (Hormone Receptor positive [HR+]/Human Epidermal Growth Factor receptor 2-positive [HER-2+]) BC. The patient presented with asymptomatic brain metastases two years after radical surgery for modified breast cancer and developed right lower abdominal pain during relief therapy. Electronic gastroenteroscopy revealed inflammatory changes in the cecal mucosa. These changes were confirmed on pathology to be cecal metastasis from BC. The patient's condition was stabilised after treatment with an antibody-drug conjugate (ADC). For patients with BC who develop appendicitis-like symptoms after treatment for invasive ductal carcinoma of the breast, clinicians should be fully aware that the possibility of cecal metastasis needs to be considered, despite the very low probability of occurrence.}, }
@article {pmid37824772, year = {2023}, author = {Dieu Vuong, L and Ngoc Nguyen, Q}, title = {ABERRANT METHYLATION OF CANCER-RELATED GENES IN VIETNAMESE BREAST CANCER PATIENTS: ASSOCIATIONS WITH CLINICOPATHOLOGICAL FEATURES.}, journal = {Experimental oncology}, volume = {45}, number = {2}, pages = {195-202}, doi = {10.15407/exp-oncology.2023.02.195}, pmid = {37824772}, issn = {2312-8852}, mesh = {Humans ; Aged ; Female ; *Breast Neoplasms/genetics/pathology ; Southeast Asian People ; Promoter Regions, Genetic ; DNA Methylation ; ErbB Receptors/genetics ; }, abstract = {BACKGROUND: Epigenetic alteration is one of the most common molecular changes identified in the progression of breast cancer (BC).<br><br>AIM: To study the frequency and relation between methylation of BRCA1, MLH1, MGMT, GSTP1, APC, RASSF1A, p16, WIF, and EGFR and the clinicopathological features in Vietnamese BC patients.<br><br>MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (MS-PCR) and SPSS 20.0 software were utilized in order to identify methylated frequency as well as evaluate its relationship with the patient's clinical features.<br><br>RESULTS: In 162 BC cases, the methylation rates of the selected genes were 53.7%, 22.8%, 38.9%, 34.6%, 29.0%, 46.3%, 20.4%, 18.5%, and 28.4% respectively. In 32 cases of benign breast diseases (BBD) - 12.5%, 15.6%, 6.3%, 3.1%, 12.5%, 21.9%, 3.1%, 15.6% and 3.1%. BC samples displayed higher BRCA1, MGMT, GSTP1, APC, RASSF1A, WIF1, and p16 methylation levels than BBD samples (p < 0.001). Hypermethylation of BRCA1, GSTP1, and RASSF1A was predominant in the invasive ductal carcinoma, while hypermethylation of BRCA1, GSTP1, RASSF1A, WIF-1, and p16 was found to significantly correlate with lymph node metastasis (p < 0.05). Hypermethylation of BRCA1, MGMT, and GSTP1 was more common in stage III (p < 0.05) than in stages I/II, whereas MLH1 methylation was predominant in stage I and APC methylation was less common in stage III (p = 0.03). In addition, methylation of RASSF1A and EGFR was more frequent in younger patients (p < 0.01) than in elder patients.<br><br>CONCLUSION: These data suggest that a gene panel (BRCA1/MGMT/GSTP1) can be used to support the diagnosis and screening of Vietnamese patients' BC with a sensitivity of 70%, and a specificity of 85%.}, }
@article {pmid37800299, year = {2023}, author = {Takashima, Y and Terasawa, R and Hirata, A and Morita, S and Kimura, K and Iwamoto, M and Hayashi, M}, title = {[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {50}, number = {9}, pages = {1009-1011}, pmid = {37800299}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Combined Antibody Therapeutics ; *COVID-19 ; COVID-19 Drug Treatment ; Mastectomy ; }, abstract = {The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.}, }
@article {pmid37761331, year = {2023}, author = {Al-Refai, R and Bendari, A and Morrar, D and Sham, S and Kataw, L and Garajayev, A and Hajiyeva, S}, title = {Immunohistochemical Staining Characteristics of Low-Grade Invasive Ductal Carcinoma Using the ADH5 Cocktail (CK5/14, P63, and CK7/18): A Potential Interpretative Pitfall.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, pmid = {37761331}, issn = {2075-4418}, abstract = {Background: In our practice, the antibody cocktail ADH5 (CK5/14, p63, and CK7/18) helps with diagnostic challenges, such as identifying microinvasion and foci of invasive carcinoma, differentiating atypical ductal hyperplasia from hyperplasia of the usual type, and distinguishing basal phenotypes in triple-negative carcinomas. However, the ADH5 cocktail does have pitfalls and caveats. Methods: We describe our experience with the ADH5 cocktail of antibodies in breast pathology. Institutional knowledge and a literature search form our data sources. Results: We analyzed 44 cases. Four out of a total of 44 cases (9.1%)-two tubular carcinomas and two low-grade invasive breast carcinomas of no special type (ductal) with tubular features-showed an expected pattern of staining for ADH5 with a loss of brown (P63, CK5/14) staining around invasive glands and diffuse red (CK7/18) expression. Forty out of 44 (90.9%) cases showed an unexpected staining pattern (mixture of cytoplasmic brown and red). All 44 cases (100%) showed negative myoepithelial staining around invasive foci when separately stained for P63 and SMMH (Smooth Muscle Myosin Heavy). Conclusions: The unexpected staining pattern of ADH5 in low-grade invasive ductal carcinomas can be challenging to interpret in these lesions with low-grade cytology. The occurrence can cause confusion among users who employ multiplex stains, and it is important for users to be aware of this potential pitfall.}, }
@article {pmid37749321, year = {2023}, author = {Taylor, J and Uhl, L and Moll, I and Hasan, SS and Wiedmann, L and Morgenstern, J and Giaimo, BD and Friedrich, T and Alsina-Sanchis, E and De Angelis Rigotti, F and Mülfarth, R and Kaltenbach, S and Schenk, D and Nickel, F and Fleming, T and Sprinzak, D and Mogler, C and Korff, T and Billeter, AT and Müller-Stich, BP and Berriel Diaz, M and Borggrefe, T and Herzig, S and Rohm, M and Rodriguez-Vita, J and Fischer, A}, title = {Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.}, journal = {Nature cancer}, volume = {}, number = {}, pages = {}, pmid = {37749321}, issn = {2662-1347}, support = {394046768 - SFB1366//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1118-A04/S01//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BO 1639/9-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.}, }
@article {pmid37747019, year = {2023}, author = {Choi, JH and Yu, J and Jung, M and Jekal, J and Kim, KS and Jung, SU}, title = {Prognostic significance of TP53 and PIK3CA mutations analyzed by next-generation sequencing in breast cancer.}, journal = {Medicine}, volume = {102}, number = {38}, pages = {e35267}, pmid = {37747019}, issn = {1536-5964}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics ; Prognosis ; Mastectomy ; High-Throughput Nucleotide Sequencing ; Class I Phosphatidylinositol 3-Kinases/genetics ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Breast cancer is one of the most prevalent malignant tumors affecting women globally. It is a heterogeneous disease characterized by mutations in several genes. Several gene panels have been applied to assess the risk of breast cancer and determine the appropriate treatment. As a powerful tool, Next-generation sequencing (NGS) has been widely utilized in cancer research due to its advantages, including high speed, high throughput, and high accuracy. In this study, we aim to analyze the correlation between somatic mutations in breast cancer, analyzed using NGS, and the prognosis of patients. Between May 2018 and May 2019, a total of 313 patients with breast cancer underwent surgical treatment, which included total mastectomy and breast-conserving surgery. Among these patients, 265 were diagnosed with invasive ductal carcinoma. In this study, we analyzed the NGS results, clinicopathological characteristics, and their correlation with prognosis. Using a gene panel, we examined 143 somatic mutations in solid cancers. Notably, the study population included patients who had received neoadjuvant chemotherapy. The mean age of the patients was 53.1 (±10.28) years, and the median follow-up time was 48 months (range, 8-54). Among the 265 patients, 68 had received prior systemic therapy. Of these, 203 underwent breast-conserving surgery, and 62 underwent a mastectomy. Various somatic mutations were observed in NGS, with the most frequent mutation being PIK3CA mutations, which accounted for 44% of all mutations. TP53 mutations were the second most frequent, and ERBB2 mutations were the third most frequent. TP53 mutations were associated with poor disease-free survival (P = .027), while PIK3CA mutations were associated with better disease-free survival (P = .035) than PIK3CA wild-type. In our study, we identified various somatic mutations in breast cancer. Particularly, we found that TP53 and PIK3CA mutations are potentially associated with the prognosis of breast cancer. These findings suggest that the presence of specific mutations may have implications for predicting the prognosis of breast cancer. Further research and validation are needed to gain a deeper understanding of the role of these mutations and their mechanisms in prognosis prediction.}, }
@article {pmid37743485, year = {2023}, author = {Pourriahi, R and Omranipour, R and Alipour, S and Hajimaghsoudi, L and Mashoori, N and Kenary, AY and Motamedi, M and Tavakol, M and Mohammadzadeh, M and Hessamiazar, S and Shabani, S and Mahmoodi, F and Goodarzi, MM and Eslami, B}, title = {Clinical characteristics of breast cancer patients admitted to academic surgical wards in Tehran, Iran: an analytical cross-sectional study.}, journal = {BMC women's health}, volume = {23}, number = {1}, pages = {511}, pmid = {37743485}, issn = {1472-6874}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/epidemiology ; Iran/epidemiology ; Cross-Sectional Studies ; Hospitalization ; Palpation ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women. Knowledge of the clinical characteristics of BC in a population may be informative for disease prediction or diagnosis and for developing screening and diagnostic guidelines. This study aimed to evaluate the clinical characteristics of female patients with BC who were admitted to academic surgical wards in Tehran, Iran.<br><br>METHODS: In this cross-sectional study, demographic information and clinical characteristics of Iranian females with BC who had undergone breast surgery from 2017-2021 in four academic Breast Surgery Units were extracted from medical files and recorded via a pre-designed checklist.<br><br>RESULTS: A total of 1476 patients with a mean age of 48.03 (&#xb1;&#x2009;11.46) years were enrolled. Among them, 10.4% were aged less than 35. In younger patients, Triple-negative and Her2-enriched subtypes of BC were significantly higher compared to older ones. Overall, 85.7% of tumors were invasive ductal carcinoma, 43.3% were grade 2, 41.4% were located in the UOQ, and 65.2% had presented with mass palpation. The mean pathologic tumor size was 28.94 mm, and the most common subtype was luminal B.<br><br>CONCLUSIONS: Many characteristics of breast cancer in this study were similar to other countries and previous studies in Iran. However, a higher proportion of young BC compared with Western countries, and even with older studies in Iran, suggest a trend toward lower age for BC in recent years. These results indicate the need for preventive measures and screening in Iranian women at a younger age.}, }
@article {pmid37737015, year = {2023}, author = {Sijnesael, T and Richard, F and Rätze, MA and Koorman, T and Bassey-Archibong, B and Rohof, C and Daniel, J and Desmedt, C and Derksen, PW}, title = {Canonical Kaiso target genes define a functional signature that associates with breast cancer survival and the invasive lobular carcinoma histological type.}, journal = {The Journal of pathology}, volume = {261}, number = {4}, pages = {477-489}, doi = {10.1002/path.6205}, pmid = {37737015}, issn = {1096-9896}, support = {2018NovPCC1297/BBC_/Breast Cancer Now/United Kingdom ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/metabolism ; Neoplasm Recurrence, Local ; Prognosis ; Cadherins/genetics/metabolism ; Transcription Factors/metabolism ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes. Here, we examined whether an anchorage-independent and ILC-specific transcriptional program correlated with clinical parameters in breast cancer. Based on the presence of a canonical Kaiso-binding consensus sequence (cKBS) in the promoters of genes that are upregulated under anchorage-independent conditions, we defined an ILC-specific anoikis resistance transcriptome (ART). Converting the ART genes into human orthologs and adding published Kaiso target genes resulted in the Kaiso-specific ART (KART) 33-gene signature, used subsequently to study correlations with histological and clinical variables in primary breast cancer. Using publicly available data for ER[POS] Her2[NEG] breast cancer, we found that expression of KART was positively associated with the histological ILC breast cancer type (p < 2.7E-07). KART expression associated with younger patients in all invasive breast cancers and smaller tumors in invasive ductal carcinoma of no special type (IDC-NST) (<2 cm, p < 6.3E-10). We observed associations with favorable long-term prognosis in both ILC (hazard ratio [HR] = 0.51, 95% CI = 0.29-0.91, p < 3.4E-02) and IDC-NST (HR = 0.79, 95% CI = 0.66-0.93, p < 1.2E-04). Our analysis thus defines a new mRNA expression signature for human breast cancer based on canonical Kaiso target genes that are upregulated in E-cadherin deficient ILC. The KART signature may enable a deeper understanding of ILC biology and etiology. © 2023 The Authors. The Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, }
@article {pmid37697863, year = {2023}, author = {Lu, D and Li, F and Zhao, C and Ye, Y and Zhang, X and Yang, P and Zhang, X}, title = {A Remineralizing and Antibacterial Coating for Arresting Caries.}, journal = {Journal of dental research}, volume = {102}, number = {12}, pages = {1315-1325}, doi = {10.1177/00220345231189992}, pmid = {37697863}, issn = {1544-0591}, mesh = {Humans ; *Dental Caries/prevention &amp; control ; Dental Caries Susceptibility ; *Tooth Demineralization/prevention &amp; control ; Dental Enamel ; Composite Resins ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Tooth Remineralization/methods ; }, abstract = {Dental caries is a dynamic disease induced by the unbalance between demineralization of dental hard tissues caused by biofilm and remineralization of them; however, although various effective remineralization methods have been well documented, it is a challenge to reestablish the balance by enhancing remineralization alone while ignoring the antibacterial therapy. Therefore, the integration of remineralizing and antibacterial technologies offers a promising strategy to halt natural caries progression in clinical practice. Here, the conception of interrupting dental caries (IDC) was proposed based on the development of dual-functional coating with remineralizing and antibacterial properties. In this study, bovine serum albumin (BSA) loaded octenidine (OCT) successfully to form a BSA-OCT composite. Subsequently, through fast amyloid-like aggregation, the phase-transited BSA-OCT (PTB-OCT) coating can be covered on teeth, resin composite, or sealant surfaces in 30 min by a simple smearing process. The PTB-OCT coating showed satisfactory effects in promoting the remineralization of demineralized enamel and dentin in vitro. Moreover, this coating also exerted significant acid-resistance stability and anti-biofilm properties. Equally importantly, this coating exhibited promising abilities in reducing the microleakage between the tooth and resin composite in vitro and preventing primary and secondary caries in vivo. In conclusion, this novel dual-functional PTB-OCT coating could reestablish the balance between demineralization and remineralization in the process of caries, thereby potentially preventing or arresting caries.}, }
@article {pmid37683019, year = {2023}, author = {Moon, SY and Lim, KR and Son, JS}, title = {The role of infectious disease consultations in the management of patients with fever in a long-term care facility.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0291421}, pmid = {37683019}, issn = {1932-6203}, mesh = {Humans ; Long-Term Care ; Retrospective Studies ; Nursing Homes ; Fever ; Referral and Consultation ; Tertiary Care Centers ; *Cardiomyopathy, Dilated ; *Communicable Diseases/therapy ; }, abstract = {BACKGROUND: Infectious disease (ID) clinicians can provide essential services for febrile patients in tertiary hospitals. The aim of this study was to evaluate the role of ID consultations (IDC) in managing hospitalized patients with infections in an oriental medical hospital (OMH), which serves as a long-term care facility. To our knowledge, this is the first study on the role of IDCs in managing patients in an OMH.<br><br>METHODS: This retrospective study was conducted in an OMH in Seoul, Korea, from June 2006 to June 2013.<br><br>RESULTS: Among the 465 cases of hospital-acquired fever, 141 (30.3%) were referred for ID. The most common cause of fever was infection in both groups. The peak body temperature of the patient was higher in IDC group (38.8&#xb1;0.6&#xb0;C vs. 38.6&#xb1;0.5&#xb0;C, p<0.001). Crude mortality at 30 days (14.6% vs. 7.8%, p = 0.043) and infection-attributable mortality (15.3% vs. 6.7%, p = 0.039) were higher in the No-IDC group. Multivariable analysis showed that infection as the focus of fever (adjusted Odd ratio [aOR] 3.49, 95% confidence interval (CI) 1.64-7.44), underlying cancer (aOR 10.32, 95% CI 4.34-24.51,), and multiorgan dysfunction syndrome (aOR 15.68, 95% CI 2.06-119.08) were associated with increased 30-day mortality. Multivariate analysis showed that in patients with infectious fever, appropriate antibiotic therapy (aOR 0.19, 95% CI 0.05-0.76) was the only factor associated with decreased infection-attributable mortality while underlying cancer (aOR 7.80, 95% CI 2.555-23.807) and severe sepsis or septic shock at the onset of fever (aOR 10.15, 95% CI 1.00-102.85) were associated with increased infection-attributable mortality.<br><br>CONCLUSION: Infection was the most common cause of fever in patients hospitalized for OMH. Infection as the focus of fever, underlying cancer, and MODS was associated with increased 30-day mortality in patients with nosocomial fever. Appropriate antibiotic therapy was associated with decreased infection-attributable mortality in patients with infectious fever.}, }
@article {pmid37637763, year = {2023}, author = {Abbasi, A and Ghaffarizadeh, F and Mojdeganlou, H}, title = {Prognostic Significance of Microvessel Density in Invasive Ductal Carcinoma of Breast.}, journal = {International journal of hematology-oncology and stem cell research}, volume = {17}, number = {2}, pages = {100-105}, pmid = {37637763}, issn = {2008-3009}, abstract = {Background: Breast cancer is the most common malignant tumor and cause of death in women. Factors that play role in tumor metastasis are lymph node involvement, lack of tumor differentiation and hormone receptor expression, high proliferation rate, and angiogenesis. In the present study, we tried to evaluate the microvessel density (MVD) using Immunohistochemistry for the CD34 marker to investigate the amount of angiogenesis in breast cancer and its relationship with other histopathological parameters and compare it with normal tissue. Materials and Methods: 58 paraffin-embedded samples of breast cancer were enrolled. All blocks were sectioned and stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2(HER 2/neu), ki67, and CD34 by immunohistochemistry (IHC) method. Results: The mean age of patients in this study was 49.6 ± 10.6 years. Statistically, there was a significant relationship between the grade of the tumor (P = 0.01), absence of expression of estrogen receptor (P = 0.008), and progesterone receptor (P = 0.003) with MVD. Conclusion: Due to the association between MVD, tumor grade, and absence of ER and PR expression, this valuable marker can play an important role in the prediction of prognosis in breast cancer patients and can lead to new-targeted therapy in the future.}, }
@article {pmid37635979, year = {2023}, author = {Barlier, A and Romanet, P and Pellegata, NS}, title = {Editorial: New insights into multiple endocrine neoplasia type 1.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1266148}, pmid = {37635979}, issn = {1664-2392}, mesh = {Humans ; *Multiple Endocrine Neoplasia Type 1/genetics ; }, }
@article {pmid37559588, year = {2023}, author = {Bai, X and Fang, C and Liu, B and Huagn, J and Chen, X and Xie, X and Zhang, Q and Liu, M and Liang, J and Guo, J and Song, L and Lan, X and Chen, L and Huang, S and Deng, W and Luo, Z and Du, C}, title = {Breast cancer metastases to the thyroid and stomach: A case report.}, journal = {Oncology letters}, volume = {26}, number = {3}, pages = {386}, pmid = {37559588}, issn = {1792-1082}, abstract = {The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (-), progesterone receptor (-), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner.}, }
@article {pmid37558640, year = {2023}, author = {Doi, K and Fujii, T and Hanamoto, M and Takamura, K and Nakada, T and Sato, Y and Ogura, K}, title = {[A Case of BRCA2 Mutation-Positive Intraductal Carcinoma of the Prostate].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {69}, number = {7}, pages = {189-192}, doi = {10.14989/ActaUrolJap_69_7_189}, pmid = {37558640}, issn = {0018-1994}, mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Prostate-Specific Antigen ; Hematuria ; *Prostatic Neoplasms/drug therapy/genetics/pathology ; Disease Progression ; Mutation ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology ; BRCA2 Protein/genetics ; }, abstract = {A 75-year-old man presented with macroscopic hematuria and a high serum prostate-specific antigen (PSA) level. Macroscopic hematuria had subsided by the time of consultation. The PSA level was 38.590 ng/ml, which, along with rectal examination and magnetic resonance imaging findings, led to the suspicion of prostate cancer. Transrectal needle biopsy of the prostate revealed intraductal carcinoma of the prostate (IDC-P). Computed tomography and bone scintigraphy were performed, and the prostate cancer was classified as cT2cN0M0. After 6 months of combined androgen blockade therapy, a radical prostatectomy was performed; however, PSA levels continued to increase, and the patient was diagnosed with castration resistant prostate cancer. Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued. The IDC-P was found to be positive for the BRCA2 mutation by BRACAnalysis® performed at the start of cabazitaxel therapy. To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.}, }
@article {pmid37548682, year = {2023}, author = {Mooshage, CM and Schimpfle, L and Kender, Z and Tsilingiris, D and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Kurz, FT and Jende, JME}, title = {Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.}, journal = {Clinical neuroradiology}, volume = {}, number = {}, pages = {}, pmid = {37548682}, issn = {1869-1447}, abstract = {INTRODUCTION/AIMS: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.<br><br>METHODS: A&#xa0;total of 18&#xa0;patients with type&#xa0;2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10&#xa0;healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (K[trans]), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp).<br><br>RESULTS: The K[trans] (HC 0.031&#x202f;min[-1]&#x202f;&#xb1;&#x2009;0.009, T2D 0.043&#x202f;min[-1]&#x202f;&#xb1;&#x2009;0.015; p&#x202f;=&#x2009;0.033) and Ve (HC 1.2%&#x202f;&#xb1;&#x2009;1.5, T2D: 4.1%&#x202f;&#xb1;&#x2009;5.1; p&#x202f;=&#x2009;0.027) were lower in T2D patients compared to controls. In T2D patients, compound z&#x2011;scores of thermal and mechanical detection correlated with K[trans] (r&#x202f;=&#x2009;0.73; p&#x202f;=&#x2009;0.001, and r&#x202f;=&#x2009;0.57; p&#x202f;=&#x2009;0.018, respectively) and Ve (r&#x202f;=&#x2009;0.67; p&#x202f;=&#x2009;0.002, and r&#x202f;=&#x2009;0.69; p&#x202f;=&#x2009;0.003, respectively). Compound z&#x2011;scores of thermal pain and Vp (r&#x202f;=&#x2009;-0.57; p&#x202f;=&#x2009;0.015) correlated negatively.<br><br>DISCUSSION: The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A&#xa0;reduced capillary permeability may result in a&#xa0;loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a&#xa0;gain of function.}, }
@article {pmid37536436, year = {2023}, author = {Abdollahi, E and Mozdarani, H}, title = {Epigenetic regulation of circ-HIPK3, circ-PVT1, miR-25, and miR-149 in radiosensitivity of breast cancer.}, journal = {Experimental and molecular pathology}, volume = {132-133}, number = {}, pages = {104865}, doi = {10.1016/j.yexmp.2023.104865}, pmid = {37536436}, issn = {1096-0945}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics/radiotherapy ; Epigenesis, Genetic ; Leukocytes, Mononuclear ; Radiation Tolerance/genetics ; *MicroRNAs/genetics ; Cell Proliferation ; Protein Serine-Threonine Kinases ; Intracellular Signaling Peptides and Proteins ; }, abstract = {Assessing the radiosensitivity of cells before administering radiation therapy (RT) to individuals diagnosed with breast cancer (BC) can facilitate the selection of appropriate treatment regimens and minimize the incidence of adverse side effects in patients undergoing radiation exposure. In this research, blood samples were obtained from 60 women who had been diagnosed with Invasive Ductal Carcinoma (IDC) Breast Cancer. The average age of the patients was 47 ± 9.93. Additionally, the study incorporated 20 healthy women, with an average age of 44.43 ± 6.7. A standard G2 assay was conducted to predict the cellular response to radiation. Out of the 60 samples, the G2 assay identified 20 patients with breast cancer who exhibited radiosensitivity. Hence, molecular investigations were ultimately conducted on two equivalent cohorts comprising 20 subjects each, one with and the other without cellular radiosensitivity. The expression levels of miR-149, miR-25, circ-PVT1, and circ-HIPK3 in peripheral blood mononuclear cells (PBMCs) were evaluated using quantitative polymerase chain reaction (qPCR). Receiver Operating Characteristic (ROC) curves were used to evaluate the sensitivity and specificity of the RNAs. An analysis using binary logistic regression was performed to investigate the relationship between RNAs and both BC and cellular radiosensitivity (CR) in patients with BC. The findings revealed a significant upregulation of Circ-HIPK3 and circ-PVT1 in individuals diagnosed with BC. The levels of Circ-HIPK3 and Circ-PVT1 were found to be directly associated with CR in BC patients. The analysis of the ROC curve demonstrated that circ-HIPK3 and circ-PVT1 exhibit favorable specificity and sensitivity in accurately predicting both BC and CR in patients with BC. The findings from the binary logistic regression analysis demonstrated that circ-HIPK3 and circ-PVT1 were effective predictors of both BC and CR. The ROC curve and binary logistic regression analyses provide evidence that miR-25 is a reliable predictor for BC patients exclusively. Our research has demonstrated that circ-HIPK3, circ-PVT1, and miR-25 may be involved in BC regulatory processes. The circular RNAs Circ-HIPK3 and circ-PVT1, as well as miR-25, among other significant biomarkers, could potentially serve as promising biomarkers for predicting BC. Furthermore, Circ-HIPK3 and circ-PVT1 have the potential to serve as biomarkers for predicting CR in BC patients.}, }
@article {pmid37530887, year = {2023}, author = {Kishore, A and Venkataramana, L and Prasad, DVV and Mohan, A and Jha, B}, title = {Enhancing the prediction of IDC breast cancer staging from gene expression profiles using hybrid feature selection methods and deep learning architecture.}, journal = {Medical &amp; biological engineering &amp; computing}, volume = {61}, number = {11}, pages = {2895-2919}, pmid = {37530887}, issn = {1741-0444}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; Transcriptome ; Neoplasm Staging ; *Deep Learning ; Gene Expression Profiling/methods ; }, abstract = {Prediction of the stage of cancer plays an important role in planning the course of treatment and has been largely reliant on imaging tools which do not capture molecular events that cause cancer progression. Gene-expression data-based analyses are able to identify these events, allowing RNA-sequence and microarray cancer data to be used for cancer analyses. Breast cancer is the most common cancer worldwide, and is classified into four stages - stages 1, 2, 3, and 4 [2]. While machine learning models have previously been explored to perform stage classification with limited success, multi-class stage classification has not had significant progress. There is a need for improved multi-class classification models, such as by investigating deep learning models. Gene-expression-based cancer data is characterised by the small size of available datasets, class imbalance, and high dimensionality. Class balancing methods must be applied to the dataset. Since all the genes are not necessary for stage prediction, retaining only the necessary genes can improve classification accuracy. The breast cancer samples are to be classified into 4 classes of stages 1 to 4. Invasive ductal carcinoma breast cancer samples are obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets and combined. Two class balancing techniques are explored, synthetic minority oversampling technique (SMOTE) and SMOTE followed by random undersampling. A hybrid feature selection pipeline is proposed, with three pipelines explored involving combinations of filter and embedded feature selection methods: Pipeline 1 - minimum-redundancy maximum-relevancy (mRMR) and correlation feature selection (CFS), Pipeline 2 - mRMR, mutual information (MI) and CFS, and Pipeline 3 - mRMR and support vector machine-recursive feature elimination (SVM-RFE). The classification is done using deep learning models, namely deep neural network, convolutional neural network, recurrent neural network, a modified deep neural network, and an AutoKeras generated model. Classification performance post class-balancing and various feature selection techniques show marked improvement over classification prior to feature selection. The best multiclass classification was found to be by a deep neural network post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with a Cohen-Kappa score of 0.303 and a classification accuracy of 53.1%. For binary classification into early and late-stage cancer, the best performance is obtained by a modified deep neural network (DNN) post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with an accuracy of 81.0% and a Cohen-Kappa score (CKS) of 0.280. This pipeline also showed improved multiclass classification performance on neuroblastoma cancer data, with a best area under the receiver operating characteristic (auROC) curve score of 0.872, as compared to 0.71 obtained in previous work, an improvement of 22.81%. The results and analysis reveal that feature selection techniques play a vital role in gene-expression data-based classification, and the proposed hybrid feature selection pipeline improves classification performance. Multi-class classification is possible using deep learning models, though further improvement particularly in late-stage classification is necessary and should be explored further.}, }
@article {pmid37530324, year = {2023}, author = {Cakir, Y and Talu, CK and Trabulus, DC and Mermut, O}, title = {The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {66}, number = {3}, pages = {456-464}, doi = {10.4103/ijpm.ijpm_284_21}, pmid = {37530324}, issn = {0974-5130}, mesh = {Humans ; Female ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Galectin 3/genetics ; *Triple Negative Breast Neoplasms/pathology ; Retrospective Studies ; *Carcinoma, Ductal ; *Breast Neoplasms ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers.<br><br>AIM: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas.<br><br>MATERIALS AND METHODS: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs.<br><br>STATISTICAL ANALYSIS: Data was analyzed with t-tests and Chi-square tests. Kaplan-Meier and Log-rank tests were used for survival analysis.<br><br>RESULTS: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs.<br><br>CONCLUSIONS: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.}, }
@article {pmid37517027, year = {2023}, author = {Amato, S and Ramsey, J and Ahern, TP and Rovnak, J and Barlow, J and Weaver, D and Eyasu, L and Singh, R and Cintolo-Gonzalez, J}, title = {Exploring the presence of bovine leukemia virus among breast cancer tumors in a rural state.}, journal = {Breast cancer research and treatment}, volume = {202}, number = {2}, pages = {325-334}, pmid = {37517027}, issn = {1573-7217}, mesh = {Cattle ; Humans ; Female ; Animals ; Sheep/genetics ; Male ; *Breast Neoplasms/epidemiology/genetics ; *Leukemia Virus, Bovine/genetics ; DNA, Viral/genetics ; Breast ; *Mammary Neoplasms, Animal ; }, abstract = {PURPOSE: The bovine leukemia virus (BLV) is a deltaretrovirus that causes malignant lymphoma and lymphosarcomas in cattle globally and has high prevalence among large scale U.S. dairy herds. Associations between presence of BLV DNA in human mammary tissue and human breast cancer incidence have been reported. We sought to estimate the prevalence of BLV DNA in breast cancer tissue samples in a rural state with an active dairy industry.<br><br>METHODS: We purified genomic DNA from 56 fresh-frozen breast cancer tissue samples (51 tumor samples, 5 samples representing adjacent normal breast tissue) banked between 2016 and 2019. Using nested PCR assays, multiple BLV tax sequence primers and primers for the long terminal repeat (LTR) were used to detect BLV DNA in tissue samples and known positive control samples, including the permanently infected fetal lamb kidney cell line (FLK-BLV) and blood from BLV positive cattle.<br><br>RESULTS: The median age of patients from which samples were obtained at the time of treatment was 60 (40-93) and all were female. Ninety percent of patients had invasive ductal carcinoma. The majority were poorly differentiated (60%). On PCR assay, none of the tumor samples tested positive for BLV DNA, despite having consistent signals in positive controls.<br><br>CONCLUSION: We did not find BLV DNA in fresh-frozen breast cancer tumors from patients presenting to a hospital in Vermont. Our findings suggest a low prevalence of BLV in our patient population and a need to reevaluate the association between BLV and human breast cancer.}, }
@article {pmid37513591, year = {2023}, author = {Hardt, LM and Herrmann, HJ and Reljic, D and Jaensch, P and Zerth, J and Neurath, MF and Zopf, Y}, title = {Are Guideline Recommendations on Supportive Nutrition and Exercise Therapy for Cancer Patients Implemented in Clinical Routine? A National Survey with Real-Life Data.}, journal = {Nutrients}, volume = {15}, number = {14}, pages = {}, pmid = {37513591}, issn = {2072-6643}, support = {MED1710//Hector-Stiftung/ ; N.N.//Research Foundation for Medicine at the University Hospital Erlangen/ ; }, mesh = {Humans ; Quality of Life ; Nutritional Support ; *Malnutrition/diagnosis ; *Neoplasms/complications/therapy ; Exercise Therapy ; }, abstract = {Malnutrition and cancer cachexia are highly prevalent comorbidities of cancer, limiting patients' quality of life and being relevant to prognosis. International and national clinical guidelines recommend supportive nutrition and exercise therapy for cancer patients. However, there is little current epidemiological evidence on the implementation of these guideline recommendations in clinical routine. To close this data gap, a national survey in Germany using an online questionnaire was conducted. There were 261 of a total of 5074 contacted hospitals and medical offices who participated in the survey (5.1% response rate). The data indicated that nutrition and exercise therapy for cancer patients is so far inadequately implemented, with 59% of the respondents reporting nutrition therapy as an integral part of oncological treatment, 66.7% having a nutrition specialist/team, and 65.1% routinely conducting a screening for nutritional status. Only half of the participants stated that there are defined goals in nutrition therapy. The majority of respondents (85.8%) generally recommend exercise therapy, but only a few of them provide specific offers at their own institution (19.6%) or at cooperation partners (31.7%). In order to implement the recommended combined nutrition and exercise therapy as part of regular care, there is a need for nationwide availability of multidisciplinary nutrition teams and targeted offers of individualized exercise therapy. Health policy support would be important to create the structural, financial, and staff conditions for appropriate guideline implementation in order to achieve the optimal treatment of cancer patients.}, }
@article {pmid37500355, year = {2023}, author = {Ding, W and Ye, D and Zhu, H and Lin, Y and Li, Z and Ruan, G}, title = {Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method.}, journal = {Clinical breast cancer}, volume = {23}, number = {7}, pages = {e441-e450}, doi = {10.1016/j.clbc.2023.07.004}, pmid = {37500355}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Retrospective Studies ; Biomarkers, Tumor ; Prognosis ; Chemotherapy, Adjuvant ; Proportional Hazards Models ; Neoplasm Recurrence, Local/pathology ; }, abstract = {INTRODUCTION: The role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial.<br><br>METHODS: A retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors.<br><br>RESULTS: Among 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P&#xa0;=&#xa0;.014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS).<br><br>CONCLUSION: Patients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.}, }
@article {pmid37496230, year = {2023}, author = {Konishi, K and Araya, J and Nagabuchi, M and Sakamoto, T and Ogino, J and Hirano, S}, title = {[A Case of Breast Carcinoma That Changed Subtype to Squamous Cell Carcinoma after Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {50}, number = {7}, pages = {825-827}, pmid = {37496230}, issn = {0385-0684}, mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/surgery/pathology ; Docetaxel/therapeutic use ; Mastectomy ; Quality of Life ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Carcinoma, Squamous Cell/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Cyclophosphamide/therapeutic use ; *Liver Neoplasms/drug therapy/surgery/secondary ; }, abstract = {Metaplastic carcinoma is a rare histological malignancy, often triple-negative, and has a poor prognosis. Here, we report a case of breast cancer in which the primary lesion degenerated into squamous cell carcinoma(triple negative)after drug treatment for invasive ductal carcinoma(Luminal type). The patient was a 41-year-old woman who was diagnosed with Stage Ⅳ left breast cancer T2N2bM1(HEP)(ER 90%, PR 70%, HER2 2+, FISH-)at another hospital and participated in the PATHWAY study(tamoxifen plus goserelin plus palbociclib/placebo). Since the primary lesion and liver metastasis increased in size, the study was discontinued after 8 weeks. She was treated at our hospital thereafter, with capecitabine plus cyclophosphamide, palbociclib plus fulvestrant plus leuprorelin, paclitaxel plus bevacizumab, eribulin, EC therapy, and docetaxel. However, both the primary lesion and liver metastasis increased. In particular, the increase in primary lesion size was remarkable, and the QOL significantly reduced due to bleeding and exudation. Biopsy performed during docetaxel treatment revealed metaplastic/squamous cell carcinoma(ER-, PR-, HER2 0, Ki-67 90-100%)histopathological findings. BRCA and microsatellite instability tests were negative, and PDL1 expression was less than 1%. Although Mohs ointment was used, tumor bleeding, exudate, and stink were poorly controlled, and the patient experienced painful symptoms due to the weight of the tumor. Therefore, left mastectomy plus pectoralis major muscle resection was performed. The patient died one month after the operation.}, }
@article {pmid37495452, year = {2023}, author = {Bódis, K and Bombrich, M and Schön, M and Knebel, B and Zaharia, OP and Bönhof, G and Karusheva, Y and Strassburger, K and Kupriyanova, Y and Kotzka, J and Guthoff, R and Schrauwen-Hinderling, V and Al-Hasani, H and Burkart, V and Szendroedi, J and Wagner, R and Markgraf, DF and Roden, M and , }, title = {Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes.}, journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD}, volume = {33}, number = {9}, pages = {1785-1796}, doi = {10.1016/j.numecd.2023.06.004}, pmid = {37495452}, issn = {1590-3729}, mesh = {Humans ; Male ; Case-Control Studies ; *Diabetes Mellitus, Type 2/diagnosis/genetics/complications ; *Insulin Resistance/genetics ; Liver/metabolism ; *Liver Neoplasms ; Membrane Proteins/genetics/metabolism ; *Non-alcoholic Fatty Liver Disease/diagnosis/genetics/complications ; Polymorphism, Single Nucleotide ; Triglycerides/metabolism ; }, abstract = {BACKGROUND AND AIMS: Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2[EK]; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.<br><br>METHODS AND RESULTS: Males with recent-onset type 2 diabetes with (TM6SF2[EK]: n&#xa0;=&#xa0;16) or without (TM6SF2[EE]: n&#xa0;=&#xa0;16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-[2]H2]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with [1]H-magnetic-resonance-spectroscopy. A subset of both groups (n&#xa0;=&#xa0;24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2[EK] had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2[EE]. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2[EE] only.<br><br>CONCLUSIONS: The TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.}, }
@article {pmid37490055, year = {2023}, author = {Choo, ZY and Xu, AZ}, title = {Predictors and outcomes of cutaneous metastatic breast carcinoma: a retrospective, single-institution review.}, journal = {Archives of dermatological research}, volume = {315}, number = {9}, pages = {2725-2728}, pmid = {37490055}, issn = {1432-069X}, mesh = {Humans ; Female ; Retrospective Studies ; *Breast Neoplasms/therapy ; Skin/pathology ; Administration, Cutaneous ; *Carcinoma, Lobular/pathology/secondary ; }, }
@article {pmid37480503, year = {2023}, author = {D'Iorio, A and Aiello, EN and Amboni, M and Vitale, C and Verde, F and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B and Santangelo, G}, title = {Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson's disease patients.}, journal = {Aging clinical and experimental research}, volume = {35}, number = {10}, pages = {2157-2163}, pmid = {37480503}, issn = {1720-8319}, mesh = {Humans ; *Parkinson Disease/complications/diagnosis ; Retrospective Studies ; Mental Status and Dementia Tests ; *Cognitive Dysfunction/diagnosis/etiology ; Language ; }, abstract = {BACKGROUND: This study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson's disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties.<br><br>METHODS: A retrospective cohort of N&#x2009;=&#x2009;237 non-demented PD patients having been administered the MoCA was addressed, of whom N&#x2009;=&#x2009;169 further underwent the Mini-Mental State Examination (MMSE) and N&#x2009;=&#x2009;68 the Parkinson's Disease Cognitive Rating Scale (PD-CRS). A subsample (N&#x2009;=&#x2009;60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score.<br><br>RESULTS: The MoCA was associated with both PD-CRS scores (p&#x2009;<&#x2009;.001) and the vast majority of second-level cognitive measures (ps&#x2009;<&#x2009;.003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and&#x2009;<&#x2009;19.015 is herewith suggested as indexing cognitive impairment in this population (AUC&#x2009;=&#x2009;.92; sensitivity&#x2009;=&#x2009;.92; specificity&#x2009;=&#x2009;.80).<br><br>DISCUSSION: The Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.}, }
@article {pmid37480256, year = {2023}, author = {White, D and Sadough Shahmirzadi, M and Boulmay, B}, title = {Multi-Phenotypic Breast Cancer Post-Radiotherapy for Hodgkin Lymphoma: A Case of Secondary Malignancy.}, journal = {Journal of investigative medicine high impact case reports}, volume = {11}, number = {}, pages = {23247096231188251}, pmid = {37480256}, issn = {2324-7096}, mesh = {Female ; Humans ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; *Breast Neoplasms/radiotherapy ; *Hodgkin Disease/radiotherapy ; Mastectomy ; Breast/pathology ; *Neoplasms, Second Primary/etiology ; }, abstract = {Morbidity and mortality associated with radiation-induced secondary malignancies (RISMs) have shifted treatment paradigms to minimize or eliminate radiation from treatment regimens. In this case, a 48-year-old woman was diagnosed with Hodgkin lymphoma (HL) and treated with radiotherapy in 2000. In 2018, she was diagnosed with ductal carcinoma in situ (DCIS) of the right breast and treated with a mastectomy. Soon after, she developed triple-negative invasive ductal carcinoma (IDC) in her reconstructed breast. The patient underwent a left lumpectomy, and pathology showed ER-/PR-/HER2+ IDC. This patient's multi-phenotypic DCIS and IDC presentation are suspected to be RISM due to her previous HL treatment regimen.}, }
@article {pmid37478120, year = {2023}, author = {Shi, K and Liu, XL and Guo, Q and Zhang, YQ and Fan, ST and Dai, L and Jiang, N and Li, D}, title = {TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0285817}, pmid = {37478120}, issn = {1932-6203}, mesh = {Female ; Humans ; *Endometrial Neoplasms/pathology ; Prognosis ; Nomograms ; RNA ; Biomarkers, Tumor/genetics/metabolism ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression.<br><br>METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC.<br><br>RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications.<br><br>CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.}, }
@article {pmid37470893, year = {2023}, author = {Chen, BF and Tsai, YF and Lien, PJ and Lin, YS and Feng, CJ and Chen, YJ and Cheng, HF and Tseng, LM and Huang, CC}, title = {Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {547-560}, pmid = {37470893}, issn = {1573-7217}, support = {V110E-005-3//Taipei Veterans General Hospital/ ; V111E-006-3//Taipei Veterans General Hospital/ ; V112E-004-3//Taipei Veterans General Hospital/ ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/epidemiology/genetics/therapy ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Taiwan/epidemiology ; Mastectomy ; Neoplasm Recurrence, Local/pathology ; Treatment Outcome ; Registries ; Retrospective Studies ; }, abstract = {PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry.<br><br>METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the &#x3c7;2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model.<br><br>RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.}, }
@article {pmid37439959, year = {2023}, author = {Tsunokake, S and Iwabuchi, E and Miki, Y and Kanai, A and Onodera, Y and Sasano, H and Ishida, T and Suzuki, T}, title = {SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {499-513}, pmid = {37439959}, issn = {1573-7217}, mesh = {Humans ; Female ; *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use ; Sodium-Glucose Transporter 2/metabolism ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; *Breast Neoplasms/drug therapy/genetics ; Glucose/metabolism ; *Carcinoma, Ductal ; }, abstract = {PURPOSE: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro.<br><br>METHODS: SGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors.<br><br>RESULTS: The SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation.<br><br>CONCLUSION: High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.}, }
@article {pmid37435234, year = {2023}, author = {Li, S and Tong, J and Li, H and Mao, C and Shen, W and Lei, Y and Hu, P}, title = {L. pneumophila Infection Diagnosed by tNGS in a Lady with Lymphadenopathy.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {4435-4442}, pmid = {37435234}, issn = {1178-6973}, abstract = {We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, Legionella pneumophila was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.}, }
@article {pmid37408309, year = {2023}, author = {Ji, H and Englmaier, F and Morigny, P and Giroud, M and Gräsle, P and Brings, S and Szendrödi, J and Berriel Diaz, M and Plettenburg, O and Herzig, S and Rohm, M}, title = {Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {31}, number = {8}, pages = {2408-2421}, pmid = {37408309}, issn = {1525-0024}, support = {R01 GM129325/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Adipose Tissue/metabolism ; *AMP-Activated Protein Kinases/metabolism ; Cachexia/drug therapy/etiology/metabolism ; *Neoplasms/complications/metabolism ; Peptides/pharmacology ; Pharmaceutical Preparations/metabolism ; Quality of Life ; }, abstract = {Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key event in cachexia-related adipose tissue dysfunction and developed an adeno-associated virus (AAV)-based approach to prevent AMPK degradation and prolong cachexia-free survival. Here, we show the development and optimization of a prototypic peptide, Pen-X-ACIP, where the AMPK-stabilizing peptide ACIP is fused to the cell-penetrating peptide moiety penetratin via a propargylic glycine linker to enable late-stage functionalization using click chemistry. Pen-X-ACIP was efficiently taken up by adipocytes, inhibited lipolysis, and restored AMPK signaling. Tissue uptake assays showed a favorable uptake profile into adipose tissue upon intraperitoneal injection. Systemic delivery of Pen-X-ACIP into tumor-bearing animals prevented the progression of cancer cachexia without affecting tumor growth and preserved body weight and adipose tissue mass with no discernable side effects in other peripheral organs, thereby achieving proof of concept. As Pen-X-ACIP also exerted its anti-lipolytic activity in human adipocytes, it now provides a promising platform for further (pre)clinical development toward a novel, first-in-class approach against cancer cachexia.}, }
@article {pmid37402637, year = {2023}, author = {Shulder, S and Tamma, PD and Fiawoo, S and Dzintars, K and Escobar, D and Livorsi, DJ and Malani, AN and Palacio, D and Spivak, ES and Zimmerman, M and Bork, JT}, title = {Infectious Diseases Consultation Associated With Reduced Mortality in Gram-Negative Bacteremia.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {9}, pages = {1234-1237}, doi = {10.1093/cid/ciad383}, pmid = {37402637}, issn = {1537-6591}, mesh = {Humans ; *Communicable Diseases ; Cohort Studies ; *Bacteremia ; Referral and Consultation ; Retrospective Studies ; *Gram-Negative Bacterial Infections ; }, abstract = {Gram-negative bacteremia (GN-BSI) can cause significant morbidity and mortality, but the benefit of infectious diseases consultation (IDC) is not well defined. A 24-site observational cohort study of unique hospitalized patients with 4861 GN-BSI episodes demonstrated a 40% decreased risk of 30-day mortality in patients with IDC compared to those without IDC.}, }
@article {pmid37385107, year = {2023}, author = {Chen, J and Gao, P and Xiao, W and Cheng, G and Krishna, S and Wang, J and Wong, YK and Wang, C and Gu, L and Yang, DH and Wang, J}, title = {Multi-omics dissection of stage-specific artemisinin tolerance mechanisms in Kelch13-mutant Plasmodium falciparum.}, journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy}, volume = {70}, number = {}, pages = {100978}, doi = {10.1016/j.drup.2023.100978}, pmid = {37385107}, issn = {1532-2084}, mesh = {Humans ; Plasmodium falciparum/genetics ; Multiomics ; Drug Resistance/genetics ; Protozoan Proteins/genetics/pharmacology/therapeutic use ; *Artemisinins/pharmacology/therapeutic use ; *Antimalarials/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; Mutation ; }, abstract = {AIMS: We investigated the stage-specific mechanisms of partial resistance to artemisinin (ART, an antimalarial drug) in Plasmodium falciparum (P. falciparum) carrying the Kelch13 C580Y mutation.<br><br>METHODS: Using fluorescence labeling and activity-based protein profiling, we systematically profile the ART activation levels in P. falciparum during the entire intra-erythrocytic developmental cycle (IDC), and determined the ART-targets profile of the ART-sensitive and -resistant strains at different stages. We retrieved and integrated datasets of single-cell transcriptomics and label-free proteomics across three IDC stages of wild-type P. falciparum. We also employed lipidomics to validate lipid metabolic reprogramming in the resistant strain.<br><br>RESULTS: The activation and expression patterns of genes and proteins of ART-targets in both ART-sensitive and resistant strains varied at different stages and periods of P. falciparum development, with the late trophozoite stage harboring the largest number of ART targets. We identified and validated 36 overlapping targets, such as GAPDH, EGF-1a, and SpdSyn, during the IDC stages in both strains. We revealed the ART-insensitivity of fatty acid-associated activities in the partially resistant strain at both the early ring and early trophozoite stages.<br><br>CONCLUSIONS: Our multi-omics strategies provide novel insights into the mechanisms of ART partial resistance in Kelch13 mutant P. falciparum, demonstrating the stage-specific interaction between ART and malaria parasites.}, }
@article {pmid37371442, year = {2023}, author = {Maggi, G and Vitale, C and Delle Curti, A and Amboni, M and Santangelo, G}, title = {Unawareness of Apathy in Parkinson's Disease: The Role of Executive Dysfunction on Symptom Recognition.}, journal = {Brain sciences}, volume = {13}, number = {6}, pages = {}, pmid = {37371442}, issn = {2076-3425}, abstract = {Altered self-awareness or anosognosia may impact patients' everyday life by interfering with their safe and independent functioning. Symptom awareness has been linked to executive dysfunctions caused by damage to frontal regions. Apathy is a frequent neuropsychiatric manifestation of Parkinson's disease (PD) and is considered a consequence of altered functioning of cortico-subcortical circuitries connecting the prefrontal cortex (PFC) with the basal ganglia. Thus, apathetic PD patients may be not be fully aware of their condition due to shared neuropathophysiological mechanisms. The present study aimed to explore the awareness of apathy in PD patients by comparing the self-reported evaluations with their caregivers' ratings. Moreover, we explored the clinical predictors of possible discrepancies and their consequences on patients' self-reported evaluation of quality of life (QoL). We found a fair agreement between patients' self-reports and caregivers' ratings on apathy scores, with patients reporting less severe apathetic symptoms, especially those related to executive and auto-activation processing, compared to their caregivers' reports. Executive functioning was found to mediate the relationship between disease stage and awareness of the apathetic state. Awareness of executive apathy impacted patients' self-reported QoL. Therefore, PD patients might be unaware of their apathetic symptoms, especially those with worse executive functioning, which plays a key role in metacognitive processes such as self-monitoring and error detection. Anosognosia for apathy in PD patients may affect their QoL perception and leads to misleading self-report evaluations that delay diagnosis and treatment.}, }
@article {pmid37363526, year = {2023}, author = {Kara Tahhan, N and Abou Azan, A and Jomaa Al Ali, I and Abdul Aziz, J and Sara, S}, title = {Cutaneous metastases as a primary manifestation of invasive ductal carcinoma of the breast: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {6}, pages = {3062-3065}, pmid = {37363526}, issn = {2049-0801}, abstract = {UNLABELLED: Cutaneous metastases as the first sign of invasive ductal carcinoma are not common. The ambiguous presentation of asymptomatic lesions may result in various diagnoses including dermatologic causes. Early diagnosis is essential in such cases.<br><br>CASE PRESENTATION: A 43-year-old woman with no risk factors for developing breast cancer at a young age was diagnosed with invasive ductal carcinoma of the left breast after dermatologic complaints of diffuse lesions on the left-back and right subclavian region. The patient remained asymptomatic except for the recent cutaneous presentation, which did not arouse much suspicion.<br><br>CONCLUSION: Cutaneous metastases of breast cancer remain uncommon, but at the same time represent a poor prognosis for the patient, and when they do occur, treatment options are limited. The delay in taking the proper diagnostic measures in such cases imposes a need to adopt a wider perspective when dealing with the possible occurrence of advanced disease. This also adds up to the importance of breast self-examination by women at a young age and full examination by physicians, especially when they encounter a misguiding presentation.}, }
@article {pmid37363420, year = {2023}, author = {Singh, S and Singh, AL and Pal, KK and Reddy, KK and Gangadhara, K and Dey, R and Mahatma, MK and Verma, A and Kumar, N and Patel, CB and Thawait, LK and Ahmed, S and Navapara, R and Rani, K and Kona, P}, title = {Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.}, journal = {Physiology and molecular biology of plants : an international journal of functional plant biology}, volume = {29}, number = {5}, pages = {725-737}, pmid = {37363420}, issn = {0971-5894}, abstract = {UNLABELLED: Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe[2+]) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml[-1]), carotenoid accumulation (1.96-2.08 µg ml[-1]), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm[-1]) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.}, }
@article {pmid37363122, year = {2023}, author = {Wani, K and Patel, K and Dabak, V}, title = {Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40871}, pmid = {37363122}, issn = {2168-8184}, abstract = {Cancer cells proliferate using various mechanisms. One mechanism of preventing tumor cell growth is blockade of the cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors - ribociclib, palbociclib, and abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive ductal carcinoma. She was treated with letrozole and ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started palbociclib but experienced elevated transaminases within two weeks, needing discontinuation of palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed disease progression, and she was started on fulvestrant. We considered adding abemaciclib, but the patient declined and has had stable disease for more than a year on fulvestrant. CDK 4/6 inhibitors are used to treat metastatic breast cancer and are generally well tolerated. The most common side effect is neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in hormone-positive metastatic breast cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the drug, and we must continue to assess the risk versus benefit profile when offering them to our patients.}, }
@article {pmid37324312, year = {2023}, author = {Jain, AK}, title = {Locally Advanced Breast Cancer: Response Evaluation to Neoadjuvant Chemotherapy by Clinico-Histopathological Parameters and Molecular Imaging.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {2}, pages = {279-287}, pmid = {37324312}, issn = {0975-7651}, abstract = {In India, breast cancer (BC) is not only the commonest cancer but also the commonest cause of cancer mortality among females. Advanced BC constitutes >70% of BC cases at initial presentation in India, among which locally advanced breast cancer (LABC) requires a multi-disciplinary approach with a combination of systemic and locoregional therapies. This descriptive hospital-based study was conducted over 1½ years after seeking approval from the institutional ethics committee. Fifty-five patients satisfying all the criteria of the study were enrolled. The data, thus, collected was pooled into Excel spreadsheet and analyzed using appropriate statistical tools. Most of the patients were postmenopausal, multiparous with breast lump being the commonest symptom. Mean baseline characteristics were age - 48 years, SUV max - 9.2, and Ki-67 - 17.8%. cT4 and cN2 were the commonest pre-NACT tumor and lymph node stage. Invasive ductal carcinoma was the commonest tumor type with the most common tumor grade being grade 3. Hormone receptor positivity and HER2 overexpression were seen in 33 and 17 patients respectively. Post-NACT 32 patients underwent breast-conserving surgery. Pathological complete response (pCR), i.e., ypT0N0, was seen in 13 patients (23.6%). There was slight alteration in hormone receptor status, HER2 expression and Ki-67 in the post-NACT resected tumor. pCR, which is a surrogate marker for improved clinical outcome (DFS and OS) in LABC patients, occurred more commonly in patients with pre-NACT grade 3 tumors, high Ki-67, hormone receptor-negative, and HER2 overexpressing BC (overall, in triple negative BC) but was statistically significant only with Ki-67. Post-NACT, SUV max with a cut off ≤1.5, and ΔSUV max of >80% correlated closely with pCR.}, }
@article {pmid37301537, year = {2023}, author = {Wu, K and Li, W and Liu, H and Niu, C and Shi, Q and Zhang, J and Gao, G and Sun, H and Liu, F and Fu, L}, title = {Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis.}, journal = {The American journal of pathology}, volume = {193}, number = {9}, pages = {1267-1283}, doi = {10.1016/j.ajpath.2023.05.010}, pmid = {37301537}, issn = {1525-2191}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Disease-Free Survival ; *Carcinoma, Papillary/pathology ; *Breast Neoplasms/metabolism ; Metabolome ; Methyltransferases/metabolism ; Prognosis ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; Repressor Proteins/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.}, }
@article {pmid37290673, year = {2023}, author = {Nieborak, A and Lukauskas, S and Capellades, J and Heyn, P and Santos, GS and Motzler, K and Zeigerer, A and Bester, R and Protzer, U and Schelter, F and Wagner, M and Carell, T and Hruscha, A and Schmid, B and Yanes, O and Schneider, R}, title = {Depletion of pyruvate kinase (PK) activity causes glycolytic intermediate imbalances and reveals a PK-TXNIP regulatory axis.}, journal = {Molecular metabolism}, volume = {74}, number = {}, pages = {101748}, pmid = {37290673}, issn = {2212-8778}, mesh = {Animals ; *Pyruvate Kinase/genetics ; Reactive Oxygen Species ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; *Neoplasms/genetics/metabolism ; Thioredoxins/chemistry/metabolism ; }, abstract = {OBJECTIVE: Cancer cells convert more glucose into lactate than healthy cells, what contributes to their growth advantage. Pyruvate kinase (PK) is a key rate limiting enzyme in this process, what makes it a promising potential therapeutic target. However, currently it is still unclear what consequences the inhibition of PK has on cellular processes. Here, we systematically investigate the consequences of PK depletion for gene expression, histone modifications and metabolism.<br><br>METHODS: Epigenetic, transcriptional and metabolic targets were analysed in different cellular and animal models with stable knockdown or knockout of PK.<br><br>RESULTS: Depleting PK activity reduces the glycolytic flux and causes accumulation of glucose-6-phosphate (G6P). Such metabolic perturbation results in stimulation of the activity of a heterodimeric pair of transcription factors MondoA and MLX but not in a major reprogramming of the global H3K9ac and H3K4me3 histone modification landscape. The MondoA:MLX heterodimer upregulates expression of thioredoxin-interacting protein (TXNIP) - a tumour suppressor with multifaceted anticancer activity. This effect of TXNIP upregulation extends beyond immortalised cancer cell lines and is applicable to multiple cellular and animal models.<br><br>CONCLUSIONS: Our work shows that actions of often pro-tumorigenic PK and anti-tumorigenic TXNIP are tightly linked via a glycolytic intermediate. We suggest that PK depletion stimulates the activity of MondoA:MLX transcription factor heterodimers and subsequently, increases cellular TXNIP levels. TXNIP-mediated inhibition of thioredoxin (TXN) can reduce the ability of cells to scavenge reactive oxygen species (ROS) leading to the oxidative damage of cellular structures including DNA. These findings highlight an important regulatory axis affecting tumour suppression mechanisms and provide an attractive opportunity for combination cancer therapies targeting glycolytic activity and ROS-generating pathways.}, }
@article {pmid37283256, year = {2023}, author = {Bukamal, Z and AlRayes, A}, title = {Prevalence of BRCA1 and BRCA2 Mutations Among High-risk Bahraini Patients with Breast Cancer.}, journal = {The Gulf journal of oncology}, volume = {1}, number = {42}, pages = {22-25}, pmid = {37283256}, issn = {2078-2101}, mesh = {Humans ; Female ; Male ; *Breast Neoplasms/epidemiology/genetics/diagnosis ; Bahrain/epidemiology ; Retrospective Studies ; Prevalence ; Mutation ; *Carcinoma, Ductal ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; }, abstract = {OBJECTIVE: The purpose is to study the prevalence of BRCA1 and BRCA2 mutations in high-risk Bahraini patients diagnosed with breast cancer, its relation to family history, and to determine the clinicopathologic features of breast cancer associated with these genetic mutations, over a period of 7 years.<br><br>BACKGROUND: Breast cancer is the most common type of cancer occurring in women and the second most common type generally. Approximately 12% of women worldwide will develop carcinoma of the breast sometime during their life. Additionally, 72% of women with an inherited BRCA1 mutation and 69% of those with a mutated BRCA2 will develop breast cancer by 80 years of age. The incidence of breast cancer in Bahraini women have increased over the last decade. Still, the data on BRCA1 &amp; BRCA2 mutations in relation to breast cancer patients is limited in the Arab region, not omitting Bahrain as a country with deficient BRCA prevalence data.<br><br>METHODS: This retrospective study was carried out in Salmaniya Medical Complex, Bahrain, to determine the prevalence of BRCA1 and BRCA2 mutations and to observe the breast cancer's histopathologic features that are associated with these mutations.<br><br>RESULTS: 271 patients underwent the BRCA gene testing between 2013 and 2019. Out of 271 patients, 35 were excluded. Out of the 236 breast cancer patients, 219 (93%) did not have the mutation. The BRCA gene was carried by a total of 17 (7%) patients; 13 (5%) BRCA1 and 4 (2%) BRCA2. Thirteen BRCA carrier patients had invasive ductal carcinoma (IDC) (76%), 2 had ductal carcinoma in situ (DCIS) (12%), while 2 patients' histopathology was not available. Molecular subtypes showed 4 triple negative basal sub-type (TNBC), 10 positive ER and PR hormonal status, 1 positive HER-2, while 2 patients' hormonal receptor status was not available. Two BRCA1 carriers had both breast and ovarian cancers. A total of 5 (2%) breast cancer male patients were among the tested population, out of which, 1 (0.4% of the total and 20% of the male patients) was a BRCA2 carrier. Out of the 236 patients, 76 (32%) were younger than 40 years of age at the time of diagnosis. Then again, out of the 17 BRCA carrier patients, 7 (41%) were younger than 40 years.<br><br>CONCLUSION: The prevalence of BRCA mutation in high risk Bahraini breast cancer patients is 7%. Among those patients, BRCA1 mutation is the most prevalent (5%) and invasive ductal carcinoma (IDC) is the most common histopathological subtype. However, there was not enough data to conclude the most prevalent molecular subtype of breast cancer in BRCA carriers due to deficiency of overseas pathology reports for patients operated outside Bahrain. When developing treatment plans for younger patients with breast cancer, inherited syndromes and precisely BRCA mutations need to be considered. Bahrain is implementing genetic testing for breast cancer patients &#x2264; 50 years of age since 2018, according to NCCN guidelines. We will continue to build our database to better characterize breast cancer subtypes and determine their hereditary pattern for identification of high risk families in Bahrain and for future development of more specific therapeutic approaches.<br><br>KEY WORDS: Breast cancer, BRCA1, BRCA2, BRCA mutation, Bahrain, Arab region.}, }
@article {pmid37251671, year = {2023}, author = {Kender, Z and von Rauchhaupt, E and Schwarz, D and Tsilingiris, D and Schimpfle, L and Bartl, H and Longo, VD and Bendszus, M and Kopf, S and Herzig, S and Heiland, S and Szendroedi, J and Sulaj, A}, title = {Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1143799}, pmid = {37251671}, issn = {1664-2392}, mesh = {Humans ; Action Potentials ; *Diabetes Mellitus, Type 2/complications/pathology ; *Diabetic Neuropathies/diagnosis ; Fasting ; Pain ; }, abstract = {BACKGROUND AND AIM: Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D).<br><br>STUDY DESIGN AND METHODS: Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 &#xb1; 1.3% [61.4 &#xb1; 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention.<br><br>RESULTS: Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both.<br><br>CONCLUSIONS: Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients.<br><br>CLINICAL TRIAL REGISTRATION: https://drks.de/search/en/trial/DRKS00014287, identifier DRKS00014287.}, }
@article {pmid37246414, year = {2023}, author = {Lee, J and Park, S and Jung, HA and Lee, SH and Seo, S and Kim, SB and Kim, JW and Lee, KW and Kang, EJ and Kim, JW and Choi, YJ and Shim, BY and An, HJ and Park, LC and Shin, SH and Kim, JJ and Oh, SY and Kim, MK and Ahn, MJ}, title = {A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.}, journal = {Cancer}, volume = {129}, number = {19}, pages = {2966-2974}, doi = {10.1002/cncr.34892}, pmid = {37246414}, issn = {1097-0142}, mesh = {Humans ; Female ; Docetaxel/therapeutic use ; Micelles ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Trastuzumab/therapeutic use ; Receptor, ErbB-2/genetics/metabolism ; *Carcinoma, Ductal ; Salivary Glands/metabolism ; *Breast Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab.<br><br>METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of &#x2265;2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of &#x2265;2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75&#xa0;mg/m[2]) and trastuzumab-pkrb (8&#xa0;mg/kg in the first cycle and 6&#xa0;mg/kg in subsequent cycles) every 3&#xa0;weeks. Primary end point was objective response rate (ORR).<br><br>RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio &#x2265;2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively.<br><br>CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC.<br><br>PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9&#xa0;months, median duration of response of 6.7&#xa0;months, and median overall survival of 23.3&#xa0;months.}, }
@article {pmid37222952, year = {2023}, author = {Abdollahi, E and Mozdarani, H and Alizadeh, BZ}, title = {Role of circ-FOXO3 and miR-23a in radiosensitivity of breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {5}, pages = {714-726}, pmid = {37222952}, issn = {1880-4233}, support = {Grant Number: IG-39711//Tarbiat Modares University/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/radiotherapy ; Leukocytes, Mononuclear ; Apoptosis/genetics ; *Carcinoma ; *Drug-Related Side Effects and Adverse Reactions ; *MicroRNAs/genetics ; Cell Proliferation ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Forkhead Box Protein O3/genetics ; }, abstract = {Identifying the radiosensitivity of cells before radiotherapy (RT) in breast cancer (BC) patients allows appropriate switching between routinely used treatment regimens and reduces adverse side effects in exposed patients. In this study, blood was collected from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC and 20 healthy women. To predict cellular radiosensitivity, a standard G2-chromosomal assay was performed. From these 60 samples, 20 BC patients were found to be radiosensitive based on the G2 assay. Therefore, molecular studies were finally performed on two equal groups (20 samples each) of patients with and without cellular radiosensitivity. QPCR was performed to examine the expression levels of circ-FOXO3 and miR-23a in peripheral blood mononuclear cells (PBMCs) and RNA sensitivity and specificity were determined by plotting Receiver Operating Characteristic (ROC) curves. Binary logistic regression was performed to identify RNA involvement in BC and cellular radiosensitivity (CR) in BC patients. Meanwhile, qPCR was used to compare differential RNA expression in the radiosensitive MCF-7 and radioresistant MDA-MB-231 cell lines. An annexin -V FITC/PI binding assay was used to measure cell apoptosis 24 and 48 h after 2 Gy, 4 Gy, and 8 Gy gamma-irradiation. Results indicated that circ-FOXO3 was downregulated and miR-23a was upregulated in BC patients. RNA expression levels were directly associated with CR. Cell line results showed that circ-FOXO3 overexpression induced apoptosis in the MCF-7 cell line and miR-23a overexpression inhibited apoptosis in the MDA-MB-231 cell line. Evaluation of the ROC curves revealed that both RNAs had acceptable specificity and sensitivity in predicting CR in BC patients. Binary logistic regression showed that both RNAs were also successful in predicting breast cancer. Although only circ-FOXO3 has been shown to predict CR in BC patients, circ-FOXO3 may function as a tumor suppressor and miR-23a may function as oncomiR in BC. Circ-FOXO3 and miR-23a may be promising potential biomarkers for BC prediction. Furthermore, Circ-FOXO3 could be a potential biomarker for predicting CR in BC patients.}, }
@article {pmid37217416, year = {2023}, author = {Rummel, KA and Gao, RW and Francis, LN and Petersen, IA and Mutter, RW and Corbin, KS}, title = {Secondary breast angiosarcoma following accelerated partial breast irradiation with intracavitary multicatheter applicator brachytherapy.}, journal = {Brachytherapy}, volume = {22}, number = {4}, pages = {487-490}, doi = {10.1016/j.brachy.2023.04.007}, pmid = {37217416}, issn = {1873-1449}, mesh = {Female ; Humans ; Aged ; *Hemangiosarcoma/etiology ; *Brachytherapy/methods ; *Breast Neoplasms/surgery ; Breast/pathology ; Mastectomy, Segmental ; }, abstract = {PURPOSE: Secondary angiosarcoma of the breast is a rare complication of breast radiotherapy and is associated with a poor prognosis. There are many reported cases of secondary angiosarcoma following whole breast irradiation (WBI), however development of secondary angiosarcoma following brachytherapy-based accelerated partial breast irradiation (APBI) is not as well characterized.<br><br>METHODS AND MATERIALS: We reviewed and reported a case of a patient who developed secondary angiosarcoma of the breast following intracavitary multicatheter applicator brachytherapy APBI.<br><br>RESULTS: A 69-year-old female was originally diagnosed with T1N0M0 invasive ductal carcinoma of the left breast and treated with lumpectomy followed by adjuvant intracavitary multicatheter applicator brachytherapy APBI. Seven years following her treatment, she developed secondary angiosarcoma. However, the diagnosis of secondary angiosarcoma was delayed due to nonspecific imaging findings and a negative biopsy.<br><br>CONCLUSIONS: Our case highlights the need for secondary angiosarcoma to be considered in the differential diagnosis when patients present with symptoms such as breast ecchymosis and skin thickening following WBI or APBI. Prompt diagnosis and referral to a high-volume sarcoma treatment center for multidisciplinary evaluation is vital.}, }
@article {pmid37202608, year = {2023}, author = {Shawky, A and Sabit, H and Nazih, M and Baraka, K and El-Zawahry, M}, title = {CYP2C19 Polymorphism in Ischemic Heart Disease Patients Taking Clopidogrel After Percutaneous Coronary Intervention in Egypt.}, journal = {Journal of epidemiology and global health}, volume = {13}, number = {2}, pages = {374-383}, pmid = {37202608}, issn = {2210-6014}, mesh = {Humans ; *Cardiovascular Diseases ; Clopidogrel/adverse effects/metabolism/therapeutic use ; Cytochrome P-450 CYP2C19/genetics/metabolism ; Egypt/epidemiology ; *Myocardial Ischemia/genetics/therapy/chemically induced ; *Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/adverse effects/metabolism/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study.<br><br>METHODS: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1&#xa0;year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded.<br><br>RESULTS: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n&#x2009;=&#x2009;15), CYP2C19*1/*3 (n&#x2009;=&#x2009;1), CYP2C19*1/*17 (n&#x2009;=&#x2009;35), and CYP2C19*2/*17 (n&#x2009;=&#x2009;1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution.<br><br>CONCLUSION: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.}, }
@article {pmid37201361, year = {2023}, author = {Mekni, K and Mejri, O and Ayadi, A and ElFekif, C}, title = {Unexpected association between breast cancer and molar pregnancy in a 52-year-old woman: A case report.}, journal = {International journal of surgery case reports}, volume = {107}, number = {}, pages = {108253}, pmid = {37201361}, issn = {2210-2612}, abstract = {INTRODUCTION: There was no prior discussion about the association between breast cancer and molar pregnancy, particularly at an advanced age. Through our case and a systematic review, we will discuss the relevance of ovarian castration in hormone-receptor-positive breast cancer.<br><br>CASE PRESENTATION: We reported the case of a 52-year-old woman, not yet menopausal, who was diagnosed with a right breast tumor classified as BI-RADS category 4. The anatomopathological analysis of mammary biopsy revealed an invasive ductal carcinoma of no special type (grade 2). Hormone receptors were positive. It was a HER2-negative Breast cancer. It was then decided to treat the patient with radical surgery followed by chemotherapy, radiotherapy, and hormonotherapy. The patient had a "Patey operation". The postoperative course was without significant complications. No medical or surgical castration was indicated in the expectation that chemotherapy would cause ovarian failure. Unlikely, during chemotherapy course our patient developed a molar pregnancy.<br><br>CLINICAL DISCUSSION: Our case illustrates the possibility of pregnancy in non-menopausal women with estrogen-receptor-positive breast cancer. The combination of tamoxifen or aromatase inhibitors with ovarian suppression as standard adjuvant therapy may be recommended in such cases.<br><br>CONCLUSIONS: Ovarian function suppression in non-menopausal women with hormone receptor-positive breast cancer seems to be necessary. So that, we can avoid unexpected manifestations like molar pregnancy.}, }
@article {pmid37201100, year = {2023}, author = {Koçberber, Z and Willemsen, N and Bartelt, A}, title = {The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1176733}, pmid = {37201100}, issn = {1664-2392}, mesh = {Animals ; Mice ; *Adipocytes, Brown/metabolism ; *Proteasome Endopeptidase Complex/metabolism ; Adipose Tissue, Brown/metabolism ; Adipogenesis/genetics ; Temperature ; Nuclear Proteins/metabolism ; }, abstract = {INTRODUCTION: Brown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function.<br><br>METHODS: We measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function.<br><br>RESULTS: We found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST.<br><br>DISCUSSION: In summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.}, }
@article {pmid37200388, year = {2023}, author = {Amer, NN and Khairat, R and Hammad, AM and Kamel, MM}, title = {DDX43 mRNA expression and protein levels in relation to clinicopathological profile of breast cancer.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0284455}, pmid = {37200388}, issn = {1932-6203}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Neoplasm Proteins/genetics ; RNA, Messenger/genetics ; Prognosis ; Disease Progression ; Biomarkers, Tumor/genetics/analysis ; DEAD-box RNA Helicases/genetics/metabolism ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most often diagnosed cancer in women globally. Cancer cells appear to rely heavily on RNA helicases. DDX43 is one of DEAD- box RNA helicase family members. But, the relationship between clinicopathological, prognostic significance in different BC subtypes and DDX43 expression remains unclear. Therefore, the purpose of this study was to assess the clinicopathological significance of DDX43 protein and mRNA expression in different BC subtypes.<br><br>MATERIALS AND METHODS: A total of 80 females newly diagnosed with BC and 20 control females that were age-matched were recruited for this study. DDX43 protein levels were measured by ELISA technique. We used a real-time polymerase chain reaction quantification (real-time PCR) to measure the levels of DDX43 mRNA expression. Levels of DDX43 protein and mRNA expression within BC patients had been compared to those of control subjects and correlated with clinicopathological data.<br><br>RESULTS: The mean normalized serum levels of DDX43 protein were slightly higher in control than in both benign and malignant groups, but this result was non-significant. The mean normalized level of DDX43 mRNA expression was higher in the control than in both benign and malignant cases, although the results were not statistically significant and marginally significant, respectively. Moreover, the mean normalized level of DDX43 mRNA expression was significantly higher in benign than in malignant cases. In malignant cases, low DDX43 protein expression was linked to higher nuclear grade and invasive duct carcinoma (IDC), whereas high mRNA expression was linked to the aggressive types of breast cancer such as TNBC, higher tumor and nuclear grades.<br><br>CONCLUSION: This study explored the potential of using blood DDX43 mRNA expression or protein levels, or both in clinical settings as a marker of disease progression in human breast cancer. DDX43 mRNA expression proposes a less invasive method for discriminating benign from malignant BC.}, }
@article {pmid37195240, year = {2023}, author = {Murata, S and Yamashita, H and Kido, S and Harada, D and Ohtsuru, S and Sato, N}, title = {DYNAMIC METABOLIC CHANGES OBSERVED IN AN LPS-INDUCED SYSTEMIC INFLAMMATION RAT MODEL USING CONTINUOUS LONG-TERM INDIRECT CALORIMETRY EXPERIMENTS.}, journal = {Shock (Augusta, Ga.)}, volume = {60}, number = {1}, pages = {130-136}, pmid = {37195240}, issn = {1540-0514}, mesh = {Humans ; *Lipopolysaccharides/toxicity ; Calorimetry, Indirect/methods ; *Critical Illness ; Energy Metabolism/physiology ; Critical Care ; }, abstract = {Background : Nutritional management is crucial for severely ill patients. Measuring metabolism is believed to be necessary for the acute sepsis phase to accurately estimate nutrition. Indirect calorimetry (IDC) is assumed to be useful for acute intensive care; however, there are few studies on long-term IDC measurement in patients with systemic inflammation. Methods : Rats were categorized into the LPS received or control groups; LPS rats were categorized into underfeeding (UF), adjusted feeding (AF), and overfeeding (OF) groups. Indirect calorimetry measurement was performed until 72 or 144 h. Body composition was measured at -24 and 72 or 144 h, and tissue weight was measured at 72 or 144 h. Results : Low energy consumption and loss of diurnal variation of resting energy expenditure were observed in the LPS group compared with the control group until 72 h, after which the LPS group recovered. The resting energy expenditure in the OF group was higher than that in the UF and AF groups. In the first phase, low energy consumption was observed in all groups. In the second and third phases, higher energy consumption occurred in the OF group than in the UF and AF groups. In the third phase, diurnal variation recovered in all groups. Muscle atrophy caused body weight loss, but fat tissue loss did not occur. Conclusions : We observed metabolic changes with IDC during the acute systemic inflammation phase owing to differences in calorie intake. This is the first report of long-term IDC measurement using the LPS-induced systemic inflammation rat model.}, }
@article {pmid37186041, year = {2023}, author = {Wei, S and Bao, M and Zhu, Y and Zhang, W and Jiang, L}, title = {Identifying potential targets for lung cancer intervention by analyzing the crosstalk of cancer-associated fibroblasts and immune and metabolism microenvironment.}, journal = {Environmental toxicology}, volume = {38}, number = {8}, pages = {1951-1967}, doi = {10.1002/tox.23821}, pmid = {37186041}, issn = {1522-7278}, support = {82103309//Youth Found of National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Cancer-Associated Fibroblasts/metabolism/pathology ; *Lung Neoplasms/pathology ; Lung/pathology ; Signal Transduction ; Glycerophospholipids/metabolism ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to play a crucial role in the tumor microenvironment and progression.<br><br>METHODS: The data used in this study were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, and all analyses were performed using R software.<br><br>RESULTS: We first quantified the CAFs infiltration through single sample gene set enrichment analysis in the TCGA and combined GEO cohort (GSE30219, GSE37745, and GSE50081). Our result showed that patients with high levels of CAF infiltration were associated with worse clinical features and poor prognosis. Immune microenvironment analysis indicated that high CAF infiltration might result in increased infiltration of immune cells, including aDC, B cells, CD8+ T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, neutrophils, NK CD56dim cells, NK cells, pDC, and T cells. Correlation analysis showed a significant positive correlation between CAFs and M2 macrophages, while a negative correlation was found between CAFs and glycerophospholipid metabolism. Kaplan-Meier survival curves indicated that glycerophospholipid metabolism was a protective factor against lung cancer. Biological enrichment analysis showed that pathways such as allograft rejection, epithelial-mesenchymal transition, KRAS signaling, TNF-&#x3b1; signaling, myogenesis, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling were upregulated in the patients with high CAF infiltration. Moreover, patients with high CAF infiltration had a lower proportion of immunotherapy responders. Genome analysis showed that low CAFs infiltration was associated with high genome instability. We identified FGF5 and CELF3 as key genes involved in the interaction between CAFs, M2 macrophages, and glycerophospholipid metabolism, and further analyzed FGF5. In vitro experiments showed that FGF5 promoted the proliferation, invasion and migration of lung cancer cells and was primarily localized in the nucleoli fibrillar center.<br><br>CONCLUSIONS: Our study provides novel insights into the roles of CAFs in lung cancer progression and the underlying crosstalk of tumor metabolism and immune microenvironment.}, }
@article {pmid37171457, year = {2023}, author = {Traberg, WC and Uribe, J and Druet, V and Hama, A and Moysidou, CM and Huerta, M and McCoy, R and Hayward, D and Savva, A and Genovese, AMR and Pavagada, S and Lu, Z and Koklu, A and Pappa, AM and Fitzgerald, R and Inal, S and Daniel, S and Owens, RM}, title = {Organic Electronic Platform for Real-Time Phenotypic Screening of Extracellular-Vesicle-Driven Breast Cancer Metastasis.}, journal = {Advanced healthcare materials}, volume = {12}, number = {27}, pages = {e2301194}, doi = {10.1002/adhm.202301194}, pmid = {37171457}, issn = {2192-2659}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology ; Cell Line, Tumor ; Early Detection of Cancer ; *Triple Negative Breast Neoplasms/drug therapy/pathology ; *Extracellular Vesicles ; Epithelial-Mesenchymal Transition/genetics ; Cell Movement ; }, abstract = {Tumor-derived extracellular vesicles (TEVs) induce the epithelial-to-mesenchymal transition (EMT) in nonmalignant cells to promote invasion and cancer metastasis, representing a novel therapeutic target in a field severely lacking in efficacious antimetastasis treatments. However, scalable technologies that allow continuous, multiparametric monitoring for identifying metastasis inhibitors are absent. Here, the development of a functional phenotypic screening platform based on organic electrochemical transistors (OECTs) for real-time, noninvasive monitoring of TEV-induced EMT and screening of antimetastatic drugs is reported. TEVs derived from the triple-negative breast cancer cell line MDA-MB-231 induce EMT in nonmalignant breast epithelial cells (MCF10A) over a nine-day period, recapitulating a model of invasive ductal carcinoma metastasis. Immunoblot analysis and immunofluorescence imaging confirm the EMT status of TEV-treated cells, while dual optical and electrical readouts of cell phenotype are obtained using OECTs. Further, heparin, a competitive inhibitor of cell surface receptors, is identified as an effective blocker of TEV-induced EMT. Together, these results demonstrate the utility of the platform for TEV-targeted drug discovery, allowing for facile modeling of the transient drug response using electrical measurements, and provide proof of concept that inhibitors of TEV function have potential as antimetastatic drug candidates.}, }
@article {pmid37170638, year = {2023}, author = {Antón Rodriguez, &#xc1; and Odriozola Herrán, A and Echavarría Rodríguez, VJ and Alonso Fernández, S}, title = {Secondary sclerosing cholangitis induced by systemic chemotherapy.}, journal = {Revista espanola de enfermedades digestivas}, volume = {}, number = {}, pages = {}, doi = {10.17235/reed.2023.9653/2023}, pmid = {37170638}, issn = {1130-0108}, abstract = {There are multiple causes of secondary sclerosing cholangitis (SSC), including mechanical obstruction, ischemia, congenital abnormalities, cholangiopathy of the critically ill patient and, rarely, chemotherapy (1,2). We present the case of a 52-year-old woman with a history of left breast invasive ductal carcinoma treated with neoadjuvant chemotherapy (adriamycin, cyclophosphamide and paclitaxel), surgery and radiotherapy in March 2021. She was admitted in July 2022 for painless jaundice and pruritus with marked serum cholestasis. Magnetic resonance cholangiopancreatography showed multiple strictures and dilatations involving the intra and extrahepatic bile ducts (Figure 1.A), without any extrinsic stenotic cause. Findings were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy (Figure 1.B). Biopsies were negative for malignancy and IgG4 disease. In addition, autoantibodies were negative and serum IgG4 levels were normal. Because of these findings and the history of recent chemotherapy, the patient was diagnosed with paclitaxel-induced sclerosing cholangitis, initiating treatment with ursodeoxycholic acid. Over the following two months, she suffered two episodes of Klebsiella Pneumoniae bacteraemia due to acute cholangitis. Dilatation and placement of plastic stents in both biliary trees were performed and prophylactic antibiotherapy was started. The patient had a poor evolution, she was not candidate to liver transplantation on account of recent neoplasia. She died six months later due to sepsis secondary to multiple hepatic abscesses.}, }
@article {pmid37143728, year = {2023}, author = {Cipolletti, M and Leone, S and Bartoloni, S and Acconcia, F}, title = {A functional genetic screen for metabolic proteins unveils GART and the de novo purine biosynthetic pathway as novel targets for the treatment of luminal A ERα expressing primary and metastatic invasive ductal carcinoma.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1129162}, pmid = {37143728}, issn = {1664-2392}, mesh = {Female ; Humans ; Estrogen Receptor alpha/genetics/metabolism ; Biosynthetic Pathways ; Neoplasm Recurrence, Local ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast ; Purines ; *Carbon-Nitrogen Ligases/metabolism ; Phosphoribosylglycinamide Formyltransferase/metabolism ; }, abstract = {Targeting tumor cell metabolism is a new frontier in cancer management. Thus, metabolic pathway inhibitors could be used as anti-estrogen receptor α (ERα) breast cancer (BC) drugs. Here, the interplay among metabolic enzyme(s), the ERα levels and cell proliferation was studied. siRNA-based screen directed against different metabolic proteins in MCF10a, MCF-7 and MCF-7 cells genetically resistant to endocrine therapy (ET) drugs and metabolomic analyses in numerous BC cell lines unveil that the inhibition of GART, a key enzyme in the purine de novo biosynthetic pathway, induces ERα degradation and prevent BC cell proliferation. We report here that a reduced GART expression correlates with a longer relapse-free-survival (RFS) in women with ERα-positive BCs. ERα-expressing luminal A invasive ductal carcinomas (IDCs) are sensitive to GART inhibition and GART expression is increased in receptor-positive IDCs of high grade and stage and plays a role in the development of ET resistance. Accordingly, GART inhibition reduces ERα stability and cell proliferation in IDC luminal A cells where it deregulates 17β-estradiol (E2):ERα signaling to cell proliferation. Moreover, the GART inhibitor lometrexol (LMX) and drugs approved for clinical treatment of primary and metastatic BC (4OH-tamoxifen and the CDK4/CDK6 inhibitors) exert synergic antiproliferative effects in BC cells. In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.}, }
@article {pmid37139855, year = {2023}, author = {Tsilingiris, D and Schimpfle, L and von Rauchhaupt, E and Sulaj, A and Seebauer, L and Bartl, H and Herzig, S and Szendroedi, J and Kopf, S and Kender, Z}, title = {Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {108}, number = {10}, pages = {e979-e988}, pmid = {37139855}, issn = {1945-7197}, mesh = {Humans ; Male ; *Diabetes Mellitus, Type 2/complications ; *Metabolic Syndrome/complications/epidemiology ; *Peripheral Nervous System Diseases/epidemiology/etiology ; *Insulin Resistance ; Glycation End Products, Advanced ; }, abstract = {AIM: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development.<br><br>METHODS: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence.<br><br>RESULTS: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011).<br><br>CONCLUSION: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.}, }
@article {pmid37121885, year = {2023}, author = {Ikegami, M}, title = {Prognostic benefit of comprehensive genomic profiling in clinical practice remains uncertain.}, journal = {Cancer science}, volume = {114}, number = {7}, pages = {3053-3055}, pmid = {37121885}, issn = {1349-7006}, support = {#22K15571//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Pancreatic Neoplasms/pathology ; Prognosis ; *Adenocarcinoma/genetics ; Retrospective Studies ; Genomics ; *Carcinoma, Pancreatic Ductal/genetics/therapy ; }, abstract = {The overall survival of patients who received genomically matched therapy was not significantly longer than that of patients receiving treatment only other than genomically matched therapy in the breast invasive ductal carcinoma (A), colorectal adenocarcinoma (B), and pancreatic adenocarcinoma (C) cohorts.}, }
@article {pmid37101747, year = {2023}, author = {Xiang, S and Wei, M and Zhao, L and Lin, A and Xiong, Z}, title = {Integrated Analyses of the Expression and Prognostic Value of EPHB6 in Cervical Cancer and Its Correlation with Immune Infiltrates.}, journal = {Journal of oncology}, volume = {2023}, number = {}, pages = {2258906}, pmid = {37101747}, issn = {1687-8450}, abstract = {Among women, cervical cancer (CC) ranks as the third most frequent form of carcinoma and the fourth greatest cancer-related cause of deaths. There is increasing evidence that points to the dysregulation of EPH receptor B6 (EPHB6) in various cancers. On the other hand, neither the expression nor the function of EPHB6 in CC has been researched. In the first part of this investigation, we analyzed the data from the TCGA and discovered that the level of EPHB6 was much lower in CC tissues than in normal cervical tissues. ROC assays revealed that high EPHB6 expression had an AUC value of 0.835 for CC. The survival study revealed that both the overall and disease-specific survivals in this condition were considerably lower among patients who had a low EPHB6 level compared to those who had a high EPHB6 level. It is important to note that the multivariate COX regression analysis indicated that the expression of EPHB6 was an independent predictive factor. In addition to this, the C-indexes and calibration plots of a nomogram derived from multivariate assays revealed an accurate prediction performance among patients with CC. Immune infiltration analysis indicated that the expression of EPHB6 was positively associated with the levels of Tcm, TReg, B cells, T cells, iDC, T helper cells, cytotoxic cells, and DC, while negatively associated with NK CD56bright cells and neutrophils. In summary, the downregulation of EPHB6 was strongly linked to a more aggressive clinical development of CC, suggesting its potential utility as a diagnostic and therapeutic target in CC.}, }
@article {pmid37095978, year = {2023}, author = {Norooznezhad, AH and Yarani, R and Payandeh, M and Hoseinkhani, Z and Mahmoudi, H and Kiani, S and Mansouri, K}, title = {Treatment of persistent chemotherapy-induced hair loss (Alopecia) with human mesenchymal stromal cells exosome enriched extracellular vesicles: A case report.}, journal = {Heliyon}, volume = {9}, number = {4}, pages = {e15165}, pmid = {37095978}, issn = {2405-8440}, abstract = {INTRODUCTION: Cancer is among the leading causes of death worldwide and affects a considerable number of individuals. Chemotherapy is one the most common treatment for this condition and hair loss is among one of the most prevalent side effects. In this study, we report successful treatment of a patient suffering from persistent chemotherapy-induced alopecia (PCIA) with extracellular enriched vesicles (EVs) derived from human placental mesenchymal stromal cells (MSCs).<br><br>CASE PRESENTATION: The patient was a 36-year-old woman with a history of invasive ductal carcinoma, underwent six courses of chemotherapy with paclitaxel and adriamycin. Following this treatment and for almost 18 months, she, unfortunately, had no regrowth of hair except some light vellus hairs on the scalp. She then received MSC-derived EVs with scalp injection (subcutaneous) every 4 weeks for 3 continuous months at which point she presented complete regrowth of terminal hair on her scalp.<br><br>CONCLUSION: This report demonstrates that MSC-derived EVs could be a possible treatment for permanent chemotherapy-induced alopecia; however, further studies and trials are necessary.}, }
@article {pmid37094629, year = {2023}, author = {Chovsepian, A and Prokopchuk, O and Petrova, G and Gjini, T and Kuzi, H and Heisz, S and Janssen, KP and Martignoni, ME and Friess, H and Hauner, H and Rohm, M}, title = {Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status.}, journal = {Molecular metabolism}, volume = {73}, number = {}, pages = {101729}, pmid = {37094629}, issn = {2212-8778}, mesh = {Humans ; Cachexia/metabolism ; Retrospective Studies ; C-Reactive Protein ; *Diabetes Mellitus, Type 2/complications ; *Pancreatic Neoplasms/complications/metabolism ; Body Weight ; Obesity/complications ; Biomarkers ; *Colorectal Neoplasms/complications ; }, abstract = {OBJECTIVES: Cancer is considered an emerging diabetes complication, with higher incidence and worse prognosis in patients with diabetes. Cancer is frequently associated with cachexia, a systemic metabolic disease causing wasting. It is currently unclear how diabetes affects the development and progression of cachexia.<br><br>METHODS: We investigated the interplay between diabetes and cancer cachexia retrospectively in a cohort of 345 patients with colorectal and pancreatic cancer. We recorded body weight, fat mass, muscle mass, clinical serum values, and survival of these patients. Patients were grouped either into diabetic/non-diabetic groups based on previous diagnosis, or into obese/non-obese groups based on body mass index (BMI &#x2265;30&#xa0;kg/m[2] was considered obese).<br><br>RESULTS: The pre-existence of type 2 diabetes, but not obesity, in patients with cancer led to increased cachexia incidence (80%, compared to 61% without diabetes, p&#xa0;&#x2264;&#xa0;0.05), higher weight loss (8.9% vs. 6.0%, p&#xa0;&#x2264;&#xa0;0.001), and reduced survival probability (median survival days: 689 vs. 538, Chi square&#xa0;=&#xa0;4.96, p&#xa0;&#x2264;&#xa0;0.05) irrespective of the initial body weight or tumor progression. Patients with diabetes and cancer showed higher serum levels of C-reactive protein (0.919&#xa0;&#x3bc;g/mL vs. 0.551&#xa0;&#x3bc;g/mL, p&#xa0;&#x2264;&#xa0;0.01) and interleukin 6 (5.98&#xa0;pg/mL vs. 3.75&#xa0;pg/mL, p&#xa0;&#x2264;&#xa0;0.05) as well as lower serum albumin levels (3.98&#xa0;g/dL vs. 4.18&#xa0;g/dL, p&#xa0;&#x2264;&#xa0;0.05) than patients with cancer without diabetes. In a sub-analysis of patients with pancreatic cancer, pre-existing diabetes worsened weight loss (9.95% vs. 6.93%, p&#xa0;&#x2264;&#xa0;0.01), and increased the duration of hospitalization (24.41 days vs. 15.85 days, p&#xa0;&#x2264;&#xa0;0.001). Further, diabetes aggravated clinical manifestations of cachexia, as changes in the aforementioned biomarkers were more pronounced in patients with diabetes and cachexia co-existence, compared to cachectic patients without diabetes (C-reactive protein: 2.300&#xa0;&#x3bc;g/mL vs. 0.571&#xa0;&#x3bc;g/mL, p&#xa0;&#x2264;&#xa0;0.0001; hemoglobin: 11.24&#xa0;g/dL vs. 12.52&#xa0;g/dL, p&#xa0;&#x2264;&#xa0;0.05).<br><br>CONCLUSIONS: We show for the first time that pre-existing diabetes aggravates cachexia development in patients with colorectal and pancreatic cancer. This is important when considering cachexia biomarkers and weight management in patients with co-existing diabetes and cancer.}, }
@article {pmid37085500, year = {2023}, author = {Zhou, D and Li, M and Yasin, MH and Lu, Q and Fu, J and Jiang, K and Hong, R and Wang, S and Xu, F}, title = {The prognostic value and immune microenvironment association of AR in HER2+ nonmetastatic breast cancer.}, journal = {NPJ breast cancer}, volume = {9}, number = {1}, pages = {30}, pmid = {37085500}, issn = {2374-4677}, support = {320.6750.2021-10-97//Ministry of Health of China | Wu Jieping Medical Foundation/ ; 2019A1515011945//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; }, abstract = {This study aimed to investigate the prognostic value of AR in HER2+ nonmetastatic breast invasive ductal carcinoma (IDC) and its relationship with the immune microenvironment. HER2+ nonmetastatic breast IDC patients diagnosed by pathology who underwent surgery at Sun Yat-sen University Cancer Center from 2016 to 2017 were included. AR+ and AR- breast IDC samples were matched 1:1 in age, T stage, and N stage for immune infiltration analysis. A total of 554 patients with HER2+ nonmetastatic breast cancer were included in this retrospective study, regardless of HR status. The cut-off value for AR was set at 10%. ER+ (p < 0.001) and PR+ (p < 0.001) were associated with positive AR expression. Kaplan-Meier survival curve analysis suggested that AR was closely correlated with overall survival (OS) (p = 0.001) but not disease-free survival (DFS) (p = 0.051). After eliminating the potential impact caused by HR, AR also predicted longer OS (p = 0.014) and was an independent predictive factor for OS of HER2+HR- nonmetastatic breast IDC patients, as revealed by multivariate analysis (p = 0.036). For AR+ and AR- matched HER2+HR- patients, TILs (p = 0.043) and PD-L1 (p = 0.027) levels were significantly lower in AR+ patients. The strongest negative correlation was observed between AR and PD-L1 (Pearson's r = -0.299, p = 0.001). AR+ status was markedly related to better OS in HER2+HR- nonmetastatic breast cancer patients, while a negative correlation was observed between AR and PD-L1/TILs. We provide new insights into the prognostic value of AR and its association with the immune microenvironment to optimize treatment strategies in HER2+ nonmetastatic breast IDCs.}, }
@article {pmid37085014, year = {2023}, author = {van Balkom, IDC and Burdeus-Olavarrieta, M and Cooke, J and de Cuba, AG and Turner, A and ,  and Vogels, A and Maruani, A}, title = {Consensus recommendations on mental health issues in Phelan-McDermid syndrome.}, journal = {European journal of medical genetics}, volume = {66}, number = {6}, pages = {104770}, doi = {10.1016/j.ejmg.2023.104770}, pmid = {37085014}, issn = {1878-0849}, mesh = {Humans ; Consensus ; *Mental Health ; Quality of Life ; *Chromosome Disorders/genetics/psychology ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics ; }, abstract = {Phelan-McDermid syndrome is a rare genetic condition caused by a deletion encompassing the 22q13.3 region or a pathogenic variant of the gene SHANK3. The clinical presentation is variable, but main characteristics include global developmental delay/intellectual disability (ID), marked speech impairment or delay, along with other features like hypotonia and somatic or psychiatric comorbidities. This publication delineates mental health, developmental and behavioural themes across the lifetime of individuals with PMS as informed by parents/caregivers, experts, and other key professionals involved in PMS care. We put forward several recommendations based on the available literature concerning mental health and behaviour in PMS. Additionally, this article aims to improve our awareness of the importance of considering developmental level of the individual with PMS when assessing mental health and behavioural issues. Understanding how the discrepancy between developmental level and chronological age may impact concerning behaviours offers insight into the meaning of those behaviours and informs care for individuals with PMS, enabling clinicians to address unmet (mental health) care needs and improve quality of life.}, }
@article {pmid37083566, year = {2023}, author = {Bilici, A and Olmez, OF and Kaplan, MA and Oksuzoglu, B and Sezer, A and Karadurmus, N and Cubukcu, E and Sendur, MAN and Aksoy, S and Erdem, D and Basaran, G and Cakar, B and Shbair, ATM and Arslan, C and Sumbul, AT and Sezgin Goksu, S and Karadag, I and Cicin, I and Gumus, M and Selcukbiricik, F and Harputluoglu, H and Demirci, U}, title = {Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {62}, number = {4}, pages = {381-390}, doi = {10.1080/0284186X.2023.2202330}, pmid = {37083566}, issn = {1651-226X}, mesh = {Humans ; Female ; Trastuzumab/therapeutic use ; *Breast Neoplasms/pathology ; Neoadjuvant Therapy/methods ; Docetaxel ; Retrospective Studies ; Receptor, ErbB-2 ; Neoplasm Recurrence, Local/drug therapy/genetics ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting.<br><br>METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR.<br><br>RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p&#x2009;<&#x2009;0.001) and lower relapse (4.5 vs. 12.2%, p&#x2009;<&#x2009;0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p&#x2009;<&#x2009;0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p&#x2009;<&#x2009;0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p&#x2009;<&#x2009;0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p&#x2009;<&#x2009;0.001) and NCT-HP (41.5 vs. 32.1%, p&#x2009;<&#x2009;0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p&#x2009;<&#x2009;0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p&#x2009;<&#x2009;0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p&#x2009;<&#x2009;0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p&#x2009;<&#x2009;0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p&#x2009;=&#x2009;0.008) significantly predicted the pCR.<br><br>CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.}, }
@article {pmid37082801, year = {2023}, author = {Hacking, SM and Yakirevich, E and Wang, Y}, title = {Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED).}, journal = {The journal of pathology. Clinical research}, volume = {9}, number = {4}, pages = {313-321}, pmid = {37082801}, issn = {2056-4538}, mesh = {Humans ; *Triple Negative Breast Neoplasms/genetics/pathology ; Biomarkers, Tumor/analysis ; Tumor Suppressor Protein p53/genetics ; Retinoblastoma Protein/genetics/metabolism ; Retrospective Studies ; *Neuroendocrine Tumors/pathology ; *Carcinoma, Neuroendocrine/pathology ; *Carcinoma, Ductal, Breast ; Cell Differentiation ; RNA, Messenger ; Repressor Proteins ; }, abstract = {Primary breast neuroendocrine (NE) neoplasms are uncommon, and definitions harbor controversy. We retrospectively collected 73 triple-negative breast cancers (TNBC) and evaluated NE biomarker expression along with p53 aberrant staining (which correlates with TP53 gene mutation) and Rb protein loss by immunohistochemistry. In the study cohort, we found 11 (15%) cases of TNBC with neuroendocrine differentiation (TNBC-NED) showing positivity for one or more NE markers (synaptophysin/chromogranin/insulinoma-associated protein 1 [INSM1]). We also identified one separate small cell neuroendocrine carcinoma. Histologic types for these 11 TNBC-NED cases were as follows: 8 invasive ductal carcinoma (IDC) not otherwise specified (NOS), 2 IDC with apocrine features, 1 IDC with solid papillary features. INSM1 had the highest positivity and was seen in all 11 carcinomas. Seven (64%) cases showed p53 aberrant staining, 6 (55%) had Rb protein loss, while 6 (55%) had p53/Rb co-aberrant staining/protein loss. TNBC-NED was associated with Rb protein loss (p < 0.001), as well as p53/Rb co-aberrant staining/protein loss (p < 0.001). In 61 cases negative for NE markers, 37 (61%) showed p53 aberrant staining, while 5 (8%) had Rb protein loss. We also analyzed genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) PanCancer Atlas of 171 basal/TNBC patients. Transcriptomic analysis revealed mRNA expression of RB1 to be correlated negatively with SYN1 mRNA expression (p = 0.0400) and INSM1 mRNA expression (p = 0.0106) in this cohort. We would like to highlight the importance of these findings. TNBC-NED is currently diagnosed as TNBC, and although it overlaps morphologically with TNBC without NED, the unique p53/Rb signature highlights a genetic overlap with NE carcinomas of the breast.}, }
@article {pmid37061239, year = {2023}, author = {López-Janeiro, &#xc1; and Rodriguez, AM and Mendiola, M and Sabbagh, RN and Feliu, J and Villadóniga, A and Mendez, MDC}, title = {Pancreatic intraductal papillary mucinous neoplasm with sarcomatous transformation. A case report.}, journal = {Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia}, volume = {56}, number = {2}, pages = {124-128}, doi = {10.1016/j.patol.2021.05.004}, pmid = {37061239}, issn = {1988-561X}, mesh = {Female ; Humans ; Aged ; *Pancreatic Intraductal Neoplasms ; *Carcinoma, Pancreatic Ductal/pathology ; *Adenocarcinoma, Mucinous/genetics/pathology ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology ; }, abstract = {Mixed pancreatic epithelial and mesenchymal tumors are rare, usually invasive, entities. Intraductal papillary mucinous neoplasm (IPMN) is a precursor of invasive ductal carcinoma and shares mutations with its invasive counterparts. We report the case of a 72-year-old female with a previously undescribed sarcomatous transformation of a residual IPMN with no evidence of an invasive component. The mesenchymal component showed no heterologous differentiation. Both the epithelial and the mesenchymal populations showed aberrant expression of p53 protein and the same point mutation in KRAS gene. After a 6 month follow up, there were no signs of local or distant relapse. The present case suggests that sarcomatous transformation is possible in non-invasive, intraductal pancreatic lesions.}, }
@article {pmid37055018, year = {2023}, author = {De Angelis Rigotti, F and Wiedmann, L and Hubert, MO and Vacca, M and Hasan, SS and Moll, I and Carvajal, S and Jiménez, W and Starostecka, M and Billeter, AT and Müller-Stich, B and Wolff, G and Ekim-Üstünel, B and Herzig, S and Fandos-Ramo, C and Krätzner, R and Reich, M and Keitel-Anselmino, V and Heikenwälder, M and Mogler, C and Fischer, A and Rodriguez-Vita, J}, title = {Semaphorin 3C exacerbates liver fibrosis.}, journal = {Hepatology (Baltimore, Md.)}, volume = {78}, number = {4}, pages = {1092-1105}, doi = {10.1097/HEP.0000000000000407}, pmid = {37055018}, issn = {1527-3350}, mesh = {Animals ; Humans ; Mice ; *Hepatic Stellate Cells/metabolism ; Liver/pathology ; Liver Cirrhosis/pathology ; Phosphorylation ; *Semaphorins/genetics/metabolism ; Transforming Growth Factor beta/metabolism ; }, abstract = {BACKGROUND AND AIMS: Chronic liver disease is a growing epidemic, leading to fibrosis and cirrhosis. TGF-β is the pivotal profibrogenic cytokine that activates HSC, yet other molecules can modulate TGF-β signaling during liver fibrosis. Expression of the axon guidance molecules semaphorins (SEMAs), which signal through plexins and neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis. This study aims at determining their function in the regulation of HSCs.<br><br>APPROACH AND RESULTS: We analyzed publicly available patient databases and liver biopsies. We used transgenic mice, in which genes are deleted only in activated HSCs to perform ex vivo analysis and animal models. SEMA3C is the most enriched member of the semaphorin family in liver samples from patients with cirrhosis. Higher expression of SEMA3C in patients with NASH, alcoholic hepatitis, or HBV-induced hepatitis discriminates those with a more profibrotic transcriptomic profile. SEMA3C expression is also elevated in different mouse models of liver fibrosis and in isolated HSCs on activation. In keeping with this, deletion of SEMA3C in activated HSCs reduces myofibroblast marker expression. Conversely, SEMA3C overexpression exacerbates TGF-&#x3b2;-mediated myofibroblast activation, as shown by increased SMAD2 phosphorylation and target gene expression. Among SEMA3C receptors, only NRP2 expression is maintained on activation of isolated HSCs. Interestingly, lack of NRP2 in those cells reduces myofibroblast marker expression. Finally, deletion of either SEMA3C or NRP2, specifically in activated HSCs, reduces liver fibrosis in mice.<br><br>CONCLUSION: SEMA3C is a novel marker for activated HSCs that plays a fundamental role in the acquisition of the myofibroblastic phenotype and liver fibrosis.}, }
@article {pmid37028455, year = {2023}, author = {Lin, Y and Amkul, K and Laosatit, K and Liu, J and Yimram, T and Chen, J and Yuan, X and Chen, X and Somta, P}, title = {Fine mapping of QTL conferring resistance to calcareous soil in mungbean reveals VrYSL3 as candidate gene for the resistance.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {332}, number = {}, pages = {111698}, doi = {10.1016/j.plantsci.2023.111698}, pmid = {37028455}, issn = {1873-2259}, mesh = {Quantitative Trait Loci/genetics ; *Vigna/genetics/metabolism ; Genome-Wide Association Study ; Soil ; Iron/metabolism ; *Iron Deficiencies ; }, abstract = {Iron is a crucial nutrient for biological functions in plants. High-pH and calcareous soil is a major stress causing iron deficiency chlorosis (IDC) symptoms and yield losses in crops. Use of calcareous soil-tolerance genetic resources is the most effective preventative method to combat the effects of high-pH and calcareous soils. A previous study using a mungbean recombinant inbred line (RIL) population of the cross Kamphaeg Saen 2 (KPS2; IDC susceptible) × NM-10-12 identified a major quantitative trait locus (QTL), qIDC3.1, which controls resistance and explains more than 40% of IDC variation. In this study, we fine-mapped qIDC3.1 and identified an underlying candidate gene. A genome wide association analysis (GWAS) using 162 mungbean accessions identified single nucleotide polymorphisms (SNPs) on chromosome 6; several SNPs were associated with soil plant analysis development (SPAD) values and IDC visual scores of mungbeans planted on calcareous soil, respectively. These SNPs corresponded to qIDC3.1. Using the same RIL population as in the previous study and an advanced backcross population developed from KPS2 and IDC-resistant inbred line RIL82, qIDC3.1 was further confirmed and fine-mapped to an interval of 217 kilobases harboring five predicted genes, including LOC106764181 (VrYSL3), which encodes a yellow stripe1-like-3 (YSL3) protein, YSL3 is involved in iron deficiency resistance. Gene expression analysis revealed that VrYSL3 was highly expressed in mungbean roots. In calcareous soil, expression of VrYSL3 was significantly up-regulated, and it was more obviously upregulated in the roots of RIL82, than in those of KPS2. Sequence comparison of VrYSL3 between the RIL82 and KPS2 revealed four SNPs that result in amino acid changes in the VrYSL3 protein and a 20-bp insertion/deletion in the promoter where a cis-regulatory element resides. Transgenic Arabidopsis thaliana plants overexpressing VrYSL3 showed enhanced iron and zinc contents in the leaves. Taken together, these results indicate that VrYSL3 is a strong candidate gene responsible for calcareous soil resistance in mungbean.}, }
@article {pmid37020090, year = {2023}, author = {Kawaguchi, S and Kinowaki, K and Tamura, N and Masumoto, T and Nishikawa, A and Shibata, A and Tanaka, K and Kobayashi, Y and Ogura, T and Sato, J and Kawabata, H}, title = {High-accuracy prediction of axillary lymph node metastasis in invasive lobular carcinoma using focal cortical thickening on magnetic resonance imaging.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {637-646}, pmid = {37020090}, issn = {1880-4233}, mesh = {Humans ; Female ; Middle Aged ; Aged ; *Breast Neoplasms/pathology ; Lymphatic Metastasis/diagnostic imaging/pathology ; *Carcinoma, Lobular/diagnostic imaging/surgery/pathology ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; Lymph Nodes/pathology ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC.<br><br>METHOD: This retrospective analysis included 120 female patients (mean&#x2009;&#xb1;&#x2009;standard deviation age, 57.2&#x2009;&#xb1;&#x2009;11.2&#xa0;years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH).<br><br>RESULTS: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively.<br><br>CONCLUSIONS: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required.}, }
@article {pmid37017594, year = {2023}, author = {Zheng, L and Wu, H and Wen, N and Zhang, Y and Wang, Z and Peng, X and Tan, Y and Qiu, L and Qu, F and Tan, W}, title = {Aptamer-Functionalized Nanovaccines: Targeting In Vivo DC Subsets for Enhanced Antitumor Immunity.}, journal = {ACS applied materials &amp; interfaces}, volume = {15}, number = {15}, pages = {18590-18597}, doi = {10.1021/acsami.2c20846}, pmid = {37017594}, issn = {1944-8252}, mesh = {Humans ; *Cancer Vaccines ; Immunotherapy/methods ; T-Lymphocytes ; Antigens, Neoplasm/genetics ; *Neoplasms/therapy ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Dendritic Cells ; }, abstract = {Cancer vaccines, which directly pulsed in vivo dendritic cells (DCs) with specific antigens and immunostimulatory adjuvants, showed great potential for cancer immunoprevention. However, most of them were limited by suboptimal outcomes, mainly owing to overlooking the complex biology of DC phenotypes. Herein, based on adjuvant-induced antigen assembly, we developed aptamer-functionalized nanovaccines for in vivo DC subset-targeted codelivery of tumor-related antigens and immunostimulatory adjuvants. We chose two aptamers, iDC and CD209, and tested their performance on DC targeting. Our results verified that these aptamer-functionalized nanovaccines could specifically recognize circulating classical DCs (cDCs), a subset of DCs capable of priming naïve T cells, noting that iDC outperformed CD209 in this regard. With excellent cDC-targeting capability, the iDC-functionalized nanovaccine induced potent antitumor immunity, leading to effective inhibition of tumor occurrence and metastasis, thus providing a promising platform for cancer immunoprevention.}, }
@article {pmid37013774, year = {2023}, author = {Oh, J and Oh, JM and Cho, SY}, title = {METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {6}, pages = {2561-2570}, doi = {10.26355/eurrev_202303_31793}, pmid = {37013774}, issn = {2284-0729}, mesh = {Humans ; *Adenocarcinoma of Lung ; Carcinogenesis ; *Colonic Neoplasms ; Down-Regulation ; *Lung Neoplasms/genetics/pathology ; *Methyltransferases/genetics ; *Serine-Arginine Splicing Factors/genetics ; }, abstract = {OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms.<br><br>MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression.<br><br>RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression.<br><br>CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.}, }
@article {pmid37008917, year = {2023}, author = {Kender, Z and Jende, JME and Kurz, FT and Tsilingiris, D and Schimpfle, L and Sulaj, A and von Rauchhaupt, E and Bartl, H and Mooshage, C and Göpfert, J and Nawroth, P and Herzig, S and Szendroedi, J and Bendszus, M and Kopf, S}, title = {Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1046690}, pmid = {37008917}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/pathology ; Anisotropy ; Intermediate Filaments ; Sciatic Nerve/diagnostic imaging/pathology ; *Diabetic Neuropathies/complications ; Lower Extremity/diagnostic imaging ; Biomarkers ; }, abstract = {BACKGROUND: Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve's FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL).<br><br>MATERIALS AND METHODS: Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage.<br><br>RESULTS: Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls (p<0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p<0.001 and r=0.6; p<0.001) and sural sensory NCV (r=0.50; p<0.001). Participants with reduced sciatic nerve&#xb4;s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p<0.01 and r=0.3; p<0.01) and lower (r=0.5; p<0.001 and r=0.3; p=<0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p<0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve&#xb4;s FA (r=-0.5; p<0.001 and r= -0.3, p= 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain.<br><br>CONCLUSION: This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.}, }
@article {pmid36976351, year = {2023}, author = {Aiello, EN and D'Iorio, A and Solca, F and Torre, S and Bonetti, R and Scheveger, F and Colombo, E and Maranzano, A and Maderna, L and Morelli, C and Doretti, A and Amboni, M and Vitale, C and Verde, F and Ferrucci, R and Barbieri, S and Zirone, E and Priori, A and Pravettoni, G and Santangelo, G and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B}, title = {Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {130}, number = {5}, pages = {687-696}, pmid = {36976351}, issn = {1435-1463}, mesh = {Humans ; *Parkinson Disease/complications/diagnosis/psychology ; Reproducibility of Results ; Cross-Sectional Studies ; Feasibility Studies ; Neuropsychological Tests ; *Cognitive Dysfunction/etiology/complications ; Language ; }, abstract = {BACKGROUND: This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients.<br><br>METHODS: N&#x2009;=&#x2009;109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N&#x2009;=&#x2009;96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a &#x2248; 6-month interval, within a subsample of patients (N&#x2009;=&#x2009;33).<br><br>RESULTS: The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach.<br><br>DISCUSSION: The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.}, }
@article {pmid36973739, year = {2023}, author = {Cheng, X and Jia, X and Wang, C and Zhou, S and Chen, J and Chen, L and Chen, J}, title = {Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation.}, journal = {World journal of surgical oncology}, volume = {21}, number = {1}, pages = {112}, pmid = {36973739}, issn = {1477-7819}, support = {2021Y29//Medical science and technology program in Ningbo/ ; }, mesh = {Female ; Humans ; Phosphofructokinase-2/genetics/metabolism ; Cell Proliferation ; Cell Line, Tumor ; *MicroRNAs/genetics ; *Hyperglycemia/complications/genetics ; Phenotype ; *Carcinoma, Ductal/genetics ; Cell Movement ; Gene Expression Regulation, Neoplastic ; }, abstract = {BACKGROUND: Breast cancer is the most common tumor in women worldwide. Diabetes mellitus is a global chronic metabolic disease with increasing incidence. Diabetes mellitus has been reported to positively regulate the development of many tumors. However, the specific mechanism of hyperglycemic environment regulating breast cancer remains unclear. PFKFB3 (6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3) is a key regulatory factor of the glycolysis process in diabetes mellitus, as well as a promoter of breast cancer. So, we want to explore the potential link between PFKFB3 and the poor prognosis of breast cancer patients with hyperglycemia in this study.<br><br>METHODS: Cell culture was utilized to construct different-glucose breast cancer cell lines. Immunohistochemistry was adopted to analyze the protein level of PFKFB3 in benign breast tissues, invasive ductal carcinoma with diabetes and invasive ductal carcinoma without diabetes. The Kaplan-Meier plotter database and GEO database (GSE61304) was adopted to analyze the survival of breast cancer patients with different PFKFB3 expression. Western blot was adopted to analyze the protein level of PFKFB3, epithelial-mesenchymal transition (EMT)-related protein and extracellular regulated protein kinases (ERK) in breast cancer cells. Gene Set Cancer Analysis (GSCA) was utilized to investigate the potential downstream signaling pathways of PFKFB3. TargetScan and OncomiR were utilized to explore the potential mechanism of PFKFB3 overexpression by hyperglycemia. Transfections (including siRNAs and miRNA transfection premiers) was utilized to restrain or mimic the expression of the corresponding RNA. Cell functional assays (including cell counting, MTT, colony formation, wound-healing, and cell migration assays) were utilized to explore the proliferation and migration of breast cancer cells.<br><br>RESULTS: In this study, we demonstrated that the expression of PFKFB3 in breast cancer complicated with hyperglycemia was higher than that in breast cancer with euglycemia through cell experiment in vitro and histological experiment. PFKFB3 overexpression decreased the survival period of breast cancer patients and was correlated with a number of clinicopathological parameters of breast cancer complicated with diabetes. PFKFB3 promoted the proliferation and migration of breast cancer in a hyperglycemic environment and might be regulated by miR-26. In addition, PFKFB3 stimulated epithelial-mesenchymal transition of breast cancer in a hyperglycemic environment. In terms of downstream mechanism exploration, we predicted and verified the cancer-promoting effect of PFKFB3 in breast cancer complicated with hyperglycemia through RAS/MAPK pathway.<br><br>CONCLUSIONS: In conclusion, PFKFB3 could be overexpressed by hyperglycemia and might be a potential therapeutic target for breast cancer complicated with diabetes.}, }
@article {pmid36973678, year = {2023}, author = {Tong, S and Jiang, N and Wan, JH and Chen, CR and Wang, SH and Wu, CY and Guo, Q and Xiao, XY and Huang, H and Zhou, T}, title = {The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {275}, pmid = {36973678}, issn = {1471-2407}, mesh = {Humans ; Cyclin D1 ; Prognosis ; *Lung Neoplasms/pathology ; *Adenocarcinoma of Lung/genetics ; Biomarkers, Tumor/genetics ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Inhibition of Serum Amyloid A-like 1 (SAAL1) expression could inhibit cancer progression and improve the prognosis of cancer patients. At present, the correlation between SAAL1 and lung adenocarcinoma (LAC) remains unclear. Therefore, this study surveyed the worth and pathway of SAAL1 in LAC progression and immunity.<br><br>METHODS: Bioinformatics and immunohistochemistry were used to identify the SAAL1 expression in LAC. The roles of SAAL1 expression in the existence values of LAC patients were explored, and the nomograms were constructed. Clinical values of SAAL1 co-expressed genes were evaluated by COX regression, survival, and Receiver operating characteristic (ROC) analysis. EDU and western blotting methods were used to inquiry the functions and pathways of the SAAL1 in cell growths. The correlation between the SAAL1 level and immune microenvironment was visualized using correlation research.<br><br>RESULTS: SAAL1 level was elevated in LAC tissues, and was observed in cancer tissues of dead patients. SAAL1 overexpression had something to do with shorter overall survival, progression-free interval, and disease-specific survival in LAC. The area under the curve of SAAL1 was 0.902 in normal tissues and cancer tissues. Inhibition of SAAL1 expression could inhibit cancer cell proliferation, which may be related to the decreased expression of cyclin D1 and Bcl-2 proteins. In LAC, SAAL1 level had something to do with stromal, immune, and estimate scores, and correlated with macrophages, T cells, Th2 cells, CD8 T cells, NK CD56dim cells, DC, eosinophils, NK CD56bright cells, pDC, iDC, cytotoxic cells, Tgd, aDC cells, B cells, Tcm, and TFH levels. SAAL1 overexpression had something to do with existence values and the immunity in LAC.<br><br>CONCLUSIONS: Inhibition of SAAL1 expression could regulate cancer growth via cyclin D1 and Bcl-2. SAAL1 is a promising prognostic biomarker in LAC patients.}, }
@article {pmid36939123, year = {2023}, author = {Mareti, E and Vavoulidis, E and Papanastasiou, A and Maretis, T and Tsampazis, N and Margioula-Siarkou, C and Chatzinikolaou, F and Giasari, S and Nasioutziki, M and Daniilidis, A and Zepiridis, L and Dinas, K}, title = {Evaluating the potential role of human papilloma virus infection in breast carcinogenesis via real-time polymerase chain reaction analyzes of breast fine needle aspiration samples from Greek patients.}, journal = {Diagnostic cytopathology}, volume = {51}, number = {7}, pages = {414-422}, doi = {10.1002/dc.25130}, pmid = {36939123}, issn = {1097-0339}, mesh = {Humans ; Female ; Biopsy, Fine-Needle ; Real-Time Polymerase Chain Reaction ; Human Papillomavirus Viruses ; Greece/epidemiology ; *Papillomavirus Infections ; *Breast Neoplasms/pathology ; Carcinogenesis ; Papillomaviridae/genetics ; }, abstract = {BACKGROUND: Human papilloma virus (HPV), in addition to its known clinical contribution to cervical cancer is probably actively involved in the development of breast tumors in various populations worldwide. Predominant HPV types in breast cancer patients vary geographically. The present study further examines HPV incidence in Greece, based on molecular analysis of clinical cytological samples.<br><br>METHODS: Greek patient fine needle aspiration (FNA) biopsy samples were examined using RT-PCR and immunohistological staining. FNA biopsy samples were collected from 114 female patients, diagnosed between the years 2018 and 2021, 57 with C5 diagnosed breast cancer lesions and 57 diagnosed with benign diseases.<br><br>RESULTS: A total of three different HPV types were identified within the patient sample. HPV-39 was found only in the control group, in 1.8% of patients, while HPV-59 was present in both control and study groups in 1.8% and 3.5% respectively. HPV-16, on the other hand, was present only in the study group in 12.3% of cases. HPV type presence was statistically differentiated between histological groups. HPV-16 was exclusively in IDC, HPV-39 was present in one cyst diagnosed sample and HPV-59 was present in 3 samples that included fibroadenoma, IDC and LN diagnosis.<br><br>CONCLUSION: More international comparative studies are required to investigate population differences and HPV genotype distribution to offer definite answers to the effect that certain HPV types might have a role in breast cancer, as this study also supports, albeit in a cofactory role.}, }
@article {pmid36934657, year = {2023}, author = {Varun, K and Zoltan, K and Alba, S and Manuel, B and Elisabeth, K and Dimitrios, T and Jan B, G and Maik, B and Khurrum, S and Berend, I and Stephen, H and Thomas, F and Julia, S and Peter, N and Stefan, K}, title = {Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes.}, journal = {EBioMedicine}, volume = {90}, number = {}, pages = {104516}, pmid = {36934657}, issn = {2352-3964}, mesh = {Mice ; Animals ; *Diabetes Mellitus, Type 2/complications ; Follow-Up Studies ; Interleukin-6 ; *Prediabetic State ; Albuminuria/complications ; Cross-Sectional Studies ; Prospective Studies ; *Lung Diseases ; Fibrosis ; DNA Damage ; Cellular Senescence ; }, abstract = {BACKGROUND: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes.<br><br>METHODS: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and &#x264;H2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-&#x3b2;1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years.<br><br>FINDINGS: db/db mice showed an increased nuclear &#x264;H2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression.<br><br>INTERPRETATION: In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis.<br><br>FUNDING: This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Research and the Arts, Baden-W&#xfc;rttemberg (Kompetenznetzwerk Pr&#xe4;ventivmedizin).}, }
@article {pmid36933394, year = {2023}, author = {Vormittag-Nocito, E and Acosta, AM and Agarwal, S and Narayan, KD and Kumar, R and Al Rasheed, MRH and Kajdacsy-Balla, A and Behm, FG and Mohapatra, G}, title = {In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {36}, number = {6}, pages = {100130}, doi = {10.1016/j.modpat.2023.100130}, pmid = {36933394}, issn = {1530-0285}, mesh = {Male ; Humans ; *Prostatic Intraepithelial Neoplasia/genetics/pathology ; *Prostatic Neoplasms/pathology ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostatectomy ; }, abstract = {Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.}, }
@article {pmid36931261, year = {2023}, author = {Cardona Barberán, A and Bonte, D and Boel, A and Thys, V and Paredis, R and Machtelinckx, F and De Sutter, P and De Croo, I and Leybaert, L and Stoop, D and Coucke, P and Vanden Meerschaut, F and Heindryckx, B}, title = {Assisted oocyte activation does not overcome recurrent embryo developmental problems.}, journal = {Human reproduction (Oxford, England)}, volume = {38}, number = {5}, pages = {872-885}, doi = {10.1093/humrep/dead051}, pmid = {36931261}, issn = {1460-2350}, mesh = {Pregnancy ; Child ; Humans ; Male ; Female ; Animals ; Mice ; *Sperm Injections, Intracytoplasmic/methods ; *Calcium ; Ionomycin ; Calcimycin ; Prospective Studies ; Semen ; Pregnancy Rate ; Oocytes ; Embryonic Development ; Retrospective Studies ; Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; }, abstract = {STUDY QUESTION: Can recurrent embryo developmental problems after ICSI be overcome by assisted oocyte activation (AOA)?<br><br>SUMMARY ANSWER: AOA did not improve blastocyst formation in our patient cohort with recurrent embryo developmental problems after ICSI.<br><br>WHAT IS KNOWN ALREADY: The use of AOA to artificially induce calcium (Ca2+) rises by using Ca2+ ionophores (mainly calcimycin and ionomycin) has been reported as very effective in overcoming fertilization failure after ICSI, especially in patients whose Ca2+ dynamics during fertilization are deficient. However, there is only scarce and contradictory literature on the use of AOA to overcome embryo developmental problems after ICSI, and it is not clear whether abnormal Ca2+ patterns during fertilization disturb human preimplantation embryo development. Moreover, poor embryo development after ICSI has also been linked to genetic defects in the subcortical maternal complex (SCMC) genes.<br><br>STUDY DESIGN, SIZE, DURATION: This prospective cohort single-center study compared ICSI-AOA cycles and previous ICSI cycles in couples with normal fertilization rates (&#x2265;60%) but impaired embryonic development (&#x2264;15% blastocyst formation) in at least two previous ICSI cycles. In total, 42 couples with embryo developmental problems were included in this study from January 2018 to January 2021.<br><br>Of the 42 couples included, 17 underwent an ICSI-AOA cycle consisting of CaCl2 injection and double ionomycin exposure. Fertilization, blastocyst development, pregnancy, and live birth rates after ICSI-AOA were compared to previous ICSI cycles. In addition, the calcium pattern induced by the male patient's sperm was investigated by mouse oocyte calcium analysis. Furthermore, all 42 couples underwent genetic screening. Female patients were screened for SCMC genes (TLE6, PADI6, NLRP2, NLRP5, NLRP7, and KHDC3L) and male patients were screened for the sperm-oocyte-activating factor PLCZ1.<br><br>We compared 17 AOA cycles to 44 previous ICSI cycles from the same patient cohort. After AOA, a total fertilization rate of 68.95% (131/190), a blastocyst development rate of 13.74% (18/131), a pregnancy rate of 29.41% (5/17), and a live birth rate of 23.53% (4/17) were achieved, which was not different from the previous ICSI cycles (76.25% (321/421, P-value&#x2009;=&#x2009;0.06); 9.35% (30/321, P-value&#x2009;=&#x2009;0.18), 25.00% (11/44, P-value&#x2009;=&#x2009;0.75), and 15.91% (7/44, P-value&#x2009;=&#x2009;0.48), respectively). Calcium analysis showed that patient's sperm induced calcium patterns similar to control sperm samples displaying normal embryo developmental potential. Genetic screening revealed 10 unique heterozygous variants (in NLRP2, NLRP5, NLRP7, TLE6, and PADI6) of uncertain significance (VUS) in 14 females. Variant NLRP5 c.623-12_623-11insTTC (p.?) was identified in two unrelated individuals and variant NLRP2 c.1572T>C (p.Asp524=) was identified in four females. Interestingly, we identified a previously reported homozygous mutation PLCZ1, c.1499C>T (p.Ser500Leu), in a male patient displaying impaired embryonic development, but not showing typical fertilization failure.<br><br>Our strict inclusion criteria, requiring at least two ICSI cycles with impaired embryo development, reduced cycle-to-cycle variability, while the requirement of a lower blastocyst development not influenced by a poor fertilization excluded couples who otherwise would be selective cases for AOA; however, these criteria limited the sample size of this study. Targeted genetic screening might be too restricted to identify a genetic cause underlying the phenotype of poor embryo development for all patients. Moreover, causality of the identified VUS should be further determined.<br><br>Strong evidence for AOA overcoming impaired embryonic development is still lacking in the literature. Thus far, only one article has reported a beneficial effect of AOA (using calcimycin) compared to previous ICSI cycles in this patient population, whilst two more recent sibling-oocyte control studies (one using calcimycin and the other ionomycin) and our research (using ionomycin) could not corroborate these findings. Although no major abnormalities have been found in children born after AOA, this technique should be reserved for couples with a clear Ca2+-release deficiency. Finally, genetic screening by whole-exome sequencing may reveal novel genes and variants linked to embryo developmental problems and allow the design of more personalized treatment options, such as wild-type complementary RNA or recombinant protein injection.<br><br>This study was supported by the Flemish Fund for Scientific Research (grant FWO.OPR.2015.0032.01 to B.H. and grant no. 1298722N to A.B.). A.C.B., D.B., A.B., V.T., R.P., F.M., I.D.C., L.L., D.S., P.D.S., P.C., and F.V.M. have nothing to disclose. B.H. reports a research grant from the Flemish Fund for Scientific Research and reports being a board member of the Belgian Society for Reproductive Medicine and the Belgian Ethical Committee on embryo research.<br><br>TRIAL REGISTRATION NUMBER: NCT03354013.}, }
@article {pmid36927911, year = {2023}, author = {Mitsuyoshi, A and Yanagawa, T and Kikumori, K and Hori, A and Oshima, K and Shinke, G and Katsuyama, S and Ikeshima, R and Hiraki, M and Ohmura, Y and Sugimura, K and Masuzawa, T and Hata, T and Takeda, Y and Murata, K}, title = {[A Case of De Novo Stage Ⅳ Breast Cancer with Umbilical Metastasis and Peritoneal Dissemination].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {50}, number = {3}, pages = {366-368}, pmid = {36927911}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; Peritoneum ; *Breast Neoplasms/surgery/pathology ; Positron Emission Tomography Computed Tomography ; Umbilicus/surgery/pathology ; *Carcinoma, Ductal ; }, abstract = {The patient was a 48-year-old woman. At the time of consultation, a hard mass of 30 mm in size was palpated in area A of the right breast, and a firm mass of about 10 mm was seen in the umbilical region. Histological diagnosis of the breast mass was invasive ductal carcinoma. PET-CT scan showed accumulation in the right breast, as well as suspicion of umbilical metastasis and peritoneal dissemination, uterine mass, and left ovarian cancer. Since this is an atypical metastatic site for invasive ductal carcinoma of the breast, and the possibility of peritoneal dissemination due to gynecological cancer complications cannot be ruled out, resection of the umbilical mass and laparoscopy was performed. The review laparoscopy revealed no evidence of primary cancer in the uterine body or left ovary, and a white nodular lesion of suspected seeding in the peritoneum around the left ovary. The histology and immunostaining results of the umbilical mass and left peri-ovarian nodule both showed glandular luminal structures similar to those of the primary breast cancer, and the left peri-ovarian nodule was ER positive, GATA3 positive, and PAX8 negative, leading to the diagnosis of umbilical metastasis and peritoneal seeding derived from breast cancer. Umbilical metastasis is often referred to as Sister Mary Joseph's nodule in the case of visceral malignancies and is often associated with peritoneal dissemination and is often caused by invasive metastasis of peritoneal dissemination lesions on the dorsal side of the umbilical region. In this case, histological examination of the umbilical specimen showed no disseminated lesion on the peritoneal side, so it was not considered to be an invasive metastasis due to peritoneal dissemination.}, }
@article {pmid36897545, year = {2023}, author = {Kikuchi, M and Gomi, N and Ueki, A and Osako, T and Terauchi, T}, title = {Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {577-583}, pmid = {36897545}, issn = {1880-4233}, mesh = {*Breast Neoplasms/diagnostic imaging/genetics/pathology ; Magnetic Resonance Imaging ; Risk ; *Genetic Predisposition to Disease ; Japan ; Ataxia Telangiectasia Mutated Proteins/genetics ; Fanconi Anemia Complementation Group N Protein/genetics ; Antigens, CD/genetics ; Cadherins/genetics ; Tumor Suppressor Protein p53/genetics ; *Early Detection of Cancer/methods ; *Genes, Neoplasm ; Neoplasm Staging ; Humans ; Female ; Adult ; Middle Aged ; Aged ; }, abstract = {BACKGROUND: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer.<br><br>METHODS: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021. MRI exams were evaluated independently by two radiologists. Final histopathological diagnosis for malignant lesions were obtained from surgical specimen.<br><br>RESULTS: A total of 16 patients included TP53, CDH1, PALB2, ATM pathogenic variants and 3 variant of unknown significance. 2 patients with TP53 pathogenic variants were detected breast cancer by annual MRI surveillance. The rate of cancer detection was 12.5% (2/16). One patient was detected synchronous bilateral breast cancer and unilateral multiple breast cancers (3 lesions in 1 patient), so there were 4 malignant lesions in total. Surgical pathology of 4 lesions were 2 ductal carcinoma in situ, 1 invasive lobular carcinoma, and 1 invasive ductal carcinoma. MRI findings of 4 malignant lesions were detected as 2 non mass enhancement, 1 focus and 1 small mass. All of 2 patients with PALB2 pathogenic variants had previously developed breast cancer.<br><br>CONCLUSIONS: Germline TP53 and PALB2 were strongly associated with breast cancer, suggesting that MRI surveillance is essential for breast cancer-related hereditary predisposition.}, }
@article {pmid36893606, year = {2023}, author = {Göransson, S and Chen, S and Olofsson, H and Larsson, O and Strömblad, S}, title = {An extracellular matrix stiffness-induced breast cancer cell transcriptome resembles the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC).}, journal = {Biochemical and biophysical research communications}, volume = {654}, number = {}, pages = {73-79}, doi = {10.1016/j.bbrc.2023.03.001}, pmid = {36893606}, issn = {1090-2104}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Transcriptome ; Extracellular Matrix/genetics/pathology ; *Breast Neoplasms/genetics/pathology ; *Carcinoma in Situ ; }, abstract = {Identifying mechanisms driving the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer remains a challenge in breast cancer research. Breast cancer progression is accompanied by remodelling and stiffening of the extracellular matrix, leading to increased proliferation, survival, and migration. Here, we studied stiffness-dependent phenotypes in MCF10CA1a (CA1a) breast cancer cells cultured on hydrogels with stiffness corresponding to normal breast and breast cancer. This revealed a stiffness-associated morphology consistent with acquisition of an invasive phenotype in breast cancer cells. Surprisingly, this strong phenotypic switch was accompanied by relatively modest transcriptome-wide alterations in mRNA levels, as independently quantified using both DNA-microarrays and bulk RNA sequencing. Strikingly, however, the stiffness-dependent alterations in mRNA levels overlapped with those contrasting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). This supports a role of matrix stiffness in driving the pre-invasive to invasive transition and suggests that mechanosignalling may be a target for prevention of invasive breast cancer.}, }
@article {pmid36890060, year = {2023}, author = {Verspyck, E and Attal, N}, title = {Diagnosing nociplastic pain in cancer survivors: a major step forward.}, journal = {British journal of anaesthesia}, volume = {130}, number = {5}, pages = {515-518}, doi = {10.1016/j.bja.2023.02.006}, pmid = {36890060}, issn = {1471-6771}, mesh = {Humans ; *Cancer Survivors ; Pain ; *Fibromyalgia/complications/diagnosis/therapy ; Headache ; Pain Management ; *Neoplasms/complications ; }, abstract = {Nociplastic pain syndromes include particular fibromyalgia, irritable bowel syndrome, headache, complex regional pain syndrome, and idiopathic orofacial pain. Several mechanisms have been proposed to account for nociplastic pain including central sensitisation, alterations of pain modulatory controls, epigenetic changes, and peripheral mechanisms. Importantly, nociplastic pain might also be present in patients with cancer pain, particularly those with pain related to complications of cancer treatment. Increased awareness of nociplastic pain associated with cancer should have important implications for monitoring and managing such patients.}, }
@article {pmid36883155, year = {2022}, author = {Ali Khadem, Z and Abdul Wadood Al-Shammaree, S}, title = {Prognostic Value of Intracellular Transcription of Factors HIF-1α and p53 and Their Relation to Estradiol and TNM Parameters of Breast Cancer Tissues in Women with Invasive Ductal Carcinoma in Thi-Qar Province, Iraq.}, journal = {Archives of Razi Institute}, volume = {77}, number = {4}, pages = {1341-1348}, pmid = {36883155}, issn = {2008-9872}, mesh = {Adolescent ; Adult ; Female ; Humans ; Young Adult ; *Breast Neoplasms/chemistry/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/chemistry/genetics/metabolism/pathology ; *Estradiol/analysis/genetics/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/analysis/genetics/metabolism ; Iraq/epidemiology ; Prognosis ; *Tumor Suppressor Protein p53/analysis/genetics/metabolism ; }, abstract = {Breast cancer is the most common malignancy affecting women's health, with an increasing incidence worldwide. This study aimed to measure the intracellular concentration of the hypoxia-inducible factor 1 α (HIF-1α), tumor suppression protein p53, and estradiol (E2) in tumor tissues of adult females with breast cancer and their relation to tumor grade, tumor size, and lymph node metastases (LNM). The study was conducted on 65 adult female participants with breast mass admitted to the operating theater in Al-Hussein Teaching Hospital and Al-Habboby Teaching Hospital in Nasiriyah, Iraq, from January to November 2021. Fresh breast tumor tissues were collated and homogenized for intracellular biochemical analysis using the enzyme-linked immunosorbent assay method. In total, 44 (58%) out of 65 patients, in the age range of 18-42 years and the mean±SD age of 32.55±6.40 years, had fibroadenomas, and other 21 (42%) cases, in the age range of 32-80 years and the mean±SD age of 56±14.4 years had invasive ductal carcinoma (IDC) breast cancer. Intracellular levels of HIF-1α, p53, and E2 were elevated significantly (P<0.001) in IDC cases compared to the benign group. The most malignant tumors of IDC cases were in grade III and sizes T2 and T3. The tissue concentrations of HIF-1α, P53, and E2 were significantly elevated in patients with tumor stage T3 compared to T2 and T1. A significant elevation was found in the levels of HIF-1α, p53, and E2 in the positive LNM subgroup compared to the negative LNM group. Based on the obtained results, the prognostic value of the intracellular HIF-1α is considered to be a useful prognostic factor in Iraqi women with ICD and the combination of a HIF-1α protein with the nonfunctional p53 and E2 tends to indicate the proliferation, invasiveness, and metastases of the breast tumors.}, }
@article {pmid36868097, year = {2023}, author = {Aktan, &#xc7; and Küçükaslan, A&#x15e; and Türk, BA and Yildirim, I}, title = {Expression analysis of novel long non-coding RNAs for invasive ductal and invasive lobular breast carcinoma cases.}, journal = {Pathology, research and practice}, volume = {244}, number = {}, pages = {154391}, doi = {10.1016/j.prp.2023.154391}, pmid = {36868097}, issn = {1618-0631}, mesh = {Female ; Humans ; *RNA, Long Noncoding/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Treatment Outcome ; *Breast Neoplasms/pathology ; }, abstract = {AIM: Long non-coding RNAs (LncRNAs) serve as important regulatory molecules of gene expression and protein functionality at multiple biological levels, and their deregulation plays a key role in tumorigenesis including in breast cancer metastasis. Therefore, in this study, we aim to compare the expression of novel lncRNAs in the landscape of invasive ductal carcinoma (IDC) and invasive lobular (ILC) carcinoma of breast.<br><br>MAIN METHODS: We have designed an in-silico approach to find the lncRNAs that regulate the breast cancer. Then, we used the clinical samples to carry out the verification of our in silico finding. In the present study, the tissues of breast cancer were deparaffinized. RNA was extracted by the TRIzole method. After synthesizing cDNA from the extracted RNA, expression levels of lncRNAs were analyzed by qPCR using primers specifically designed and validated for the targeted lncRNAs. In this study, breast biopsy materials from 41 female patients with IDC and 10 female patients with ILC were examined histopathological and expression changes of candidate lncRNAs were investigated in line with the findings. The results were analyzed using IBM SPSS Statistics 25 version.<br><br>RESULTS: The mean age of the cases was 53.78&#xa0;&#xb1;&#xa0;14.96. The minimum age was 29, while the maximum age was 87. While 27 of the cases were pre-menopausal, 24 cases were post-menopausal. The number of hormone receptor-positive cases was found to be 40, 35, and 27 for ER, PR, and cerb2/neu, respectively. While the expressions of LINC00501, LINC00578, LINC01209, LINC02015, LINC02584, ABCC5-AS1, PEX5L-AS2, SHANK2-AS3 and SOX2-OT showed significant differences (p&#xa0;<&#xa0;0.05), the expressions of LINC01206, LINC01994, SHANK2-AS1, and TPRG1-AS2 showed no significant differences (p&#xa0;>&#xa0;0.05). In addition, it was determined that the regulation of all lncRNAs could be able to involve in the development of cancer such as the NOTCH1, NFKB, and estrogen receptor signalings.<br><br>CONCLUSION: As a result, it was thought that the discovery of novel lncRNAs might be an important player in the diagnosis, prognosis and therapeutic development of breast cancer.}, }
@article {pmid36797734, year = {2023}, author = {Arias Ramos, D and Alzate, JA and Moreno Gómez, GA and Hoyos Pulgarín, JA and Olaya Gómez, JC and Cortés Bonilla, I and Vargas Mosquera, C}, title = {Empirical treatment and mortality in bacteremia due to extended spectrum β-lactamase producing Enterobacterales (ESβL-E), a retrospective cross-sectional study in a tertiary referral hospital from Colombia.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {22}, number = {1}, pages = {13}, pmid = {36797734}, issn = {1476-0711}, mesh = {Humans ; Retrospective Studies ; Cross-Sectional Studies ; *Escherichia coli Infections/drug therapy ; Tertiary Care Centers ; Colombia/epidemiology ; beta-Lactamases/genetics ; Anti-Bacterial Agents/therapeutic use ; Risk Factors ; *Bacteremia/drug therapy/microbiology ; }, abstract = {BACKGROUND: Infections caused by extended spectrum β-lactamase (ESβL) producing bacteria are common and problematic. When they cause bloodstream infections, they are associated with significant morbidity and mortality.<br><br>METHODS: A retrospective cross-sectional observational study was conducted in a single center in Pereira, Colombia. It included people hospitalized with bacteremia due to gram-negative bacilli with the extended-spectrum &#x3b2;-lactamase producing phenotype. A logistic regression analysis was constructed. Clinical characteristics and risk factors for death from sepsis were established.<br><br>RESULTS: The prevalence of bacteremia due to Enterobacterales with extended-spectrum &#x3b2;-lactamase producing phenotype was 17%. 110 patients were analyzed. Most patients were men (62%) with a median age of 58&#xa0;years, hospital mortality was 38%. Admission to intensive care was 45%. The following risk factors for mortality were established: shock requiring vasoactive support, Pitt score&#x2009;>&#x2009;3 points, and not having an infectious disease consultation (IDC).<br><br>CONCLUSIONS: bacteremia due to Enterobacterales with extended-spectrum &#x3b2;-lactamase producing phenotype have a high mortality. Early recognition of sepsis, identification of risk factors for antimicrobial resistance, and prompt initiation of appropriate empiric antibiotic treatment are important. An infectious disease consultation may help improve outcomes.}, }
@article {pmid36781838, year = {2023}, author = {Sekido, N and Matsuoka, M and Takahashi, R and Sengoku, A and Nomi, M and Matsuyama, F and Murata, T and Kitta, T and Mitsui, T}, title = {Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.}, journal = {Spinal cord series and cases}, volume = {9}, number = {1}, pages = {3}, pmid = {36781838}, issn = {2058-6124}, mesh = {Humans ; *Urinary Catheters/adverse effects ; Cross-Sectional Studies ; Urinary Catheterization/adverse effects ; Japan/epidemiology ; *Urinary Tract Infections/epidemiology/etiology ; Spinal Cord ; }, abstract = {STUDY DESIGN: Cross-sectional study by members of patient advocacy groups.<br><br>OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan.<br><br>SETTING: An internet survey.<br><br>METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC).<br><br>RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p&#x2009;=&#x2009;0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p&#x2009;=&#x2009;0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC.<br><br>CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.}, }
@article {pmid36769184, year = {2023}, author = {Górnicki, T and Lambrinow, J and Mrozowska, M and Romanowicz, H and Smolarz, B and Piotrowska, A and Gomułkiewicz, A and Podhorska-Okołów, M and Dzięgiel, P and Grzegrzółka, J}, title = {Expression of RBMS3 in Breast Cancer Progression.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36769184}, issn = {1422-0067}, mesh = {Humans ; Female ; *Breast Neoplasms/metabolism ; Breast/metabolism ; *Carcinoma, Ductal, Breast/pathology ; MCF-7 Cells ; RNA, Messenger/genetics ; Cell Line, Tumor ; Trans-Activators/metabolism ; RNA-Binding Proteins/metabolism ; }, abstract = {The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(-) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.}, }
@article {pmid36765396, year = {2023}, author = {Sui, Y and Li, S and Fu, XQ and Zhao, ZJ and Xing, S}, title = {Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {109}, pmid = {36765396}, issn = {1479-5876}, mesh = {Humans ; *Lupus Erythematosus, Systemic/genetics ; Janus Kinases/therapeutic use ; *Neoplasms ; Carcinogenesis ; Computational Biology ; RNA, Messenger/metabolism ; }, abstract = {BACKGROUND: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up.<br><br>METHODS: Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses.<br><br>RESULTS: The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway.<br><br>CONCLUSION: The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the&#xa0;IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.}, }
@article {pmid36763857, year = {2023}, author = {Langley, RG and Sofen, H and Dei-Cas, I and Reich, K and Sigurgeirsson, B and Warren, RB and Paul, C and Szepietowski, JC and Tsai, TF and Hampele, I and You, R and Charef, P and Papavassilis, C}, title = {Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.}, journal = {The British journal of dermatology}, volume = {188}, number = {2}, pages = {198-207}, doi = {10.1093/bjd/ljac040}, pmid = {36763857}, issn = {1365-2133}, mesh = {Humans ; Quality of Life ; *Nasopharyngitis/chemically induced ; Antibodies, Monoclonal, Humanized/adverse effects ; *Psoriasis/drug therapy ; *Respiratory Tract Infections ; Treatment Outcome ; Severity of Illness Index ; Double-Blind Method ; }, abstract = {BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis.<br><br>OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis.<br><br>METHODS: Responders with &#x2265; 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150&#x2005;mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300&#x2005;mg continuing on their dose, while those on secukinumab 150&#x2005;mg or placebo received secukinumab 150 or 300&#x2005;mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595.<br><br>RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300&#x2005;mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively.<br><br>CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.}, }
@article {pmid36730303, year = {2023}, author = {Chang, H and Hu, T and Hu, J and Ding, T and Wang, Q and Cheng, J}, title = {Complete response in patient with liver metastasis of HER2-positive breast cancer following therapy with margetuximab: a case report.}, journal = {Anti-cancer drugs}, volume = {34}, number = {7}, pages = {883-887}, pmid = {36730303}, issn = {1473-5741}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/pathology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Trastuzumab ; Receptor, ErbB-2/metabolism ; *Liver Neoplasms/drug therapy/etiology ; }, abstract = {Metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer has a poor prognosis and few effective targeted therapies. However, several anti-HER2 agents are emerging in conjunction with chemotherapy, which may lead to increased rates of pathological complete response in patients with HER2-positive metastatic breast cancer. Among them, margetuximab demonstrated a significant improvement in progression-free survival compared with trastuzumab, when combined with chemotherapy in pretreated patients. Here we present a case of a 67-year-old female patient who was diagnosed with HER2-positive, histological grade III and invasive ductal carcinoma of the left breast in September 2018. She received postoperative adjuvant therapy with EC-TH plus radiotherapy, followed by therapy with HER2-targeted trastuzumab for 1 year (till December 2019). In May 2020, routine reexamination showed a supraclavicular lymph node and bone metastasis. Patient was then treated with pyrotinib, capecitabine and bisphosphonate for a period of 3 months. In December 2020, liver MRI revealed multiple liver metastases. The patient received eight cycles of second-line therapy (vinorelbine plus margetuximab) from January 2021. Since the ninth cycle, the patient was continued with only margetuximab. In March 2021, MRI showed a 70% decrease in the liver metastasis lesions. By June 2021, liver lesions were totally disappeared. During therapy, patient experienced only grade-1 anemia. This case demonstrates that margetuximab plus chemotherapy is safe and might bring clinical benefits for patients with HER2-positive breast cancer with liver metastasis. Further studies evaluating the efficacy and safety of margetuximab in Chinese HER2-positive breast cancer patients are needed.}, }
@article {pmid36708642, year = {2023}, author = {Maggi, G and Vitale, C and Cerciello, F and Santangelo, G}, title = {Sleep and wakefulness disturbances in Parkinson's disease: A meta-analysis on prevalence and clinical aspects of REM sleep behavior disorder, excessive daytime sleepiness and insomnia.}, journal = {Sleep medicine reviews}, volume = {68}, number = {}, pages = {101759}, doi = {10.1016/j.smrv.2023.101759}, pmid = {36708642}, issn = {1532-2955}, mesh = {Humans ; *REM Sleep Behavior Disorder/etiology/complications ; *Parkinson Disease/complications/epidemiology/drug therapy ; Wakefulness ; *Sleep Initiation and Maintenance Disorders/epidemiology/complications ; Quality of Life ; Prevalence ; Sleep ; *Disorders of Excessive Somnolence/epidemiology/diagnosis ; *Sleep Wake Disorders ; }, abstract = {Sleep disorders (SDs) are common non-motor symptoms of Parkinson's disease (PD) with wide variability in their prevalence rates. The etiology of SDs in PD is multifactorial because the degenerative processes underlying the disease and their interaction with drugs and clinical features may promote REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS) and insomnia. Therefore, we designed a meta-analytic study to provide a reliable estimate of the prevalence and associated clinical and neuropsychiatric aspects of SDs in PD. A systematic literature search was performed up to February 2022. Pooled RBD prevalence was 46%, and its occurrence was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose (LEDD), worse motor and autonomic manifestations, poorer quality of life and autonomy, and more severe neuropsychiatric symptoms. The pooled prevalence of EDS was 35% and was associated with older age, longer disease duration, worse motor and autonomic symptoms, higher LEDD, reduced autonomy, and more severe neuropsychiatric symptoms. Insomnia was reported in 44% of PD patients and was related to longer disease duration, higher LEDD, and more severe depression. SDs are associated with a more severe PD clinical phenotype; further studies should explore the pathophysiological mechanisms underlying SDs and develop targeted therapeutic strategies.}, }
@article {pmid36678422, year = {2023}, author = {Feredj, E and Audureau, E and Boueilh, A and Fihman, V and Fourati, S and Lelièvre, JD and Gallien, S and Grimbert, P and Matignon, M and Melica, G}, title = {Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {36678422}, issn = {2076-0817}, abstract = {BACKGROUND: Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined.<br><br>METHODS: We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs.<br><br>RESULTS: We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97-6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43-7.74)) and HCV (OR = 3.76 (1.58-8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26-0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.}, }
@article {pmid36671532, year = {2023}, author = {Yang, Y and Luo, D and Gao, W and Wang, Q and Yao, W and Xue, D and Ma, B}, title = {Combination Analysis of Ferroptosis and Immune Status Predicts Patients Survival in Breast Invasive Ductal Carcinoma.}, journal = {Biomolecules}, volume = {13}, number = {1}, pages = {}, pmid = {36671532}, issn = {2218-273X}, support = {81602337//National Natural Science Foundation of China/ ; 81702564//National Natural Science Foundation of China/ ; 81570579//National Natural Science Foundation of China/ ; UNPYSCT-2017062//Education Department of Heilongjiang Province/ ; LH2021H050//Natural Science Foundation of Heilongjiang Province/ ; }, mesh = {Humans ; *Ferroptosis/genetics ; Algorithms ; Cell Death ; Iron ; *Carcinoma, Ductal ; }, abstract = {Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients' prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients' prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients' prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC.}, }
@article {pmid36653542, year = {2023}, author = {Maggi, G and D'Iorio, A and Aiello, EN and Poletti, B and Ticozzi, N and Silani, V and Amboni, M and Vitale, C and Santangelo, G}, title = {Psychometrics and diagnostics of the Italian version of the Beck Depression Inventory-II (BDI-II) in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {5}, pages = {1607-1612}, pmid = {36653542}, issn = {1590-3478}, mesh = {Humans ; Psychometrics ; *Depression/diagnosis/etiology ; *Parkinson Disease/complications/diagnosis/psychology ; Quality of Life ; Reproducibility of Results ; Psychiatric Status Rating Scales ; }, abstract = {INTRODUCTION: Depression is one of the most disabling neuropsychiatric manifestations of Parkinson's disease (PD) and requires proper screening and diagnosis because it affects the overall prognosis and quality of life of patients. This study aimed to assess the psychometric and diagnostic properties of the Beck Depression Inventory-II (BDI-II) in an Italian PD cohort.<br><br>MATERIALS AND METHODS: Fifty consecutive outpatients with PD underwent the Italian version of the BDI-II and other questionnaires to evaluate anxiety and apathetic symptoms. Patients' caregivers completed the depression/dysphoria domain of the Neuropsychiatric Inventory (NPI-D). We evaluated the internal consistency, convergent and divergent validity, and factorial structure of BDI-II. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were computed using ROC analyses, and an optimal cutoff was defined using the Youden index.<br><br>RESULTS: The BDI-II proved to be internally consistent (Cronbach's &#x3b1; = 0.840) and substantially met the bi-factorial structure. Regarding construct validity, the BDI-II was substantially related to anxiety measures, but not to apathy. With the combination of the NPI-D and anxiety score used as the gold standard, the BDI-II overall showed good accuracy (AUC = 0.859) with adequate sensitivity (75%) and specificity (87%). The optimal cutoff point was defined at 14.50.<br><br>CONCLUSIONS: We provide evidence of the psychometric and diagnostic properties of the Italian version of the BDI-II as a screening tool for depression in patients with PD. The BDI-II was found to be reliable and valid for the measurement of depression in patients with PD; therefore, it is available for use in clinical research and practice.}, }
@article {pmid36641657, year = {2022}, author = {Manginstar, C and Oley, MH and Oley, MC and Merung, M and Langi, FLFG and Kepel, BJ and Rusli, LV and Islam, AA and Faruk, M}, title = {Correlation analysis of HIF-1α and Ca15-3 in response to neoadjuvant chemotherapy in locally advanced breast cancer: A cohort study in Indonesia.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {481-487}, doi = {10.3233/BD-229004}, pmid = {36641657}, issn = {1558-1551}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Prognosis ; Biomarkers, Tumor/metabolism ; Cohort Studies ; Neoadjuvant Therapy ; Prospective Studies ; Hypoxia-Inducible Factor 1, alpha Subunit/therapeutic use ; Indonesia ; Hypoxia ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC.<br><br>METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically&#xa0;confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1&#x3b1; and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks).<br><br>RESULTS: Among the 11 patients included in this study, HIF-1&#x3b1;, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p =&#xa0;0.019).<br><br>CONCLUSIONS: There was a decrease in HIF-1&#x3b1;, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment.}, }
@article {pmid36641655, year = {2022}, author = {Kridis, WB and Feki, A and Khmiri, S and Toumi, N and Chaabene, K and Daoud, J and Ayedi, I and Khanfir, A}, title = {Prognostic factors in inflammatory breast cancer: A single-center study.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {461-469}, doi = {10.3233/BD-220034}, pmid = {36641655}, issn = {1558-1551}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics ; Hormones ; *Inflammatory Breast Neoplasms/diagnosis/genetics ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Adult ; Aged ; Aged, 80 and over ; }, abstract = {BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes.<br><br>METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity.<br><br>RESULTS: During a period of 12 years (2008-2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26-87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse.<br><br>CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.}, }
@article {pmid36637351, year = {2023}, author = {Zhi, R and Wu, K and Zhang, J and Liu, H and Niu, C and Li, S and Fu, L}, title = {PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.}, journal = {Cancer science}, volume = {114}, number = {5}, pages = {1912-1928}, pmid = {36637351}, issn = {1349-7006}, support = {31870860//National Natural Science Foundation of China/ ; 81872164//National Natural Science Foundation of China/ ; 82173344//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Breast/pathology ; *Breast Neoplasms/pathology ; Histones ; *Carcinoma, Papillary/metabolism ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n = 25) and IDC (n = 26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.}, }
@article {pmid36602069, year = {2022}, author = {Serrano-Quintero, A and Sequeda-Juárez, A and Pérez-Hernández, CA and Sosa-Delgado, SM and Mendez-Tenorio, A and Ramón-Gallegos, E}, title = {Immunogenic analysis of epitope-based vaccine candidate induced by photodynamic therapy in MDA-MB-231 triple-negative breast cancer cells.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {40}, number = {}, pages = {103174}, doi = {10.1016/j.pdpdt.2022.103174}, pmid = {36602069}, issn = {1873-1597}, mesh = {Humans ; Female ; Photosensitizing Agents ; *Photochemotherapy/methods ; Calreticulin/metabolism/therapeutic use ; Epitopes/therapeutic use ; *Triple Negative Breast Neoplasms/drug therapy ; *Breast Neoplasms ; Chromatography, Liquid ; Tandem Mass Spectrometry ; *Vaccines/therapeutic use ; Cytokines/metabolism ; Cell Line, Tumor ; }, abstract = {BACKGROUND: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231).<br><br>METHODS: MDA-MB-231 cells were exposed to PDT using ALA (160&#xa0;&#xb5;g/mL)/630&#xa0;nm at 8&#xa0;J/cm[2]. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry.<br><br>RESULTS: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF.<br><br>CONCLUSION: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.}, }
@article {pmid36587134, year = {2023}, author = {Levy-Jurgenson, A and Tekpli, X and Kristensen, VN and Yakhini, Z}, title = {Analysis of Spatial Molecular Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2614}, number = {}, pages = {349-356}, pmid = {36587134}, issn = {1940-6029}, mesh = {Humans ; *Neoplasms/diagnosis/genetics ; Phenotype ; Algorithms ; Microscopy/methods ; }, abstract = {Digital analysis of pathology whole-slide images has been recently gaining interest in the context of cancer diagnosis and treatment. In particular, deep learning methods have demonstrated significant potential in supporting pathology analysis, recently detecting molecular traits never before recognized in pathology H&amp;E whole-slide images (WSIs). Alongside these advancements in the digital analysis of WSIs, it is becoming increasingly evident that both spatial and overall tumor heterogeneity may be significant determinants of cancer prognosis and treatment outcome. In this chapter, we describe methods that aim to support these two elements. We describe both an end-to-end deep learning pipeline for producing limited spatial transcriptomics from WSIs with associated bulk gene expression data, as well as an algorithm for quantifying spatial tumor heterogeneity based on the results of this pipeline.}, }
@article {pmid36574856, year = {2023}, author = {Ying, Z and van Eenige, R and Beerepoot, R and Boon, MR and Kloosterhuis, NJ and van de Sluis, B and Bartelt, A and Rensen, PCN and Kooijman, S}, title = {Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway.}, journal = {Pharmacological research}, volume = {187}, number = {}, pages = {106634}, doi = {10.1016/j.phrs.2022.106634}, pmid = {36574856}, issn = {1096-1186}, mesh = {Animals ; Humans ; Mice ; *Adipose Tissue, Brown ; Adrenergic Agonists/metabolism/pharmacology ; Apolipoproteins E/genetics/metabolism ; *Atherosclerosis/drug therapy/metabolism ; Cholesterol/metabolism ; Fatty Acids/metabolism ; Lipoproteins, LDL/metabolism ; Liver/metabolism ; Triglycerides ; Receptors, LDL/metabolism ; }, abstract = {Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used β3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a humanized lipoprotein metabolism model with a functional ApoE-LDLR clearance pathway. Mirabegron activated BAT and induced white adipose tissue (WAT) browning, accompanied by selectively increased fat oxidation and attenuated fat mass gain. Mirabegron increased the uptake of fatty acids derived from triglyceride (TG)-rich lipoproteins by BAT and WAT, which was coupled to increased hepatic uptake of the generated cholesterol-enriched core remnants. Mirabegron also promoted hepatic very low-density lipoprotein (VLDL) production, likely due to an increased flux of fatty acids from WAT to the liver, and resulted in transient elevation in plasma TG levels followed by a substantial decrease in plasma TGs. These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to substantial metabolic benefits in APOE*3-Leiden.CETP mice, and mirabegron treatment is certainly not atherogenic. These data underscore the importance of the choice of experimental models when investigating the effect of BAT activation on lipoprotein metabolism and atherosclerosis.}, }
@article {pmid36572997, year = {2023}, author = {Bendarkawi, Y and Cherif Chefchaouni, A and Lkhoyaali, S and Bechar, H and Boudina, Y and Abercha, Y and Belahcen, MJ and Rahali, Y}, title = {Tamoxifen induced hands deformities.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {29}, number = {5}, pages = {1246-1250}, doi = {10.1177/10781552221147507}, pmid = {36572997}, issn = {1477-092X}, mesh = {Humans ; Female ; Middle Aged ; *Tamoxifen/adverse effects ; Antineoplastic Agents, Hormonal/adverse effects ; *Breast Neoplasms/pathology ; Arthralgia/chemically induced ; }, abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer. In this article, we report a case of a patient who developed hand deformities following long-term administration of tamoxifen.<br><br>CASE REPORT: A 57-year-old woman, followed for invasive ductal carcinoma of the left breast under tamoxifen for 7 years, presenting joint pain with deformities in her fingers.<br><br>MANAGEMENT &amp; OUTCOME: Following the appearance of the adverse effect, tamoxifen was stopped. A series of biologic and radiologic analysis were performed in order to explain the appearance of this event. A substitution treatment was discussed and a rheumatologist's opinion was requested.<br><br>DISCUSSION: Tamoxifen appears to be associated with the development of inflammatory osteoarthritis resembling rheumatoid arthritis. Possible mechanisms of such an effect are discussed.}, }
@article {pmid36563298, year = {2023}, author = {Braun, A and Reddy, S and Cheng, L and Gattuso, P and Yan, L}, title = {Clinicopathologic Review of Metastatic Breast Cancer to the Gynecologic Tract.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {42}, number = {4}, pages = {414-420}, doi = {10.1097/PGP.0000000000000920}, pmid = {36563298}, issn = {1538-7151}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; *Genital Neoplasms, Female/secondary ; *Krukenberg Tumor ; *Ovarian Neoplasms ; }, abstract = {Metastatic spread is the single most significant predictor of poor survival in breast cancer. Some of the most common metastatic sites are the bones, lungs, liver, brain, and peritoneal cavity. Clinically metastatic breast cancer to the gynecologic tract is usually asymptomatic and diagnosed as an incidental finding during a histologic examination of gynecologic specimens resected for other reasons. Cases of metastatic breast cancer to gynecologic organs diagnosed from August 1995 to January 2021 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. The most common site of metastasis was the ovary which was involved in about 79% (22 of 28 cases) of metastases to the gynecologic tract. Clinically, only 8 cases (36%) presented with ovarian mass detected in imaging studies and the rest of the cases were all incidental findings. Among ovarian metastasis, 59% of cases were invasive lobular carcinoma and 41% were invasive ductal carcinoma. In 5 cases, metastatic breast cancer was found in the endometrium, including 2 cases with endometrial metastasis only and 3 cases with multiple gynecologic organs involved. Metastatic breast cancer rarely involved the lower gynecologic tract, with only 7% vaginal metastasis and 4% found in the vulva. The absolute majority of metastatic breast cancer outside of the ovaries were lobular carcinoma (88%). Most of the metastatic breast carcinomas were positive for estrogen receptor on immunohistochemistry (27 of 28 cases, 96%). Her-2/neu immunostaining was positive in 4 cases only (14%). Metastatic breast cancer needs to be distinguished from gynecologic primary neoplasms and metastatic tumors from adjacent urinary and GI tracts. A careful review of the patient's history and adequate immunohistochemistry panel are helpful to render the diagnosis.}, }
@article {pmid36548300, year = {2022}, author = {Shapiro-Kulnane, L and Selengut, M and Salz, HK}, title = {Safeguarding Drosophila female germ cell identity depends on an H3K9me3 mini domain guided by a ZAD zinc finger protein.}, journal = {PLoS genetics}, volume = {18}, number = {12}, pages = {e1010568}, pmid = {36548300}, issn = {1553-7404}, support = {R01 GM129478/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Male ; *Drosophila/metabolism ; Drosophila melanogaster/genetics/metabolism ; *Drosophila Proteins/genetics/metabolism ; Germ Cells/metabolism ; Homeodomain Proteins/metabolism ; Zinc Fingers/genetics ; Female ; }, abstract = {H3K9me3-based gene silencing is a conserved strategy for securing cell fate, but the mechanisms controlling lineage-specific installation of this epigenetic mark remain unclear. In Drosophila, H3K9 methylation plays an essential role in securing female germ cell fate by silencing lineage inappropriate phf7 transcription. Thus, phf7 regulation in the female germline provides a powerful system to dissect the molecular mechanism underlying H3K9me3 deposition onto protein coding genes. Here we used genetic studies to identify the essential cis-regulatory elements, finding that the sequences required for H3K9me3 deposition are conserved across Drosophila species. Transposable elements are also silenced by an H3K9me3-mediated mechanism. But our finding that phf7 regulation does not require the dedicated piRNA pathway components, piwi, aub, rhino, panx, and nxf2, indicates that the mechanisms of H3K9me3 recruitment are distinct. Lastly, we discovered that an uncharacterized member of the zinc finger associated domain (ZAD) containing C2H2 zinc finger protein family, IDENTITY CRISIS (IDC; CG4936), is necessary for H3K9me3 deposition onto phf7. Loss of idc in germ cells interferes with phf7 transcriptional regulation and H3K9me3 deposition, resulting in ectopic PHF7 protein expression. IDC's role is likely to be direct, as it localizes to a conserved domain within the phf7 gene. Collectively, our findings support a model in which IDC guides sequence-specific establishment of an H3K9me3 mini domain, thereby preventing accidental female-to-male programming.}, }
@article {pmid36527274, year = {2022}, author = {Ansari, N and Nisar, MI and Khalid, F and Mehmood, U and Usmani, AA and Shaheen, F and Hotwani, A and Begum, K and Barkat, A and Yoshida, S and Manu, AA and Sazawal, S and Baqui, AH and Bahl, R and Jehan, F}, title = {Prevalence and risk factors of Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in peri-urban communities in Pakistan: A prospective cohort study.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05055}, pmid = {36527274}, issn = {2047-2986}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Child ; Female ; Humans ; Child, Preschool ; *COVID-19/epidemiology ; Seroepidemiologic Studies ; Prevalence ; Pakistan/epidemiology ; Prospective Studies ; Antibodies, Viral ; Risk Factors ; }, abstract = {BACKGROUND: Population-based seroepidemiological surveys provide accurate estimates of disease burden. We compare the COVID-19 prevalence estimates from two serial serological surveys and the associated risk factors among women and children in a peri-urban area of Karachi, Pakistan.<br><br>METHODS: The AMANHI-COVID-19 study enrolled women and children between November 2020 and March 2021. Blood samples were collected from March to June 2021 (baseline) and September to December 2021 (follow-up) to test for anti-SARS-CoV-2 antibodies using ROCHE Elecsys&#xae;. Participants were visited or called weekly during the study for recording symptoms of COVID-19. We report the proportion of participants with anti-SARS-CoV-2 antibodies and symptoms in each survey and describe infection risk factors using step-wise binomial regression analysis.<br><br>RESULTS: The adjusted seroprevalence among women was 45.3% (95% confidence interval (CI)&#x2009;=&#x2009;42.6-47.9) and 82.3% (95% CI&#x2009;=&#x2009;79.9-84.4) at baseline and follow-up survey, respectively. Among children, it was 18.4% (95% CI&#x2009;=&#x2009;16.1-20.7) and 57.4% (95% CI&#x2009;=&#x2009;54.3-60.3) at baseline and follow-up, respectively. Of the women who were previously seronegative, 404 (74.4%) tested positive at the follow-up survey, as did 365 (50.4%) previously seronegative children. There was a high proportion of asymptomatic infection. At baseline, being poorest and lacking access to safe drinking water lowered the risk of infection for both women (risk ratio (RR)&#x2009;=&#x2009;0.8, 95% CI&#x2009;=&#x2009;0.7-0.9 and RR&#x2009;=&#x2009;1.2, 95% CI&#x2009;=&#x2009;1.1-1.4, respectively) and children (RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.5-1.0 and RR&#x2009;=&#x2009;1.4, 95% CI&#x2009;=&#x2009;1.0-1.8, respectively). At the follow-up survey, the risk of infection was lower for underweight women and children (RR&#x2009;=&#x2009;0.4, 95% CI&#x2009;=&#x2009;0.3-0.7 and RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.5-0.8, respectively) and for women in the 30-39 years age group and children who were 24-36 months of age (RR&#x2009;=&#x2009;0.6, 95% CI&#x2009;=&#x2009;0.4-0.9 and RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.5-0.9, respectively). In both surveys, paternal employment was an important predictor of seropositivity among children (RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.6-0.9 and RR&#x2009;=&#x2009;0.8, 95% CI&#x2009;=&#x2009;0.7-1.0, respectively).<br><br>CONCLUSION: There was a high rate of seroconversion among women and children. Infection was generally mild. Parental education plays an important role in protection of children from COVID-19.}, }
@article {pmid36519609, year = {2023}, author = {Yuce, E and Karakullukcu, S and Bulbul, H and Alandag, C and Saygin, I and Kavgaci, H}, title = {The effect of the change in hemoglobin-albumin-lymphocyte-platelet scores occurring with neoadjuvant chemotherapy on clinical and pathological responses in breast cancer.}, journal = {Bratislavske lekarske listy}, volume = {124}, number = {1}, pages = {59-63}, doi = {10.4149/BLL_2023_009}, pmid = {36519609}, issn = {0006-9248}, mesh = {Female ; Humans ; Male ; Albumins/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; Hemoglobins ; Ki-67 Antigen ; Lymphocytes ; *Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Adult ; Middle Aged ; }, abstract = {INTRODUCTION: Breast-cancer is a common-cause of death in women.(1) We investigated the effects of before/after-NACT on hemoglobin-albumin-lymphocyte-platelet (HALP) scores and of changes therein on clinical/pathological-responses.<br><br>MATERIALS AND METHODS: One-hundred-twenty-seven breast-cancer-patients receiving-NACT between December 2009 - January 2019 were investigated retrospectively.<br><br>RESULTS: The mean - age was 50.3&#xb1;12.3 (min 27 - max 79), and 125 patients (98.4 %) were women. Fifty-four (42.5 %) were premenopausal and 71 (55.9 %) postmenopausal. Invasive-ductal-carcinoma was present in 111 patients (92.5 %). Eighty patients (70.2 %) were &#x2264; T2 and 34 (29.8 %) > T2. Lymph-node-status was positive in 99 patients (83.2 %) and negative in 20 (16.8 %). Ki-67 was &#x2264; 10 % in 22 (28.9 %), 11-20 % in 23 (30.3 %), and > 20 % in 31 (40.8 %). Complete clinical response was observed in 27 (21.3 %), partial-response in 76 (59.8 %), stable-disease in 21 (16.5 %), and progressive-disease in 3 patients (2.4 %). The objective-response-rate (ORR) was 103 (81.1 %). Pathological-complete-response (pCR) was observed in 24 patients (18.9 %). ORR was higher in Ki-67 > 20 % compared to &#x2264; 10 % and 10-20 % (90.3 % vs 59.0 % / 78.3 %, respectively, p: 0.027), but no difference occurred in pCR. Neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR), prognostic-nutritional-index (PNI), and HALP were measured before/after NACT. Associations with ORR and pCR were investigated via changes in these with NACT (excepting-PNI), but no-significant results emerged.<br><br>CONCLUSIONS: Higher ORR occurred post-NACT in patients with Ki-67 >20 %, while NLR, PLR, PNI, and HALP before/after-NACT and post-NACT-changes (excepting-PNI) had no-effect on ORR/pCR (Tab. 5, Ref. 21). Text in PDF www.elis.sk Keywords: breast cancer, objective response rate (ORR), pathological complete response (pCR), hemoglobin-albumin-lymphocyte-platelet (HALP) score.}, }
@article {pmid36510982, year = {2022}, author = {Azmat, H and Faridi, J and Habib, HM and Bugti, UJ and Sheikh, AK and Riaz, SK}, title = {Correlation of B-cell lymphoma 2 immunoexpression in invasive carcinoma of breast, no special type with hormone receptor status, proliferation index, and molecular subtypes.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {Supplement}, pages = {S313-S319}, doi = {10.4103/jcrt.JCRT_735_20}, pmid = {36510982}, issn = {1998-4138}, mesh = {Humans ; Female ; Receptor, ErbB-2/genetics/metabolism ; Ki-67 Antigen/genetics/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; *Carcinoma/pathology ; *Breast Neoplasms/pathology ; Prognosis ; Hormones ; Cell Proliferation/genetics ; Proto-Oncogene Proteins c-bcl-2 ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: B-cell lymphoma 2 is involved in various cancers including breast carcinoma. Its expression in breast cancer has been associated with good prognostic factors such as hormone receptor expression, low Ki-67, low grade, and earlier stage. It is also considered to be an independent prognostic factor for luminal and triple-negative tumors.<br><br>OBJECTIVE: We aimed to determine the expression of B-cell lymphoma 2 (BCL2) in different molecular subtypes of invasive ductal carcinoma of breast and its association with prognostic indicators.<br><br>MATERIALS AND METHODS: Fifty samples of invasive carcinoma of breast, no special type (NST), were categorized into molecular subtypes according to immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 and then evaluated for BCL2 expression. The expression of BCL2 was correlated with ER, PR, HER2, and Ki-67 and compared between luminal and nonluminal subtypes.<br><br>RESULTS: The BCL2 expression was seen in 68% of the cases with a significant association with ER, PR, and luminal subtypes. No significant association of BCL2 expression was seen with grade, HER2 and Ki-67 status of the tumor, or age group of the patients. BCL2 expression is significantly associated with ER, PR, and luminal subtypes in breast cancer.<br><br>CONCLUSION: BCL2 is a marker of good prognosis in invasive carcinoma of breast, NST.}, }
@article {pmid36505983, year = {2022}, author = {Gupta, NK and Gaur, S and Pal, DK}, title = {Role of videourodynamics in the identification of causes of lower urinary tract symptoms and low uroflow in young men.}, journal = {Urology annals}, volume = {14}, number = {4}, pages = {332-335}, pmid = {36505983}, issn = {0974-7796}, abstract = {INTRODUCTION: The etiology of lower urinary tract symptoms (LUTS) is multifactorial with causes attributed either to the dysfunction of the bladder or its outlet. Although the etiologies are well studied in aged men, very limited research trials are available in young men with LUTS. Most of the time young men presenting with chronic irritative or obstructive symptoms are labeled with chronic prostatitis or prostatodynia and are treated empirically. In this study using videourodynamics, we prospectively investigated the etiologies of LUTS and low uroflow in young men.<br><br>MATERIALS AND METHODS: Fifty male patients, 18-50 years of age attending the urology outpatient department at a tertiary care center from January 2021 to December 2021 with symptoms suggestive of chronic LUTS and low uroflow (maximum urinary flow rate [Qmax] <15 ml/s at a voided volume >150 ml) were included in the study and underwent multichannel videourodynamic study (VUDS). Clinical characteristics and urodynamic results in different diagnostic groups were tabulated and analyzed. The P &#x2264; 0.05 was considered statistically significant.<br><br>RESULTS: Out of 50 enrolled patients, primary bladder neck obstruction was seen in 21 patients (42%), dysfunctional voiding in 14 (28%), impaired detrusor contractility (IDC) in 9 (18%), and benign prostatic obstruction (BPO) was noted in 6 patients (12%). The mean age and size of the prostate of patients with BPO were greater than those in the remaining groups and patients with IDC had lower Qmax and Pdet at Qmax than those in the remaining patients.<br><br>CONCLUSION: Chronic LUTS in young men has a variety of underlying etiologies and VUDS in this population is helpful in attaining an accurate diagnosis and thus may guide toward efficient management.}, }
@article {pmid36501121, year = {2022}, author = {Leikin-Frenkel, A and Schnaider Beeri, M and Cooper, I}, title = {How Alpha Linolenic Acid May Sustain Blood-Brain Barrier Integrity and Boost Brain Resilience against Alzheimer's Disease.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, pmid = {36501121}, issn = {2072-6643}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Blood-Brain Barrier/metabolism ; alpha-Linolenic Acid/metabolism ; Brain/metabolism ; Apolipoprotein E4/genetics/metabolism ; }, abstract = {Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood-brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers.}, }
@article {pmid36472800, year = {2023}, author = {Chang, YS and Tu, SJ and Chen, HD and Hsu, MH and Chen, YC and Chao, DS and Chung, CC and Chou, YP and Chang, CM and Lee, YT and Yen, JC and Jeng, LB and Chang, JG}, title = {Integrated genomic analyses of hepatocellular carcinoma.}, journal = {Hepatology international}, volume = {17}, number = {1}, pages = {97-111}, pmid = {36472800}, issn = {1936-0541}, support = {DMR-111-135//China Medical University Hospital/ ; MOST-109-2320-B-039-052//Ministry of Science and Technology (TW)/ ; MOST-110-2321-B-039-002//Ministry of Science and Technology (TW)/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology ; *Liver Neoplasms/genetics/pathology ; Mutation ; Genomics ; Gene Expression Profiling ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; }, abstract = {BACKGROUND: Genomic alterations play important roles in the development of cancer. We explored the impact of protein-coding genes and transcriptomic changes on clinical and molecular alterations in Taiwanese hepatocellular carcinoma (HCC) patients.<br><br>METHODS: We analyzed 147 whole-exome sequencing and 100 RNA sequencing datasets of HCC and compared them with The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma cohort and develop a panel of 81 apoptosis-related genes for molecular classification.<br><br>RESULTS: TERT (50%), TP53 (25%), CTNNB1 (14%), ARID1A (12%), and KMT2C (11%) were the most common genetic alterations of cancer-related genes. ALDH2 and KMT2C mutated at much higher frequencies in our cohort than in TCGA, whereas CTNNB1 was found only in 14% of our Taiwanese patients. A high germline mutation rate of ALDH2 in the APOBEC mutational signature and herb drug-related aristolochic acid-associated signature was also observed. Groups A and B of HCC were identified when we used apoptosis-related genes for molecular classification. The latter group, which had poorer survival outcomes, had significantly more aDC, CD4+&#x2009;Tem, macrophages M2, NKT, plasma cells, and Th1 cells, and less CD4+&#x2009;memory T cells, CD8+&#x2009;Tcm, cDC, iDC, and Th2 cells, as well as more inter-chromosome fusion genes. Metatranscriptomic analysis revealed 54 cases of HBV infection. Moreover, we found that the main target gene of HBV integration is ALB.<br><br>CONCLUSIONS: Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.}, }
@article {pmid36472640, year = {2023}, author = {Maalmi, H and Strom, A and Petrera, A and Hauck, SM and Strassburger, K and Kuss, O and Zaharia, OP and Bönhof, GJ and Rathmann, W and Trenkamp, S and Burkart, V and Szendroedi, J and Ziegler, D and Roden, M and Herder, C and , }, title = {Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy.}, journal = {Diabetologia}, volume = {66}, number = {3}, pages = {579-589}, pmid = {36472640}, issn = {1432-0428}, mesh = {Adult ; Humans ; Biomarkers ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2 ; *Diabetic Neuropathies/diagnosis ; Intermediate Filaments ; *Polyneuropathies/diagnosis/complications ; }, abstract = {AIMS/HYPOTHESIS: No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.<br><br>METHODS: This cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.<br><br>RESULTS: DSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p&#x2264;0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.<br><br>CONCLUSIONS/INTERPRETATION: Our findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.}, }
@article {pmid36472055, year = {2022}, author = {Ortiz-Rey, JA and Bellas-Pereira, A and San Miguel-Fraile, P and Morellón-Baquera, R and Domínguez-Arístegui, P and González-Carreró Fojón, J}, title = {Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature.}, journal = {Archivos espanoles de urologia}, volume = {75}, number = {9}, pages = {738-745}, doi = {10.56434/j.arch.esp.urol.20227509.108}, pmid = {36472055}, issn = {0004-0614}, mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Prostatic Intraepithelial Neoplasia/genetics/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; Prostatectomy ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/surgery ; }, abstract = {OBJECTIVES: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma.<br><br>MATERIAL AND METHODS: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens.<br><br>RESULTS: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period.<br><br>CONCLUSIONS: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia.}, }
@article {pmid36444584, year = {2022}, author = {Shahi, V and Agarwal, P and Qayoom, S and Kumar, V and Tewari, S and Raghuvanshi, S and Singh, US and Goel, MM}, title = {Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F, EA- 2R) along with Epstein-Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {11}, pages = {3717-3723}, pmid = {36444584}, issn = {2476-762X}, mesh = {Humans ; Female ; *Breast Neoplasms ; Herpesvirus 4, Human/genetics ; *Epstein-Barr Virus Infections/complications ; Reproducibility of Results ; Epstein-Barr Virus Nuclear Antigens ; India/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Ductal ; }, abstract = {INTRODUCTION: Worldwide, breast cancer (BC) is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world's population. Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India.<br><br>METHODOLOGY: In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)- EBV PCR and Epstein-Barr virus latent membrane protein 1 (LMP1) IHC.<br><br>RESULTS: Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection.<br><br>CONCLUSION: The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.}, }
@article {pmid36434575, year = {2022}, author = {Gupta, RB and Dang, H and Albreiki, D and Dollin, ML and Weston, B and Gottlieb, CC}, title = {Acute annular outer retinopathy preceded by invasive ductal breast carcinoma: a case report.}, journal = {BMC ophthalmology}, volume = {22}, number = {1}, pages = {452}, pmid = {36434575}, issn = {1471-2415}, mesh = {Humans ; Female ; Fluorescein Angiography/methods ; *Retinal Diseases/complications/diagnosis ; Tomography, Optical Coherence/methods ; Vision Disorders ; Acute Disease ; Atrophy ; *Breast Neoplasms/complications/diagnosis ; }, abstract = {BACKGROUND: Acute annular outer retinopathy (AAOR) is an uncommon disease. To date, there are few documented cases in the literature. Our case report is the first to describe a case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma.<br><br>CASE PRESENTATION: The patient presented with photopsias and visual loss approximately 3&#xa0;weeks prior to a diagnosis of invasive ductal breast carcinoma. We have documented the outer annular white ring seen in the acute phase of this disease and correlate it anatomically with Spectral-domain optical coherence tomography (SD-OCT) imaging. We identified RPE atrophy with nodular hyperreflectivity and loss of ellipsoid layer within the white annular ring with corresponding visual field loss. Fundus autofluorescence correlated with structural alterations seen on SD-OCT and showed both presumed active hyperautofluorescent zones with patchy hypoautofluorescent zones of atrophy and a classic annular hyperautofluorescent border. This case provides additional information about the natural history of this rare entity and its prognosis and varied presentation.<br><br>CONCLUSIONS: The authors report a single case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma with the corresponding SD-OCT, fundus autofluorescence and visual field findings, during the acute phase of the disease. These findings provide new insight into the characteristic features, etiology and progression of this rare disease.}, }
@article {pmid36414494, year = {2023}, author = {Zhang, C and Liang, Z and Feng, Y and Xiong, Y and Manwa, C and Zhou, Q}, title = {Risk Factors for Lymphovascular Invasion in Invasive Ductal Carcinoma Based on Clinical and Preoperative Breast MRI Features: a Retrospective Study.}, journal = {Academic radiology}, volume = {30}, number = {8}, pages = {1620-1627}, doi = {10.1016/j.acra.2022.10.029}, pmid = {36414494}, issn = {1878-4046}, mesh = {Humans ; Retrospective Studies ; Lymphatic Metastasis ; *Magnetic Resonance Imaging ; Risk Factors ; *Carcinoma, Ductal ; }, abstract = {RATIONALE AND OBJECTIVES: Lymphovascular invasion (LVI) plays an important role in the prediction of metastasis and prognosis in breast cancer (BC) patients. The present study assessed correlations between preoperative breast MRI, clinical features, and LVI in patients with invasive ductal carcinoma (IDC) and identified risk factors based on these correlation factors.<br><br>MATERIALS AND METHODS: Patients confirmed with IDC between 01/2012 and 12/2021 were retrospectively reviewed at our hospital. A total of 5 clinical and 14 MRI features to characterize tumours were extracted. LVI evaluated in hematoxylin and eosin sections. T-test and chi-square tests were used to compare the differences in clinical and MRI features between the LVI positive and negative groups. The associations between individual features and LVI were analysed by univariable logistic regression analysis, and risk factors for LVI were identified by multivariable logistic regression analysis based on these correlation factors.<br><br>RESULTS: This study included 353 patients with IDC, including 130 with positive LVI. Age, CEA, CA-153, amount of fibroglandular tissue (FGT), background parenchymal enhancement, tumour size, shape, skin thickening, nipple retraction, adjacent vessel sign, and axillary lymph node (ALN) size in the LVI positive group were significantly different from the LVI negative group (all p<0.05). Multivariate logistic regression analysis revealed that age (odds ratio OR&#xa0;=&#xa0;1.030), CA-153 (OR&#xa0;=&#xa0;1.018), heterogeneous FGT (OR&#xa0;=&#xa0;2.484), shape (OR&#xa0;=&#xa0;2.157), and ALN size (OR&#xa0;=&#xa0;1.051) were risk factors for LVI (all p<0.05).<br><br>CONCLUSION: Preoperative breast MRI and clinical features correlated with LVI, age, CA-153, heterogeneous FGT, shape, and ALN size are risk factors for LVI in patients with IDC.}, }
@article {pmid36412439, year = {2022}, author = {Abbas, Z and Nouroz, F and Ejaz, S}, title = {Exceptional behavior of breast cancer-associated type 1 gene in breast invasive carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {6}, pages = {1743-1753}, doi = {10.4103/jcrt.JCRT_1310_20}, pmid = {36412439}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Genes, BRCA1 ; BRCA1 Protein/genetics ; *Carcinoma/genetics ; *Antineoplastic Agents ; }, abstract = {BACKGROUND: Cellular expression level of Breast Cancer-Associated Type 1 (BRCA1) encoded protein is the sign of genome integrity, stability, and surveillance. BRCA1 after sensing DNA damage activates repairing system and if mutated leaves genomic lesions unrepaired and triggers transformation of normal breast cells into cancerous ones.<br><br>AIMS OF STUDY: We conducted in silico study to have a holistic view of BRCA1's correlation with multiple variables of breast invasive carcinoma.<br><br>MATERIALS AND METHODS: We used user-friendly online GeneCardsSuite pathway-level enrichment analysis, UALCAN portal differential expression analysis, cBioPortal cancer genome platform for mutatome map construction, and cancer cell lines encyclopedia genomics of drug sensitivity toolkit to understand correlation of BRCA1 expression with the effectiveness of anti-cancer drugs.<br><br>RESULTS: Contrary to general behavior of a tumor suppressor gene our study revealed BRCA1 overexpression under all circumstances. This novel finding needs to be explored further to understand functional impact of BRCA1 overexpression on the expression of many genes which are transcriptionally regulated by BRCA1 and promotion of tumriogenesis.<br><br>CONCLUSION: Our study highlights the potential role of BRCA1-regulated genes in oncogenesis and recommends use of BRCA1-linked genes as future therapeutic targets for effective disease management.}, }
@article {pmid36411355, year = {2022}, author = {Kalyan, VSRK and Meena, S and Karthikeyan, S and Jawahar, D}, title = {Isolation, screening, characterization, and optimization of bacteria isolated from calcareous soils for siderophore production.}, journal = {Archives of microbiology}, volume = {204}, number = {12}, pages = {721}, pmid = {36411355}, issn = {1432-072X}, support = {E28ACC//Science and Engineering Research Board/ ; }, mesh = {*Siderophores ; *Soil ; India ; Bacteria/genetics ; Iron Chelating Agents ; }, abstract = {The most effective agricultural practice to prevent iron deficiency in calcareous soils is fertilizing with synthetic chelates. These compounds are non-biodegradable, and persistent in the environment; hence, there is a risk of leaching metals into the soil horizon. To tackle iron deficiency-induced chlorosis (IDC) in crops grown on calcareous soils, environmentally friendly solutions are needed rather than chemical application as it affects the soil health further. Hence, the present work focused on isolating and screening calcareous soil-specific bacteria capable of producing iron-chelating siderophores. Siderophore-producing bacteria (SPB) was isolated from the groundnut (Arachis hypogea L.) rhizosphere region, collected from Coimbatore district, Tamil Nadu, of which 17 bacterial isolates were positive for siderophore production assayed by chrome azurol sulphonate. The performance of SPB isolates was compared for siderophore kinetics, level of siderophore production, type of siderophore produced and iron-chelating capacity under 15 mM KHCO3. Four best performing isolates were screened, with average siderophores yield ranging ∼60-80% under pH 8, with sucrose as carbon source and NH2SO4 as nitrogen source at 37 °C. The four efficient SPB were molecularly identified as B. licheniformis, B. subtilis, B. licheniformis, and O. grignonense based on 16S rDNA sequencing. The simultaneous inhibition method showed T.viride has the highest antagonistic effect against S.rolfsii, and M.phaseolina with a reduction of mycelial growth by 69.3 and 65.1%, respectively, compared to control. Our results indicate that the optimized conditions enhanced siderophores chelation by suppressing the stem and root rot fungi, which could help in a cost-effective and environmentally friendly manner.}, }
@article {pmid36395590, year = {2022}, author = {Lin, Z and He, Y and Qiu, C and Yu, Q and Huang, H and Yiwen Zhang,  and Li, W and Qiu, T and Xiaoping Li, }, title = {A multi-omics signature to predict the prognosis of invasive ductal carcinoma of the breast.}, journal = {Computers in biology and medicine}, volume = {151}, number = {Pt A}, pages = {106291}, doi = {10.1016/j.compbiomed.2022.106291}, pmid = {36395590}, issn = {1879-0534}, mesh = {Humans ; *Breast ; Area Under Curve ; ROC Curve ; Risk Factors ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: Precisely evaluating the prognosis of invasive ductal carcinoma (IDC) of the breast is challenging as most prognostic signatures use single-omics data based on gene or clinical information.<br><br>METHODS: Whole-slide images (WSIs), transcriptome, and clinical data of breast IDC were collected from the Cancer Genome Atlas Database. The cancer-associated fibroblast (CAF) gene sets were downloaded from the Molecular Signatures Database. The WSI feature was extracted by artificial feature engineering. The CAF prognostic genes were determined by the Gene Set Enrichment Analysis, the Wilcoxon test, and univariate Cox regression. The IDC patients were divided into the training and test sets. The prognostic signatures based on WSIs, IDC-CAFs, bi-omics, and tri-omics were constructed using multivariate Cox regression. The samples were divided into low- and high-risk groups according to the median risk score. The Kaplan-Meier survival and receiver operating characteristic curves were applied to validate the prediction performance of the four signatures.<br><br>RESULTS: In total, 508 IDC patients with complete data were included. The area under the curve (AUC) of single-omics signature based on WSI characteristics and CAFs was 0.765 and 0.775, whereas the AUC of bi-omics was 0.823. The tri-omics signature based on WSIs, CAFs, and lymph node status demonstrated the best predictive value with an AUC of 0.897.<br><br>CONCLUSION: The multi-omics signature based on WSIs, CAFs, and clinical characteristics showed excellent prediction ability in breast IDC patients, whose risk factors can also provide a valuable diagnostic reference for the clinical course.}, }
@article {pmid36394689, year = {2023}, author = {Mamtani, A and Grabenstetter, A and Sevilimedu, V and Morrow, M and Gemignani, ML}, title = {Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?.}, journal = {Breast cancer research and treatment}, volume = {197}, number = {2}, pages = {417-423}, pmid = {36394689}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30CA008748//NIH/NCI Cancer Center Support Grant/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Lobular/pathology ; *Carcinoma, Ductal, Breast/pathology ; Neoadjuvant Therapy ; Breast/pathology ; }, abstract = {PURPOSE: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown.<br><br>METHODS: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated.<br><br>RESULTS: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2&#x2009;+&#x2009;(25% versus 7%) and TN (21% versus 0%, all p&#x2009;<&#x2009;0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR.<br><br>CONCLUSION: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.}, }
@article {pmid36376280, year = {2022}, author = {Haythorne, E and Lloyd, M and Walsby-Tickle, J and Tarasov, AI and Sandbrink, J and Portillo, I and Exposito, RT and Sachse, G and Cyranka, M and Rohm, M and Rorsman, P and McCullagh, J and Ashcroft, FM}, title = {Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6754}, pmid = {36376280}, issn = {2041-1723}, support = {MR/V011979/1/MRC_/Medical Research Council/United Kingdom ; BB/R017220/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/T002107/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Glucose/metabolism ; Glycolysis/physiology ; Insulin/metabolism ; *Hyperglycemia/metabolism ; Pyruvic Acid/metabolism ; *Islets of Langerhans/metabolism ; *Diabetes Mellitus/metabolism ; }, abstract = {Chronic hyperglycaemia causes a dramatic decrease in mitochondrial metabolism and insulin content in pancreatic β-cells. This underlies the progressive decline in β-cell function in diabetes. However, the molecular mechanisms by which hyperglycaemia produces these effects remain unresolved. Using isolated islets and INS-1 cells, we show here that one or more glycolytic metabolites downstream of phosphofructokinase and upstream of GAPDH mediates the effects of chronic hyperglycemia. This metabolite stimulates marked upregulation of mTORC1 and concomitant downregulation of AMPK. Increased mTORC1 activity causes inhibition of pyruvate dehydrogenase which reduces pyruvate entry into the tricarboxylic acid cycle and partially accounts for the hyperglycaemia-induced reduction in oxidative phosphorylation and insulin secretion. In addition, hyperglycaemia (or diabetes) dramatically inhibits GAPDH activity, thereby impairing glucose metabolism. Our data also reveal that restricting glucose metabolism during hyperglycaemia prevents these changes and thus may be of therapeutic benefit. In summary, we have identified a pathway by which chronic hyperglycaemia reduces β-cell function.}, }
@article {pmid36357366, year = {2022}, author = {Willemsen, N and Kotschi, S and Bartelt, A}, title = {Fire up the pyre: inosine thermogenic signaling for obesity therapy.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {375}, pmid = {36357366}, issn = {2059-3635}, support = {PROTEOFIT/ERC_/European Research Council/International ; }, mesh = {Humans ; *Bacterial Proteins ; *Signal Transduction ; Inosine ; Obesity/genetics ; }, }
@article {pmid36353989, year = {2023}, author = {Vos, DY and Wijers, M and Smit, M and Huijkman, N and Kloosterhuis, NJ and Wolters, JC and Tissink, JJ and Pronk, ACM and Kooijman, S and Rensen, PCN and Kuivenhoven, JA and van de Sluis, B}, title = {Cargo-Specific Role for Retriever Subunit VPS26C in Hepatocyte Lipoprotein Receptor Recycling to Control Postprandial Triglyceride-Rich Lipoproteins.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {43}, number = {1}, pages = {e29-e45}, doi = {10.1161/ATVBAHA.122.318169}, pmid = {36353989}, issn = {1524-4636}, mesh = {Animals ; Humans ; Mice ; Hepatocytes/metabolism ; Lipoproteins/metabolism ; *Low Density Lipoprotein Receptor-Related Protein-1/genetics ; Mice, Knockout ; *Proprotein Convertase 9/genetics/metabolism ; Receptors, LDL ; Triglycerides/metabolism ; }, abstract = {BACKGROUND: The copper metabolism MURR1 domains/coiled-coil domain containing 22/coiled-coil domain containing 93 (CCC) complex is required for the transport of low-density lipoprotein receptor (LDLR) and LRP1 (LDLR-related protein 1) from endosomes to the cell surface of hepatocytes. Impaired functioning of hepatocytic CCC causes hypercholesterolemia in mice, dogs, and humans. Retriever, a protein complex consisting of subunits VPS26C, VPS35L, and VPS29, is associated with CCC, but its role in endosomal lipoprotein receptor transport is unclear. We here investigated the contribution of retriever to hepatocytic lipoprotein receptor recycling and plasma lipids regulation.<br><br>METHODS: Using somatic CRISPR/Cas9 gene editing, we generated liver-specific VPS35L or VPS26C-deficient mice. We determined total and surface levels of LDLR and LRP1 and plasma lipids. In addition, we studied the protein levels and composition of CCC and retriever.<br><br>RESULTS: Hepatocyte VPS35L deficiency reduced VPS26C levels but had minimal impact on CCC composition. VPS35L deletion decreased hepatocytic surface expression of LDLR and LRP1, accompanied by a 21% increase in plasma cholesterol levels. Hepatic VPS26C ablation affected neither levels of VPS35L and CCC subunits, nor plasma lipid concentrations. However, VPS26C deficiency increased hepatic LDLR protein levels by 2-fold, probably compensating for reduced LRP1 functioning, as we showed in VPS26C-deficient hepatoma cells. Upon PCSK9 (proprotein convertase subtilisin/kexin type 9)-mediated LDLR elimination, VPS26C ablation delayed postprandial triglyceride clearance and increased plasma triglyceride levels by 26%.<br><br>CONCLUSIONS: Our study suggests that VPS35L is shared between retriever and CCC to facilitate LDLR and LRP1 transport from endosomes to the cell surface. Conversely, retriever subunit VPS26C selectively transports LRP1, but not LDLR, and thereby may control hepatic uptake of postprandial triglyceride-rich lipoprotein remnants.}, }
@article {pmid36350000, year = {2022}, author = {Chen, W and Wang, G and Zhang, G}, title = {Insights into the transition of ductal carcinoma in situ to invasive ductal carcinoma: morphology, molecular portraits, and the tumor microenvironment.}, journal = {Cancer biology &amp; medicine}, volume = {19}, number = {10}, pages = {1487-1495}, pmid = {36350000}, issn = {2095-3941}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Tumor Microenvironment/genetics ; *Carcinoma, Ductal, Breast/pathology ; Biomarkers, Tumor ; *Breast Neoplasms/genetics ; }, }
@article {pmid36335424, year = {2022}, author = {Mekheal, E and Kania, BE and Kumari, P and Kumar, V and Maroules, M}, title = {Gynecomastia and Malignancy: A Case of Male Invasive Ductal Breast Carcinoma Treated with Neoadjuvant Chemotherapy.}, journal = {The American journal of case reports}, volume = {23}, number = {}, pages = {e937370}, pmid = {36335424}, issn = {1941-5923}, mesh = {Humans ; Male ; Female ; Neoadjuvant Therapy ; *Breast Neoplasms/pathology ; Receptors, Progesterone/therapeutic use ; Receptor, ErbB-2 ; Receptors, Estrogen/therapeutic use ; Mastectomy ; *Breast Neoplasms, Male/surgery ; *Gynecomastia/etiology/drug therapy/surgery ; Estrogens/therapeutic use ; *Carcinoma, Ductal/drug therapy/surgery ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Chemotherapy, Adjuvant ; }, abstract = {BACKGROUND Male breast cancer represents a rare malignancy with identifiable risk factors, including genetics, radiation exposure, liver dysfunction, and concomitant diagnosis of Klinefelter syndrome. Gynecomastia can commonly present in these patients, and despite increased estrogen levels in adipose breast tissue, gynecomastia has not been proven to be a significant risk factor for carcinoma development. Male patients with new-onset breast masses are recommended to undergo diagnostic mammograms and breast ultrasound for further evaluation. Those diagnosed with breast cancer most commonly have invasive ductal carcinoma of the breast, and over half of these patients are found to have estrogen and progesterone receptor (ER/PR) positivity. CASE REPORT In this case report, we present a Black man with gynecomastia and an areolar lesion for a 6-month duration following a traumatic event. He was initially referred to the surgical team for further evaluation, and subsequent imaging and biopsy data revealed ER/PR-positive invasive ductal carcinoma. Multidisciplinary discussions were held, and the patient was arranged to begin neoadjuvant treatment with doxorubicin hydrochloride and cyclophosphamide, followed by treatment with paclitaxel (AC-T) chemotherapy, followed by bilateral mastectomy and adjuvant hormonal therapy. CONCLUSIONS The treatment of male breast cancer has remained relatively like that of female breast cancer, which may be due to the limited data in the treatment of male breast cancer. Thus far, studies involving neoadjuvant chemotherapy of female patients have demonstrated promising responses to expand surgical options for patients and possibly decrease the rates of recurrence. Additional studies are warranted to discern optimal therapy for the male patient population.}, }
@article {pmid36332363, year = {2022}, author = {Davis, AA and Gerratana, L and Clifton, K and Medford, AJ and Velimirovic, M and Hensing, WL and Bucheit, L and Shah, AN and D'Amico, P and Reduzzi, C and Zhang, Q and Dai, CS and Denault, EN and Bagegni, NA and Opyrchal, M and Ademuyiwa, FO and Bose, R and Gradishar, WJ and Behdad, A and Ma, CX and Bardia, A and Cristofanilli, M}, title = {Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer.}, journal = {EBioMedicine}, volume = {86}, number = {}, pages = {104316}, pmid = {36332363}, issn = {2352-3964}, support = {UL1 TR001422/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Circulating Tumor DNA/genetics ; Retrospective Studies ; DNA Copy Number Variations ; Phosphatidylinositol 3-Kinases/genetics ; }, abstract = {BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology.<br><br>METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360&#x2122;. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies.<br><br>FINDINGS: ILC was significantly associated with HR+&#xa0;HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P&#xa0;<&#xa0;0.05). In multivariable analysis, HR+&#xa0;HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q&#xa0;<&#xa0;0.05).<br><br>INTERPRETATION: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment.<br><br>FUNDING: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422.}, }
@article {pmid36309875, year = {2022}, author = {Chen, K and Chen, X and Su, Y}, title = {Is conservative treatment a good choice for pediatric intervertebral disc calcification in children?.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {31}, number = {12}, pages = {3324-3329}, pmid = {36309875}, issn = {1432-0932}, mesh = {Humans ; Male ; Female ; Child ; Child, Preschool ; Conservative Treatment ; *Intervertebral Disc Degeneration/diagnostic imaging/therapy/complications ; *Ossification of Posterior Longitudinal Ligament/complications ; Longitudinal Ligaments ; *Calcinosis/diagnostic imaging/therapy/complications ; Magnetic Resonance Imaging ; *Intervertebral Disc/diagnostic imaging/pathology ; *Intervertebral Disc Displacement/complications ; }, abstract = {PURPOSE: Paediatric intervertebral disc calcification (PIDC) is a rare disease, and its aetiology remains unknown. This study aimed to analyse the characteristics and clinical outcomes of patients with PIDC.<br><br>METHODS: After applying the exclusion and inclusion criteria, 159 children diagnosed with PIDC were analysed at our hospital between January 2010 and November 2020. Patients' demographic and clinical data were collected, such as sex, pain, duration time, physical examination, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and radiography, computed tomography, and magnetic resonance imaging findings. Patients were followed up for at least 6&#xa0;months, and radiography or symptoms were evaluated. Fisher's exact test or &#x3c7;[2]-test was used for statistical analyses.<br><br>RESULTS: One hundred and fifty-nine patients were ultimately followed up with for about 12.5&#x2009;&#xb1;&#x2009;5.8&#xa0;months. There were 103 male and 56 female, with an average age of 6.08&#x2009;&#xb1;&#x2009;2.62&#xa0;years (2&#xa0;months to 12&#xa0;years). A total of 109 patients had only one PIDC, 29 patients had two PIDCs, and 21 patients had multiple PIDCs. Thirty patients were found incidentally and were asymptomatic. A total of 106 patients had neck torticollis. Sixteen patients had IDC herniations, fifteen patients had posterior longitudinal ligament calcification, two patients had anterior longitudinal ligament calcification, and 17 patients had herniation of the vertebral canal. All patients underwent conservative treatment, and none underwent surgery. All patients' symptoms resolved after either collar fixation or neck traction.<br><br>CONCLUSION: PIDC can be treated conservatively, even when accompanied by herniation, longitudinal ligament calcification, or clinical neck symptoms.<br><br>LEVEL OF EVIDENCE: IV.}, }
@article {pmid36308374, year = {2022}, author = {Gautam, P and Feroz, Z and Tiwari, S and Vijayraghavalu, S and Shukla, GC and Kumar, M}, title = {Investigating the Role of Glutathione S- Transferase Genes, Histopathological and Molecular Subtypes, Gene-Gene Interaction and Its Susceptibility to Breast Carcinoma in Ethnic North- Indian Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {10}, pages = {3481-3490}, pmid = {36308374}, issn = {2476-762X}, support = {R15 CA252997/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; *Breast Neoplasms/epidemiology/genetics ; Case-Control Studies ; *Genetic Predisposition to Disease ; Genotype ; Glutathione ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Risk Factors ; }, abstract = {BACKGROUND: Breast Cancer (BC) is a genetically and clinically heterogeneous disease including complex interactions between gene-gene and gene-environment components. This study aimed, to explore whether the Glutathione S- transferase (GSTs) gene polymorphism has role in BC susceptibility. We further evaluated the frequency of four subtypes of BC based on molecular classification followed by microscopic histological analysis to study the grades of invasive ductal carcinoma (IDC).<br><br>MATERIALS AND METHOD: Polymorphism in GST genes in North-Indian BC patients was assessed by multiplex-PCR and PCR-RFLP methods. 105 BC patients and 145 healthy controls were enrolled for this study. Data was analyzed by calculating the odds ratio (OR) and 95% CI from logistic regression analyses.<br><br>RESULTS: Our findings revealed that GSTM1 null genotype (OR = 2.231; 95% CI = 1.332-3.737; p-value= 0.002) is significantly associated to BC risk in ethnic North- Indian population. However, the risk for BC susceptibility in North-Indians does not appear to be associated with GSTT1 null genotype. The GSTP1 (Val/Val) genotype (OR=1.545; CI=0.663-3.605; p-value= 0.314) was also found to be susceptible for BC risk. Combination of three high risk GST genotypes association exhibiting gene-gene interaction further confirmed the increased risk to BC in this region.<br><br>CONCLUSIONS: The results of present study indicated that polymorphism in GSTM1 and rs1695 of GSTP1 genes may influence BC development among North-Indian women. Thus, the screening of GSTM1 and GSTP1 gene should be recommended for the earlier investigation for BC as a precautionary measure.}, }
@article {pmid36303871, year = {2022}, author = {Al-Saoudi, E and Christensen, MMB and Nawroth, P and Fleming, T and Hommel, EE and Jørgensen, ME and Fleischer, J and Hansen, CS}, title = {Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {891442}, pmid = {36303871}, issn = {1664-2392}, mesh = {Young Adult ; Humans ; *Diabetic Neuropathies/complications ; *Diabetes Mellitus, Type 1/complications ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2/complications ; Lipids ; }, abstract = {AIMS/HYPOTHESIS: Advanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).<br><br>METHODS: This cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) "glycolytic dysfunction", ii) "lipid peroxidation", iii) "oxidative stress", and iv) "glucotoxicity".<br><br>RESULTS: A higher z-score of "glycolytic dysfunction" was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), "lipid peroxidation" was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and "glucotoxicity" was associated with lower SDNN (-4.20% (95% CI -8.1416; -0.0896), p = 0.047). No significance remained after adjustment for multiple testing.<br><br>CONCLUSIONS/INTERPRETATIONS: In young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.}, }
@article {pmid36284635, year = {2022}, author = {Zhang, H and Yuan, J and Xiang, Y and Liu, Y}, title = {Comprehensive Analysis of NPSR1-AS1 as a Novel Diagnostic and Prognostic Biomarker Involved in Immune Infiltrates in Lung Adenocarcinoma.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {2099327}, pmid = {36284635}, issn = {1687-8450}, abstract = {The incidence of lung adenocarcinoma (LUAD), the most common subtype of lung cancer, continues to make lung cancer the largest cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been shown to have a significant role in both the onset and progression of lung cancer. In this study, we aimed to investigate the clinical significance and underlying mechanism of lncRNA NPSR1-AS1 (NPSR1-AS1) in LUAD. First, we performed an analysis on TCGA and identified 229 differentially expressed lncRNAs (DELs) (including 216 upregulated lncRNAs and 13 downregulated lncRNAs). Then, we carried out a screening of the lncRNAs associated with survival, and a total of 382 survival-related lncRNAs were found. 15 survival-related DELs were identified. Among them, our attention focused on NPSR1-AS1. We found that the expression of NPSR1-AS1 was much higher in LUAD specimens compared to nontumor tissues. According to the results of the ROC assays, high NPSR1-AS1 expression had an AUC value of 0.904 for LUAD, with a 95% confidence interval ranging from 0.881 to 0.927. The expression of NPSR1-AS1 was shown to be significantly elevated in a wide variety of cancers, according to the findings of a pancancer investigation. Functional enrichment analysis confirmed that NPSR1-AS1 was involved in LUAD progression via regulating several tumor-related pathways. Patients with high levels of NPSR1-AS1 expression were shown to have a shorter disease-specific survival (DSS) or overall survival (OS) than those with low levels of NPSR1-AS1 expression, according to the findings of a clinical investigation. It was determined by multivariate analysis that NPSR1-AS1 expressions served as an independent prognostic factor for the overall survival of LUAD patients. The results of immune cell infiltration revealed that the expressions of NPSR1-AS1 were negatively associated with CD8 T cells, pDC, cytotoxic cells, mast cells, iDC, neutrophils, NK CD56dim cells, DC, Th17 cells, Tgd, and macrophages, while they were positively associated with NK CD56bright cells and B cells. Overall, our findings revealed that NPSR1-AS1 could serve as a potential biomarker to assess the clinical outcome and immune infiltration level in LUAD.}, }
@article {pmid36245246, year = {2022}, author = {Blawski, R and Toska, E}, title = {A Unique FOXA1-Associated Chromatin State Dictates Therapeutic Resistance in Lobular Breast Cancer.}, journal = {Cancer research}, volume = {82}, number = {20}, pages = {3668-3670}, pmid = {36245246}, issn = {1538-7445}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; R21 CA252530/CA/NCI NIH HHS/United States ; K22 CA245487/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Receptors, Estrogen/genetics/metabolism ; Retrospective Studies ; Tamoxifen/pharmacology/therapeutic use ; }, abstract = {Invasive lobular carcinomas (ILC) are the second most common histologic subtype of breast cancer, accounting for up to 15% of cases. ILC is estrogen receptor (ER) positive, yet its biology is distinct from invasive ductal carcinomas (IDC), and retrospective analyses have indicated a poorer outcome with endocrine therapy. In this issue of Cancer Research, Nardone and colleagues investigated the mechanisms of this differential therapy response in ILC, which cannot be solely explained by the genetic profile of these tumors. The authors conducted a thorough examination of the epigenome of ILC compared with IDC in clinical and preclinical models and revealed an alternative chromatin accessibility state in ILC driven by the pioneer factor FOXA1. FOXA1 regulates its own expression in a feed-forward mechanism by binding to an ILC-unique FOXA1 enhancer site. This results in a FOXA1-ER axis that promotes the transcription of genes associated with tumor progression and tamoxifen resistance. Targeting the FOXA1 enhancer region blocks this transcriptional program and inhibits ILC proliferation. These results shed light on a new epigenetic mechanism driving ILC tumor progression and treatment resistance, which may have profound therapeutic implications. See related article by Nardone et al., p. 3673.}, }
@article {pmid36243006, year = {2022}, author = {Sekar, R and Motzler, K and Kwon, Y and Novikoff, A and Jülg, J and Najafi, B and Wang, S and Warnke, AL and Seitz, S and Hass, D and Gancheva, S and Kahl, S and Yang, B and Finan, B and Schwarz, K and Okun, JG and Roden, M and Blüher, M and Müller, TD and Krahmer, N and Behrends, C and Plettenburg, O and Miaczynska, M and Herzig, S and Zeigerer, A}, title = {Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes.}, journal = {Cell metabolism}, volume = {34}, number = {11}, pages = {1824-1842.e9}, doi = {10.1016/j.cmet.2022.09.022}, pmid = {36243006}, issn = {1932-7420}, mesh = {Animals ; Mice ; *Diabetes Mellitus, Type 2/metabolism ; Endosomes/metabolism ; Glucagon/metabolism ; Glucose/metabolism ; Lipids ; Liver/metabolism ; Mammals/metabolism ; Mice, Inbred C57BL ; *Receptors, Glucagon/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; }, abstract = {During mammalian energy homeostasis, the glucagon receptor (Gcgr) plays a key role in regulating both glucose and lipid metabolisms. However, the mechanisms by which these distinct signaling arms are differentially regulated remain poorly understood. Using a Cy5-glucagon agonist, we show that the endosomal protein Vps37a uncouples glucose production from lipid usage downstream of Gcgr signaling by altering intracellular receptor localization. Hepatocyte-specific knockdown of Vps37a causes an accumulation of Gcgr in endosomes, resulting in overactivation of the cAMP/PKA/p-Creb signaling pathway to gluconeogenesis without affecting β-oxidation. Shifting the receptor back to the plasma membrane rescues the differential signaling and highlights the importance of the spatiotemporal localization of Gcgr for its metabolic effects. Importantly, since Vps37a knockdown in animals fed with a high-fat diet leads to hyperglycemia, although its overexpression reduces blood glucose levels, these data reveal a contribution of endosomal signaling to metabolic diseases that could be exploited for treatments of type 2 diabetes.}, }
@article {pmid36238494, year = {2022}, author = {Zhao, W and Wu, T and Zhan, J and Dong, Z}, title = {Identification of the Immune Status of Hypertrophic Cardiomyopathy by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.}, journal = {Computational and mathematical methods in medicine}, volume = {2022}, number = {}, pages = {7153491}, pmid = {36238494}, issn = {1748-6718}, mesh = {Animals ; Biomarkers ; *Cardiomyopathy, Hypertrophic/genetics/metabolism ; Gene Regulatory Networks ; Mice ; *MicroRNAs ; Sequence Analysis, RNA ; }, abstract = {OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy and immune infiltration is considered an indispensable factor involved in its pathogenesis. In this study, we attempted to combine bulk sequencing and single-cell sequencing to map the immune infiltration-related genes in hypertrophic cardiomyopathy.<br><br>METHODS: The GSE36961, GSE160997, and GSE122930 datasets were obtained from the Gene Expression Omnibus database. The compositional patterns of the 18 types of immune cell fraction and pathway enrichment score in control and HCM patients were estimated based on the GSE36961 cohort using xCell algorithm. The Weighted Gene Coexpression Network Analysis (WGCNA) was performed to identify genes associated with immune infiltration for hypertrophic cardiomyopathy. The area under the curve (AUC) value was obtained and used to evaluate the discriminatory ability of common immune-related DEGs. "NetworkAnalyst" platform was used to identify TF-gene and TF-miRNA interaction with identified common genes. Heat map was used to determine the association between common DEGs and various immune cells.<br><br>RESULTS: Immune infiltration analysis by the xCell algorithm showed a higher level of CD8+ naive T cells, CD8+ T cells, as well as a lower level of activated dendritic cells (aDC), dendritic cells (DC), immature dendritic cells (iDC), conventional dendritic cells (cDC), macrophages, M1 macrophages, monocytes, and NKT cell in HCM compared with the control group in GSE36961 dataset. aDC, macrophages, and M1 macrophages were the top three discriminators between HCM and control groups with the area under the curve (AUC) of 0.907, 0.867, and 0.941. WGCNA analysis showed that 1258 immune-related genes were included in four different modules. Of these modules, the turquoise module showed a pivotal correlation with HCM. 13 common immune-related DEGs were found by intersecting common DEGs in GSE36961 and GSE160997 datasets with genes from the genes in turquoise module. 5 hub immune-related genes (S100A9, TYROBP, FCER1G, CD14, and S100A8) were identified by protein interaction network. Through analysis of single-cell sequencing data, S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory macrophage cells in the heart immune microenvironment while Cd14 was expressed by infiltrated M1 proinflammatory macrophage cells and M2 macrophages in transverse aortic constriction (TAC) mice at 1 week. Higher M2 macrophage and M1 proinflammatory macrophage infiltration as well as lower Ccr2-M1 proinflammatory macrophage and dendritic cells were shown in TAC 1week mice compared with sham mice.<br><br>CONCLUSIONS: There was a difference in immune infiltration between HCM patients and normal groups. aDC, macrophages, and M1 macrophages were the top three discriminator immune cell subsets between HCM and control groups. S100A9, TYROBP, FCER1G, CD14, and S100A8 were identified as potential biomarkers to discriminate HCM from the control group. S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory cells in the heart immune microenvironment while Cd14 was expressed by M2 macrophages in transverse aortic constriction (TAC) mice at 1 week.}, }
@article {pmid36230503, year = {2022}, author = {Chang, YS and Chou, YP and Chung, CC and Lee, YT and Yen, JC and Jeng, LB and Chang, JG}, title = {Molecular Classification of Hepatocellular Carcinoma Using Wnt-Hippo Signaling Pathway-Related Genes.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230503}, issn = {2072-6694}, support = {DMR-111-131//China Medical University Hospital/ ; MOST-109-2320-B-039-052 and MOST-110-2321-B-039-002//Ministry of Science and Technology of Taiwan/ ; }, abstract = {In Taiwan, a combination of hepatitis B and C infection, economic boom-related food and alcohol overconsumption, and Chinese medicine prescriptions has led to a high rate of hepatocellular carcinoma (HCC). However, the causative factors and underlying tumor biology for this unique HCC environment have not been identified. Wnt and Hippo signaling pathways play an important regulatory role in HCC development, and their functions are generally considered as positive and negative regulators of cell proliferation, respectively. In this study, we characterized the molecular features of HCC using a newly developed classification system based on the expression of the Wnt-Hippo signaling pathway-related genes. RNA sequencing (RNA-Seq) was performed on liver tumor tissues from 100 patients with liver cancer. RNA-Seq data for 272 previously characterized Wnt-Hippo signaling pathway-related genes were used for hierarchical clustering. We analyzed the data in terms of prognostic value, transcriptome features, immune infiltration, and clinical characteristics, and compared the resulting subclasses with previously published classifications. Four subclasses of HCC (HCCW1-4) were identified. Subclass HCCW1 displayed the highest PCDHB4 expression. Subclass HCCW2 displayed lower Edmondson-Steiner grades (I and II) and CTNNB1 mutation frequencies. Subclass HCCW3 was associated with a good prognosis, the highest PCDHGB7 expression, high CD8+ naïve T cells abundance, and relatively low TP53 mutation rates. Subclass HCCW4 was associated with a poor prognosis, the highest PCDHB2 and PCDHB6 expression, a relatively high abundance of Th1 cells, NKT and class-switched memory B cells, relatively low enrichment of cDC, iDC, and CD4+ memory T cells, and high Edmondson-Steiner grades (III and IV). We also identified Wnt-Hippo signaling pathway-related genes that may influence immune cell infiltration. We developed a panel of 272 Wnt-Hippo signaling pathway-related genes to classify HCC into four groups based on Taiwanese HCC and The Cancer Genome Atlas Liver Hepatocellular Carcinoma datasets. This novel molecular classification system may aid the treatment of HCC.}, }
@article {pmid36229464, year = {2022}, author = {Wong, HY and Sheng, Q and Hesterberg, AB and Croessmann, S and Rios, BL and Giri, K and Jackson, J and Miranda, AX and Watkins, E and Schaffer, KR and Donahue, M and Winkler, E and Penson, DF and Smith, JA and Herrell, SD and Luckenbaugh, AN and Barocas, DA and Kim, YJ and Graves, D and Giannico, GA and Rathmell, JC and Park, BH and Gordetsky, JB and Hurley, PJ}, title = {Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6036}, pmid = {36229464}, issn = {2041-1723}, support = {S10 OD023475/OD/NIH HHS/United States ; R01 CA194024/CA/NCI NIH HHS/United States ; S10 OD016355/OD/NIH HHS/United States ; T32 CA009582/CA/NCI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; R01 CA214494/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; R01 CA217987/CA/NCI NIH HHS/United States ; R01 CA211695/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; }, mesh = {Apolipoproteins E ; *Carcinoma, Intraductal, Noninfiltrating/genetics ; Extracellular Matrix Proteins ; Humans ; Ligands ; Male ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; RNA ; Receptors, Antigen, T-Cell ; Single-Cell Analysis ; Tumor Microenvironment/genetics ; }, abstract = {Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1[+]ASPN[+]FAP[+]ENG[+]) along with fewer T cells, elevated T cell dysfunction, and increased C1QB[+]TREM2[+]APOE[+]-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.}, }
@article {pmid36223973, year = {2022}, author = {Singh, N and Singh, R and Decker, B and Robins, D and Vidal, G}, title = {Metastatic triple negative breast cancer with NTRK gene fusion on tissue but not on ctDNA molecular profile.}, journal = {BMJ case reports}, volume = {15}, number = {10}, pages = {}, pmid = {36223973}, issn = {1757-790X}, mesh = {*Breast Neoplasms/genetics/pathology ; Carcinoma ; *Circulating Tumor DNA/genetics ; Female ; Gene Fusion ; Humans ; Oncogene Proteins, Fusion/genetics ; Protein Kinase Inhibitors ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; }, abstract = {A woman presented to medical oncology with almost 4 years of untreated, slowly progressing, triple negative metastatic breast cancer to the lung. About 15 years prior, she was diagnosed with invasive ductal carcinoma of the right breast with ipsilateral chest wall recurrence 6 years later. Comprehensive molecular profiling of a metastatic lesion detected a hotspot ETV6-NTRK3 fusion, which was not present on circulating tumour DNA or molecular profile performed 4 years prior. A second look pathological examination demonstrated tumour characteristics consistent with secretory breast carcinoma. Identification of ETV6--NKRT3 fusion allowed for treatment with larotrectinib, a tyrosine kinase inhibitor specifically indicated for secretory breast carcinoma. After 3 months, she experienced a partial response.}, }
@article {pmid36208091, year = {2023}, author = {Lu, X and Ying, Y and Zhang, W and Li, R and Zhang, J}, title = {High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma.}, journal = {Cell biology international}, volume = {47}, number = {1}, pages = {201-215}, doi = {10.1002/cbin.11925}, pmid = {36208091}, issn = {1095-8355}, support = {182102410095//Science and Technology Department of Henan Province/ ; 212102310466//Science and Technology Department of Henan Province/ ; 2019GGJS004//Education Department of Henan Province/ ; LHGJ20220473//Health Commission of Henan Province/ ; SBGJ202002119//Health Commission of Henan Province/ ; }, mesh = {Female ; Humans ; *Endometrial Neoplasms/diagnosis/pathology ; *MutS Homolog 2 Protein/genetics/metabolism ; Promoter Regions, Genetic ; *Biomarkers, Tumor/genetics/metabolism ; }, abstract = {Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.}, }
@article {pmid36206823, year = {2022}, author = {Maggi, G and Di Meglio, D and Vitale, C and Amboni, M and Obeso, I and Santangelo, G}, title = {The impact of executive dysfunctions on Theory of Mind abilities in Parkinson's disease.}, journal = {Neuropsychologia}, volume = {176}, number = {}, pages = {108389}, doi = {10.1016/j.neuropsychologia.2022.108389}, pmid = {36206823}, issn = {1873-3514}, mesh = {Humans ; *Theory of Mind/physiology ; *Parkinson Disease/complications/psychology ; Neuropsychological Tests ; Executive Function/physiology ; *Cognitive Dysfunction ; }, abstract = {Theory of Mind (ToM) is the ability to infer and reason about others' mental states, a process impaired by Parkinson's disease (PD). ToM performance in PD seems to be strongly related to executive functioning but the exact nature of this relationship is still unclear. We aim to investigate the direct impact of several executive dysfunctions on ToM deficits (Affective and Cognitive ToM) in PD patients. Sixty-eight PD patients underwent neuropsychological tests evaluating executive control such as inhibition, cognitive flexibility, processing speed or working memory and Cognitive and Affective ToM. We divided participants into two groups based on their performance on executive tests: PD patients with poor executive functioning (PD-EF-) and those with preserved executive functioning (PD-EF+). To explore the direct impact of executive subdomains on ToM abilities, two mediation models were executed in the whole sample. We found that PD patients with poor executive functioning reported poorer scores on Affective and Cognitive ToM tasks than PD patients with preserved executive functions, controlling for age and education. Moreover, parallel mediation models, conducted in the whole sample, indicated that performance on phonological fluency mediated the relationships between educational level and both Affective and Cognitive ToM, controlling the effect of other executive tests. These findings further support the idea that executive functions are crucial in ToM processes. Particularly, phonological fluency, whose execution requires both verbal abilities and cognitive flexibility, mediated ToM performance controlling the effect of other executive functions. The identification of neuropsychological processes underpinning ToM abilities might represent a plausible target for cognitive training to strengthen ToM abilities in PD.}, }
@article {pmid36189356, year = {2022}, author = {Saeed, U and Piracha, ZZ and Uppal, SR and Waheed, Y and Uppal, R}, title = {SARS-CoV-2 induced hepatic injuries and liver complications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {726263}, pmid = {36189356}, issn = {2235-2988}, mesh = {Aged ; *COVID-19/complications ; *Carcinoma, Hepatocellular ; *Gastrointestinal Diseases ; Humans ; Liver/pathology ; *Liver Neoplasms/pathology ; Pandemics ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction.<br><br>DISCUSSION: Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver.<br><br>CONCLUSION: During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.}, }
@article {pmid36178915, year = {2022}, author = {Mussa, FM and Massawe, HP and Bhalloo, H and Moledina, S and Assenga, E}, title = {Magnitude and associated factors of anti-retroviral therapy adherence among children attending HIV care and treatment clinics in Dar es Salaam, Tanzania.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0275420}, pmid = {36178915}, issn = {1932-6203}, mesh = {Child ; Cross-Sectional Studies ; *HIV Infections/complications/drug therapy/epidemiology ; Humans ; Odds Ratio ; Surveys and Questionnaires ; Tanzania/epidemiology ; }, abstract = {INTRODUCTION: The HIV pandemic continues to contribute significantly towards childhood mortality and morbidity. The up-scaling of the Anti-retroviral therapy (ART) access has seen more children surviving and sanctions great effort be made on ensuring adherence. Adherence is a dynamic process that changes over time and is determined by variable factors. This necessitates the urgency to conduct studies to determine the potential factors affecting adherence in our setting and therefore achieve the 90-90-90 goal of sustainable viral suppression.<br><br>OBJECTIVES: To assess the magnitude and associated factors of ART adherence among children (1-14 years) attending HIV care and treatment clinics during the months of July to November 2018 in Dar es Salaam.<br><br>METHODS: A cross-sectional clinic-based study, conducted in three selected HIV care and treatment clinics in urban Dar es Salaam; Muhimbili National Hospital (MNH), Temeke Regional Referral Hospital (TRRH), Infectious Disease Centre- DarDar Paediatric Program (IDC-DPP) HIV clinics during the months of July to November 2018. HIV-infected children aged 1-14 years who had been on treatment for at least six months were consecutively enrolled until the sample size was achieved. A structured questionnaire was used for data collection. Four-day self-report, one-month self-recall report and missed clinic appointments were used to assess adherence. Frequencies and percentages were used to describe categorical data. The odds ratio was used to analyse the possible factors affecting ART adherence Logistic regression models were used to determine the factors associated with ART adherence. Analysis was conducted using SPSS version 20.0 and p-value <0.05 were considered statistically significant.<br><br>RESULTS: 333 participants were recruited. The overall good adherence (&#x2265;95%) was approximated to be 60% (CI-54.3-65.1) when subjected to all three measures. On multivariable logistic regression, factors associated with higher odds of poor adherence were found to be caregivers aged 17-25 years [AOR = 3.5, 95%CI-(1.5-8.4)], children having an inter-current illness [AOR = 10.8, 95%CI-(2.3-50.4)], disbelief in ART effectiveness [AOR = 5.495; 95%CI-(1.669-18.182)] and advanced clinical stage [AOR = 1.972; 95% CI-(1.119-3.484)]. The major reasons reported by caregivers for missing medications included forgetfulness (41%), high pill burden (21%), busy schedule (11%) and long waiting hours at the clinic (9%).<br><br>In the urban setting of Dar es Salaam, ART adherence among children was found to be relatively low when combined adherence measures were used. Factors associated with poor ART adherence found were younger aged caregivers, and child intercurrent illness, while factors conferring good adherence were belief in ART effectiveness and lower HIV clinical stage. More attention and support should be given to younger aged caregivers, children with concomitant illness and advanced HIV clinical stages. Educating caregivers on ART effectiveness may also aid in improving adherence.}, }
@article {pmid36175695, year = {2022}, author = {Silva, FHS and Underwood, A and Almeida, CP and Ribeiro, TS and Souza-Fagundes, EM and Martins, AS and Eliezeck, M and Guatimosim, S and Andrade, LO and Rezende, L and Gomes, HW and Oliveira, CA and Rodrigues, RC and Borges, IT and Cassali, GD and Ferreira, E and Del Puerto, HL}, title = {Transcription factor SOX3 upregulated pro-apoptotic genes expression in human breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {39}, number = {12}, pages = {212}, pmid = {36175695}, issn = {1559-131X}, support = {05/20160//PRPq UFMG/ ; }, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Caspase 3 ; Female ; Fluorescein-5-isothiocyanate ; Humans ; RNA, Messenger ; SOXB1 Transcription Factors ; Tumor Suppressor Proteins ; Up-Regulation ; bcl-2-Associated X Protein ; }, abstract = {BACKGROUND: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples.<br><br>RESULTS: Apoptotic rate was higher in cells transfected with pEF1-SOX3&#x2009;+&#x2009;(56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3&#x2009;+&#x2009;presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p&#x2009;<&#x2009;0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases.<br><br>CONCLUSION: Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis.}, }
@article {pmid36172685, year = {2022}, author = {Alinezhadi, M and Makvandi, M and Kaydani, GA and Jazayeri, SN and Charostad, J and Talaeizadeh, AT and Angali, KA}, title = {Detection of High-Risk Human Papillomavirus DNA in Invasive Ductal Carcinoma Specimens.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {9}, pages = {3201-3207}, pmid = {36172685}, issn = {2476-762X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Alphapapillomavirus/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; Case-Control Studies ; DNA ; DNA, Viral/genetics ; Female ; *Fibroadenoma/genetics ; Formaldehyde ; Humans ; Middle Aged ; Papillomaviridae/genetics ; *Papillomavirus Infections ; Paraffin Embedding ; Young Adult ; }, abstract = {BACKGROUND: According to several studies, there is an association between human papillomavirus (HPV) and breast cancer. Therefore, detection and genotyping of HPV seem important. The present study aimed to investigate the presence of HPV DNA in breast tissues by analyzing the L1 gene.<br><br>MATERIALS AND METHODS: This case-control study was conducted on 63 formalin-fixed paraffin-embedded (FFPE) tissues of invasive ductal carcinoma (IDC) as the case group and 32 FFPE tissues of fibroadenoma as the control group. HPV DNA was detected using the polymerase chain reaction assay. Positive samples were then subjected to genotyping. All statistical analyses were performed in SPSS version 22.0.<br><br>RESULTS: The patients' age ranged from 15 to 92 years, with a mean age of 43.54&#xb1;16.36 years. HPV DNA was detected in 17/95 (17.89%) samples, including 9/32 (28.12%) fibroadenoma samples and 8/63 (12.69%) IDC samples. No significant difference was observed regarding the presence of HPV DNA between the IDC and fibroadenoma tissues (P=0.08). However, a significant difference was found in the detection of high-risk HPV (HR-HPV) between the case and control groups (P=0.03). In the case group, 87.5% of the detected viruses (7/8 samples) were HR-HPV, while in the control group, 22.22% of positive samples (2/9 samples) were HR-HPV (P=0.03). Based on the results, HR-HPV and low-risk HPV genotypes were detected in 53% (9/17) and 47% (8/17) of positive samples, respectively.<br><br>CONCLUSION: In this study, 12.69% of IDC samples were positive for HPV genomes, and HR-HPV was detected in 87.5% of these samples. The present results suggest the important role of HR-HPV in the development of breast cancer.}, }
@article {pmid36168441, year = {2022}, author = {Wenger, D and Kurumety, S and Aydi, ZB}, title = {A case report: invasive ductal carcinoma in mosaic Li-Fraumeni syndrome.}, journal = {Journal of surgical case reports}, volume = {2022}, number = {9}, pages = {rjac408}, pmid = {36168441}, issn = {2042-8812}, abstract = {Li-Fraumeni syndrome (LFS) is a rare autosomal dominant condition caused by pathogenic variants in the TP53 tumor suppressor gene and characterized by a high lifetime risk of various cancers with a very early age of onset. We are presenting a 41-year-old woman with right invasive ductal cancer and no family history of cancers, diagnosed with mosaic LFS confirmed with blood and skin punch biopsy samples. She was treated with neoadjuvant chemotherapy, mastectomy and sentinel node biopsy with completion axillary dissection. Adjuvant radiation was not recommended due to increased risk of secondary cancers. She also elected to undergo risk reducing contralateral mastectomy. Further research is warranted to determine the appropriate clinical management and surveillance strategies in patients with mosaic LFS as whether individuals with mosaic LFS have differing cancer risks in comparison to classic germline LFS is unknown.}, }
@article {pmid36107313, year = {2022}, author = {Walth-Hummel, AA and Herzig, S and Rohm, M}, title = {Nuclear Receptors in Energy Metabolism.}, journal = {Advances in experimental medicine and biology}, volume = {1390}, number = {}, pages = {61-82}, pmid = {36107313}, issn = {0065-2598}, mesh = {Adipose Tissue/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Energy Metabolism/physiology ; Humans ; *Metabolic Diseases/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; }, abstract = {Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic β-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined.}, }
@article {pmid36082773, year = {2022}, author = {Ryder, JH and Van Schooneveld, TC and Lyden, E and El Ramahi, R and Stohs, EJ}, title = {The interplay of infectious diseases consultation and antimicrobial stewardship in candidemia outcomes: A retrospective cohort study from 2016 to 2019.}, journal = {Infection control and hospital epidemiology}, volume = {}, number = {}, pages = {1-6}, doi = {10.1017/ice.2022.209}, pmid = {36082773}, issn = {1559-6834}, abstract = {OBJECTIVE: To evaluate the need for mandatory infectious diseases consultation (IDC) for candidemia in the setting of antimicrobial stewardship guidance.<br><br>DESIGN: Retrospective cohort study from January 2016 to December 2019.<br><br>SETTING: Academic quaternary-care referral center.<br><br>PATIENTS: All episodes of candidemia in adults (n = 92), excluding concurrent bacterial infection or death or hospice care within 48 hours.<br><br>METHODS: Primary outcome was all-cause 30-day mortality. Secondary outcomes included guideline-adherence and treatment choice. Guideline-adherence was assessed with the EQUAL Candida score.<br><br>RESULTS: Of 186 episodes of candidemia, 92 episodes in 88 patients were included. Central venous catheters (CVCs) were present in 66 episodes (71.7%) and were the most common infection source (N = 38, 41.3%). The most frequently isolated species was Candida glabrata (40 of 94, 42.6%). IDC was performed in 84 (91.3%) of 92 candidemia episodes. Mortality rates were 20.8% (16 of 77) in the IDC group versus 25% (2 of 8) in the no-IDC group (P = .67). Other comparisons were numerically different but not significant: repeat blood culture (98.8% vs 87.5%; P = .17), echocardiography (70.2% vs 50%; P = .26), CVC removal (91.7% vs 83.3%; P = .45), and initial echinocandin treatment (67.9% vs 50%; P = .44). IDC resulted in more ophthalmology examinations (67.9% vs 12.5%; P = .0035). All patients received antifungal therapy. Antimicrobial stewardship recommendations were performed in 19 episodes (20.7%). The median EQUAL Candida score with CVC was higher with IDC (16 vs 11; P = .001) but not in episodes without CVC (12 vs 11.5; P = .81).<br><br>CONCLUSIONS: In the setting of an active antimicrobial stewardship program and high consultation rates, mandatory IDC may not be warranted for candidemia.}, }
@article {pmid36074318, year = {2022}, author = {Pellegata, NS and Berriel Diaz, M and Rohm, M and Herzig, S}, title = {Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases.}, journal = {Cancer metastasis reviews}, volume = {41}, number = {3}, pages = {517-547}, pmid = {36074318}, issn = {1573-7233}, mesh = {Adipose Tissue ; *Adrenergic Agents ; Extracellular Matrix ; Humans ; *Neoplasms/epidemiology ; Obesity/complications ; }, abstract = {Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.}, }
@article {pmid36065259, year = {2022}, author = {Malakzai, HA and Haidary, AM and Gulzar, S and Haidari, M and Ibrahimkhil, AS and Saadaat, R and Hakimi, A and Sadat Hofiani, SM and Rahmani, S and Abdul-Ghafar, J}, title = {Prevalence, Distribution, and Histopathological Features of Malignant Tumors Reported at Tertiary Level in Afghanistan: A 3-Year Study.}, journal = {Cancer management and research}, volume = {14}, number = {}, pages = {2569-2582}, pmid = {36065259}, issn = {1179-1322}, support = {001/WHO_/World Health Organization/International ; }, abstract = {PURPOSE: Cancer is one of the leading causes of mortality and morbidity, and therefore, tremendous research work is continuously being done around the world with consideration of etiopathogenesis as well as identification of therapeutic targets. Decades of continuous war in Afghanistan has left the medical infrastructure of the country in a miserable situation. There is a serious deficiency in research work in the fields of pathology and oncology at the moment with minimal data available to elaborate about the demographic characteristics of various malignant disorders in the country, which would be indispensable to pave the way for further research and development.<br><br>PATIENTS AND METHODS: A descriptive cross-sectional study was conducted to describe the prevalence, distribution, and important histopathological features of malignant tumors reported at tertiary level in Afghanistan.<br><br>RESULTS: Out of 2328 consecutive cases of solid malignant tumors included in our study, 93.8% were primary and 6.2% were metastatic. Breast was the most common site of origin for primary malignancy (29.5%) in females; however, in males, esophagus was the leading site for primary malignant tumors (16.3%). Invasive ductal carcinoma was the most common histologic type of malignancy in females (87.9%). However, in both genders, squamous cell carcinoma of esophagus and skin, osteosarcoma of bone and soft tissue, and glioblastoma of central nervous system were the most common histologic types of malignancies diagnosed. Small intestine was a frequently involved site affected by extranodal non-Hodgkin lymphomas. Overall, the majority of the cancers were diagnosed in stage-II.<br><br>CONCLUSION: Findings in our study were somewhat similar to data presented elsewhere in the world, with some significant differences that could be related to the local factors. Our study revealed that most of the malignant tumors were diagnosed in later stages of the disease, attributable to scarcity of specialized oncology institutions and public awareness.}, }
@article {pmid36040027, year = {2023}, author = {Thompson, LDR and Bishop, JA}, title = {Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification.}, journal = {Advances in anatomic pathology}, volume = {30}, number = {2}, pages = {112-129}, pmid = {36040027}, issn = {1533-4031}, mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Salivary Gland Neoplasms/pathology ; Transcription Factors ; Salivary Glands/pathology ; Biomarkers, Tumor/genetics ; }, abstract = {Salivary gland intraductal carcinoma (IDC) is a very uncommon group of neoplasms. Many names, variations in diagnostic criteria, and newly observed molecular findings (including NCOA4 :: RET , TRIM27 :: RET , HRAS point mutations, and PIK3CA pathway alterations) have generated further confusion in being able to recognize and categorize this group of tumors. Different histologic appearances and patterns of growth suggest there is more than one tumor category, with intercalated duct, apocrine, oncocytic, and hybrid features seen. Frankly destructive invasion further complicates the category, as the name "intraductal" would suggest an "in situ" neoplasm. Recent evidence on fusion-positive IDC demonstrates the same molecular underpinnings in both the ductal and the myoepithelial cells, which aids in further separating these tumors. This article summarizes the historical group of 183 neoplasms classified under the umbrella of IDC and highlights the unique histologic, immunohistochemistry, and molecular features that may further guide nomenclature standardization and harmonization.}, }
@article {pmid36012443, year = {2022}, author = {Kmiecik, A and Ratajczak-Wielgomas, K and Grzegrzółka, J and Romanowicz, H and Smolarz, B and Dziegiel, P}, title = {Expression of NUCB2/NESF-1 in Breast Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, pmid = {36012443}, issn = {1422-0067}, support = {STM.A350.20.064//Wroc&#x142;aw Medical University/ ; }, mesh = {*Breast Neoplasms/genetics/metabolism ; *Carcinoma, Ductal, Breast/pathology ; Cytoplasm/metabolism ; Female ; Humans ; RNA, Messenger/genetics/metabolism ; }, abstract = {Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.}, }
@article {pmid36002899, year = {2022}, author = {Molinaro, J and DeVries, P and Ha, J and Knight, JM}, title = {New-onset hallucinations with amiodarone: a case report.}, journal = {Annals of general psychiatry}, volume = {21}, number = {1}, pages = {34}, pmid = {36002899}, issn = {1744-859X}, abstract = {BACKGROUND: Amiodarone is a commonly used antiarrhythmic for the treatment of atrial fibrillation with a unique pharmacokinetic profile. While general side effects can be frequently associated with amiodarone, psychiatric adverse reactions to this medication are uncommon. The relationship between amiodarone and hallucinations independent of delirium has been rarely reported in the literature.<br><br>CASE PRESENTATION: We report the case of a 63-year-old female with a history of estrogen and progesterone receptor positive invasive ductal carcinoma with osseous metastases to the ribs and skull, major depressive disorder, and unspecified anxiety. She was diagnosed with invasive ductal carcinoma 12&#xa0;years prior and underwent a lumpectomy with axillary lymph node dissection and radiation, currently maintained on anastrozole and trastuzumab for the past 11&#xa0;years. Her symptoms of major depressive disorder and anxiety have remained in remission on a regimen of bupropion extended release, duloxetine, and trazodone without recent dose changes. This patient presented to the emergency department with dyspnea and was admitted to the general medical floor with new-onset atrial fibrillation. She was subsequently started on amiodarone for rhythm control. Shortly after its initiation, the patient developed new onset auditory and visual hallucinations with an unremarkable extensive medical evaluation. Auditory hallucinations consisted of music and unintelligible conversations, while visual hallucinations were of a family member crying on the floor and a man carrying a gun. The differential diagnoses included depression with psychotic features, delirium, and amiodarone-induced hallucinations. Given the lack of current depressive symptoms, absence of altered cognition, and the temporal relationship between the initiation of amiodarone and the onset of hallucinations, amiodarone was suspected to be probable etiology of her hallucinations. For this reason, amiodarone was replaced with dronedarone. Visual and auditory hallucinations ceased within less than 3&#xa0;days after the discontinuation of amiodarone.<br><br>CONCLUSIONS: Psychiatric adverse events from amiodarone are uncommon, and associated isolated hallucinations have only been rarely reported in the literature. While the risk of visual and auditory hallucinations appears to be low with amiodarone initiation, clinicians should be aware of this potential side effect.}, }
@article {pmid35982591, year = {2022}, author = {Kovalenko, I and Roy, P and Soni, B and Sangha, L and Toom, S}, title = {Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report.}, journal = {The American journal of case reports}, volume = {23}, number = {}, pages = {e936665}, pmid = {35982591}, issn = {1941-5923}, mesh = {*Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma/pathology ; *Carcinoma, Ductal/genetics/surgery ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Mastectomy ; Translocation, Genetic ; }, abstract = {BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.}, }
@article {pmid35976519, year = {2023}, author = {Eum, SY and Schurhoff, N and Teglas, T and Wolff, G and Toborek, M}, title = {Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.}, journal = {Molecular and cellular biochemistry}, volume = {478}, number = {3}, pages = {581-595}, pmid = {35976519}, issn = {1573-4919}, support = {DA050528/DA/NIDA NIH HHS/United States ; DA047157/DA/NIDA NIH HHS/United States ; DA039576/DA/NIDA NIH HHS/United States ; MH128022/MH/NIMH NIH HHS/United States ; MH122235/MH/NIMH NIH HHS/United States ; DA040537/DA/NIDA NIH HHS/United States ; HL126559/HL/NHLBI NIH HHS/United States ; DA044579/DA/NIDA NIH HHS/United States ; MH072567/MH/NIMH NIH HHS/United States ; MH128022/MH/NIMH NIH HHS/United States ; MH122235/MH/NIMH NIH HHS/United States ; MH072567/MH/NIMH NIH HHS/United States ; DA044579/DA/NIDA NIH HHS/United States ; DA039576/DA/NIDA NIH HHS/United States ; DA040537/DA/NIDA NIH HHS/United States ; DA050528/DA/NIDA NIH HHS/United States ; DA047157/DA/NIDA NIH HHS/United States ; HL126559/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Catenins/genetics ; *Circadian Rhythm ; Gene Expression Regulation ; }, abstract = {We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.}, }
@article {pmid35963427, year = {2022}, author = {Brecklinghaus, T and Albrecht, W and Duda, J and Kappenberg, F and Gründler, L and Edlund, K and Marchan, R and Ghallab, A and Cadenas, C and Rieck, A and Vartak, N and Tolosa, L and Castell, JV and Gardner, I and Halilbasic, E and Trauner, M and Ullrich, A and Zeigerer, A and Demirci Turgunbayer, &#xd6; and Damm, G and Seehofer, D and Rahnenführer, J and Hengstler, JG}, title = {In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay.}, journal = {Toxicology letters}, volume = {368}, number = {}, pages = {33-46}, doi = {10.1016/j.toxlet.2022.08.006}, pmid = {35963427}, issn = {1879-3169}, mesh = {*Chemical and Drug Induced Liver Injury/etiology ; *Drug-Related Side Effects and Adverse Reactions ; *Fatty Liver/chemically induced ; Hepatocytes ; Humans ; Oxazines/toxicity ; }, abstract = {The accumulation of lipid droplets in hepatocytes is a key feature of drug-induced liver injury (DILI) and can be induced by a subset of hepatotoxic compounds. In the present study, we optimized and evaluated an in vitro technique based on the fluorescent dye Nile Red, further named Nile Red assay to quantify lipid droplets induced by the exposure to chemicals. The Nile Red assay and a cytotoxicity test (CTB assay) were then performed on cells exposed concentration-dependently to 60 different compounds. Of these, 31 were known to induce hepatotoxicity in humans, and 13 were reported to also cause steatosis. In order to compare in vivo relevant blood concentrations, pharmacokinetic models were established for all compounds to simulate the maximal blood concentrations (Cmax) at therapeutic doses. The results showed that several hepatotoxic compounds induced an increase in lipid droplets at sub-cytotoxic concentrations. To compare how well (1) the cytotoxicity test alone, (2) the Nile Red assay alone, and (3) the combination of the cytotoxicity test and the Nile Red assay (based on the lower EC10 of both assays) allow the differentiation between hepatotoxic and non-hepatotoxic compounds, a previously established performance metric, the Toxicity Separation Index (TSI) was calculated. In addition, the Toxicity Estimation Index (TEI) was calculated to determine how well blood concentrations that cause an increased DILI risk can be estimated for hepatotoxic compounds. Our findings indicate that the combination of both assays improved the TSI and TEI compared to each assay alone. In conclusion, the study demonstrates that inclusion of the Nile Red assay into in vitro test batteries may improve the prediction of DILI compounds.}, }
@article {pmid35958350, year = {2022}, author = {Fujita, K and Okamura, M and Imakita, T and Yamamoto, Y and Sawai, S and Moriyoshi, K and Mio, T}, title = {Natural course of pulmonary hyalinizing granuloma over a decade.}, journal = {Respiratory medicine case reports}, volume = {39}, number = {}, pages = {101715}, pmid = {35958350}, issn = {2213-0071}, abstract = {BACKGROUND: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response.<br><br>CASE PRESENTATION: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG.<br><br>CONCLUSIONS: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.}, }
@article {pmid35950920, year = {2022}, author = {Nardone, A and Qiu, X and Spisak, S and Nagy, Z and Feiglin, A and Feit, A and Cohen Feit, G and Xie, Y and Font-Tello, A and Guarducci, C and Hermida-Prado, F and Syamala, S and Lim, K and Munoz Gomez, M and Pun, M and Cornwell, M and Liu, W and Ors, A and Mohammed, H and Cejas, P and Brock, JB and Freedman, ML and Winer, EP and Fu, X and Schiff, R and Long, HW and Metzger Filho, O and Jeselsohn, R}, title = {A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer.}, journal = {Cancer research}, volume = {82}, number = {20}, pages = {3673-3686}, pmid = {35950920}, issn = {1538-7445}, support = {K08 CA191058/CA/NCI NIH HHS/United States ; P01 CA250959/CA/NCI NIH HHS/United States ; R01 CA237414/CA/NCI NIH HHS/United States ; R01 CA193910/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Prognosis ; Receptors, Estrogen/metabolism ; Tamoxifen/pharmacology/therapeutic use ; }, abstract = {UNLABELLED: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor-positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1-estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1-ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1-ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.<br><br>SIGNIFICANCE: A unique FOXA1-ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668.}, }
@article {pmid35945526, year = {2022}, author = {Xu, A and Chu, X and Zhang, S and Zheng, J and Shi, D and Lv, S and Li, F and Weng, X}, title = {Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {872}, pmid = {35945526}, issn = {1471-2407}, support = {2021KY1161 and 2022KY1316//Medical and Health Research Project of Zhejiang Province/ ; 2021ZA138//Zhejiang Province Chinese Medicine Science Research Fund Project/ ; }, mesh = {Bayes Theorem ; *Breast Neoplasms/diagnostic imaging/genetics ; *Carcinoma, Ductal ; China ; Female ; Humans ; Ki-67 Antigen ; Nomograms ; Retrospective Studies ; }, abstract = {BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status.<br><br>METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n&#x2009;=&#x2009;128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n&#x2009;=&#x2009;86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 (http://keyan.deepwise.com/), then radiomics feature extraction was implemented with PyRadiomics library. Recursive&#xa0;feature&#xa0;elimination&#xa0;(RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA).<br><br>RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical&#xa0;factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p&#x2009;=&#x2009;0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p&#x2009;=&#x2009;0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and&#xa0;the DCA verified the benefits of the nomogram.<br><br>CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.}, }
@article {pmid35943964, year = {2022}, author = {Sorotos, M and Paolini, G and D'Orsi, G and Firmani, G and Timmermans, FW and Santanelli di Pompeo, F}, title = {Oncologic Outcome of 1000 Postmastectomy Breast Reconstructions with Fat Transfer: A Single-Center, Matched Case-Control Study.}, journal = {Plastic and reconstructive surgery}, volume = {150}, number = {}, pages = {4S-12S}, doi = {10.1097/PRS.0000000000009494}, pmid = {35943964}, issn = {1529-4242}, mesh = {Adipose Tissue/pathology ; *Breast Neoplasms/etiology ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; *Mammaplasty/adverse effects ; Mastectomy/adverse effects ; Neoplasm Recurrence, Local/epidemiology/etiology/prevention &amp; control ; Retrospective Studies ; }, abstract = {BACKGROUND: Autologous fat transfer has an important role in breast reconstructive surgery. Nevertheless, some concerns remain with regard to its oncologic safety. The authors present a single-center, case-matching study analyzing the impact of autologous fat transfer in the cumulative incidence of local recurrences.<br><br>METHODS: From a prospectively maintained database, the authors identified 902 patients who underwent 1025 breast reconstructions from 2005 to 2017. Data regarding demographics, tumor characteristics, surgery details, and follow-up were collected. Exclusion criteria were patients with distant metastases at diagnosis, recurrent tumor, or incomplete data regarding primary tumor; and patients who underwent prophylactic mastectomies and breast-conserving operations. Statistical analysis was conducted to evaluate the impact of the variables on the incidence of local recurrence. A value of p < 0.05 was considered statistically significant.<br><br>RESULTS: After 1: n case-matching, we selected 919 breasts, of which 425 patients (46.2 percent) received at least one autologous fat transfer session versus 494 control cases (53.8 percent). Local recurrences had an overall rate of 6.8 percent, and we found local recurrences in 14 autologous fat transfer cases (3.0 percent) and 54 controls (9.6 percent). Statistical analysis showed that autologous fat transfer did not increase the risk of local recurrences (hazard ratio, 0.337; CI, 0.173 to 0.658; p = 0.00007). Multivariate analysis identified invasive ductal carcinoma subtype and lymph node metastases to have an increased risk of local recurrences (hazard ratio >1). Conversely, positive hormonal receptor status was associated with a reduced risk of events (hazard ratio <1).<br><br>CONCLUSIONS: Autologous fat transfer was not associated with a higher probability of locoregional recurrence in patients undergoing breast reconstruction; therefore, it can be safely used for total breast reconstruction or aesthetic refinements.<br><br>Risk, II.}, }
@article {pmid35932126, year = {2022}, author = {Yaltirik Bilgin, E and Unal, O and Ciledag, N}, title = {Vasogenic Edema Pattern in Brain Metastasis.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {32}, number = {8}, pages = {1020-1025}, doi = {10.29271/jcpsp.2022.08.1020}, pmid = {35932126}, issn = {1681-7168}, mesh = {Brain/pathology ; *Brain Edema/diagnostic imaging/etiology ; *Brain Neoplasms/complications/diagnostic imaging/pathology ; Cross-Sectional Studies ; Edema/etiology ; Humans ; *Lung Neoplasms/complications ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {OBJECTIVE: To determine the relationship of the presence and amount of vasogenic edema with origin, type, and grade of primary cancer.<br><br>STUDY DESIGN: Cross-sectional study.<br><br>PLACE AND DURATION OF STUDY: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiology Clinic, Ankara, Turkey, from July 2017 to October 2021.<br><br>METHODOLOGY: Brain MRI scans of 292 patients were retrospectively evaluated. Age, gender, origin, type, and grade of primary cancer were determined. Metastasis type, and presence of vasogenic edema accompanying metastatic lesion were questioned. In cases of vasogenic edema accompanying metastatic lesions, the largest diameter of the vasogenic edema mass complex was measured in T2 sequences. In the contrast-enhanced series, the largest diameter of the metastatic lesion was measured, and the edema-mass ratio (EMR) was calculated by proportioning the diameter of the edema mass complex to the diameter of the mass.<br><br>RESULTS: The frequency of vasogenic edema was found higher in patients with lung cancer compared to other primaries. The EMR was found statistically significantly higher in patients with primary lung cancer (p=0.001). This was particularly evident in the adenocarcinoma group. In the patient group with primary breast cancer, EMR was found significantly lower in patients with invasive ductal carcinoma. (IDC&#x2192;1.95&#xb1;0.66 vs. Other&#x2192;2.48&#xb1;0.52, Z=-2.301, p=0.021).<br><br>CONCLUSION: The amount and presence of vasogenic edema in patients with brain metastases may differ according to the origin and type of primary tumour.<br><br>KEY WORDS: Brain edema, Metastatic disease, Magnetic resonance imaging.}, }
@article {pmid35929120, year = {2023}, author = {Kim, KN and Salerno, M and Shah, PD and Matro, J and LaRiviere, MJ}, title = {Severe acute radiation dermatitis after palbociclib therapy in the setting of palliative radiotherapy.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {29}, number = {3}, pages = {764-767}, doi = {10.1177/10781552221118841}, pmid = {35929120}, issn = {1477-092X}, mesh = {Humans ; Female ; Middle Aged ; Retrospective Studies ; Pyridines/adverse effects ; *Breast Neoplasms/drug therapy/radiotherapy/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Dermatitis/drug therapy/etiology ; Protein Kinase Inhibitors/therapeutic use ; }, abstract = {INTRODUCTION: Cyclin-dependent-kinase 4/6(CDK4/6) inhibitors are widely used as a first-line systemic treatment for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer. Although many patients with metastatic breast cancer require palliative radiotherapy (RT), there are limited data on the safety of combining a CDK4/6 inhibitor with palliative RT.<br><br>CASE REPORT: Presented is a case of acute high-grade radiation dermatitis with low-dose palliative RT following administration of palbociclib. A 49-year-old woman with newly diagnosed hormone receptor-positive invasive ductal carcinoma of the left breast presented with lytic bone lesions in the left femur and lumbar spine. The patient initiated treatment with goserelin, tamoxifen, and palbociclib. She underwent prophylactic surgical fixation of the left femur and received post-operative RT encompassing the entire surgical nail (30 Gy/10 fractions) and palliative RT to the lumbar spine for pain relief (20 Gy/5 fractions). During cycle 4, palbociclib was stopped 3 days prior to the start of RT to reduce the risk of toxicity risk. However, 16 days after starting RT, she developed painful erythematous papules and bullae with moist desquamation on the left groin and lumbar spine.<br><br>MANAGEMENT &amp; OUTCOME: Her symptoms were managed with topical Aquaphor-lidocaine, silver sulfadiazine, and aluminum acetate soaks. Dermatitis subsided to dry desquamation within 2 weeks. The patient denied late toxicity at 11 months follow-up.<br><br>DISCUSSION: Larger retrospective or prospective studies are needed to further elucidate the safety of combined CDK4/6 inhibitors and RT. In the meantime, special precautions are warranted in patients receiving combined therapy.}, }
@article {pmid35909232, year = {2023}, author = {Yang, ZJ and Liu, YX and Huang, Y and Chen, ZJ and Zhang, HZ and Yu, Y and Wang, X and Cao, XC}, title = {The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score.}, journal = {Cancer medicine}, volume = {12}, number = {3}, pages = {2493-2504}, pmid = {35909232}, issn = {2045-7634}, mesh = {Humans ; Female ; Ki-67 Antigen/metabolism ; *Receptor, ErbB-2/metabolism ; Retrospective Studies ; *Breast Neoplasms/pathology ; Disease-Free Survival ; Receptors, Progesterone/metabolism ; Biomarkers, Tumor/metabolism ; Prognosis ; }, abstract = {BACKGROUND: Breast cancer (BC) remains the leading cause of cancer-related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed.<br><br>METHODS: In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2-negative breast invasive ductal carcinoma. According to the expression level of PR and Ki-67 index, the Luminal B (HER2-negative) BCs were divided into three groups: ER+PR-Ki67low (ER-positive, PR-negative, and Ki-67 index <20%), ER+PR+Ki67high (ER-positive, PR-positive, and Ki-67 index &#x2265;20%), and ER+PR-Ki67high (ER-positive, PR-negative, and Ki-67 index &#x2265;20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log-rank &#x3c7;[2] value.<br><br>RESULTS: The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival (p&#x2009;<&#x2009;0.001) and disease-free survival (DFS) (p&#x2009;<&#x2009;0.001). Interestingly, patients in the ER+PR-Ki67high subgroup have the worst survival outcome in Luminal B (HER2-negative) subtype, similar to Triple-negative patients. Besides, the ER+PR+Ki67high has worse 5-year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) (p&#x2009;<&#x2009;0.001). Moreover, the results showed that patients in ER+PR-Ki67high subtype were more likely to have high RI for distance recurrence (RI-DR) and local recurrence (RI-LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2-negative) BC patients, which may help in clinical decision-making for individual treatment.}, }
@article {pmid35907957, year = {2022}, author = {Oehler, D and Spychala, A and Gödecke, A and Lang, A and Gerdes, N and Ruas, J and Kelm, M and Szendroedi, J and Westenfeld, R}, title = {Full-length transcriptomic analysis in murine and human heart reveals diversity of PGC-1α promoters and isoforms regulated distinctly in myocardial ischemia and obesity.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {169}, pmid = {35907957}, issn = {1741-7007}, mesh = {Alternative Splicing ; Animals ; Humans ; Mice ; *Myocardial Ischemia/genetics ; Obesity/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; Protein Isoforms/genetics ; RNA, Messenger/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) acts as a transcriptional coactivator and regulates mitochondrial function. Various isoforms are generated by alternative splicing and differentially regulated promoters. In the heart, total PGC-1α deficiency knockout leads to dilatative cardiomyopathy, but knowledge on the complexity of cardiac isoform expression of PGC-1α remains sparse. Thus, this study aims to generate a reliable dataset on cardiac isoform expression pattern by long-read mRNA sequencing, followed by investigation of differential regulation of PGC-1α isoforms under metabolic and ischemic stress, using high-fat-high-sucrose-diet-induced obesity and a murine model of myocardial infarction.<br><br>RESULTS: Murine (C57Bl/6J) or human heart tissue (obtained during LVAD-surgery) was used for long-read mRNA sequencing, resulting in full-length transcriptomes including 58,000 mRNA isoforms with 99% sequence accuracy. Automatic bioinformatic analysis as well as manual similarity search against exonic sequences leads to identification of putative coding PGC-1&#x3b1; isoforms, validated by PCR and Sanger sequencing. Thereby, 12 novel transcripts generated by hitherto unknown splicing events were detected. In addition, we postulate a novel promoter with homologous and strongly conserved sequence in human heart. High-fat diet as well as ischemia/reperfusion (I/R) injury transiently reduced cardiac expression of PGC-1&#x3b1; isoforms, with the most pronounced effect in the infarcted area. Recovery of PGC-1&#x3b1;-isoform expression was even more decelerated when I/R was performed in diet-induced obese mice.<br><br>CONCLUSIONS: We deciphered for the first time a complete full-length transcriptome of the murine and human heart, identifying novel putative PGC-1&#x3b1; coding transcripts including a novel promoter. These transcripts are differentially regulated in I/R and obesity suggesting transcriptional regulation and alternative splicing that may modulate PGC-1&#x3b1; function in the injured and metabolically challenged heart.}, }
@article {pmid35906698, year = {2022}, author = {Lee, S and Osmanbeyoglu, HU}, title = {Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.}, journal = {Breast cancer research : BCR}, volume = {24}, number = {1}, pages = {54}, pmid = {35906698}, issn = {1465-542X}, support = {R00 CA207871/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Chromatin/genetics ; Female ; Humans ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored.<br><br>METHODS: Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq)&#xa0;dataset.<br><br>RESULTS: We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC.<br><br>CONCLUSIONS: This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.}, }
@article {pmid35898837, year = {2023}, author = {Suzuki, Y and Hoshi, K and Tominaga, K and Inaba, Y and Yoshinaga, T and Kojimahara, S and Maki, R and Nemoto, R and Tetsuka, Y and Kawata, Y and Yamamiya, A and Sugaya, T and Iso, Y and Takada-Owada, A and Ishida, K and Goda, K and Irisawa, A}, title = {A case of obstructive jaundice caused by metastasis of breast cancer to the intra/extrahepatic bile duct.}, journal = {DEN open}, volume = {3}, number = {1}, pages = {e144}, pmid = {35898837}, issn = {2692-4609}, abstract = {A 38-year-old woman was admitted to our hospital for a detailed examination of jaundice. Three years before, she had undergone a right total mastectomy and axillary lymph node dissection of her right breast because of cancer. Histopathological evaluation revealed invasive ductal carcinoma. Postoperatively, because multiple bone metastases were found, she underwent chemoradiotherapy. Endoscopic retrograde cholangiopancreatography was performed, which revealed widespread multiple stenoses with a smooth surface from the intrahepatic to the extrahepatic bile duct. A transpapillary biliary biopsy was performed. Histopathological examination revealed adenocarcinoma extending into the subepithelium of the bile duct. The obtained cancer cells were similar to those of the earlier invasive breast cancer. This rare case demonstrates bile duct metastasis of breast cancer with specific endoscopic retrograde cholangiopancreatography findings.}, }
@article {pmid35880762, year = {2022}, author = {Billeter, AT and Scheurlen, KM and Israel, B and Straub, BK and Schirmacher, P and Kopf, S and Nawroth, PP and Müller-Stich, BP}, title = {Gastric Bypass Resolves Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Low-BMI Patients: A Prospective Cohort Study.}, journal = {Annals of surgery}, volume = {276}, number = {5}, pages = {814-821}, pmid = {35880762}, issn = {1528-1140}, mesh = {Adipokines ; Adolescent ; Adult ; Aged ; Blood Glucose/metabolism ; Body Mass Index ; C-Peptide ; *Diabetes Mellitus, Type 2/complications ; *Gastric Bypass ; *Gastrointestinal Hormones/metabolism ; Glucagon ; Glycated Hemoglobin/metabolism ; Humans ; Insulin ; *Liver Diseases/complications ; Middle Aged ; *Obesity, Morbid/complications/metabolism/surgery ; Prospective Studies ; Sirtuin 1 ; Young Adult ; }, abstract = {OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.<br><br>METHODS: Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35&#xa0;kg/m 2 , glucagon-stimulated C-peptide of >1.5&#xa0;ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.<br><br>RESULTS: MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45&#xb1;0.27% to 7.09&#xb1;0.26%, P =0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and &#x3b2;-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.<br><br>CONCLUSIONS: RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.}, }
@article {pmid35880695, year = {2023}, author = {Zhang, J and Lin, H and Hou, L and Xiao, H and Gong, X and Guo, X and Cao, X and Liu, Z}, title = {Exploration of the breast ductal carcinoma in situ signature and its prognostic implications.}, journal = {Cancer medicine}, volume = {12}, number = {3}, pages = {3758-3772}, pmid = {35880695}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Prognosis ; Prospective Studies ; *Breast Neoplasms/pathology ; Kaplan-Meier Estimate ; Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/pathology ; Protein Serine-Threonine Kinases ; NIMA-Related Kinases ; }, abstract = {Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%-50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time-dependent receiver operating characteristic (ROC), Kaplan-Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein-protein interaction). A unique six-gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision-making for individual care.}, }
@article {pmid35866222, year = {2022}, author = {Khanam, R and Islam, S and Rahman, S and Ahmed, S and Islam, A and Hasan, T and Hasan, E and Chowdhury, NH and Roy, AD and Jaben, IA and Nehal, AA and Yoshida, S and Manu, AA and Raqib, R and McCollum, ED and Shahidullah, M and Jehan, F and Sazawal, S and Bahl, R and Baqui, AH}, title = {Sero-prevalence and risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in a rural district of Bangladesh: A cohort study.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05030}, pmid = {35866222}, issn = {2047-2986}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Antibodies, Viral ; Bangladesh/epidemiology ; *COVID-19/epidemiology ; Child ; Cohort Studies ; Communicable Disease Control ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Seroepidemiologic Studies ; }, abstract = {BACKGROUND: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh.<br><br>METHODS: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n&#x2009;=&#x2009;2683) and their children (n&#x2009;=&#x2009;2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys&#xae; test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models.<br><br>RESULTS: Overall, about one-third of women (35.8%, 95% CI&#x2009;=&#x2009;33.7-37.9) and one-fifth of children (21.3%, 95% CI&#x2009;=&#x2009;19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR&#x2009;=&#x2009;1.19,95% CI&#x2009;=&#x2009;1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR&#x2009;=&#x2009;1.16, &#x2009;95% CI&#x2009;=&#x2009;1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR&#x2009;=&#x2009;1.37, 95% CI&#x2009;=&#x2009;1.10-1.71) than in children with a paternal education of &#x2264;5 years.<br><br>CONCLUSIONS: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential.}, }
@article {pmid35864546, year = {2022}, author = {Zhu, S and Zhao, J and Nie, L and Yin, W and Zhang, Y and Zhao, F and Ni, Y and Zhang, X and Wang, Z and Dai, J and Liu, Z and Chen, J and Zeng, Y and Wang, Z and Sun, G and Liang, J and Zhao, X and Zhu, X and Tao, R and Yang, J and He, B and Chen, N and Shen, P and Zeng, H}, title = {Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {237}, pmid = {35864546}, issn = {1741-7015}, mesh = {*Adenocarcinoma/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Homologous Recombination/genetics ; Humans ; Male ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.<br><br>METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.<br><br>RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score&#x2265;21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.<br><br>CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.}, }
@article {pmid35855704, year = {2022}, author = {Bhatia, JK and Chaudhary, T and Boruah, D and Bharadwaj, R}, title = {Study of angiogenesis in invasive breast carcinoma by morphometry and immunohistochemistry.}, journal = {Medical journal, Armed Forces India}, volume = {78}, number = {3}, pages = {345-354}, pmid = {35855704}, issn = {0377-1237}, abstract = {BACKGROUND: Breast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma.<br><br>METHODS: Angiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences&#xa0;(Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients &#x3c1; were calculated.<br><br>RESULTS: The vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (&#x3c1;&#xa0;=&#xa0;0.467), MVD-CD34 (&#x3c1;&#xa0;=&#xa0;0.422) and VC-CD34 (&#x3c1;&#xa0;=&#xa0;0.482); and moderate positive correlation with TVBD-CD34 (&#x3c1;&#xa0;=&#xa0;0.615), VC-CD105 (&#x3c1;&#xa0;=&#xa0;0.527), and TVBD-CD105 (&#x3c1;&#xa0;=&#xa0;0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (&#x3c1;&#xa0;=&#xa0;0.295), TVBD-CD34 (&#x3c1;&#xa0;=&#xa0;0.339), and TVBD-CD105 ((&#x3c1;&#xa0;=&#xa0;0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber&#xa0;vessels.<br><br>CONCLUSIONS: In this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.}, }
@article {pmid35855193, year = {2022}, author = {Somashekhar, SP and Jaiswal, R and Kumar, R and Ashok, BC and Rakshit, S and Rauthan, A and Patil, P and Yashas, N and Karthik, HK and Prasad, A and Islam, H and Ashwin, KR}, title = {An Overview of the Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy in Operable Breast Cancer in a Tertiary Care Centre in South India.}, journal = {European journal of breast health}, volume = {18}, number = {3}, pages = {271-278}, pmid = {35855193}, issn = {2587-0831}, abstract = {OBJECTIVE: The incidence of female breast cancer in the world is 11.7% with a mortality rate of 6.9%. According to Globocon 2020, breast cancer is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer-related death amongst women worldwide. The purpose of this study was to analyze the impact of Body Mass Index (BMI) on pathological complete response (pCR) rates for operable breast cancer after neoadjuvant chemotherapy (NACT). The primary endpoint was to assess histopathological features of the surgical specimen in response to NACT and to investigate the relationship with pre-chemotherapy BMI taking into account the various molecular subtypes of breast cancer.<br><br>MATERIALS AND METHODS: Patients with biopsy-proven breast carcinoma who underwent surgery after NACT between January 2017 and May 2021 were included. All patients were initially divided into three groups depending on their pre-chemotherapy BMI. With BMI <22.9 as normal or underweight category, BMI of 23-27.4, was taken as overweight category and BMI &#x2265;27.5 as obese category.<br><br>RESULTS: The study included 184 patients. Normal weight patients had the highest rate of pCR (75%) and the lowest was seen in the obese category (33.75%). Furthermore, the subtype most likely to achieve pCR was HER2+/ER negative followed by triple negative BC with odds ratios of 3.46 and 2.21, respectively.<br><br>CONCLUSION: This retrospective study established that overweight and obese patients suffering from breast carcinoma had a lessened pCR rate following NACT in comparison with those who were under-/normal weight.}, }
@article {pmid35852797, year = {2022}, author = {Tokura, M and Nakayama, J and Prieto-Vila, M and Shiino, S and Yoshida, M and Yamamoto, T and Watanabe, N and Takayama, S and Suzuki, Y and Okamoto, K and Ochiya, T and Kohno, T and Yatabe, Y and Suto, A and Yamamoto, Y}, title = {Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ.}, journal = {Cancer research}, volume = {82}, number = {18}, pages = {3236-3248}, doi = {10.1158/0008-5472.CAN-22-0090}, pmid = {35852797}, issn = {1538-7445}, mesh = {Biomarkers ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Female ; Gene Expression Profiling ; Humans ; }, abstract = {UNLABELLED: Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The frequency of DCIS is increasing because of routine mammography; however, the biological features and intratumoral heterogeneity of DCIS remain obscure. To address this deficiency, we performed single-cell transcriptomic profiling of DCIS and invasive ductal carcinoma (IDC). DCIS was found to be composed of several transcriptionally distinct subpopulations of cancer cells with specific functions. Several transcripts, including long noncoding RNAs, were highly expressed in IDC compared with DCIS and might be related to the invasive phenotype. Closeness centrality analysis revealed extensive heterogeneity in DCIS, and the prediction model for cell-to-cell interactions implied that the interaction network among luminal cells and immune cells in DCIS was comparable with that in IDC. In addition, transcriptomic profiling of HER2+ luminal DCIS indicated HER2 genomic amplification at the DCIS stage. These data provide novel insight into the intratumoral heterogeneity and molecular features of DCIS, which exhibit properties similar to IDC.<br><br>SIGNIFICANCE: Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.}, }
@article {pmid35842661, year = {2022}, author = {Zhang, WT and Zhu, GL and Xu, WQ and Zhang, W and Wang, HZ and Wang, YB and Li, YX}, title = {Association of PD-1/PD-L1 expression and Epstein--Barr virus infection in patients with invasive breast cancer.}, journal = {Diagnostic pathology}, volume = {17}, number = {1}, pages = {61}, pmid = {35842661}, issn = {1746-1596}, support = {No.2008085QH408//Natural Science Foundation of Anhui Province/ ; No.81874063//National Natural Science Foundation of China/ ; }, mesh = {B7-H1 Antigen/metabolism ; Biomarkers, Tumor/analysis ; *Breast Neoplasms ; *Epstein-Barr Virus Infections/complications ; Female ; Herpesvirus 4, Human ; Humans ; Ligands ; Prognosis ; Programmed Cell Death 1 Receptor ; }, abstract = {PURPOSE: Causative factors of breast cancer include infections, such as Epstein-Barr virus (EBV) infection. The aim of this study was to analyze the clinicopathological features of EBV-positive (IBC) and determine if EBV affects programmed cell death receptor 1 (PD-1)/PD ligand 1 (PD-L1) expression in IBC, similar to other EBV-infected tumors with PD-L1/PD-1 expression.<br><br>METHODS: We collected 140 samples of IBC tissues and 25 samples of adjacent tissues. All patients were followed-up by telephone from the day of surgery to December 2020. Chromogenic in-situ hybridization was performed to evaluate EBV-encoded RNA (EBER). Immunohistochemistry was performed to evaluate PD-L1 and PD-1 expressions. The correlation between PD1/PDL1 expression and clinicopathological features was also analyzed.<br><br>RESULTS: EBER was detected in 57 of 140 (40.7%) IBC tissues and not detected in any adjacent tissue (P&#x2009;<&#x2009;0.05). Clinicopathologic features of patients were consistent with EBV-associated IBC. EBV infection was correlated with the mass size, menopausal status, axillary lymph node metastasis, vascular invasion, Ki-67 index, clinical stage, and estrogen receptor and progesterone receptor expressions (all P&#x2009;<&#x2009;0.05), but not with the histological type, invasive ductal carcinoma histological grade, or human epidermal growth factor receptor 2 (HER2) expression (all P&#x2009;>&#x2009;0.05). The positive rate of PD-1/PD-L1 expression was higher in the EBV-positive group than in the EBV-negative group (P&#x2009;<&#x2009;0.05). The Kaplan-Meier univariate survival analysis showed that EBV was associated with poor disease-free survival and overall survival in patients with IBC. PD-L1/PD-1 expression could predict a poor prognosis.<br><br>CONCLUSIONS: In this study, clinicopathologic characteristics of patients were consistent with EBV-infected IBC. Patients with EBV-positive breast cancer were more likely to have elevated PD-1/PDL-1 expression compared to those with EBV-negative breast cancer. This finding could serve as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC.}, }
@article {pmid35834927, year = {2022}, author = {Syamsu, SA and Setiady, R and Smaradania, N and Prihantono,  and Irsandy, F and Faruk, M}, title = {Synchronous breast cancer and non-Hodgkin lymphoma: A case report.}, journal = {International journal of surgery case reports}, volume = {97}, number = {}, pages = {107398}, pmid = {35834927}, issn = {2210-2612}, abstract = {INTRODUCTION: Among women, breast cancer (BC) is the most prevalent type of cancer and the top cause of cancer deaths. Although non-Hodgkin lymphoma (NHL) is the most prevalent hematological cancer, it is rarely reported synchronous with BC. Moreover, which malignancy appears first can rarely be explained because they are usually detected incidentally while diagnosing and treating other malignancies. This paper reports a case of invasive ductal carcinoma (IDC) concomitant with NHL.<br><br>PRESENTATION OF CASE: A 35-year-old woman presented with simultaneous IDC in the left breast and NHL in a lymph node in the neck. The patient underwent a modified radical mastectomy for stage IIIA IDC and received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for stage I NHL.<br><br>CLINICAL DISCUSSION: Treating BC and NHL remains challenging due to their significantly different management, the lack of guidelines for treating BC and lymphoma simultaneously, and uncertainty about whether synchronous tumors should be treated separately as distinct clinical entities or as one disease with treatment covering both. Therefore, the best approach continues to be focusing on the most biologically aggressive malignancies.<br><br>CONCLUSION: The enlargement of lymph nodes not in the lymphatic drainage of the primary tumor should be suspected of indicating multiple primary malignancies until proven otherwise. For patients with luminal-B BC, NHL chemotherapy can involve receiving the R-CHOP regimen, including doxorubicin and cyclophosphamide, which can help to mitigate BC.}, }
@article {pmid35821630, year = {2022}, author = {Ciudad, P and Escandón, JM and Manrique, OJ and Gutierrez-Arana, J and Mayer, HF}, title = {Lymphedema prevention and immediate breast reconstruction with simultaneous gastroepiploic vascularized lymph node transfer and deep inferior epigastric perforator flap: A case report.}, journal = {Microsurgery}, volume = {42}, number = {6}, pages = {617-621}, doi = {10.1002/micr.30939}, pmid = {35821630}, issn = {1098-2752}, mesh = {*Breast Neoplasms/complications/surgery ; Female ; Humans ; Lymph Nodes/blood supply ; *Lymphedema/etiology/prevention &amp; control/surgery ; *Mammaplasty/adverse effects/methods ; Mastectomy/adverse effects ; Middle Aged ; *Perforator Flap/blood supply ; }, abstract = {Breast cancer-related lymphedema following axillary lymph node dissection (ALND) has been documented in 6%-55% of patients, mostly occurring within the next 3 years after radiation or surgery. We present a case of a 53-year-old patient with hormone positive, stage IB, left breast invasive ductal carcinoma treated with immediate lymphatic and microvascular breast reconstruction (MBR) using vascularized lymph node transfer (VLNT) for lymphedema prevention. A deep inferior epigastric perforator (DIEP) flap (18.3 × 11.2-cm) and simultaneous prophylactic gastroepiploic-VLNT (7 × 3-cm), orthotopically inset in the axilla, were used for reconstruction following mastectomy and radical ALND. The procedure was uneventful. The patient did not display increased postoperative arm circumferences. ICG lymphography did not show any changes at 2- and 3-years after surgery. Preventive lymphatic reconstruction with GE-VLNT and immediate MBR using the DIEP flap offers a new possibility for the primary prevention of lymphedema and simultaneous immediate autologous breast reconstruction without the risk of iatrogenic lymphedema. Further studies will be directed to unveil the external validity of these findings and the risk reduction rate of this approach.}, }
@article {pmid35804316, year = {2022}, author = {Chang, C and Zhu, J and Li, H and Yang, Q}, title = {Enhanced magnetic resonance imaging manifestations of paediatric intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: case report and literature review.}, journal = {BMC pediatrics}, volume = {22}, number = {1}, pages = {400}, pmid = {35804316}, issn = {1471-2431}, mesh = {*Calcinosis/diagnostic imaging ; Cervical Vertebrae/diagnostic imaging ; Child ; Female ; Humans ; *Intervertebral Disc/diagnostic imaging/pathology ; Longitudinal Ligaments/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; *Ossification of Posterior Longitudinal Ligament/complications/diagnostic imaging ; Osteogenesis ; }, abstract = {BACKGROUND: Since the first description of paediatric intervertebral disc calcification (IDC) by Báron in 1924, only approximately 400 cases have been reported in the literature. Paediatric IDC combined with ossification of the posterior longitudinal ligament (OPLL) is an even rarer condition, with only 8 cases described in detail to date. In this paper, we present a review of the disease characteristics described in the relevant English language literature and discuss the possible mechanisms of lesion enhancement in contrast-enhanced magnetic resonance imaging (MRI).<br><br>CASE PRESENTATION: In May 2020, a 6-year-old Han nationality girl presented with the chief complaint of neck pain that had lasted for a week. She did not report a history of trauma or a past illness. On admission, there was no personal and family history, congenital diseases, or non-specific infections such as tuberculosis, among others. Further physical examination revealed that the movement of her cervical spine was limited. Computed tomography (CT) and MRI revealed ossification of the intervertebral discs and posterior longitudinal ligament (PLL) at the C4/5 levels and an absence of obvious spinal cord compression. When contrast-enhanced MRI was performed, significant enhancement was observed in the intervertebral discs and PLL at the C4/5 level. We adopted a non-interventional approach and performed an imaging re-examination 8 months later. Both the plain and contrast-enhanced MRI scans indicated swelling in the C4/5 intervertebral discs and disappearance of the previously observed enhancement in the nucleus pulposus (NP) and PLL at the corresponding levels; CT examination revealed that the ossified lesions had been completely resorbed.<br><br>CONCLUSION: Obvious lesion enhancement in contrast-enhanced MRI is an extremely rare manifestation of paediatric IDC combined with OPLL. However, the exact mechanisms of this phenomenon remain unclear. We surmise that it may be caused by a series of biophysical changes related to vertebral endplate injury and repair, but further research will be required for in-depth investigation.}, }
@article {pmid35776197, year = {2022}, author = {Rakshit, S and Sunny, JS and George, M and Hanna, LE and Leela, KV and Sarkar, K}, title = {T helper cell-mediated epitranscriptomic regulation via m6A RNA methylation bridges link between coronary artery disease and invasive ductal carcinoma.}, journal = {Journal of cancer research and clinical oncology}, volume = {148}, number = {12}, pages = {3421-3436}, pmid = {35776197}, issn = {1432-1335}, support = {ECR/2016/000965//Science and Engineering Research Board/ ; }, mesh = {Humans ; Female ; Methylation ; *Coronary Artery Disease/genetics ; Tumor Suppressor Protein p53 ; RNA/genetics ; T-Lymphocytes, Helper-Inducer ; Lactate Dehydrogenases ; *Carcinoma, Ductal ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) and coronary artery disease (CAD), remains the greatest cause of death annually in women, driven by complex signalling pathways and shared several predisposing risk factors together. Therefore, it is important to find out the common epigenetic modifications which are responsible for possible disease progression from CAD to IDC.<br><br>METHODS: CD4+T cell isolation by MACS, RT2 profiler PCR array, Gene ontology study, m6A RNA methylation, ChIP-qPCR, Q-PCR, CRISPR/Cas9-mediated knockout/overexpression, Lactate dehydrogenase release assay, RDIP-qPCR.<br><br>RESULTS: We have identified several epigenetic regulators (e.g., VEGFA, AIMP1, etc.) which are mainly involved in inflammatory pathways in both the diseased conditions. Epitranscriptomic alterations such as m6A RNA methylation found abnormal in CD4+T helper cells in both IDC as well as CAD. CRISPR-Cas9 mediated knockout/overexpression of specific gene (BRCA1) are promising therapeutic approaches in diseased conditions by regulating m6A RNA methylation and also tumor suppressor gene P53. It also affected the R-loop formation which is vulnerable to DNA damage and BRCA1 can also induce CTL mediated cytotoxicity in breast cancer cells.<br><br>CONCLUSIONS: Therefore, by understanding the modifications of epigenetic mechanisms, their alterations and interactions will aid in the development of newer therapeutic approaches to stop the possible spread from one disease to another.}, }
@article {pmid35749404, year = {2022}, author = {Hardeman, AA and Han, YJ and Grushko, TA and Mueller, J and Gomez, MJ and Zheng, Y and Olopade, OI}, title = {Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.}, journal = {PloS one}, volume = {17}, number = {6}, pages = {e0268693}, pmid = {35749404}, issn = {1932-6203}, support = {K12 CA139160/CA/NCI NIH HHS/United States ; UL1 RR024999/RR/NCRR NIH HHS/United States ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; DNA Copy Number Variations ; Female ; Humans ; Protein Serine-Threonine Kinases ; RNA, Messenger/genetics ; *Triple Negative Breast Neoplasms/genetics ; }, abstract = {Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.}, }
@article {pmid35749114, year = {2022}, author = {Weis, S and Hagel, S and Palm, J and Scherag, A and Kolanos, S and Bahrs, C and Löffler, B and Schmitz, RPH and Rißner, F and Brunkhorst, FM and Pletz, MW and , }, title = {Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {5}, number = {6}, pages = {e2218515}, pmid = {35749114}, issn = {2574-3805}, mesh = {Adolescent ; Aged ; *Bacteremia/therapy ; *Communicable Diseases ; Female ; Hospitals ; Humans ; Male ; Referral and Consultation ; Retrospective Studies ; *Staphylococcal Infections/therapy ; Staphylococcus aureus ; Telephone ; Treatment Outcome ; }, abstract = {IMPORTANCE: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals.<br><br>OBJECTIVES: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB.<br><br>This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n&#x2009;=&#x2009;59); palliative care (n&#x2009;=&#x2009;41); recurrence of SAB (n&#x2009;=&#x2009;9); discharge from the hospital before enrollment (n&#x2009;=&#x2009;77); age younger than 18 years (n&#x2009;=&#x2009;5); duplicate report from a single patient (n&#x2009;=&#x2009;26); late report (n&#x2009;=&#x2009;17); blood culture reported during the washout phase (n&#x2009;=&#x2009;48); and no signed informed consent for other or unknown reasons (n&#x2009;=&#x2009;361).<br><br>INTERVENTIONS: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included.<br><br>MAIN OUTCOMES AND MEASURES: Thirty-day all-cause mortality.<br><br>RESULTS: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P&#x2009;=&#x2009;.81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P&#x2009;=&#x2009;.62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P&#x2009;=&#x2009;.89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P&#x2009;=&#x2009;.90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P&#x2009;=&#x2009;.01).<br><br>CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB.<br><br>TRIAL REGISTRATION: drks.de Identifier: DRKS00010135.}, }
@article {pmid35743985, year = {2022}, author = {Ortega, MA and Fraile-Martinez, O and García-Montero, C and Borja-Vergel, S and Torres-Carranza, D and Pekarek, L and Arribas, CB and De León-Luis, JA and Sánchez-Rojo, C and Alvarez-Mon, MA and García-Honduvilla, N and Buján, J and Coca, S and Alvarez-Mon, M and Saez, MA and Guijarro, LG}, title = {Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {6}, pages = {}, pmid = {35743985}, issn = {1648-9144}, support = {MITICAD//Comunidad de Madrid/ ; }, mesh = {*Breast Neoplasms/drug therapy/genetics ; *Carcinoma, Ductal, Breast/diagnosis/drug therapy/genetics ; *Carcinoma, Lobular/pathology ; Cyclin D1/therapeutic use ; Cyclooxygenase 2 ; Female ; Humans ; Insulin Receptor Substrate Proteins/genetics ; }, abstract = {Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.}, }
@article {pmid35739035, year = {2022}, author = {Clawson, A and Zahir, SF and Stewart, S and Torr, S and Hempenstall, N and Vernon, C and Subedi, S}, title = {Characteristics and outcomes of hospitalised inpatients with indwelling urinary catheter-a retrospective study from a large regional hospital in Queensland.}, journal = {Infection, disease &amp; health}, volume = {27}, number = {4}, pages = {219-226}, doi = {10.1016/j.idh.2022.05.004}, pmid = {35739035}, issn = {2468-0869}, mesh = {Adult ; Humans ; Urinary Catheters/adverse effects ; Catheters, Indwelling/adverse effects ; Retrospective Studies ; Urinary Catheterization/adverse effects ; *Catheter-Related Infections/epidemiology/etiology ; Inpatients ; Queensland/epidemiology ; *Urinary Tract Infections/epidemiology/etiology ; Hospitals ; }, abstract = {BACKGROUND: Indwelling urinary catheters (IDCs) are a common invasive device in hospitalised patients. Their use is associated with increased risks of developing catheter associated urinary tract infections (CAUTI), and blood stream infections (BSI).<br><br>AIMS: To examine the characteristics and outcomes of adult inpatients with an IDC inserted in hospital and identify risk factors for developing CAUTI and BSI.<br><br>METHODS: We performed a retrospective observational study of 430 patients with IDC admitted to medical and surgical units of a leading (tertiary) hospital between Nov 2019 till April 2020. Multiple logistic regression analysis was performed to determine independent risk factors for developing urinary tract infection and blood stream infection.<br><br>RESULTS: The prevalence of CAUTI in our study was 7.4%. Results of multiple logistic regression indicated that with each day of IDC in situ, the likelihood of UTI development increased by 9% (OR 1.09; 95% CI 1.00 to 1.18; p&#xa0;=&#xa0;0.03). Age, gender, and catheter reinsertion were not associated with UTI development.<br><br>CONCLUSIONS: Longer duration of IDC was associated with elevated risk of developing CAUTI. CAUTI rates were higher than some of those previously published. There was no statistical significance in frequency of CAUTI between medical and surgical patients. No statistically significant variables that contributed to the development of BSI were found. Interventions targeted at reducing catheter days should be used to improve CAUTI rates.}, }
@article {pmid35714104, year = {2022}, author = {Icht, M and Bergerzon-Bitton, O and Ben-David, BM}, title = {Validation and cross-linguistic adaptation of the Frenchay Dysarthria Assessment (FDA-2) speech intelligibility tests: Hebrew version.}, journal = {International journal of language &amp; communication disorders}, volume = {57}, number = {5}, pages = {1023-1049}, pmid = {35714104}, issn = {1460-6984}, mesh = {Aged ; *Dysarthria/psychology ; Humans ; Linguistics ; Reproducibility of Results ; Speech Disorders/complications ; *Speech Intelligibility ; Speech Production Measurement/methods ; Young Adult ; }, abstract = {'Dysarthria' is a group of motor speech disorders resulting from a disturbance in neuromuscular control. Most individuals with dysarthria cope with communicative restrictions due to speech impairments and reduced intelligibility. Thus, language-sensitive measurements of intelligibility are important in dysarthria neurological assessment. The Frenchay Dysarthria Assessment, 2nd edition (FDA-2), is a validated tool for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. The current study conducted a careful culture- and linguistic-sensitive adaption of the two intelligibility subtests of the FDA-2 to Hebrew (words and sentences) and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (acquired dysarthria, n = 15; and developmental dysarthria, n = 19). Analysis indicated that the new subtests were found to be specific and sensitive, valid and reliable, as scores significantly differ between healthy older adults and adults with dysarthria, correlated with other subjective measures of intelligibility, and showed high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers, thus may be an important addition to the speech-language pathologist's toolbox, for clinical work as well as for research purposes. WHAT THIS PAPER ADDS: What is already known on the subject 'Dysarthria' is a group of disorders reflecting impairments in the strength, speed and precision of movements required for adequate control of the various speech subsystems. Reduced speech intelligibility is one of the main consequences of all dysarthria subtypes, irrespective of their underlying cause. Indeed, most individuals with dysarthria cope with communicative restrictions due to speech impairments. Thus, language-sensitive measurements of intelligibility are important in dysarthria assessment. The FDA-2's words and sentences subtests present standardized and validated tools for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. What this paper adds to existing knowledge The lack of assessment tools in Hebrew poses challenges to clinical evaluation as well as research purposes. The current study conducted a careful culture- and linguistic-sensitive adaption of the FDA-2 intelligibility subtests to Hebrew and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (adults with acquired dysarthria, n = 15; and young adults with developmental dysarthria, n = 19). What are the potential or actual clinical implications of this work? Analyses indicated that the new word and sentence subtests are specific, sensitive, valid and reliable. Namely, (1) they successfully differentiate between healthy individuals and individuals with dysarthria; (2) they correlate with other subjective measures of intelligibility; and (3) they show high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers. Thus, they may be an important addition to the speech-language pathologist's toolbox, for clinical and research purposes. The methods described here can be emulated for the adaptation of speech assessment tools to other languages.}, }
@article {pmid35711899, year = {2022}, author = {Choi, JDW and Hughes, TMD and Marx, G and Boyages, J and Rutovitz, J and Hasovits, C and Parasyn, A and Edirimanne, S and Ngui, NK}, title = {The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.}, journal = {The breast journal}, volume = {2022}, number = {}, pages = {1199245}, pmid = {35711899}, issn = {1524-4741}, mesh = {Australia ; *Breast Neoplasms/drug therapy/genetics/pathology ; Female ; Gene Expression Profiling/methods ; Humans ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Receptors, Estrogen/genetics ; Retrospective Studies ; }, abstract = {INTRODUCTION: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score.<br><br>METHODS: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS&#x2009;<&#x2009;11) (n&#x2009;=&#x2009;10, 14%), intermediate risk (RS 11-25) (n&#x2009;=&#x2009;45, 63%), and high risk (RS&#x2009;>&#x2009;25) (n&#x2009;=&#x2009;16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20&#x2009;mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67%&#x2009;>&#x2009;14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%).<br><br>CONCLUSION: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.}, }
@article {pmid35697697, year = {2022}, author = {Rebbeck, CA and Xian, J and Bornelöv, S and Geradts, J and Hobeika, A and Geiger, H and Alvarez, JF and Rozhkova, E and Nicholls, A and Robine, N and Lyerly, HK and Hannon, GJ}, title = {Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3399}, pmid = {35697697}, issn = {2041-1723}, support = {A21143/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; Homeodomain Proteins/genetics/metabolism ; Humans ; Transcription Factors/genetics ; Transcriptome ; }, abstract = {Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.}, }
@article {pmid35695947, year = {2023}, author = {Gur, N and Zimmerman-Brenner, S and Fattal-Valevski, A and Rotstein, M and Pilowsky Peleg, T}, title = {Group comprehensive behavioral intervention for tics contribution to broader cognitive and emotion regulation in children.}, journal = {European child &amp; adolescent psychiatry}, volume = {32}, number = {10}, pages = {1925-1933}, pmid = {35695947}, issn = {1435-165X}, mesh = {Adolescent ; Child ; Humans ; *Tics/therapy/complications ; *Emotional Regulation ; Severity of Illness Index ; *Tic Disorders/psychology ; *Tourette Syndrome/psychology ; Cognition ; }, abstract = {There is increasing evidence for the effectiveness of behavioral techniques in managing tics in youth with Tourette syndrome and tics disorders (TDs). One such intervention is Comprehensive Behavioral Intervention for Tics (CBIT), which focuses on reducing tic severity by training control and regulation. In view of the regulation deficits characteristic to TDs, in the current study, we aimed to explore the contribution of CBIT beyond tic control, to a wider expression of regulation abilities-cognitive inhibition and emotion regulation. A total of 55 participants with TDs, aged 8-15, who were randomly assigned to group-CBIT or group-Educational Intervention for Tics, were compared on cognitive inhibition tests and use of emotion-regulation strategies, pre- and post-intervention. Whereas on none of the scales a significant interaction effect was found reflecting superiority of CBIT over EIT, repeated measures ANOVA revealed a significant time effect, with post hoc analyses indicating that cognitive inhibition and cognitive reappraisal significantly increased following CBIT intervention only. Within the group-CBIT, the increase in cognitive reappraisal was associated with higher intellectual ability. These findings may lead to a broader understanding of CBIT contribution to more than tic control, but rather to better cognitive and emotional regulation abilities.}, }
@article {pmid35695563, year = {2022}, author = {Agostinetto, E and Nader-Marta, G and Paesmans, M and Ameye, L and Veys, I and Buisseret, L and Neven, P and Taylor, D and Fontaine, C and Duhoux, FP and Canon, JL and Denys, H and Coussy, F and Chakiba, C and Ribeiro, JM and Piccart, M and Desmedt, C and Ignatiadis, M and Aftimos, P}, title = {ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.}, journal = {Future oncology (London, England)}, volume = {18}, number = {22}, pages = {2383-2392}, doi = {10.2217/fon-2022-0358}, pmid = {35695563}, issn = {1744-8301}, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; Cadherins ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/pathology ; Clinical Trials, Phase II as Topic ; Female ; Humans ; Neoadjuvant Therapy ; Protein-Tyrosine Kinases/therapeutic use ; Proto-Oncogene Proteins ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.}, }
@article {pmid35687769, year = {2022}, author = {Silva, DJ and Miranda, G and Mesquita, A}, title = {Clinical relevance of receptor conversion in metastatic breast cancer: Case report.}, journal = {Medicine}, volume = {101}, number = {23}, pages = {e29136}, pmid = {35687769}, issn = {1536-5964}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/therapy ; Disease Progression ; Female ; Humans ; Mastectomy ; Quality of Life ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {INTRODUCTION: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression.<br><br>PATIENT CONCERNS: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012.<br><br>DIAGNOSIS: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative.<br><br>INTERVENTIONS: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300&#x200a;mg twice daily for 28 days was initiated.<br><br>OUTCOMES: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events.<br><br>CONCLUSION: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.}, }
@article {pmid35666367, year = {2022}, author = {Zhang, Y and Luo, X and Chen, M and Yang, L and Lei, T and Pu, T and Wei, B and Bu, H and Zhang, Z}, title = {Biomarker profile of invasive lobular carcinoma: pleomorphic versus classic subtypes, clinicopathological characteristics and prognosis analyses.}, journal = {Breast cancer research and treatment}, volume = {194}, number = {2}, pages = {279-295}, pmid = {35666367}, issn = {1573-7217}, support = {2022YFS0376//Department of Science and Technology of Sichuan Province/ ; }, mesh = {*Breast Neoplasms ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Lobular/pathology ; Female ; Humans ; Ki-67 Antigen/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; }, abstract = {PURPOSE: To compare the clinicopathologic features and prognosis of pleomorphic invasive lobular carcinoma (P-ILC) and classic ILC (C-ILC) according to the biomarker profile.<br><br>METHODS: A total of 667 C-ILCs and 133 P-ILCs between 2011 and 2021 were included. Clinicopathologic features and stromal tumor-infiltrating lymphocytes (sTILs) status were evaluated. P-ILCs were divided into subtypes based on ER/PR and HER2 expression. The overall survival and disease-free survival (DFS) of patients were compared among matched P-ILCs, C-ILCs, and invasive ductal carcinomas (IDCs) with biomarker subtypes.<br><br>RESULTS: Compared to C-ILCs, P-ILCs had greater tumor sizes and stages, fewer ER-positive, more HER2-positive, triple negative (TN), and Ki-67&#x2009;>&#x2009;20% tumors (P&#x2009;<&#x2009;0.05). P-ILCs were subdivided into ER+&#x2009;(63.1%), HER2+&#x2009;(21.1%) and TN (15.8%). ER+&#x2009;P-ILCs were mainly&#xa0;showed trabecular and solid&#xa0;growth patterns. Apocrine and solid features&#xa0;were more strongly associated with HER2+&#x2009;P-ILCs and TN-P-ILCs, respectively.&#xa0;The prognosis of each biomarker group (ER+, HER2+ and TN) differed by subtype. The P-ILC biomarker subtypes had&#xa0;worse prognosis than the same subtypes in the IDC group, while there was&#xa0;no difference between the P-ILC and the C-ILC counterparts. Solid variants of P-ILC&#xa0;had the worst prognosis. Bone was the most common metastatic site in ER+&#x2009;P-ILCs and TN-P-ILCs. HER2+&#x2009;P-ILCs tended to metastasize to the brain and liver. DFS of HER2+&#x2009;P-ILCs and TN-P-ILCs were worse than that of ER+&#x2009;P-ILCs. Lacking lobular carcinoma in situ and sTILs&#x2009;&#x2264;&#x2009;10% were associated with worse survival of ER+&#x2009;P-ILCs and TN-P-ILCs, respectively. For HER2+&#x2009;P-ILCs, Ki-67&#x2009;>&#x2009;20% and sTILs&#x2009;&#x2264;&#x2009;10% were significant factors for lower DFS.<br><br>CONCLUSION: P-ILCs is an aggressive subtype of ILCs. Analyzing the prognostic factors of P-ILCs with heterogeneous morphological and biomarker characteristics is helpful for creating an individualized treatment.}, }
@article {pmid35665642, year = {2022}, author = {Elangovan, A and Hooda, J and Savariau, L and Puthanmadhomnarayanan, S and Yates, ME and Chen, J and Brown, DD and McAuliffe, PF and Oesterreich, S and Atkinson, JM and Lee, AV}, title = {Loss of E-cadherin Induces IGF1R Activation and Reveals a Targetable Pathway in Invasive Lobular Breast Carcinoma.}, journal = {Molecular cancer research : MCR}, volume = {20}, number = {9}, pages = {1405-1419}, pmid = {35665642}, issn = {1557-3125}, support = {F30 CA250167/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA224909/CA/NCI NIH HHS/United States ; R01 CA252378/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/pathology ; Cadherins/genetics/metabolism ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; Female ; Humans ; Receptor, IGF Type 1/genetics/metabolism ; Signal Transduction ; }, abstract = {UNLABELLED: No special-type breast cancer [NST; commonly known as invasive ductal carcinoma (IDC)] and invasive lobular carcinoma (ILC) are the two major histological subtypes of breast cancer with significant differences in clinicopathological and molecular characteristics. The defining pathognomonic feature of ILC is loss of cellular adhesion protein, E-cadherin (CDH1). We have previously shown that E-cadherin functions as a negative regulator of the IGF1R and propose that E-cadherin loss in ILC sensitizes cells to growth factor signaling that thus alters their sensitivity to growth factor-signaling inhibitors and their downstream activators. To investigate this potential therapeutic vulnerability, we generated CRISPR-mediated CDH1 knockout (CDH1 KO) IDC cell lines (MCF7, T47D, and ZR75.1) to uncover the mechanism by which loss of E-cadherin results in IGF pathway activation. CDH1 KO cells demonstrated enhanced invasion and migration that was further elevated in response to IGF1, serum and collagen I. CDH1 KO cells exhibited increased sensitivity to IGF resulting in elevated downstream signaling. Despite minimal differences in membranous IGF1R levels between wild-type (WT) and CDH1 KO cells, significantly higher ligand-receptor interaction was observed in the CDH1 KO cells, potentially conferring enhanced downstream signaling activation. Critically, increased sensitivity to IGF1R, PI3K, Akt, and MEK inhibitors was observed in CDH1 KO cells and ILC patient-derived organoids.<br><br>IMPLICATIONS: Overall, this suggests that these targets require further exploration in ILC treatment and that CDH1 loss may be exploited as a biomarker of response for patient stratification.}, }
@article {pmid35662504, year = {2022}, author = {Lone, Z and Benidir, T and Rainey, M and Nair, M and Davicioni, E and Gibb, EA and Williamson, S and Gupta, S and Chaim Ornstein, M and Tendulkar, R and Weight, C and Nguyen, JK and Klein, EA and Mian, OY}, title = {Transcriptomic Features of Cribriform and Intraductal Carcinoma of the Prostate.}, journal = {European urology focus}, volume = {8}, number = {6}, pages = {1575-1582}, doi = {10.1016/j.euf.2022.05.005}, pmid = {35662504}, issn = {2405-4569}, support = {L30 CA220908/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Prostate ; *Carcinoma, Intraductal, Noninfiltrating/genetics/surgery ; Genomics ; *Prostatic Neoplasms/genetics/surgery ; }, abstract = {BACKGROUND: Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.<br><br>OBJECTIVE: The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.<br><br>We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+).<br><br>Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (>0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status.<br><br>RESULTS AND LIMITATIONS: A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p&#xa0;<&#xa0;0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p&#xa0;<&#xa0;0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p&#xa0;<&#xa0;0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p&#xa0;=&#xa0;0.046). Other enriched pathways included E2F targets (NES: 1.69, p&#xa0;=&#xa0;0.031) and oxidative phosphorylation (NES: 1.68, =0 .033).<br><br>CONCLUSIONS: This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures.<br><br>PATIENT SUMMARY: Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.}, }
@article {pmid35661214, year = {2022}, author = {Sulaj, A and Kopf, S and von Rauchhaupt, E and Kliemank, E and Brune, M and Kender, Z and Bartl, H and Cortizo, FG and Klepac, K and Han, Z and Kumar, V and Longo, V and Teleman, A and Okun, JG and Morgenstern, J and Fleming, T and Szendroedi, J and Herzig, S and Nawroth, PP}, title = {Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {107}, number = {8}, pages = {2167-2181}, pmid = {35661214}, issn = {1945-7197}, support = {236360313-SFB 1118//German Research Foundation/ ; //Deutsches Zentrum f&#xfc;r Diabetesforschung/ ; 82DZD07C2G//Diabetes Research/ ; 236360313-SFB 1118//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Albuminuria/etiology ; Biomarkers ; Creatinine ; DNA/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy ; *Diabetic Nephropathies/etiology ; Fasting ; Humans ; *Insulin Resistance ; Lipids ; Receptors, Urokinase Plasminogen Activator ; }, abstract = {CONTEXT: Novel fasting interventions have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome.<br><br>OBJECTIVE: Assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways.<br><br>DESIGN/PARTICIPANTS: Proof-of-concept study where individuals with type 2 diabetes (n = 40) and increased albumin-to-creatinine ratio (ACR) were randomly assigned to receive a monthly fasting-mimicking diet (FMD) or a Mediterranean diet for 6 months with 3-month follow-up.<br><br>MAIN OUTCOMES MEASURES: Change in ACR was assessed by analysis of covariance adjusted for age, sex, weight loss, and baseline value. Prespecified subgroup analysis for patients with micro- vs macroalbuminuria at baseline was performed. Change in homeostatic model assessment for insulin resistance (HOMA-IR), circulating markers of dicarbonyl detoxification (methylglyoxal-derived hydroimidazolone 1, glyoxalase-1, and hydroxyacetone), DNA-damage/repair (phosphorylated histone H2AX), lipid oxidation (acylcarnitines), and senescence (soluble urokinase plasminogen activator receptor) were assessed as exploratory endpoints.<br><br>RESULTS: FMD was well tolerated with 71% to 95% of the participants reporting no adverse effects. After 6 months, change in ACR was comparable between study groups [110.3 (99.2, 121.5) mg/g; P = 0.45]. FMD led to a reduction of ACR in patients with microalbuminuria levels at baseline [-30.3 (-35.7, -24.9) mg/g; P &#x2264; 0.05] but not in those with macroalbuminuria [434.0 (404.7, 463.4) mg/g; P = 0.23]. FMD reduced HOMA-IR [-3.8 (-5.6, -2.0); P &#x2264; 0.05] and soluble urokinase plasminogen activator receptor [-156.6 (-172.9, -140.4) pg/mL; P &#x2264; 0.05], while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in acylcarnitines was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction [-1.9 (-3.7, -0.1), P &#x2264; 0.05]) was sustained.<br><br>CONCLUSIONS: Improvement of microalbuminuria and of markers of insulin resistance, lipid oxidation, and senescence suggest the potential beneficial effects of periodic fasting in type 2 diabetes.}, }
@article {pmid35647336, year = {2022}, author = {Hamed, MM and Gouida, MS and Abd El-Aziz, SR and El-Sokkary, AMA}, title = {Evaluation PD-L1, CD8 and CD20 as early predictor and tracking markers for breast cancer (BC) in Egypt.}, journal = {Heliyon}, volume = {8}, number = {5}, pages = {e09474}, pmid = {35647336}, issn = {2405-8440}, abstract = {BACKGROUND: Breast cancer (BC) is considered as a common type of cancer threatening women throughout the world. Therefore, development of early predication biomarkers for BC got more concern especially for Egyptian females. This study was aimed to evaluate PD-L1, CD8, and CD20 as early prediction breast cancer biomarkers.<br><br>METHODS: Flow cytometry (FC), immunohistochemistry (IHC), Western Blot, and q-PCR were used to compare PD-L1, CD20, and CD8 levels in tissues and blood samples of Breast Cancer and controls.<br><br>RESULTS: Blood samples showed a significant increase in PD-L1, CD20, and CD8 compared to controls (p&#x2c2;0.005). A Significant correlation was shown between PD-L1, CD8, and CD20 in tissue and breast cancer subtypes. Whereas, invasive lobular carcinoma (ILC) was characterized by superior PD-L1 and CD20 levels compared to invasive ductal carcinoma (IDC). FC studies on Blood showed 83% and 45.7% PD-L1 expressions for IDC and ILC, respectively. CD20 in ILC and IDC were 78.2% and 62.5%, respectively. Nevertheless, CD8 was 74.2% for IDC and 67.7% for ILC. Whereas, FC studies for PD-L1, CD20, and CD8 in ILC in tissues gave 34.4%, 30.2% and 35.1%, respectively. In addition, IDC tissue samples showed 16%, 12.5, and 13.5% for PD-L1, CD20, and CD8. The moderate stage of adenocarcinoma caused expression of PD-L1 within inflammatory cells, while expression was within neoplastic glandular cells in late stage.<br><br>CONCLUSION: PD-L1, CD8, and CD20 are considered as early predictor and tracking markers for breast cancer.}, }
@article {pmid35636710, year = {2022}, author = {Willemsen, N and Arigoni, I and Studencka-Turski, M and Krüger, E and Bartelt, A}, title = {Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3.}, journal = {Molecular metabolism}, volume = {62}, number = {}, pages = {101518}, pmid = {35636710}, issn = {2212-8778}, mesh = {Adipocytes, Brown/metabolism ; *Adipogenesis/genetics ; Animals ; Inflammation/metabolism ; *Lipodystrophy/metabolism ; Mice ; Proteasome Endopeptidase Complex/metabolism ; }, abstract = {OBJECTIVE: Regulation of proteasomal activity is an essential component of cellular proteostasis and function. This is evident in patients with mutations in proteasome subunits and associated regulators, who suffer from proteasome-associated autoinflammatory syndromes (PRAAS). These patients display lipodystrophy and fevers, which may be partly related to adipocyte malfunction and abnormal thermogenesis in adipose tissue. However, the cell-intrinsic pathways that could underlie these symptoms are unclear. Here, we investigate the impact of two proteasome subunits implicated in PRAAS, Psmb4 and Psmb8, on differentiation, function and proteostasis of brown adipocytes.<br><br>METHODS: In immortalized mouse brown pre-adipocytes, levels of Psmb4, Psmb8, and downstream effectors genes were downregulated through reverse transfection with siRNA. Adipocytes were differentiated and analyzed with various assays of adipogenesis, lipogenesis, lipolysis, inflammation, and respiration.<br><br>RESULTS: Loss of Psmb4, but not Psmb8, disrupted proteostasis and adipogenesis. Proteasome function was reduced upon Psmb4 loss, but partly recovered by the activation of Nuclear factor, erythroid-2, like-1 (Nfe2l1). In addition, cells displayed higher levels of surrogate inflammation and stress markers, including Activating transcription factor-3 (Atf3). Simultaneous silencing of Psmb4 and Atf3 lowered inflammation and restored adipogenesis.<br><br>CONCLUSIONS: Our study shows that Psmb4 is required for adipocyte development and function in cultured adipocytes. These results imply that in humans with PSMB4 mutations, PRAAS-associated lipodystrophy is partly caused by disturbed adipogenesis. While we uncover a role for Nfe2l1 in the maintenance of proteostasis under these conditions, Atf3 is a key effector of inflammation and blocking adipogenesis. In conclusion, our work highlights how proteasome dysfunction is sensed and mitigated by the integrated stress response in adipocytes with potential relevance for PRAAS patients and beyond.}, }
@article {pmid35621626, year = {2022}, author = {Cho, YA and Ko, SY and Suh, YJ and Kim, S and Park, JH and Park, HR and Seo, J and Choi, HG and Kang, HS and Lim, H and Park, HY and Kwon, MJ}, title = {PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy.}, journal = {Current oncology (Toronto, Ont.)}, volume = {29}, number = {5}, pages = {2895-2908}, pmid = {35621626}, issn = {1718-7729}, mesh = {*Asian People/genetics ; B7-H1 Antigen/metabolism ; *Breast Neoplasms/drug therapy/genetics/surgery ; Chemotherapy, Adjuvant ; *Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Microsatellite Instability ; Middle Aged ; Mutation ; Prognosis ; }, abstract = {Background: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy. Methods: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data. Conclusions: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.}, }
@article {pmid35606411, year = {2022}, author = {Shah, RB and Palsgrove, DN and Desai, NB and Gagan, J and Mennie, A and Raj, G and Hannan, R}, title = {Enrichment of "Cribriform" morphologies (intraductal and cribriform adenocarcinoma) and genomic alterations in radiorecurrent prostate cancer.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {35}, number = {10}, pages = {1468-1474}, doi = {10.1038/s41379-022-01093-9}, pmid = {35606411}, issn = {1530-0285}, mesh = {*Adenocarcinoma/genetics/pathology/radiotherapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Genomics ; Humans ; Male ; Neoplasm Grading ; Neoplasm Recurrence, Local/genetics/pathology/radiotherapy ; Prostatectomy ; *Prostatic Neoplasms/genetics/pathology/radiotherapy ; }, abstract = {Locally relapsed prostate cancer (PCa) after radiation therapy (RT) is associated with substantial morbidity and mortality. Morphological and molecular consequences that may contribute to RT resistance and local recurrence remain poorly understood. Locally recurrent PCa tissue from 53 patients with clinically localized PCa who failed with primary RT and subsequently underwent salvage radical prostatectomy (RP) was analyzed for tumor focality, clinicopathological, molecular, and genomic characteristics. Targeted next-generation sequencing with full exon coverage of 1,425 cancer-related genes was performed on 10 representative radiorecurrent PCas exhibiting no RT effect with matched adjacent benign prostate tissue. At RP, 37 (70%) of PCas had no RT effect with the following characteristics: grade group (GG) ≥ 3 (70%), unifocal tumor (75%), extraprostatic disease (78%), lymph node metastasis (8%), and "cribriform" morphologies (84%) [cribriform PCa (78%) or intraductal carcinoma (IDC-P) (61%)] at a median percentage of approximately 80% of tumor volume. In the setting of multifocal tumors (25%) at RP, the cribriform morphologies were restricted to index tumors. Of 32 patients with available pre-RT biopsy information, 16 had GG1 PCa, none had cribriform morphologies at baseline but 81% demonstrated cribriform morphologies at RP. Notable alterations detected in the sequenced tumors included: defects in DNA damage response and repair (DDR) genes (70%) (TP53, BRCA2, PALB2, ATR, POLQ), PTEN loss (50%), loss of 8p (80%), and gain of MYC (70%). The median tumor mutational burden was 4.18 mutations/Mb with a range of 2.16 to 31.86. Our findings suggest that most radiorecurrent PCas are enriched in cribriform morphologies with potentially targetable genomic alterations. Understanding this phenotypic and genotypic diversity of radiorecurrent PCa is critically important to facilitate optimal patient management.}, }
@article {pmid35590107, year = {2022}, author = {Bean, GR and Najjar, S and Shin, SJ and Hosfield, EM and Caswell-Jin, JL and Urisman, A and Jones, KD and Chen, YY and Krings, G}, title = {Genetic and immunohistochemical profiling of small cell and large cell neuroendocrine carcinomas of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {35}, number = {10}, pages = {1349-1361}, pmid = {35590107}, issn = {1530-0285}, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Large Cell/genetics/pathology ; *Carcinoma, Neuroendocrine/pathology ; Carrier Proteins ; Cell Cycle Proteins ; Class I Phosphatidylinositol 3-Kinases/metabolism ; Female ; Humans ; *Neuroendocrine Tumors/pathology ; Proto-Oncogene Proteins/metabolism ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Neuroendocrine carcinomas (NEC) of the breast are exceedingly rare tumors, which are classified in the WHO system as small cell (SCNEC) and large cell (LCNEC) carcinoma based on indistinguishable features from their lung counterparts. In contrast to lung and enteropancreatic NEC, the genomics of breast NEC have not been well-characterized. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of 13 breast NEC (7 SCNEC, 4 LCNEC, 2 NEC with ambiguous small versus large cell morphology [ANEC]). Co-alterations of TP53 and RB1 were identified in 86% (6/7) SCNEC, 100% (2/2) ANEC, and 50% (2/4) LCNEC. The one SCNEC without TP53/RB1 alteration had other p53 pathway aberrations (MDM2 and MDM4 amplification) and was immunohistochemically RB negative. PIK3CA/PTEN pathway alterations and ZNF703 amplifications were each identified in 46% (6/13) NEC. Two tumors (1 SCNEC, 1 LCNEC) were CDH1 mutated. By immunohistochemistry, 100% SCNEC (6/6) and ANEC (2/2) and 50% (2/4) LCNEC (83% NEC) showed RB loss, compared to 0% (0/8) grade 3 neuroendocrine tumors (NET) (p < 0.001) and 38% (36/95) grade 3 invasive ductal carcinomas of no special type (IDC-NST) (p = 0.004). NEC were also more often p53 aberrant (60% vs 0%, p = 0.013), ER negative (69% vs 0%, p = 0.005), and GATA3 negative (67% vs 0%, p = 0.013) than grade 3 NET. Two mixed NEC had IDC-NST components, and 69% (9/13) of tumors were associated with carcinoma in situ (6 neuroendocrine DCIS, 2 non-neuroendocrine DCIS, 1 non-neuroendocrine LCIS). NEC and IDC-NST components of mixed tumors were clonally related and immunophenotypically distinct, lacking ER and GATA3 expression in NEC relative to IDC-NST, with RB loss only in NEC of one ANEC. The findings provide insight into the pathogenesis of breast NEC, underscore their classification as a distinct tumor type, and highlight genetic similarities to extramammary NEC, including highly prevalent p53/RB pathway aberrations in SCNEC.}, }
@article {pmid35585552, year = {2022}, author = {Oride, Y and Koi, Y and Sasada, T and Kajitani, K and Ohara, M and Kondo, T and Daimaru, Y and Kawamura, S}, title = {Endobronchial ultrasound-guided transbronchial needle aspiration facilitating diagnosis of sarcoidosis in a breast cancer patient with multiple lymphadenopathy: a case report.}, journal = {Journal of medical case reports}, volume = {16}, number = {1}, pages = {194}, pmid = {35585552}, issn = {1752-1947}, mesh = {Aged ; *Breast Neoplasms/complications/pathology ; Bronchoscopy/methods ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods ; Female ; Fluorodeoxyglucose F18 ; Humans ; *Lung Neoplasms/pathology ; Lymph Nodes/diagnostic imaging/pathology ; *Lymphadenopathy/diagnostic imaging/pathology ; Mastectomy ; Mediastinum/pathology ; Receptors, Interleukin-2 ; *Sarcoidosis/complications/diagnosis/pathology ; }, abstract = {BACKGROUND: Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology. Cell-mediated immunity disorder is often found in sarcoidosis patients, and an association between malignant tumors and sarcoidosis has been suggested. Sarcoidosis and malignant disease can occur simultaneously or sequentially, leading to misdiagnosis and mistreatment. Sarcoidosis is diagnosed clinically, radiologically, and histologically. We report herein a case of sarcoidosis diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration from the mediastinal lymph nodes of a breast cancer patient.<br><br>CASE PRESENTATION: The patient was a 70-year-old Asian woman who presented with right breast tumor. A 20-mm movable mass was identified in the inferolateral quadrant of the right breast, and mammography revealed a spiculated mass with calcification. Ultrasonography revealed a mass with internal hypoechogenicity, and biopsy revealed estrogen receptor-positive, human epidermal growth factor receptor 2-positive invasive ductal carcinoma. Positron emission tomography/computed tomography showed multiple lymphadenopathy including mediastinal lymph nodes, with fluorodeoxyglucose accumulation in those nodes suggesting breast cancer metastases. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymph node revealed noncaseous epithelioid granuloma. Due to a history of uveitis and elevated soluble interleukin 2 receptor, lymphadenopathy due to sarcoidosis and stage IIA breast cancer were diagnosed. Right partial mastectomy and axillary lymph node dissection were performed after preoperative chemotherapy. No exacerbation of sarcoidosis symptoms has been observed during treatment.<br><br>CONCLUSION: We report a case of breast cancer in which sarcoidosis could be diagnosed based on endobronchial ultrasound-guided transbronchial needle aspiration, a history of uveitis, and elevated soluble interleukin 2 receptor despite fluorodeoxyglucose positron emission tomography/computed tomography suggesting multiple lymph node metastases. This report emphasizes the importance of differential diagnosis of lymph node involvements in cancer patients.}, }
@article {pmid35578939, year = {2022}, author = {Higashi, T and Ozawa, K and Takei, S and Takagi, S and Yokoyama, M and Mase, K and Moriya, T and Takeshita, A and Mizutani, M}, title = {[A Case of Postoperative Pulmonary Metastasis of Breast Cancer with Complete Response by Abemaciclib plus Fulvestrant Therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {49}, number = {5}, pages = {581-583}, pmid = {35578939}, issn = {0385-0684}, mesh = {Aged ; Aged, 80 and over ; Aminopyridines ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Benzimidazoles ; *Breast Neoplasms/drug therapy/pathology/surgery ; Female ; Fulvestrant/therapeutic use ; Humans ; *Lung Neoplasms/drug therapy/surgery ; Mastectomy ; Neoplasm Recurrence, Local/surgery ; }, abstract = {A 66-year-old woman underwent total mastectomy with level Ⅰ and Ⅱ axillary lymph node dissection for right breast cancer in July 2007. The pathology results indicated the presence of T2N0M0 invasive ductal carcinoma(tubule forming type), that was estrogen receptor-positive and human epidermal growth factor 2-negative. She received postoperative adjuvant therapy with oral anastrozole(ANA)for 5 years. Eleven years after surgery, at the age of 77 years, a chest X-ray examination during a routine health checkup identified a mass shadow in the right lung. Further investigation revealed bilateral multiple lung metastases due to breast cancer recurrence. Histological examination of a tissue obtained by computed tomography(CT)-guided lung biopsy confirmed that the histological type and subtype were identical to those found in the initial surgery. Hence, endocrine therapy with ANA plus CDK4/6 inhibitor was started in November 2018. However, the first CDK4/6 inhibitor, palbociclib, caused severe myelosuppression even when the dose was reduced by 2 levels. Therefore in January 2019, the patient was switched to abemaciclib, with the dose reduced by 1 level initially and then reduced by 2 levels from August 2019. In June 2019, new multiple lung metastases appeared, and the patient was switched from ANA to fulvestrant, after which complete response was achieved in 6 months. CT in June 2021 showed no recurrence, and the patient(now 80-year-old)continues to take abemaciclib plus fulvestrant therapy.}, }
@article {pmid35576836, year = {2022}, author = {He, S and Jia, Q and Zhou, L and Wang, Z and Li, M}, title = {SIRT5 is involved in the proliferation and metastasis of breast cancer by promoting aerobic glycolysis.}, journal = {Pathology, research and practice}, volume = {235}, number = {}, pages = {153943}, doi = {10.1016/j.prp.2022.153943}, pmid = {35576836}, issn = {1618-0631}, mesh = {*Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Glucose/metabolism ; Glycolysis/genetics ; Humans ; *Sirtuins/metabolism/pharmacology ; }, abstract = {OBJECTIVE: Breast cancer (BC) is the most commonly diagnosed cancer among females and has a poor prognosis, breast invasive ductal carcinoma is the most common histological type. The occurrence and development of BC is closely related to aberrant glucose metabolism. In the hyperglycemic environment caused by abnormal glucose metabolism, hypoxia-inducible factor-1 alpha (HIF-1α) enables tumor cells to absorb large amounts of glucose and enhance glycolysis by inducing the expression of glucose transporter type1 (GLUT1) and glycolysis genes, thus promoting tumor cell proliferation and metastasis. Mitochondrial Sirtuin5 (SIRT5) plays a role in the rewiring of glucose metabolism during the progression of cancers. Thus, we aimed to elucidate whether SIRT5 promotes BC proliferation and metastasis by facilitating aerobic glycolysis in BC.<br><br>METHODS: The expression of SIRT5 in breast carcinoma tissue and cells was evaluated using immunohistochemical staining, western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis to confirm the biological role of SIRT5 in breast carcinoma. We established a stable cell line with SIRT5 knockdown using lentiviral transduction in T47D cells to reduce SIRT5 expression and then evaluated the effect of SIRT5 on cells cultured in the presence of high glucose (4500&#xa0;mg/L) and normal glucose (2000&#xa0;mg/L) concentrations. Cell proliferation was detected using the CCK-8 assay, the cell cycle and cell apoptosis were measured using flow cytometry and Annexin V staining, and cell migration was tested by performing Celigo scratch and Transwell assays. The expression of PKM2, HK2, mTOR and HIF-1&#x3b1;, which play roles in aerobic glycolysis, was investigated using western blot.<br><br>RESULTS: SIRT5 was overexpressed in BC tissues compared with paired normal tissues. Prognostic and OS analyses showed that the SIRT5 expression level was an individual prognostic factor for patients with BC. SIRT5 knockdown inhibited proliferation and metastasis and slightly increased apoptosis in T47D cells under high-glucose conditions. Furthermore, the downregulation of HK2 and HIF-1&#x3b1; caused by SIRT5 knockdown was a high glucose-dependent process, while the downregulation of PKM2 was mediated by a high glucose-independent process.<br><br>CONCLUSIONS: SIRT5 is an independent prognostic factor for BC and contributes to cell proliferation and metastasis in a high glucose-dependent manner to some degree, which might be mediated by promoting aerobic glycolysis.}, }
@article {pmid35567670, year = {2022}, author = {Wilson, GM and Dinh, P and Pathmanathan, N and Graham, JD}, title = {Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {27}, number = {1}, pages = {101-131}, pmid = {35567670}, issn = {1573-7039}, mesh = {Biomarkers ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Disease Progression ; Female ; Humans ; Tumor Microenvironment/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC), whereby if left untreated, approximately 12% of patients develop invasive disease. The current standard of care is surgical removal of the lesion, to prevent potential progression, and radiotherapy to reduce risk of recurrence. There is substantial overtreatment of DCIS patients, considering not all DCIS lesions progress to invasive disease. Hence, there is a critical imperative to better predict which DCIS lesions are destined for poor outcome and which are not, allowing for tailored treatment. Active surveillance is currently being trialed as an alternative management practice, but this approach relies on accurately identifying cases that are at low risk of progression to invasive disease. Two DCIS-specific genomic profiling assays that attempt to distinguish low and high-risk patients have emerged, but imperfections in risk stratification coupled with a high price tag warrant the continued search for more robust and accessible prognostic biomarkers. This search has largely turned researchers toward the tumor microenvironment. Recent evidence suggests that a spectrum of cell types within the DCIS microenvironment are genetically and phenotypically altered compared to normal tissue and play critical roles in disease progression. Uncovering the molecular mechanisms contributing to DCIS progression has provided optimism for the search for well-validated prognostic biomarkers that can accurately predict the risk for a patient developing IDC. The discovery of such markers would modernize DCIS management and allow tailored treatment plans. This review will summarize the current literature regarding DCIS diagnosis, treatment, and pathology.}, }
@article {pmid35547416, year = {2022}, author = {Smith, PD and Bhenderu, LS and Kommuri, S and Fleener, EE and Hoover, JM}, title = {Treatment of Leptomeningeal Carcinomatosis Following Treatment of Cerebellar Metastasis of HER2+ (Human Epidermal Growth Factor Receptor 2 Positive) Breast Cancer: Case Report and Review of Literature.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24008}, pmid = {35547416}, issn = {2168-8184}, abstract = {Leptomeningeal carcinomatosis (LC) after metastasis of breast cancer is a rare occurrence with potentially devastating complications. Treatment options are limited, and there is a lack of literature on this topic. We report the case of a 38-year-old woman with estrogen/progesterone receptor negative (ER/PR-), human epidermal growth factor receptor 2 positive (HER2+) invasive ductal carcinoma of the left breast who underwent bilateral mastectomies with axillary lymph node dissection and chemotherapy treatment. The patient returned 11 months later with persistent headaches. Imaging and resection found cerebellar metastasis of the breast carcinoma. The brain metastasis was treated with further chemotherapy and stereotactic radiosurgery. Follow-up imaging showed the development of small lesions outside the radiation site. Metabolic studies were performed to determine if the new lesions were due to tumor recurrence or radiation necrosis, but the studies were inconclusive as to the etiology of these lesions. The patient later developed LC that was successfully treated with full resolution of the disease using intrathecal trastuzumab. There are currently no consensuses on treatment guidelines for treating LC. Here, we demonstrate successful treatment of LC from an ER/PR-, HER2+ breast carcinoma with intrathecal trastuzumab.}, }
@article {pmid35538300, year = {2022}, author = {D'Iorio, A and Baiano, C and Maraucci, G and Vitale, C and Amboni, M and Santangelo, G}, title = {A longitudinal study on the effects of COVID-19 pandemic on non-motor symptoms in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {8}, pages = {4605-4609}, pmid = {35538300}, issn = {1590-3478}, mesh = {Aged ; Anhedonia ; *COVID-19 ; Humans ; Longitudinal Studies ; Pandemics ; *Parkinson Disease/complications/diagnosis/epidemiology ; Quality of Life/psychology ; }, abstract = {INTRODUCTION: The COVID-19 pandemic led to psychological consequences on people's mental health, representing a condition of increased vulnerability for the weakest sections of population, including elderly patients with Parkinson's disease (PD). This longitudinal study aimed at exploring the impact of the most frequent non-motor symptoms and their contribute on health-related quality of life of PD patients after the COVID-19 outbreak, in comparison with the pre-pandemic status.<br><br>METHODS: Forty-two non-demented PD patients underwent a first assessment between December 2018 and January 2020 (T0). Then, between March and May 2021 (T1), they were contacted again and asked to complete the second assessment. Levels of global functioning, several non-motor symptoms (i.e. depression, apathy, anxiety, anhedonia) and health-related quality of life were investigated.<br><br>RESULTS: Results of the the paired Wilcoxon signed-rank test showed that at T1, PD patients scored lower on the emotional subscale of the DAS, Z&#x2009;=&#x2009;&#x2009;-&#x2009;2.49; p&#x2009;=&#x2009;0.013; Cohen dz&#x2009;=&#x2009;0.691. Higher scores of the TEPS total score, Z&#x2009;=&#x2009;&#x2009;-&#x2009;2.38; p&#x2009;=&#x2009;0.025; Cohen dz&#x2009;=&#x2009;0.621, and LEDD, Z&#x2009;=&#x2009;&#x2009;-&#x2009;2.63; p&#x2009;=&#x2009;0.008; Cohen dz&#x2009;=&#x2009;0.731, were also reported at T1.<br><br>CONCLUSION: The present study suggested that self-isolation at home might lead to a reduction of apathy and anhedonia in PD patients due to the increase in social support provided by families during COVID-19 restrictions. This evidence brings out the need of a consistent and persistent social support which might be represented by caregivers or/and social assistive robotics.}, }
@article {pmid35538223, year = {2022}, author = {Simond, AM and Bui, T and Zuo, D and Sanguin-Gendreau, V and Rao, T and Phillips, WA and Cardiff, RD and Muller, WJ}, title = {Physiological expression of PI3K H1047R mutation reveals its anti-metastatic potential in ErbB2-driven breast cancer.}, journal = {Oncogene}, volume = {41}, number = {25}, pages = {3445-3451}, pmid = {35538223}, issn = {1476-5594}, support = {FDN-148373//CIHR/Canada ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Mutation ; Phosphatidylinositol 3-Kinase/genetics ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Receptor, ErbB-2/genetics ; }, abstract = {p110α is a catalytic subunit of phosphoinositide 3-kinase (PI3K), a major downstream effector of receptor tyrosine kinase ErbB2, that is amplified and overexpressed in 20-30% of breast cancers, 40% of which have an activating mutation in p110α. Despite the high frequency of PIK3CA gain-of-function mutations, their prognostic value is controversial. Here, we employ a knock-in transgenic strategy to restrict the expression of an activated form of ErbB2 and p110α kinase domain mutation (p110α[HR]) in the mammary epithelium. Physiological levels of transgene expression under the control of their endogenous promoters did not result in a major synergistic effect. However, tumors arising in ErbB2/p110α[HR] bi-genic strain metastasized to the lung with significantly reduced capacity compared to tumors expressing ErbB2 alone. The reduced metastasis was further associated with retention of the myoepithelial layer reminiscent of ductal carcinoma in situ (DCIS), a non-invasive stage of human breast cancer. Molecular and biochemical analyses revealed that these poorly metastatic tumors exhibited a significant decrease in phospho-myosin light chain 2 (MLC2) associated with cellular contractility and migration. Examination of human samples for MLC2 activity revealed a progressive increase in cellular contractility between non-invasive DCIS and invasive ductal carcinoma. Collectively, these data argue that p110α[HR] mutation attenuates metastatic behavior in the context of ErbB2-driven breast cancer.}, }
@article {pmid35522890, year = {2022}, author = {Butcher, MR and White, MJ and Rooper, LM and Argani, P and Cimino-Mathews, A}, title = {MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas.}, journal = {The American journal of surgical pathology}, volume = {46}, number = {7}, pages = {878-888}, doi = {10.1097/PAS.0000000000001913}, pmid = {35522890}, issn = {1532-0979}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Adenoid Cystic/diagnosis/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; In Situ Hybridization ; RNA ; *Salivary Gland Neoplasms/pathology ; *Triple Negative Breast Neoplasms/diagnosis/genetics/pathology ; }, abstract = {Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.}, }
@article {pmid35478129, year = {2022}, author = {Salih, MM and Higgo, AA and Khalifa, AS and Eed, EM}, title = {Incidence of Epstein-Barr Virus Among Women With Breast Cancer Using Monoclonal Antibodies for Latent Membrane Protein 1 (LMP1).}, journal = {In vivo (Athens, Greece)}, volume = {36}, number = {3}, pages = {1513-1518}, pmid = {35478129}, issn = {1791-7549}, mesh = {Adult ; Antibodies, Monoclonal ; *Antineoplastic Agents, Immunological ; *Breast Neoplasms/epidemiology/pathology ; *Carcinoma, Ductal/complications ; *Epstein-Barr Virus Infections/complications/epidemiology/pathology ; Female ; Herpesvirus 4, Human ; Humans ; Incidence ; Male ; Membrane Proteins ; Middle Aged ; Viral Proteins ; }, abstract = {BACKGROUND/AIM: Breast cancer is a common type of cancer in Sudan. Numerous studies propose viral oncogenesis as an etiological factor for breast cancer. The aim of the study was to analyze the presence of the Epstein-Barr virus (EBV) using monoclonal antibodies against latent membrane protein 1 (LAMP1) and determine the correlation between the presence of EBV and clinicopathological characteristics.<br><br>PATIENTS AND METHODS: This study used immunohistochemistry to analyze the presence of EBV in 202 samples from Sudanese women diagnosed with breast cancer. Clinicopathological data were collected from patient records from the Radiation and Isotopes Centre in Khartoum State, Republic of Sudan.<br><br>RESULTS: This study included 202 patients 168 (83.2%), 16 (7.9%), and 18 (8.9%), diagnosed with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. Axillary lymph node metastasis was present in 57 (28.2%) of cases, while 11 patients (5.4%) tested positive for EBV. The mean age of patients was 48.14&#xb1;14.4 years. EBV infection was more frequently detected in invasive ductal carcinoma cases, and EBV positivity was not associated with cancer type, grade, progesterone levels, and HER2 expression. On the other hand, a statistically significant association was found between EBV presence and lymph node involvement, estrogen receptor status, and age group.<br><br>CONCLUSION: EBV may not play a vital role in the pathogenesis of breast carcinoma in Sudanese women.}, }
@article {pmid35456414, year = {2022}, author = {Zadrożna-Nowak, A and Romanowicz, H and Zadrożny, M and Bryś, M and Forma, E and Smolarz, B}, title = {Analysis of Long Non-Coding RNA (lncRNA) uc.38 and uc.63 Expression in Breast Carcinoma Patients.}, journal = {Genes}, volume = {13}, number = {4}, pages = {}, pmid = {35456414}, issn = {2073-4425}, mesh = {*Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Staging ; *RNA, Long Noncoding/genetics/metabolism ; }, abstract = {Background. The role of the transcribed ultra-conserved regions (T-UCRs) has not yet been fully discovered, but the studies showed some indications that impaired expression of T-UCRS were present in malignant tumors, including breast cancer. Aim. The presented work assessed the expression of two transcribed-ultra conserved regions−uc.63 and uc.38−in breast cancer tissue samples. Material and methods. The research was carried out on a group of 100 patients with invasive ductal carcinoma and 100 patients (test group) with benign tumors in breast tissue (control group). Results. As a result of the statistical analysis, it was shown that the expression of uc.63 and uc.38 is statistically significant, and, accordingly, higher (p < 0.0001) and lower (p < 0.0001) in the test group than in the control group. Statistical dependency analysis of the expression of uc.63 and uc.38 and the selected clinical and pathological factors showed that the expression of uc.63 statistically drops with the patient’s age (p = 0.04), and is higher in the breast cancer tissue type M1 according to the TNM classification (p = 0.036) and in tissues with overexpressed HER2 (p = 0.035). Conclusion. The obtained results of the statistical analysis indicate a relationship between the expression of uc.63 and uc.38 and the occurrence of breast cancer.}, }
@article {pmid35405500, year = {2022}, author = {Acevedo, DS and Fang, WB and Rao, V and Penmetcha, V and Leyva, H and Acosta, G and Cote, P and Brodine, R and Swerdlow, R and Tan, L and Lorenzi, PL and Cheng, N}, title = {Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2/CCR2 signaling interactions with MET receptor tyrosine kinases.}, journal = {Neoplasia (New York, N.Y.)}, volume = {28}, number = {}, pages = {100791}, pmid = {35405500}, issn = {1476-5586}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/metabolism/pathology ; *Carcinoma, Ductal, Breast/metabolism/pathology ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Cell Line, Tumor ; *Chemokine CCL2/genetics/metabolism ; Disease Progression ; Female ; Humans ; Neoplasm Recurrence, Local/metabolism/pathology ; *Proto-Oncogene Proteins c-met/metabolism ; *Receptors, CCR2/metabolism ; }, abstract = {With over 60,000 cases diagnosed annually in the US, ductal carcinoma in situ (DCIS) is the most prevalent form of early-stage breast cancer. Because many DCIS cases never progress to invasive ductal carcinomas (IDC), overtreatment remains a significant problem. Up to 20% patients experience disease recurrence, indicating that standard treatments do not effectively treat DCIS for a subset of patients. By understanding the mechanisms of DCIS progression, we can develop new treatment strategies better tailored to patients. The chemokine CCL2 and its receptor CCR2 are known to regulate macrophage recruitment during inflammation and cancer progression. Recent studies indicate that increased CCL2/CCR2 signaling in breast epithelial cells enhance formation of IDC. Here, we characterized the molecular mechanisms important for CCL2/CCR2-mediated DCIS progression. Phospho-protein array profiling revealed that CCL2 stimulated phosphorylation of MET receptor tyrosine kinases in breast cancer cells. Co-immunoprecipitation and proximity ligation assays demonstrated that CCL2-induced MET activity depended on interactions with CCR2 and SRC. Extracellular flux analysis and biochemical assays revealed that CCL2/CCR2 signaling in breast cancer cells enhanced glycolytic enzyme expression and activity. CRISPR knockout and pharmacologic inhibition of MET revealed that CCL2/CCR2-induced breast cancer cell proliferation, survival, migration and glycolysis through MET-dependent mechanisms. In animals, MET inhibitors blocked CCR2-mediated DCIS progression and metabolism. CCR2 and MET were significantly co-expressed in patient DCIS and IDC tissues. In summary, MET receptor activity is an important mechanism for CCL2/CCR2-mediated progression and metabolism of early-stage breast cancer, with important clinical implications.}, }
@article {pmid35397740, year = {2022}, author = {Ensenyat-Mendez, M and Rünger, D and Orozco, JIJ and Le, J and Baker, JL and Weidhaas, J and Marzese, DM and DiNome, ML}, title = {Epigenetic Signatures Predict Pathologic Nodal Stage in Breast Cancer Patients with Estrogen Receptor-Positive, Clinically Node-Positive Disease.}, journal = {Annals of surgical oncology}, volume = {29}, number = {8}, pages = {4716-4724}, pmid = {35397740}, issn = {1534-4681}, support = {CP17/00188//European Regional Development Fund/ ; PI19/01514)//European Regional Development Fund/ ; UL1TR000124UCLA//CTSI UCLA/ ; }, mesh = {Axilla/pathology ; *Breast Neoplasms/genetics/metabolism/surgery ; Epigenesis, Genetic ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Receptors, Estrogen/metabolism ; Sentinel Lymph Node Biopsy/methods ; }, abstract = {BACKGROUND: Breast cancer patients with clinically positive nodes who undergo upfront surgery are often recommended for axillary lymph node dissection (ALND), yet more than half are found to have limited nodal disease (≤ 3 positive nodes, pN1) at surgery. In this study, we examined the efficiency of molecular classifiers in stratifying patients with clinically positive nodes to pN1 versus > pN1 disease.<br><br>METHODS: We evaluated the clinical and epigenetic data of patients in The Cancer Genome Atlas with estrogen receptor-positive, human epidermal growth factor receptor 2-negative invasive ductal carcinoma who underwent ALND for node-positive disease. Patients were divided into control (pN1, &#x2264;&#x2009;3 positive nodes) and case (>&#x2009;pN1, >&#x2009;3 positive nodes) groups. Machine learning algorithms were trained on 50% of the cohort and validated on the remaining 50% to identify DNA methylation signatures that predict >&#x2009;pN1 disease. Clinical variables and epigenetic signatures were compared.<br><br>RESULTS: Controls (n&#xa0;=&#xa0;34) and case (n&#xa0;=&#xa0;24) cohorts showed similar mean age (56.4&#xa0;&#xb1;&#xa0;12.2 vs. 57.6&#xa0;&#xb1;&#xa0;16.7&#xa0;years; p&#xa0;=&#xa0;0.77), number of nodes removed (16.1&#xa0;&#xb1;&#xa0;7.3 vs. 17.5&#xa0;&#xb1;&#xa0;6.2; p&#xa0;=&#xa0;0.45), tumor grade (p&#xa0;=&#xa0;0.76), presence of lymphovascular invasion (p&#xa0;=&#xa0;0.18), extranodal extension (p&#xa0;=&#xa0;0.17), tumor laterality (p&#xa0;=&#xa0;0.89), and tumor location (p&#xa0;=&#xa0;0.42). The mean number of positive nodes was significantly different (1.76&#xa0;&#xb1;&#xa0;0.82, pN1; 8.83&#xa0;&#xb1;&#xa0;5.36, >&#x2009;pN1; p&#xa0;<&#xa0;0.001). Three epigenetic signatures (EpiSig14, EpiSig13, EpiSig10) based on DNA methylation patterns of the primary tumors demonstrated high accuracy in predicting >&#x2009;pN1 disease (area under the curve 0.98).<br><br>CONCLUSIONS: Epigenetic signatures have an excellent diagnostic accuracy for stratifying nodal disease in patients with clinically positive nodes. Validation of this tool is warranted and may provide an accurate and cost-effective method of identifying patients with predicted low nodal burden who could be spared the morbidity of ALND.}, }
@article {pmid35393463, year = {2022}, author = {Foroozani, E and Akbari, A and Amanat, S and Rashidi, N and Bastam, D and Ataee, S and Sharifnia, G and Faraouei, M and Dianatinasab, M and Safdari, H}, title = {Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case-control study.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {5859}, pmid = {35393463}, issn = {2045-2322}, mesh = {*Breast Neoplasms/complications/etiology ; *Carcinoma, Ductal, Breast/complications/etiology ; *Carcinoma, Lobular/epidemiology/etiology/pathology ; Case-Control Studies ; Diet, Western ; Female ; Humans ; }, abstract = {Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case-control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients' medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants' dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.}, }
@article {pmid35389579, year = {2022}, author = {Clarey, D and DiMaio, D and Trowbridge, R}, title = {Deep Sweet Syndrome Secondary to Pegfilgrastim.}, journal = {Journal of drugs in dermatology : JDD}, volume = {21}, number = {4}, pages = {422-424}, doi = {10.36849/JDD.4794}, pmid = {35389579}, issn = {1545-9616}, mesh = {Filgrastim/adverse effects ; Granulocyte Colony-Stimulating Factor/adverse effects ; Humans ; Polyethylene Glycols/adverse effects ; *Sweet Syndrome/chemically induced/diagnosis/drug therapy ; }, abstract = {Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and a neutrophilic infiltrate that typically involves the papillary dermis. Although development is most commonly idiopathic, medications are also frequently associated with the eruption, notably, the granulocyte colony-stimulating factor (G-CSF), filgrastim. Pegylated G-CSF, despite similar activity, is not commonly reported, with only four published cases. We present a case of drug-induced sweet syndrome with unique histologic features (deep inflammatory infiltrate) in association with the usage of pegfilgrastim in the treatment of invasive ductal carcinoma of the breast. J Drugs Dermatol. 2022;21(4):422-424. doi:10.36849/JDD.4794.}, }
@article {pmid35384456, year = {2022}, author = {Bhaludin, BN and Tunariu, N and Koh, DM and Messiou, C and Okines, AF and McGrath, SE and Ring, AE and Parton, MM and Sharma, B and Gagliardi, T and Allen, SD and Pope, R and Johnston, SRD and Downey, K}, title = {A review on the added value of whole-body MRI in metastatic lobular breast cancer.}, journal = {European radiology}, volume = {32}, number = {9}, pages = {6514-6525}, pmid = {35384456}, issn = {1432-1084}, mesh = {*Bone Neoplasms/secondary ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Lobular/diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; Magnetic Resonance Imaging/methods ; Positron Emission Tomography Computed Tomography/methods ; Positron-Emission Tomography/methods ; Whole Body Imaging/methods ; }, abstract = {Invasive lobular breast carcinomas (ILC) account for approximately 15% of breast cancer diagnoses. They can be difficult to diagnose both clinically and radiologically, due to their infiltrative growth pattern. The pattern of metastasis of ILC is unusual, with spread to the serosal surfaces (pleura and peritoneum), retroperitoneum and gastrointestinal (GI)/genitourinary (GU) tracts and a higher rate of leptomeningeal spread than IDC. Routine staging and response assessment with computed tomography (CT) can be undertaken quickly and measurements can be reproduced easily, but this is challenging with metastatic ILC as bone-only/bone-predominant patterns are frequently seen and assessment of the disease status is limited in these scenarios. Functional imaging such as whole-body MRI (WBMRI) allows the assessment of bone and soft tissue disease by providing functional information related to differences in cellular density between malignant and benign tissues. A number of recent studies have shown that WBMRI can detect additional sites of disease in metastatic breast cancer (MBC), resulting in a change in systemic anti-cancer therapy. Although WBMRI and fluorodeoxyglucose-positron-emission tomography-computed tomography (FDG-PET/CT) have a comparable performance in the assessment of MBC, WBMRI can be particularly valuable as a proportion of ILC are non-FDG-avid, resulting in the underestimation of the disease extent. In this review, we explore the added value of WBMRI in the evaluation of metastatic ILC and compare it with other imaging modalities such as CT and FDG-PET/CT. We also discuss the spectrum of WBMRI findings of the different metastatic sites of ILC with CT and FDG-PET/CT correlation. KEY POINTS: • ILC has an unusual pattern of spread compared to IDC, with metastases to the peritoneum, retroperitoneum and GI and GU tracts, but the bones and liver are the commonest sites. • WBMRI allows functional assessment of metastatic disease, particularly in bone-only and bone-predominant metastatic cancers such as ILC where evaluation with CT can be challenging and limited. • WBMRI can detect more sites of disease compared with CT, can reveal disease progression earlier and provides the opportunity to change ineffective systemic treatment sooner.}, }
@article {pmid35372457, year = {2022}, author = {Niknam, K and Safaei, A and Ghaderi, A}, title = {Evaluation of the Prognostic Value of CD56 (140 kDa Isoform) Expression in Breast Cancer Tissues: an Eight-Year Retrospective Study.}, journal = {Iranian biomedical journal}, volume = {26}, number = {3}, pages = {175-182}, pmid = {35372457}, issn = {2008-823X}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/pathology ; *CD56 Antigen/genetics ; Female ; Humans ; Mastectomy ; Prognosis ; Protein Isoforms/genetics ; Retrospective Studies ; }, abstract = {BACKGROUND: Identification of specific antigens is highly beneficial for early detection, diagnosis, staging, and outcome prediction of cancer. This study aimed to evaluate the expression and prognostic value of CD56 (140 kDa isoform) in invasive ductal carcinoma (IDC).<br><br>METHODS: Sixty-five patients with IDC who underwent radical surgery or mastectomy as the primary treatment were included. Proper formalin-fixed and paraffin embedded tissue blocks of the patients were prepared and stained by IHC for CD56 (140 kDa isoform) molecule. Chi-square and fisher exact tests were used to compare the results against the clinicopathologic data of patients. Kaplan-Meier and log-rank test were employed to study the prognostic value of the target antigen.<br><br>RESULTS: The expression pattern of CD56 was granular and cytoplasmic. There were significant associations between the intensity of CD56 expression in invasive cells and carcinoma in situ (p = 0.005) and normal ducts (p = 0.010). Among all clinicipathologic parameters, there was only a significant association between the expression of estrogen receptor (ER) and CD56 (p = 0.023). Neither OS (overall survival; p = 0.356) nor DFS (disease-free survival; p = 0.976) had significant correlation with CD56 expression.<br><br>CONCLUSION: Our data indicated that the CD56 marker offers no prognostic value in terms of predicting the OS or DFS for up to eight years after primary surgery. Furthermore, the intensity of its expression is similar between normal, non-invasive, and invasive cells. Considering the generally better outcome of ER+ BC patients than their ER-counterparts, the CD56 marker may be indirectly associated with a more favorable prognosis among IDC patients.}, }
@article {pmid35364707, year = {2023}, author = {Wu, Y and Sun, S and Huang, Y and Xiao, M and Zhao, X and Lu, X and Xia, B and Qiao, K and Zhang, S and Wu, Q and Xiong, J and Cheng, S and Song, Y}, title = {Correlation analysis between androgen receptor and the clinicopathological features and prognosis of mammary Paget's disease.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {3}, pages = {1175-1184}, pmid = {35364707}, issn = {1432-1335}, support = {No.HLJ2019010//Ministry of Education Chunhui Project Cooperative Research Project/ ; No.LH2020H120//Heilongjiang Natural Science Foundation of China/ ; No.JJZD2020-04//Haiyan Research Fund of Harbin Medical University Cancer Hospital/ ; }, mesh = {Humans ; Female ; *Paget's Disease, Mammary/complications/metabolism/pathology ; Receptors, Androgen ; Prognosis ; Gene Expression ; *Breast Neoplasms/complications ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {PURPOSE: Little is known about the prognostic value of androgen receptor (AR) status in mammary Paget's disease (MPD). The purpose of this study was to explore AR status and the distribution of molecular subtypes in MPD as well as the relationship between AR expression and clinicopathological factors and to evaluate its prognostic value.<br><br>METHODS: We analyzed 170 MPD patients of varying subtypes. AR expression was verified by immunohistochemical staining, and the correlations between AR expression and clinicopathological characteristics and survival status were analyzed. We further investigated 91 MPD patients with invasive ductal carcinoma (MPD-IDC).<br><br>RESULTS: AR was expressed in 55.3% of overall MPD patients, and 78.2% had the human epidermal growth factor receptor 2 (HER2) overexpression subtype. AR positivity was significantly correlated with BMI (P&#x2009;=&#x2009;0.037) and pathological N stage (P&#x2009;=&#x2009;0.023). Multivariate analysis indicated that pathological T stage and pathological N stage were independent prognostic factors for overall survival (OS). The positive AR group was significantly associated with better OS (P&#x2009;=&#x2009;0.014). Among 91 MPD-IDC patients, AR was expressed in 56.0%, and 80.0% had the HER2 overexpression subtype. AR positivity was significantly correlated with pathological N stage (P&#x2009;=&#x2009;0.033). Multivariate analysis indicated that AR and pathological T stage were independent prognostic factors for OS. Furthermore, AR positivity was significantly related to better OS (P&#x2009;=&#x2009;0.005) in MPD-IDC patients as well as in patients with the HER2 overexpression subtype (P&#x2009;=&#x2009;0.029).<br><br>CONCLUSION: Our results confirmed that AR is a potential biomarker for evaluating the prognosis of patients.}, }
@article {pmid35348974, year = {2022}, author = {Sivadas, A and Kok, VC and Ng, KL}, title = {Multi-omics analyses provide novel biological insights to distinguish lobular ductal types of invasive breast cancers.}, journal = {Breast cancer research and treatment}, volume = {193}, number = {2}, pages = {361-379}, pmid = {35348974}, issn = {1573-7217}, support = {MOST 109-2221-E-468-013//Ministry of Science and Technology, Taiwan/ ; MOST 108-2221-E-468-020//Ministry of Science and Technology, Taiwan/ ; 07-Asia-02//Asia University Taiwan/ ; 107-Asia-09//Asia University Taiwan/ ; IA/E/19/1/504945//The Wellcome Trust DBT India Alliance/ ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/pathology ; Female ; Humans ; *Immediate-Early Proteins ; Prognosis ; Receptors, G-Protein-Coupled ; Survival Analysis ; Tumor Suppressor Proteins ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) treatment is similar to invasive ductal carcinoma (IDC; now invasive carcinoma-no special type, IBC-NST), based on its intrinsic subtype. However, further investigation is required for an integrative understanding of differentially perturbed molecular patterns and pathways in these histotypes.<br><br>METHODS: A dataset of 780 IDC and 201 ILC samples from the TCGA-BRCA project for cross-platform multi-omics was analyzed. We leveraged a consensus approach integrating different bioinformatic algorithms to analyze mutations, CNAs, mRNA, miRNA abundance, methylation, and protein abundance to understand the complex crosstalks that distinguish ILC and IDC samples. A histotype-matched comparison was performed. We performed Cox survival analyses for prognosis based on our identified 53 histotype-specific and four discordant genes.<br><br>RESULTS: Approximately 90% of ILC cases were of the luminal subtype. Somatic mutations in CDH1 were higher in ILC than in IDC (FDR-adjusted p&#x2009;<&#x2009;0.01). Fifty-three significant oncogenic or tumor-suppressive DEGs were identified in a single histotype. PPAR signaling and lipolysis regulation in adipocytes were significantly enriched in ILC tumors. CDH1 protein had the highest differential abundance (AUC: 0.85). Moreover, BTG2, GSTA2, GPR37L1, and PGBD5 amplification was associated with poorer OS in ILC compared with no alteration. RIMS2, NACA4P, MYC, ZFPM2, and POU5F1B amplification showed a lower overall survival in patients with IDC. miR-195 showed an IDC-specific downregulation, causing overexpression of CCNE1. Integrative multi-omics supervised analysis identified 296 differentially expressed genes that successfully distinguished IDC and ILC histotypes.<br><br>CONCLUSIONS: Our findings identify novel molecular candidates that potentially drive and modify the disease differentially among these histotypes.}, }
@article {pmid35348061, year = {2021}, author = {Khan, NA and Nguyen, ST and Teh, PG and Ranpura, VN and Bhatia, T}, title = {Duodenal Metastasis in Triple-Negative Invasive Ductal Breast Carcinoma With Negative Mammography: A Case Report and Review of the Literature.}, journal = {The Permanente journal}, volume = {25}, number = {}, pages = {}, pmid = {35348061}, issn = {1552-5775}, mesh = {*Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/secondary ; *Carcinoma, Lobular/pathology/secondary ; Female ; Humans ; Mammography ; Receptors, Estrogen ; }, abstract = {Breast cancer metastasis to the gastrointestinal tract is uncommon, and duodenal involvement is exceptionally rare. Those cases that do metastasize are reported to be lobular, with ductal carcinomas comprising only a small percentage of reported cases. Furthermore, these invasive carcinomas are typically estrogen receptor-, progesterone receptor-positive ± human epidermal growth factor receptor 2 malignancies. We present a unique case of a patient with duodenal metastasis as the first sign of metastatic breast cancer. The rarity of this case is highlighted by the fact that the patient had no known breast malignancy, and pathological findings revealed triple-negative invasive ductal carcinoma consistent with primary breast cancer. Diagnostic mammogram and ultrasound were negative for any lesions.}, }
@article {pmid35343265, year = {2022}, author = {Zhao, CM and Li, LL and Xu, JW and Li, ZW and Shi, P and Jiang, R}, title = {LINC00092 Suppresses the Malignant Progression of Breast Invasive Ductal Carcinoma Through Modulating SFRP1 Expression by Sponging miR-1827.}, journal = {Cell transplantation}, volume = {31}, number = {}, pages = {9636897221086967}, pmid = {35343265}, issn = {1555-3892}, mesh = {*Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; }, abstract = {Breast invasive ductal carcinoma (IDC) is a most common kind of breast cancer (BC), yet to date the corresponding effective therapies are limited. Extensive evidence has indicated that lncRNAs are involved in multiple cancers, and the potential mechanism of lncRNAs, such as LINC00092, mentioned in IDC remains elusive. IDC clinical samples from TCGA database were used to analyze the expression levels of LINC00092, miR-1827 and SFRP1. Kaplan-Meier method was applied to plot the overall survival curves. KEGG and GO were employed to screen the pathway that LINC00092 participated in. Pearson's correlation analysis determined the relationship between LINC00092 and SFRP1. Bioinformatics analysis and dual-luciferase reporter assay examined the association among LINC00092, miR-1827, and SFRP1. Cell counting kit-8, colony formation and transwell assays were performed to detect cell viability, colony formation, and migration and invasion, respectively. Quantitative reverse-transcription polymerase chain reaction and western blot were utilized to investigate the expression at RNA and protein levels. LINC00092 expression was down-regulated in IDC tissues and cells, which was correlated with poor prognosis. Down-regulated LINC00092 facilitated cell proliferation, colony formation, and cell migration and invasion, while up-regulated LINC00092 inhibited cell malignant behaviors. LINC00092/SFRP1 physically bound to miR-1827 in IDC. SFRP1 expression was proportional to LINC00092 expression and inversely proportional to miR-1827 expression. The inhibitory effects of LINC00092 on cell aggressive behaviors were partially regulated by miR-1827/SFRP1. In summary, our results indicated that overexpression of LINC00092 inhibited the development of IDC through modulating miR-1827/SFRP1 axis, suggesting new therapeutic targets to treat IDC.}, }
@article {pmid35340411, year = {2022}, author = {Du, W and Miao, Y and Zhang, G and Luo, G and Yang, P and Chen, F and Zhang, B and Yang, C and Li, G and Chang, J}, title = {The Regulatory Role of Neuropeptide Gene Glucagon in Colorectal Cancer: A Comprehensive Bioinformatic Analysis.}, journal = {Disease markers}, volume = {2022}, number = {}, pages = {4262600}, pmid = {35340411}, issn = {1875-8630}, mesh = {Biomarkers, Tumor/metabolism ; *Colonic Neoplasms/genetics ; Computational Biology ; Gene Expression Regulation, Neoplastic ; *Glucagon/genetics/metabolism ; Humans ; }, abstract = {BACKGROUND: Colorectal cancer is highly prevalent and causes high global mortality, and glucagon axis has been implicated in colon cancer. The present study is aimed at investigating the regulating mechanisms of glucagon involvement in colorectal cancer.<br><br>METHODS: Publicly available data from the TCGA database was utilized to explore the expression pattern and regulating role of glucagon (GCG) in colorectal cancer (COADREAD) including colon adenocarcinomas (COAD) and rectum adenocarcinomas (READ). Statistical analyses were performed using the R software packages and public web servers. The expression pattern and prognostic significance of GCG gene in pan-cancer and TCGA-COADREAD data were investigated by performing unpaired and paired sample analyses. The association of GCG expression with clinical characteristics was investigated using logistic regression analysis. Univariate cox regression analysis was performed to test the prognostic value of GCG expression for overall survival in COADREAD patients. GCG-significantly correlated genes were obtained. Biological functions and signaling pathways were identified by performing functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Additionally, the potential involvement of GCG in tumor immunity was researched by investigating the correlation between GCG expression and 24 tumor infiltrating immune cells.<br><br>RESULTS: GCG was found to be significantly downregulated in COADREAD tumor samples compared with healthy control samples. GCG gene was shown to be associated with the prognostic outcomes of COADREAD, whereby its upregulation predicted improved survival outcomes. Functional enrichment analysis showed that the top 100 positively and top 100 negatively GCG-correlated genes were mainly enriched in three signaling pathways including ribosome, nitrogen metabolism, and proximal tubule bicarbonate reclamation. The GSEA showed that GCG-significantly correlated genes were mainly enriched in cell cycle-related pathways (reactome cell cycle, reactome cell cycle mitotic, reactome cell cycle checkpoints, reactome M phase, Reactome G2 M DNA damage checkpoint, and Reactome G2 M checkpoints), neuropeptide ligand receptor interaction, RHO GTPases signaling, WNT signaling, RUNX1 signaling, NOTCH signaling, ESR signaling, HCMV infection, and oxidative stress-related signaling. GCG was positively correlated with Th17 cells, pDC, macrophages, TFH cells, iDC, Tem, B cells, dendritic cells, neutrophils, mast cells, and eosinophils and was negatively associated with NK cells.<br><br>CONCLUSIONS: GCG dysregulation with high prognostic value in COADREAD was noted. Several tumor progression-related pathways and tumor immune-modulatory cells were linked to GCG expression in COADREAD. Therefore, GCG may be regarded as a potential therapeutic target for treating colorectal cancer.}, }
@article {pmid35337805, year = {2022}, author = {Rajabi, F and Mozdarani, H}, title = {Expression level of miR-155, miR-15a and miR-19a in peripheral blood of ductal carcinoma breast cancer patients: Possible bioindicators for cellular inherent radiosensitivity.}, journal = {Experimental and molecular pathology}, volume = {126}, number = {}, pages = {104758}, doi = {10.1016/j.yexmp.2022.104758}, pmid = {35337805}, issn = {1096-0945}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/genetics/radiotherapy ; Environmental Biomarkers ; Female ; Humans ; *MicroRNAs ; ROC Curve ; Radiation Tolerance/genetics ; }, abstract = {Examination of cellular radiosensitivity (RS) helps prevent the adverse side-effects of radiotherapy in radioresistant tumors. We aim to study whether miRNA-155 (miR-155), miR-19a and miR-15a can predict inherent RS according to cellular RS in breast cancer (BC) patients. This study was done on the blood samples of 40 invasive ductal carcinoma (IDC) BC patients and 15 healthy women. G2 assay was performed to evaluate cellular RS. To study the expression level of these miRNAs in blood, qRT-PCR was used. The sensitivity and specificity of the studied miRNAs were assessed by the receiver operating characteristic (ROC) curve. The yield of spontaneous (SY) and radiation-induced (RIY) chromatid breaks (CBs) was significantly different between control and patient groups (p < 0.0001). A cut-off value was specified to recognize the patients with cellular RS from those without. Expression of miR-15a was significantly downregulated (p < 0.0001) in BC patients. However, miR-19a showed upregulation in the blood of BC patients. It was also found the expression level of miR-155 and miR-19a were significantly associated with frequency of CBs (FCB) (p < 0.05). ROC curve analysis manifested that the miR-15a and miR-19a differentiate BC patients and healthy women with 0.91 and 0.68 yielding an area under the ROC curve, respectively. miR-155 and miR-19a discriminate between BC patients with and without cellular RS with area under the ROC curve 0.98 and 0.68. Our findings uncovered miR-155 and miR-19a could be applied as a bioindicator to predict cellular radiosensitivity of BC patients.}, }
@article {pmid35324454, year = {2022}, author = {Wang, K and Schütze, I and Gulde, S and Bechmann, N and Richter, S and Helm, J and Lauseker, M and Maurer, J and Reul, A and Spoettl, G and Klink, B and William, D and Knösel, T and Friemel, J and Bihl, M and Weber, A and Fankhauser, M and Schober, L and Vetter, D and Broglie Däppen, M and Ziegler, CG and Ullrich, M and Pietzsch, J and Bornstein, SR and Lottspeich, C and Kroiss, M and Fassnacht, M and Wenter, VUJ and Ladurner, R and Hantel, C and Reincke, M and Eisenhofer, G and Grossman, AB and Pacak, K and Beuschlein, F and Auernhammer, CJ and Pellegata, NS and Nölting, S}, title = {Personalized drug testing in human pheochromocytoma/paraganglioma primary cultures.}, journal = {Endocrine-related cancer}, volume = {29}, number = {6}, pages = {285-306}, doi = {10.1530/ERC-21-0355}, pmid = {35324454}, issn = {1479-6821}, mesh = {*Adrenal Gland Neoplasms/drug therapy/genetics/metabolism ; Animals ; *Antineoplastic Agents/pharmacology/therapeutic use ; Everolimus/therapeutic use ; Humans ; Mice ; *Paraganglioma/drug therapy/genetics/pathology ; *Pheochromocytoma/drug therapy/genetics/metabolism ; Zoledronic Acid/therapeutic use ; }, abstract = {Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.}, }
@article {pmid35311108, year = {2022}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Anesthesia With Propofol Sedation Reduces Locoregional Recurrence in Patients With Breast Cancer Receiving Total Mastectomy Compared With Non-Propofol Anesthesia.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {708632}, pmid = {35311108}, issn = {2234-943X}, abstract = {PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.<br><br>PATIENTS AND METHODS: Patients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).<br><br>RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28-0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 1, and pN stage 2-3 were 1.16 (1.04-2.08), 1.28 (1.07-2.12), 3.71 (1.82-7.59), 4.67 (1.65-13.18), 1.09 (1.02-1.21), 1.17 (1.03-2.16), 1.10 (1.03-1.33), and 1.22 (1.06-2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64-0.94) compared with that for no adjuvant RT.<br><br>CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.}, }
@article {pmid35272171, year = {2022}, author = {Acikgoz, E and Duzagac, F and Guven, U and Yigitturk, G and Kose, T and Oktem, G}, title = {"Double hit" strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cells.}, journal = {International immunopharmacology}, volume = {107}, number = {}, pages = {108684}, doi = {10.1016/j.intimp.2022.108684}, pmid = {35272171}, issn = {1878-1705}, mesh = {Animals ; *Cancer Vaccines/therapeutic use ; Dendritic Cells ; Mice ; N-Acetylneuraminic Acid ; *Neoplasms ; Neoplastic Stem Cells ; }, abstract = {Cancer stem cells (CSCs), which represent the root cause of resistance to conventional treatments, recurrence, and metastasis, constitute the critical point of failure in cancer treatments. Targeting CSCs with dendritic cell (DC)-based vaccines have been an effective strategy, but sialic acids on the surface of DCs limit the interaction with loaded antigens. We hypothesized that removal of sialic acid moieties on immature DCs (iDCs) could significantly affect DC-CSC-antigen loading, thereby leading to DC maturation and improving immune recognition and activity. The lysate of CD44[+]/CD24[-/low] breast CSCs (BCSCs) was pulsed with sialidase-treated DCs to obtain mature dendritic cells (mDCs). The roles of cytoskeletal elements in antigen uptake and dendritic cell maturation were determined by immunofluorescence staining, flow cytometry, and cytokine measurement, respectively. To test the efficacy of the vaccine in vivo, CSCs tumor-bearing mice were immunized with iDC or mDC. Pulsing DCs with antigen increased the expression levels of actin, gelsolin, talin, WASp, and Arp2, especially in podosome-like regions. Compared with iDCs, mDCs expressed high levels of CD40, CD80, CD86 costimulatory molecules and increased IL-12 production. Vaccination with mDC: i) increased CD8+ and CD4 + T-cell numbers, ii) prevented tumor growth with anti-mitotic activity and apoptotic induction, iii) suppressed metastasis by decreasing Snail, Slug, and Twist expressions. This study reveals for the first time that sialic acid removal and loading with CSC antigens induces significant molecular, morphological, and functional changes in DCs and that this new DC identity may be considered for future combined immunotherapy strategies against breast tumors.}, }
@article {pmid35266635, year = {2022}, author = {Karabid, NM and Wiedemann, T and Gulde, S and Mohr, H and Segaran, RC and Geppert, J and Rohm, M and Vitale, G and Gaudenzi, G and Dicitore, A and Ankerst, DP and Chen, Y and Braren, R and Kaissis, G and Schilling, F and Schillmaier, M and Eisenhofer, G and Herzig, S and Roncaroli, F and Honegger, JB and Pellegata, NS}, title = {Angpt2/Tie2 autostimulatory loop controls tumorigenesis.}, journal = {EMBO molecular medicine}, volume = {14}, number = {5}, pages = {e14364}, pmid = {35266635}, issn = {1757-4684}, mesh = {*Angiopoietin-2/metabolism ; Animals ; Carcinogenesis ; Endothelial Cells/metabolism ; Heterografts ; Humans ; Mice ; Neoplasm Recurrence, Local ; *Pituitary Neoplasms/genetics/metabolism/pathology ; Rats ; Receptor, TIE-2/genetics/metabolism ; Zebrafish ; }, abstract = {Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.}, }
@article {pmid35262438, year = {2022}, author = {Jones, VM and Pearce, JB and Khalil, M and Cain, O and Coldren, D and Martin, H and Howard-McNatt, M and Levine, E and Chiba, A}, title = {Upstage Rate of Complex Sclerosing Lesions/Radial Scars.}, journal = {The American surgeon}, volume = {88}, number = {5}, pages = {964-967}, doi = {10.1177/00031348211056282}, pmid = {35262438}, issn = {1555-9823}, mesh = {Biopsy, Large-Core Needle/methods ; Breast/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/pathology/surgery ; Cicatrix/pathology ; Female ; Humans ; Mammography ; Retrospective Studies ; }, abstract = {BACKGROUND: Radial scars (RS) and complex sclerosing lesions (CSL) are breast radiologic findings described as small, stellate lesions causing architectural distortion. This can mimic malignancy. Core needle biopsy (CNB) is often performed. Advances in breast imaging have led to increased detection of RS/CSL. The upstage rate of RS/CSL to in situ or invasive disease is 0-40%. We sought to determine the upstaging rate of RS/CSL to in situ, invasive disease, or high-risk lesion at our institution to create excision guidelines.<br><br>METHODS: The pathology database of a single center was searched for RS/CSL, from January 2013 to September 2020. We included CNB without malignancy or high-risk lesion (eg, atypical ductal hyperplasia). Patient demographics, indications for biopsy, imaging findings, biopsy procedure, and final pathology were collected.<br><br>RESULTS: Forty-four patients were included. 52.3% had CNB for architectural distortion on mammography, 18.2% for mass, 11.4% for calcifications, 2.3% for abnormal MRI, and 15.9% for multiple reasons (eg, calcifications and mass). Most had an ultrasound: 43.2% had no abnormality and 34.1% had a mass. All CNB were vacuum assisted, 65.9% with 9-gauge needle, and averaged 10.0 cores. 77.3% were stereotactic biopsies, 13.6% ultrasound, and 6.8% MRI. 59.1% had excision after CNB. 82.1% of patients did not upstage. One patient upstaged to invasive ductal carcinoma (3.6%) and two patients to high-risk lesion (7.1%).<br><br>DISCUSSION: There was low upstage rate of RS/CSL on excisional biopsy. Centers could consider close surveillance for RS/CSL on CNB. Longer follow-up in cases of deferred excision is needed to ensure oncologic safety.}, }
@article {pmid35260605, year = {2022}, author = {McLamore, Q and Syropoulos, S and Leidner, B and Hirschberger, G and Young, K and Zein, RA and Baumert, A and Bilewicz, M and Bilgen, A and van Bezouw, MJ and Chatard, A and Chekroun, P and Chinchilla, J and Choi, HS and Euh, H and Gomez, A and Kardos, P and Khoo, YH and Li, M and Légal, JB and Loughnan, S and Mari, S and Tan-Mansukhani, R and Muldoon, O and Noor, M and Paladino, MP and Petrović, N and Selvanathan, HP and Uluğ, &#xd6;M and Wohl, MJ and Yeung, WLV and Burrows, B}, title = {Trust in scientific information mediates associations between conservatism and coronavirus responses in the U.S., but few other nations.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {3724}, pmid = {35260605}, issn = {2045-2322}, support = {2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; }, mesh = {Adult ; Aged ; Attitude ; COVID-19/*epidemiology/virology ; Canada ; Female ; Health Behavior ; Humans ; Indonesia ; Male ; Middle Aged ; *Politics ; Quarantine ; SARS-CoV-2/isolation &amp; purification ; Surveys and Questionnaires ; *Trust ; United States/epidemiology ; }, abstract = {U.S.-based research suggests conservatism is linked with less concern about contracting coronavirus and less preventative behaviors to avoid infection. Here, we investigate whether these tendencies are partly attributable to distrust in scientific information, and evaluate whether they generalize outside the U.S., using public data and recruited representative samples across three studies (Ntotal = 34,710). In Studies 1 and 2, we examine these relationships in the U.S., yielding converging evidence for a sequential indirect effect of conservatism on compliance through scientific (dis)trust and infection concern. In Study 3, we compare these relationships across 19 distinct countries. Although the relationships between trust in scientific information about the coronavirus, concern about coronavirus infection, and compliance are consistent cross-nationally, the relationships between conservatism and trust in scientific information are not. These relationships are strongest in North America. Consequently, the indirect effects observed in Studies 1-2 only replicate in North America (the U.S. and Canada) and in Indonesia. Study 3 also found parallel direct and indirect effects on support for lockdown restrictions. These associations suggest not only that relationships between conservatism and compliance are not universal, but localized to particular countries where conservatism is more strongly related to trust in scientific information about the coronavirus pandemic.}, }
@article {pmid35247977, year = {2022}, author = {Foster, GJ and Sievert, MAC and Button-Simons, K and Vendrely, KM and Romero-Severson, J and Ferdig, MT}, title = {Cyclical regression covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasite Plasmodium falciparum.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {180}, pmid = {35247977}, issn = {1471-2164}, support = {P01 AI127338/AI/NIAID NIH HHS/United States ; P01 AI127338/NH/NIH HHS/United States ; }, mesh = {Animals ; *Antimalarials/pharmacology/therapeutic use ; Drug Resistance ; Genes, Developmental ; Humans ; *Malaria, Falciparum/parasitology ; *Parasites/genetics ; Plasmodium falciparum ; Protozoan Proteins/genetics ; }, abstract = {BACKGROUND: The cyclical nature of gene expression in the intraerythrocytic development cycle (IDC) of the malaria parasite, Plasmodium falciparum, confounds the accurate detection of specific transcriptional differences, e.g. as provoked by the development of drug resistance. In lab-based studies, P. falciparum cultures are synchronized to remove this confounding factor, but the rapid detection of emerging resistance to artemisinin therapies requires rapid analysis of transcriptomes extracted directly from clinical samples. Here we propose the use of cyclical regression covariates (CRC) to eliminate the major confounding effect of developmentally driven transcriptional changes in clinical samples. We show that elimination of this confounding factor reduces both Type I and Type II errors and demonstrate the effectiveness of this approach using a published dataset of 1043 transcriptomes extracted directly from patient blood samples with different patient clearance times after treatment with artemisinin.<br><br>RESULTS: We apply this method to two publicly available datasets and demonstrate its ability to reduce the confounding of differences in transcript levels due to misaligned intraerythrocytic development time. Adjusting the clinical 1043 transcriptomes dataset with CRC results in detection of fewer functional categories than previously reported from the same data set adjusted using other methods. We also detect mostly the same functional categories, but observe fewer genes within these categories. Finally, the CRC method identifies genes in a functional category that was absent from the results when the dataset was adjusted using other methods. Analysis of differential gene expression in the clinical data samples that vary broadly for developmental stage resulted in the detection of far fewer transcripts in fewer functional categories while, at the same time, identifying genes in two functional categories not present in the unadjusted data analysis. These differences are consistent with the expectation that CRC reduces both false positives and false negatives with the largest effect on datasets from samples with greater variance in developmental stage.<br><br>CONCLUSIONS: Cyclical regression covariates have immediate application to parasite transcriptome sequencing directly from clinical blood samples and to cost-constrained in vitro experiments.}, }
@article {pmid35245349, year = {2022}, author = {Hophan, SL and Odnokoz, O and Liu, H and Luo, Y and Khan, S and Gradishar, W and Zhou, Z and Badve, S and Torres, MA and Wan, Y}, title = {Ductal Carcinoma In Situ of Breast: From Molecular Etiology to Therapeutic Management.}, journal = {Endocrinology}, volume = {163}, number = {4}, pages = {}, pmid = {35245349}, issn = {1945-7170}, support = {R01 CA245699/CA/NCI NIH HHS/United States ; UG3 CA256967/CA/NCI NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; }, mesh = {Breast ; *Breast Neoplasms/genetics/therapy ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/therapy ; Female ; Humans ; }, abstract = {Ductal carcinoma in situ (DCIS) makes up a majority of noninvasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms by which approximately half of all DCIS lesions progress to an invasive status. New strategies that pinpoint molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement.}, }
@article {pmid35238350, year = {2023}, author = {Egea, V and Megens, RTA and Santovito, D and Wantha, S and Brandl, R and Siess, W and Khani, S and Soehnlein, O and Bartelt, A and Weber, C and Ries, C}, title = {Properties and fate of human mesenchymal stem cells upon miRNA let-7f-promoted recruitment to atherosclerotic plaques.}, journal = {Cardiovascular research}, volume = {119}, number = {1}, pages = {155-166}, pmid = {35238350}, issn = {1755-3245}, mesh = {Mice ; Animals ; Humans ; *MicroRNAs/genetics ; *Plaque, Atherosclerotic ; *Atherosclerosis/genetics ; Cytokines ; Immunologic Factors ; *Mesenchymal Stem Cells ; }, abstract = {AIMS: Atherosclerosis is a chronic inflammatory disease of the arteries leading to the formation of atheromatous plaques. Human mesenchymal stem cells (hMSCs) are recruited from the circulation into plaques where in response to their environment they adopt a phenotype with immunomodulatory properties. However, the mechanisms underlying hMSC function in these processes are unclear. Recently, we described that miRNA let-7f controls hMSC invasion guided by inflammatory cytokines and chemokines. Here, we investigated the role of let-7f in hMSC tropism to human atheromas and the effects of the plaque microenvironment on cell fate and release of soluble factors.<br><br>METHODS AND RESULTS: Incubation of hMSCs with LL-37, an antimicrobial peptide abundantly found in plaques, increased biosynthesis of let-7f and N-formyl peptide receptor 2 (FPR2), enabling chemotactic invasion of the cells towards LL-37, as determined by qRT-PCR, flow cytometry, and cell invasion assay analysis. In an Apoe-/- mouse model of atherosclerosis, circulating hMSCs preferentially adhered to athero-prone endothelium. This property was facilitated by elevated levels of let-7f in the hMSCs, as assayed by ex vivo artery perfusion and two-photon laser scanning microscopy. Exposure of hMSCs to homogenized human atheromatous plaque material considerably induced the production of various cytokines, chemokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinases, as studied by PCR array and western blot analysis. Moreover, exposure to human plaque extracts elicited differentiation of hMSCs into cells of the myogenic lineage, suggesting a potentially plaque-stabilizing effect.<br><br>CONCLUSIONS: Our findings indicate that let-7f promotes hMSC tropism towards atheromas through the LL-37/FPR2 axis and demonstrate that hMSCs upon contact with human plaque environment develop a potentially athero-protective signature impacting the pathophysiology of atherosclerosis.}, }
@article {pmid35231053, year = {2022}, author = {Troughton, LD and O'Loughlin, DA and Zech, T and Hamill, KJ}, title = {Laminin N-terminus α31 is upregulated in invasive ductal breast cancer and changes the mode of tumour invasion.}, journal = {PloS one}, volume = {17}, number = {3}, pages = {e0264430}, pmid = {35231053}, issn = {1932-6203}, support = {BB/L020513/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P0257731/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal ; Cell Line, Tumor ; Cell Movement ; Female ; Humans ; Immunohistochemistry ; Laminin/genetics/metabolism ; Neoplasm Invasiveness ; }, abstract = {Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt α31 expression and distribution were analysed by immunohistochemistry in human breast tissue biopsy sections and tissue microarrays covering 232 breast cancer samples. This analysis revealed LaNt α31 to be upregulated in 56% of invasive ductal carcinoma specimens compared with matched normal tissue, and further increased in nodal metastasis compared with the tumour mass in 45% of samples. 65.8% of triple negative cases displayed medium to high LaNt α31 expression. To study LaNt α31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. 2D cell migration and invasion into collagen hydrogels were not significantly different between LaNt α31 overexpressing cells and control treated cells. However, LaNt α31 overexpression reduced the proliferation rate of MCF-7 and MDA-MB-231 cells. Moreover, LaNt α31 overexpressing MDA-MB-231 cells displayed a striking change in their mode of invasion into laminin-containing Matrigel; changing from multicellular streaming to individual cellular-invasion. In agreement with these results, 66.7% of the tumours with the highest LaNt α31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt α31 expression could contribute to the processes involved in tumour invasion and may represent a new therapeutic target.}, }
@article {pmid35220223, year = {2022}, author = {Dantas, FT and Felix-Silva, PH and Angotti-Carrara, HH and Dos-Reis, FJC and Junior, MT and DE-Souza, SLS and Palioto, DB}, title = {A New Method for Obtaining Tumor Interstitial Fluid Applied to Cytokine Analysis of Breast Carcinoma Samples.}, journal = {Anticancer research}, volume = {42}, number = {3}, pages = {1327-1332}, doi = {10.21873/anticanres.15600}, pmid = {35220223}, issn = {1791-7530}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Biopsy, Large-Core Needle ; Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Enzyme-Linked Immunosorbent Assay ; Extracellular Fluid/*immunology ; Female ; Humans ; Interleukin-1beta/*analysis ; Middle Aged ; Tumor Microenvironment ; }, abstract = {BACKGROUND/AIM: Tumor interstitial fluid (TIF), a component of the tumor microenvironment, is a valuable source of molecules and substances that help in diagnosis and prognosis of solid tumors. There is still no consensus on the optimal method for collecting TIF. Therefore, this study aimed to evaluate the effectiveness of a new method of collecting TIF in invasive ductal carcinoma (IDC) samples for cytokine interleukin 1β (IL1β) quantification.<br><br>MATERIALS AND METHODS: Forty women allowed the collection of TIF using absorbent paper strips during the performance of the core biopsy. The samples were stored at a temperature of -80&#xb0;C and then analyzed using an enzyme-linked immunoassay.<br><br>RESULTS: The mean values for IL1&#x3b2; and total protein were 11.39 mg/ml and 2.15 mg/ml, respectively.<br><br>CONCLUSION: it was possible to quantify the cytokine IL1&#x3b2; and the total protein concentration present in the tumor tissue through TIF collection with the use of absorbent paper filters, demonstrating the effectiveness of this new method in oncology.}, }
@article {pmid35207775, year = {2022}, author = {Huang, CC and Chang, CL and Sun, M and Chiang, MF and Sum, SY and Zhang, J and Wu, SY}, title = {Adjuvant Radiotherapy Is Associated with an Increase in the Survival of Old (Aged over 80 Years) and Very Old (Aged over 90 Years) Women with Breast Cancer Receiving Breast-Conserving Surgery.}, journal = {Journal of personalized medicine}, volume = {12}, number = {2}, pages = {}, pmid = {35207775}, issn = {2075-4426}, abstract = {This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT. Background: To date, no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available for old (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS). Patients and Methods: We enrolled old (≥80 years old) and very old (≥90 years old) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We grouped them based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed. Results: Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT. In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44-0.70). The aHRs (95% CIs) of LRR and DM for adjuvant WBRT were 0.29 (0.19-0.45) and 0.45 (0.32-0.62), respectively, compared with no adjuvant WBRT. Conclusions: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.}, }
@article {pmid35200056, year = {2022}, author = {Hannarici, Z and Yılmaz, A and Buyukbayram, ME and Turhan, A and Tekin, SB and Bilici, M}, title = {Lipegfilgrastim may cause hyperleukocytosis.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {28}, number = {8}, pages = {1902-1905}, doi = {10.1177/10781552221082645}, pmid = {35200056}, issn = {1477-092X}, mesh = {Humans ; Female ; Middle Aged ; Filgrastim/therapeutic use ; *Allopurinol ; *Uric Acid ; Polyethylene Glycols ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Pain/chemically induced ; }, abstract = {INTRODUCTION: Granulocyte colony-stimulating factors (G-CSF) are utilized both in the treatment and prophylaxis of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting G-CSF. Albeit it provides ease of administration compared to short-acting GCSFs, some lipegfilgrastim-related adverse events may occur. Bone pain, widespread body pain, and feeling of fever are among common adverse effects, while rare but more serious adverse effects such as leukocytosis, spleen rupture, interstitial pneumonia, acute respiratory distress syndrome, capillary leak syndrome, hypokalemia, and glomerulonephritis may occur as well.<br><br>CASE REPORT: We reported a case of hyperleukocytosis that developed due to prophylactic administration of lipegfilgrastim following the first course of neoadjuvant pertuzumab (840-420&#x2005;mg), trastuzumab (8-6mg/kg), and docetaxel (75&#x2005;mg/m2) in a 45-year-old female patient with a diagnosis of breast invasive ductal carcinoma. The patient, who presented with weakness, loss of appetite, and oral intake disorder, had elevated white blood cell (WBC), lactate dehydrogenase (LDH), and uric acid levels in her test results. Peripheral smear (PS) had a left shift.<br><br>MANAGEMENT AND OUTCOME: Intravenous 0.9% NaCl and peroral allopurinol were started to be administered to the patient. On the ninth day of hospitalization, the patient's clinical manifestation improved, and her WBC, LDH, uric acid, and PS returned to normal. Besides, the progression to tumor lysis syndrome (TLS) was prevented by appropriate hydration and allopurinol treatment. In subsequent chemotherapies (CTs), lipegfilgrastim was discontinued and filgrastim was started. The patient whose hyperleukocytosis did not recur was operated on following neoadjuvant CT. The patient's routine follow-up continues without any problems.<br><br>DISCUSSION: Although lipegfilgrastim-induced hyperleukocytosis has not been reported in the literature, it should be borne in mind that hyperleukocytosis and related complications may occur, as in our case.}, }
@article {pmid35187122, year = {2022}, author = {Neves, EGA and Koh, CC and Souza-Silva, TG and Passos, LSA and Silva, ACC and Velikkakam, T and Villani, F and Coelho, JS and Brodskyn, CI and Teixeira, A and Gollob, KJ and Nunes, MDCP and Dutra, WO}, title = {T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {787423}, pmid = {35187122}, issn = {2297-055X}, abstract = {Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4[+], CD8[+], and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8[+] T-cells were highly activated in CCC as compared to IDC, CD4[+] T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.}, }
@article {pmid35178446, year = {2022}, author = {Li, X and Zhao, G and Mi, X and Xu, T and Li, X and Liu, B}, title = {Ajuba Overexpression Promotes Breast Cancer Chemoresistance and Glucose Uptake through TAZ-GLUT3/Survivin Pathway.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {3321409}, pmid = {35178446}, issn = {2314-6141}, mesh = {*Breast Neoplasms/drug therapy/genetics ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Glucose ; Glucose Transporter Type 3/genetics ; Humans ; *LIM Domain Proteins/genetics ; Survivin/genetics ; TEA Domain Transcription Factors/genetics ; }, abstract = {The LIM protein Ajuba has been implicated in the development of human cancers. To date, its expression pattern and biological significance in breast cancers (BC) have not been fully investigated. In the current study, we examined Ajuba protein levels in 93 invasive ductal carcinoma specimens by immunohistochemistry. The Ajuba expression level was elevated in breast cancer tissue compared with normal tissue. Ajuba overexpression is correlated with advanced tumor-node-metastasis (TNM) stage, positive node status, and adverse patient outcomes. The Ajuba protein level was also higher in BC cell lines compared to normal breast epithelial cell line MCF-10A. Ectopically expressed Ajuba in MCF-7 cells stimulated in vitro and in vivo cell growth, invasion, cell cycle progression, and decreased paclitaxel-induced apoptosis. RNA-sequencing (RNA-seq) followed by gene set enrichment analysis (GSEA) analysis showed that Ajuba overexpression regulated the Hippo signaling pathway. Ajuba overexpression also increased glucose uptake and increased expression of TAZ, GLUT3, and Survivin. TAZ knockdown abolished the role of Ajuba on GLUT3 and Survivin induction. The ChIP assay showed that TEAD4, a major TAZ binding transcription factor, could bind to the GLUT3 and Survivin promoter regions. In conclusion, our data demonstrated that elevated Ajuba expression is correlated with poor BC prognosis and regulated malignant behavior through TAZ-GLUT3/Survivin signaling in BC cells.}, }
@article {pmid35159086, year = {2022}, author = {Pantazopoulos, H and Diop, MK and Grosset, AA and Rouleau-Gagné, F and Al-Saleh, A and Boblea, T and Trudel, D}, title = {Intraductal Carcinoma of the Prostate as a Cause of Prostate Cancer Metastasis: A Molecular Portrait.}, journal = {Cancers}, volume = {14}, number = {3}, pages = {}, pmid = {35159086}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate (IDC-P) is one of the most aggressive types of prostate cancer (PCa). IDC-P is identified in approximately 20% of PCa patients and is associated with recurrence, metastasis, and PCa-specific death. The main feature of this histological variant is the colonization of benign glands by PCa cells. Although IDC-P is a well-recognized independent parameter for metastasis, mechanisms by which IDC-P cells can spread and colonize other tissues are not fully known. In this review, we discuss the molecular portraits of IDC-P determined by immunohistochemistry and genomic approaches and highlight the areas in which more research is needed.}, }
@article {pmid35159065, year = {2022}, author = {Chen, YC and Chen, WM and Chiang, MF and Shia, BC and Wu, SY}, title = {Association between Pre-Existing Sleep Disorders and Survival Rates of Patients with Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {3}, pages = {}, pmid = {35159065}, issn = {2072-6694}, abstract = {PURPOSE: To investigate the effects of pre-existing sleep disorders on the survival outcomes of women receiving standard treatments for breast invasive ductal carcinoma (IDC).<br><br>METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received surgery for clinical stage I-III breast IDC. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching.<br><br>RESULTS: In the multivariate Cox regression analysis, the adjusted hazard ratio for all-cause mortality for Group 1 compared with Group 2 was 1.51 (95% confidence interval: 1.19, 1.91; p < 0.001).<br><br>CONCLUSION: Our study demonstrated that the sleep disorder group had poorer survival rates than the non-sleep disorder group in breast cancer. Therefore, patients should be screened and evaluated for pre-existing sleep disorders prior to breast surgery, with such disorders serving as a predictor of survival in patients with breast cancer. Future studies may investigate the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with breast cancer.}, }
@article {pmid35155685, year = {2022}, author = {Zhang, L and Du, J and Song, Q and Zhang, C and Wu, X}, title = {A Novel In Situ Dendritic Cell Vaccine Triggered by Rose Bengal Enhances Adaptive Antitumour Immunity.}, journal = {Journal of immunology research}, volume = {2022}, number = {}, pages = {1178874}, pmid = {35155685}, issn = {2314-7156}, mesh = {Adaptive Immunity ; Animals ; Antigen Presentation ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cancer Vaccines/*immunology ; Cell Differentiation ; Dendritic Cells/*immunology/transplantation ; Humans ; Immunization ; Immunotherapy/*methods ; Lung Neoplasms/*immunology/secondary ; Lymphocytes, Tumor-Infiltrating/*immunology ; Melanoma/*immunology/pathology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Rose Bengal/metabolism ; }, abstract = {Dendritic cell- (DC-) based vaccination has emerged as a promising antitumour immunotherapy. However, overcoming immune tolerance and immunosuppression in the tumour microenvironment (TME) is still a great challenge. Recent studies have shown that Rose Bengal (RB) can effectively induce immunogenic cell death (ICD) in cancer cells, presenting whole tumour antigens for DC processing and presentation. However, the synergistic antitumour effect of combining intralesional RB with immature DCs (RB-iDCs) remains unclear. In the present study, we investigated whether RB-iDCs have superior antitumour effects compared with either single agent and evaluated the immunological mechanism of RB-iDCs in a murine lung cancer model. The results showed that intralesional RB-iDCs suppressed subcutaneous tumour growth and lung metastasis, which resulted in 100% mouse survival and significantly increased TNF-α production by CD8[+] T cells. These effects were closely related to the induction of the expression of distinct ICD hallmarks by RB in both bulk cancer cells and cancer stem cells (CSCs), especially calreticulin (CRT), thus enhancing immune effector cell (i.e., CD4[+], CD8[+], and memory T cells) infiltration and attenuating the accumulation of immunosuppressive cells (i.e., Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs)) in the TME. This study reveals that the RB-iDC vaccine can synergistically destroy the primary tumour, inhibit distant metastasis, and prevent tumour relapse in a lung cancer mouse model, which provides important preclinical data for the development of a novel combinatorial immunotherapy.}, }
@article {pmid35151355, year = {2022}, author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY}, title = {Adjuvant postmastectomy radiotherapy might be associated with better survival in women with heart failure receiving total mastectomy.}, journal = {Radiation oncology (London, England)}, volume = {17}, number = {1}, pages = {33}, pmid = {35151355}, issn = {1748-717X}, mesh = {Adult ; Aged ; Female ; Heart Failure/*complications ; Humans ; *Mastectomy, Simple ; Middle Aged ; Radiotherapy, Adjuvant ; Survival Rate ; Unilateral Breast Neoplasms/*complications/*mortality/*radiotherapy/surgery ; Young Adult ; }, abstract = {BACKGROUND: To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).<br><br>PATIENTS AND METHODS: We enrolled 646 women with left-breast IDC at clinical stages I-IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).<br><br>RESULTS: In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37-0.74) was a significant independent prognostic factor for all-cause death (P&#x2009;=&#x2009;0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79-0.96; P&#x2009;=&#x2009;0.0356) and 0.89 (0.54-1.50; P&#x2009;=&#x2009;0.6854), respectively, compared with the nonadjuvant PMRT group.<br><br>CONCLUSION: Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.}, }
@article {pmid35137951, year = {2022}, author = {Weiser, R and Polychronopoulou, E and Hatch, SS and Haque, W and Ghani, HA and He, J and Kuo, YF and Gradishar, WJ and Klimberg, VS}, title = {Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: A National Cancer Database analysis.}, journal = {Cancer}, volume = {128}, number = {9}, pages = {1738-1747}, doi = {10.1002/cncr.34127}, pmid = {35137951}, issn = {1097-0142}, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/drug therapy/genetics ; *Carcinoma, Lobular/drug therapy/genetics/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Prognosis ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients.<br><br>METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy.<br><br>RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2&#xa0;&#xb1;&#xa0;9.1 and 57.2&#xa0;&#xb1;&#xa0;9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P&#xa0;<&#xa0;.0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease.<br><br>CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease.<br><br>LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.}, }
@article {pmid35130270, year = {2022}, author = {Khanam, R and Applegate, J and Nisar, I and Dutta, A and Rahman, S and Nizar, A and Ali, SM and Chowdhury, NH and Begum, F and Dhingra, U and Tofail, F and Mehmood, U and Deb, S and Ahmed, S and Muhammad, S and Das, S and Ahmed, S and Mittal, H and Minckas, N and Yoshida, S and Bahl, R and Jehan, F and Sazawal, S and Baqui, AH}, title = {Burden and risk factors for antenatal depression and its effect on preterm birth in South Asia: A population-based cohort study.}, journal = {PloS one}, volume = {17}, number = {2}, pages = {e0263091}, pmid = {35130270}, issn = {1932-6203}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adult ; Asia/epidemiology ; Bangladesh/epidemiology ; Cohort Studies ; Depression/complications/*epidemiology ; Female ; Humans ; Infant, Newborn ; Pakistan/epidemiology ; Pregnancy ; Pregnancy Complications/epidemiology/psychology ; Pregnancy Outcome/*epidemiology/psychology ; Premature Birth/*epidemiology ; Prenatal Care/statistics &amp; numerical data ; Risk Factors ; Young Adult ; }, abstract = {INTRODUCTION: Women experience high rates of depression, particularly during pregnancy and the postpartum periods. Using population-based data from Bangladesh and Pakistan, we estimated the burden of antenatal depression, its risk factors, and its effect on preterm birth.<br><br>METHODS: The study uses the following data: maternal depression measured between 24 and 28 weeks of gestation using the 9-question Patient Health Questionnaire (PHQ-9); data on pregnancy including an ultrasound before 19 weeks of gestation; data on pregnancy outcomes; and data on woman's age, education, parity, weight, height, history of previous illness, prior miscarriage, stillbirth, husband's education, and household socioeconomic data collected during early pregnancy. Using PHQ-9 cutoff score of &#x2265;12, women were categorized into none to mild depression or moderate to moderately severe depression. Using ultrasound data, preterm birth was defined as babies born <37 weeks of gestation. To identify risk ratios (RR) for antenatal depression, unadjusted and adjusted RR and 95% confidence intervals (CI) were calculated using log- binomial model. Log-binomial models were also used for determining the effect of antenatal depression on preterm birth adjusting for potential confounders. Data were analyzed using Stata version 16 (StataCorp LP).<br><br>RESULTS: About 6% of the women reported moderate to moderately severe depressive symptoms during the antenatal period. A parity of &#x2265;2 and the highest household wealth status were associated with an increased risk of depression. The overall incidence of preterm birth was 13.4%. Maternal antenatal depression was significantly associated with the risk of preterm birth (ARR, 95% CI: 1.34, 1.02-1.74).<br><br>CONCLUSION: The increased risk of preterm birth in women with antenatal depression in conjunction with other significant risk factors suggests that depression likely occurs within a constellation of other risk factors. Thus, to effectively address the burden of preterm birth, programs require developing and providing integrated care addressing multiple risk factors.}, }
@article {pmid35114136, year = {2022}, author = {Bechmann, N and Barthel, A and Schedl, A and Herzig, S and Varga, Z and Gebhard, C and Mayr, M and Hantel, C and Beuschlein, F and Wolfrum, C and Perakakis, N and Poston, L and Andoniadou, CL and Siow, R and Gainetdinov, RR and Dotan, A and Shoenfeld, Y and Mingrone, G and Bornstein, SR}, title = {Sexual dimorphism in COVID-19: potential clinical and public health implications.}, journal = {The lancet. Diabetes &amp; endocrinology}, volume = {10}, number = {3}, pages = {221-230}, pmid = {35114136}, issn = {2213-8595}, support = {CH/16/3/32406/BHF_/British Heart Foundation/United Kingdom ; RG/16/14/32397/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology/physiopathology ; Female ; *Health Status Disparities ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Public Health ; *Sex Characteristics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.}, }
@article {pmid35077053, year = {2022}, author = {Yariv, O and Benouaich-Amiel, A and Kab, T and Yust-Katz, S and Yerushalmi, R and Goldvaser, H}, title = {[RAPIDLY PROGRESSING PARAPARESIS AND LOSS OF SENSATION BELOW T10 DURING NEOADJUVANT CHEMOTHERAPY FOR BREAST CANCER].}, journal = {Harefuah}, volume = {161}, number = {1}, pages = {14-16}, pmid = {35077053}, issn = {0017-7768}, mesh = {Adult ; *Breast Neoplasms/diagnosis/drug therapy ; Female ; *Guillain-Barre Syndrome ; Humans ; Neoadjuvant Therapy ; Paraparesis ; Sensation ; }, abstract = {A 35 years old woman was diagnosed with clinical stage 2, grade 3, hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative invasive ductal carcinoma, with ki-67 of 60%. She was treated with neoadjuvant chemotherapy with dose dense adriamycin and cyclophosphamide followed by paclitaxel. Six days following the third cycle of paclitaxel the patient presented with rapidly progressive weakness, proximal paresthesia and decreased sensation in both legs. Physical examination revealed hypoesthesia below level, proximal and distal weakness in both lower limbs and absence of reflexes. MRI of the spine demonstrated diffuse leptomeningeal enhancement from T11 to S1 including the cauda equina roots. The rapidly progressive neurological symptoms and the MRI findings were initially interpreted as leptomeningeal spread. High dose dexamethasone was promptly initiated and the patient was urgently planned for radiotherapy and received the first fraction of 3 Gy to level T11-S1. Further workup included lumbar puncture which showed elevated protein level (350 mg/dL), negative cytology for malignancy and EMG which demonstrated demyelinating injury compatible with Guillain-Barre syndrome (GBS). A diagnosis of GBS was made and treatment with intravenous immunoglobulins (IVIG) was initiated, followed by a gradual clinical improvement. Two months after the initial diagnosis, she had a near complete resolution of her neurological deficits. This case illustrates both the tendency to ascribe new symptoms and clinical findings in cancer patients to progressive disease, and the importance of keeping a wide differential diagnosis for non-cancer etiologies when treating our patients.}, }
@article {pmid35074971, year = {2022}, author = {Kumari, S and Mishra, S and Husain, N and Verma, T and Tiwari, V and Kaif, M and Agarwal, A and Rastogi, M and Shukla, S and Sonkar, AA}, title = {Comparison of circulating DNA in malignant neoplasia from diverse locations: Investigating a diagnostic role.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {65}, number = {1}, pages = {93-99}, doi = {10.4103/IJPM.IJPM_474_20}, pmid = {35074971}, issn = {0974-5130}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/genetics ; Brain Neoplasms/blood/diagnosis/genetics ; Carcinoma, Squamous Cell/blood/diagnosis/genetics ; Cell-Free Nucleic Acids/*blood ; Female ; Gallbladder Neoplasms/blood/diagnosis/genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms/blood/classification/*diagnosis/*genetics ; Young Adult ; }, abstract = {CONTEXT: Circulating free DNA (cfDNA) analysis has emerged as novel noninvasive diagnostic biomarker in several solid tumors. Raised levels have been reported in several malignancies and may correlate with clinicopathological and treatment response. The current study was designed to assess the diagnostics of cfDNA in different tumor types of malignancies correlating with tumor (T), nodes (N), and metastases (M) stage.<br><br>DESIGN: Serum samples were collected from treatment na&#xef;ve cases with histologically diagnosed tumors including 23 brain tumors, 48 breasts, 50 gallbladder carcinoma (GBC), 13 lungs, 68 oral squamous cell carcinoma (OSCC), and 25 normal controls. CfDNA was quantified with real-time polymerase chain reaction (PCR), Invasive ductal carcinoma (IDC) using beta-globin gene amplification. Cut off values for diagnostics were calculated using receiver operating curve analysis.<br><br>RESULTS: Contrary to other cfDNA studies where it was postulated that cfDNA would not cross the blood-brain barrier and reach the systemic circulation, we found detectable cfDNA in glioma with median (Q1-Q3) of 349.22 ng/ml (19.87-1276.58). Median cfDNA concentration in breast, gallbladder, lung, oral and normal controls was 328.72 (128.38-624.44), 778.50 (589.88-1864.35), 348.73 (194.67-483.61), 386.27 (47.88-959.67), and 74.12 (49.66-120.00), respectively. Grades I and II glioma had significantly lower levels compared to Grades III and IV (P = 0.0001). Significant difference in median cfDNA values in IDC and GBC was observed with increasing tumor grades, stage, T stage, nodal stage and metastasis and with stage of OSCC cases.<br><br>CONCLUSION: CfDNA levels showed good diagnostic discrimination in glioma, GBC, breast, lung carcinoma, and OSCC. Significant increase in titers was evident with increase in cancer stage from I to IV in breast, GBC and OSCC.}, }
@article {pmid35071526, year = {2022}, author = {Wang, L and Jiang, Q and He, MY and Shen, P}, title = {HER2 changes to positive after neoadjuvant chemotherapy in breast cancer: A case report and literature review.}, journal = {World journal of clinical cases}, volume = {10}, number = {1}, pages = {260-267}, pmid = {35071526}, issn = {2307-8960}, abstract = {BACKGROUND: As the most common cancer in women, breast cancer is the leading cause of death. Most patients are initially diagnosed as stage I-III. Among those without distant metastases, 64% are local tumors and 27% are regional tumors. Patients in stage IIA-IIIC and those who meet the breast-conserving criterion with the exception of tumor size can consider neoadjuvant chemotherapy (NACT). It is worth noting that the status of tumor cell biomarkers is not consistently static. Endocrine-related estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) encoded by erythroblastic leukemia viral oncogene homolog 2 gene can all alter from positive to negative or vice versa, especially in luminal B subtype after NACT. In addition, determination of HER2 status currently mainly relies on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), but FISH is commonly used when the result of IHC is uncertain. HER2 is regarded as negative when the IHC result is 0/1+ without the addition of FISH. To the best of our knowledge, this is the first report of a case harboring HER2 status transformation and IHC1+ with positive amplification by FISH after NACT.<br><br>CASE SUMMARY: A 49-year-old woman discovered a mass in her right breast and underwent diagnostic workup. Biopsies of the right breast lesion and axillary lymph nodes were obtained. The results pointed to invasive ductal carcinoma with the IHC result for ER (80%), PR (60%), Ki-67 (20%) and ambiguous expression of HER2 (IHC 2+) with negative amplification by FISH (HER2/CEP17 ratio of 1.13). She underwent surgery after NACT. The pathological findings of the surgically resected sample supported invasive ductal carcinoma with the tumor measuring 1.1 cm &#xd7; 0.8 cm &#xd7; 0.5 cm and had spread to one of fifteen dissected lymph nodes. Retesting of the specimen showed that the tumor was positive for ER (2+, 85%) and PR (2+, 10%) but negative for HER2 by IHC (1+). Also Ki-67 had dropped to 2%. The patient was regularly monitored every 3 mo without evidence of recurrence.<br><br>CONCLUSION: Biomarker status should be reassessed after NACT especially in luminal subtypes.}, }
@article {pmid35064153, year = {2022}, author = {Tewari, SG and Kwan, B and Elahi, R and Rajaram, K and Reifman, J and Prigge, ST and Vaidya, AB and Wallqvist, A}, title = {Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {1167}, pmid = {35064153}, issn = {2045-2322}, support = {T32 AI138953/AI/NIAID NIH HHS/United States ; R01 AI154499/AI/NIAID NIH HHS/United States ; W81XWH-15-C-0061//U.S. Army Medical Research and Development Command (MRDC)/ ; R01 AI132508/AI/NIAID NIH HHS/United States ; T32 AI007417/AI/NIAID NIH HHS/United States ; R01AI125534//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; W81XWH-20-C-0031//U.S. Army Medical Research and Development Command (MRDC)/ ; R01 AI098413/AI/NIAID NIH HHS/United States ; W81XWH-14-2-0134//U.S. Army Medical Research and Development Command (MRDC)/ ; }, mesh = {Antimalarials/*pharmacology/therapeutic use ; Carbohydrate Metabolism/drug effects/genetics ; Dose-Response Relationship, Drug ; Drug Resistance ; Erythrocytes/parasitology ; Gene Expression Profiling ; Humans ; Inositol/biosynthesis ; Malaria, Falciparum/*drug therapy/parasitology ; Metabolomics ; Oxidative Stress ; Plasmodium falciparum/*drug effects/genetics/metabolism ; Pyrazoles/*pharmacology/therapeutic use ; RNA, Protozoan/biosynthesis ; }, abstract = {Due to the recurring loss of antimalarial drugs to resistance, there is a need for novel targets, drugs, and combination therapies to ensure the availability of current and future countermeasures. Pyrazoleamides belong to a novel class of antimalarial drugs that disrupt sodium ion homeostasis, although the exact consequences of this disruption in Plasmodium falciparum remain under investigation. In vitro experiments demonstrated that parasites carrying mutations in the metabolic enzyme PfATP4 develop resistance to pyrazoleamide compounds. However, the underlying mechanisms that allow mutant parasites to evade pyrazoleamide treatment are unclear. Here, we first performed experiments to identify the sublethal dose of a pyrazoleamide compound (PA21A092) that caused a significant reduction in growth over one intraerythrocytic developmental cycle (IDC). At this drug concentration, we collected transcriptomic and metabolomic data at multiple time points during the IDC to quantify gene- and metabolite-level alterations in the treated parasites. To probe the effects of pyrazoleamide treatment on parasite metabolism, we coupled the time-resolved omics data with a metabolic network model of P. falciparum. We found that the drug-treated parasites adjusted carbohydrate metabolism to enhance synthesis of myoinositol-a precursor for phosphatidylinositol biosynthesis. This metabolic adaptation caused a decrease in metabolite flux through the pentose phosphate pathway, causing a decreased rate of RNA synthesis and an increase in oxidative stress. Our model analyses suggest that downstream consequences of enhanced myoinositol synthesis may underlie adjustments that could lead to resistance emergence in P. falciparum exposed to a sublethal dose of a pyrazoleamide drug.}, }
@article {pmid35046349, year = {2021}, author = {Adachi, K and Kubota, H and Suzuki, S and Hirano, T and Ishibashi, N and Sakurai, K}, title = {[Hereditary Breast and Ovarian Cancer(HBOC)in a Young Adult-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {48}, number = {13}, pages = {1843-1845}, pmid = {35046349}, issn = {0385-0684}, mesh = {Adult ; Axilla ; *Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Lymph Nodes ; Mastectomy ; *Ovarian Neoplasms/genetics/surgery ; }, abstract = {We report a case of hereditary breast and ovarian cancer(HBOC)in a young adult. A 31-year-old woman consulted at our hospital for a lump on her left breast. Ultrasonography revealed an irregular-shaped mass. A core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. There were multiple enlarged lymph nodes in the axilla and internal mammary areas but no evidence of metastasis. She underwent mastectomy and axially dissection. The pathological findings from the surgically resected specimens showed scirrhous carcinoma positive for ER and PgR and negative for HER2/neu protein expression. The tumor size was 16 mm, and 3 axillary lymph node metastases were seen. We identified the pathological stage as T1cN3bM0, stage ⅢC. She received chemotherapy, radiotherapy, and endocrine therapy after surgery. At present, 1 year after surgery, the patient is alive without recurrence. With a low age of onset and a family history of ovarian cancer, she was diagnosed with HBOC as a result of breast cancer susceptibility gene(BRCA)genetic testing. In addition to the recommended surveillance, prophylactic surgery will be performed in the future.}, }
@article {pmid35029184, year = {2022}, author = {Hussain, M and Abbott, M and Zargham, R and Pabani, A and Khan, OF}, title = {Evolution of an invasive ductal carcinoma to a small cell carcinoma of the breast: A case report.}, journal = {Medicine}, volume = {101}, number = {2}, pages = {e28433}, pmid = {35029184}, issn = {1536-5964}, mesh = {*Breast Neoplasms/diagnosis/therapy ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; *Carcinoma, Small Cell/diagnosis/therapy ; Female ; Humans ; *Lymphadenopathy ; Middle Aged ; Retrospective Studies ; }, abstract = {RATIONALE: Small cell carcinoma (SCC) is a rare subtype of breast cancer and presents a complex diagnostic and treatment challenge, due to paucity of data. To the best of our knowledge, most cases of breast SCC reported in the literature describe a de novo breast primary. Our case is unique as it describes the evolution of an invasive ductal carcinoma after treatment into a SCC of the breast.<br><br>We report a case of a 53-year-old female, lifelong non-smoker, who initially presented with breast mass noted on self examination. Breast and axillary lymph node biopsy demonstrated a hormone receptor positive invasive ductal carcinoma with a metastatic T3 lesion.<br><br>INTERVENTION: She was treated with first-line palbociclib/letrozole with initial clinical response, and at progression was switched to capecitabine with no response. Repeat biopsy of the axillary lesion showed evolution of the tumor into a triple negative breast cancer. She was then treated with third-line paclitaxel and radiation therapy with good initial response. She eventually had further disease progression and presented with a new mediastinal lymphadenopathy causing SVC syndrome. Biopsy of this showed a small cell variant of breast neuroendocrine carcinoma. Due to the evolution of histology in this case, a retrospective review of her initial breast specimen as well as the second biopsy from the axilla was conducted which confirmed that the mediastinal lymphadenopathy was metastatic from the original breast tumor.<br><br>OUTCOMES AND LESSONS: We speculate that the initial treatment allowed a minority of treatment-resistant neuroendocrine cells to grow and become the dominant face of the tumor. Our patient had an excellent response to carboplatin/etoposide and consolidative locoregional radiotherapy but presented with an early intracranial recurrence. This is a similar pattern of metastases as seen in lung SCC and highlights a potential role for prophylactic cranial irradiation in breast SCC. Further studies are needed to better understand the biology and treatment of breast SCC which continues to present a challenge for clinicians.}, }
@article {pmid35011590, year = {2021}, author = {Greulich, F and Bielefeld, KA and Scheundel, R and Mechtidou, A and Strickland, B and Uhlenhaut, NH}, title = {Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages.}, journal = {Cells}, volume = {11}, number = {1}, pages = {}, pmid = {35011590}, issn = {2073-4409}, support = {GR 5179/1-1//Deutsche Forschungsgemeinschaft/ ; UH 275/1-1//Deutsche Forschungsgemeinschaft/ ; ERC-2014-StG 638573/ERC_/European Research Council/International ; TRR205, The Adrenal//Deutsche Forschungsgemeinschaft/ ; CRC1064 Chromatin Dynamics//Deutsche Forschungsgemeinschaf/ ; }, mesh = {Acetylation/drug effects ; Animals ; Binding Sites ; *Enhancer Elements, Genetic ; Gene Expression Profiling ; *Gene Expression Regulation/drug effects ; Glucocorticoids/*pharmacology ; Histones/metabolism ; Lysine/metabolism ; Macrophages/drug effects/*metabolism ; Male ; Mice, Inbred C57BL ; Nuclear Proteins/metabolism ; Organ Specificity/drug effects ; RNA/*genetics/metabolism ; Receptors, Glucocorticoid/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects ; }, abstract = {Glucocorticoids are potent anti-inflammatory drugs; however, their molecular mode of action remains complex and elusive. They bind to the glucocorticoid receptor (GR), a nuclear receptor that controls gene expression in almost all tissues in a cell type-specific manner. While GR's transcriptional targets mediate beneficial reactions in immune cells, they also harbor the potential of adverse metabolic effects in other cell types such as hepatocytes. Here, we have profiled nascent transcription upon glucocorticoid stimulation in LPS-activated primary murine macrophages using 4sU-seq. We compared our results to publicly available nascent transcriptomics data from murine liver and bioinformatically identified non-coding RNAs transcribed from intergenic GR binding sites in a tissue-specific fashion. These tissue-specific enhancer RNAs (eRNAs) correlate with target gene expression, reflecting cell type-specific glucocorticoid responses. We further associate GR-mediated eRNA expression with changes in H3K27 acetylation and BRD4 recruitment in inflammatory macrophages upon glucocorticoid treatment. In summary, we propose a common mechanism by which GR-bound enhancers regulate target gene expression by changes in histone acetylation, BRD4 recruitment and eRNA expression. We argue that local eRNAs are potential therapeutic targets downstream of GR signaling which may modulate glucocorticoid response in a cell type-specific way.}, }
@article {pmid34999280, year = {2022}, author = {Kotschi, S and Jung, A and Willemsen, N and Ofoghi, A and Proneth, B and Conrad, M and Bartelt, A}, title = {NFE2L1-mediated proteasome function protects from ferroptosis.}, journal = {Molecular metabolism}, volume = {57}, number = {}, pages = {101436}, pmid = {34999280}, issn = {2212-8778}, mesh = {Animals ; *Ferroptosis ; Homeostasis ; Humans ; Mice ; Mitochondria/metabolism ; *NF-E2-Related Factor 1/genetics/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Proteasome Endopeptidase Complex/metabolism ; }, abstract = {OBJECTIVE: Ferroptosis continues to emerge as a novel modality of cell death with important therapeutic implications for a variety of diseases, most notably cancer and degenerative diseases. While susceptibility, initiation, and execution of ferroptosis have been linked to reprogramming of cellular lipid metabolism, imbalances in iron-redox homeostasis, and aberrant mitochondrial respiration, the detailed mechanisms of ferroptosis are still insufficiently well understood.<br><br>METHODS AND RESULTS: Here we show that diminished proteasome function is a new mechanistic feature of ferroptosis. The transcription factor nuclear factor erythroid-2, like-1 (NFE2L1) protects from ferroptosis by sustaining proteasomal activity. In cellular systems, loss of NFE2L1 reduced cellular viability after the induction of both chemically and genetically induced ferroptosis, which was linked to the regulation of proteasomal activity under these conditions. Importantly, this was reproduced in a Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) patient-derived cell line carrying mutated glutathione peroxidase-4 (GPX4), a critical regulator of ferroptosis. Also, reduced proteasomal activity was associated with ferroptosis in Gpx4-deficient mice. In a mouse model for genetic Nfe2l1 deficiency, we observed brown adipose tissue (BAT) involution, hyperubiquitination of ferroptosis regulators, including the GPX4 pathway, and other hallmarks of ferroptosis.<br><br>CONCLUSION: Our data highlight the relevance of the NFE2L1-proteasome pathway in ferroptosis. Manipulation of NFE2L1 activity might enhance ferroptosis-inducing cancer therapies as well as protect from aberrant ferroptosis in neurodegeneration, general metabolism, and beyond.}, }
@article {pmid34987224, year = {2022}, author = {Rasmussen, M and Reddy, M and Nolan, R and Camunas-Soler, J and Khodursky, A and Scheller, NM and Cantonwine, DE and Engelbrechtsen, L and Mi, JD and Dutta, A and Brundage, T and Siddiqui, F and Thao, M and Gee, EPS and La, J and Baruch-Gravett, C and Santillan, MK and Deb, S and Ame, SM and Ali, SM and Adkins, M and DePristo, MA and Lee, M and Namsaraev, E and Gybel-Brask, DJ and Skibsted, L and Litch, JA and Santillan, DA and Sazawal, S and Tribe, RM and Roberts, JM and Jain, M and Høgdall, E and Holzman, C and Quake, SR and Elovitz, MA and McElrath, TF}, title = {RNA profiles reveal signatures of future health and disease in pregnancy.}, journal = {Nature}, volume = {601}, number = {7893}, pages = {422-427}, pmid = {34987224}, issn = {1476-4687}, support = {P50 HD103556/HD/NICHD NIH HHS/United States ; }, mesh = {*Cell-Free Nucleic Acids/blood ; Female ; Humans ; *Pre-Eclampsia/diagnosis/genetics ; Predictive Value of Tests ; Pregnancy ; *RNA/blood ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden[1]. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method[2]. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.}, }
@article {pmid34975349, year = {2021}, author = {Rafiq, MT and Hamid, MSA and Hafiz, E}, title = {Short-Term Effects of Strengthening Exercises of the Lower Limb Rehabilitation Protocol on Pain, Stiffness, Physical Function, and Body Mass Index among Knee Osteoarthritis Participants Who Were Overweight or Obese: A Clinical Trial.}, journal = {TheScientificWorldJournal}, volume = {2021}, number = {}, pages = {6672274}, pmid = {34975349}, issn = {1537-744X}, mesh = {*Body Mass Index ; *Exercise Therapy ; Female ; Humans ; Lower Extremity/*physiopathology ; Male ; Middle Aged ; Obesity/*complications ; Osteoarthritis, Knee/complications/physiopathology/*rehabilitation ; Overweight/*complications ; Pain/*complications ; Range of Motion, Articular ; Single-Blind Method ; }, abstract = {BACKGROUND: Osteoarthritis (OA) of the knee is defined as a progressive disease of the synovial joints and is characterized by wear and tear of the cartilage and underlying bone. This study aimed to determine the short-term effects of the lower limb rehabilitation protocol (LLRP) on pain, stiffness, physical function, and body mass index (BMI) among knee OA participants who were overweight or obese. Methodology. A single-blinded randomized controlled trial of one-month duration was conducted at Rehmatul-Lil-Alameen Postgraduate Institute, Lahore, Pakistan. Fifty overweight or obese participants with knee OA were randomly divided into two groups by a computer-generated number. Participants in the rehabilitation protocol group (RPG) were provided with leaflets explaining the strengthening exercises of the LLRP and instruction of daily care (IDC), while the participants in the control group (CG) were provided with leaflets explaining the IDC only for a duration of four weeks. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function. The secondary outcome measures were BMI, exercise adherence, and patients' satisfaction assessed by using the numeric rating scale ranging from 0 to 10. The paired-sample t-test was used to analyze the differences within groups from baseline to posttest evaluations. The analysis of variance 2 × 2 factor was used to analyze the differences in BMI, knee pain, stiffness, and physical function between the groups.<br><br>RESULTS: Participants in the RPG and CG reported a statistically significant reduction in knee pain and stiffness (p &#x2264; 0.05) within the group. The reduction in the scores of knee pain was higher in participants in the RPG than that in participants in the CG (p=0.001). Additionally, participants in the RPG reported greater satisfaction (p=0.001) and higher self-reported exercise adherence (p=0.010) and coordinator-reported exercise adherence (p=0.046) than the participants in the CG.<br><br>CONCLUSION: Short-term effects of the LLRP appear to reduce knee pain and stiffness only, but not physical function and BMI.}, }
@article {pmid34972731, year = {2022}, author = {Salih, MM and Higgo, AA and Eed, EM}, title = {Prognostic Significance of p16 Protein Expression in Breast Cancer.}, journal = {In vivo (Athens, Greece)}, volume = {36}, number = {1}, pages = {336-340}, pmid = {34972731}, issn = {1791-7549}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Female ; Humans ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND/AIM: Breast cancer is the most common cancer in Sudan. The p16 protein plays a vital role in the regulation of the cell cycle.<br><br>PATIENTS AND METHODS: This study analysed the protein expression of p16 in 202 paraffin blocks from Sudanese women with breast cancer using immunohistochemistry.<br><br>RESULTS: This study included 168 (83.2%), 16 (7.9%), and 18 (8.9%) patients with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. There were 95 cases (47.0%) with grade III, 70 cases (34.6%) with grade II, and 23 cases (11.4%) with grade I breast cancer. The hormone receptor status was available for 119 of the cases, and 31 (15.3%), 25 (12.4%), and 63 (31.2%) cases were positive for oestrogen, progesterone, and HER2 receptors, respectively.<br><br>CONCLUSION: p16 protein expression was associated with high histologic grade, lymph node metastasis, and poor prognosis. p16 protein expression may potentially be used as a prognostic marker.}, }
@article {pmid34969739, year = {2022}, author = {Takada, K and Kashiwagi, S and Asano, Y and Goto, W and Morisaki, T and Shibutani, M and Tanaka, H and Hirakawa, K and Ohira, M}, title = {The Effect of Smoking on Progression from Ductal Carcinoma In Situ to Invasive Ductal Breast Carcinoma: A Retrospective Study.}, journal = {Anticancer research}, volume = {42}, number = {1}, pages = {311-320}, doi = {10.21873/anticanres.15487}, pmid = {34969739}, issn = {1791-7530}, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/chemically induced/*diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology/pathology ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis/*diagnosis/diagnostic imaging/pathology ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy/methods ; Smoking/*adverse effects ; }, abstract = {BACKGROUND/AIM: If ductal carcinoma in situ (DCIS) is diagnosed by needle biopsy, invasion is often found by removing the entire tumor and performing pathological examination. Smoking is a risk factor for carcinogenesis in breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients diagnosed with DCIS by preoperative biopsy.<br><br>PATIENTS AND METHODS: We examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy.<br><br>RESULTS: Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Number of pack-years was not an independent factor (p=0.349, OR=0.329), but current-smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327).<br><br>CONCLUSION: Tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.}, }
@article {pmid34949235, year = {2021}, author = {Mavhungu, R and Bhuiyan, M and Ooko, F}, title = {Profile of patients seen at Pietersburg and Mankweng breast cancer clinics in Limpopo.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {111}, number = {11b}, pages = {1129-1131}, doi = {10.7196/SAMJ.2021.v111i11b.16108}, pmid = {34949235}, issn = {2078-5135}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/pathology ; Breast Neoplasms, Male/epidemiology/pathology ; Female ; Humans ; Incidence ; Male ; Mammography ; Middle Aged ; Neoplasm Staging ; Prevalence ; Retrospective Studies ; South Africa/epidemiology ; }, abstract = {BACKGROUND: Breast cancer is the most common cancer diagnosed among women worldwide. It is the most prevalent cancer and leading cause of death among South African (SA) women. The increasing incidence of breast cancer is a major health concern. Until now, the distribution of breast cancer demography, stage at first presentation, and histological characterisation have not been studied in Limpopo Province, SA.<br><br>OBJECTIVES: To record the demographic profile of breast cancer patients, to report the stage at the time of presentation and to characterise the pattern of malignant disease in Limpopo, SA.<br><br>METHODS: We conducted a retrospective descriptive review of the records of patients managed at Pietersburg Hospital oncology and Mankweng Hospital breast cancer clinics during the period 1 March 2015 - 28 February 2017. Stata was used to analyse data.<br><br>RESULTS: A total of 248 patients with a mean age of 55 years were included for analysis, 7 males (3%) and 241 females (97%). Capricorn and Vhembe districts constituted 32% and 27% respectively. The majority (69%) of patients were diagnosed with disease stage III or IV. The&#xa0;most common histological type was invasive ductal cell carcinoma (IDC) (87%).<br><br>CONCLUSIONS: More than one-third of patients were younger than 50 years. The majority (69%) had an advanced breast cancer (stage III or&#xa0;IV). We recommend provision of mammography services in regional hospitals.}, }
@article {pmid34945830, year = {2021}, author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY}, title = {Adjuvant Whole Breast Radiotherapy Improve Survival in Women with Heart Failure with Reduced Ejection Fraction Receiving Breast-Conserving Surgery.}, journal = {Journal of personalized medicine}, volume = {11}, number = {12}, pages = {}, pmid = {34945830}, issn = {2075-4426}, abstract = {BACKGROUND: to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).<br><br>PATIENTS AND METHODS: we included 294 women with left-breast IDC at clinical stages IA-IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).<br><br>RESULTS: in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44-0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24-0.71; p = 0.0017) and 0.37 (0.22-0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group.<br><br>CONCLUSION: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.}, }
@article {pmid34928689, year = {2022}, author = {Shoshani, A and Kor, A}, title = {The mental health effects of the COVID-19 pandemic on children and adolescents: Risk and protective factors.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {14}, number = {8}, pages = {1365-1373}, doi = {10.1037/tra0001188}, pmid = {34928689}, issn = {1942-969X}, mesh = {Child ; Female ; Adolescent ; Humans ; Male ; *Pandemics/prevention &amp; control ; *COVID-19 ; Mental Health ; Protective Factors ; Communicable Disease Control ; }, abstract = {OBJECTIVE: The restrictions to contain the coronavirus disease 2019 (COVID-19) pandemic have led to considerable social isolation, posing significant threats to mental health worldwide. The preventive lockdowns may be especially difficult for children and adolescents, who rely extensively on their daily routines and peer connections for stability and optimal development. However, there is a dearth of longitudinal research examining the mental health and daily life impact of the pandemic among children and adolescents. This study addresses this gap by examining the influence of the COVID-19 pandemic on children and adolescents' mental health and well-being, and potential risk and protective moderators of mental health change.<br><br>METHOD: In the present study, 1,537 Israeli children and adolescents (Mage = 13.97; 52% girls) completed a battery of questionnaires in September 2019; before the COVID-19 outbreak and immediately after an 8-week lockdown period when schools reopened in May 2020.<br><br>RESULTS: A repeated measures multivariant analysis of variance (MANOVA) revealed significantly greater anxiety, depression, and panic symptoms, increases in video game, Internet and TV screen time use, and decreases in positive emotions, life satisfaction, social media use, and peer support during the pandemic. Participants with higher baseline mental health symptoms showed greater symptoms after the lockdown period. Perceived social support and consistent daily routines were found to act as significant protective factors against symptomatology.<br><br>CONCLUSIONS: The results highlight the significant mental health consequences of the pandemic on children and adolescents, and substantiate the significant parents' and peers' roles in children's and adolescents' coping during this global pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, }
@article {pmid34899603, year = {2021}, author = {Kopf, S and Kumar, V and Kender, Z and Han, Z and Fleming, T and Herzig, S and Nawroth, PP}, title = {Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {765201}, pmid = {34899603}, issn = {1664-2392}, mesh = {Animals ; DNA Damage/genetics ; Diabetes Complications/blood/*complications/genetics ; Diabetes Mellitus, Type 1/blood/*complications/genetics ; Diabetes Mellitus, Type 2/blood/*complications/genetics ; Humans ; Pulmonary Fibrosis/blood/*etiology/genetics ; }, abstract = {Patients with diabetes are over-represented among the total cases reported with "idiopathic" pulmonary fibrosis (IPF). This raises the question, whether this is an association only or whether diabetes itself can cause pulmonary fibrosis. Recent studies in mouse models of type 1 and type 2 diabetes demonstrated that diabetes causes pulmonary fibrosis. Both types of diabetes trigger a cascade, starting with increased DNA damage, an impaired DNA repair, and leading to persistent DNA damage signaling. This response, in turn, induces senescence, a senescence-associated-secretory phenotype (SASP), marked by the release of pro-inflammatory cytokines and growth factors, finally resulting in fibrosis. Restoring DNA repair drives fibrosis into remission, thus proving causality. These data can be translated clinically to patients with type 2 diabetes, characterized by long-term diabetes and albuminuria. Hence there are several arguments, to substitute the term "idiopathic" pulmonary fibrosis (IPF) in patients with diabetes (and exclusion of other causes of lung diseases) by the term "diabetes-induced pulmonary fibrosis" (DiPF). However, future studies are required to establish this term and to study whether patients with diabetes respond to the established therapies similar to non-diabetic patients.}, }
@article {pmid34884926, year = {2021}, author = {Kang, M and Lee, H and Byeon, SJ and Kwon, GY and Jeon, SS}, title = {Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884926}, issn = {1422-0067}, support = {NRF-2020R1A2C2007662//National Research Foundation of Korea/ ; NRF-2020R1C1C1005054//National Research Foundation of Korea/ ; }, mesh = {Animals ; DNA Repair/genetics ; Genomic Instability ; Humans ; Male ; *Mutation ; Precision Medicine ; Prostatic Neoplasms/*genetics/*pathology/therapy ; Xenograft Model Antitumor Assays ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2-ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate-ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.}, }
@article {pmid34884498, year = {2021}, author = {Betz, IR and Qaiyumi, SJ and Goeritzer, M and Thiele, A and Brix, S and Beyhoff, N and Grune, J and Klopfleisch, R and Greulich, F and Uhlenhaut, NH and Kintscher, U and Foryst-Ludwig, A}, title = {Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884498}, issn = {1422-0067}, mesh = {Animals ; Cardiomegaly/chemically induced/*drug therapy/metabolism/pathology ; Cardiotonic Agents/*pharmacology ; Catecholamines/*toxicity ; Fatty Acids, Monounsaturated/*pharmacology ; Gene Expression Regulation/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/drug effects/metabolism/pathology ; PPAR alpha/genetics/*metabolism ; PPAR delta/genetics/*metabolism ; }, abstract = {Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.}, }
@article {pmid34881777, year = {2022}, author = {Sidhanth, C and Bindhya, S and Shabna, A and Krishnapriya, S and Manasa, P and Nagare, RP and Joshua, T and Sneha, S and Murhekar, K and Ganesan, TS}, title = {LASP-1 interacts with ErbB2 in ovarian cancer cells.}, journal = {The Biochemical journal}, volume = {479}, number = {1}, pages = {23-38}, doi = {10.1042/BCJ20210173}, pmid = {34881777}, issn = {1470-8728}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adult ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Ovarian Epithelial/*metabolism/pathology ; Cell Line, Tumor ; Cohort Studies ; Cytoskeletal Proteins/genetics/*metabolism ; Female ; HEK293 Cells ; Humans ; LIM Domain Proteins/genetics/*metabolism ; Lapatinib/pharmacology ; Middle Aged ; Ovarian Neoplasms/*metabolism/pathology ; Phosphorylation/drug effects/genetics ; Plasmids ; Protein Kinase Inhibitors/pharmacology ; Quinazolines/pharmacology ; Receptor, ErbB-2/genetics/*metabolism ; Signal Transduction/drug effects/*genetics ; Transfection ; }, abstract = {LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76 Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40 kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n = 101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (P < 0.001). Analysis of the expression of an independent dataset of ovarian and breast tumours from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (P < 0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.}, }
@article {pmid34851990, year = {2021}, author = {D'Amora, P and Silva, IDCG and Budib, MA and Ayache, R and Silva, RMS and Silva, FC and Appel, RM and Júnior, SS and Pontes, HBD and Alvarenga, AC and Arima, EC and Martins, WG and Silva, NLF and Diaz, RS and Salzgeber, MB and Palma, AM and Evans, SS and Nagourney, RA}, title = {Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0259909}, pmid = {34851990}, issn = {1932-6203}, support = {UL1 TR001414/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Area Under Curve ; COVID-19/mortality/*pathology/virology ; Carnitine/metabolism ; Citrulline/metabolism ; Female ; Glutamic Acid/metabolism ; Humans ; Kynurenine/metabolism ; Male ; *Metabolome ; Metabolomics/*methods ; Middle Aged ; Ornithine/metabolism ; ROC Curve ; Risk Factors ; SARS-CoV-2/isolation &amp; purification ; Severity of Illness Index ; Tryptophan/metabolism ; }, abstract = {This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.}, }
@article {pmid34841287, year = {2021}, author = {Erener, S and Ellis, CE and Ramzy, A and Glavas, MM and O'Dwyer, S and Pereira, S and Wang, T and Pang, J and Bruin, JE and Riedel, MJ and Baker, RK and Webber, TD and Lesina, M and Blüher, M and Algül, H and Kopp, JL and Herzig, S and Kieffer, TJ}, title = {Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice.}, journal = {Cell reports. Medicine}, volume = {2}, number = {11}, pages = {100434}, pmid = {34841287}, issn = {2666-3791}, support = {//CIHR/Canada ; }, mesh = {Animals ; Apoptosis ; Base Sequence ; Cell Line, Tumor ; Cell Movement ; Diet, High-Fat ; *Disease Progression ; *Gene Deletion ; Humans ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism/*pathology ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/*genetics/metabolism ; Organ Specificity ; Pancreatic Neoplasms/*genetics/*pathology ; Rats ; }, abstract = {miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size, β-cell mass, and insulin levels. Single-cell RNA sequencing reveals a subpopulation of β-cells with upregulated acinar cell markers under a high-fat diet. miR-216a is induced by TGF-β signaling, and inhibition of miR-216a increases apoptosis and decreases cell proliferation in pancreatic cells. Deletion of miR-216a in the pancreatic cancer-prone mouse line Kras[G12D];Ptf1a[CreER] reduces the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels are elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA and also suggests miR-216a as a potential biomarker for diagnosis of pancreatic diseases.}, }
@article {pmid34829743, year = {2021}, author = {Liu, PF and Shu, CW and Yang, HC and Lee, CH and Liou, HH and Ger, LP and Tzeng, YT and Wang, WC}, title = {Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.}, journal = {Biomedicines}, volume = {9}, number = {11}, pages = {}, pmid = {34829743}, issn = {2227-9059}, support = {MOST 108-2320-B-037-038, MOST 109-2320-B-037-015-MY3//The Ministry of Science and Technology/ ; KMU-Q109008; KMU-Q110002//Kaohsiung Medical University Research Foundation/ ; NSYSUKMU 109-I007; NSYSUKMU-110-I006//The National Sun Yat-sen University-KMU Joint Research Project/ ; KMU-TC108A04//Kaohsiung Medical University Research Center Grant/ ; VGHKS106-015; VGHKS107-014//Kaohsiung Veterans General Hospital/ ; }, abstract = {Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.}, }
@article {pmid34816360, year = {2022}, author = {Mizukoshi, K and Fujii, M and Yamauchi, Y and Fukuda, A and Seno, H}, title = {A rare case of malignant biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma.}, journal = {Clinical journal of gastroenterology}, volume = {15}, number = {1}, pages = {199-204}, pmid = {34816360}, issn = {1865-7265}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal/surgery ; Constriction, Pathologic/etiology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Retroperitoneal Neoplasms/surgery ; }, abstract = {A 50-year-old woman was referred to our hospital for elevated hepatobiliary enzymes. She had a medical history of mastectomy for left breast invasive ductal carcinoma about 10 years ago, and no apparent recurrence had been observed. Contrast-enhanced computed tomography (CT) revealed soft-tissue shadows surrounding the portal vein, celiac artery, and other vessels. The lesions involved the hilar bile duct, and the upstream bile ducts were dilated. Endoscopic retrograde cholangiography showed an obstruction in the hilar bile duct, and biopsies were taken at the site of biliary stenosis. H&amp;E staining showed that cells with strong nuclear atypia and prominent chromatin staining infiltrated in the stroma. Immunohistochemical analysis revealed that the cells were positive for CK7, GATA3 and weakly positive for CK20. Based on these results, we made the diagnosis of biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma. Biliary inside stents were placed across the biliary stricture, and she received chemotherapy plus endocrine therapy for breast cancer. So far, the partial response has been maintained for 1 year since the diagnosis of retroperitoneal metastasis. Although retroperitoneal metastasis from breast cancer, especially breast invasive ductal carcinoma, is extremely rare, it could be a differential diagnosis for biliary stenosis.}, }
@article {pmid34812516, year = {2022}, author = {Verbrugge, SAJ and Alhusen, JA and Kempin, S and Pillon, NJ and Rozman, J and Wackerhage, H and Kleinert, M}, title = {Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise.}, journal = {Journal of cellular biochemistry}, volume = {123}, number = {2}, pages = {202-214}, doi = {10.1002/jcb.30179}, pmid = {34812516}, issn = {1097-4644}, mesh = {Animals ; *Blood Glucose/genetics/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Humans ; Insulin Resistance/*genetics ; Muscle, Skeletal/*metabolism ; Physical Endurance/*genetics ; *Resistance Training ; }, abstract = {Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise.}, }
@article {pmid34812466, year = {2021}, author = {Feresin, RG and Johnson, SA and Elam, ML and Pourafshar, S and Navaei, N and Akhavan, NS and Tenenbaum, G and Figueroa, A and Arjmandi, BH}, title = {Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.}, journal = {Food &amp; function}, volume = {12}, number = {24}, pages = {12526-12534}, doi = {10.1039/d1fo01555a}, pmid = {34812466}, issn = {2042-650X}, mesh = {Aged ; Biomarkers/blood ; Bone Density/*drug effects ; Bone Resorption/blood/drug therapy ; Female ; *Fragaria ; Humans ; Hypertension/blood/complications/*drug therapy ; Middle Aged ; Osteoporosis, Postmenopausal/blood/complications/*prevention &amp; control ; Plant Extracts/blood/*pharmacology ; Polyphenols/blood/*pharmacology ; Postmenopause ; }, abstract = {Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m[-2]; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.}, }
@article {pmid34801929, year = {2022}, author = {Mampel, A and Sottile, ML and Denita-Juárez, SP and Vargas, AL and Vargas-Roig, LM}, title = {Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer.}, journal = {Cancer genetics}, volume = {260-261}, number = {}, pages = {14-17}, doi = {10.1016/j.cancergen.2021.11.003}, pmid = {34801929}, issn = {2210-7762}, mesh = {Adult ; Aged ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Heterozygote ; Humans ; Male ; Neoplasms, Second Primary/*genetics ; Pedigree ; *Point Mutation ; Sequence Analysis, DNA ; *Sequence Deletion ; }, abstract = {Double heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. The proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants NM_007300.4(BRCA1):c.4201C>T (p.Gln1401Ter), and NM_000059.3(BRCA2):c.5146_5149del (p.Tyr1716fs). . The patient's son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. There are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.}, }
@article {pmid34781971, year = {2021}, author = {Kostoglou, A and Vlastos, D and Bakalis, A and Ghosh, D}, title = {Breast cancer-associated opsoclonus-myoclonus syndrome: a case report.}, journal = {World journal of surgical oncology}, volume = {19}, number = {1}, pages = {328}, pmid = {34781971}, issn = {1477-7819}, mesh = {Adult ; *Breast Neoplasms/complications ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Opsoclonus-Myoclonus Syndrome/etiology ; Positron Emission Tomography Computed Tomography ; Prognosis ; }, abstract = {BACKGROUND: Paraneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment.<br><br>CASE PRESENTATION: A 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up.<br><br>CONCLUSIONS: In conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.}, }
@article {pmid34781210, year = {2021}, author = {Jeong, JS and Cho, KJ and Kim, D and Lee, YS and Song, JS}, title = {Genomic alteration in rare subtype of sarcomatoid salivary duct carcinoma.}, journal = {Pathology, research and practice}, volume = {228}, number = {}, pages = {153678}, doi = {10.1016/j.prp.2021.153678}, pmid = {34781210}, issn = {1618-0631}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Ductal/genetics/*pathology ; Humans ; Male ; Middle Aged ; Salivary Ducts/pathology ; Salivary Gland Neoplasms/genetics/*pathology ; }, abstract = {AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary gland neoplasm with a poor prognosis. Morphologically, it has many variants including sarcomatoid SDC. We evaluated the morphological features, immunohistochemistry profile, and genomic alteration of the rare variant, sarcomatoid SDC.<br><br>METHODS AND RESULTS: We evaluated the clinicopathological and molecular pathology for rare variant of sarcomatoid SDC. Among 102 SDC patients, three had sarcomatoid SDC. Review of clinicopathological features and immunohistochemistry and targeted exome sequencing was performed according to carcinomatous and sarcomatoid areas, respectively. The tumors were present in two submandibular glands and one parotid gland. In one case, a SDC arose in carcinoma ex pleomorphic adenoma. All consisted of a conventional invasive ductal carcinoma area and sarcomatoid features including spindle cells and multinucleated giant cells. AR and epithelial membrane antigen (EMA) were positive in both carcinoma and sarcomatoid areas. Cytokeratin AE1/AE3 were negative in all sarcomatoid areas. Targeted exome sequencing revealed multiple heterogeneous alterations including PIK3CA and TP53. Genomic alterations were nearly identical between typical carcinoma and sarcomatoid areas.<br><br>CONCLUSIONS: Clinicopathological features of sarcomatoid SDCs were not different from typical SDC, and genomic alteration according to subtypes was also similar to that of the conventional type. Androgen receptor (AR) expression is helpful in the diagnosis of SDC. The findings indicate that EMA and AR are useful in diagnosing sarcomatoid SDC when the tumor is composed of predominantly sarcomatoid components.}, }
@article {pmid34778983, year = {2022}, author = {O'Donnell, AJ and Greischar, MA and Reece, SE}, title = {Mistimed malaria parasites re-synchronize with host feeding-fasting rhythms by shortening the duration of intra-erythrocytic development.}, journal = {Parasite immunology}, volume = {44}, number = {3}, pages = {e12898}, pmid = {34778983}, issn = {1365-3024}, support = {/WT_/Wellcome Trust/United Kingdom ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Circadian Rhythm/physiology ; Fasting ; *Malaria/parasitology/prevention &amp; control ; *Parasites ; *Plasmodium chabaudi/physiology ; }, abstract = {AIMS: Malaria parasites exhibit daily rhythms in the intra-erythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding-fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how.<br><br>METHODS: We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10&#xa0;days, before and after the peak in asexual densities. We compare how the duration, synchrony and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12&#xa0;hours and ask whether the density of parasites affects the rescheduling process.<br><br>RESULTS AND CONCLUSIONS: Our experiments reveal parasites shorten the IDC duration by 2-3&#xa0;hours to become realigned to host feeding-fasting rhythms with 5-6&#xa0;days, in a density-independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs.}, }
@article {pmid34769077, year = {2021}, author = {Kohlhase, DR and McCabe, CE and Singh, AK and O'Rourke, JA and Graham, MA}, title = {Comparing Early Transcriptomic Responses of 18 Soybean (Glycine max) Genotypes to Iron Stress.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769077}, issn = {1422-0067}, support = {3625-21220-006-00D//USDA-ARS/ ; IOW04714//USDA/ ; FAR0024859//North Central Soybean Research Program/ ; }, mesh = {*Gene Expression Regulation, Plant ; Genome-Wide Association Study ; Iron/*metabolism ; Quantitative Trait Loci ; Soybeans/*genetics/metabolism ; Stress, Physiological ; Transcriptome ; }, abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress that negatively affects soybean (Glycine max [L.] Merr.) production. Much of our knowledge of IDC stress responses is derived from model plant species. Gene expression, quantitative trait loci (QTL) mapping, and genome-wide association studies (GWAS) performed in soybean suggest that stress response differences exist between model and crop species. Our current understanding of the molecular response to IDC in soybeans is largely derived from gene expression studies using near-isogenic lines differing in iron efficiency. To improve iron efficiency in soybeans and other crops, we need to expand gene expression studies to include the diversity present in germplasm collections. Therefore, we collected 216 purified RNA samples (18 genotypes, two tissue types [leaves and roots], two iron treatments [sufficient and deficient], three replicates) and used RNA sequencing to examine the expression differences of 18 diverse soybean genotypes in response to iron deficiency. We found a rapid response to iron deficiency across genotypes, most responding within 60 min of stress. There was little evidence of an overlap of specific differentially expressed genes, and comparisons of gene ontology terms and transcription factor families suggest the utilization of different pathways in the stress response. These initial findings suggest an untapped genetic potential within the soybean germplasm collection that could be used for the continued improvement of iron efficiency in soybean.}, }
@article {pmid34765304, year = {2021}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Long-term oncologic outcomes of breast conserving surgery with propofol-based total intravenous anesthesia or volatile inhalational general anesthesia without propofol: a propensity score-matched, population-based cohort study.}, journal = {American journal of cancer research}, volume = {11}, number = {10}, pages = {4966-4980}, pmid = {34765304}, issn = {2156-6976}, abstract = {To estimate oncologic outcomes (overall survival [OS], locoregional recurrence [LRR], and distant metastasis [DM]) in patients with breast intraductal carcinoma (IDC) receiving breast conserving surgery (BCS) under propofol-based total intravenous anesthesia (TIVA) or volatile inhalational (INHA) general anesthesia (GA) without propofol. Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized by anesthesia techniques into propofol-based TIVA-GA and non-propofol-based INHA-GA groups, respectively. Cox regression analysis was performed to calculate hazard ratios and 95% confidence intervals (CIs). In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of all-cause mortality for TIVA-GA with propofol compared with INHA-GA without propofol was 0.94 (0.83-1.31). The aHR (95% CI) of LRR for TIVA-GA with propofol group compared with INHA-GA without propofol was 0.77 (0.58-0.87). The aHR (95% CI) of DM for TIVA-GA with propofol compared with INHA-GA without propofol was 0.91 (0.82-1.24). Propofol-based TIVA-GA might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with non-propofol-based INHA-GA.}, }
@article {pmid34763167, year = {2021}, author = {Mallapasi, MN and Kusumanegara, J and Kabo, P and Usman, U and Mulyono, MT and Faruk, M}, title = {Cardiac metastasis of triple-negative breast cancer mimicking myxoma: A case report.}, journal = {International journal of surgery case reports}, volume = {88}, number = {}, pages = {106552}, pmid = {34763167}, issn = {2210-2612}, abstract = {INTRODUCTION: Metastatic heart tumors are rare, occurring in 1.5-20% of cancer patient autopsies. Lymphoma, melanoma, leukemia, and carcinomas of the lung, esophagus, and breast are the most prevalent causes of these metastases, although they can originate from any malignant tumor. Here we report a case of triple-negative breast cancer with cardiac metastasis mimicking myxoma.<br><br>PRESENTATION OF CASE: A 39-year-old woman presented at the emergency department with shortness of breath. Vital signs were hypotension and tachypnea. There were coarse crackles at the bases of both lungs. Electrocardiography results showed a normal sinus rhythm. Chest X-ray revealed cardiomegaly with signs of pulmonary edema. Echocardiography revealed a large left atrial (LA) mass protruding to the mitral valve and attached to the interatrial septum during diastole. The patient was diagnosed with cardiogenic shock, acute kidney injury, elevated liver enzymes, and an LA mass. Surgical excision through median sternotomy was planned. Intraoperatively, an LA mass was found. The histopathology evaluation showed an LA mass with invasive ductal carcinoma of metastatic breast tumors. Immunohistochemistry (IHC) confirmed the diagnosis of triple-negative breast cancer that had metastasized to the heart. Postoperative echocardiography confirmed complete excision of the tumor.<br><br>DISCUSSION: Breast cancer that has metastasized to the heart is uncommon. This patient was referred to the surgical oncology section for the treatment of triple-negative breast cancer with cardiac metastasis.<br><br>CONCLUSION: A heart mass should be suspected of having metastasized if the patient has a history of malignancy, even if it occurred several years earlier.}, }
@article {pmid34753585, year = {2021}, author = {Othong, J and Boonmak, J and Cheansirisomboon, A and Puangmali, T and Phanchai, W and Youngme, S}, title = {pH modulated luminescent switching and discriminative detection of amino acid based on metal-organic framework.}, journal = {Analytica chimica acta}, volume = {1187}, number = {}, pages = {339157}, doi = {10.1016/j.aca.2021.339157}, pmid = {34753585}, issn = {1873-4324}, mesh = {Amino Acids ; Humans ; Hydrogen-Ion Concentration ; Luminescence ; *Metal-Organic Frameworks ; Reproducibility of Results ; }, abstract = {The detection of glutamic (Glu) or aspartic (Asp) acids is vital for human nutrition and diagnosis of disease. Herein, the dht ligand containing hydroxy group (-OH) is used to design and synthesize a 2D luminescent [Cd2(idc)(dht)(H2O)4] (1); H2idc = 4,5-imidazoledicarboxylic acid and H2dht = 2,5-dihydroxyterephthalic acid for sensing amino acids. The compound 1 can discriminatively detect Asp and Glu among other amino acids through blue-shifted emission (yellow → green). The dual sensing mechanism may be attributed to the intermolecular excited-state proton transfer between MOF and water to produce keto form along with the subsequent switching of keto form to enol form by protonation causing the increased band gap energy. This material can serve several benefits in terms of high selectivity, fast response (30s), good reproducibility and low LOD value of 11.34 μM which is less than the harmful concentration of Glu for human health (>400 μM). In addition, 1 shows the broad range detection of Glu covering in safe and unsafe levels. For on-site detection of Glu, MOF-based paper is devised and can be applied through color-scanning application in smartphone. Besides, this sensor can serve to detect Glu in real samples with good recovery.}, }
@article {pmid34725819, year = {2022}, author = {Chen, X and Zhang, C and Guo, D and Wang, Y and Hu, J and Hu, J and Wang, S and Liu, X}, title = {Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.}, journal = {European journal of clinical investigation}, volume = {52}, number = {4}, pages = {e13704}, doi = {10.1111/eci.13704}, pmid = {34725819}, issn = {1365-2362}, support = {2017YFC0108602//The National Key Research and Development Program of China/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*mortality/pathology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate ; }, abstract = {OBJECTIVE: To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis.<br><br>METHOD: We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry.<br><br>RESULT: Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: &#x3c7;[2] &#xa0;=&#xa0;18784, p&#xa0;<&#xa0;0.001; &#x3c7;[2] &#xa0;=&#xa0;47.1, p&#xa0;<&#xa0;0.001; &#x3c7;[2] &#xa0;=&#xa0;20, p&#xa0;<&#xa0;0.001).<br><br>CONCLUSION: The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.}, }
@article {pmid34717732, year = {2021}, author = {Ropri, AS and DeVaux, RS and Eng, J and Chittur, SV and Herschkowitz, JI}, title = {Cis-acting super-enhancer lncRNAs as biomarkers to early-stage breast cancer.}, journal = {Breast cancer research : BCR}, volume = {23}, number = {1}, pages = {101}, pmid = {34717732}, issn = {1465-542X}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Line ; Disease Progression ; Enhancer Elements, Genetic/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Proteins/genetics ; MicroRNAs/genetics ; RNA, Long Noncoding/*genetics ; Receptors, Estrogen/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; }, abstract = {BACKGROUND: Increased breast cancer screening over the past four decades has led to a substantial rise in the diagnosis of ductal carcinoma in situ (DCIS). Although DCIS lesions precede invasive ductal carcinoma (IDC), they do not always transform into cancer. The current standard-of-care for DCIS is an aggressive course of therapy to prevent invasive and metastatic disease resulting in over-diagnosis and over-treatment. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive disease. Recent studies show that super-enhancers, in addition to promoting other gene transcription, are themselves transcribed producing super-enhancer associated long noncoding RNAs (SE-lncRNAs). These SE-lncRNAs can interact with their associated enhancer regions in cis and influence activities and expression of neighboring genes. Furthermore, they represent a novel, untapped group of therapeutic targets.<br><br>METHODS: With an integrative analysis of enhancer loci with global expression of SE-lncRNAs in the MCF10A progression series, we have identified differentially expressed SE-lncRNAs which can identify mechanisms for DCIS to IDC progression. Furthermore, cross-referencing these SE-lncRNAs with patient samples in the The Cancer Genome Atlas (TCGA) database, we have unveiled 27 clinically relevant SE-lncRNAs that potentially interact with their enhancer to regulate nearby gene expression. To complement SE-lncRNA expression studies, we conducted an unbiased global analysis of super-enhancers that are acquired or lost in progression.<br><br>RESULTS: Here we designate SE-lncRNAs RP11-379F4.4 and RP11-465B22.8 as potential markers of progression of DCIS to IDC through regulation of the expression of their neighboring genes (RARRES1 and miR-200b, respectively). Moreover, we classified 403 super-enhancer regions in MCF10A normal cells, 627 in AT1, 1053 in DCIS, and 320 in CA1 cells. Comparison analysis of acquired/lost super-enhancer regions with super-enhancer regions classified in 47 ER positive patients, 10 triple negative breast cancer (TNBC) patients, and 11 TNBC cell lines reveal critically acquired pathways including STAT signaling and NF-kB signaling. In contrast, protein folding, and local estrogen production are identified as major pathways lost in progression.<br><br>CONCLUSION: Collectively, these analyses identify differentially expressed SE-lncRNAs and acquired/lost super-enhancers in progression of breast cancer important for promoting DCIS lesions to IDC.}, }
@article {pmid34716548, year = {2021}, author = {Cattaneo, C and Rieg, S and Schwarzer, G and Müller, MC and Blümel, B and Kern, WV}, title = {Enterococcus faecalis bloodstream infection: does infectious disease specialist consultation make a difference?.}, journal = {Infection}, volume = {49}, number = {6}, pages = {1289-1297}, pmid = {34716548}, issn = {1439-0973}, mesh = {Adult ; Aged ; *Bacteremia/epidemiology ; *Communicable Diseases ; Enterococcus faecalis ; *Gram-Positive Bacterial Infections/epidemiology ; Humans ; Referral and Consultation ; Retrospective Studies ; Risk Factors ; *Sepsis ; }, abstract = {PURPOSE: To evaluate the relationship between mortality or relapse of bloodstream infection (BSI) due to Enterococcus faecalis and infectious diseases specialist consultation (IDC) and other factors potentially associated with outcomes.<br><br>METHODS: In a tertiary-care center, consecutive adult patients with E. faecalis BSI between January 1, 2016 and January 31, 2019, were prospectively followed. The management of E. faecalis BSI was evaluated in terms of adherence to evidence-based quality-of-care indicators (QCIs). IDC and other factors potentially associated with 90-day-mortality or relapse of E. faecalis BSI were analyzed by multivariate logistic regression.<br><br>RESULTS: A total of 151 patients with a median age of 68&#xa0;years were studied. IDC was performed in 38% of patients with E. faecalis BSI. 30 cases of endocarditis (20%) were diagnosed. All-cause in-hospital mortality was 23%, 90-day mortality was 37%, and 90-day relapsing E. faecalis BSI was 8%. IDC was significantly associated with better adherence to 5 QCIs. Factors significantly associated with 90-day mortality or relapsing EfB in multivariate analysis were severe sepsis or septic shock at onset (HR 4.32, CI 2.36e7.88) and deep-seated focus of infection (superficial focus HR 0.33, CI 0.14e0.76).<br><br>CONCLUSION: Enterococcus faecalis bacteremia is associated with a high mortality. IDC contributed to improved diagnostic and therapeutic management.}, }
@article {pmid34708717, year = {2021}, author = {Wang, YY and Liu, C and Chen, X and Ji, J and Zhu, SL and Sun, Q and Zhang, K and Zhu, J and Zhao, S and Wang, YW and Ma, R and Wang, JL}, title = {Heat shock protein 90α in nipple discharge as a potential tumor marker for breast cancer.}, journal = {The Chinese journal of physiology}, volume = {64}, number = {5}, pages = {251-256}, doi = {10.4103/cjp.cjp_72_21}, pmid = {34708717}, issn = {0304-4920}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnosis ; Female ; HSP90 Heat-Shock Proteins/*genetics ; Humans ; *Nipple Discharge ; }, abstract = {Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.}, }
@article {pmid34707969, year = {2021}, author = {Blum, K and Bowirrat, A and Gondre Lewis, MC and Simpatico, TA and Ceccanti, M and Steinberg, B and Modestino, EJ and Thanos, PK and Baron, D and McLaughlin, T and Brewer, R and Badgaiyan, RD and Ponce, JV and Lott, L and Gold, MS}, title = {Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development.}, journal = {Current psychopharmacology}, volume = {10}, number = {}, pages = {}, pmid = {34707969}, issn = {2211-5560}, support = {I01 CX000479/CX/CSRD VA/United States ; }, abstract = {BACKGROUND: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait.<br><br>OBJECTIVE: The primary issue involves the question of whether there exists a mixed hypo or hyper-dopaminergia in this population.<br><br>METHOD: Genetic Addiction Risk Score (GARS&#xae;) testing was carried out of 24 Caucasians of ages 12-19, derived from families with RDS.<br><br>RESULTS: We have found that adolescents from this cohort, derived from RDS parents, displayed a high risk for any addictive behavior (a hypodopaminergia), especially, drug-seeking (95%) and alcohol-seeking (64%).<br><br>CONCLUSION: The adolescents in our study, although more work is required, show a hypodopaminergic trait, derived from a family with Reward Deficiency Syndrome (RDS). Certainly, in future studies, we will analyze GARS in non-RDS Caucasians between the ages of 12-19. The suggestion is first to identify risk alleles with the GARS test and, then, use well-researched precision, pro-dopamine neutraceutical regulation. This "two-hit" approach might prevent tragic fatalities among adolescents, in the face of the American opioid/psychostimulant epidemic.}, }
@article {pmid34702045, year = {2021}, author = {Ilbeigi, S and Naeimzadeh, Y and Davoodabadi Farahani, M and Rafi Monjezi, M and Dastsooz, H and Daraei, A and Farahani, F and Dastgheib, A and Mansoori, Y and Tabei, SMB}, title = {Clinical values of two estrogen receptor signaling targeted lncRNAs in invasive ductal breast carcinoma.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {34}, number = {5}, pages = {382-391}, doi = {10.48095/ccko2021382}, pmid = {34702045}, issn = {1802-5307}, mesh = {Adult ; Aged ; Breast/metabolism ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cell Line, Tumor ; Computational Biology ; Female ; Humans ; Middle Aged ; *RNA, Long Noncoding ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of quickly emerging new data regarding the molecular heterogeneity of invasive cancers, far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in the heterogeneity feature of BC.<br><br>METHODS: In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues. And finally, bio-informatic evaluation has been done.<br><br>RESULTS: The results of quantitative polymerase chain reaction showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P = 0.0085 and P = 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P = 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with the age at menarche < 14 years compared to patients with the age at menarche 14 (P = 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P = 0.047). And finally, using bio-informatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA zinc finger and BTB domain containing 10 (ZBTB10).<br><br>CONCLUSION: Altogether, our findings suggest that these lncRNAs with potential oncogenic roles are involved in the pathogenesis of IDC with clinical significance and they may therefore serve as novel markers for the dia-gnosis and treatment of IDC.}, }
@article {pmid34698916, year = {2022}, author = {Deshpande, SS and Malik, SC and Conforti, P and Lin, JD and Chu, YH and Nath, S and Greulich, F and Dumbach, MA and Uhlenhaut, NH and Schachtrup, C}, title = {P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.}, journal = {Cell and tissue research}, volume = {387}, number = {3}, pages = {415-431}, pmid = {34698916}, issn = {1432-0878}, support = {1442/8-1//Deutsche Forschungsgemeinschaft/ ; 1442/9-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Lateral Ventricles/metabolism ; Mice ; *Neural Stem Cells ; Neurogenesis ; Receptor, Nerve Growth Factor/metabolism ; *Stroke ; }, abstract = {Stroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75[NTR-/-]) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75[NTR-/-] NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75[NTR] abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75[NTR-/-] NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75[NTR-/-] NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75[NTR] abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.}, }
@article {pmid34689837, year = {2021}, author = {Rafiq, MT and Abdul Hamid, MS and Hafiz, E}, title = {The effect of rehabilitation protocol using mobile health in overweight and obese patients with knee osteoarthritis: a clinical trial.}, journal = {Advances in rheumatology (London, England)}, volume = {61}, number = {1}, pages = {63}, pmid = {34689837}, issn = {2523-3106}, mesh = {Clinical Protocols ; Humans ; Middle Aged ; *Obesity/complications ; *Osteoarthritis, Knee/rehabilitation ; *Overweight/complications ; *Telemedicine ; Treatment Outcome ; }, abstract = {OBJECTIVE: The objective of this randomized controlled trial (RCT) was to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) combined with mobile health (mHealth) applications on knee pain, mobility, functional activity and activities of daily living (ADL) among knee osteoarthritis (OA) patients who were overweight and obese.<br><br>METHODS: This study was a single-blind, RCT conducted at Teaching Bay of Rehmatul-Lil-Alameen Post Graduate Institute of Cardiology between February and November 2020. 114 knee OA patients who were overweight and obese were randomly divided by a computer-generated number into the rehabilitation group with mHealth (RGw-mHealth) to receive LLRP&#x2009;+ instructions of daily care (IDC) combined with mHealth intervention, rehabilitation group without mHealth (RGwo-mHealth) to receive LLRP&#x2009;+&#x2009;IDC intervention and control group (CG) to receive IDC intervention. All three groups were also provided leaflets explaining about their intervention. The primary outcome measure was knee pain measured by the Western Ontario and McMaster Universities Osteoarthritis Index score. The secondary outcome measures were mobility measured by the Timed up and go (TUG) test, functional activity measured by the patient-specific functional scale (PSFS), and ADL measured by the Katz Index of independence in ADL scores.<br><br>RESULTS: Among the 114 patients who were randomized (mean age, 53&#xa0;years), 96 (84%) completed the trial. After 3-months of intervention, patients in all three groups had statistically significant knee pain reduction (RGw-mHealth: 2.54; RGwo-mHealth: 1.47; and CG: 0.37) within groups (P&#x2009;<&#x2009;0.05). Furthermore, patients in the RGw-mHealth and RGwo-mHealth had statistically significant improvement in mobility, functional activity, and ADL within groups (P&#x2009;<&#x2009;0.05), but no improvement was noted in the CG (p&#x2009;>&#x2009;0.05). As indicated in the overall analysis of covariance, there were statistically significant differences in the mean knee pain, mobility, functional activity, and ADL changes between groups after 3-months (p&#x2009;<&#x2009;0.001). The pairwise between-group comparisons (Bonferroni post hoc analysis) of the knee pain, mobility, functional activity, and ADL scores at 3-months revealed that patients in the RGw-mHealth had significantly higher mean change in the knee pain, TUG test, functional activity, and ADL scores compared to patients in the RGwo-mHealth or CG.<br><br>CONCLUSION: Reduction in knee pain, improvement in mobility, functional activity, and ADL were more among patients in the RGw-mHealth compared with the RGwo-mHealth or CG. Trial registration National Medical Research Registry: NMRR-20-1094-52911. Date of registration: 05-05-2020. URL: https://www.nmrr.gov.my .}, }
@article {pmid34673584, year = {2021}, author = {Senel, F}, title = {The hormone receptor status in breast cancer and the relationship of subtypes with clinicopathological features.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {4}, pages = {671-676}, doi = {10.4103/IJPM.IJPM_606_20}, pmid = {34673584}, issn = {0974-5130}, mesh = {Adult ; Age Factors ; Biomarkers, Tumor/*genetics/*metabolism ; Breast Neoplasms/*genetics/*metabolism/*physiopathology ; Female ; Genetic Variation ; Genotype ; Humans ; Middle Aged ; Pathology, Clinical/methods ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Retrospective Studies ; }, abstract = {AIM: We aimed to determine the hormone receptor status in breast cancers and to investigate the relationship between single hormone receptor-positive, double hormone receptor-positive, double hormone receptor negativity, and human epidermal growth factor receptor 2 (HER2) status and some clinicopathological features.<br><br>MATERIALS AND METHODS: The study includes 85 patients who were diagnosed in our center between 2018 and 2019 and having surgical specimens were included in the study. Data of the cases, such as estrogen receptor (ER), progesterone receptor (PR), HER2 status, silver in situ hybridization (SISH) evaluation results, age distribution, histopathological findings were recorded.<br><br>RESULTS AND CONCLUSIONS: We investigated the relationship between age, grade, tumor size, lymph node metastases and ER, PR, and HER2. However, there was not a significant association between ER, PR, and HER2 and age, tumor size, lymph node metastases (P > 0.05). On the other hand, we found a significant association between grades and ER (P = 0.02) and PR (P = 0.004), but not between grades and HER2 (P > 0.05). High-grade tumors were tumors with the lowest ER, PR positivity rate. Considering the four subtypes, cases aged above 45 years were at most double hormone receptor-positive (75%) and ER-positive/PR-negative (56%), respectively (P < 0.001). High-grade tumors were mostly double hormone receptor-negative and at least double hormone receptor positive. The ER-positive/PR-negative subtype was between these two groups (P < 0.001). The increased tumor size (T3) and increased metastatic lymph node number (N2 and N3) were observed at least in the ER-positive/PR-negative subtype. The majority of cases are in the older age group and invasive ductal carcinoma (IDC) is the most common tumor type. Older cases are most frequently double hormone receptor-positive and ER-positive/PR-negative, respectively. The ER, PR positivity rate is low in high-grade tumors. ER-positive/PR-negative tumors are of a higher grade than double hormone receptor-positive tumors, but they are of a lower grade than double hormone receptor-negative tumors. The increased tumor size and increased lymph node metastasis number are at most in the double hormone negative subtype and at least in the ER-positive/PR-negative subtype. The ER-negative/PR-positive subtype is observed very rarely, which raises the question of whether ER-negative/PR-positive tumors really exist. Further studies are needed to investigate this subtype and its properties.}, }
@article {pmid34672684, year = {2021}, author = {Yadav, S and Hu, C and Nathanson, KL and Weitzel, JN and Goldgar, DE and Kraft, P and Gnanaolivu, RD and Na, J and Huang, H and Boddicker, NJ and Larson, N and Gao, C and Yao, S and Weinberg, C and Vachon, CM and Trentham-Dietz, A and Taylor, JA and Sandler, DR and Patel, A and Palmer, JR and Olson, JE and Neuhausen, S and Martinez, E and Lindstrom, S and Lacey, JV and Kurian, AW and John, EM and Haiman, C and Bernstein, L and Auer, PW and Anton-Culver, H and Ambrosone, CB and Karam, R and Chao, E and Yussuf, A and Pesaran, T and Dolinsky, JS and Hart, SN and LaDuca, H and Polley, EC and Domchek, SM and Couch, FJ}, title = {Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {39}, number = {35}, pages = {3918-3926}, pmid = {34672684}, issn = {1527-7755}, support = {P01 CA087969/CA/NCI NIH HHS/United States ; R01 CA097396/CA/NCI NIH HHS/United States ; K07 CA092044/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R35 CA253187/CA/NCI NIH HHS/United States ; Z01 ES044005/ImNIH/Intramural NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; R01 CA049449/CA/NCI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; R01 CA185623/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States ; U01 CA199277/CA/NCI NIH HHS/United States ; R01 CA225662/CA/NCI NIH HHS/United States ; UM1 CA164917/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; HHSN268201600002C/HL/NHLBI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; R01 CA098663/CA/NCI NIH HHS/United States ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; R01 CA204819/CA/NCI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; R01 CA067264/CA/NCI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; R01 CA058860/CA/NCI NIH HHS/United States ; R01 CA047147/CA/NCI NIH HHS/United States ; U01 CA082004/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 CA077398/CA/NCI NIH HHS/United States ; U01 CA164920/CA/NCI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; Z01 ES049033/ImNIH/Intramural NIH HHS/United States ; R01 CA192393/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Genetic Predisposition to Disease ; Genetic Testing/*methods ; *Germ-Line Mutation ; Humans ; Middle Aged ; Prognosis ; Young Adult ; }, abstract = {PURPOSE: To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast.<br><br>MATERIALS AND METHODS: The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC).<br><br>RESULTS: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC.<br><br>CONCLUSION: The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.}, }
@article {pmid34668757, year = {2021}, author = {Saelens, JW and Petersen, JEV and Freedman, E and Moseley, RC and Konaté, D and Diakité, SAS and Traoré, K and Vance, N and Fairhurst, RM and Diakité, M and Haase, SB and Taylor, SM}, title = {Impact of Sickle Cell Trait Hemoglobin on the Intraerythrocytic Transcriptional Program of Plasmodium falciparum.}, journal = {mSphere}, volume = {6}, number = {5}, pages = {e0075521}, pmid = {34668757}, issn = {2379-5042}, support = {R21 AI125988/AI/NIAID NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Hemoglobin A/*genetics ; Hemoglobin, Sickle/*genetics ; Hemoglobins/metabolism ; Humans ; Malaria, Falciparum/blood/*genetics/parasitology ; Male ; Plasmodium falciparum/physiology ; Sickle Cell Trait/blood/*genetics/parasitology ; Transcriptional Activation ; }, abstract = {Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS confers these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with parasite neutralization in HbAS red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium falciparum in normal (HbAA) and HbAS erythrocytes during both in vitro cultivation of reference parasite strains and naturally occurring P. falciparum infections in Malian children with HbAA or HbAS. During in vitro cultivation, parasites matured normally in HbAS RBCs, and the temporal expression was largely unperturbed of the highly ordered transcriptional program that underlies the parasite's maturation throughout the intraerythrocytic development cycle (IDC). However, differential expression analysis identified hundreds of transcripts aberrantly expressed in HbAS, largely occurring late in the IDC. Surprisingly, transcripts encoding members of the Maurer's clefts were overexpressed in HbAS despite impaired parasite protein export in these RBCs, while parasites in HbAS RBCs underexpressed transcripts associated with the endoplasmic reticulum and those encoding serine repeat antigen proteases that promote parasite egress. Analyses of P. falciparum transcriptomes from 32 children with uncomplicated malaria identified stage-specific differential expression: among infections composed of ring-stage parasites, only cyclophilin 19B was underexpressed in children with HbAS, while trophozoite-stage infections identified a range of differentially expressed transcripts, including downregulation in HbAS of several transcripts associated with severe malaria in collateral studies. Collectively, our comparative transcriptomic screen in vitro and in vivo indicates that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Because HbAS consistently protects from severe P. falciparum, modulation of these responses may offer avenues by which to neutralize P. falciparum parasites. IMPORTANCE Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening malaria, yet the molecular mechanisms that underlie HbAS protection from severe malaria remain incompletely understood. Here, we used transcriptome sequencing (RNA-seq) to measure the impact of HbAS on the blood-stage transcriptome of Plasmodium falciparum in in vitro time series experiments and in vivo samples from natural infections. Our in vitro time series data reveal that, during its blood stage, P. falciparum's gene expression in HbAS is impacted primarily through alterations in the abundance of gene products as opposed to variations in the timing of gene expression. Collectively, our in vitro and in vivo data indicate that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Due to the persistent association of HbAS and protection from severe disease, these processes that are modified in HbAS may offer strategies to neutralize P. falciparum.}, }
@article {pmid34659834, year = {2021}, author = {Ntirenganya, F and Twagirumukiza, JD and Bucyibaruta, G and Rugwizangoga, B and Rulisa, S}, title = {Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study.}, journal = {International journal of breast cancer}, volume = {2021}, number = {}, pages = {5560559}, pmid = {34659834}, issn = {2090-3170}, abstract = {BACKGROUND: Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women's cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women.<br><br>OBJECTIVES: The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda.<br><br>METHODS: This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis.<br><br>RESULTS: 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake (AOR = 3.73, 95%CI&#x2009;2.19 - 6.32, p < 0.001), obesity/overweight in adolescence or early adulthood (AOR = 10.86, 95%CI&#x2009;4.82 - 24.4, p < 0.001), history of primary infertility (AOR = 33.8, 95%CI&#x2009;3.5 - 321.5, p = 0.002), nulliparity (AOR = 3.75, 95%CI&#x2009;1.61 - 8.75, p = 0.002), and a history of benign breast disease (AOR = 6.06, 95%CI&#x2009;1.19 - 30.73, p = 0.03) were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype.<br><br>CONCLUSION: Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.}, }
@article {pmid34657058, year = {2021}, author = {Takagi, H and Fukai, H and Misawa, S and Kurogochi, A and Kirii, Y}, title = {[A Case of Bone Marrow Carcinomatosis Associated with Breast Cancer with Anemia and Thrombocytopenia Successfully Treated with Aromatase Inhibitor Therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {48}, number = {10}, pages = {1255-1257}, pmid = {34657058}, issn = {0385-0684}, mesh = {*Anemia/drug therapy/etiology ; Aromatase Inhibitors ; Bone Marrow ; *Breast Neoplasms/complications/drug therapy/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Peritoneal Neoplasms ; *Thrombocytopenia/drug therapy/etiology ; }, abstract = {The patient was a 61-year-old woman who presented to the hospital with the chief complaints of anemia and thrombocytopenia. There was a mass in her left breast, and a needle biopsy with pathology revealed invasive ductal carcinoma, which was HR-positive and HER2-negative. A PET scan revealed multiple bone metastases, which were confirmed on bone marrow biopsy, leading to the diagnosis of bone marrow carcinomatosis. As the patient was in good general condition, an aromatase inhibitor(AI)therapy was selected. Rapid improvements in her hemoglobin level and platelet count were observed. At 19 months after the start of treatment, we were able to perform a left mastectomy with left axillary lymph node dissection. The histological evaluation of her response to treatment was Grade 2a, and severe lymph node metastasis was observed. The patient continued to receive the AI postoperatively. Thirty-two months after the start of treatment, there was no evidence of cancer on clinical imaging. Although it is rare for bone marrow carcinomatosis to occur, as in the present case, it is also notable that the patient had been in long-term remission with consistent AI therapy.}, }
@article {pmid34645713, year = {2021}, author = {Teodorescu, K and Plonsky, O and Ayal, S and Barkan, R}, title = {Frequency of enforcement is more important than the severity of punishment in reducing violation behaviors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {42}, pages = {}, pmid = {34645713}, issn = {1091-6490}, mesh = {COVID-19/*prevention &amp; control/virology ; Decision Making ; Humans ; Probability ; *Punishment ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {External enforcement policies aimed to reduce violations differ on two key components: the probability of inspection and the severity of the punishment. Different lines of research offer different insights regarding the relative importance of each component. In four studies, students and Prolific crowdsourcing participants (Ntotal = 816) repeatedly faced temptations to commit violations under two enforcement policies. Controlling for expected value, we found that a policy combining a high probability of inspection with a low severity of fines (HILS) was more effective than an economically equivalent policy that combined a low probability of inspection with a high severity of fines (LIHS). The advantage of prioritizing inspection frequency over punishment severity (HILS over LIHS) was greater for participants who, in the absence of enforcement, started out with a higher violation rate. Consistent with studies of decisions from experience, frequent enforcement with small fines was more effective than rare severe fines even when we announced the severity of the fine in advance to boost deterrence. In addition, in line with the phenomenon of underweighting of rare events, the effect was stronger when the probability of inspection was rarer (as in most real-life inspection probabilities) and was eliminated under moderate inspection probabilities. We thus recommend that policymakers looking to effectively reduce recurring violations among noncriminal populations should consider increasing inspection rates rather than punishment severity.}, }
@article {pmid34634714, year = {2021}, author = {Kufel, WD and Mastro, KA and Steele, JM and Wang, D and Riddell, SW and Paolino, KM and Thomas, SJ}, title = {Impact of a pharmacist-facilitated, evidence-based bundle initiative on Staphylococcus aureus bacteremia management.}, journal = {Diagnostic microbiology and infectious disease}, volume = {101}, number = {4}, pages = {115535}, doi = {10.1016/j.diagmicrobio.2021.115535}, pmid = {34634714}, issn = {1879-0070}, mesh = {Adult ; Anti-Bacterial Agents/*therapeutic use ; Antimicrobial Stewardship ; Bacteremia/*drug therapy/microbiology ; Female ; Humans ; Male ; Middle Aged ; *Patient Care Bundles ; Patient Compliance ; *Pharmacists ; Referral and Consultation ; Staphylococcal Infections/*drug therapy/microbiology ; Staphylococcus aureus/drug effects/isolation &amp; purification ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate a pharmacist-facilitated evidence-based bundle (EBB) initiative with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia (SAB).<br><br>METHODS: This was a before-and-after quasi-experimental study of adult patients with SAB before and after the pharmacist-facilitated EBB initiative, which included IDC, timely definitive antibiotics, source control, echocardiography, and repeat blood cultures.<br><br>RESULTS: Ninety and 111 patients were included in pre- and post-intervention cohorts, respectively. We observed significant increases in adherence to all 5 (4.4% vs 68.5%, P < 0.001) and 4 (10.0% vs 76.6%, P < 0.001) EBB elements. Time to definitive antibiotics (48 vs 16 hours, P < 0.001), time to IDC (43.5 vs 32 hours, P < 0.001), SAB duration (95 vs 66 hours, P&#xa0;=&#xa0;0.009), persistent SAB (18.9% vs 9.0%, P&#xa0;=&#xa0;0.041), and length of stay (14 vs 13 days, P&#xa0;=&#xa0;0.027) also improved. No statistically significant differences for SAB-related readmission or all-cause mortality were observed.<br><br>CONCLUSIONS: Our pharmacist-facilitated SAB initiative was associated with improved EBB adherence and clinical outcomes.}, }
@article {pmid34624832, year = {2021}, author = {Mohammed, AA}, title = {The clinical behavior of different molecular subtypes of breast cancer.}, journal = {Cancer treatment and research communications}, volume = {29}, number = {}, pages = {100469}, doi = {10.1016/j.ctarc.2021.100469}, pmid = {34624832}, issn = {2468-2942}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous group of tumors classified, according to different gene expressions that encodes for the hormone receptor status, into 4 main categories which are: luminal types A and B, triple negative/basal-like, and Her-2 molecular subtypes.<br><br>PATIENTS AND METHODS: This retrospective study included 311 breast cancer females. Patients were classified according to the expression of hormone receptors into: Luminal-A, luminal-B, HER-2 enriched and basal-like types. All groups were then studied for differences in clinical course of the disease.<br><br>RESULTS: Luminal-B type was the commonest molecular type (43.73%). Invasive ductal carcinoma was the commonest histological type (89.1%). Stages IIB and IIIA were the commonest clinical stages (24.4% &amp; 22.2%) respectively. Most patients had no recurrence (85.5%), the commonest recurrence was local and axillary ones (7.1%). Low grade tumors were less frequent than intermediate and high grades (3.5%, 51.1%, and 45.3%). We found a significant correlation between molecular subtypes and survival status, tumor grade, and histopathological types (P values 0.029, 0.001, and 0.006) respectively, while it was not significant with age, BMI, recurrence &amp; metastatic disease, overall survival, and TNM stage (P values 0.648, 0.398, 0.5, 0.063 and 0.319).<br><br>CONCLUSION: Luminal types A and B are the commonest molecular subtypes of breast cancer. Luminal type A is associated with improved survival, and basal like has the highest breast cancer fatality rates. Invasive ductal carcinomas of specific types mostly found in patients with luminal types A and B, while other rare forms like Paget's disease was diagnosed HER-2 enriched types.}, }
@article {pmid34610495, year = {2021}, author = {Rousseau, S and Katz, D and Shlomi-Polachek, I and Frenkel, TI}, title = {Prospective risk from prenatal anxiety to post traumatic stress following childbirth: The mediating effects of acute stress assessed during the postnatal hospital stay and preliminary evidence for moderating effects of doula care.}, journal = {Midwifery}, volume = {103}, number = {}, pages = {103143}, doi = {10.1016/j.midw.2021.103143}, pmid = {34610495}, issn = {1532-3099}, mesh = {Anxiety/etiology ; *Doulas ; Female ; Humans ; Length of Stay ; Parturition ; Postpartum Period ; Pregnancy ; Prospective Studies ; *Stress Disorders, Post-Traumatic/etiology ; }, abstract = {OBJECTIVE: Growing literature has identified childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth. The current study is the first to prospectively examine a pathway of risk from mothers' prenatal trait-anxiety, to Acute-Stress-Immediately-Following-Childbirth, and later symptoms of Post-Traumatic-Stress-Following-Childbirth, in a low-risk community sample. Auxiliary analyses explored whether doula care during childbirth moderated risk.<br><br>METHOD: 149 pregnant women were randomly selected. Prenatal trait-anxiety was assessed toward the end of pregnancy, Acute-Stress-Immediately-Following-Childbirth at two-days post-partum, and symptoms of Post-Traumatic-Stress-Following-Childbirth at one-month post-partum.<br><br>RESULTS: Results indicated a significant indirect pathway from prenatal trait-anxiety to Post-Traumatic-Stress-Following-Childbirth, through Acute-Stress-Immediately-Following-Childbirth. Two groups were generated ad hoc for auxiliary analyses: participants who opted to receive doula care during childbirth (n=21; 14%) versus participants who received care as usual (n=128; 86%). Analyses provided preliminary support for doula care as a potential moderator of risk.<br><br>CONCLUSIONS: Results point toward prenatal trait-anxiety and Acute-Stress-Immediately-Following-Childbirth as significant risk factors for Post-Traumatic-Stress-Following-Childbirth. Findings inform preventive screening implicating the prenatal period as well as the postnatal hospital stay as important time windows for preventive screening. Finally, preliminary support for moderating effects of doula care suggest that preventive interventions administered during the perinatal period may effectively reduce anxiety-related risk for Post-Traumatic-Stress-Following-Childbirth.}, }
@article {pmid34597458, year = {2021}, author = {Viswanathan, K and Sadow, PM and Maleki, Z and Nishino, M and Baloch, ZW and Abbott, TE and Rao, R and Faquin, WC}, title = {Cytomorphologic features of intraductal salivary gland carcinoma: A multi-institutional study of 13 FNA cases with histologic, molecular, and clinical correlations.}, journal = {Cancer cytopathology}, volume = {129}, number = {12}, pages = {928-946}, pmid = {34597458}, issn = {1934-6638}, support = {P01 CA240239/CA/NCI NIH HHS/United States ; 1PO1CA240239-01//National Cancer Institute of the National Institutes of Health/ ; }, mesh = {Biopsy, Fine-Needle/methods ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Gene Fusion ; Humans ; *Salivary Gland Neoplasms/pathology ; Salivary Glands/pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of the salivary gland (IDC) is a rare cancer with potential actionable targets, including RET fusions. Histologic and molecular features of IDC were recently reported, but cytomorphologic data are limited. In the largest multi-institutional fine-needle aspiration (FNA) series, the authors describe the cytomorphologic features of 13 IDC cases with available clinical, radiologic, histopathologic, and molecular data.<br><br>METHODS: The cases included 13 FNAs for 9 low-grade (LG) IDCs and 4 high-grade (HG) IDCs with corresponding histopathology and available molecular, imaging, and clinical data. Smears and liquid-based preparations available for 12 FNAs were semiquantitatively scored for key cytomorphologic findings and correlated with the corresponding resection.<br><br>RESULTS: LG IDC FNAs showed a cellular, biphasic population of large, atypical ductal cells with mildly pleomorphic nuclei in a clean background and a minor population of small, uniform myoepithelial cells. In contrast, all HG IDC FNAs showed predominantly ductal cells with marked nuclear pleomorphism, coarse chromatin, and necrosis. With the Milan system, most LG and HG IDC FNAs were classified as either salivary gland neoplasms of uncertain malignant potential (54%) or malignant (31%). Immunohistochemistry showed ductal epithelial reactivity with mammaglobin, androgen receptor, and S100, whereas myoepithelial cells were positive for p63 and/or calponin. Among cases with next-generation sequencing, 4 LG IDCs showed NCOA4-RET gene fusions, whereas an HG IDC showed HRAS and PIK3CA mutations.<br><br>CONCLUSIONS: The cytomorphology of IDC overlaps with other benign and malignant salivary gland neoplasms. Immunohistochemistry limits the differential diagnosis, but definitive classification requires molecular analysis. A diagnosis of IDC has potential implications for patient management.}, }
@article {pmid34592934, year = {2021}, author = {Mathew, D and Gupta, S and Ashman, N}, title = {A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies.}, journal = {BMC nephrology}, volume = {22}, number = {1}, pages = {324}, pmid = {34592934}, issn = {1471-2369}, mesh = {Adult ; Autoantibodies/*blood ; Breast Neoplasms/*complications ; Estrogen Receptor beta/analysis ; Female ; Glomerulonephritis, Membranous/*complications/immunology ; Humans ; Kidney/pathology ; Receptors, Phospholipase A2/*immunology ; }, abstract = {BACKGROUND: Testing for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer.<br><br>CASE PRESENTATION: We describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome.<br><br>DISCUSSION AND CONCLUSIONS: Case series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.}, }
@article {pmid34587404, year = {2021}, author = {Yang, L and Xiong, Y and Sun, Z and Lin, X and Ni, H}, title = {Neferine Inhibits 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumorigenesis by Suppression of Cell Proliferation and Induction of Apoptosis via Modulation of the PI3K/AKT/NF-κB Signaling Pathway.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {40}, number = {3}, pages = {51-61}, doi = {10.1615/JEnvironPatholToxicolOncol.2021038118}, pmid = {34587404}, issn = {2162-6537}, mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Animals ; Antineoplastic Agents, Phytogenic/*pharmacology ; Apoptosis/*drug effects/physiology ; Benzylisoquinolines/*pharmacology ; Body Weight/drug effects ; Carcinogens/toxicity ; Cell Proliferation/drug effects/physiology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Lipid Peroxidation/drug effects ; Mammary Neoplasms, Experimental/chemically induced/*drug therapy/metabolism/pathology ; NF-kappa B/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Signal Transduction/drug effects ; }, abstract = {AIM: To investigate the anticancer mechanism of neferine on DMBA-prompted mammary tumorigenesis in animals.<br><br>METHODS: Mammary cancer was prompted by the subcutaneous injection of 25 mg DMBA mixed in 1 ml of the vehicle (sunflower oil [0.5 ml] and saline [0.5 ml]). We analyzed the biochemical and molecular expression of cell-proliferation and apoptotic markers in normal and DMBA-induced rats.<br><br>RESULTS: We detected low body weight, elevated quantities of lipid peroxidation, and low antioxidant enzyme activities in mammary tissues of DMBA-induced animals. We also found an invasive ductal carcinoma in DMBA-induced animals by histopathological assessment. Furthermore, western blotting findings displayed an augmented expression of PI3K, AKT, NF-&#x3ba;B, PCNA, cyclin D1, Ki-67, and Bcl-2, while reducing expression of p53, Bax, caspase-3, and caspase-9 in DMBA-induced cancer-bearing animals. RT-PCR results found upregulation of cyclin D1, PCNA, and Ki-67, and reduced expression of p53 in DMBA-prompted animals. The oral administration of neferine effectually inhibited mammary tumors via improved antioxidants and prevented lipid peroxidation activities when compared with tumor-bearing rats. Furthermore, neferine also modulated PI3K/AKT/NF-&#x3ba;B signaling through inhibiting cell proliferation and induced apoptosis in tumor-bearing rats.<br><br>CONCLUSION: In our findings, we concluded that neferine has an anti-proliferative and enhancing apoptotic property against DMBA-induced mammary cancer.}, }
@article {pmid34561670, year = {2021}, author = {Kumar, V and Nawroth, PP}, title = {Is the association between diabetes mellitus and pulmonary fibrosis real?.}, journal = {Nature reviews. Endocrinology}, volume = {17}, number = {12}, pages = {703-704}, pmid = {34561670}, issn = {1759-5037}, mesh = {*Diabetes Mellitus/epidemiology ; Humans ; *Pulmonary Fibrosis/epidemiology ; Risk Factors ; }, }
@article {pmid34560418, year = {2021}, author = {Wan, D and Zhang, Y and Yu, Q and Li, F and Zhuo, J}, title = {14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression.}, journal = {Pathology, research and practice}, volume = {227}, number = {}, pages = {153619}, doi = {10.1016/j.prp.2021.153619}, pmid = {34560418}, issn = {1618-0631}, mesh = {14-3-3 Proteins/genetics/*metabolism ; Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Nuclear Proteins/analysis ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*analysis ; Tumor Suppressor Protein p53/analysis ; Up-Regulation ; Young Adult ; Zinc Finger Protein Gli2/analysis ; }, abstract = {BACKGROUND: HER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14-3-3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too.<br><br>METHODS: Immunohistochemistry experiment was performed to detect expression status of 14-3-3&#x3b6;, HER2, TGF-&#x3b2;, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC.<br><br>RESULTS: The positive expression rates of 14-3-3&#x3b6;/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14-3-3&#x3b6; was significantly increased in ADH, DCIS and IDC groups. 14-3-3&#x3b6; was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14-3-3&#x3b6; overexpression was significantly different between DCIS group and IDC with DCIS group (P&#xa0;=&#xa0;0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14-3-3&#x3b6; was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14-3-3&#x3b6; and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14-3-3&#x3b6; and HER2 was positively correlated with occurrence of lymph node metastasis (P&#xa0;=&#xa0;0.048). TGF-&#x3b2; was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-&#x3b2; expression was significantly increased in the IDC group with lymph node metastasis (P&#xa0;=&#xa0;0.015). In IDC cases with 14-3-3&#x3b6; and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P&#xa0;=&#xa0;0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P&#xa0;=&#xa0;0.038). The co-overexpression of 14-3-3&#x3b6; and HER2 was positively correlated with ER negative expression (P&#xa0;<&#xa0;0.001) and PR negative expression (P&#xa0;=&#xa0;0.038), respectively.<br><br>CONCLUSION: 14-3-3&#x3b6; synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14-3-3&#x3b6; and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14-3-3&#x3b6; and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.}, }
@article {pmid34557972, year = {2021}, author = {Han, J and Harrison, L and Patzelt, L and Wu, M and Junker, D and Herzig, S and Berriel Diaz, M and Karampinos, DC}, title = {Imaging modalities for diagnosis and monitoring of cancer cachexia.}, journal = {EJNMMI research}, volume = {11}, number = {1}, pages = {94}, pmid = {34557972}, issn = {2191-219X}, support = {SFB824/A9//deutsche forschungsgemeinschaft/ ; }, abstract = {Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities-that is, computed tomography, magnetic resonance imaging, ([18]F) fluoro-2-deoxy-D-glucose ([18]FDG) PET and dual-energy X-ray absorptiometry-shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.}, }
@article {pmid34556291, year = {2021}, author = {Mangiardi-Veltin, M and Chamming's, F and Jaffre, A and Rousvoal, A and Tunon de Lara, C and Brouste, V and Hoppe, S and Sénéchal, C}, title = {[Prophylactic mastectomy and occult cancer: a ten-year experience at a cancer center].}, journal = {Bulletin du cancer}, volume = {108}, number = {11}, pages = {999-1009}, doi = {10.1016/j.bulcan.2021.05.007}, pmid = {34556291}, issn = {1769-6917}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*epidemiology/genetics ; Cancer Care Facilities ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Middle Aged ; Mutation ; Neoplasms, Unknown Primary/diagnostic imaging/*epidemiology/genetics ; Postoperative Complications/*epidemiology ; Prevalence ; Prophylactic Mastectomy/*adverse effects/methods ; Reoperation ; Retrospective Studies ; Time Factors ; }, abstract = {INTRODUCTION: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers.<br><br>METHODS: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts.<br><br>RESULTS: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%).<br><br>DISCUSSION: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.}, }
@article {pmid34555180, year = {2022}, author = {Giroud, M and Jodeleit, H and Prentice, KJ and Bartelt, A}, title = {Adipocyte function and the development of cardiometabolic disease.}, journal = {The Journal of physiology}, volume = {600}, number = {5}, pages = {1189-1208}, doi = {10.1113/JP281979}, pmid = {34555180}, issn = {1469-7793}, mesh = {Adipocytes, Brown/metabolism ; Adipose Tissue, Brown/physiology ; Adipose Tissue, White/metabolism ; Animals ; *Cardiovascular Diseases/etiology/metabolism ; Diet, High-Fat/adverse effects ; Energy Metabolism ; Mice ; Obesity/metabolism ; Thermogenesis/physiology ; }, abstract = {Obesity is a medical disorder caused by multiple mechanisms of dysregulated energy balance. A major consequence of obesity is an increased risk to develop diabetes, diabetic complications and cardiovascular disease. While a better understanding of the molecular mechanisms linking obesity, insulin resistance and cardiovascular disease is needed, translational research of the human pathology is hampered by the available cellular and rodent model systems. Major barriers are the species-specific differences in energy balance, vascular biology and adipose tissue physiology, especially related to white and brown adipocytes, and adipose tissue browning. In rodents, non-shivering thermogenesis is responsible for a large part of energy expenditure, but humans possess much less thermogenic fat, which means temperature is an important variable in translational research. Mouse models with predisposition to dyslipidaemia housed at thermoneutrality and fed a high-fat diet more closely reflect human physiology. Also, adipocytes play a key role in the endocrine regulation of cardiovascular function. Adipocytes secrete a variety of hormones, lipid mediators and other metabolites that directly influence the local microenvironment as well as distant tissues. This is specifically apparent in perivascular depots, where adipocytes modulate vascular function and inflammation. Altogether, these mechanisms highlight the critical role of adipocytes in the development of cardiometabolic disease.}, }
@article {pmid34547924, year = {2022}, author = {Moghalu, O and Stoffel, JT and Elliott, SP and Welk, B and Zhang, C and Presson, A and Myers, J}, title = {Time-Related Changes in Patient Reported Bladder Symptoms and Satisfaction after Spinal Cord Injury.}, journal = {The Journal of urology}, volume = {207}, number = {2}, pages = {392-399}, pmid = {34547924}, issn = {1527-3792}, support = {UL1 RR025764/RR/NCRR NIH HHS/United States ; UL1 TR000105/TR/NCATS NIH HHS/United States ; UL1 TR001067/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Catheters, Indwelling/*adverse effects/statistics &amp; numerical data ; Cross-Sectional Studies ; Female ; Humans ; Intermittent Urethral Catheterization/*adverse effects/psychology/statistics &amp; numerical data ; Male ; Patient Reported Outcome Measures ; Patient Satisfaction/*statistics &amp; numerical data ; Prospective Studies ; Quality of Life ; Registries ; Self Report/statistics &amp; numerical data ; Spinal Cord Injuries/*complications/therapy ; Time Factors ; Urinary Bladder/physiopathology ; Urinary Bladder, Neurogenic/etiology/psychology/*therapy ; Young Adult ; }, abstract = {PURPOSE: Increased time after spinal cord injury (SCI) is associated with a migration to bladder managements with higher morbidity such as indwelling catheter (IDC). Still, it is unclear how this affects bladder-related quality of life (QoL). We hypothesized that time from injury (TFI) would be associated with changes in bladder management, symptoms and satisfaction.<br><br>MATERIALS AND METHODS: Cross-sectional analysis of time-related changes in patient-reported bladder management, symptoms and satisfaction using the Neurogenic Bladder Research Group SCI Registry. Outcomes included Neurogenic Bladder Symptom Score (NBSS) and bladder-related satisfaction (NBSS-satisfaction). Multivariable regression was performed to assess associations between TFI and outcomes, adjusting for participant characteristics, injury specifics, and psychosocial aspects of health-related QoL. Participants with TFI <1 year were excluded and TFI was categorized 1-5 (reference), 6-10, 11-15, 16-20 and >20 years.<br><br>RESULTS: Of 1,420 participants mean age at injury was 29.7 years (SD 13.4) and mean TFI was 15.2 years (SD 11.6). Participants grouped by TFI included 298 (21%) 1-5, 340 (24%) 6-10, 198 (14%) 11-15, 149 (10%) 16-20 and 435 (31%) >20 years. As TFI increased, clean intermittent catheterization (CIC) declined (55% 1-5 vs 45% >20 years, p <0.001) and IDC increased (16% 1-5 vs 21% >20 years, p <0.001). On multivariable analysis, increased TFI was associated with fewer bladder symptoms at >20 years from injury (-3.21 [CI -1.29, -5.14, p <0.001]) and better satisfaction (6-10 years -0.20 [CI -0.41, 0.01, p=0.070], 11-15 years -0.36 [CI -0.60, -0.11, p=0.002], 16-20 years -0.59 [CI -0.86, -0.32, p <0.001], >20 years -0.85 [CI -1.07, -0.63, <0.001]).<br><br>CONCLUSIONS: After SCI, CIC decreases and IDC increases over time; however, increasing TFI is associated with reduced urinary symptoms and improved bladder-related satisfaction.}, }
@article {pmid34538726, year = {2022}, author = {Ramotar, M and Chua, MLK and Truong, H and Hosni, A and Pintilie, M and Davicioni, E and Fleshner, NE and Dicker, AP and Bristow, RG and He, HH and van der Kwast, T and Den, RB and Berlin, A}, title = {Subpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapy.}, journal = {Urologic oncology}, volume = {40}, number = {1}, pages = {5.e1-5.e13}, doi = {10.1016/j.urolonc.2021.08.013}, pmid = {34538726}, issn = {1873-2496}, mesh = {Adult ; Aged ; Cohort Studies ; Combined Modality Therapy ; Genome ; Humans ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; *Prostatectomy ; Prostatic Neoplasms/*classification/genetics/*radiotherapy/surgery ; }, abstract = {PURPOSE/OBJECTIVE: Risk-stratification for post-prostatectomy radiotherapy (PORT) using conventional clinicopathologic indexes leads to substantial over- and under-treatment. Better patient selection could spare unnecessary toxicities and improve outcomes. We investigated the prognostic utility of unfavorable subpathologies intraductal carcinoma and cribriform architecture (IDC/CA), and a 22-gene Decipher genomic classifier (GC) in prostate cancer (PCa) patients receiving PORT.<br><br>MATERIAL/METHODS: A cohort of 302 men who received PORT at 2 academic institutions was pooled. PORT was predominately delivered as salvage (62% of cases); 20% received HT+PORT. Specimens were centrally reviewed for IDC/CA presence. In 104 cases, GC scores were determined. Endpoints were biochemical relapse-free (bRFR) and metastasis-free (mFR) rates.<br><br>RESULTS: After a median follow-up of 6.49-years, 135 (45%) and 40 (13%) men experienced biochemical relapse and metastasis, respectively. IDC/CA were identified in 160 (53%) of cases. Men harboring IDC/CA experienced inferior bRFR (HR 2.6, 95%CI 1.8-3.2, P<0.001) and mFR (HR 3.1, 95%CI 1.5-6.4, P&#x202f;=&#x202f;0.0014). Patients with GC scores, 22 (21%) were stratified low-, 30 (29%) intermediate-, and 52 (50%) high-risk. GC low-risk was associated with superior bRFR (HR 0.25, 95%CI 0.1-0.5, P<0.001) and mFR (HR 0.15, 95%CI 0.03-0.8, P&#x202f;=&#x202f;0.025). On multivariable analyses, IDC/CA and GC independently predicted for bRFR, corresponding to improved discrimination (C-index&#x202f;=&#x202f;0.737 (95%CI 0.662-0.813)).<br><br>CONCLUSIONS: IDC/CA subpathologies and GC predict for biochemical relapse and metastasis beyond conventional clinicopathologic indexes in the PORT setting. Patients harboring IDC/CA are at higher risk of relapse after maximal local therapies, thus warranting consideration for treatment intensification strategies. Conversely, for men with absence of IDC/CA and low GC scores, de-intensification strategies could be explored.}, }
@article {pmid34535389, year = {2022}, author = {Lin, X and He, Y and Fu, S and Lin, S and Xue, E and Lin, L}, title = {The Ultrasonographic Characteristics of Focal Fibrocystic Change of the Breast and Analysis of Misdiagnosis.}, journal = {Clinical breast cancer}, volume = {22}, number = {3}, pages = {252-260}, doi = {10.1016/j.clbc.2021.08.004}, pmid = {34535389}, issn = {1938-0666}, mesh = {*Breast Neoplasms/diagnostic imaging/surgery ; *Calcinosis ; Capsules ; Diagnostic Errors/prevention &amp; control ; Female ; Humans ; Male ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {INTRODUCTION: To investigate ultrasonographic features and analyze causes of misdiagnosis of focal fibrocystic change (FC) of the breast.<br><br>MATERIALS AND METHODS: The ultrasonographic features of 95 women (104 lesions) with postoperatively pathologically confirmed focal FC (Group 1) were retrospectively analyzed and compared with those of 105 women (107 lesions) with ductal carcinoma in situ (DCIS) (Group 2), and 164 women (177 lesions) with invasive ductal carcinoma (IDC) (Group 3).<br><br>RESULTS: There were significant differences in 12 features among groups. The sizes and distributions of cystic changes among the groups were significantly different. In group 1, the incidence of cystic changes was 75%(78/104), and the main manifestation was scattered cystic changes (88.5%, 69/78) and microcapsules (81.8%, 63/78). Among focal FC lesions, 36.5% were preoperative BI-RADS classifications 4b-5 (30.8% 4b and 4c). Lesions misdiagnosed as malignant showed solid or cystic solid mixed echoes, and 70.2% of group 1 were irregularly shaped, and 63.5% had unclear edges. In group 1, 5 cases had "hyperechoic halo," 11.5% (12/104) appeared echo attenuation behind the mass, and 21 cases appeared punctate hyperechoic.<br><br>CONCLUSION: FC frequently exhibits low heterogeneity, scattered microcapsules with posterior enhancement, "pit-like" or "grid-like" changes, posterior enhancement, rare hyperechoic halo, calcification, and lack of blood supply. Certain focal FC are irregularly shaped with unclear edges, with malignant signs such as crab feet and burr, hyperechoic halo, and calcification, which ultrasound BI-RADS classification may easily misdiagnose as malignant. Local magnification function should be considered, and the internal structure should be carefully observed to prevent misdiagnosis.}, }
@article {pmid34528573, year = {2021}, author = {Trontzas, IP and Syrigos, NK and Kotteas, EA}, title = {A case of trastuzumab-induced dermatomyositis.}, journal = {Journal of cancer research and therapeutics}, volume = {17}, number = {4}, pages = {1112-1114}, doi = {10.4103/jcrt.JCRT_209_19}, pmid = {34528573}, issn = {1998-4138}, mesh = {Antineoplastic Agents, Immunological/*adverse effects ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Dermatomyositis/chemically induced/*pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; Trastuzumab/*adverse effects ; }, abstract = {Human epidermal growth factor receptor 2 (HER-2) is a checkpoint, controlling cell proliferation and differentiation. Trastuzumab, a humanized monoclonal antibody directed against HER-2, is nowadays standard treatment for breast cancer patients whose tumors express HER-2. It is generally well tolerated, with a small number of patients developing mild adverse reactions. Dermatomyositis is a rare adverse event of trastuzumab therapy not well described in the literature. We herein present a case of a patient treated for hormone-sensitive invasive ductal carcinoma, who presented with symptoms of proximal muscle weakness, arthralgias, skin rash, and generalized fatigue. The symptoms started after the sixth cycle of trastuzumab and progressively deteriorated. The patient's medical and family history was unremarkable. Disease progression as a possible cause of dermatomyositis had been ruled out, and laboratory evaluation revealed moderate elevation of serum muscle proteins and acute-phase reactants. Trastuzumab treatment was discontinued, and 3 months later, the patient was free of symptoms without any further intervention.}, }
@article {pmid34527961, year = {2021}, author = {Loft, A and Herzig, S and Schmidt, SF}, title = {Purification of GFP-tagged nuclei from frozen livers of INTACT mice for RNA- and ATAC-sequencing.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100805}, pmid = {34527961}, issn = {2666-1667}, mesh = {Animals ; Cell Nucleus/*chemistry/metabolism ; *Chromatin Immunoprecipitation Sequencing ; Cytological Techniques/*methods ; Female ; Green Fluorescent Proteins/*chemistry/genetics/metabolism ; Liver/chemistry/*cytology ; Male ; Mice ; *RNA-Seq ; }, abstract = {Isolation of nuclei tagged in specific cell types (INTACT) allows for stress-free and high-throughput analyses of cellular subpopulations. Here, we present an improved protocol for isolation of pure and high-quality GFP-labeled nuclei from frozen livers of INTACT mice, as well as protocols for downstream sequencing analyses. The adaptation to frozen tissue provides a pause point that allows sampling at multiple time points and/or phenotypic characterization of livers prior to nuclei isolation and downstream analyses. For complete details on the use of this protocol, please refer to Loft et al. (2021).}, }
@article {pmid34466203, year = {2021}, author = {Zingue, S and Atenguena, EO and Zingue, LL and Tueche, AB and Njamen, D and Nkoum, AB and Ndom, P}, title = {Epidemiological and clinical profile, and survival of patients followed for breast cancer between 2010 and 2015 at the Yaounde General Hospital, Cameroon.}, journal = {The Pan African medical journal}, volume = {39}, number = {}, pages = {182}, pmid = {34466203}, issn = {1937-8688}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Cameroon/epidemiology ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/pathology ; Early Detection of Cancer/methods ; Female ; Hospitals, General ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Retrospective Studies ; Risk Factors ; Survival Rate ; Young Adult ; }, abstract = {INTRODUCTION: approximately 6000 Cameroonian women died of cancer in 2018, and the breast is the most affected with 2625 new cases. The aim of this study was to establish a pattern of malignant breast tumours in Yaoundé (Cameroon).<br><br>METHODS: this study was a descriptive and analytical retrospective study of breast cancer between January 2010 and December 2015 in Yaound&#xe9; General Hospital (YGH) after the Institutional ethics committee approval. The variables studied were the socio-demographic characteristics, risk factors for breast cancer, types of tumours and type of treatments. The 5-year survival was analyzed by the Kaplan-Meier method. The adjusted hazard ratios and their 95% confidence intervals were calculated to assess the association between studied variables and patient survival through the cox regression using SPSS 23 software. The difference was considered significant at p < 0.05.<br><br>RESULTS: among the 344 files collected in this study, breast cancer patients were predominantly female (96.64%, n = 288) aged 45.39 &#xb1; 13.35 years, with invasive ductal carcinoma (68.03%, n = 270), located in the left breast (52%, n= 147). The average tumour size was ~6.5 &#xb1; 0.3 cm and diagnosed in grade II of Scarf Bloom Richardson (SBR) in 60% (n= 150) of cases. The 5-year survival was 43.3%. Factors associated with this poor survival were the religion (aHR 5.05, 95% CI: 1.57 - 16.25; p = 0.007 for animist and aHR 4.2, 95% CI: 1.53 - 11.46; p = 0.005 for protestant), location of the tumour (aHR 6.24, 95% CI: 1.58 - 24.60; p = 0.012), tumor height (aHR 0.21, 95% CI: 0.04 - 1.11; p = 0.011) and the time spent before medical treatment (aHR 5.12, 95% CI: 0.39 - 8.38; p = 0.011).<br><br>CONCLUSION: the young age, large tumour size and high histological grade in our studied population suggest a weak awareness of women about breast cancer. Action should be taken in early screening to improve the management of breast cancer in Cameroon.}, }
@article {pmid34461516, year = {2022}, author = {Meng, J and Yang, Q and Wan, W and Zhu, Q and Zeng, X}, title = {Physicochemical properties and adaptability of amine-producing Enterobacteriaceae isolated from traditional Chinese fermented fish (Suan yu).}, journal = {Food chemistry}, volume = {369}, number = {}, pages = {130885}, doi = {10.1016/j.foodchem.2021.130885}, pmid = {34461516}, issn = {1873-7072}, mesh = {Animals ; *Biogenic Amines ; China ; Enterobacter ; *Enterobacteriaceae/genetics ; Fermentation ; }, abstract = {The formation of biogenic amines (BAs) is an important potential danger in traditional fermented fish (Suan yu), and Enterobacteriaceae play an important role in the formation of BAs. The amine production abilities of 97 strains of Enterobacteriaceae screened from traditional fermented Suan yu were analyzed by reversed-phased high-performance liquid chromatography (HPLC). The genotypic diversity of amino acid decarboxylase on 23 strains of high-yield BAs was verified by PCR. Enterobacteriaceae with the highest production of amines was determined by analysis of the effects of physicochemical factors (pH, NaCl, temperature, and aerobic/anaerobic) on BA production and principal component analysis (PCA). The adaptability of the strains was examined using surimi simulation fermentation system, and the correlations among the indicators were analyzed using Cytoscape. Results showed that 97 strains of Enterobacteriaceae had strong amine-producing ability. Furthermore, 23 strains producing high yields of putrescine, cadaverine, and histamine were identified. All of the strains carried Idc, odc, speA, speB, and adiA, and five strains carried hdc. pH mainly affected the BA production of amine-producing bacteria. Three strains (Enterobacter asburiae 26C3, Klebsiella pneumoniae 47C2, and Morganella morganii 45C3) had the best amine-producing ability and used as the inoculated group. In this group, the values of BA (228.70-290.05 mg/kg) and the total volatile base nitrogen (TVB-N, 173.87-221.87 mg/100 g) exceeded the limit. Moreover, myofibrillar protein degradation was significant as indicated by the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis and decreased FAA content. Cytoscape software and principal component analysis (PCA) indicated that Enterobacteriaceae and pH were related to BA formation in Suan yu. These results provide a theoretical basis for controlling the BA of fermented fish products.}, }
@article {pmid34452576, year = {2021}, author = {Ameli, F and Ghafourina Nassab, F and Masir, N and Kahtib, F}, title = {Tumor-Derived Matrix Metalloproteinase-13 (MMP-13) Expression in Benign and Malignant Breast Lesions.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {22}, number = {8}, pages = {2603-2609}, pmid = {34452576}, issn = {2476-762X}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/enzymology/*pathology ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Matrix Metalloproteinase 13/*metabolism ; Middle Aged ; Neoplasms/enzymology/*pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).<br><br>MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.<br><br>RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.<br><br>CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.}, }
@article {pmid34449311, year = {2021}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Paravertebral block in regional anesthesia with propofol sedation reduces locoregional recurrence in patients with breast cancer receiving breast conservative surgery compared with volatile inhalational without propofol in general anesthesia.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {142}, number = {}, pages = {111991}, doi = {10.1016/j.biopha.2021.111991}, pmid = {34449311}, issn = {1950-6007}, mesh = {Adult ; Aged ; Anesthesia, Conduction/*methods ; Anesthesia, General/*methods ; Anesthetics, Inhalation/administration &amp; dosage ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Cohort Studies ; Databases, Factual ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Staging ; Nerve Block/methods ; Propofol/administration &amp; dosage ; Radiotherapy, Adjuvant/methods ; Sevoflurane/administration &amp; dosage ; Young Adult ; }, abstract = {PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving breast conservative surgery (BCS) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.<br><br>PATIENTS AND METHODS: Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).<br><br>RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.67 (0.46-0.99) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 2-3, and Her-2 positivity were 1.87 (1.03-3.42), 2.31 (1.20-4.44), 1.67 (1.09-2.56), 2.43 (1.18-4.97), 1.17 (1.03-1.19), 1.28 (1.13-2.24), 1.20 (1.05-2.22), and 1.59 (1.01-2.51), respectively, compared with those for differentiation grade I, clinical stage I, pT1, pN0, and HER-2 negativity. The aHR of LRR for adjuvant radiotherapy was 0.60 (0.38-0.97) compared with that for no adjuvant radiotherapy.<br><br>CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with INHA-GA without propofol.}, }
@article {pmid34448091, year = {2021}, author = {Jimbo, H and Horimoto, Y and Okazaki, M and Ishizuka, Y and Kido, H and Saito, M}, title = {Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {197}, pmid = {34448091}, issn = {2198-7793}, abstract = {BACKGROUND: Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.<br><br>CASE PRESENTATION: A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38&#xa0;&#xb0;C and visited the emergency outpatient clinic 3&#xa0;days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5&#xa0;mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.<br><br>CONCLUSIONS: The onset of this disease is known to usually occur within 2&#xa0;weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.}, }
@article {pmid34437555, year = {2021}, author = {Shulman, D and Shnitzer-Akuka, M and Reifen-Tagar, M}, title = {The cost of attributing moral blame: Defensiveness and resistance to change when raising awareness to animal suffering in factory farming.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0254375}, pmid = {34437555}, issn = {1932-6203}, mesh = {Diet, Vegan/ethics ; Farms/*ethics ; Female ; Food Industry/*ethics ; Humans ; Male ; Meat ; *Morals ; *Motivation ; }, abstract = {Social change campaigns often entail raising awareness of harm caused by people's behavior. For example, campaigns to reduce meat eating frequently highlight the suffering endured by animals. Such messages may simultaneously attribute moral blame to individuals for causing the harm described. Given people's motivation to protect their moral self-image, we expected that information about the suffering of animals in the meat industry presented with a blaming (versus absolving) frame would generate greater defensiveness and correspondingly resistance to change in support of veg*nism (veganism/vegetarianism). We ran three studies to test this expectation. In two studies, we found that raising awareness of animal suffering using a blaming frame increased defensiveness, leading to lower veg*n-supporting attitudes and behavioral intentions. In one study, our hypothesis was not supported, however, a mini-meta analysis across the three studies suggests the overall pattern is robust. This work expands our understanding of the role of moral self-image preservation in defensiveness and resistance to change, and has applied relevance for the development of effective communication strategies in social and moral campaigns.}, }
@article {pmid34427055, year = {2021}, author = {Morigny, P and Kaltenecker, D and Zuber, J and Machado, J and Mehr, L and Tsokanos, FF and Kuzi, H and Hermann, CD and Voelkl, M and Monogarov, G and Springfeld, C and Laurent, V and Engelmann, B and Friess, H and Zörnig, I and Krüger, A and Krijgsveld, J and Prokopchuk, O and Fisker Schmidt, S and Rohm, M and Herzig, S and Berriel Diaz, M}, title = {Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {12}, number = {5}, pages = {1333-1351}, pmid = {34427055}, issn = {2190-6009}, support = {J 4224/FWF_/Austrian Science Fund FWF/Austria ; J4224-B34/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {1-Alkyl-2-acetylglycerophosphocholine Esterase ; Animals ; Benzaldehydes ; Biomarkers ; *Cachexia/drug therapy/etiology ; Humans ; Mice ; Oximes ; *Pancreatic Neoplasms ; Prospective Studies ; }, abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour-derived and host-derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.<br><br>METHODS: Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia-inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well-established mouse models of CCx and in different cohorts of weight-stable and weight-losing cancer patients with different tumour entities. Genetic PLA2G7 knock-down in tumours and pharmacological treatment using the well-studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour-bearing mice.<br><br>RESULTS: High expression and secretion of PLA2G7 were hallmarks of cachexia-inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock-down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.<br><br>CONCLUSIONS: Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre-cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.}, }
@article {pmid34423517, year = {2021}, author = {Yun, NK and Slostad, JA and Naqib, A and Frankenberger, C and Perez, CB and Ghai, R and Usha, L}, title = {Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.}, journal = {The oncologist}, volume = {26}, number = {12}, pages = {1000-1005}, pmid = {34423517}, issn = {1549-490X}, mesh = {*Breast Neoplasms/genetics ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Precision Medicine ; Sequence Analysis, DNA ; }, abstract = {Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. Histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.}, }
@article {pmid34417460, year = {2021}, author = {Gonzalez-Rellan, MJ and Fondevila, MF and Fernandez, U and Rodríguez, A and Varela-Rey, M and Veyrat-Durebex, C and Seoane, S and Bernardo, G and Lopitz-Otsoa, F and Fernández-Ramos, D and Bilbao, J and Iglesias, C and Novoa, E and Ameneiro, C and Senra, A and Beiroa, D and Cuñarro, J and Dp Chantada-Vazquez, M and Garcia-Vence, M and Bravo, SB and Da Silva Lima, N and Porteiro, B and Carneiro, C and Vidal, A and Tovar, S and Müller, TD and Ferno, J and Guallar, D and Fidalgo, M and Sabio, G and Herzig, S and Yang, WH and Cho, JW and Martinez-Chantar, ML and Perez-Fernandez, R and López, M and Dieguez, C and Mato, JM and Millet, O and Coppari, R and Woodhoo, A and Fruhbeck, G and Nogueiras, R}, title = {O-GlcNAcylated p53 in the liver modulates hepatic glucose production.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {5068}, pmid = {34417460}, issn = {2041-1723}, mesh = {Acetylglucosamine/*metabolism ; Animals ; Base Sequence ; Caloric Restriction ; Cell Line ; Colforsin/pharmacology ; Diabetes Mellitus, Type 2/complications/metabolism ; Epinephrine/metabolism ; Glucagon/metabolism ; Glucocorticoids/metabolism ; Gluconeogenesis/drug effects ; Glucose/*metabolism ; Glycosylation ; Hepatocytes/drug effects/metabolism ; Humans ; Hydrocortisone/metabolism ; Hyperglycemia/complications/metabolism ; Insulin Resistance ; Intracellular Signaling Peptides and Proteins/metabolism ; Liver/drug effects/*metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications/metabolism ; Phosphoenolpyruvate Carboxykinase (GTP)/metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding/drug effects ; Protein Stability/drug effects ; Pyruvic Acid/metabolism ; RNA, Messenger/genetics/metabolism ; Transcription, Genetic/drug effects ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.}, }
@article {pmid34413744, year = {2021}, author = {Moghimi, M and Khodadadi, K}, title = {Dermatomyositis following Biosimilar Trastuzumab in a Breast Cancer Patient: A Case Report.}, journal = {Case reports in oncology}, volume = {14}, number = {2}, pages = {1134-1138}, pmid = {34413744}, issn = {1662-6575}, abstract = {Trastuzumab, as a recombinant IgG1 kappa, is a humanized monoclonal antibody against human epidermal growth factor receptor 2. Accordingly, it is widely used in breast cancers at early and advanced stages. Dermatomyositis is a rare adverse event of trastuzumab therapy, which is not well documented yet. In this study, a patient was treated for invasive ductal carcinoma with some symptoms of rash and generalized fatigue. These symptoms started after the fifth cycle of trastuzumab, which were gradually deteriorating. This patient's medical and family histories were unremarkable. The progression of the disease was ruled out as a possible cause of dermatomyositis, and the laboratory evaluation revealed a moderate increase in serum muscle protein (CPK). So, trastuzumab treatment was discontinued, and by passing 1 month from the start of prednisolone and hydroxychloroquine, the patient had no symptoms.}, }
@article {pmid34409828, year = {2021}, author = {Shabanov, GA and Rybchenko, AA and Lugovaya, EA and Vdovenko, SI}, title = {[Biological age estimation based on the spectral analysis of the human brain bioelectric activity.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {34}, number = {3}, pages = {466-471}, pmid = {34409828}, issn = {1561-9125}, mesh = {*Aging ; *Brain ; Cell Differentiation ; Humans ; Risk Factors ; }, abstract = {For the first time, the research work offers a method of estimating human biological age based on the spectral analysis of the brain bioelectric activity. IDC decentralization index, which could consider summary degree of reduction of the background neurotrophic influences of the brain activating system on the peripheral tissues and organs, was developed. The close to linear dependence of the IDC index on the age of healthy people aged 10-90 as well as on the oncological patients' cancer G1-G4 cells differentiation was obtained. The cell disorders and mutations in relation with the age from 10 to 90 could be seen in growth of the IDC index from 100 to 900 units. The greater amount of the cell mutations in the oncological patients with the G1-G4 differentiation resulted in the IDC index growth up to the 3 000 units and more. All the obtained data allowed estimating the real biological age after a 10-minute registration of the human brain bioelectric activity. The accuracy increased with the averaging several surveys taken from one particular person. The technology will be highly efficient for scientific researches in the field of gerontology, monitoring of healthy people, revealing of risk groups, and for controlling of the cancer patients' medical treatment.}, }
@article {pmid34401774, year = {2021}, author = {Madhavan, BK and Han, Z and Sickmann, A and Pepperkok, R and Nawroth, PP and Kumar, V}, title = {A laser-mediated photo-manipulative toolbox for generation and real-time monitoring of DNA lesions.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100700}, pmid = {34401774}, issn = {2666-1667}, mesh = {Biomechanical Phenomena/*physiology ; DNA/genetics ; DNA Breaks, Double-Stranded ; DNA Breaks, Single-Stranded ; DNA Damage/genetics ; DNA Repair/genetics/*physiology ; Kinetics ; Lasers ; Microscopy, Confocal/*methods ; }, abstract = {With the advancement of laser-based microscopy tools, it is now possible to explore mechano-kinetic processes occurring inside the cell. Here, we describe the advanced protocol for studying the DNA repair kinetics in real time using the laser to induce the DNA damage. This protocol can be used for inducing, testing, and studying the repair mechanisms associated with DNA double-strand breaks, interstrand cross-link repair, and single-strand break repair. For complete details on the use and execution of this protocol, please refer to Kumar et al. (2017, 2020).}, }
@article {pmid34396426, year = {2021}, author = {Kobayashi, H and Nakai, T and Nakanishi, Y and Esumi, M and Masuda, S}, title = {Phylogenetic analysis of combined lobular and ductal carcinoma of the breast.}, journal = {Molecular medicine reports}, volume = {24}, number = {4}, pages = {}, pmid = {34396426}, issn = {1791-3004}, mesh = {Adult ; Breast ; Breast Neoplasms/*classification/genetics/pathology ; Carcinoma, Ductal, Breast/*classification/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Carcinoma, Lobular/*classification/genetics/pathology ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Mutation ; *Phylogeny ; Polymorphism, Single Nucleotide ; }, abstract = {Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal‑lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D‑loop, digital PCR targeting of chromosomes 1q and 16q, as well as next‑generation sequencing. DNA was extracted from formalin‑fixed paraffin‑embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non‑neoplastic mammary gland and extramammary organs, using laser‑assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele‑specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.}, }
@article {pmid34392891, year = {2021}, author = {Roberts, WC and Jeong, M}, title = {Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {157}, number = {}, pages = {101-106}, doi = {10.1016/j.amjcard.2021.07.023}, pmid = {34392891}, issn = {1879-1913}, mesh = {Adult ; Aged ; Cardiomyopathies/complications/epidemiology ; Cardiomyopathy, Dilated/*complications/epidemiology ; Female ; Follow-Up Studies ; *Forecasting ; Heart Failure/epidemiology/etiology/surgery ; Heart Transplantation ; Humans ; Incidence ; Middle Aged ; Peripartum Period ; Pregnancy ; *Pregnancy Complications, Cardiovascular ; Retrospective Studies ; Texas/epidemiology ; Young Adult ; }, abstract = {Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.}, }
@article {pmid34379693, year = {2021}, author = {He, X and Anthony, DC and Catoni, Z and Cao, W}, title = {Pulmonary tumor embolism: A retrospective study over a 30-year period.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0255917}, pmid = {34379693}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Autopsy ; Breast Neoplasms/complications/diagnosis/pathology ; Carcinoma, Ductal/complications/diagnosis/pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/complications/diagnosis/*pathology ; Pulmonary Embolism/complications/*diagnosis ; Retrospective Studies ; Urinary Bladder Neoplasms/complications/diagnosis/pathology ; }, abstract = {BACKGROUND: Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.<br><br>METHODS: We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE. We also analyzed the discrepancies between antemortem clinical and postmortem diagnosis in 1999, 2009 and 2019 by using the Goldman criteria. Goldman category major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival.<br><br>RESULTS: We found 20 (3%) cases with PTE out of the 658 autopsy cases with solid malignancies. Out of these 20 cases, urothelial carcinoma (30%, 6/20) and invasive ductal carcinoma of the breast (4/20, 20%) were the most common primary malignancies. Seven patients with shortness of breath died within 3-17 days (average 8.4&#xb1;2.2 days) after onset of the symptoms. Pulmonary embolism was clinically suspected in seven out of twenty (35%, 7/20) patients before death, but only two patients (10, 2/20) were diagnosed by imaging studies before death. The rate of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019. Although the rate of Goldman category major 1 appeared decreasing, the difference was not statistically significant. The autopsy rate was significantly higher in 2019 (8.4%, 116/1386) than in 2009 (4.4%, 55/1240).<br><br>CONCLUSIONS: The incidence of PTE is uncommon. Despite the advances of the radiological techniques, radiological imaging studies did not detect the majority of PTEs. The discrepancy between the antemortem clinical and the postmortem diagnosis has not improved significantly over the past 30 years, emphasizing the value of autopsy.}, }
@article {pmid34359556, year = {2021}, author = {Zhang, JQ and Cheng, TM and Lin, WC and Chiu, KC and Wu, SY}, title = {Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study.}, journal = {Cancers}, volume = {13}, number = {15}, pages = {}, pmid = {34359556}, issn = {2072-6694}, abstract = {PURPOSE: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments.<br><br>METHODS: we recruited women with clinical stage I-III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group).<br><br>RESULTS: PSM yielded 2319 patients with stage I-III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83-1.22). The aHRs (95% CIs) of all-cause mortality for &#x2265;1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18-2.36) compared with no COPDAE.<br><br>CONCLUSION: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I-III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.}, }
@article {pmid34349234, year = {2021}, author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL}, title = {Validity of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.}, journal = {Spinal cord}, volume = {59}, number = {9}, pages = {948-958}, pmid = {34349234}, issn = {1476-5624}, support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; 90IF0121/ACL/ACL HHS/United States ; 90IF0121/ACL/ACL HHS/United States ; }, mesh = {Catheters, Indwelling ; Humans ; Psychometrics ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; }, abstract = {STUDY DESIGN: Descriptive Psychometrics Study OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), or "neurogenic bladder" is a common and disruptive condition for individuals with spinal cord injury (SCI) and disease (including multiple sclerosis, MS). Our team has developed patient-centered instruments of urinary symptoms specific to patients with NLUTD, across bladder management methods. Validity evidence is needed to support the use of two new instruments, Urinary Symptom Questionnaires for people with Neurogenic Bladder (USQNB) for those who manage their bladder with indwelling catheters (IDC), or who void (V).<br><br>SETTING: Online surveys completed by individuals in the United States with NLUTD due to either SCI or MS who manage their bladder with indwelling catheters (SCI, n&#x2009;=&#x2009;306; MS, n&#x2009;=&#x2009;8), or by voiding (SCI, n&#x2009;=&#x2009;103; MS, n&#x2009;=&#x2009;383). A total of n&#x2009;=&#x2009;381 USQNB-IDC respondents (five control groups), and 351 USQNB-V respondents (four control groups), contributed to our convergent and divergent validity evidence.<br><br>METHODS: Data were collected online to estimate key aspects of psychometric validity (content, reflection of the construct to be measured; face, recognizability of the contents as representing the construct to be measured; structural, the extent to which the instrument captures recognizable dimensions of the construct to be measured). Divergent and convergent validity evidence was derived from multiple control groups, while evidence of criterion validity was derived from attribution of each item to their experience "with a UTI".<br><br>RESULTS: Evidence of face, content, criterion, convergent, and divergent validity was compiled for each instrument.<br><br>CONCLUSIONS: The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.}, }
@article {pmid34345005, year = {2021}, author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL}, title = {Reliability of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.}, journal = {Spinal cord}, volume = {59}, number = {9}, pages = {939-947}, pmid = {34345005}, issn = {1476-5624}, support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; }, mesh = {Bayes Theorem ; Catheters, Indwelling ; Humans ; Reproducibility of Results ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; United States ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; }, abstract = {STUDY DESIGN: This is a descriptive psychometrics study.<br><br>OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), also called Neurogenic Bladder (NB), is a common and disruptive condition in a variety of neurologic diagnoses. Our team developed patient-centered instruments, Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB), specific to people with NLUTD who manage their bladders with intermittent catheterization (IC), indwelling catheters (IDC), or who void (V). This article reports evidence of reliability of the IDC and V instruments.<br><br>SETTING: Online surveys completed by individuals in the United States with NLUTD due to spinal cord injury (SCI), or multiple sclerosis (MS) who manage their bladder with IDC (SCI, n&#x2009;=&#x2009;306), or by voiding (SCI, n&#x2009;=&#x2009;103; MS, n&#x2009;=&#x2009;383).<br><br>METHODS: Reliability estimates were based on endorsement of the items on the USQNB-IDC and USQNB-V. Reliability evidence was representativeness of these symptoms for a national sample (by determining if endorsement&#x2009;>&#x2009;10%); internal consistency estimates (by Cronbach's alpha and item correlation coefficient, ICC); and interrelatedness of the items (by inferred Bayesian network, BN). We also tested whether a one-factor conceptualization of "urinary symptoms in NLUTD" was supportable for either instrument.<br><br>RESULTS: All items were endorsed by >20% of our samples. Urine quality symptoms tended to be the most commonly endorsed on both instruments. Cronbach's alpha and ICC estimates were high (>0.74), but not suggestive of redundancy. BNs showed interpretable associations among the items, and did not discover uninterpretable or unexpected associations. Neither instrument fit a one-factor model, as expected.<br><br>CONCLUSIONS: The USQNB-IDC and USQNB-V instruments show sufficient, multidimensional reliability for implementation and further study.}, }
@article {pmid34340541, year = {2021}, author = {Pickford, AK and Michel-Todó, L and Dupuy, F and Mayor, A and Alonso, PL and Lavazec, C and Cortés, A}, title = {Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans.}, journal = {mBio}, volume = {12}, number = {4}, pages = {e0163621}, pmid = {34340541}, issn = {2150-7511}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antigens, Protozoan/immunology ; *Gene Expression Profiling ; *Genetic Variation ; Host-Parasite Interactions/*genetics/immunology ; Humans ; Malaria, Falciparum/immunology/*parasitology ; Plasmodium falciparum/*genetics/immunology ; Protozoan Proteins/*genetics/immunology ; Transcriptome ; }, abstract = {Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum to fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail for only a few specific gene families. Here, we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occurred in CVGs. In particular, we observed a major increase in the transcript levels of most genes of the pfmc-2tm and gbp families and of specific genes of other families, such as phist, hyp10, rif, or stevor, in addition to previously reported changes in var and clag3 gene expression. Increased transcript levels of individual pfmc-2tm, rif, and stevor genes involved activation in small subsets of parasites. Large transcriptional differences correlated with changes in the distribution of heterochromatin, confirming their epigenetic nature. Furthermore, the similar expression of several CVGs between parasites collected at different time points along the blood infection suggests that the epigenetic memory for multiple CVG families is lost during transmission stages, resulting in a reset of their transcriptional state. Finally, the CVG expression patterns observed in a volunteer likely infected by a single sporozoite suggest that new epigenetic patterns are established during liver stages. IMPORTANCE The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites. However, how these genes are expressed under the natural conditions of the human circulation and how their expression is affected by passage through transmission stages are not well understood. Here, we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences with in vitro-cultured parasites. We also show that, during transmission stages, the previous expression patterns for many CVG families are lost, and new patterns are established.}, }
@article {pmid34336518, year = {2021}, author = {McCray, E and Naron, R and White, S and Messersmith, S and Stewart, C}, title = {Metastatic Breast Cancer Masked as Constipation.}, journal = {Cureus}, volume = {13}, number = {6}, pages = {e16031}, pmid = {34336518}, issn = {2168-8184}, abstract = {Even though screening mammography has been attributed to decreased mortality in recent decades, breast cancer is one of the leading causes of death among women in the United States. Disruption of screening protocols and variation in the presentation may alter the course of detection and management. We report a case of hormone receptor-positive breast cancer that presented as vague gastrointestinal symptoms in a patient with a delayed workup for a self-discovered breast lump during the coronavirus disease global pandemic. A 48-year-old woman with a history of gastroesophageal reflux and hypertension presented to the emergency department with primary complaints of constipation and abdominal distention with associated flatus and nausea. Vitals were within normal limits, and physical examination was notable for abdominal distention and diffuse tenderness to palpation. Labs demonstrated hypercalcemia and an unremarkable complete blood count. A chest X-ray showed a right hilar mass, and a CT chest revealed multiple lytic bone lesions diffusely scattered throughout the entire skeleton; no hilar mass was noted on the CT chest. A CT scan of the abdomen and pelvis incidentally revealed a right breast mass. A bone marrow biopsy identified invasive ductal carcinoma. Mammography and biopsy of the breast mass identified estrogen receptor/progesterone receptor-positive invasive ductal carcinoma, consistent with the bone marrow biopsy, confirming the diagnosis of metastatic breast cancer. Unpredicted disruptions in screening processes may result in delayed cancer diagnoses. This case illustrates the importance of routine self-breast examinations, screening mammography, and maintaining a broad differential diagnosis.}, }
@article {pmid34330920, year = {2021}, author = {Thomson-Luque, R and Votborg-Novél, L and Ndovie, W and Andrade, CM and Niangaly, M and Attipa, C and Lima, NF and Coulibaly, D and Doumtabe, D and Guindo, B and Tangara, B and Maiga, F and Kone, AK and Traore, K and Kayentao, K and Ongoiba, A and Doumbo, S and Thera, MA and Traoré, B and Seydel, K and Osório, NS and Portugal, S}, title = {Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4711}, pmid = {34330920}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI099628/AI/NIAID NIH HHS/United States ; }, mesh = {Blood Circulation Time ; Erythrocytes/parasitology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Bacterial ; Gene Ontology ; Genes, Bacterial/genetics ; Humans ; Malaria, Falciparum/*blood/parasitology/physiopathology ; Parasitemia/*blood/parasitology/physiopathology ; Plasmodium falciparum/*genetics/physiology ; }, abstract = {Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum's tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.}, }
@article {pmid34321100, year = {2021}, author = {Meyer, D and Kames, J and Bar, H and Komar, AA and Alexaki, A and Ibla, J and Hunt, RC and Santana-Quintero, LV and Golikov, A and DiCuccio, M and Kimchi-Sarfaty, C}, title = {Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {122}, pmid = {34321100}, issn = {1756-994X}, support = {R01 HL151392/HL/NHLBI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; *Codon ; *Codon Usage ; Computational Biology/*methods ; *Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genome-Wide Association Study ; Genomics/methods ; Humans ; Kaplan-Meier Estimate ; Neoplasms/*diagnosis/*genetics/mortality ; Prognosis ; Transcriptome ; }, abstract = {BACKGROUND: Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.<br><br>METHODS: We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.<br><br>RESULTS: We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.<br><br>CONCLUSIONS: Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.}, }
@article {pmid34320711, year = {2021}, author = {Fan, T and Wang, CQ and Li, XT and Yang, H and Zhou, J and Song, YJ}, title = {MiR-22-3p Suppresses Cell Migration and Invasion by Targeting PLAGL2 in Breast Cancer.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {31}, number = {8}, pages = {937-940}, doi = {10.29271/jcpsp.2021.08.937}, pmid = {34320711}, issn = {1681-7168}, mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; China ; DNA-Binding Proteins/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *MicroRNAs/genetics ; RNA-Binding Proteins/genetics ; Transcription Factors/genetics ; }, abstract = {OBJECTIVE: To investigate the expression of miR-22-3p in breast cancer and the mechanism of targeting PLAGL2 to inhibit the invasion and migration in human breast cancer.<br><br>STUDY DESIGN: An experimental study.<br><br>PLACE AND DURATION OF STUDY: Department of Oncology and Department of General Surgery, The People's Hospital of China Three Gorges University, China, from March 2019 to December 2020.<br><br>METHODOLOGY: The miR-22-3p expression level in 41 paired human primary breast invasive ductal carcinoma tissues and para-cancer tissues was obtained by real-time fluorescence quantitative reverse transcriptase PCR (qRT-PCR). The effect of miR-22-3p on the proliferation of breast cancer cells was detected by growth curve method. Online software TargetScan was used to predict the target genes of miR-22-3p. The prediction results were verified by luciferase reporter gene assay and qRT&#x2043;PCR.<br><br>RESULTS: MiR-22-3p expression was significantly decreased in the breast cancer tissues than in para&#x2043;carcinoma normal breast tissues (p<0.05). Over-expression of miR-22-3p can inhibit the proliferation of MCF-7 cells significantly. Pleomorphic adenoma gene-like protein 2(PLAGL2)&#xa0;is the predicted target gene of miR-22-3p. MiR-22-3p binds to its predicted target gene PLAGL2-3'UTR. The expression of miR-22-3p was negatively correlated with PLAGL2 in MCF-7 cells.<br><br>CONCLUSION: MiR-22-3p could suppress the proliferation of breast cancer by targeting PLAGL2. This suggests that miR-22-3p may be a strategy of choice for targeted therapy of breast cancer. Key Words: Breast cancer, MiR-22-3p, PLAGL2, Cell proliferation.}, }
@article {pmid34316107, year = {2021}, author = {Ramani, SK and Rastogi, A and Nair, N and Shet, TM and Thakur, MH}, title = {Hyperechoic Lesions on Breast Ultrasound: All Things Bright and Beautiful?.}, journal = {The Indian journal of radiology &amp; imaging}, volume = {31}, number = {1}, pages = {18-23}, pmid = {34316107}, issn = {0971-3026}, abstract = {Ultrasound (US) lexicon of the Breast Imaging Reporting and Data System (BI-RADS) defines an echogenic breast mass as a lesion that is hyperechoic in comparison with subcutaneous adipose tissue. However, at sonography, only 0.6 to 5.6% of breast masses are echogenic and the majority of these lesions are benign. approximately, 0.5% of malignant breast lesions appear hyperechoic. The various benign pathologic entities that appear echogenic on US are lipoma, hematoma, seroma, fat necrosis, abscess, pseudoangiomatous stromal hyperplasia, galactocele, etc. The malignant diagnoses that may present as hyperechoic lesions on breast US are invasive ductal carcinoma, invasive lobular carcinoma, metastasis, lymphoma, and angiosarcoma. Echogenic breast masses need to be correlated with mammographic findings and clinical history. Lesions with worrisome features such as a spiculated margin, interval enlargement, interval vascularity, or association with suspicious microcalcifications on mammography require biopsy. In this article, we would like to present a pictorial review of patients who presented to our department with echogenic breast masses and were subsequently found to have various malignant as well as benign etiologies on histopathology.}, }
@article {pmid34315379, year = {2021}, author = {Rafiq, MT and Hamid, MSA and Hafiz, E and Chaudhary, FA and Khan, MI}, title = {Feasibility and Acceptability of Instructions of Daily Care in Overweight and Obese Knee Osteoarthritis Participants.}, journal = {Current rheumatology reviews}, volume = {17}, number = {4}, pages = {421-427}, doi = {10.2174/1573397117666210727095552}, pmid = {34315379}, issn = {1875-6360}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Feasibility Studies ; Humans ; *Obesity/complications ; *Osteoarthritis, Knee/drug therapy/therapy ; *Overweight/complications ; Pain ; *Self Care/methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: Knee Osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of Instructions of Daily Care (IDC) on pain, mobility, and Body Mass Index (BMI) among knee OA participants who are overweight or obese.<br><br>MATERIALS AND METHODS: The study was an open-label randomized controlled trial of six weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation.<br><br>RESULTS: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05). The results of descriptive statistics showed a significantly higher satisfaction score for participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention.<br><br>CONCLUSION: The IDC is effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.}, }
@article {pmid34297787, year = {2021}, author = {Ahmed, F and Adnan, M and Malik, A and Tariq, S and Kamal, F and Ijaz, B}, title = {Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0255243}, pmid = {34297787}, issn = {1932-6203}, mesh = {Adult ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/*genetics ; Female ; Humans ; MicroRNAs/genetics/*metabolism ; Middle Aged ; Pakistan ; Smad2 Protein/genetics/metabolism ; Smad4 Protein/genetics/metabolism ; Transforming Growth Factor beta/genetics/*metabolism ; }, abstract = {Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient's data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients' biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.}, }
@article {pmid34293926, year = {2021}, author = {Chen, X and Li, X and Wang, J and Zhao, L and Peng, X and Zhang, C and Liu, K and Huang, G and Lai, Y}, title = {Breast invasive ductal carcinoma diagnosis with a three-miRNA panel in serum.}, journal = {Biomarkers in medicine}, volume = {15}, number = {12}, pages = {951-963}, doi = {10.2217/bmm-2020-0785}, pmid = {34293926}, issn = {1752-0371}, mesh = {Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/blood/diagnosis/*genetics ; Carcinoma, Ductal, Breast/blood/diagnosis/*genetics ; Cohort Studies ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; }, abstract = {Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials &amp; methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC = 0.880, sensitivity = 86.25%, specificity = 81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.}, }
@article {pmid34293708, year = {2021}, author = {Okcu, O and Öztürk, &#xc7; and Şen, B and Arpa, M and Bedir, R}, title = {Tumor Budding is a reliable predictor for death and metastasis in invasive ductal breast cancer and correlates with other prognostic clinicopathological parameters.}, journal = {Annals of diagnostic pathology}, volume = {54}, number = {}, pages = {151792}, doi = {10.1016/j.anndiagpath.2021.151792}, pmid = {34293708}, issn = {1532-8198}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/diagnosis/*mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/diagnosis/*pathology ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Prognosis ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND AND OBJECTIVE: Breast cancers are the most common type of cancer and the most common cause of mortality in women worldwide. Different prognostic factors are the subject of research to differentiate the prognosis even between cases at a similar stage and identify risky patients earlier and create individual treatment approaches. Tumor budding (TB) has been identified as a poor prognostic factor in many types of cancer, especially colorectal carcinomas. In our study, we aimed to determine the prognostic significance of the TB by evaluating the TB in line with clinicopathological parameters in breast invasive ductal carcinoma cases.<br><br>MATERIALS AND METHODS: 311 breast carcinoma cases operated in our hospital between January 2010 and April 2020 were included in the study. In hematoxylin-eosin (H&amp;E) sections of the cases, TB was evaluated in a single high-power field (HPF). ROC analysis was performed with overall survival data, and low, and high TB cutoffs were obtained. The relationship of the high TB with clinicopathological parameters was evaluated, and survival analysis was performed.<br><br>RESULTS: We determined that high TB in breast invasive ductal carcinoma cases was associated with low survival time, metastasis, axillary lymph node metastasis, angiolymphatic invasion, advanced stage (pT3), high Ki-67 proliferation index, progesterone receptor (PR) loss, and advanced age. Tumor budding was identified as an independent risk factor in overall and disease-free survival analysis.<br><br>CONCLUSION: Tumor budding is a prognostic parameter that can be easily evaluated in all centers since it does not cause additional cost to routine pathological examinations. We think it may be helpful to establish a standard methodology in evaluating tumor bud in breast carcinomas and including it in regular pathology reporting.}, }
@article {pmid34279157, year = {2021}, author = {Ren, X and Ju, Y and Wang, C and Wei, R and Sun, H and Zhang, Q}, title = {MARCKS on Tumor-Associated Macrophages is Correlated with Immune Infiltrates and Poor Prognosis in Hepatocellular Carcinoma.}, journal = {Cancer investigation}, volume = {39}, number = {9}, pages = {756-768}, doi = {10.1080/07357907.2021.1950757}, pmid = {34279157}, issn = {1532-4192}, mesh = {Biomarkers, Tumor/*genetics/metabolism ; Carcinoma, Hepatocellular/*genetics/metabolism/pathology ; Cell Line, Tumor ; Exosomes/genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/*genetics/metabolism/pathology ; MicroRNAs/genetics ; Myristoylated Alanine-Rich C Kinase Substrate/*genetics/metabolism ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; THP-1 Cells ; Tumor-Associated Macrophages/*metabolism ; }, abstract = {BACKGROUND: Hepatocellular carcinoma is the fourth most common cause of cancer-related death. However, the cross-talk between tumor immune microenvironment and hepatocellular carcinoma (HCC) remains unclear.<br><br>MATERIAL AND METHODS: We analyzed the expression of miR-143-3p in exosomes from different HCC cell lines. Differentially expressed genes (DEGs) in Tumor-associated macrophages (TAMs) co-cultured with HCC cell lines were overlapped with miR-143-3p target genes. We used the Oncomine, Kaplan-Meier plotter, and The Cancer Genome Atlas (TCGA) databases to assess Myristoylated alanine-rich C-kinase substrate (MARCKS) expression in various types of cancers. The relationship between patient clinicopathological characteristics and MARCKS expression level was identified using the Kaplan-Meier plotter database. Last, we analyzed how MARCKS expression correlated with immune infiltration makers using the TCGA database, Tumor IMmune Estimation Resource (TIMER), and Gene Expression Profiling Interactive Analysis (GEPIA).<br><br>RESULTS: Exosomal miR-143-3p was elevated after IL-6 treatment in the HCC cell line. MARCKS, a target gene of miR-143-3p, was up-regulated in Tumor-associated macrophages co-cultured with high-metastatic-potential HCC cell line. MARCKS expression was identified as significantly correlated with outcome in multiple types of cancer, especially in HCC. High MARCKS expression level was associated with poorer overall survival (OS), Progress-free survival (PFS), and also with patient gender, race, hepatitis virus background, stage, grade, AJCC_T, and vascular invasion. MARCKS was positively associated with levels of T follicular helper cells (TFH) (R&#x2009;=&#x2009;.48, p&#x2009;<&#x2009;.001), T helper type 2 (Th2) cells (R&#x2009;=&#x2009;.47, p&#x2009;<&#x2009;.001), macrophages (R&#x2009;=&#x2009;.41, p&#x2009;&#x2264;&#x2009;.001), T helper cells (R&#x2009;=&#x2009;.40, p&#x2009;<&#x2009;.001), T helper type 1 (Th1) cells (R&#x2009;=&#x2009;.38, p&#x2009;<&#x2009;.001), T cells (R&#x2009;=&#x2009;.34, p&#x2009;<&#x2009;.001), NK CD56bright cells (R&#x2009;=&#x2009;.34, p&#x2009;<&#x2009;.001) and immature DC (iDC) (R&#x2009;=&#x2009;.33, p&#x2009;<&#x2009;.001), and negatively associated with levels of T helper 17 (Th17) cells. Also, MARCKS may influence the M2 polarization and immune escape.<br><br>CONCLUSION: The present study suggests that MARCKS on TAMs is associated with poor prognosis and immune cell infiltration in HCC.}, }
@article {pmid34278746, year = {2021}, author = {Qi, H and Schmöhl, F and Li, X and Qian, X and Tabler, CT and Bennewitz, K and Sticht, C and Morgenstern, J and Fleming, T and Volk, N and Hausser, I and Heidenreich, E and Hell, R and Nawroth, PP and Kroll, J}, title = {Reduced Acrolein Detoxification in akr1a1a Zebrafish Mutants Causes Impaired Insulin Receptor Signaling and Microvascular Alterations.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {18}, pages = {e2101281}, pmid = {34278746}, issn = {2198-3844}, support = {CRC1118//Deutsche Forschungsgemeinschaft/ ; IRTG1874/2 DIAMICOM//Deutsche Forschungsgemeinschaft/ ; CSC 201806230275//China Scholarship Council/ ; 81800390//National Natural Science Foundation of China/ ; }, mesh = {Acrolein/*metabolism ; Animals ; Diabetes Mellitus, Experimental/*metabolism ; Disease Models, Animal ; Glucose/*metabolism ; Homeostasis ; Larva/metabolism ; Liver/*metabolism ; Metabolomics/methods ; Receptor, Insulin/*metabolism ; Signal Transduction ; Transcriptome ; Zebrafish/metabolism ; }, abstract = {Increased acrolein (ACR), a toxic metabolite derived from energy consumption, is associated with diabetes and its complications. However, the molecular mechanisms are mostly unknown, and a suitable animal model with internal increased ACR does not exist for in vivo studying so far. Several enzyme systems are responsible for acrolein detoxification, such as Aldehyde Dehydrogenase (ALDH), Aldo-Keto Reductase (AKR), and Glutathione S-Transferase (GST). To evaluate the function of ACR in glucose homeostasis and diabetes, akr1a1a[-/-] zebrafish mutants are generated using CRISPR/Cas9 technology. Accumulated endogenous acrolein is confirmed in akr1a1a[-/-] larvae and livers of adults. Moreover, a series of experiments are performed regarding organic alterations, the glucose homeostasis, transcriptome, and metabolomics in Tg(fli1:EGFP) zebrafish. Akr1a1a[-/-] larvae display impaired glucose homeostasis and angiogenic retina hyaloid vasculature, which are caused by reduced acrolein detoxification ability and increased internal ACR concentration. The effects of acrolein on hyaloid vasculature can be reversed by acrolein-scavenger l-carnosine treatment. In adult akr1a1a[-/-] mutants, impaired glucose tolerance accompanied by angiogenic retina vessels and glomerular basement membrane thickening, consistent with an early pathological appearance in diabetic retinopathy and nephropathy, are observed. Thus, the data strongly suggest impaired ACR detoxification and elevated ACR concentration as biomarkers and inducers for diabetes and diabetic complications.}, }
@article {pmid34272624, year = {2021}, author = {Considine, B and Adeniran, A and Hurwitz, ME}, title = {Current Understanding and Management of Intraductal Carcinoma of the Prostate.}, journal = {Current oncology reports}, volume = {23}, number = {9}, pages = {110}, pmid = {34272624}, issn = {1534-6269}, mesh = {Carcinoma, Ductal/*genetics/pathology/therapy ; DNA Mismatch Repair/*genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; *Microsatellite Instability ; *Mutation ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/pathology/therapy ; Signal Transduction/genetics ; }, abstract = {PURPOSE OF REVIEW: This review will discuss current understanding and management approaches of Intraductal carcinoma of the prostate (IDC-P). IDC-P is a histological finding characterized by neoplastic cells that expand but do not invade prostate ducts.<br><br>RECENT FINDINGS: The presence of IDC-P on a prostate biopsy is almost always associated with an invasive disease component and is independently associated with worse clinical outcomes in both early and late disease. These tumors are enriched for mutations in homologous DNA recombination repair (HRR) leading to high genomic instability. Multiparametric MRI with targeted biopsy may aid in diagnosis. Given the poor clinical outcomes associated with this histologic entity, its presence in biopsies should warrant consideration of aggressive management.}, }
@article {pmid34249415, year = {2021}, author = {Lin, Q and Chen, X and Meng, F and Ogawa, K and Li, M and Song, R and Zhang, S and Zhang, Z and Kong, X and Xu, Q and He, F and Liu, D and Bai, X and Sun, B and Hung, MC and Liu, L and Wands, JR and Dong, X}, title = {Multi-organ metastasis as destination for breast cancer cells guided by biomechanical architecture.}, journal = {American journal of cancer research}, volume = {11}, number = {6}, pages = {2537-2567}, pmid = {34249415}, issn = {2156-6976}, abstract = {A majority of breast cancer patients die of widespread aggressive multidrug-resistant tumors. Aspartate β-hydroxylase (ASPH) is an α-ketoglutarate-dependent dioxygenase and oncofetal antigen involved in embryogenesis. To illustrate if ASPH could be targeted for metastatic breast cancer, embedded and on-top three-dimensional (3-D) cultures, 3-D invasion, mammosphere formation, immunofluorescence, immunohistochemistry, Western blot, co-IP and microarray were conducted. In vitro metastasis was developed to imitate how cancer cells invade basement membrane at the primary site, transendothelially migrate, consequently colonize and outgrow at distant sites. Orthotopic and experimental pulmonary metastatic (tail vein injection) murine models were established using stable breast cancer cell lines. Cox proportional hazards regression models and Kaplan-Meier plots were applied to assess clinical outcome of breast cancer patients. In adult non-cancerous breast tissue, ASPH is undetectable. Pathologically, ASPH expression re-emerged at ductal carcinoma in situ (DCIS), and enhanced with disease progression, from early-stage invasive ductal carcinoma (IDC) to late-stage carcinoma. ASPH at moderate to high levels contribute to aggressive molecular subtypes, early relapse or more frequent progression and metastases, whereas substantially shortened overall survival and disease-free survival of breast cancer patients. Through direct physical interactions with A disintegrin and metalloproteinase domain-containing protein (ADAM)-12/ADAM-15, ASPH could activate SRC cascade, thus upregulating downstream components attributed to multifaceted metastasis. ASPH-SRC axis initiated pro-invasive invadopodium formation causing breakdown/disorganization of extracellular matrix (ECM), simultaneously potentiated epithelial-mesenchymal transition (EMT), induced cancer stem cell markers (CD44 and EpCAM), enhanced mammosphere formation and intensified 3-dimentional invasion. Oncogenic SRC upregulated matrix metallopeptidases (MMPs) were assembled by invadopodia, acting as executive effectors for multi-step metastasis. ASPH-SRC signal guided multi-organ metastases (to lungs, liver, bone, spleen, lymph nodes, mesentery or colon) in immunocompromised mice. Malignant phenotypes induced by ASPH-SRC axis were reversed by the third-generation small molecule inhibitor (SMI) specifically against β-hydroxylase activity of ASPH in pre-clinical models of metastatic breast cancer. Collectively, ASPH could activate ADAMs-SRC-MMPs cascades to promote breast cancer tumor progression and metastasis. ASPH could direct invadopodium construction as a biomechanical sensor and pro-metastatic outlet. ASPH-mediated cancer progression could be specifically/efficiently subverted by SMIs of β-hydroxylase activity. Therefore, ASPH emerges as a therapeutic target for breast cancer.}, }
@article {pmid34243714, year = {2021}, author = {Chiong, F and Wasef, MS and Liew, KC and Cowan, R and Tsai, D and Lee, YP and Croft, L and Harris, O and Gwini, SM and Athan, E}, title = {The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study.}, journal = {BMC infectious diseases}, volume = {21}, number = {1}, pages = {671}, pmid = {34243714}, issn = {1471-2334}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/mortality/surgery ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; Prospective Studies ; Pseudomonas Infections/*drug therapy/mortality/surgery ; *Pseudomonas aeruginosa ; *Referral and Consultation ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB.<br><br>METHODS: This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality.<br><br>RESULTS: A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p&#x2009;<&#x2009;0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p&#x2009;<&#x2009;0.01), undergo removal of infected catheter (27.5% vs 13.5%; p&#x2009;=&#x2009;0.049) and undergo surgical intervention (20.9% vs 5.4%, p&#x2009;=&#x2009;0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR]&#x2009;=&#x2009;10.63, p&#x2009;<&#x2009;0.001) and adjusted analysis (adjusted OR&#x2009;=&#x2009;7.84; 95% confidence interval, 2.95-20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups.<br><br>CONCLUSION: Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.}, }
@article {pmid34238275, year = {2021}, author = {Samson, J and Derlipanska, M and Zaheed, O and Dean, K}, title = {Molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {790}, pmid = {34238275}, issn = {1471-2407}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; }, abstract = {BACKGROUND: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.<br><br>METHODS: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile.<br><br>RESULTS: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in pathways involving receptor tyrosine kinases and DNA replication/cell cycle programs and in gene sets responsible for extracellular matrix organisation and ion transport.<br><br>CONCLUSIONS: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.}, }
@article {pmid34230895, year = {2021}, author = {Muthumani, K and Xu, Z and Jeong, M and Maslow, JN and Kalyanaraman, VS and Srinivasan, A}, title = {Preexisting vs. de novo antibodies against SARS-CoV-2 in individuals without or with virus infection: impact on antibody therapy, vaccine research and serological testing.}, journal = {Translational medicine communications}, volume = {6}, number = {1}, pages = {13}, pmid = {34230895}, issn = {2396-832X}, abstract = {The causative agent of the ongoing pandemic in the world is SARS-CoV-2. The research on SARS-CoV-2 has progressed with lightning speed on various fronts, including clinical research and treatment, virology, epidemiology, drug development, and vaccine research. Recent studies reported that sera from healthy individuals, who were confirmed negative for SARS-CoV-2 by RT-PCR method, tested positive for antibodies against spike and nucleocapsid proteins of SARS-CoV-2. Further, such antibodies also exhibited neutralizing activity against the virus. These observations have prompted us to prepare a commentary on this topic. While the preexisting antibodies are likely to protect against SARS-CoV-2 infection, they may also complicate serological testing results. Another unknown is the influence of preexisting antibodies on immune responses in individuals receiving vaccines against SARS-CoV-2. The commentary identifies the potential limitations with the serological tests based on spike and nucleocapsid proteins as these tests may overestimate the seroprevalence due to cross-reactive antibodies. The inclusion of tests specific to SARS-CoV-2 (such as RBD of spike protein) could overcome these limitations.}, }
@article {pmid34225099, year = {2021}, author = {Pariyar, M and Johns, A and Thorne, RF and Scott, RJ and Avery-Kiejda, KA}, title = {Copy number variation in triple negative breast cancer samples associated with lymph node metastasis.}, journal = {Neoplasia (New York, N.Y.)}, volume = {23}, number = {8}, pages = {743-753}, pmid = {34225099}, issn = {1476-5586}, mesh = {*Biomarkers, Tumor ; Chromosome Mapping ; Computational Biology/methods ; *DNA Copy Number Variations ; DNA Methylation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Ontology ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Molecular Sequence Annotation ; Neoplasm Staging ; Prognosis ; Triple Negative Breast Neoplasms/*etiology/mortality/*pathology ; }, abstract = {Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for "regulation of complement activation," "regulation of protein activation cascade," "regulation of humoral immune response," "oxytocin signalling pathway," and "TRAIL binding" pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.}, }
@article {pmid34219706, year = {2022}, author = {Avau, F and Chintinne, M and Baudry, S and Buxant, F}, title = {Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {5-13}, doi = {10.3233/BD-210001}, pmid = {34219706}, issn = {1558-1551}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*complications/drug therapy/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/complications/drug therapy/*secondary ; Carcinoma, Papillary/classification/*diagnostic imaging/drug therapy ; Humans ; Male ; Mammography ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {Intracystic papillary carcinoma (IPC) is a rare tumor with good prognosis that occurs in only 5% to 7.5% of male breast cancer. We report a case of a 46-year-old man who presented a brown nipple discharge a few months ago. He had a bilateral IPC and an invasive ductal carcinoma on the right breast. A double mastectomy was then performed with a bilateral sentinel lymph node biopsy, and he received chemotherapy, radiotherapy, and hormonotherapy. Two years after the diagnosis, the patient recovered and was free of recurrence. Considering the scarcity of this tumor type, we conducted a systematic literature review on the PubMed of all the cases of IPC in men. The clinical presentation, imaging, and treatment of the 43 case reports from the 41 articles selected were described. Furthermore, no clear guidelines for IPC management are available. Conservative surgery should also be preferred, and a sentinel lymph node biopsy should be performed systematically. Moreover, radiotherapy should be proposed in the case of conservative surgery, and hormone therapy could be proposed in the case of invasive IPC or IPC associated with a ductal carcinoma in situ.}, }
@article {pmid34204158, year = {2021}, author = {Itani, MM and Nassar, FJ and Tfayli, AH and Talhouk, RS and Chamandi, GK and Itani, ARS and Makoukji, J and Boustany, RN and Hou, L and Zgheib, NK and Nasr, RR}, title = {A Signature of Four Circulating microRNAs as Potential Biomarkers for Diagnosing Early-Stage Breast Cancer.}, journal = {International journal of molecular sciences}, volume = {22}, number = {11}, pages = {}, pmid = {34204158}, issn = {1422-0067}, support = {R. NASR Grant//Lebanese National Council for Scientific Research (CNRS-L)/ ; R NASR proposal//Medical Practice Plan, AUB/ ; R Nasr proposal//Northwestern University Kiphart award/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood/*genetics ; Breast Neoplasms/*blood/*diagnosis/genetics/pathology ; Circulating MicroRNA/*blood/*genetics ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Statistics, Nonparametric ; Young Adult ; }, abstract = {Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.}, }
@article {pmid34198053, year = {2021}, author = {Sela, Y and Bar-Or, RL and Kor, A and Lev-Ran, S}, title = {The Internet addiction test: Psychometric properties, socio-demographic risk factors and addictive co-morbidities in a large adult sample.}, journal = {Addictive behaviors}, volume = {122}, number = {}, pages = {107023}, doi = {10.1016/j.addbeh.2021.107023}, pmid = {34198053}, issn = {1873-6327}, mesh = {Adult ; *Behavior, Addictive/epidemiology ; Cross-Sectional Studies ; Humans ; Internet ; *Internet Addiction Disorder ; Prevalence ; Psychometrics ; Reproducibility of Results ; Risk Factors ; Surveys and Questionnaires ; }, abstract = {The Internet Addiction Test (IAT) (Young, 1998) is one of the most utilized diagnostic instruments to evaluate internet addiction. Despite the wide use of IAT in research and clinical settings, there is lack of an empirical validation of this scale among a largescale adult population. The present study aimed to: (1) investigate the psychometric properties of a Hebrew version of the IAT among large-scale Israeli adult sample. (2) Assess the socio-demographic characteristics of individuals who suffer from IA. (3) Assess the co-morbidity of IA in relation to substance and behavioral addictions. A cross sectional study was conducted, by constructing a representative sample (N = 4035) of the Jewish adult (18-70 y/o, M = 40.5, SD = 14.5) population in Israel. Participants responded an online survey, that measured IAT, socio-demographic characteristics, substance and behavioral addictions. Results showed that two-factor model (Emotional and Cognitive Preoccupation with the Internet and Loss of Control and Interference with Daily Life) has good psychometric properties and fits the data well. Young age, not being married (Risk Ratio [RR] = 1.98, 95% CI [1.51-2.63]), and having a low socio-economic status (RR = 1.41, 95% CI [1.05-1.90]) were found to be associated with IA. Drug (RR = 4.50, 95% CI [2.89-7.01]) and alcohol (RR = 3.54, 95% CI [1.50-5.42]) use disorders were associated with IA. High co-morbidity between behavioral addictions and IA was also found (RR = 15.24, 95% CI [11.17-20.78]). Overall, results show that the Hebrew version of the IAT is a valid and reliable instrument, and provide a comprehensive picture of IA prevalence and profile in adult Israeli sample.}, }
@article {pmid34188137, year = {2021}, author = {Mayopoulos, GA and Ein-Dor, T and Li, KG and Chan, SJ and Dekel, S}, title = {COVID-19 positivity associated with traumatic stress response to childbirth and no visitors and infant separation in the hospital.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13535}, pmid = {34188137}, issn = {2045-2322}, support = {R21 HD100817/HD/NICHD NIH HHS/United States ; R21HD100817//National Institute of Child Health and Human Development/ ; }, mesh = {Adult ; Anxiety/diagnosis ; Birth Weight ; COVID-19/diagnosis/*psychology/virology ; Female ; Hospitals ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Pain/pathology ; Parturition/*psychology ; Patient Admission/statistics &amp; numerical data ; Pregnancy ; Pregnant Women/*psychology ; SARS-CoV-2/isolation &amp; purification ; Stress Disorders, Post-Traumatic/*diagnosis ; Stress, Psychological ; Surveys and Questionnaires ; }, abstract = {As the novel coronavirus (COVID-19) has spread globally, a significant portion of pregnant and delivering women were infected with COVID-19. While emerging studies examined birth outcomes in COVID-19 positive women, knowledge of the psychological experience of childbirth and maternal wellness remains lacking. This matched-control survey-based study included a sample of women recruited during the first wave of the pandemic in the US who gave birth in the previous six months. Women reporting confirmed/suspected COVID-19 (n = 68) during pregnancy or childbirth were matched on background factors with women reporting COVID-19 negativity (n = 2,276). We found nearly 50% of COVID positive women endorsed acute traumatic stress symptoms at a clinical level in response to childbirth. This group was more than twice as likely to endorse acute stress and to have no visitors during maternity hospitalization than COVID negative women; they were also less likely to room-in with newborns. The COVID positive group reported higher levels of pain in delivery, lower newborn weights, and more infant admission to neonatal intensive care units. Our findings suggest COVID-19 affected populations are at increased risk for traumatic childbirth and associated risk for psychiatric morbidity. Attention to delivering women's wellbeing is warranted during the pandemic.}, }
@article {pmid34185954, year = {2022}, author = {Zhao, J and Sun, G and Zhu, S and Dai, J and Chen, J and Zhang, M and Ni, Y and Zhang, H and Shen, P and Zhao, X and Zhang, B and Pan, X and Nie, L and Yin, X and Liang, J and Zhang, X and Wang, Z and Zhu, X and Liao, B and Liu, Z and Armstrong, CM and Gao, AC and Huang, H and Chen, N and Zeng, H}, title = {Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate.}, journal = {BJU international}, volume = {129}, number = {3}, pages = {345-355}, doi = {10.1111/bju.15530}, pmid = {34185954}, issn = {1464-410X}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Circulating Tumor DNA/genetics ; Humans ; Male ; Phenotype ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; }, abstract = {OBJECTIVES: To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC-P).<br><br>PATIENTS AND METHODS: We performed targeted sequencing of plasma cell-free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC-P and 84 without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored.<br><br>RESULTS: We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC-P harboured genomic alterations in DNA repair pathways, respectively (P&#x2009;=&#x2009;0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carriers (11.8% [19/161] vs 2.4% [two of 84], P&#x2009;=&#x2009;0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin-dependent kinase 12 (CDK12) defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC-P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P&#x2009;=&#x2009;0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC-P proportion of &#x2265;10% vs those with an IDC-P proportion of <10% (6.4% [five of 78] vs 18.1% [15/83], P&#x2009;=&#x2009;0.045). For IDC-P carriers, tumour protein p53 (TP53) mutation was associated with shorter castration-resistant-free survival (median 10.9 vs 28.9&#x2009;months, P&#x2009;=&#x2009;0.026), and BRCA2 alteration was related to rapid prostate-specific antigen progression for those receiving abiraterone treatment (median 9.1 vs 11.9&#x2009;months, P&#x2009;=&#x2009;0.036).<br><br>CONCLUSION: Our findings provide genomic evidence explaining the aggressive phenotype of tumours with IDC-P, highlighting the potential therapeutic strategies for this patient population.}, }
@article {pmid34185678, year = {2021}, author = {Fedorov, A and Longabaugh, WJR and Pot, D and Clunie, DA and Pieper, S and Aerts, HJWL and Homeyer, A and Lewis, R and Akbarzadeh, A and Bontempi, D and Clifford, W and Herrmann, MD and Höfener, H and Octaviano, I and Osborne, C and Paquette, S and Petts, J and Punzo, D and Reyes, M and Schacherer, DP and Tian, M and White, G and Ziegler, E and Shmulevich, I and Pihl, T and Wagner, U and Farahani, K and Kikinis, R}, title = {NCI Imaging Data Commons.}, journal = {Cancer research}, volume = {81}, number = {16}, pages = {4188-4193}, pmid = {34185678}, issn = {1538-7445}, support = {P41 EB015898/EB/NIBIB NIH HHS/United States ; HHSN261201500003C/CA/NCI NIH HHS/United States ; HHSN261201000031C/CA/NCI NIH HHS/United States ; HHSN261201500001C/CA/NCI NIH HHS/United States ; HHSN261201500001G/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; P41 EB028741/EB/NIBIB NIH HHS/United States ; HHSN261201500001W/CA/NCI NIH HHS/United States ; }, mesh = {Biomedical Research/trends ; Cloud Computing ; Computational Biology/methods ; Computer Graphics ; Computer Security ; Data Interpretation, Statistical ; Databases, Factual ; Diagnostic Imaging/*methods/standards ; Humans ; Image Processing, Computer-Assisted ; *National Cancer Institute (U.S.) ; Neoplasms/*diagnostic imaging/*genetics ; Pilot Projects ; Programming Languages ; Radiology/methods/standards ; Reproducibility of Results ; Software ; United States ; User-Computer Interface ; }, abstract = {The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a national cloud-based data science infrastructure. Imaging Data Commons (IDC) is a new component of CRDC supported by the Cancer Moonshot. The goal of IDC is to enable a broad spectrum of cancer researchers, with and without imaging expertise, to easily access and explore the value of deidentified imaging data and to support integrated analyses with nonimaging data. We achieve this goal by colocating versatile imaging collections with cloud-based computing resources and data exploration, visualization, and analysis tools. The IDC pilot was released in October 2020 and is being continuously populated with radiology and histopathology collections. IDC provides access to curated imaging collections, accompanied by documentation, a user forum, and a growing number of analysis use cases that aim to demonstrate the value of a data commons framework applied to cancer imaging research. SIGNIFICANCE: This study introduces NCI Imaging Data Commons, a new repository of the NCI Cancer Research Data Commons, which will support cancer imaging research on the cloud.}, }
@article {pmid34181649, year = {2021}, author = {Aftab, F and Ahmed, I and Ahmed, S and Ali, SM and Amenga-Etego, S and Ariff, S and Bahl, R and Baqui, AH and Begum, N and Bhutta, ZA and Biemba, G and Cousens, S and Das, V and Deb, S and Dhingra, U and Dutta, A and Edmond, K and Esamai, F and Ghosh, AK and Gisore, P and Grogan, C and Hamer, DH and Herlihy, J and Hurt, L and Ilyas, M and Jehan, F and Juma, MH and Kalonji, M and Khanam, R and Kirkwood, BR and Kumar, A and Kumar, A and Kumar, V and Manu, A and Marete, I and Mehmood, U and Minckas, N and Mishra, S and Mitra, DK and Moin, MI and Muhammad, K and Newton, S and Ngaima, S and Nguwo, A and Nisar, MI and Otomba, J and Quaiyum, MA and Sarrassat, S and Sazawal, S and Semrau, KE and Shannon, C and Singh, VP and Soofi, S and Soremekun, S and Suleiman, AM and Sunday, V and Dilip, TR and Tshefu, A and Wasan, Y and Yeboah-Antwi, K and Yoshida, S and Zaidi, AK and , }, title = {Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.}, journal = {PLoS medicine}, volume = {18}, number = {6}, pages = {e1003644}, pmid = {34181649}, issn = {1549-1676}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adolescent ; Adult ; Africa South of the Sahara/epidemiology ; Asia/epidemiology ; Female ; Humans ; Infant ; *Infant Mortality ; Infant, Newborn ; *Maternal Mortality ; Pregnancy ; Pregnancy Complications/diagnosis/*mortality ; Pregnancy Outcome ; Prospective Studies ; Risk Assessment ; Risk Factors ; Stillbirth/*epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa.<br><br>METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes.<br><br>CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths.<br><br>TRIAL REGISTRATION: The study is not a clinical trial.}, }
@article {pmid34180038, year = {2021}, author = {Uomori, T and Horimoto, Y and Takanashi, M and Shikanai, A and Nakai, K and Arakawa, A and Saito, M}, title = {Cerebral hemorrhage due to amyloid angiopathy that was difficult to differentiate from breast cancer metastasis: a case report.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {150}, pmid = {34180038}, issn = {2198-7793}, abstract = {BACKGROUND: Breast cancer patients are known to develop brain metastasis at a relatively high frequency. However, imaging findings of brain metastases vary, and it is sometimes very difficult to distinguish these from other tumorous lesions and non-neoplastic lesions, such as cerebral hemorrhage. Meanwhile, there are various causes of cerebral hemorrhage; a major one is cerebral amyloid angiopathy (CAA). With the advancement of imaging technology, CAA-related cerebral hemorrhage can be more precisely diagnosed with magnetic resonance imaging (MRI), but definitive diagnosis of CAA can only be made based on pathological assessment. Herein, we report a case of consciousness disorder appearing during adjuvant therapy for breast cancer. We initially considered that the patient's cerebral hemorrhage was due to a metastatic tumor, but based on excisional biopsy, she was diagnosed with CAA.<br><br>CASE PRESENTATION: A 73-year-old Japanese woman underwent curative surgery for left breast cancer. Her disease was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma (pStage IIB). While receiving adjuvant treatment, she developed disorientation, and emergent imaging revealed multiple cerebral hemorrhages. There was no apparent enhancement in the cerebral parenchyma on MRI, and differential diagnosis included hemorrhage due to a metastatic tumor, intravascular large B-cell lymphoma, CAA and thrombotic intracranial bleeding. After hospitalization, the bleeding lesion enlarged, resulting in cerebral hernia, and she needed emergency drainage surgery. The tissue surrounding the hemorrhage was pathologically assessed, and she was diagnosed with CAA. Although we initially suspected the lesion to be a metastatic tumor from breast cancer, there were no tumorous cells.<br><br>CONCLUSION: Atypical MRI findings made diagnosis difficult in this case, but it should be considered for differential diagnosis when multiple cerebral hemorrhages in elderly patients are observed, especially in cases with symptoms such as transient multifocal neurological deficits and dementia.}, }
@article {pmid34166430, year = {2021}, author = {Nkadimeng, MV and Makombe, G and Mapiye, O and Mapiye, C and Oluwatayo, I and Dzama, K and Mojapelo, C and Mollel, N and Ngambi, J and Mautjana, MH}, title = {A gross margin analysis for Nguni cattle farmers in Limpopo Province, South Africa.}, journal = {PloS one}, volume = {16}, number = {6}, pages = {e0253657}, pmid = {34166430}, issn = {1932-6203}, mesh = {Animal Husbandry/*economics ; Animals ; Cattle ; *Farmers ; Farms/*economics ; Humans ; South Africa ; }, abstract = {Factors such as increases in population, urbanization, growth in per capita income and changes in consumer taste and preferences are causing gradual increases in livestock product consumption and demand. South Africa is addressing this predicted increase in livestock products demand by commercializing smallholder livestock producers. The Limpopo Industrial Development Corporation (IDC) Nguni Cattle Development Project is an example of such effort. The economic performance of these efforts needs to be evaluated. We use gross margin analysis to evaluate the performance of the Limpopo IDC Nguni Cattle Development Project. Additionally, we use regression analysis to identify factors influencing gross margins. Our results indicate that although smallholders show potential to commercialize, they lack commercial farming experience and require that a strong extension support system be used as one of the strategies to improve profitability. We also noted that individual farmers were more profitable than group farmers. Multiple regression analysis shows that three variables could be used to stimulate gross margin among the Limpopo IDC Nguni Cattle Development Project farmers. These are herd size, distance to market and farm size. Since farm size is a given, policy should focus on assisting farmers to build their herds and to have better access to markets.}, }
@article {pmid34142156, year = {2021}, author = {Nakamura, T and Okabe, K and Hirayama, S and Chirifu, M and Ikemizu, S and Morioka, H and Nakabeppu, Y and Yamagata, Y}, title = {Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer.}, journal = {Nucleic acids research}, volume = {49}, number = {12}, pages = {7154-7163}, pmid = {34142156}, issn = {1362-4962}, mesh = {Adenine ; Adenomatous Polyposis Coli/genetics ; Amino Acid Motifs ; Animals ; DNA/chemistry ; DNA Glycosylases/*chemistry/genetics ; DNA Repair ; DNA Replication ; Guanine/analogs &amp; derivatives ; Humans ; Mice ; Models, Molecular ; Mutation ; Proliferating Cell Nuclear Antigen/chemistry ; Zinc ; }, abstract = {Mammalian MutY homologue (MUTYH) is an adenine DNA glycosylase that excises adenine inserted opposite 8-oxoguanine (8-oxoG). The inherited variations in human MUTYH gene are known to cause MUTYH-associated polyposis (MAP), which is associated with colorectal cancer. MUTYH is involved in base excision repair (BER) with proliferating cell nuclear antigen (PCNA) in DNA replication, which is unique and critical for effective mutation-avoidance. It is also reported that MUTYH has a Zn-binding motif in a unique interdomain connector (IDC) region, which interacts with Rad9-Rad1-Hus1 complex (9-1-1) in DNA damage response, and with apurinic/apyrimidinic endonuclease 1 (APE1) in BER. However, the structural basis for the BER pathway by MUTYH and its interacting proteins is unclear. Here, we determined the crystal structures of complexes between mouse MUTYH and DNA, and between the C-terminal domain of mouse MUTYH and human PCNA. The structures elucidated the repair mechanism for the A:8-oxoG mispair including DNA replication-coupled repair process involving MUTYH and PCNA. The Zn-binding motif was revealed to comprise one histidine and three cysteine residues. The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9-1-1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function.}, }
@article {pmid34133406, year = {2021}, author = {Akhavan, AA and Wirtz, EC and Ollila, DW and Bhatt, N}, title = {An Unusual Case of BIA-ALCL Associated with Prolonged/Complicated Biocell-Textured Expander, followed by Smooth Round Breast Implant Exposure, and Concurrent Use of Adalimumab.}, journal = {Plastic and reconstructive surgery}, volume = {148}, number = {2}, pages = {299-303}, doi = {10.1097/PRS.0000000000008155}, pmid = {34133406}, issn = {1529-4242}, mesh = {Adalimumab/*adverse effects ; Breast Implantation/*adverse effects/instrumentation ; Breast Implants/*adverse effects ; Breast Neoplasms/diagnosis/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/therapy ; Chemotherapy, Adjuvant/adverse effects/methods ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/*diagnosis/etiology/surgery ; Mastectomy/adverse effects ; Middle Aged ; Surface Properties ; Tissue Expansion Devices/*adverse effects ; }, abstract = {Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a malignancy associated with textured breast implants. BIA-ALCL is typically restricted to the periprosthetic capsule, presenting as a unilateral recurrent seroma years after placement of a textured breast implant. Current estimates suggest an incidence of one in 3300 for patients with Allergan Biocell textured implants. As of February 6, 2019, U.S. Medical Device Reporting associated with BIA-ALCL showed 457 unique cases of BIA-ALCL, with 24 "unverified and potentially inaccurate" cases associated with a nontextured implant. As of February of 2019, there were 688 reported cases to date worldwide. To date, there are no published case reports of BIA-ALCL associated exclusively with smooth implants or with smooth implants after textured expanders, and there has been no reported smooth-only case in any registry, database, or journal worldwide. The authors present a case of BIA-ALCL associated with smooth round implants and textured tissue expanders. A 56-year-old woman was treated for left stage IIA invasive ductal carcinoma with bilateral mastectomies and immediate reconstruction with bilateral subpectoral textured tissue expanders. She underwent exchange to Mentor smooth-round implants, and completed adjuvant chemotherapy. Magnetic resonance imaging and examination 4.5 years after implant placement showed no abnormal findings. The patient had left breast trauma 5 years following implant placement while taking adalimumab, and developed an open wound requiring explantation. A recurrent seroma developed, and tested positive for BIA-ALCL on cytology. Surgical pathologic examination after total capsulectomy demonstrated stage IA BIA-ALCL. To the authors' knowledge, this is the first case report of BIA-ALCL in a patient with textured expanders followed by prolonged exposure to smooth round implants.}, }
@article {pmid34119440, year = {2021}, author = {Gnangnon, B and Duraisingh, MT and Buckee, CO}, title = {Deconstructing the parasite multiplication rate of Plasmodium falciparum.}, journal = {Trends in parasitology}, volume = {37}, number = {10}, pages = {922-932}, doi = {10.1016/j.pt.2021.05.001}, pmid = {34119440}, issn = {1471-5007}, mesh = {Animals ; Erythrocytes/parasitology ; Host-Parasite Interactions ; Humans ; Malaria, Falciparum/parasitology ; *Plasmodium falciparum/growth &amp; development ; *Protozoan Proteins/metabolism ; }, abstract = {Epidemiological indicators describing population-level malaria transmission dynamics are widely used to guide policy recommendations. However, the determinants of malaria outcomes within individuals are still poorly understood. This conceptual gap partly reflects the fact that there are few indicators that robustly predict the trajectory of individual infections or clinical outcomes. The parasite multiplication rate (PMR) is a widely used indicator for the Plasmodium intraerythrocytic development cycle (IDC), for example, but its relationship to clinical outcomes is complex. Here, we review its calculation and use in P. falciparum malaria research, as well as the parasite and host factors that impact it. We also provide examples of metrics that can help to link within-host dynamics to malaria clinical outcomes when used alongside the PMR.}, }
@article {pmid34117742, year = {2021}, author = {Fortunato, A and Mallo, D and Rupp, SM and King, LM and Hardman, T and Lo, JY and Hall, A and Marks, JR and Hwang, ES and Maley, CC}, title = {A new method to accurately identify single nucleotide variants using small FFPE breast samples.}, journal = {Briefings in bioinformatics}, volume = {22}, number = {6}, pages = {}, pmid = {34117742}, issn = {1477-4054}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; }, mesh = {*Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Computational Biology/*methods ; DNA, Neoplasm ; Female ; Genetic Heterogeneity ; Genetic Testing/methods/standards ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; *Polymorphism, Single Nucleotide ; Workflow ; }, abstract = {Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic pipeline to use existing variant-calling strategies to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing tools. We found that the SNV-identification accuracy declined when there was less than 40 ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ of the breast to their adjacent invasive ductal carcinoma samples. We observed an increased number of mutations (paired-samples sign test, P < 0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, P < 0.01). Our method provides a significant improvement in detecting SNVs in FFPE samples over previous approaches.}, }
@article {pmid34103599, year = {2021}, author = {Bin Kanner, Y and Ganoth, A and Tsfadia, Y}, title = {Extracellular mutation induces an allosteric effect across the membrane and hampers the activity of MRP1 (ABCC1).}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12024}, pmid = {34103599}, issn = {2045-2322}, mesh = {Allosteric Regulation ; Amino Acid Substitution ; Humans ; Multidrug Resistance-Associated Proteins/*chemistry/*genetics ; *Mutation, Missense ; Protein Domains ; Protein Structure, Secondary ; }, abstract = {Dynamic conformational changes play a major role in the function of proteins, including the ATP-Binding Cassette (ABC) transporters. Multidrug Resistance Protein 1 (MRP1) is an ABC exporter that protects cells from toxic molecules. Overexpression of MRP1 has been shown to confer Multidrug Resistance (MDR), a phenomenon in which cancer cells are capable to defend themselves against a broad variety of drugs. In this study, we used varied computational techniques to explore the unique F583A mutation that is known to essentially lock the transporter in a low-affinity solute binding state. We demonstrate how macro-scale conformational changes affect MRP1's stability and dynamics, and how these changes correspond to micro-scale structural perturbations in helices 10-11 and the nucleotide-binding domains (NBDs) of the protein in regions known to be crucial for its ATPase activity. We demonstrate how a single substitution of an outward-facing aromatic amino acid causes a long-range allosteric effect that propagates across the membrane, ranging from the extracellular ECL5 loop to the cytoplasmic NBD2 over a distance of nearly 75 Å, leaving the protein in a non-functional state, and provide the putative allosteric pathway. The identified allosteric structural pathway is not only in agreement with experimental data but enhances our mechanical understanding of MRP1, thereby facilitating the rational design of chemosensitizers toward the success of chemotherapy treatments.}, }
@article {pmid34101373, year = {2021}, author = {Icht, M and Zukerman, G and Ben-Itzchak, E and Ben-David, BM}, title = {Keep it simple: Identification of basic versus complex emotions in spoken language in individuals with autism spectrum disorder without intellectual disability: A meta-analysis study.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {14}, number = {9}, pages = {1948-1964}, doi = {10.1002/aur.2551}, pmid = {34101373}, issn = {1939-3806}, mesh = {*Autism Spectrum Disorder/complications ; Emotions ; Humans ; *Intellectual Disability/complications ; Language ; }, abstract = {Daily functioning involves identifying emotions in spoken language, a fundamental aspect of social interactions. To date, there is inconsistent evidence in the literature on whether individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) experience difficulties in identification of spoken emotions. We conducted a meta-analysis (literature search following the PRISMA guidelines), with 26 data sets (taken from 23 peer-reviewed journal articles) comparing individuals with ASD-without-ID (N = 614) and typically-developed (TD) controls (N = 640), from nine countries and in seven languages (published until February 2020). In our analyses there was no sufficient evidence to suggest that individuals with HF-ASD differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, individuals with ASD-without-ID were found to perform significantly worse than controls in identification of complex prosodic emotions (e.g., envy and boredom). The level of the semantic content of the stimuli presented (e.g., sentences vs. strings of digits) was not found to have an impact on the results. In conclusion, the difference in findings between simple and complex emotions calls for a new-look on emotion processing in ASD-without-ID. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions and target improved performance with complex emotions. LAY SUMMARY: Individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) do not differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, they were found to perform significantly worse than controls in the identification of complex prosodic emotions (e.g., envy, boredom). This was found in a meta-analysis of 26 data sets with 1254 participants from nine countries and in seven languages. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions.}, }
@article {pmid34098822, year = {2021}, author = {Maitre, T and Ok, V and Calin, R and Lassel, L and Canestri, A and Denis, M and Hamidi, M and Tavolaro, S and Verdet, C and Parrot, A and Cadranel, J and Pialoux, G}, title = {Pyogenic lung abscess in an infectious disease unit: a 20-year retrospective study.}, journal = {Therapeutic advances in respiratory disease}, volume = {15}, number = {}, pages = {17534666211003012}, pmid = {34098822}, issn = {1753-4666}, mesh = {Hospital Units ; Humans ; *Liver Abscess, Pyogenic/epidemiology/therapy ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Pyogenic lung abscesses are rare and poorly described infections. This study aimed to describe their prognostic factors.<br><br>METHODS: We retrospectively included all patients hospitalized between 1 January 1998 and 1 June 2018, with an International Classification of Diseases, version 10 (IDC-10) diagnosis of pyogenic lung abscess, from the Diamm based medical records (Micro6, Nancy, France). Parasitic, fungal, or mycobacterial lung abscesses were excluded.<br><br>RESULTS: A total of 64 patients were included. Abscesses were associated with immunosuppression in 28 patients, including HIV infection and immunosuppressive therapy for eight and 12 patients, respectively. Bacterial identification was obtained for 36 patients. Nine patients (14%) developed lung abscesses after hematogenous dissemination. They differed from bronchogenic abscesses by their younger age (p&#x2009;=&#x2009;0.03), the absence of smoking or emphysema (p&#x2009;=&#x2009;0.05), Staphylococcus aureus (p&#x2009;=&#x2009;0.001) or Streptococcus spp. (p&#x2009;=&#x2009;0.05) isolation, and the smaller size of their abscess (p&#x2009;=&#x2009;0.02). Overall, evolution was marked by radiological sequelae (46.9%), relapse (12.5%), and death (4.8%). Radiological sequelae occurred more frequently during the course of bronchogenic abscesses (p&#x2009;=&#x2009;0.02), particularly when they spontaneously discharged (p&#x2009;=&#x2009;0.04). Relapses were more frequent in patients with emphysema (p&#x2009;=&#x2009;0.04) and when Haemophilus influenzae was isolated (p&#x2009;=&#x2009;0.04). In multivariate analysis, poor outcomes, including death, sequelae, and relapse occurred more frequently in patients who had bronchogenic abscess (p&#x2009;=&#x2009;0.02), and in those who received antibiotics during less than 6&#x2009;weeks (p&#x2009;=&#x2009;0.05).<br><br>CONCLUSION: A duration of antibiotic treatment of less than 6&#x2009;weeks and bronchogenic presentation were globally associated with poor outcome of pyogenic lung abscesses. These data should be considered when proposing guidelines for the care of pyogenic lung abscesses.The reviews of this paper are available via the supplemental material section.}, }
@article {pmid34096509, year = {2021}, author = {Badak, B and Aykanat, NEB and Kacar, S and Sahinturk, V and Arik, D and Canaz, F}, title = {Effects of astaxanthin on metastasis suppressors in ductal carcinoma. A preliminary study.}, journal = {Annali italiani di chirurgia}, volume = {92}, number = {}, pages = {565-574}, pmid = {34096509}, issn = {2239-253X}, mesh = {*Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; Neoplasm Metastasis ; Xanthophylls/pharmacology ; }, abstract = {BACKGROUND: Breast cancer (BC) is a major public health problem diagnosed in more than 2 million women worldwide in 2018, causing more than 600,000 deaths. 90% of deaths due to breast cancer are caused by metastasis. Metastasis is a complex process that is divided into several steps, including separation of tumor cells from the primary tumor, invasion, cell migration, intravasation, vasculature survival, extravasation, and colonization of the secondary site. Astaxanthin (AXT) is a marine-based ketocarotenoid that has many different potential functions such as anti-oxidant, anti-inflammatory and oxidative stress-reducing properties to potentially reduce the incidence of cancer or inhibit the expansion of tumor cells. This study aims to investigate the effects of astaxanthin as a new metastasis inhibitor on T47D human invasive ductal carcinoma breast cancer cell.<br><br>MATERIAL AND METHODS: To investigate the effects of the astaxanthin as a new metastasis inhibitor on T47D cell, expression levels of anti-maspin, anti-Kai1, anti-BRMS1, and anti-MKK4 were examined by western blot. Also, we evaluated differences of these suppressors expression levels in tissue sections of 10 patients diagnosed with in situ and invasive ductal carcinoma by immunohistochemistry method.<br><br>RESULT: 250 &#x3bc;M astaxanthin increased the activation of all metastasis suppressing proteins. Also, these metastasis suppressors showed higher expression in invasive ductal carcinoma tissues than in situ ductal carcinoma patients.<br><br>CONCLUSION: We think that astaxanthin is a promising therapeutic agent for invasive ductal carcinoma patients. The effects of astaxanthin on metastasis in breast cancer should be investigated further based on these results.<br><br>KEY WORDS: Breast, cancer, metastasis.}, }
@article {pmid34083791, year = {2021}, author = {Zhao, E and Stone, MR and Ren, X and Guenthoer, J and Smythe, KS and Pulliam, T and Williams, SR and Uytingco, CR and Taylor, SEB and Nghiem, P and Bielas, JH and Gottardo, R}, title = {Spatial transcriptomics at subspot resolution with BayesSpace.}, journal = {Nature biotechnology}, volume = {39}, number = {11}, pages = {1375-1384}, pmid = {34083791}, issn = {1546-1696}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; F30 CA254168/CA/NCI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; }, mesh = {Bayes Theorem ; Cluster Analysis ; Gene Expression Profiling/methods ; Sequence Analysis, RNA/methods ; *Single-Cell Analysis/methods ; *Transcriptome/genetics ; }, abstract = {Recent spatial gene expression technologies enable comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing analysis methods do not address the limited resolution of the technology or use the spatial information efficiently. Here, we introduce BayesSpace, a fully Bayesian statistical method that uses the information from spatial neighborhoods for resolution enhancement of spatial transcriptomic data and for clustering analysis. We benchmark BayesSpace against current methods for spatial and non-spatial clustering and show that it improves identification of distinct intra-tissue transcriptional profiles from samples of the brain, melanoma, invasive ductal carcinoma and ovarian adenocarcinoma. Using immunohistochemistry and an in silico dataset constructed from scRNA-seq data, we show that BayesSpace resolves tissue structure that is not detectable at the original resolution and identifies transcriptional heterogeneity inaccessible to histological analysis. Our results illustrate BayesSpace's utility in facilitating the discovery of biological insights from spatial transcriptomic datasets.}, }
@article {pmid34062284, year = {2021}, author = {Salles, DC and Vidotto, T and Faisal, FA and Tosoian, JJ and Guedes, LB and Muranyi, A and Bai, I and Singh, S and Yan, D and Shanmugam, K and Lotan, TL}, title = {Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {23}, number = {8}, pages = {1030-1041}, pmid = {34062284}, issn = {1943-7811}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; P50 CA058236/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Biomarkers, Tumor ; Humans ; Immunohistochemistry/methods ; Kaplan-Meier Estimate ; Male ; Middle Aged ; *Molecular Diagnostic Techniques/methods/standards ; Neoplasm Grading ; Neoplasm Staging ; PTEN Phosphohydrolase/genetics/*metabolism ; Prognosis ; Prostate/metabolism/*pathology ; Prostatic Neoplasms/*diagnosis/genetics/*metabolism/mortality ; Protein Binding ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; Reproducibility of Results ; }, abstract = {This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.}, }
@article {pmid34058243, year = {2021}, author = {Hesterberg, AB and Gordetsky, JB and Hurley, PJ}, title = {Cribriform Prostate Cancer: Clinical Pathologic and Molecular Considerations.}, journal = {Urology}, volume = {155}, number = {}, pages = {47-54}, pmid = {34058243}, issn = {1527-9995}, support = {R01 CA211695/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Molecular Diagnostic Techniques ; Neoplasm Grading ; Prostatic Neoplasms/*diagnosis/*genetics/pathology ; }, abstract = {Intraductal cribriform (IDC) and invasive cribriform morphologies are associated with worse prostate cancer outcomes. Limited retrospective studies have associated IDC and cribriform morphology with germline mutations in DNA repair genes, particularly BRCA2. These findings, which prompted the National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer and Genetic/Familial High- Risk Assessment to consider germline testing for individuals with IDC/cribriform histology, have been questioned in a recent prospective study. A deepened understanding of the molecular mechanisms driving disease aggressiveness in cribriform morphology is critical to provide more clarity in clinical decision making. This review summarizes the current understanding of IDC and cribriform prostate cancer, with an emphasis on clinical outcomes and molecular alterations.}, }
@article {pmid34048471, year = {2021}, author = {Brock, EJ and Jackson, RM and Boerner, JL and Li, Q and Tennis, MA and Sloane, BF and Mattingly, RR}, title = {Sprouty4 negatively regulates ERK/MAPK signaling and the transition from in situ to invasive breast ductal carcinoma.}, journal = {PloS one}, volume = {16}, number = {5}, pages = {e0252314}, pmid = {34048471}, issn = {1932-6203}, support = {F31 CA213807/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R25 GM058905/GM/NIGMS NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism ; Cell Line, Tumor ; Cells, Cultured ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mitogen-Activated Protein Kinase 1/genetics/*metabolism ; Mitogen-Activated Protein Kinase 3/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; }, abstract = {Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Patients often receive surgery and radiotherapy, but this early intervention has not produced substantial decreases in late-stage disease. Sprouty proteins are important regulators of ERK/MAPK signaling and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry, we found reduced Sprouty4 expression in IDC patient samples compared to DCIS, and that ERK/MAPK phosphorylation had an inverse relationship to Sprouty4 expression. These observations were reproduced using a 3D culture model of disease progression. Knockdown of Sprouty4 in MCF10.DCIS cells increased ERK/MAPK phosphorylation as well as their invasive capability, while overexpression of Sprouty4 in MCF10.CA1d IDC cells reduced ERK/MAPK phosphorylation, invasion, and the aggressive phenotype exhibited by these cells. Immunofluorescence experiments revealed reorganization of the actin cytoskeleton and relocation of E-cadherin back to the cell surface, consistent with the restoration of adherens junctions. To determine whether these effects were due to changes in ERK/MAPK signaling, MEK1/2 was pharmacologically inhibited in IDC cells. Nanomolar concentrations of MEK162/binimetinib restored an epithelial-like phenotype and reduced pericellular proteolysis, similar to Sprouty4 overexpression. From these data we conclude that Sprouty4 acts to control ERK/MAPK signaling in DCIS, thus limiting the progression of these premalignant breast lesions.}, }
@article {pmid34044580, year = {2021}, author = {Markus, HS and Egle, M and Croall, ID and Sari, H and Khan, U and Hassan, A and Harkness, K and MacKinnon, A and O'Brien, JT and Morris, RG and Barrick, TR and Blamire, AM and Tozer, DJ and Ford, GA and , }, title = {PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease.}, journal = {Stroke}, volume = {52}, number = {8}, pages = {2484-2493}, doi = {10.1161/STROKEAHA.120.032054}, pmid = {34044580}, issn = {1524-4628}, mesh = {Aged ; Antihypertensive Agents/*therapeutic use ; Blood Pressure ; Cerebral Small Vessel Diseases/complications/*diagnostic imaging/physiopathology ; *Cognition ; Diffusion Tensor Imaging ; Disease Progression ; Female ; Humans ; Hypertension/complications/*drug therapy/physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; *Patient Care Planning ; Stroke, Lacunar/complications/*diagnostic imaging/physiopathology ; White Matter/*diagnostic imaging ; }, abstract = {[Figure: see text].}, }
@article {pmid34031394, year = {2021}, author = {Amit, I and Iancu, O and Levy-Jurgenson, A and Kurgan, G and McNeill, MS and Rettig, GR and Allen, D and Breier, D and Ben Haim, N and Wang, Y and Anavy, L and Hendel, A and Yakhini, Z}, title = {CRISPECTOR provides accurate estimation of genome editing translocation and off-target activity from comparative NGS data.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3042}, pmid = {34031394}, issn = {2041-1723}, mesh = {Algorithms ; *CRISPR-Cas Systems ; Computational Biology/*methods ; DNA-Binding Proteins/genetics ; Gene Editing/*methods ; HEK293 Cells ; Homeodomain Proteins/genetics ; Humans ; Nuclear Proteins/genetics ; Software ; Transcription Factors/genetics ; }, abstract = {Controlling off-target editing activity is one of the central challenges in making CRISPR technology accurate and applicable in medical practice. Current algorithms for analyzing off-target activity do not provide statistical quantification, are not sufficiently sensitive in separating signal from noise in experiments with low editing rates, and do not address the detection of translocations. Here we present CRISPECTOR, a software tool that supports the detection and quantification of on- and off-target genome-editing activity from NGS data using paired treatment/control CRISPR experiments. In particular, CRISPECTOR facilitates the statistical analysis of NGS data from multiplex-PCR comparative experiments to detect and quantify adverse translocation events. We validate the observed results and show independent evidence of the occurrence of translocations in human cell lines, after genome editing. Our methodology is based on a statistical model comparison approach leading to better false-negative rates in sites with weak yet significant off-target activity.}, }
@article {pmid34022480, year = {2021}, author = {Hoshina, H and Takei, H and Nakamura, M and Nishimoto, F and Hanamura, S}, title = {Carcinomatous cirrhosis as radiographically occult liver metastases of breast cancer: A systematic literature review.}, journal = {Cancer treatment and research communications}, volume = {28}, number = {}, pages = {100388}, doi = {10.1016/j.ctarc.2021.100388}, pmid = {34022480}, issn = {2468-2942}, mesh = {Ascites/*diagnosis/etiology ; Breast Neoplasms/*pathology ; Female ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Liver Neoplasms/complications/*diagnosis/secondary ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; }, abstract = {In the present study, we aimed to clarify features of carcinomatous cirrhosis from breast cancer presenting as refractory transudate ascites and acute liver failure. In our systematic literature review, we identified 26 studies and 31 cases including our case of this rare condition. Our patient was a 49-year-old woman with a history of ascites and liver failure for the past 4 years and currently being treated for invasive ductal breast cancer. On radiography, she had occult liver metastases that were confirmed using laparoscopic liver biopsy. In the 31 cases, data on the reported year, age, type of primary breast cancer, time from breast cancer diagnosis, presence of ascites and/or varices, liver biopsy, diagnostic modalities, outcomes, and survival were documented and analyzed. All cases were reported during 1984-2020, with a mean patient age of 52.9 years. Eighteen patients (58.1%) were diagnosed with ductal breast cancer. Twenty-two patients (70.9%) had ascites. All patients had gradual progression to liver dysfunction. The following tests were performed: computed tomography (77.4%); ultrasound (58.0%); liver biopsy (100%); postmortem biopsy (35.5%), transjugular liver biopsy (32.3%), and laparoscopic liver biopsy (3.2%). Outcomes were reported for 29 patients, of whom 24 (82.3%) died after 1 day to 16 months. Invasive ductal carcinoma was the most common histological type; however, invasive lobular carcinoma was more frequent (32.3%) than its reported incidence in the breast. Carcinomatous cirrhosis has poor prognosis at relatively rash and is difficult to diagnose with usual modalities. It may be associated with E-cadherin loss or CD44 pronouncement.}, }
@article {pmid34016966, year = {2021}, author = {Georgiadi, A and Lopez-Salazar, V and Merahbi, RE and Karikari, RA and Ma, X and Mourão, A and Klepac, K and Bühler, L and Alfaro, AJ and Kaczmarek, I and Linford, A and Bosma, M and Shilkova, O and Ritvos, O and Nakamura, N and Hirose, S and Lassi, M and Teperino, R and Machado, J and Scheideler, M and Dietrich, A and Geerlof, A and Feuchtinger, A and Blutke, A and Fischer, K and Müller, TD and Kessler, K and Schöneberg, T and Thor, D and Hornemann, S and Kruse, M and Nawroth, P and Pivovarova-Ramich, O and Pfeiffer, AFH and Sattler, M and Blüher, M and Herzig, S}, title = {Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2999}, pmid = {34016966}, issn = {2041-1723}, mesh = {3T3-L1 Cells ; Adipocytes/metabolism ; Adipose Tissue, White/cytology/*metabolism ; Adolescent ; Adult ; Aged ; Animals ; CHO Cells ; Cohort Studies ; Cricetulus ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood/metabolism/prevention &amp; control ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Female ; Gene Knockdown Techniques ; Glucose/metabolism ; HEK293 Cells ; Hep G2 Cells ; Humans ; Insulin/metabolism ; Insulin Resistance ; Islets of Langerhans/metabolism ; Liver/metabolism ; Male ; Membrane Proteins/administration &amp; dosage/blood/genetics/*metabolism ; Mice ; Mice, Knockout ; Middle Aged ; NIH 3T3 Cells ; Prediabetic State/blood/drug therapy/etiology/*metabolism ; Primary Cell Culture ; Proteins/analysis/*metabolism ; Receptors, G-Protein-Coupled/blood/genetics/*metabolism ; Recombinant Fusion Proteins/administration &amp; dosage/genetics/isolation &amp; purification ; Young Adult ; }, abstract = {The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.}, }
@article {pmid34016957, year = {2021}, author = {Egea, V and Kessenbrock, K and Lawson, D and Bartelt, A and Weber, C and Ries, C}, title = {Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release.}, journal = {Cell death &amp; disease}, volume = {12}, number = {6}, pages = {516}, pmid = {34016957}, issn = {2041-4889}, mesh = {Animals ; Cell Communication/physiology ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Chemokine CXCL12/*metabolism ; Disease Models, Animal ; Female ; Humans ; Mammary Neoplasms, Experimental/genetics/*metabolism/pathology ; Mesenchymal Stem Cells/*metabolism/pathology ; Mice ; Mice, Inbred BALB C ; MicroRNAs/biosynthesis/*genetics ; Transfection ; Tumor Hypoxia/*physiology ; }, abstract = {Bone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.}, }
@article {pmid34015750, year = {2021}, author = {de Araújo, RA and Cordero da Luz, FA and da Costa Marinho, E and Mendes, TR and Nascimento, CP and Ribeiro Delfino, PF and Antonioli, RM and Ruas, AC and Alves, AR and Araújo, BJ and de Paula Machado, JP and Guedes Pereira, TO and França do Espírito Santo, M and Barbosa Silva, MJ}, title = {Operable breast cancer: How not to worsen the prognosis, especially in triple negative and stage II tumors.}, journal = {Surgical oncology}, volume = {38}, number = {}, pages = {101596}, doi = {10.1016/j.suronc.2021.101596}, pmid = {34015750}, issn = {1879-3320}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; *Margins of Excision ; Mastectomy/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*surgery ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/pathology/*surgery ; }, abstract = {INTRODUCTION: Oncological surgery must follow some fundamental principles to be truly curative, one of which is the resection of the tumor with surgical margins free of neoplasia. In breast cancer, surgery with positive margins should be expanded immediately. There are probably different intensities, between the stages and molecular subtypes of operable breast cancer, of worsening prognosis due to the surgical margin compromised by the neoplasia in women not submitted to the necessary enlargement of the positive surgical margin. MATERIALS AND.<br><br>METHODS: Seven hundred and forty-seven women with invasive ductal carcinoma of the breast, analyzing anatomical-pathological information, types of surgery, molecular subtypes, and the presence or absence of the surgical margin compromised by neoplasia.<br><br>RESULTS: Sixty-one (8.2%) patients had positive surgical margin, causing 2.85 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis. In subgroup analysis, among stages I, II and III, stage II was the most negatively impacted, with those patients presenting 2.42 times more risk of distant metastasis and 4.94 times more risk of locoregional relapses compared to negative surgical margin by multivariate analysis. Among the molecular subtypes, Triple Negative tumors with a positive surgical margin had 3.56 times more risk of death, 4.98 times more risk of distant metastasis and 5.55 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis.<br><br>CONCLUSIONS: The positive surgical margin, especially in Stage II and Triple-Negative breast cancer patients negatively impact the patient's evolution, increasing risk of distant metastasis and death.}, }
@article {pmid34014371, year = {2021}, author = {Giroud, M and Tsokanos, FF and Caratti, G and Kotschi, S and Khani, S and Jouffe, C and Vogl, ES and Irmler, M and Glantschnig, C and Gil-Lozano, M and Hass, D and Khan, AA and Garcia, MR and Mattijssen, F and Maida, A and Tews, D and Fischer-Posovszky, P and Feuchtinger, A and Virtanen, KA and Beckers, J and Wabitsch, M and Uhlenhaut, H and Blüher, M and Tuckermann, J and Scheideler, M and Bartelt, A and Herzig, S}, title = {HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling.}, journal = {Diabetologia}, volume = {64}, number = {8}, pages = {1850-1865}, pmid = {34014371}, issn = {1432-0428}, mesh = {Adipocytes/*metabolism ; Adipogenesis/physiology ; Adipose Tissue, Brown/metabolism ; Adult ; Aged ; Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cross-Sectional Studies ; Female ; Gene Expression Regulation/*physiology ; Gene Silencing ; Glucocorticoids/*pharmacology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Obesity/*genetics ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transcription Factors/*genetics ; Young Adult ; }, abstract = {AIMS/HYPOTHESIS: Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we investigate the role of heart and neural crest derivatives-expressed 2 (HAND2) in adipogenesis.<br><br>METHODS: Human white adipose tissue (WAT) was collected from two cross-sectional studies of 318 and 96 individuals. In vitro, for mechanistic experiments we used primary adipocytes from humans and mice as well as human multipotent adipose-derived stem (hMADS) cells. Gene silencing was performed using siRNA or genetic inactivation in primary adipocytes from loxP and or tamoxifen-inducible Cre-ERT2 mouse models with Cre-encoding mRNA or tamoxifen, respectively. Adipogenesis and adipocyte metabolism were measured by Oil Red O staining, quantitative PCR (qPCR), microarray, glucose uptake assay, western blot and lipolysis assay. A combinatorial RNA sequencing (RNAseq) and ChIP qPCR approach was used to identify target genes regulated by HAND2. In vivo, we created a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter (Hand2[AdipoqCre]) and performed a large panel of metabolic tests.<br><br>RESULTS: We found that HAND2 is an obesity-linked white adipocyte transcription factor regulated by glucocorticoids that was necessary but insufficient for adipocyte differentiation in vitro. In a large cohort of humans, WAT HAND2 expression was correlated to BMI. The HAND2 gene was enriched in white adipocytes compared with brown, induced early in differentiation and responded to dexamethasone (DEX), a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in hMADS cells or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by glucocorticoids via GR in vitro and in vivo. Furthermore, we identified gene clusters indirectly regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that HAND2 was required at stages prior to Adipoq expression.<br><br>CONCLUSIONS/INTERPRETATION: In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in humans and mice.<br><br>DATA AVAILABILITY: Array data have been submitted to the GEO database at NCBI (GSE148699).}, }
@article {pmid34011405, year = {2021}, author = {Dinca, SC and Greiner, D and Weidenfeld, K and Bond, L and Barkan, D and Jorcyk, CL}, title = {Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment.}, journal = {Breast cancer research : BCR}, volume = {23}, number = {1}, pages = {56}, pmid = {34011405}, issn = {1465-542X}, support = {R25 GM123927/GM/NIGMS NIH HHS/United States ; 1C06RR020533/GM/NIGMS NIH HHS/United States ; P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; 0619737//National Science Foundation/ ; 0923535//National Science Foundation/ ; AR298//Smylie Family Cancer Fund (US)/ ; 2017237//United States - Israel Binational Science Foundation/ ; }, mesh = {Amino Acid Oxidoreductases/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Collagen Type I/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Matrix/*metabolism ; Female ; Glycosylation ; Humans ; Inflammation ; Neoplasm Metastasis ; Oncostatin M/genetics/*metabolism/pharmacology ; Oncostatin M Receptor beta Subunit/genetics/metabolism ; Prognosis ; Signal Transduction ; Tumor Microenvironment ; Up-Regulation/genetics ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is a serious problem for patients as it metastasizes, decreasing 5-year patient survival from > 95 to ~ 27%. The breast tumor microenvironment (TME) is often saturated with proinflammatory cytokines, such as oncostatin M (OSM), which promote epithelial-to-mesenchymal transitions (EMT) in IDC and increased metastasis. The extracellular matrix (ECM) also plays an important role in promoting invasive and metastatic potential of IDC. Specifically, the reorganization and alignment of collagen fibers in stromal ECM leads to directed tumor cell motility, which promotes metastasis. Lysyl oxidase like-2 (LOXL2) catalyzes ECM remodeling by crosslinking of collagen I in the ECM. We propose a novel mechanism whereby OSM induces LOXL2 expression, mediating stromal ECM remodeling of the breast TME.<br><br>METHODS: Bioinformatics was utilized to determine survival and gene correlation in patients. IDC cell lines were treated with OSM (also IL-6, LIF, and IL-1&#x3b2;) and analyzed for LOXL2 expression by qRT-PCR and immunolabelling techniques. Collagen I contraction assays, 3D invasion assays, and confocal microscopy were performed with and without LOXL2 inhibition to determine the impact of OSM-induced LOXL2 on the ECM.<br><br>RESULTS: Our studies demonstrate that IDC patients with high LOXL2 and OSM co-expression had worse rates of metastasis-free survival than those with high levels of either, individually, and LOXL2 expression is positively correlated to OSM/OSM receptor (OSMR) expression in IDC patients. Furthermore, human IDC cells treated with OSM resulted in a significant increase in LOXL2 mRNA, which led to upregulated protein expression of secreted, glycosylated, and enzymatically active LOXL2. The expression of LOXL2 in IDC cells did not affect OSM-promoted EMT, and LOXL2 was localized to the cytoplasm and/or secreted. OSM-induced LOXL2 promoted an increase in ECM collagen I fiber crosslinking, which led to significant fiber alignment between cells and increased IDC cell invasion.<br><br>CONCLUSIONS: Aligned collagen fibers in the ECM provide pathways for tumor cells to migrate more easily through the stroma to nearby vasculature and tissue. These results provide a new paradigm through which proinflammatory cytokine OSM promotes tumor progression. Understanding the nuances in IDC metastasis will lead to better potential therapeutics to combat against the possibility.}, }
@article {pmid34009452, year = {2021}, author = {Kusafuka, K and Ito, I and Hirata, K and Miyamoto, K and Shimizu, T and Satomi, H and Inagaki, H and Suzuki, M}, title = {A rare case of high-grade intraductal carcinoma of the upper lip: immunohistochemical and genetic analyses.}, journal = {Medical molecular morphology}, volume = {54}, number = {3}, pages = {281-288}, pmid = {34009452}, issn = {1860-1499}, mesh = {Asian People ; Biomarkers, Tumor/analysis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/surgery ; ErbB Receptors/analysis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Japan ; Keratin-19/analysis/genetics ; Keratin-5/analysis/genetics ; Keratin-6/analysis/genetics ; Lip/surgery ; Lip Neoplasms/*diagnosis/metabolism/surgery ; Middle Aged ; Receptors, Androgen/analysis/genetics ; SOXE Transcription Factors/analysis/genetics ; }, abstract = {Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.}, }
@article {pmid34002584, year = {2021}, author = {Lei, S and Zheng, R and Zhang, S and Chen, R and Wang, S and Sun, K and Zeng, H and Wei, W and He, J}, title = {Breast cancer incidence and mortality in women in China: temporal trends and projections to 2030.}, journal = {Cancer biology &amp; medicine}, volume = {18}, number = {3}, pages = {900-909}, pmid = {34002584}, issn = {2095-3941}, support = {2018-I2M-3-003//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 2018YFC1315305//National Key Research and Development Program of China/ ; }, abstract = {OBJECTIVE: Breast cancer was the most common cancer and the fifth cause of cancer deaths among women in China in 2015. The evaluation of the long-term incidence and mortality trends and the prediction of the future burden of breast cancer could provide valuable information for developing prevention and control strategies.<br><br>METHODS: The burden of breast cancer in China in 2015 was estimated by using qualified data from 368 cancer registries from the National Central Cancer Registry. Incident cases and deaths in 22 cancer registries were used to assess the time trends from 2000 to 2015. A Bayesian age-period-cohort model was used to project the burden of breast cancer to 2030.<br><br>RESULTS: Approximately 303,600 new cases of breast cancer (205,100 from urban areas and 98,500 from rural areas) and 70,400 breast cancer deaths (45,100 from urban areas and 24,500 from rural areas) occurred in China in 2015. Urban regions of China had the highest incidence and mortality rates. The most common histological subtype of breast cancer was invasive ductal carcinoma, followed by invasive lobular carcinoma. The age-standardized incidence and mortality rates increased by 3.3% and 1.0% per year during 2000-2015, and were projected to increase by more than 11% until 2030. Changes in risk and demographic factors between 2015 and 2030 in cases are predicted to increase by approximately 13.3% and 22.9%, whereas deaths are predicted to increase by 13.1% and 40.9%, respectively.<br><br>CONCLUSIONS: The incidence and mortality of breast cancer continue to increase in China. There are no signs that this trend will stop by 2030, particularly in rural areas. Effective breast cancer prevention strategies are therefore urgently needed in China.}, }
@article {pmid34001921, year = {2021}, author = {Hosio, M and Urpilainen, E and Hautakoski, A and Marttila, M and Arffman, M and Sund, R and Ahtikoski, A and Puistola, U and Läärä, E and Karihtala, P and Jukkola, A}, title = {Association of antidiabetic medication and statins with survival from ductal and lobular breast carcinoma in women with type 2 diabetes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {10445}, pmid = {34001921}, issn = {2045-2322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/complications/*mortality/therapy ; Carcinoma, Ductal, Breast/complications/*mortality/therapy ; Carcinoma, Lobular/complications/*mortality/therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Female ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Hypoglycemic Agents/*therapeutic use ; Middle Aged ; Prognosis ; Registries/statistics &amp; numerical data ; Survival Analysis ; }, abstract = {We investigated the survival of female patients with pre-existing type 2 diabetes (T2D) diagnosed with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of breast, in relation to the use of metformin, other antidiabetic medication (ADM) and statins. The study cohort consisted of 3,165 women (2,604 with IDC and 561 with ILC). The cumulative mortality from breast cancer (BC) and from other causes was calculated using the Aalen-Johansen estimator. The cause-specific mortality rates were analysed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of different medications. No evidence of an association of metformin use with BC mortality was observed in either IDC (HR 0.92, 95% confidence interval [CI] 0.64-1.31) or ILC (HR 0.68, 95% CI 0.32-1.46) patients, when compared to other oral ADMs. The mortality from other causes was found to be lower amongst the IDC patients using metformin (HR 0.64, 95% CI 0.45-0.89), but amongst ILC patients the evidence was inconclusive (HR 1.22, 95% CI 0.64-2.32). Statin use was consistently associated with reduced mortality from BC in IDC patients (HR 0.77, 95% CI 0.62-0.96) and ILC patients (HR 0.59, 95% CI 0.37-0.96), and also mortality from other causes in IDC patients (HR 0.81, 95% CI 0.67-0.96) and in ILC patients (HR 0.66, 95% CI 0.43-1.01). We found no sufficient evidence for the possible effects of metformin and statins on the prognosis of BC being different in the two histological subtypes.}, }
@article {pmid33983449, year = {2022}, author = {March, DS and Lai, KB and Neal, T and Graham-Brown, MPM and Highton, PJ and Churchward, DR and Young, HML and Dungey, M and Stensel, DJ and Smith, AC and Bishop, NC and Szeto, CC and Burton, JO}, title = {Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {37}, number = {2}, pages = {366-374}, doi = {10.1093/ndt/gfab178}, pmid = {33983449}, issn = {1460-2385}, mesh = {*Endotoxins ; Exercise ; Humans ; Inflammation/etiology ; Physical Fitness ; *Renal Dialysis/adverse effects ; }, abstract = {BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes.<br><br>METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n&#x2009;=&#x2009;46) or usual care only (control group; n&#x2009;=&#x2009;46). Outcome measures were obtained at baseline and then again at 6 months.<br><br>RESULTS: There was no significant (P&#x2009;=&#x2009;0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34&#x2009;&#xb1;&#x2009;0.08 EU/mL; control group: 0.37&#x2009;&#xb1;&#x2009;0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio.<br><br>CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.}, }
@article {pmid33966256, year = {2021}, author = {Tsokanos, FF and Muley, C and Khani, S and Hass, D and Fleming, T and Wolff, G and Bartelt, A and Nawroth, P and Herzig, S}, title = {Methylglyoxal Drives a Distinct, Nonclassical Macrophage Activation Status.}, journal = {Thrombosis and haemostasis}, volume = {121}, number = {11}, pages = {1464-1475}, doi = {10.1055/s-0041-1726346}, pmid = {33966256}, issn = {2567-689X}, support = {Deutsche Forschungsgemeinschaft//SFB1118/ ; }, mesh = {Animals ; Cells, Cultured ; Gene Expression Profiling ; Glycolysis/*drug effects ; Macrophage Activation/*drug effects ; Macrophages/*drug effects/immunology/metabolism ; Mice ; Phenotype ; Phosphorylation ; Pyruvaldehyde/*toxicity ; Signal Transduction ; Transcriptome ; p38 Mitogen-Activated Protein Kinases/metabolism ; }, abstract = {Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.}, }
@article {pmid33960872, year = {2021}, author = {Alvarez, DR and Ospina, A and Barwell, T and Zheng, B and Dey, A and Li, C and Basu, S and Shi, X and Kadri, S and Chakrabarti, K}, title = {The RNA structurome in the asexual blood stages of malaria pathogen plasmodium falciparum.}, journal = {RNA biology}, volume = {18}, number = {12}, pages = {2480-2497}, pmid = {33960872}, issn = {1555-8584}, mesh = {Erythrocytes/*metabolism ; *Gene Expression Regulation ; Humans ; *Life Cycle Stages ; Malaria, Falciparum/*parasitology ; *Nucleic Acid Conformation ; Plasmodium falciparum/*genetics/growth &amp; development/pathogenicity ; Protozoan Proteins/genetics/metabolism ; RNA, Protozoan/*chemistry ; Transcriptome ; }, abstract = {Plasmodium falciparum is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and non-coding transcripts from the asexual developmental cycle in P. falciparum in human red blood cells. Our comprehensive analysis that combined high-throughput nuclease mapping of RNA structures by duplex RNA-seq, SHAPE-directed RNA structure validation, immunoaffinity purification and characterization of antisense RNAs collectively measured differentially base-paired RNA regions throughout the parasite's asexual RBC cycle. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, approximately 71% of the genes with secondary structures are found to be protein coding mRNAs. The mapping pattern of these base-paired RNAs corresponded to all regions of mRNAs, including the 5' UTR, CDS and 3' UTR as well as the start and stop codons. Histone family genes which are known to form secondary structures in their mRNAs and transcripts from genes which are important for transcriptional and post-transcriptional control, such as the unique plant-like transcription factor family, ApiAP2, DNA-/RNA-binding protein, Alba3 and proteins important for RBC invasion and malaria cytoadherence also showed strong accumulation of duplex RNA reads in various asexual stages in P. falciparum. Intriguingly, our study determined stage-specific, dynamic relationships between mRNA structural contents and translation efficiency in P. falciparum asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs. Abbreviations: CDS: Coding Sequence; DNA: Deoxyribonucleic Acid; dsRNA: double-stranded RNA; IDC: Intra-erythrocytic Developmental Cycle (IDC); m6A: N6-methyladenosine; mRNA: Messenger RNA; ncRNA: Non-coding RNA; RBC: Red Blood cells; RBP: RNA-Binding Protein; REC: Relative Expression Counts; RNA-seq: RNA-sequencing; RNA: Ribonucleic Acid; RNP: Ribonucleoprotein; RPKM: Reads Per Kilobase of transcript Per Million; rRNA: Ribosomal RNA 16. RUFs: RNAs of Unknown Function; SHAPE: Selective 2'-hydroxyl acylation analysed by primer extension; snoRNA: Small Nucleolar RNA; snRNA: Small Nuclear RNA; SRP-RNA: Signal Recognition Particle RNA; ssRNA: (Single-stranded RNA); TE: Translation Efficiency; tRNA: transfer RNA; UTR: Untranslated Region.}, }
@article {pmid33947745, year = {2021}, author = {Sottnik, JL and Bordeaux, EK and Mehrotra, S and Ferrara, SE and Goodspeed, AE and Costello, JC and Sikora, MJ}, title = {Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Coregulator in Invasive Lobular Carcinoma of the Breast.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {8}, pages = {1270-1282}, pmid = {33947745}, issn = {1557-3125}, support = {P30 CA046934/CA/NCI NIH HHS/United States ; R00 CA193734/CA/NCI NIH HHS/United States ; T32 GM007635/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Breast/pathology ; Breast Neoplasms/drug therapy/*genetics/pathology ; Carcinoma, Lobular/drug therapy/*genetics/pathology ; Cell Cycle Proteins/*genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Female ; Humans ; MCF-7 Cells ; Promoter Regions, Genetic/drug effects/genetics ; Receptors, Estrogen/*genetics ; Signal Transduction/genetics ; Tamoxifen/therapeutic use ; Transcriptome/drug effects/genetics ; }, abstract = {Invasive lobular carcinoma (ILC) is the most common special histologic subtype of breast cancer, and nearly all ILC tumors express estrogen receptor alpha (ER). However, clinical and laboratory data suggest ILC are strongly estrogen-driven but not equally antiestrogen-sensitive. We hypothesized ILC-specific ER coregulators mediate ER functions and antiestrogen resistance in ILC, and profiled ER-associated proteins by mass spectrometry. Three ER[+] ILC cell lines (MDA MB 134VI, SUM44PE, and BCK4) were compared with ER[+] invasive ductal carcinoma (IDC) line data, and we examined whether siRNA of identified proteins suppressed ER-driven proliferation in ILC cells. This identified mediator of DNA damage checkpoint 1 (MDC1), a tumor suppressor in DNA damage response (DDR), as a novel ER coregulator in ILC. We confirmed ER:MDC1 interaction was specific to ILC versus IDC cells, and found MDC1 knockdown suppressed ILC cell proliferation and tamoxifen resistance. Using RNA-sequencing, we found in ILC cells MDC1 knockdown broadly dysregulates the ER transcriptome, with ER:MDC1 target genes enriched for promoter hormone response elements. Importantly, our data are inconsistent with MDC1 tumor suppressor functions in DDR, but suggest a novel oncogenic role for MDC1 as an ER coregulator. Supporting this, in breast tumor tissue microarrays, MDC1 protein was frequently low or absent in IDC, but MDC1 loss was rare in ER[+] ILC. ER:MDC1 interaction and MDC1 coregulator functions may underlie ER function in ILC and serve as targets to overcome antiestrogen resistance in ILC. IMPLICATIONS: MDC1 has novel ER coregulator activity in ILC, which may underlie ILC-specific ER functions, estrogen response, and antiestrogen resistance.}, }
@article {pmid33945869, year = {2021}, author = {Sethy, C and Goutam, K and Das, B and Dash, SR and Kundu, CN}, title = {Nectin-4 promotes lymphangiogenesis and lymphatic metastasis in breast cancer by regulating CXCR4-LYVE-1 axis.}, journal = {Vascular pharmacology}, volume = {140}, number = {}, pages = {106865}, doi = {10.1016/j.vph.2021.106865}, pmid = {33945869}, issn = {1879-3649}, mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; *Cell Adhesion Molecules/metabolism ; Female ; Humans ; Lymphangiogenesis/physiology ; Lymphatic Metastasis/pathology ; *Lymphatic Vessels/metabolism ; *Nectins/metabolism ; *Receptors, CXCR4/metabolism ; *Vesicular Transport Proteins/metabolism ; }, abstract = {Tumor-induced lymphangiogenesis promotes tumor progression by generating new lymphatic vessels that helps in tumor dissemination to regional lymph nodes and distant sites. Recently, the role of Nectin-4 in cancer metastasis and angiogenesis has been studied, but its role in lymphangiogenesis is unknown. Here, we systematically delineated the role of Nectin-4 in lymphangiogenesis and its regulation in invasive duct carcinoma (IDC). Nectin-4 expression positively correlated with occurrence risk factors associated with breast cancer (alcohol, smoke, lifestyle habit, etc), CXCR4 expression, and LYVE-1-lymphatic vessel density (LVD). LVD was significantly higher in axillary lymph node (ALN) than primary tumor. Depleting Nectin-4, VEGF-C or both attenuated the important lymphangiogenic marker LYVE-1 expression, tube formation, and migration of ALN derived primary cells. Nectin-4 stimulated the expressions of CXCR4 and CXCL12 under hypoxic conditions in ALN derived primary cells. Further, Nectin-4 augmented expressions of lymphatic metastatic markers (e.g. eNOS, TGF-β, CD-105) and MMPs. Induced expressions of Nectin-4 along with other representative metastatic markers were noted in lymph and blood circulating tumor cells (LCTCs and BCTCs) of local and distant metastatic samples. Thus, Nectin-4 displayed a predominant role in promoting tumor-induced lymphangiogenesis and lymphatic metastasis by modulating CXCR4/CXCL12-LYVE-1- axis.}, }
@article {pmid33930678, year = {2021}, author = {Solomon, Z and Ginzburg, K and Ohry, A and Mikulincer, M}, title = {Overwhelmed by the news: A longitudinal study of prior trauma, posttraumatic stress disorder trajectories, and news watching during the COVID-19 pandemic.}, journal = {Social science &amp; medicine (1982)}, volume = {278}, number = {}, pages = {113956}, pmid = {33930678}, issn = {1873-5347}, mesh = {*COVID-19 ; Humans ; Israel/epidemiology ; Longitudinal Studies ; Pandemics ; *Prisoners of War ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic/epidemiology/etiology ; *Veterans ; }, abstract = {RATIONALE: It has been recognized that exposure to mass trauma tends to increase the time spent watching television (TV) news. Yet, research on the effects of this tendency on individuals' well-being yielded inconclusive findings.<br><br>OBJECTIVE: The aim of this longitudinal study is to examine the effects of prior trauma and posttraumatic stress disorder (PTSD) on changes in the amount of TV news watching and its effect on subsequent PTSD. More specifically, we examined the interrelations of prior exposure to war captivity, long-term PTSD trajectories, and amount of change TV news watching with PTSD severity during the COVID-19 pandemic, among aging Israeli combat veterans.<br><br>METHODS: One-hundred-and-twenty Israeli ex-prisoners of war (ex-POWs) from 1973 Yom Kippur War and 65 matched controls (combat veterans from the same war) were followed up at five points of time: 1991 (T1), 2003 (T2), 2008 (T3), 2015 (T4), and in April-May 2020 (T5), during the outbreak of the COVID-19 pandemic.<br><br>RESULTS: Ex-POWs had higher odds of COVID-19 related increase in TV news watching, which, in turn, contributed to PTSD severity at T5. In addition, delayed PTSD trajectory was associated with COVID-19 related increase in TV news watching, which, in turn, contributed to more severe PTSD at T5.<br><br>CONCLUSIONS: These findings highlight the negative implications of TV news watching during a mass trauma for traumatized individuals. More specifically, they demonstrate its potential pathogenic role in exacerbating prior PTSD among trauma survivors.}, }
@article {pmid33927073, year = {2021}, author = {Huang, X and Cai, S and Wu, P and Huang, S and Yao, M}, title = {Clinical and X-ray characteristics for expressions of different receptors in patients with breast cancer.}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {46}, number = {3}, pages = {263-271}, doi = {10.11817/j.issn.1672-7347.2021.190371}, pmid = {33927073}, issn = {1672-7347}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnostic imaging/genetics ; Female ; Humans ; Receptor, ErbB-2/genetics ; Receptors, Estrogen ; Receptors, Progesterone ; X-Rays ; }, abstract = {OBJECTIVES: Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer.<br><br>METHODS: A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed.<br><br>RESULTS: Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all P<0.001). The age in the human epidermal growth factor 2 (HER2) overexpression type group was older, the proportions of menopause, the calcification score, and the calcification score with 9-12 were higher, the sizes of the tumor were greater in the HER2 overexpression type group than those in the other 3 molecular subtype groups (age P<0.05, the rest P<0.01). The proportions of regular shape, edge indistinct, and high-grade invasive ductal carcinoma in the triple-negative type group were higher than those in the other 3 molecular subtype groups (all P<0.001). The proportions of non-menopausal patients and spiculate tumors in the estrogen receptor (ER) positive and/or progesterone receptor (PR) positive groups were higher than those in both ER and PR negative group (P<0.001 and P=0.001, respectively). The proportions of calcification fraction and high-grade invasive ductal carcinoma were higher, tumor sizes were greater in the HER2 positive group, Ki-67&#x2265;20% group than those in the HER2 negative group, Ki-67<20% group, respectively (P<0.001 or P<0.05, respectively).<br><br>CONCLUSIONS: Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.}, }
@article {pmid33921735, year = {2021}, author = {Oprean, CM and Badau, LM and Segarceanu, NA and Ciocoiu, AD and Rivis, IA and Vornicu, VN and Hoinoiu, T and Grujic, D and Bredicean, C and Dema, A}, title = {Unilateral Orbital Metastasis as the Unique Symptom in the Onset of Breast Cancer in a Postmenopausal Woman: Case Report and Review of the Literature.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {33921735}, issn = {2075-4418}, abstract = {The orbit represents an unusual metastases site for patients diagnosed with cancer, however, breast cancer is the main cause of metastases at this level. These orbital metastases were discovered in patients with a history of breast cancer as unique or synchronous lesions. We present a rare case of a unique retroocular metastasis as the first initial symptom of a tubulo-lobular mammary carcinoma in a postmenopausal woman. A 57-year-old patient complains of diplopia, diminishing visual acuity, orbital tenderness, slight exophthalmia and ptosis of the left eyelid, with insidious onset. Clinical examination and subsequent investigations revealed a left breast cancer cT2 cN1 pM1 stage IV. Breast conserving surgery was performed on the left breast. Pathological examination with immunohistochemistry staining established the complete diagnostic: pT2pN3aM1 Stage IV breast cancer, luminal B subtype. After two years from the initial breast cancer diagnosis, the patient was diagnosed by the psychiatrist with a depressive disorder and was treated accordingly. Orbital metastases are usually discovered in known breast cancer patients and they are found in the context of a multi-system end-stage disease. Most reports cite that up to 25% of the total orbital metastases cases are discovered before the diagnosis of the primary tumor, as our case did. MRI is the gold standard for evaluating orbital tumors. The ILC histological subtype metastasizes in the orbitals more frequently than invasive ductal carcinoma. The prognosis of patients with orbital metastases is poor. The median survival after diagnosis of orbital metastases from a breast cancer primary is ranging from 22 to 31 months. Overall survival of our patient was 56 months, longer than the median survival reported in literature. Orbital metastases must be taken into account when patients accuse ophthalmologic symptoms even in the absence of a personal history of cancer. Objective examination of every patient that incriminates these types of symptoms is essential, and breast palpation must be made in every clinical setting. Orbital biopsy is necessary for the confirmation of the diagnosis and for an adequate treatment. Although recommendations for management of orbital metastases are controversial, it appears that multidisciplinary treatment of both metastases and primary cancer improves overall survival.}, }
@article {pmid33915261, year = {2021}, author = {López-Salazar, V and Tapia, MS and Tobón-Cornejo, S and Díaz, D and Alemán-Escondrillas, G and Granados-Portillo, O and Noriega, L and Tovar, AR and Torres, N}, title = {Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil.}, journal = {The Journal of nutritional biochemistry}, volume = {94}, number = {}, pages = {108751}, doi = {10.1016/j.jnutbio.2021.108751}, pmid = {33915261}, issn = {1873-4847}, mesh = {Animals ; Bacteria/classification/genetics ; Cells, Cultured ; Coconut Oil/*pharmacology ; Computational Biology ; DNA, Bacterial/genetics ; Feces/chemistry ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Regulation/drug effects ; Genotype ; Glucose Intolerance ; Hepatocytes/drug effects ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/genetics/metabolism ; Non-alcoholic Fatty Liver Disease/*prevention &amp; control ; Olive Oil/*pharmacology ; Oxygen Consumption/drug effects ; PPAR alpha/genetics/*metabolism ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S ; Random Allocation ; Soybean Oil/*pharmacology ; Toll-Like Receptor 4/genetics/metabolism ; }, abstract = {Diets rich in mono or polyunsaturated fats have been associated with a healthy phenotype, but there is controversial evidence about coconut oil (CO), which is rich in saturated medium-chain fatty acids. Therefore, the purpose of the present work was to study whether different types of oils rich in polyunsaturated (soybean oil, SO), monounsaturated (olive oil, OO), or saturated fatty acids (coconut oil, CO) can regulate the gut microbiota, insulin sensitivity, inflammation, mitochondrial function in wild type and PPARα KO mice. The group that received SO showed the highest microbial diversity, increase in Akkermansia muciniphila, high insulin sensitivity and low grade inflammation, The OO group showed similar insulin sensitivity and insulin signaling than SO, increase in Bifidobacterium, increase in fatty acid oxidation and low grade inflammation. The CO consumption led to the lowest bacterial diversity, a 9-fold increase in the LPS concentration leading to metabolic endotoxemia, hepatic steatosis, increased lipogenesis, highest LDL-cholesterol concentration and the lowest respiratory capacity and fatty acid oxidation in the mitochondria. The absence of PPARα decreased alpha diversity and increased LPS concentration particularly in the CO group, and increased insulin sensitivity in the groups fed SO or OO. These results indicate that consuming mono or polyunsaturated fatty acids produced health benefits at the recommended intake but a high concentration of oils (three times the recommended oil intake in rodents) significantly decreased the microbial alpha-diversity independent of the type of oil.}, }
@article {pmid33907159, year = {2021}, author = {He, Q and Xue, S and Wa, Q and He, M and Feng, S and Chen, Z and Chen, W and Luo, X}, title = {Mining immune-related genes with prognostic value in the tumor microenvironment of breast invasive ductal carcinoma.}, journal = {Medicine}, volume = {100}, number = {17}, pages = {e25715}, pmid = {33907159}, issn = {1536-5964}, support = {No. 81572769, No. 81372238//National Natural Science Foundation of China/ ; 2016ZDXM006//Natural Science Foundation of Chongqing (CN)/ ; No. 20PJ198//Scientific Research Foundation of Health Commission of Sichuan Provinc/ ; }, mesh = {Biomarkers, Tumor/*genetics ; *Breast Neoplasms/genetics/immunology/pathology ; *Carcinoma, Ductal/genetics/immunology/pathology ; Databases, Genetic ; Female ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; Gene Ontology ; Humans ; Kaplan-Meier Estimate ; Molecular Targeted Therapy/methods ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; *Tumor Microenvironment/genetics/immunology ; }, abstract = {The tumor microenvironment (TME) plays an important role in the development of breast cancer. Due to limitations in experimental conditions, the molecular mechanism of TME in breast cancer has not yet been elucidated. With the development of bioinformatics, the study of TME has become convenient and reliable.Gene expression and clinical feature data were downloaded from The Cancer Genome Atlas database and the Molecular Taxonomy of Breast Cancer International Consortium database. Immune scores and stromal scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data algorithm. The interaction of genes was examined with protein-protein interaction and co-expression analysis. The function of genes was analyzed by gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis. The clinical significance of genes was assessed with Kaplan-Meier analysis and univariate/multivariate Cox regression analysis.Our results showed that the immune scores and stromal scores of breast invasive ductal carcinoma (IDC) were significantly lower than those of invasive lobular carcinoma. The immune scores were significantly related to overall survival of breast IDC patients and both the immune and stromal scores were significantly related to clinical features of these patients. According to the level of immune/stromal scores, 179 common differentially expressed genes and 5 hub genes with prognostic value were identified. In addition, the clinical significance of the hub genes was validated with data from the molecular taxonomy of breast cancer international consortium database, and gene set enrichment analysis analysis showed that these hub genes were mainly enriched in signaling pathways of the immune system and breast cancer.We identified five immune-related hub genes with prognostic value in the TME of breast IDC, which may partly determine the prognosis of breast cancer and provide some direction for development of targeted treatments in the future.}, }
@article {pmid33888263, year = {2021}, author = {Schaub, JR and Tang, SC}, title = {Delayed Gemcitabine-Induced Posterior Reversible Encephalopathy Syndrome.}, journal = {The American journal of the medical sciences}, volume = {361}, number = {6}, pages = {795-798}, doi = {10.1016/j.amjms.2020.10.030}, pmid = {33888263}, issn = {1538-2990}, mesh = {Antimetabolites, Antineoplastic/*adverse effects ; Deoxycytidine/adverse effects/*analogs &amp; derivatives ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Posterior Leukoencephalopathy Syndrome/*chemically induced/*diagnostic imaging ; Time Factors ; Gemcitabine ; }, abstract = {INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiographic syndrome that has been expanding rapidly in the world of clinical medical oncology and hematology. In this article, we provide a unique patient case of delayed gemcitabine-induced PRES.<br><br>BRIEF CASE REPORT: A 60-year-old African American female with significant past medical history of ER+/PR+/HER2- invasive ductal carcinoma of the left breast is seen in the medical oncology clinic with vague, mild complaints of lightheadedness. She had progressed on multiple lines of chemotherapy and was ultimately switched to gemcitabine. One month after her third dose of gemcitabine, she developed acute vision loss and soon developed generalized tonic-clonic seizure. Extensive workup was unrevealing other than PRES and she slowly improved with supportive care and withdrawal of the medication.<br><br>DISCUSSION: Multiple case reports have described PRES in the context of combination chemotherapy with gemcitabine and a platinum agent in the treatment of gastrointestinal malignancies. With growing evidence, this case is consistent with the hypothesis that gemcitabine as monotherapy has a direct association with PRES. This case highlights a unique aspect in that PRES can occur at a delayed time interval, much further than the expected hours to days after the previous treatment.}, }
@article {pmid33863935, year = {2021}, author = {Nobili, S and Mannini, A and Parenti, A and Raggi, C and Lapucci, A and Chiorino, G and Paccosi, S and Di Gennaro, P and Vezzosi, V and Romagnoli, P and Susini, T and Coronnello, M}, title = {Establishment and characterization of a new spontaneously immortalized ER[-]/PR[-]/HER2[+] human breast cancer cell line, DHSF-BR16.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8340}, pmid = {33863935}, issn = {2045-2322}, mesh = {Aged ; Breast Neoplasms/drug therapy/*genetics/*pathology/surgery ; CD24 Antigen/genetics/metabolism ; Carcinoma, Ductal/drug therapy/*genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Movement ; Chemotherapy, Adjuvant ; Epithelial Cell Adhesion Molecule/genetics/metabolism ; Female ; Humans ; Hyaluronan Receptors/genetics/metabolism ; Intracellular Membranes/metabolism ; Keratin-7/genetics/metabolism ; Keratin-8/genetics/metabolism ; Neoadjuvant Therapy ; *Receptor, ErbB-2 ; *Receptors, Estrogen ; *Receptors, Progesterone ; Spheroids, Cellular/pathology ; }, abstract = {Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women's health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER[-]/PR[-]/HER2[+], and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44[+]/CD24[-/low]), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within - 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.}, }
@article {pmid33863525, year = {2021}, author = {D'Iorio, A and Esposito, M and Maggi, G and Amboni, M and Vitale, C and Santangelo, G}, title = {Neuropsychological correlates of prospective memory: A comparison between tremor-dominant Parkinson's disease and cervical dystonia.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {87}, number = {}, pages = {156-161}, doi = {10.1016/j.jocn.2021.03.006}, pmid = {33863525}, issn = {1532-2653}, mesh = {Aged ; Cognitive Dysfunction/diagnosis/etiology/*psychology ; Executive Function/physiology ; Female ; Humans ; Male ; Memory Disorders/diagnosis/etiology/psychology ; *Memory, Episodic ; Middle Aged ; *Neuropsychological Tests ; Parkinson Disease/complications/diagnosis/*psychology ; Retrospective Studies ; Torticollis/complications/diagnosis/*psychology ; Tremor/complications/diagnosis/*psychology ; }, abstract = {Cervical Dystonia (CD) and Parkinson's disease, particularly tremor-dominant motor phenotype (TD-PD), showed a selective deficit of time-based prospective memory (TBPM). The two movement disorders are mainly characterized by dysfunctions of basal-ganglia and prefrontal cortex but it is reported that cerebellum also plays a key role in their pathogenesis. These cerebral structures are specifically involved in TBPM rather than in event-based PM (EBPM), but until now no study directly compared these two components of PM between CD and TD-PD patients. Therefore, the present study aimed at investigating if differences in PM functioning between CD and TD-PD patients might exist and if the type of movement disorder moderated the relationship between deficit of PM and deficit of executive functions and retrospective memory. Thirty TD-PD, 27CD patients and 29 healthy subjects (HCs), matched for demographic features, underwent neuropsychological tests for PM, executive functions, retrospective memory and self-rated questionnaires. The three groups did not differ on neuropsychological variables except for TBPM where TD-PD and CD patients performed worse than HCs; moreover, TD-PD performed worse than CD patients. Moderation analysis indicated that the type of movement disorder moderated the relationship between executive dysfunction and TBPM, but not EBPM. In conclusion, selective deficit of TBPM characterizes both CD and TD-PD but it is associated with executive dysfunction only in TD-PD. It might be possible to speculate that the involvement of the cerebellum, responsible for internal timing processes, could explain the impairment of TBPM in both movement disorders. This issue deserves to be explored in future neuroimaging studies.}, }
@article {pmid33850160, year = {2021}, author = {Fayad, R and Rojas, MV and Partisani, M and Finetti, P and Dib, S and Abelanet, S and Virolle, V and Farina, A and Cabaud, O and Lopez, M and Birnbaum, D and Bertucci, F and Franco, M and Luton, F}, title = {EFA6B regulates a stop signal for collective invasion in breast cancer.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2198}, pmid = {33850160}, issn = {2041-1723}, mesh = {Animals ; Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Knockout Techniques ; Guanine Nucleotide Exchange Factors/*genetics/*metabolism ; Humans ; Mice ; Mice, Nude ; Transcriptome ; cdc42 GTP-Binding Protein ; }, abstract = {Cancer is initiated by somatic mutations in oncogenes or tumor suppressor genes. However, additional alterations provide selective advantages to the tumor cells to resist treatment and develop metastases. Their identification is of paramount importance. Reduced expression of EFA6B (Exchange Factor for ARF6, B) is associated with breast cancer of poor prognosis. Here, we report that loss of EFA6B triggers a transcriptional reprogramming of the cell-to-ECM interaction machinery and unleashes CDC42-dependent collective invasion in collagen. In xenograft experiments, MCF10 DCIS.com cells, a DCIS-to-IDC transition model, invades faster when knocked-out for EFA6B. In addition, invasive and metastatic tumors isolated from patients have lower expression of EFA6B and display gene ontology signatures identical to those of EFA6B knock-out cells. Thus, we reveal an EFA6B-regulated molecular mechanism that controls the invasive potential of mammary cells; this finding opens up avenues for the treatment of invasive breast cancer.}, }
@article {pmid33835493, year = {2021}, author = {Nash, Y and Ganoth, A and Borenstein-Auerbach, N and Levy-Barazany, H and Goldsmith, G and Kopelevich, A and Pozyuchenko, K and Sakhneny, L and Lazdon, E and Blanga-Kanfi, S and Alhadeff, R and Benromano, T and Landsman, L and Tsfadia, Y and Frenkel, D}, title = {From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {5}, pages = {e21374}, doi = {10.1096/fj.201901945R}, pmid = {33835493}, issn = {1530-6860}, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; Diabetes Mellitus, Experimental/etiology/pathology/*therapy ; Diabetes Mellitus, Type 1/etiology/pathology/*therapy ; Diabetes Mellitus, Type 2/etiology/pathology/*therapy ; Enzyme Inhibitors/administration &amp; dosage ; Female ; Herpesvirus 3, Human/physiology ; Insulin/*metabolism ; Insulysin/*antagonists &amp; inhibitors/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Peptide Fragments/*administration &amp; dosage ; Viral Envelope Proteins/*metabolism ; }, abstract = {Inhibition of insulin-degrading enzyme (IDE) is a possible target for treating diabetes. However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE's catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella-zoster virus (VZV), we constructed a VZV-based inhibitor. We computationally characterized its interaction site with IDE showing that the peptide specifically binds inside IDE's central cavity, however, not in close proximity to the zinc ion. We confirmed the peptide's effective inhibition on IDE activity in vitro and showed its efficacy in ameliorating insulin-related defects in types 1 and 2 diabetes mouse models. In addition, we suggest that inhibition of IDE may ameliorate the pro-inflammatory profile of CD4[+] T-cells toward insulin. Together, we propose a potential role of a designed VZV-derived peptide to serve as a selectively-targeted and as an efficient diabetes therapy.}, }
@article {pmid33828234, year = {2022}, author = {Hu, A and Hong, F and Li, D and Xie, Q and Chen, K and Zhu, L and He, H}, title = {KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/β-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.}, journal = {Cancer gene therapy}, volume = {29}, number = {2}, pages = {215-224}, pmid = {33828234}, issn = {1476-5500}, mesh = {Adaptor Proteins, Signal Transducing/genetics/metabolism ; Animals ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/metabolism ; LIM Domain Proteins ; Mice ; Mice, Nude ; Neoplasm Invasiveness/genetics ; Proto-Oncogene Proteins/genetics/metabolism ; Wnt Signaling Pathway ; beta Catenin/genetics/metabolism ; }, abstract = {Breast cancer is the most common malignancy for women, with invasive ductal carcinoma being the largest subtype of breast cancers, accounting for 75-80% of cases. However, the underlying mechanism of invasive ductal carcinoma remains unclear. In this study, we investigate the possible effects KDM3B-ETF1 fusion gene has on breast cancer cell metastasis, invasion and its downstream signaling mediators as revealed from RNA sequence data analysis. As predicted, KDM3B-ETF1 expression was increased in breast cancer tissues and cells. Overexpression of KDM3B-ETF1 in cancer cell lines promoted the growth and invasion of breast cancer cells, while KDM3B-ETF1 knockdown showed the opposite effects on malignant cell growth and invasion both in vivo and in vitro as evidenced by cell counting kit-8, Transwell assay and tumor xenograft in nude mice. On the contrary, LIM Domain Only 2 (LMO2) expression was significantly reduced in breast cancer tissues and cells. According to chromatin immunoprecipitation and Western blot analysis, KDM3B-ETF1 targets LMO2 and reduced the expression of LMO2, leading to an increase in WNT/β-catenin signaling pathway and thus promoting invasion. In conclusion, fusion gene KDM3B-ETF1 inhibits LMO2, activates the Wnt/β-catenin signaling pathway that leads to increased breast cancer cell invasion and metastasis, providing a novel insight into developing therapeutic strategies. These results provide novel insights into the molecular mechanism of invasive ductal carcinomas, which may lead to potential therapeutic targets.}, }
@article {pmid33827325, year = {2021}, author = {Weaver, KD and Isom, J and Esnakula, A and Daily, K and Asirvatham, JR}, title = {Acinic Cell Carcinoma of the Breast: Report of a Case With Immunohistochemical and Next-Generation Sequencing Studies.}, journal = {International journal of surgical pathology}, volume = {29}, number = {8}, pages = {882-886}, doi = {10.1177/10668969211008508}, pmid = {33827325}, issn = {1940-2465}, mesh = {Adult ; Anoctamin-1/analysis/metabolism ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Breast/*pathology/surgery ; Carcinoma, Acinar Cell/*diagnosis/genetics/pathology ; DNA Mutational Analysis ; Female ; GATA3 Transcription Factor/analysis/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Mastectomy ; Neoplasm Proteins/analysis/metabolism ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/genetics/pathology ; Proto-Oncogene Proteins c-ret/genetics ; Sentinel Lymph Node Biopsy ; Triple Negative Breast Neoplasms/*diagnosis/genetics/pathology ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.}, }
@article {pmid33824828, year = {2021}, author = {Khanam, R and Fanous, IS and Fadhel, EN and Hyder, T and Brufsky, A}, title = {Voltage-Gated Calcium Channel Antibody-Induced Oropharyngeal Dysphagia Presenting as a Paraneoplastic Neurological Complication in Breast Cancer.}, journal = {Cureus}, volume = {13}, number = {3}, pages = {e13677}, pmid = {33824828}, issn = {2168-8184}, abstract = {Paraneoplastic neurologic syndromes (PNS) are a group of disorders characterized by an autoimmune response against the nervous system due to cross-reactivity between malignant and normal neural tissue. The most commonly associated malignancies include small cell lung cancer, ovarian cancer, breast cancer, and lymphoma. Multiple PNS have been reported including paraneoplastic cerebellar degeneration, retinopathy, sensorimotor peripheral neuropathy, encephalopathy, opsoclonus-myoclonus syndrome, and stiff-person syndrome. We report a case of a 67-year-old woman with breast cancer who presented with a history of progressive oropharyngeal dysphagia as a paraneoplastic neurologic complication. She was diagnosed with invasive ductal carcinoma, nuclear grade 3 with moderate peritumoral lymphoid infiltrate. Hormone receptors were weakly positive for estrogen receptor (ER) (H score 15), weakly positive for progesterone receptor (PR) (H score 30), and negative for human epidermal growth factor receptor 2 (HER-2/NEU). The patient underwent a localized segmental mastectomy but declined any further adjuvant treatment. Three years after being diagnosed with invasive ductal carcinoma of the breast, she developed progressive oropharyngeal dysphagia that warranted percutaneous endoscopic gastrostomy (PEG) tube placement. Testing for onconeural antibodies was positive for voltage-gated calcium channel antibody. An extensive workup was negative for any alternative etiology that would explain her neurological symptoms. The patient declined further treatment and eventually succumbed to her illness.}, }
@article {pmid33824344, year = {2021}, author = {Kricheli-Katz, T and Regev, T}, title = {The effect of language on performance: do gendered languages fail women in maths?.}, journal = {NPJ science of learning}, volume = {6}, number = {1}, pages = {9}, pmid = {33824344}, issn = {2056-7936}, abstract = {Research suggests that gendered languages are associated with gender inequality. However, as languages are embedded in cultures, evidence for causal effects are harder to provide. We contribute to this ongoing debate by exploring the relationship between gendered languages and the gender gap in mathematics achievements. We provide evidence for causality by exploiting the prominent (but not exclusive) practice in gendered languages of using masculine generics to address women. In an experiment on a large representative sample of the Hebrew-speaking adult population in Israel, we show that addressing women in the feminine, compared to addressing them in the masculine, reduces the gender gap in mathematics achievements by a third. These effects are stronger among participants who acquired the Hebrew language early in childhood rather than later in life, suggesting that it is the extent of language proficiency that generates one's sensitivity to being addressed in the masculine or in the feminine. Moreover, when women are addressed in the masculine, their efforts (in terms of time spent on the maths test) decrease and they report feeling that "science is for men" more than when addressed in the feminine. We supplement the analysis with two experiments that explore the roles of general and task-specific stereotypes in generating these effects.}, }
@article {pmid33818021, year = {2021}, author = {Alyami, H and Yoo, TK and Cheun, JH and Lee, HB and Jung, SM and Ryu, JM and Bae, SJ and Jeong, J and Yoon, CI and Ahn, J and Paik, PS and Cho, MK and Park, WC}, title = {Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.}, journal = {Journal of breast cancer}, volume = {24}, number = {2}, pages = {175-182}, pmid = {33818021}, issn = {1738-6756}, abstract = {PURPOSE: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations.<br><br>METHODS: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea.<br><br>RESULTS: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer.<br><br>CONCLUSION: As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.}, }
@article {pmid33795819, year = {2021}, author = {Nagasawa, S and Kuze, Y and Maeda, I and Kojima, Y and Motoyoshi, A and Onishi, T and Iwatani, T and Yokoe, T and Koike, J and Chosokabe, M and Kubota, M and Seino, H and Suzuki, A and Seki, M and Tsuchihara, K and Inoue, E and Tsugawa, K and Ohta, T and Suzuki, Y}, title = {Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {438}, pmid = {33795819}, issn = {2399-3642}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Female ; GATA3 Transcription Factor/genetics/metabolism ; *Gene Amplification ; Gene Expression Profiling ; Humans ; Middle Aged ; *Mutation ; Receptor, ErbB-2/genetics/metabolism ; Young Adult ; }, abstract = {In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.}, }
@article {pmid33785437, year = {2021}, author = {Garcia, AM and Bishop, EL and Li, D and Jeffery, LE and Garten, A and Thakker, A and Certo, M and Mauro, C and Tennant, DA and Dimeloe, S and Evelo, CT and Coort, SL and Hewison, M}, title = {Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {211}, number = {}, pages = {105891}, pmid = {33785437}, issn = {1879-1220}, support = {MR/T016736/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Adipogenesis ; *Cell Differentiation ; Cells, Cultured ; Dendritic Cells/drug effects/immunology/*metabolism ; Fatty Acids/*biosynthesis ; Glycolysis ; Humans ; *Immune Tolerance ; Vitamin D/*analogs &amp; derivatives/pharmacology ; }, abstract = {The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of immune function, promoting anti-inflammatory, tolerogenic T cell responses by modulating antigen presentation by dendritic cells (DC). Transcriptomic analyses indicate that DC responses to 1,25D involve changes in glycolysis, oxidative phosphorylation, electron transport and the TCA cycle. To determine the functional impact of 1,25D-mediated metabolic remodelling, human monocyte-derived DC were differentiated to immature (+vehicle, iDC), mature (+LPS, mDC), and immature tolerogenic DC (+1,25D, itolDC) and characterised for metabolic function. In contrast to mDC which showed no change in respiration, itolDC showed increased basal and ATP-linked respiration relative to iDC. Tracer metabolite analyses using [13]C -labeled glucose showed increased lactate and TCA cycle metabolites. Analysis of lipophilic metabolites of [13]C-glucose revealed significant incorporation of label in palmitate and palmitoleate, indicating that 1,25D promotes metabolic fatty acid synthesis in itolDC. Inhibition of fatty acid synthesis in itolDC altered itolDC morphology and suppressed expression of CD14 and IL-10 by these cells. These data indicate that the ability of 1,25D to induce tolerogenic DC involves metabolic remodelling leading to synthesis of fatty acids.}, }
@article {pmid33776732, year = {2021}, author = {Sugimoto, H and Oda, G and Yokoyama, M and Hayashi, K and Yoshino, M and Ogawa, A and Hosoya, T and Nakagawa, T and Uetake, H}, title = {Hydronephrosis Caused by Metastatic Breast Cancer.}, journal = {Case reports in oncology}, volume = {14}, number = {1}, pages = {378-385}, pmid = {33776732}, issn = {1662-6575}, abstract = {Breast cancer metastasizes mainly to organs such as bone, lung, and liver, whereas metastases to the peritoneum and urinary tract are rare. Metastasis to the peritoneum or urinary tract may result in renal dysfunction, infection, and painful hydronephrosis. In our hospital, 1,409 breast cancer surgeries were performed between January 2004 and December 2015, and 7 cases of hydronephrosis associated with recurrence were observed. The median age of patients was 69 years (57-79 years). The median time from surgery to diagnosis of hydronephrosis was 47 months (20-70 months). Histology was invasive ductal carcinoma (IDC) in 6 cases and invasive lobular carcinoma (ILC) in 1 case. There were 6 bilateral cases and 1 unilateral case of hydronephrosis. The causes were retroperitoneal metastasis in 5 cases and lymph node metastasis in 2 cases. The hydronephrosis was untreated in 2 cases, and treated with a ureteral stent in 2 cases, nephrostomy in 1 case, and nephrostomy due to ureteral stent failure in 2 cases. The median survival from the onset of hydronephrosis was 12 months (3-57 months). Although the probability of hydronephrosis in breast cancer recurrence was not high, care must be taken to avoid renal dysfunction, infection, or pain, which may require treatment.}, }
@article {pmid33759307, year = {2021}, author = {Zhang, J and Zhou, B and Sun, J and Chen, H and Yang, Z}, title = {Betulin ameliorates 7,12-dimethylbenz(a)anthracene-induced rat mammary cancer by modulating MAPK and AhR/Nrf-2 signaling pathway.}, journal = {Journal of biochemical and molecular toxicology}, volume = {35}, number = {7}, pages = {e22779}, doi = {10.1002/jbt.22779}, pmid = {33759307}, issn = {1099-0461}, mesh = {9,10-Dimethyl-1,2-benzanthracene/*toxicity ; Animals ; Female ; MAP Kinase Signaling System/*drug effects ; Mammary Neoplasms, Animal/chemically induced/drug therapy/*metabolism/pathology ; NF-E2-Related Factor 2/*metabolism ; Neoplasm Proteins/*metabolism ; Rats ; Receptors, Aryl Hydrocarbon/*metabolism ; Triterpenes/*pharmacology ; }, abstract = {The aim of the present study is to explore the preventive efficacy of betulin (BE) in 7,12-dimethylbenz(a)anthracene (DMBA)-administered mammary cancer by modulating Ahr/Nrf2 signaling in experimental models. The mammary cancer was stimulated by the addition of DMBA (25 mg/kg/b.Wt) mixed in 1 ml of vehicle solution (sunflower oil and saline 1:1) through subcutaneous injection. The DMBA-exposed mammary tumor models showed low bodyweight, elevated quantities of lipid peroxidation molecules (TBARS and LOOH), and low enzymatic (GPx, SOD, and CAT), and nonenzymatic (GSH, vitamin C, and vitamin E) antioxidant activities in plasma and mammary tissues. Moreover, histopathological studies confirmed that invasive ductal carcinoma was observed in DMBA-induced mammary tissue of the experimental model. Dietary oral supplementation of BE prevents the loss of bodyweight, overproduces lipid peroxidation, and restores the antioxidant activities in DMBA-exposed experimental animals. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial antioxidant protein that involves preventing numerous cancers. Therefore, Nrf2-associated signaling concern is a significant target for preventing mammary cancer. This study observed an increased expression of MAPKs, Keap1, ARNT, AhR, and CYP1A1, whereas decreased expression of HO-1 and Nrf2 in DMBA-induced cancer-bearing experimental animals. The oral supplementation of BE effectively modulates the expression of MAPKs, AhR/Nrf2-associated protein expressions in DMBA-exposed experimental animals. This current study concluded that BE is a strong antioxidant, which triggers the MAPKs-mediated oxidative stress and inhibits proliferative markers by restoring the activity of Nrf2 signaling.}, }
@article {pmid33753865, year = {2021}, author = {Bergeron, A and MacGrogan, G and Bertaut, A and Ladoire, S and Arveux, P and Desmoulins, I and Bonnefoi, H and Loustalot, C and Auriol, S and Beltjens, F and Degrolard-Courcet, E and Charon-Barra, C and Richard, C and Boidot, R and Arnould, L}, title = {Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {34}, number = {7}, pages = {1282-1296}, pmid = {33753865}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Lobular/genetics/metabolism/*pathology ; DNA Mutational Analysis ; Female ; Humans ; Middle Aged ; Mutation ; Phosphatidylinositol 3-Kinases/genetics ; Receptor, ErbB-2/genetics ; Receptors, Androgen/genetics/*metabolism ; Receptors, Estrogen/*genetics ; Triple Negative Breast Neoplasms/*genetics/metabolism/*pathology ; }, abstract = {Primary triple-negative invasive lobular breast carcinomas (TN-ILCs), which do not express hormone receptors and HER2 at diagnosis, are rare and poorly known. In this study, we analyzed the largest TN-ILC series ever reported in the literature, in comparison to phenotypically similar breast tumor subtypes: triple-negative invasive ductal carcinoma (TN-IDC) and hormone receptor-positive invasive lobular carcinoma (HR + ILC). All primary TN-ILCs registered in our database between 2000 and 2018 (n = 38) were compared to tumors from control groups, matched by stage and Elston/Ellis grade, with regard to clinical, pathologic, and immunohistochemical characteristics. A comparative molecular analysis (whole-exome and RNA sequencing using next-generation technology) was also performed. We found that TN-ILC patients were older than those with HR + ILC (P = 0.002) or TN-IDC (P < 0.001). Morphologically, TN-ILCs had aggressive phenotypes, with more pleomorphism (P = 0.003) and higher nuclear grades than HR + ILCs (P = 0.009). Immunohistochemistry showed that TN-ILCs less frequently expressed basal markers (CK5/6, EGFR and SOX10) than TN-IDCs (P < 0.001), while androgen receptor (AR) positivity was more prevalent (P < 0.001). Survival curves analysis did not show differences between TN-ILC and TN-IDC patients, while overall and distant metastasis-free survival were significantly worse compared to those with HR + ILCs (P = 0.047 and P = 0.039, respectively). At a molecular level, we found that TN-ILCs had particular transcriptomic profiles, characterized by increased AR signaling, and associated with frequent alterations in the PI3K network and ERBB2. Interestingly, whole-exome analysis also identified three specific recurrent ESRRA hotspot mutations in these tumors, which have never been described in breast cancer to date and which were absent in the other two tumor subtypes. Our findings highlight that TN-ILC is a unique aggressive breast cancer associated with elderly age, which belong to the luminal androgen receptor subtype as determined by immunohistochemistry and transcriptomic profiling. Moreover, it harbors specific molecular alterations (PI3K, ERBB2 and ESRRA) which may pave the way for new targeted therapeutic strategies.}, }
@article {pmid33735776, year = {2021}, author = {Levin, Y and Lev Bar-Or, R and Forer, R and Vaserman, M and Kor, A and Lev-Ran, S}, title = {The association between type of trauma, level of exposure and addiction.}, journal = {Addictive behaviors}, volume = {118}, number = {}, pages = {106889}, doi = {10.1016/j.addbeh.2021.106889}, pmid = {33735776}, issn = {1873-6327}, mesh = {*Alcoholism ; *Behavior, Addictive/epidemiology ; Checklist ; Humans ; Risk Factors ; *Substance-Related Disorders/epidemiology ; }, abstract = {Exposure to trauma is considered a risk factor for the development of addictive disorders. Currently, there is a knowledge gap concerning specific links between types and levels of exposure to traumatic events and addiction.In this study we explored the associations between interpersonal trauma and risk of addictive behaviors, stratified by type of trauma (physical, weapon, sexual assault, and combat) and level of exposure (direct/indirect), focusing on a wide range of substances and behaviors. Data from an online representative sample of 4025 respondents were collected, including the Life Events Checklist (LEC-5), substance use disorders and behavioral addictions metrics, and sociodemographic data. Substantial differences were found between specific types of trauma and risk of addiction. Among those exposed to sexual assault, the risk of alcohol use disorder was found to 15.4%, 95%CI[14.4-16.4%], compared to 12.1%,95%CI[11.3-12.8] among those exposed to combat-related trauma. Both direct and indirect exposure to trauma were found to be significantly related with risk of addiction. While direct exposure was most highly associated with addictions across several types of trauma, in the case of combat-related trauma, indirect exposure was more highly associated with alcohol and pornography addiction (14.5%,95%CI[13.2-15.8%] and 10.0%, 95%CI[6.3-15.0%], respectively) compared to direct exposure (10.7%,95%CI[9.9-11.6%] and 7.4%, 95%CI[4.7-11.6%], respectively). Our findings emphasize the strong association between all types of trauma and the risk of several specific substance and behavioral addictions. Specifically, the role of indirect exposure to trauma is highlighted.}, }
@article {pmid33730716, year = {2021}, author = {Bar-Or, RL and Kor, A and Jaljuli, I and Lev-Ran, S}, title = {The Epidemiology of Substance Use Disorders among the Adult Jewish Population in Israel.}, journal = {European addiction research}, volume = {27}, number = {5}, pages = {362-370}, doi = {10.1159/000513776}, pmid = {33730716}, issn = {1421-9891}, mesh = {Adult ; *Alcoholism ; Humans ; Israel/epidemiology ; Jews/statistics &amp; numerical data ; Prevalence ; *Substance-Related Disorders/epidemiology ; Young Adult ; }, abstract = {INTRODUCTION: Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors.<br><br>METHODS: Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data.<br><br>RESULTS: We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]).<br><br>CONCLUSIONS: These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.}, }
@article {pmid33725931, year = {2021}, author = {Oh, BH and Woo, CG and Lee, YJ and Park, YS}, title = {Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.}, journal = {Medicine}, volume = {100}, number = {11}, pages = {e24373}, pmid = {33725931}, issn = {1536-5964}, support = {NRF-2019R1A2C1085809//Chungbuk National University Korea National University Development Project (2020)/ ; }, mesh = {Brain Neoplasms/metabolism/*secondary ; Breast Neoplasms, Male/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Humans ; Male ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {RATIONALE: Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis.<br><br>PATIENT CONCERNS: we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen).<br><br>DIAGNOSES: Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0&#x200a;&#xd7;&#x200a;4.2&#x200a;cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -).<br><br>INTERVENTIONS: The patient was successfully treated with surgery and whole brain irradiation (3 Gy&#x200a;&#xd7;&#x200a;10 fractions).<br><br>OUTCOMES: There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care.<br><br>LESSONS: Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.}, }
@article {pmid33710293, year = {2021}, author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY}, title = {Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity.}, journal = {JAMA network open}, volume = {4}, number = {3}, pages = {e211785}, pmid = {33710293}, issn = {2574-3805}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/*drug therapy/*mortality/pathology ; Carcinoma, Ductal/chemistry/*drug therapy/*mortality/pathology ; Cause of Death ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Receptor, ErbB-2/analysis ; Young Adult ; }, abstract = {IMPORTANCE: Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer.<br><br>OBJECTIVE: To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT.<br><br>This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020.<br><br>EXPOSURES: NET vs NACT for IDC with strong HR positivity and ERBB2 negativity.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments.<br><br>RESULTS: A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P&#x2009;<&#x2009;.001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P&#x2009;=&#x2009;.002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P&#x2009;<&#x2009;.001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P&#x2009;<&#x2009;.001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P&#x2009;=&#x2009;.009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P&#x2009;=&#x2009;.005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P&#x2009;<&#x2009;.001).<br><br>CONCLUSIONS AND RELEVANCE: The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.}, }
@article {pmid33704190, year = {2020}, author = {Bondy, S and Tajzler, C and Hotte, SJ and Kapoor, A and Zbuk, K and Lalani, AA}, title = {Genomic and Clinical Correlates of Adrenocortical Carcinoma in an Adult Patient with Li-Fraumeni Syndrome: A Case Report.}, journal = {Current oncology (Toronto, Ont.)}, volume = {28}, number = {1}, pages = {226-232}, pmid = {33704190}, issn = {1718-7729}, mesh = {*Adrenal Cortex Neoplasms/genetics ; *Adrenocortical Carcinoma/diagnosis/genetics ; Adult ; *Breast Neoplasms ; Female ; Genomics ; Humans ; *Li-Fraumeni Syndrome/genetics ; Mastectomy ; Neoplasm Recurrence, Local ; }, abstract = {Li-Fraumeni Syndrome (LFS) is defined by germline mutations of the p53 tumour suppressor gene. Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that is commonly associated with LFS. Most LFS-linked ACC cases occur in children, and limited research has been dedicated to the clinical outcomes and genomics of adult cases with LFS-linked ACC. We report on a 34-year-old female who was diagnosed with three separate malignancies: stage III invasive ductal carcinoma of the right breast, metastatic ACC from the right adrenal gland, and grade 2 pleomorphic sarcoma of the left hand. Her invasive breast ductal carcinoma was treated with neoadjuvant chemotherapy, and she received a bilateral mastectomy after her LFS was confirmed with genetic blood testing. Adrenal ACC was initially treated with a right nephrectomy and adrenalectomy, followed by adjuvant mitotane and two lines of chemotherapy after disease recurrence. Her hand sarcoma was treated by second ray amputation. Further, we conducted deep next-generation sequencing of each of her unique tumour tissue samples using FoundationONE CDx. A whole-genome shot capture followed by in vitro sequencing performed by the Illumina[®] HiSeq platform revealed a germline P191fs*18 TP53 mutation across all three tissue samples. This case provides insight into the genomics and clinical characteristics of LFS-linked adult-onset ACC and demonstrated that p53 mutations were preserved throughout each malignancy, without apparent treatment pressures on genomic profiling. This case reinforces the critical importance of adopting best practices for LFS, which include the implementation of highly vigilant screening and management of care in a multidisciplinary setting.}, }
@article {pmid33692758, year = {2021}, author = {Togashi, K and Nishitsuka, K and Hayashi, S and Namba, H and Goto, S and Takeda, Y and Suzuki, S and Kato, T and Yamada, Y and Konno, E and Yoshioka, T and Yamakawa, M and Sonoda, Y and Suzuki, T and Yamashita, H}, title = {Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {625663}, pmid = {33692758}, issn = {1664-2392}, mesh = {Breast Neoplasms/complications/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/complications/diagnostic imaging/*secondary ; Exophthalmos/diagnostic imaging/*etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Orbital Neoplasms/complications/diagnostic imaging/*secondary ; }, abstract = {BACKGROUND: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function.<br><br>CASE PRESENTATION: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation.<br><br>CONCLUSION: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.}, }
@article {pmid33676449, year = {2021}, author = {Ji, L and Cheng, L and Zhu, X and Gao, Y and Fan, L and Wang, Z}, title = {Risk and prognostic factors of breast cancer with liver metastases.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {238}, pmid = {33676449}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/secondary/therapy ; Chemoradiotherapy, Adjuvant/methods ; Datasets as Topic ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Liver/diagnostic imaging/pathology ; Liver Neoplasms/*epidemiology/secondary/therapy ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/methods ; Prognosis ; Receptor, ErbB-2/analysis/antagonists &amp; inhibitors/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/mortality/*pathology/therapy ; Young Adult ; }, abstract = {BACKGROUND: Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).<br><br>METHODS: Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.<br><br>RESULTS: Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0&#x2009;months in the SEER database and 27.3&#x2009;months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0&#x2009;months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6&#x2009;months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR)&#x2009;=&#x2009;2.62; 95% confidence interval (CI)&#x2009;=&#x2009;1.88-3.66; P&#x2009;<&#x2009;0.001) and HR-/HER2+ (HR&#x2009;=&#x2009;3.43; 95% CI&#x2009;=&#x2009;2.28-5.15; P&#x2009;<&#x2009;0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR&#x2009;=&#x2009;0.74; 95% CI&#x2009;=&#x2009;0.58-0.95; P&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.}, }
@article {pmid33667646, year = {2021}, author = {He, B and Chen, J and Song, W and Bai, Y}, title = {miR-646/TET1 mediated demethylation of IRX1 promoter upregulates HIST2H2BE and promotes the progression of invasive ductal carcinoma.}, journal = {Genomics}, volume = {113}, number = {3}, pages = {1469-1481}, doi = {10.1016/j.ygeno.2020.12.044}, pmid = {33667646}, issn = {1089-8646}, mesh = {*Carcinoma, Ductal ; Cell Line, Tumor ; DNA Methylation ; Demethylation ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; *MicroRNAs/genetics/metabolism ; Mixed Function Oxygenases/genetics/metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: This study aimed to explore role of miR-646 in breast IDC.<br><br>METHODS: miR-646, TET1, IRX1, and HIST2H2BE expression was detected by RT-qPCR and/or Western blot analysis. The methylation status of IRX1 promoter region was evaluated by methylation specific PCR. ChIP assay was used to determine the enrichment of TET1 at IRX1 promoter region. Loss- and gain-of functions were performed to determine the roles of miR-646, TET1, IRX1, and HIST2H2BE in cell proliferation, migration, invasion, and apoptosis. The tumor growth, volume, weight, and apoptosis status were measured.<br><br>RESULTS: miR-646 was upregulated while TET1 was downregulated in IDC tissues. miR-646 targeted TET1. Downregulated TET1 impairs demethylation of IRX1 promoter region resulting in reduced expression of IRX1, which subsequently leads to upregulation of HIST2H2BE in IDC. Consequently, elevated HIST2H2BE promotes progression of IDC.<br><br>CONCLUSION: Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.}, }
@article {pmid33667422, year = {2021}, author = {Schwartz, CJ and Boroujeni, AM and Khodadadi-Jamayran, A and Heguy, A and Snuderl, M and Jour, G and Cotzia, P and Darvishian, F}, title = {Molecular analysis of encapsulated papillary carcinoma of the breast with and without invasion.}, journal = {Human pathology}, volume = {111}, number = {}, pages = {67-74}, doi = {10.1016/j.humpath.2021.02.005}, pmid = {33667422}, issn = {1532-8392}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Papillary/*genetics/*pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Retrospective Studies ; }, abstract = {Encapsulated papillary carcinomas (EPCs) of the breast are a unique variant of papillary carcinoma confined to a cystic space with absent or attenuated myoepithelial cell layer. Although staged as an in situ lesion, it can be associated with invasive ductal carcinoma (IDC). We sought to compare the genomic characteristics of pure EPC and EPC with associated invasive carcinoma (EPCi) at the genomic level. All cases of EPCi harbored recurrent hotspot mutations in PIK3CA. PIK3CA, KMT2A, and CREBBP deleterious somatic events were found across both tumor groups, irrespective of invasion status. At the whole transcriptomic level, EPCi cases displayed remarkably similar mRNA profiles when compared to EPC. When EPCi cases were compared with their corresponding IDC, despite significant overlap, we identified differential gene expression in 39 genes with enrichment of multiple pathways including extracellular matrix regulation, cell adhesion, and collagen fibril organization. Despite morphologic, genotypic, and transcriptomic overlap between pure EPC and EPCi, the latter tumors are likely advanced lesions with PIK3CA activating mutations and enrichment of stromal-related genes implicated in the switch to IDC.}, }
@article {pmid33665961, year = {2021}, author = {Hartleben, G and Schorpp, K and Kwon, Y and Betz, B and Tsokanos, FF and Dantes, Z and Schäfer, A and Rothenaigner, I and Monroy Kuhn, JM and Morigny, P and Mehr, L and Lin, S and Seitz, S and Tokarz, J and Artati, A and Adamsky, J and Plettenburg, O and Lutter, D and Irmler, M and Beckers, J and Reichert, M and Hadian, K and Zeigerer, A and Herzig, S and Berriel Diaz, M}, title = {Combination therapies induce cancer cell death through the integrated stress response and disturbed pyrimidine metabolism.}, journal = {EMBO molecular medicine}, volume = {13}, number = {4}, pages = {e12461}, pmid = {33665961}, issn = {1757-4684}, mesh = {*Antineoplastic Agents ; Cell Death ; Humans ; *Neoplasms ; Niclosamide ; Pyrimidines ; }, abstract = {By accentuating drug efficacy and impeding resistance mechanisms, combinatorial, multi-agent therapies have emerged as key approaches in the treatment of complex diseases, most notably cancer. Using high-throughput drug screens, we uncovered distinct metabolic vulnerabilities and thereby identified drug combinations synergistically causing a starvation-like lethal catabolic response in tumor cells from different cancer entities. Domperidone, a dopamine receptor antagonist, as well as several tricyclic antidepressants (TCAs), including imipramine, induced cancer cell death in combination with the mitochondrial uncoupler niclosamide ethanolamine (NEN) through activation of the integrated stress response pathway and the catabolic CLEAR network. Using transcriptome and metabolome analyses, we characterized a combinatorial response, mainly driven by the transcription factors CHOP and TFE3, which resulted in cell death through enhanced pyrimidine catabolism as well as reduced pyrimidine synthesis. Remarkably, the drug combinations sensitized human organoid cultures to the standard-of-care chemotherapy paclitaxel. Thus, our combinatorial approach could be clinically implemented into established treatment regimen, which would be further facilitated by the advantages of drug repurposing.}, }
@article {pmid33663447, year = {2021}, author = {Mills, MN and Walker, C and Thawani, C and Naz, A and Figura, NB and Kushchayev, S and Etame, A and Yu, HM and Robinson, TJ and Liu, J and Vogelbaum, MA and Forsyth, PA and Czerniecki, BJ and Soliman, HH and Han, HS and Ahmed, KA}, title = {Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {223}, pmid = {33663447}, issn = {1471-2407}, mesh = {Ado-Trastuzumab Emtansine/adverse effects/*therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Brain/pathology ; Brain Neoplasms/*secondary ; Breast Neoplasms/chemistry/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Humans ; Middle Aged ; Necrosis ; *Radiosurgery/adverse effects ; Radiotherapy Dosage ; Receptor, ErbB-2/*analysis ; }, abstract = {BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation.<br><br>METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6&#x2009;months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging.<br><br>RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21&#x2009;Gy (14-24&#x2009;Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25&#x2009;Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2&#x2009;months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis.<br><br>CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.}, }
@article {pmid33662042, year = {2021}, author = {Mohamed, RI and Bargal, SA and Mekawy, AS and El-Shiekh, I and Tuncbag, N and Ahmed, AS and Badr, E and Elserafy, M}, title = {The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine.}, journal = {PloS one}, volume = {16}, number = {3}, pages = {e0247837}, pmid = {33662042}, issn = {1932-6203}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; *DNA Repair ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; Precision Medicine ; Transcriptome ; Up-Regulation ; }, abstract = {In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients' response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients' samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients' samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients' samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.}, }
@article {pmid33645934, year = {2021}, author = {Da Costa, I and Belnou, P and Soulier, A and Lapidus, N and Tsai, ES and Bourcier, E and Moisi, L and Sautet, A and Bonnet, F and Lescot, T and Verdonk, F}, title = {Impact of delayed patient flow on surgical outcomes after hip fracture: An observational study.}, journal = {European journal of anaesthesiology}, volume = {38 Suppl 1}, number = {}, pages = {S67-S68}, doi = {10.1097/EJA.0000000000001271}, pmid = {33645934}, issn = {1365-2346}, mesh = {Aged ; Aged, 80 and over ; Female ; France/epidemiology ; Hemorrhage/*epidemiology/etiology ; Hip Fractures/complications/*surgery ; Humans ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Postoperative Complications/epidemiology ; Recovery of Function/*physiology ; Time Factors ; Time-to-Treatment/*statistics &amp; numerical data ; Treatment Outcome ; }, }
@article {pmid33641217, year = {2021}, author = {Pramod, N and Nigam, A and Basree, M and Mawalkar, R and Mehra, S and Shinde, N and Tozbikian, G and Williams, N and Majumder, S and Ramaswamy, B}, title = {Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer.}, journal = {The oncologist}, volume = {26}, number = {6}, pages = {e943-e953}, pmid = {33641217}, issn = {1549-490X}, mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular/genetics/therapy ; Female ; Humans ; Mastectomy, Segmental ; }, abstract = {Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER)-positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. Lobular cancer presents significant challenges in detection and clinical management given its multifocality and multicentricity at presentation. Despite the unique features of ILC, it is often lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. Despite both being treated as ER-positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as E-cadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). Moreover, compared with patients with IDC, patients with ILC are less likely to undergo breast-conserving surgery, with lower rates of complete response following therapy as these tumors are less chemosensitive. Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies. Long-term survival and clinical outcomes in patients with ILC are worse than in stage- and grade-matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC's unique biology. This comprehensive review highlights the histologic and clinicopathologic features that distinguish ILC from IDC, with an in-depth discussion of ILC's molecular alterations and biomarkers, clinical trials and treatment strategies, and future targets for therapy. IMPLICATIONS FOR PRACTICE: The majority of invasive lobular breast cancers (ILCs) are hormone receptor (HR)-positive and low grade. Clinically, ILC is treated similar to HR-positive invasive ductal cancer (IDC). However, ILC differs distinctly from IDC in its clinicopathologic characteristics and molecular alterations. ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. Patients with ILC have worse clinical outcomes with late recurrences. Despite these differences, clinical trials treat HR-positive breast cancers as a single disease, and there is an unmet need for studies addressing the unique challenges faced by patients diagnosed with ILC.}, }
@article {pmid33628571, year = {2021}, author = {Sarawagi, A and Maxwell, J}, title = {Chyle Leak after Right Axillary Lymph Node Dissection in a Patient with Breast Cancer.}, journal = {Case reports in surgery}, volume = {2021}, number = {}, pages = {8812315}, pmid = {33628571}, issn = {2090-6900}, abstract = {BACKGROUND: A female patient was diagnosed with a right-sided chyle leak following right skin sparing mastectomy, axillary lymph node dissection, and immediate tissue expander placement in the setting of invasive ductal carcinoma status post neoadjuvant chemotherapy. Summary. Our patient underwent a level I and II right axillary lymph node dissection followed by an axillary drain placement. On the first postoperative day, a change from serosanguinous to milky fluid in this drain was noted. The patient was diagnosed with a chyle leak based on the milky appearance and elevated triglyceride levels in the fluid. While chyle leaks are rare after an axillary dissection and even rarer to present on the right side, it is a complication of which breast surgeons should be aware. The cause of this complication is thought to be due to injury of the main thoracic duct, its branches, the subclavian duct, or its tributaries. Management is usually conservative; however, awareness of this potential complication even on the right side is of the utmost importance.<br><br>CONCLUSION: Chyle leaks are an uncommon complication of axillary node dissections and even rarer for them to present on the right side. It can be diagnosed by monitoring the drainage for changes in appearance and volume and by conducting supporting laboratory tests. Conservative management is generally suggested.}, }
@article {pmid33626496, year = {2021}, author = {Lozano, R and Salles, DC and Sandhu, S and Aragón, IM and Thorne, H and López-Campos, F and Rubio-Briones, J and Gutierrez-Pecharroman, AM and Maldonado, L and di Domenico, T and Sanz, A and Prieto, JD and García, I and Pacheco, MI and Garcés, T and Llacer, C and Romero-Laorden, N and Zambrana, F and López-Casas, PP and Lorente, D and Mateo, J and Pritchard, CC and Antonarakis, ES and Olmos, D and Lotan, TL and Castro, E}, title = {Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {147}, number = {}, pages = {74-83}, doi = {10.1016/j.ejca.2021.01.027}, pmid = {33626496}, issn = {1879-0852}, support = {R01 CA185297/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; BRCA2 Protein/*genetics ; Biomarkers, Tumor/*genetics ; Case-Control Studies ; DNA Mutational Analysis ; Gene Deletion ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; *Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/genetics ; Phenotype ; Prostatic Neoplasms/*genetics/pathology ; Risk Assessment ; Risk Factors ; Spain ; }, abstract = {BACKGROUND: Intraductal (IDC) and cribriform (CRIB) histologies in prostate cancer have been associated with germline BRCA2 (gBRCA2) mutations in small retrospective series, leading to the recommendation of genetic testing for patients with IDC in the primary tumour.<br><br>PATIENTS AND METHODS: To examine the association of gBRCA2 mutations and other tumour molecular features with IDC and/or cribriform (CRIB) histologies, we conducted a case-control study in which primary prostate tumours from 58 gBRCA2 carriers were matched (1:2) by Gleason Grade Group and specimen type to 116 non-carriers. Presence/absence of IDC and CRIB morphologies was established by two expert uropathologists blinded to gBRCA2 status. Fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect BRCA2 alterations, PTEN deletions and TMPRSS2-ERG fusions. Chi-squared tests were used to compare the frequency of IDC and CRIB in gBRCA2 carriers and controls&#xa0;and to assess associations with other variables. Logistic regression models were constructed to identify independent factors associated with both histology patterns.<br><br>RESULTS: No significant differences between gBRCA2 carriers and non-carriers were observed in the prevalence of IDC (36% gBRCA2 versus 50% non-carriers, p&#xa0;=&#xa0;0.085) or CRIB (53% gBRCA2 versus 43% non-carriers p&#xa0;=&#xa0;0.197) patterns. However, IDC histology was independently associated with bi-allelic BRCA2 alterations (OR 4.3, 95%CI 1.1-16.2) and PTEN homozygous loss (OR 5.2, 95%CI 2.1-13.1). CRIB morphology was also independently associated with bi-allelic BRCA2 alterations (OR 5.6, 95%CI 1.7-19.3).<br><br>CONCLUSIONS: While we found no association between gBRCA2 mutations and IDC or CRIB histologies, bi-allelic BRCA2 loss in primary prostate tumours was significantly associated with both variant morphologies, independently of other clinical-pathologic factors.}, }
@article {pmid33625616, year = {2021}, author = {Chandrika, M and Chua, PJ and Muniasamy, U and Huang, RYJ and Thike, AA and Ng, CT and Tan, PH and Yip, GW and Bay, BH}, title = {Prognostic significance of phosphoglycerate dehydrogenase in breast cancer.}, journal = {Breast cancer research and treatment}, volume = {186}, number = {3}, pages = {655-665}, pmid = {33625616}, issn = {1573-7217}, support = {NMRC/CIRG/1370/2013//National Medical Research Council/ ; }, mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; *Phosphoglycerate Dehydrogenase/genetics ; Prognosis ; Serine ; }, abstract = {PURPOSE: Breast cancer is the most common type of cancer affecting women worldwide. Phosphoglycerate dehydrogenase (PHGDH) is an oxidoreductase in the serine biosynthesis pathway. Although it has been reported to affect growth of various tumors, its role in breast cancer is largely unknown. This study aimed to analyze the expression of PHGDH in breast cancer tissue samples and to determine if PHGDH regulates breast cancer cell proliferation.<br><br>METHODS: Tissue microarrays consisting of 305 cases of breast invasive ductal carcinoma were used for immunohistochemical evaluation of PHGDH expression. The role of PHGDH in breast cancer was investigated in vitro by knocking down its expression and determining the effect on cell proliferation and cell cycling, and in ovo by using a chorioallantoic membrane (CAM) assay.<br><br>RESULTS: Immunohistochemical examination showed that PHGDH is mainly localized in the cytoplasm of breast cancer cells and significantly associated with higher cancer grade, larger tumor size, increased PCNA expression, and lymph node positivity. Analysis of the GOBO dataset of 737 patients demonstrated that increased PHGDH expression was associated with poorer overall survival. Knockdown of PHGDH expression in breast cancer cells in vitro resulted in a decrease in cell proliferation, reduction in cells entering the S phase of the cell cycle, and downregulation of various cell cycle regulatory genes. The volume of breast tumor in an in ovo CAM assay was found to be smaller when PHGDH was silenced.<br><br>CONCLUSION: The findings suggest that PHGDH has a regulatory role in breast cancer cell proliferation and may be a potential prognostic marker and therapeutic target in breast cancer.}, }
@article {pmid33621744, year = {2021}, author = {Gupta, V and Agarwal, P and Deshpande, P}, title = {Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer.}, journal = {Annals of diagnostic pathology}, volume = {52}, number = {}, pages = {151722}, doi = {10.1016/j.anndiagpath.2021.151722}, pmid = {33621744}, issn = {1532-8198}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/pathology ; Carcinoma, Lobular/diagnosis/epidemiology/pathology ; Cross-Sectional Studies ; DNA Methylation ; Disease Progression ; Epigenesis, Genetic/*genetics ; Female ; Humans ; India/epidemiology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging/methods ; Phyllodes Tumor/diagnosis/epidemiology/pathology ; Prognosis ; Promoter Regions, Genetic/*genetics ; Tumor Suppressor Proteins/*genetics ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women caused by genetic and epigenetic changes. Promoter DNA methylation in tumor suppressor gene plays a major role in breast cancer. The study determined the association of promoter DNA methylation of RASSF1A gene with clinicopathological features in tumor and non-tumor tissue.<br><br>MATERIALS AND METHODS: A cross sectional study was conducted in the Department of Pathology, Government Institute of Medical Sciences, Greater Noida and Molecular Pathology Laboratory, Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences. Two sections, one from tumor and the other from non-tumor tissue, were obtained and processed for DNA extraction and bisulphite conversion. Methylation specific PCR was done and results of RASSF1A promoter methylation were statistically correlated with clinicopathological features.<br><br>RESULTS: Of the 27 breast cancer tissue, 22 showed invasive ductal carcinoma, one showed invasive lobular carcinoma, another showed ductal carcinoma in situ and three cases showed malignant phyllodes tumor of breast. DNA promoter methylation was found in all the cases. 93% of tumor tissue samples and 67% of the non-tumor tissue samples were found to be aberrantly methylated. Tumor size and histological grade were found to be significantly (p-val <0.05) associated with the RASSF1A gene promoter methylation.<br><br>CONCLUSION: A significant association of higher tumor size and tumor histological grade with promoter methylation of RASSF1A gene exists suggestive of its being an important determinant of prognostic staging. This critical event in tumorigenesis may be of clinical utility in assessing breast cancer progression.<br><br>MICRO ABSTRACT: The study focuses on the RASSF1A gene promoter methylation and its impact on the clinicopathological features in Indian breast cancer patients highlighting the differences from other genetically different population. We found that RASFF1A gene methylation has significant impact on tumor size and tumor grade. The work carries high significance because it addresses the DNA methylation of tumor suppressor gene in relevance of breast cancer. It may also be the first such report on Indian patients with breast cancer.}, }
@article {pmid33611829, year = {2021}, author = {Huang, D and Zhou, B and Luo, ZZ and Yu, SC and Tang, B}, title = {Cigarette smoke extract promotes DNA methyltransferase 3a expression in dendritic cells, inducing Th-17/Treg imbalance via the c-Jun/allograft inflammatory factor 1 axis.}, journal = {The Kaohsiung journal of medical sciences}, volume = {37}, number = {7}, pages = {594-603}, doi = {10.1002/kjm2.12367}, pmid = {33611829}, issn = {2410-8650}, support = {//The Science and Technology Plan of Jiangxi Province Health Committee, Grant/Award Number: 20204366/ ; //The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee, Grant/Award Number: 20181001/ ; 20204366//The Science and Technology Plan of Jiangxi Province Health Committee/ ; 20181001//The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee/ ; }, mesh = {Allografts ; Animals ; Anthracenes/pharmacology ; CD4-Positive T-Lymphocytes/cytology ; Calcium-Binding Proteins/*metabolism ; Cell Differentiation ; Cells, Cultured ; DNA Methyltransferase 3A/*metabolism ; Dendritic Cells/metabolism ; Disease Models, Animal ; Enzyme Inhibitors/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Microfilament Proteins/*metabolism ; Proto-Oncogene Proteins c-jun/*metabolism ; Pulmonary Disease, Chronic Obstructive/genetics ; Signal Transduction ; *Smoke ; Smoking/*adverse effects ; T-Lymphocytes, Regulatory/*metabolism ; Tetrazolium Salts/pharmacology ; Th17 Cells/metabolism ; Thiazoles/pharmacology ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder. Although numerous studies on COPD have been conducted, therapeutic strategies for COPD are limited, and its pathological mechanism is still unclear. The present study aimed to explore the role of DNA methyltransferase 3a (DNMT3a) in dendritic cells (DCs) and the possible role of the Th-17/Treg cell balance in COPD. Immature DCs (iDCs) were induced and cocultured with CD4[+] T cells. An in vitro COPD model was established by treatment with cigarette smoke extract (CSE). DNMT3a or allograft inflammatory factor 1 (AIF1) and c-Jun N-terminal kinase (JNK) were inhibited and overexpressed, respectively, by transfection with sh-DNMT3a or sh-AIF1 and JNK overexpression plasmids. The 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability. The Th17/Treg cell ratio was determined by flow cytometry. The expression levels of DNMT3a, c-Jun and AIF1 were measured using RT-qPCR or western blotting. Chromatin immunoprecipitation (CHIP) was used to confirm the interaction between c-Jun and the AIF1 promoter region. CSE stimulation promoted the expression of DNMT3a, and AIF1, and the ratio of p-c-Jun/c-Jun in iDCs. Besides, the iDC-mediated differentiation of Th17 cells was in a dose-dependent manner. However, knockdown of DNMT3a or AIF1 reversed the above effects caused by CSE. Inhibition of c-Jun signaling by treatment with the JNK inhibitor SP600125 also suppressed the iDC-mediated differentiation of Th17 cells, which was promoted by CSE. CHIP analysis showed that c-Jun could bind to the promoter region of AIF1. DNMT3a could regulate the iDC-mediated Th17/Treg balance by regulating the c-Jun/AIF1 axis.}, }
@article {pmid33608011, year = {2021}, author = {O'Donnell, AJ and Reece, SE}, title = {Ecology of asynchronous asexual replication: the intraerythrocytic development cycle of Plasmodium berghei is resistant to host rhythms.}, journal = {Malaria journal}, volume = {20}, number = {1}, pages = {105}, pmid = {33608011}, issn = {1475-2875}, support = {UF110155//The Royal Society/ ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; NF140517//The Royal Society/ ; RGP0046/2013//Human Frontier Science Program/ ; }, mesh = {Animals ; Anopheles/parasitology/*physiology ; *Circadian Rhythm ; Erythrocytes/parasitology ; Female ; Mosquito Vectors/parasitology/*physiology ; Plasmodium berghei/growth &amp; development/*physiology ; *Reproduction, Asexual ; }, abstract = {BACKGROUND: Daily periodicity in the diverse activities of parasites occurs across a broad taxonomic range. The rhythms exhibited by parasites are thought to be adaptations that allow parasites to cope with, or exploit, the consequences of host activities that follow daily rhythms. Malaria parasites (Plasmodium) are well-known for their synchronized cycles of replication within host red blood cells. Whilst most species of Plasmodium appear sensitive to the timing of the daily rhythms of hosts, and even vectors, some species present no detectable rhythms in blood-stage replication. Why the intraerythrocytic development cycle (IDC) of, for example Plasmodium chabaudi, is governed by host rhythms, yet seems completely independent of host rhythms in Plasmodium berghei, another rodent malaria species, is mysterious.<br><br>METHODS: This study reports a series of five experiments probing the relationships between the asynchronous IDC schedule of P. berghei and the rhythms of hosts and vectors by manipulating host time-of-day, photoperiod and feeding rhythms.<br><br>RESULTS: The results reveal that: (i) a lack coordination between host and parasite rhythms does not impose appreciable fitness costs on P. berghei; (ii) the IDC schedule of P. berghei is impervious to host rhythms, including altered photoperiod and host-feeding-related rhythms; (iii) there is weak evidence for daily rhythms in the density and activities of transmission stages; but (iv), these rhythms have little consequence for successful transmission to mosquitoes.<br><br>CONCLUSIONS: Overall, host rhythms do not affect the performance of P. berghei and its asynchronous IDC is resistant to the scheduling forces that underpin synchronous replication in closely related parasites. This suggests that natural variation in the IDC schedule across species represents different parasite strategies that maximize fitness. Thus, subtle differences in the ecological interactions between parasites and their hosts/vectors may select for the evolution of very different IDC schedules.}, }
@article {pmid33605547, year = {2021}, author = {Xu, F and Gao, Y and Diao, X and Li, J and Jiang, H and Zhao, H}, title = {Diagnostic value of sialyl-Tn immunocytochemistry in breast cancer presenting with pathological nipple discharge.}, journal = {Cancer medicine}, volume = {10}, number = {5}, pages = {1783-1790}, pmid = {33605547}, issn = {2045-7634}, mesh = {Adult ; Antigens, Tumor-Associated, Carbohydrate/*analysis ; Biomarkers, Tumor/analysis ; Biopsy ; Breast/immunology/pathology ; Breast Neoplasms/complications/*immunology/pathology ; Carcinoma, Ductal, Breast/complications/*immunology/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*immunology/pathology ; Confidence Intervals ; Female ; Humans ; Hyperplasia/immunology/pathology ; Immunohistochemistry ; Logistic Models ; Nipple Discharge/*immunology ; Odds Ratio ; Papilloma, Intraductal/complications/*immunology/pathology ; Receptor, ErbB-2/analysis ; Risk Factors ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Mucin-associated sialyl-Tn (sTn) antigen is overexpressed and related with adverse outcome in breast cancer (BC). The role of sTn in BC has not been well defined in pathological nipple discharge (PND) cytology. The authors examined sTn immunocytochemistry (ICC) in PND to determine whether it could be a biomarker of malignancy or aggressive disease.<br><br>METHODS: PND was subjected to immunocytochemical staining for sTn antigen expression and thinprep cytology test (TCT) for enhancing the sensitivity and specificity. The examination data was compared with histological findings of subsequent biopsy specimens. Logistic regression analysis was used to determine which factors were most associated with malignant breast lesions.<br><br>RESULTS: PND specimens were collected including 120 cases of intraductal papilloma, 24 cases of hyperplasia, 45 cases of ductal carcinoma in situ (DCIS), and 48 cases of invasive ductal carcinoma (IDC). STn ICC differentiated BC from benign intraductal lesions with a low sensitivity of 41.9% and a high specificity of 95.8%, but increased in combination with TCT to 64.5% and 100%, respectively. A high degree of concordance was observed between the results of sTn expression in cell smears and histological specimens. Moreover, the sTn expression was strongly associated with HER2-positive IDC (p&#xa0;=&#xa0;0.039). Multivariate logistic analysis showed that positive sTn expression (OR: 14.241, 95%CI: 2.574, 78.794, p&#xa0;=&#xa0;0.010) and accompanying mass (OR: 3.307, 95%CI: 1.073, 10.188, p&#xa0;=&#xa0;0.037) were statistically significant independent risk factors for malignant PND.<br><br>CONCLUSIONS: Mucin-associated sTn expression in PND cytology appears to be a reliable diagnostic marker for BC patients with the chief complaint of malignant nipple discharge and indicates a more aggressive behavior in IDC.}, }
@article {pmid33593316, year = {2021}, author = {Liu, J and Zheng, X and Han, Z and Lin, S and Han, H and Xu, C}, title = {Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {168}, pmid = {33593316}, issn = {1471-2407}, mesh = {Adenocarcinoma/*mortality/pathology/therapy ; Aged ; Breast Neoplasms/*mortality/pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program/*statistics &amp; numerical data ; Survival Rate ; }, abstract = {BACKGROUND: The prognositc factors in patient with invasive cribriform carcinoma (ICC) of breast is still remain controversal. The study aims to establish a nomogram to predict the survival outcomes in patients with ICC based on the Surveillance, Epidemiology and End Results (SEER) database.<br><br>METHODS: We retrieved SEER database for clinical data about patients including ICC and infiltrating ductal carcinoma (IDC) from 2004 to 2015. Kaplan-Meier survival was used to compare the difference survival outcomes between ICC and IDC. ICC patients were randomly allocated to training cohort and validation cohort. A nomogram was built to predict individual patient's 3-year and 5-year survival status for ICC. The established TMN model and the newly established nomogram was further evaluated by the concordance index (C-index) and the decision curve analysis (DCA).<br><br>RESULTS: Comparing the baseline clinical data between IDC and ICC, a significant of smaller tumor mass, less infiltrated lymph nodes, lower metastases rate, better tumor differentiation degree, higher proportion of estrogen receptor (ER) and progesterone receptor (PR) positive and lower rate of chemotherapy and radiotherapy was found in ICC. Age at diagnosis, marriage status, tumor location, T stage, M stage, ER status, surgery were independent significant prognostic factors for the overall survival (OS). A significantly higher C-index was found in nomogram compared with established TNM model in validation cohort.<br><br>CONCLUSIONS: The prognosis of ICC patients is better than that of IDC patients. The nomogram is recommended for future patient with ICC to survival analysis.}, }
@article {pmid33582923, year = {2021}, author = {Hu, XQ and Peng, L and Wintermark, M and Lipson, JA and Zhang, YR and Gao, Y}, title = {Shear Wave Elastography of Invasive Ductal Carcinoma: Correlations between Shear Wave Velocity and Histological Prognostic Factors.}, journal = {Current medical science}, volume = {41}, number = {1}, pages = {173-179}, pmid = {33582923}, issn = {2523-899X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/classification/*diagnostic imaging/pathology ; Carcinoma, Ductal/classification/*diagnostic imaging/pathology ; Elasticity Imaging Techniques/*methods/standards ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/genetics ; Sensitivity and Specificity ; }, abstract = {The correlations between shear wave velocity (SWV) calculated from virtual touch tissue imaging quantification (VTIQ) technique and histological prognostic factors of invasive ductal carcinoma was investigated. A total of 76 breast tumors histologically confirmed as invasive ductal carcinomas were included in this study. SWV values were measured by VTIQ for each lesion preoperatively or prior to breast biopsy. The maximum values were recorded for statistical analysis. Medical records were reviewed to determine tumor size, histological grade, lymph node status and immunohistochemical results. Tumor subtypes were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative. The correlations between SWV and histological prognostic factors were analyzed. It was found that tumor size showed positive association with SWV (r=0.465, P<0.001). Larger tumors had significantly higher SWV than smaller ones (P=0.001). Histological grade 1 tumors had significantly lower SWV values than those with higher histological grade (P=0.015). The Ki67 expression, tumor subtypes and lymph node status showed no statistically significant correlations with SWV, although triple negative tumors and lymph node-positive tumors showed higher SWV values. It was concluded that tumor size was significantly associated with SWV. Higher histological grade was associated with increased SWV. There was no statistically significant correlations between SWV and other histological prognostic factors.}, }
@article {pmid33581714, year = {2021}, author = {Saeed, U and Uppal, SR and Piracha, ZZ and Rasheed, A and Aftab, Z and Zaheer, H and Uppal, R}, title = {Evaluation of SARS-CoV-2 antigen-based rapid diagnostic kits in Pakistan: formulation of COVID-19 national testing strategy.}, journal = {Virology journal}, volume = {18}, number = {1}, pages = {34}, pmid = {33581714}, issn = {1743-422X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Viral/immunology/*isolation &amp; purification ; COVID-19/*diagnosis/epidemiology/immunology/virology ; COVID-19 Serological Testing/*methods ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pakistan/epidemiology ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; SARS-CoV-2/genetics/immunology/*isolation &amp; purification ; Young Adult ; }, abstract = {Rapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands.}, }
@article {pmid33567280, year = {2021}, author = {Greulich, F and Wierer, M and Mechtidou, A and Gonzalez-Garcia, O and Uhlenhaut, NH}, title = {The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers.}, journal = {Cell reports}, volume = {34}, number = {6}, pages = {108742}, pmid = {33567280}, issn = {2211-1247}, mesh = {Animals ; Enhancer Elements, Genetic/*immunology ; Inflammation/genetics/immunology ; Macrophages/*immunology ; Mice ; *Multiprotein Complexes/genetics/immunology ; *RNA-Seq ; *Receptors, Glucocorticoid/genetics/immunology ; Transcription, Genetic/*immunology ; }, abstract = {Glucocorticoids (GCs) are effective anti-inflammatory drugs; yet, their mechanisms of action are poorly understood. GCs bind to the glucocorticoid receptor (GR), a ligand-gated transcription factor controlling gene expression in numerous cell types. Here, we characterize GR's protein interactome and find the SETD1A (SET domain containing 1A)/COMPASS (complex of proteins associated with Set1) histone H3 lysine 4 (H3K4) methyltransferase complex highly enriched in activated mouse macrophages. We show that SETD1A/COMPASS is recruited by GR to specific cis-regulatory elements, coinciding with H3K4 methylation dynamics at subsets of sites, upon treatment with lipopolysaccharide (LPS) and GCs. By chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq, we identify subsets of GR target loci that display SETD1A occupancy, H3K4 mono-, di-, or tri-methylation patterns, and transcriptional changes. However, our data on methylation status and COMPASS recruitment suggest that SETD1A has additional transcriptional functions. Setd1a loss-of-function studies reveal that SETD1A/COMPASS is required for GR-controlled transcription of subsets of macrophage target genes. We demonstrate that the SETD1A/COMPASS complex cooperates with GR to mediate anti-inflammatory effects.}, }
@article {pmid33561470, year = {2021}, author = {Kabay, S and Kabay, SC}, title = {The Sustained Therapeutic Effects of Percutaneous Posterior Tibial Nerve Stimulation in the Treatment of Neurogenic Lower Urinary Tract Symptoms in Patients with Parkinson's Disease: 24-months Clinical and Urodynamic Results.}, journal = {Urology}, volume = {153}, number = {}, pages = {49-55}, doi = {10.1016/j.urology.2021.01.044}, pmid = {33561470}, issn = {1527-9995}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Lower Urinary Tract Symptoms/etiology/*therapy ; Male ; Middle Aged ; Parkinson Disease/complications ; Prospective Studies ; *Tibial Nerve ; Time Factors ; *Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Urinary Bladder, Neurogenic/etiology/*therapy ; Urodynamics ; }, abstract = {OBJECTIVE: To determine the sustained therapeutic effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment in Parkinson's disease patients with detrusor activity during 24 months.<br><br>METHODS: After 12 weeks therapy, PTNS was applied at 14-day intervals for 3 months, 21-day intervals for 3 months and 28-day intervals through 24 months. The patients completed a 3-day voiding diary and ICIQ-SF, OAB-V8, OAB-q SF questionnaires at 3[rd], 6[th], 9[th],12[th] and 24[th] month.<br><br>RESULTS: A total of 76 patients were enrolled in the study. Of these 44 (57.9%) were men and 32 (42.1%) women. The differences of compared parameters at baseline and at the end of 24 months were as follows; daytime frequency decreased by 4.6 voids daily, urge incontinence decreased by 4.2 episodes daily, urgency episodes decreased by 6.2 episodes daily, nocturia decreased by 2.4 voids (P <.001) and voided volume improved by a mean of 71.4 cc (P <.05). When compared with baseline significant improvements were seen in the volume at the first involuntary detrusor contraction (1st IDCV), maximum cystometric capacity (MCC), maximal detrusor pressure at first involuntary detrusor contraction (1st IDC Pdetmax), maximal detrusor pressure at MCC (MCC Pdetmax), detrusor pressure at maximal flow (PdetQmax) and post-void residual volume (PVR) after PTNS treatment at 3, 12, 24 months (P <.001 for each) except maximal flow rate (Qmax) value (P &#x2c3;.05).<br><br>CONCLUSIONS: These results have demonstrated the significant improvements both on voiding and urodynamic parameters under PTNS treatment with a tapering protocol for during 24-months in Parkinson's disease with detrusor activity.}, }
@article {pmid33554951, year = {2020}, author = {Şahin, S and Cakir, A and Gonul, II and Seckin, S and Uluoglu, O}, title = {Clinicopathological significance of insulin-like growth factor-1 receptor expression in breast cancer.}, journal = {Annali italiani di chirurgia}, volume = {91}, number = {}, pages = {583-591}, pmid = {33554951}, issn = {2239-253X}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Prognosis ; Receptor, IGF Type 1/*genetics ; }, abstract = {OBJECTIVE: Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer.<br><br>MATERIAL AND METHODS: IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically.<br><br>RESULTS: IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P<0.001), mostly HER2+ phenotype. IGF1R expression was found to be higher in invasive ductal carcinoma (IDC) than invasive lobular carcinoma (ILC) (P=0.036). Both IGF1R and Ki67 expression were negatively correlated with disease-free survival (DFS) (P=0.020, P=0.023, respectively) and overall survival (OS) [P<0.001, each] rates. The inverse association between IGF1R overexpression and OS rate was also supported by multivariate analyses (P=0.025).<br><br>CONCLUSIONS: Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis.<br><br>KEY WORDS: Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.}, }
@article {pmid33536239, year = {2021}, author = {Bühler, L and Maida, A and Vogl, ES and Georgiadi, A and Takacs, A and Kluth, O and Schürmann, A and Feuchtinger, A and von Toerne, C and Tsokanos, FF and Klepac, K and Wolff, G and Sakurai, M and Ekim Üstünel, B and Nawroth, P and Herzig, S}, title = {Lipocalin 13 enhances insulin secretion but is dispensable for systemic metabolic control.}, journal = {Life science alliance}, volume = {4}, number = {4}, pages = {}, pmid = {33536239}, issn = {2575-1077}, mesh = {Animals ; Biomarkers ; *Energy Metabolism ; Fluorescent Antibody Technique ; Gene Expression ; Gene Knockdown Techniques ; Glucose/metabolism ; *Insulin Secretion ; Islets of Langerhans/cytology/metabolism ; Lipid Metabolism ; Lipocalins/blood/*genetics/*metabolism ; Liver/metabolism ; Male ; Mice ; Obesity/etiology/metabolism ; }, abstract = {Members of the lipocalin protein family serve as biomarkers for kidney disease and acute phase inflammatory reactions, and are under preclinical development for the diagnosis and therapy of allergies. However, none of the lipocalin family members has made the step into clinical development, mostly due to their complex biological activity and the lack of in-depth mechanistic knowledge. Here, we show that the hepatokine lipocalin 13 (LCN13) triggers glucose-dependent insulin secretion and cell proliferation of primary mouse islets. However, inhibition of endogenous LCN13 expression in lean mice did not alter glucose and lipid homeostasis. Enhanced hepatic secretion of LCN13 in either diet-induced or genetic obesity led to no discernible impact on systemic glucose and lipid metabolism, neither in preventive nor therapeutic setting. Of note, loss or forced LCN13 hepatic secretion did not trigger any compensatory regulation of related lipocalin family members. Together, these data are in stark contrast to the suggested gluco-regulatory and therapeutic role of LCN13 in obesity, and imply complex regulatory steps in LCN13 biology at the organismic level mitigating its principal insulinotropic effects.}, }
@article {pmid33534078, year = {2021}, author = {Oses, G and Cases, C and Valduvieco, I and Farrús, B and Alonso, I and Caparrós, X and Mases, J and Muñoz-Guglielmetti, D and Biete, A and Castro, C and Escudero, E and Molina, M and Herreros, A and Saez, J and Mollà, M}, title = {Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {23}, number = {8}, pages = {1593-1600}, pmid = {33534078}, issn = {1699-3055}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*radiation effects ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/secondary/surgery ; Electrons/*therapeutic use ; Female ; Fibrosis/pathology ; Humans ; Intraoperative Period ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/prevention &amp; control ; Postoperative Complications ; Prospective Studies ; Radiation Injuries/pathology ; Radiotherapy Dosage ; Treatment Outcome ; }, abstract = {PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost.<br><br>MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12&#xa0;Gy boost was prescribed to 42 patients and 4 patients received a 20&#xa0;Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0.<br><br>RESULTS: The median age was 64.5&#xa0;years (40-90). The median follow-up was 62&#xa0;months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16&#xa0;mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema.<br><br>CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.}, }
@article {pmid33530236, year = {2021}, author = {Liu, N and Li, S and Jia, J and Qiao, Y and Li, Y}, title = {Advanced breast cancer with cachexia: A case report.}, journal = {Medicine}, volume = {100}, number = {4}, pages = {e24397}, pmid = {33530236}, issn = {1536-5964}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*complications/therapy ; Cachexia/etiology/*therapy ; Fatal Outcome ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; }, abstract = {RATIONALE: Cachexia is a clinically relevant syndrome in cancer that is associated with reduced tolerance to anticancer therapy, reduced quality of life, and reduced survival rates. Cachexia is most prevalent in pancreatic, gastric, colorectal, lung, and head and neck cancers. It is rarely documented in breast cancer patients.<br><br>PATIENT CONCERNS: In our case report of a breast cancer patient with bone metastasis who was monitored throughout the course of her treatment, we document the development of cachexia using image analyses in relation to her metastatic burden. In the 2-year period, from April 10, 2015, to February 09, 2017, she lost 16% of her baseline weight. During this time, she was repeatedly hospitalized for chest tightness, edema of both lower limbs, numbness and pain in the left lower extremity and backache.<br><br>DIAGNOSES: Our patient was a 46-year-old premenopausal woman when she was firstly diagnosed. Several years after surgery for invasive ductal carcinoma of the left breast, she had multiple systemic bone metastases (the thoracic spine, the ribs, etc), lung metastasis, bilateral axillary lymph node metastasis, and metastasis of the right neck lymph node in IV area.<br><br>INTERVENTIONS: The patient completed 6 cycles of postoperative adjuvant chemotherapy and long-term endocrine therapy after a radical mastectomy for breast cancer. During the fourth progression, 6 cycles of rescue chemotherapy were performed. Local lumbosacral radiotherapy, and lumbar surgery were carried out to relieve symptoms after several progressions.<br><br>OUTCOMES: She became extremely thin, weighing only 50&#x200a;kg at admission on July 23, 2018. This eventually led to multiple organ failure and death.<br><br>LESSONS: We noted a strong negative correlation between the abdominal muscle area and the metastatic tumor area at the second lumbar vertebral (L2) level. The monitoring of abdominal muscle wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and the extent of metastatic disease. This is especially true with breast cancer, where metastasis to bone is frequent. Our data from a computational tomography radiological quantification, may provide clinicians with early indications of the extent of cachexia in metastatic breast cancer patients.}, }
@article {pmid33513952, year = {2021}, author = {O'Rourke, JA and Graham, MA}, title = {Gene Expression Responses to Sequential Nutrient Deficiency Stresses in Soybean.}, journal = {International journal of molecular sciences}, volume = {22}, number = {3}, pages = {}, pmid = {33513952}, issn = {1422-0067}, support = {Project 5030-21220-006-00D//United States Department of Agriculture, Agricultural Research Service/ ; }, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant/genetics ; Iron/metabolism ; Nutrients/*metabolism ; Phosphates/metabolism ; Plant Roots/genetics/growth &amp; development ; Soybeans/*genetics/growth &amp; development/metabolism ; Stress, Physiological/*genetics ; Transcriptome/*genetics ; }, abstract = {Throughout the growing season, crops experience a multitude of short periods of various abiotic stresses. These stress events have long-term impacts on plant performance and yield. It is imperative to improve our understanding of the genes and biological processes underlying plant stress tolerance to mitigate end of season yield loss. The majority of studies examining transcriptional changes induced by stress focus on single stress events. Few studies have been performed in model or crop species to examine transcriptional responses of plants exposed to repeated or sequential stress exposure, which better reflect field conditions. In this study, we examine the transcriptional profile of soybean plants exposed to iron deficiency stress followed by phosphate deficiency stress (-Fe-Pi). Comparing this response to previous studies, we identified a core suite of genes conserved across all repeated stress exposures (-Fe-Pi, -Fe-Fe, -Pi-Pi). Additionally, we determined transcriptional response to sequential stress exposure (-Fe-Pi) involves genes usually associated with reproduction, not stress responses. These findings highlight the plasticity of the plant transcriptome and the complexity of unraveling stress response pathways.}, }
@article {pmid33495219, year = {2021}, author = {Tewari, SG and Rajaram, K and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Metabolic Survival Adaptations of Plasmodium falciparum Exposed to Sublethal Doses of Fosmidomycin.}, journal = {Antimicrobial agents and chemotherapy}, volume = {65}, number = {4}, pages = {}, pmid = {33495219}, issn = {1098-6596}, support = {R01 AI065853/AI/NIAID NIH HHS/United States ; R01 AI125534/AI/NIAID NIH HHS/United States ; T32 AI007417/AI/NIAID NIH HHS/United States ; }, mesh = {*Antimalarials/therapeutic use ; *Apicoplasts ; *Fosfomycin/analogs &amp; derivatives/pharmacology/therapeutic use ; Humans ; *Malaria, Falciparum/drug therapy ; Plasmodium falciparum/genetics ; }, abstract = {The malaria parasite Plasmodium falciparum contains the apicoplast organelle that synthesizes isoprenoids, which are metabolites necessary for posttranslational modification of Plasmodium proteins. We used fosmidomycin, an antibiotic that inhibits isoprenoid biosynthesis, to identify mechanisms that underlie the development of the parasite's adaptation to the drug at sublethal concentrations. We first determined a concentration of fosmidomycin that reduced parasite growth by ∼50% over one intraerythrocytic developmental cycle (IDC). At this dose, we maintained synchronous parasite cultures for one full IDC and collected metabolomic and transcriptomic data at multiple time points to capture global and stage-specific alterations. We integrated the data with a genome-scale metabolic model of P. falciparum to characterize the metabolic adaptations of the parasite in response to fosmidomycin treatment. Our simulations showed that, in treated parasites, the synthesis of purine-based nucleotides increased, whereas the synthesis of phosphatidylcholine during the trophozoite and schizont stages decreased. Specifically, the increased polyamine synthesis led to increased nucleotide synthesis, while the reduced methyl-group cycling led to reduced phospholipid synthesis and methyltransferase activities. These results indicate that fosmidomycin-treated parasites compensate for the loss of prenylation modifications by directly altering processes that affect nucleotide synthesis and ribosomal biogenesis to control the rate of RNA translation during the IDC. This also suggests that combination therapies with antibiotics that target the compensatory response of the parasite, such as nucleotide synthesis or ribosomal biogenesis, may be more effective than treating the parasite with fosmidomycin alone.}, }
@article {pmid33484951, year = {2021}, author = {Lemmer, IL and Willemsen, N and Hilal, N and Bartelt, A}, title = {A guide to understanding endoplasmic reticulum stress in metabolic disorders.}, journal = {Molecular metabolism}, volume = {47}, number = {}, pages = {101169}, pmid = {33484951}, issn = {2212-8778}, mesh = {Adipocytes/metabolism ; Animals ; Autophagy ; Diabetes Mellitus, Type 2/metabolism ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress/*physiology ; Humans ; Inflammation/metabolism ; Insulin Resistance ; Lipid Metabolism ; Metabolic Diseases/*metabolism ; Obesity/metabolism ; Proteins/metabolism ; Ubiquitin ; Unfolded Protein Response ; }, abstract = {BACKGROUND: The global rise of metabolic disorders, such as obesity, type 2 diabetes, and cardiovascular disease, demands a thorough molecular understanding of the cellular mechanisms that govern health or disease. The endoplasmic reticulum (ER) is a key organelle for cellular function and metabolic adaptation and, therefore disturbed ER function, known as "ER stress," is a key feature of metabolic disorders.<br><br>SCOPE OF REVIEW: As ER stress remains a poorly defined phenomenon, this review provides a general guide to understanding the nature, etiology, and consequences of ER stress in metabolic disorders. We define ER stress by its type of stressor, which is driven by proteotoxicity, lipotoxicity, and/or glucotoxicity. We discuss the implications of ER stress in metabolic disorders by reviewing evidence implicating ER phenotypes and organelle communication, protein quality control, calcium homeostasis, lipid and carbohydrate metabolism, and inflammation as key mechanisms in the development of ER stress and metabolic dysfunction.<br><br>MAJOR CONCLUSIONS: In mammalian biology, ER is a phenotypically and functionally diverse platform for nutrient sensing, which is critical for cell type-specific metabolic control by hepatocytes, adipocytes, muscle cells, and neurons. In these cells, ER stress is a distinct, transient state of functional imbalance, which is usually resolved by the activation of adaptive programs such as the unfolded protein response (UPR), ER-associated protein degradation (ERAD), or autophagy. However, challenges to proteostasis also impact lipid and glucose metabolism and vice versa. In the ER, sensing and adaptive measures are integrated and failure of the ER to adapt leads to aberrant metabolism, organelle dysfunction, insulin resistance, and inflammation. In conclusion, the ER is intricately linked to a wide spectrum of cellular functions and is a critical component in maintaining and restoring metabolic health.}, }
@article {pmid33478862, year = {2021}, author = {Zhang, H and Ge, XY and Qiao, HQ}, title = {Analysis of prognostic risk factors in 3427 patients with invasive ductal carcinoma of breast: Results based on the SEER database.}, journal = {Asian journal of surgery}, volume = {44}, number = {3}, pages = {577-579}, doi = {10.1016/j.asjsur.2020.12.014}, pmid = {33478862}, issn = {0219-3108}, mesh = {Breast/pathology ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Neoplasm Staging ; Prognosis ; Risk Factors ; }, }
@article {pmid33468810, year = {2020}, author = {Ishihara, S and Kashiwagi, S and Asano, Y and Kawano, Y and Kouhashi, R and Yabumoto, A and Tauchi, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Dermatitis Caused by Metronidazole Gel That Needed to Be Differentiated from Breast Cancer Skin Metastasis].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {47}, number = {13}, pages = {2089-2091}, pmid = {33468810}, issn = {0385-0684}, mesh = {Aged ; Axilla ; *Breast Neoplasms/drug therapy ; *Dermatitis/drug therapy/etiology ; Female ; Humans ; Metronidazole ; Trastuzumab/adverse effects ; }, abstract = {Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.}, }
@article {pmid33462507, year = {2021}, author = {Gao, R and Bai, S and Henderson, YC and Lin, Y and Schalck, A and Yan, Y and Kumar, T and Hu, M and Sei, E and Davis, A and Wang, F and Shaitelman, SF and Wang, JR and Chen, K and Moulder, S and Lai, SY and Navin, NE}, title = {Delineating copy number and clonal substructure in human tumors from single-cell transcriptomes.}, journal = {Nature biotechnology}, volume = {39}, number = {5}, pages = {599-608}, pmid = {33462507}, issn = {1546-1696}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA240526/CA/NCI NIH HHS/United States ; T32 CA217789/CA/NCI NIH HHS/United States ; R01 CA236864/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Pancreatic Ductal/*genetics/pathology ; *Clonal Evolution ; DNA Copy Number Variations/*genetics ; Gene Expression Regulation, Neoplastic ; Genomics/trends ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation/genetics ; Single-Cell Analysis ; Transcriptome/*genetics ; Tumor Microenvironment/genetics ; }, abstract = {Single-cell transcriptomic analysis is widely used to study human tumors. However, it remains challenging to distinguish normal cell types in the tumor microenvironment from malignant cells and to resolve clonal substructure within the tumor. To address these challenges, we developed an integrative Bayesian segmentation approach called copy number karyotyping of aneuploid tumors (CopyKAT) to estimate genomic copy number profiles at an average genomic resolution of 5 Mb from read depth in high-throughput single-cell RNA sequencing (scRNA-seq) data. We applied CopyKAT to analyze 46,501 single cells from 21 tumors, including triple-negative breast cancer, pancreatic ductal adenocarcinoma, anaplastic thyroid cancer, invasive ductal carcinoma and glioblastoma, to accurately (98%) distinguish cancer cells from normal cell types. In three breast tumors, CopyKAT resolved clonal subpopulations that differed in the expression of cancer genes, such as KRAS, and signatures, including epithelial-to-mesenchymal transition, DNA repair, apoptosis and hypoxia. These data show that CopyKAT can aid in the analysis of scRNA-seq data in a variety of solid human tumors.}, }
@article {pmid33462216, year = {2021}, author = {Deshpande, D and Agarwal, N and Fleming, T and Gaveriaux-Ruff, C and Klose, CSN and Tappe-Theodor, A and Kuner, R and Nawroth, P}, title = {Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {426}, pmid = {33462216}, issn = {2041-1723}, mesh = {Aged ; Aged, 80 and over ; Animals ; Diabetes Mellitus, Experimental/chemically induced/*complications ; Diabetic Neuropathies/etiology/*pathology ; Female ; Ganglia, Spinal/cytology/pathology ; Humans ; Lysosomes ; Male ; Mice ; Mice, Knockout ; Nociception/*physiology ; Pro-Opiomelanocortin/*deficiency/genetics ; Proteolysis ; Receptors, Opioid, mu/genetics/metabolism ; Sensory Receptor Cells/*pathology ; Streptozocin/toxicity ; }, abstract = {Painful neuropathy is a frequent complication in diabetes. Proopiomelanocortin (POMC) is an endogenous opioid precursor peptide, which plays a protective role against pain. Here, we report dysfunctional POMC-mediated antinociception in sensory neurons in diabetes. In streptozotocin-induced diabetic mice the Pomc promoter is repressed due to increased binding of NF-kB p50 subunit, leading to a loss in basal POMC level in peripheral nerves. Decreased POMC levels are also observed in peripheral nervous system tissue from diabetic patients. The antinociceptive pathway mediated by POMC is further impaired due to lysosomal degradation of μ-opioid receptor (MOR). Importantly, the neuropathic phenotype of the diabetic mice is rescued upon viral overexpression of POMC and MOR in the sensory ganglia. This study identifies an antinociceptive mechanism in the sensory ganglia that paves a way for a potential therapy for diabetic neuropathic pain.}, }
@article {pmid33445940, year = {2020}, author = {Bartovská, Z and Andrle, F and Beran, O and Zlámal, M and Řezáč, D and Murinova, I and Holub, M}, title = {Data from the first wave of Covid-19 from the Central Military Hospital, Prague, Czech Republic.}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {69}, number = {4}, pages = {164-171}, pmid = {33445940}, issn = {1210-7913}, mesh = {COVID-19/diagnosis/*epidemiology/therapy ; Czech Republic/epidemiology ; Female ; Hospitals, Military ; Humans ; Male ; Middle Aged ; Retrospective Studies ; United States ; }, abstract = {AIMS: To process data from the first wave of Covid-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) collected in the Infectious Diseases Clinic (IDC) of the First Faculty of Medicine and Central Military Hospital, Prague. To analyse some clinical, diagnostic and therapeutic aspects of Covid-19 in the context of the Czech Republic and to compare them with the data from the most recent literature.<br><br>PATIENTS AND METHODS: This retrospective study analysed data on patients admitted to the IDC between 12 March 2020 and 5 May 2020. The study cohort included 53 patients with Covid-19, 25 females and 28 males, with an average age of 57 years. The parameters analysed were clinical symptoms, average length of hospital stay, complications, and death. Additional data concerned the age, weight, smoking habits, history of comorbidities, and selected laboratory results.&#xa0; These data were compared between groups of patients differing in severity of the course of Covid-19. Finally, imaging findings, serology results, and therapy outcomes were studied. Statistical analysis was performed using the SigmaStat software.<br><br>RESULTS: Eleven (20.8%) patients had a mild course of the disease, 16 (30.2%) patients had a moderate course, 22 (41.5%) patients had a severe course, and four (7.5%) patients had a critical course. The study patients presented with the following clinical symptoms: fever in 88.5% of cases, cough in 84.6% of cases, difficulty breathing in 77.4% of cases, diarrhoea in 23.1% of cases, chest pain in 17.3% of cases, and anosmia in 11.5% of cases. The average length of hospital stay was eight days. The most common complication was a bacterial superinfection, reported in 17 (32.1%) study patients. The overall case fatality rate for Covid-19 in our study was 5.7%. The average age of the study cohort was 57 years, and patients with a severe course of the disease were of older average age than those with a less severe course of the disease (p < 0.05). The predominant comorbidities were hypertension and diabetes mellitus. The analysis of the baseline laboratory data showed significant differences between the groups of patients differing in severity of the course of Covid-19 in CRP, procalcitonin, and d-dimers but not in lymphocyte count. High resolution computed tomography (HRCT) scan of the lungs was performed in 22 patients, and 21 of them had typical findings for Covid-19. The average MuLBSTA score for Covid-19 pneumonia severity in our study cohort was 11.5 points and was not associated with the severity of the course of the disease. Serology tests were performed in 43 study patients, with 29 (67.4%) of them turning out positive in the first test and other five (11.6%) testing positive when retested. Hydroxychloroquine (HCQ) was given experimentally as monotherapy or in combination with azithromycin (AZI) to 24 (45.3%) patients. Two patients on HCQ therapy also received inosinum pranobexum (isoprinosine) for severe lymphopenia, one patient received convalescent plasma, six patients were given AZI alone, and one patient was treated with inosinum pranobexum alone. Altogether 37.7% of study patients were prescribed other antibiotics for confirmed or suspected bacterial superinfection. Standard clinical and pharmaceutical care was provided to patients with particular focus on the safety of off-label drug use. HCQ was with drawn in three patients due to a prolonged corrected QT interval (QTc).<br><br>CONCLUSIONS: In the first wave of the SARS-CoV-2 epidemic, our study patients showed comorbidities and risk factors which are consistent with the international literature, but the course of the disease was mostly moderate to severe, with a low proportion of critically ill patients and fatal outcomes. As soon as new information became available, new diagnostic and therapeutic options were introduced into routine practice. Based on our experience, we are well prepared for a possible second wave of SARS-CoV-2 in terms of the diagnostics, but the therapeutic options still remain very limited.}, }
@article {pmid33443130, year = {2021}, author = {Trinh, A and Gil Del Alcazar, CR and Shukla, SA and Chin, K and Chang, YH and Thibault, G and Eng, J and Jovanović, B and Aldaz, CM and Park, SY and Jeong, J and Wu, C and Gray, J and Polyak, K}, title = {Genomic Alterations during the In Situ to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {4}, pages = {623-635}, pmid = {33443130}, issn = {1557-3125}, support = {R35 CA197623/CA/NCI NIH HHS/United States ; U01 CA195469/CA/NCI NIH HHS/United States ; U54 CA209988/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; U24 CA224331/CA/NCI NIH HHS/United States ; R50 CA211482/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*immunology ; Carcinoma, Ductal, Breast/*genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*immunology ; Female ; Genomics ; Humans ; Immune System ; }, abstract = {The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions. Immune "hot" and "cold" tumors can arise as early as DCIS and are subtype-specific. Topologic analysis showed a similar degree of pan-leukocyte-tumor mixing in both DCIS and IDC but differ when assessing specific immune subpopulations such as CD4 T cells and CD68 macrophages. Tumor-specific copy-number aberrations in MHC-I presentation machinery and losses in 3p, 4q, and 5p are associated with differences in immune signaling in estrogen receptor (ER)-negative IDC. Common oncogenic hotspot mutations in genes including TP53 and PIK3CA are predicted to be neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition, and are associated with differences in immune signaling. We highlight both tumor and immune-specific changes in the transition of pure DCIS to IDC, including genetic changes in tumor cells that may have a role in modulating immune function and assist in immune escape, driving the transition to IDC. IMPLICATIONS: We demonstrate that the in situ to IDC evolutionary bottleneck is shaped by both tumor and immune cells.}, }
@article {pmid33437736, year = {2020}, author = {Abdolahi, M and Salehi, M and Shokatian, I and Reiazi, R}, title = {Artificial intelligence in automatic classification of invasive ductal carcinoma breast cancer in digital pathology images.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {34}, number = {}, pages = {140}, pmid = {33437736}, issn = {1016-1430}, abstract = {Background: Breast cancer is one of the most causes of death in women. Early diagnosis and detection of Invasive Ductal Carcinoma (IDC) is an important key for the treatment of IDC. Computer-aided approaches have great potential to improve diagnosis accuracy. In this paper, we proposed a deep learning-based method for the automatic classification of IDC in whole slide images (WSI) of breast cancer. Furthermore, different types of deep neural networks training such as training from scratch and transfer learning to classify IDC were evaluated. Methods: In total, 277524 image patches with 50×50-pixel size form original images were used for model training. In the first method, we train a simple convolutional neural network (named it baseline model) on these images. In the second approach, we used the pre-trained VGG-16 CNN model via feature extraction and fine-tuning for the classification of breast pathology images. Results: Our baseline model achieved a better result for the automatic classification of IDC in terms of F-measure and accuracy (83%, 85%) in comparison with original paper on this data set and achieved a comparable result with a new study that introduced accepted-rejected pooling layer. Also, transfer learning via feature extraction yielded better results (81%, 81%) in comparison with handcrafted features. Furthermore, transfer learning via feature extraction yielded better classification results in comparison with the baseline model. Conclusion: The experimental results demonstrate that using deep learning approaches yielded better results in comparison with handcrafted features. Also, using transfer learning in histopathology image analysis yielded significant results in comparison with training from scratch in much less time.}, }
@article {pmid33433431, year = {2021}, author = {Xia, Y and Liu, X and Li, W and Zhu, Y}, title = {Potential role of significant GATA3 mutation in male breast cancer responding to endocrine therapy: A case report.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {1}, pages = {161-164}, doi = {10.4103/IJPM.IJPM_160_19}, pmid = {33433431}, issn = {0974-5130}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast/pathology ; Breast Neoplasms, Male/diagnostic imaging/*drug therapy/*genetics/secondary ; Endocrine System/drug effects ; GATA3 Transcription Factor/*genetics ; Humans ; Male ; Middle Aged ; *Mutation ; Positron Emission Tomography Computed Tomography ; }, abstract = {A 60-year-old Chinese male with a hard mass, pressure pain, and ulcerous skin under his left axilla was first diagnosed with apocrine carcinoma, most likely metastasis from breast cancer. PET/CT scan detected multiple bone metastasis and enlarged lymph nodes at left axilla, mediastinal area 7, and left pulmonary hilus. Lumpectomy was performed to remove the mass followed by chemotherapy and radiotherapy against focal bone metastasis, left axillary lesion, and left subcutaneous chest wall. PET/CT examination showed progressive disease after the completion of the treatments. Two nontender hard nodules were noticed on the patient's left upper arm and multiple immobile nodules were palpated under his left axillary skin. Immunohistochemistry (HER2++, ER+, PR+, AR-) of the biopsy tissue combined with histopathology indicated invasive ductal carcinoma with neuroendocrine differentiation. Metastatic Luminal B subtype breast cancer was preferred. Anti-estrogen endocrine therapy was then performed and PET/CT scan showed partial remission after one month's fulvestrant administration. Two significant somatic mutations, AR R616H and GATA3 S408Afs*99, were detected in the biopsy tissue by next-generation sequencing. GATA3 is associated with estrogen receptor signaling and was identified as a driver gene of female breast cancer. However, the function of GATA3 in male breast cancer remains controversial. Report of this case hopefully will contribute to exploring the role of GATA3 mutation in molecular mechanisms and endocrine therapy of male breast cancer.}, }
@article {pmid33433407, year = {2021}, author = {Farrag, MS and Anter, AH and Farrag, NS and Ibrahiem, AT}, title = {"Switch of E-Cadherin to N-Cadherin expression in different molecular subtypes of breast invasive duct carcinomas and its correlation with clinicopathological features".}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {1}, pages = {38-46}, doi = {10.4103/IJPM.IJPM_924_19}, pmid = {33433407}, issn = {0974-5130}, mesh = {Antigens, CD/*genetics ; Biomarkers, Tumor ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/classification/*genetics/*pathology/secondary ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paraffin Embedding ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: In breast cancer, metastasis and recurrence is the main culprit in treatment failure. This study aimed to explore the role of E-cadherin/N-cadherin Switch in progression, spread and metastasis in breast invasive duct carcinoma.<br><br>MATERIALS AND METHODS: A cross-sectional study on 118 formalinfixed paraffinembedded mastectomy specimens of invasive breast duct carcinoma. Primary antibodies for E-cadherin (monoclonal, clone HECD-1; Zymed Laboratories; dilution 1:600) and N-cadherin (monoclonal, clone 3B9; Zymed Laboratories, Inc., Montrouge, France; dilution 1:200) were applied for all cases. The study revealed that E-cadherin high expression was significantly associated with advanced TNM clinical stage (P = 0.021), and nodal metastasis (P < 0.001). High expression of N-cadherin was significantly positively correlated with tumor sizes (P < 0.00), advanced clinical stage (P < 0.00), and nodal metastasis (P < 0.008). Mean OS was 39.99 months in cases with negative expression versus 41.8 months in cases with positive expression. Mean DFS in cases with positive E. cadh expression was 41.89 months was higher than mean DFS in cases with negative E. cadh expression which was 40.52 months, but it showed no statistical significance (P = 0.57).<br><br>CONCLUSIONS/SIGNIFICANCE: This study demonstrated that loss of E-cadherin and gain of N-cadherin promotes invasion, migration, and metastasis in invasive ductal carcinoma cells. Importantly, these findings may exploit new cancer therapies using N-cadherin antagonists.}, }
@article {pmid33429799, year = {2021}, author = {Karatas, M and Zengel, B and Durusoy, R and Tasli, F and Adibelli, Z and Simsek, C and Uslu, A}, title = {Clinicopathologic features of single bone metastasis in breast cancer.}, journal = {Medicine}, volume = {100}, number = {1}, pages = {e24164}, pmid = {33429799}, issn = {1536-5964}, mesh = {Adult ; Aged ; Bone Neoplasms/*classification/pathology ; Bone and Bones/*pathology/physiopathology ; Breast Neoplasms/*complications ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis/*physiopathology ; }, abstract = {The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.}, }
@article {pmid33428505, year = {2021}, author = {Nevagi, RJ and Good, MF and Stanisic, DI}, title = {Plasmodium infection and drug cure for malaria vaccine development.}, journal = {Expert review of vaccines}, volume = {20}, number = {2}, pages = {163-183}, doi = {10.1080/14760584.2021.1874923}, pmid = {33428505}, issn = {1744-8395}, mesh = {Animals ; Antigens, Protozoan/immunology ; Antimalarials/administration &amp; dosage ; Humans ; Malaria/immunology/parasitology/*prevention &amp; control ; Malaria Vaccines/*administration &amp; dosage/immunology ; Plasmodium/*immunology/parasitology ; }, abstract = {Introduction: Despite decades of research into the development of a vaccine to combat the malaria parasite, a highly efficacious malaria vaccine is not yet available. Different whole parasite-based vaccine approaches, including deliberate Plasmodium infection and drug cure (IDC), have been evaluated in pre-clinical and early phase clinical trials. The advantage of whole parasite vaccines is that they induce immune responses against multiple parasite antigens, thus lowering the impact of antigenic diversity. Deliberate Plasmodium IDC, as a vaccine approach, involves administering infectious, live parasites in combination with an anti-malarial drug, which controls the infection and enables induction of protective immune responses.}, }
@article {pmid33421821, year = {2021}, author = {Hoshina, H and Takei, H and Sakatani, T and Naito, Z}, title = {CDX2-positive breast cancer presented with axillary lymph node metastases: A case report.}, journal = {Cancer treatment and research communications}, volume = {26}, number = {}, pages = {100300}, doi = {10.1016/j.ctarc.2020.100300}, pmid = {33421821}, issn = {2468-2942}, mesh = {Axilla ; Biopsy, Large-Core Needle ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*diagnosis/pathology/therapy ; CDX2 Transcription Factor/analysis/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Ultrasonography ; }, abstract = {BACKGROUND: The caudal type homeobox 2 transcription factor (CDX2) is a specific and sensitive marker for intestinal carcinoma, but usually not expressed in breast cancer. In CDX2-positive metastatic cancer of occult primary, the origin is highly suspicious of an enteric carcinoma.<br><br>CASE PRESENTATION: A 50-year-old woman complained of enlarged lymph nodes (LNs) in the right axilla. Mammography and ultrasonography scans showed no abnormal findings in her breasts. Core needle biopsy (CNB) revealed metastatic adenocarcinoma. Immunohistochemical staining was positive for CDX2 intensely. The primary tumor was suspicious of intestinal adenocarcinoma. A dynamic contrast-enhanced magnetic resonance imaging scan revealed an accentuated lesion which was detected using a second-look ultrasound, and diagnosed invasive ductal carcinoma by CNB. A partial mastectomy of the right breast with level I and II axillary LN dissection was performed. A few cells of primary cancer were expressed CDX2 and estrogen receptor. The final pathological diagnosis was T1bN3aM0 stage IIIC. The fluorescent double staining showed that CDX2 simultaneously expressed on the Ki67 positive cells of metastatic tumors. The adjuvant treatment included chemotherapy and radiation, followed by tamoxifen administration. The patient survived without any recurrences over the following 36 months.<br><br>CONCLUSIONS: We report a rare case of CDX2-positive metastatic breast cancer in the axillary LNs. As some literatures reported vitamin D pathways induced cancer cell apoptosis and inhibition, these metastatic cells of our case might play the effort of autoregulation of inhibiting progression.}, }
@article {pmid33416185, year = {2021}, author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD}, title = {miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {45}, number = {2}, pages = {706-716}, pmid = {33416185}, issn = {1791-2431}, mesh = {Animals ; Breast/pathology/surgery ; Breast Neoplasms/*genetics/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics/mortality/secondary/surgery ; Cell Line, Tumor ; DNA-Binding Proteins/*genetics ; Disease Progression ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mastectomy ; Mice ; MicroRNAs/genetics/*metabolism ; Neoplasm Recurrence, Local/*epidemiology/genetics ; RNA-Binding Proteins/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {MicroRNA (miRNA/mir)‑490‑3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR‑490‑3p has been shown to function as a tumor suppressor and promoter in a context‑dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR‑490‑3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor‑adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA‑MB‑231, compared to the non‑metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA‑MB‑468. The expression of miR‑490‑3p was induced following transforming growth factor (TGF)‑β‑induced epithelial‑to‑mesenchymal transition (EMT) in MCF10A cells. Gain‑and loss‑of‑function assays revealed that the expression of miR‑490‑3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA‑MB‑468 and MDA‑MB‑231 cells. The knockdown of miR‑490‑3p expression in MDA‑MB‑231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR‑490‑3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR‑490‑3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR‑490‑3p expression in patients with IDC compared to those with DCIS. The expression of miR‑490‑3p was negatively associated with both overall and disease‑free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro‑metastatic role of miR‑490‑3p in IDC, establishing it as a biomarker for disease progression in these patients.}, }
@article {pmid33415472, year = {2022}, author = {Zimmerman-Brenner, S and Pilowsky-Peleg, T and Rachamim, L and Ben-Zvi, A and Gur, N and Murphy, T and Fattal-Valevski, A and Rotstein, M}, title = {Group behavioral interventions for tics and comorbid symptoms in children with chronic tic disorders.}, journal = {European child &amp; adolescent psychiatry}, volume = {31}, number = {4}, pages = {637-648}, pmid = {33415472}, issn = {1435-165X}, mesh = {Behavior Therapy ; Child ; Comorbidity ; Humans ; Severity of Illness Index ; *Tic Disorders/complications/therapy ; *Tics/therapy ; *Tourette Syndrome/complications/therapy ; }, abstract = {Exposure and Response Prevention (ERP), Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT) are effective in reducing tic severity. ERP and HRT have recently gained primary support in a group setting, while CBIT has not been examined similarly. We compared the efficacy of group-CBIT to group-Educational Intervention for Tics (group-EIT) for tics and comorbid symptoms. Children with Tourette Syndrome (TS) or Chronic Tic Disorder (CTD) were randomized to group-CBIT or group-EIT. Tics and comorbid symptoms were assessed in forty-six children pre- and postintervention, and 3-month later. Yale Global Tic Severity Scale (YGTSS) Motor tic severity decreased following both interventions, and was maintained at follow-up for group-CBIT only. The Parent Tic Questionnaire (PTQ) showed significant decrease in total and motor tic severity following group-CBIT only, a gain maintained three months later. YGTSS impairment score decreased following both interventions and was maintained at follow-up. YGTSS vocal tic severity score increased following both interventions, and then decreased significantly at follow up. Co-morbid symptoms including anxiety, behavioral problems, and aggressive behavior decreased following both interventions. Children with behavioral problems benefitted less while children with higher intellectual ability benefit more from intervention. Both group interventions showed efficacy in reducing tic impairment and comorbid symptoms. Group-CBIT was superior to group-EIT in reducing motor tic severity at 3-month follow-up, showing an advantage for tic-focused treatment. Based on the PTQ, group-CBIT was superior to group-EIT in reducing motor, vocal, and total tic scores, a gain maintained three months later. Clinical trial registry information-Group Intervention for Children with Chronic Tics Syndrome: CBIT vs Psychoeducational Intervention URL: http://clinicaltrials.gov , Identifier: NCT02407951, http://www.controlled-trials.com).}, }
@article {pmid33413755, year = {2020}, author = {Zeng, XQ and Jiang, SS and Peng, YY and Liu, MF and Ye, CS and Dong, JY}, title = {Trastuzumab-Induced Severe Thrombocytopenia:A Case Report and Literature Review.}, journal = {Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih}, volume = {35}, number = {4}, pages = {377-382}, doi = {10.24920/003799}, pmid = {33413755}, issn = {1001-9294}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Platelet Count ; Thrombocytopenia/blood/*chemically induced/drug therapy ; Trastuzumab/*adverse effects ; }, abstract = {We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×10[9]/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.}, }
@article {pmid33402291, year = {2021}, author = {Mnejja, M and Kallel, S and Thabet, W and Regaieg, M and Kallel, R and Boudawara, T and Daoud, J and Hammami, B and Charfeddine, I}, title = {[Ductal carcinomas of the parotid gland].}, journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique}, volume = {25}, number = {2}, pages = {155-160}, doi = {10.1016/j.canrad.2020.06.034}, pmid = {33402291}, issn = {1769-6658}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology/secondary/*surgery ; Carcinoma, Ductal, Breast/pathology/secondary ; Facial Nerve/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neck Dissection/statistics &amp; numerical data ; Neoplasm Invasiveness ; Parotid Gland/diagnostic imaging/surgery ; Parotid Neoplasms/diagnostic imaging/pathology/secondary/*surgery ; Prognosis ; Retrospective Studies ; Skin Neoplasms/pathology ; }, abstract = {PURPOSE: To describe the clinical, therapeutic and prognostic features of ductal carcinomas of the parotid gland.<br><br>MATERIAL AND METHODS: Five patients with ductal carcinoma of the parotid gland (primary and secondary carcinoma) treated, between 2007 and 2019, in our ENT department, were reviewed.<br><br>RESULTS: Four men and one woman were included. The mean age was 61,4 years. One patient had a history of an invasive ductal carcinoma of the breast. Four patients consulted for swelling in the parotid region. One patient referred to our department for dysfunction of facial nerve. Skin invasion was found in one case. Four patients underwent total parotidectomy with sacrifice of the facial nerve (three cases). One patient underwent extended parotidectomy involving the skin. An ipsilateral selective neck dissection was performed in four cases. One patient had a parotid gland biopsy. Ductal carcinoma was primary in four cases and metastatic from breast origin in one case. Four patients were treated with postoperative radiotherapy. Remission was obtained in three cases. One patient had a local and meningeal recurrence. The patient with metastatic carcinoma had pulmonary, bone, hepatic and brain progression.<br><br>CONCLUSION: Ductal carcinoma is a rare and aggressive tumor of the parotid gland. It can be primary or secondary. The treatment is based on surgery and radiotherapy. The prognosis is poor.}, }
@article {pmid33391657, year = {2020}, author = {De Pauw, V and Navez, J and Holbrechts, S and Lemaitre, J}, title = {Acute appendicitis as an unusual cause of invasive ductal breast carcinoma metastasis.}, journal = {Journal of surgical case reports}, volume = {2020}, number = {12}, pages = {rjaa535}, pmid = {33391657}, issn = {2042-8812}, abstract = {Acute appendicitis is one of the most common causes of abdominal pain at the emergency room. In rare cases, it can be caused by malignancy, even metastatic lesions from extra-abdominal neoplasia. Herein, we report a case of a 64-year-old female with a history of invasive ductal carcinoma of the breast treated by chemotherapy, surgery, radiotherapy and hormonotherapy, relapsing several years later as a bone and a pleura metastasis successfully cured by locoregional therapy and hormonal treatment. She presented with acute abdominal pain without signs of peritonitis. Abdominal computed tomodensitometry showed sign of appendicitis. Therefore, laparoscopic exploration and appendicectomy was performed. During surgery, multiple peritoneal nodules were found and harvested. Pathology showed metastatic nodules of invasive ductal breast carcinoma, including in the appendicular wall, concluding to peritoneal carcinomatosis. The postoperative course was uneventful, but the patient died 1 year later after refusing anticancer treatment.}, }
@article {pmid33371069, year = {2020}, author = {Yue, L and Wentao, L and Xin, Z and Jingjing, H and Xiaoyan, Z and Na, F and Tonghui, M and Dalin, L}, title = {Human epidermal growth factor receptor 2-positive metastatic breast cancer with novel epidermal growth factor receptor -ZNF880 fusion and epidermal growth factor receptor E114K mutations effectively treated with pyrotinib: A case report.}, journal = {Medicine}, volume = {99}, number = {51}, pages = {e23406}, pmid = {33371069}, issn = {1536-5964}, mesh = {Acrylamides/administration &amp; dosage/*therapeutic use ; Adult ; Aminoquinolines/administration &amp; dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; ErbB Receptors/*genetics/*metabolism ; Female ; Humans ; Mastectomy ; Neoplasm Metastasis ; Neoplasm Staging ; Receptor, ErbB-2/antagonists &amp; inhibitors/metabolism ; }, abstract = {INTRODUCTION: In about 15% to 20% of breast cancer cases, human epidermal growth factor receptor 2 (HER2) over-expression or gene-amplification is associated with poor prognosis. Thanks to the development of target therapies, HER2 positive patients can be managed using HER2-targeting drugs. There are several kinds ofHER2 inhibitors, such as trastuzumab, lapatinib, and pyrotinib. Pyrotinib which exert different functions, of note, the latest generation of the drug, is an irreversible small-molecule tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) (HER1) and/or HER2 and/or HER4. Both lapatinib and pyrotinib potentially target EGFR and/or HER2, but in some instances, induces different responses of patients with EGFR and/or HER2 mutations. This is attributed to the different mutations in EGFR and HER2 genes, which may form distinct types of HER2 dimers, with different binding capacities to drugs.<br><br>PATIENT CONCERNS: Five years ago, a patient underwent a radical mastectomy in an external hospital. Results of the resection histopathology revealed an invasive ductal carcinoma, pT3N0M0, stage IIB, HER2 positive. The lady patient received 6 cycles of adjuvant chemotherapy and was subjected to adjuvant trastuzumab therapy for 1 year. After a regular 1-year follow-up and in March 2018, she complained of chest pain and visited our hospital. We diagnosed her with metastatic breast cancer, positive for HER2.<br><br>DIAGNOSIS: positron emission tomography/computed tomography showed multiple metastases in the lung and sternum, while the breast lesions did not progress, the curative effect of which we evaluated as a progressive disease. Then, lapatinib integrated with chemotherapy was administered to the patient. After 5 cycles of the treatment, the patient experienced lower back pain. Through CT examination, it was revealed that she had multiple metastases in the lung and sternum, in addition to new metastases in the lumbar spine and right lobe of the liver. Moreover, magnetic resonance imaging revealed multiple metastases in the brain, and the disease further progressed. The results of circulating tumor DNA assays showed that other than HER2 amplification, novel EGFR-ZNF880 fusion and EGFR E114K mutations developed.<br><br>INTERVENTIONS: The patient was administered with a combination of pyrotinib with chemotherapy.<br><br>OUTCOMES: After 2 months of pyrotinib treatment, the metastases of the lung, sternum, lumbar spine, and right lobe of the liver disappeared. Also, the size of the brain metastases reduced while bone metastases were relieved. The curative effect was evaluated as a partial response. Following the results of circulating tumor DNA assays, HER2 amplification, EGFR-ZNF880 fusion, and EGFR E114K mutations disappeared. However, since a small lesion was present in the brain, the patient was subjected to radiotherapy in the head. Notably, after 9 months treatment with pyrotinib, enhanced CT indicated that tumors in the breast, liver, both lungs, brain, and bone were under control. The patient continually received oral pyrotinib, however, a new brain lesion appeared 6 months later. Overall, we managed to regulate the efficacy of pyrotinib for up to 15 months.<br><br>CONCLUSION: This case report demonstrates that EGFR-ZNF880 fusion and EGFR E114K mutations may contribute or lead to the formation of a special HER2 dimer, which is rapidly resistant to lapatinib but sensitive to pyrotinib. Of note, this is the first report that such a new fusion has been found.}, }
@article {pmid33370550, year = {2021}, author = {Wang, M and Zeng, W and Zhang, Z and Zhang, W and Su, H and Zhang, Z and Jiang, L and Liu, Y and Shi, Q}, title = {The Improvement of Immune Effect of Recombinant Human Beta-Defensin 2 on Hepatitis B Vaccine in Mice.}, journal = {Viral immunology}, volume = {34}, number = {2}, pages = {96-111}, doi = {10.1089/vim.2020.0052}, pmid = {33370550}, issn = {1557-8976}, mesh = {Animals ; *Hepatitis B/prevention &amp; control ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens/genetics ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Immunity ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/immunology/therapeutic use ; *beta-Defensins/immunology/therapeutic use ; }, abstract = {Immunization with hepatitis B vaccine is an effective measure for prevention and control of hepatitis B Virus (HBV) infection. Although lots of efforts to improve the effect of hepatitis B vaccine have been made, the function of human beta defensin 2 (hBD2) on hepatitis B vaccine keeps unclear. In this article, we report that hBD2 not only promoted the activation and maturation of immature dendritic cells (iDCs) by increasing MHC II and CD86 expression, but it also significantly upregulated the mRNA level of IL-6 and IL-12B in mouse bone marrow-derived dendritic cells. The serum concentrations of IFN-γ in mice stimulated with 300 ng hBD2 increased from 25.21 to 42.04 pg/mL, with a time extension from 4 to 12 h post-injection. During the process of three times immunization (1, 14, 28 days) with 3 μg hepatitis B vaccine combined with or without 300 ng hBD2 with a 2 week interval in BALB/c mice, the antibody against HBsAg (HBsAb) concentration in serum at every time point of observation in the combined group was statistically higher than the hepatitis B vaccine group. The serum concentration of IgG2a subclass HBsAb on the 14th day post last injection in the combined group was significantly higher than the hepatitis B vaccine group. Further, the splenic cells from the mice treated with both hBD2 and hepatitis B vaccine possessed a greater ability to produce a surface antigen of hepatitis B virus (HBsAg) specific IFN-γ than those treated with hepatitis B vaccine alone. The percentages of CD3[+]/CD4[+] T cells and CD3[+]/CD8[+] T lymphocytes in spleens from the mice treated with 300 ng hBD2 were statistically higher than the phosphate buffered saline group. These data suggest that hBD2 improves iDC maturation and the immune efficiency of hepatitis B vaccine in BALB/c mice.}, }
@article {pmid33356097, year = {2021}, author = {Zhong, S and Wong, HC and Low, HY and Zhao, R}, title = {Phototriggerable Transient Electronics via Fullerene-Mediated Degradation of Polymer:Fullerene Encapsulation Layer.}, journal = {ACS applied materials &amp; interfaces}, volume = {13}, number = {1}, pages = {904-911}, doi = {10.1021/acsami.0c18795}, pmid = {33356097}, issn = {1944-8252}, abstract = {Transient electronics is an emerging class of electronics that has attracted a lot of attention because of its potential as an environmental-friendly alternative to the existing end-of-life product disposal or treatments. However, the controlled degradation of transient electronics under environmentally benign conditions remains a challenge. In this work, the tunable degradation of transient electronics including passive resistor devices and active memory devices was realized by photodegradable thin polymer films comprising fullerene derivatives, [6,6]-phenyl-C61-butyric acid methyl esters (PCBM). The photodegradation of polymer:PCBM under an aqueous environment is triggered by ultraviolet (UV) light. Experimental results demonstrate that the addition of PCBM in commodity polymers, including but not limited to polystyrene, results in a catalytic effect on polymer photodegradation when triggered by UV light. The degradation mechanism of transient electronics is ascribed to the photodegradation of polymer:PCBM encapsulation layers caused by the synergistic effect between UV and water exposure. The polymer:PCBM encapsulation system presented herein offers a simple way to achieve the realization of light-triggered device degradation for bioapplication and expands the material options for tailorable degradation of transient electronics.}, }
@article {pmid33348399, year = {2020}, author = {Reis, APAM and Teixeira, CMS and Medeiros, ARL and Chaves, KZC and Albuquerque, CR and Melo, MR}, title = {Sociodemographic and Clinical-pathological Study of Molecular Subtitles of Breast Carcinoma in a Reference Unit of Maranhão.}, journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia}, volume = {42}, number = {12}, pages = {820-828}, pmid = {33348399}, issn = {1806-9339}, mesh = {Brazil/epidemiology ; Breast Neoplasms/*epidemiology/etiology/pathology ; Cross-Sectional Studies ; Demography ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Medical Records ; Middle Aged ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Social Class ; }, abstract = {OBJECTIVE: To evaluate the distribution of the main sociodemographic and clinical-pathological characteristics in women with breast cancer according to the molecular profile by immunohistochemistry.<br><br>METHODS: &#x2003;A cross-sectional, retrospective, analytical and quantitative study was performed, with an analysis of 137 medical records from January 2015 to December 2018 of women attending the High Complexity in Oncology Unit of the city of Imperatriz, state of Maranh&#xe3;o, Brazil. The immunohistochemical profile of tumors based on the estrogen and progesterone receptor, Human Epidermal growth factor Receptor-type 2 (HER2) overexpression and Ki67 cell proliferation index was defined, from which six molecular subtypes were determined: luminal A, luminal B-HER2 negative, luminal B-HER2 positive, triple negative, overexpression of HER2 and inconclusive.<br><br>RESULTS: &#x2003;A total of 52.6% of the patients were postmenopausal, mean age 52.1 years old, brown (56.2%), had a schooling level&#x2009;<&#x2009;9 years (40%), staging&#x2009;>&#x2009;IIB (52.6%) and 23.4% had metastasis. Invasive ductal carcinoma accounted for 84.7%, tumor size was 2 to 5&#x2009;cm (48.9%), with lymph node involvement (56.2%), axillary lymphadenectomy in 67.2%, and mastectomy in 73.7% of the patients. The most frequent molecular subtype was the luminal B-HER2 negative (36.5%), and the luminal A subtype showed characteristics of better prognosis when compared with the others.<br><br>CONCLUSION: &#x2003;It was concluded that in the association of molecular subtypes with sociodemographic and clinical-pathological characteristics, there were no statistically significant results obtained, except for complementary therapy, referring to hormone therapy, and there was a high index of metastasis at diagnosis, which was a worrying factor and indicative of failures in the screening and early diagnosis of this population.}, }
@article {pmid33342987, year = {2020}, author = {Shinseki, K and Takahashi, M and Kushima, A and Nakamoto, T and Wakata, M and Nakajima, T and Toda, T and Ito, K and Fujibayashi, M}, title = {[One Case of Accessory Breast Cancer Complicated by Contralateral Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {47}, number = {12}, pages = {1703-1705}, pmid = {33342987}, issn = {0385-0684}, mesh = {Axilla ; *Breast Diseases ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/complications/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {We experienced a case of right sided accessory breast cancer complicated by contralateral breast cancer. A 50-year-old woman came to us for an examination because a tumor in her left breast was pointed out at breast cancer screening. A breast MRI confirmed a tumor in her left breast and a tumor continuing from the skin to the subcutis of the right axilla. A skin biopsy for the tumor in the right axilla and a core needle biopsy(CNB)for the tumor in the left breast were performed. The pathological result of the CNB for the left breast indicated an invasive ductal carcinoma of the tubular formative scirrhous type. Although the tumor of the right axilla was poorly differentiated adenocarcinoma demonstrating cord-like arrays, it was examined by skin biopsy and therefore no deep part of the tissue was included. We conducted immunostaining, in consideration of the possibility of metastasis from the left sided breast cancer. ER, PgR, mammaglobin, GATA 3 were positive, strongly suggesting that the tumor in the right axilla was also derived from a mammary gland. We also performed a wide local excision of the right axilla plus axillary dissection(level Ⅰ)in addition to conducting a left mastectomy plus sentinel lymph node biopsy, in consideration of the possibility of primary right sided accessory breast cancer. The pathological result following surgery confirmed a difference in the histologic features between both sides, residual normal accessory mammary glands around the tumor on the right side, and the presence of rich DCIS and a lobular replacement image, leading to a definitive diagnosis of primary invasive ductal carcinoma of the accessory breast on the right side.}, }
@article {pmid33336932, year = {2021}, author = {Liang, RB and Yu, K and Wu, JL and Liu, JX and Lin, Q and Li, B and Zhang, YQ and Ge, QM and Li, QY and Shu, HY and Shao, Y}, title = {Risk factors and their diagnostic values for ocular metastases in invasive ductal carcinoma.}, journal = {Cancer medicine}, volume = {10}, number = {3}, pages = {824-832}, pmid = {33336932}, issn = {2045-7634}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/epidemiology/metabolism/*pathology/surgery ; Case-Control Studies ; Eye Neoplasms/epidemiology/metabolism/*secondary/surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; }, abstract = {Invasive ductal carcinoma (IDC) is a major type of breast cancer. Ocular metastasis (OM) in IDC is rarely seen, but patients with OM often have a poor prognosis. Furthermore, OM is difficult to detect in the early stages by common imaging examinations. In the present study, we tried to figure out the risk factors of OM in IDC and evaluate their diagnostic values for early detection. There were 1192 IDC patients who were divided into two groups according to ocular metastasis involved in this study. Clinical parameters of those patients were used to detect differences. The binary logistic regression test was then used to determine the risk factors of OM in IDC. Furthermore, ROC curves of both single and combined risk factors were established to examine their diagnostic values. The incidence of axillary lymph node metastases was significantly higher in the OM group (p = 0.002). Higher carbohydrate antigen 153 (CA153), lower apolipoprotein A1 (ApoA1), and hemoglobin (Hb) were risk factors for OM in IDC (p < 0.001, p < 0.001, p = 0.038, respectively). In the single risk factor ROC analysis, cutoff values of CA153, ApoA1, and Hb were 43.3 u/mL (CI: 0.966-0.984, p < 0.001), 1.11 g/L (CI: 0.923-0.951, p < 0.001), and 112 g/L (CI: 0.815-0.857, p < 0.001), respectively. Among the ROC curves of combined risk factors, CA153+ApoA1+Hb had the best accuracy, with the sensitivity and specificity of 89.47% and 99.32%, respectively (CI: 0.964-0.983, p < 0.001). CA153, ApoA1, and Hb are risk factors for OM in IDC. In clinical practice, the three parameters could be used as predictive factors for the early detection of OM.}, }
@article {pmid33335279, year = {2021}, author = {Zeng, Y and Gao, W and Chen, X and Shen, K}, title = {Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component.}, journal = {British journal of cancer}, volume = {124}, number = {5}, pages = {975-981}, pmid = {33335279}, issn = {1532-1827}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.<br><br>METHODS: Consecutive ER-positive, HER2-negative, N0-1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.<br><br>RESULTS: A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P&#x2009;=&#x2009;0.038). IDC/DCIS patients more often had a low-risk RS (P&#x2009;=&#x2009;0.018) or intermediate-risk RS (P&#x2009;=&#x2009;0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.<br><br>CONCLUSIONS: IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.}, }
@article {pmid33331427, year = {2020}, author = {Bertoldi, AS and Guetter, CR and Coltro, GA and Vosgerau, LM and Brighenti, LMV and Fauat, NI and Kubrusly, FB and Marques, CAM and Kubrusly, LF}, title = {CARVEDILOL AS PRIMARY PROPHYLAXIS FOR GASTRIC VARICEAL BLEEDING IN PORTAL HYPERTENSION MODEL IN RATS.}, journal = {Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery}, volume = {33}, number = {3}, pages = {e1525}, pmid = {33331427}, issn = {2317-6326}, mesh = {Adrenergic beta-Antagonists/*administration &amp; dosage ; Animals ; Antihypertensive Agents/*administration &amp; dosage ; Carvedilol/*administration &amp; dosage ; Esophageal and Gastric Varices/complications/prevention &amp; control ; Gastrointestinal Hemorrhage/etiology/*prevention &amp; control ; Hypertension, Portal/*complications ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy.<br><br>AIM: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model.<br><br>METHOD: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days.<br><br>RESULTS: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups.<br><br>CONCLUSION: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.}, }
@article {pmid33329538, year = {2020}, author = {Niespolo, C and Johnston, JM and Deshmukh, SR and Satam, S and Shologu, Z and Villacanas, O and Sudbery, IM and Wilson, HL and Kiss-Toth, E}, title = {Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {574046}, pmid = {33329538}, issn = {1664-3224}, support = {PG/16/44/32146/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {3' Untranslated Regions ; Animals ; Binding Sites ; Cell Line, Tumor ; Cytokines/*metabolism ; Gene Expression Regulation ; Humans ; Inflammation ; Interleukin-8/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism/*physiology ; Macrophages/*metabolism ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/genetics/*metabolism ; Phenotype ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Protein Serine-Threonine Kinases/*antagonists &amp; inhibitors/genetics/metabolism/physiology ; RNA, Messenger/genetics/metabolism ; }, abstract = {The pseudokinase TRIB1 controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation via the COP1 ubiquitin ligase. TRIB1 regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, TRIB1 has also been implicated in the pathogenesis of prostate cancer, where it is often overexpressed, even in the absence of genetic amplification. Well described TRIB1 effectors include MAP kinases and C/EBP transcription factors, both in immune cells and in carcinogenesis. However, the mechanisms that regulate TRIB1 itself remain elusive. Here, we show that the long and conserved 3'untranslated region (3'UTR) of TRIB1 is targeted by miRNAs in macrophage and prostate cancer models. By using a systematic in silico analysis, we identified multiple "high confidence" miRNAs potentially binding to the 3'UTR of TRIB1 and report that miR-101-3p and miR-132-3p are direct regulators of TRIB1 expression and function. Binding of miR-101-3p and miR-132-3p to the 3'UTR of TRIB1 mRNA leads to an increased transcription and secretion of interleukin-8. Our data demonstrate that modulation of TRIB1 by miRNAs alters the inflammatory profile of both human macrophages and prostate cancer cells.}, }
@article {pmid33328559, year = {2020}, author = {Wu, SG and Yang, SP and Zhang, WW and Wang, J and Lian, CL and Chen, YX and He, ZY}, title = {The longitudinal risk of mortality between invasive ductal carcinoma and metaplastic breast carcinoma.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {22070}, pmid = {33328559}, issn = {2045-2322}, mesh = {Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; Survival Rate ; }, abstract = {The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.}, }
@article {pmid33316685, year = {2021}, author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY}, title = {Pathologic response rates for breast cancer stages as a predictor of outcomes in patients receiving neoadjuvant chemotherapy followed by breast-conserving surgery.}, journal = {Surgical oncology}, volume = {36}, number = {}, pages = {91-98}, doi = {10.1016/j.suronc.2020.11.015}, pmid = {33316685}, issn = {1879-3320}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*pathology/therapy ; Chemotherapy, Adjuvant/*methods ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoadjuvant Therapy/*methods ; Prognosis ; Young Adult ; }, abstract = {PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.<br><br>PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients' PRRs; other independent predictors were controlled for or stratified in the analysis.<br><br>RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13-0.56), 0.36 (0.15-0.85), and 0.15 (0.08-0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35-0.89), 0.91 (0.62-0.96), and 0.63 (0.43-0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06-2.24), 1.08 (1.03-1.82), and 1.19 (1.07-2.01) for all-cause mortality, LRR, and DM, respectively.<br><br>CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.}, }
@article {pmid33302909, year = {2020}, author = {Desa, DE and Strawderman, RL and Wu, W and Hill, RL and Smid, M and Martens, JWM and Turner, BM and Brown, EB}, title = {Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {1217}, pmid = {33302909}, issn = {1471-2407}, support = {R21 CA208921/CA/NCI NIH HHS/United States ; W81XWH-15-1-0040//U.S. Department of Defense/ ; W81XWH-17-1-0011//U.S. Department of Defense/ ; R21CA208921//Foundation for the National Institutes of Health/ ; }, mesh = {Breast Neoplasms/chemistry/*ultrastructure ; Carcinoma, Ductal, Breast/chemistry/secondary/*ultrastructure ; *Estrogens ; Female ; Fibrillar Collagens/*ultrastructure ; Humans ; Image Processing, Computer-Assisted ; *Neoplasm Metastasis ; Neoplasm Proteins/*ultrastructure ; Neoplasms, Hormone-Dependent/chemistry/*ultrastructure ; Prognosis ; Risk ; *Second Harmonic Generation Microscopy ; Single-Blind Method ; Stromal Cells/chemistry/ultrastructure ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Metastases are the leading cause of breast cancer-related deaths. The tumor microenvironment impacts cancer progression and metastatic ability. Fibrillar collagen, a major extracellular matrix component, can be studied using the light scattering phenomenon known as second-harmonic generation (SHG). The ratio of forward- to backward-scattered SHG photons (F/B) is sensitive to collagen fiber internal structure and has been shown to be an independent prognostic indicator of metastasis-free survival time (MFS). Here we assess the effects of heterogeneity in the tumor matrix on the possible use of F/B as a prognostic tool.<br><br>METHODS: SHG imaging was performed on sectioned primary tumor excisions from 95 untreated, estrogen receptor-positive, lymph node negative invasive ductal carcinoma patients. We identified two distinct regions whose collagen displayed different average F/B values, indicative of spatial heterogeneity: the cellular tumor bulk and surrounding tumor-stroma interface. To evaluate the impact of heterogeneity on F/B's prognostic ability, we performed SHG imaging in the tumor bulk and tumor-stroma interface, calculated a 21-gene recurrence score (surrogate for OncotypeDX&#xae;, or S-ODX) for each patient and evaluated their combined prognostic ability.<br><br>RESULTS: We found that F/B measured in tumor-stroma interface, but not tumor bulk, is prognostic of MFS using three methods to select pixels for analysis: an intensity threshold selected by a blinded observer, a histogram-based thresholding method, and an adaptive thresholding method. Using both regression trees and Random Survival Forests for MFS outcome, we obtained data-driven prediction rules that show F/B from tumor-stroma interface, but not tumor bulk, and S-ODX both contribute to predicting MFS in this patient cohort. We also separated patients into low-intermediate (S-ODX <&#x2009;26) and high risk (S-ODX &#x2265;26) groups. In the low-intermediate risk group, comprised of patients not typically recommended for adjuvant chemotherapy, we find that F/B from the tumor-stroma interface is prognostic of MFS and can identify a patient cohort with poor outcomes.<br><br>CONCLUSIONS: These data demonstrate that intratumoral heterogeneity in F/B values can play an important role in its possible use as a prognostic marker, and that F/B from tumor-stroma interface of primary tumor excisions may provide useful information to stratify patients by metastatic risk.}, }
@article {pmid33278619, year = {2021}, author = {Hadano, Y and Kakuma, T and Matsumoto, T and Ishibashi, K and Isoda, M and Yasunaga, H}, title = {Reduction of 30-day death rates from Staphylococcus aureus bacteremia by mandatory infectious diseases consultation: Comparative study interventions with and without an infectious disease specialist.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {103}, number = {}, pages = {308-315}, doi = {10.1016/j.ijid.2020.11.199}, pmid = {33278619}, issn = {1878-3511}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/microbiology/mortality ; Case Management ; Female ; Hospitals ; Humans ; Japan ; Male ; Middle Aged ; *Quality of Health Care ; Referral and Consultation ; Retrospective Studies ; Specialization ; Staphylococcal Infections/*drug therapy/microbiology ; Staphylococcus aureus/*drug effects ; Treatment Outcome ; }, abstract = {OBJECTIVES: Most Japanese hospitals need to keep to higher Staphylococcus aureus bacteremia (SAB) quality-of-care indicators (QCIs) and create strategies that can maximize the effect of these QCIs with only a small number of infectious disease specialists. This study aimed to evaluate the clinical outcomes of patients with SAB before and after the enhancement of the mandatory infectious disease consultations (IDCs).<br><br>METHODS: This retrospective study was conducted at a tertiary care hospital in Japan. The primary outcome was the 30-day mortality between each period. A generalized structural equation model was employed to examine the effect of the mandatory IDC enhancement on 30-day mortality among patients with SAB.<br><br>RESULTS: A total of 114 patients with SAB were analyzed. The 30-day all-cause mortality differed significantly between the two periods (17.3% vs. 4.8%, P = 0.02). Age, three-QCI point &#x2265; 1, and Pitt bacteremia score &#x2265; 3 were the significant risk factors for 30-day mortality. The intervention was also significantly associated with improved adherence to QCIs.<br><br>CONCLUSION: Mandatory IDCs for SAB improved 30-day mortality and adherence to QCIs after the intervention. In Japan, improving the quality of management in patients with SAB should be an important target.}, }
@article {pmid33263939, year = {2021}, author = {D'Alfonso, TM and Pareja, F and Da Cruz Paula, A and Vahdatinia, M and Gazzo, A and Ferrando, L and da Silva, EM and Cheng, E and Sclafani, L and Chandarlapaty, S and Zhang, H and Hoda, SA and Wen, HY and Brogi, E and Weigelt, B and Reis-Filho, JS}, title = {Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma.}, journal = {The journal of pathology. Clinical research}, volume = {7}, number = {2}, pages = {113-120}, pmid = {33263939}, issn = {2056-4538}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; K12 CA184746/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/complications/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; *DNA Copy Number Variations ; DNA Mutational Analysis ; Female ; Humans ; Mutation ; Papilloma/complications/diagnosis/*genetics/pathology ; Exome Sequencing ; }, abstract = {Juvenile papillomatosis (JP) of the breast is a rare benign mass-forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole-exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC-NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC-NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC-NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)-positive breast cancers. We observed JP to harbor a dominant aging-related mutational signature, whereas coexisting DCIS and IDC-NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop.}, }
@article {pmid33251496, year = {2020}, author = {Li, X and Schmöhl, F and Qi, H and Bennewitz, K and Tabler, CT and Poschet, G and Hell, R and Volk, N and Poth, T and Hausser, I and Morgenstern, J and Fleming, T and Nawroth, PP and Kroll, J}, title = {Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish.}, journal = {iScience}, volume = {23}, number = {12}, pages = {101763}, pmid = {33251496}, issn = {2589-0042}, abstract = {Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of gluconeogenesis. Adult akr1a1b [-/-] mutant zebrafish developed fasting hypoglycemia, which was caused by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression as rate-limiting enzyme of gluconeogenesis. Subsequently, glucogenic amino acid glutamate as substrate for gluconeogenesis accumulated in the kidneys, but not in livers, and induced structural and functional pronephros alterations in 48-hpf akr1a1b [-/-] embryos. Akr1a1b [-/-] mutants displayed increased nitrosative stress as indicated by increased nitrotyrosine, and increased protein-S-nitrosylation. Inhibition of nitrosative stress using the NO synthase inhibitor L-NAME prevented kidney damage and normalized PEPCK expression in akr1a1b [-/-] mutants. Thus, the data have identified Akr1a1b as a regulator of gluconeogenesis in zebrafish and thereby controlling glucose homeostasis.}, }
@article {pmid33247280, year = {2020}, author = {Puzis, R and Farbiash, D and Brodt, O and Elovici, Y and Greenbaum, D}, title = {Increased cyber-biosecurity for DNA synthesis.}, journal = {Nature biotechnology}, volume = {38}, number = {12}, pages = {1379-1381}, pmid = {33247280}, issn = {1546-1696}, mesh = {*Computer Security ; DNA/*biosynthesis ; Genetic Engineering ; Plasmids/genetics ; }, }
@article {pmid33243732, year = {2020}, author = {Xu, X and Wang, J and Yan, C and Men, Y and Jiang, H and Fang, H and Xu, X and Yang, J}, title = {[Association of JMJD3, MMP-2 and VEGF expressions with clinicopathological features of invasive ductal breast carcinoma].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {40}, number = {11}, pages = {1593-1600}, pmid = {33243732}, issn = {1673-4254}, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A ; }, abstract = {OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells.<br><br>METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR.<br><br>RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue (P < 0.05). The positivity rates of JMJD3, MMP-2 and VEGF in breast cancer tissues were significantly correlated with tumor diameter, differentiation, TNM stage, lymph node metastasis, and molecular subtypes (P < 0.05). KaplanMeier analysis showed that JMJD3 expression level was positively while MMP-2 and VEGF were inversely correlated with the disease-free survival time of the patients (P < 0.05). Cox regression analysis identified JMJD3, MMP-2, VEGF and tumor differentiation as independent prognostic factors of breast cancer. Spearman correlation analysis suggested a negative correlation of JMJD3 with MMP2 (r=-0.569, P < 0.05) and VEGF (r=-0.533, P < 0.05) and a positive correlation between MMP2 and VEGF (r=0.923, P < 0.05). In MDA-MB-231 cells, overexpression of JMJD3 inhibited the proliferation of MDA-MB-231 cells and the expression of MMP-2 and VEGF.<br><br>CONCLUSIONS: The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.}, }
@article {pmid33239449, year = {2021}, author = {Chen, J and Fleming, T and Katz, S and Dewenter, M and Hofmann, K and Saadatmand, A and Kronlage, M and Werner, MP and Pokrandt, B and Schreiter, F and Lin, J and Katz, D and Morgenstern, J and Elwakiel, A and Sinn, P and Gröne, HJ and Hammes, HP and Nawroth, PP and Isermann, B and Sticht, C and Brügger, B and Katus, HA and Hagenmueller, M and Backs, J}, title = {CaM Kinase II-δ Is Required for Diabetic Hyperglycemia and Retinopathy but Not Nephropathy.}, journal = {Diabetes}, volume = {70}, number = {2}, pages = {616-626}, doi = {10.2337/db19-0659}, pmid = {33239449}, issn = {1939-327X}, mesh = {Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism ; Diabetes Mellitus, Type 2/genetics/*metabolism ; Diabetic Nephropathies/genetics/*metabolism ; Diabetic Retinopathy/genetics/*metabolism ; Gene Expression ; Hyperglycemia/genetics/*metabolism ; Mice ; Mice, Knockout ; Receptors, Leptin/genetics/metabolism ; }, abstract = {Type 2 diabetes has become a pandemic and leads to late diabetic complications of organs, including kidney and eye. Lowering hyperglycemia is the typical therapeutic goal in clinical medicine. However, hyperglycemia may only be a symptom of diabetes but not the sole cause of late diabetic complications; instead, other diabetes-related alterations could be causative. Here, we studied the role of CaM kinase II-δ (CaMKIIδ), which is known to be activated through diabetic metabolism. CaMKIIδ is expressed ubiquitously and might therefore affect several different organ systems. We crossed diabetic leptin receptor-mutant mice to mice lacking CaMKIIδ globally. Remarkably, CaMKIIδ-deficient diabetic mice did not develop hyperglycemia. As potential underlying mechanisms, we provide evidence for improved insulin sensing with increased glucose transport into skeletal muscle and also reduced hepatic glucose production. Despite normoglycemia, CaMKIIδ-deficient diabetic mice developed the full picture of diabetic nephropathy, but diabetic retinopathy was prevented. We also unmasked a retina-specific gene expression signature that might contribute to CaMKII-dependent retinal diabetic complications. These data challenge the clinical concept of normalizing hyperglycemia in diabetes as a causative treatment strategy for late diabetic complications and call for a more detailed analysis of intracellular metabolic signals in different diabetic organs.}, }
@article {pmid33238981, year = {2020}, author = {Huang, Z and Hu, C and Liu, K and Yuan, L and Li, Y and Zhao, C and Hu, C}, title = {Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {1145}, pmid = {33238981}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*secondary/therapy ; Brain Neoplasms/*secondary/therapy ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*secondary/therapy ; Male ; Middle Aged ; *Nomograms ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients.<br><br>METHODS: IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University.<br><br>RESULTS: This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally.<br><br>CONCLUSION: These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies.}, }
@article {pmid33238073, year = {2021}, author = {Okada, K and Takahara, T and Suzuki, Y and Kohno, K and Sakakibara, A and Satou, A and Takahashi, E and Nakamura, S}, title = {Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression.}, journal = {Pathology international}, volume = {71}, number = {1}, pages = {24-32}, doi = {10.1111/pin.13044}, pmid = {33238073}, issn = {1440-1827}, mesh = {Adolescent ; Adult ; Aged ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/analysis ; *Dendritic Cell Sarcoma, Follicular/immunology/metabolism/pathology ; Dendritic Cells/metabolism/pathology ; Female ; Histiocytes/metabolism/pathology ; *Histiocytic Sarcoma/immunology/metabolism/pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Japan ; Langerhans Cell Sarcoma/immunology/metabolism/pathology ; Lymphoma, Follicular/immunology/metabolism/pathology ; Male ; Middle Aged ; Retrospective Studies ; T-Lymphocytes/metabolism ; }, abstract = {Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.}, }
@article {pmid33229203, year = {2021}, author = {Madabhavi, I and Sarkar, M and Chavan, C and Trivedi, M}, title = {Maxillary bone metastasis, as an early sign of breast cancer; an unusual &amp; rare site of metastasis from the common cancer.}, journal = {Oral oncology}, volume = {115}, number = {}, pages = {105098}, doi = {10.1016/j.oraloncology.2020.105098}, pmid = {33229203}, issn = {1879-0593}, mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Maxilla/*pathology ; Maxillary Neoplasms/*secondary ; Neoplasm Metastasis ; }, abstract = {Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Due to their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. In this article we present a rare, unusual &amp; exceptional case of left maxillary mass which on further evaluation leading to diagnosis of left breast carcinoma with metastasis to isolated left maxillary bone. Sixty five year old postmenopausal woman of low socioeconomic status with good performance status presented with a 3 months history of progressive pain and swelling in the left maxillary region. Fine Needle Aspiration Cytology (FNAC) from the maxillary mass shows invasive ductal carcinoma. On further clinical, radiographic, and histopathological examination findings from the breast lesion confirmed the diagnosis of hormone receptor positive metastatic breast carcinoma. In view of painful metastatic maxillary lesion with breast disease she was managed with a palliative radiotherapy to the maxillary lesion and palliative chemotherapy with Doxorubicin-Cyclophosphamide and bhisphosphonate-Zolendronic acid. Patient responded very well to palliative radiotherapy and chemotherapy, in view of hormone receptor positive breast cancer, now she is on Tab. Anastrazole 1 mg once a day along with monthly Zolendronic acid injection since last 13 months without any symptoms of disease evolution. A high index of clinical thought of metastatic cancer to maxilla is necessary when evaluating patients who complain of maxillary pain and swelling without a history of pain or swelling in the head and neck &amp; non-head and neck region. To the best of our knowledge, this is the first reported case of a metastatic isolated solitary maxillary bone metastasis presenting as an early sign of breast cancer.}, }
@article {pmid33209168, year = {2020}, author = {Fouhi, ME and Benider, A and Gaëtan, KZA and Mesfioui, A}, title = {[Epidemiological and anatomopathological profile of breast cancer at the Ibn Rochd University Hospital, Casablanca].}, journal = {The Pan African medical journal}, volume = {37}, number = {}, pages = {41}, pmid = {33209168}, issn = {1937-8688}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Delayed Diagnosis ; Female ; Hospitals, University ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Young Adult ; }, abstract = {The present study aims to determine the various epidemiological characteristics among newly diagnosed patients with breast cancer in Casablanca during 2018. During that period, 668 cases were collected, the average age was 51.6 years, the female was the most represented with 662 cases (99.1%) and men with 6 cases (0.9%), a sex ratio (M/F) of 0.009. The average age of menopause was 49.8 years and the average age of menarche was 13.5 years, 31.7% had a history of cancer (breast 14.1%, stomach and 9% liver 7%). The average diagnosis delay was 10 months, the thyroid disease was the most represented pathology, the left breast was diagnosed in 50.2% and the right breast in 44.7% and 1.3% in the bilateral location. The most common histological type was invasive ductal carcinoma (73.2%). The vascular and lymphatic invasion was observed in 42.2%, axillary nodes were affected in 71.1% of cases. The histological prognosis (SBR) revealed a predominance of grade II in 55.9% of cases. The Luminal B continues to be the most common phenotype (46%) followed by Triple Negative (15.3%) and Luminal A (14.2%) and HER2 (7.4%). The immediate prognosis is a cause for concern because of delayed diagnosis. It seems urgent to develop the health information policy and education.}, }
@article {pmid33204409, year = {2020}, author = {Missori, G and Serra, F and Prestigiacomo, G and Ricciardolo, AA and Brugioni, L and Gelmini, R}, title = {Case Report: Metastatic breast cancer to the gallbladder.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {343}, pmid = {33204409}, issn = {2046-1402}, mesh = {Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; *Cholecystitis, Acute/etiology/surgery ; Female ; *Gallbladder Neoplasms/secondary/surgery ; Humans ; }, abstract = {Cholecystitis is one of the leading causes of emergency surgical interventions; the occurrence of metastases to the gallbladder is rare and has only been reported in the literature exceptionally. Metastatic breast cancer to the gallbladder is even less frequent; in fact, breast cancer usually metastasizes to bone, lung, lymph nodes, liver and brain. We report the case of an 83-year-old female patient with a previous history of breast surgery with axillary dissection in 1997, followed by adjuvant chemotherapy due to invasive ductal carcinoma of the left breast. The patient was admitted at the emergency department for sepsis and an episode of acute kidney failure, anuria and fever. Right-upper quadrant abdominal pain triggered by food intake and abdominal tenderness was also present, placing the diagnostic suspicion of biliary sepsis due to acute cholecystitis. The histological examination of the surgical specimen highlighted the presence of metastasis from an infiltrating ductal breast carcinoma with positive hormone receptors. We also report here the results of a review of the literature looking at articles describing cases of gallbladder metastasis from breast cancer.}, }
@article {pmid33191115, year = {2021}, author = {Shah, OS and Soran, A and Sahin, M and Knapick, BA and Ugras, S and Celik, E and Lucas, PC and Lee, AV}, title = {Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.}, journal = {Clinical breast cancer}, volume = {21}, number = {3}, pages = {210-217}, doi = {10.1016/j.clbc.2020.08.009}, pmid = {33191115}, issn = {1938-0666}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Lobular/genetics ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; }, abstract = {BACKGROUND: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples.<br><br>MATERIALS AND METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n&#xa0;= 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants.<br><br>RESULTS: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs - ERBB2, FGFR1, and AR copy number gains and 5 SNVs - IDH1.R132H, TP53.E204&#x2217;, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively.<br><br>CONCLUSION: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeq[TM]. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.}, }
@article {pmid33163280, year = {2020}, author = {Zhang, J and Sun, M and Chang, E and Lu, CY and Chen, HM and Wu, SY}, title = {Pathologic response as predictor of recurrence, metastasis, and survival in breast cancer patients receiving neoadjuvant chemotherapy and total mastectomy.}, journal = {American journal of cancer research}, volume = {10}, number = {10}, pages = {3415-3427}, pmid = {33163280}, issn = {2156-6976}, abstract = {To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in breast invasive ductal carcinoma (IDC) patients receiving neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we used the pathologic response (PR) of primary breast diseases (T stages), nodal diseases (N stages), and combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) based on existing clinical and pathologic reports as predictors. We enrolled patients with IDC who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) of PR; other independent predictors were controlled for or stratified in the analysis. We analyzed 3654 IDC patients (1031, 1215, 1003, and 405 patients with clinical stages IIB, IIIA, IIIB, and IIIC, respectively) receiving NACT and TM. After multivariate Cox regression analyses, the adjusted HRs (aHRs) (95% CI) for all-cause mortality, LRR, and DM were noted to be 0.21 (0.13-0.34), 0.19 (0.08-0.48), and 0.33 (0.23-0.47), respectively, for pCR; 0.56 (0.48-0.65), 0.67 (0.51-0.89), and 0.61 (0.52-0.70), respectively, for AJCC downstaging; and 1.85 (1.56-2.18), 1.17 (0.84-1.62), and 1.61 (1.36-1.90), respectively, for AJCC upstaging. The PR parameters used in the study are easily applied because they are based on existing staging records, and they can strongly predict OS, LRR, and DM in IDC patients receiving NACT and TM, regardless of clinical stage. The results can be used to guide adjuvant treatment.}, }
@article {pmid33163131, year = {2021}, author = {Chung, HL and Leung, JWT}, title = {Breast cancer recurrences in myocutaneous flap reconstruction.}, journal = {Radiology case reports}, volume = {16}, number = {1}, pages = {40-46}, pmid = {33163131}, issn = {1930-0433}, abstract = {Autologous flap reconstruction is widely used after skin sparing mastectomy to reconstruct the appearance of the breast. We present 2 cases of breast cancer recurrence in a deep inferior epigastric perforator reconstruction, including a 65-year-old female with history of papillary carcinoma and a 35-year-old female with history of a high grade invasive ductal carcinoma with extensive ductal carcinoma in situ. Differential imaging considerations of the post mastectomy patient are reviewed. Typical appearance of a deep inferior epigastric perforator flap reconstruction as well as location and timing of presentation may help differentiate a recurrence from the more commonly encountered postsurgical etiologies.}, }
@article {pmid33154304, year = {2020}, author = {Oral, O and Unverdi, H and Kumcu, E and Turkbey, D and Dogan, S and Hucumenoglu, S}, title = {Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {4}, pages = {551-558}, doi = {10.4103/IJPM.IJPM_637_18}, pmid = {33154304}, issn = {0974-5130}, mesh = {Adenocarcinoma, Mucinous/genetics/pathology ; Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Mucin 5AC/*genetics ; Mucin-1/*genetics ; Mucin-2/*genetics ; Mucin-6/*genetics ; Prognosis ; }, abstract = {AIMS: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters.<br><br>MATERIALS AND METHODS: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas.<br><br>RESULTS: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion.<br><br>CONCLUSIONS: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.}, }
@article {pmid33148662, year = {2021}, author = {Chen, F and Ding, K and Priedigkeit, N and Elangovan, A and Levine, KM and Carleton, N and Savariau, L and Atkinson, JM and Oesterreich, S and Lee, AV}, title = {Single-Cell Transcriptomic Heterogeneity in Invasive Ductal and Lobular Breast Cancer Cells.}, journal = {Cancer research}, volume = {81}, number = {2}, pages = {268-281}, pmid = {33148662}, issn = {1538-7445}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD/genetics/metabolism ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Cadherins/antagonists &amp; inhibitors/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Mutation ; Prognosis ; Single-Cell Analysis/*methods ; *Transcriptome ; Tumor Cells, Cultured ; }, abstract = {Invasive lobular breast carcinoma (ILC), one of the major breast cancer histologic subtypes, exhibits unique features compared with the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell RNA sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knockout (KO). Inspection of intracell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a preadaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFNγ-mediated growth inhibition via activation of IRF1. This study reveals single-cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance. SIGNIFICANCE: This study represents a key step towards understanding heterogeneity in cancer cell lines and the role of E-cadherin depletion in contributing to the molecular features of invasive lobular breast carcinoma.}, }
@article {pmid33148628, year = {2022}, author = {Pareja, F and Vahdatinia, M and Marchio, C and Lee, SSK and Da Cruz Paula, A and Derakhshan, F and da Silva, EM and Selenica, P and Dopeso, H and Chandarlapaty, S and Wen, HY and Vincent-Salomon, A and Brogi, E and Weigelt, B and Reis-Filho, JS}, title = {Neuroendocrine tumours of the breast: a genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites.}, journal = {Journal of clinical pathology}, volume = {75}, number = {1}, pages = {10-17}, pmid = {33148628}, issn = {1472-4146}, support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Chromosome Aberrations ; Female ; Genomics ; Humans ; Lung Neoplasms/*genetics/pathology ; Mutation ; Neuroendocrine Tumors/*genetics/pathology ; Pancreatic Neoplasms/*genetics/pathology ; Receptors, Estrogen/genetics ; Transcription Factors/genetics ; *Transcriptome ; Exome Sequencing ; }, abstract = {AIMS: Breast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.<br><br>METHODS: On histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).<br><br>RESULTS: Breast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of PIK3CA mutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, PIK3CA mutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.<br><br>CONCLUSIONS: Breast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.}, }
@article {pmid33140128, year = {2021}, author = {Chen, XY and Thike, AA and Koh, VCY and Nasir, NDM and Bay, BH and Tan, PH}, title = {Breast ductal Carcinoma in situ associated with microinvasion induces immunological response and predicts ipsilateral invasive recurrence.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {478}, number = {4}, pages = {679-686}, pmid = {33140128}, issn = {1432-2307}, support = {SHF/FG668S/2015//SingHealth Foundation/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*immunology/metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*immunology/metabolism/*pathology/prevention &amp; control ; Prognosis ; Proportional Hazards Models ; }, abstract = {Although microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and established invasive ductal carcinoma, survival outcomes and biological behaviour of DCIS-Mi are still poorly understood. This study investigated the potential influence of Mi on disease-free survival (DFS) and assessed its correlations with clinicopathological parameters, prognosis, molecular, and immune markers. CD4, CD8, forkhead box P3 (FOXP3), CD68, CD163, programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression in pure DCIS and DCIS-Mi, from a cohort of 198 patients, were determined by immunohistochemistry. DFS, clinicopathological parameters, immune markers, and biomarker expression were correlated with presence of Mi. Twelve out of 198 DCIS cases were associated with Mi. DCIS-Mi was significantly linked with ipsilateral invasive recurrence (p = 0.032). Kaplan-Meier analysis revealed that DCIS-Mi had worse DFS for ipsilateral invasive recurrence (p = 0.011) and this was affirmed by multivariate Cox regression analysis (95% CI 1.181-9.010, HR = 3.262, p = 0.023). DCIS-Mi was associated with higher densities of immune infiltrates positive for CD4 (p = 0.037), FOXP3 (p = 0.037), CD163 (p = 0.01), and PD-L1 (p = 0.015). This study demonstrated that DCIS-Mi was correlated with high densities of immune infiltrates and predicted ipsilateral invasive recurrence.}, }
@article {pmid33135196, year = {2021}, author = {Bishop, JA and Nakaguro, M and Whaley, RD and Ogura, K and Imai, H and Laklouk, I and Faquin, WC and Sadow, PM and Gagan, J and Nagao, T}, title = {Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations.}, journal = {Histopathology}, volume = {79}, number = {3}, pages = {338-346}, pmid = {33135196}, issn = {1365-2559}, support = {P01 CA240239/CA/NCI NIH HHS/United States ; //UT Southwestern Medical Center/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Carcinoma, Ductal/diagnosis/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Mutation ; Oncogene Fusion ; Oxyphil Cells/pathology ; Proto-Oncogene Proteins B-raf/*genetics ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/diagnosis/genetics/pathology ; Salivary Glands/pathology ; Sequence Analysis, RNA ; Transcription Factors/*genetics ; }, abstract = {AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC.<br><br>METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75&#xa0;years (mean, 63&#xa0;years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23&#xa0;months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations.<br><br>CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.}, }
@article {pmid33132109, year = {2021}, author = {Zong, Y and Montironi, R and Massari, F and Jiang, Z and Lopez-Beltran, A and Wheeler, TM and Scarpelli, M and Santoni, M and Cimadamore, A and Cheng, L}, title = {Intraductal Carcinoma of the Prostate: Pathogenesis and Molecular Perspectives.}, journal = {European urology focus}, volume = {7}, number = {5}, pages = {955-963}, doi = {10.1016/j.euf.2020.10.007}, pmid = {33132109}, issn = {2405-4569}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Pelvis/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P), a clinicopathological entity characterized by malignant prostatic epithelial cells growing within ducts and/or acini, has a distinct architectural pattern, cytological features, and biological behavior. Whereas most IDC-P tumors could be derived from adjacent high-grade invasive cancer via retrograde spreading of cancer cells along benign ducts and acini, a small subset of IDC-P may arise from the transformation and intraductal proliferation of precancerous cells induced by various oncogenic events. These isolated IDC-P tumors possess a distinct mutational profile and may function as a carcinoma in situ lesion with de novo intraductal outgrowth of malignant cells. Further molecular characterization of these two types of IDC-P and better understanding of the mechanisms underlying IDC-P formation and progression could be translated into valuable biomarkers for differential diagnosis and actionable targets for therapeutic interventions. PATIENT SUMMARY: Intraductal carcinoma of the prostate is an aggressive type of prostate cancer associated with high risk for local recurrence and distant metastasis. In this review, we discussed pathogenesis, biomarkers, differential diagnoses, and therapeutic strategies for this tumor.}, }
@article {pmid33130707, year = {2020}, author = {Kosaka, Y and Kikuchi, M and Nishimiya, H and Katoh, H and Kawaguchi, R and Araki, N and Shimazu, M and Tsumura, H and Waraya, M and Takada, F and Sengoku, N and Sangai, T}, title = {[In Situ Ductal Carcinoma with Hereditary Breast and Ovarian Cancer Syndrome in a Patient Who Received Contralateral Risk-Reducing Mastectomy-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {47}, number = {9}, pages = {1387-1389}, pmid = {33130707}, issn = {0385-0684}, mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating ; Child ; Female ; *Hereditary Breast and Ovarian Cancer Syndrome/genetics/surgery ; Humans ; Mastectomy ; }, abstract = {A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy(CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.}, }
@article {pmid33126344, year = {2020}, author = {Liu, C and Wang, C and Du, Z and Xue, H and Liu, Z}, title = {Clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia.}, journal = {Medicine}, volume = {99}, number = {44}, pages = {e22904}, pmid = {33126344}, issn = {1536-5964}, mesh = {Age Factors ; Anticarcinogenic Agents/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; China/epidemiology ; Female ; Humans ; Imatinib Mesylate/*therapeutic use ; Incidence ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/diagnosis/epidemiology/pathology ; Male ; Middle Aged ; *Neoplasms, Multiple Primary/blood/diagnosis/epidemiology/pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Time Factors ; }, abstract = {This study was to investigate clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia (CML-DPMNs). Clinical data of thirteen CML-DPMN patients who were admitted to the First Hospital of Jilin University from May 2008 to December 2018 were collected and retrospectively analyzed. Female patients (9/13) were predominant in this cohort study. Nine patients were metachronous DPMNs (metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia) with 5 years median interval time from primary malignancy to secondary malignancy. The other 4 patients were diagnosed as synchronous CML-DPMNs. Seven of the metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia suffered from CML following many years of comprehensive anti-cancer therapy. Two of CML-MDPMN patients had invasive ductal carcinoma of breast after many years of treatment with imatinib. There was no difference between treatment-related CML group and non-treatment-related CML group in regard as the gender, age, white blood cell count, hemoglobin level, platelet count, and risk level. The median overall survival time of these thirteen patients with CML-DPMNs was not reached. In conclusion, female patients are more likely to suffer from the CML-DPMNs in the present article. Overall survival time of patients with DPMNs involving CML could be promising if timely and effective treatment therapy is adopted.}, }
@article {pmid33106505, year = {2020}, author = {Tsai, HT and Huang, CS and Tu, CC and Liu, CY and Huang, CJ and Ho, YS and Tu, SH and Tseng, LM and Huang, CC}, title = {Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {18276}, pmid = {33106505}, issn = {2045-2322}, mesh = {Bayes Theorem ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Calcinosis/*diagnosis/genetics ; Early Detection of Cancer ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Taiwan ; Exome Sequencing ; }, abstract = {Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ[2]-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.}, }
@article {pmid33097605, year = {2021}, author = {Kurley, SJ and Tischler, V and Bierie, B and Novitskiy, SV and Noske, A and Varga, Z and Zürrer-Härdi, U and Brandt, S and Carnahan, RH and Cook, RS and Muller, WJ and Richmond, A and Reynolds, AB}, title = {A requirement for p120-catenin in the metastasis of invasive ductal breast cancer.}, journal = {Journal of cell science}, volume = {134}, number = {6}, pages = {}, pmid = {33097605}, issn = {1477-9137}, support = {R01 CA200681/CA/NCI NIH HHS/United States ; IK6 BX005225/BX/BLRD VA/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P50 CA098131/CA/NCI NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; R01 CA055724/CA/NCI NIH HHS/United States ; P01 CA099031/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; P30 HD015052/HD/NICHD NIH HHS/United States ; R01 CA243326/CA/NCI NIH HHS/United States ; R01 CA111947/CA/NCI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/genetics ; Cadherins/genetics ; Catenins/genetics ; Cell Adhesion ; Female ; Humans ; Mice ; Tumor Microenvironment ; Delta Catenin ; }, abstract = {We report here the effects of targeted p120-catenin (encoded by CTNND1; hereafter denoted p120) knockout (KO) in a PyMT mouse model of invasive ductal (mammary) cancer (IDC). Mosaic p120 ablation had little effect on primary tumor growth but caused significant pro-metastatic alterations in the tumor microenvironment, ultimately leading to a marked increase in the number and size of pulmonary metastases. Surprisingly, although early effects of p120-ablation included decreased cell-cell adhesion and increased invasiveness, cells lacking p120 were almost entirely unable to colonized distant metastatic sites in vivo The relevance of this observation to human IDC was established by analysis of a large clinical dataset of 1126 IDCs. As reported by others, p120 downregulation in primary IDC predicted worse overall survival. However, as in the mice, distant metastases were almost invariably p120 positive, even in matched cases where the primary tumors were p120 negative. Collectively, our results demonstrate a strong positive role for p120 (and presumably E-cadherin) during metastatic colonization of distant sites. On the other hand, downregulation of p120 in the primary tumor enhanced metastatic dissemination indirectly via pro-metastatic conditioning of the tumor microenvironment.}, }
@article {pmid33090732, year = {2020}, author = {Morigny, P and Zuber, J and Haid, M and Kaltenecker, D and Riols, F and Lima, JDC and Simoes, E and Otoch, JP and Schmidt, SF and Herzig, S and Adamski, J and Seelaender, M and Berriel Diaz, M and Rohm, M}, title = {High levels of modified ceramides are a defining feature of murine and human cancer cachexia.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {11}, number = {6}, pages = {1459-1475}, pmid = {33090732}, issn = {2190-6009}, support = {J 4224/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; *Cachexia/etiology ; *Ceramides/metabolism ; Humans ; Mice ; Muscular Atrophy ; *Neoplasms/complications ; Quality of Life ; }, abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial energy-wasting syndrome reducing the efficiency of anti-cancer therapies, quality of life, and survival of cancer patients. In the past years, most studies focused on the identification of tumour and host-derived proteins contributing to CCx. However, there is still a lack of studies addressing the changes in bioactive lipids. The aim of this study was to identify specific lipid species as a hallmark of CCx by performing a broad range lipid analysis of plasma from well-established CCx mouse models as well as cachectic and weight stable cancer patients.<br><br>METHODS: Plasma from non-cachectic (PBS-injected mice, NC26 tumour-bearing mice), pre-cachectic and cachectic mice (C26 and LLC tumour-bearing mice, Apc[Min/+] mutant mice), and plasma from weight stable and cachectic patients with gastrointestinal cancer, were analysed using the Lipidyzer&#x2122; platform. In total, 13 lipid classes and more than 1100 lipid species, including sphingolipids, neutral and polar glycerolipids, were covered by the analysis. Correlation analysis between specific lipid species and readouts of CCx were performed. Lipidomics data were confirmed by gene expression analysis of metabolic organs to analyse enzymes involved in sphingolipid synthesis and degradation.<br><br>RESULTS: A decrease in several lysophosphatidylcholine (LPC) species and an increase in numerous sphingolipids including sphingomyelins (SMs), ceramides (CERs), hexosyl-ceramides (HCERs) and lactosyl-ceramides (LCERs), were mutual features of CCx in both mice and cancer patients. Notably, sphingolipid levels gradually increased during cachexia development. Key enzymes involved in ceramide synthesis were elevated in liver but not in adipose, muscle, or tumour tissues, suggesting that ceramide turnover in the liver is a major contributor to elevated sphingolipid levels in CCx. LPC(16:1), LPC(20:3), SM(16:0), SM(24:1), CER(16:0), CER(24:1), HCER(16:0), and HCER(24:1) were the most consistently affected lipid species between mice and humans and correlated negatively (LPCs) or positively (SMs, CERs and HCERs) with the severity of body weight loss.<br><br>CONCLUSIONS: High levels of sphingolipids, specifically ceramides and modified ceramides, are a defining feature of murine and human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the inhibition of anabolic signals. The progressive increase in sphingolipids during cachexia development supports their potential as early biomarkers for CCx.}, }
@article {pmid33086236, year = {2021}, author = {Bishop, JA and Rooper, LM and Sangoi, AR and Gagan, J and Thompson, LDR and Inagaki, H}, title = {The Myoepithelial Cells of Salivary Intercalated Duct-type Intraductal Carcinoma Are Neoplastic: A Study Using Combined Whole-slide Imaging, Immunofluorescence, and RET Fluorescence In Situ Hybridization.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {4}, pages = {507-515}, doi = {10.1097/PAS.0000000000001605}, pmid = {33086236}, issn = {1532-0979}, mesh = {Aged ; Automation, Laboratory ; *Biomarkers, Tumor/analysis/genetics ; Calcium-Binding Proteins/*analysis ; *Carcinoma, Ductal/chemistry/genetics/pathology ; Female ; *Fluorescent Antibody Technique ; Gene Fusion ; Humans ; Image Interpretation, Computer-Assisted ; *In Situ Hybridization, Fluorescence ; Male ; Microfilament Proteins/*analysis ; Middle Aged ; Predictive Value of Tests ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/chemistry/genetics/pathology ; }, abstract = {Intraductal carcinoma (IDC) is a salivary gland tumor currently believed to be analogous to breast ductal carcinoma in situ, consisting of a complex neoplastic epithelial proliferation surrounded by a continuous layer of myoepithelial cells presumed to be native and non-neoplastic. Recent molecular insights have shown that there are at least 3 different types of IDC: (1) intercalated duct-like, with frequent NCOA4-RET fusions; (2) apocrine, with multiple mutations similar to salivary duct carcinoma; and (3) mixed intercalated duct-like and apocrine with frequent RET fusions, especially TRIM27-RET. Recent observations (eg, IDC occurring in lymph nodes) have challenged the notion that the myoepithelial cells of IDC are non-neoplastic. Five IDCs with known RET fusions by RNA sequencing were retrieved from the authors' archives, including 4 intercalated duct-like IDCs with NCOA4-RET, and 1 mixed intercalated duct-like/apocrine IDC with TRIM27-RET. A panel of immunohistochemistry antibodies (S100 protein, p63 or p40, mammaglobin, smooth muscle actin, calponin, androgen receptor) was tested. To precisely localize RET split-positive cells, each case was subjected to sequential retrieval of whole-slide imaging data of hematoxylin and eosin (HE) staining, immunofluorescence staining for calponin, and fluorescence in situ hybridization (FISH) for RET. Because NCOA4-RET is an inversion difficult to visualize on conventional RET FISH, a novel 3-color FISH technique was utilized to demonstrate it clearly. In all 5 cases, the proliferative ducts were completely surrounded by a layer of myoepithelial cells that were positive for p63 or p40, smooth muscle actin, and calponin. Using combined HE, calponin immunofluorescence, and RET FISH imaging, the positive signals were unmistakably identified in both calponin-negative ductal cells and peripheral, calponin-positive myoepithelial cells in all 5 cases. Utilizing combined HE, calponin immunofluorescence, and RET FISH imaging, we demonstrated that IDCs with RET fusions harbored this alteration in both the ductal and myoepithelial cells. This is compelling evidence that the myoepithelial cells of IDC are not mere bystanders, but are rather a component of the neoplasm itself, similar to other biphasic salivary gland neoplasms like pleomorphic adenoma and epithelial-myoepithelial carcinoma. This finding raises questions about the appropriate terminology, classification, and staging of IDC.}, }
@article {pmid33073677, year = {2020}, author = {Qi, P and Bai, QM and Yao, QL and Yang, WT and Zhou, XY}, title = {Performance of Automated Dissection on Formalin-Fixed Paraffin-Embedded Tissue Sections for the 21-Gene Recurrence Score Assay.}, journal = {Technology in cancer research &amp; treatment}, volume = {19}, number = {}, pages = {1533033820960760}, pmid = {33073677}, issn = {1533-0338}, mesh = {Breast Neoplasms/*genetics/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Paraffin Embedding ; Real-Time Polymerase Chain Reaction/*methods ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Transcriptome/*genetics ; }, abstract = {This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases each, LN tissue and a mixture of IDC and LN tissue from the other tissue block of the same 4 patients were mesodissected to evaluate the influence of infiltrating lymphocyte levels on the RS values of AOIs. In our experience, the MilliSect instrument, which provides process management documentation, required more time than manual macrodissection (on average, approximately 9.1 min per sample versus 5.8 min per sample, respectively). The RNA yield and quality of the dissected tissues were comparable for the 2 methods. However, the tumor-adjacent tissues of the AOIs may influence the RS to some extent. Tumor-infiltrating lymphocytes (TILs) can dramatically increase RSs, far exceeding the influence of tumor-adjacent fibrocollagenous and epithelial tissues. In conclusion, MilliSect mesodissection is comparable to manual dissection. This mesodissection tool may facilitate AOI alignment and the dissection process for the 21-gene RS assay. Samples whose adjacent tissues are intermixed with TILs warrant special attention.}, }
@article {pmid33049657, year = {2020}, author = {Zhang, J and Lu, CY and Qin, L and Chen, HM and Wu, SY}, title = {Breast-conserving surgery with or without irradiation in women with invasive ductal carcinoma of the breast receiving preoperative systemic therapy: A cohort study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {54}, number = {}, pages = {139-147}, pmid = {33049657}, issn = {1532-3080}, mesh = {Adult ; Antineoplastic Protocols ; Breast/pathology ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/mortality/*therapy ; Chemotherapy, Adjuvant/methods/*mortality ; Cohort Studies ; Combined Modality Therapy ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy, Segmental/methods/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/etiology/pathology ; Neoplasm Staging ; Neoplasm, Residual ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant/methods/*mortality ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; }, abstract = {PURPOSE: To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival.<br><br>PATIENTS AND METHODS: Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs).<br><br>RESULTS: Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2-4) or nodal (ypN2-3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03-0.81), 0.32 (0.16-0.64), 0.43 (0.23-0.79), 0.23 (0.13-0.42), 0.52 (0.20-1.33), and 0.34 (0.13-0.87) in the ypT0, ypT1, ypT2-4, ypN0, ypN1, and ypN2-3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00-4.07), 0.46 (0.26-0.83), 0.18 (0.06-0.51), 0.28 (0.06-1.34), 0.25 (0.10-0.63), 0.47 (0.23-0.88), and 0.32 in the cT0-1, cT2, cT3, cT4, cN0, cN1, and cN2-3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST.<br><br>CONCLUSION: WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response.}, }
@article {pmid33047834, year = {2021}, author = {Nishimoto, A and Kuwahara, H and Ohashi, R and Ansai, SI}, title = {Multicentric endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma of the skin: A case report.}, journal = {Journal of cutaneous pathology}, volume = {48}, number = {1}, pages = {165-170}, doi = {10.1111/cup.13896}, pmid = {33047834}, issn = {1600-0560}, mesh = {Adenocarcinoma, Mucinous/*pathology ; Aged ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Humans ; Mucins ; Neoplasms, Multiple Primary/*pathology ; Skin Neoplasms/*pathology ; Sweat Gland Neoplasms/*pathology ; Uterine Neoplasms/pathology ; }, abstract = {Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma. EMPSGC is thought to be a precursor to mucinous carcinoma of the skin (MCS). Since the first description of EMPSGC in 1997, only a few cases have been reported, and its etiology and mechanisms remain unknown. In this report, we describe a 71-year-old Japanese woman with two isolated EMPSGC and one MCS lesion on her face. She was simultaneously diagnosed with invasive ductal carcinoma of the breast. She had a history of uterine cancer of unknown histopathological diagnosis 24 years previously. The presence of in situ lesions confirmed by myoepithelial cells suggested that the cutaneous lesions were primary tumors. To the best of our knowledge, this is the first case of multiple primary EMPSGC/MCS tumors. Additionally, this might be the first case with multiple primary carcinomas including adnexal cutaneous tumors, breast cancer, and uterine cancer, which may share the common feature of expressing female hormonal receptors. This case indicates that EMPSGC/MCS may be triggered by a hormonal receptor abnormality, perhaps because of genetic defects. A larger number of reports examining this issue may be necessary to further assess our initial observations.}, }
@article {pmid33039708, year = {2020}, author = {Bitencourt, AGV and Gibbs, P and Rossi Saccarelli, C and Daimiel, I and Lo Gullo, R and Fox, MJ and Thakur, S and Pinker, K and Morris, EA and Morrow, M and Jochelson, MS}, title = {MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103042}, pmid = {33039708}, issn = {2352-3964}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Biomarkers ; Breast Neoplasms/*diagnostic imaging/*genetics/therapy ; Female ; *Gene Expression ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; *Machine Learning ; *Magnetic Resonance Imaging/methods ; Middle Aged ; Neoadjuvant Therapy ; ROC Curve ; Receptor, ErbB-2/*genetics/metabolism ; Young Adult ; }, abstract = {BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC).<br><br>METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20).<br><br>FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test).<br><br>INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients.<br><br>FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.}, }
@article {pmid33027710, year = {2021}, author = {Thongpiya, J and Sa-Nguanraksa, D and Samarnthai, N and Sarasombath, PT}, title = {Filariasis of the breast caused by Brugia pahangi: A concomitant finding with invasive ductal carcinoma.}, journal = {Parasitology international}, volume = {80}, number = {}, pages = {102203}, pmid = {33027710}, issn = {1873-0329}, mesh = {Animals ; Breast Diseases/*diagnosis/parasitology ; Breast Neoplasms/*pathology ; Brugia pahangi/classification/*isolation &amp; purification ; Carcinoma, Ductal, Breast/*pathology ; DNA, Ribosomal Spacer/analysis ; Female ; Filariasis/*diagnosis/parasitology ; Humans ; Middle Aged ; RNA, Helminth/analysis ; RNA, Ribosomal/analysis ; Thailand ; }, abstract = {Extralymphatic filariasis is an uncommon phenomenon that can be caused by several lymphatic filarial species, including zoonotic filaria of animal origins. In this study, we report a case of a 64-year-old Thai woman who presented with a lump in her left breast that was diagnosed with invasive ductal carcinoma. At the same time, a small nodule was found in her right breast, via imaging study, without any abnormal symptoms. A core needle biopsy of the right breast nodule revealed a filarial-like nematode compatible with the adult stage of Brugia sp. A molecular identification of the nematode partial mt 12rRNA gene and ITS1 suggested the causative species as closely related to Brugia pahangi, a zoonotic lymphatic filaria of animals such as cats and dogs. The sequence of the partial mt 12rRNA and ITS1 gene in this patient was 94% and 99% identical to the previously reported sequence of mt 12rRNA and ITS1 genes of B. pahangi. The sequence of ITS1 gene is 99% similar to B. pahangi microfilaria from infected dogs in Bangkok, which was highly suspected of having a zoonotic origin. As far as we know, this is the first case report of B. pahangi filariasis presented with a breast mass concomitantly found in a patient with invasive ductal carcinoma. This raised serious concern regarding the zoonotic transmission of filariasis from natural animal reservoirs.}, }
@article {pmid33027370, year = {2020}, author = {Gewehr, DM and Salgueiro, GR and Noronha, L and Kubrusly, FB and Kubrusly, LF and Coltro, GA and Preto, PC and Bertoldi, AS and Vieira, HI}, title = {Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension.}, journal = {Arquivos brasileiros de cardiologia}, volume = {115}, number = {3}, pages = {480-490}, pmid = {33027370}, issn = {1678-4170}, mesh = {Animals ; Humans ; *Hypertension, Pulmonary/chemically induced ; Hypertrophy, Right Ventricular/chemically induced ; Male ; Monocrotaline/toxicity ; *Pulmonary Arterial Hypertension ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans.<br><br>OBJECTIVE: To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival.<br><br>METHODS: Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%.<br><br>RESULTS: In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000).<br><br>CONCLUSION: The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490).}, }
@article {pmid33024608, year = {2020}, author = {Matich, A and Sud, S and Buxi, TBS and Dogra, V}, title = {Idiopathic Granulomatous Mastitis and its Mimics on Magnetic Resonance Imaging: A Pictorial Review of Cases from India.}, journal = {Journal of clinical imaging science}, volume = {10}, number = {}, pages = {53}, pmid = {33024608}, issn = {2156-7514}, abstract = {OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is a rare inflammatory disease of the breast, which is benign but potentially morbid. Mammographic and sonographic findings have been well characterized, but magnetic resonance imaging (MRI) findings have been less thoroughly documented. The objective of this study was to demonstrate characteristic findings for IGM and its mimics via a retrospective review.<br><br>MATERIAL AND METHODS: Breast MRI examinations performed at Sir Ganga Ram Hospital in New Delhi, India between 2014 and 2019 were retrospectively reviewed to identify cases in which a pattern suggestive of granulomatous mastitis was seen. Cases of known malignancy were excluded. Any available breast pathology results were then obtained, and cases with presumptive or definitive diagnoses were compiled for analysis.<br><br>RESULTS: Overall, cases identified with characteristic imaging findings and confirmed diagnosis included seven cases of IGM, four cases of invasive ductal carcinoma, two cases of tuberculous mastitis, one case of non- tuberculous infectious mastitis, one case of foreign body mastitis, and one case of eosinophilc mastitis. One case of IGM with masses rather than of non-mass enhancement was also identified.<br><br>CONCLUSION: In our review, cases with clustered ring enhancement were found to have inflammatory, idiopathic, infectious and malignant etiologies. While, these etiologies can only be reliably differentiated on pathology, familiarity with the pattern and an awareness of the differential may lead to decreased morbidity due to delays in diagnosis.}, }
@article {pmid33023170, year = {2020}, author = {Petre, AR and Craciunescu, R and Fratu, O}, title = {Design, Implementation and Simulation of a Fringing Field Capacitive Humidity Sensor.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {19}, pages = {}, pmid = {33023170}, issn = {1424-8220}, support = {51675/09.07.2019, SMIS code 125125//Operational Programme Human Capital of the Ministry of European Funds through the Financial Agreement/ ; 33PCCDI/2018//Ministry of Innovation and Research, UEFISCDI, MultiMonD2 within PNCDI III/ ; }, abstract = {The world population is growing in an accelerated way urging the need for a more efficient and sustainable agricultural industry. Initially developed for smart cities which face the same challenges caused by an increasing population, Internet of Things (IoT) technologies have evolved rapidly over the last few years and are now moving successfully to agriculture. Wireless Sensor Networks (WSNs) have been reported to be used in the agri-food sector and could answer the call for a more optimized agricultural management. This paper investigates a PCB-made interdigited capacitive (IDC) soil humidity sensor as a low-price alternative to the existing ones on the market. An in-depth comparative study is performed on 30 design variations, part of them also manufactured for further investigations. By measurements and simulations, the influence of the aspect ratio and dielectric thickness on the sensitivity and capacitance of the sensor are studied. In the end, a Humidity and Temperature Measurement Wireless Equipment (HTMWE) for IoT agriculture applications is implemented with this type of sensor.}, }
@article {pmid33016589, year = {2019}, author = {Merry, R and Butenhoff, K and Campbell, BW and Michno, JM and Wang, D and Orf, JH and Lorenz, AJ and Stupar, RM}, title = {Identification and Fine-Mapping of a Soybean Quantitative Trait Locus on Chromosome 5 Conferring Tolerance to Iron Deficiency Chlorosis.}, journal = {The plant genome}, volume = {12}, number = {3}, pages = {1-13}, doi = {10.3835/plantgenome2019.01.0007}, pmid = {33016589}, issn = {1940-3372}, mesh = {Genome-Wide Association Study ; *Iron Deficiencies ; *Plant Diseases ; Quantitative Trait Loci ; Soybeans/*genetics ; }, abstract = {CORE IDEAS: 'Fiskeby III' harbors a combination of abiotic stress traits, including iron deficiency chlorosis (IDC) tolerance. An IDC quantitative trait locus on chromosome Gm05 was identified in genome-wide association studies and biparental populations. Fine-mapping resolved a 137-kb interval containing strong candidate genes. Iron deficiency chlorosis (IDC) is an important nutrient stress for soybean [Glycine max (L.) Merr.] grown in high-pH soils. Despite numerous agronomic attempts to alleviate IDC, genetic tolerance remains the most effective preventative measure against symptoms. In this study, two association mapping populations and a biparental mapping population were used for genetic mapping of IDC tolerance. Quantitative trait loci (QTLs) were identified on chromosomes Gm03, Gm05, and Gm06. Heterogenous inbred families were developed to fine-map the Gm05 QTL, which was uniquely supported in all three mapping populations. Fine-mapping resulted in a QTL with an interval size of 137 kb on the end of the short arm of Gm05, which produced up to a 1.5-point reduction in IDC severity on a 1 to 9 scale in near isogenic lines.}, }
@article {pmid33011829, year = {2021}, author = {Sadeghalvad, M and Mohammadi-Motlagh, HR and Rezaei, N}, title = {Immune microenvironment in different molecular subtypes of ductal breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {185}, number = {2}, pages = {261-279}, pmid = {33011829}, issn = {1573-7217}, support = {41086//Tehran University of Medical Sciences/ ; }, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/genetics/immunology ; *Carcinoma, Ductal, Breast ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; *Immunity, Cellular ; Prognosis ; *Tumor Microenvironment ; }, abstract = {PURPOSE: Ductal breast carcinoma as a heterogeneous disease has different molecular subtypes associated with clinical prognosis and patients' survival. The role of immune system as a consistent part of the tumor microenvironment (TME) has been documented in progression of ductal breast carcinoma. Here, we aimed to describe the important immune cells and the immune system-associated molecules in Ductal Carcinoma In situ (DCIS) and Invasive Ductal Carcinoma (IDC) with special emphasis on their associations with different molecular subtypes and patients' prognosis.<br><br>RESULTS: The immune cells have a dual role in breast cancer (BC) microenvironment depending on the molecular subtype or tumor grade. These cells with different frequencies are present in the TME of DCIS and IDC. The presence of regulatory cells including Tregs, MDSC, Th2, Th17, M2 macrophages, HLADR[-] T cells, and T&#x3b3;&#x3b4; cells is related to more immunosuppressive microenvironment, especially in ER[-] and TN subtypes. In contrast, NK cells, CTL, Th, and Tfh cells are associated to the anti-tumor activity. These cells are higher in ER[+] BC, although in other subtypes such as TN or HER2[+] are associated with a favorable prognosis.<br><br>CONCLUSION: Determining the specific immune response in each subtype could be helpful in estimating the possible behavior of the tumor cells in TME. It is important to realize that different frequencies of immune cells in BC environment likely determine the patients' prognosis and their survival in each subtype. Therefore, elucidation of the distinct immune players in TME would be helpful toward developing targeted therapies in each subtype.}, }
@article {pmid33011180, year = {2020}, author = {Roberts, WC and Everett, BP and Won, VS and Kondapalli, N}, title = {Diagnostic Usefulness of Histological Examination of the Left Ventricular "Core" Excised to Insert a Left Ventricular Assist Device in Patients With Severe Heart Failure.}, journal = {The American journal of cardiology}, volume = {137}, number = {}, pages = {71-76}, doi = {10.1016/j.amjcard.2020.09.038}, pmid = {33011180}, issn = {1879-1913}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Female ; Heart Failure/*diagnosis/physiopathology/therapy ; *Heart-Assist Devices ; Humans ; Male ; Middle Aged ; Myocardium/*pathology ; Severity of Illness Index ; Stroke Volume/*physiology ; Ventricular Function, Left/*physiology ; Young Adult ; }, abstract = {The left ventricular assist device (LVAD) has proven to be beneficial for patients with severe heart failure poorly responsive to anti heart failure medicine. To examine both grossly and histologically the portion of left ventricular (LV) free wall excised ("the left ventricular core") to insert a LVAD in 337 patients with severe heart failure from a variety of causes. We collected together all photographs of LV "cores" and the histologic sections prepared from them and reexamined both. Despite the fact that these LV cores usually weighed >100 times the quantity of myocardium available to examine compared with that available by biotome inserted via a transvenous catheter, the number in which histologic study allowed an unequivocal diagnosis was limited. Examination of the clinical records usually was required to establish the definitive diagnosis. Although the presence of a scarred myocardial wall usually suggested ischemic cardiomyopathy (IC), the scarring may not have involved the LV apex resulting in a nonscarred portion of myocardium simulating idiopathic dilated cardiomyopathy (IDC). Moreover, about 10% of the patients with IDC have myocardial scars thus simulating IC. Involvement of the LV core by amyloid, sarcoid, myocarditis, and acute infarction, of course, allowed a specific anatomic diagnosis. Despite the presence of ample tissue to secure a definitive diagnosis, the combination of clinical input and morphologic assessment was required to arrive at a definite diagnosis in most patients.}, }
@article {pmid32995936, year = {2021}, author = {Doello, K and Conde, V and Perez, MC and Mendoza, I and Mesas, C and Prados, J}, title = {Unusual long survival in a case of heterotaxy and polysplenia.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {43}, number = {4}, pages = {607-611}, pmid = {32995936}, issn = {1279-8517}, mesh = {Bone Neoplasms/diagnosis/secondary ; Breast Neoplasms/diagnosis/therapy ; Carcinoma, Ductal, Breast/diagnosis/therapy ; Chemoradiotherapy, Adjuvant ; Contrast Media/administration &amp; dosage ; Female ; Heterotaxy Syndrome/*diagnosis ; Humans ; Incidental Findings ; Liver Neoplasms/diagnosis/secondary ; Mastectomy, Segmental ; Middle Aged ; Spleen/*abnormalities/diagnostic imaging ; Time Factors ; Tomography, X-Ray Computed ; }, abstract = {Heterotaxy syndrome with polysplenia is an extremely rare congenital disorder caused by a disruption in the embryonic development that results in an abnormal arrangement of the abdominal and thoracic organs. We present the case of a 59-year-old female patient with invasive ductal carcinoma of the right breast (luminal A type) and CT findings of heterotaxy syndrome with polysplenia. The most remarkable anomalies identified were a left inferior vena cava draining into the hemiazygos vein, absent inferior vena cava at the thoracic level, and hepatic veins directly draining into the right atrium. Moreover, an atrial septal defect was identified, explaining the pulmonary hypertension of unknown cause previously detected in the patient. The relevance of this case lies in the unusual anatomical abnormalities found and the large patient survival, having in to account the great rate of heterotaxy syndrome mortality in the first years of life.}, }
@article {pmid32988889, year = {2020}, author = {Yildirim, E and Bektas, S and Gundogar, O and Findik, D and Alcicek, S and Erdogan, KO and Yildiz, M}, title = {The Relationship of GATA3 and Ki-67 With Histopathological Prognostic Parameters, Locoregional Recurrence and Disease-free Survival in Invasive Ductal Carcinoma of the Breast.}, journal = {Anticancer research}, volume = {40}, number = {10}, pages = {5649-5657}, doi = {10.21873/anticanres.14578}, pmid = {32988889}, issn = {1791-7530}, mesh = {Adult ; Biomarkers, Tumor ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; Disease-Free Survival ; Estrogens/genetics ; Female ; GATA3 Transcription Factor/*genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/*genetics ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*genetics/pathology ; Progesterone/genetics ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND: In recent years, GATA-binding protein 3 (GATA3) has been indicated as a marker showing good prognosis in breast cancer. In luminal breast cancer, which has good a prognosis, it shows more significant elevation in small-sized and low-grade tumors. In contrast, Ki-67 is defined as a poor prognostic factor. The aim of this study was to emphasise the prognostic importance of GATA3 and the inverse relationship with Ki-67.<br><br>MATERIALS AND METHODS: In our study, 90 patients with invasive ductal breast cancer were immunohistochemically evaluated for Ki-67 and GATA3 expression. The relationship between GATA3 and Ki-67 expression was examined. In addition, the relationship between these two factors with estrogen, progesterone, human epidermal growth factor 2 receptor antibodies and other prognostic parameters such as disease-free survival and local recurrence was investigated. We accepted the level of &#x2265;5% n&#xfc;clear reaction as positive for GATA 3. A Ki-67 cut-off value of 20% was accepted as positive.<br><br>RESULTS: In GATA3 positive breast cancers, good prognostic parameters were seen including high estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, small tumor size and low histological grade as well as low Ki-67 expression. In breast cancers showing high Ki-67 expression, ER, PR, and GATA3 positivity were lower and there was higher human epidermal growth factor receptor 2 (HER2) positivity and high histological grade while the tumor size was larger.<br><br>CONCLUSION: Our study has revealed that GATA3 has an inverse relationship with Ki-67, whereas it has a positive releationship with good prognostic factors.}, }
@article {pmid32980661, year = {2020}, author = {Lou, B and Boger, M and Bennewitz, K and Sticht, C and Kopf, S and Morgenstern, J and Fleming, T and Hell, R and Yuan, Z and Nawroth, PP and Kroll, J}, title = {Elevated 4-hydroxynonenal induces hyperglycaemia via Aldh3a1 loss in zebrafish and associates with diabetes progression in humans.}, journal = {Redox biology}, volume = {37}, number = {}, pages = {101723}, pmid = {32980661}, issn = {2213-2317}, mesh = {*Aldehyde Dehydrogenase/genetics ; Aldehydes ; Animals ; *Diabetes Mellitus ; Gene Knockout Techniques ; Humans ; *Hyperglycemia/genetics ; *Zebrafish/genetics ; }, abstract = {Increased methylglyoxal (MG) formation is associated with diabetes and its complications. In zebrafish, knockout of the main MG detoxifying system Glyoxalase 1, led to limited MG elevation but significantly elevated aldehyde dehydrogenases (ALDH) activity and aldh3a1 expression, suggesting the compensatory role of Aldh3a1 in diabetes. To evaluate the function of Aldh3a1 in glucose homeostasis and diabetes, aldh3a1[-/-] zebrafish mutants were generated using CRISPR-Cas9. Vasculature and pancreas morphology were analysed by zebrafish transgenic reporter lines. Corresponding reactive carbonyl species (RCS), glucose, transcriptome and metabolomics screenings were performed and ALDH activity was measured for further verification. Aldh3a1[-/-] zebrafish larvae displayed retinal vasodilatory alterations, impaired glucose homeostasis, which can be aggravated via pdx1 silencing induced hyperglycaemia. Unexpectedly, MG was not altered, but 4-hydroxynonenal (4-HNE), another prominent lipid peroxidation RCS exhibited high affinity with Aldh3a1, was increased in aldh3a1 mutants. 4-HNE was responsible for the retinal phenotype via pancreas disruption induced hyperglycaemia and can be rescued via l-Carnosine treatment. Furthermore, in type 2 diabetic patients, serum 4-HNE was increased and correlated with disease progression. Thus, our data suggest impaired 4-HNE detoxification and elevated 4-HNE concentration as biomarkers but also the possible inducers for diabetes, from genetic susceptibility to the pathological progression.}, }
@article {pmid32975612, year = {2020}, author = {Yoshida, Y and Matsumoto, I and Tanaka, T and Yamao, K and Hayashi, A and Kamei, K and Satoi, S and Takebe, A and Nakai, T and Takenaka, M and Takeyama, Y}, title = {Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report.}, journal = {Surgical case reports}, volume = {6}, number = {1}, pages = {222}, pmid = {32975612}, issn = {2198-7793}, abstract = {BACKGROUND: Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion.<br><br>CASE PRESENTATION: A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854&#xa0;IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15&#x2009;&#xd7;&#x2009;15&#xa0;mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor.<br><br>CONCLUSIONS: Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.}, }
@article {pmid32957504, year = {2020}, author = {Griffin, N and Marsland, M and Roselli, S and Oldmeadow, C and Attia, J and Walker, MM and Hondermarck, H and Faulkner, S}, title = {The Receptor Tyrosine Kinase TrkA Is Increased and Targetable in HER2-Positive Breast Cancer.}, journal = {Biomolecules}, volume = {10}, number = {9}, pages = {}, pmid = {32957504}, issn = {2218-273X}, support = {G1101013//Faculty of Health and Medicine, University of Newcastle Australia/International ; }, mesh = {Biomarkers, Tumor/antagonists &amp; inhibitors/*biosynthesis/genetics ; Breast Neoplasms/drug therapy/genetics/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/genetics/metabolism ; Carcinoma, Lobular/drug therapy/genetics/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunohistochemistry ; Middle Aged ; Molecular Targeted Therapy/methods ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Receptor, ErbB-2/*metabolism ; Receptor, trkA/antagonists &amp; inhibitors/*biosynthesis/genetics ; Survival Analysis ; }, abstract = {The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), 158 invasive lobular carcinomas (ILC) and 50 ductal carcinomas in situ (DCIS). TrkA was expressed in cancer epithelial and myoepithelial cells, with higher levels of TrkA positively associated with IDC (39% of cases) (p < 0.0001). Interestingly, TrkA was significantly increased in tumours expressing the human epidermal growth factor receptor-2 (HER2), with expression in 49% of HER2-positive compared to 25% of HER2-negative tumours (p = 0.0027). A panel of breast cancer cells were used to confirm TrkA protein expression, demonstrating higher levels of TrkA (total and phosphorylated) in HER2-positive cell lines. Functional investigations using four different HER2-positive breast cancer cell lines indicated that the Trk tyrosine kinase inhibitor GNF-5837 reduced cell viability, through decreased phospho-TrkA (Tyr490) and downstream AKT (Ser473) activation, but did not display synergy with Herceptin. Overall, these data highlight a relationship between the tyrosine kinase receptors TrkA and HER2 and suggest the potential of TrkA as a novel or adjunct target for HER2-positive breast tumours.}, }
@article {pmid32947148, year = {2020}, author = {Zhang, J and Lu, CY and Chen, CH and Chen, HM and Wu, SY}, title = {Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis.}, journal = {Breast (Edinburgh, Scotland)}, volume = {54}, number = {}, pages = {70-78}, pmid = {32947148}, issn = {1532-3080}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Chemotherapy, Adjuvant ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Staging ; Postoperative Period ; Proportional Hazards Models ; *Radiotherapy, Adjuvant ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; }, abstract = {PURPOSE: To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).<br><br>PATIENTS AND METHODS: We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.<br><br>RESULTS: After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52-0.81, P&#xa0;<&#xa0;0.0001) and 0.58 (0.47-0.71, P&#xa0;<&#xa0;0.0001) in postchemotherapy pathologic tumor stages T2-4 (ypT3-4) and postchemotherapy pathologic nodal stages N2-3 (ypN2-3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38-0.69, P&#xa0;<&#xa0;0.0001), 0.60 (0.40-0.88, P&#xa0;=&#xa0;0.0096), and 0.64 (0.48-0.86, P&#xa0;=&#xa0;0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0-4, ypN0-3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.<br><br>CONCLUSION: For patients with breast cancer ypT3-4, ypN2-3, or pathologic stages IIIA-IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.}, }
@article {pmid32943456, year = {2020}, author = {Richard, F and Majjaj, S and Venet, D and Rothé, F and Pingitore, J and Boeckx, B and Marchio, C and Clatot, F and Bertucci, F and Mariani, O and Galant, C and Eynden, GVD and Salgado, R and Biganzoli, E and Lambrechts, D and Vincent-Salomon, A and Pruneri, G and Larsimont, D and Sotiriou, C and Desmedt, C}, title = {Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {23}, pages = {6254-6265}, doi = {10.1158/1078-0432.CCR-20-2268}, pmid = {32943456}, issn = {1557-3265}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/immunology/metabolism/*secondary ; Carcinoma, Lobular/genetics/immunology/metabolism/*secondary ; Female ; Follow-Up Studies ; Genomics/*methods ; Humans ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Stromal Cells/*immunology ; Survival Rate ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level.<br><br>EXPERIMENTAL DESIGN: We retrospectively assembled the multicentric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor-infiltrating lymphocytes (sTILs) were assessed by experienced pathologists. Targeted sequencing and low pass whole-genome sequencing were conducted to detect mutations and copy-number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n = 135) and IDC (n = 563) from MSK-IMPACT.<br><br>RESULTS: Low sTIL levels were observed in ILC metastases, with higher levels in the mixed nonclassic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that >50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2, or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1, and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared with IDC metastases.<br><br>CONCLUSIONS: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared with IDC metastases.}, }
@article {pmid32920553, year = {2020}, author = {Bartlett, H and Elghobashy, M and Deshmukh, N and Rao, R and Shaaban, AM}, title = {Radiation-Associated Primary Osteosarcoma of the Breast.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {87}, number = {5}, pages = {322-326}, doi = {10.1159/000509580}, pmid = {32920553}, issn = {1423-0291}, mesh = {Aged ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/*etiology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Osteosarcoma/*diagnostic imaging/*etiology/surgery ; Radiation Injuries/complications ; Radiotherapy/*adverse effects ; }, abstract = {INTRODUCTION: Non-epithelial primary mammary osteosarcomas are extremely rare. The differentials include metaplastic carcinoma and malignant phyllodes tumour. This is the first published case of primary breast osteosarcoma arising after local radiotherapy.<br><br>CASE PRESENTATION: A 73-year-old female presented with a right-sided breast lump. The same breast had been irradiated 11 years previously for invasive ductal carcinoma. Diagnostic excision revealed a highly cellular, malignant spindle-cell lesion merged with an osteoid matrix and foci of calcification and bone formation. Immunohistochemistry and molecular studies showed no lines of differentiation. Due to the lack of epithelial/glandular differentiation, in situ carcinoma or leaf-like pattern, the diagnosis of post-irradiation osteosarcoma was made. She underwent mastectomy and is disease-free at 8 months of follow-up.<br><br>CONCLUSION: Post-irradiation osteosarcoma should be considered in the differential diagnosis of breast lesions showing malignant osteoid. Extensive sampling and careful search for epithelial differentiation is required to guide management. Complete surgical excision is recommended.}, }
@article {pmid32884534, year = {2020}, author = {Liu, IC and Giap, F and Mailhot-Vega, RB and Bradley, JA and Mendenhall, NP and Okunieff, P and Lu, L and Jantz, MA and Daily, K and Spiguel, L and Lockney, NA}, title = {Concomitant Radiation Recall Dermatitis and Organizing Pneumonia following Breast Radiotherapy: A Case Report.}, journal = {Case reports in oncology}, volume = {13}, number = {2}, pages = {875-882}, pmid = {32884534}, issn = {1662-6575}, abstract = {PURPOSE: Radiation recall dermatitis (RRD) is a rare complication that occurs after completion of radiation therapy (RT) and initiation of a precipitating agent, most commonly chemotherapeutic medications. Various theories attempt to explain the mechanism, including activation of the body's inflammatory pathways through nonimmune activation. Likewise, radiation-induced organizing pneumonia (RIOP) is an infrequent but potentially life-threatening complication of RT that, while not fully understood, is suspected to be partly an autoimmune reaction.<br><br>PATIENT: We present the case of a 71-year-old female with a history of type 2 diabetes mellitus, hypothyroidism, interstitial cystitis, and osteoarthritis who presented with clinical stage T1N0M0 ER+/PR-/HER2- invasive ductal carcinoma of the lower outer quadrant of the left breast, for which she underwent left segmental mastectomy and sentinel lymph node biopsy followed by completion axillary lymph node dissection. Her final pathologic stage was T1N1M0.<br><br>RESULT: The patient developed RRD and later RIOP following receipt of radiation and chemotherapy, which resolved with steroid administration.<br><br>CONCLUSIONS: The rarity of both RRD and RIOP occurring in a patient, as in our case, suggests a shared pathophysiology behind these two complications. As both reactions involve some degree of inflammation and respond to corticosteroids, it seems likely that the etiologies of RRD and RIOP lie within the inflammatory pathway. However, further investigation should evaluate the frequency, duration, and triggering of concomitant RRD and RIOP.}, }
@article {pmid32877689, year = {2020}, author = {Rohm, M and Herzig, S}, title = {An Antibody Attack against Body Wasting in Cancer.}, journal = {Cell metabolism}, volume = {32}, number = {3}, pages = {331-333}, doi = {10.1016/j.cmet.2020.08.003}, pmid = {32877689}, issn = {1932-7420}, mesh = {Adipose Tissue ; Animals ; *Cachexia/etiology ; Growth Differentiation Factor 15 ; Humans ; Mice ; *Neoplasms/complications ; }, abstract = {Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals.}, }
@article {pmid32876204, year = {2020}, author = {Salim, TR and Andrade, TM and Klein, CH and Oliveira, GMM}, title = {Inequalities in Mortality Rates from Malformations of Circulatory System Between Brazilian Macroregions in Individuals Younger Than 20 Years.}, journal = {Arquivos brasileiros de cardiologia}, volume = {115}, number = {6}, pages = {1164-1173}, pmid = {32876204}, issn = {1678-4170}, mesh = {Brazil/epidemiology ; *Cardiovascular Diseases ; *Cardiovascular System ; Cause of Death ; Female ; *Heart Defects, Congenital ; Humans ; Male ; Mortality ; }, abstract = {BACKGROUND: Deaths from malformations of the circulatory system (MCS) have a major impact on mortality reduction. given that most cases are avoidable with correct diagnosis and treatment.<br><br>OBJECTIVES: To describe the distribution of mortality from MCS by sex. age. and macroregion in Brazil. in individuals under the age of 20. between 2000 and 2015.<br><br>METHODS: A descriptive study of mortality rates and proportional mortality (PM) from MCS. other congenital malformations (OCM). circulatory system disease (CSD). ill-defined causes (IDC). and external causes (EC) in Brazil.<br><br>RESULTS: There were 1.367.355 deaths from all causes in individuals younger than 20. 55.0% under 1 year of age. A total of 144.057 deaths were caused by congenital malformations. 39% of them by MCS. In both sexes. the annual mortality from MCS was 5.3/100.000. PM from MCS was 4.2%. CSD 2.2%. IDC 6.2% and EC 24.9%. Unspecified MCS showed the highest PM rates in both sexes and age groups. especially in the north and northeast regions (60%). Deaths from malformations occurred 5.7 times more frequently during the first year of life than in other ages (MCS: 5.0; OCM: 6.4).<br><br>CONCLUSIONS: MCS was the leading cause of death among all malformations. being twice as important as CSD. mainly under 1 year of age. The frequency of misdiagnosis of MCS as cause of death was high in all ages and both sexes. especially in the north and northeast regions. These findings highlight the need for the development of public health strategies focused on correct diagnosis and early treatment of congenital cardiopathies. leading to a reduction in mortality. (Arq Bras Cardiol. 2020; 115(6):1164-1173).}, }
@article {pmid32871469, year = {2020}, author = {Molocea, CE and Tsokanos, FF and Herzig, S}, title = {Exploiting common aspects of obesity and cancer cachexia for future therapeutic strategies.}, journal = {Current opinion in pharmacology}, volume = {53}, number = {}, pages = {101-116}, doi = {10.1016/j.coph.2020.07.006}, pmid = {32871469}, issn = {1471-4973}, mesh = {Animals ; Appetite Regulation ; *Cachexia/etiology/immunology/metabolism/therapy ; Humans ; Inflammation Mediators/immunology ; Macrophages/immunology ; *Neoplasms/complications/immunology/metabolism/therapy ; *Obesity/immunology/metabolism/therapy ; }, abstract = {Obesity and cancer cachexia are diseases at opposite ends of the BMI. However, despite the apparent dichotomy, these pathologies share some common underlying mechanisms that lead to profound metabolic perturbations. Insulin resistance, adipose tissue lipolysis, skeletal muscle atrophy and systemic inflammation are key players in both diseases. Several strategies for pharmacological treatments have been employed in obesity and cancer cachexia but demonstrated only limited effects. Therefore, there is still a need to develop novel, more effective strategies. In this review we summarize existing therapies and discuss potential novel strategies that could arise by bridging common aspects between obesity and cachexia. We discuss the potential role of macrophage manipulation and the modulation of inflammation by targeting Nuclear Receptors (NRs) as potential novel therapeutic strategies.}, }
@article {pmid32868877, year = {2020}, author = {Murray, AS and Hyland, TE and Sala-Hamrick, KE and Mackinder, JR and Martin, CE and Tanabe, LM and Varela, FA and List, K}, title = {The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy.}, journal = {Oncogene}, volume = {39}, number = {41}, pages = {6421-6436}, pmid = {32868877}, issn = {1476-5594}, support = {R25 GM058905/GM/NIGMS NIH HHS/United States ; F31 CA217148/CA/NCI NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; R01 CA160565/CA/NCI NIH HHS/United States ; R01 CA222359/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use ; Apoptosis/drug effects/genetics ; Breast/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Cell Line, Tumor ; Cell Survival/genetics ; Datasets as Topic ; Disease Progression ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Experimental/drug therapy/genetics/*pathology ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Serine Endopeptidases/genetics/*metabolism ; Triple Negative Breast Neoplasms/drug therapy/genetics/*pathology ; }, abstract = {Breast cancer progression is accompanied by increased expression of extracellular and cell-surface proteases capable of degrading the extracellular matrix as well as cleaving and activating downstream targets. The type II transmembrane serine proteases (TTSPs) are a family of cell-surface proteases that play critical roles in numerous types of cancers. Therefore, the aim of this study was to identify novel and uncharacterized TTSPs with differential expression in breast cancer and to determine their potential roles in progression. Systematic in silico data analysis followed by immunohistochemical validation identified increased expression of the TTSP family member, TMPRSS13 (transmembrane protease, serine 13), in invasive ductal carcinoma patient tissue samples compared to normal breast tissue. To test whether loss of TMPRSS13 impacts tumor progression, TMPRSS13 was genetically ablated in the oncogene-induced transgenic MMTV-PymT tumor model. TMPRSS13 deficiency resulted in a significant decrease in overall tumor burden and growth rate, as well as a delayed formation of detectable mammary tumors, thus suggesting a causal relationship between TMPRSS13 expression and the progression of breast cancer. Complementary studies using human breast cancer cell culture models revealed that siRNA-mediated silencing of TMPRSS13 expression decreases proliferation, induces apoptosis, and attenuates invasion. Importantly, targeting TMPRSS13 expression renders aggressive triple-negative breast cancer cell lines highly responsive to chemotherapy. At the molecular level, knockdown of TMPRSS13 in breast cancer cells led to increased protein levels of the tumor-suppressive protease prostasin. TMPRSS13/prostasin co-immunoprecipitation and prostasin zymogen activation experiments identified prostasin as a potential novel target for TMPRSS13. Regulation of prostasin levels may be a mechanism that contributes to the pro-oncogenic properties of TMPRSS13 in breast cancer. TMPRSS13 represents a novel candidate for targeted therapy in combination with standard of care chemotherapy agents in patients with hormone receptor-negative breast cancer or in patients with tumors refractory to endocrine therapy.}, }
@article {pmid32856854, year = {2020}, author = {Chowdhury, SS and Khatun, M and Khan, TH and Laila, AB}, title = {Mutation in Exon2 of BRCA1 Gene in Adult Bengali Bangladeshi Female Patients with Breast Cancer: An Experience from Two Tertiary-Care Hospitals.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {8}, pages = {2265-2270}, pmid = {32856854}, issn = {2476-762X}, mesh = {Adult ; BRCA1 Protein/*genetics ; Bangladesh/epidemiology ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/epidemiology/genetics/*pathology ; Cross-Sectional Studies ; *Exons ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Tertiary Care Centers ; }, abstract = {BACKGROUND: The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer.<br><br>METHODS: In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software.<br><br>RESULTS: We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study.<br><br>CONCLUSIONS: Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.}, }
@article {pmid32853021, year = {2021}, author = {Bakhtari, N and Mozdarani, H and Salimi, M and Omranipour, R}, title = {Association study of miR-22 and miR-335 expression levels and G2 assay related inherent radiosensitivity in peripheral blood of ductal carcinoma breast cancer patients.}, journal = {Neoplasma}, volume = {68}, number = {1}, pages = {190-199}, doi = {10.4149/neo_2020_200225N185}, pmid = {32853021}, issn = {0028-2685}, mesh = {Adult ; Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/blood/genetics/radiotherapy ; Female ; Humans ; Leukocytes, Mononuclear/metabolism ; *MicroRNAs/biosynthesis/blood ; Middle Aged ; ROC Curve ; Radiation Tolerance ; }, abstract = {Identifying patient's cellular radiosensitivity before radiotherapy (RT) in breast cancer (BC) patients allows proper alternations in routinely used treatment programs and reduces the adverse side effects in exposed patients. This study was conducted on blood samples taken from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC (mean age: 47±9.93) and 30 healthy women (mean age: 44.43±6.7). The standard G2 assay was performed to predict cellular radiosensitivity. To investigate miR-22 and miR-335 expression levels in peripheral blood mononuclear cells (PBMCs), qPCR was performed. The sensitivity and specificity of the mentioned miRNAs were assessed by plotting the Receiver Operating Characteristic (ROC) curve. Binary logistic regression was performed to identify the miRNA involvement in BC and cellular radiosensitivity (CR) of BC patients. The frequency of spontaneous and radiation-induced chromatid breaks (CBs) was significantly different between control and patient groups (p<0.05). A cut-off value was determined to differentiate the patients with and without cellular radiosensitivity. miR-22 and miR-335 were significantly downregulated in BC patients. miRNAs expression levels were directly associated with CR. ROC curve assessment identified that both miRNAs had acceptable specificity and sensitivity in the prediction of BC and CR of BC patients. Binary logistic regression showed that both miRNAs could also predict BC successfully. Although only miR-22 was shown potent to predict CR of BC patients, both miR-22 and miR-335 might act as tumor suppressor miRNAs in BC. miR-22 and miR-335 may be promising potential biomarkers in BC prediction along with other important biomarkers. Moreover, mirR-22 might be a potential biomarker for the prediction of CR in BC patients.}, }
@article {pmid32846803, year = {2020}, author = {Li, G and Yao, J and Wu, T and Chen, Y and Wang, Z and Wang, Y and Wang, F and Zhong, R and Yang, S}, title = {Triple metachronous primary cancer of uterus, colon, and breast cancer: A case report and review of the literature.}, journal = {Medicine}, volume = {99}, number = {34}, pages = {e21764}, pmid = {32846803}, issn = {1536-5964}, mesh = {Aged ; Breast Neoplasms/*complications/pathology/therapy ; Colonic Neoplasms/*complications ; Female ; Humans ; Mammography ; Mastectomy ; Sentinel Lymph Node Biopsy ; Uterine Neoplasms/*complications ; }, abstract = {RATIONALE: Triple or more primary malignancies are rare, with only 23 previous cases including breast cancer reported in the English language studies between January 1990 and December 2019.<br><br>PATIENT CONCERNS: The patient was a 67-year-old woman with a mass in her right breast. She had a previous history of uterine and colon cancer. Both ultrasonography and mammography revealed a Breast Imaging Reporting and Data System (BI-RADS) category 3 breast lesion, in which proliferative nodules are more likely. Given her previous history of 2 malignancies, her doctors strongly recommended a biopsy.<br><br>DIAGNOSIS AND INTERVENTIONS: The biopsy pathology suggested intraductal breast cancer. Mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological diagnosis was invasive ductal carcinoma, grade II, stage I. The sample was positive for estrogen receptor and progesterone receptor and negative for cerbB-2. No radiotherapy or chemotherapy was administered except for endocrine therapy. A follow-up at 19 months showed no breast recurrence or distant metastases.<br><br>OUTCOMES: No recurrence or distant metastasis occurred within the 19-month, 11-year, and 20-year follow-ups for breast, colon, and uterine cancers, respectively.<br><br>LESSONS: To our knowledge, this is the first review of triple or more primary malignancies including breast cancer. These malignancies occur predominantly in older female patients. The most prevalent tumors of triple or more primary malignancies including breast cancer occur in the colon, uterus, and lung. A favorable prognosis is associated with early-stage malignancies.}, }
@article {pmid32816842, year = {2020}, author = {Vaidya, JS and Bulsara, M and Baum, M and Wenz, F and Massarut, S and Pigorsch, S and Alvarado, M and Douek, M and Saunders, C and Flyger, HL and Eiermann, W and Brew-Graves, C and Williams, NR and Potyka, I and Roberts, N and Bernstein, M and Brown, D and Sperk, E and Laws, S and Sütterlin, M and Corica, T and Lundgren, S and Holmes, D and Vinante, L and Bozza, F and Pazos, M and Le Blanc-Onfroy, M and Gruber, G and Polkowski, W and Dedes, KJ and Niewald, M and Blohmer, J and McCready, D and Hoefer, R and Kelemen, P and Petralia, G and Falzon, M and Joseph, DJ and Tobias, JS}, title = {Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial.}, journal = {BMJ (Clinical research ed.)}, volume = {370}, number = {}, pages = {m2836}, pmid = {32816842}, issn = {1756-1833}, support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; 14/49/13/DH_/Department of Health/United Kingdom ; HTA/14/49/13/DH_/Department of Health/United Kingdom ; }, mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; Intraoperative Care ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; Radiotherapy Dosage ; Survival Rate ; }, abstract = {OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.<br><br>DESIGN: Prospective, open label, randomised controlled clinical trial.<br><br>SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.<br><br>PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).<br><br>INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).<br><br>MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.<br><br>RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).<br><br>CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.<br><br>TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.}, }
@article {pmid32811533, year = {2020}, author = {Chao, X and Liu, L and Sun, P and Yang, X and Li, M and Luo, R and Huang, Y and He, J and Yun, J}, title = {Immune parameters associated with survival in metaplastic breast cancer.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {92}, pmid = {32811533}, issn = {1465-542X}, mesh = {Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/*immunology/metabolism ; Biomarkers, Tumor/*immunology/metabolism ; Breast Neoplasms/*immunology/*mortality/pathology/therapy ; CD8-Positive T-Lymphocytes/*immunology ; Carcinoma, Squamous Cell/immunology/mortality/pathology/therapy ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Programmed Cell Death 1 Receptor/*immunology/metabolism ; Survival Rate ; Tumor Microenvironment/*immunology ; }, abstract = {BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.<br><br>METHODS: A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm[2]) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm[2]), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A &#x2265;&#x2009;1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.<br><br>RESULTS: We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p&#x2009;=&#x2009;0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p&#x2009;<&#x2009;0.001). Thirty (50%) patients exhibited positive (&#x2265;&#x2009;1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (&#x2265;&#x2009;1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (&#x2265;&#x2009;1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (&#x2265;&#x2009;1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (>&#x2009;300/mm[2], 20%), CD4+ TILs (>&#x2009;250/mm[2]), and CD8+ TILs (>&#x2009;70/mm[2]) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (&#x2265;&#x2009;1%) and PD1 in stromal cells (&#x2265;&#x2009;1%) were also associated with longer survival.<br><br>CONCLUSIONS: The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.}, }
@article {pmid32789812, year = {2021}, author = {Wakefield, B and Diko, S and Gilmer, R and Connell, KA and DeWitt, PE and Hurt, KJ}, title = {Accuracy of obstetric laceration diagnoses in the electronic medical record.}, journal = {International urogynecology journal}, volume = {32}, number = {7}, pages = {1907-1915}, pmid = {32789812}, issn = {1433-3023}, mesh = {Anal Canal/injuries ; Delivery, Obstetric ; Electronic Health Records ; Female ; Humans ; *Lacerations/diagnosis/epidemiology ; Perineum/injuries ; Pregnancy ; Retrospective Studies ; Risk Factors ; }, abstract = {INTRODUCTION AND HYPOTHESIS: Patient safety data including rates of obstetric anal sphincter injury (OASI) are often derived from hospital discharge codes. With the transition to electronic medical records (EMRs), we hypothesized that electronic provider-entered delivery data would more accurately document obstetric perineal injury than traditional billing/diagnostic codes.<br><br>METHODS: We evaluated the accuracy of perineal laceration diagnoses after singleton vaginal deliveries during one calendar year at an American tertiary academic medical center. We reviewed the entire hospital chart to determine the most likely laceration diagnosis and compared that expert review diagnosis (ExpRD) with documentation in the EMR delivery summary (EDS) and ICD-9 diagnostic codes (IDCs).<br><br>RESULTS: We retrospectively selected 354 total delivery records. OASI complicated 56 of those. 303 records (86%) were coded identically by the EDS and IDCs. Diagnoses from the IDCs and the EDS were mostly correct compared with ExpRD (sensitivity&#x2009;=&#x2009;96%, specificity&#x2009;=&#x2009;100%). There was no systematic over- or under-diagnosis of OASI for either the EDS (p&#x2009;=&#x2009;0.070) or the IDCs (p&#x2009;=&#x2009;0.447). When considering all laceration types the EDS was correct for 21 (5.9%) lacerations that were incorrect according to the IDCs. Overall, the EDS was more accurate (p&#x2009;<&#x2009;0.05) owing to errors in IDC minor laceration diagnoses.<br><br>CONCLUSIONS: Electronic medical record delivery summary data and EMR-derived diagnostic codes similarly characterize OASI. The EDS does not improve OASI reporting, but may be more accurate when considering all perineal lacerations. This assumes that providers have correctly identified and categorized the lacerations that they record in the EMR.}, }
@article {pmid32785515, year = {2020}, author = {Souza, TO and Souza, ER and Pinto, LW}, title = {Analysis of the correlation of socioeconomic, sanitary, and demographic factors with homicide deaths - Bahia, Brazil, 2013-2015.}, journal = {Revista brasileira de enfermagem}, volume = {73}, number = {6}, pages = {e20190346}, doi = {10.1590/0034-7167-2019-0346}, pmid = {32785515}, issn = {1984-0446}, mesh = {Brazil/epidemiology ; Demography ; Educational Status ; *Homicide ; Humans ; Socioeconomic Factors ; }, abstract = {OBJECTIVE: To analyze the correlation of socioeconomic, sanitary, and demographic factors with homicides in Bahia, from 2013 to 2015.<br><br>METHODS: Ecological study, using data from the Information System on Mortality and from the Superintendence of Economic and Social Studies. The depending variable is the corrected homicide rate. Explanatory variables were categorized in four axes. Simple and multiple negative binomial regression models were used.<br><br>RESULTS: Positive associations were found between homicides and the Index of Economy and Finances (IEF), the Human Development Index, the Gini Index, population density, and legal intervention death rates (LIDR). The variables Index of Education Levels (IEL), rates of death with undetermined intentions (RDUI), and the proportion of ill-defined causes (IDC) presented a negative association with the homicide rates.<br><br>CONCLUSION: The specific features of the context of each community, in addition to broader socioeconomic municipal factors, directly interfere in life conditions and increase the risk of dying by homicide.}, }
@article {pmid32783993, year = {2020}, author = {Domínguez-de-la-Cruz, E and Muñoz, ML and Pérez-Muñoz, A and García-Hernández, N and Moctezuma-Meza, C and Hinojosa-Cruz, JC}, title = {Reduced mitochondrial DNA copy number is associated with the haplogroup, and some clinical features of breast cancer in Mexican patients.}, journal = {Gene}, volume = {761}, number = {}, pages = {145047}, doi = {10.1016/j.gene.2020.145047}, pmid = {32783993}, issn = {1879-0038}, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism ; Case-Control Studies ; DNA Copy Number Variations/*genetics ; DNA, Mitochondrial/*genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes/genetics ; Humans ; Mexico/epidemiology ; Middle Aged ; Mitochondria/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.}, }
@article {pmid32782013, year = {2020}, author = {Kurozumi, S and Alsaleem, M and Monteiro, CJ and Bhardwaj, K and Joosten, SEP and Fujii, T and Shirabe, K and Green, AR and Ellis, IO and Rakha, EA and Mongan, NP and Heery, DM and Zwart, W and Oesterreich, S and Johnston, SJ}, title = {Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {85}, pmid = {32782013}, issn = {1465-542X}, support = {AAM127669/WT_/Wellcome Trust/United Kingdom ; SAC160073/KOMEN/Susan G. Komen/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Computer Simulation ; Databases, Genetic/statistics &amp; numerical data ; Female ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.<br><br>METHODS: We performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I-III primary ILC (N&#x2009;=&#x2009;279) and invasive ductal carcinoma (IDC, N&#x2009;=&#x2009;1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines.<br><br>RESULTS: ILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N&#x2009;=&#x2009;16 vs. 1.4%, N&#x2009;=&#x2009;18, p&#x2009;<&#x2009;0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N&#x2009;=&#x2009;3 vs. 1.8%, N&#x2009;=&#x2009;23; p&#x2009;=&#x2009;0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66&#x2009;months vs. 211&#x2009;months for ERBB2 wild-type (p&#x2009;=&#x2009;0.0001), and 159 vs. 166&#x2009;months (p&#x2009;=&#x2009;0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS-but only in ILC (hazard ratio, HR&#x2009;=&#x2009;3.7, 95% CI 1.2-11.0; p&#x2009;=&#x2009;0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC&#x2009;=&#x2009;2.3, 95% CI 1.04-5.05; p&#x2009;=&#x2009;0.040).<br><br>CONCLUSIONS: Targetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.}, }
@article {pmid32781417, year = {2020}, author = {Lu, K and Wang, X and Zhang, W and Ye, H and Lao, L and Zhou, X and Yao, S and Lv, F}, title = {Clinicopathological and genomic features of breast mucinous carcinoma.}, journal = {Breast (Edinburgh, Scotland)}, volume = {53}, number = {}, pages = {130-137}, pmid = {32781417}, issn = {1532-3080}, mesh = {Adenocarcinoma, Mucinous/*genetics/*pathology ; Adult ; Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cohort Studies ; Female ; Gene Expression Profiling ; Genome ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prospective Studies ; SEER Program ; Young Adult ; }, abstract = {INTRODUCTION: Mucinous carcinoma (MC) of the breast is a special histological type of breast cancer. Clinicopathological characteristics and genomic features of MC is not fully understood.<br><br>MATERIALS AND METHODS: 186,497 primary breast cancer patients from SEER database diagnosed with invasive ductal carcinoma (IDC) or MC were included. 801 primary IDC or MC patients from TCGA cohort were included for transcriptomic and genomic analysis.<br><br>RESULTS: MC patients were older, had lower tumor grade and T and N stage, higher hormone receptor positive proportions and lower HER2 positive proportions than IDC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of MC patients was significantly better than IDC patients (P&#xa0;<&#xa0;0.001). However, after adjusting for clinicopathological factors, survival advantage of MC disappeared. In terms of genomic features of MC, representative upregulated genes of MC in transcriptomic level were MUC2, TFF1 and CARTPT. Upregulated pathways of MC included neurotransmitter-related pathways. Moreover, MC was featured by the amplification of 6p25.2, 6q12 and 11q12.3.<br><br>CONCLUSION: MC is a distinct histological subtype compared with IDC in terms of clinicopathological characteristics and genomic features. Further investigation need to be conducted to explore the formation of this specific histological subtype.}, }
@article {pmid32776387, year = {2020}, author = {Takahara, T and Satou, A and Sugie, M and Watanabe, M and Kanao, K and Sumitomo, M and Tsuzuki, T}, title = {Prognostic significance of p16 expression in high-grade prostate adenocarcinoma.}, journal = {Pathology international}, volume = {70}, number = {10}, pages = {743-751}, doi = {10.1111/pin.12997}, pmid = {32776387}, issn = {1440-1827}, mesh = {Adenocarcinoma/*diagnosis/drug therapy/metabolism/pathology ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate/metabolism/pathology ; Prostatic Neoplasms, Castration-Resistant/*diagnosis/drug therapy/metabolism/pathology ; }, abstract = {Management of advanced hormone-naïve prostate cancer (HNPC) is a critical public health issue. Useful prognostic markers are thus needed to select patients who will benefit from recently introduced upfront therapies. p16 expression is an adverse prognostic marker in prostate cancer. The present study aimed to determine whether p16 expression would serve as an adverse prognostic marker in advanced HNPC. A total of 79 patients diagnosed by needle biopsy with adenocarcinoma Gleason score ≥8 between 2010 and 2013 at Aichi Medical University were included in this study. The median patient age was 73 (range 52-87) years. The median follow-up was 62 months (range 2-98). Fourteen patients had p16-positive samples. Fifteen patients died from prostate cancer, 10 of whom were in the p16-positive group. p16 positivity was associated with clinical T stage (P < 0.001), presence of IDC-P (P < 0.001), distant metastasis (P < 0.001) and lymph node metastasis (P < 0.001). These results indicate that p16 expression is associated with adverse prognostic factor of prostate cancer and suggest that p16 expression may provide useful information for treatment planning and identifying suitable candidates for upfront chemotherapy or androgen receptor axis-targeted therapy.}, }
@article {pmid32758491, year = {2020}, author = {Sechrist, H and Glasgow, A and Bomeisl, P and Gilmore, H and Harbhajanka, A}, title = {Concordance of breast cancer biomarker status between routine immunohistochemistry/in situ hybridization and Oncotype DX qRT-PCR with investigation of discordance, a study of 591 cases.}, journal = {Human pathology}, volume = {104}, number = {}, pages = {54-65}, doi = {10.1016/j.humpath.2020.07.022}, pmid = {32758491}, issn = {1532-8392}, mesh = {Aged ; *Biomarkers, Tumor/analysis/genetics ; Breast Neoplasms/*chemistry/*genetics/pathology/therapy ; Clinical Decision-Making ; Female ; *Gene Expression Profiling ; Humans ; *Immunohistochemistry ; *In Situ Hybridization ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Receptor, ErbB-2/analysis/genetics ; Receptors, Estrogen/analysis/genetics ; Receptors, Progesterone/analysis/genetics ; Retrospective Studies ; *Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Risk Factors ; Transcriptome ; Treatment Outcome ; }, abstract = {Patients with estrogen receptor (ER)+/human epidermal growth factor receptor (HER)2-, lymph node- breast cancer with high recurrence risk benefit from adjuvant chemotherapy in addition to hormonal therapy. This study compares ER, progesterone receptor (PR), and HER2 status between routine immunohistochemistry (IHC)/in situ hybridization (ISH) and Oncotype DX (ODX) in 591 cases. ODX recurrence score (RS) and clinicopathologic features were compared between ER/PR-concordant and discordant cases. Hematoxylin and eosin (H&amp;E) slides from ER discordant cases were reexamined. Concordance was high between ODX and IHC for ER status (580/591, 98.1%) and moderate for PR status (512/591, 86.6%). All 11 ER discordant cases were ER+ by IHC but ER- by ODX and high risk by ODX. Histologically, all of these cases were grade III invasive ductal carcinoma (IDC), except one case diagnosed as IDC with apocrine features. Although this case was grade I and ER/PR+ by IHC, this patient received chemotherapy because of high RS. Of 79 PR discordant cases, 60 were PR+ by IHC but PR- by ODX. Five hundred eighty-four cases had available HER2 data, with high negative agreement (580/582, 99.7%). However, both HER2+ cases by ISH were HER2- by ODX. Mean RS was higher for ER discordant than concordant cases (48.0 versus 17.1, P < 0.0001) and for PR discordant (IHC+/ODX-) than concordant cases (27.2 versus 16.7, P < 0.0001) with no significant differences in recurrence or metastasis. Overall, detection was more sensitive by IHC, and high RS of discordant cases suggests possible risk overestimation. Therapeutic decisions for discordant cases should continue to be based on clinicopathologic correlation and not oncotype alone.}, }
@article {pmid32753069, year = {2020}, author = {Choridah, L and Sari, WK and Dwianingsih, EK and Widodo, I and Suwardjo,  and Anwar, SL}, title = {Advanced lesions of synchronous bilateral mammary Paget's disease: a case report.}, journal = {Journal of medical case reports}, volume = {14}, number = {1}, pages = {119}, pmid = {32753069}, issn = {1752-1947}, support = {PPUPT 2274/2019//Kementerian Riset, Teknologi dan Pendidikan Tinggi/ ; Dana Masyarakat 1499/2019//Universitas Gadjah Mada/ ; RTA Nr 133/2607-2020//Universitas Gadjah Mada/ ; 1/2018//NUS-UGM-Tahir Foundation/ ; }, mesh = {*Breast Neoplasms/diagnosis/surgery ; Female ; Humans ; Indonesia ; Mastectomy ; Middle Aged ; Nipples ; *Paget's Disease, Mammary/diagnostic imaging/surgery ; }, abstract = {BACKGROUND: Mammary Paget's disease is an eczematous eruption on the nipple and areola with underlying breast malignancy. It is often misinterpreted as chronic dermatitis or psoriasis causing a delayed diagnosis. Synchronous bilateral mammary Paget's disease is exceptionally rare and an advanced case with underlying invasive carcinoma might require long-term treatment and follow-up that could affect a patient's physical, psychological, and social aspects of well-being.<br><br>CASE PRESENTATION: A 54-year-old Javanese woman presented in our clinic with a 2-year history of itching and chronic eczema in both areolae. Bilateral nipple retraction and retro-areolar palpable lumps were observed during the first presentation. Breast ultrasound revealed hypoechoic lesions in her left and right breasts. Mammograms showed an irregular hyperdense lesion and multiple microcalcifications. Histopathology from biopsy and bilateral mastectomy demonstrated infiltration of large Paget's cells in the epidermis of the areola with underlying lesions of invasive ductal carcinoma, diagnosed solid type with high nuclear grade and negative expression of estrogen receptor and progesterone receptor, with positive expression of human epidermal growth receptor-2(HER2) and Ki-67 (45%).<br><br>CONCLUSIONS: In a patient with suspicious chronic inflammation of the nipple and areolae, prompt biopsy should be performed to avoid a delayed diagnosis of any malignant breast lesion.}, }
@article {pmid32748295, year = {2020}, author = {Kato, M and Hirakawa, A and Kobayashi, Y and Yamamoto, A and Naito, Y and Tochigi, K and Sano, T and Ishida, S and Funahashi, Y and Fujita, T and Matsukawa, Y and Hattori, R and Tsuzuki, T}, title = {Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer.}, journal = {International journal of clinical oncology}, volume = {25}, number = {12}, pages = {2130-2137}, pmid = {32748295}, issn = {1437-7772}, mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/*methods ; Bone Neoplasms/secondary ; Carcinoma, Ductal/mortality/*pathology ; Hormones ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/mortality/*pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC).<br><br>METHODS: We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed:&#x2009;&#x2264;&#x2009;5, 6-9, and&#x2009;&#x2265;&#x2009;10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates.<br><br>RESULTS: For patients who underwent&#x2009;&#x2265;&#x2009;10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P&#x2009;=&#x2009;0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P&#x2009;=&#x2009;0.322 and&#x2009;&#x2264;&#x2009;5; P&#x2009;=&#x2009;0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent&#x2009;&#x2265;&#x2009;10 and 6-9 core needle biopsies (P&#x2009;=&#x2009;0.0002 and 0.017, respectively), but not in those who underwent&#x2009;&#x2264;&#x2009;5 core biopsies (P&#x2009;=&#x2009;0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had&#x2009;&#x2265;&#x2009;10 core biopsies (P&#x2009;=&#x2009;0.016, and P&#x2009;=&#x2009;0.0014, respectively).<br><br>CONCLUSIONS: Given the IDC-P detection and its value as a prognostic marker, we propose the performance of&#x2009;&#x2265;&#x2009;10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.}, }
@article {pmid32745951, year = {2020}, author = {Altinoz, A and Al Ameri, M and Qureshi, W and Boush, N and Nair, SC and Abdel-Aziz, A}, title = {Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates.}, journal = {Breast (Edinburgh, Scotland)}, volume = {53}, number = {}, pages = {119-124}, pmid = {32745951}, issn = {1532-3080}, mesh = {Adult ; Arabs/genetics ; Breast Neoplasms/ethnology/*genetics/pathology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Predisposition to Disease/*epidemiology/ethnology/genetics ; Genetic Testing/statistics &amp; numerical data ; Hereditary Breast and Ovarian Cancer Syndrome/ethnology/*genetics/pathology ; Humans ; Middle Aged ; Prevalence ; Retrospective Studies ; United Arab Emirates/epidemiology ; }, abstract = {INTRODUCTION: Breast cancer is the most prevalent cancer in the United Arab Emirates (UAE). This is the first study to provide data on predisposition of breast cancer susceptibility genes with associated clinical and pathological aspects in the UAE.<br><br>MATERIAL &amp; METHODS: A retrospective chart review for breast cancer patients undergoing genetic testing from 2016 to 2018. According to National Comprehensive Cancer Network (NCCN) guidelines genetic testing was offered. The analyzed data included; age, ethnicity, family cancer history, pathogenic variant, histopathology, stage, molecular subtype and proliferation.<br><br>RESULTS: 309 patients underwent genetic testing with a positive result in 130 patients (11.9%) over a period of 36 months. In 34.6% pathogenic and likely pathogenic variants were identified. BRCA2 was the most common gene identified. The mean age was 42.9 years (&#xb1;9.01). Positive family history was identified in 66 patients (50.7%). Majority had stage 1 or 2 disease (66.2%), invasive ductal carcinoma (81.5%) and hormone receptor positive cancer (45.3%).<br><br>CONCLUSIONS: This is the first study in the UAE to describe the clinical and pathological characteristics of hereditary breast cancer in a mixed ethnic group with dominant Arabic population. Further genetic studies will be required in the UAE population, as the prevalence of breast cancer continues to rise.}, }
@article {pmid32740271, year = {2020}, author = {Granek, L and Nakash, O}, title = {Prevalence and risk factors for suicidality in cancer patients and oncology healthcare professionals strategies in identifying suicide risk in cancer patients.}, journal = {Current opinion in supportive and palliative care}, volume = {14}, number = {3}, pages = {239-246}, pmid = {32740271}, issn = {1751-4266}, mesh = {Age Factors ; Cancer Care Facilities/organization &amp; administration ; Health Personnel/education/*organization &amp; administration ; Humans ; Inservice Training ; Mass Screening/organization &amp; administration ; Neoplasms/pathology/*psychology ; Prevalence ; Risk Factors ; Sex Factors ; Socioeconomic Factors ; Suicide/*statistics &amp; numerical data ; }, abstract = {PURPOSE OF REVIEW: The aim of this study was to summarize the literature on prevalence and risk factors for suicidality in cancer patients and to document the research on oncology healthcare professionals' strategies in identifying this risk.<br><br>RECENT FINDINGS: Cancer patients exhibit increased risk of suicidality compared with the general population. Various risk factors have been identified including sociodemographic factors such as poverty, being male and elderly as well as disease-related attributes such as cancer type and stage. The literature on how healthcare professionals identify suicide risk is sparse. Ten articles were found that focused on two main themes. These included information on systematic strategies in identifying suicide risk and factors that affect healthcare professionals' ability to identify risk in their patients.<br><br>SUMMARY: Although there is an immense amount of literature documenting the problem of suicidality among patients, the research on how healthcare professionals identify and respond to these indications in patients is nearly nonexistent. Cancer centres should implement standardized and systematic screening of cancer patients for suicidality and research on this patient population should collect and report these data. Ongoing training and education for healthcare professionals who work in the oncology setting on how to identify and respond to suicide risk among cancer patients is urgently needed.}, }
@article {pmid32738354, year = {2021}, author = {Camacho Londoño, JE and Kuryshev, V and Zorn, M and Saar, K and Tian, Q and Hübner, N and Nawroth, P and Dietrich, A and Birnbaumer, L and Lipp, P and Dieterich, C and Freichel, M}, title = {Transcriptional signatures regulated by TRPC1/C4-mediated Background Ca[2+] entry after pressure-overload induced cardiac remodelling.}, journal = {Progress in biophysics and molecular biology}, volume = {159}, number = {}, pages = {86-104}, doi = {10.1016/j.pbiomolbio.2020.07.006}, pmid = {32738354}, issn = {1873-1732}, support = {Z01 ES101684/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena/physiology ; Calcium/*metabolism ; Calcium Signaling ; Cardiomegaly/metabolism ; Gene Expression Regulation ; Humans ; Ion Channels/genetics/metabolism ; Male ; Mice ; Mice, Knockout ; Myocytes, Cardiac/*metabolism ; TRPC Cation Channels/*metabolism ; Transcriptional Activation/physiology ; Ventricular Remodeling/*physiology ; }, abstract = {AIMS: After summarizing current concepts for the role of TRPC cation channels in cardiac cells and in processes triggered by mechanical stimuli arising e.g. during pressure overload, we analysed the role of TRPC1 and TRPC4 for background Ca[2+] entry (BGCE) and for cardiac pressure overload induced transcriptional remodelling.<br><br>METHODS AND RESULTS: Mn[2+]-quench analysis in cardiomyocytes from several Trpc-deficient mice revealed that both TRPC1 and TRPC4 are required for BGCE. Electrically-evoked cell shortening of cardiomyocytes from TRPC1/C4-DKO mice was reduced, whereas parameters of cardiac contractility and relaxation assessed in&#xa0;vivo were unaltered. As pathological cardiac remodelling in mice depends on their genetic background, and the development of cardiac remodelling was found to be reduced in TRPC1/C4-DKO mice on a mixed genetic background, we studied TRPC1/C4-DKO mice on a C57BL6/N genetic background. Cardiac hypertrophy was reduced in those mice after chronic isoproterenol infusion (-51.4%) or after one week of transverse aortic constriction (TAC;&#xa0;-73.0%). This last manoeuvre was preceded by changes in the pressure overload induced transcriptional program as analysed by RNA sequencing. Genes encoding specific collagens, the Mef2 target myomaxin and the gene encoding the mechanosensitive channel Piezo2 were up-regulated after TAC in wild type but not in TRPC1/C4-DKO hearts.<br><br>CONCLUSIONS: Deletion of the TRPC1 and TRPC4 channel proteins protects against development of pathological cardiac hypertrophy independently of the genetic background. To determine if the TRPC1/C4-dependent changes in the pressure overload induced alterations in the transcriptional program causally contribute to cardio-protection needs to be elaborated in future studies.}, }
@article {pmid32719289, year = {2020}, author = {Dhia, SB and Belaid, I and Stita, W and Hochlaf, M and Ezzairi, F and Ahmed, SB}, title = {Bilateral parotid gland metastasis from a breast invasive ductal carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {16}, number = {3}, pages = {672-674}, doi = {10.4103/jcrt.JCRT_1047_17}, pmid = {32719289}, issn = {1998-4138}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*pathology/therapy ; Palliative Care ; Parotid Neoplasms/*secondary/therapy ; }, abstract = {Metastases to the parotid gland are very rare. We report the second case of bilateral metastases to the parotid gland from a breast invasive ductal carcinoma. A 50-year-old female was treated for an early left breast cancer in 2007. A pulmonary metastatic relapse was diagnosed in 2013. A metastatic skin extension required several lines of treatment from June 2014 to July 2016. Bilateral parotid gland metastases from a breast invasive ductal carcinoma were confirmed in December 2016. The patient died on May 2017 from cerebral metastases. Only 16 cases of metastasis to the parotid gland from breast cancer have been reported in the literature. Only one case had a bilateral involvement. Prognosis is poor, and there are no specific guidelines for the treatment.}, }
@article {pmid32710711, year = {2020}, author = {Jones, B and Thomas, G and Sprenger, J and Nofech-Mozes, S and Khorasani, M and Vitkin, A}, title = {Peri-tumoural stroma collagen organization of invasive ductal carcinoma assessed by polarized light microscopy differs between OncotypeDX risk group.}, journal = {Journal of biophotonics}, volume = {13}, number = {11}, pages = {e202000188}, doi = {10.1002/jbio.202000188}, pmid = {32710711}, issn = {1864-0648}, support = {PJT-156110//CIHR/Canada ; }, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/genetics ; Collagen ; Female ; Humans ; Microscopy, Polarization ; Risk Factors ; }, abstract = {A commercially available genomic test, OncotypeDX has emerged as a useful postsurgical treatment guide for early stage breast cancer. Despite widespread clinical adoption, there remain logistical issues with its implementation. Collagenous stromal architecture has been shown to hold prognostic value that may complement OncotypeDX. Polarimetric analysis of breast cancer surgical samples allows for the quantification of collagenous stroma abundance and organization. We examine intratumoural collagen abundance and alignment along the tumor-host interface for 45 human samples of invasive ductal carcinoma categorized as low or higher risk by OncotypeDX. Furthermore, we probe the separatory power of collagen alignment patterns to classify unlabeled samples as low or higher OncotypeDX risk group using a linear discriminant (LD) model. No significant difference in mean collagen abundance was found between the two risk groups. However, collagen alignment along the tumor boundary was found to be significantly lower in higher risk samples. The LD model achieved a 71% total accuracy and 81% sensitivity to higher risk samples. Prognostic information extracted from the stromal morphology has potential to complement OncotypeDX as an easy-to-implement prescreening methodology.}, }
@article {pmid32700071, year = {2020}, author = {Richards, D and Ayala, AA and Wu, Y and Middleton, LP}, title = {Carcinoma In Situ Involving Sclerosing Adenosis on Core Biopsy: Diagnostic Pearls to Aid the Practicing Clinician and Avoid Overtreatment.}, journal = {Oncology and therapy}, volume = {8}, number = {1}, pages = {81-89}, pmid = {32700071}, issn = {2366-1089}, abstract = {INTRODUCTION: Involvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician.<br><br>METHODS: Our database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and clinical follow-up was also obtained.<br><br>RESULTS: Thirty-one cases of DCIS or LN involving SA were obtained (12 cases of DCIS, 19 cases of LN including LCIS and ALH). Histomorphologic features commonly seen with DCIS or LN involving SA included lobulocentric architecture (31/31, 100%), myoepithelial cells visible by H&amp;E at least focally (31/31, 100%), and separate areas of SA not involved by neoplasia (29/31, 93.5%). Features that were sometimes seen included hyaline basement membranes surrounding the lesion (14/31, 45.2%), DCIS/LN apart from the area of involvement by SA (16/31, 51.6%), and calcifications associated with DCIS/LN/SA (12/31, 38.7%). Features that were not commonly seen included desmoplasia (6/31, 19.4%), dense inflammation (4/31, 12.9%), and single epithelial cells enveloped by flattened myoepithelial cells (6/31, 19.4%). Of the ten cases of DCIS with known follow-up, four showed DCIS involving either SA or a complex SA on excision (4/10, 40%), four had only DCIS (4/10, 40%), one had DCIS with a small 1.8-mm focus of predominantly tubular carcinoma (1/10, 10%), and one showed invasive ductal carcinoma on excision (1/10, 10%). The latter case of invasive ductal carcinoma occurred in a patient who had a delay of 3&#xa0;years from diagnosis to surgical resection. Of the eight cases of LN with surgical follow-up, seven had LCIS (7/8, 87.5%), and one showed only fibroadenoma and SA with no residual LN in the excised specimen (1/8, 12.5%). Importantly, no invasive carcinoma was identified in any of the resections for LN involving SA.<br><br>CONCLUSIONS: In our series of carcinoma in situ (CIS) involving sclerosing adenosis diagnosed on core biopsy, lobular lesions involving SA were more common than ductal lesions. Ductal and lobular carcinoma in situ involving adenosis were best diagnosed by the low-power appearance of a lobulocentric pattern of growth. The most helpful diagnostic feature was the observation of additional foci of carcinoma in situ away from the adenosis. Immunohistochemical stains for myoepithelial cells were useful in particularly difficult cases. The presence of stromal desmoplasia does not preclude the diagnosis of carcinoma in situ involving adenosis. Knowledge of these diagnostic pearls can reduce over-interpretation of CIS on core biopsy and subsequent overtreatment.}, }
@article {pmid32694843, year = {2019}, author = {Seitz, S and Kwon, Y and Hartleben, G and Jülg, J and Sekar, R and Krahmer, N and Najafi, B and Loft, A and Gancheva, S and Stemmer, K and Feuchtinger, A and Hrabe de Angelis, M and Müller, TD and Mann, M and Blüher, M and Roden, M and Berriel Diaz, M and Behrends, C and Gilleron, J and Herzig, S and Zeigerer, A}, title = {Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity.}, journal = {Nature metabolism}, volume = {1}, number = {10}, pages = {1009-1026}, pmid = {32694843}, issn = {2522-5812}, mesh = {Adiposity ; Adult ; Animals ; Autophagy ; Blood Glucose/*metabolism ; Cholesterol/blood ; Female ; Homeostasis ; Humans ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria, Liver/*metabolism ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/metabolism ; Up-Regulation ; rab GTP-Binding Proteins/genetics/*metabolism ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) represents a key feature of obesity-related type 2 diabetes with increasing prevalence worldwide. To our knowledge, no treatment options are available to date, paving the way for more severe liver damage, including cirrhosis and hepatocellular carcinoma. Here, we show an unexpected function for an intracellular trafficking regulator, the small Rab GTPase Rab24, in mitochondrial fission and activation, which has an immediate impact on hepatic and systemic energy homeostasis. RAB24 is highly upregulated in the livers of obese patients with NAFLD and positively correlates with increased body fat in humans. Liver-selective inhibition of Rab24 increases autophagic flux and mitochondrial connectivity, leading to a strong improvement in hepatic steatosis and a reduction in serum glucose and cholesterol levels in obese mice. Our study highlights a potential therapeutic application of trafficking regulators, such as RAB24, for NAFLD and establishes a conceptual functional connection between intracellular transport and systemic metabolic dysfunction.}, }
@article {pmid32686908, year = {2020}, author = {Ma, L and Qi, L and Li, S and Yin, Q and Liu, J and Wang, J and She, C and Li, P and Liu, Q and Wang, X and Li, W}, title = {Aberrant HDAC3 expression correlates with brain metastasis in breast cancer patients.}, journal = {Thoracic cancer}, volume = {11}, number = {9}, pages = {2493-2505}, pmid = {32686908}, issn = {1759-7714}, support = {81702481//National Natural Science Foundation of China/ ; 15JCQNJC44800//Natural Science Foundation of Tianjin City/ ; 18JCYBJC27600//Natural Science Foundation of Tianjin City/ ; }, mesh = {Brain Neoplasms/*enzymology/*secondary ; Breast Neoplasms/*complications/*enzymology/pathology ; Female ; Histone Deacetylases/*metabolism ; Humans ; Middle Aged ; }, abstract = {BACKGROUND: Brain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan-histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy.<br><br>METHODS: Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin-peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis-free survival/post-brain metastatic survival were evaluated using Kaplan-Meier curves and Cox regression analyses.<br><br>RESULTS: HDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post-brain metastasis.<br><br>CONCLUSIONS: Our studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine.<br><br>KEY POINTS: Significant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis-free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated.}, }
@article {pmid32665190, year = {2020}, author = {Escott, CE and Zaenger, D and Switchencko, JM and Lin, JY and Abugideiri, M and Arciero, CA and Pfister, NT and Xu, KM and Meisel, JL and Subhedar, P and Torres, M and Curran, WJ and Patel, PR}, title = {The Influence of Histologic Grade on Outcomes of Elderly Women With Early Stage Breast Cancer Treated With Breast Conserving Surgery With or Without Radiotherapy.}, journal = {Clinical breast cancer}, volume = {20}, number = {6}, pages = {e701-e710}, pmid = {32665190}, issn = {1938-0666}, support = {P30 CA138292/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/diagnosis/mortality/pathology/*therapy ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental/*statistics &amp; numerical data ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant/statistics &amp; numerical data ; SEER Program/statistics &amp; numerical data ; Treatment Outcome ; }, abstract = {BACKGROUND: Two large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy.<br><br>MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup.<br><br>RESULTS: A total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P&#xa0;< .01) and had fewer T1a tumors (11% vs. 13%; P&#xa0;= .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P&#xa0;< .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P&#xa0;= .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P&#xa0;= .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P&#xa0;= .043).<br><br>CONCLUSION: In this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions.}, }
@article {pmid32662684, year = {2020}, author = {Shan, Z and Liu, L and Shen, J and Hao, H and Zhang, H and Lei, L and Liu, F and Wang, Z}, title = {Enhanced UV Resistance Role of Death Domain-Associated Protein in Human MDA-MB-231 Breast Cancer Cells by Regulation of G2 DNA Damage Checkpoint.}, journal = {Cell transplantation}, volume = {29}, number = {}, pages = {963689720920277}, pmid = {32662684}, issn = {1555-3892}, mesh = {Adult ; Breast Neoplasms/*genetics ; Cell Proliferation ; DNA Damage/*genetics ; Death Domain/*genetics ; Female ; G2 Phase Cell Cycle Checkpoints ; Humans ; Immunohistochemistry/*methods ; Middle Aged ; }, abstract = {PURPOSE: Death domain-associated protein (DAXX) is a multifunctional nuclear protein involved in apoptosis, transcription, deoxyribonucleic acid damage response, and tumorigenesis. However, the role of DAXX in breast cancer development and progression remains elusive. In this study, we examined the expression patterns and function of DAXX in human breast cancer samples and cell lines.<br><br>METHODS: Immunohistochemistry was used to analyze the expression and localization patterns of DAXX. Additionally, we investigated whether DAXX played an intrinsic role in the cellular response to damage induced by ultraviolet (UV) irradiation in MDA-MB-231 breast cancer cells (isolated at M D Anderson from a pleural effusion of a patient with invasive ductal carcinoma).<br><br>RESULTS: Our results showed that nucleus size, chromatin organization, and DAXX localization were altered in breast cancer tissues compared with those in control tissues. Compared with cytoplasmic and nuclear expression in benign breast tissues, DAXX was colocalized with promyelocytic leukemia in nuclei with a granular distribution. Endogenous DAXX messenger ribonucleic acid levels were upregulated upon UV radiation in MDA-MB-231 cells. DAXX-deficient cells tended to be more sensitive to irradiation than control cells. Conversely, DAXX-overexpressing cells exhibited reduced&#xa0;phosphorylated histone H2AX (&#x3b3;-H2AX) accumulation, increased cell survival, and resistance to UV-induced damage. The protective effects of DAXX may be related to the activation of the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (ATM-CHK2)-cell division cycle 25c (CDC25c) signaling pathways in Gap2/Mitosis (G2/M) checkpoint and ultimately cell cycle arrest at G2/M phase.<br><br>CONCLUSIONS: Taken together, these results suggested that DAXX may be an essential component in breast cancer initiation, malignant progression, and radioresistance.}, }
@article {pmid32661669, year = {2021}, author = {Rooper, LM and Thompson, LDR and Gagan, J and Oliai, BR and Weinreb, I and Bishop, JA}, title = {Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion.}, journal = {Head and neck pathology}, volume = {15}, number = {1}, pages = {179-185}, pmid = {32661669}, issn = {1936-0568}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Ductal/genetics/*pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Parotid Neoplasms/genetics/*pathology ; }, abstract = {Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.}, }
@article {pmid32661241, year = {2020}, author = {Tasdemir, N and Ding, K and Savariau, L and Levine, KM and Du, T and Elangovan, A and Bossart, EA and Lee, AV and Davidson, NE and Oesterreich, S}, title = {Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {11487}, pmid = {32661241}, issn = {2045-2322}, support = {5F30CA203154/NH/NIH HHS/United States ; K99CA237736/NH/NIH HHS/United States ; 1F31CA203055-01/NH/NIH HHS/United States ; }, mesh = {Autoantigens/genetics ; Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma, Lobular/*genetics/pathology ; Cell Differentiation/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Inhibitor of Differentiation Protein 1/genetics ; Inhibitor of Differentiation Proteins/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Membrane Proteins/genetics ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Proteins/genetics ; Phosphatidylinositol 3-Kinases/genetics ; *Proteomics ; Proto-Oncogene Proteins c-akt/genetics ; Ribosomal Protein S6 Kinases, 90-kDa/genetics ; Signal Transduction/genetics ; Transcriptome/*genetics ; }, abstract = {Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.}, }
@article {pmid32650989, year = {2020}, author = {Kaviani, A and Tabary, M and Zand, S and Araghi, F and Patocskai, E and Nouraie, M}, title = {Oncoplastic Repair in Breast Conservation: Comprehensive Evaluation of Techniques and Oncologic Outcomes of 937 Patients.}, journal = {Clinical breast cancer}, volume = {20}, number = {6}, pages = {511-519}, doi = {10.1016/j.clbc.2020.05.016}, pmid = {32650989}, issn = {1938-0666}, mesh = {Adult ; Breast/pathology/surgery ; Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Chemotherapy, Adjuvant/statistics &amp; numerical data ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Iran/epidemiology ; Mammaplasty/*adverse effects/methods/statistics &amp; numerical data ; Margins of Excision ; Mastectomy, Segmental/*adverse effects/statistics &amp; numerical data ; Middle Aged ; Neoadjuvant Therapy/methods/statistics &amp; numerical data ; Neoplasm Recurrence, Local/*epidemiology ; Neoplasm Staging ; Postoperative Complications/*epidemiology/etiology ; Prospective Studies ; Reoperation/statistics &amp; numerical data ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast-conserving surgery, especially with oncoplastic breast surgery (OBS), is becoming the standard of care in the surgical management of breast cancer. We investigated the applied technique of OBS and oncologic outcomes in a large series of patients.<br><br>PATIENTS AND METHODS: This study was conducted between January 2008 and June 2018 in two centers in Iran. Patients underwent OBS. Early and late postoperative complications, oncologic outcomes, and follow-up data were documented.<br><br>RESULTS: Nine hundred thirty-seven patients with a mean &#xb1; standard deviation age of 48.1 &#xb1; 11.3 underwent OBS. Most of the patients were diagnosed with early-stage disease, of which the most common pathology was invasive ductal carcinoma (83.3%). Lateral oncoplasty was the most commonly used OBS technique (324 cases, 34.6%). The most common complication was seroma formation. Reduction-type OBS technique had the highest rate of complications (13.1%). Thirty-four patients (5.4%) experienced local recurrence, with a median recurrence time of 26.4 months. Nine patients (1.3%) died from cancer recurrence.<br><br>CONCLUSION: OBS is a safe procedure with minor complications and good oncologic outcomes. These techniques can be applied to most patients who are candidates for breast-conserving surgery.}, }
@article {pmid32637252, year = {2020}, author = {Jones, B and Thomas, G and Westreich, J and Nofech-Mozes, S and Vitkin, A and Khorasani, M}, title = {Novel quantitative signature of tumor stromal architecture: polarized light imaging differentiates between myxoid and sclerotic human breast cancer stroma.}, journal = {Biomedical optics express}, volume = {11}, number = {6}, pages = {3246-3262}, pmid = {32637252}, issn = {2156-7085}, abstract = {As a leading cause of death in women, breast cancer is a global health concern for which personalized therapy remains largely unrealized, resulting in over- or under-treatment. Recently, tumor stroma has been shown to carry important prognostic information, both in its relative abundance and morphology, but its current assessment methods are few and suboptimal. Herein, we present a novel stromal architecture signature (SAS) methodology based on polarized light imaging that quantifies patterns of tumor connective tissue. We demonstrate its ability to differentiate between myxoid and sclerotic stroma, two pathology-derived categories associated with significantly different patient outcomes. The results demonstrate a 97% sensitivity and 88% specificity for myxoid stroma identification in a pilot study of 102 regions of interest from human invasive ductal carcinoma breast cancer surgical specimens (20 patients). Additionally, the SAS numerical score is indicative of the wide range of stromal characteristics within these binary classes and highlights ambiguous mixed-morphology regions prone to misclassification. The enabling polarized light microscopy technique is inexpensive, fast, fully automatable, applicable to fresh or embedded tissue without the need for staining and thus potentially translatable into research and/or clinical settings. The SAS metric yields quantifiable and objective stromal characterization with promise for prognosis in many types of cancers beyond breast carcinoma, enabling researchers and clinicians to further investigate the emerging and important role of stromal architectural patterns in solid tumors.}, }
@article {pmid32636849, year = {2020}, author = {Siegers, GM and Dutta, I and Kang, EY and Huang, J and Köbel, M and Postovit, LM}, title = {Aberrantly Expressed Embryonic Protein NODAL Alters Breast Cancer Cell Susceptibility to γδ T Cell Cytotoxicity.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1287}, pmid = {32636849}, issn = {1664-3224}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Intraepithelial Lymphocytes/*immunology ; Middle Aged ; Nodal Protein/*immunology/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Triple Negative Breast Neoplasms/*immunology/metabolism ; Tumor Escape/*immunology ; Tumor Microenvironment/*immunology ; }, abstract = {Gamma delta (γδ) T cells kill transformed cells, and increased circulating γδ T cells levels correlate with improved outcome in cancer patients; however, their function within the breast tumor microenvironment (TME) remains controversial. As tumors progress, they begin to express stem-cell associated proteins, concomitant with the emergence of therapy resistant metastatic disease. For example, invasive breast cancers often secrete the embryonic morphogen, NODAL. NODAL has been shown to promote angiogenesis, therapy resistance and metastasis in breast cancers. However, to date, little is known about how this secreted protein may interact with cells in the TME. Herein we explore how NODAL in the TME may influence γδ T cell function. We have assessed the proximity of γδ T cells to NODAL in a cohort of triple negative breast tumors. In all cases in which γδ T cells could be identified in these tumors, γδ T cells were found in close proximity to NODAL-expressing tumor cells. Migration of γδ and αβ T cells was similar toward MDA-MB-231 cells in which NODAL had been knocked down (shN) and MDA-MB-231 scrambled control cells (shC). Furthermore, Vδ1 γδ T cells did not migrate preferentially toward conditioned medium from these cell lines. While 24-h exposure to NODAL did not impact CD69, PD-1, or T cell antigen receptor (TCR) expression on γδ T cells, long term exposure resulted in decreased Vδ2 TCR expression. Maturation of γδ T cells was not significantly influenced by NODAL stimulation. While neither short- nor long-term NODAL stimulation impacted the ability of γδ T cells to kill MCF-7 breast cancer cells, the absence of NODAL resulted in greater sensitivity of targets to γδ T cell cytotoxicity, while overexpression of NODAL conferred resistance. This appeared to be at least in part due to an inverse correlation between NODAL and surface MICA/B expression on breast cancer target lines. As such, it appears that NODAL may play a role in strategies employed by breast cancer cells to evade γδ T cell targeting, and this should be considered in the development of safe and effective γδ T cell immunotherapies.}, }
@article {pmid32619221, year = {2020}, author = {Escoter-Torres, L and Greulich, F and Quagliarini, F and Wierer, M and Uhlenhaut, NH}, title = {Anti-inflammatory functions of the glucocorticoid receptor require DNA binding.}, journal = {Nucleic acids research}, volume = {48}, number = {15}, pages = {8393-8407}, pmid = {32619221}, issn = {1362-4962}, mesh = {Animals ; DNA/*genetics/metabolism ; DNA-Binding Proteins/*genetics ; Gene Expression Regulation/genetics ; Glucocorticoids/genetics/metabolism ; Humans ; Inflammation/*genetics/pathology ; Mice ; Protein Interaction Domains and Motifs/genetics ; RNA-Seq ; Receptors, Glucocorticoid/*genetics ; Transcriptional Activation/genetics ; }, abstract = {The glucocorticoid receptor is an important immunosuppressive drug target and metabolic regulator that acts as a ligand-gated transcription factor. Generally, GR's anti-inflammatory effects are attributed to the silencing of inflammatory genes, while its adverse effects are ascribed to the upregulation of metabolic targets. GR binding directly to DNA is proposed to activate, whereas GR tethering to pro-inflammatory transcription factors is thought to repress transcription. Using mice with a point mutation in GR's zinc finger, that still tether via protein-protein interactions while being unable to recognize DNA, we demonstrate that DNA binding is essential for both transcriptional activation and repression. Performing ChIP-Seq, RNA-Seq and proteomics under inflammatory conditions, we show that DNA recognition is required for the assembly of a functional co-regulator complex to mediate glucocorticoid responses. Our findings may contribute to the development of safer immunomodulators with fewer side effects.}, }
@article {pmid32618211, year = {2020}, author = {Bhattad, PB and Jain, V}, title = {Diffuse Sarcoidosis Masquerading as Widespread Malignant Disease: A Rare Case Report and Literature Review.}, journal = {Journal of investigative medicine high impact case reports}, volume = {8}, number = {}, pages = {2324709620938942}, pmid = {32618211}, issn = {2324-7096}, mesh = {Biopsy ; Breast Neoplasms/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Lung/*pathology ; Lymph Nodes/*pathology ; Lymphoma/*pathology ; Magnetic Resonance Imaging ; Mediastinum/*pathology ; Middle Aged ; Neoplasm Metastasis/diagnosis ; Positron Emission Tomography Computed Tomography ; Sarcoidosis/complications/*diagnosis ; }, abstract = {Sarcoidosis is a multisystem granulomatous disease commonly involving the lungs and mediastinal lymph nodes with the exact etiology being unclear. The simultaneous presence of malignant disease such as breast cancer and sarcoidosis has been reported. Sarcoidosis preceding a diagnosis of malignancy and that occurring years after treatment of malignant disease has been noted in the past. The presence of sarcoidosis in the setting of malignant disease carries a high risk of misdiagnosis. In this article, we report the case of a 45-year-old female with stage IA invasive ductal carcinoma of left breast that was in remission for 2 years; however, radiological imaging including magnetic resonance imaging of thoracic spine and positron emission tomography-computed tomography scanning were highly suspicious for malignant disease metastasis versus lymphoma with the widespread lymphadenopathy. Multiple tissue biopsies with histopathological evaluation allowed us to definitively exclude malignant disease metastasis and to correctly diagnose her atypical presentation of sarcoidosis.}, }
@article {pmid32617838, year = {2021}, author = {Hashinokuchi, A and Akamine, T and Kometani, T and Shikada, Y and Nozoe, T and Kato, S}, title = {Spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer: a case report and literature review.}, journal = {General thoracic and cardiovascular surgery}, volume = {69}, number = {1}, pages = {137-141}, pmid = {32617838}, issn = {1863-6713}, mesh = {Aged ; *Breast Neoplasms ; Female ; Humans ; Neoplasm Recurrence, Local ; Pleurodesis ; *Pneumothorax/etiology/therapy ; Quality of Life ; Recurrence ; Thoracic Surgery, Video-Assisted ; }, abstract = {We report a 69-year-old woman with spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer. She was treated for right breast cancer (invasive ductal carcinoma, ypT4bN1M0, stage IIIB) 2 years earlier, and was admitted for right pneumothorax and chest computed tomography, which showed multiple small cavitating lesions in bilateral lungs. The pneumothorax was treated conservatively with chest drainage, but subsequently recurred ipsilaterally. During video-assisted thoracic surgery, we detected small white nodules with visceral pleural rupture; therefore, we performed partial lung resection. The pathological findings revealed metastatic breast cancer with pleural invasion. Forty days later, ipsilateral pneumothorax recurred, and chemical pleurodesis was performed, which resolved the pneumothorax and prevented subsequent recurrence. Early diagnosis and definitive treatment, including pleurodesis, should be considered to prevent recurrence of spontaneous pneumothorax and improve patients' quality of life, even in patients with advanced malignancy.}, }
@article {pmid32609836, year = {2020}, author = {Sreekumar, S and Levine, KM and Sikora, MJ and Chen, J and Tasdemir, N and Carter, D and Dabbs, DJ and Meier, C and Basudan, A and Boone, D and McAuliffe, PF and Jankowitz, RC and Lee, AV and Atkinson, JM and Oesterreich, S}, title = {Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.}, journal = {Endocrinology}, volume = {161}, number = {9}, pages = {}, pmid = {32609836}, issn = {1945-7170}, mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; Cell Line, Tumor ; Estradiol/pharmacology ; Estrogen Receptor alpha/*genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Neoplasm Invasiveness ; Protein Processing, Post-Translational/drug effects ; Proteolysis/drug effects ; Ubiquitination/drug effects ; }, abstract = {Invasive lobular breast carcinoma (ILC) accounts for 10% to 15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P = 0.002) and ERα protein (P = 0.038) in ER+ ILC (n = 137) compared to IDC (n = 554), and further confirmed the mRNA difference in a local UPMC cohort (ILC, n = 143; IDC, n = 877; P < 0.005). In both datasets, the correlation between ESR1 mRNA and ERα protein was weaker in ILC, suggesting differential post-transcriptional regulation of ERα. In vitro, 17β-estradiol (E2) decreased the rate of degradation and increased the half-life of ERα in ILC cell lines, whereas the opposite was observed in IDC cell lines. Further, E2 failed to induce robust ubiquitination of ERα in ILC cells. To determine the potential clinical relevance of these findings, we evaluated the effect of 2 selective estrogen receptor downregulators (SERDs), ICI 182,780 and AZD9496, on ERα turnover and cell growth. While ICI 182,780 and AZD9496 showed similar effects in IDC cells, in ILC cell lines, AZD9496 was not as effective as ICI 182,780 in decreasing ERα stability and E2-induced proliferation. Furthermore, AZD9496 exhibited partial agonist activity in growth assays in ILC cell lines. Our study provides evidence for a distinct ERα regulation by SERDs in ILC cell lines, and therefore it is important to include ILC models into preclinical and clinical testing of novel SERDs.}, }
@article {pmid32599083, year = {2020}, author = {Grabenstetter, A and Mohanty, AS and Rana, S and Zehir, A and Brannon, AR and D'Alfonso, TM and DeLair, DF and Tan, LK and Ross, DS}, title = {E-cadherin immunohistochemical expression in invasive lobular carcinoma of the breast: correlation with morphology and CDH1 somatic alterations.}, journal = {Human pathology}, volume = {102}, number = {}, pages = {44-53}, pmid = {32599083}, issn = {1532-8392}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD/biosynthesis/*genetics ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/genetics/*pathology ; Cadherins/biosynthesis/*genetics ; Carcinoma, Lobular/diagnosis/genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Immunohistochemistry ; Mutation ; }, abstract = {E-cadherin (ECAD) immunohistochemical (IHC) expression is lost in ∼90% of invasive lobular carcinomas (ILCs) owing to genomic alterations of CDH1. We examined morphologic features and ECAD IHC expression in invasive breast carcinomas (BCs) with known CDH1 alterations. Between January 2014 and May 2018, 202 cases of BC with a CDH1 somatic alteration were identified. ECAD expression was lost in 77% (155/202) of cases and was retained in 23% (47/202) cases. Most (90%, 139/155) ECAD-negative cases were morphologically classified as ILC, while the remaining (10%, 16/155) were invasive mammary carcinoma with mixed ductal and lobular features (IMC). Of 47 cases with ECAD staining, 62% (29/47) were classified as ILC, 23% (11/47) were classified as IMC, and 15% (7/47) were classified as invasive ductal carcinoma (IDC). Of note, 51% (24/47) of ECAD-positive cases were initially diagnosed as IDC or IMC based on ECAD expression alone. For ECAD-negative BCs, 98% (152/155) of CDH1 alterations were truncating, and 2% (3/155) were variants of unknown significance (VUS). Truncating CDH1 alterations were identified in the majority of ECAD-positive BCs (72%, 34/47); however, VUS-type CDH1 alterations were more prevalent (28%, 13/47) in ECAD-positive BCs than in ECAD-negative BCs. Although 90% of ECAD-negative tumors were compatible with ILC in this study, 17% (29/168) of ILC cases were ECAD positive. In addition, CDH1 truncating alterations were seen in ECAD-positive ILC, supporting the notion of aberrant ECAD staining. Therefore, ECAD IHC expression must be interpreted in conjunction with morphology, and BC with classic histologic features of ILC should not be reclassified as IDC/IMC based solely on the status of ECAD IHC expression.}, }
@article {pmid32589068, year = {2021}, author = {Epstein, JI and Amin, MB and Fine, SW and Algaba, F and Aron, M and Baydar, DE and Beltran, AL and Brimo, F and Cheville, JC and Colecchia, M and Comperat, E and da Cunha, IW and Delprado, W and DeMarzo, AM and Giannico, GA and Gordetsky, JB and Guo, CC and Hansel, DE and Hirsch, MS and Huang, J and Humphrey, PA and Jimenez, RE and Khani, F and Kong, Q and Kryvenko, ON and Kunju, LP and Lal, P and Latour, M and Lotan, T and Maclean, F and Magi-Galluzzi, C and Mehra, R and Menon, S and Miyamoto, H and Montironi, R and Netto, GJ and Nguyen, JK and Osunkoya, AO and Parwani, A and Robinson, BD and Rubin, MA and Shah, RB and So, JS and Takahashi, H and Tavora, F and Tretiakova, MS and True, L and Wobker, SE and Yang, XJ and Zhou, M and Zynger, DL and Trpkov, K}, title = {The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {145}, number = {4}, pages = {461-493}, doi = {10.5858/arpa.2020-0015-RA}, pmid = {32589068}, issn = {1543-2165}, mesh = {Biomarkers, Tumor/analysis/genetics ; Biopsy, Needle/standards ; Consensus ; Humans ; Image-Guided Biopsy/standards ; Immunohistochemistry/standards ; Magnetic Resonance Imaging/standards ; Male ; Molecular Diagnostic Techniques/standards ; Neoplasm Grading/*standards ; Pathology/*standards ; Predictive Value of Tests ; Prostatic Neoplasms/chemistry/genetics/*pathology ; }, abstract = {CONTEXT.&#x2014;: Controversies and uncertainty persist in prostate cancer grading.<br><br>OBJECTIVE.&#x2014;: To update grading recommendations.<br><br>DATA SOURCES.&#x2014;: Critical review of the literature along with pathology and clinician surveys.<br><br>CONCLUSIONS.&#x2014;: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.}, }
@article {pmid32586354, year = {2020}, author = {Blohmer, M and Zhu, L and Atkinson, JM and Beriwal, S and Rodríguez-López, JL and Rosenzweig, M and Brufsky, AM and Tseng, G and Lucas, PC and Lee, AV and Oesterreich, S and Jankowitz, RC}, title = {Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {70}, pmid = {32586354}, issn = {1465-542X}, support = {SAC160073/KOMEN/Susan G. Komen/United States ; CCR14300865/KOMEN/Susan G. Komen/United States ; SAC150021/KOMEN/Susan G. Komen/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; U24 CA180921/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*pathology/*radiotherapy ; Carcinoma, Ductal, Breast/metabolism/pathology/radiotherapy ; Carcinoma, Lobular/metabolism/*mortality/pathology/radiotherapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Orbital Neoplasms/metabolism/radiotherapy/*secondary ; Prognosis ; Radiotherapy, Intensity-Modulated ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival.<br><br>METHODS: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.<br><br>RESULTS: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p&#x2009;=&#x2009;0.007). Median time to first OM in the OM cohort was 46.7&#x2009;months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4&#x2009;months) was significantly shorter than that of patients with IDC (55.3&#x2009;months, p&#x2009;=&#x2009;0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p&#x2009;=&#x2009;0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM.<br><br>CONCLUSIONS: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.}, }
@article {pmid32585364, year = {2020}, author = {Erener, S}, title = {Diabetes, infection risk and COVID-19.}, journal = {Molecular metabolism}, volume = {39}, number = {}, pages = {101044}, pmid = {32585364}, issn = {2212-8778}, mesh = {Adult ; Aged ; Animals ; *Betacoronavirus ; COVID-19 ; Child ; Comorbidity ; Coronavirus Infections/*epidemiology/immunology/pathology/virology ; Cytokines/metabolism ; Diabetes Mellitus, Type 1/*epidemiology/immunology ; Diabetes Mellitus, Type 2/*epidemiology/immunology ; Female ; Humans ; Immunity, Cellular ; Immunity, Innate ; Incidence ; Male ; Mice ; Middle Aged ; Pandemics ; Pneumonia, Viral/*epidemiology/immunology/pathology/virology ; Risk Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19.<br><br>SCOPE OF REVIEW: In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided.<br><br>MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.}, }
@article {pmid32581209, year = {2020}, author = {Lan, T and Lu, Y and Luo, H and He, J and He, J and Hu, Z and Xu, H}, title = {Effects of Marital Status on Prognosis in Women with Infiltrating Ductal Carcinoma of the Breast: A Real-World 1: 1 Propensity-Matched Study.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {26}, number = {}, pages = {e923630}, pmid = {32581209}, issn = {1643-3750}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal/mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Marital Status/*statistics &amp; numerical data ; Middle Aged ; Multivariate Analysis ; Prognosis ; Propensity Score ; Proportional Hazards Models ; Protective Factors ; Risk Factors ; SEER Program ; United States/epidemiology ; }, abstract = {BACKGROUND The effects of marital status on infiltrating ductal carcinoma of breast cancer (IDC) have not been studied in detail. This study investigated the impact of marital status on IDC patients. MATERIAL AND METHODS SEER databases were searched from 2010 to 2015 for subjects who were married, divorced, single, and widowed. The influence of marital status on breast cancer-specific survival (BCSS) and overall survival (OS) of IDC patients was investigated through multivariate Cox regression analysis and Kaplan-Meier analysis. To prevent bias, propensity score matching (PSM) analysis was performed. RESULTS The 5-year OS was 89.6%in married patients, 84.9% in divorced patients, 83.5% in single patients, and 71.3% in widowed patients (p<0.001). The 5-year BCSS were 92.9%, 90.2%, 87.6%, and 86.4%, respectively (p<0.001). Multivariate Cox regression analysis revealed that marriage was a protective factor for patients with IDC in terms of OS (divorced: HR, 1.27; 95% CI, 1.21-1.32; p<0.001; single: HR, 1.36; 95% CI, 1.31-1.42; p<0.001; widowed: HR, 1.42; 95% CI, 1.36-1.48; p<0.001) and BCSS (divorced: HR, 1.15; 95% CI, 1.09-1.21; p<0.001; single: HR, 1.27; 95% CI, 1.21-1.33; p<0.001; widowed: HR, 1.32; 95% CI, 1.25-1.40; p<0.001). Following subgroup and PSM analysis, married patients were shown to have better OS and BCSS as opposed to divorced, single, or widowed patients. CONCLUSIONS We identify marital status as a predictor of survival in those with IDC. Widowed patients showed the highest mortality risk.}, }
@article {pmid32580398, year = {2020}, author = {Kim, HM and Koo, JS}, title = {Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32580398}, issn = {1422-0067}, support = {2016 (6-2016-0163)//faculty research grant from Yonsei University College of Medicine/ ; }, mesh = {Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/immunology/metabolism/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; Forkhead Transcription Factors/metabolism ; Humans ; Lymphocytes, Tumor-Infiltrating/*classification/*immunology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; STAT6 Transcription Factor/metabolism ; Survival Rate ; }, abstract = {The clinical significance of immune cell subtypes in breast cancer remains poorly understood. To identify tumor-infiltrating immune cell subtypes in breast cancer and investigate their implications, tissue microarrays were constructed using 334 cases of invasive ductal carcinoma (luminal A type: 162 (48.5%), luminal B type: 96 (28.7%), HER-2 type: 21 (6.3%), and triple negative breast cancer: 55 (16.5%)). Hormone receptors (ER, PR, and HER-2), Ki-67, and immune cell subtype-related proteins (STAT4, STAT6, FOXP3, CD8, CD68, and CD163) were assessed immunohistochemically. The proportion of highly expressed STAT6, FOXP3, CD8, CD68, and CD163 proteins was found to be lowest in luminal A type but highest in the HER-2 type. Additionally, high-level STAT6, FOXP3, CD68, and CD163 protein expression was associated with higher histologic grade. ER negativity was associated with high STAT6, FOXP3, and CD163 expression levels, whereas PR negativity and high Ki-67 labeling index were associated with high CD163 expression. Univariate (p = 0.003) and multivariate Cox (hazard ratio: 2.435, 95% CI: 1.110-5.344, p = 0.049) analyses showed that high CD8 expression is an independent factor associated with shorter disease-free survival. Immune cell subtype-related protein expression is dependent on breast cancer molecular subtypes, and CD8 expression is associated with patient prognosis.}, }
@article {pmid32563094, year = {2020}, author = {Yoneyama, K and Nakagawa, M and Hara, A}, title = {Local recurrence of breast cancer caused by core needle biopsy: Case report and review of the literature.}, journal = {International journal of surgery case reports}, volume = {72}, number = {}, pages = {318-321}, pmid = {32563094}, issn = {2210-2612}, abstract = {INTRODUCTION: Needle tract seeding is the implantation of tumor cells at the site of needle passage during needle biopsy. Histopathological examination of resected specimens after biopsy shows an incidence of 22%-50%. However, reports of actual local recurrence are extremely rare. Here we report such a case.<br><br>PRESENTATION OF CASE: A 67-year-old woman was diagnosed with ductal carcinoma by histopathology and underwent right mastectomy and sentinel lymph node biopsy. Histopathological examination revealed non-invasive ductal carcinoma. One year after the first operation, a mass was found at the site of the core needle biopsy (CNB) scar near the previous surgical wound on the right chest. Histological examination revealed the tumor as adenocarcinoma, and a skin lesion resection was performed. After surgery, radiation therapy and endocrine therapy were performed. She remains relapse-free as of this writing, 9 months after resection.<br><br>DISCUSSION: Reports of local recurrence due to needle tract seeding are extremely rare. We found nine cases of mastectomy and seven cases of partial resection performed for the first surgery; six patients received radiation therapy and 10 did not. Histological diagnosis at the time of the first operation was invasive carcinoma in all cases.<br><br>CONCLUSION: The risk of seeding is high with multiple punctures in CNB, in cases with a short period until surgery, and in mucinous carcinoma. Considering these factors, CNB puncture should preferably be at a site that is included in the resection area during surgery. If not resected, close follow-up is necessary considering the possibility of local recurrence.}, }
@article {pmid32561662, year = {2020}, author = {Sestak, I and Filipits, M and Buus, R and Rudas, M and Balic, M and Knauer, M and Kronenwett, R and Fitzal, F and Cuzick, J and Gnant, M and Greil, R and Dowsett, M and Dubsky, P}, title = {Prognostic Value of EndoPredict in Women with Hormone Receptor-Positive, HER2-Negative Invasive Lobular Breast Cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {17}, pages = {4682-4687}, doi = {10.1158/1078-0432.CCR-20-0260}, pmid = {32561662}, issn = {1557-3265}, support = {5032/CRUK_/Cancer Research UK/United Kingdom ; C569/A16891/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast/*pathology/surgery ; Breast Neoplasms/genetics/*mortality/pathology/therapy ; Carcinoma, Lobular/genetics/*mortality/pathology/therapy ; Chemotherapy, Adjuvant/methods ; Clinical Trials, Phase III as Topic ; Datasets as Topic ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/genetics/pathology ; Prognosis ; Randomized Controlled Trials as Topic ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Risk Assessment/methods ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) accounts for approximately 5%-15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients with invasive ductal carcinoma (IDC) or without distinction between the subtypes. Here, we investigate the prognostic value of EndoPredict (EPclin) in a large cohort of ILCs pooled from three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC).<br><br>EXPERIMENTAL DESIGN: The primary objective of this analysis was to determine the prognostic value of EPclin for distant recurrence (DR) in years 0-10 in postmenopausal women with ILC. The primary outcome was DR.<br><br>RESULTS: 470 women (17.9%) presented with ILC, 1,944 (73.9%) with IDC, and 216 (8.2%) with other histologic types. EPclin was highly prognostic in women with ILC [HR = 3.32 (2.54-4.34)] and provided more prognostic value than the Clinical Treatment Score [CTS; HR = 2.17 (1.73-2.72)]. 63.4% of women were categorized into the low EPclin risk group and they had a 10-year DR of 4.8% (2.7-8.4) compared with 36.6% of women in the high-risk group with a 10-year DR risk of 26.6% (20.0-35.0). EPclin also provided highly prognostic information in women with node-negative disease [HR = 2.56 (1.63-4.02)] and node-positive disease [HR = 3.70 (2.49-5.50)].<br><br>CONCLUSIONS: EPclin provided highly significant prognostic value and significant risk stratification for women with ILC. Ten-year DR risk in the EPclin low-risk groups were similar between ILC and IDC. Our results show that EPclin is informative in women with ILC and suggest that it is equally valid in both histologic subtypes.}, }
@article {pmid32551954, year = {2020}, author = {Bosso, G and Valvano, A and Apuzzi, V and Mercurio, V and Di Simone, V and Cittadini, A and Napoli, R and Oliviero, U}, title = {Peripheral Vascular Function in Dilated Cardiomyopathy of Different Etiology.}, journal = {Angiology}, volume = {71}, number = {8}, pages = {726-733}, doi = {10.1177/0003319720932803}, pmid = {32551954}, issn = {1940-1574}, mesh = {Aged ; Brachial Artery/diagnostic imaging/*physiopathology ; Cardiomyopathy, Dilated/diagnostic imaging/*etiology/*physiopathology ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*complications/diagnosis/physiopathology ; Prognosis ; Risk Assessment ; Risk Factors ; *Vascular Stiffness ; *Vasodilation ; }, abstract = {Vascular function in dilated cardiomyopathy of different etiology has been poorly investigated. Moreover, reference values of flow-mediated dilation (FMD) in chronic heart failure (CHF) need to be updated according to the new standardized protocols. We characterized the vascular impairment in different stages of post-ischemic dilated cardiomyopathy (PI-DC) or idiopathic dilated cardiomyopathy (I-DC). Eighty consecutive outpatients with CHF in different New York Heart Association (NYHA) classes (45 PI-DC, 35 I-DC) and 50 control subjects underwent FMD and brachial distensibility coefficient measurement. Patients with CHF showed a marked impairment in FMD compared with controls that worsened from classes NYHA I-II to III-IV, independently of etiology (P < .05). New York Heart Association I-II PI-DC patients showed a worse FMD compared with NYHA I-II I-DC patients (P < .05). Brachial distensibility coefficient values were significantly lower in patients with CHF compared with controls (P < .001) without differences between PI-DC and I-DC. In conclusion, advanced CHF is characterized by vascular impairment that is independent of etiology. In the early stages of CHF, endothelial dysfunction is more severe in patients with PI-DC compared with I-DC probably due to the high cardiovascular risk profile. In I-DC, vascular function impairment is independent of cardiovascular risk factors and could participate in the pathogenesis of I-DC.}, }
@article {pmid32548206, year = {2020}, author = {Arensman, K and Dela-Pena, J and Miller, JL and LaChance, E and Beganovic, M and Anderson, M and Rivelli, A and Wieczorkiewicz, SM}, title = {Impact of Mandatory Infectious Diseases Consultation and Real-time Antimicrobial Stewardship Pharmacist Intervention on Staphylococcus aureus Bacteremia Bundle Adherence.}, journal = {Open forum infectious diseases}, volume = {7}, number = {6}, pages = {ofaa184}, pmid = {32548206}, issn = {2328-8957}, abstract = {BACKGROUND: The purpose of this study was to evaluate the impact of infectious diseases consultation (IDC) and a real-time antimicrobial stewardship (AMS) review on the management of Staphylococcus aureus bacteremia (SAB).<br><br>METHODS: This retrospective study included adult inpatients with SAB from January 2016 to December 2018 at 7 hospitals. Outcomes were compared between 3 time periods: before mandatory IDC and AMS review (period 1), after mandatory IDC and before AMS review (period 2), and after mandatory IDC and AMS review (period 3). The primary outcome was bundle adherence, defined as appropriate intravenous antimicrobial therapy, appropriate duration of therapy, appropriate surveillance cultures, echocardiography, and removal of indwelling intravenous catheters, if applicable. Secondary end points included individual bundle components, source control, length of stay (LOS), 30-day bacteremia-related readmission, and in-hospital all-cause mortality.<br><br>RESULTS: A total of 579 patients met inclusion criteria for analysis. Complete bundle adherence was 65% in period 1 (n&#x2005;=&#x2005;241/371), 54% in period 2 (n&#x2005;=&#x2005;47/87), and 76% in period 3 (n&#x2005;=&#x2005;92/121). Relative to period 3, bundle adherence was significantly lower in period 1 (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.37-0.93; P&#x2005;=&#x2005;.02) and period 2 (OR, 0.37; 95% CI, 0.20-0.67; P&#x2005;=&#x2005;.0009). No difference in bundle adherence was noted between periods 1 and 2. Significant differences were seen in obtaining echocardiography (91% vs 83% vs 100%; P&#x2005;<&#x2005;.001), source control (34% vs 45% vs 45%; P&#x2005;=&#x2005;.04), and hospital LOS (10.5 vs 8.9 vs 12.0 days; P&#x2005;=&#x2005;.01). No differences were noted for readmission or mortality.<br><br>CONCLUSIONS: The addition of AMS pharmacist review to mandatory IDC was associated with significantly improved quality care bundle adherence.}, }
@article {pmid32544183, year = {2020}, author = {Moon, HR and Ospina-Muñoz, N and Noe-Kim, V and Yang, Y and Elzey, BD and Konieczny, SF and Han, B}, title = {Subtype-specific characterization of breast cancer invasion using a microfluidic tumor platform.}, journal = {PloS one}, volume = {15}, number = {6}, pages = {e0234012}, pmid = {32544183}, issn = {1932-6203}, support = {P30 CA023168/CA/NCI NIH HHS/United States ; UL1 TR000006/TR/NCATS NIH HHS/United States ; HHSN261201400021C/CA/NCI NIH HHS/United States ; }, mesh = {CD24 Antigen/metabolism ; Carcinoma, Ductal, Breast/classification/genetics/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Humans ; Microfluidics/methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Triple Negative Breast Neoplasms/classification/genetics/*pathology ; *Tumor Microenvironment ; }, abstract = {Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.}, }
@article {pmid32532588, year = {2020}, author = {Brings, S and Fleming, T and Herzig, S and Nawroth, PP and Kopf, S}, title = {Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study.}, journal = {Journal of diabetes and its complications}, volume = {34}, number = {9}, pages = {107648}, doi = {10.1016/j.jdiacomp.2020.107648}, pmid = {32532588}, issn = {1873-460X}, mesh = {*Albuminuria/diagnosis/etiology ; Cathepsin D/urine ; Cathepsin L/*urine ; Cohort Studies ; *Diabetes Mellitus, Type 2/complications/diagnosis ; *Glycation End Products, Advanced/urine ; Humans ; Tandem Mass Spectrometry ; }, abstract = {AIMS: Cathepsin D (CTSD) and L (CTSL) are lysosomal proteases which degrade and detoxify advanced glycation end product (AGE)-modified proteins which are predictive of the development of diabetic nephropathy. We aimed to quantify cathepsin levels in urine from patients with type 2 diabetes and to relate these to the amount of urinary free AGEs at baseline and with kidney function after four years of follow-up in this closed cohort study.<br><br>METHODS: We established and validated a LC MS/MS method for the quantification of CTSD and CTSL in urine. Patients with type 2 diabetes were screened for diabetic kidney disease and 141 patients were seen at baseline and after four years. CTSD and CTSL and free AGEs were quantified in urine by LC MS/MS at baseline in these patients.<br><br>RESULTS: The detection limit of CTSD and CTSL in urine was 2.4&#x202f;ng/l and 19.1&#x202f;ng/l, respectively. CTSD (p&#x202f;<&#x202f;0.0001, r&#x202f;=&#x202f;0.555) and CTSL (p&#x202f;<&#x202f;0.0001, r&#x202f;=&#x202f;0.608) correlated positively with albuminuria at time of recruitment. In addition levels of the proteases but not albuminuria correlated with urinary levels of the major cross-linking AGE glucosepane (CTSD: p&#x202f;=&#x202f;0.012, r&#x202f;=&#x202f;0.225; CTSL: p&#x202f;<&#x202f;0.001, r&#x202f;=&#x202f;0.376). A strong non-linear association between CTSD (r&#x202f;=&#x202f;0.568), CTSL (r&#x202f;=&#x202f;0.588) and change in albuminuria over four years was present. High levels of CTSL (p&#x202f;=&#x202f;0.007, beta&#x202f;=&#x202f;-0.366) were associated with an improvement of albuminuria after four years.<br><br>CONCLUSIONS: A sensitive LC MS/MS assay for the quantification of CTSD and CTSL in urine was established. High CTSL baseline levels were associated with an improvement in albuminuria at follow-up. An increased excretion and thus detoxification of the free form of the pathogenic cross-linking AGE glucosepane could explain the positive predictive value of high CTSL levels on albuminuria.}, }
@article {pmid32511899, year = {2020}, author = {Yamaguchi, T and Akahane, T and Harada, O and Kato, Y and Aimono, E and Takei, H and Tasaki, T and Noguchi, H and Nishihara, H and Kamata, H and Tanimoto, A}, title = {Next-generation sequencing in residual liquid-based cytology specimens for cancer genome analysis.}, journal = {Diagnostic cytopathology}, volume = {48}, number = {11}, pages = {965-971}, doi = {10.1002/dc.24511}, pmid = {32511899}, issn = {1097-0339}, mesh = {Carcinoma/*genetics ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Gene Frequency/genetics ; Genome/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lymph Nodes/pathology ; Mutation/genetics ; Neoplasms/*genetics ; Sequence Analysis, DNA/methods ; Thyroid Gland/pathology ; }, abstract = {BACKGROUND: Cancer genome profiling of cytology specimens using next-generation sequencing (NGS) requires adequate and good-quality DNA. Genomic examination of cytology samples was conventionally performed on cell block (CB) or smear specimens than on residual liquid-based cytology (LBC) specimens, which are high-quality DNA sources even after long-term storage.<br><br>METHODS: We estimated tumor fractions of 37 residual LBC specimens, including 30 fine needle aspiration (FNA) samples from the thyroid (12 papillary thyroid carcinomas and two malignant lymphomas), lymph node (13 metastatic carcinomas and one malignant lymphoma), and breast cancer (one phyllodes tumor and one invasive ductal carcinoma), two pancreatic carcinoma samples, and five liquid (ascites, pleural effusion, and cerebrospinal fluid) samples. The DNA was extracted from all samples and subjected to NGS using a customized cancer gene panel comprising 28 cancer-related genes.<br><br>RESULTS: NGS analysis revealed somatic mutations corresponding to pathological diagnosis with adequate variant allele frequency (VAF) in 24 LBC specimens, which had significantly higher tumor fraction (72.5%&#x2009;&#xb1;&#x2009;4.9%). Ten cases, including the five fluid samples, had very small tumor fractions (7.5%&#x2009;&#xb1;&#x2009;2.3%) to obtain sufficient VAF. Other two samples had high tumor fractions but showed very low VAF, indicating the presence of fusion genes. The remaining one sample yielded no DNA recovery.<br><br>CONCLUSION: The residual LBC specimens collected by FNA from the thyroid gland and lymph node were verified to carry high tumor fraction and could serve as an alternate source for molecular testing to screen and diagnose cancers without the use of CB or smears.}, }
@article {pmid32509097, year = {2020}, author = {Lv, X and Ye, J and Jiang, G and Wang, Y and Lv, J and Wang, Y}, title = {Simultaneous multiple primary cancers with concomitant inflammatory myofibroblastic tumor: a case report.}, journal = {International journal of clinical and experimental pathology}, volume = {13}, number = {5}, pages = {1212-1215}, pmid = {32509097}, issn = {1936-2625}, abstract = {Multiple primary cancers are of rare occurrence. Most multiple primary cancers are metachronous multiple primary cancers, while simultaneous multiple primary cancers are rare. Inflammatory myofibroblastic tumors are rare. Inflammatory myofibroblastic tumor occurs most frequently in children and young adults. Herein, we report a rare case of simultaneous multiple primary cancers and inflammatory myofibroblastic tumor. A 44-year-old woman was admitted for a breast mass evaluation. The patient was positive for antinuclear, anti-mitochondrial, and anti-RO52 antibodies. Breast magnetic resonance imaging revealed a right breast mass. After neoadjuvant chemotherapy, modified radical mastectomy was performed. Postoperative histopathology revealed an invasive ductal carcinoma. Two months later, computed tomography revealed a nodule in the right upper lobe and ground-glass opacity in the lower lobe of the lungs. Lobectomy and lobe biopsy were performed. Postoperative histopathology revealed that the mass in the right upper lobe was an inflammatory myofibroblastic tumor and the right lower lobe lesion was an invasive adenocarcinoma. Immunohistochemistry of the inflammatory myofibroblastic tumor revealed negativity for anaplastic lymphoma kinase. At the 4-month follow-up, the patient showed good recovery. The etiology of multiple primary cancers and inflammatory myofibroblastic tumors is still unknown; in this case, we believe that autoimmune factors are the main cause of multiple primary cancers with concomitant inflammatory myofibroblastic tumor. Tissue biopsy is needed to ensure correct diagnosis of multiple primary cancers and inflammatory myofibroblastic tumor. Surgery-based comprehensive therapy is recommended. The prognosis is favorable and regular follow-up is necessary.}, }
@article {pmid32488076, year = {2020}, author = {Subudhi, AK and O'Donnell, AJ and Ramaprasad, A and Abkallo, HM and Kaushik, A and Ansari, HR and Abdel-Haleem, AM and Ben Rached, F and Kaneko, O and Culleton, R and Reece, SE and Pain, A}, title = {Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2763}, pmid = {32488076}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Caenorhabditis elegans Proteins ; Circadian Rhythm/*physiology ; Disease Models, Animal ; Erythropoiesis/*physiology ; Female ; Gene Expression ; Host-Parasite Interactions/genetics/*physiology ; Humans ; Malaria/*metabolism/parasitology ; Mice ; Mice, Knockout ; Plasmodium chabaudi/genetics/growth &amp; development ; Plasmodium falciparum/genetics/growth &amp; development ; Protozoan Proteins/genetics/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Rodentia ; Secologanin Tryptamine Alkaloids/*metabolism ; Transcriptome ; }, abstract = {Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.}, }
@article {pmid32480118, year = {2020}, author = {Chan, SJ and Ein-Dor, T and Mayopoulos, PA and Mesa, MM and Sunda, RM and McCarthy, BF and Kaimal, AJ and Dekel, S}, title = {Risk factors for developing posttraumatic stress disorder following childbirth.}, journal = {Psychiatry research}, volume = {290}, number = {}, pages = {113090}, doi = {10.1016/j.psychres.2020.113090}, pmid = {32480118}, issn = {1872-7123}, mesh = {Adult ; Delivery, Obstetric/*psychology/statistics &amp; numerical data ; Female ; Humans ; Labor, Obstetric/*psychology ; Mental Health ; Parturition/*psychology ; Postpartum Period/*psychology ; Pregnancy ; Pregnancy Complications/*epidemiology ; Pregnancy Outcome/epidemiology/psychology ; Prevalence ; Risk Factors ; Stress Disorders, Post-Traumatic/*epidemiology ; Surveys and Questionnaires ; }, abstract = {Women can develop childbirth-related posttraumatic stress disorder (CB-PTSD) in at-term delivery with healthy baby outcome as well as following pre-term delivery and neonatal complications, a potential added stressor. No study compares risk factors of CB-PTSD associated with different infant outcomes. We investigated CB-PTSD risk factors by comparing women with or without neonatal complications. Analysis reveals the importance of antepartum and birth-related risk factors in CB-PTSD above and beyond child outcomes, suggesting childbirth is an independent stressor capable of evoking CB-PTSD.}, }
@article {pmid32467291, year = {2020}, author = {Shan, NL and Minden, A and Furmanski, P and Bak, MJ and Cai, L and Wernyj, R and Sargsyan, D and Cheng, D and Wu, R and Kuo, HD and Li, SN and Fang, M and Maehr, H and Kong, AN and Suh, N}, title = {Analysis of the Transcriptome: Regulation of Cancer Stemness in Breast Ductal Carcinoma In Situ by Vitamin D Compounds.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {13}, number = {8}, pages = {673-686}, pmid = {32467291}, issn = {1940-6215}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 AT007036/AT/NCCIH NIH HHS/United States ; R01 AT009152/AT/NCCIH NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology/*prevention &amp; control ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; DNA Methylation/drug effects ; Datasets as Topic ; Disease Progression ; Down-Regulation/drug effects ; Epithelial-Mesenchymal Transition/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasm Invasiveness/pathology/prevention &amp; control ; Neoplastic Stem Cells/*drug effects/pathology ; RNA-Seq ; Signal Transduction/drug effects/genetics ; Up-Regulation/drug effects ; Vitamin D/*administration &amp; dosage/analogs &amp; derivatives ; }, abstract = {Ductal carcinoma in situ (DCIS), which accounts for one out of every five new breast cancer diagnoses, will progress to potentially lethal invasive ductal carcinoma (IDC) in about 50% of cases. Vitamin D compounds have been shown to inhibit progression to IDC in the MCF10DCIS model. This inhibition appears to involve a reduction in the cancer stem cell-like population in MCF10DCIS tumors. To identify genes that are involved in the vitamin D effects, a global transcriptomic analysis was undertaken of MCF10DCIS cells grown in mammosphere cultures, in which cancer stem-like cells grow preferentially and produce colonies by self-renewal and maturation, in the presence and absence of 1α25(OH)2D3 and a vitamin D analog, BXL0124. Using next-generation RNA-sequencing, we found that vitamin D compounds downregulated genes involved in maintenance of breast cancer stem-like cells (e.g., GDF15), epithelial-mesenchymal transition, invasion, and metastasis (e.g., LCN2 and S100A4), and chemoresistance (e.g., NGFR, PPP1R1B, and AGR2), while upregulating genes associated with a basal-like phenotype (e.g., KRT6A and KRT5) and negative regulators of breast tumorigenesis (e.g., EMP1). Gene methylation status was analyzed to determine whether the changes in expression induced by vitamin D compounds occurred via this mechanism. Ingenuity pathway analysis was performed to identify upstream regulators and downstream signaling pathway genes differentially regulated by vitamin D, including TP63 and vitamin D receptor -mediated canonical pathways in particular. This study provides a global profiling of changes in the gene signature of DCIS regulated by vitamin D compounds and possible targets for chemoprevention of DCIS progression to IDC in patients.}, }
@article {pmid32457515, year = {2020}, author = {Goodes, LM and King, GK and Goodwin, DM and Watts, A and Bardsley, J and Middleton, J and Bragge, P and Dunlop, SA}, title = {Barriers and facilitators to optimising inpatient bladder management after spinal cord injury.}, journal = {Spinal cord}, volume = {58}, number = {12}, pages = {1291-1300}, pmid = {32457515}, issn = {1476-5624}, mesh = {Humans ; Inpatients ; Longitudinal Studies ; *Spinal Cord Injuries/therapy ; *Urinary Bladder, Neurogenic/etiology/therapy ; }, abstract = {STUDY DESIGN: Qualitative survey.<br><br>OBJECTIVES: Examine clinicians' perspectives on adherence to published evidence-based guidelines and clinician-perceived barriers, and facilitators to optimising inpatient bladder management within one Spinal Cord Injury (SCI) service.<br><br>SETTING: Surgical Hospital (acute care) and SCI Unit (sub-acute, rehabilitation) in Western Australia (WA).<br><br>METHODS: Clinicians reviewed an 'Evidence Matrix' summarising published clinical practice guidelines and recommendations for SCI bladder management. Focus groups examined the extent to which current practice adhered to recommendations and identified perceived barriers and facilitators to optimal management. Data were analysed thematically using a deductive approach.<br><br>RESULTS: Current management closely mirrors published recommendations. Key facilitators included long-standing prioritisation of rapid progression from urethral indwelling (IDC) to a 6&#x2009;hourly intermittent catheterisation (IC) protocol; regular competency audits of catheterisation technique; and a Spinal Urology Clinical Nurse Consultant (CNC) position. Barriers included limited resources/staffing; restricted access to Neuro-urology consultation; inter-disciplinary communication gaps; and delays in determining and implementing long-term bladder management.<br><br>CONCLUSIONS: Inpatient SCI bladder care in WA closely emulates published evidence, although adherence at other sites may reveal different practices. Bladder management was found to have been facilitated by a strong culture of practice led by Neuro-urologists, informed by evidence and embraced by Senior Clinicians. Further reduction in duration of initial IDC, provision of early and ongoing Neuro-urology consultations as part of standard care, increased interdisciplinary communication and dedicated SCI Urology theatre lists would further optimise management.}, }
@article {pmid32439746, year = {2020}, author = {Bacorn, C and Kim, E and Borowsky, AD and Lin, LK}, title = {Previously undiagnosed neuroendocrine tumour mimicking breast cancer metastasis to the orbit.}, journal = {BMJ case reports}, volume = {13}, number = {5}, pages = {}, pmid = {32439746}, issn = {1757-790X}, mesh = {Adenocarcinoma/*pathology/therapy ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*secondary/therapy ; Diplopia ; Female ; Humans ; Intestinal Neoplasms/*pathology/therapy ; Neuroendocrine Tumors/*pathology/therapy ; Octreotide/therapeutic use ; Orbit ; Orbital Neoplasms/*secondary/therapy ; Pancreatic Neoplasms/*pathology/therapy ; Stomach Neoplasms/*pathology/therapy ; }, abstract = {Metastatic neuroendocrine neoplasms to the breast are rare and histopathologic overlap with mammary carcinomas has led to misdiagnosis. We present a case of a middle-aged woman with diplopia and a right medial rectus mass. Metastatic breast cancer was initially suspected based on a history of invasive ductal carcinoma. Detailed immunohistochemistry of the orbital biopsy, gallium-68 dotatate positron emission tomography-CT, and reevaluation of her prior breast specimen, demonstrated that her initial breast carcinoma diagnosis was in error and she was ultimately diagnosed with a previously unknown gastrointestinal neuroendocrine tumour metastatic to both the orbit and breast. This case highlights the challenges of differentiating between metastatic neuroendocrine tumours and invasive mammary carcinomas with neuroendocrine differentiation both in the breast and in the orbit. It is important to recognise the overlap so that a primary neuroendocrine neoplasm is not missed, or treatment significantly delayed.}, }
@article {pmid32438745, year = {2020}, author = {Moran Lauter, AN and Rutter, L and Cook, D and O'Rourke, JA and Graham, MA}, title = {Examining Short-Term Responses to a Long-Term Problem: RNA-Seq Analyses of Iron Deficiency Chlorosis Tolerant Soybean.}, journal = {International journal of molecular sciences}, volume = {21}, number = {10}, pages = {}, pmid = {32438745}, issn = {1422-0067}, support = {Project 5030-21220-006-00D//Agricultural Research Service/ ; }, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant ; Gene Ontology ; *Iron Deficiencies ; Plant Leaves/genetics ; Plant Necrosis and Chlorosis/*genetics ; Plant Roots/genetics ; *RNA-Seq ; Signal Transduction ; Soybeans/*genetics ; Stress, Physiological/genetics ; Transcription Factors/metabolism ; }, abstract = {Iron deficiency chlorosis (IDC) is a global crop production problem, significantly impacting yield. However, most IDC studies have focused on model species, not agronomically important crops. Soybean is the second largest crop grown in the United States, yet the calcareous soils across most of the upper U.S. Midwest limit soybean growth and profitability. To understand early soybean iron stress responses, we conducted whole genome expression analyses (RNA-sequencing) of leaf and root tissue from the iron efficient soybean (Glycine max) cultivar Clark, at 30, 60 and 120 min after transfer to iron stress conditions. We identified over 10,000 differentially expressed genes (DEGs), with the number of DEGs increasing over time in leaves, but decreasing over time in roots. To investigate these responses, we clustered our expression data across time to identify suites of genes, their biological functions, and the transcription factors (TFs) that regulate their expression. These analyses reveal the hallmarks of the soybean iron stress response (iron uptake and homeostasis, defense, and DNA replication and methylation) can be detected within 30 min. Furthermore, they suggest root to shoot signaling initiates early iron stress responses representing a novel paradigm for crop stress adaptations.}, }
@article {pmid32424149, year = {2020}, author = {Cheung, SM and Husain, E and Masannat, Y and Miller, ID and Wahle, K and Heys, SD and He, J}, title = {Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy.}, journal = {British journal of cancer}, volume = {123}, number = {2}, pages = {261-267}, pmid = {32424149}, issn = {1532-1827}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Female ; Glycolysis/genetics ; Humans ; Lactate Dehydrogenase 5/genetics/metabolism ; Lactic Acid/isolation &amp; purification/*metabolism ; Magnetic Resonance Spectroscopy ; Middle Aged ; *Prognosis ; Receptors, Estrogen/genetics/*metabolism ; }, abstract = {BACKGROUND: Precision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically.<br><br>METHODS: Thirty female patients (age 39-78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically.<br><br>RESULTS: There was a significantly higher lactate concentration (t&#x2009;=&#x2009;2.2224, p&#x2009;=&#x2009;0.0349) in grade III (7.7&#x2009;&#xb1;&#x2009;2.9&#x2009;mM) than in grade II (5.5&#x2009;&#xb1;&#x2009;2.4&#x2009;mM). Lactate concentration was correlated with NPI (&#x3c1;&#x2009;=&#x2009;0.3618, p&#x2009;=&#x2009;0.0495), but not with Ki-67 (&#x3c1;&#x2009;=&#x2009;0.3041, p&#x2009;=&#x2009;0.1023) or tumour size (r&#x2009;=&#x2009;0.1716, p&#x2009;=&#x2009;0.3645). Lactate concentration was negatively correlated with LDH-A (&#x3c1;&#x2009;=&#x2009;-0.3734, p&#x2009;=&#x2009;0.0421).<br><br>CONCLUSION: Our results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.}, }
@article {pmid32423910, year = {2020}, author = {O'Connor, P and Bhadbhade, P and Khan, Q and Williamson, S}, title = {Acral vascular syndrome during an immune checkpoint inhibitor.}, journal = {BMJ case reports}, volume = {13}, number = {5}, pages = {}, pmid = {32423910}, issn = {1757-790X}, mesh = {Black or African American ; Diagnosis, Differential ; Female ; Fingers/blood supply/pathology ; Gangrene/chemically induced/*diagnostic imaging/*pathology/surgery ; Humans ; Immune Checkpoint Inhibitors/*adverse effects ; Middle Aged ; Raynaud Disease/chemically induced/*diagnostic imaging/*pathology/surgery ; Thrombosis ; Vasculitis ; }, abstract = {Immune checkpoint inhibitors, including antiprogrammed death cell protein 1 (anti-PD-1) and anti cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), have been associated with a range of autoimmune-related side effects since their introduction in cancer treatment. Small vessel digital necrosis, referred to as the acral vascular syndrome, is a rare but serious complication that can result in loss of digits. Here we present a case report of acral vascular syndrome and review possible aetiologies. A 45- year-old woman with invasive ductal carcinoma of the left breast presented to the emergency department during neoadjuvant treatment with carboplatin, docetaxel and pembrolizumab with complaints of severe pain in her right third digit. She had physical findings consistent with ischaemic necrosis and gangrene of the distal phalanx. Angiography demonstrated Raynaud's phenomenon in the distal portion of the digits. Laboratory testing showed a weakly positive RNA polymerase III antibody level. Her case resulted in surgical amputation of her affected digit after partial resolution of symptoms with prednisone, vasodilators and antibiotics.}, }
@article {pmid32416533, year = {2020}, author = {Syed, AP and Greulich, F and Ansari, SA and Uhlenhaut, NH}, title = {Anti-inflammatory glucocorticoid action: genomic insights and emerging concepts.}, journal = {Current opinion in pharmacology}, volume = {53}, number = {}, pages = {35-44}, doi = {10.1016/j.coph.2020.03.003}, pmid = {32416533}, issn = {1471-4973}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Genomics ; Glucocorticoids/*pharmacology ; Humans ; RNA, Untranslated ; Receptors, Glucocorticoid/genetics ; Transcription, Genetic ; }, abstract = {Glucocorticoids (GCs) are widely used immunomodulators. They regulate gene expression by binding and activating the Glucocorticoid Receptor (GR), but underlying transcriptional mechanisms remain enigmatic. This review summarizes recent findings identifyingspecific GR-bound DNA sequences whose configuration may affect transcriptional output. Additional factors affecting GR's anti-inflammatory actions, including different chromatin states such as DNAse hypersensitive regions and histone marks will be discussed, together with the relevant transcriptional co-regulators and promoter/enhancer features. Furthermore, the involvement of non-coding RNAs such as lncRNAs, miRNAs and eRNAs adds another level of regulation to the GR's transcriptional activity. Characterizing and understanding these multiple mechanisms will be crucial for developing more targeted immunomodulatory therapies with reduced adverse effects such as obesity, diabetes and osteoporosis.}, }
@article {pmid32408395, year = {2020}, author = {Solagna, F and Nogara, L and Dyar, KA and Greulich, F and Mir, AA and Türk, C and Bock, T and Geremia, A and Baraldo, M and Sartori, R and Farup, J and Uhlenhaut, H and Vissing, K and Krüger, M and Blaauw, B}, title = {Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling.}, journal = {Acta physiologica (Oxford, England)}, volume = {230}, number = {1}, pages = {e13496}, pmid = {32408395}, issn = {1748-1716}, mesh = {Animals ; Chromatin/*chemistry ; Exercise ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*metabolism ; *Physical Conditioning, Animal ; Protein Biosynthesis ; *Serum Response Factor/genetics/metabolism ; *Signal Transduction ; Transcription Factors/*metabolism ; }, abstract = {AIM: Resistance exercise increases muscle mass over time. However, the early signalling events leading to muscle growth are not yet well-defined. Here, we aim to identify new signalling pathways important for muscle remodelling after exercise.<br><br>METHODS: We performed a phosphoproteomics screen after a single bout of exercise in mice. As an exercise model we used unilateral electrical stimulation in vivo and treadmill running. We analysed muscle biopsies from human subjects to verify if our findings in murine muscle also translate to exercise in humans.<br><br>RESULTS: We identified a new phosphorylation site on Myocardin-Related Transcription Factor B (MRTF-B), a co-activator of serum response factor (SRF). Phosphorylation of MRTF-B is required for its nuclear translocation after exercise and is accompanied by the transcription of the SRF target gene Fos. In addition, high-intensity exercise also remodels chromatin at specific SRF target gene loci through the phosphorylation of histone 3 on serine 10 in myonuclei of both mice and humans. Ablation of the MAP kinase member MSK1/2 is sufficient to prevent this histone phosphorylation, reduce induction of SRF-target genes, and prevent increases in protein synthesis after exercise.<br><br>CONCLUSION: Our results identify a new exercise signalling fingerprint in vivo, instrumental for exercise-induced protein synthesis and potentially muscle growth.}, }
@article {pmid32408270, year = {2020}, author = {Pedro, J and Cunha, FM and Neto, V and Hespanhol, V and Martins, DF and Guimarães, S and Varela, A and Carvalho, D}, title = {Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?.}, journal = {Endocrinology, diabetes &amp; metabolism case reports}, volume = {2020}, number = {}, pages = {}, pmid = {32408270}, issn = {2052-0573}, abstract = {SUMMARY: We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up.<br><br>LEARNING POINTS: The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.}, }
@article {pmid32404955, year = {2020}, author = {Tille, JC and Vieira, AF and Saint-Martin, C and Djerroudi, L and Furhmann, L and Bidard, FC and Kirova, Y and Tardivon, A and Reyal, F and Carton, M and Vincent-Salomon, A}, title = {Tumor-infiltrating lymphocytes are associated with poor prognosis in invasive lobular breast carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {11}, pages = {2198-2207}, pmid = {32404955}, issn = {1530-0285}, mesh = {Age Factors ; Breast Neoplasms/immunology/metabolism/mortality/*pathology ; Carcinoma, Lobular/immunology/metabolism/mortality/*pathology ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology/*pathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {The prognostic impact of tumor-infiltrating lymphocytes (TILs) within invasive lobular carcinoma (ILC) remains to be better characterized. In estrogen receptor (ER)-negative invasive ductal carcinomas of no special type (IDC-NST), TILs are associated with good prognosis. The aim of this study was to examine TILs in ILC, with particular focus on prognostic and clinicopathologic features. A cohort comprising 459 consecutive ILCs diagnosed in a single institution from 2005 to 2008 met the eligibility criteria for this study. The percentage of tumor area occupied by TILs was quantified by two breast pathologists and categorized into three groups: no TILs, ≤5%, >5%. Clinicopathologic features were tested by Fisher's exact tests or Chi[2] tests. Overall survival (OS) and invasive disease-free survival (iDFS) were estimated by Kaplan-Meier and Cox proportional hazard statistics. There were 239 TIL-negative cases, 185 cases with ≤5% TILs, and 35 cases with >5% TILs. TILs were associated with younger age, larger tumors, lymph node involvement, poor Nottingham prognostic index, HER2 amplification, multinucleation, and prominent nucleoli (p < 0.05). Poor OS was significantly associated with increasing TILs in the univariate Cox proportional hazards model (p < 0.001) and Kaplan-Meier estimator (p < 0.05, log-rank test). Similar results were observed for iDFS (p = 0.004 for Cox univariate and p = 0.005 for log-rank test). Notably, TILs can identify a subset of ILC patients with poor OS independently of molecular subtype and lymph node metastases (multivariate Cox, p < 0.001, OS hazard ratio (HR) = 4.38 and HR = 6.15, for ≤5% and >5% TILs, respectively, vs. absence of TILs). Prominent nucleoli was the only nuclear feature associated with poor OS (p = 0.05) and iDFS (p = 0.05) in univariate Cox survival analysis. TILs represent a promising new morphologic biomarker associated with poor outcome of ILC, in contrast with that observed in ER-negative IDC-NST.}, }
@article {pmid32381867, year = {2020}, author = {Tamaoki, M and Nio, Y and Tamaoki, M and Sakamoto, M and Uesugi, K and Sakamoto, T and Imai, S and Maruyama, R}, title = {[Radiation-Associated Angiosarcoma That Developed in the Irradiated Residual Breast after Breast-Conserving Surgery for Breast Cancer-A Case Report and Review of the Literature].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {47}, number = {1}, pages = {77-81}, pmid = {32381867}, issn = {0385-0684}, mesh = {Aged ; *Breast Neoplasms/radiotherapy ; Female ; *Hemangiosarcoma/etiology ; Humans ; Japan ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; *Neoplasms, Radiation-Induced ; *Skin Neoplasms ; }, abstract = {We report a radiation-associated angiosarcoma(RAAS)of the breast, which is a rare but important complication after breast-conserving surgery(BCS)and radiotherapy(RT)for breast cancer. A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. She noticed a bloody cutaneous bulla in the right breast 64 months later, and the skin lesions gradually expanded. She was brought to our clinic for the treatment of massive bleeding from the skin lesions. Ulcer biopsy revealed cutaneous AS(cells were CD31[+], CD34[+], VEGF[-], and VEGF-R[+]). She underwent mastectomy and latissimus dorsal flap surgery. She died of local recurrence and liver metastasis 13 months later. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature.}, }
@article {pmid32380439, year = {2020}, author = {Rodriguez-Ibarria, NG and Pinar, MB and García, L and Cabezón, MA and Lloret, M and Rey-Baltar, MD and Rdguez-Melcón, JI and Lara, PC}, title = {Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {52}, number = {}, pages = {45-49}, pmid = {32380439}, issn = {1532-3080}, mesh = {Aged ; Brachytherapy/*methods ; Breast Neoplasms/*radiotherapy ; Carcinoma, Ductal, Breast/*radiotherapy ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*radiotherapy ; Radiotherapy Dosage ; }, abstract = {Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008-December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3-1.9) and 98.3% (95% CI 97.3-99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.}, }
@article {pmid32371885, year = {2020}, author = {Schwarz, D and Hidmark, AS and Sturm, V and Fischer, M and Milford, D and Hausser, I and Sahm, F and Breckwoldt, MO and Agarwal, N and Kuner, R and Bendszus, M and Nawroth, PP and Heiland, S and Fleming, T}, title = {Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {7593}, pmid = {32371885}, issn = {2045-2322}, mesh = {Animals ; Biopsy ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 1/complications ; Diabetic Neuropathies/*diagnostic imaging/etiology/*pathology ; Disease Models, Animal ; Humans ; Image Processing, Computer-Assisted ; *Magnetic Resonance Imaging/methods/standards ; Mice ; Microscopy ; Microscopy, Electron ; }, abstract = {In light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves' fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.}, }
@article {pmid32365829, year = {2020}, author = {Cortes-Urrea, C and Bueno-Gutiérrez, F and Solarte, M and Guevara-Burbano, M and Tobar-Tosse, F and Vélez-Varela, PE and Bonilla, JC and Barreto, G and Velasco-Medina, J and Moreno, PA and Rivas, JL}, title = {Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations.}, journal = {Biomolecules}, volume = {10}, number = {5}, pages = {}, pmid = {32365829}, issn = {2218-273X}, support = {PI18/00591//Instituto de Salud Carlos III/International ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; *Exome ; Female ; Humans ; Middle Aged ; *Mutation ; Oncogenes ; }, abstract = {Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-β pathway.}, }
@article {pmid32362500, year = {2020}, author = {Dianatinasab, M and Rezaian, M and HaghighatNezad, E and Bagheri-Hosseinabadi, Z and Amanat, S and Rezaeian, S and Masoudi, A and Ghiasvand, R}, title = {Dietary Patterns and Risk of Invasive Ductal and Lobular Breast Carcinomas: A Systematic Review and Meta-analysis.}, journal = {Clinical breast cancer}, volume = {20}, number = {4}, pages = {e516-e528}, doi = {10.1016/j.clbc.2020.03.007}, pmid = {32362500}, issn = {1938-0666}, mesh = {Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diet Surveys/*statistics &amp; numerical data ; *Feeding Behavior ; Female ; Humans ; Risk Assessment/statistics &amp; numerical data ; Risk Factors ; }, abstract = {The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case-control studies (RR = 0.47; 95% CI, 0.39-0.55; I[2] = 85.1%; P < .001). However, the association was nonsignificant in cohort studies (RR = 0.98; 95% CI, 0.92-1.05; I[2] = 88.8%; P = .003). The pooled analysis also suggested a significant and direct association between the WD and the risk of IDC (RR = 1.36; 95% CI, 1.18-1.53; I[2] = 63.7%; P = .017). The risk of ILC for the highest compared to the lowest category of MD was highly protective (RR = 0.76; 95% CI, 0.64-0.87; I[2] = 89.2%; P < .001), and a marginally significant association was found between the WD and risk of ILC (RR = 1.45; 95% CI, 1.04-1.86), with no heterogeneity (I[2] = 0; P = .52). This meta-analysis provides supporting evidence for the association between MD decreased risk of IDC and ILC of the breast and the association between WD and increased risk of IDC and ILC. Further investigations are needed to better understand the reasons behind the etiologic mechanisms of how dietary patterns affect patients differently by common breast cancer subtypes, including IDC and ILC.}, }
@article {pmid32354932, year = {2020}, author = {Fujii, T and Tokuda, S and Nakazawa, Y and Kurozumi, S and Obayashi, S and Yajima, R and Shirabe, K}, title = {Relationship Between FDG Uptake and the Platelet/lymphocyte Ratio in Patients With Breast Invasive Ductal Cancer.}, journal = {In vivo (Athens, Greece)}, volume = {34}, number = {3}, pages = {1365-1369}, pmid = {32354932}, issn = {1791-7549}, mesh = {Aged ; Biomarkers, Tumor ; Breast Neoplasms/*diagnostic imaging/etiology/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Leukocyte Count ; *Lymphocyte Count ; Middle Aged ; Neutrophils ; *Platelet Count ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Tumor Microenvironment ; }, abstract = {BACKGROUND/AIM: We investigated the relationship between F18-fluorodeoxyglucose (FDG) uptake and the platelet/lymphocyte ratio (PLR), as both represent inflammation.<br><br>PATIENTS AND METHODS: We retrospectively analyzed the cases of 143 consecutive invasive ductal carcinoma patients who had undergone preoperative FDG-PET and surgery. We divided the patients into groups based on their maximum standardized uptake value (SUVmax) values: low (<2.5) and high (&#x2265;2.5) and based on their PLRs: low (<130) and high (&#x2265;130). We determined the relationships between the SUVmax or PLR and clinicopathological features.<br><br>RESULTS: Seventy-three patients (51.0%) had a high SUVmax in their primary tumor. There were significant associations between SUVmax and the PLR. A multivariate analysis revealed that high PLR, but not NLR, was independent factor associated with a high SUVmax. Seventy-four patients (51.7%) had a high PLR; The factors significantly associated with high PLR were large tumor size, presence of node metastasis, presence of vascular invasion, high NLR, and high SUVmax.<br><br>CONCLUSION: In breast cancer patients, the PLR is independently associated with the SUVmax, but not with recurrent disease. In breast cancer patients with a high SUVmax and/or PLR, these values may reflect the tumor microenvironment.}, }
@article {pmid32343605, year = {2021}, author = {Liu, CR and Meng, FH}, title = {DNASE1L2, as a Carcinogenic Marker, Affects the Phenotype of Breast Cancer Cells Via Regulating Epithelial-Mesenchymal Transition Process.}, journal = {Cancer biotherapy &amp; radiopharmaceuticals}, volume = {36}, number = {2}, pages = {180-188}, doi = {10.1089/cbr.2019.3504}, pmid = {32343605}, issn = {1557-8852}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Proliferation/physiology ; Deoxyribonuclease I/*metabolism ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Middle Aged ; Phenotype ; Prognosis ; Transfection ; }, abstract = {Purpose: The authors explore the role of DNASE1L2 in breast cancer (BC) and its affect on the cell phenotype. Methods: Breast invasive ductal carcinoma RNA-Seq data set was downloaded from The Cancer Genome Atlas database for analyzing DNASE1L2 levels. Overall survival curve was plotted by Kaplan-Meier methods. The correlations between DNASE1L2 expression and clinical characteristics were analyzed by chi-square tests. Cox regression models were implemented for analyzing the potential prognosticators of BC. Small interference RNA-DNASE1L2 and pcDNA3.1-DNASE1L2 were transfected into BC cells to silence and overexpress DNASE1L2, respectively. Relative mRNA and protein levels were determined by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Cell counting Kit-8, clone formation, and Transwell assays were employed to measure the proliferative, invasive, and migratory abilities. Results: Bioinformatics analysis showed that the levels of DNASE1L2 were found to be elevated in BC tissues, which was further proved by qRT-PCR tests. Besides, high expression of DNASE1L2 was dramatically led to a poor overall survival. Furthermore, DNASE1L2 expression was remarkably associated with age and pathologic-stage. Silencing DNASE1L2 showed an inhibitory effect on the proliferation, invasion, and migration of MCF7 cells, whereas overexpression of DNASE1L2 in BT549 cells presented the opposite results. Mechanistically, downregulation of DNASE1L2 could significantly enhance the levels of E-cadherin, as well as suppress the levels of Vimentin, N-cadherin and Snail, whereas upregulation of DNASE1L2 showed the reverse outcomes. Conclusion: This study for the first time demonstrated that DNASE1L2 was upregulated in BC cells, and acted as an oncogene to affect the phenotype of BC cells by modulating the epithelial-mesenchymal transition process, which suggested that DNASE1L2 might be considered as a useful biomarker for BC therapeutics.}, }
@article {pmid32338774, year = {2020}, author = {Kumar, V and Agrawal, R and Pandey, A and Kopf, S and Hoeffgen, M and Kaymak, S and Bandapalli, OR and Gorbunova, V and Seluanov, A and Mall, MA and Herzig, S and Nawroth, PP}, title = {Compromised DNA repair is responsible for diabetes-associated fibrosis.}, journal = {The EMBO journal}, volume = {39}, number = {11}, pages = {e103477}, pmid = {32338774}, issn = {1460-2075}, support = {R37 AG046320/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; //Helmholtz Cross Program Topic Metabolic Dysfunction/ ; //Foundation for Diabetes Research/ ; GRK 1874-DIAMICOM//Deutsche Forschungsgemeinschaft (DFG)/ ; R01 AG027237/AG/NIA NIH HHS/United States ; P01 AG051449/AG/NIA NIH HHS/United States ; SFB1118//Deutsche Forschungsgemeinschaft (DFG)/ ; }, mesh = {A549 Cells ; *DNA End-Joining Repair ; Diabetes Mellitus, Type 1/genetics/*metabolism/pathology ; Diabetes Mellitus, Type 2/genetics/*metabolism/pathology ; Fibrosis ; HEK293 Cells ; Humans ; }, abstract = {Diabetes-associated organ fibrosis, marked by elevated cellular senescence, is a growing health concern. Intriguingly, the mechanism underlying this association remained unknown. Moreover, insulin alone can neither reverse organ fibrosis nor the associated secretory phenotype, favoring the exciting notion that thus far unknown mechanisms must be operative. Here, we show that experimental type 1 and type 2 diabetes impairs DNA repair, leading to senescence, inflammatory phenotypes, and ultimately fibrosis. Carbohydrates were found to trigger this cascade by decreasing the NAD[+] /NADH ratio and NHEJ-repair in vitro and in diabetes mouse models. Restoring DNA repair by nuclear over-expression of phosphomimetic RAGE reduces DNA damage, inflammation, and fibrosis, thereby restoring organ function. Our study provides a novel conceptual framework for understanding diabetic fibrosis on the basis of persistent DNA damage signaling and points to unprecedented approaches to restore DNA repair capacity for resolution of fibrosis in patients with diabetes.}, }
@article {pmid32317515, year = {2020}, author = {Pyla, RD and Potekar, RM and Patil, VS and Reddy, AK and Sathyashree, KV}, title = {Quantitative mast cell analysis and hormone receptor study (ER, PR and HER2/neu) in invasive carcinoma of breast.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {2}, pages = {200-204}, doi = {10.4103/IJPM.IJPM_155_19}, pmid = {32317515}, issn = {0974-5130}, mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/*pathology ; Female ; Humans ; Immunohistochemistry ; Mast Cells/immunology/*pathology ; Middle Aged ; Prospective Studies ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tumor Microenvironment/*immunology ; }, abstract = {CONTEXT: Breast cancer constitutes nearly one third of cancers among women. Immune responses caused by neoplastic cells lead to the accumulation of inflammatory cells like mast cells (MCs), macrophages, lymphocytes, and plasma cells around the tumor tissue forming the tumor microenvironment.<br><br>AIM: The study aims at quantifying the role of MCs in different grades of invasive carcinoma of breast with respect to estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2/neu).<br><br>MATERIALS AND METHODS: This study included 60 cases of invasive carcinoma of breast. Toluidine blue staining was used for quantitative MC analysis and correlated with immunohistochemistry analysis for hormonal markers' positivity-ER, PR and HER2/neu.<br><br>RESULTS: The mean age was 52 years (range: 25-75 years). The average number of MCs in Grade I, II, and III were 24.05, 18.4, and 7.9, respectively, with a significant P value. ER, PR, and HER2/neu positivity was found in 60%, 55%, and 32% of the cases, respectively. ER positivity with mean MC count of 23.55 was found in 36 cases, and 33 cases were positive for PR with a mean MC count of 24.18 and a significant P value. HER2 positive cases were 28 with a mean MC count of 20.82.<br><br>CONCLUSION: The presence of MCs in breast cancer is inversely proportional to the grade of tumor, i.e., a maximum number of MCs were seen in low grade tumors. In addition, there is a positive correlation between ER and PR receptor positivity with the presence of MCs in the stroma of breast cancer.}, }
@article {pmid32310154, year = {2020}, author = {Suhani, S and Kazi, M and Parshad, R and Seenu, V and Verma, E and Mathur, S and Gupta, SD and Haresh, KP}, title = {An audit of over 1000 breast cancer patients from a tertiary care center of Northern India.}, journal = {Breast disease}, volume = {39}, number = {2}, pages = {91-99}, doi = {10.3233/BD-190435}, pmid = {32310154}, issn = {1558-1551}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/physiopathology ; Breast Neoplasms, Male/*epidemiology/physiopathology ; Female ; Humans ; India/epidemiology ; Male ; *Medical Audit ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers/*statistics &amp; numerical data ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the commonest cancer among women. India along with United States and China collectively account for one third of the global burden. The present study reports the clinico-epidemiological data of our patient population. This may help in better understanding of the disease in our population and also form ground for conducting further breast cancer research in India.<br><br>METHODS: The study was conducted at an apex teaching and medical research institution in India from September 2013 to April 2015 as a retrospective review of prospectively collected data of breast cancer patients. The socio-demographic characteristics, reproductive risk factors, clinical presentation, TNM staging and histopathological characteristics for breast cancer in these patients were recorded. The data was recorded on an Xcel spreadsheet and analyzed using IBM SPSS 21.<br><br>RESULTS: The study comprised of 1310 breast cancer patients with males comprising 1.1%. The median age of presentation was 47 years, and menarche 14 years. Most of women were married and multiparous. More than half of the women were postmenopausal at presentation. All patients were symptomatic at presentation with median duration of symptom of 5 months and median lump size of 5&#xa0;cm. Most common stage at presentation was Stage II and most common histopathology was Invasive ductal carcinoma. 61.9% tumors were hormone receptor positive. Triple negative cancers formed one third of all tumors.<br><br>CONCLUSION: Breast cancer in the Indian scenario is a disease of younger woman who lack the characteristic reproductive and demographic risk factors. This calls for a need to study the clinico-demographic risk factors and characteristics of our own population.}, }
@article {pmid32299754, year = {2020}, author = {El Abbass, KA and Abdellateif, MS and Gawish, AM and Zekri, AN and Malash, I and Bahnassy, AA}, title = {The Role of Breast Cancer Stem Cells and Some Related Molecular Biomarkers in Metastatic and Nonmetastatic Breast Cancer.}, journal = {Clinical breast cancer}, volume = {20}, number = {4}, pages = {e373-e384}, doi = {10.1016/j.clbc.2019.11.008}, pmid = {32299754}, issn = {1938-0666}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast/*pathology/surgery ; Breast Neoplasms/diagnosis/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*genetics/secondary/therapy ; Case-Control Studies ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Healthy Volunteers ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplastic Stem Cells/*pathology ; Primary Cell Culture ; Retrospective Studies ; Signal Transduction/genetics ; Tumor Cells, Cultured ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer stem cells (BCSCs) play important role(s) in the development and progression of invasive duct carcinoma (IDC). We assessed the role of BCSC marker expression and the number of mammospheres in cultures of breast cancer (BC) tissues and correlated these data to relevant clinicopathologic features of the patients and overall survival (OS).<br><br>METHODS: Fresh tumor tissue samples were collected from 44 Egyptian female patients with IDC of the breast and 25 healthy women undergoing reduction mammoplasty as a control. The mammosphere number and the RNA expression levels of some cancer stem cell-related genes (PTEN, PI3K, AKT, Wnt, and &#x3b2;-catenin) were assessed by reverse-transcriptase polymerase chain reaction at different stages of BCSC differentiation compared with control samples.<br><br>RESULTS: The number of CD44[+]CD24[-/low] cells associated significantly at the end of culture with the expression level of Wnt, &#x3b2;-catenin, and distant metastasis (P&#xa0;< .001, P&#xa0;= .015 and P&#xa0;= .003, respectively). There was significant association between the mammosphere number and CD44[+]CD24[-/low] cells as well as AKT expression (P&#xa0;= .040 and .021, respectively). PTEN messenger RNA expressed significantly in BC (P&#xa0;< .05). Wnt-RNA expression associated significantly with high tumor stage, positive lymph node status, Her2-neu overexpression, and metastasis (P&#xa0;= .009, .012, .026, and .001, respectively), whereas OS associated significantly with distant metastasis, Wnt, and PTEN expressions (P&#xa0;< .001, P&#xa0;= .001, P&#xa0;= .014, respectively).<br><br>CONCLUSION: BCSCs and their related genes (PTEN, PI3K, AKT, Wnt, and &#x3b2;-catenin) play important roles in the development and progression of BC and they can be used as potential prognostic and predictive biomarkers for patients with BC or as target therapy.}, }
@article {pmid32279596, year = {2020}, author = {Duman, B and Kuşman, A and Çolak, B and Şenler, F&#xc7; and Kumbasar, H}, title = {Tamoxifen-induced acute mania: A case report.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {26}, number = {8}, pages = {2025-2027}, doi = {10.1177/1078155220915959}, pmid = {32279596}, issn = {1477-092X}, mesh = {Acute Disease ; Antineoplastic Agents, Hormonal/*adverse effects ; Breast Neoplasms/*drug therapy ; Female ; Humans ; Mania/*chemically induced ; Middle Aged ; Tamoxifen/*adverse effects ; }, abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer, osteoporosis, and post-menopausal symptoms. Also, tamoxifen is currently under investigation for its anti-manic properties. In this article, we report a case who developed manic episode following the initiation of tamoxifen and remitted with discontinuation of the medication.<br><br>CASE REPORT: A 58-year-old woman was diagnosed with breast cancer. Pathologic diagnosis was invasive ductal carcinoma. Following bilateral total mastectomy operation, trastuzumab was initiated with intervals of 21&#x2009;days. Five days before the fourth application of trastuzumab, tamoxifen was added. On the sixth day following the initiation of tamoxifen, manic symptoms were developed and she was diagnosed as acute mania.<br><br>MANAGEMENT AND OUTCOME: The oncology department suggested withdrawing tamoxifen due to a possible association between tamoxifen initiation and behavioral symptoms. Manic symptoms were rapidly (approximately 24&#x2009;h) improved following cessation of tamoxifen. Psychiatric evaluation on the fifth day following cessation of tamoxifen revealed no manic symptoms. An aromatase inhibitor-exemestane was initiated and she showed no side effects with this medication since then.<br><br>DISCUSSION: To our knowledge, this is the first case report of probable tamoxifen-induced mania. Our case report at least indicates that there were possibly some patients who were sensitive to the tamoxifen's nervous system effects, mainly to manic effects. In conclusion, clinicians should be aware of these rare behavioral adverse effects of tamoxifen.}, }
@article {pmid32272928, year = {2020}, author = {Sutham, K and Khuwuthyakorn, P and Thinnukool, O}, title = {Thailand medical mobile application for patients triage base on criteria based dispatch protocol.}, journal = {BMC medical informatics and decision making}, volume = {20}, number = {1}, pages = {66}, pmid = {32272928}, issn = {1472-6947}, mesh = {*Emergency Medical Services ; Humans ; *Mobile Applications ; Patients ; Reproducibility of Results ; Retrospective Studies ; Thailand ; Triage ; }, abstract = {BACKGROUND: Before patients are admitted into the emergency department, it is important to undertake a pre-hospital process, both in terms of treatment performance and a request for resources from an emergency unit. The existing system to triage patients in Thailand is not functioning to its full capacity in either the primary medical system or pre-hospital treatment with shortcomings in the areas of speed, features, and appropriate systems. There is a high possibility of issuing a false Initial Dispatch Code (IDC), which will cause the over or underutilisation of emergency resources, such as rescue teams, community hospitals and emergency medical volunteers.<br><br>METHODS: A usability system design, together with a reliability test, was applied to develop an application to optimise the pre-hospital process, specifically to sort patients, using an IDC to improve the request for emergency resources. The triage mobile application was developed on both iOS and Android operating systems to support patient triage based on Criteria Based Dispatch (CBD). The 25 main symptom categories covered by CBD were used to design and develop the application, and 12 emergency medical staff, including doctors and nurses, were asked to test the system in the aspects of triage protocol correction, triage reliability, usability and user satisfaction.<br><br>RESULTS: The results of testing the proposed triage application were compared with the time used to triage by experienced staff and it was found that, in non-trauma cases, it was faster and more effective to use the application for emergency operations and to correct the IDC code representation.<br><br>CONCLUSIONS: The triage application will be utilised to support the pre-hospital process and to classify patients' conditions before they are admitted to the Emergency Department (ED). The application is suitable for users who are not medical emergency staff. Patients with non-trauma symptoms may be a suitable group to use the application in terms of time used to identify IDC for their own symptoms. The use of the application can be beneficial for those who wish to self-identify their symptoms before requesting medical services.}, }
@article {pmid32269189, year = {2020}, author = {Lee, YH and Kwon, MJ and Park, JH and Jeong, SJ and Kim, TH and Jeong, HW and Lee, SH}, title = {Neurofibromatosis Type 1 with the Development of Pheochromocytoma and Breast Cancer.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {59}, number = {13}, pages = {1665-1669}, pmid = {32269189}, issn = {1349-7235}, mesh = {Adrenal Gland Neoplasms/*complications/surgery ; Adrenalectomy ; Adult ; Biopsy ; Breast Neoplasms/*complications/therapy ; Cafe-au-Lait Spots/pathology ; Female ; Humans ; Incidental Findings ; Neurofibromatosis 1/*complications ; Pheochromocytoma/*complications ; Skin Neoplasms/pathology ; }, abstract = {A 40-year-old woman presented with a left adrenal incidentaloma. Based on the presence of café-au-lait spots, cutaneous neurofibroma, and family history, she was diagnosed with neurofibromatosis type 1 (NF1). Adrenal incidentaloma screening showed an elevated normetanephrine level; the left adrenal mass showed the uptake of I-123 meta-iodobenzylguanidine. She underwent left adrenalectomy, and pheochromocytoma was diagnosed. One year later, the results of a biopsy of a palpable mass in the left breast suggested invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy followed by left breast-conserving surgery. We herein report a rare case of an NF1 patient who developed both pheochromocytoma and breast cancer.}, }
@article {pmid32266446, year = {2020}, author = {Zong, L and Mo, S and Yu, S and Zhou, Y and Zhang, M and Chen, J and Xiang, Y}, title = {Expression of the immune checkpoint VISTA in breast cancer.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {69}, number = {8}, pages = {1437-1446}, doi = {10.1007/s00262-020-02554-3}, pmid = {32266446}, issn = {1432-0851}, support = {81672648//National Natural Science Foundation of China/International ; 81971475//National Natural Science Foundation of China/International ; CAMS-2017-I2M-1-002//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; CAMS-2016-I2M-1-001//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; B7 Antigens/*metabolism ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/*metabolism/pathology ; Carcinoma, Ductal, Breast ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/*metabolism ; Survival Rate ; }, abstract = {V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint that is an emerging target for cancer immunotherapy. This study aimed to investigate the expression of VISTA and its association with clinicopathologic parameters as well as with the key immune markers including programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) in invasive ductal carcinoma (IDC) of the breast [corrected]. Immunohistochemistry was used to detect VISTA, PD-1, PD-L1, and CD8 in tissue microarrays from 919 patients with IDC (N = 341 in the exploratory cohort and = 578 in the validation cohort). VISTA was expressed on the immune cells of 29.1% (267/919) of the samples and on the tumor cells of 8.2% (75/919). VISTA was more frequently expressed in samples that were estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2-positive, poorly differentiated, human epidermal growth factor receptor 2-enriched, and consisting of basal-like tumors. VISTA on immune cells correlated with PD-1, PD-L1, stromal CD8, and tumor-infiltrating lymphocyte expression and was an independent prognostic factor for improved relapse-free and disease-specific survival in patients with estrogen receptor-negative, progesterone receptor-negative, and basal-like IDC. These findings support therapeutic strategies that modulate VISTA expression, perhaps in combination with PD-1/PD-L1 blockade, in human breast cancer immunotherapy.}, }
@article {pmid32246378, year = {2020}, author = {Le, AN and Harton, J and Desai, H and Powers, J and Zelley, K and Bradbury, AR and Nathanson, KL and Shah, PD and Doucette, A and Freedman, GM and Gabriel, P and Domchek, SM and MacFarland, SP and Maxwell, KN}, title = {Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome.}, journal = {Breast cancer research and treatment}, volume = {181}, number = {1}, pages = {181-188}, pmid = {32246378}, issn = {1573-7217}, support = {K08 CA215312/CA/NCI NIH HHS/United States ; K08CA21531//National Cancer Institute (US)/ ; ITMAT MHB//University of Pennsylvania/ ; 1017184//Burroughs Wellcome Fund/ ; }, mesh = {Adolescent ; Adult ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/pathology/*radiotherapy ; Carcinoma, Lobular/pathology/*radiotherapy ; Female ; Follow-Up Studies ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/*complications ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasms, Radiation-Induced/*etiology/pathology ; Prognosis ; Radiotherapy, Adjuvant/*adverse effects ; Retrospective Studies ; Survival Rate ; Tumor Suppressor Protein p53/genetics ; Young Adult ; }, abstract = {PURPOSE: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy.<br><br>METHODS: A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses.<br><br>RESULTS: We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+&#x2009;(58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the&#xa0;control cohort.<br><br>CONCLUSIONS: We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients.}, }
@article {pmid32239352, year = {2020}, author = {Maggi, G and D'Iorio, A and Di Meglio, D and Vinciguerra, A and Amboni, M and Vitale, C and Santangelo, G}, title = {The role of the motor subtypes on the relationship between anxiety and cognitive dysfunctions in Parkinson's disease.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {127}, number = {6}, pages = {893-898}, doi = {10.1007/s00702-020-02179-x}, pmid = {32239352}, issn = {1435-1463}, mesh = {Anxiety/etiology ; *Cognitive Dysfunction/etiology ; *Gait Disorders, Neurologic ; Humans ; Neuropsychological Tests ; *Parkinson Disease/complications ; }, abstract = {Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD). Until now, anxiety has been consistently related to cognitive deficits and severity of motor symptoms, whereas the association between anxiety and motor subtypes (TD-PD, tremor dominant and PIGD-PD, postural instability/gait disturbances dominant) revealed contrasting results. The present study aims to investigate the relationship between PD motor subtypes and anxiety and to explore whether the relationship between anxiety and cognitive deficits occurs in a specific PD motor subtype. Consecutive PD outpatients were recruited and divided into TD-PD and PIGD-PD groups according to Jankovic et al.'s criteria. All participants underwent a neuropsychological battery to evaluate anxiety, apathy, the global cognitive functioning, memory abilities, executive and visuo-constructional functions. Thirty-six patients with TD-PD and 35 patients with PIGD-PD were enrolled. The two groups did not differ on demographical and clinical variables. As for the severity of anxiety, no significant difference between the two groups was found. Regression analysis revealed that higher anxiety score was associated with poorer performance on constructional visuospatial test in both TD-PD and PIGD-PD. Clinical variables were not associated with anxiety in the two groups. Our findings indicated that the severity of anxiety was not associated with any PD motor subtypes. Moreover, regression analysis revealed that impaired visuo-constructional abilities are related to anxiety independently of PD motor subtypes. Since altered fronto-parietal network might be one of the pathogenetic mechanisms underpinning anxiety and constructional visuospatial deficits, the treatment of cognitive dysfunctions might reduce anxious symptoms.}, }
@article {pmid32236595, year = {2020}, author = {Gao, X and Bao, H and Liu, L and Zhu, W and Zhang, L and Yue, L}, title = {Systematic analysis of lysine acetylome and succinylome reveals the correlation between modification of H2A.X complexes and DNA damage response in breast cancer.}, journal = {Oncology reports}, volume = {43}, number = {6}, pages = {1819-1830}, pmid = {32236595}, issn = {1791-2431}, mesh = {Acetylation ; Adult ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Case-Control Studies ; Cell Line, Tumor ; Cell Survival ; *DNA Damage ; Female ; Gene Expression Regulation, Neoplastic ; Histones/*metabolism ; Humans ; Lysine/*chemistry ; MCF-7 Cells ; Middle Aged ; Nuclear Proteins/metabolism ; Nucleophosmin ; Proteomics/*methods ; Succinic Acid/chemistry ; Up-Regulation ; }, abstract = {Abnormal protein acetylation and succinylation in lysine residues can cause the initiation and development of numerous different types of tumors. However, to the best of our knowledge, there is currently a lack of systematic investigation in breast cancer. Using proteomic techniques, the present study systematically investigated the two modifications of all proteins in invasive ductal carcinoma tissues to identify potential targets. The results revealed significantly higher modification levels for the majority of proteins in breast cancer tissue when compared with para‑carcinomous normal tissue. The bioinformatic analysis demonstrated that either highly acetylated or succinylated proteins were significantly enriched in histone H2A.X (H2A.X) complexes and nucleophosmin (NPM1) may be the key member among them. The results of further analyses revealed that H2A.X complexes were associated with DNA damage response (DDR), and the proteomic results for protein quantification provided further evidence for the abnormal DDR condition in breast cancer tissues. Later, the western blotting results validated the high acetylation and succinylation levels of the majority of proteins, including the modification of NPM1 and its correlation with cell viability. Finally, the upregulation of H2A.X in breast cancer tissues further demonstrated the association between H2A.X complex modification and DDR in breast cancer. Overall, the present study systematically investigated the protein acetylation and succinylation in breast cancer and provided evidence to support H2A.X complexes as potential targets. These results broaden the horizon for breast cancer investigation and link it with epigenetics.}, }
@article {pmid32220886, year = {2020}, author = {Pareja, F and Brown, DN and Lee, JY and Da Cruz Paula, A and Selenica, P and Bi, R and Geyer, FC and Gazzo, A and da Silva, EM and Vahdatinia, M and Stylianou, AA and Ferrando, L and Wen, HY and Hicks, JB and Weigelt, B and Reis-Filho, JS}, title = {Whole-Exome Sequencing Analysis of the Progression from Non-Low-Grade Ductal Carcinoma In Situ to Invasive Ductal Carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {14}, pages = {3682-3693}, pmid = {32220886}, issn = {1557-3265}, support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Breast/pathology ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; DNA Copy Number Variations ; DNA Mutational Analysis ; Disease Progression ; Female ; *Genetic Heterogeneity ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/diagnosis/*genetics/pathology ; Exome Sequencing ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Here, we sought to investigate the level of intralesion genetic heterogeneity in DCIS and the patterns of clonal architecture changes in the progression from DCIS to invasive disease.<br><br>EXPERIMENTAL DESIGN: Synchronous DCIS (n = 27) and invasive ductal carcinomas of no special type (IDC-NSTs; n = 26) from 25 patients, and pure DCIS (n = 7) from 7 patients were microdissected separately and subjected to high-depth whole-exome (n = 56) or massively parallel sequencing targeting &#x2265;410 key cancer-related genes (n = 4). Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic analyses were defined using validated computational methods.<br><br>RESULTS: DCIS revealed genetic alterations similar to those of synchronously diagnosed IDC-NSTs and of non-related IDC-NSTs from The Cancer Genome Atlas (TCGA), whereas pure DCIS lacked PIK3CA mutations. Clonal decomposition and phylogenetic analyses based on somatic mutations and copy number alterations revealed that the mechanisms of progression of DCIS to invasive carcinoma are diverse, and that clonal selection might have constituted the mechanism of progression from DCIS to invasive disease in 28% (7/25) of patients. DCIS displaying a pattern of clonal selection in the progression to invasive cancer harbored higher levels of intralesion genetic heterogeneity than DCIS where no clonal selection was observed.<br><br>CONCLUSIONS: Intralesion genetic heterogeneity is a common feature in DCIS synchronously diagnosed with IDC-NST. DCIS is a nonobligate precursor of IDC-NST, whose mechanisms of progression to invasive breast cancer are diverse and vary from case to case.}, }
@article {pmid32212794, year = {2020}, author = {Rasmy, A and Sorour, Y}, title = {Effect of Obesity on Neoadjuvant Systemic Therapy Outcomes in Patients with Early Breast Cancer: A Retrospective Institutional Study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {3}, pages = {683-691}, pmid = {32212794}, issn = {2476-762X}, mesh = {Adult ; Aged ; Body Mass Index ; Breast Neoplasms/complications/*therapy ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Obesity/*complications ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Obesity and overweight are usually considered as poor prognostic factors in early breast cancer. Body mass index (BMI) is a significant predictive factor for lower pathologic complete response (pCR) rates after neo-adjuvant systemic therapy (NST). The relationship between obesity and breast cancer prognosis varies according to patient and tumor characteristics such as menopausal status and tumor subtype, respectively.<br><br>PATIENTS AND METHODS: Between March 2010 and October 2013, 80 patients with early breast cancer who had received standard NST from KFSH Saudi Arabia were included in this study. For statistical analysis, the study participants were categorized into two groups based on their BMI, as normal (BMI < 25 kg/m2) and obese groups (BMI &#x2265; 25 kg/m2). pCR was defined as non-invasive cancer in the breast/axillary tissue.<br><br>RESULTS: The median age of our patients was 48 (range, 38-68) years. Invasive ductal carcinoma (IDC) subtype was identified in 93.8% of the cases. Additionally, 26 (32.5%) and 33 (41.25%) patients were diagnosed with stage II and stage IIIA breast cancer, respectively. Lymphovascular invasion was detected in 32.5%, whereas intermediate and high-grade malignancy were found in 61.25% and 32.5% of the patients, respectively. Forty-four patients (55%) were obese. pCR was achieved in 56 patients (70%), and the comparison between patients with and without pCR revealed that those in the former group had significantly lower tumor grades. Significantly, lower relapse and mortality rates were distinguished in patients who achieved pCR than in those who did not. Additionally, comparison between normal and obese patients revealed that a high number of patients in both groups were post-menopausal (p = 0.001). However, survival analysis indicated the absence of significant differences in disease-free survival between the two groups based on BMI (p = 0.19). Conversely, patients with normal BMI had significantly better overall survival than obese patients (p = 0.029), with a higher mortality rate noted in the obese group (16.7% vs 2.3%, p = 0.037).<br><br>CONCLUSIONS: In the present study, 58.3% of patients that failed to achieve pCR had BMI above the normal level; they moreover had higher relapse rates and lower survival compared with normal BMI patients. This finding needs to be verified through further prospective studies to determine if BMI is a risk factor for breast cancer.}, }
@article {pmid32209879, year = {2020}, author = {Liu, Q and Zhang, J and Kulkarni, HR and Baum, RP}, title = {177Lu-DOTATOC Peptide Receptor Radionuclide Therapy in a Patient With Neuroendocrine Breast Carcinoma and Breast Invasive Ductal Carcinoma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {5}, pages = {e232-e235}, doi = {10.1097/RLU.0000000000003005}, pmid = {32209879}, issn = {1536-0229}, mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/pathology/*radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Neuroendocrine Tumors/diagnostic imaging/metabolism/pathology/*radiotherapy ; Octreotide/*analogs &amp; derivatives/therapeutic use ; Positron Emission Tomography Computed Tomography ; Receptors, Somatostatin/*metabolism ; Treatment Outcome ; }, abstract = {Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.}, }
@article {pmid32202536, year = {2020}, author = {Szentirmai, E and Giannico, GA}, title = {Intraductal carcinoma of the prostate.}, journal = {Pathologica}, volume = {112}, number = {1}, pages = {17-24}, pmid = {32202536}, issn = {1591-951X}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Prostatectomy/trends ; Prostatic Neoplasms/*diagnosis/*genetics/therapy ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a diagnostic entity characterized by architecturally or cytologically malignant-appearing prostatic glandular epithelium confined to prostatic ducts. Despite its apparent in situ nature, this lesion is associated with aggressive prostatic adenocarcinoma and is a predictor for poor prognosis when identified on biopsy or radical prostatectomy. This review discusses diagnosis, clinical features, histogenesis, and management of IDC-P, as well as current research and controversies surrounding this entity.}, }
@article {pmid32190711, year = {2020}, author = {Lee, RA and Vo, DT and Zurko, JC and Griffin, RL and Rodriguez, JM and Camins, BC}, title = {Infectious Diseases Consultation Is Associated With Decreased Mortality in Enterococcal Bloodstream Infections.}, journal = {Open forum infectious diseases}, volume = {7}, number = {3}, pages = {ofaa064}, pmid = {32190711}, issn = {2328-8957}, abstract = {BACKGROUND: Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown.<br><br>METHODS: This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients&#x2005;>18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture.<br><br>RESULTS: Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P&#x2005;<&#x2005;.001), echocardiography (79% vs 45%; P&#x2005;<&#x2005;.001), surgical intervention (20% vs 7%; P&#x2005;=&#x2005;0.01), and have appropriate antibiotic duration (90% vs 46%; P&#x2005;<&#x2005;.001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P&#x2005;<&#x2005;.007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76).<br><br>CONCLUSIONS: Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia.}, }
@article {pmid32161717, year = {2020}, author = {Guo, T and Chen, Z and Xu, J and Zhang, Y}, title = {Change of Pathological Type to Metaplastic Squamous Cell Carcinoma of the Breast During Disease Recurrence: Case Report and Literature Review.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {32}, pmid = {32161717}, issn = {2234-943X}, abstract = {Background: Metaplastic squamous cell carcinoma (SCC) of the breast is a rare and heterogeneous group of primary breast malignancies. The etiology, pathogenesis, and proper treatment for this kind rare breast cancer are still unclear. Case presentation: We reported a case of a 55-year-old woman with a palpable lump in the inner quadrant of the right breast. She underwent a right breast mass resection and sentinel lymph node biopsy, which revealed that the tumor was an invasive ductal carcinoma, followed by four cycles of doxorubicin plus cyclophosphamide and four cycles of docetaxel as adjuvant chemotherapy, and then simultaneous integrated boost intensity modulated radiotherapy to the whole right breast. After 2 years' follow-up, she had biopsy-proven disease recurrence in the right breast, which revealed SCC, and a mammogram showed abnormalities in the lower inner quadrant of the right breast and left axillary lymph nodes. Then we performed bilateral breast modified radical mastectomy, which confirmed that the recurrent tumors were metaplastic SCC, followed by adjuvant chemotherapy and adjuvant radiotherapy of the left supraclavicular and apical axillary regions. There has been no recurrent or metastatic evidence in the 16 months' follow-up since the second surgery. Conclusion: This case report shows that evolution of pathology type in recurrent breast cancer after initial treatment is possible. Detailed pathologic and immunohistochemical analyses are needed for identification of this change. Surgery and adjuvant radiation and chemotherapy are appropriate treatments for recurrent primary SCC of the breast.}, }
@article {pmid32157060, year = {2019}, author = {Egawa, C and Yanai, A and Yanagawa, T and Takatsuka, Y and Takeno, A and Masuzawa, T and Hata, T and Kagawa, Y and Ohmura, Y and Katsura, Y and Murakami, K and Sakamoto, T and Kawai, K and Takeda, Y and Murata, K}, title = {[Long-Term Survival in a Case of Breast Cancer with Brain Metastases and No Other Distant Metastases Treated by Surgical Removal and Gamma Knife Radiosurgery].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {13}, pages = {2063-2065}, pmid = {32157060}, issn = {0385-0684}, mesh = {Adult ; *Brain Neoplasms/radiotherapy/secondary ; *Breast Neoplasms/radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; *Radiosurgery ; }, abstract = {A 44-year-oldwoman was diagnosedwith right breast cancer andund erwent mastectomy andaxillary lymph node dissection in February 2006. She was pathologically diagnosed with invasive ductal carcinoma without lymph node metastasis. Immunohistochemical examination showedthat the tumor was estrogen receptor positive, progesterone receptor negative, andhada HER2 status score of 0. She received 4 cycles of AC, followedby leuprorelin andtamoxifen. Several metastases were identified in the right supraclavicular lymph nodes in August 2008 during the endocrine therapy. Then, she received S-1 as the first-line chemotherapy. Although metastases showed complete response, she developed an eye disorder caused by S-1 and thus the treatment agent was changedto leuprorelin andanastrozole. She complainedof headache andright homonymous hemianopsia in November 2013. MRI showeda 42mm diameter tumor in the left occipital lobe, suspectedto be brain metastasis from breast cancer. Craniotomy was performedto remove the brain tumor, which was pathologically diagnosedas metastasis from breast cancer. In the brain tumor, the estrogen receptor status hadchangedto negative, but the HER2 status remained unchanged, showing a score of 0. Vinorelbine was administered after the brain surgery. Unfortunately, brain metastasis was foundin the dura mater near the surgical cavity, andgamma knife radiosurgery was performedin January 2014. Thereafter, brain metastases were repeatedly found, and gamma knife radiosurgery was again performed in January 2015, September 2016, and February 2017. In addition, a large tumor appearedin the left occipital lobe andwas surgically removed in June 2016. No other distant metastases were found, andvinorelbine was continueduntil February 2018. Because the patient developed dyslexia caused by gamma knife-induced radiation necrosis, bevacizumab was administered between November 2018 and April 2019. MRI showed that the edema due to radiation necrosis reduced and dyslexia symptoms improved. As of now, she has survivedfor 5 years and 6 months after the diagnosis of brain metastases.}, }
@article {pmid32156965, year = {2019}, author = {Kinoshita, H and Teraoka, H and Mori, T and Hasegawa, T and Noda, E and Takashima, T and Hirakawa, K and Ohira, M}, title = {[A Case of Breast Cancer Liver Metastases with Jaundice Responding to Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {13}, pages = {2461-2463}, pmid = {32156965}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy/secondary ; Female ; Humans ; *Jaundice/etiology ; *Liver Neoplasms/drug therapy/secondary ; Middle Aged ; Paclitaxel ; }, abstract = {A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.}, }
@article {pmid32156942, year = {2019}, author = {Morisaki, T and Takashima, T and Asano, Y and Kashiwagi, S and Noda, S and Onoda, N and Ohira, M}, title = {[Two Cases of Orbital Metastasis from Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {13}, pages = {2392-2394}, pmid = {32156942}, issn = {0385-0684}, mesh = {Adult ; *Breast Neoplasms ; Eye Neoplasms/*secondary ; Female ; Humans ; *Liver Neoplasms ; Magnetic Resonance Imaging ; }, abstract = {Orbital metastasis from breast cancer is a rare condition. Here, we describe 2 cases of orbital metastasis from breast cancer. The first patient was a 26-year-old woman diagnosed with triple-negative invasive ductal carcinoma. She underwent surgery after neoadjuvant chemotherapy. One year after surgery, she had multiple bone metastases and then multiple liver metastases developed. During chemotherapy for metastatic disease, she complained ofheadaches and visual disturbances. Findings ofa MRI scan suggested a metastatic tumor in the left orbit. A total of 30 Gy of radiation therapy was administered, but she died a month after the orbital metastasis was discovered. The second patient was a 42-year-old woman, who had advanced breast cancer with bone metastasis. Diplopia developed 8 months after initiation of chemotherapy. Meningeal dissemination was suspected because ophthalmological examination revealed swelling ofbilateral optic discs. She lost her sight within a month. She died 2 months after the diagnosis oforbital metastasis. There was no evidence ofcentral nervous system metastasis in either case. Loss ofvision severely impairs patients' quality oflif e. It is important to know that there is rarely such a rapid progression ofdisease, especially in young patients with triple-negative disease.}, }
@article {pmid32156914, year = {2019}, author = {Nakama, Y and Maruyama, Y and Hisaka, T and Yasumoto, M and Okabe, Y and Naito, Y and Yamaguchi, M and Tanaka, M and Tanaka, H and Akagi, Y and Okuda, K}, title = {[A Vesected Case of Pancreatic Metastasis from Breast Cancer Which Recurred Six Years after Breast Surgery].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {13}, pages = {2309-2311}, pmid = {32156914}, issn = {0385-0684}, mesh = {*Adenocarcinoma/secondary/surgery ; Adult ; *Breast Neoplasms/surgery ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/secondary ; }, abstract = {A 43-year-old woman who underwent surgical resection of invasive ductal carcinoma in the left breast at the age of 37 years old presented at our hospital for evaluation of pancreatic tumor. The original tumor was estrogen receptor(ER)progesterone receptor(PgR)and HER2 positive. At that time, she underwent radical mastectomy with no evident nodal disease. Postoperatively, the patient was placed on adjuvant tamoxifen therapy for several years. Six years following the original diagnosis of breast cancer, she was referred to the hospital for routine check-up while asymptomatic. Follow-up examination showed a solitary hypodense mass approximately 0.9 cm in size in the pancreas body on dynamic CT scan. The patient underwent a standard distal pancreatectomy with standard regional lymphadenectomy. Histopathological examination and immunohistochemical features revealed that the tumor was compatible with metastatic pancreatic adenocarcinoma from breast cancer.}, }
@article {pmid32139710, year = {2020}, author = {Roy, S and Kumar, R and Mittal, V and Gupta, D}, title = {Classification models for Invasive Ductal Carcinoma Progression, based on gene expression data-trained supervised machine learning.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {4113}, pmid = {32139710}, issn = {2045-2322}, support = {SRF//Council of Scientific and Industrial Research (CSIR)/International ; SRF//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/PR6963/BID/7/427/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/BI/25/066/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; }, mesh = {Algorithms ; Breast Neoplasms/*classification/genetics ; Carcinoma, Ductal, Breast/*classification/genetics ; Databases, Genetic ; Datasets as Topic ; Early Detection of Cancer ; Female ; Gene Ontology ; Humans ; Machine Learning ; Microarray Analysis ; Models, Biological ; Neoplasm Staging ; Protein Interaction Maps ; RNA, Neoplasm ; RNA-Seq ; Reproducibility of Results ; *Supervised Machine Learning ; *Transcriptome ; }, abstract = {Early detection of breast cancer and its correct stage determination are important for prognosis and rendering appropriate personalized clinical treatment to breast cancer patients. However, despite considerable efforts and progress, there is a need to identify the specific genomic factors responsible for, or accompanying Invasive Ductal Carcinoma (IDC) progression stages, which can aid the determination of the correct cancer stages. We have developed two-class machine-learning classification models to differentiate the early and late stages of IDC. The prediction models are trained with RNA-seq gene expression profiles representing different IDC stages of 610 patients, obtained from The Cancer Genome Atlas (TCGA). Different supervised learning algorithms were trained and evaluated with an enriched model learning, facilitated by different feature selection methods. We also developed a machine-learning classifier trained on the same datasets with training sets reduced data corresponding to IDC driver genes. Based on these two classifiers, we have developed a web-server Duct-BRCA-CSP to predict early stage from late stages of IDC based on input RNA-seq gene expression profiles. The analysis conducted by us also enables deeper insights into the stage-dependent molecular events accompanying IDC progression. The server is publicly available at http://bioinfo.icgeb.res.in/duct-BRCA-CSP.}, }
@article {pmid32138738, year = {2020}, author = {Sun, T and Yang, W and Toprani, SM and Guo, W and He, L and DeLeo, AB and Ferrone, S and Zhang, G and Wang, E and Lin, Z and Hu, P and Wang, X}, title = {Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram.}, journal = {Cell communication and signaling : CCS}, volume = {18}, number = {1}, pages = {36}, pmid = {32138738}, issn = {1478-811X}, support = {R01 CA226981/CA/NCI NIH HHS/United States ; R03 CA216114/CA/NCI NIH HHS/United States ; }, mesh = {*Antineoplastic Agents/administration &amp; dosage/pharmacology ; Breast Neoplasms/*drug therapy/pathology/radiotherapy ; Cell Line, Tumor ; *Disulfiram/administration &amp; dosage/pharmacology ; *Drug Repositioning ; Female ; Humans ; Immunogenic Cell Death/*drug effects ; Neoplastic Stem Cells ; Radiation Tolerance/*drug effects ; }, abstract = {BACKGROUND: The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response.<br><br>METHODS: High aldehyde dehydrogenase activity (ALDH)[bright] and CD44[+]/CD24[-]/ESA[+] cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors.<br><br>CONCLUSION: DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.}, }
@article {pmid32135221, year = {2020}, author = {Shete, A and Kurle, S and Dhayarkar, S and Patil, A and Kulkarni, S and Ghate, M and Sangale, S and Medhe, U and Rajan, S and Verma, V and Gangakhedkar, R}, title = {High IL-5 levels possibly contributing to HIV viremia in virologic non-responders at one year after initiation of anti-retroviral therapy.}, journal = {Microbial pathogenesis}, volume = {143}, number = {}, pages = {104117}, doi = {10.1016/j.micpath.2020.104117}, pmid = {32135221}, issn = {1096-1208}, mesh = {Adolescent ; Adult ; Anti-HIV Agents/*therapeutic use ; CD4-CD8 Ratio ; Drug Resistance, Viral/genetics ; Female ; HIV Infections/*drug therapy/virology ; Humans ; Interleukin-5/*blood ; Male ; Middle Aged ; Treatment Failure ; Viremia/blood/*drug therapy ; Young Adult ; }, abstract = {Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.}, }
@article {pmid32119669, year = {2020}, author = {Rangel, GW and Clark, MA and Kanjee, U and Goldberg, JM and MacInnis, B and José Menezes, M and Ferreira, MU and Duraisingh, MT}, title = {Plasmodium vivax transcriptional profiling of low input cryopreserved isolates through the intraerythrocytic development cycle.}, journal = {PLoS neglected tropical diseases}, volume = {14}, number = {3}, pages = {e0008104}, pmid = {32119669}, issn = {1935-2735}, support = {R01 AI140751/AI/NIAID NIH HHS/United States ; R01 HL139337/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U19 AI089681/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Culture Media/chemistry ; Erythrocytes/*parasitology ; Female ; *Gene Expression Profiling ; *Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Malaria, Vivax/*parasitology ; Male ; Parasitology/methods ; Plasmodium vivax/genetics/*growth &amp; development ; Sequence Analysis, RNA ; }, abstract = {Approximately one-third of the global population is at risk of Plasmodium vivax infection, and an estimated 7.51 million cases were reported in 2017. Although, P. vivax research is currently limited by the lack of a robust continuous in vitro culture system for this parasite, recent work optimizing short-term ex vivo culture of P. vivax from cryopreserved isolates has facilitated quantitative assays on synchronous parasites. Pairing this improved culture system with low-input Smart-seq2 RNAseq library preparation, we sought to determine whether transcriptional profiling of P. vivax would provide insight into the differential survival of parasites in different culture media. To this end we probed the transcriptional signature of three different ex vivo P. vivax samples in four different culture media using only 1000 cells for each time point taken during the course of the intraerythrocytic development cycle (IDC). Using this strategy, we achieved similar quality transcriptional data to previously reported P. vivax transcriptomes. We found little effect with varying culture media on parasite transcriptional signatures, identified many novel gametocyte-specific genes from transcriptomes of FACS-isolated gametocytes, and determined invasion ligand expression in schizonts in biological isolates and across the IDC. In total, these data demonstrate the feasibility and utility of P. vivax RNAseq-based transcriptomic studies using minimal biomass input to maximize experimental capacity.}, }
@article {pmid32103749, year = {2020}, author = {Tewari, SG and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite.}, journal = {Malaria journal}, volume = {19}, number = {1}, pages = {94}, pmid = {32103749}, issn = {1475-2875}, support = {R01 AI125534/AI/NIAID NIH HHS/United States ; R01 AI065853/NH/NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; W81XWH-15-C-0061//U.S. Army Medical Research and Development Command/ ; }, mesh = {Erythrocytes/*metabolism/parasitology ; Malaria, Falciparum/*metabolism/parasitology ; Parasitemia/*metabolism/parasitology ; Plasmodium falciparum/*growth &amp; development ; }, abstract = {BACKGROUND: Human blood cells (erythrocytes) serve as hosts for the malaria parasite Plasmodium falciparum during its 48-h intraerythrocytic developmental cycle (IDC). Established in vitro protocols allow for the study of host-parasite interactions during this phase and, in particular, high-resolution metabolomics can provide a window into host-parasite interactions that support parasite development.<br><br>METHODS: Uninfected and parasite-infected erythrocyte cultures were maintained at 2% haematocrit for the duration of the IDC, while parasitaemia was maintained at 7% in the infected cultures. The parasite-infected cultures were synchronized to obtain stage-dependent information of parasite development during the IDC. Samples were collected in quadruplicate at six time points from the uninfected and parasite-infected cultures and global metabolomics was used to analyse cell fractions of these cultures.<br><br>RESULTS: In uninfected and parasite-infected cultures during the IDC, 501 intracellular metabolites, including 223 lipid metabolites, were successfully quantified. Of these, 19 distinct metabolites were present only in the parasite-infected culture, 10 of which increased to twofold in abundance during the IDC. This work quantified approximately five times the metabolites measured in previous studies of similar research scope, which allowed for more detailed analyses. Enrichment in lipid metabolism pathways exhibited a time-dependent association with different classes of lipids during the IDC. Specifically, enrichment occurred in sphingolipids at the earlier stages, and subsequently in lysophospholipid and phospholipid metabolites at the intermediate and end stages of the IDC, respectively. In addition, there was an accumulation of 18-, 20-, and 22-carbon polyunsaturated fatty acids, which produce eicosanoids and promote gametocytogenesis in infected erythrocyte cultures.<br><br>CONCLUSIONS: The current study revealed a number of heretofore unidentified metabolic components of the host-parasite system, which the parasite may exploit in a time-dependent manner to grow over the course of its development in the blood stage. Notably, the analyses identified components, such as precursors of immunomodulatory molecules, stage-dependent lipid dynamics, and metabolites, unique to parasite-infected cultures. These conclusions are reinforced by the metabolic alterations that were characterized during the IDC, which were in close agreement with those known from previous studies of blood-stage infection.}, }
@article {pmid32088208, year = {2020}, author = {Guillet, C and Rechsteiner, M and Bellini, E and Choschzick, M and Moskovszky, L and Dedes, K and Papassotiropoulos, B and Varga, Z}, title = {Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations.}, journal = {Human pathology}, volume = {98}, number = {}, pages = {64-73}, doi = {10.1016/j.humpath.2020.02.002}, pmid = {32088208}, issn = {1532-8392}, mesh = {Adult ; Age of Onset ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; Heredity ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; *Mutation ; Papilloma/*genetics/pathology/surgery ; Pedigree ; Phenotype ; Proto-Oncogene Proteins c-akt/*genetics ; }, abstract = {Juvenile papillomatosis (JP), the so-called Swiss cheese disease, is a rare benign breast disease of young adults. An association (up to 28%) with breast cancer within the family of affected patients has been reported. A multinodular cystic breast mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal papillomas, usual ductal hyperplasia, ductectasias, perifocal sclerosing adenosis, and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family history in context with a comprehensive review of the JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were women with a median age of 38 years (26-50 years). Follow-up information was available for 11 of 13 patients. Sufficient paraffin-embedded tissue and good DNA quality for next-generation sequencing (NGS) was available for 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease; the tissue cores underwent NGS analysis using the Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations; in 2 of 10 patients, we found AKT1 mutations in known hot spot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1, and GNAS genes were detected in individual patients. Some of these mutations were present at high allele frequencies suggesting germ line mutations. Two of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hot spot mutations in PIK3CA and AKT1 genes in JP associated with positive family history for breast cancer, although these mutations are not specific for JP. The genetic link between JP, positive family history, and subsequent risk of breast cancer needs to be analyzed in further studies.}, }
@article {pmid32086991, year = {2020}, author = {Luo, Y and Kishi, S and Sasaki, T and Ohmori, H and Fujiwara-Tani, R and Mori, S and Goto, K and Nishiguchi, Y and Mori, T and Kawahara, I and Kondoh, M and Kuniyasu, H}, title = {Targeting claudin-4 enhances chemosensitivity in breast cancer.}, journal = {Cancer science}, volume = {111}, number = {5}, pages = {1840-1850}, pmid = {32086991}, issn = {1349-7006}, support = {17KJB320010//Natural Science Foundation of Jiangsu Education Department Project/ ; 16H05164//Ministry of Education, Culture, Sports, Science and Technology/ ; 17K19923//Ministry of Education, Culture, Sports, Science and Technology/ ; 81702723//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Antibodies/pharmacology/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Claudin-1 ; Claudin-4/chemistry/genetics/*immunology ; Drug Synergism ; Female ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Paclitaxel/pharmacology/therapeutic use ; Tamoxifen/pharmacology/therapeutic use ; Triple Negative Breast Neoplasms/drug therapy/metabolism/pathology ; Tumor Microenvironment/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Triple negative breast cancer (TNBC) is characterized by highly aggressive phenotype, limited treatment options and a poor prognosis. In the present study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDC (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and was correlated with histological grade. In contrast, expression of CLDN4 was correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors and increased the intratumoral pH. Moreover, concurrent treatment with 4D3, PTX and tamoxifen, or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in a bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects.}, }
@article {pmid32079470, year = {2020}, author = {Yin, S and Fan, Y and He, X and Wei, G and Wen, Y and Zhao, Y and Shi, M and Wei, J and Chen, H and Han, J and Jiang, L and Zhang, Q}, title = {The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum.}, journal = {RNA biology}, volume = {17}, number = {6}, pages = {828-842}, pmid = {32079470}, issn = {1555-8584}, mesh = {Computational Biology/methods ; Erythrocytes/parasitology ; Exosome Multienzyme Ribonuclease Complex ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Ontology ; Humans ; Life Cycle Stages ; Malaria, Falciparum/*parasitology ; Plasmodium falciparum/*genetics/*growth &amp; development ; *RNA Splicing ; RNA Stability ; RNA, Messenger/genetics ; RNA, Protozoan/*genetics ; RNA, Untranslated/genetics ; }, abstract = {The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored. Here we profiled the transcription dynamics of nascent RNAs by rRNA-depleted and stranded RNA sequencing over the course of 48-h intraerythrocytic developmental cycle (IDC). We identified the genome-wide sources of a total of 2252 ns-ncRNAs, mostly originating from intergenic and untranslated regions of annotated genes. By integrating the nascent RNA abundances with ATAC-seq and ChIP-seq analysis, we uncovered the euchromatic microenvironment surrounding the ns-ncRNA loci, and revealed a positive correlation between ns-ncRNAs and corresponding mRNA abundances. Finally, by gene knock-down strategy, we showed that the cooperation of RNA exosome catalytic subunit PfDis3 and PfMtr4 cofactor played a major role in ns-ncRNAs degradation. Collectively, this study contributes to understanding of the potential roles of short-lived nascent ncRNAs in regulating gene expression in malaria parasites.}, }
@article {pmid32063604, year = {2020}, author = {Granados, K and Hüser, L and Federico, A and Sachindra, S and Wolff, G and Hielscher, T and Novak, D and Madrigal-Gamboa, V and Sun, Q and Vierthaler, M and Larribère, L and Umansky, V and Utikal, J}, title = {T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells.}, journal = {British journal of cancer}, volume = {122}, number = {7}, pages = {1023-1036}, pmid = {32063604}, issn = {1532-1827}, support = {OAICE-CAB-09-133-2015//Universidad de Costa Rica (University of Costa Rica)/International ; PED-054-2015-2//Ministerio de Ciencia Tecnolog&#xed;a y Telecomunicaciones (Ministerio de Ciencia Tecnolog&#xed;a y Telecomunicaciones de Costa Rica)/International ; 259332240 / RTG 2099//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; }, mesh = {Animals ; Calcium Channels, T-Type/*genetics ; Disease Models, Animal ; Female ; Humans ; Melanoma/*drug therapy/pathology ; Mice ; Protein Kinase Inhibitors/pharmacology/*therapeutic use ; Proto-Oncogene Mas ; }, abstract = {BACKGROUND: Drug resistance remains as one of the major challenges in melanoma therapy. It is well known that tumour cells undergo phenotypic switching during melanoma progression, increasing melanoma plasticity and resistance to mitogen-activated protein kinase inhibitors (MAPKi).<br><br>METHODS: We investigated the melanoma phenotype switching using a partial reprogramming model to de-differentiate murine melanoma cells and target melanoma therapy adaptation against MAPKi.<br><br>RESULTS: Here, we show that partially reprogrammed cells are a less proliferative and more de-differentiated cell population, expressing a gene signature for stemness and suppressing melanocyte-specific markers. To investigate adaptation to MAPKi, cells were exposed to B-Raf Proto-Oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. De-differentiated cells became less sensitive to MAPKi, showed increased cell viability and decreased apoptosis. Furthermore, T-type calcium channels expression increased in adaptive murine cells and in human adaptive melanoma cells. Treatment with the calcium channel blocker mibefradil induced cell death, differentiation and susceptibility to MAPKi in vitro and in vivo.<br><br>CONCLUSION: In summary, we show that partial reprogramming of melanoma cells induces de-differentiation and adaptation to MAPKi. Moreover, we postulated a calcium channel blocker such as mibefradil, as a potential candidate to restore sensitivity to MAPKi in adaptive melanoma cells.}, }
@article {pmid32062352, year = {2020}, author = {Kanwar, N and Carmine-Simmen, K and Nair, R and Wang, C and Moghadas-Jafari, S and Blaser, H and Tran-Thanh, D and Wang, D and Wang, P and Wang, J and Pasculescu, A and Datti, A and Mak, T and Lewis, JD and Done, SJ}, title = {Amplification of a calcium channel subunit CACNG4 increases breast cancer metastasis.}, journal = {EBioMedicine}, volume = {52}, number = {}, pages = {102646}, pmid = {32062352}, issn = {2352-3964}, mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Calcium/metabolism ; Calcium Channels/chemistry/*genetics/metabolism ; Calcium Signaling ; Cell Line ; Cell Movement/genetics ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/genetics/metabolism ; Disease Progression ; Female ; *Gene Amplification ; Gene Expression ; Humans ; Immunohistochemistry ; Mice ; Models, Biological ; Neoplasm Metastasis ; Neoplasm Staging ; Protein Interaction Domains and Motifs ; }, abstract = {BACKGROUND: Previously, we found that amplification of chromosome 17q24.1-24.2 is associated with lymph node metastasis, tumour size, and lymphovascular invasion in invasive ductal carcinoma. A gene within this amplicon, CACNG4, an L-type voltage-gated calcium channel gamma subunit, is elevated in breast cancers with poor prognosis. Calcium homeostasis is achieved by maintaining low intracellular calcium levels. Altering calcium influx/efflux mechanisms allows tumour cells to maintain homeostasis despite high serum calcium levels often associated with advanced cancer (hypercalcemia) and aberrant calcium signaling.<br><br>METHODS: In vitro 2-D and 3-D assays, and intracellular calcium influx assays were utilized to measure tumourigenic activity in response to altered CANCG4 levels and calcium channel blockers. A chick-CAM model and mouse model for metastasis confirmed these results in vivo.<br><br>FINDINGS: CACNG4 alters cell motility in vitro, induces malignant transformation in 3-dimensional culture, and increases lung-specific metastasis in vivo. CACNG4 functions by closing the channel pore, inhibiting calcium influx, and altering calcium signaling events involving key survival and metastatic pathway genes (AKT2, HDAC3, RASA1 and PKC&#x3b6;).<br><br>INTERPRETATION: CACNG4 may promote homeostasis, thus increasing the survival and metastatic ability of tumour cells in breast cancer. Our findings suggest an underlying pathway for tumour growth and dissemination regulated by CACNG4 that is significant with respect to developing treatments that target these channels in tumours with aberrant calcium signaling.<br><br>FUNDING: Canadian Breast Cancer Foundation, Ontario; Canadian Institutes of Health Research.}, }
@article {pmid32051475, year = {2020}, author = {Beetch, M and Harandi-Zadeh, S and Yang, T and Boycott, C and Chen, Y and Stefanska, B and Mohammed, SI}, title = {DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {2415}, pmid = {32051475}, issn = {2045-2322}, mesh = {Animals ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/*veterinary ; *DNA Methylation ; Disease Progression ; Dog Diseases/*genetics/pathology ; Dogs/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Triple Negative Breast Neoplasms/genetics/pathology/*veterinary ; }, abstract = {Triple-negative breast cancer (TNBC) is a subtype of breast cancer unresponsive to traditional receptor-targeted treatments, leading to a disproportionate number of deaths. Invasive breast cancer is believed to evolve from non-invasive ductal carcinoma in situ (DCIS). Detection of triple-negative DCIS (TN-DCIS) is challenging, therefore strategies to study molecular events governing progression of pre-invasive TN-DCIS to invasive TNBC are needed. Here, we study a canine TN-DCIS progression and investigate the DNA methylation landscape of normal breast tissue, atypical ductal hyperplasia (ADH), DCIS and invasive breast cancer. We report hypo- and hypermethylation of genes within functional categories related to cancer such as transcriptional regulation, apoptosis, signal transduction, and cell migration. DNA methylation changes associated with cancer-related genes become more pronounced at invasive breast cancer stage. Importantly, we identify invasive-only and DCIS-specific DNA methylation alterations that could potentially determine which lesions progress to invasive cancer and which could remain as pre-invasive DCIS. Changes in DNA methylation during TN-DCIS progression in this canine model correspond with gene expression patterns in human breast tissues. This study provides evidence for utilizing methylation status of gene candidates to define late-stage (DCIS and invasive), invasive stage only or DCIS stage only of TN-DCIS progression.}, }
@article {pmid32050925, year = {2020}, author = {Dettogni, RS and Stur, E and Laus, AC and da Costa Vieira, RA and Marques, MMC and Santana, IVV and Pulido, JZ and Ribeiro, LF and de Jesus Parmanhani, N and Agostini, LP and Dos Reis, RS and de Vargas Wolfgramm Dos Santos, E and Alves, LNR and Garcia, FM and Santos, JA and do Prado Ventorim, D and Reis, RM and Louro, ID}, title = {Potential biomarkers of ductal carcinoma in situ progression.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {119}, pmid = {32050925}, issn = {1471-2407}, support = {0468/2015//Funda&#xe7;&#xe3;o Estadual de Amparo &#xe0; Pesquisa do Estado do Esp&#xed;rito Santo/ ; 66141494/2014//Funda&#xe7;&#xe3;o Estadual de Amparo &#xe0; Pesquisa do Estado do Esp&#xed;rito Santo/ ; 66271126/2014//Funda&#xe7;&#xe3;o Estadual de Amparo &#xe0; Pesquisa do Estado do Esp&#xed;rito Santo/ ; 0698/2015//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Espirito Santo-Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior (FAPES-CAPES)/ ; }, mesh = {Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Carcinoma, Ductal, Breast/*diagnosis/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics/metabolism ; Computational Biology ; Disease Progression ; Disease Susceptibility ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Protein Interaction Mapping ; Protein Interaction Maps ; Transcriptome ; }, abstract = {BACKGROUND: Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.<br><br>METHODS: In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter&#xae; PanCancer Pathways panel of NanoString Technologies.<br><br>RESULTS: The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.<br><br>CONCLUSIONS: We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.}, }
@article {pmid32050826, year = {2020}, author = {Mostyka, M and Jessurun, J and Matrai, C}, title = {Sarcoid-Like Granulomatosis in a Patient With Breast Cancer Mimicking Refractory Metastatic Disease.}, journal = {International journal of surgical pathology}, volume = {28}, number = {6}, pages = {668-671}, doi = {10.1177/1066896920905887}, pmid = {32050826}, issn = {1940-2465}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Granuloma, Respiratory Tract/chemically induced/*pathology ; Humans ; Lung/pathology ; Pulmonary Fibrosis/chemically induced/pathology ; }, abstract = {Sarcoid-like granulomatosis is a known but rare adverse reaction to immune checkpoint inhibitors and chemotherapy in the treatment of advanced solid tumors. We present a case of a 29-year-old female with a pathologically confirmed poorly differentiated invasive ductal carcinoma of the breast with presumed metastases to the lungs, hilar lymph nodes, liver, and spleen. Despite appropriate chemotherapy, the patient developed pulmonary lesions that were interpreted on imaging studies as progression of malignancy. Autopsy revealed disseminated sarcoid-like granulomatosis with multiple noncaseating granulomata with associated fibrosis in the lungs, liver, and spleen. No residual invasive carcinoma or metastatic disease was identified. This case illustrates the difficulty in differentiating this nonneoplastic process from progressive disease in the clinical setting.}, }
@article {pmid32043593, year = {2020}, author = {Shahir, M and Mahmoud Hashemi, S and Asadirad, A and Varahram, M and Kazempour-Dizaji, M and Folkerts, G and Garssen, J and Adcock, I and Mortaz, E}, title = {Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells.}, journal = {Journal of cellular physiology}, volume = {235}, number = {10}, pages = {7043-7055}, pmid = {32043593}, issn = {1097-4652}, mesh = {Animals ; Biomarkers/metabolism ; Cell Communication/immunology ; Cell Proliferation/physiology ; Cells, Cultured ; Cytokines/immunology/metabolism ; Dendritic Cells/*immunology/metabolism ; Exosomes/*immunology/metabolism ; Female ; Immune Tolerance/*immunology ; Immunity/immunology ; Inflammation/immunology/metabolism ; Lymphocytes/immunology/metabolism ; Mesenchymal Stem Cells/*immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; }, abstract = {Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T-cell activation via direct cell-cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T-cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC-derived exosomes on the induction of mouse tolDCs, murine adipose-derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick-TC kits. BM-derived DCs (BMDCs) were prepared and cocultured with MSCs-derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester-labeled BALB/C-derived splenocytes p. Interleukin-6 (IL-6), IL-10, and transforming growth factor-β (TGF-β) release were measured by enzyme-linked immunosorbent assay. MSC-derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells (≤ .05). MSC-derived exosomes decrease IL-6 release but augment IL-10 and TGF-β release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC-derived exosomes. CMSC-derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC-induced immune responses.}, }
@article {pmid32031117, year = {2020}, author = {Söyleyici, NA and Aslan, F and Avcýkurt, AS and Akgün, GA}, title = {Importance of MACC1 expression in breast cancer and its relationship with pathological prognostic markers.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {1}, pages = {19-24}, doi = {10.4103/IJPM.IJPM_658_19}, pmid = {32031117}, issn = {0974-5130}, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/surgery ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Middle Aged ; Prognosis ; Trans-Activators/*genetics ; Vascular Endothelial Growth Factor A/genetics ; }, abstract = {BACKGROUND: Metastasis associated colon cancer gene 1 (MACC1) is a gene that was first described as a c-Met transcription regulator causing the progression of colon cancer. In this study, protein and messenger RNA (mRNA) expression of MACC1 in breast cancer and its relationship with clinicopathological prognostic parameters were investigated.<br><br>METHODS: Sixty-six cases with tumors underwent radical mastectomy for invasive ductal carcinoma and 25 control cases operated for mammoplasty were included in the study. In paraffin blocks of tumor and control tissues, MACC1 expression was investigated by the immunohistochemical method and Real-time polymerase chain reaction (Real-Time PCR). In addition, vascular endothelial growth factor (VEGF) expression was examined immunohistochemically in tumor tissues. The relationship between MACC1 expression in tumor tissues, clinicopathological prognostic parameters, and VEGF was investigated.<br><br>RESULTS: In this study, protein and mRNA expressions of MACC1 were found to be higher in tumor tissues compared with normal breast tissues. MACC1 protein expression was also associated with significant poor prognostic markers, such as high histologic grade, ER negativity, and HER2 positivity. However, there was no correlation between MACC1 expression and VEGF.<br><br>CONCLUSION: According to these results, MACC1 expression may be a marker of breast carcinoma as well as an independent predictor of poor prognosis. In addition, MACC1 may not affect angiogenesis in breast cancer or even if it has an effect, it may not be associated with VEGF. However, it would be appropriate to support these results in a larger series by investigating in vivo and in vitro studies.}, }
@article {pmid32031116, year = {2020}, author = {Varma, K and Chauhan, A and Bhargava, M and Misra, V and Srivastava, S}, title = {Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {1}, pages = {13-18}, doi = {10.4103/IJPM.IJPM_419_19}, pmid = {32031116}, issn = {0974-5130}, mesh = {Breast Neoplasms/classification/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cyclin D1/*genetics ; Female ; Genetic Association Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; beta Catenin/*genetics ; }, abstract = {BACKGROUND: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet.<br><br>MATERIALS AND METHODS: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association.<br><br>RESULTS: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns.<br><br>CONCLUSION: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.}, }
@article {pmid32029638, year = {2020}, author = {Aminian, A and Zajichek, A and Arterburn, DE and Wolski, KE and Brethauer, SA and Schauer, PR and Nissen, SE and Kattan, MW}, title = {Predicting 10-Year Risk of End-Organ Complications of Type 2 Diabetes With and Without Metabolic Surgery: A Machine Learning Approach.}, journal = {Diabetes care}, volume = {43}, number = {4}, pages = {852-859}, pmid = {32029638}, issn = {1935-5548}, support = {R01 DK105960/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Bariatric Surgery/statistics &amp; numerical data ; Computer Simulation ; Diabetes Complications/*diagnosis/epidemiology/pathology ; Diabetes Mellitus, Type 2/*complications/*diagnosis/epidemiology/*surgery ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; *Machine Learning ; Male ; Middle Aged ; Organs at Risk/pathology ; Prognosis ; Retrospective Studies ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVE: To construct and internally validate prediction models to estimate the risk of long-term end-organ complications and mortality in patients with type 2 diabetes and obesity that can be used to inform treatment decisions for patients and practitioners who are considering metabolic surgery.<br><br>RESEARCH DESIGN AND METHODS: A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI &#x2265;30 kg/m[2] and type 2 diabetes who received usual care with follow-up through December 2018. Multivariable time-to-event regression and random forest machine learning models were built and internally validated using fivefold cross-validation to predict the 10-year risk for four outcomes of interest. The prediction models were programmed to construct user-friendly web-based and smartphone applications of Individualized Diabetes Complications (IDC) Risk Scores for clinical use.<br><br>RESULTS: The prediction tools demonstrated the following discrimination ability based on the area under the receiver operating characteristic curve (1 = perfect discrimination and 0.5 = chance) at 10 years in the surgical and nonsurgical groups, respectively: all-cause mortality (0.79 and 0.81), coronary artery events (0.66 and 0.67), heart failure (0.73 and 0.75), and nephropathy (0.73 and 0.76). When a patient's data are entered into the IDC application, it estimates the individualized 10-year morbidity and mortality risks with and without undergoing metabolic surgery.<br><br>CONCLUSIONS: The IDC Risk Scores can provide personalized evidence-based risk information for patients with type 2 diabetes and obesity about future cardiovascular outcomes and mortality with and without metabolic surgery based on their current status of obesity, diabetes, and related cardiometabolic conditions.}, }
@article {pmid32019280, year = {2020}, author = {Wu, J and Ding, S and Lin, L and Fei, X and Lin, C and Andriani, L and Goh, C and Huang, J and Hong, J and Gao, W and Zhu, S and Wang, H and Huang, O and Chen, X and He, J and Li, Y and Shen, K and Chen, W and Zhu, L}, title = {Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study.}, journal = {Cancer research and treatment}, volume = {52}, number = {3}, pages = {671-679}, pmid = {32019280}, issn = {2005-9256}, support = {81572581//National Natural Science Foundation of China/ ; 81772797//National Natural Science Foundation of China/ ; 14411950200//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 14411950201//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 16411966- 900//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 201840323//Grant of Shanghai municipal commission of health and family planning/ ; }, mesh = {Adenocarcinoma, Mucinous/metabolism/pathology/*therapy ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/metabolism/pathology/*therapy ; Carcinoma, Ductal, Breast/metabolism/pathology/*therapy ; China/epidemiology ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis/epidemiology/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; *Transcriptome ; }, abstract = {PURPOSE: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).<br><br>MATERIALS AND METHODS: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.<br><br>RESULTS: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).<br><br>CONCLUSION: RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.}, }
@article {pmid32007118, year = {2019}, author = {Komaei, I and Guccione, F and Sarra, F and Palmeri, E and Ieni, A and Cardia, R and Currò, G and Navarra, G and Palmeri, R}, title = {Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review.}, journal = {Il Giornale di chirurgia}, volume = {40}, number = {6}, pages = {544-550}, pmid = {32007118}, issn = {1971-145X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/*etiology/pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/drug therapy/*radiotherapy/surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/administration &amp; dosage ; Diagnosis, Differential ; Epirubicin/administration &amp; dosage ; Female ; Humans ; Letrozole/administration &amp; dosage ; Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis ; Neoplasms, Radiation-Induced/diagnosis/*etiology/pathology/therapy ; Photons ; Radiotherapy, High-Energy/*adverse effects ; Sarcoma/diagnosis/*etiology/pathology/therapy ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare, but aggressive subtype of sarcoma that can develop in radiotherapy (RT)-treated breast cancer patients. Due to the low incidence, there are many uncertainties regarding the adequate management of these tumors. We present a rare case of radiation-induced UPS in a 63-year-old woman who had undergone breast conserving therapy for invasive ductal carcinoma of the left breast, six years prior to presentation.<br><br>CASE PRESENTATION: A 63-year-old woman presented with a rapidly growing left breast mass. She had been diagnosed with invasive ductal carcinoma of the left breast for which she underwent a left upper outer quadrantectomy and ipsilateral axillary dissection followed by RT, six years previously. During her routine oncologic follow-up, the mammography revealed a dense, nodular opacity with microcalcifications. The breast ultrasound (US) confirmed the presence of the nodule. US-guided fine needle aspiration biopsy was performed and the diagnosis of UPS was made, the reason for which the patient underwent wide local excision of the left breast.<br><br>CONCLUSION: The diagnosis of RT-induced UPS is challenging and often missed due to the low incidence, long latency period, unspecific imaging findings, and difficulties in clinical and histological detection of these lesions. These tumors should be considered in differential diagnoses of rapidly-growing breast masses in previously RT-treated breast cancer patients, as they can mimic the local recurrence of the primary tumor. Since the prevalence of breast-conserving surgery followed by RT has been increasing, the careful monitoring of at risk patients is of utmost importance, as UPSs are highly aggressive tumors associated with very poor outcomes.}, }
@article {pmid31992198, year = {2020}, author = {Assefa, T and Zhang, J and Chowda-Reddy, RV and Moran Lauter, AN and Singh, A and O'Rourke, JA and Graham, MA and Singh, AK}, title = {Deconstructing the genetic architecture of iron deficiency chlorosis in soybean using genome-wide approaches.}, journal = {BMC plant biology}, volume = {20}, number = {1}, pages = {42}, pmid = {31992198}, issn = {1471-2229}, support = {NA//Iowa Soybean Association/ ; NA//Iowa State University/ ; NA//North Central Soybean Research Program (US)/ ; NA//Agricultural Research Service/ ; NA//National Institute of Food and Agriculture/ ; }, mesh = {Epistasis, Genetic ; Gene Expression Profiling ; Genes, Plant ; Genome, Plant ; *Genome-Wide Association Study ; Iron/*metabolism ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Seed Bank ; Soybeans/*genetics ; Stress, Physiological/*genetics ; }, abstract = {BACKGROUND: Iron (Fe) is an essential micronutrient for plant growth and development. Iron deficiency chlorosis (IDC), caused by calcareous soils or high soil pH, can limit iron availability, negatively affecting soybean (Glycine max) yield. This study leverages genome-wide association study (GWAS) and a genome-wide epistatic study (GWES) with previous gene expression studies to identify regions of the soybean genome important in iron deficiency tolerance.<br><br>RESULTS: A GWAS and a GWES were performed using 460 diverse soybean PI lines from 27 countries, in field and hydroponic iron stress conditions, using more than 36,000 single nucleotide polymorphism (SNP) markers. Combining this approach with available RNA-sequencing data identified significant markers, genomic regions, and novel genes associated with or responding to iron deficiency. Sixty-nine genomic regions associated with IDC tolerance were identified across 19 chromosomes via the GWAS, including the major-effect quantitative trait locus (QTL) on chromosome Gm03. Cluster analysis of significant SNPs in this region deconstructed this historically prominent QTL into four distinct linkage blocks, enabling the identification of multiple candidate genes for iron chlorosis tolerance. The complementary GWES identified SNPs in this region interacting with nine other genomic regions, providing the first evidence of epistatic interactions impacting iron deficiency tolerance.<br><br>CONCLUSIONS: This study demonstrates that integrating cutting edge genome wide association (GWA), genome wide epistasis (GWE), and gene expression studies is a powerful strategy to identify novel iron tolerance QTL and candidate loci from diverse germplasm. Crops, unlike model species, have undergone selection for thousands of years, constraining and/or enhancing stress responses. Leveraging genomics-enabled approaches to study these adaptations is essential for future crop improvement.}, }
@article {pmid31992119, year = {2020}, author = {Billena, C and Padia, S and O'Brien, B and Knoble, J and Gokhale, A and Rajagopalan, M}, title = {Radiation recall dermatitis after treatment of stage IV breast cancer with nivolumab: a case report.}, journal = {Immunotherapy}, volume = {12}, number = {2}, pages = {123-130}, doi = {10.2217/imt-2019-0020}, pmid = {31992119}, issn = {1750-7448}, mesh = {Aged ; Antineoplastic Agents, Immunological/*therapeutic use ; Breast Neoplasms/complications/*drug therapy/*radiotherapy ; Carcinoma, Ductal, Breast/complications/*drug therapy/*radiotherapy ; Female ; Humans ; Nivolumab/*therapeutic use ; Radiodermatitis/complications/*etiology ; Radiotherapy, Adjuvant ; }, abstract = {Radiation recall dermatitis (RRD) is an uncommon dermatologic reaction provoked notably by chemotherapy in an area of skin irradiated weeks to years prior. We report a case of RRD with nivolumab in a woman with breast cancer. The patient was diagnosed with invasive ductal carcinoma of the left breast with an isolated spinal metastasis approached in an oligometastatic fashion with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiotherapy. Unfortunately, after progression of bony metastases treated with radiotherapy, the patient received nivolumab and subsequently developed a rash corresponding to the adjuvant radiation field. This case highlights the unpredictable nature and characteristic rash of RRD. It is an important differential diagnosis for multidisciplinary teams who also see chemotherapy-induced dermatitis and immune-related adverse events.}, }
@article {pmid31980982, year = {2020}, author = {Zhao, Y and Wang, Y and Zhu, F and Zhang, J and Ma, X and Zhang, D}, title = {Gene expression profiling revealed MCM3 to be a better marker than Ki67 in prognosis of invasive ductal breast carcinoma patients.}, journal = {Clinical and experimental medicine}, volume = {20}, number = {2}, pages = {249-259}, pmid = {31980982}, issn = {1591-9528}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/therapy ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*genetics ; Middle Aged ; Minichromosome Maintenance Complex Component 3/*genetics ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; }, abstract = {Invasive ductal carcinoma (IDC) is the most common breast cancer. Our study used gene microarray data to select differentially expressed genes between normal and IDC mammary tissues. From these, we selected genes related to the proliferation of tumor cells and compared their prognostic value with known biomarker Ki67 for IDC. Analysis of publicly available Gene Expression Omnibus (GEO) data revealed 24 differentially expressed genes (DEGs) in normal and 31 DEGS in IDC tissues that were used for further analyses. Gene chip analysis software was used to identify DEGs. DEG profiles were confirmed using quantitative PCR (qPCR). DEG functions where shown to be related to cell proliferation. We confirmed MCM3 expression using immunohistochemical staining in 45 IDC patients. The relationship between MCM3 expression and survival was investigated using Kaplan-Meier survival curves and Cox proportional hazard regression models. A total of 1307 differentially expressed genes were identified between IDC and normal tissues, which were enriched in 32 Gene Ontology (GO) terms and 9 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. qPCR demonstrated that both COL1A1 and MCM3 were significantly up-regulated in IDC tissues, of which only MCM3 was related to cell proliferation. Ki67 is closely associated with the tumor grade, ER status, PR status and HER2 status, while MCM3 was shown to relate to tumor size, lymph node, and PR status. There was significant association between survival and MCM3, but not for Ki67. High MCM3 expression demonstrated statistically significant associations with poor prognosis in IDC patients. Findings from the gene microarray data analysis confirmed that MCM3 is associated with the response to cell proliferation. MCM3 represents a better proliferation marker than Ki67 making it a valuable prognostic tool that is independent of ER and HER2 status.}, }
@article {pmid31941968, year = {2020}, author = {Elmetwali, T and Salman, A and Wei, W and Hussain, SA and Young, LS and Palmer, DH}, title = {CD40L membrane retention enhances the immunostimulatory effects of CD40 ligation.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {342}, pmid = {31941968}, issn = {2045-2322}, mesh = {Antigens, CD/metabolism ; Antigens, Neoplasm/metabolism ; Apoptosis/drug effects ; CD40 Antigens/metabolism ; CD40 Ligand/genetics/*metabolism/pharmacology ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Line, Tumor ; Cell Membrane/*metabolism ; Cell Proliferation ; Dendritic Cells/cytology/immunology/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Genetic Vectors/genetics/metabolism ; Humans ; Immunoglobulins/metabolism ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Leukocytes, Mononuclear/cytology/metabolism ; Membrane Glycoproteins/metabolism ; T-Lymphocytes/cytology/*immunology/metabolism ; Urinary Bladder Neoplasms/immunology/metabolism/pathology ; }, abstract = {In carcinomas, the nature of CD40 ligand shapes the outcome of CD40 ligation. To date, the consequences of membrane-bound CD40L (mCD40L) on its immune-stimulatory function are unknown. Here, we examined the impact of mCD40L versus soluble CD40L (sCD40L) on T24 bladder carcinoma gene expression profiling. Of 410 differentially expressed genes, 286 were upregulated and 124 downregulated by mCD40L versus sCD40L. Gene ontology enrichment analysis revealed immune-stimulatory function as the most significant enriched biological process affected by upregulated transcripts, while those downregulated were critical for cell growth and division. Furthermore, immature dendritic cells (iDC) responded to mCD40L with enhanced maturation and activation over sCD40L evidenced by higher expression levels of CD83, CD86, HLA-DR and CD54, increased secretion of IL12 and IL10 and higher tumour-antigen (TA) uptake capacity. Furthermore, autologus CD3+ T cells responded to TA-loaded mCD40L-activated DC with increased proliferation and cytotoxic response (CD107a and IFN-γ-producing CD3+ CD8+ T cells) to the tumour-loaded autologous PBMCs compared to sCD40L. Thus, these data indicate that mCD40L enhances the immunostimulatory capacity over sCD40L. Furthermore, the ability of mCD40L to also directly induce cell death in CD40-expressing carcinomas, subsequently releasing tumour-specific antigens into the tumour microenvironment highlights the potential for mCD40L as a multi-faceted anti-cancer immunotherapeutic.}, }
@article {pmid31937300, year = {2020}, author = {Westwood, ML and O'Donnell, AJ and Schneider, P and Albery, GF and Prior, KF and Reece, SE}, title = {Testing possible causes of gametocyte reduction in temporally out-of-synch malaria infections.}, journal = {Malaria journal}, volume = {19}, number = {1}, pages = {17}, pmid = {31937300}, issn = {1475-2875}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; UF110155//Royal Society/ ; }, mesh = {Animals ; *Circadian Rhythm/immunology ; Erythrocytes/*parasitology ; Female ; Flow Cytometry ; Gametogenesis/physiology ; Linear Models ; Malaria/blood/immunology/*parasitology ; Male ; Merozoites/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Plasmodium chabaudi/genetics/growth &amp; development/immunology/*physiology ; Random Allocation ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Tumor Necrosis Factor-alpha/*administration &amp; dosage/blood/immunology ; }, abstract = {BACKGROUND: The intraerythrocytic development cycle (IDC) of the rodent malaria Plasmodium chabaudi is coordinated with host circadian rhythms. When this coordination is disrupted, parasites suffer a 50% reduction in both asexual stages and sexual stage gametocytes over the acute phase of infection. Reduced gametocyte density may not simply follow from a loss of asexuals because investment into gametocytes ("conversion rate") is a plastic trait; furthermore, the densities of both asexuals and gametocytes are highly dynamic during infection. Hence, the reasons for the reduction of gametocytes in infections that are out-of-synch with host circadian rhythms remain unclear. Here, two explanations are tested: first, whether out-of-synch parasites reduce their conversion rate to prioritize asexual replication via reproductive restraint; second, whether out-of-synch gametocytes experience elevated clearance by the host's circadian immune responses.<br><br>METHODS: First, conversion rate data were analysed from a previous experiment comparing infections of P. chabaudi that were in-synch or 12&#xa0;h out-of-synch with host circadian rhythms. Second, three new experiments examined whether the inflammatory cytokine TNF varies in its gametocytocidal efficacy according to host time-of-day and gametocyte age.<br><br>RESULTS: There was no evidence that parasites reduce conversion or that their gametocytes become more vulnerable to TNF when out-of-synch with host circadian rhythms.<br><br>CONCLUSIONS: The factors causing the reduction of gametocytes in out-of-synch infections remain mysterious. Candidates for future investigation include alternative rhythmic factors involved in innate immune responses and the rhythmicity in essential resources required for gametocyte development. Explaining why it matters for gametocytes to be synchronized to host circadian rhythms might suggest novel approaches to blocking transmission.}, }
@article {pmid31932496, year = {2020}, author = {Jelacic, TM and Ribot, WJ and Chua, J and Boyer, AE and Woolfitt, AR and Barr, JR and Friedlander, AM}, title = {Human Innate Immune Cells Respond Differentially to Poly-γ-Glutamic Acid Polymers from Bacillus anthracis and Nonpathogenic Bacillus Species.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {204}, number = {5}, pages = {1263-1273}, pmid = {31932496}, issn = {1550-6606}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Bacillus anthracis/*immunology ; Bacillus licheniformis/*immunology ; Bacillus subtilis/*immunology ; Cytokines/immunology ; Dendritic Cells/*immunology ; Female ; Humans ; *Immunity, Innate ; Macrophages/*immunology ; Male ; Monocytes/*immunology ; Polyglutamic Acid/*immunology ; }, abstract = {The poly-γ-glutamic acid (PGA) capsule produced by Bacillus anthracis is composed entirely of d-isomer glutamic acid, whereas nonpathogenic Bacillus species produce mixed d-, l-isomer PGAs. To determine if B. anthracis PGA confers a pathogenic advantage over other PGAs, we compared the responses of human innate immune cells to B. anthracis PGA and PGAs from nonpathogenic B. subtilis subsp. chungkookjang and B. licheniformis Monocytes and immature dendritic cells (iDCs) responded differentially to the PGAs, with B. anthracis PGA being least stimulatory and B. licheniformis PGA most stimulatory. All three elicited IL-8 and IL-6 from monocytes, but B. subtilis PGA also elicited IL-10 and TNF-α, whereas B. licheniformis PGA elicited all those plus IL-1β. Similarly, all three PGAs elicited IL-8 from iDCs, but B. subtilis PGA also elicited IL-6, and B. licheniformis PGA elicited those plus IL-12p70, IL-10, IL-1β, and TNF-α. Only B. licheniformis PGA induced dendritic cell maturation. TLR assays also yielded differential results. B. subtilis PGA and B. licheniformis PGA both elicited more TLR2 signal than B. anthracis PGA, but only responses to B. subtilis PGA were affected by a TLR6 neutralizing Ab. B. licheniformis PGA elicited more TLR4 signal than B. anthracis PGA, whereas B. subtilis PGA elicited none. B. anthracis PGA persisted longer in high m.w. form in monocyte and iDC cultures than the other PGAs. Reducing the m.w. of B. anthracis PGA reduced monocytes' cytokine responses. We conclude that B. anthracis PGA is recognized less effectively by innate immune cells than PGAs from nonpathogenic Bacillus species, resulting in failure to induce a robust host response, which may contribute to anthrax pathogenesis.}, }
@article {pmid31931856, year = {2020}, author = {Yoosuf, N and Navarro, JF and Salmén, F and Ståhl, PL and Daub, CO}, title = {Identification and transfer of spatial transcriptomics signatures for cancer diagnosis.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {6}, pmid = {31931856}, issn = {1465-542X}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/classification/*diagnosis/genetics ; Carcinoma, Ductal, Breast/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Female ; Humans ; *Machine Learning ; Molecular Typing/*methods ; ROC Curve ; Spatial Analysis ; *Transcriptome ; }, abstract = {BACKGROUND: Distinguishing ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) regions in clinical biopsies constitutes a diagnostic challenge. Spatial transcriptomics (ST) is an in situ capturing method, which allows quantification and visualization of transcriptomes in individual tissue sections. In the past, studies have shown that breast cancer samples can be used to study their transcriptomes with spatial resolution in individual tissue sections. Previously, supervised machine learning methods were used in clinical studies to predict the clinical outcomes for cancer types.<br><br>METHODS: We used four publicly available ST breast cancer datasets from breast tissue sections annotated by pathologists as non-malignant, DCIS, or IDC. We trained and tested a machine learning method (support vector machine) based on the expert annotation as well as based on automatic selection of cell types by their transcriptome profiles.<br><br>RESULTS: We identified expression signatures for expert annotated regions (non-malignant, DCIS, and IDC) and build machine learning models. Classification results for 798 expression signature transcripts showed high coincidence with the expert pathologist annotation for DCIS (100%) and IDC (96%). Extending our analysis to include all 25,179 expressed transcripts resulted in an accuracy of 99% for DCIS and 98% for IDC. Further, classification based on an automatically identified expression signature covering all ST spots of tissue sections resulted in prediction accuracy of 95% for DCIS and 91% for IDC.<br><br>CONCLUSIONS: This concept study suggest that the ST signatures learned from expert selected breast cancer tissue sections can be used to identify breast cancer regions in whole tissue sections including regions not trained on. Furthermore, the identified expression signatures can classify cancer regions in tissue sections not used for training with high accuracy. Expert-generated but even automatically generated cancer signatures from ST data might be able to classify breast cancer regions and provide clinical decision support for pathologists in the future.}, }
@article {pmid31929965, year = {2019}, author = {Lin, L and Wang, X and Tang, C and Liang, J}, title = {Clinical Characteristics and Prognosis of Gastrointestinal Metastases in Solid Tumor Patients: A Retrospective Study and Review of Literatures.}, journal = {Analytical cellular pathology (Amsterdam)}, volume = {2019}, number = {}, pages = {4508756}, pmid = {31929965}, issn = {2210-7185}, mesh = {Adenocarcinoma/mortality/pathology/*secondary ; Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal/mortality/pathology/*secondary ; Female ; Gastrointestinal Neoplasms/mortality/*secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms/mortality/*pathology ; }, abstract = {BACKGROUND: According to the literature and our experience, patients with gastrointestinal metastases are relatively rare. Numerous case reports and literature reviews have been reported. We present one of the larger case series of gastrointestinal metastases.<br><br>OBJECTIVES: To explore the clinical characteristics and prognosis of patients with gastrointestinal tract metastases, which are rare metastatic sites.<br><br>METHODS: Patients with gastrointestinal metastases in the setting of stage IV primary carcinomas treated at Beijing Ditan Hospital and Peking University International Hospital from November 1992 to August 2017 were included in this study. The diagnosis of gastrointestinal tract metastases was based on histopathology.<br><br>RESULTS: 30 patients (median age 56 years, 56.7% female) were included. The most common primary carcinomas associated with gastrointestinal metastases were breast (11 patients, 36.7%), stomach (9 patients, 30.0%), and lung (4 patients, 13.3%) cancer. The major pathological types were adenocarcinoma (16 patients, 53.3%) and ductal carcinoma (9 patients, 30.0%). Ten patients (33.3%) underwent local gastrointestinal treatment, and 20 patients (66.7%) underwent nonlocal treatment (involving chemotherapy alone or best supportive care). For breast cancer patients and gastric cancer patients who underwent local therapy, a significant survival advantage was observed (p = 0.001 and p = 0.012, respectively). The presence of other common metastases was identified as an independent poor prognostic factor through multivariate analysis with a HR (hazard ratio) of survival of 0.182 (95% confidence interval (CI) 0.11-0.523, p = 0.031).<br><br>CONCLUSION: Gastrointestinal metastases are most frequently from breast invasive ductal carcinoma. The presentation of other common metastases with gastrointestinal metastasis indicates poor prognosis, and selected patients may benefit from surgical intervention.}, }
@article {pmid31929443, year = {2020}, author = {Eckert, L and Mattia, L and Patel, S and Okumura, R and Reynolds, P and Stuiver, I}, title = {Reducing the Risk of Indwelling Catheter-Associated Urinary Tract Infection in Female Patients by Implementing an Alternative Female External Urinary Collection Device: A Quality Improvement Project.}, journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society}, volume = {47}, number = {1}, pages = {50-53}, doi = {10.1097/WON.0000000000000601}, pmid = {31929443}, issn = {1528-3976}, mesh = {Adult ; California ; Catheter-Related Infections/prevention &amp; control ; Catheters, Indwelling/*adverse effects/microbiology ; Female ; Humans ; Quality Improvement ; Urinary Tract Infections/*prevention &amp; control ; Urine Specimen Collection/methods/*standards/statistics &amp; numerical data ; }, abstract = {PURPOSE: The purpose of this quality improvement project was to reduce catheter-associated urinary tract infection (CAUTI) risk for female patients by implementing a female external urinary collection (FEUC) device with suction as an alternative to indwelling catheter (IDC).<br><br>PARTICIPANTS AND SETTING: Participants were female patients admitted to our 386-bed community hospital in Southern California and who required urinary management.<br><br>APPROACH: We implemented a comprehensive CAUTI prevention program in 2014 that was in place for 1.5 years before this project was started. The CAUTI prevention program was based on the US Center for Disease Control and Prevention's CAUTI prevention recommendations. To supplement our CAUTI prevention efforts in our female patients, we implemented the FEUC device in our intensive care, telemetry, medical-surgical, orthopedic, and acute rehabilitations inpatient care units. Indwelling catheter use and CAUTI cases were identified by our Infection Prevention department.<br><br>OUTCOMES: Prior to introduction of the FEUC device, in 2015, the baseline female IDC utilization rate was 31.7% (7181 IDC device-days/22,656 patient-days) and the female CAUTI rate was 1.11 (8 cases/7181 IDC device-days) per 1000 days. Following introduction of the device, both rates declined. In 2016, the IDC utilization rate was 29.7% (P = .000) and the CAUTI rate was 0% (P =.005). We continued to observe a reduction in 2017 IDC utilization rates of 26% (P = .000); the 2017 CAUTI rate of 0.90 was not significantly different to our prior year rate (P = .726).<br><br>IMPLICATIONS FOR PRACTICE: We found that the introduction of the FEUC device reduced the risk for CAUTI. We will continue to prioritize the use of external devices for urinary management to help reduce the risk of our patients developing CAUTI.}, }
@article {pmid31927471, year = {2020}, author = {Mema, E and Schnabel, F and Chun, J and Kaplowitz, E and Price, A and Goodgal, J and Moy, L}, title = {The relationship of breast density in mammography and magnetic resonance imaging in women with triple negative breast cancer.}, journal = {European journal of radiology}, volume = {124}, number = {}, pages = {108813}, doi = {10.1016/j.ejrad.2020.108813}, pmid = {31927471}, issn = {1872-7727}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast Density/*physiology ; Cohort Studies ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/*diagnostic imaging ; Young Adult ; }, abstract = {PURPOSE: To evaluate the relationship between mammographic density, background parenchymal enhancement and fibroglandular tissue on MRI in women with triple negative breast cancer (TNBC) compared to women with non-triple negative breast cancer (non-TNBC).<br><br>METHODS: The institutional Breast Cancer Database was queried to identify the clinicopathologic and imaging characteristics among women who underwent mammography and breast MRI between 2010-2018. Statistical analyses included Pearson's Chi Square, Wilcoxon Rank-Sum and logistic regression.<br><br>RESULTS: Of 2995 women, 225 (7.5 %) had TNBC with a median age of 60 years (23-96) and median follow-up of 5.69 years. Compared to women with non-TNBC, TNBC was associated with African-American race 36/225 (16 %), BRCA1,2 positivity 34/225 (15.1 %), previous history of breast cancer 35/225 (15.6 %), presenting on breast exam 126/225 (56 %) or MRI 13/225 (5.8 %), palpability 133/225 (59.1 %), more invasive ductal carcinoma (IDC) 208/225 (92.4 %), higher stage (stage III) 37/225 (16.5 %), higher grade (grade 3) 186/225 (82.7 %) (all p < 0.001), lower mammographic breast density (MBD) 18/225 (8 %) (p = 0.04), lower fibroglandular tissue (FGT) 17/225 (7.6 %) (p = 0.01), and lower background parenchymal enhancement (BPE) 89/225 (39.8 %) (p = 0.02). Nine of 225 (4 %) women with TNBC experienced recurrence with no significant association with MBD, FGT, or BPE. There was no significant difference in median age of our TNBC and non-TNBC cohorts.<br><br>CONCLUSIONS: The higher proportion of women with lower MBD, FGT and BPE in women with TNBC suggests that MBD, amount of FGT and degree of BPE may be associated with breast cancer risk in women with TNBC.}, }
@article {pmid31907974, year = {2020}, author = {DeVaux, RS and Ropri, AS and Grimm, SL and Hall, PA and Herrera, EO and Chittur, SV and Smith, WP and Coarfa, C and Behbod, F and Herschkowitz, JI}, title = {Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling.}, journal = {Journal of cellular biochemistry}, volume = {121}, number = {7}, pages = {3465-3478}, pmid = {31907974}, issn = {1097-4644}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R21 CA185460/CA/NCI NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Interleukin-6/*genetics ; Neoplasm Invasiveness ; RNA, Antisense/*genetics ; RNA, Long Noncoding/*genetics ; STAT3 Transcription Factor/*metabolism ; Signal Transduction ; Tumor Microenvironment ; }, abstract = {Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive breast cancer. Only a small percentage of DCIS cases are predicted to progress; however, there is no method to determine which DCIS lesions will remain innocuous from those that will become invasive disease. Therefore, DCIS is treated aggressively creating a current state of overdiagnosis and overtreatment. There is a critical need to identify functional determinants of progression of DCIS to invasive ductal carcinoma (IDC). Interrogating biopsies from five patients with contiguous DCIS and IDC lesions, we have shown that expression of the long noncoding RNA BHLHE40-AS1 increases with disease progression. BHLHE40-AS1 expression supports DCIS cell proliferation, motility, and invasive potential. Mechanistically, BHLHE40-AS1 modulates interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) activity and a proinflammatory cytokine signature, in part through interaction with interleukin enhancer-binding factor 3. These data suggest that BHLHE40-AS1 supports early breast cancer progression by engaging STAT3 signaling, creating an immune-permissive microenvironment.}, }
@article {pmid31902979, year = {2019}, author = {Sultan, G and Zubair, S and Tayubi, IA and Dahms, HU and Madar, IH}, title = {Towards the early detection of ductal carcinoma (a common type of breast cancer) using biomarkers linked to the PPAR(γ) signaling pathway.}, journal = {Bioinformation}, volume = {15}, number = {11}, pages = {799-805}, pmid = {31902979}, issn = {0973-2063}, abstract = {Breast cancer is a leading cause of morbidity and mortality among women comprising about 12% females worldwide. The underlying alteration in the gene expression, molecular mechanism and metabolic pathways responsible for incidence and progression of breast tumorigenesis are yet not completely understood. In the present study, potential biomarker genes involved in the early progression for early diagnosis of breast cancer has been detailed. Regulation and Gene profiling of Ductal Carcinoma In-situ (DCIS), Invasive Ductal Carcinoma (IDC) and healthy samples have been analyzed to follow their expression pattern employing normalization, statistical calculation, DEGs annotation and Protein-Protein Interaction (PPI) network. We have performed a comparative study on differentially expressed genes among Healthy vs DCIS, Healthy vsIDC and DCIS vs IDC. We found MCM102 and SLC12A8as consistently over-expressed and LEP, SORBS1, SFRP1, PLIN1, FABP4, RBP4, CD300LG, ID4, CRYAB, ECRG4, G0S2, FMO2, ADAMTS5, CAV1, CAV2, ABCA8, MAMDC2, IGFBP6, CLDN11, TGFBR3as under-expressed genes in all the 3 conditions categorized for pre-invasive and invasive ductal breast carcinoma. These genes were further studied for the active pathways where PPAR(γ) signaling pathway was found to be significantly involved. The gene expression profile database can be a potential tool in the early diagnosis of breast cancer.}, }
@article {pmid31902119, year = {2020}, author = {Acun, T and Senses, KM}, title = {Downregulation of DNAJC10 (ERDJ5) is associated with poor survival in breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {27}, number = {3}, pages = {483-489}, pmid = {31902119}, issn = {1880-4233}, support = {2017-50737594-02//B&#xfc;lent Ecevit &#xdc;niversitesi/ ; 217S251//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;tirma Kurumu/ ; }, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*mortality/pathology ; DNA Copy Number Variations ; *DNA Methylation ; Down-Regulation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; HSP40 Heat-Shock Proteins/genetics/*metabolism ; Humans ; *Mutation ; Prognosis ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; Survival Rate ; }, abstract = {BACKGROUND: DNAJC10 (ERDJ5), a member of HSP40 family, was considered as an anti-oncogenic gene in neuroblastoma, prostate and colon cancers. But, the role and importance of DNAJC10 gene in breast cancer is currently unknown. In this study, in vitro/in vivo expression, biomarker potential and genetic/epigenetic alterations of DNAJC10 were analyzed in breast cancer.<br><br>METHODS: Real-time qRT-PCR and immunohistochemistry methods were used to determine the expression level of DNAJC10 gene in breast cancer cell lines and clinical samples. The Kaplan-Meier plotter was used to evaluate the survival prognostic value of DNAJC10 mRNA expression in breast cancer patients. Mutation screening software and methylation-specific PCR were used to screen genetic alterations and methylation status of DNAJC10 promoter regions, respectively.<br><br>RESULTS: DNAJC10 mRNA expression was significantly reduced in 3 out of 4 breast cancer cell lines compared to the nontumorigenic mammary epithelial cell line (MCF 10A). DNAJC10 protein expression was significantly less frequent in invasive ductal carcinoma samples (n&#x2009;=&#x2009;121) compared with adjacent normal breast tissues (n&#x2009;=&#x2009;32) (p&#x2009;<&#x2009;0.0001). Downregulation of DNAJC10 mRNA was associated with poor overall survival (OS) (n&#x2009;=&#x2009;626) (p&#x2009;=&#x2009;0.0096) and relapse-free survival (n&#x2009;=&#x2009;1764) (p&#x2009;=&#x2009;5.3e-12). According to the COSMIC and cBioPortal databases, point mutations and copy number variations of DNAJC10 were very rare in breast cancer samples. Besides, no genetic alterations on the experimentally validated promoter regions were found in breast cell lines. CpG island located in the promoter regions of DNAJC10 gene was found to be frequently hypomethylated in breast cell lines.<br><br>CONCLUSIONS: In the light of previous knowledge regarding the role of DNAJC10 in carcinogenesis, findings of this study suggest that DNAJC10 is a potential diagnostic/prognostic biomarker and tumor suppressor candidate for breast cancer. Epigenetic factors other than promoter methylation could contribute to the downregulation of DNAJC10 expression.}, }
@article {pmid31894281, year = {2020}, author = {Zhao, C and Zheng, S and Yan, Z and Deng, Z and Wang, R and Zhang, B}, title = {CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.}, journal = {Oncology reports}, volume = {43}, number = {2}, pages = {571-580}, doi = {10.3892/or.2019.7426}, pmid = {31894281}, issn = {1791-2431}, mesh = {Adult ; Aged ; Animals ; Annexin A2/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Chemokines, CC/*metabolism ; Disease Progression ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/metabolism/*pathology/*secondary ; MCF-7 Cells ; Mice ; Middle Aged ; Neoplasm Transplantation ; Tumor Burden ; }, abstract = {Chemokine (C‑C motif) ligand 18 (CCL18) is derived from breast tumor‑associated macrophages (TAMs), which are primarily a macrophage subpopulation with an M2 phenotype. CCL18 binds to its receptor, PYK2 N‑terminal domain interacting receptor 1 (Nir1), and promotes tumor progression and metastasis by inducing epithelial‑mesenchymal transition (EMT) via the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer cells. Recent research shows that Annexin A2 (AnxA2) plays a significant role in the invasion, metastasis, angiogenesis, proliferation, F‑actin polymerization and multidrug resistance to chemotherapy of breast cancer. The present study aimed to elucidate the molecular mechanisms by which CCL18 promotes breast cancer progression through AnxA2 which are not fully understood. Western blot analysis showed that the expression of AnxA2 was upregulated in highly invasive breast cancer cell lines and invasive ductal carcinoma. Furthermore, through chemotaxis, scratch, Matrigel invasion, and spontaneous metastasis assays, it was demonstrated that AnxA2 enhanced the invasion of breast cancer cells and the metastasis of human breast cancer cells to lungs of SCID mice with CCL18 stimulation. Cellular F‑actin measurement assay showed that reduction of AnxA2 suppressed CCL18‑induced F‑actin polymerization though phosphorylation of integrin β1 in breast cancer cells. Immunofluorescence and western blot analysis revealed that AnxA2 promoted CCL18‑induced EMT via the PI3K/Akt/GSK3β/Snail signaling pathway, and LY294002 inhibited the phosphorylation of AnxA2 in vitro. In brief, AnxA2, as a downstream molecule of Nir 1 binding to CCL18, promotes invasion and metastasis by EMT through the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer. This study suggests that AnxA2 is a potential anti‑invasion/metastasis target for therapeutic intervention in breast cancer.}, }
@article {pmid31876826, year = {2020}, author = {Phan Sy, O and Rouchy, RC and De Leiris, N and Nika, E and Djaileb, L}, title = {FDG PET/CT of a Supraclavicular Silicone Granuloma at Follow-up of a Breast Carcinoma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {3}, pages = {e169-e170}, doi = {10.1097/RLU.0000000000002894}, pmid = {31876826}, issn = {1536-0229}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/complications/*surgery ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Granuloma/*diagnostic imaging/*etiology/pathology ; Humans ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Silicones/*adverse effects ; }, abstract = {We report herein the case of a 33-year-old woman who was referred for FDG PET/CT staging prior to pregnancy after a 4-year lost to follow-up for a breast invasive ductal carcinoma (pT2N1 SBRII). FDG PET/CT revealed right supraclavicular lymphadenopathy potentially caused by breast carcinoma recurrence. No additional site was involved. Supraclavicular ultrasonography showed typical "snowstorm" appearance. MRI revealed signs of breast implant intracapsular rupture and signal intensity of silicone within a supraclavicular node. Fine-needle aspiration and microbiopsy of adenopathy finally confirmed silicone granuloma and ruled out breast cancer recurrence.}, }
@article {pmid31871301, year = {2020}, author = {Chen, G and Ding, XF and Pressley, K and Bouamar, H and Wang, B and Zheng, G and Broome, LE and Nazarullah, A and Brenner, AJ and Kaklamani, V and Jatoi, I and Sun, LZ}, title = {Everolimus Inhibits the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer Via Downregulation of MMP9 Expression.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {6}, pages = {1486-1496}, pmid = {31871301}, issn = {1557-3265}, support = {P30 CA054174/CA/NCI NIH HHS/United States ; R01 CA192564/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Down-Regulation ; Everolimus/*pharmacology ; Female ; Humans ; Matrix Metalloproteinase 9/chemistry/*metabolism ; Mice ; Mice, Nude ; Mice, Transgenic ; Receptor, ErbB-2/genetics/metabolism ; Spheroids, Cellular/drug effects/metabolism/pathology ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: We evaluated the role of everolimus in the prevention of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) progression.<br><br>EXPERIMENTAL DESIGN: The effects of everolimus on breast cancer cell invasion, DCIS formation, and DCIS progression to IDC were investigated in a 3D cell culturing model, intraductal DCIS xenograft model, and spontaneous MMTV-Her2/neu mouse model. The effect of everolimus on matrix metalloproteinase 9 (MMP9) expression was determined with Western blotting and IHC in these models and in patients with DCIS before and after a window trial with rapamycin. Whether MMP9 mediates the inhibition of DCIS progression to IDC by everolimus was investigated with knockdown or overexpression of MMP9 in breast cancer cells.<br><br>RESULTS: Everolimus significantly inhibited the invasion of human breast cancer cells in vitro. Daily intragastric treatment with everolimus for 7 days significantly reduced the number of invasive lesions from intraductal DCIS foci and inhibited DCIS progression to IDC in the MMTV-Her2/neu mouse mammary tumor model. Mechanistically, everolimus treatment decreased the expression of MMP9 in the in vitro and in vivo models, and in breast tissues from patients with DCIS treated with rapamycin for 1 week. Moreover, overexpression of MMP9 stimulated the invasion, whereas knockdown of MMP9 inhibited the invasion of breast cancer cell-formed spheroids in vitro and DCIS in vivo. Knockdown of MMP9 also nullified the invasion inhibition by everolimus in vitro and in vivo.<br><br>CONCLUSIONS: Targeting mTORC1 can inhibit DCIS progression to IDC via MMP9 and may be a potential strategy for DCIS or early-stage IDC therapy.}, }
@article {pmid31861274, year = {2019}, author = {Micus, S and Kirsten, I and Haupt, M and Gresser, GT}, title = {Analysis of Hot Bar Soldering, Insulation Displacement Connections (IDC), and Anisotropic Conductive Adhesives (ACA), for the Automated Production of Smart Textiles.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {1}, pages = {}, pmid = {31861274}, issn = {1424-8220}, abstract = {Despite all the growth forecasts of the smart textiles market, there is no stable automated manufacturing process for attaching classic electronics to textiles. The great amount of manual production steps causes high prices, which slow down market growth. During the production process, the contacting step offers the greatest potential to reduce manual manufacturing steps. For this reason, we have analyzed various contacting methods for electronic parts on conductive yarns that have a high potential for automation. The chosen methods were thermode soldering, insulation-displacement connectors and anisotropic conductive adhesives. In order to ensure reliable mechanical contacting, the samples were tested in a peeling experiment. The examination of the contact resistances took place in the context of a resistance test using four-wire measuring technology.}, }
@article {pmid31856858, year = {2019}, author = {Wan, L and Liu, T and Hong, Z and Pan, Y and Sizemore, ST and Zhang, J and Ma, Z}, title = {NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {148}, pmid = {31856858}, issn = {1465-542X}, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Nedd4 Ubiquitin Protein Ligases/*genetics/metabolism ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Receptor, IGF Type 1/metabolism ; Young Adult ; }, abstract = {BACKGROUND: A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4.<br><br>METHODS: The impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445&#x2009;BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n&#x2009;=&#x2009;37), invasive ductal carcinomas (IDC, n&#x2009;=&#x2009;408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan-Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method.<br><br>RESULTS: NEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P&#x2009;=&#x2009;0.030), nodal status (P&#x2009;=&#x2009;0.001), estrogen receptor status (P&#x2009;=&#x2009;0.035), and progesterone receptor status (P&#x2009;=&#x2009;0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P&#x2009;=&#x2009;0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P&#x2009;=&#x2009;0.0024 and P&#x2009;=&#x2009;0.0011, respectively).<br><br>CONCLUSIONS: NEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment.}, }
@article {pmid31856344, year = {2020}, author = {Giles, M and Graham, L and Ball, J and King, J and Watts, W and Harris, A and Oldmeadow, C and Ling, R and Paul, M and O'Brien, A and Parker, V and Wiggers, J and Foureur, M}, title = {Implementation of a multifaceted nurse-led intervention to reduce indwelling urinary catheter use in four Australian hospitals: A pre- and postintervention study.}, journal = {Journal of clinical nursing}, volume = {29}, number = {5-6}, pages = {872-886}, doi = {10.1111/jocn.15142}, pmid = {31856344}, issn = {1365-2702}, support = {//NSW Ministry of Health Translational Research Grants Scheme/ ; }, mesh = {Adult ; Catheter-Related Infections/etiology/*prevention &amp; control ; Catheters, Indwelling/*adverse effects ; Controlled Before-After Studies ; Female ; Humans ; Male ; New South Wales ; Patient Care Bundles/*nursing ; Practice Patterns, Nurses' ; Urinary Catheters/*adverse effects ; Urinary Tract Infections/etiology/*prevention &amp; control ; }, abstract = {AIMS AND OBJECTIVES: This study aimed to reduce indwelling urinary catheter (IDC) use and duration through implementation of a multifaceted "bundled" care intervention.<br><br>BACKGROUND: Indwelling urinary catheters present a risk for patients through the potential development of catheter-associated urinary tract infection (CAUTI), with duration of IDC a key risk factor. Catheter-associated urinary tract infection is considered preventable yet accounts for over a third of all hospital-acquired infections. The most effective CAUTI reduction strategy is to avoid IDC use where ever possible and to remove the IDC as early as appropriate.<br><br>DESIGN: A cluster-controlled pre- and poststudy at a facility level with a phased intervention implementation approach.<br><br>METHODS: A multifaceted intervention involving a "No CAUTI" catheter care bundle was implemented, in 4 acute-care hospitals, 2 in metropolitan and 2 in rural locations, in New South Wales, Australia. Indwelling urinary catheter point prevalence and duration data were collected at the bedside on 1,630 adult inpatients at preintervention and 1,677 and 1,551 at 4 and 9&#xa0;months postintervention. This study is presented in line with the StaRI checklist (see Appendix S1).<br><br>RESULTS: A nonsignificant trend towards reduction in IDC prevalence was identified, from 12% preintervention to 10% of all inpatients at 4 and 9&#xa0;months. Variability in preintervention IDC prevalence existed across hospitals (8%-16%). Variability in reduction was evident across hospitals at 4&#xa0;months (between -2% and 4%) and 9&#xa0;months (between 0%-8%). Hospitals with higher preintervention prevalence showed larger decreases, up to 50% when preintervention prevalence was 16%. Indwelling urinary catheter duration increased as more of the short-term IDC placements were avoided.<br><br>CONCLUSIONS: Implementation of a multifaceted intervention resulted in reduced IDC use in four acute-care hospitals in Australia. This result was not statistically significant but did reflect a positive trend of reduction. There was a significant reduction in short-term IDC use at 9&#xa0;months postintervention.<br><br>Clinical nurse leaders can effectively implement change strategies that influence patient outcomes. Implementation of the evidence-based "No CAUTI" bundle increased awareness of appropriate indications and provided nurses with the tools to inform decision-making related to insertion and removal of IDCs in acute inpatient settings. Working in partnership with inpatients and the multidisciplinary team is essential in minimising acute-care IDC use.}, }
@article {pmid31856180, year = {2019}, author = {Walzer, KA and Fradin, H and Emerson, LY and Corcoran, DL and Chi, JT}, title = {Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging.}, journal = {PLoS genetics}, volume = {15}, number = {12}, pages = {e1008506}, pmid = {31856180}, issn = {1553-7404}, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Developmental ; In Situ Hybridization, Fluorescence/*methods ; Life Cycle Stages ; Microfluidic Analytical Techniques ; Multigene Family ; Plasmodium falciparum/genetics/*growth &amp; development ; Protozoan Proteins/*genetics ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; }, abstract = {Malaria parasites follow a complex life cycle that consists of multiple stages that span from the human host to the mosquito vector. Among the species causing malaria, Plasmodium falciparum is the most lethal, with clinical symptoms manifesting during the intraerythrocytic developmental cycle (IDC). During the IDC, P. falciparum progresses through a synchronous and continuous cascade of transcriptional programming previously established using population analyses. While individual parasites are known to exhibit transcriptional variations to evade the host immune system or commit to a sexual fate, such rare expression heterogeneity is largely undetectable on a population level. Therefore, we combined single-cell RNA-sequencing (scRNA-seq) on a microfluidic platform and fluorescence imaging to delineate the transcriptional variations among individual parasites during late asexual and sexual stages. The comparison between asexual and sexual parasites uncovered a set of previously undefined sex-specific genes. Asexual parasites were segregated into three distinct clusters based on the differential expression of genes encoding SERAs, rhoptry proteins, and EXP2 plus transporters. Multiple pseudotime analyses revealed that these stage-specific transitions are distinct. RNA fluorescent in situ hybridization of cluster-specific genes validated distinct stage-specific expression and transitions during the IDC and defined the highly variable transcriptional pattern of EXP2. Additionally, these analyses indicated huge variations in the stage-specific transcript levels among parasites. Overall, scRNA-seq and RNA-FISH of P. falciparum revealed distinct stage transitions and unexpected degrees of heterogeneity with potential impact on transcriptional regulation during the IDC and adaptive responses to the host.}, }
@article {pmid31849934, year = {2019}, author = {Alexia, C and Cren, M and Louis-Plence, P and Vo, DN and El Ahmadi, Y and Dufourcq-Lopez, E and Lu, ZY and Hernandez, J and Shamilov, F and Chernysheva, O and Vasilieva, M and Vorotnikov, I and Vishnevskay, Y and Tupitsyn, N and Rossi, JF and Villalba, M}, title = {Polyoxidonium[®] Activates Cytotoxic Lymphocyte Responses Through Dendritic Cell Maturation: Clinical Effects in Breast Cancer.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2693}, pmid = {31849934}, issn = {1664-3224}, mesh = {Adenocarcinoma/*drug therapy/immunology ; Adjuvants, Immunologic/*therapeutic use ; Adult ; Aged ; Breast Neoplasms/*drug therapy/immunology ; Cell Differentiation/drug effects/immunology ; Chemotherapy, Adjuvant/methods ; Dendritic Cells/*drug effects/immunology ; Female ; Humans ; Killer Cells, Natural/drug effects/immunology ; Lymphocyte Activation/drug effects/immunology ; Lymphocytes, Tumor-Infiltrating/drug effects/immunology ; Middle Aged ; Neoadjuvant Therapy/methods ; Piperazines/*therapeutic use ; Polymers/*therapeutic use ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; }, abstract = {Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4[+] T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 μg/ml, and it stimulates expression of several DC co-stimulatory molecules, inducing the proliferation of allogeneic T cells. In contrast, PO decreases DC viability when added at day 5 post-expansion. PO is not toxic for NK cells at doses up to 100 μM and does not affect their activation, maturation, and cytotoxicity but tends to increase degranulation. This could be beneficial against target cells that show low sensitivity to NK cells, e.g., solid tumor cells. Finally, we have found great variability in PO response between donors. In summary, our in vitro results show that PO increases the number of costimulatory molecules on DC that prime T cells, favoring the production of effector T cells. This may support the future clinical development of PO in cancer treatment.}, }
@article {pmid31849088, year = {2020}, author = {Arispe Angulo, KR and Jawa, Z and Visotcky, A and Majidi, SS and Chitambar, CR and Jorns, JM}, title = {A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology.}, journal = {Histopathology}, volume = {76}, number = {5}, pages = {661-670}, doi = {10.1111/his.14049}, pmid = {31849088}, issn = {1365-2559}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Chemotherapy, Adjuvant/methods ; Female ; Humans ; Middle Aged ; Mitotic Index ; Neoadjuvant Therapy/methods ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIMS: Neoadjuvant chemotherapy (NAC) is frequently used for the treatment of breast cancer. We sought to analyse the clinical, morphological and immunohistochemical features of tumours from patients who did not achieve pathological complete response following NAC.<br><br>METHODS AND RESULTS: We identified stage I-III post-NAC breast cancers from surgical resections (2000-2016) with evaluable residual invasive carcinoma [ypT1a(m) or greater and &#x2265;15% tumour cellularity]. One hundred and forty-three tumours from 142 patients were included. On univariable analysis, a high (score 3) post-NAC mitotic score (as compared with 1 or 2) was significantly associated with invasive ductal carcinoma (IDC) subtype (P&#xa0;=&#xa0;0.023), high grade, pushing borders with zones of necrosis, hormone receptor and triple-negative status, lack of hormonal therapy, higher cellularity (P&#xa0;<&#xa0;0.001), and a higher percentage of tumour-infiltrating lymphocytes (P&#xa0;=&#xa0;0.016). Multivariable analysis showed a high post-NAC mitotic score to be significantly associated with recurrence, distant metastasis, and shortened survival (hazard ratios of 5.73, 4.49, and 3.68, respectively). High post-NAC mitotic score tumours (n&#xa0;=&#xa0;32) were IDC and had a high Ki67 proliferation index (median, 55%). Of these, 24 (75%) had pushing borders with zones of necrosis; 19 (79.2%) of these had necrosis on preoperative imaging, and 24 (75%), 15 (46.9%) and four (12.5%) lacked androgen receptor, GATA-3 and cytokeratin 18 expression, respectively.<br><br>CONCLUSIONS: High post-NAC mitotic score breast cancers cause high morbidity and mortality, frequently have pushing borders and zones of necrosis, and may show loss of common 'breast cancer markers'. Our findings support that necrosis in pretreatment studies and post-NAC mitotic score should be routinely reported, as they offer significant additional prognostic information to guide management.}, }
@article {pmid31844635, year = {2019}, author = {Redell, M and Sierra-Hoffman, M and Assi, M and Bochan, M and Chansolme, D and Gandhi, A and Sheridan, K and Soosaipillai, I and Walsh, T and Massey, J}, title = {The CHROME Study, a Real-world Experience of Single- and Multiple-Dose Oritavancin for Treatment of Gram-Positive Infections.}, journal = {Open forum infectious diseases}, volume = {6}, number = {11}, pages = {ofz479}, pmid = {31844635}, issn = {2328-8957}, abstract = {BACKGROUND: Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens.<br><br>METHODS: Data collected from a retrospective observational program (2014-2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections.<br><br>RESULTS: Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2-10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%.<br><br>CONCLUSIONS: We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.}, }
@article {pmid31844357, year = {2019}, author = {Amadi, OF and Okeke, IB and Ndu, IK and Ekwochi, U and Nduagubam, OC and Ezenwosu, OU and Asinobi, IN and Osuorah, CD}, title = {Cancer Mortality in the Niger Delta Region of Nigeria: A Case Study of the University of Port Harcourt Teaching Hospital.}, journal = {Nigerian medical journal : journal of the Nigeria Medical Association}, volume = {60}, number = {5}, pages = {262-267}, pmid = {31844357}, issn = {0300-1652}, abstract = {AIM: The aim of this study is to determine the pattern of cancer mortality (CM) seen in the University of Port Harcourt Teaching Hospital (UPTH) which is a cancer reference center in the Niger Delta Region.<br><br>METHODOLOGY: This is a 6-year retrospective study of cancer-related deaths in UPTH using patients' admission registers in all the wards and emergency units. Furthermore, the death certificates of cases were reviewed.<br><br>RESULTS: Three hundred and sixteen cases of cancer-related deaths occurred, involving 174 females and 142 males, in a female-to-male sex ratio of 1.2:1. All age groups were affected, with age group 40-49 years accounting for the majority (20.6%). CM was seen in all the systems, except the central nervous system. Cancers of the gastrointestinal tract and its accessory organs (liver and gall bladder) caused most mortality (27.9%), in a female-to-male ratio of 0.8:1. The single most involved organ in CM is the female breast (20.6%), distantly followed by mortality due to prostate cancers and hematolymphoid cancers which accounted for 9.2% each. Colorectal cancers accounted for 7.3% of cancer deaths and ranked 4[th]. Cancers of both cervix and stomach each accounted for 5.7% of mortality. The major histologic diagnoses were carcinomas (adenocarcinoma; 36.7%, invasive ductal carcinoma; 20.3%, squamous cell carcinomas; 8.2% and hepatocellular carcinomas; 4.4%). Leukemias and lymphomas accounted for 9.2% of cases, whereas sarcomas accounted for 5.1% of cases.<br><br>CONCLUSION: Infection-related and noninfection-related cancers cause most mortality in UPTH. The 5[th] decade was the most commonly affected, while female breast was the single most involved organ. Breast, prostate and hematolymphoid malignancies are common causes of CM with death from breast occurring earliest. Majority of the deceased were educated, working-class urban dwellers. More advocacies on public acceptance of cancer screening and cancer preventive lifestyles as well as governments' improvement on workforce training and treatment infrastructure will improve the current CM profile in Port Harcourt.}, }
@article {pmid31814295, year = {2020}, author = {Li, Y and Su, P and Wang, Y and Zhang, H and Liang, Y and Zhang, N and Song, X and Li, X and Li, J and Yang, Q}, title = {Impact of histotypes on preferential organ-specific metastasis in triple-negative breast cancer.}, journal = {Cancer medicine}, volume = {9}, number = {3}, pages = {872-881}, pmid = {31814295}, issn = {2045-7634}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*epidemiology/secondary ; Brain Neoplasms/*epidemiology/secondary ; Breast/pathology ; Carcinoma, Ductal, Breast/*epidemiology/secondary ; Carcinoma, Lobular/*epidemiology/secondary ; Female ; Humans ; Liver Neoplasms/*epidemiology/secondary ; Lung Neoplasms/*epidemiology/secondary ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; SEER Program/statistics &amp; numerical data ; Triple Negative Breast Neoplasms/mortality/*pathology ; Young Adult ; }, abstract = {BACKGROUND: The distant metastasis was the most predictive characters of poor prognosis for triple-negative breast cancer (TNBC). We aimed to evaluate the correlation between patient characters and preferential distant metastatic sites (DMS) and its effects on prognosis.<br><br>METHODS: Using the 2010-2014 Surveillance, Epidemiology, and End Results Program (SEER) data, patients with TNBC were classified into eight histologic subtypes. Patient characters were compared using a chi-squared test. Logistic regression was used for identification of predictive factors. The log-rank testing was utilized with disease-specific survival (DSS) and overall survival (OS) as the primary outcomes.<br><br>RESULTS: A total of 23&#xa0;270 patients with TNBC were involved, including 1544 patients with distant metastatic cancer. Bone metastasis was diagnosed in 559 cases, brain metastasis in 124 cases, liver metastasis found in 369 cases and lung metastasis in 492 cases. Histologic subtypes including metaplastic breast carcinoma and invasive lobular carcinoma showed significant differences in preferential DMS compared with invasive ductal carcinoma. Furthermore, we found different histologic subtypes with specific DMS showed various prognosis. We also evaluated different DMS of specific histologic subtypes showed different prognosis.<br><br>CONCLUSION: Certain histologic subtypes of breast cancer are associated with preferential DMS and prognosis; this knowledge may help to further understand the mechanism of breast cancer metastasis and to monitor the prognosis of patients with TNBC.}, }
@article {pmid31809502, year = {2019}, author = {Pick, FC and Fish, KE and Biggs, CA and Moses, JP and Moore, G and Boxall, JB}, title = {Application of enhanced assimilable organic carbon method across operational drinking water systems.}, journal = {PloS one}, volume = {14}, number = {12}, pages = {e0225477}, pmid = {31809502}, issn = {1932-6203}, mesh = {Carbon/*analysis/metabolism ; Drinking Water/chemistry/microbiology/*standards ; Flow Cytometry/methods ; Organic Chemicals/*analysis/metabolism ; Pseudomonas fluorescens/metabolism ; Reproducibility of Results ; Spirillum/metabolism ; Water Microbiology/*standards ; Water Purification ; Water Quality/*standards ; }, abstract = {Assimilable organic carbon (AOC) is known to correlate with microbial growth, which can consequently degrade drinking water quality. Despite this, there is no standardised AOC test that can be applied to drinking water distribution systems (DWDS). Herein we report the development of a quick, robust AOC that incorporates known strains Pseudomonas fluorescens strain P-17 and Spirillum strain NOX, a higher inoculum volume and enumeration using flow cytometry to generate a quicker (total test time reduced from 14 to 8 days), robust method. We apply the developed AOC test to twenty drinking water treatment works (WTW) to validate the method reproducibility and resolution across a wide range of AOC concentrations. Subsequently, AOC was quantified at 32 sample points, over four DWDS, for a year in order to identify sinks and sources of AOC in operative networks. Application of the developed AOC protocol provided a previously unavailable insight and novel evidence of pipes and service reservoirs exhibiting different AOC and regrowth behaviour. Observed correlations between AOC and microbial growth highlight the importance of monitoring AOC as an integral part of managing drinking water quality at the consumers tap.}, }
@article {pmid31791269, year = {2019}, author = {Lee, CH and Hsieh, JC and Wu, TM and Yeh, TS and Wang, HM and Lin, YC and Chen, JS and Lee, CL and Huang, WK and Hung, TM and Yen, TT and Chan, SC and Chou, WC and Kuan, FC and Hu, CC and Chang, PH}, title = {Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {1167}, pmid = {31791269}, issn = {1471-2407}, support = {CMRPG2D0171, CMRPG2D0172, CMRPG2G0681, CMRPG2G0682//Chang Gung Memorial Hospital/ ; CMRPG2D0173//Chang Gung Memorial Hospital/ ; PMRPG3G0791, CMRPG3G0771, CORPG3F0731, CMRPG3E1631-33//Chang Gung Memorial Hospital/ ; CMRPG3G1131-1133, CMRPG3H0871-73//Chang Gung Memorial Hospital/ ; MOST-108-2628-B-182A-001//Ministry of Science and Technology, Taiwan/ ; MOST-107-2314-B-182-053, MOST-104-2314-B-182-031-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {AC133 Antigen/immunology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/*mortality/pathology ; Cell Count ; Female ; Humans ; Liquid Biopsy ; Middle Aged ; Neoplastic Cells, Circulating/immunology/*pathology ; Neoplastic Stem Cells/immunology/*pathology ; Prognosis ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy.<br><br>METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM[+]Hoechst[+]CD45[-] cells and cCSCs as CD133[+]EpCAM[+]Hoechst[+]CD45[-] cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses.<br><br>RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p&#xa0;<&#x2009;0.001), overall survival (OS; median: 27.7&#x2009;months vs. not reached, p&#x2009;<&#x2009;0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0&#x2009;months, p&#x2009;<&#x2009;0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS.<br><br>CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.}, }
@article {pmid31789065, year = {2020}, author = {Tijani, S and Sharma, K and Yuen, H and Shaaban, A}, title = {Metastatic "Ductal Carcinoma In Situ-Like" Lobular Carcinoma in a Lymph Node: A Case Report and Review of the Literature.}, journal = {International journal of surgical pathology}, volume = {28}, number = {4}, pages = {436-439}, doi = {10.1177/1066896919888744}, pmid = {31789065}, issn = {1940-2465}, mesh = {Axilla ; Biomarkers, Tumor/analysis/metabolism ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/secondary/surgery ; Carcinoma, Lobular/*diagnosis/secondary/surgery ; Diagnosis, Differential ; Diagnostic Errors/prevention &amp; control ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy ; Middle Aged ; }, abstract = {Metastatic breast cancer resembling ductal carcinoma in situ (DCIS) is a rare phenomenon. In this article, we present a unique case of metastatic lobular carcinoma with DCIS-like morphology in the left axillary lymph nodes of a 52-year-old female. She presented with 2 lesions in the left breast on mammography, and a mastectomy with axillary lymph node dissection was performed. Gross examination showed a 3.5 × 2.5 × 1.0 cm indistinct tumor in the lower outer quadrant and a 2.5 × 2.5 × 1.8 cm tumor in the upper outer quadrant. Microscopic assessment revealed a pleomorphic lobular carcinoma in the lower outer quadrant and a grade 2 invasive ductal carcinoma in the upper outer quadrant. Sixteen of the 17 axillary lymph nodes showed metastatic lobular carcinoma with foci of solid and comedo-type DCIS-like features. Immunohistochemical analysis of the primary and metastatic lobular carcinoma showed no expression of E-cadherin and p63 antibodies. To our knowledge, metastatic lobular carcinoma exhibiting this pattern has not been reported. The case suggests that lobular carcinoma can morphologically recreate a primary microenvironment at a distant site and simulate in situ growth. Recognition of this pattern is important to avoid misdiagnosis.}, }
@article {pmid31779581, year = {2019}, author = {Luo, K and Wang, S and Fu, Y and Zhou, P and Huang, X and Gu, Q and Li, W and Wang, Y and Hu, F and Liu, S}, title = {Rapid genomic DNA variation in newly hybridized carp lineages derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂).}, journal = {BMC genetics}, volume = {20}, number = {1}, pages = {87}, pmid = {31779581}, issn = {1471-2156}, mesh = {Animals ; Carps/genetics/*physiology ; Evolution, Molecular ; Female ; Fish Proteins/genetics ; *Genetic Variation ; Goldfish/genetics/*physiology ; Homeodomain Proteins/*genetics ; Hybridization, Genetic ; Male ; Multigene Family ; Sequence Analysis, DNA/veterinary ; }, abstract = {BACKGROUND: Distant hybridization can generate changes in phenotypes and genotypes that lead to the formation of new hybrid lineages with genetic variation. In this study, the establishment of two bisexual fertile carp lineages, including the improved diploid common carp (IDC) lineage and the improved diploid scattered mirror carp (IDMC) lineage, from the interspecific hybridization of common carp (Cyprinus carpio, 2n = 100) (♀) × blunt snout bream (Megalobrama amblycephala, 2n = 48) (♂), provided a good platform to investigate the genetic relationship between the parents and their hybrid progenies.<br><br>RESULT: In this study, we investigated the genetic variation of 12 Hox genes in the two types of improved&#xa0;carp lineages derived from common carp (&#x2640;)&#x2009;&#xd7;&#x2009;blunt snout bream (&#x2642;). Hox gene clusters were abundant in the first generation of IDC, but most were not stably inherited in the second generation. In contrast, we did not find obvious mutations in Hox genes in the first generation of IDMC, and almost all the Hox gene clusters were stably inherited from the first generation to the second generation of IDMC. Interestingly, we found obvious recombinant clusters of Hox genes in both&#xa0;improved carp lineages, and partially recombinant clusters of Hox genes were stably inherited from the first generation to the second generation in both types of improved&#xa0;carp lineages. On the other hand, some Hox genes were gradually becoming pseudogenes, and some genes were completely pseudogenised in IDC or IDMC.<br><br>CONCLUSIONS: Our results provided important evidence that distant hybridization produces rapid genomic DNA changes that may or may not be stably inherited, providing novel insights into the function of hybridization in the establishment of improved lineages used as new fish resources for aquaculture.}, }
@article {pmid31765735, year = {2020}, author = {Morimoto, M and Horikoshi, Y and Nakaso, K and Kurashiki, T and Kitagawa, Y and Hanaki, T and Sakamoto, T and Honjo, S and Umekita, Y and Fujiwara, Y and Matsura, T}, title = {Oncogenic role of TYRO3 receptor tyrosine kinase in the progression of pancreatic cancer.}, journal = {Cancer letters}, volume = {470}, number = {}, pages = {149-160}, doi = {10.1016/j.canlet.2019.11.028}, pmid = {31765735}, issn = {1872-7980}, mesh = {Aged ; Animals ; Carcinogenesis ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MAP Kinase Signaling System ; Male ; Mice ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Pancreas/pathology ; Pancreatic Neoplasms/mortality/*pathology ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {The expression and functions of TYRO3, a member of the TAM receptor tyrosine kinase family, in pancreatic cancer (PC) have not been specifically elucidated. In this study, we confirmed TYRO3 expression in five human PC cell lines (PANC-1, MIA PaCa-2, BxPC-3, AsPC-1, and PK-9) using Western blotting. TYRO3 silencing and overexpression studies have revealed that TYRO3 promotes cell proliferation and invasion in PC via phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK). Using a mouse xenograft model, we showed that tumor growth was significantly suppressed in mice subcutaneously inoculated with TYRO3-knockdown PC cells compared with mice inoculated with control PC cells. Furthermore, TYRO3 expression was examined in PC tissues obtained from 106 patients who underwent pancreatic resection for invasive ductal carcinoma through immunohistochemical staining. TYRO3-positive patients had poor prognoses for overall survival and disease-specific survival compared with TYRO3-negative patients. Multivariate analysis revealed that TYRO3 expression is an independent prognostic factor for overall survival. Our study demonstrates the critical role of TYRO3 in PC progression through Akt and ERK activation and suggests TYRO3 as a novel promising target for therapeutic strategies against PC.}, }
@article {pmid31748977, year = {2020}, author = {Petry, V and Bonadio, RC and Cagnacci, AQC and Senna, LAL and Campos, RDNG and Cotti, GC and Hoff, PM and Fragoso, MCBV and Estevez-Diz, MDP}, title = {Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li-Fraumeni syndrome).}, journal = {Familial cancer}, volume = {19}, number = {1}, pages = {47-53}, pmid = {31748977}, issn = {1573-7292}, mesh = {Adult ; Brazil/epidemiology ; Breast Neoplasms/genetics/*radiotherapy ; Female ; Fibrosarcoma/epidemiology ; Follow-Up Studies ; *Genes, p53 ; *Germ-Line Mutation ; Humans ; Leiomyosarcoma/epidemiology ; Li-Fraumeni Syndrome/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Radiation-Induced/*epidemiology ; Radiotherapy, Adjuvant/adverse effects ; Retrospective Studies ; Young Adult ; }, abstract = {The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li-Fraumeni syndrome (LFS) or Li-Fraumeni Like (LFL) patients. However, the type of TP53 pathogenic germline variant may possibly influence this risk. TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenic TP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germline TP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by the Hereditary Cancer Group of an academic cancer center. Our primary objective was to evaluate the occurrence of RIMs after adjuvant radiotherapy. Sixteen patients were evaluated; 10 (62.5%) had a germline TP53 p.R337H pathogenic variant. Median age was 39.8 years. Thirteen patients had invasive ductal carcinoma: 8 (61.5%) were hormone receptor-positive; 6 (46.1%), human epithelial growth factor receptor 2 (HER2)-amplified. Three patients had ductal carcinoma in situ. Most patients (N = 12/16, 75%) received adjuvant radiotherapy. After a median follow-up of 52.5 months, 2 patients (2/12, 16.6%) had RIMs. One had a fibrosarcoma and the other, a low-grade leiomyosarcoma. In the group treated with radiotherapy, one distant recurrence was diagnosed (1/12), and no loco-regional recurrence occurred. Among 4 patients who did not receive radiotherapy, 2 presented with loco-regional recurrence. In this cohort of patients with LFS enriched in TP53 p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature. Nevertheless, rates of RIMs were still alarming. Early molecular diagnosis and careful evaluation of treatment risks and benefits are essential for these patients.}, }
@article {pmid31744918, year = {2019}, author = {Xie, M and Leroy, H and Mascarau, R and Woottum, M and Dupont, M and Ciccone, C and Schmitt, A and Raynaud-Messina, B and Vérollet, C and Bouchet, J and Bracq, L and Benichou, S}, title = {Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction.}, journal = {mBio}, volume = {10}, number = {6}, pages = {}, pmid = {31744918}, issn = {2150-7511}, mesh = {CD4-Positive T-Lymphocytes/metabolism/virology ; Dendritic Cells/metabolism/virology ; HIV Infections/*metabolism/*virology ; HIV-1/*physiology ; Humans ; Macrophages/metabolism/virology ; Myeloid Cells/metabolism/virology ; SAM Domain and HD Domain-Containing Protein 1/*metabolism ; *Viral Tropism ; *Virus Replication ; }, abstract = {Dendritic cells (DCs) and macrophages as well as osteoclasts (OCs) are emerging as target cells of HIV-1 involved in virus transmission, dissemination, and establishment of persistent tissue virus reservoirs. While these myeloid cells are poorly infected by cell-free viruses because of the high expression levels of cellular restriction factors such as SAMHD1, we show here that HIV-1 uses a specific and common cell-to-cell fusion mechanism for virus transfer and dissemination from infected T lymphocytes to the target cells of the myeloid lineage, including immature DCs (iDCs), OCs, and macrophages, but not monocytes and mature DCs. The establishment of contacts with infected T cells leads to heterotypic cell fusion for the fast and massive transfer of viral material into OC and iDC targets, which subsequently triggers homotypic fusion with noninfected neighboring OCs and iDCs for virus dissemination. These two cell-to-cell fusion processes are not restricted by SAMHD1 and allow very efficient spreading of virus in myeloid cells, resulting in the formation of highly virus-productive multinucleated giant cells. These results reveal the cellular mechanism for SAMHD1-independent cell-to-cell spreading of HIV-1 in myeloid cell targets through the formation of the infected multinucleated giant cells observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients.IMPORTANCE We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive multinucleated giant cells as observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. Since myeloid cells are emerging as important target cells of HIV-1, these results contribute to a better understanding of the role of these myeloid cells in pathogenesis, including cell-associated virus sexual transmission, cell-to-cell virus spreading, and establishment of long-lived viral tissue reservoirs.}, }
@article {pmid31737920, year = {2020}, author = {Taylor, AS and Morgan, TM and Wallington, DG and Chinnaiyan, AM and Spratt, DE and Mehra, R}, title = {Correlation between cribriform/intraductal prostatic adenocarcinoma and percent Gleason pattern 4 to a 22-gene genomic classifier.}, journal = {The Prostate}, volume = {80}, number = {2}, pages = {146-152}, pmid = {31737920}, issn = {1097-0045}, support = {P50 CA069568/CA/NCI NIH HHS/United States ; P50 CA186786/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/*genetics/*pathology ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal/*genetics/*pathology ; Cell Growth Processes/genetics ; Cohort Studies ; Genetic Predisposition to Disease ; Genomics/methods ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/*pathology ; RNA, Neoplasm/*genetics ; }, abstract = {BACKGROUND: The Decipher test measures expression of 22 RNA biomarkers associated with aggressive prostate cancer used to improve risk stratification of patients to help guide management. To date, Decipher's genomic classification has not been extensively correlated with specific histologic growth patterns in prostatic adenocarcinoma. With a growing understanding of the clinical aggressiveness associated with cribriform growth pattern (CF), intraductal carcinoma (IDC), and percent Gleason pattern 4 (G4%), we sought to determine if their presence was associated with an increased genomic risk as measured by the Decipher assay.<br><br>DESIGN: Clinical use of the Decipher assay was performed on the highest Gleason score (GS) tumor nodule of prostatectomy specimens from a prospective cohort of 48 patients, with GS varying from 7 through 9 to help guide clinical risk stratification. The tumors were reviewed for CF, IDC, and G4%, which were then compared to the Decipher score (0-1) and risk stratification (high vs not high).<br><br>RESULTS: The presence of CF/IDC was significantly associated with Decipher risk score (P&#x2009;=&#x2009;.007), with a high-risk Decipher score in 22% vs 56% of patients without or with CF/IDC. On binary logistic regression analysis, G4% (odds ratio [OR]&#xa0;1.04 per percent increase&#xa0;[95% confidence interval [CI], 1.02-1.06];&#xa0;P&#x2009;=&#x2009;.0004) and CF predominant (OR, 9.60&#xa0;[95%CI, 1.48-62.16];&#xa0;P&#x2009;=&#x2009;.02) were significantly associated with a high-risk GC score. IDC did not reach significance (OR, 1.92&#xa0;[95%CI, 0.65-5.67];&#xa0;P&#x2009;=&#x2009;.24).<br><br>CONCLUSIONS: Our findings add to an expanding knowledge base that supports G4% and CF/IDC as molecularly unique and clinically relevant features in prostatic adenocarcinoma. These histologic features should be standardly reported as they are associated with more aggressive prostate cancer. Future work should determine the independent information of these histologic findings that are&#xa0;relative to genomic assessment on long-term outcomes.}, }
@article {pmid31734782, year = {2020}, author = {Kim, K and Kim, IJ and Pak, K and Kim, SJ and Choi, SJ and Park, H and Kang, T and Kong, IJ and Shin, YB and Kim, H and Yoon, JA}, title = {The feasibility of quantitative parameters of lymphoscintigraphy without significant dermal backflow for the evaluation of lymphedema in post-operative patients with breast cancer.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {47}, number = {5}, pages = {1094-1102}, pmid = {31734782}, issn = {1619-7089}, mesh = {Axilla ; *Breast Neoplasms/diagnostic imaging/surgery ; Feasibility Studies ; Humans ; Lymph Node Excision ; *Lymphedema/diagnostic imaging/etiology ; Lymphoscintigraphy ; Mastectomy ; }, abstract = {PURPOSE: We aimed to evaluate the potential role of quantitative methods associated with lymphoscintigraphy for the assessment of severity of lymphedema post-operatively in patients with breast cancer who did not show definite dermal backflow activity on the lymphoscintigraphy.<br><br>METHODS: We evaluated 47 lymphoscintigraphies without dermal backflow in patients with lymphedema who received a mastectomy and axillary dissection or sentinel lymph node dissection for invasive ductal carcinoma of the breast. The quantitative asymmetry indices (QAIs) of both arms were calculated for each axilla, upper arm, forearm, and the whole arm. The QAI was defined as the radiopharmaceutical uptake ratio of the affected side to the unaffected side. Arm circumference was measured at four locations per arm to identify the maximal circumference difference (MCD) between affected and unaffected sides.<br><br>RESULTS: The total and forearm QAIs of each side arm were significantly higher in the group with above moderate stage lymphedema compared with the mild stage group. Previous radiotherapy also had a significant effect on radiotracer retention expressed as QAI. The MCD was significantly correlated with QAI values of the forearm and the whole arm. The QAI of axillary areas was not significantly correlated with circumferential measurements of the arm.<br><br>CONCLUSIONS: The QAIs have significant value for the diagnosis and severity of lymphedema and may therefore potentially be used as an objective tool for the assessment of lymphedema.}, }
@article {pmid31711023, year = {2019}, author = {Zhou, J and Tan, H and Bai, Y and Li, J and Lu, Q and Chen, R and Zhang, M and Feng, Q and Wang, M}, title = {Evaluating the HER-2 status of breast cancer using mammography radiomics features.}, journal = {European journal of radiology}, volume = {121}, number = {}, pages = {108718}, doi = {10.1016/j.ejrad.2019.108718}, pmid = {31711023}, issn = {1872-7727}, mesh = {Area Under Curve ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/*genetics ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics ; China ; Female ; Genes, erbB-2/*genetics ; Humans ; Mammography/*methods ; Middle Aged ; Preoperative Care ; ROC Curve ; Sensitivity and Specificity ; Support Vector Machine ; }, abstract = {PURPOSE: The aim of our study was to evaluate the HER-2 status in breast cancer patients using mammography (MG) radiomics features.<br><br>METHODS: A total of 306 Chinese female patients with invasive ductal carcinoma of no special type (IDC-NST) enrolled from January 2013 to July 2018 were divided into a training set (n&#x202f;=&#x202f;244) and a testing set (n&#x202f;=&#x202f;62). One hundred and eighty-six radiomics features were extracted from digital MG images based on the training set. The least absolute shrinkage and selection operator (LASSO) method was used to select the optimal predictive features for HER-2 status from the training set. Both support vector machine (SVM) and logistic regression models were employed based on the selected features. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training set and testing set were used to evaluate the predictive performance of the models.<br><br>RESULTS: Compared with the SVM model, the performance of the logistic regression model using a combination of cranial caudal (CC) and mediolateral oblique (MLO) MG views was optimal. In the training set, the sensitivity, specificity, accuracy and area under the curve (AUC) values of the logistic regression model for evaluating HER-2 status based on quantitative radiomics features were 87.29%, 58.73%, 80.00% and 0.846 (95% confidence interval (CI), 0.800-0.887), respectively, and in the testing set, the values were 73.91%, 68.75%, 77.00% and 0.787 (95% CI, 0.673-0.885), respectively.<br><br>CONCLUSIONS: Radiomics features could be an efficient tool for the preoperative evaluation of HER-2 status in patients with breast cancer.}, }
@article {pmid31710002, year = {2020}, author = {Zhu, S and Zhao, JG and Chen, JR and Liu, ZH and Sun, GX and Wang, ZP and Ni, YC and Dai, JD and Shen, PF and Zeng, H}, title = {Intraductal carcinoma of the prostate in prostate biopsy samples: correlation with aggressive pathological features after radical prostatectomy and prognostic value in high-risk prostate cancer.}, journal = {Asian journal of andrology}, volume = {22}, number = {5}, pages = {519-525}, pmid = {31710002}, issn = {1745-7262}, mesh = {Aged ; Biopsy ; Carcinoma, Ductal/blood/*pathology/surgery ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Nomograms ; Prognosis ; Proportional Hazards Models ; Prostate/pathology ; Prostate-Specific Antigen/*blood ; Prostatectomy ; Prostatic Neoplasms/blood/*pathology/surgery ; Risk Factors ; Seminal Vesicles/pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive pathological pattern of prostate cancer (PCa). We investigated the association of IDC-P in prostate biopsy (PBx) with several pathological features after radical prostatectomy (RP) and its prognostic value in high-risk PCa. A total of 418 patients with high-risk PCa after RP were included in this study. IDC-P and its architectural patterns were identified according to the 2016 World Health Organization Classification. Chi-squared test and logistic regression were used to investigate the correlation between IDC-P and post-RP pathological features. Kaplan-Meier curves and Cox regression were applied to explore the prognostic value of IDC-P. IDC-P was identified in PBx in 36/418 (8.6%) patients. Logistic regression indicated that IDC-P in PBx was independently associated with several pathological features of RP, including Gleason score 8-10 (P < 0.001), seminal vesicular invasion (P < 0.001), and pathological T (pT) 3a (P = 0.043). Patients with IDC-P in PBx manifested poorer biochemical-free survival (BFS) than those without IDC-P (37.47 months vs not reached, P < 0.001). The addition of IDC-P in several prognostic nomograms could improve the predictive accuracy of these tools. We conclude that IDC-P in PBx is positively associated with several aggressive pathological features after RP in high-risk PCa. In addition, IDC-P in PBx could effectively predict the BFS of high-risk PCa patients after RP.}, }
@article {pmid31706703, year = {2019}, author = {Quagliarini, F and Mir, AA and Balazs, K and Wierer, M and Dyar, KA and Jouffe, C and Makris, K and Hawe, J and Heinig, M and Filipp, FV and Barish, GD and Uhlenhaut, NH}, title = {Cistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet.}, journal = {Molecular cell}, volume = {76}, number = {4}, pages = {531-545.e5}, pmid = {31706703}, issn = {1097-4164}, support = {K99 CA154887/CA/NCI NIH HHS/United States ; R00 CA154887/CA/NCI NIH HHS/United States ; R01 DK108987/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Blood Glucose/metabolism ; Chromatin/*metabolism ; *Circadian Clocks/genetics ; *Circadian Rhythm/genetics ; *Diet, High-Fat ; Dietary Fats/administration &amp; dosage/blood/*metabolism ; Disease Models, Animal ; *Energy Metabolism/genetics ; Fasting/metabolism ; Gene Expression Regulation ; Glucocorticoids/metabolism ; Gluconeogenesis ; Ligands ; Liver/*metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/blood/genetics/*metabolism ; PPAR alpha/genetics/metabolism ; Postprandial Period ; Receptors, Glucocorticoid/deficiency/genetics/*metabolism ; STAT5 Transcription Factor/genetics/metabolism ; Secretory Pathway ; Signal Transduction ; Time Factors ; Transcription, Genetic ; Triglycerides/blood ; }, abstract = {The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.}, }
@article {pmid31677352, year = {2020}, author = {Chen, HH and Chen, DY and Huang, LG and Chen, YM and Hsieh, CW and Hung, WT and Tang, KT and Chen, G}, title = {Association between periodontitis and the risk of inadequate disease control in patients with rheumatoid arthritis under biological treatment.}, journal = {Journal of clinical periodontology}, volume = {47}, number = {2}, pages = {148-159}, doi = {10.1111/jcpe.13213}, pmid = {31677352}, issn = {1600-051X}, mesh = {Arthritis, Rheumatoid/*complications/*drug therapy/*epidemiology ; Humans ; Periodontitis/*complications/*epidemiology/*therapy ; Prospective Studies ; }, abstract = {AIM: To assess the association between periodontitis (PD) and inadequate disease control (IDC) in patients with rheumatoid arthritis (RA) receiving biological therapy.<br><br>MATERIALS AND METHODS: In total, 111 RA patients receiving biological therapy for at least 3&#xa0;months were assessed for periodontal disease at baseline. RA disease activity was assessed at baseline and at 3&#xa0;months of follow-up. A multivariable logistic regression analysis was used to estimate the association between PD and IDC, adjusting for age, sex, smoking, diabetes, and baseline RA disease activity. An additional exploratory model further controlled for disease characteristics and other medications.<br><br>RESULTS: Among 111 patients, 84 (75.7%) had PD, of whom 37 (44.0%) received periodontal treatment. Thirty-four (40.5%) of PD patients had IDC; 12 (32.4%) of treated PD patients and 22 (46.8%) of untreated patients had IDC, respectively. The ORs (95% CIs) for IDC were 1.45 (0.50-4.23) in PD patients and 1.84 (0.59-5.76) in untreated PD patients. In the exploratory model, the ORs (95% CIs) for IDC were 5.00 (1.19-21.03) in PD patients and 6.26 (1.34-29.34) in untreated PD patients.<br><br>CONCLUSION: This single-centre, prospective study failed to demonstrate a consistently positive correlation between PD and IDC in RA patients receiving biological treatment.}, }
@article {pmid31673038, year = {2019}, author = {Golberg, A and Sheviryov, J and Solomon, O and Anavy, L and Yakhini, Z}, title = {Molecular harvesting with electroporation for tissue profiling.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {15750}, pmid = {31673038}, issn = {2045-2322}, mesh = {Animals ; Electroporation/*methods ; Female ; Gene Ontology ; Genomics ; Hep G2 Cells ; Humans ; Kidney/*metabolism/pathology ; Liver/*metabolism/pathology ; Mice ; Mice, Nude ; Neoplasm Proteins/metabolism ; Neoplasms/genetics/metabolism/pathology ; Proteomics ; RNA, Neoplasm/metabolism ; Transplantation, Heterologous ; }, abstract = {Recent developments in personalized medicine are based on molecular measurement steps that guide personally adjusted medical decisions. A central approach to molecular profiling consists of measuring DNA, RNA, and/or proteins in tissue samples, most notably in and around tumors. This measurement yields molecular biomarkers that are potentially predictive of response and of tumor type. Current methods in cancer therapy mostly use tissue biopsy as the starting point of molecular profiling. Tissue biopsies involve a physical resection of a small tissue sample, leading to localized tissue injury, bleeding, inflammation and stress, as well as to an increased risk of metastasis. Here we developed a technology for harvesting biomolecules from tissues using electroporation. We show that tissue electroporation, achieved using a combination of high-voltage short pulses, 50 pulses 500 V cm[-1], 30 µs, 1 Hz, with low-voltage long pulses 50 pulses 50 V cm[-1], 10 ms, delivered at 1 Hz, allows for tissue-specific extraction of RNA and proteins. We specifically tested RNA and protein extraction from excised kidney and liver samples and from excised HepG2 tumors in mice. Further in vivo development of extraction methods based on electroporation can drive novel approaches to the molecular profiling of tumors and of tumor environment and to related diagnosis practices.}, }
@article {pmid31672492, year = {2020}, author = {Kim, JE and Kim, BG and Jang, Y and Kang, S and Lee, JH and Cho, NH}, title = {The stromal loss of miR-4516 promotes the FOSL1-dependent proliferation and malignancy of triple negative breast cancer.}, journal = {Cancer letters}, volume = {469}, number = {}, pages = {256-265}, doi = {10.1016/j.canlet.2019.10.039}, pmid = {31672492}, issn = {1872-7980}, mesh = {Antineoplastic Agents/pharmacology ; Cancer-Associated Fibroblasts/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/drug effects/genetics ; Disease Progression ; Exosome Multienzyme Ribonuclease Complex/genetics ; Exosomes/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MicroRNAs/*genetics ; Proto-Oncogene Proteins c-fos/*genetics ; Stromal Cells/metabolism/pathology ; Triple Negative Breast Neoplasms/*drug therapy/genetics/pathology ; }, abstract = {Stroma-derived exosomal microRNA (exomiR) contributes to tumor progression, however, which remains poorly understood. In our study, we analyzed exomiRs from the cancer-associated fibroblast (CAF) and normal fibroblast (NF) isolated from an invasive ductal carcinoma (IDC) patient and found that the level of microRNA (miR)-4516 was approximately 5-fold lower in CAF-derived exosomes than NF-derived ones. In gene annotation analysis, miR-4516 target genes were mainly associated with the regulation of proliferation. miR-4516 overexpression or mimic treatment suppressed the proliferation of breast cancer cells, especially triple negative breast cancer (TNBC) cells. Among miR-4516 targets, FOSL1 was overexpressed in TNBC cells compared to non-TNBC cells and promoted tumor proliferation. The expression of miR-4516 and FOSL1 was reversely correlated in breast cancer patient tissues. Particularly, TNBC patients with high FOSL1 expression showed a significant poorer survival than those with low FOSL1 expression. Our results show that the loss of miR-4516 from CAF-derived exosomes is associated with FOSL1-dependent TNBC progression and suggest that miR-4516 can be used as an anti-cancer drug for TNBC.}, }
@article {pmid31666416, year = {2019}, author = {Autenshlyus, AI and Davletova, KI and Studenikina, AA and Mikhaylova, ES and Varaksin, NA and Zhurakovsky, IP and Proskura, AV and Sidorov, SV and Lyakhovich, VV}, title = {[Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type].}, journal = {Biomeditsinskaia khimiia}, volume = {65}, number = {5}, pages = {424-431}, doi = {10.18097/PBMC20196505424}, pmid = {31666416}, issn = {2310-6972}, mesh = {Breast Neoplasms/*immunology ; Carcinoma, Ductal/*immunology ; Cytokines/*immunology ; *Extracellular Matrix ; Female ; Humans ; Lymphatic Metastasis ; *Tumor Microenvironment ; }, abstract = {The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1β; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.}, }
@article {pmid31661032, year = {2019}, author = {Klomek, AB}, title = {Prevention of postpartum suicidality in Israel.}, journal = {Israel journal of health policy research}, volume = {8}, number = {1}, pages = {77}, pmid = {31661032}, issn = {2045-4015}, mesh = {Child ; Female ; Humans ; Israel ; Postpartum Period ; Pregnancy ; Risk Factors ; *Suicide ; USSR ; }, abstract = {Postpartum suicidality in Israel had not been systematically studied until the recent important investigation by Glasser and colleagues. The authors review rates, trends, and characteristics of postpartum women who considered, attempted, or completed suicide in Israel. This commentary argues that, although postpartum suicidality is relatively rare, it is extremely tragic-not just for the women, but for the entire family and community. The main aim of this commentary is to emphasize that preventive efforts should continue and expand, especially among at-risk groups. At-risk groups include the youngest age group, postpartum Arab women, and postpartum former Soviet Union immigrants. Identification of women at risk or suffering from postpartum depression (PPD) is mandated in Israel. Efforts should include broader screening for various types of suicide ideation and behavior. Assessments should specifically include passive suicide ideation, active suicide ideation with method, intent, and plan, as well as various types of suicide attempts and preparatory behaviors. In addition, specific interventions formulated on evidence-based psychotherapies should be provided in family practice, obstetric, and pediatric settings. These settings are less stigmatized in comparison to mental health settings. Potential therapies can be (among others) Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), which are effective in preventing perinatal depression.}, }
@article {pmid31660917, year = {2019}, author = {Peng, Z and Klomek, AB and Li, L and Su, X and Sillanmäki, L and Chudal, R and Sourander, A}, title = {Associations between Chinese adolescents subjected to traditional and cyber bullying and suicidal ideation, self-harm and suicide attempts.}, journal = {BMC psychiatry}, volume = {19}, number = {1}, pages = {324}, pmid = {31660917}, issn = {1471-244X}, mesh = {Adolescent ; Adolescent Behavior ; Bullying/*statistics &amp; numerical data ; Child ; China/epidemiology ; Crime Victims/*statistics &amp; numerical data ; Cyberbullying/statistics &amp; numerical data ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; Self-Injurious Behavior/*epidemiology/etiology ; Students/statistics &amp; numerical data ; *Suicidal Ideation ; Suicide, Attempted/*statistics &amp; numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The incidence of bullying is high among adolescents. Adolescents who were victims of bullying have a higher risk of self-harm and suicidal behavior than adolescents who were non-victims. However, research on suicide and both traditional and cyber bullying was limited in China. Therefore, this study examined the associations between Chinese adolescents who were the victims of traditional and cyber bullying and the prevalence of suicidal ideation, self-harm and suicide attempts.<br><br>METHODS: This was a population-based study of 2647 students (51.2% girls) with a mean age of 13.6&#x2009;&#xb1;&#x2009;1.1&#x2009;years from 10 junior high schools in Shantou, China. Information on bullying victimization, suicidal ideation, self-harm and suicide attempts were collected using a self-administered questionnaire and the psychopathology of the students was assessed using the Strengths and Difficulties Questionnaire (SDQ). The associations were examined with multinomial logistic regression, adjusted for covariates.<br><br>RESULTS: Traditional bullying victimization was reported by 16.7% of the adolescents, cyber bullying victimization by 9.0% and both by 3.5%. The prevalence of suicidal ideation was 23.5%, self-harm was 6.2% and suicide attempts was 4.2%. Psychopathology symptoms were risk factors for suicide ideation only, ideation plus self-harm, self-harm only and suicide attempts. Victims of both traditional and cyber bullying had the highest risk of suicidal ideation only, ideation plus self-harm and suicide attempts, compared to those reporting one form of bullying. Victims of cyber bullying only had the second highest risk of suicidal ideation only and suicidal ideation plus self-harm compared to non-victims.<br><br>CONCLUSIONS: Adolescents who were victims of both traditional and cyber bullying had greater risks of adverse outcomes of suicidal ideation only, suicidal ideation plus self-harm and suicide attempts. The results of the current study suggest that those exposed to both forms of bullying should be routinely screened for suicidal risk. In addition, school-based anti-bully interventions should also target cyber bullying.}, }
@article {pmid31656498, year = {2019}, author = {Mohammedi, L and Doula, FD and Mesli, F and Senhadji, R}, title = {Cyclin D1 overexpression in Algerian breast cancer women: correlation with CCND1 amplification and clinicopathological parameters.}, journal = {African health sciences}, volume = {19}, number = {2}, pages = {2140-2146}, pmid = {31656498}, issn = {1729-0503}, mesh = {Adult ; Aged ; Algeria ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cyclin D1/*genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Prognosis ; }, abstract = {BACKGROUND: Cyclin D1 which is associated with cell cycle regulation is solidly established as an oncogene with an important pathogenetic role in breast carcinomas.<br><br>OBJECTIVES: The aim of this study was to relate the Cyclin D1 protein overexpression with the amplification of its gene CCND1 in Estrogen Receptors (ER) positive breast carcinomas, in order to investigate the prognostic effect of their aberrations in relation to ER status, also to correlate the Cyclin D1 overexpression with other prognostic parameters.<br><br>MATERIALS AND METHODS: Chromogenic in situ hybridization (CISH) was used to identify CCND1 amplification on formalin-fixed paraffin-embedded invasive ductal carcinoma, in which immunohistochemistry (IHC) had previously been performed in order to evaluate the pathological relevance of Cyclin D1 overexpression in human breast cancer (n = 138).<br><br>RESULTS: CCND1 amplification was identified in 17/138 (12.3%) tumors and 78/138 (56.5%) tumors have overexpressed Cyclin D1. A significant correlation was identified between CCND1 amplification and Cyclin D1 overexpression (P < 0.001) and both Cyclin D1 and CCND1 were related with ER expression.<br><br>CONCLUSION: Our results show a significant correlation between Cyclin D1 overexpression and CCND1 amplification. Overexpression of Cyclin D1was observed in high proportion of breast cancer which should be considered for routine diagnosis.}, }
@article {pmid31647159, year = {2020}, author = {Seckin, ZI and Brumble, LM and Libertin, CR}, title = {Serologic screening and infectious disease consultation (IDC): Indicated in heart, lung, liver (HLL) solid organ transplants (SOT) for measles, mumps, rubella, and varicella.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {1}, pages = {e13202}, doi = {10.1111/tid.13202}, pmid = {31647159}, issn = {1399-3062}, mesh = {Adult ; Antibodies, Viral/*blood ; Chickenpox/etiology/immunology/prevention &amp; control ; Communicable Disease Control/*methods ; Communicable Diseases/*etiology/immunology ; Humans ; Measles/etiology/immunology/prevention &amp; control ; Mumps/etiology/immunology/prevention &amp; control ; *Organ Transplantation ; *Referral and Consultation ; Retrospective Studies ; Rubella/etiology/immunology/prevention &amp; control ; *Serologic Tests ; Vaccination ; }, abstract = {BACKGROUND: Solid organ transplant (SOT) recipients are a special group of patients who require comprehensive evaluation for preventable infectious diseases before transplantation. The main aim of our study was to investigate the number of heart, lung, and liver (HLL) transplant recipients who were evaluated for their immune status against measles, mumps, rubella (MMR), and varicella (VZV). As a secondary aim, we investigated whether pre-transplant infectious disease consultation (IDC) improves vaccination rates.<br><br>METHODS: This study was an institution-based retrospective analysis of HLL transplant recipients born in or after 1957 and evaluated at Mayo Clinic, FL Transplant Center between January 1st, 2016 and December 31st, 2017. Data collection was obtained from electronic medical records. The vaccination rates were compared by univariate analysis based on IDC and no ID consultation (NIDC).<br><br>RESULTS: One hundred and eighty-seven (77%) of a total 242 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 187 IDC candidates. Among the 187 IDC patients, mumps, measles, and rubella IgG serologies were performed in 9 (5%), 21 (11%), and 51 (27%), respectively. Among all 242 patients,&#xa0;vaccines given included 2 (0.8%) MMR, 10 (4.1%) varicella and 85 (35.12%) Zostavax. Univariate analysis revealed that Zostavax was given to 76 (40.6%) pre-transplant IDC patients and only in 9 (16.7%) NIDC patients (P&#xa0;<&#xa0;.001).<br><br>CONCLUSIONS: Despite the relatively high IDC rate, patients' screened numbers for MMR IgG levels were low. Results pointed out the need for MMR protocol-driven serologic screening as well as for VZV and IDC prior to transplantation to increase vaccination rates.}, }
@article {pmid36133137, year = {2019}, author = {Amiri, A and Hastert, F and Stühn, L and Dietz, C}, title = {Structural analysis of healthy and cancerous epithelial-type breast cells by nanomechanical spectroscopy allows us to obtain peculiarities of the skeleton and junctions.}, journal = {Nanoscale advances}, volume = {1}, number = {12}, pages = {4853-4862}, pmid = {36133137}, issn = {2516-0230}, abstract = {The transition of healthy epithelial cells to carcinoma is associated with an alteration in the structure and organization of the cytoskeleton of the cells. A comparison of the mechanical properties of cancerous and healthy cells indicated a higher deformability of the cancer cells based on averaging the mechanical properties of single cells. However, the exact reason for softening of the cancerous cells compared to their counterparts remains unclear. Here, we focused on nanomechanical spectroscopy of healthy and cancerous ductal epithelial-type breast cells by means of atomic force microscopy with high lateral and depth precision. As a result, based on atomic force microscopy measurements formation of significantly fewer microtubules in cancerous cells which was observed in our study is most likely one of the main causes for the overall change in mechanical properties without any phenotypic shift. Strikingly, in a confluent layer of invasive ductal carcinoma cells, we observed the formation of cell-cell junctions that have the potential for signal transduction among neighboring cells such as desmosomes and adherens junctions. This increases the possibility of cancerous cell collaboration in malignancy, infiltration or metastasis phenomena.}, }
@article {pmid31617074, year = {2020}, author = {Sethy, C and Goutam, K and Nayak, D and Pradhan, R and Molla, S and Chatterjee, S and Rout, N and Wyatt, MD and Narayan, S and Kundu, CN}, title = {Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse.}, journal = {Journal of cancer research and clinical oncology}, volume = {146}, number = {1}, pages = {245-259}, pmid = {31617074}, issn = {1432-1335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/*genetics/metabolism ; Carcinoma, Ductal, Breast/*blood supply/*genetics/metabolism ; Cell Adhesion Molecules/biosynthesis/*genetics/metabolism ; Female ; Humans ; Middle Aged ; NF-kappa B/metabolism ; Neovascularization, Pathologic/genetics/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; }, abstract = {PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs).<br><br>METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens.<br><br>RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors.<br><br>CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p&#x2009;<&#x2009;0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NF&#x3ba;&#x3b2; pathway.}, }
@article {pmid31612916, year = {2019}, author = {Shimmura, H and Kuramochi, H and Jibiki, N and Katagiri, S and Nishino, T and Araida, T}, title = {Dramatic response of FOLFIRINOX regimen in a collision pancreatic adenocarcinoma patient with a germline BRCA2 mutation: a case report.}, journal = {Japanese journal of clinical oncology}, volume = {49}, number = {11}, pages = {1049-1054}, doi = {10.1093/jjco/hyz141}, pmid = {31612916}, issn = {1465-3621}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; BRCA2 Protein/genetics ; Carcinoma, Ductal, Breast/*drug therapy/genetics ; Carcinoma, Pancreatic Ductal/*drug therapy ; Female ; Fluorouracil/therapeutic use ; Genetic Testing ; Germ Cells ; Germ-Line Mutation ; Humans ; Irinotecan/therapeutic use ; Leucovorin/therapeutic use ; Liver Neoplasms/*drug therapy/secondary ; Lymph Node Excision ; Middle Aged ; Mutation ; Oxaliplatin/therapeutic use ; Pancreatic Neoplasms/*drug therapy ; Pancreaticoduodenectomy ; }, abstract = {Germline BRCA1 and BRCA2 mutations are the most common gene mutations in familial pancreatic adenocarcinoma. Several reports have demonstrated the utility of platinum-based chemotherapy for treating cancer patients who harbour a BRCA mutation. Here we discuss a 47-year-old Japanese female with no relevant past history who presented with epigastralgia and fever in September 2016. A computed tomography scan revealed a low-density, low-enhanced tumour 15 mm in diameter in the head of the pancreas. The pathological diagnosis was a ductal pancreatic carcinoma. A 6 mm low-enhanced metastatic tumour was also detected in segment 4 of the liver. Because she had early onset of the disease and a family history-her mother died of pancreatic adenocarcinoma at age 48-we considered a diagnosis of familial pancreatic adenocarcinoma. She received modified FOLFIRINOX. Two months after starting chemotherapy, she was diagnosed with an invasive ductal carcinoma in the right breast. FOLFIRINOX was continued for 8 cycles (4 months); the primary pancreatic adenocarcinoma shrank and the liver metastatic foci disappeared, but the size of the breast tumour increased. Total right breast excision and sentinel lymph node dissection were performed. FOLFIRINOX was continued and after 12 cycles (6 months), both her pancreatic adenocarcinoma and liver metastasis were no longer visible using imaging. Pancreatoduodenectomy was performed and the primary tumour had shrunk to 2.5 mm. Genetic testing revealed a germline BRCA2 mutation. The FOLFIRINOX regimen showed dramatic effects on the collision pancreatic but not on the breast cancer.}, }
@article {pmid31594782, year = {2019}, author = {Jakharia-Shah, A and Wheatley, H and Beesley, M}, title = {Reminder of an important clinical lesson: breast cancer metastasis to the parotid gland.}, journal = {BMJ case reports}, volume = {12}, number = {10}, pages = {}, pmid = {31594782}, issn = {1757-790X}, mesh = {Biopsy, Fine-Needle/methods ; Breast Neoplasms/complications/diagnostic imaging/pathology/*secondary ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Parotid Gland/*pathology/surgery ; Parotid Neoplasms/pathology/*secondary/surgery ; Positron Emission Tomography Computed Tomography/methods ; Receptor, ErbB-2/metabolism ; Treatment Outcome ; }, abstract = {A 59-year-old woman presented to an otolaryngology clinic with an 8-week history of a painless lump over her left parotid gland. Her medical history included an invasive ductal carcinoma (33 mm) and a ductal carcinoma in situ (70 mm) of the right breast, for which she had a mastectomy and various adjuvant therapies. The primary tumour presented 8 years prior to the metachronous metastasis. This patient was a non-smoker and had no significant family history. Post-superficial parotidectomy pathology revealed the parotid gland tumour to be oestrogen receptor-positive and HER2 receptor-positive, thus ruling out the initial differential diagnosis of a pleomorphic adenoma. A consequential total parotidectomy with a posterolateral neck dissection was performed with sparing of the facial nerve. The patient recovered well having only encountered a self-resolving salivary fistula. She portrayed no signs of facial nerve palsy and subsequent imaging scans showed no abnormalities.}, }
@article {pmid31584185, year = {2020}, author = {Xu, Q and Rangaswamy, US and Wang, W and Robbins, SH and Harper, J and Jin, H and Cheng, X}, title = {Evaluation of Newcastle disease virus mediated dendritic cell activation and cross-priming tumor-specific immune responses ex vivo.}, journal = {International journal of cancer}, volume = {146}, number = {2}, pages = {531-541}, doi = {10.1002/ijc.32694}, pmid = {31584185}, issn = {1097-0215}, mesh = {Animals ; Chlorocebus aethiops ; Coculture Techniques ; *Cross-Priming ; Dendritic Cells/*immunology/metabolism ; Female ; HeLa Cells ; Humans ; Immunotherapy/*methods ; Interferon Type I/immunology/metabolism ; Neoplasms/immunology/*therapy ; Newcastle disease virus/genetics/immunology ; Oncolytic Virotherapy/*methods ; Oncolytic Viruses/genetics/immunology ; RNA/administration &amp; dosage/genetics ; RNA, Viral/administration &amp; dosage/genetics ; T-Lymphocytes/immunology ; Vero Cells ; }, abstract = {We have developed an oncolytic Newcastle disease virus (NDV) that has potent in vitro and in vivo anti-tumor activities and attenuated pathogenicity in chickens. In this ex vivo study using the same recombinant NDV backbone with GFP transgene (NDV-GFP, designated as rNDV), we found that rNDV induces maturation of monocyte-derived immature dendritic cells (iDCs) by both direct and indirect mechanisms, which promote development of antigen-specific T cell responses. Addition of rNDV directly to iDCs culture induced DC maturation, as demonstrated by the increased expression of costimulatory and antigen-presenting molecules as well as the production of type I interferons (IFNs). rNDV infection of the HER-2 positive human breast cancer cell line (SKBR3) resulted in apoptotic cell death, release of proinflammatory cytokines, and danger-associated molecular pattern molecules (DAMPs) including high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70). Addition of rNDV-infected SKBR3 cells to iDC culture resulted in greatly enhanced upregulation of the maturation markers and release of type I IFNs by DCs than rNDV-infected DCs only. When co-cultured with autologous T cells, DCs pre-treated with rNDV-infected SKBR3 cells cross-primed T cells in an antigen-specific manner. Altogether, our data strongly support the potential of oncolytic NDV as efficient therapeutic agent for cancer treatment.}, }
@article {pmid31578784, year = {2020}, author = {Patel, DP and Herrick, JS and Stoffel, JT and Elliott, SP and Lenherr, SM and Presson, AP and Welk, B and Jha, A and Myers, JB and , }, title = {Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry.}, journal = {Neurourology and urodynamics}, volume = {39}, number = {1}, pages = {211-219}, doi = {10.1002/nau.24172}, pmid = {31578784}, issn = {1520-6777}, mesh = {Adult ; Female ; Health Behavior ; Humans ; Intermittent Urethral Catheterization/*adverse effects ; Male ; Middle Aged ; Patient Compliance ; Patient Satisfaction ; *Quality of Life ; Registries ; Spinal Cord Injuries/*complications ; Urinary Bladder, Neurogenic/*etiology ; Urinary Tract Infections/*etiology ; }, abstract = {INTRODUCTION: Clean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder-related quality of life (QoL) and the reasons for CIC cessation.<br><br>METHODS: The Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder-related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder-related QoL.<br><br>RESULTS: There were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), &#x2265;4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI-QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI-QoL difficulties).<br><br>CONCLUSIONS: Tetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.}, }
@article {pmid31576258, year = {2019}, author = {Marsili, C and Wilson, CM and Gura, N}, title = {Prospective Surveillance Screenings to Identify Physical Therapy Needs During Breast Cancer Diagnosis and Surviviorship: A Case Report.}, journal = {Cureus}, volume = {11}, number = {7}, pages = {e5265}, pmid = {31576258}, issn = {2168-8184}, abstract = {Breast cancer and its treatments can cause detrimental effects to function and quality of life (QoL). These patients do not conventionally receive physical therapy services until impairments and functional limitations have become extensive. Emerging treatment models advocate for early rehabilitation screenings and proactive interventions, which are termed prospective surveillance. The purpose of this case report was to describe two prospective surveillance screenings at initial diagnosis and survivorship and subsequent physical therapy episodes of care for a patient with breast cancer. A 39-year-old female was diagnosed with invasive ductal carcinoma of the right breast. Approximately three months after the initial diagnosis, the patient had a right nipple-sparing mastectomy and immediate reconstruction with an expander. In addition, one lymph node was removed and underwent a biopsy, which was negative for metastases. The patient was screened by a physical therapist after her initial cancer diagnosis at the breast multidisciplinary clinic. This was after her mastectomy with an expander; the therapist recommended an episode of outpatient physical therapy due to impairments in pain, fatigue, loss of range of motion, weakness, and limitations in performance of her activities of daily living. The patient was seen initially for five visits. She underwent her final reconstructive surgery one month after discharge from physical therapy. Six months after her final reconstructive surgery, she was screened by the same physical therapist in the cancer survivorship clinic. Once again, therapy was recommended due to pain as well as deficits to her range of motion, strength, and functional status. The second episode of care lasted 14 visits and the patient showed improvements in pain, range of motion, shoulder strength and gains in the patient-specific functional scale and upper extremity functional index. This case reflects the importance of prospective surveillance screenings to overall patient outcomes. This patient may not have otherwise received physical therapy and its associated benefits without the prospective screenings by the physical therapist.}, }
@article {pmid34191158, year = {2019}, author = {Aarstad, EM and Nordhaug, P and Naghavi-Behzad, M and Larsen, LB and Gerke, O and Hildebrandt, MG}, title = {Prevalence of focal incidental breast uptake on FDG-PET/CT and risk of malignancy: a systematic review and meta-analysis.}, journal = {European journal of hybrid imaging}, volume = {3}, number = {1}, pages = {16}, pmid = {34191158}, issn = {2510-3636}, support = {//Danmarks Frie Forskningsfond/ ; //Syddansk Universitet/ ; }, abstract = {BACKGROUND: FDG-PET/CT is increasingly used for oncologic and inflammatory diseases. Focal incidental FDG uptake occurs rarely in breast tissue but has often significant consequences. This study aimed to systematically review literature regarding focal incidental breast uptake (FIBU) on FDG-PET/CT in order to yield an update on the prevalence and risk of malignancy for FIBU.<br><br>METHODS: A systematic search for relevant articles published between 2012 and 2018 was performed through MEDLINE, Embase, and Cochrane databases. Studies addressing the detection of FIBU in patients without a previous history of breast malignancy were included. The QUADAS-2 was used for quality assessment, and eligible data were pooled using a fixed-effects model. I[2] was calculated for the heterogeneity between studies.<br><br>RESULTS: Eight studies containing 180,002 scans were included in the systematic review. The median prevalence of FIBU for both genders was 0.52% (range 0.18-22.5%). Prevalence for women was mentioned separately in five studies and varied from 0.51 to 23.5%. One study reporting a high prevalence was based on patients being staged for known malignancy, and the word "breast" was used in the search, which may have caused selection bias. Data from four studies were eligible for meta-analysis. A high degree of heterogeneity was observed for prevalence data (I[2] of 97.5%), while moderate heterogeneity was observed for data on malignancy risk assessment (I[2] of 62.8%). The pooled prevalence of FIBU in women was 0.61% (range 0.56-0.66%), and the pooled prevalence of malignancy of FIBUs was 38.7% (range 34.4-43.0%). The most commonly detected malignancy was invasive ductal carcinoma.<br><br>CONCLUSION: FIBU occurs rarely on FDG-PET/CT for female patients but yields a high risk of malignancy according to the results of published papers. Therefore, it should be considered relevant to further elucidate patients with incidentally detected FDG uptake in breast in clinical practice.}, }
@article {pmid31539353, year = {2019}, author = {Gonzalez, SM and Aguilar-Jimenez, W and Alvarez, N and Rugeles, MT}, title = {Cholecalciferol modulates the phenotype of differentiated monocyte-derived dendritic cells without altering HIV-1 transfer to CD4+ T cells.}, journal = {Hormone molecular biology and clinical investigation}, volume = {40}, number = {1}, pages = {}, doi = {10.1515/hmbci-2019-0003}, pmid = {31539353}, issn = {1868-1891}, mesh = {CD4-Positive T-Lymphocytes/*drug effects/immunology/virology ; Cells, Cultured ; Cholecalciferol/*pharmacology ; Dendritic Cells/*drug effects/immunology/virology ; HIV Infections/*immunology/prevention &amp; control/transmission/virology ; HIV-1/*drug effects/immunology/physiology ; Humans ; Immunologic Factors/pharmacology ; Monocytes/drug effects/immunology/virology ; Virus Internalization/drug effects ; Vitamins/*pharmacology ; }, abstract = {Background Dendritic cells (DCs) play a crucial role during HIV-1 transmission due to their ability to transfer virions to susceptible CD4+ T cells, particularly in the lymph nodes during antigen presentation which favors the establishment of systemic infection. As mature dendritic cells (mDCs) exhibit a greater ability to transfer virions, compared to immature DCs (iDCs), maintenance of an iDC phenotype could decrease viral transmission. The immunomodulatory vitamin D (VitD) has been shown to reduce activation and maturation of DCs; hence, we hypothesized that it would reduce viral transference by DCs. Materials and methods We evaluated the effect of in vitro treatment with a precursor of VitD, cholecalciferol, on the activation/maturation phenotype of differentiated monocyte-derived DCs and their ability to transfer HIV-1 to autologous CD4+ T cells. Results Our findings show that although cholecalciferol decreases the activation of iDCs, it did not impact the maturation phenotype after LPS treatment nor iDCs' ability to transfer viral particles to target cells. Conclusion These findings suggest that despite cholecalciferol potentially modulates the phenotype of mucosal iDCs in vivo, such modulation might not impact the ability of these cells to transfer HIV-1 to target CD4+ T cells.}, }
@article {pmid31538688, year = {2020}, author = {Haynes, HR and Rose, DSC}, title = {Synchronous small lymphocytic lymphoma and metastatic breast carcinoma in axillary lymph nodes: Preservation of follicular architecture only in the portions of affected lymph nodes involved by metastatic carcinoma.}, journal = {The breast journal}, volume = {26}, number = {2}, pages = {245-246}, doi = {10.1111/tbj.13538}, pmid = {31538688}, issn = {1524-4741}, mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {We present a case of metastatic ductal carcinoma of breast with the incidental discovery of small lymphocytic lymphoma (SLL) in regional axillary nodes. The co-occurence of metastatic carcinoma and low-grade lymphoma in lymph nodes is rare but well recognized. However, in this case, in the lymph nodes in which sizeable metastatic carcinoma deposits were present, the follicular structures between the sinusoidal carcinomatous infiltrates were preserved, whereas the uninvolved portions of the nodes were overrun by SLL. This is the first description of this phenomenon. We suggest that further cases displaying this previously unpublished pattern are collated in order that we may begin to investigate the underlying etiological mediators.}, }
@article {pmid31529566, year = {2019}, author = {van Kooten, XF and Petrini, LFT and Kashyap, A and Voith von Voithenberg, L and Bercovici, M and Kaigala, GV}, title = {Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {58}, number = {43}, pages = {15259-15262}, doi = {10.1002/anie.201907150}, pmid = {31529566}, issn = {1521-3773}, support = {607322//FP7 People: Marie-Curie Actions/International ; 727761//H2020 European Research Council/International ; }, mesh = {Breast Neoplasms/*genetics/pathology ; DNA, Neoplasm/analysis/metabolism ; Female ; Formaldehyde/chemistry ; Genotype ; Humans ; MCF-7 Cells ; Microscopy, Confocal ; Paraffin Embedding ; Point Mutation ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Proto-Oncogene Proteins p21(ras)/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {We have developed a method for spatially resolved genetic analysis of formalin-fixed paraffin-embedded (FFPE) cell block and tissue sections. This method involves local sampling using hydrodynamic flow confinement of a lysis buffer, followed by electrokinetic purification of nucleic acids from the sampled lysate. We characterized the method by locally sampling an array of points with a circa 200 μm diameter footprint, enabling the detection of single KRAS and BRAF point mutations in small populations of RKO and MCF-7 FFPE cell blocks. To illustrate the utility of this approach for genetic analysis, we demonstrate spatially resolved genotyping of FFPE sections of human breast invasive ductal carcinoma.}, }
@article {pmid31512354, year = {2020}, author = {Ali Mlees, M}, title = {Diagnosis and surgical treatment of pathologic nipple discharge using ultrasound-guided wire localization of focal ductal dilatation.}, journal = {The breast journal}, volume = {26}, number = {2}, pages = {139-143}, doi = {10.1111/tbj.13493}, pmid = {31512354}, issn = {1524-4741}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/pathology ; Dilatation, Pathologic/*diagnosis/pathology ; Feasibility Studies ; Female ; Humans ; Image-Guided Biopsy ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Papilloma/*diagnosis/pathology ; Ultrasonography, Interventional ; }, abstract = {Nipple discharge is the third breast complaint after pain and lumps. The modern high-resolution ultrasound techniques are becoming more sensitive for the visualization of intraductal changes especially focal ductal dilatation (FDD), hypothesized as a radiographic manifestation of the lesion itself and that ultrasound-guided wire localization of this finding would enable identification and excision of the causative lesion. The aim of this study was to evaluate the safety, feasibility, efficiency and outcome of ultrasound-guided wire localization of FDD as possible cause of pathological nipple discharge (PND). The present study was conducted on 56 patients with PND presented to Surgical Oncology Unit at General Surgery Department, Tanta University Hospital from January 2018 to January 2019. The patients subjected to ultrasound-guided wire localization of FDD on the day of surgery, the involved duct was cannulated with a lacrimal duct probe, the targeted tissue was excised, and the specimen was sent for histopathological examination. The patients' age ranged between 26 and 71 years with a mean age of 48 years. The bloody nipple discharge was the commonest presenting symptom in 44 out of 56 patients (78.5%). The duct dilatation on study ultrasound ranged from 2.1 to 3.7 mm with a mean of 2.6 mm. Preoperative ultrasound-guided wire localization of the site of FDD was successfully performed in all cases. Papilloma alone founded in 40 out of 56 patients (71.4%), papilloma + ductal carcinoma in situ (DCIS) in six patients (10.7%), papilloma + invasive ductal carcinoma in six patients (10.7%), DCIS in two patients (3.6%) and duct ectasia in two patients (3.6%). Ultrasound-guided wire localization of FDD is an easy and safe technique for evaluation, precise localization, and targeted excision of the underlying lesions of PND.}, }
@article {pmid31508769, year = {2019}, author = {Couto, MSA and Firme, VAC and Guerra, MR and Bustamante-Teixeira, MT}, title = {The effect of redistribution of ill-defined causes of death on the mortality rate of breast cancer in Brazil.}, journal = {Ciencia &amp; saude coletiva}, volume = {24}, number = {9}, pages = {3517-3528}, doi = {10.1590/1413-81232018249.31402017}, pmid = {31508769}, issn = {1678-4561}, mesh = {Brazil/epidemiology ; Breast Neoplasms/*mortality ; Cause of Death/*trends ; Cities/statistics &amp; numerical data ; Female ; Humans ; Mortality/*trends ; }, abstract = {The relevance of breast cancer for women has driven research about mortality of this disease. However, these studies are affected by problems generated by deaths due to ill-defined causes (IDC). To highlight distortions caused by IDC in studies that evaluate mortality, we calculated the age-standardized mortality rates of breast cancer, with and without adjustment for IDC for the years 1990, 2000, and 2010. Then, panel data regression models were estimated and enabled us to identify that the adjustment for IDC: has elevated breast cancer mortality rate of Brazilian municipalities by 9% in the period considered; has drawn mortality rates of the South, Southeast, Northeast and North regions closer; has reduced the increasing trend of mortality by almost 60%, mainly in the Southeast and South regions; has increased, more sharply, the mortality in cities with less than 5 thousand inhabitants; has curbed the significance of most factors associated with breast cancer; has revealed that the effect of longevity and the public health expenditure may be overestimated. These results highlight the importance of adjustment for IDC in producing reliable mortality indicators.}, }
@article {pmid31488082, year = {2019}, author = {McQuerry, JA and Jenkins, DF and Yost, SE and Zhang, Y and Schmolze, D and Johnson, WE and Yuan, Y and Bild, AH}, title = {Pathway activity profiling of growth factor receptor network and stemness pathways differentiates metaplastic breast cancer histological subtypes.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {881}, pmid = {31488082}, issn = {1471-2407}, support = {U54CA209978/NH/NIH HHS/United States ; U54 CA209978/CA/NCI NIH HHS/United States ; U01 CA220413/CA/NCI NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; R01 GM127430/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bcl-2-Like Protein 11/metabolism ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cohort Studies ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Osteonectin/genetics ; Phenotype ; Prognosis ; RNA-Seq/methods ; Receptors, Growth Factor/*metabolism ; Signal Transduction/*genetics ; Snail Family Transcription Factors/metabolism ; Transcriptome/*genetics ; Triple Negative Breast Neoplasms/*genetics/pathology ; }, abstract = {BACKGROUND: Gene expression profiling of rare cancers has proven challenging due to limited access to patient materials and requirement of intact, non-degraded RNA for next-generation sequencing. We customized a gene expression panel compatible with degraded RNA from formalin-fixed, paraffin-embedded (FFPE) patient cancer samples and investigated its utility in pathway activity profiling in patients with metaplastic breast cancer (MpBC).<br><br>METHODS: Activity of various biological pathways was profiled in samples from nineteen patients with MpBC and 8 patients with invasive ductal carcinoma with triple negative breast cancer (TNBC) phenotype using a custom gene expression-based assay of 345 genes.<br><br>RESULTS: MpBC samples of mesenchymal (chondroid and/or osteoid) histology demonstrated increased SNAI1 and BCL2L11 pathway activity compared to samples with non-mesenchymal histology. Additionally, late cornified envelope and keratinization genes were downregulated in MpBC compared to TNBC, and epithelial-to-mesenchymal transition (EMT) and collagen genes were upregulated in MpBC. Patients with high activity of an invasiveness gene expression signature, as well as high expression of the mesenchymal marker and extracellular matrix glycoprotein gene SPARC, experienced worse outcomes than those with low invasiveness activity and low SPARC expression.<br><br>CONCLUSIONS: This study demonstrates the utility of gene expression profiling of metaplastic breast cancer FFPE samples with a custom counts-based assay. Gene expression patterns identified by this assay suggest that, although often histologically triple negative, patients with MpBC have distinct pathway activation compared to patients with invasive ductal TNBC. Incorporation of targeted therapies may lead to improved outcome for MpBC patients, especially in those patients expressing increased activity of invasiveness pathways.}, }
@article {pmid31486035, year = {2020}, author = {Delaunay, T and Achard, C and Grégoire, M and Tangy, F and Boisgerault, N and Fonteneau, JF}, title = {A Functional Assay to Determine the Capacity of Oncolytic Viruses to Induce Immunogenic Tumor Cell Death.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2058}, number = {}, pages = {127-132}, doi = {10.1007/978-1-4939-9794-7_8}, pmid = {31486035}, issn = {1940-6029}, mesh = {Animals ; Antigen-Presenting Cells/immunology/metabolism ; Cell Death/immunology ; Dendritic Cells/immunology/metabolism ; Genetic Therapy/methods ; Genetic Vectors/*genetics ; Humans ; *Immunomodulation ; Immunophenotyping ; Monocytes/immunology/metabolism ; Neoplasms/*immunology/metabolism/pathology/therapy ; Oncolytic Virotherapy ; Oncolytic Viruses/*genetics/immunology ; }, abstract = {Oncolytic immunotherapy efficacy relies partially on the induction of immunogenic tumor cell death following infection with oncolytic viruses (OV) to induce an antitumor immune response. Here, we describe a method to determine if an OV is able to induce such an immunogenic tumor cell death. This method consists in testing whether tumor cells lysed by an OV are able to induce the maturation of human monocyte-derived immature dendritic cells (Mo-iDC).}, }
@article {pmid31467444, year = {2020}, author = {Sarhan, MS and Mourad, EF and Nemr, RA and Abdelfadeel, MR and Daanaa, HA and Youssef, HH and Goda, HA and Hamza, MA and Fayez, M and Eichler-Löbermann, B and Ruppel, S and Hegazi, NA}, title = {An inoculum-dependent culturing strategy (IDC) for the cultivation of environmental microbiomes and the isolation of novel endophytic Actinobacteria.}, journal = {The Journal of antibiotics}, volume = {73}, number = {1}, pages = {66-71}, pmid = {31467444}, issn = {1881-1469}, mesh = {Actinobacteria/*chemistry ; Bacteriological Techniques ; Colony Count, Microbial ; Culture Media ; Endophytes/*chemistry ; *Microbiota ; Plant Roots/microbiology ; Plant Shoots/microbiology ; Plants/microbiology ; }, abstract = {The recent introduction of plant-only-based culture media enabled cultivation of not-yet-cultured bacteria that exceed 90% of the plant microbiota communities. Here, we further prove the competence and challenge of such culture media, and further introduce "the inoculum-dependent culturing strategy, IDC". The strategy depends on direct inoculating plant serial dilutions onto plain water agar plates, allowing bacteria to grow only on the expense of natural nutrients contained in the administered inoculum. Developed colonies are successively transferred/subcultured onto plant-only-based culture media, which contains natural nutrients very much alike to those found in the prepared plant inocula. Because of its simplicity, the method is recommended as a powerful tool in screening programs that require microbial isolation from a large number of diverse plants. Here, the method comfortably and successfully recovered several isolates of endophytic Actinobacteria represented by the six genera of Curtobacterium spp., Plantibacter spp., Agreia spp., Herbiconiux spp., Rhodococcus spp., and Nocardioides spp. Furthermore, two of the isolates are most likely novel species belonging to Agreia spp. and Herbiconiux spp.}, }
@article {pmid31452673, year = {2019}, author = {Dobbels, AA and Lorenz, AJ}, title = {Soybean iron deficiency chlorosis high throughput phenotyping using an unmanned aircraft system.}, journal = {Plant methods}, volume = {15}, number = {}, pages = {97}, pmid = {31452673}, issn = {1746-4811}, abstract = {BACKGROUND: Iron deficiency chlorosis (IDC) is an abiotic stress in soybean [Glycine max (L.) Merr.] that causes significant yield reductions. Symptoms of IDC include interveinal chlorosis and stunting of the plant. While there are management practices that can overcome these drastic yield losses, the preferred way to manage IDC is growing tolerant soybean varieties. To develop varieties tolerant to IDC, breeders may easily phenotype up to thousands of candidate soybean lines every year for severity of symptoms related to IDC, a task traditionally done with a 1-5 visual rating scale. The visual rating scale is subjective and, because it is time consuming and laborious, can typically only be accomplished once or twice during a growing season.<br><br>RESULTS: The goal of this study was to use an unmanned aircraft system (UAS) to improve field screening for tolerance to soybean IDC. During the summer of 2017, 3386 plots were visually scored for IDC stress on two different dates. In addition, images were captured with a DJI Inspire 1 platform equipped with a modified dual camera system which simultaneously captures digital red, green, blue images as well as red, green, near infrared (NIR) images. A pipeline was created for image capture, orthomosaic generation, processing, and analysis. Plant and soil classification was achieved using unsupervised classification resulting in 95% overall classification accuracy. Within the plant classified canopy, the green, yellow, and brown plant pixels were classified and used as features for random forest and neural network models. Overall, the random forest and neural network models achieved similar misclassification rates and classification accuracy, which ranged from 68 to 77% across rating dates. All 36 trials in the field were analyzed using a linear model for both visual score and UAS predicted values on both dates. In 32 of the 36 tests on date 1 and 33 of 36 trials on date 2, the LSD associated with UAS image-based IDC scores was lower than the LSD associated with visual scores, indicating the image-based scores provided more precise measurements of IDC severity.<br><br>CONCLUSIONS: Overall, the UAS was able to capture differences in IDC stress and may be used for evaluations of candidate breeding lines in a soybean breeding program. This system was both more efficient and precise than traditional scoring methods.}, }
@article {pmid31440248, year = {2019}, author = {Escoter-Torres, L and Caratti, G and Mechtidou, A and Tuckermann, J and Uhlenhaut, NH and Vettorazzi, S}, title = {Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1859}, pmid = {31440248}, issn = {1664-3224}, mesh = {Animals ; Gene Expression Regulation/*drug effects/*immunology ; Glucocorticoids/*immunology/pharmacology ; Humans ; Immunosuppressive Agents/*immunology/pharmacology ; Receptors, Glucocorticoid/*immunology ; }, abstract = {For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Glucocorticoids exert their effects by binding to the Glucocorticoid Receptor (GR), a ligand-activated transcription factor which both positively, and negatively regulates gene expression. Extensive research during the past several years has uncovered novel mechanisms by which the GR activates and represses its target genes. Genome-wide studies and mouse models have provided valuable insight into the molecular mechanisms of inflammatory gene regulation by GR. This review focusses on newly identified target genes and GR co-regulators that are important for its anti-inflammatory effects in innate immune cells, as well as mutations within the GR itself that shed light on its transcriptional activity. This research progress will hopefully serve as the basis for the development of safer immune suppressants with reduced side effect profiles.}, }
@article {pmid31437176, year = {2019}, author = {Santos Junior, OR and da Costa Rocha, MO and Rodrigues de Almeida, F and Sales da Cunha, PF and Souza, SCS and Saad, GP and Santos, TADQ and Ferreira, AM and Tan, TC and Nunes, MCP}, title = {Speckle tracking echocardiographic deformation indices in Chagas and idiopathic dilated cardiomyopathy: Incremental prognostic value of longitudinal strain.}, journal = {PloS one}, volume = {14}, number = {8}, pages = {e0221028}, pmid = {31437176}, issn = {1932-6203}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/complications/*diagnostic imaging/mortality/physiopathology ; Chagas Cardiomyopathy/complications/*diagnostic imaging/mortality/physiopathology ; Female ; Follow-Up Studies ; Heart Failure/*diagnostic imaging/etiology/mortality/physiopathology ; Heart Transplantation/statistics &amp; numerical data ; Hospitalization/statistics &amp; numerical data ; Humans ; Male ; Middle Aged ; Prognosis ; Stroke Volume/physiology ; Survival Analysis ; Ventricular Function, Left/physiology ; }, abstract = {BACKGROUND: Chagas cardiomyopathy (CDC) is associated with a poor prognosis compared to other cardiomyopathies. Speckle tracking echocardiography (STE), which provides direct assessment of myocardial fiber deformation, may be useful in predicting prognosis.<br><br>OBJECTIVE: This study assessed STE in CDC and compared with idiopathic cardiomyopathy (IDC), and also examined the incremental prognostic information of STE over left ventricular ejection fraction (LVEF) in these patients.<br><br>METHODS: We enrolled 112 patients, age of 56.7 &#xb1; 11.8 years, 81 with CDC and 31 with IDC. STE indices were obtained at baseline in all patients. The endpoint was a composite of death, hospitalization for heart failure, or need for heart transplantation.<br><br>RESULTS: Patients with IDC had worse LV systolic function compared to CDC, with LVEF of 34.5% vs 41.3%, p = 0.004, respectively. After adjustment for LVEF, there were no differences in STE values between CDC and IDC. During a median follow-up of 18.2 months (range, 11 to 22), 26 patients met the composite end point (24%). LV longitudinal strain was a strong predictor of adverse events, incremental to LVEF and E/e' ratio (HR 1.463, 95% CI 1.130-1.894; p = 0.004). The risk of cardiac events increased significantly in patients with GLS > - 12% (log-rank p = 0.035).<br><br>CONCLUSIONS: STE indices were abnormal in patients with dilated cardiomyopathy, without differences between CDC and IDC. LV longitudinal strain was a powerful predictor of outcome, adding prognostic information beyond that provided by LVEF and E/e' ratio.}, }
@article {pmid31427562, year = {2019}, author = {Sun, Y and Lei, B and Huang, Q}, title = {SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR).}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {25}, number = {}, pages = {6244-6254}, pmid = {31427562}, issn = {1643-3750}, mesh = {Adenylate Kinase/*metabolism ; Apoptosis/physiology ; Carcinoma, Hepatocellular/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Cell Survival/physiology ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms/genetics/*metabolism/*pathology ; Neoplasm Invasiveness ; SOXF Transcription Factors/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. It has been verified that the expression of SOX18 is correlated to poor clinical prognosis in patients with ovarian cancer, non-small cell lung cancer, or breast invasive ductal carcinoma. However, the expression pattern and biological function of SOX18 in HCC tissues remains unclear. In this study, we set out to investigate the associated biological function and potential molecular mechanism of the SOX18 gene in HCC cells. MATERIAL AND METHODS The mRNA and protein expression levels of experimental related genes were detected by real-time polymerase chain reaction and western blotting assay, respectively. The MTT method was used to assess cell viability, and cell apoptosis analysis was performed by means of FACScan flow cytometry. Wound-healing assay and Transwell analysis were performed to evaluate the ability of cell migration and invasiveness, respectively. RESULTS SOX18 was highly expressed in various HCC cell lines. In addition, SOX18 promoted cell viability, migration, and invasion and simultaneously induce cell apoptosis. SOX18 promoted epithelial-to-mesenchymal transition (EMT) progression, and SOX18 downregulation activated the autophagy signaling pathway AMPK/mTOR in HCC cells. CONCLUSIONS SOX18 downregulation in HCC cells suppressed cell viability and metastasis, induced cell apoptosis and hindered the occurrence and progression of tumor cells by participating in the EMT process and regulating the autophagy signaling pathway AMPK/mTOR.}, }
@article {pmid31424026, year = {2020}, author = {Chen, JR and Zhao, JG and Zhu, S and Zhang, MN and Chen, N and Liu, JD and Sun, GX and Shen, PF and Zeng, H}, title = {Clinical and oncologic findings of extraprostatic extension on needle biopsy in de novo metastatic prostate cancer.}, journal = {Asian journal of andrology}, volume = {22}, number = {4}, pages = {427-431}, pmid = {31424026}, issn = {1745-7262}, mesh = {Abiraterone Acetate/therapeutic use ; Adenocarcinoma/metabolism/*secondary/therapy ; Aged ; Androgen Antagonists/therapeutic use ; Antineoplastic Agents/therapeutic use ; Biopsy, Large-Core Needle ; Bone Neoplasms/metabolism/*secondary/therapy ; Docetaxel/therapeutic use ; Functional Status ; Humans ; Kaplan-Meier Estimate ; Male ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neuroendocrine Tumors ; Orchiectomy ; Prognosis ; Progression-Free Survival ; Proportional Hazards Models ; Prostate-Specific Antigen/metabolism ; Prostatectomy ; Prostatic Neoplasms/metabolism/*pathology/therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism/pathology/therapy ; Retrospective Studies ; Survival Rate ; }, abstract = {This study aimed to explore the clinical and oncologic findings in patients with de novo metastatic prostate cancer (mPCa) and extraprostatic extension (EPE) on biopsy. We retrospectively evaluated data on 630 patients with de novo mPCa between January 2009 and December 2017 in the West China Hospital (Chengdu, China), including evaluating the relationships between EPE and other variables and the association of EPE with survival outcomes by the Chi-square test, Kaplan-Meier curves, and the Cox proportional-hazards model. EPE was found in 70/630 patients, making a prevalence of 11.1%. The presence of EPE on biopsy was associated with higher Gleason scores and higher incidence of neuroendocrine differentiation (NED), intraductal carcinoma of the prostate (IDC-P), and perineural invasion (PNI). Compared with those without EPE, patients with EPE had shorter castration-resistant prostate cancer-free survival (CFS; median: 14.1 vs 17.1 months, P = 0.015) and overall survival (OS; median: 43.7 vs 68.3 months, P = 0.032). According to multivariate analysis, EPE was not an independent predictor for survival. Subgroup analyses demonstrated that patients with favorable characteristics, including negative NED or IDC-P status, Eastern Cooperative Oncology Group (ECOG) score <2, and prostate-specific antigen (PSA) <50 ng ml[-1], had worse prognoses if EPE was detected. In patients with PSA <50 ng ml[-1], EPE was a negative independent predictor for OS (hazard ratio [HR]: 4.239, 95% confidence interval [CI]: 1.218-14.756, P = 0.023). EPE was strongly associated with other aggressive clinicopathological features and poorer CFS and OS. These data suggest that EPE may be an indicator of poor prognosis, particularly in patients, otherwise considered likely to have favorable survival outcomes.}, }
@article {pmid31391072, year = {2019}, author = {Tan, X and Li, Z and Ren, S and Rezaei, K and Pan, Q and Goldstein, AT and Macri, CJ and Cao, D and Brem, RF and Fu, SW}, title = {Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {89}, pmid = {31391072}, issn = {1465-542X}, mesh = {3' Untranslated Regions ; Breast Neoplasms/*genetics/*pathology/therapy ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; DNA Damage ; Disease Progression ; Drug Resistance, Neoplasm/*genetics ; Epithelial-Mesenchymal Transition/genetics ; Female ; Forkhead Box Protein M1/genetics ; *Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Humans ; MicroRNAs/*genetics ; Models, Biological ; RNA Interference ; Radiation Tolerance/*genetics ; }, abstract = {BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment.<br><br>METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed.<br><br>RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability.<br><br>CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.}, }
@article {pmid31390230, year = {2019}, author = {Ortega, A and Olea-Herrero, N and Arenas, MI and Vélez-Vélez, E and Moreno-Gómez-Toledano, R and Muñoz-Moreno, C and Lázaro, A and Esbrit, P and Tejedor, A and Bosch, RJ}, title = {Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity.}, journal = {American journal of physiology. Renal physiology}, volume = {317}, number = {4}, pages = {F874-F880}, doi = {10.1152/ajprenal.00091.2019}, pmid = {31390230}, issn = {1522-1466}, mesh = {Acute Kidney Injury/*chemically induced/pathology/*urine ; Animals ; Antineoplastic Agents/*toxicity ; Biomarkers/urine ; Cisplatin/*toxicity ; Creatinine/urine ; Kidney/pathology ; Kidney Function Tests ; Male ; Parathyroid Hormone-Related Protein/*urine ; Rats ; Rats, Wistar ; }, abstract = {Parathyroid hormone-related protein (PTHrP) and its receptor are abundantly expressed throughout the renal parenchyma, where PTHrP exerts a modulatory action on renal function. PTHrP upregulation is a common event associated with the mechanism of renal injury and repair. However, no study has yet explored the putative excretion of PTHrP in urine, including its potential relationship with renal function. In the present study, we tested this hypothesis by studying the well-known rat model of acute renal injury induced by the chemotherapeutic agent cisplatin. Using Western blot analysis, we could detect a single protein band, corresponding to intact PTHrP, in the urine of both control and cisplatin-injected rats, whose levels were significantly higher in the latter group. PTHrP was detected in rat urine by dot blot, and its quantification with two specific ELISA kits showed that, compared with control rats, those treated with cisplatin displayed a significant increase in urinary PTHrP (expressed as the PTHrP-to-creatinine ratio or 24-h excretion). In addition, a positive correlation between urinary PTHrP excretion and serum creatinine was found in these animals. In conclusion, our data demonstrate that PTHrP is excreted in rat urine and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker.}, }
@article {pmid31388122, year = {2020}, author = {Goodes, LM and King, GK and Rea, A and Murray, K and Boan, P and Watts, A and Bardsley, J and Hartshorn, C and Thavaseelan, J and Rawlins, M and Brock, JA and Dunlop, SA}, title = {Early urinary tract infection after spinal cord injury: a retrospective inpatient cohort study.}, journal = {Spinal cord}, volume = {58}, number = {1}, pages = {25-34}, pmid = {31388122}, issn = {1476-5624}, mesh = {Adult ; Catheters, Indwelling/statistics &amp; numerical data ; Humans ; Incidence ; Inpatients/statistics &amp; numerical data ; Length of Stay/*statistics &amp; numerical data ; Middle Aged ; Retrospective Studies ; Spinal Cord Injuries/complications/*epidemiology ; Time Factors ; Urinary Catheterization/adverse effects/*statistics &amp; numerical data ; Urinary Tract Infections/*epidemiology/etiology ; Western Australia/epidemiology ; }, abstract = {STUDY DESIGN: Retrospective audit.<br><br>OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI).<br><br>SETTING: Western Australian Hospitals managing SCI patients.<br><br>METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts.<br><br>RESULTS: Across the cohort (n&#x2009;=&#x2009;70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having &#x2265;1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values&#x2009;<&#x2009;0.001). For patients with &#x2265;1 UTIs (n&#x2009;=&#x2009;43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1&#x2009;SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n&#x2009;=&#x2009;38/70), protocols were followed (85.7%&#x2009;&#x2264;&#x2009;6&#x2009;h apart, 96.1%&#x2009;<&#x2009;8&#x2009;h), but 26% of IC volumes exceeded 500&#x2009;mL; occasional volumes&#x2009;>&#x2009;800&#x2009;mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value&#x2009;<&#x2009;0.001 respectively).<br><br>CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS.<br><br>SPONSORSHIP: None.}, }
@article {pmid31357083, year = {2019}, author = {Arabpour, M and Rasolmali, R and Talei, AR and Mehdipour, F and Ghaderi, A}, title = {Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes.}, journal = {Molecular immunology}, volume = {114}, number = {}, pages = {172-178}, doi = {10.1016/j.molimm.2019.07.019}, pmid = {31357083}, issn = {1872-9142}, mesh = {Adult ; Aged ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD40 Ligand/immunology ; Carcinoma, Ductal/immunology ; Female ; Granzymes/*immunology ; Humans ; Interleukins/immunology ; Lymph Nodes/*immunology ; Lymphocyte Activation/*immunology ; Middle Aged ; Perforin/immunology ; }, abstract = {B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB[+] B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB[+] B cells were perforin-negative. Both naïve (CD24[low]CD27[-]) and active/memory (CD24[hi]CD27[+]) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB[+] B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB[+] B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB[+] B cells in breast tumor immunity.}, }
@article {pmid31354196, year = {2019}, author = {Ogunleye, AJ and Olanrewaju, AJ and Arowosegbe, M and Omotuyi, OI}, title = {Molecular docking based screening analysis of GSK3B.}, journal = {Bioinformation}, volume = {15}, number = {3}, pages = {201-208}, pmid = {31354196}, issn = {0973-2063}, abstract = {GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.}, }
@article {pmid31352554, year = {2019}, author = {Zacharioudakis, K and Kontoulis, T and Vella, JX and Zhao, J and Ramakrishnan, R and Cunningham, DA and Mufti, RA and Leff, DR and Thiruchelvam, P and Hogben, K and Hadjiminas, DJ}, title = {Can we see what is invisible? The role of MRI in the evaluation and management of patients with pathological nipple discharge.}, journal = {Breast cancer research and treatment}, volume = {178}, number = {1}, pages = {115-120}, pmid = {31352554}, issn = {1573-7217}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Preoperative Period ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: The aim of this study was to determine the ability of MRI to identify and assess the extent of disease in patients with pathological nipple discharge (PND) with an occult malignancy not evident on standard pre-operative evaluation with mammography and ultrasound.<br><br>METHODS: Patients presenting to the breast unit of Imperial College Healthcare NHS Trust between December 2009 and December 2018 with PND and normal imaging were enrolled in the study. Pre-operative bilateral breast MRI was performed in all patients as part of our protocol and all patients were offered diagnostic microdochectomy.<br><br>RESULTS: A total of 82 patients fulfilled our selection criteria and were enrolled in our study. The presence of an intraductal papilloma (IDP) was identified as the cause of PND in 38 patients (46.3%), 14 patients had duct ectasia (DE-17%) and 5 patients had both an IDP and DE. Other benign causes were identified in 11 patients (13.4%). Despite normal mammography and ultrasound a malignancy was identified in 14 patients (17%). Eleven patients had DCIS (13.4%), two had invasive lobular carcinoma and one patient had an invasive ductal carcinoma. The sensitivity of MRI in detecting an occult malignancy was 85.71% and the specificity was 98.53%. The positive predictive value was 92.31% and the negative predictive value was 97.1%.<br><br>CONCLUSIONS: Although a negative MRI does not exclude the presence of an occult malignancy the high sensitivity and specificity of this diagnostic modality can guide the surgeon and alter the management of patients&#xa0;with PND.}, }
@article {pmid31351155, year = {2019}, author = {Ding, Q and Chen, H and Lim, B and Damodaran, S and Chen, W and Tripathy, D and Piha-Paul, S and Luthra, R and Meric-Bernstam, F and Sahin, AA}, title = {HER2 somatic mutation analysis in breast cancer: correlation with clinicopathological features.}, journal = {Human pathology}, volume = {92}, number = {}, pages = {32-38}, doi = {10.1016/j.humpath.2019.07.006}, pmid = {31351155}, issn = {1532-8392}, mesh = {Breast/*pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Receptor, ErbB-2/*genetics/metabolism ; Retrospective Studies ; }, abstract = {HER2 mutations have been reported in approximately 2% of breast cancers. Regardless of HER2 overexpression or amplification status, breast cancer with HER2 mutations may respond to HER2-targeted therapy. As HER2 mutation is rare, the clinical and pathological features of HER2-mutated breast cancers, such as hormonal status, histological grade, and metastasis, remain poorly defined. Therefore, the identification of HER2-mutated breast cancer has clinical significance. We retrospectively screened patients with metastatic breast cancer in whom molecular profiling had been performed using next-generation sequencing from 2012 to 2015; we identified 18 patients with HER2 mutation. Mutations were found on next-generation sequencing-based panels, including Ion AmpliSeq Cancer Hotspot, Oncomine, FoundationOne, and Guardant360. HER2 mutations were identified in both the tyrosine kinase (n = 14) and extracellular (n = 4) domains. Of the 14 cases with tyrosine kinase domain mutations, 13 were estrogen receptor positive; the 4 cases with extracellular domain mutations were exclusively estrogen receptor negative. In addition, 11 of 14 patients with tyrosine kinase domain mutations had bone metastasis, whereas no patients with HER2 extracellular domain mutations had bone metastasis. Histologically, 13 patients had invasive ductal carcinoma, 1 had metaplastic carcinoma, and 4 had invasive lobular carcinoma (ILC). All 4 ILCs were high grade and pleomorphic, and not only had an HER2 mutation in the kinase domain but also had an HER2 mutation involving the L755 site. Specific mutation sites may be involved in the pathogenesis of nonclassic ILC.}, }
@article {pmid31350286, year = {2019}, author = {Lourenco, C and Kalkat, M and Houlahan, KE and De Melo, J and Longo, J and Done, SJ and Boutros, PC and Penn, LZ}, title = {Modelling the MYC-driven normal-to-tumour switch in breast cancer.}, journal = {Disease models &amp; mechanisms}, volume = {12}, number = {7}, pages = {}, pmid = {31350286}, issn = {1754-8411}, support = {//CIHR/Canada ; }, mesh = {Breast/*metabolism/pathology ; Breast Neoplasms/metabolism/*pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Female ; Gene Expression Regulation, Neoplastic ; *Genes, myc ; Humans ; *Models, Biological ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction ; }, abstract = {The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the phosphoinositide 3 kinase pathway (PIK3CA[H1047R]) led to the development of organised acinar structures in mice. Expressing both PIK3CA[H1047R] and deregulated MYC led to the development of invasive ductal carcinoma. Therefore, the deregulation of MYC expression in this setting creates a MYC-dependent normal-to-tumour switch that can be measured in vivo These MYC-driven tumours exhibit classic hallmarks of human breast cancer at both the pathological and molecular level. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent model of breast cancer, which can be used to assay invivo tumour signalling pathways, proliferation and transformation from normal breast acini to invasive breast carcinoma. We anticipate that this novel MYC-driven transformation model will be a useful research tool to better understand the oncogenic function of MYC and for the identification of therapeutic vulnerabilities.}, }
@article {pmid31338037, year = {2019}, author = {Rodriguez, J and Schulz, S and Giraldo, BF and Voss, A}, title = {Risk Stratification in Idiopathic Dilated Cardiomyopathy Patients Using Cardiovascular Coupling Analysis.}, journal = {Frontiers in physiology}, volume = {10}, number = {}, pages = {841}, pmid = {31338037}, issn = {1664-042X}, abstract = {Cardiovascular diseases are one of the most common causes of death; however, the early detection of patients at high risk of sudden cardiac death (SCD) remains an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analyses in order to introduce new indices for noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). High-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded in 91 IDC patients and 49 healthy subjects (CON). The patients were stratified by their SCD risk as high risk (IDCHR) when after two years the subject either died or suffered life-threatening complications, and as low risk (IDCLR) when the subject remained stable during this period. Values were extracted from ECG and BP signals, the beat-to-beat interval, and systolic and diastolic blood pressure, and analyzed using the segmented Poincaré plot analysis (SPPA), the high-resolution joint symbolic dynamics (HRJSD) and the normalized short time partial directed coherence methods. Support vector machine (SVM) models were built to classify these patients according to SCD risk. IDCHR patients presented lowered HRV and increased BPV compared to both IDCLR patients and the control subjects, suggesting a decrease in their vagal activity and a compensation of sympathetic activity. Both, the cardio -systolic and -diastolic coupling strength was stronger in high-risk patients when comparing with low-risk patients. The cardio-systolic coupling analysis revealed that the systolic influence on heart rate gets weaker as the risk increases. The SVM IDCLR vs. IDCHR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. The IDC and the CON groups obtained 93.6% and 0.94 accuracy and AUC, respectively. To simulate a circumstance in which the original status of the subject is unknown, a cascade model was built fusing the aforementioned models, and achieved 94.4% accuracy. In conclusion, this study introduced a novel method for SCD risk stratification for IDC patients based on new indices from coupling analysis and non-linear HRV and BPV. We have uncovered some of the complex interactions within the autonomic regulation in this type of patient.}, }
@article {pmid31331321, year = {2019}, author = {Nkinda, L and Patel, K and Njuguna, B and Ngangali, JP and Memiah, P and Bwire, GM and Majigo, MV and Mizinduko, M and Pastakia, SD and Lyamuya, E}, title = {C - reactive protein and interleukin - 6 levels among human immunodeficiency virus -infected patients with dysglycemia in Tanzania.}, journal = {BMC endocrine disorders}, volume = {19}, number = {1}, pages = {77}, pmid = {31331321}, issn = {1472-6823}, support = {-//Intra-ACP academic mobility scholarship/ ; }, mesh = {Biomarkers/*blood ; Blood Glucose/*analysis ; C-Reactive Protein/*analysis ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Glucose Intolerance/*blood/epidemiology/virology ; HIV/*isolation &amp; purification ; HIV Infections/*complications/virology ; Humans ; Incidence ; Interleukin-6/*blood ; Male ; Middle Aged ; Prognosis ; Tanzania/epidemiology ; }, abstract = {BACKGROUND: Chronic inflammation has been associated with dysglycemia among people living with HIV (PLHIV). There is however, limited data regarding this phenomenon in sub-Sahara Africa (SSA). Therefore we assessed the levels of C-reactive protein (CRP) and Interleukin 6 (IL-6) on a cohort of PLHIV and its associations with dysglycemia in Tanzania.<br><br>METHODS: We conducted a cross-sectional study at the Infectious Disease Clinic (IDC) in Tanzania from March to May 2018. Purposive sampling was used to identify participants who had an undetectable viral load, were on 1st line anti-retroviral therapy (ART) and had an overnight fast. The WHO stepwise approach for non-communicable disease (NCD) surveillance was used to collect data. Fasting blood glucose and blood glucose after 75&#x2009;g oral glucose load was measured, and Enzyme-linked immunosorbent assay (ELISA) was used to test for inflammatory markers (IL-6 and CRP). Associations were explored using the Chi square test and binary logistic regression was performed to estimate the odds ratios. A p-value less than 0.05 was considered statistically significant.<br><br>RESULTS: A total of 240 participants were enrolled. Forty two percent were overweight/obese (>&#x2009;25&#x2009;kg/m[2]), 89% had a high waist to height ratio. The median ART duration was 8(5-10) years. The prevalence of dysglycemia among our cohort of PLHIV was 32%. High CRP was associated with a 2.05 increased odds of having dysglycemia OR 2.05 (1.15-3.65) (p&#x2009;=&#x2009;0.01). Taking stavudine was associated with a 1.99 odds of having dysglycemia OR 1.99 (1.04-3.82) (p&#x2009;=&#x2009;0.03).We did not find a significant association between IL-6 and dysglycemia.<br><br>CONCLUSION: High CRP and taking stavudine were significantly associated with dysglycemia among PLHIV with undetectable viral load.}, }
@article {pmid31319513, year = {2019}, author = {Fang, A and Dong, J and Zhang, R}, title = {Simulation of Heavy Metals Migration in Soil-Wheat System of Mining Area.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {14}, pages = {}, pmid = {31319513}, issn = {1660-4601}, mesh = {China ; Edible Grain/chemistry ; Environmental Monitoring ; Metals, Heavy/analysis/*metabolism ; Mining ; Regression Analysis ; Soil ; Soil Pollutants/analysis/*metabolism ; Triticum/*metabolism ; }, abstract = {Heavy metals in the soil of mining areas have become a primary source of pollution, which could cause deleterious health effects in people exposed through soil-plant systems via multi-pathways. A long-term field experiment under natural conditions was carried out to explore the distribution characteristic and migration law of heavy metals in a soil-wheat system of a mining area in Xuzhou. According to the second level standard of environmental quality standards for soils of China (GB 15618-1995), 30.8 g of CrCl3·6H2O, 8.3 g of Pb(CH3COO)2·3H2O, and 16.5 g of ZnSO4·7H2O were added into the soil of three experimental sites, respectively. The other experimental site with no additional compounds was used as the control site. The Cr, Pb, and Zn concentrations in the soil-wheat system were counted and their corresponding migration models were constructed. From 2014 to 2017, the mean concentrations of Cr (49.09 mg·kg[-1]), Pb (20.08 mg·kg[-1]), and Zn (39.11 mg·kg[-1]) in the soil of the addition sites were higher than that of the control site. The mean concentrations of Cr, Pb, and Zn in wheat of the addition sites were greater than that of the control site with the values of 3.29, 0.06, and 29 mg·kg[-1]. In comparison, the Cr, Pb, and Zn concentrations in the soil of all experimental sites were lower than the second level standard of environmental quality standards for soils of China (GB 15618-1995), whereas the Cr concentration exceeded its corresponding soil background value of Xuzhou in 2017. The Pb concentration in soil of the addition site was greater than its corresponding background value from 2014 to 2016. The Pb and Zn concentrations in wheat of all experimental sites were lower than the national hygienic standard for grains of China (GB2715-2005) and the national guidelines for cereals of China (NY 861-2004), but the Cr concentration significantly exceeded the national guidelines for cereals of China (NY 861-2004). By constructing the Identical-Discrepant-Contrary (IDC) gray connection models, the result showed that there was a non-linear relationship of Cr, Pb, and Zn concentrations in the soil-wheat system, and the absolute values of most correlation coefficients r were lower than 0.5 and the values of greyness f G (r) were more than 0.5. The curvilinear regression models could not reflect the relationship of Cr, Pb, and Zn concentrations in the soil-wheat system with the regression coefficient r 2 values far less than 1. Due to the values of regression coefficient r 2 being close to 1, this study suggested that the allocation estimation models could be used for simulating the Cr, Pb, and Zn migration in the soil-wheat system of a mining area in Xuzhou.}, }
@article {pmid31312338, year = {2019}, author = {Traoré, B and Koulibaly, M and Diallo, A and Bah, M}, title = {Molecular profile of breast cancers in Guinean oncological settings.}, journal = {The Pan African medical journal}, volume = {33}, number = {}, pages = {22}, pmid = {31312338}, issn = {1937-8688}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/genetics/*pathology ; Breast Neoplasms, Male/epidemiology/genetics/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Female ; Guinea/epidemiology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/epidemiology/*pathology ; }, abstract = {Breast cancer is a complex disease characterized by the accumulation of multiple molecular alterations giving each tumor phenotype and an own evolutionary potential. This study aimed to describe the distribution of the profile and molecular subtypes of breast cancers followed at Surgical Oncology Unit of Donka National Hospital. This was retrospective and descriptive study on cases of breast cancer in which the hormone receptor status and expression of the Her2 oncogene have been performed from 2007 to 2016. We recorded 58 cases including 56 (96.6%) women and 2 (3.4%) men. The average age was 48.2 ± 10.9. Invasive ductal carcinoma accounted for 50 (86.2%) cases. The SBR grade was II in 31(53.4%) cases, III in 21 (36.2%) cases and I in 6 (10.3%) cases. The tumor was classified as T4 in 36 (62.1%) cases; it was metastatic in 11(19.0%) cases. Estrogen receptors were positive in 29 (50.0%) cases, progesterone receptors positive in 25 (43.1%) cases, the Her2 oncogene was positive in 22 (39.3%) cases. The distribution of molecular sub-types was: 20 (34.5%) luminal A, 15 (25.9%) triple negative, 13 (22.4%) Her2 overexpressed, 8 (13.8%) luminal B and 2 (3.2%) undetermined. This preliminary study showed the poor accessibility of immunohistochemistry for the molecular diagnosis of breast cancer in our country. Luminal A subtypes and triple negatives were more common. The determination of molecular subtypes is a rational basis for hormone therapy and targeted therapy, thus personalizing the treatment of breast cancer.}, }
@article {pmid31308566, year = {2019}, author = {Malik, SS and Baig, M and Khan, MB and Masood, N}, title = {Survival analysis of breast cancer patients with different treatments: a multicentric clinicopathological study.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {69}, number = {7}, pages = {976-980}, pmid = {31308566}, issn = {0030-9982}, mesh = {Adult ; Age Factors ; Antineoplastic Agents/*therapeutic use ; Body Mass Index ; Breast Neoplasms/epidemiology/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/epidemiology/mortality/pathology/*therapy ; Cohort Studies ; Combined Modality Therapy ; Consanguinity ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy/*methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Obesity/epidemiology ; Overweight/epidemiology ; Pakistan/epidemiology ; Prospective Studies ; Radiotherapy/*methods ; Risk Factors ; Survival Analysis ; Survival Rate ; }, abstract = {OBJECTIVE: To explore and better understand clinic pathological details of breast cancer patients and analyse their survival rate among different treatment groups.<br><br>METHODS: The prospective cohort, multi-centric study was conducted from September, 2014, to February, 2018, at five hospitals in Rawalpindi and Islamabad, Pakistan, and comprised histo-pathologically confirmed breast cancer cases. Patient characteristics and medical history were collected using a detailed questionnaire. All the subjects were followed up, and information regarding their current health and treatment status was collected. Data was analysed using SPSS 24.<br><br>RESULTS: There were 347 subjects with a mean age of 44.3&#xb1;12.2 years and body mass index of 27.9&#xb1;4.0 kg/m2. Younger age, increased body mass index, consanguinity and family history were major contributing factors in breast cancer development (p<0.05). Overall, 267(77%) had invasive ductal carcinoma and Grade II tumour 234(67%) was more frequent. A total of 221(64%) cases had positive lymph nodes and 97(28%) had metastasis to different body organs. Overall survival analysis showed statistically significant role (p<0.0001) of all treatment options.<br><br>CONCLUSIONS: Combination of different treatments can provide more promising health outcomes in breast cancer cases.}, }
@article {pmid31299411, year = {2019}, author = {Molina, J and Noguer, M and Lepe, JA and Pérez-Moreno, MA and Aguilar-Guisado, M and Lasso de la Vega, R and Peñalva, G and Crespo-Rivas, JC and Gil-Navarro, MV and Salvador, J and Cisneros, JM}, title = {Clinical impact of an educational antimicrobial stewardship program associated with infectious diseases consultation targeting patients with cancer: Results of a 9-year quasi-experimental study with an interrupted time-series analysis.}, journal = {The Journal of infection}, volume = {79}, number = {3}, pages = {206-211}, doi = {10.1016/j.jinf.2019.07.002}, pmid = {31299411}, issn = {1532-2742}, mesh = {*Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; Communicable Diseases/drug therapy/*epidemiology/etiology ; Drug Utilization/statistics &amp; numerical data ; Female ; Health Plan Implementation ; Humans ; Male ; Neoplasms/complications/*epidemiology ; *Referral and Consultation ; Time Factors ; }, abstract = {OBJECTIVES: Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. However, their effectiveness or safety in immunocompromised hosts needs to be proved.<br><br>METHODS: An ecologic quasi-experimental study was performed from January 2009 to June 2017 in the Oncology department of a tertiary-care hospital. A stable program of Infectious Diseases consultation (IDC) already existed at this unit, and an educational ASP was added in 2011. Its main intervention consisted of face-to-face educational interviews. Antibiotic consumption was assessed through quarterly Defined Daily Doses (DDD) per 100 occupied bed-days. Mortality was evaluated in patients with bloodstream infections through the quarterly incidence density per 1000 admissions, and the annual mortality rates at 7 and 30-days. Time-trends were analysed through segmented-regression analysis, and the impact of the ASP was assessed through before-after interrupted time-series analysis.<br><br>RESULTS: Mortality significantly decreased throughout the study period (-13.3% annual reduction for 7-day mortality rate, p&#xa0;<&#xa0;0.01; -8.1% annual reduction for 30-day mortality, p&#x202f;=&#x202f;0.03), parallel to a reduction in antibiotic consumption (quarterly reduction -0.4%, p&#x202f;=&#x202f;0.01), especially for broader-spectrum antibiotics. The before-after study settled a significant inflexion point on the ASP implementation for the reduction of antibiotic consumption (change in level 0.95 DDD, p&#x202f;=&#x202f;0.71; change in slope -1.98 DDD per quarter, p&#xa0;<&#xa0;0.01). The decreasing trend for mortality before the ASP also continued after its implementation.<br><br>CONCLUSIONS: The combination of an ASP with IDC improved antibiotic use among patients with cancer, and was accompanied by a reduction of mortality of bacteraemic infections. Implementation of the ASP was necessary to effectively change antibiotic use.}, }
@article {pmid31291711, year = {2020}, author = {Xu, Q and Shao, Y and Zhang, J and Zhang, H and Zhao, Y and Liu, X and Guo, Z and Chong, W and Gu, F and Ma, Y}, title = {Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response.}, journal = {Cancer research and treatment}, volume = {52}, number = {1}, pages = {218-245}, pmid = {31291711}, issn = {2005-9256}, support = {81572851//National Scientific Foundation of China/ ; 81672636//National Scientific Foundation of China/ ; }, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*drug therapy/*etiology/mortality ; Carrier Proteins/*genetics ; Cell Transformation, Neoplastic/*genetics ; *Disease Susceptibility ; Female ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Proteins/*genetics ; Prognosis ; Recurrence ; Treatment Outcome ; Tumor Burden ; }, abstract = {PURPOSE: Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression.<br><br>MATERIALS AND METHODS: AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3's correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3's impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected.<br><br>RESULTS: AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines.<br><br>CONCLUSION: AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.}, }
@article {pmid31288210, year = {2019}, author = {Shelef, L and Klomek, AB and Fruchter, E and Kedem, R and Mann, JJ and Zalsman, G}, title = {Suicide ideation severity is associated with severe suicide attempts in a military setting.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {61}, number = {}, pages = {49-55}, doi = {10.1016/j.eurpsy.2019.06.005}, pmid = {31288210}, issn = {1778-3585}, mesh = {Adult ; Female ; Humans ; Intention ; Male ; Middle Aged ; Military Personnel/*psychology ; Risk Factors ; Self Report ; Self-Control/*psychology ; *Severity of Illness Index ; *Suicidal Ideation ; Suicide, Attempted/psychology ; Veterans/*psychology ; Young Adult ; }, abstract = {BACKGROUND: There is an ongoing debate on the effectiveness of suicidal behavior prevention measures in the military. The association of three widely used tools with severe suicide attempts was assessed in this setting.<br><br>METHODS: Thirty-nine Israeli soldiers (59% males), mean age 19 yrs., who attempted suicide during military service were divided into two groups: severe (n&#x2009;=&#x2009;14; 35.9%) and moderate suicide attempts, and were assessed using the Scale for Suicide Ideation (SSI), Suicide Intent Scale (SIS) and the Columbia Suicide Severity Rating Scale (C-SSRS).<br><br>RESULTS: Seven items from the SSI (p&#x2009;=&#x2009;0.008), two items from SIS and one item from C-SSRS were associated with severe suicide attempts. Kendall's tau-b correlation with bootstrap demonstrated stability of these correlations.<br><br>CONCLUSION: Greater severity of suicidal ideation was associated with more severe suicide attempts. The combination of male gender, available firearms and current severe suicide ideation is high-risk danger sign in a military setting, even when reported intent to die is low.}, }
@article {pmid31284267, year = {2019}, author = {Liu, S and Wei, H and Li, Y and Diao, L and Lian, R and Zhang, X and Zeng, Y}, title = {Characterization of dendritic cell (DC)-10 in recurrent miscarriage and recurrent implantation failure.}, journal = {Reproduction (Cambridge, England)}, volume = {158}, number = {3}, pages = {247-255}, doi = {10.1530/REP-19-0172}, pmid = {31284267}, issn = {1741-7899}, mesh = {Abortion, Habitual/*immunology/metabolism ; Adult ; Cell Differentiation ; Dendritic Cells/immunology/*metabolism ; Embryo Implantation/*immunology ; Female ; Humans ; Interleukin-10/*metabolism ; Interleukin-6/metabolism ; Pregnancy ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {During pregnancy, the maternal immune system must tolerate the persistence of semi-allogeneic fetus in the maternal tissue. Inadequate recognition of fetal antigens may lead to pregnancy complications, such as recurrent miscarriage (RM) and recurrent implantation failure (RIF). Dendritic cells (DCs) are key regulators of protective immune responses and the development and maintenance of tolerance. Regarding that DCs are important in the establishment of immune tolerance in human pregnancy, it would be important to study the microenvironment in which DCs reside or are activated may affect their functions toward tolerance rather than active immune response. IL-10 plays a critical role in the maintenance of normal pregnancy, and the increased production of IL-10 is associated with successful pregnancy. In this study, we provide an in-depth comparison of the phenotype and cytokine production by DC-10 and other DC subsets, such as iDC and mDC. CD14+ monocyte-derived DCs were differentiated in the presence of IL-10 (DC-10) in vitro from ten normal fertile controls, six RM women and seven RIF women, and characterized for relevant markers. DC-10 was characterized by relatively low expression of costimulatory molecule CD86, as well as MHC class II molecule HLA-DR, high expression of tolerance molecules HLA-G, ILT2, ILT4 and immunosuppressive cytokine IL-10, but produced little or no proinflammatory cytokines, such as TNF-α, IL-6 and IL-12p70. Our study provides a better understanding of the phenotypical properties of DC-10, which may participate in the complex orchestration that leads to maternal immune tolerance and homeostatic environment in human pregnancy.}, }
@article {pmid31275451, year = {2019}, author = {Simeunovic, D and Odanovic, N and Pljesa-Ercegovac, M and Radic, T and Radovanovic, S and Coric, V and Milinkovic, I and Matic, M and Djukic, T and Ristic, A and Risimic, D and Seferovic, P and Simic, T and Simic, D and Savic-Radojevic, A}, title = {Glutathione Transferase P1 Polymorphism Might Be a Risk Determinant in Heart Failure.}, journal = {Disease markers}, volume = {2019}, number = {}, pages = {6984845}, pmid = {31275451}, issn = {1875-8630}, mesh = {Aged ; Cardiomyopathy, Dilated/complications/*genetics ; Coronary Artery Disease/complications/*genetics ; Female ; Glutathione S-Transferase pi/*genetics ; Heart Failure/etiology/*genetics ; Humans ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; }, abstract = {Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0.031), which was higher when combined with the variant GSTA1∗B allele (OR = 2.2, p = 0.034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 "risk-associated" genotype (OR = 2.8, p = 0.033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2.1, p = 0.056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗AA/GSTP1∗IleIle carriers (p = 0.021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0.041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0.041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF.}, }
@article {pmid31256281, year = {2019}, author = {D'Iorio, A and Maggi, G and Vitale, C and Amboni, M and Di Meglio, D and Trojano, L and Santangelo, G}, title = {Prospective memory in Parkinson's disease: the role of the motor subtypes.}, journal = {Journal of neurology}, volume = {266}, number = {10}, pages = {2505-2511}, pmid = {31256281}, issn = {1432-1459}, mesh = {Aged ; Cognitive Dysfunction/etiology/*physiopathology ; Executive Function/physiology ; Female ; Humans ; Hypokinesia/etiology/*physiopathology ; Male ; *Memory, Episodic ; Middle Aged ; Muscle Rigidity/etiology/*physiopathology ; Parkinson Disease/classification/complications/*physiopathology ; Tremor/etiology/*physiopathology ; }, abstract = {BACKGROUND: Prospective memory (PM) is defined as memory for future intentions and it is typically divided into time-based and event-based PM. Deficit of PM has been reported in patients with Parkinson's disease (PD) but no study has yet explored the association between motor subtypes (tremor dominant and rigidity/bradykinesia dominant) and performance on PM tasks. The aim of the study was to explore the role of motor subtypes in the defect of PM.<br><br>METHODS: Consecutive outpatients with tremor dominant (TD-PD) or rigidity/bradykinesia dominant (PIGD-PD) PD and healthy subjects (HCs) were enrolled and underwent a neuropsychological battery assessing PM, verbal memory and executive functions and questionnaires assessing apathy, functional autonomy, and perceived memory disturbances.<br><br>RESULTS: We enrolled 28 patients with TD-PD, 28 patients with PIGD-PD and 50 HCs. The three groups did not differ on demographic and cognitive variables. Patients with TD-PD performed worse on time-based PM tasks than patients with PIGD-PD and HCs; no significant difference was found among the three groups on event-based PM tasks. Executive dysfunctions contributed to reduced time-based PM scores in TD-PD. Moreover, severe deficit of time-based and more frequency of perceived failures of PM contributed to reduced functional autonomy in TD-PD.<br><br>CONCLUSION: The finding of a poorer performance of patients with TD-PD than ones with PIGD-PD and HCs suggests a selective deficit of time-based PM abilities in TD-PD group; therefore, deficit of time-based PM might be considered as a distinctive non-motor symptom of TD-PD and it might affect the functional autonomy in this subtype of PD.}, }
@article {pmid31244288, year = {2019}, author = {Ghaderi, F and Mehdipour, F and Hosseini, A and Talei, A and Ghaderi, A}, title = {Establishment and Characterization of a New Triple Negative Breast Cancer Cell Line from an Iranian Breast Cancer Tissue.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {6}, pages = {1683-1689}, pmid = {31244288}, issn = {2476-762X}, mesh = {Adult ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Culture Techniques ; Cell Line, Tumor ; *Cell Movement ; *Cell Proliferation ; *Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Triple Negative Breast Neoplasms/metabolism/*pathology ; }, abstract = {Breast cancer is the most common malignancy and the leading cause of cancer-related death among women worldwide. The underlying mechanisms for breast cancer development, especially in young women, are not completely understood. Although there are several experimental models to understand the biology of breast cancer such as immortalized cell lines, many of these cell lines have been in culture for decades and most of them have been derived from Caucasians or African-Americans. So, it is required to establish a new cell line derived from primary tumors and Asian women. In this study Pari-Institute for Cancer Research (Pari-ICR) was derived from the primary breast tumor of a 36-years old patient with invasive ductal carcinoma. We characterized the cell line by examining morphology, expression of different markers, and functional profile. Immunocytochemistry showed that this cell line does not express estrogen and progesterone receptors as well as human epidermal growth factor receptor 2 (HER2). Pari-ICR cell line expresses high levels of Vimentin, Ezrin, and S100 but does not express EpCAM, Cytokeratin19, Pan-cytokeratin, Nestin, and Desmin. Its doubling time of Pari-ICR was about 22h and was able to grow as colonies in soft agar. It displayed a higher ability of migration and invasion in comparison with MCF-7 cell line. This breast cancer cell line can serve as a model for understanding the molecular mechanisms of breast carcinogenesis. Moreover, it can be used as an appropriate resource to find novel biomarkers or assess new drugs.}, }
@article {pmid31243309, year = {2019}, author = {Zwarts, I and van Zutphen, T and Kruit, JK and Liu, W and Oosterveer, MH and Verkade, HJ and Uhlenhaut, NH and Jonker, JW}, title = {Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {9299}, pmid = {31243309}, issn = {2045-2322}, mesh = {Adipose Tissue/metabolism ; Animals ; Diet ; Duodenum/metabolism ; Fructose/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Glucose Transporter Type 5/*metabolism ; HEK293 Cells ; Haplorhini ; Humans ; Hydrocarbons, Fluorinated/pharmacology ; Ligands ; Liver X Receptors/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Response Elements ; Sulfonamides/pharmacology ; Transcription, Genetic ; }, abstract = {Fructose has become a major constituent of our modern diet and is implicated as an underlying cause in the development of metabolic diseases. The fructose transporter GLUT5 (SLC2A5) is required for intestinal fructose absorption. GLUT5 expression is induced in the intestine and skeletal muscle of type 2 diabetes (T2D) patients and in certain cancers that are dependent on fructose metabolism, indicating that modulation of GLUT5 levels could have potential in the treatment of these diseases. Using an unbiased screen for transcriptional control of the human GLUT5 promoter we identified a strong and specific regulation by liver X receptor α (LXRα, NR1H3). Using promoter truncations and site-directed mutagenesis we identified a functional LXR response element (LXRE) in the human GLUT5 promoter, located at -385 bp relative to the transcriptional start site (TSS). Finally, mice treated with LXR agonist T0901317 showed an increase in Glut5 mRNA and protein levels in duodenum and adipose tissue, underscoring the in vivo relevance of its regulation by LXR. Together, our findings show that LXRα regulates GLUT5 in mice and humans. As a ligand-activated transcription factor, LXRα might provide novel pharmacologic strategies for the selective modulation of GLUT5 activity in the treatment of metabolic disease as well as cancer.}, }
@article {pmid31240968, year = {2021}, author = {Shenkman, G and Pardo Aviv, L and Hain, D and Goren, O and Shapira, S and Nakash, O and Brunstein Klomek, A and Berant, E}, title = {The moderation of attachment in the association between depressive symptoms and self-harm among a clinical sample.}, journal = {Journal of mental health (Abingdon, England)}, volume = {30}, number = {1}, pages = {58-65}, doi = {10.1080/09638237.2019.1630723}, pmid = {31240968}, issn = {1360-0567}, mesh = {Anxiety/epidemiology ; Anxiety Disorders ; *Depression/epidemiology ; Humans ; Object Attachment ; *Self-Injurious Behavior/epidemiology ; }, abstract = {BACKGROUND: Self-harm is a severe health problem worldwide and in particular in clinical settings. The association of depression and self-harm has been extensively studied alongside various variables that have been examined as moderating this association. However, no previous study has examined the moderating role of attachment in this association.<br><br>AIM: We explored the role of attachment orientation in moderating the association between depressive symptoms and self-harm among a sample of patients in a community mental health clinic.<br><br>METHOD: This study was a de-identified archival study of patients' medical charts, and used a convenience sample of 199 patients, which completed self-report measures following the initial intake appointment as part of clinic procedures.<br><br>RESULTS: Findings showed that both attachment anxiety and avoidance moderated the association between depressive symptoms and self-harm, such that depressive symptoms were positively associated with self-harm only when attachment anxiety scores were high, and attachment avoidance scores were high or average.<br><br>CONCLUSIONS: Attachment anxiety and avoidance should be assessed in the initial intake of patients as it has a contribution to understanding self-harm vulnerability among new patients. Future studies should explore this moderation longitudinally so causality could be inferred.}, }
@article {pmid31238731, year = {2019}, author = {Farsang, A and Bódi, I and Fölker, O and Minkó, K and Benyeda, Z and Bálint, &#xc1; and Oláh, I}, title = {Avian coronavirus infection induces mannose-binding lectin production in dendritic cell precursors of chicken lymphoid organs.}, journal = {Acta veterinaria Hungarica}, volume = {67}, number = {2}, pages = {183-196}, doi = {10.1556/004.2019.020}, pmid = {31238731}, issn = {0236-6290}, mesh = {Animals ; Avian Proteins/metabolism ; Cecum/*immunology ; *Chickens ; Coronavirus Infections/metabolism/*veterinary ; Dendritic Cells/*metabolism ; Gammacoronavirus/physiology ; Mannose-Binding Lectins/*metabolism ; Poultry Diseases/*metabolism ; Specific Pathogen-Free Organisms ; Spleen/*immunology ; }, abstract = {The aim of this immunocytochemical study was to compare mannose-binding lectin (MBL) production induced by avian coronavirus in the spleen and caecal tonsil (CT). One-day-old specific-pathogen-free (SPF) chickens were experimentally infected with six QX field isolates and the H120 vaccine strain. In the negative control birds, the spleen was MBL negative, while the CT showed scattered MBL-positive cells in close proximity and within the surface epithelium and germinal centre (GC)-like cell clusters. MBL was detectable in the ellipsoid-associated cells (EACs) and cell clusters in the periarterial lymphoid sheath (PALS) by 7 days post infection (dpi). In both organs, the MBL-positive cells occupy antigen-exposed areas, indicating that GC formation depends on resident precursors of dendritic cells. The majority of MBL-positive EACs express the CD83 antigen, providing evidence that coronavirus infection facilitated the maturation of dendritic cell precursors. Surprisingly, co-localisation of MBL and CD83 was not detectable in the CT. In the spleen (associated with circulation), the EACs producing MBL and expressing CD83 are a common precursor of both follicular (FDC) and interdigitating dendritic cells (IDC). In the CT (gut-associated lymphoid tissue, GALT) the precursors of FDC and IDC are MBL-producing cells and CD83-positive cells, respectively. In the CT the two separate precursors of lymphoid dendritic cells provide some 'autonomy' for the GALT.}, }
@article {pmid31229512, year = {2019}, author = {Cao, L and Basudan, A and Sikora, MJ and Bahreini, A and Tasdemir, N and Levine, KM and Jankowitz, RC and McAuliffe, PF and Dabbs, D and Haupt, S and Haupt, Y and Lucas, PC and Lee, AV and Oesterreich, S and Atkinson, JM}, title = {Frequent amplifications of ESR1, ERBB2 and MDM4 in primary invasive lobular breast carcinoma.}, journal = {Cancer letters}, volume = {461}, number = {}, pages = {21-30}, pmid = {31229512}, issn = {1872-7980}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis ; Biomarkers, Tumor ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Cell Cycle Checkpoints ; Cell Cycle Proteins/*genetics/metabolism ; Cell Proliferation ; DNA Copy Number Variations ; Estrogen Receptor alpha/*genetics ; Female ; Follow-Up Studies ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics/metabolism/*pathology ; Prognosis ; Proto-Oncogene Proteins/*genetics/metabolism ; Receptor, ErbB-2/*genetics ; Retrospective Studies ; Survival Rate ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). To identify potential genetic drivers of ILC progression, we used NanoString nCounter technology to investigate the DNA copy number (CN) in 70 well-curated primary ILC samples. We confirmed prior observations of frequent amplification of CCND1 (33%), and MYC (17%) in ILC, but additionally identified a substantial subset of ILCs with ESR1 and ERBB2 (19%) amplifications. Of interest, tumors with ESR1 CN gains (14%) and amplification (10%) were more likely to recur compared to those with normal CN. Finally, we observed that MDM4 (MDMX) was amplified in 17% of ILC samples. MDM4 knockdown in TP53 wild-type ILC cell lines caused increased apoptosis, decreased proliferation associated with cell cycle arrest, and concomitant activation of TP53 target genes. Similar effects were seen in TP53 mutant cells, indicting a TP53-independent role for MDM4 in ILC. To conclude, amplification of ESR1 and MDM4 are potential genetic drivers of ILC. These amplifications may represent actionable, targetable tumor dependencies, and thus have potential clinical implications and warrant further study.}, }
@article {pmid31222554, year = {2019}, author = {Arya, BK and Bhattacharya, SD and Harigovind, G and Das, RS and Khan, T and Ganaie, F and Niyogi, SK and Ravikumar, KL and Manoharan, A and Bhattacharyya, S and Panda, S and Mandal, S and Acharya, B}, title = {Streptococcus pneumoniae Acquisition and Carriage in Vaccine Naïve Indian Children with HIV and their Parents: A Longitudinal Household Study.}, journal = {Indian journal of pediatrics}, volume = {86}, number = {11}, pages = {1002-1010}, pmid = {31222554}, issn = {0973-7693}, support = {Fulbright-Nehru Doctoral Research Award 2014-15//United States Department of State's Bureau of Educational and Cultural Affairs, and USIEF, New Delhi/International ; 5/7/463/2010-RHN//Indian Council of Medical Research/International ; }, mesh = {Carrier State/*microbiology ; Child ; Child, Preschool ; Female ; HIV Infections/*complications/epidemiology/microbiology ; Humans ; India ; Longitudinal Studies ; Male ; Microbial Sensitivity Tests ; Nasopharynx/microbiology ; Parents ; Pneumococcal Infections/epidemiology/*microbiology/transmission/virology ; Pneumococcal Vaccines/*administration &amp; dosage ; Prevalence ; Prospective Studies ; Serogroup ; Serotyping ; Streptococcus pneumoniae/immunology/*pathogenicity ; Vaccination ; }, abstract = {OBJECTIVES: To investigate the difference in pneumococcal carriage, acquisition, antibiotic resistance profiles and serotype distribution, in human immunodeficiency virus (HIV) affected and unaffected families.<br><br>METHODS: A prospective cohort study was conducted in children with and without HIV in West Bengal from March 2012 through August 2014, prior to 13-valent pneumococcal conjugate vaccine (PCV-13) immunization. One thousand four hundred forty one nasopharyngeal swabs were collected and cultured at five-time points from children and their parents for pneumococcal culture, and serotyping by Quellung method.<br><br>RESULTS: One hundred twenty five HIV infected children and their parents, and 47 HIV uninfected children and their parents participated. Two hundred forty pneumococcal isolates were found. In children under 6 y, the point prevalence of colonization was 31% in children living with HIV (CLH) and 32% in HIV uninfected children (HUC), p&#x2009;=&#x2009;0.6. The most common vaccine type (VT) serotypes were 6A, 6B and 19A. All isolates from parents and 71% from children in the HIV uninfected cohort were PCV-13 representative, compared to 33% of isolates from CLH and their parents. Acquisition rate in children was 1.77 times that of parents (OR&#x2009;=&#x2009;1.77, 95%CI: 1.18-2.65). The HIV status of child or parent did not affect acquisition. Isolates from CLH were more frequently resistant to multiple antibiotics (p&#x2009;=&#x2009;0.02).<br><br>CONCLUSIONS: While the rate of pneumococcal carriage and acquisition did not differ between CLH and HUC, HIV affected families had exposure to a wider range of serotypes including non-vaccine type serotypes and antibiotic resistant serotypes, than HIV unaffected families.}, }
@article {pmid31217350, year = {2019}, author = {Lodd, E and Wiggenhauser, LM and Morgenstern, J and Fleming, TH and Poschet, G and Büttner, M and Tabler, CT and Wohlfart, DP and Nawroth, PP and Kroll, J}, title = {The combination of loss of glyoxalase1 and obesity results in hyperglycemia.}, journal = {JCI insight}, volume = {4}, number = {12}, pages = {}, pmid = {31217350}, issn = {2379-3708}, mesh = {Animals ; CRISPR-Cas Systems ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/genetics ; Diet ; Disease Models, Animal ; Gene Knockout Techniques ; Genetic Predisposition to Disease ; Glucose/metabolism ; Hyperglycemia/*etiology/genetics ; Insulin Resistance ; Lactoylglutathione Lyase/genetics/*physiology ; Liver/metabolism ; Male ; Obesity/*complications ; Pyruvaldehyde/metabolism ; Retina/pathology ; Zebrafish/growth &amp; development ; }, abstract = {The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1-/- zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced-obesity zebrafish model was used to analyze glo1-/- zebrafish under high nutrient intake. Glo1-/- zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1-/- zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1-/- zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.}, }
@article {pmid31203172, year = {2019}, author = {Raetz, AG and David, SS}, title = {When you're strange: Unusual features of the MUTYH glycosylase and implications in cancer.}, journal = {DNA repair}, volume = {80}, number = {}, pages = {16-25}, pmid = {31203172}, issn = {1568-7856}, support = {R01 CA067985/CA/NCI NIH HHS/United States ; R29 CA067985/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA/metabolism ; *DNA Damage ; DNA Glycosylases/*metabolism ; *DNA Repair ; Guanine/analogs &amp; derivatives/metabolism ; Humans ; Neoplasms/genetics/*metabolism ; *Signal Transduction ; }, abstract = {MUTYH is a base-excision repair glycosylase that removes adenine opposite 8-oxoguanine (OG). Variants of MUTYH defective in functional activity lead to MUTYH-associated polyposis (MAP), which progresses to cancer with very high penetrance. Whole genome and whole exome sequencing studies have found MUTYH deficiencies in an increasing number of cancer types. While the canonical OG:A repair activity of MUTYH is well characterized and similar to bacterial MutY, here we review more recent evidence that MUTYH has activities independent of OG:A repair and appear centered on the interdomain connector (IDC) region of MUTYH. We summarize evidence that MUTYH is involved in rapid DNA damage response (DDR) signaling, including PARP activation, 9-1-1 and ATR signaling, and SIRT6 activity. MUTYH alters survival and DDR to a wide variety of DNA damaging agents in a time course that is not consistent with the formation of OG:A mispairs. Studies that suggest MUTYH inhibits the repair of alkyl-DNA damage and cyclopyrimidine dimers (CPDs) is reviewed, and evidence of a synthetic lethal interaction with mismatch repair (MMR) is summarized. Based on these studies we suggest that MUTYH has evolved from an OG:A mispair glycosylase to a multifunctional scaffold for DNA damage response signaling.}, }
@article {pmid31200836, year = {2019}, author = {Jeyapala, R and Savio, AJ and Olkhov-Mitsel, E and Kamdar, S and Zhao, F and Cuizon, C and Liu, RSC and Zlotta, A and Fleshner, N and van der Kwast, T and Bapat, B}, title = {GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.}, journal = {European urology oncology}, volume = {2}, number = {3}, pages = {231-238}, doi = {10.1016/j.euo.2018.08.003}, pmid = {31200836}, issn = {2588-9311}, mesh = {Biomarkers, Tumor/genetics ; Carcinoma, Intraductal, Noninfiltrating/blood/genetics/mortality/pathology ; Cell Line, Tumor ; DNA Methylation ; DNA-Binding Proteins/genetics ; Dioxygenases ; Epigenesis, Genetic ; Homeodomain Proteins/*genetics ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*genetics/metabolism/*pathology/surgery ; Proto-Oncogene Proteins/genetics ; Recurrence ; Survival Analysis ; }, abstract = {BACKGROUND: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.<br><br>OBJECTIVE: To investigate tumor-specific methylation of the transcription factor GBX2 as a novel prognosticator and predictor of BCR in PCa patients stratified by histopathologic features including IDC/C.<br><br>Using genome-wide methylome profiling, we identified higher GBX2 methylation in grade group (GG) 4 tumors compared to GG1 (discovery cohort). The prognostic nature of GBX2 methylation was validated in silico using The Cancer Genome Atlas data (n=478) and a quantitative methylation assay for radical prostatectomy samples (n=254). Regulation of GBX2 methylation was investigated in prostate cells using methyl-CpG-binding domain sequencing and methylation analysis in functional knockouts of TET2, a key epigenetic player in prostate carcinogenesis.<br><br>The association of GBX2 methylation with Gleason score (GS), pathologic stage (pT), IDC/C, and BCR was analyzed using Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression analyses were used to predict BCR.<br><br>RESULTS: GBX2 methylation was associated with GS (p<0.05), pT (p<0.01), and BCR (p<0.05). GBX2 methylation (p=0.004), GS (p<0.001), pT (p=0.012), and prostate-specific antigen (p=0.005) were independent predictors of BCR. Among IDC/C-negative patients, GBX2 methylation improved prediction of BCR (p=0.002). Loss of TET2 in prostate cells resulted in greater GBX2 methylation.<br><br>CONCLUSIONS: We identified GBX2 methylation as a novel prognostic factor in PCa and an independent predictor of BCR. We demonstrated the additive value of GBX2 methylation in predicting BCR among IDC/C-negative patients and elucidated a novel TET2-mediated upstream epigenetic regulatory mechanism of GBX2.<br><br>PATIENT SUMMARY: We identified GBX2 methylation as a promising prognostic biomarker that could improve the identification of prostate cancer patients at higher risk of biochemical recurrence.}, }
@article {pmid31192864, year = {2019}, author = {Horimoto, Y and Terao, T and Tsutsumi, Y and Tanabe, M and Mogushi, K and Hlaing, MT and Sasaki, R and Saeki, H and Okazaki, M and Sonoue, H and Arakawa, A and Saito, M}, title = {Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 Protein Without Gene Amplification.}, journal = {The American journal of surgical pathology}, volume = {43}, number = {9}, pages = {1221-1228}, doi = {10.1097/PAS.0000000000001300}, pmid = {31192864}, issn = {1532-0979}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Female ; Gene Amplification ; Genes, erbB-2 ; Humans ; Middle Aged ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/metabolism ; }, abstract = {Overexpression of human epidermal growth factor receptor 2 (HER2) protein is well known to be more frequent in ductal carcinoma in situ (DCIS) than in invasive ductal carcinoma (IDC). However, the reasons for this difference are poorly understood. On the basis of the high frequency of estrogen receptor-positive (ER+) and HER2-positive (HER2+) DCIS, we hypothesized that this tumor type overexpresses HER2 protein without gene amplification and retrospectively investigated the HER2/neu gene status of 71 ER(+)HER2(+) DCIS, surgically removed during the 2007 to 2017 period, employing fluorescence in situ hybridization (FISH). To compare HER2 protein expressions between in situ and invasive components of individual tumors, 86 pT1mi/1a IDC with predominantly in situ disease were also examined. Furthermore, for comparison of FISH status between in situ and coexisting invasive components, another patient cohort, 78 FISH-positive IDC cases, were employed. To elucidate biological differences among DCIS with various combinations of ER and HER2 protein expressions, we also analyzed public microarray data of mRNA. HER2 gene amplification was observed in 35% of ER(+) and HER2 protein-overexpressing specimens, significantly lower than the 94% in ER-negative (ER-) and HER2 protein-overexpressing specimens (P<0.001). HER2 protein expression was decreased in the invasive component as compared with coexisting in situ portions in 40% of individual tumors, whereas the FISH status of these 2 components was well preserved. Moreover, ER(+) and HER2 protein-overexpressing DCIS showed significantly higher hypoxia-inducible factor-1α protein expression than the ER(+) and HER2 protein-nonoverexpressing tumors (P=0.016). We revealed that ER(+) and HER2 protein-overexpressing DCIS, especially ER-high tumors, frequently overexpress HER2 protein without gene amplification. Our data may provide novel insights for understanding the biology of DCIS.}, }
@article {pmid31192530, year = {2019}, author = {Zhang, J and Zhao, B and Jin, F}, title = {The assessment of 8th edition AJCC prognostic staging system and a simplified staging system for breast cancer: The analytic results from the SEER database.}, journal = {The breast journal}, volume = {25}, number = {5}, pages = {838-847}, doi = {10.1111/tbj.13347}, pmid = {31192530}, issn = {1524-4741}, mesh = {Breast Neoplasms/*classification/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/genetics ; Female ; Humans ; Middle Aged ; Neoplasm Staging/*standards/statistics &amp; numerical data ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; SEER Program ; United States ; }, abstract = {The prognostic value of the prognostic staging system that incorporated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (Her-2), and histological grade has been validated in breast cancer (BC) patients, but the staging system seems to be somewhat complex. Recently, an updated bioscore system based on these tumor biological factors was proposed. The purpose of this study was to compare the prognostic stratification between prognostic staging system of American Joint Commission on Cancer (AJCC) and a simplified staging system based on the bioscore system and anatomic TNM staging for BC patients. A total of 44 593 patients with invasive ductal carcinoma who underwent radical resection between 2010 and 2011 were reviewed using the SEER database. The patients were reclassified into different groups according to the anatomic staging system, prognostic staging system, risk bioscore system, and simplified staging system, respectively. The prognostic differences between different groups were compared and clinicopathologic features were analyzed. The anatomic TNM staging failed to clearly distinguish the prognostic difference between stage IIIB and stage IIIC. Therefore, we proposed an adjusted anatomic staging, in which T1N3 and T2N3 were downstaged from stage IIIC to stage IIIB, and T4N2 was upstaged from stage IIIB to stage IIIC. Histological grade III, ER(-), PR(-), and Her-2(-) were identified as independent prognostic factors in the multivariate analysis, and these factors were separately marked as 1 point. There were significant survival differences among different risk points except for the comparison between 0 and 1 point. The higher the risk points, the poorer the prognosis of BC patients. In addition, the curve distance between stage IIA and stage IIB was not significantly broaden according to the prognostic staging system. However, the prognostic stratification for BC patients could be significantly improved by the simplified staging system incorporated the bioscore system and adjusted anatomic staging. Several drawbacks may still exist in the prognostic staging system of AJCC. A simplified staging system that incorporated risk score system and the anatomic staging could provide more accurate prognostic information for BC patients.}, }
@article {pmid31182966, year = {2019}, author = {Bao, Y and Wang, L and Shi, L and Yun, F and Liu, X and Chen, Y and Chen, C and Ren, Y and Jia, Y}, title = {Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.}, journal = {Cellular &amp; molecular biology letters}, volume = {24}, number = {}, pages = {38}, pmid = {31182966}, issn = {1689-1392}, mesh = {Breast Neoplasms/*genetics ; Down-Regulation/genetics ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Receptors, Cell Surface/*metabolism ; Reproducibility of Results ; Sequence Analysis, RNA ; Signal Transduction/*genetics ; Transcriptome/genetics ; Up-Regulation/genetics ; }, abstract = {BACKGROUND: Exploration of the genes with abnormal expression during the development of breast cancer is essential to provide a deeper understanding of the mechanisms involved. Transcriptome sequencing and bioinformatics analysis of invasive ductal carcinoma and paracancerous tissues from the same patient were performed to identify the key genes and signaling pathways related to breast cancer development.<br><br>METHODS: Samples of breast tumor tissue and paracancerous breast tissue were obtained from 6 patients. Sequencing used the Illumina HiSeq platform. All. Only perfectly matched clean reads were mapped to the reference genome database, further analyzed and annotated based on the reference genome information. Differentially expressed genes (DEGs) were identified using the DESeq R package (1.10.1) and DEGSeq R package (1.12.0). Using KOBAS software to execute the KEGG bioinformatics analyses, enriched signaling pathways of DEGs involved in the occurrence of breast cancer were determined. Subsequently, quantitative real time PCR was used to verify the accuracy of the expression profile of key DEGs from the RNA-seq result and to explore the expression patterns of novel cancer-related genes on 8 different clinical individuals.<br><br>RESULTS: The transcriptomic sequencing results showed 937 DEGs, including 487 upregulated and 450 downregulated genes in the breast cancer specimens. Further quantitative gene expression analysis was performed and captured 252 DEGs (201 downregulated and 51 upregulated) that showed the same differential expression pattern in all libraries. Finally, 6 upregulated DEGs (CST2, DRP2, CLEC5A, SCD, KIAA1211, DTL) and 6 downregulated DEGs (STAC2, BTNL9, CA4, CD300LG, GPIHBP1 and PIGR), were confirmed in a quantitative real time PCR comparison of breast cancer and paracancerous breast tissues from 8 clinical specimens. KEGG analysis revealed various pathway changes, including 20 upregulated and 21 downregulated gene enrichment pathways. The extracellular matrix-receptor (ECM-receptor) interaction pathway was the most enriched pathway: all genes in this pathway were DEGs, including the THBS family, collagen and fibronectin. These DEGs and the ECM-receptor interaction pathway may perform important roles in breast cancer.<br><br>CONCLUSION: Several potential breast cancer-related genes and pathways were captured, including 7 novel upregulated genes and 76 novel downregulated genes that were not found in other studies. These genes are related to cell proliferation, movement and adhesion. They may be important for research into breast cancer mechanisms, particularly CST2 and CA4. A key signaling pathway, the ECM-receptor interaction signal pathway, was also identified as possibly involved in the development of breast cancer.}, }
@article {pmid31182685, year = {2019}, author = {Arabpour, M and Ghods, A and Shariat, M and Talei, AR and Mehdipour, F and Ghaderi, A}, title = {Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer.}, journal = {Iranian journal of immunology : IJI}, volume = {16}, number = {2}, pages = {108-116}, doi = {10.22034/IJI.2019.80254}, pmid = {31182685}, issn = {1735-367X}, mesh = {4-1BB Ligand/*metabolism ; Adult ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Female ; Flow Cytometry ; Humans ; Lymphocyte Activation ; Middle Aged ; Neoplasm Staging ; Receptors, Estrogen/metabolism ; Sentinel Lymph Node/*metabolism ; }, abstract = {BACKGROUND: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity.<br><br>OBJECTIVE: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters.<br><br>METHODS: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti&#x2012;CD19 and anti&#x2012;4-1BBL antibodies and subjected to flow cytometry.<br><br>RESULTS: 4-1BBL expression was detected on 2.8 &#xb1; 1.7% of unstimulated B cells, while 27.4 &#xb1; 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER&#x2012; or PR&#x2012; patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage.<br><br>CONCLUSIONS: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.}, }
@article {pmid31177561, year = {2019}, author = {Downes, MR and Xu, B and van der Kwast, TH}, title = {Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome.}, journal = {Histopathology}, volume = {75}, number = {5}, pages = {715-722}, doi = {10.1111/his.13938}, pmid = {31177561}, issn = {1365-2559}, mesh = {Aged ; Aged, 80 and over ; Humans ; Lymphatic Metastasis/*pathology ; Male ; Middle Aged ; *Neoplasm Grading ; Pelvic Neoplasms/*pathology/secondary ; Prognosis ; Prostate/pathology ; Prostatectomy ; Prostatic Neoplasms/*pathology ; Retrospective Studies ; }, abstract = {AIMS: Lymph node metastases at the time of prostatectomy are an infrequent finding. The correlation of the pattern of nodal metastases with patient outcome has yet to be explored.<br><br>METHODS AND RESULTS: Lymph node-positive prostatectomies were retrospectively reviewed. The presence of cribriform carcinoma (CC), intraductal carcinoma (IDC) and ISUP grade (G) were documented. The largest nodal metastasis was assessed for the morphological patterns present. G was assigned to the metastasis based on percentage morphological patterns present. Statistical analysis used spss to assess disease-specific survival (DSS), disease-free survival (DFS) and distant metastasis-free survival (DMFS). One hundred and ten cases were identified: G5 (n&#xa0;=&#xa0;52), G4 (n&#xa0;=&#xa0;8), G3 (n&#xa0;=&#xa0;34), G2 (n&#xa0;=&#xa0;10) and no G (n&#xa0;=&#xa0;6; treatment effect). IDC or CC was present in 103 (94%) specimens. More than one positive node correlated with worse DFS [P&#xa0;=&#xa0;0.012, hazard ratio (HR)&#xa0;=&#xa0;1.951, 95% confidence interval (CI)&#xa0;=&#xa0;1.142-3.331] and DMFS (P&#xa0;=&#xa0;0.009, HR&#xa0;=&#xa0;2.647, 95% CI&#xa0;=&#xa0;1.239-5.651). G in the prostate and nodal metastasis were poorly correlated (kappa&#xa0;=&#xa0;0.073, P&#xa0;=&#xa0;0.195). The presence of pattern 5 was seen in 33 nodes (30%) and correlated with DFS (P&#xa0;=&#xa0;0.020, HR&#xa0;=&#xa0;1.903, 95% CI&#xa0;=&#xa0;1.091-3.320), DSS (P&#xa0;=&#xa0;0.021, HR&#xa0;=&#xa0;5.937, 95% CI&#xa0;=&#xa0;1.084-32.533) and DMFS (P&#xa0;=&#xa0;0.007, HR&#xa0;=&#xa0;2.695, 95% CI&#xa0;=&#xa0;1.269-5.726). Nodal cribriform pattern showed no prognostic correlation and pattern 3 metastasis showed a significant trend towards better outcome (DMFS P&#xa0;=&#xa0;0.033, HR&#xa0;=&#xa0;0.431, 95% CI&#xa0;=&#xa0;0.194-0.958).<br><br>CONCLUSIONS: IDC or CC is identified in 94% of node-positive prostate cancers. Although G in the largest nodal metastasis has prognostic significance, its G does not reflect that of the primary prostatic adenocarcinoma.}, }
@article {pmid31172621, year = {2019}, author = {Hamzah, JL and Ong, KW and Tan, BY}, title = {Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.}, journal = {The breast journal}, volume = {25}, number = {4}, pages = {706-708}, doi = {10.1111/tbj.13308}, pmid = {31172621}, issn = {1524-4741}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Nipples/*pathology ; Paget's Disease, Mammary/pathology ; Ultrasonography, Mammary ; }, abstract = {Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.}, }
@article {pmid31171819, year = {2019}, author = {Chavez, DE and Gronau, I and Hains, T and Kliver, S and Koepfli, KP and Wayne, RK}, title = {Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {8329}, pmid = {31171819}, issn = {2045-2322}, mesh = {*Adaptation, Physiological ; Animals ; Animals, Wild/genetics ; *Biological Evolution ; Body Patterning ; Canidae/*genetics ; Computational Biology ; DNA/analysis ; Diet ; Female ; *Genomics ; Genotype ; Hedgehog Proteins/genetics ; Molar ; Monte Carlo Method ; Pigmentation ; Predatory Behavior ; }, abstract = {Within the Canidae, the African wild dog (Lycaon pictus) is the most specialized with regards to cursorial adaptations (specialized for running), having only four digits on their forefeet. In addition, this species is one of the few canids considered to be an obligate meat-eater, possessing a robust dentition for taking down large prey, and displays one of the most variable coat colorations amongst mammals. Here, we used comparative genomic analysis to investigate the evolutionary history and genetic basis for adaptations associated with cursoriality, hypercanivory, and coat color variation in African wild dogs. Genome-wide scans revealed unique amino acid deletions that suggest a mode of evolutionary digit loss through expanded apoptosis in the developing first digit. African wild dog-specific signals of positive selection also uncovered a putative mechanism of molar cusp modification through changes in genes associated with the sonic hedgehog (SHH) signaling pathway, required for spatial patterning of teeth, and three genes associated with pigmentation. Divergence time analyses suggest the suite of genomic changes we identified evolved ~1.7 Mya, coinciding with the diversification of large-bodied ungulates. Our results show that comparative genomics is a powerful tool for identifying the genetic basis of evolutionary changes in Canidae.}, }
@article {pmid31171772, year = {2019}, author = {Haythorne, E and Rohm, M and van de Bunt, M and Brereton, MF and Tarasov, AI and Blacker, TS and Sachse, G and Silva Dos Santos, M and Terron Exposito, R and Davis, S and Baba, O and Fischer, R and Duchen, MR and Rorsman, P and MacRae, JI and Ashcroft, FM}, title = {Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {2474}, pmid = {31171772}, issn = {2041-1723}, support = {BB/L020874/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/International ; MR/T002107/1/MRC_/Medical Research Council/United Kingdom ; 090532/Z/09/Z//Wellcome Trust (Wellcome)/International ; 884655//Wellcome Trust (Wellcome)/International ; FC001999/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FC001999/WT_/Wellcome Trust/United Kingdom ; 095531/WT_/Wellcome Trust/United Kingdom ; BB/P018726/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/International ; FC001999/WT_/Wellcome Trust/United Kingdom ; 322620//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/International ; }, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Diabetes Mellitus, Experimental/*genetics/metabolism ; Diabetes Mellitus, Type 2/*genetics/metabolism ; Gene Expression Profiling ; Gluconeogenesis ; Glucose/*metabolism ; Glycolysis ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism ; Metabolomics ; Mice ; Mice, Transgenic ; Mitochondria/*metabolism ; NAD/metabolism ; Oxidative Phosphorylation ; Oxygen Consumption ; Potassium Channels, Inwardly Rectifying/genetics ; Proteomics ; }, abstract = {Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.}, }
@article {pmid31171763, year = {2019}, author = {Kim, SJ and Kim, JY}, title = {An Unusual Cutaneous Recurrence of Carcinoma in the Mastectomy Bed and Its Imaging Features: A Case Report.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {800-805}, pmid = {31171763}, issn = {1941-5923}, mesh = {Adult ; Biopsy, Needle ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/methods ; Mastectomy/*methods ; Neoplasm Recurrence, Local/*diagnostic imaging/surgery ; Rare Diseases ; Risk Assessment ; Skin Neoplasms/*secondary/surgery ; Ultrasonography, Doppler, Color/methods ; }, abstract = {BACKGROUND Chest wall recurrences of carcinoma after mastectomy usually involve subcutaneous tissue or the deep muscular layer. Recurrences arising in the skin are rare, and there are few reports of the associated radiologic features. This report presents an unusual case of cutaneous recurrence in the mastectomy bed and demonstrates its radiologic features using sonography and magnetic resonance imaging (MRI). CASE REPORT A 44-year-old woman presented with a palpable lump in the inferomedial area of the right chest wall. Six years ago, she had undergone total mastectomy for ductal carcinoma in situ in her right breast. Sonography showed an indistinct, oval, heterogeneous echoic mass measuring 0.9 cm, confined within the skin layer, corresponding to the palpable lump. A color Doppler sonogram showed minimal, spotted vascularity in and around the mass. Sonography-guided fine-needle aspiration biopsy was performed, revealing multiple clusters of atypical cells, suggestive of ductal carcinoma. On subsequent breast MRI, the mass, measuring 1.3 cm, was again localized to the skin; dynamic contrast-enhanced scans showed a circumscribed margin, oval shape, and rim enhancement (morphology) and slow initial enhancement and persistent delayed enhancement (kinetics). The mass was surgically excised and the pathological examination confirmed the diagnosis as recurrent invasive ductal carcinoma in the dermis. CONCLUSIONS Cutaneous recurrence in the mastectomy bed can manifest as a mass with suspicious radiologic features: indistinct margin on the sonogram and rim enhancement on the MRI. Awareness of such radiologic features may aid in differentiating between the various cutaneous manifestations encountered after mastectomy.}, }
@article {pmid31169985, year = {2019}, author = {Yamashita, H and Kurita, A and Azuma, S and Kudo, Y and Matsuzaki, N and Yazumi, S}, title = {Usefulness of immunohistochemical staining for MUC5AC in differentiating primary pancreatic cancer from pancreatic metastasis of breast cancer.}, journal = {Diagnostic cytopathology}, volume = {47}, number = {10}, pages = {1037-1041}, doi = {10.1002/dc.24249}, pmid = {31169985}, issn = {1097-0339}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Diagnosis, Differential ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Middle Aged ; Mucin 5AC/genetics/*metabolism ; Pancreatic Neoplasms/metabolism/*pathology/secondary ; }, abstract = {Diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its differentiation from metastases to the pancreas from other organs remains challenging. We report a case in which immunohistochemical staining for MUC5AC was useful in distinguishing primary pancreatic cancer from breast cancer metastasis. A 51-year-old Japanese woman who underwent curative resection of her breast cancer was referred to our hospital with a pancreatic head tumor. Although we surmised her pancreatic tumor to be metastatic breast cancer based on her past history and imaging studies, she was subsequently diagnosed with PDAC on the basis of immunohistochemical staining for MUC5AC using specimens obtained by endoscopic ultrasound-fine-needle aspiration. Thus, MUC5AC may be a useful diagnostic marker for discriminating PDAC from a secondary malignancy.}, }
@article {pmid31146042, year = {2019}, author = {Zhu, J and Sun, K and Xu, X and Sun, J and Kong, Q and Wang, S and Shi, J}, title = {A Preliminary Attempt of Nonintervention in the Treatment of Patients with Intervertebral Disc Calcification Combined with Ossification of the Posterior Longitudinal Ligament.}, journal = {World neurosurgery}, volume = {129}, number = {}, pages = {181-185}, doi = {10.1016/j.wneu.2019.05.169}, pmid = {31146042}, issn = {1878-8769}, mesh = {Child ; Female ; Humans ; Intervertebral Disc/*pathology ; Ossification of Posterior Longitudinal Ligament/*complications/pathology ; Ossification, Heterotopic/*complications/pathology ; Remission, Spontaneous ; *Watchful Waiting ; }, abstract = {BACKGROUND: Calcification of intervertebral disc is a common impairment, which has been considered as the degenerative condition of the spine. In clinical practice, we note that the onset of intervertebral disc calcification (IDC) and ossification of the posterior longitudinal ligament (OPLL) can exist simultaneously in some cases, especially in younger children. However, only 8 cases have been reported in detail previously. In addition, controversy remains in terms of the best way to treat this condition.<br><br>CASE DESCRIPTION: An 8-year-old female child was referred to our department in March 2018 complaining of severe back pain and neck pain with a sign of neurologic dysfunction. Computed tomography and magnetic resonance imaging revealed the calcified intervertebral disc and OPLL at the C5-C6 level and spinal cord compression. We performed a noninterventional strategy for the patient. The patient's symptom recovered significantly in approximately 1 month. At 6 months of follow-up, the patient felt no discomfort, and computed tomography revealed the complete resorption of ossified lesion. Magnetic resonance imaging also showed no sign of compression on the spinal cord and nerve root at the involved segment.<br><br>CONCLUSIONS: Pediatric IDC accompanied with OPLL is much less frequent, but we must be aware of this disease. Since the distribution of this disease is age-specific and sex-specific, further research is necessary. Treatment for IDC combined with OPLL needs to follow the treatment principles as described in the text.}, }
@article {pmid31142066, year = {2019}, author = {Zhao, JG and Nie, L and Chen, XQ and Chen, N and Zeng, H}, title = {[The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {57}, number = {6}, pages = {422-427}, doi = {10.3760/cma.j.issn.0529-5815.2019.06.006}, pmid = {31142066}, issn = {0529-5815}, support = {81402110, 81672547//National Natural Science Foundation of China/ ; }, mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/mortality/*pathology/secondary ; Retrospective Studies ; }, abstract = {Objective: To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups. Methods: Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS). Results: In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 μg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS. Conclusions: The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.}, }
@article {pmid31134761, year = {2019}, author = {Chen, S and Chen, H and Yi, Y and Jiang, X and Lei, H and Luo, X and Chen, Y and Liu, S and Yuan, D and Jia, X and Li, J}, title = {Comparative study of breast cancer with or without concomitant Paget disease: An analysis of the SEER database.}, journal = {Cancer medicine}, volume = {8}, number = {8}, pages = {4043-4054}, pmid = {31134761}, issn = {2045-7634}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/etiology/mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Paget's Disease, Mammary/*epidemiology/etiology/mortality/pathology ; Population Surveillance ; Prognosis ; SEER Program ; }, abstract = {BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone.<br><br>METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD.<br><br>RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P&#xa0;=&#xa0;0.182 in PD-IDC and P&#xa0;=&#xa0;0.371 in PD-DCIS), HER2 status (P&#xa0;=&#xa0;0.788 in PD-IDC and P&#xa0;=&#xa0;0.643 in PD-DCIS), and combined molecular subtype (P&#xa0;=&#xa0;0.196 in PD-IDC and P&#xa0;=&#xa0;0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS.<br><br>CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.}, }
@article {pmid31120568, year = {2019}, author = {Henry, NL and Cannon-Albright, LA}, title = {Breast cancer histologic subtypes show excess familial clustering.}, journal = {Cancer}, volume = {125}, number = {18}, pages = {3131-3138}, pmid = {31120568}, issn = {1097-0142}, support = {NU58DP0063200-01/CC/CDC HHS/United States ; HHSN261201800016I/CA/NCI NIH HHS/United States ; //University of Utah/ ; P30 CA42014//Huntsman Cancer Institute/ ; HHSN261201800016C/CA/NCI NIH HHS/United States ; //Utah Cancer Registry/ ; //Huntsman Cancer Foundation/ ; P30 CA042014/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/epidemiology/*genetics/pathology ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Lobular/epidemiology/*genetics/pathology ; Family ; Female ; Genetic Predisposition to Disease ; Humans ; Inflammatory Breast Neoplasms/epidemiology/*genetics/pathology ; Middle Aged ; Pedigree ; SEER Program ; Utah/epidemiology ; }, abstract = {BACKGROUND: The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype.<br><br>METHODS: By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives.<br><br>RESULTS: The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n&#xa0;=&#xa0;178], lobular [n&#xa0;=&#xa0;1688], and mucinous [n&#xa0;=&#xa0;542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P&#xa0;=&#xa0;.011) as well as for inflammatory breast cancers (P&#xa0;=&#xa0;.024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P&#xa0;=&#xa0;.03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P&#xa0;<&#xa0;.001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P&#xa0;=&#xa0;.00021) subtypes.<br><br>CONCLUSIONS: These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.}, }
@article {pmid31111513, year = {2019}, author = {Shah, RB and Shore, KT and Yoon, J and Mendrinos, S and McKenney, JK and Tian, W}, title = {PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma).}, journal = {The Prostate}, volume = {79}, number = {11}, pages = {1267-1273}, doi = {10.1002/pros.23831}, pmid = {31111513}, issn = {1097-0045}, mesh = {Adenocarcinoma/*genetics/metabolism/pathology ; Alleles ; Biomarkers, Tumor ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Humans ; Male ; Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/*genetics/metabolism ; Prostatic Neoplasms/*genetics/metabolism/pathology ; }, abstract = {BACKGROUND: The loss of PTEN tumor suppressor gene is one of the most common somatic genetic aberrations in prostate cancer (PCa) and is frequently associated with high-risk disease. Deletion or mutation of at least one PTEN allele has been reported to occur in 20% to 40% of localized PCa and up to 60% of metastases. The goal of this study was to determine if somatic alteration detected by PTEN immunohistochemical loss of expression is associated with specific histologic features.<br><br>METHODS: Two hundred sixty prostate core needle biopsies with PCa were assessed for PTEN loss using an analytically validated immunohistochemical assay. Blinded to PTEN status, each tumor was assessed for the Grade Group (GG) and the presence or absence of nine epithelial features. Presence of stromogenic PCa was also assessed and defined as grade 3 reactive tumor stroma as previously described: the presence of carcinoma associated stromal response with epithelial to stroma ratio of greater than 50% reactive stroma.<br><br>RESULTS: Eight-eight (34%) cases exhibited PTEN loss while 172 (66%) had intact PTEN. PTEN loss was significantly (P&#x2009;<&#x2009;0.05) associated with increasing GG, poorly formed glands (74% of total cases with loss vs 49% of intact), and three well-validated unfavorable pathological features: intraductal carcinoma of the prostate (IDC-P) (69% of total cases with loss vs 12% of intact), cribriform Gleason pattern 4 (38% of total cases with loss vs 10% of intact) and stromogenic PCa (23% of total cases with loss vs 6% of intact). IDC-P had the highest relative risk (4.993, 95% confidence interval, 3.451-7.223, P&#x2009;<&#x2009;0.001) for PTEN loss. At least one of these three unfavorable pathological features were present in 67% of PCa exhibiting PTEN loss, while only 11% of PCa exhibited PTEN loss when none of these three unfavorable pathological features were present.<br><br>CONCLUSIONS: PCa with PTEN loss demonstrates a strong correlation with known unfavorable histologic features, particularly IDC-P. This is the first study showing the association of PTEN loss with stromogenic PCa.}, }
@article {pmid31109373, year = {2019}, author = {Tan, W and Tao, L and Zhou, Z and Yin, W and Chen, Y}, title = {Tumor-to-tumor metastasis: a rare case of breast carcinoma metastasizing to a pheochromocytoma, and a literature review.}, journal = {Diagnostic pathology}, volume = {14}, number = {1}, pages = {46}, pmid = {31109373}, issn = {1746-1596}, support = {NO. JCYJ201710//the Science and Research Foundation of Peking University, Shenzhen Hospital/ ; NO. SZSM201812088//the "San-ming" Project of Medicine in Shenzhen/ ; }, mesh = {Adrenal Gland Neoplasms/*diagnostic imaging/secondary ; Adrenal Glands/diagnostic imaging/pathology ; Adult ; Breast/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Pheochromocytoma/*diagnostic imaging/secondary ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Tumor-to-tumor metastasis is a well-recognized but uncommon entity. Breast carcinoma is one of the most common metastatic donors. Breast carcinoma metastasizes commonly to adrenal glands. However, the co-existence of a metastatic lesion with an existing adrenal tumor is a rare finding.<br><br>CASE PRESENTATION: A 35-year-old woman was diagnosed with pheochromocytoma using computed tomography and ultrasound examinations. The tumor was surgically removed. Histological and immunohistochemical staining suggested that there were two components in the tumor: pheochromocytoma and metastatic cancer.<br><br>CONCLUSION: This is the second published case of pheochromocytoma with tumor-to-tumor metastasis from an invasive ductal carcinoma of the breast. Furthermore, we highlight the importance of awareness of tumor-to-tumor metastasis in pathological diagnosis.}, }
@article {pmid31107526, year = {2019}, author = {Nasir, A and Lehrke, HD and Mounajjed, T and Said, S and Zhang, L and Yasir, S and Shah, SS and Chandan, VS and Smyrk, TC and Moreira, RK and Boland Froemming, JM and Herrera Hernandez, LP and Wu, TT and Graham, RP}, title = {Albumin In Situ Hybridization Can Be Positive in Adenocarcinomas and Other Tumors From Diverse Sites.}, journal = {American journal of clinical pathology}, volume = {152}, number = {2}, pages = {190-199}, doi = {10.1093/ajcp/aqz032}, pmid = {31107526}, issn = {1943-7722}, mesh = {Adenocarcinoma/genetics/*metabolism/pathology ; Albumins/genetics/*metabolism ; Bile Duct Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Hepatocellular/genetics/*metabolism/pathology ; Cholangiocarcinoma/genetics/*metabolism/pathology ; Gallbladder Neoplasms/genetics/*metabolism/pathology ; Humans ; In Situ Hybridization ; Liver Neoplasms/genetics/*metabolism/pathology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Albumin messenger RNA (mRNA) expression is a marker of hepatocellular differentiation. Most published data are from review of tissue microarrays, and albumin in situ hybridization (ISH) expression across several tumor types is incompletely characterized.<br><br>METHODS: Sections from 221 tumors were evaluated for albumin mRNA. Immunohistochemistry was used to confirm diagnoses. Albumin ISH was performed according to manufacturer-provided instructions. Fifty-nine cases were evaluated with both commercial ISH assays.<br><br>RESULTS: Albumin mRNA was detected in all hepatocellular carcinomas (HCCs) and 81% of intrahepatic cholangiocarcinomas. Lung (20%), gallbladder (39%), hepatoid pancreatic (n = 1 of 1) adenocarcinoma, breast invasive ductal carcinoma (18%), yolk sac tumor (25%), and acinar cell carcinoma (29%) showed expression. Both assays were concordant in 93% of cases.<br><br>CONCLUSIONS: Albumin ISH was expressed in all HCCs studied. It was also positive in intrahepatic cholangiocarcinoma and patchy positive in gallbladder adenocarcinoma and a subset of other neoplasms, which can be a potential pitfall.}, }
@article {pmid31100224, year = {2018}, author = {Montironi, R and Zhou, M and Magi-Galluzzi, C and Epstein, JI}, title = {Features and Prognostic Significance of Intraductal Carcinoma of the Prostate.}, journal = {European urology oncology}, volume = {1}, number = {1}, pages = {21-28}, doi = {10.1016/j.euo.2018.03.013}, pmid = {31100224}, issn = {2588-9311}, mesh = {Biopsy ; Carcinoma, Ductal/*diagnosis/genetics ; Diagnosis, Differential ; Disease Management ; *Genomic Instability ; Humans ; Male ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/*diagnosis/genetics ; Tumor Burden ; }, abstract = {CONTEXT: Intraductal carcinoma of the prostate (IDC-P) is an intraglandular/ductal neoplastic growth of glandular epithelial cells characterized by marked abnormality of the glandular architecture and/or cytological atypia that exceeds what is typically seen in high-grade prostatic intraepithelial neoplasia (HPGIN). It has been shown that IDC-P is a strong independent indicator of poor prognosis for prostate carcinoma (PCa).<br><br>OBJECTIVE: To review the pathological and genetic features, diagnostic criteria and differential diagnosis, and clinical significance of IDC-P.<br><br>EVIDENCE ACQUISITION: PubMed was searched using keywords including prostate carcinoma, intraductal carcinoma, IDC, histology, diagnostic criteria, and prognosis. The references in relevant articles were also reviewed.<br><br>EVIDENCE SYNTHESIS: IDC-P is a distinct entity with characteristic morphological and genetic features. It is strongly associated with aggressive PCa with high Gleason score/grade groups and large tumor volume, and portends unfavorable clinical outcomes. Morphological diagnostic criteria have been established to distinguish it from other lesions with similar histological features. IDC-P is an uncommon finding in prostate biopsies, and is even rarer as an isolated finding without concomitant PCa. However, patients with isolated IDC-P in biopsy specimens are recommended to have either definitive treatment or immediate repeat biopsy.<br><br>CONCLUSIONS: It is critical to recognize and report IDC-P, especially in prostate biopsies, where the clinical impact of such a diagnosis is greatest.<br><br>PATIENT SUMMARY: Intraductal carcinoma is a unique form of aggressive prostate cancer. In this report, we review its pathological and genetic features and poor prognostic significance. It is critical for pathologists to recognize and report this lesion in prostate specimens, especially in prostate biopsies for patient management.}, }
@article {pmid31092426, year = {2019}, author = {Rusak, A and Jablonska, K and Piotrowska, A and Grzegrzolka, J and Wojnar, A and Dziegiel, P}, title = {Correlation of Expression of CHI3L1 and Nogo-A and their Role in Angiogenesis in Invasive Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {39}, number = {5}, pages = {2341-2350}, doi = {10.21873/anticanres.13351}, pmid = {31092426}, issn = {1791-7530}, mesh = {Aged ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chitinase-3-Like Protein 1/*genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Neovascularization, Pathologic/*genetics ; Nogo Proteins/*genetics ; Receptors, Cell Surface/genetics ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor C/*genetics ; Vascular Endothelial Growth Factor D/genetics ; }, abstract = {BACKGROUND/AIM: Chitinase 3 like 1 (CHI3L1) is a secretion glycoprotein. Elevated levels of this protein are observed in cancer diseases. The biological role of CHI3L1 is not yet fully known, but the connection between CHI3L1 and angiogenesis has been shown. Recent reports also describe the association of Nogo isoforms and Nogo-B receptor (NgBR) with a proliferative potential, cancer cell invasiveness, and angiogenesis. The aim of this study was to evaluate the levels of CHI3L1, Nogo-A, Nogo-A/B, and NgBR and correlate them with clinical-pathological data, to study their role in angiogenesis in invasive ductal breast carcinoma (IDC).<br><br>MATERIALS AND METHODS: A total of 77 IDC cases were used in the study. Immunohistochemistry was used to determine the level of expression of CHI3L1, Nogo-A, Nogo-A/B, NgBR and vascular endothelial growth factors (VEGFA, VEGFC and VEGFD). The obtained results were subjected to statistical analysis including clinicalpathological data.<br><br>RESULTS: A statistically significant positive correlation of CHI3L1 and Nogo-A expression (r=0.474, p>0.0001) and a positive correlation of Nogo-A and VEGFC expression (r=0.280, p=0.013) were found.<br><br>CONCLUSION: CHI3L1 and Nogo-A are important in angiogenesis in IDC.}, }
@article {pmid31087408, year = {2019}, author = {Baydoun, S and Gonzalez, P and Whitman, GJ and Dryden, M and Xi, Y and Dogan, B}, title = {Is Ductography Still Warranted in the 21st century?.}, journal = {The breast journal}, volume = {25}, number = {4}, pages = {654-662}, doi = {10.1111/tbj.13302}, pmid = {31087408}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Diseases/diagnostic imaging/*pathology ; Breast Neoplasms/diagnostic imaging/pathology ; Contrast Media ; Female ; Humans ; Image-Guided Biopsy ; Magnetic Resonance Imaging/methods ; Mammography/*methods/statistics &amp; numerical data ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {OBJECTIVE: To determine the utility of ductography in conjunction with mammography and ultrasound in patients with pathologic nipple discharge, and the incremental role of MRI after triple-modality evaluation.<br><br>MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had presented with pathologic nipple discharge and had undergone mammography and/or ultrasound and ductography between January 1, 2005, and October 31, 2010. We tested the diagnostic sensitivity, specificity and accuracy of combined triple-modality evaluation as well as of MRI performed in addition to these imaging techniques. We used the gold standard of image-guided biopsies, surgical excision, or long-term clinical and imaging follow-up.<br><br>RESULTS: Among 94 study patients, benign papillomas were identified in 42 (44.7%), abscess in one (1%), duct ectasia in four (4.3%), and malignancy (invasive ductal carcinoma or ductal carcinoma in situ) or high-risk lesion (atypical ductal hyperplasia) in 10 (10.6%). Forty-six patients (49%) underwent surgical excision; 89.1% of which had presurgical planning with ductography. In 35 (37.2%) with negative imaging, resolution of nipple discharge was confirmed on median clinical and imaging follow-up of 36&#xa0;months. Two patients with negative imaging were lost to follow-up. Sensitivity, specificity, PPV, and NPV for accurately demonstrating the etiology of pathologic nipple discharge were 13%, 97%, 89%, and 37% respectively for mammography; 73%, 97%, 98%, and 64% respectively for ultrasound; 76%, 72%, 84%, and 61% respectively for ductography; 86%, 70%, 85%, and 72% respectively for combined ultrasound and ductography; and 75%, 100%, 100% and 67% respectively for DCE-MRI.<br><br>CONCLUSION: The combination of mammography, ultrasound and ductography is highly accurate for identifying the etiology of pathologic nipple discharge. DCE-MRI can be used as an alternate to ductography if necessary.}, }
@article {pmid31063527, year = {2019}, author = {Ciurea, AI and Boca, I and Rogojan, L and Ciule, LD and Ciortea, CA}, title = {Pectoralis muscle metastases from breast cancer in a young patient detected by automated breast ultrasound.}, journal = {Medical ultrasonography}, volume = {21}, number = {2}, pages = {200-203}, doi = {10.11152/mu-1769}, pmid = {31063527}, issn = {2066-8643}, mesh = {Adult ; Breast Neoplasms/*pathology/therapy ; Fatal Outcome ; Female ; Humans ; Muscle Neoplasms/*diagnostic imaging/*secondary ; Neoplasm Recurrence, Local/*diagnostic imaging ; Pectoralis Muscles/*diagnostic imaging ; Ultrasonography, Mammary/*methods ; }, abstract = {Metastases to the skeletal muscle from breast cancer represent an unusual and rare condition. We present the case of a 27-year-old female with left breast cancer (IDC NST G3) who underwent neoadjuvant chemotherapy followed by conservativesurgery (sectorectomy and lymphadenectomy) and radiation therapy. Two months after the end of radiotherapy she presented with a 2 mm skin lesion and she was referred for a screening ultrasound. The screening automated breast ultrasound (ABUS) revealed local recurrence and pectoralis metastases, lesions evaluated also by magnetic resonance imaging. The diagnosis was confirmed by the ultrasound-guided biopsy.}, }
@article {pmid31060593, year = {2019}, author = {Petridis, C and Arora, I and Shah, V and Megalios, A and Moss, C and Mera, A and Clifford, A and Gillett, C and Pinder, SE and Tomlinson, I and Roylance, R and Simpson, MA and Sawyer, EJ}, title = {Frequency of pathogenic germline variants in BRCA1, BRCA2, PALB2, CHEK2 and TP53 in ductal carcinoma in situ diagnosed in women under the age of 50 years.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {58}, pmid = {31060593}, issn = {1465-542X}, support = {MC_PC_14105/MRC_/Medical Research Council/United Kingdom ; 8873/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Age Factors ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/epidemiology/*genetics ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/*genetics ; Case-Control Studies ; Checkpoint Kinase 2/genetics ; Computational Biology ; DNA Copy Number Variations ; Female ; *Gene Frequency ; Genotype ; *Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Neoplasm Grading ; Tumor Suppressor Protein p53/genetics ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal breast cancer, and approximately 20% of screen-detected tumours are pure DCIS. Most risk factors for breast cancer have similar associations with DCIS and IDC; however, there is limited data on the prevalence of the known high and moderate penetrance breast cancer predisposition genes in DCIS and which women with DCIS should be referred for genetic screening. The aim of this study was to assess the frequency of germline variants in BRCA2, BRCA1, CHEK2, PALB2 and TP53 in DCIS in women aged less than 50 years of age.<br><br>METHODS: After DNA extraction from the peripheral blood, Access Array technology (Fluidigm) was used to amplify all exons of these five known breast cancer predisposition genes using a custom made targeted sequencing panel in 655 cases of pure DCIS presenting in women under the age of 50&#x2009;years together with 1611 controls.<br><br>RESULTS: Case-control analysis revealed an excess of pathogenic variants in BRCA2 (OR&#x2009;=&#x2009;27.96, 95%CI 6.56-119.26, P&#x2009;=&#x2009;2.0&#x2009;&#xd7;&#x2009;10[-10]) and CHEK2 (OR&#x2009;=&#x2009;8.04, 95%CI 2.93-22.05, P&#x2009;=&#x2009;9.0&#x2009;&#xd7;&#x2009;10[-6]), with weaker associations with PALB2 (P&#x2009;=&#x2009;0.003), BRCA1 (P&#x2009;=&#x2009;0.007) and TP53 (P&#x2009;=&#x2009;0.02). For oestrogen receptor (ER)-positive DCIS the frequency of pathogenic variants was 9% under the age of 50 (14% with a family history of breast cancer) and 29% under the age of 40 (42% with a family history of breast cancer). For ER-negative DCIS, the frequency was 9% (16% with a family history of breast cancer) and 8% (11% with a family history of breast cancer) under the ages of 50 and 40, respectively.<br><br>CONCLUSIONS: This study has shown that breast tumourigenesis in women with pathogenic variants in BRCA2, CHEK2, PALB2, BRCA1 and TP53 can involve a DCIS precursor stage and that the focus of genetic testing in DCIS should be on women under the age of 40 with ER-positive DCIS.}, }
@article {pmid31057361, year = {2019}, author = {Aplin, FP and Fridman, GY}, title = {Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy.}, journal = {Frontiers in neuroscience}, volume = {13}, number = {}, pages = {379}, pmid = {31057361}, issn = {1662-4548}, support = {R01 DC009255/DC/NIDCD NIH HHS/United States ; R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; }, abstract = {Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.}, }
@article {pmid31049740, year = {2019}, author = {Sanderink, WBG and Laarhuis, BI and Strobbe, LJA and Sechopoulos, I and Bult, P and Karssemeijer, N and Mann, RM}, title = {A systematic review on the use of the breast lesion excision system in breast disease.}, journal = {Insights into imaging}, volume = {10}, number = {1}, pages = {49}, pmid = {31049740}, issn = {1869-4101}, abstract = {PURPOSE: To outline the current status of and provide insight into possible future research on the breast lesion excision system (BLES) as a diagnostic and therapeutic device.<br><br>METHODS: A systematic search of the literature was performed using PubMed, Embase, and the Cochrane databases to identify relevant studies published between January 2002 and April 2018. Studies were considered eligible for inclusion if they evaluated the diagnostic or therapeutic accuracy or safety of BLES.<br><br>RESULTS: Ultimately, 17 articles were included. The reported underestimation rates of atypical ductal hyperplasia and ductal carcinoma in situ (DCIS) ranged from 0 to 14.3% and from 0 to 22.2%, respectively. Complete excision rates for invasive ductal carcinoma and DCIS ranged from 5.3 to 76.3%. Bleeding was the most frequently reported complication (0-11.8%). Device-related complications may arise, with an empty basket being the most common (0.6-3.6%). Thermal damage of the specimen, caused by the use of a radiofrequency cutting wire, was reported in eight of the included studies. Most thermal artifacts were reported as superficial and small (0.1-1.9&#x2009;mm).<br><br>CONCLUSIONS: The BLES, an automated, image-guided, single-pass biopsy system for breast lesions using radiofrequency is designed to excise and retrieve an intact tissue specimen. It is an efficient and safe breast biopsy method with acceptable complication rates, which may be used as an alternative to vacuum-assisted biopsies. The variable rate of complete excision raises questions about the possibility to use BLES as a therapeutic device for the excision of small lesions. Further research should focus on this aspect of BLES.}, }
@article {pmid31046734, year = {2019}, author = {Aras, S and Maroun, MC and Song, Y and Bandyopadhyay, S and Stark, A and Yang, ZQ and Long, MP and Grossman, LI and Fernández-Madrid, F}, title = {Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {411}, pmid = {31046734}, issn = {1471-2407}, support = {R01 CA122277/CA/NCI NIH HHS/United States ; R01 CA122277//National Institutes of Health/ ; W81XWH-16-1-0516//U.S. Department of Defense/ ; }, mesh = {Autoantigens/metabolism ; Autoimmunity ; Breast Neoplasms/*diagnosis/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/*genetics/*metabolism ; Neoplasm Invasiveness ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Prospective Studies ; Protein Array Analysis ; Rapamycin-Insensitive Companion of mTOR Protein/genetics ; Transcription Factors/*genetics/*metabolism ; Up-Regulation ; }, abstract = {BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V.<br><br>METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1&#x3b1;. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype.<br><br>RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis.<br><br>CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.}, }
@article {pmid31045815, year = {2019}, author = {Li, JP and Zhang, XM and Zhang, Z and Zheng, LH and Jindal, S and Liu, YJ}, title = {Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma.}, journal = {Medicine}, volume = {98}, number = {18}, pages = {e15449}, pmid = {31045815}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Carcinoma, Ductal/*mortality/*pathology ; Disease-Free Survival ; Female ; Genes, p53/*physiology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Triple Negative Breast Neoplasms/*mortality/*pathology ; Tumor Suppressor Protein p53/genetics ; }, abstract = {TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.}, }
@article {pmid31040709, year = {2019}, author = {Hinnen, D and Kruger, DF}, title = {Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {12}, number = {}, pages = {447-455}, pmid = {31040709}, issn = {1178-7007}, abstract = {BACKGROUND: Patients with type 2 diabetes (T2D) are at increased cardiovascular (CV) risk compared to subjects without diabetes, with some data estimating that CV disease (CVD) risk is doubled in these individuals. Additionally, CVD remains the leading cause of death in patients with T2D, so it is paramount to determine the relationship between these two diseases.<br><br>PURPOSE: Older diabetes treatments have limited CV safety data. In 2008, the US Food and Drug Administration published guidance for manufacturers on antihyperglycemic agents, requiring studies to ensure CV safety of new therapies. Since then, manufacturers of many newer agents have conducted and published results from CV outcomes trials (CVOTs), with more trials due to publish soon. This review discusses the relationship between CVD and T2D and explores findings from the latest CVOTs of glucose-lowering agents to guide nurse practitioners in their prescribing patterns for patients with T2D.<br><br>CONCLUSION: Patients with T2D are at high risk of CVD, so CV risk should be carefully considered when managing these patients, and CV risks and benefits of antidiabetic drugs should be included in prescribing decisions.}, }
@article {pmid31023035, year = {2019}, author = {Albayrak, M and Senol, O and Demirkaya-Miloglu, F and Calik, M and Kadioglu, Y}, title = {Novel chemometrics‑assisted spectroscopic methods for diagnosis and monitoring of invasive ductal carcinoma in breast tissue.}, journal = {Bratislavske lekarske listy}, volume = {120}, number = {3}, pages = {184-187}, doi = {10.4149/BLL_2019_031}, pmid = {31023035}, issn = {0006-9248}, mesh = {Adult ; *Breast Neoplasms/diagnosis ; *Carcinoma, Ductal, Breast/diagnosis ; Female ; Humans ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; }, abstract = {OBJECTIVES: Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics‑assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples.<br><br>METHODS: Samples were deparaffinized and 20&#x2011;micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model.<br><br>RESULTS: Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones.<br><br>CONCLUSION: This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).}, }
@article {pmid31022251, year = {2019}, author = {Ishikane, M and Hayakawa, K and Kutsuna, S and Takeshita, N and Ohmagari, N}, title = {The impact of infectious disease consultation in candidemia in a tertiary care hospital in Japan over 12 years.}, journal = {PloS one}, volume = {14}, number = {4}, pages = {e0215996}, pmid = {31022251}, issn = {1932-6203}, mesh = {Aged ; Candidemia/*epidemiology/mortality ; Communicable Diseases/*epidemiology ; Female ; Humans ; Japan/epidemiology ; Kaplan-Meier Estimate ; Male ; *Referral and Consultation ; *Tertiary Care Centers ; }, abstract = {BACKGROUND: Candidemia is one of the major causes of morbidity and mortality as a hospital acquired infection. Infectious diseases consultation (IDC) might be beneficial to improve candidemia outcomes; however, only limited data from short periods of time are available thus far.<br><br>METHODS: An observational study of all candidemia patients at a large tertiary care hospital between 2002 and 2013 was conducted. A candidemia episode was defined as &#x2265; 1 positive result for Candida spp. in blood culture. Patients who died or transferred to another hospital within two days after their first positive blood culture were excluded. Independent risk factors for 30-day mortality were determined.<br><br>RESULTS: Among 275 patients with 283 episodes of candidemia, 194 (68.6%) were male, and the mean age was 70.0 &#xb1; 15.8 years. Central line-associated bloodstream infections, peripheral line-associated bloodstream infections, intra-abdominal infection, and unknown source comprised 220 (77.7%), 35 (12.4%), 13 (4.7%), and 15 (5.3%) episodes, respectively. A total of 126 patients (44.5%) received IDC. Factors independently associated with 30-day mortality in patients with candidemia were urinary catheters use (adjusted hazard ratio [HR] = 2.94; 95% confidence interval [CI] = 1.48-5.87; P = 0.002) and severe sepsis/septic shock (adjusted HR = 2.10; 95% CI = 1.20-3.65; P = 0.009). IDC was associated with a 46% reduction in 30-day mortality (adjusted HR = 0.54; 95% CI = 0.32-0.90; P = 0.017).<br><br>CONCLUSION: IDC was independently associated with a reduction in 30-day mortality. Only 44.5% of patients with candidemia in this cohort received IDC. Routine IDC should be actively considered for patients with candidemia.}, }
@article {pmid31016756, year = {2019}, author = {Zenan, H and Zixiong, L and Zhicheng, Y and Mei, H and Xiongbin, Y and Tiantian, W and Min, D and Renbin, L and Changchang, J}, title = {Clinical prognostic evaluation of immunocytes in different molecular subtypes of breast cancer.}, journal = {Journal of cellular physiology}, volume = {234}, number = {11}, pages = {20584-20602}, doi = {10.1002/jcp.28662}, pmid = {31016756}, issn = {1097-4652}, mesh = {Aging ; Biomarkers, Tumor ; Blood Platelets/classification/physiology ; Breast Neoplasms/*classification/*genetics/pathology ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Leukocytes/*classification/*physiology ; Logistic Models ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*pathology ; }, abstract = {To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of 601 patients with BC in the Third Affiliated Hospital, Sun Yat-sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER-2, and KI-67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease-free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER-2 overexpression and triple-negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER-2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER-2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.}, }
@article {pmid31004170, year = {2019}, author = {Harbertson, J and Scott, PT and Lemus, H and Michael, NL and Hale, BR}, title = {Cross-Sectional Study of Sexual Behavior, Alcohol Use, and Mental Health Conditions Associated With Sexually Transmitted Infections Among Deploying Shipboard US Military Personnel.}, journal = {Military medicine}, volume = {184}, number = {11-12}, pages = {e693-e700}, doi = {10.1093/milmed/usz070}, pmid = {31004170}, issn = {1930-613X}, mesh = {Adult ; Alcohol Drinking/adverse effects/epidemiology/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Mental Disorders/*diagnosis/epidemiology/psychology ; Middle Aged ; Military Personnel/psychology/*statistics &amp; numerical data ; Risk Factors ; Risk-Taking ; Sexual Behavior/*psychology ; Sexually Transmitted Diseases/*diagnosis/epidemiology/psychology ; Ships/statistics &amp; numerical data ; United States/epidemiology ; }, abstract = {INTRODUCTION: Limited comprehensive data exist on risk behavior associated with sexually transmitted infections (STI) among ship-assigned US military personnel during the predeployment time period (PDT). This study examined whether sexual risk behaviors, alcohol use, involuntary drug consumption (IDC), posttraumatic stress disorder (PTSD), and depression during the 12 months prior to deployment were associated with provider-diagnosed STIs in this population.<br><br>MATERIALS AND METHODS: Using cross-sectional data collected during 2012-2014 among sexually active personnel, multivariable regression assessed factors associated with STIs among all men (n = 1,831). Stratified analyses were conducted among men who have sex with women (MSW, n = 1,530), men who have sex with men or men and women (MSM, n = 83), and excluded those not reporting sexual partner gender (n = 218).<br><br>RESULTS: Among MSW, transactional sex (AOR 3.8, 95% CI 1.5-9.4) meeting sexual partners at work (AOR 4.3, 95% CI 2.0-9.2), IDC (AOR 6.6, 95% CI 3.0-14.5), and incomplete mental health assessments (AOR 4.4, 95% CI 1.6-12.0) were significantly associated with STIs after adjustment. Among all men, those who identified as MSM (AOR 4.6, 95% CI 1.9-11.2) and drug screen positive (AOR 3.3, 95% CI 1.3-8.6) were significantly more likely to report an STI.<br><br>CONCLUSIONS: Previously unreported factors significantly associated with STIs at the PDT among MSW in the adjusted analysis were meeting sexual partners at work and IDC. IDC during the PDT warrants further exploration. These results can inform tailored STI reduction interventions among shipboard personnel and similarly aged civilians undergoing similar transition/travel experiences.}, }
@article {pmid30995855, year = {2019}, author = {Mikudova, V and Rejlekova, K and Gyarfas, J and Oravcova, I and Chovanec, M and Mardiak, J and Mego, M}, title = {Leptomeningeal Metastasis in a Breast Cancer Treated with Two Lines of Intrathecal Chemotherapy - a Case Report.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {32}, number = {2}, pages = {139-142}, doi = {10.14735/amko2018139}, pmid = {30995855}, issn = {1802-5307}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*adverse effects ; Breast Neoplasms/*drug therapy/pathology ; Female ; Humans ; Injections, Spinal ; Meningeal Neoplasms/*drug therapy/secondary ; Prognosis ; }, abstract = {BACKGROUND: Leptomeningeal metastasis (LM) in breast cancer is associated with a poor prognosis. Although no randomised trial has demonstrated that intrathecal chemotherapy actually prolongs survival, this treatment is considered standard of care in this setting. The prognosis of patients with LM is poor, with a median overall survival time of less than 6 months.<br><br>METHODS: Herein, we report a case of a young woman with breast cancer who presented with LM at the time of relapse and was subsequently treated with two lines of intrathecal chemotherapy that prolonged survival.<br><br>RESULTS: A 28-year old woman without a significant past medical history was diagnosed with triple-negative invasive ductal carcinoma. Eight months after adjuvant treatment she developed multiple brain metastases and LM developed subsequently 1 month after finishing whole brain irradiation. Initially, she was treated with a combination of methotrexate, cytarabine and dexamethasone intrathecally but after 3 months she presented with a worsening clinical status and increased numbers of cancer cells in cerebrospinal fluid. Subsequently, she received a combination of thiotepa and methotrexate intrathecally, which resulted in a prolonged response lasting 10 months. The patient died 32 months after initial diagnosis and 18 months from LM infiltration due to disease progression in the liver and lungs as well as LM.<br><br>CONCLUSION: The prognosis of patients with LM remains poor because of the limited effectiveness of currently available therapies; however, intrathecal chemotherapy could substantially prolong survival in selected patients.}, }
@article {pmid30993692, year = {2019}, author = {Khani, F and Wobker, SE and Hicks, JL and Robinson, BD and Barbieri, CE and De Marzo, AM and Epstein, JI and Pritchard, CC and Lotan, TL}, title = {Intraductal carcinoma of the prostate in the absence of high-grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations.}, journal = {The Journal of pathology}, volume = {249}, number = {1}, pages = {79-89}, doi = {10.1002/path.5283}, pmid = {30993692}, issn = {1096-9896}, mesh = {Aged ; Biomarkers, Tumor/*genetics ; Carcinoma in Situ/classification/*genetics/pathology ; Carcinoma, Ductal/classification/*genetics/pathology ; DNA Copy Number Variations ; Gene Dosage ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mitogen-Activated Protein Kinases/genetics ; *Mutation ; Neoplasm Grading ; Neoplasm Invasiveness ; *Oncogenes ; PTEN Phosphohydrolase/genetics ; Phenotype ; Phosphatidylinositol 3-Kinase/genetics ; Prostatic Neoplasms/classification/*genetics/pathology ; Transcriptional Regulator ERG/genetics ; Transcriptome ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) most often appears associated with high-grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC-P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low-grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC-P (iIDC-P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC-P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC-P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC-P alterations were similar to those previously described in high-grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC-P (BRCA2, CHEK2, CDK12) and other known PCa-associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC-P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC-P and the low-grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC-P in four. Despite a CNA profile similar to conventional PCa, iIDC-P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC-P is not likely a precursor to the associated low-grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.}, }
@article {pmid30989460, year = {2019}, author = {Lee, J and Kim, HE and Song, YS and Cho, EY and Lee, A}, title = {miR-106b-5p and miR-17-5p could predict recurrence and progression in breast ductal carcinoma in situ based on the transforming growth factor-beta pathway.}, journal = {Breast cancer research and treatment}, volume = {176}, number = {1}, pages = {119-130}, pmid = {30989460}, issn = {1573-7217}, support = {NRF-2017R1D1A1B03034165//National Research Foundation of Korea/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; RNA Interference ; Signal Transduction ; Transcriptome ; Transforming Growth Factor beta/*metabolism ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence.<br><br>METHODS: Forty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-&#x3b2; downstream pathway.<br><br>RESULTS: miRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGF&#x3b2;RII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGF&#x3b2;RII, especially in cells transfected with both miRNAs.<br><br>CONCLUSION: miR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-&#x3b2; activity, leading to early breast cancer carcinogenesis.}, }
@article {pmid30985953, year = {2019}, author = {Erro, R and Picillo, M and Amboni, M and Savastano, R and Scannapieco, S and Cuoco, S and Santangelo, G and Vitale, C and Pellecchia, MT and Barone, P}, title = {Comparing postural instability and gait disorder and akinetic-rigid subtyping of Parkinson disease and their stability over time.}, journal = {European journal of neurology}, volume = {26}, number = {9}, pages = {1212-1218}, doi = {10.1111/ene.13968}, pmid = {30985953}, issn = {1468-1331}, mesh = {Aged ; Female ; Gait Disorders, Neurologic/etiology/*physiopathology ; Humans ; Hypokinesia/etiology/*physiopathology ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/classification/complications/*physiopathology ; Postural Balance/*physiology ; Tremor/etiology/*physiopathology ; }, abstract = {BACKGROUND AND PURPOSE: Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor-dominant versus postural instability and gait disorder; (ii) tremor-dominant versus akinetic-rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow-up period of 4 years.<br><br>METHODS: Newly diagnosed, untreated PD patients were classified as tremor-dominant versus postural instability and gait disorder and tremor-dominant versus akinetic-rigid at baseline and after 2 and 4&#xa0;years.<br><br>RESULTS: There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4-year subtype membership. In fact, about half of our cohort shifted category during the first 2&#xa0;years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2- to 4-year follow-up.<br><br>CONCLUSIONS: The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor-dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.}, }
@article {pmid30982780, year = {2019}, author = {Ren, W and Guan, W and Zhang, J and Wang, F and Xu, G}, title = {Pyridoxine 5'-phosphate oxidase is correlated with human breast invasive ductal carcinoma development.}, journal = {Aging}, volume = {11}, number = {7}, pages = {2151-2176}, pmid = {30982780}, issn = {1945-4589}, mesh = {Adult ; Aged ; Binding, Competitive ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MCF-7 Cells ; MicroRNAs/genetics/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Pyridoxaminephosphate Oxidase/antagonists &amp; inhibitors/genetics/*metabolism ; RNA, Long Noncoding/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Tumor Stem Cell Assay ; }, abstract = {Pyridoxine 5'-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was correlated with the overall survival of patients with metastasis at the later stages. Suppression of PNPO inhibited breast cancer cell proliferation, migration, invasion and colony formation, arrested cell cycle at the G2/M phase and induced cell apoptosis. PNPO was positively correlated with lncRNA MALAT1 which was negatively correlated with miR-216b-5p. PNPO was down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. A microRNA response element was found in both PNPO and MALAT1 transcripts for miR-216b-5p and the dual-luciferase reporter assay confirmed the binding of these transcripts. Knockdown of MALAT1 resulted in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs. Taken together, these results reveal the biological function and a regulatory mechanism of PNPO, in which the MALAT1/miR-216b-5p/PNPO axis may be important in IDC development. Targeting this axis may have therapeutic potential for breast cancer.}, }
@article {pmid30959550, year = {2019}, author = {Deva Magendhra Rao, AK and Patel, K and Korivi Jyothiraj, S and Meenakumari, B and Sundersingh, S and Sridevi, V and Rajkumar, T and Pandey, A and Chatterjee, A and Gowda, H and Mani, S}, title = {Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications.}, journal = {Molecular oncology}, volume = {13}, number = {6}, pages = {1342-1355}, pmid = {30959550}, issn = {1878-0261}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Gene Regulatory Networks/genetics ; Humans ; Prognosis ; RNA, Long Noncoding/genetics/*metabolism ; Sequence Analysis, RNA ; }, abstract = {Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was performed on six invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, seven ductal carcinoma in situ tissues, and five apparently normal breast tissues. We identified 375 differentially expressed lncRNAs (DElncRNAs) in IDC tissues compared to paired normal tissues. Antisense transcripts (~ 58%) were the largest subtype among DElncRNAs. About 20% of the 375 DElncRNAs were supported by typical split readings leveraging their detection confidence. Validation was performed in n = 52 IDC and paired normal tissue by qRT-PCR for the identified targets (ADAMTS9-AS2, EPB41L4A-AS1, WDFY3-AS2, RP11-295M3.4, RP11-161M6.2, RP11-490M8.1, CTB-92J24.3, and FAM83H-AS1). We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and report that overexpression of FAM83H-AS1 was associated with patient poor survival. We confirmed that the downregulation of ADAMTS9-AS2 in breast cancer was due to promoter hypermethylation through in vitro silencing experiments and pyrosequencing.}, }
@article {pmid30943919, year = {2019}, author = {Campbell, EJ and Dachs, GU and Morrin, HR and Davey, VC and Robinson, BA and Vissers, MCM}, title = {Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {307}, pmid = {30943919}, issn = {1471-2407}, support = {R1512//Canterbury Medical Research Foundation/ ; R1512//New Zealand Breast Cancer Foundation/ ; }, mesh = {Antigens, Neoplasm/genetics/*metabolism ; Ascorbic Acid/*metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carbonic Anhydrase IX/genetics/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins/genetics/*metabolism ; Retrospective Studies ; Survival Analysis ; Up-Regulation ; Vascular Endothelial Growth Factor A/genetics/*metabolism ; }, abstract = {BACKGROUND: The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer.<br><br>METHODS: In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1&#x3b1;, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters.<br><br>RESULTS: HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival.<br><br>CONCLUSIONS: Our findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.}, }
@article {pmid30916846, year = {2019}, author = {Leshem, R and van Lieshout, PHHM and Ben-David, S and Ben-David, BM}, title = {Does emotion matter? The role of alexithymia in violent recidivism: A systematic literature review.}, journal = {Criminal behaviour and mental health : CBMH}, volume = {29}, number = {2}, pages = {94-110}, doi = {10.1002/cbm.2110}, pmid = {30916846}, issn = {1471-2857}, mesh = {*Affective Symptoms ; Aggression/psychology ; Crime/*statistics &amp; numerical data ; Criminals/*psychology ; *Emotions ; Humans ; Male ; *Recidivism ; Recurrence ; Risk Assessment ; Risk Factors ; Violence/*psychology/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Several variables have been evidenced for their association with violent reoffending. Resultant interventions have been suggested, yet the rate of recidivism remains high. Alexithymia, characterised by deficits in emotion processing and verbal expression, might interact with these other risk factors to affect outcomes.<br><br>AIM: Our goal was to examine the role of alexithymia as a possible moderator of risk factors for violent offender recidivism. Our hypothesis was that, albeit with other risk factors, alexithymia increases the risk of violent reoffending.<br><br>METHOD: We conducted a systematic literature review, using terms for alexithymia and violent offending and their intersection.<br><br>RESULTS: (a) No study that directly tests the role of alexithymia in conjunction with other potential risk factors for recidivism and actual violent recidivism was uncovered. (b) Primarily alexithymia researchers and primarily researchers into violence have separately found several clinical features in common between aspects of alexithymia and violence, such as impulsivity (total n&#xa0;=&#xa0;24 studies). (c) Other researchers have established a relationship between alexithymia and both dynamic and static risk factors for violent recidivism (n&#xa0;=&#xa0;16 studies).<br><br>CONCLUSION: Alexithymia may be a possible moderator of risk of violent offence recidivism. Supplementing offenders' rehabilitation efforts with assessments of alexithymia may assist in designing individually tailored interventions to promote desistance among violent offenders.}, }
@article {pmid30914612, year = {2019}, author = {Oki, T and Sugimoto, T and Ogawa, M and Dabanaka, K and Hanazaki, K}, title = {[A Case of Early-Onset Breast Cancer for Which the Operative Indication for Breast Conservation Was Based on BRCA Genetic Testing].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {3}, pages = {555-557}, pmid = {30914612}, issn = {0385-0684}, mesh = {Adult ; *Breast Neoplasms/genetics/surgery ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Testing ; Humans ; Mastectomy, Segmental ; Neoadjuvant Therapy ; *Neoplasm Recurrence, Local ; }, abstract = {We report a case of a patient with early-onset breast cancer who decided to undergo adaptation for breast-conserving surgery based on the results of genetic testing. A 25-year-old woman became aware of a lump in her left breast and visited a nearby hospital, where she was diagnosed with breast cancer. She has no personal history. Her paternal grandfather was diagnosed with rectal cancer at age 60. Ultrasonography revealed an irregularly-shaped hypoechoic mass measuring 3.8 cm in the C area of her left breast and an enlarged lymph node 2.0 cm in diameter in the left axillary area. The breast tumor was pathologically diagnosed as invasive ductal carcinoma by core needle biopsy and was immunohistochemically characterized as ER(-), PgR(-), and HER2(-), s o-called triple negative. Moreover, lymph node metastasis was confirmed by fine needle aspiration cytology. She underwent neoadjuvant chemotherapy and achieved a clinical complete response. A woman with early-onset triple negative breast cancer has a high probability of hereditary breast and ovarian cancer, with a high risk of ipsilateral second breast cancer after conserving surgery. Thus, BRCA genetic testing may be necessary before surgery. As no pathogenic mutation wasfound in BRCA 1/2 in this case, the patient underwent breast-conserving surgery followed by radiation therapy for the conserved breast. The patient remained healthy and without any recurrence 4 years and 2 months after surgery.}, }
@article {pmid30914564, year = {2019}, author = {Takizawa, K and Sakata, J and Ando, T and Yuza, K and Toge, K and Hirose, Y and Nakano, T and Ishikawa, H and Katada, T and Miura, K and Nagahashi, M and Shimada, Y and Kameyama, H and Kobayashi, T and Wakai, T}, title = {[A Case of Peritoneal Recurrence of Invasive Ductal Carcinoma Derived from Intraductal Papillary Mucinous Neoplasm after Surgery Treated with Palliative Radiation Therapy and Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {2}, pages = {372-374}, pmid = {30914564}, issn = {0385-0684}, mesh = {*Adenocarcinoma, Mucinous ; Aged, 80 and over ; *Carcinoma, Pancreatic Ductal/pathology/therapy ; Combined Modality Therapy ; Humans ; Male ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology/therapy ; *Peritoneal Neoplasms/secondary/therapy ; }, abstract = {An 82-year-old man with a diagnosis ofintraductal papillary mucinous carcinoma(IPMC)underwent pancreaticoduodenectomy followed by adjuvant chemotherapy with S-1. Six months after surgery, he had upper abdominal pain, and CT demonstrated a recurrent intraabdominal tumor located at the surgical incision scar. It was diagnosed as a solitary peritoneal recurrence, and palliative radiation therapy at a dose of 30 Gy was performed for the relief of abdominal pain after administration ofoxycodone. He was free ofpain without pharmacological therapy and received subsequent chemotherapy with nabpaclitaxel plus gemcitabine(GnP). He remains free ofpain and alive without progression ofthe disease 24 months after recurrence. Hypofractionated-accelerated radiotherapy is feasible and results in pain relief for local recurrence of IPMC.}, }
@article {pmid30914555, year = {2019}, author = {Monden, K and Sakurai, K and Fujisaki, S and Kubota, H and Suzuki, Y and Adachi, K and Suzuki, S and Tomita, R}, title = {[The Diagnostic Problem of Automated Breast Volume Scanner(ABUS)for a Breast Cancer Patient with Dementia-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {2}, pages = {345-347}, pmid = {30914555}, issn = {0385-0684}, mesh = {Aged, 80 and over ; *Breast Neoplasms/complications/diagnosis ; *Dementia/complications ; Female ; Humans ; Mammography ; Mastectomy ; *Sentinel Lymph Node Biopsy ; }, abstract = {The patient was an 84-year-old woman.She had presented with a mass on her right breast.Mammography revealed an illdefined mass.Handheld ultrasonography(HHUS)revealed a low echoic mass, 25mm in diameter, on the AC area of her right breast.An automated breast volume scanner(ABUS)was not useful for detecting the lesion because the patient had dementia and restless body movements.A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma, which was positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.We examined her whole body and made a diagnosis of T2N0M0, StageⅡA.She underwent a muscle-preserving mastectomy plus sentinel lymph node biopsy.The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma, positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.The surgical margins were negative for malignancy, and no metastasis was observed in the sentinel lymph node.She was given endocrine as adjuvant therapies.Three years after the surgery, she was well without metastases.Patients with dementia could not use ABUS.HHUS will be useful for these patients.}, }
@article {pmid30913871, year = {2019}, author = {Chen, WR and Deng, JP and Wang, J and Sun, JY and He, ZY and Wu, SG}, title = {Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases.}, journal = {Cancer research and treatment}, volume = {51}, number = {4}, pages = {1437-1448}, pmid = {30913871}, issn = {2005-9256}, support = {81872459//National Natural Science Foundation of China/ ; 81803050//National Natural Science Foundation of China/ ; 2016J01635//Natural Science Foundation of Fujian Province/ ; 2018A030313666//Guangdong Academy of Sciences/ ; }, mesh = {Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Chemotherapy, Adjuvant ; Clinical Decision-Making/*methods ; Female ; Gene Expression Profiling/methods ; Humans ; Multivariate Analysis ; Neoplasm Micrometastasis/drug therapy/*genetics ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics ; SEER Program ; Treatment Outcome ; }, abstract = {PURPOSE: The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). Methods Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed.<br><br>RESULTS: We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs.<br><br>CONCLUSION: The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.}, }
@article {pmid30912402, year = {2019}, author = {Asiaf, A and Ahmad, ST and Malik, AA and Aziz, SA and Zargar, MA}, title = {Association of Protein Expression and Methylation of DAPK1 with Clinicopathological Features in Invasive Ductal Carcinoma Patients from Kashmir.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {3}, pages = {839-848}, pmid = {30912402}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; *DNA Methylation ; Death-Associated Protein Kinases/*genetics/*metabolism ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Promoter Regions, Genetic ; }, abstract = {Aims: Death-associated protein kinase-1 (DAPK1) is a pro-apoptotic Ser/Thr kinase that participates in cell apoptosis and tumor suppression. DAPK1 is frequently lost in many different tumor types including breast cancer. The aim of this study was to evaluate the promoter methylation status of DAPK1 and a possible correlation with the expression of DAPK1 and standard clinicopathological features in invasive ductal breast carcinoma patients (IDC). Methods: Methylation Specific PCR (MSP) was carried out to investigate the promoter methylation status of DAPK1 from 128 breast cancer patients. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry (n=128) and western blotting (n=56). Results: We found significant difference in DAPK1 promoter methylation frequency among breast tumors when compared with the corresponding normal tissues. Hypermethylation of DAPK1 is significantly correlated with the loss of DAPK1 protein expression (P < .001, rs= -0.361). The loss of DAPK1 protein was significantly associated with estrogen receptor (ER) negativity (p= 0.003), triple negative breast cancer (TNB) (p= 0.024) and advanced tumor stages (P = 0.001). Moreover, age at diagnosis (p= 0.041), tumor stage (p= 0.034), ER negativity (p= 0.004) and TNB cancers (p=0.003) correlated significantly with the hypermethylation of the DAPK1 promoter. Coclusion: This study indicates that DAPK1 is methylated in IDC and promoter hypermethylation could be attributed to silencing of DAPK1 gene expression in breast cancer. Thus, we consider DAPK1 inactivation by promoter hypermethylation likely plays a role in the development and progression of breast cancer.}, }
@article {pmid30905927, year = {2019}, author = {Koc-Günel, S and Tekeli, N and Smaczny, C and Vogl, T and Rohde, G}, title = {A Case of Lymphangioleiomyomatosis (LAM) of the Lung in a Patient with a History of Breast Cancer.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {390-393}, pmid = {30905927}, issn = {1941-5923}, mesh = {Breast Neoplasms/*complications ; Female ; Humans ; Lung Neoplasms/*complications/*diagnosis ; Lymphangioleiomyomatosis/*complications/*diagnosis ; Middle Aged ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare progressive cystic and nodular disease of the lung characterized by smooth muscle cell proliferation. LAM predominantly affects young premenopausal women. This report is of a case of LAM presenting in a 47-year-old woman with a past history of breast cancer and discusses the possibility of an association between the two conditions. CASE REPORT A 47-year-old woman presented as an emergency with an exacerbation of a four-month history of shortness of breath and dry cough. Her symptoms began following the start of anti-hormonal treatment with letrozole and goserelin acetate for a moderately differentiated (grade 2) invasive ductal carcinoma of the breast (pT2, pN0, M0) which was positive for expression of estrogen receptor (ER+), progesterone receptor (PR+), and human epidermal growth factor receptor 2 (HER2+). Until the previous four months, she had breast-conserving treatment with radiotherapy and tamoxifen therapy. Following hospital admission, she was found to be in type I respiratory failure. Chest X-ray, lung computed tomography (CT), and positron-emission tomography (PET) showed diffuse cystic and nodular lung lesions, consistent with a diagnosis of LAM, and antihormonal therapy was discontinued. She developed pericarditis that was treated with the anti-inflammatory agent, colchicine. Treatment with letrozole and sirolimus improved her respiratory symptoms. CONCLUSIONS A rare case of LAM is presented in a woman with a recent history of breast cancer. Because both tumors were hormone-dependent, this may support common underlying gene associations and signaling pathways between the two types of tumor.}, }
@article {pmid30900303, year = {2019}, author = {Nie, L and Pan, X and Zhang, M and Yin, X and Gong, J and Chen, X and Xu, M and Zhou, Q and Chen, N}, title = {The expression profile and heterogeneity analysis of ERG in 633 consecutive prostate cancers from a single center.}, journal = {The Prostate}, volume = {79}, number = {8}, pages = {819-825}, doi = {10.1002/pros.23785}, pmid = {30900303}, issn = {1097-0045}, mesh = {Biopsy, Large-Core Needle/methods ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Cohort Studies ; Gene Expression ; Gene Rearrangement ; Genetic Heterogeneity ; Humans ; Image-Guided Biopsy/methods ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Prostatic Neoplasms, Castration-Resistant/genetics/*metabolism/pathology ; Serine Endopeptidases/genetics/metabolism ; Transcriptional Regulator ERG/biosynthesis/genetics ; Tumor Burden ; }, abstract = {BACKGROUND: Overexpression of ERG protein resulting from TMPRSS2:ERG rearrangement is highly specific for prostate cancer (PCa). However, the biological function of this fusion protein and its relationship with clinicopathological features still remain controversial.<br><br>METHOD: In this study, we evaluated ERG protein expression/gene rearrangement and heterogeneity by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in a cohort of 633 consecutive PCa initially diagnosed by core-needle biopsy in the West China Hospital.<br><br>RESULT: Overall, ERG protein expression was detected in 16.7% (106 of 633) cases, and frequently observed in PCa patients less than 60 years of age (31.9% vs 15.5%, P&#x2009;=&#x2009;0.004) and in PCa with Gleason score less than 8 (20.0% vs 13.4%, P&#x2009;=&#x2009;0.027), but infrequently observed in cases with intraductal carcinoma of the prostate (IDC-P) (10.0% vs 18.6%, P&#x2009;=&#x2009;0.012). Follow-up analysis found that patients who progressed to castration-resistant prostate cancer (CRPC) have a lower frequency of ERG protein expression at initial biopsies compared to androgen deprivation therapy (ADT)-sensitive cases (14.1% vs 23.5%, P&#x2009;=&#x2009;0.042), but Kaplan-Meier curve showed that ERG protein expression was not an independent prognostic marker. Of all the 106 ERG-positive cases, eight cases (7.5%) exhibited heterogeneous expression of ERG protein, in which ERG was only positive in tumors with Gleason pattern 3, but negative in Gleason pattern 4. The FISH analysis was consistent with IHC in six of these cases. In the other two cases, ERG rearrangement was detected in tumors with both Gleason pattern 3 and 4 by FISH, despite the negative protein expression in Gleason pattern 4. In case 1, a repeated biopsy was performed when the disease progressed to CRPC, and no ERG-positive cells were identified neither by IHC nor FISH.<br><br>CONCLUSION: This was by far the largest series of ERG expression and heterogeneity analysis in Chinese PCa. The ERG rearrangement seemed to be frequently expressed in patients with relatively younger age and lower Gleason score and infrequently expressed in PCa with the IDC-P. PCa with positive ERG were less frequently to progress to CRPC, but there was no prognostic significance of ERG expression. In heterogeneous cases, ERG protein was detectable only in tumors with Gleason pattern 3 but not in pattern 4. Tumor cells with positive ERG expression/rearrangement seemed easily response to ADT.}, }
@article {pmid30897334, year = {2019}, author = {Wang, YF and Han, J}, title = {OTOR in breast carcinoma as a potent prognostic predictor correlates with cell proliferation, migration, and invasiveness.}, journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire}, volume = {97}, number = {6}, pages = {750-757}, doi = {10.1139/bcb-2018-0305}, pmid = {30897334}, issn = {1208-6002}, mesh = {Biomarkers, Tumor/antagonists &amp; inhibitors/*genetics/metabolism ; Breast Neoplasms/diagnosis/*genetics/metabolism/*pathology ; *Cell Movement ; Cell Proliferation ; Cells, Cultured ; Cohort Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Prognosis ; Proteins/antagonists &amp; inhibitors/*genetics/metabolism ; RNA, Small Interfering/pharmacology ; }, abstract = {Otoraplin (OTOR), recognized as an important cochlear gene, has a predicted secretory signal peptide sequence and harbors a high degree of cross-species conservation. However, its role in tumor progression is relatively unclear, especially in breast carcinoma (BC). This study investigated the clinicopathological significance of OTOR in breast infiltrating ductal carcinoma (IDC) with high metastasis to uncover its biological function in BC. OTOR was highly overexpressed in BC tissues and cells compared with normal samples. OTOR overexpression was associated with certain clinicopathological characteristics and poorer prognosis (overall survival; OS) of patients with breast IDC. As determined using CCK-8, colony formation, wound-healing, and Transwell assays, silencing OTOR using siRNA impeded BC-cell proliferation, migration, and invasiveness, which may have resulted from inactivating the mitogen-activated protein kinase - extracellular-signal-regulated kinase pathway. These results indicate that OTOR plays a crucial role in the progression of and prognosis for BC, which could help to identify future therapeutic targets for treating BC patients.}, }
@article {pmid30890538, year = {2019}, author = {Rohm, M and Zeigerer, A and Machado, J and Herzig, S}, title = {Energy metabolism in cachexia.}, journal = {EMBO reports}, volume = {20}, number = {4}, pages = {}, pmid = {30890538}, issn = {1469-3178}, mesh = {Adipose Tissue/metabolism ; Animals ; Cachexia/etiology/*metabolism ; *Energy Metabolism ; Gastrointestinal Absorption ; Humans ; Liver/metabolism ; Muscle, Skeletal/metabolism ; Neoplasms/complications/metabolism ; Organ Specificity ; }, abstract = {Cachexia is a wasting disorder that accompanies many chronic diseases including cancer and results from an imbalance of energy requirements and energy uptake. In cancer cachexia, tumor-secreted factors and/or tumor-host interactions cause this imbalance, leading to loss of adipose tissue and skeletal and cardiac muscle, which weakens the body. In this review, we discuss how energy enters the body and is utilized by the different organs, including the gut, liver, adipose tissue, and muscle, and how these organs contribute to the energy wasting observed in cachexia. We also discuss futile cycles both between the organs and within the cells, which are often used to fine-tune energy supply under physiologic conditions. Ultimately, understanding the complex interplay of pathologic energy-wasting circuits in cachexia can bring us closer to identifying effective treatment strategies for this devastating wasting disease.}, }
@article {pmid30890151, year = {2019}, author = {Tewari, SG and Rajaram, K and Schyman, P and Swift, R and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Short-term metabolic adjustments in Plasmodium falciparum counter hypoxanthine deprivation at the expense of long-term viability.}, journal = {Malaria journal}, volume = {18}, number = {1}, pages = {86}, pmid = {30890151}, issn = {1475-2875}, support = {R01 AI125534/AI/NIAID NIH HHS/United States ; AI125534//National Institute of Allergy and Infectious Diseases/ ; W81XWH-15-C-0061//Medical Research and Materiel Command/ ; }, mesh = {*Adaptation, Physiological ; Animals ; Gene Expression Profiling ; Hypoxanthine/*metabolism ; Metabolic Networks and Pathways ; Metabolomics ; Plasmodium falciparum/growth &amp; development/metabolism/*physiology ; Survival ; Time Factors ; }, abstract = {BACKGROUND: The malarial parasite Plasmodium falciparum is an auxotroph for purines, which are required for nucleic acid synthesis during the intra-erythrocytic developmental cycle (IDC) of the parasite. The capabilities of the parasite and extent to which it can use compensatory mechanisms to adapt to purine deprivation were studied by examining changes in its metabolism under sub-optimal concentrations of hypoxanthine, the primary precursor utilized by the parasite for purine-based nucleic acid synthesis.<br><br>METHODS: The concentration of hypoxanthine that caused a moderate growth defect over the course of one IDC was determined. At this concentration of hypoxanthine (0.5&#xa0;&#x3bc;M), transcriptomic and metabolomic data were collected during one IDC at multiple time points. These data were integrated with a metabolic network model of the parasite embedded in a red blood cell (RBC) to interpret the metabolic adaptation of P. falciparum to hypoxanthine deprivation.<br><br>RESULTS: At a hypoxanthine concentration of 0.5&#xa0;&#x3bc;M, vacuole-like structures in the cytosol of many P. falciparum parasites were observed after the 24-h midpoint of the IDC. Parasites grown under these conditions experienced a slowdown in the progression of the IDC. After 72&#xa0;h of deprivation, the parasite growth could not be recovered despite supplementation with 90&#xa0;&#xb5;M hypoxanthine. Simulations of P. falciparum metabolism suggested that alterations in ubiquinone, isoprenoid, shikimate, and mitochondrial metabolism occurred before the appearance of these vacuole-like structures. Alterations were found in metabolic reactions associated with fatty acid synthesis, the pentose phosphate pathway, methionine metabolism, and coenzyme A synthesis in the latter half of the IDC. Furthermore, gene set enrichment analysis revealed that P. falciparum activated genes associated with rosette formation, Maurer's cleft and protein export under two different nutrient-deprivation conditions (hypoxanthine and isoleucine).<br><br>CONCLUSIONS: The metabolic network analysis presented here suggests that P. falciparum invokes specific purine-recycling pathways to compensate for hypoxanthine deprivation and maintains a hypoxanthine pool for purine-based nucleic acid synthesis. However, this compensatory mechanism is not sufficient to maintain long-term viability of the parasite. Although P. falciparum can complete a full IDC in low hypoxanthine conditions, subsequent cycles are disrupted.}, }
@article {pmid30888194, year = {2019}, author = {Yang, M and Xu, Z and Zhang, QZ and Wang, K and Ji, XY and Xu, J and Zhang, JY and Niu, G}, title = {A breast one-patient panel of heterogeneous genomes reveals genetic alterations driving DCIS into invasive lesions.}, journal = {Future oncology (London, England)}, volume = {15}, number = {14}, pages = {1565-1576}, doi = {10.2217/fon-2018-0555}, pmid = {30888194}, issn = {1744-8301}, mesh = {Actinin/genetics ; Adult ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics/metabolism/mortality ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/metabolism ; DNA Copy Number Variations ; Female ; *Genetic Heterogeneity ; *Genetic Variation ; *Genomics/methods ; Humans ; Mammography/methods ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Precision Medicine ; Prognosis ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism ; Exome Sequencing ; }, abstract = {Aim: Utilize breast cancer samples in the same patient to indicate breast cancer development. Patients &amp; methods: We performed whole-exome analysis of spatially independent ductal carcinoma in situ (DCIS) and invasive ductal carcinoma samples from the same breast. Results: In VEGF pathway, we observed two genes disrupted in DCIS, while another four (including ACTN2) mutated in invasive ductal carcinoma. When looked up TCGA database, we identified seven breast cancer patients with ACTN2 somatic mutations and observed a dramatic decrease in the overall survival time in ACTN2 mutant patients (p = 0.0182). A further finding in the TCGA database shows that breast cancer patients with ≥2 mutated genes in VEGF pathways showed worse prognosis (p = 0.0013). Conclusion: TCGA database and special case could inform each other to reveal DCIS developmental rules.}, }
@article {pmid30879795, year = {2019}, author = {Sheaffer, WW and Gray, RJ and Wasif, N and Stucky, CC and Cronin, PA and Kosiorek, HE and Basu, A and Pizzitola, VJ and Patel, B and Giurescu, ME and Lorans, R and McCullough, AE and Ocal, IT and Pockaj, BA}, title = {Predictive factors of upstaging DCIS to invasive carcinoma in BCT vs mastectomy.}, journal = {American journal of surgery}, volume = {217}, number = {6}, pages = {1025-1029}, doi = {10.1016/j.amjsurg.2018.12.069}, pmid = {30879795}, issn = {1879-1883}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology/surgery ; Female ; Humans ; *Mastectomy, Radical ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention.<br><br>METHODS: Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging.<br><br>RESULTS: In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p&#x202f;=&#x202f;0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2-14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2-6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1-3.4) increase risk of upstaging.<br><br>CONCLUSIONS: Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT.}, }
@article {pmid30872758, year = {2019}, author = {Roth, JD and Pariser, JJ and Stoffel, JT and Lenherr, SM and Myers, JB and Welk, B and Elliott, SP}, title = {Patient subjective assessment of urinary tract infection frequency and severity is associated with bladder management method in spinal cord injury.}, journal = {Spinal cord}, volume = {57}, number = {8}, pages = {700-707}, pmid = {30872758}, issn = {1476-5624}, support = {CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; }, mesh = {Adult ; Catheters, Indwelling/adverse effects/*trends ; Cross-Sectional Studies ; *Diagnostic Self Evaluation ; Female ; Humans ; Intermittent Urethral Catheterization/adverse effects/*trends ; Male ; Middle Aged ; Prospective Studies ; Registries ; Severity of Illness Index ; Spinal Cord Injuries/*complications/diagnosis/*therapy ; Urinary Tract Infections/diagnosis/*etiology ; }, abstract = {STUDY DESIGN: The Neurogenic Bladder Research Group (NBRG) registry is a multicenter prospective observational study. This manuscript is retrospective based on a cross-sectional survey.<br><br>OBJECTIVES: To assess patient subjective assessment of urinary tract infection (UTI) frequency and severity are associated with the degree of use of catheters or incontinence products.<br><br>SETTING: Multiple hospitals across the United States.<br><br>METHODS: Eligibility included: age&#x2009;>&#x2009;18 years and acquired SCI. Over 1.5 years, 1479 eligible participants were enrolled. We excluded those with surgical reconstruction or diversion of the bladder. In total, 1282 participants were grouped by bladder management: (1) indwelling catheter (IDC), (2) clean intermittent catheterization (CIC), (3) external devices (pads/condom), and (4) volitional voiding (Void). UTI frequency was classified as 0, 1-3, 4-6, or&#x2009;>&#x2009;6 over the prior year. UTI severity was determined by hospitalization for UTI in the prior year. Multivariate regression compared these factors across groups.<br><br>RESULTS: UTIs were least frequent in Void followed by pads/condom, CIC, and IDC (all p&#x2009;&#x2264;&#x2009;0.001). UTI severity followed a similar pattern. Controlling for covariates, the adjusted odds of UTI frequency (Void&#x2009;=&#x2009;reference) were 2.28 (1.38-3.76) for pads/condom, 3.42 (2.25-5.18) for CIC, and 4.3 (2.59-6.70) for IDC (all p&#x2009;&#x2264;&#x2009;0.001).<br><br>CONCLUSIONS: Patient subjective assessment of UTI frequency is highest with IDC, followed by CIC, pads/condom, and lowest with spontaneous voiding. The odds of hospitalization for UTI were three times higher for IDC than spontaneous voiding. UTI risk should be considered when counseling patients about bladder management options. These associations do not imply causation but warrant further investigation in a prospective manner.<br><br>SPONSORSHIP: Patient-Centered Outcomes Research Institute (PCORI) Award (CER14092138).}, }
@article {pmid30872384, year = {2019}, author = {Li, Y and Zhang, N and Zhang, H and Yang, Q}, title = {Comparative prognostic analysis for triple-negative breast cancer with metaplastic and invasive ductal carcinoma.}, journal = {Journal of clinical pathology}, volume = {72}, number = {6}, pages = {418-424}, doi = {10.1136/jclinpath-2018-205544}, pmid = {30872384}, issn = {1472-4146}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/ethnology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/ethnology/mortality/*pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Metaplasia ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/ethnology/mortality/*pathology/therapy ; United States/epidemiology ; Young Adult ; }, abstract = {AIMS: Triple-negative breast cancer comprises different histological subtypes, including metaplastic breast cancer (MBC) and ductal carcinomas (IDCs). The purpose of this study was to compare triple-negative MBC (TN-MBC) with triple-negative IDC (TN-IDC) in terms of survival and predictive factors.<br><br>METHODS: With access to the Surveillance, Epidemiology and End Result (SEER) database, a total of 19&#x2009;383 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using the &#x3c7;[2] test. Univariate and multivariate analyses were applied to evaluate the disease-specific survival (DSS) and overall survival (OS). Subgroup analyses summarised the hazard ratios of TN-MBC versus TN-IDC using a forest plot.<br><br>RESULTS: A total of 586 patients with TN-MBC and 18&#x2009;797 with TN-IDC were included in this study. Patients with TN-MBC were older and presented with larger tumour sizes, relatively rare lymph node positive disease, and had received more chemotherapy. Compared with TN-IDC, the TN-MBC group showed a significantly poorer prognosis before and after the 1:3 matched case-control analysis. Further subgroup analysis indicated that patients with TN-MBC were older, were from specific races, and those with distant metastasis and not receiving radiotherapy had worse prognosis than patients with TN-IDC in terms of DFS and OS.<br><br>CONCLUSION: Our results showed that patients with TN-MBC had unique clinicopathological characteristics and poorer prognostic subtype compared with TN-IDC. This improves our understanding of the clinicopathological and prognostic features of this rare entity but also provides more convincing therapeutic guidelines for TN-MBC in patients with breast cancer.}, }
@article {pmid30864836, year = {2019}, author = {Dong, Y and Zhang, WW and Wang, J and Sun, JY and He, ZY and Wu, SG}, title = {The 21-gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer.}, journal = {Future oncology (London, England)}, volume = {15}, number = {14}, pages = {1629-1639}, doi = {10.2217/fon-2018-0967}, pmid = {30864836}, issn = {1744-8301}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/*genetics/mortality/*therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Postoperative Care ; Prognosis ; Radiotherapy, Adjuvant ; Recurrence ; SEER Program ; }, abstract = {Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p = 0.029) and after (p = 0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS.}, }
@article {pmid36338780, year = {2019}, author = {Lam, JC and Gregson, DB and Robinson, S and Somayaji, R and Welikovitch, L and Conly, JM and Parkins, MD}, title = {Infectious diseases consultation improves key performance metrics in the management of Staphylococcus aureus bacteremia: A multicentre cohort study.}, journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada}, volume = {4}, number = {1}, pages = {24-32}, pmid = {36338780}, issn = {2371-0888}, abstract = {BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. We sought to identify factors associated with infectious diseases consultation (IDC) and understand how IDC associates with SAB patient management and outcomes.<br><br>METHODS: A multicentre retrospective study was performed between 2012 and 2014 in a large Canadian Health Zone in order to determine factors associated with IDC and performance of key quality of care determinants in SAB management and clinical outcomes. Factors subject to quality of care determinants were established a priori and studied for associations with IDC and 30-day all-cause mortality using multivariable analysis.<br><br>RESULTS: Of 961 SAB episodes experienced by 892 adult patients, 605 episodes received an IDC. Patients receiving IDC were more likely to have prosthetic valves and joints and to have community-acquired and known sources of SAB, but increasing age decreased IDC occurrence. IDC was the strongest independent predictor for quality of care performance metrics, including repeat blood cultures and echocardiography. Mortality at 30 days was 20% in the cohort, and protective factors included IDC, achievement of source control, targeted therapy within 48 hours, and follow-up blood cultures but not the performance of echocardiography.<br><br>CONCLUSIONS: There were significant gaps between the treatments and investigations that patients actually received for SAB and what is considered the optimal management of their condition. IDC is associated with improved attainment of targeted SAB quality of care determinants and reduced mortality rates. Based on our findings, we propose a policy of mandatory IDC for all cases of SAB to improve patient management and outcomes.}, }
@article {pmid30843776, year = {2018}, author = {Menichetti, F and Bertolino, G and Sozio, E and Carmignani, C and Rosselli Del Turco, E and Tagliaferri, E and Sbrana, F and Ripoli, A and Barnini, S and Desideri, I and Dal Canto, L and Tascini, C and , }, title = {Impact of infectious diseases consultation as a part of an antifungal stewardship programme on candidemia outcome in an Italian tertiary-care, University hospital.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {30}, number = {5}, pages = {304-309}, doi = {10.1080/1120009X.2018.1507086}, pmid = {30843776}, issn = {1973-9478}, mesh = {Aged ; Antifungal Agents/*therapeutic use ; Antimicrobial Stewardship/methods ; Candida/drug effects ; Candidemia/*drug therapy ; Communicable Diseases/*drug therapy ; Female ; Fluconazole/therapeutic use ; Hospitals, University ; Humans ; Italy ; Male ; Referral and Consultation ; Retrospective Studies ; }, abstract = {Candidemia is a major cause of in-hospital mortality. Antifungal stewardship programme (AFSP) providing infectious diseases consultation (IDC) might improve the outcome. We evaluate the impact on candidemia mortality of IDC as part of AFSP restricting the use of all antifungals with exception of fluconazole. We retrospectively reviewed the charts of patients with documented candidemia in our hospital during the period 2012-2014 evaluating the impact of several variables on 30-days in-hospital mortality. We reviewed data on 276 patients with documented candidemia: 200 (72%) were treated without IDC and 76 (28%) with IDC. In the group without IDC, 52 patients (26%) received no antifungal therapy. Antifungals used for treating candidemia were (no IDC/IDC): azoles (74%/42%); echinocandins (0%/46%); liposomal and lipidic complex amphotericin B (0%/12%). The 30-day in-hospital mortality was respectively (no IDC/IDC) 37% vs. 20% (p = 0.011). The multivariate analysis confirmed IDC as independent factor protecting from death (OR 0.511, 95% CI 0.251-0.994; p = 0.046), together with fungemia due to non-albicans Candida (OR 0.565, 95% CI 0.327-0.977; p = 0.042). Age >65 years was associated with a higher risk of death (OR 1.989, 95% CI 1.055-3.895; p = 0.038). The additional cost for the use of echinocandins driven by IDC in the study period was €207,000. IDC, as a part of a restrictive front-end antimicrobial stewardship programme (ASP), providing a timely right choice of antifungal therapy, increases the cost of antifungal drugs but might be a contributing protective factor from mortality due to candidemia. Efforts to increase the number of IDC in patients with candidemia seems to be warranted.}, }
@article {pmid30843116, year = {2019}, author = {Goodfellow, J and Gorrie, G and Leach, V and Patel, S and Mackay, G}, title = {Cancer and motor neuron disease-causal or coincidental? Two contrasting cases.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {40}, number = {7}, pages = {1461-1463}, pmid = {30843116}, issn = {1590-3478}, mesh = {Breast Neoplasms/*complications/immunology/pathology ; Carcinoma, Ductal, Breast/*complications/immunology/pathology ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*complications/immunology/pathology/therapy ; Middle Aged ; Motor Neuron Disease/*complications/etiology/immunology ; *Paraneoplastic Syndromes, Nervous System/immunology ; Small Cell Lung Carcinoma/*complications/immunology/pathology/therapy ; }, abstract = {INTRODUCTION: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission.<br><br>CONCLUSION: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.}, }
@article {pmid30842485, year = {2019}, author = {Rossi, A and Dupaty, L and Aillot, L and Zhang, L and Gallien, C and Hallek, M and Odenthal, M and Adriouch, S and Salvetti, A and Büning, H}, title = {Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {3631}, pmid = {30842485}, issn = {2045-2322}, mesh = {Animals ; CD8-Positive T-Lymphocytes/immunology/virology ; Capsid/*immunology ; Capsid Proteins/*immunology ; Dendritic Cells/*immunology/virology ; Dependovirus/genetics/*immunology ; Genetic Vectors/*administration &amp; dosage/*immunology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; *Transduction, Genetic ; }, abstract = {AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV's low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized AAV vectors of various serotypes, but even the most efficient serotype failed to transduce iDC above background. Since AAV vectors reached the cell nucleus, we hypothesized that AAV's intracellular processing occurs suboptimal. On this basis, we screened an AAV peptide display library for capsid variants more suitable for DC transduction and identified the I/VSS family which transduced DC with efficiencies of up to 38%. This property correlated with an improved vector uncoating. To determine the consequence of this novel feature for AAV's in vivo performance, we engineered one of the lead candidates to express a cytoplasmic form of ovalbumin, a highly immunogenic model antigen, and assayed transduction efficiency as well as immunogenicity. The capsid variant clearly outperformed the parental serotype in muscle transduction and in inducing antigen-specific humoral and T cell responses as well as anti-capsid CD8[+] T cells. Hence, vector uncoating represents a major barrier hampering AAV vector-mediated transduction of DC and impacts on its use as vaccine platform.}, }
@article {pmid30825809, year = {2019}, author = {Owen, WA and Brazeal, HA and Shaw, HL and Lee, MV and Appleton, CM and Holley, SO}, title = {Focal breast pain: imaging evaluation and outcomes.}, journal = {Clinical imaging}, volume = {55}, number = {}, pages = {148-155}, doi = {10.1016/j.clinimag.2019.02.008}, pmid = {30825809}, issn = {1873-4499}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Cancer Pain/diagnostic imaging/etiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Female ; Follow-Up Studies ; Humans ; Incidental Findings ; Mammography/methods ; Mastodynia/*diagnostic imaging/etiology ; Middle Aged ; Prognosis ; Retrospective Studies ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {OBJECTIVES: To determine the number and characteristics of cancers detected and the optimal imaging evaluation in women presenting with focal breast pain (FBP).<br><br>MATERIALS AND METHODS: We performed a retrospective review of 4720 women who underwent imaging for FBP from 2001 to 2013. Women 18 and over with one or two foci of breast pain and no concurrent breast symptoms were included. 944 patients met criteria. We recorded the imaging work-up, presence and type of finding at the site of pain, BI-RADS&#xae; assessment, and pathological outcomes. Subsequent imaging and clinical follow up was recorded.<br><br>RESULTS: Imaging evaluation consisted of sonogram alone in 286 women, mammogram alone in 231 women, and both in 427 women. 113 women had an imaging finding at the site of pain; 103 were designated benign or probably benign. 12 biopsies of corresponding findings were performed: 9 benign, 1 invasive lobular carcinoma, 1 invasive ductal carcinoma, 1 ductal carcinoma in situ. All three malignancies were seen mammographically; 2 had an ultrasound correlate. At initial evaluation, 4 incidental breast cancers were diagnosed remote from the site of FBP. All were seen on mammogram and 2 of 4 had an ultrasound correlate. On follow up evaluation, 9 cancers were diagnosed at the site of pain and 13 incidental cancers were diagnosed.<br><br>CONCLUSION: FBP is rarely associated with malignancy. Targeted ultrasound may be deferred in women 40 and older with FBP, no other clinical findings, and a negative mammogram.}, }
@article {pmid30820924, year = {2019}, author = {Murakami, W and Tozaki, M and Nakamura, S and Ide, Y and Inuzuka, M and Hirota, Y and Murakami, K and Takahama, N and Ohgiya, Y and Gokan, T}, title = {The clinical impact of MRI screening for BRCA mutation carriers: the first report in Japan.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {26}, number = {5}, pages = {552-561}, pmid = {30820924}, issn = {1880-4233}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*diagnostic imaging/*genetics/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics/pathology ; Female ; Follow-Up Studies ; *Genes, BRCA1 ; *Genes, BRCA2 ; Humans ; Japan ; *Magnetic Resonance Imaging ; Mammography ; Mass Screening/methods ; Middle Aged ; *Mutation ; Public Health Surveillance/methods ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: There is no consensus on the appropriate surveillance for high-risk women with breast cancer in Japan. We investigated their imaging features and pathological characteristics to build a proper surveillance system for asymptomatic high-risk individuals in the future.<br><br>METHODS: We retrospectively reviewed 93 female (median age 43&#xa0;years) BRCA1 and BRCA2 mutation carriers from our institutional clinical database from 2011 to 2017. The study population was composed of 112 breast cancers. Mammography and MRI were reviewed by examiners blinded to patients' clinical history. Final surgical or biopsy histopathology served as the reference standard in all the patients.<br><br>RESULTS: Fifty-nine breast cancers met selection criteria; of these, 30 were BRCA1-associated tumors, and 29 were BRCA2-associated tumors. Invasive ductal carcinoma was the most prevalent type in both BRCA1 and BRCA2. There were statistically significant differences in phenotype, nuclear grade, and Ki-67 labeling index between BRCA1 and BRCA2 mutation carriers. Additionally, imaging findings on mammography and MRI were statistically different. Tumors in BRCA2 carriers demonstrated mammographic calcifications more frequently, while those in BRCA1 carriers demonstrated a mass or architectural distortion (P&#x2009;<&#x2009;0.001). Enhancement pattern on MRI also significantly differed between the two subgroups (P&#x2009;=&#x2009;0.006). The size of MRI-detected lesions was statistically smaller than the size of those detected by other modalities (P&#x2009;=&#x2009;0.004).<br><br>CONCLUSIONS: The imaging and histological characteristics of BRCA1/2 mutation carriers were consistent with other countries' studies. MRI-detected lesions were significantly smaller than lesions detected by non-MRI modality. All lesions in BRCA1 mutation carriers could be detected by MRI.}, }
@article {pmid30813596, year = {2019}, author = {Myers, MB and McKim, KL and Banda, M and George, NI and Parsons, BL}, title = {Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology.}, journal = {International journal of molecular sciences}, volume = {20}, number = {5}, pages = {}, pmid = {30813596}, issn = {1422-0067}, mesh = {Alleles ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Female ; Fluorescein/metabolism ; Humans ; Middle Aged ; Mutation/genetics ; *Mutation Rate ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/genetics ; Polymerase Chain Reaction ; *Precision Medicine ; Proto-Oncogene Proteins B-raf/genetics ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10[-5], the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pathway. These results suggest that low-frequency hotspot CDMs contribute significantly to the intertumoral and intratumoral genetic heterogeneity of IDCs, which has the potential to impact precision oncology approaches.}, }
@article {pmid30807826, year = {2019}, author = {Griggs, RB and Santos, DF and Laird, DE and Doolen, S and Donahue, RR and Wessel, CR and Fu, W and Sinha, GP and Wang, P and Zhou, J and Brings, S and Fleming, T and Nawroth, PP and Susuki, K and Taylor, BK}, title = {Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes.}, journal = {Neurobiology of disease}, volume = {127}, number = {}, pages = {76-86}, pmid = {30807826}, issn = {1095-953X}, support = {R01 DA037621/DA/NIDA NIH HHS/United States ; F31 NS083292/NS/NINDS NIH HHS/United States ; R56 NS107398/NS/NINDS NIH HHS/United States ; R01 NS062306/NS/NINDS NIH HHS/United States ; R01 NS045954/NS/NINDS NIH HHS/United States ; T32 NS077889/NS/NINDS NIH HHS/United States ; }, mesh = {Adenylyl Cyclases/*metabolism ; Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/drug effects/physiology ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Diabetes Mellitus, Type 2/complications/*metabolism ; Diabetic Neuropathies/*metabolism ; Guanine Nucleotide Exchange Factors/*metabolism ; Male ; Mice ; Pain Measurement ; Posterior Horn Cells/drug effects/metabolism ; Pyruvaldehyde/*metabolism/pharmacology ; Signal Transduction/drug effects/physiology ; TRPA1 Cation Channel/*metabolism ; }, abstract = {Painful diabetic neuropathy (PDN) is a devastating neurological complication of diabetes. Methylglyoxal (MG) is a reactive metabolite whose elevation in the plasma corresponds to PDN in patients and pain-like behavior in rodent models of type 1 and type 2 diabetes. Here, we addressed the MG-related spinal mechanisms of PDN in type 2 diabetes using db/db mice, an established model of type 2 diabetes, and intrathecal injection of MG in conventional C57BL/6J mice. Administration of either a MG scavenger (GERP10) or a vector overexpressing glyoxalase 1, the catabolic enzyme for MG, attenuated heat hypersensitivity in db/db mice. In C57BL/6J mice, intrathecal administration of MG produced signs of both evoked (heat and mechanical hypersensitivity) and affective (conditioned place avoidance) pain. MG-induced Ca[2+] mobilization in lamina II dorsal horn neurons of C57BL/6J mice was exacerbated in db/db, suggestive of MG-evoked central sensitization. Pharmacological and/or genetic inhibition of transient receptor potential ankyrin subtype 1 (TRPA1), adenylyl cyclase type 1 (AC1), protein kinase A (PKA), or exchange protein directly activated by cyclic adenosine monophosphate (Epac) blocked MG-evoked hypersensitivity in C57BL/6J mice. Similarly, intrathecal administration of GERP10, or inhibitors of TRPA1 (HC030031), AC1 (NB001), or Epac (HJC-0197) attenuated hypersensitivity in db/db mice. We conclude that MG and sensitization of a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in db/db mice. Our results warrant clinical investigation of MG scavengers, glyoxalase inducers, and spinally-directed pharmacological inhibitors of a MG-TRPA1-AC1-Epac pathway for the treatment of PDN in type 2 diabetes.}, }
@article {pmid30798329, year = {2019}, author = {Sawai, H and Kurimoto, M and Koide, S and Kiriyama, Y and Haba, S and Matsuo, Y and Morimoto, M and Koide, H and Kamiya, A and Yamao, K}, title = {Invasive Ductal Carcinoma Arising in Mucinous Cystic Neoplasm of Pancreas: A Case Report.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {242-247}, pmid = {30798329}, issn = {1941-5923}, mesh = {Adult ; Carcinoma, Pancreatic Ductal/*pathology ; Cystadenoma, Mucinous/*pathology ; Female ; Humans ; Mutation ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*pathology ; Pancreatic Neoplasms/*pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; }, abstract = {BACKGROUND Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. CASE REPORT A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. CONCLUSIONS We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinicopathological parameter.}, }
@article {pmid30789657, year = {2019}, author = {Nguyen, B and Veys, I and Leduc, S and Bareche, Y and Majjaj, S and Brown, DN and Boeckx, B and Lambrechts, D and Sotiriou, C and Larsimont, D and Desmedt, C}, title = {Genomic, Transcriptomic, Epigenetic, and Immune Profiling of Mucinous Breast Cancer.}, journal = {Journal of the National Cancer Institute}, volume = {111}, number = {7}, pages = {742-746}, doi = {10.1093/jnci/djz023}, pmid = {30789657}, issn = {1460-2105}, mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Methylation/genetics ; Epigenomics/methods ; Female ; Genomic Instability/genetics ; Genomics/methods ; Humans ; Lymphatic Metastasis ; Mucin-2/*genetics ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Transcriptome/genetics ; }, abstract = {Although invasive ductal breast cancer (IDC) represents the most common histological type of breast cancer, minor subtypes exist such as mucinous breast cancer (MuBC). MuBC are distinguished by tumor cells floating in extracellular mucin. MuBC patients are generally older and associated with a favorable prognosis. To unravel the molecular architecture of MuBC, we applied low-pass whole-genome sequencing and microscopic evaluation of stromal tumor infiltrating lymphocytes to 30 MuBC from a retrospective institutional cohort. We further analyzed two independent datasets from the International Cancer Genomics Consortium and The Cancer Genome Atlas. Genomic data (n = 26 MuBC, n = 535 estrogen receptor [ER] positive/HER2-negative IDC), methylation data (n = 28 MuBC, n = 529 ER-positive/HER2-negative IDC), and transcriptomic data (n = 27 MuBC, n = 467 ER-positive/HER2-negative IDC) were analyzed. MuBC was characterized by low tumor infiltrating lymphocyte levels (median = 0.0%, average = 3.4%, 95% confidence interval = 1.9% to 4.9%). Compared with IDC, MuBC had a lower genomic instability (P = .01, two-sided Mann-Whitney U test) and a decreased prevalence of PIK3CA mutations (39.7% in IDC vs 6.7% in MuBC, P = .01 in the International Cancer Genomics Consortium; and 34.8% vs 0.0%, P = .02 in The Cancer Genome Atlas, two-sided Fisher's exact test). Finally, our report identifies aberrant DNA methylation of MUC2 as a possible cause of extracellular production of mucin in MuBC.}, }
@article {pmid30786684, year = {2018}, author = {Hybiak, J and Domagala, P and Domagala, W}, title = {BRCA1 and PARP1 mRNA expression during progression from normal breast to ductal carcinoma in situ and invasive breast cancer: a laser microdissection study.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {69}, number = {4}, pages = {347-355}, doi = {10.5114/pjp.2018.81694}, pmid = {30786684}, issn = {1233-9687}, mesh = {BRCA1 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Humans ; Laser Capture Microdissection ; Poly (ADP-Ribose) Polymerase-1/*genetics ; RNA, Messenger ; }, abstract = {The contribution of DNA damage repair mechanisms to the progression of normal breast to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma is largely unknown. The purpose of this report was to assess the mRNA expression levels of two important genes associated with DNA repair, BRCA1 and PARP1, in normal breast tissue, DCIS G1, G2 and G3, and co-existing adjacent invasive ductal carcinoma. BRCA1 and PARP1 mRNA expression was assessed in 32 ductal carcinomas in situ of the breast using a laser microdissection and pressure catapulting system and quantitative real-time PCR. The relative expression of BRCA1 mRNA was significantly increased in DCIS G2 and DCIS G3 relative to normal breast tissue (p = 0.02, p = 0.001, respectively). Significant differences in BRCA1 expression were observed between DCIS G1 and G2 (p = 0.02) and between DCIS G1 and G3 (p = 0.0007). No significant differences in BRCA1 expression were observed between normal breast tissue and DCIS G1 and between DCIS component and adjacent invasive ductal carcinoma. No significant differences in the relative expression of PARP1 mRNA were observed between groups. Increased BRCA1 mRNA expression (but not PARP1 mRNA) occurs early in the development of breast cancer, i.e. at the noninvasive (DCIS) stage, suggesting a demand for increased activity of a DNA double-strand break repair by homologous recombination. DCIS G1 and normal breast tissue share highly similar BRCA1 and PARP1 expression level. This finding supports the idea that DCIS G1 belongs to a separate family of precursor lesions with low malignant potential.}, }
@article {pmid30772465, year = {2019}, author = {Ducommun, S and Deak, M and Zeigerer, A and Göransson, O and Seitz, S and Collodet, C and Madsen, AB and Jensen, TE and Viollet, B and Foretz, M and Gut, P and Sumpton, D and Sakamoto, K}, title = {Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates.}, journal = {Cellular signalling}, volume = {57}, number = {}, pages = {45-57}, doi = {10.1016/j.cellsig.2019.02.001}, pmid = {30772465}, issn = {1873-3913}, mesh = {AMP-Activated Protein Kinases/*metabolism ; Animals ; Guanine Nucleotide Exchange Factors/*metabolism ; Hepatocytes/metabolism ; Homeostasis/genetics/physiology ; Lipid Metabolism/genetics ; Liver/*metabolism ; Mass Spectrometry/methods ; Membrane Proteins/*metabolism ; Mice, Knockout ; Muscle Proteins/*metabolism ; Phosphorylation ; Substrate Specificity ; }, abstract = {AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis, acting as a sensor of energy and nutrient status. As such, AMPK is considered a promising drug target for treatment of medical conditions particularly associated with metabolic dysfunctions. To better understand the downstream effectors and physiological consequences of AMPK activation, we have employed a chemical genetic screen in mouse primary hepatocytes in an attempt to identify novel AMPK targets. Treatment of hepatocytes with a potent and specific AMPK activator 991 resulted in identification of 65 proteins phosphorylated upon AMPK activation, which are involved in a variety of cellular processes such as lipid/glycogen metabolism, vesicle trafficking, and cytoskeleton organisation. Further characterisation and validation using mass spectrometry followed by immunoblotting analysis with phosphorylation site-specific antibodies identified AMPK-dependent phosphorylation of Gapex-5 (also known as GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1)) on Ser902 in hepatocytes and starch-binding domain 1 (STBD1) on Ser175 in multiple cells/tissues. As new promising roles of AMPK as a key metabolic regulator continue to emerge, the substrates we identified could provide new mechanistic and therapeutic insights into AMPK-activating drugs in the liver.}, }
@article {pmid30771577, year = {2019}, author = {Liao, W and Li, C and Tang, Y and Huang, F and Kuang, H and Liang, S and Yang, Y}, title = {Aquaporin-4 antibody positive short transverse myelitis associated with breast cancer.}, journal = {Multiple sclerosis and related disorders}, volume = {30}, number = {}, pages = {119-122}, doi = {10.1016/j.msard.2019.02.011}, pmid = {30771577}, issn = {2211-0356}, mesh = {Adult ; Antibodies/*cerebrospinal fluid ; Aquaporin 4/*immunology ; Breast Neoplasms/*cerebrospinal fluid/complications/diagnostic imaging ; Carcinoma/*cerebrospinal fluid/complications/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Myelitis, Transverse/*blood/complications/diagnostic imaging ; Spinal Cord/diagnostic imaging ; }, abstract = {Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). A typical finding on spinal magnetic resonance imaging (MRI) of NMOSD is longitudinally extensive transverse myelitis (LETM). However, patients with NMOSD presenting with short-segment transverse myelitis (STM) during myelitis attacks associated with breast cancer are uncommon. We report a case of a 35-year-old woman with STM and left eye optic neuritis. The patient was positive for serum aquaporin-4 antibodies (AQP4-IgG), and a biopsy of the left breast showed invasive ductal carcinoma. The patient was diagnosed with NMOSD and breast malignancy. This is the first report of a patient with NMOSD whose spinal MRI showed STM and serum test showed that the patient's AQP4-IgG was positive and complicated by breast cancer. This case improves our understanding of the association between NMOSD and cancer and raises the question of whether it was a coincidental occurrence. It is important to search for extensive malignancies in patients presenting with atypical MRI or no reaction to traditional therapies.}, }
@article {pmid30771195, year = {2019}, author = {Miyake, M and Yamada, A and Miyake, K and Endo, I}, title = {Esophageal metastasis of breast cancer during endocrine therapy for pleural dissemination 21 years after breast surgery: a case report.}, journal = {Surgical case reports}, volume = {5}, number = {1}, pages = {22}, pmid = {30771195}, issn = {2198-7793}, abstract = {BACKGROUND: The esophageal metastasis of breast cancer is rare. Moreover, it is extremely unusual for patients to experience the symptoms of esophageal metastasis during their lifetimes. We present a case of dysphagia caused by esophageal metastasis after a long interval following a primary mastectomy.<br><br>CASE PRESENTATION: A 77-year-old woman with a history of heterochronous bilateral breast cancer and under treatment for pleural dissemination recurrence originating from right breast cancer complained of dysphagia. At the age of 56, she had undergone a right radical mastectomy for right breast cancer. The histopathological findings revealed invasive ductal carcinoma, pT3N1M0, which was estrogen receptor (ER)- and progesterone receptor (PgR)-positive. At the age of 73, she underwent a second operation, a left modified radical mastectomy. The histopathological examination revealed invasive ductal carcinoma, pT1N0M0, which was negative for ER, PgR, and human epidermal growth factor receptor 2 (HER2). Four years after completion of adjuvant therapy for the left breast cancer, pleural effusion on her left side was observed and histopathological examination of a sample revealed pleural dissemination resulting from the right breast cancer. After initiation of therapy for recurrence, she developed dysphagia and, therefore, underwent an upper gastrointestinal tract endoscopic examination. The examination revealed whole circumferential stenosis and a band unstained by Lugol's solution located 30&#x2009;cm from her incisors. Examination of a biopsy specimen revealed a subepithelial luminal structure and dysplastic cells. Immunostaining was positive for CK7 and negative for CK20; furthermore, the sample was ER and PgR-positive. Considering the pathological findings, the patient was diagnosed with esophageal metastasis of her right breast cancer.<br><br>CONCLUSIONS: Metastatic lesions in the esophagus are often located in the submucosa; therefore, they may not be definitively diagnosed by histopathological examination of mucosal biopsy specimens. Esophageal metastasis originating from breast cancer often occurs as a part of multiple organ metastases; however, esophageal metastasis is usually not considered a prognostic factor for patients. Therefore, treatment should be determined according to the severity of the other metastatic sites and the degree of esophageal stenosis.}, }
@article {pmid30770989, year = {2019}, author = {Yan, Z and Ohuchida, K and Zheng, B and Okumura, T and Takesue, S and Nakayama, H and Iwamoto, C and Shindo, K and Moriyama, T and Nakata, K and Miyasaka, Y and Ohtsuka, T and Mizumoto, K and Oda, Y and Hashizume, M and Nakamura, M}, title = {CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis.}, journal = {Journal of cancer research and clinical oncology}, volume = {145}, number = {5}, pages = {1147-1164}, pmid = {30770989}, issn = {1432-1335}, mesh = {Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor ; Carcinoma, Pancreatic Ductal/genetics/metabolism/mortality/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Survival ; Disease Models, Animal ; Disease Progression ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/secondary ; Male ; Mice ; Middle Aged ; Pancreatic Neoplasms/genetics/*metabolism/mortality/*pathology ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; Receptors, Thrombopoietin/genetics/*metabolism ; Signal Transduction ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer.<br><br>METHODS: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model.<br><br>RESULTS: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model.<br><br>CONCLUSIONS: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.}, }
@article {pmid30769363, year = {2019}, author = {Guillamat-Prats, R and Rami, M and Herzig, S and Steffens, S}, title = {Endocannabinoid Signalling in Atherosclerosis and Related Metabolic Complications.}, journal = {Thrombosis and haemostasis}, volume = {119}, number = {4}, pages = {567-575}, doi = {10.1055/s-0039-1678738}, pmid = {30769363}, issn = {2567-689X}, mesh = {Adipose Tissue/metabolism ; Animals ; Arachidonic Acid/chemistry ; Atherosclerosis/*metabolism ; Bile Acids and Salts/chemistry ; Blood Glucose/metabolism ; Cardiovascular System/metabolism ; Cytokines/metabolism ; Endocannabinoids/*metabolism ; Humans ; Inflammation ; Insulin Resistance ; Ligands ; Lipid Metabolism ; Lipids/chemistry ; Liver/metabolism ; Mice ; Mice, Knockout ; Obesity, Abdominal/metabolism ; Pancreas/metabolism ; Receptor, Cannabinoid, CB2/*metabolism ; Receptors, Cannabinoid/metabolism ; Receptors, G-Protein-Coupled/*metabolism ; Risk Factors ; *Signal Transduction ; }, abstract = {Endocannabinoids are a group of arachidonic acid-derived lipid mediators binding to cannabinoid receptors CB1 and CB2. An overactivity of the endocannabinoid system plays a pathophysiological role in the development of visceral obesity and insulin resistance. Moreover, elevated circulating endocannabinoid levels are also prevalent in atherosclerosis. The pathophysiological increase of endocannabinoid levels is due to an altered expression of endocannabinoid synthesizing and degrading enzymes induced by inflammatory mediators such as cytokines or lipids. Emerging experimental evidence suggests that enhanced endocannabinoid signalling affects atherosclerosis via multiple effects, including a modulation of vascular inflammation, leukocyte recruitment, macrophage cholesterol metabolism and consequently atherosclerotic plaque stability. In addition, recent findings in various metabolic disease models highlight the relevance of peripheral CB1 cannabinoid receptors in adipose tissue, liver and pancreas, which crucially regulate lipid and glucose metabolism as well as macrophage properties in these organs. This suggests that targeting the endocannabinoid system in the vasculature and peripheral organs might have a therapeutic potential for atherosclerosis by inhibiting vascular inflammation and improving metabolic risk factors. This review will provide a brief update on the effects of endocannabinoid signalling in atherosclerosis and related metabolic complications.}, }
@article {pmid30762822, year = {2019}, author = {Louarn, N and Dauta, A and Lechapt-Zalcman, E and Kauv, P and Itti, E}, title = {Meningeal Metastasis Relapse With Focal Involvement of Cranial Bone Flap: A Case Resolved by 18F-DOPA PET/MRI.}, journal = {Clinical nuclear medicine}, volume = {44}, number = {4}, pages = {e315-e317}, doi = {10.1097/RLU.0000000000002492}, pmid = {30762822}, issn = {1536-0229}, mesh = {Breast Neoplasms/pathology ; *Dihydroxyphenylalanine ; Female ; *Fluorine Radioisotopes ; Humans ; *Magnetic Resonance Imaging ; Meningeal Neoplasms/*diagnostic imaging/*secondary ; Middle Aged ; *Multimodal Imaging ; *Positron-Emission Tomography ; Recurrence ; Skull/diagnostic imaging/metabolism ; }, abstract = {A 63-year-old woman was referred to our PET/MRI platform to evaluate the possible relapse of a meningeal metastasis, complicating an invasive ductal carcinoma of the left breast. This metastasis was diagnosed on a left hemiparesis and treated by surgery and radiation therapy. One year later, the same symptoms led to another brain MRI examination that found a contrast-enhanced lesion in the operating site. We decided to perform a F-DOPA PET/MRI to document this lesion, which confirmed the diagnosis of a probable relapse and revealed a focal uptake on the bone flap.}, }
@article {pmid30761666, year = {2019}, author = {Yilmaz, R and Akpinar, Y and Ozyavuz, I and Önder, S and Tukenmez, M and Dursun, M}, title = {Synchronous metastatic leiomyosarcoma and primer invasive ductal carcinoma tumors in the same breast: Mammography, ultrasonography, and magnetic resonance imaging findings.}, journal = {The breast journal}, volume = {25}, number = {2}, pages = {310-311}, doi = {10.1111/tbj.13211}, pmid = {30761666}, issn = {1524-4741}, mesh = {Adult ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Leiomyosarcoma/*diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Mammography ; Ultrasonography, Mammary ; Unilateral Breast Neoplasms/*diagnostic imaging/pathology/secondary ; }, }
@article {pmid30760857, year = {2019}, author = {Alsaleem, M and Toss, MS and Joseph, C and Aleskandarany, M and Kurozumi, S and Alshankyty, I and Ogden, A and Rida, PCG and Ellis, IO and Aneja, R and Green, AR and Mongan, NP and Rakha, EA}, title = {The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {32}, number = {7}, pages = {967-976}, doi = {10.1038/s41379-019-0209-9}, pmid = {30760857}, issn = {1530-0285}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Genomic Instability/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Middle Aged ; Tissue Array Analysis ; Young Adult ; }, abstract = {E-cadherin is a tumor suppressor gene in invasive lobular breast cancer. However, a proportion of high-grade ductal carcinoma shows reduced/loss of E-cadherin. In this study, we assessed the underlying mechanisms and molecular implications of E-cadherin loss in invasive ductal carcinoma. This study used large, well-characterized cohorts of early-stage breast cancer-evaluated E-cadherin expression via various platforms including immunohistochemistry, microarray analysis using Illumina HT-12 v3, copy number analysis using Affymetrix SNP 6.0 arrays, and next-generation sequencing for differential gene expression. Our results showed 27% of high-grade invasive ductal carcinoma showed reduced/loss of E-cadherin membranous expression. CDH1 copy number loss was in 21% of invasive ductal carcinoma, which also showed low CDH1 mRNA expression (p = 0.003). CDH1 copy number was associated with copy number loss of TP53, ATM, BRCA1, and BRCA2 (p < 0.001). Seventy-nine percent of invasive ductal carcinoma with reduced CDH1 mRNA expression showed elevated expression of E-cadherin transcription suppressors TWIST2, ZEB2, NFKB1, LLGL2, CTNNB1 (p < 0.01). Reduced/loss E-cadherin expression was associated with differential expression of 2143 genes including those regulating Wnt (FZD2, GNG5, HLTF, WNT2, and CER1) and PIK3-AKT (FGFR2, GNF5, GNGT1, IFNA17, and IGF1) signaling pathways. Interestingly, key genes differentially expressed between invasive lobular carcinoma and invasive ductal tumors did not show association with E-cadherin loss in invasive ductal carcinoma. We conclude that E-cadherin loss in invasive ductal carcinoma is likely a consequence of genomic instability occurring during carcinogenesis. Potential novel regulators controlling E-cadherin expression in invasive ductal carcinoma warrant further investigation.}, }
@article {pmid30728399, year = {2019}, author = {Kaur, P and Porras, TB and Ring, A and Carpten, JD and Lang, JE}, title = {Comparison of TCGA and GENIE genomic datasets for the detection of clinically actionable alterations in breast cancer.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {1482}, pmid = {30728399}, issn = {2045-2322}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Computer Simulation ; DNA Copy Number Variations/genetics ; Databases, Genetic/*standards/*trends ; Exome/genetics ; Female ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Mutation/genetics ; Precision Medicine/methods ; }, abstract = {Whole exome sequencing (WES), targeted gene panel sequencing and single nucleotide polymorphism (SNP) arrays are increasingly used for the identification of actionable alterations that are critical to cancer care. Here, we compared The Cancer Genome Atlas (TCGA) and the Genomics Evidence Neoplasia Information Exchange (GENIE) breast cancer genomic datasets (array and next generation sequencing (NGS) data) in detecting genomic alterations in clinically relevant genes. We performed an in silico analysis to determine the concordance in the frequencies of actionable mutations and copy number alterations/aberrations (CNAs) in the two most common breast cancer histologies, invasive lobular and invasive ductal carcinoma. We found that targeted sequencing identified a larger number of mutational hotspots and clinically significant amplifications that would have been missed by WES and SNP arrays in many actionable genes such as PIK3CA, EGFR, AKT3, FGFR1, ERBB2, ERBB3 and ESR1. The striking differences between the number of mutational hotspots and CNAs generated from these platforms highlight a number of factors that should be considered in the interpretation of array and NGS-based genomic data for precision medicine. Targeted panel sequencing was preferable to WES to define the full spectrum of somatic mutations present in a tumor.}, }
@article {pmid30725231, year = {2019}, author = {Liu, Y and Pandey, PR and Sharma, S and Xing, F and Wu, K and Chittiboyina, A and Wu, SY and Tyagi, A and Watabe, K}, title = {ID2 and GJB2 promote early-stage breast cancer progression by regulating cancer stemness.}, journal = {Breast cancer research and treatment}, volume = {175}, number = {1}, pages = {77-90}, pmid = {30725231}, issn = {1573-7217}, support = {R01CA205067//National Cancer Institute (US)/ ; F31 CA200286/CA/NCI NIH HHS/United States ; F31CA200286//National Cancer Institute/ ; R01CA173499//National Cancer Institute/ ; R01 CA173499/CA/NCI NIH HHS/United States ; P30 CA012197/CA/NCI NIH HHS/United States ; R01CA185650//National Cancer Institute/ ; R01 CA205067/CA/NCI NIH HHS/United States ; R01 CA185650/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*genetics/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Proliferation ; Chalcone/analogs &amp; derivatives/chemistry/pharmacology ; Connexin 26 ; Connexins/*genetics ; Disease Models, Animal ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Inhibitor of Differentiation Protein 2/*genetics ; Mice ; Neoplasm Staging ; Neoplastic Stem Cells/*metabolism ; Prognosis ; *Promoter Regions, Genetic ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer which could progress to or recur as invasive breast cancer. The underlying molecular mechanism of DCIS progression is yet poorly understood, and appropriate biomarkers to distinguish benign form of DCIS from potentially invasive tumor are urgently needed.<br><br>METHODS: To identify the key regulators of DCIS progression, we performed gene-expression analysis of syngeneic breast cancer cell lines MCF10A, DCIS.com, and MCF10CA and cross-referenced the targets with patient cohort data.<br><br>RESULTS: We identified ID2 as a critical gene for DCIS initiation and found that ID2 promoted DCIS formation by enhancing cancer stemness of pre-malignant cells. ID2 also plays a pivotal role in survival of the aggressive cancer cells. In addition, we identified INHBA and GJB2 as key regulators for the transition of benign DCIS to aggressive phenotype. These two genes regulate migration, colonization, and stemness of invasive cancer cells. Upregulation of ID2 and GJB2 predicts poor prognosis after breast-conserving surgery. Finally, we found a natural compound Helichrysetin as ID2 inhibitor which suppresses DCIS formation in vitro and in vivo.<br><br>CONCLUSION: Our results indicate that ID2 is a key driver of DCIS formation and therefore is considered to be a potential target for prevention of DCIS, while INHBA and GJB2 play vital roles in progression of DCIS to IDC and they may serve as potential prognosis markers.}, }
@article {pmid30719718, year = {2019}, author = {Dianatinasab, M and Fararouei, M and Daneshi, N and Rezaian, S and Mohammadianpanah, M and Chaman, R and Ghiasvand, R}, title = {Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case-control study.}, journal = {International journal of cancer}, volume = {145}, number = {11}, pages = {2917-2925}, doi = {10.1002/ijc.32182}, pmid = {30719718}, issn = {1097-0215}, mesh = {Abortion, Spontaneous/epidemiology ; Adult ; Breast Feeding/statistics &amp; numerical data ; Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Humans ; Iran ; Middle Aged ; Risk Factors ; }, abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast are the most common histological subtypes of breast cancer. However, the associations and heterogeneity between histological subtypes and their risk factors are not well established. This study aimed to investigate risk factors for IDC and ILC. This case-control study included 1,009 incident breast cancer cases and 1,009 hospital controls, frequency-matched by age. Data were obtained from the patients' medical files and an interview administered via a questionnaire. Multinomial logistic regression was used and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The heterogeneity of the associations was assessed using the Wald test. Family history of breast cancer was associated with IDC (OR 2.64, 95% CI: 1.97-3.55) but not ILC (OR 0.81, 95% CI: 0.42-1.57; p for heterogeneity <0.001). Conversely, a history of miscarriage was associated with ILC (OR 1.71, 95% CI: 1.17-2.51) but not IDC (OR 1.18, 95% CI: 0.95-1.46; p for heterogeneity = 0.04). Similarly, type 2 diabetes was associated with ILC but not IDC (p for heterogeneity = 0.02). Age at first delivery and breastfeeding were significantly associated with IDC but not ILC, though p values for heterogeneity did not reach the significance level. Deliberate weight loss and age at menarche were significantly associated with ILC but not IDC (p for heterogeneity ≥0.27). Smoking, history of benign breast disease and BMI were associated with both subtypes. The present study supports the hypothesis that IDC and ILC are etiologically distinct tumours.}, }
@article {pmid30712460, year = {2020}, author = {Song, G and He, L and Yang, X and Yang, Y and Cai, X and Liu, K and Feng, G}, title = {Identification of aberrant gene expression during breast ductal carcinoma in situ progression to invasive ductal carcinoma.}, journal = {The Journal of international medical research}, volume = {48}, number = {1}, pages = {300060518815364}, pmid = {30712460}, issn = {1473-2300}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cluster Analysis ; Databases, Genetic ; *Disease Progression ; Down-Regulation/genetics ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Reproducibility of Results ; Signal Transduction/genetics ; Up-Regulation/genetics ; }, abstract = {OBJECTIVE: It has been reported that 80% of all breast carcinoma cases are invasive ductal carcinoma (IDC), and 45% to 78% of invasive breast carcinoma cases are associated with ductal carcinoma in situ (DCIS). Therefore, it is important to gain insights into transcriptome changes that occur during DCIS progression to IDC.<br><br>METHODS: We downloaded Gene Expression Omnibus databases GSE21422 and GSE3893, and performed differentially expressed gene (DEG) analysis and cluster analysis, followed by pathway enrichment analysis and Oncomine analysis.<br><br>RESULTS: Twenty-six conserved DEGs were identified in both GSE21422 and GSE3893. These genes are mainly enriched in intermediate filament-based processes, immune responses, Staphylococcus aureus infection response, and phagosomes. Among them, FCGR2A, HLA-DRA, C3AR1, and FYB were reported to be involved in DCIS progression to IDC. High expression of HLA-DRA, C3AR1, and FYB in different types of breast cancer was validated using different Oncomine datasets. Moreover, elevated HLA-DRA and FYB levels were associated with breast cancer recurrence. Importantly, the overexpression of FYB was correlated with breast cancer metastasis.<br><br>CONCLUSIONS: This study revealed the molecular characteristics associated with progression from DCIS to IDC. It also identified potential biomarkers for DCIS progression to IDC, which will aid breast cancer diagnosis and prevention.}, }
@article {pmid30692436, year = {2018}, author = {Kodera, A and Inoue, H and Ogura, K and Sakaguchi, S and Yukawa, H and Matsuoka, A and Tanaka, N and Kinoshita, J and Yoshimatsu, K and Naritaka, Y and Hirano, A}, title = {[Bevacizumab plus Paclitaxel Therapy Was Effective for Metastatic Breast Cancer with Dysphagia Due to Mediastinal Lymph Node Metastasis-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {45}, number = {13}, pages = {2276-2278}, pmid = {30692436}, issn = {0385-0684}, mesh = {Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration &amp; dosage ; *Breast Neoplasms/complications/drug therapy ; *Deglutition Disorders/drug therapy/etiology ; Female ; Humans ; Lymph Nodes ; Paclitaxel/administration &amp; dosage ; Quality of Life ; }, abstract = {A 69-year-old woman noticed a tumor of the right breast, and presented to our hospital with dysphagia. A tumor of size 10 cm exposed to the skin and swollen axillary lymph node were observed. She was diagnosed with invasive ductal carcinoma, luminal-B by core-needle biopsy. CT scan revealed primary breast cancer with lung, bone, and lymph node metastasis. Endoscopic and fluoroscopic findings of the esophagus showed severe stenosis by extrinsic compression. In order to improve the quality of life(QOL)immediately, bevacizumab plus paclitaxel therapy was initiated. After the first course, the dysphagia improved, and she was able to take normal meals after 2 courses of treatment. Primary tumor and metastatic lesions had remarkably shrunk on CT scan. After 4 courses of treatment, we changed to endocrine therapy and continued outcome treatment. Bevacizumab was effective for immediate improvement of QOL in such as an oncologic emergent case of metastatic breast cancer.}, }
@article {pmid30689164, year = {2019}, author = {da Silva Filho, AF and Vieira-de-Mello, GS and Dos Santos, PB and de Melo Rêgo, MJB and Ribeiro-Silva, A and Beltrão, EIC}, title = {N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.}, journal = {Pathology oncology research : POR}, volume = {25}, number = {2}, pages = {759-768}, pmid = {30689164}, issn = {1532-2807}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/enzymology/*pathology ; Carcinoma, Ductal, Breast/enzymology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/enzymology/*pathology ; Female ; Humans ; Middle Aged ; N-Acetylglucosaminyltransferases/analysis/*metabolism ; }, abstract = {Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), -T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.}, }
@article {pmid30675210, year = {2019}, author = {Smalley, T and Islam, SMA and Apostolatos, C and Apostolatos, A and Acevedo-Duncan, M}, title = {Analysis of PKC-ζ protein levels in normal and malignant breast tissue subtypes.}, journal = {Oncology letters}, volume = {17}, number = {2}, pages = {1537-1546}, pmid = {30675210}, issn = {1792-1074}, abstract = {It is estimated that breast cancer will be the second leading cause of cancer-associated mortality in women in 2018. Previous research has demonstrated that the atypical protein kinase C-ζ (PKC-ζ) is a component of numerous dysregulated pathways in breast cancer, including cellular proliferation, survival, and cell cycle upregulation. The present study investigated the PKC-ζ protein in breast tissue to evaluate its potential as a biomarker for breast cancer invasion, and demonstrated that an overexpression of PKC-ζ protein can be indicative of carcinogenesis. The present study analyzed the expression of PKC-ζ in individuals with no tumor complications and malignant female human breast tissue samples (lobular carcinoma in situ, invasive lobular carcinoma, ductal carcinoma in situ and invasive ductal carcinoma) with the use of western blot analysis, immunohistochemistry and statistical analysis (83 samples). The present study also evaluated the invasive behavior of MDA-MB-231 breast cancer cells following the knockdown of PKC-ζ with a Transwell invasion assay and an immunofluorescent probe for filamentous actin (F-actin) organization. The data demonstrated that PKC-ζ expression was identified to be higher in invading tissues when compared with non-invading tissues. The results also suggest that PKC-ζ is more abundant in ductal tissues when compared with lobular tissues. In addition, the protein studies also suggest that PKC-ζ is a component for invasive behavior through the Ras-related C3 botulinum toxin substrate 1 (Rac1) and Ras homolog gene family member A (RhoA) pathway, and PKC-ζ is required for the F-actin reorganization in invasive cells. Therefore, PKC-ζ should be considered to be a biomarker in the development of breast cancer as well as an indicator of invading tumor cells.}, }
@article {pmid30659137, year = {2019}, author = {Traylor, M and Tozer, DJ and Croall, ID and Lisiecka-Ford, DM and Olorunda, AO and Boncoraglio, G and Dichgans, M and Lemmens, R and Rosand, J and Rost, NS and Rothwell, PM and Sudlow, CLM and Thijs, V and Rutten-Jacobs, L and Markus, HS and , }, title = {Genetic variation in PLEKHG1 is associated with white matter hyperintensities (n = 11,226).}, journal = {Neurology}, volume = {92}, number = {8}, pages = {e749-e757}, pmid = {30659137}, issn = {1526-632X}, support = {FS/15/61/31626/BHF_/British Heart Foundation/United Kingdom ; MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; RG/16/4/32218/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Adult ; Aged ; Brain Ischemia/diagnostic imaging/*genetics ; Cerebral Small Vessel Diseases/diagnostic imaging/*genetics ; Female ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Rho Guanine Nucleotide Exchange Factors/*genetics ; Stroke/diagnostic imaging/*genetics ; Stroke, Lacunar/diagnostic imaging/genetics ; White Matter/*diagnostic imaging ; }, abstract = {OBJECTIVE: To identify novel genetic associations with white matter hyperintensities (WMH).<br><br>METHODS: We performed a genome-wide association meta-analysis of WMH volumes in 11,226 individuals, including 8,429 population-based individuals from UK Biobank and 2,797 stroke patients. Replication of novel loci was performed in an independent dataset of 1,202 individuals. In all studies, WMH were quantified using validated automated or semi-automated methods. Imputation was to either the Haplotype Reference Consortium or 1,000 Genomes Phase 3 panels.<br><br>RESULTS: We identified a locus at genome-wide significance in an intron of PLEKHG1 (rs275350, &#x3b2; [SE] = 0.071 [0.013]; p = 1.6 &#xd7; 10[-8]), a Rho guanine nucleotide exchange factor that is involved in reorientation of cells in the vascular endothelium. This association was validated in an independent sample (overall p value, 2.4 &#xd7; 10[-9]). The same single nucleotide polymorphism was associated with all ischemic stroke (odds ratio [OR] [95% confidence interval (CI)] 1.07 [1.03-1.12], p = 0.00051), most strongly with the small vessel subtype (OR [95% CI] 1.09 [1.00-1.19], p = 0.044). Previous associations at 17q25 and 2p16 reached genome-wide significance in this analysis (rs3744020; &#x3b2; [SE] = 0.106 [0.016]; p = 1.2 &#xd7; 10[-11] and rs7596872; &#x3b2; [SE] = 0.143 [0.021]; p = 3.4 &#xd7; 10[-12]). All identified associations with WMH to date explained 1.16% of the trait variance in UK Biobank, equivalent to 6.4% of the narrow-sense heritability.<br><br>CONCLUSIONS: Genetic variation in PLEKHG1 is associated with WMH and ischemic stroke, most strongly with the small vessel subtype, suggesting it acts by promoting small vessel arteriopathy.}, }
@article {pmid30659022, year = {2019}, author = {Guo, Q and Li, VZ and Nichol, JN and Huang, F and Yang, W and Preston, SEJ and Talat, Z and Lefrère, H and Yu, H and Zhang, G and Basik, M and Gonçalves, C and Zhan, Y and Plourde, D and Su, J and Torres, J and Marques, M and Habyan, SA and Bijian, K and Amant, F and Witcher, M and Behbod, F and McCaffrey, L and Alaoui-Jamali, M and Giannakopoulos, NV and Brackstone, M and Postovit, LM and Del Rincón, SV and Miller, WH}, title = {MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma In Situ.}, journal = {Cancer research}, volume = {79}, number = {7}, pages = {1646-1657}, pmid = {30659022}, issn = {1538-7445}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; R21 CA226567/CA/NCI NIH HHS/United States ; PJT-156269//CIHR/Canada ; MOP-142281//CIHR/Canada ; }, mesh = {Animals ; Breast Carcinoma In Situ/metabolism/*pathology ; Breast Neoplasms/metabolism/*pathology ; CRISPR-Cas Systems ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Heterografts ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Mice, Nude ; Nodal Protein/*metabolism ; Protein Serine-Threonine Kinases/genetics/*metabolism ; *Signal Transduction ; }, abstract = {The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often reexpressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A-derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low-grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease. SIGNIFICANCE: These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.}, }
@article {pmid30652428, year = {2019}, author = {Liu, Y and Ide, Y and Inuzuka, M and Tazawa, S and Kanada, Y and Matsunaga, Y and Kuwayama, T and Sawada, T and Akashi-Tanaka, S and Nakamura, S}, title = {BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.}, journal = {Molecular genetics &amp; genomic medicine}, volume = {7}, number = {3}, pages = {e493}, pmid = {30652428}, issn = {2324-9269}, mesh = {Adult ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/*genetics ; Female ; Genetic Testing/standards ; Humans ; Incidence ; Japan ; *Mutation ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations.<br><br>METHODS: A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR).<br><br>RESULTS: (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p&#xa0;=&#xa0;1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p&#xa0;=&#xa0;0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39&#xa0;years, compared with 46&#xa0;years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX&#xa0;&#x2265;&#xa0;2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266-20.763; p&#xa0;=&#xa0;0.022), age at diagnosis &#x2264;35&#xa0;years (OR 0.149, 95% CI 0.023-0.954, p&#xa0;=&#xa0;0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092-23.210, p&#xa0;=&#xa0;0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p&#xa0;=&#xa0;0.459 and p&#xa0;=&#xa0;0.651). (c) There was a significant difference in ER-positive tumors among BRCA2 carriers and noncarriers (p&#xa0;=&#xa0;0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p&#xa0;=&#xa0;0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR.<br><br>CONCLUSION: DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX &#x2265;2, age at diagnosis &#x2264;35&#xa0;years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.}, }
@article {pmid30621656, year = {2019}, author = {Framarino-Dei-Malatesta, M and Chiarito, A and Bianciardi, F and Fiorelli, M and Ligato, A and Naso, G and Pecorella, I}, title = {Metastases to extraocular muscles from breast cancer: case report and up-to-date review of the literature.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {36}, pmid = {30621656}, issn = {1471-2407}, mesh = {Adult ; Breast Neoplasms/*diagnosis/diagnostic imaging/drug therapy/pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Muscle Neoplasms/*diagnosis/diagnostic imaging/pathology/secondary ; Neoplasm Metastasis ; Piperazines/therapeutic use ; Pyridines/therapeutic use ; }, abstract = {BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer.<br><br>CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3&#x2009;years and letrozole in the following 3&#x2009;years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20&#x2009;months.<br><br>CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20&#x2009;months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.}, }
@article {pmid30608397, year = {2019}, author = {Bertozzi, S and Cedolini, C and Londero, AP and Baita, B and Giacomuzzi, F and Capobianco, D and Tortelli, M and Uzzau, A and Mariuzzi, L and Risaliti, A}, title = {Sentinel lymph node biopsy in patients affected by breast ductal carcinoma in situ with and without microinvasion: Retrospective observational study.}, journal = {Medicine}, volume = {98}, number = {1}, pages = {e13831}, pmid = {30608397}, issn = {1536-5964}, mesh = {Aged ; Breast/pathology ; Breast Carcinoma In Situ/mortality/pathology/*surgery ; Breast Neoplasms/mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*surgery ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Micrometastasis ; Neoplasm Recurrence, Local/pathology ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node Biopsy/*mortality ; }, abstract = {With the introduction of an organized mammographic screening, the incidence of ductal carcinoma in situ (DCIS) has experienced an important increase. Our experience with sentinel lymph node biopsy (SLNB) among patients with DCIS is reviewed.We collected retrospective data on patients operated on their breasts for DCIS (pTis), DCIS with microinvasion (DCISM) (pT1mi) and invasive ductal carcinoma (IDC) sized ≤2 cm (pT1) between January 2002 and June 2016, focusing on the result of SLNB.543 DCIS, 84 DCISM, and 2111 IDC were included. In cases of DCIS and DCISM, SLNB resulted micrometastatic respectively in 1.7% and 6.0% of cases and macrometastatic respectively in 0.9% and 3.6% of cases. 5-year disease-free survival and overall survival in DCISM and IDC were similar, while significantly longer in DCIS. 5-year local recurrence rate of DCIS and DCISM were respectively 2.5% and 7.9%, and their 5-year distant recurrence rate respectively 0% and 4%. IDC, tumor grading ≥2 and lymph node (LN) macrometastasis were significant predictors for decreased overall survival. Significant predictors for distant metastases were DCISM, IDC, macroscopic nodal metastasis, and tumor grading ≥2. Predictors for the microinvasive component in DCIS were tumor multifocality/multicentricity, grading ≥2, ITCs and micrometastases.Our study suggests that despite its rarity, sentinel node metastasis may also occur in case of DCIS, which in most cases are micrometastases. Even in the absence of an evident invasive component, microinvasion should always be suspected in these cases, and their management should be the same as for IDC.}, }
@article {pmid30607556, year = {2019}, author = {Wang, G and Zhou, C and Conklin, C and Hayes, MM and Villamil, CF and Ostry, A and Jones, EC}, title = {Metastatic breast carcinoma to the urinary bladder-a report of 11 cases including a tumor to tumor metastasis.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {474}, number = {3}, pages = {333-339}, pmid = {30607556}, issn = {1432-2307}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary/therapy ; Carcinoma, Lobular/chemistry/mortality/*secondary/therapy ; Carcinoma, Squamous Cell/chemistry/mortality/*pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Time Factors ; Urinary Bladder Neoplasms/chemistry/mortality/*secondary/therapy ; }, abstract = {Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.}, }
@article {pmid30594914, year = {2019}, author = {Khorshidi, H and Azari, I and Oskooei, VK and Taheri, M and Ghafouri-Fard, S}, title = {DSCAM-AS1 up-regulation in invasive ductal carcinoma of breast and assessment of its potential as a diagnostic biomarker.}, journal = {Breast disease}, volume = {38}, number = {1}, pages = {25-30}, doi = {10.3233/BD-180351}, pmid = {30594914}, issn = {1558-1551}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Carcinoma, Ductal, Breast/*diagnosis/*genetics ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Association Studies ; Humans ; Middle Aged ; RNA, Long Noncoding/*genetics ; Real-Time Polymerase Chain Reaction ; Tamoxifen/therapeutic use ; Up-Regulation ; }, abstract = {BACKGROUND: The long non-coding RNA (lncRNA) DSCAM-AS1 has been demonstrated to participate in the pathogenesis of breast cancer and tamoxifen resistance.<br><br>OBJECTIVE: To evaluate expression profile of DSCAM-AS1&#xa0;in invasive ductal carcinoma of breast and its suitability as a biomarker for diagnosis of breast cancer.<br><br>METHODS: We evaluated expression of DSCAM-AS1&#xa0;in 108 breast tissues including tumoral and adjacent non-cancerous tissues (ANCTs) by means of quantitative real time PCR.<br><br>RESULTS: DSCAM-AS1&#xa0;was up-regulated in tumoral tissues compared with ANCTs (Fold change = 2.86, P =&#xa0;0.011). Its expression was significantly higher in patients aged less than 55 compared with older patients (P =&#xa0;0.02). However, its expression levels had not a good performance as a diagnostic biomarker for breast cancer.<br><br>CONCLUSIONS: The significant up-regulation of DSCAM-AS1&#xa0;in tumoral tissues compared with ANCTs provides further evidences for participation of this lncRNA in the pathogenesis of breast cancer.}, }
@article {pmid30587740, year = {2018}, author = {Yano, Y and Kuga, T and Harada, T and Sano, F and Inokuchi, T and Fujii, Y}, title = {[A Case of Suspected Therapy-Related Leukemia after Chemotherapy for Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {45}, number = {12}, pages = {1775-1777}, pmid = {30587740}, issn = {0385-0684}, mesh = {*Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; Female ; Humans ; *Leukemia/chemically induced ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasms, Second Primary ; Sentinel Lymph Node Biopsy ; }, abstract = {Therapy-related leukemia(TRL)is a distinctive clinical syndrome that occurs after exposure to chemotherapy or radiotherapy. We report a case of suspected TRLafter chemotherapy in a patient with breast cancer. A 61-year-old woman underwent total mastectomy and sentinel lymph node biopsy(negative)for her breast cancer. Histopathologic analysis showed invasive ductal carcinoma, pStage I. Her subtype histology was Luminal B-type, and postoperative adjuvant chemotherapy and endocrine therapy were administered. Four years after chemotherapy, a blood examination showed pancytopenia. Bone marrow examination showed acute promyelocytic leukemia. She was treated with chemotherapy and achieved complete remission. Breast cancer provides long-term survival after treatment. Attention should be paid to the occurrence of TRLin breast cancer surveillance.}, }
@article {pmid30582225, year = {2019}, author = {Bertagnolo, V and Grassilli, S and Volinia, S and Al-Qassab, Y and Brugnoli, F and Vezzali, F and Lambertini, E and Palomba, M and Piubello, Q and Orvieto, E and Natali, C and Piva, R and Croce, CM and Capitani, S}, title = {Ectopic expression of PLC-β2 in non-invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR-146a.}, journal = {Molecular carcinogenesis}, volume = {58}, number = {5}, pages = {708-721}, pmid = {30582225}, issn = {1098-2744}, support = {FIRB RBAP10Z7FS_002//Italian MIUR/International ; IG 170631//Associazione Italiana per la Ricerca sul Cancro/International ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Proliferation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplastic Stem Cells/metabolism/*pathology ; Phospholipase C beta/genetics/*metabolism ; Prognosis ; Tumor Cells, Cultured ; }, abstract = {Cells in non-invasive breast lesions are widely believed to possess molecular alterations that render them either susceptible or refractory to the acquisition of invasive capability. One such alteration could be the ectopic expression of the β2 isoform of phosphoinositide-dependent phospholipase C (PLC-β2), known to counteract the effects of hypoxia in low-invasive breast tumor-derived cells. Here, we studied the correlation between PLC-β2 levels and the propensity of non-invasive breast tumor cells to acquire malignant features. Using archival FFPE samples and DCIS-derived cells, we demonstrate that PLC-β2 is up-regulated in DCIS and that its forced down-modulation induces an epithelial-to-mesenchymal shift, expression of the cancer stem cell marker CD133, and the acquisition of invasive properties. The ectopic expression of PLC-β2 in non-transformed and DCIS-derived cells is, to some extent, dependent on the de-regulation of miR-146a, a tumor suppressor miRNA in invasive breast cancer. Interestingly, an inverse relationship between the two molecules, indicative of a role of miR-146a in targeting PLC-β2, was not detected in primary DCIS from patients who developed a second invasive breast neoplasia. This suggests that alterations of the PLC-β2/miR-146a relationship in DCIS may constitute a molecular risk factor for the appearance of new breast lesions. Since neither traditional classification systems nor molecular characterizations are able to predict the malignant potential of DCIS, as is possible for invasive ductal carcinoma (IDC), we propose that the assessment of the PLC-β2/miR-146a levels at diagnosis could be beneficial for identifying whether DCIS patients may have either a low or high propensity for invasive recurrence.}, }
@article {pmid30577784, year = {2018}, author = {Ssemmanda, S and Katagirya, E and Bukirwa, P and Alele, D and Lukande, R and Kalungi, S}, title = {Breast diseases histologically diagnosed at a tertiary facility in Uganda (2005-2014).}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1285}, pmid = {30577784}, issn = {1471-2407}, mesh = {Adult ; Breast Diseases/diagnosis/*epidemiology/pathology ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Female ; Fibroadenoma/diagnosis/*epidemiology/pathology ; Humans ; Male ; Risk Factors ; Uganda/epidemiology ; }, abstract = {BACKGROUND: The prevalence and distribution of histologically diagnosed breast disease are not well documented in low income countries, Uganda inclusive. Although the greater majority of breast lesions globally are benign, breast cancer is the most frequently diagnosed cancer all over the world. We aimed at documenting the prevalence of different breast diseases histologically diagnosed at the histopathology laboratory of the Department of Pathology of the Makerere University College of Health Sciences (MakCHS Lab) over a decade (2005-2014). We also describe the demographic characteristics of the patients in Uganda diagnosed with breast disease at the MakCHS Lab during the same period.<br><br>METHODS: This was a 10&#x2009;year retrospective study of histologically diagnosed breast disease between 2005 and 2014 inclusive at the MakCHS Lab. We extracted information from hard copies of all 2510 histopathology reports retrieved from archives of the Department of Pathology at the MakCHS Lab. 640 records that were either damaged beyond recognition of key details, were duplicated, were implausible or had no conclusive diagnosis made were excluded. Information to be analyzed was then entered into Epidata (version 3.1) on a password protected laptop. Data analysis was done using SPSS software (v16 for Windows &#xd7;&#x2009;64).<br><br>RESULTS: From the 1870 patients' records eventually analyzed, breast disease was most diagnosed in female patients (97.1%). The overall mean age for breast disease diagnosis was 33&#x2009;years (S.D&#x2009;&#xb1;&#x2009;16.46) and median age 26&#x2009;years (IQR: 20-43). Fibroadenoma (40.1%) was the most diagnosed breast disease overall. We noticed steadily increasing frequency of diagnosis of cancerous breast diseases over the last half of the study period. Invasive ductal carcinoma was the most diagnosed breast cancer (326 cases, 55.6%). A high female to male breast cancer ratio of 48:1 was observed. The highest regional breast cancer proportion was from the Western region of the Country.<br><br>CONCLUSIONS: There is need for more research into the picture of breast disease in the country, covering various demographic characteristics of the country's population for all regions and informing about its incidence rates and prevalence and also the breast cancer risk estimate for benign breast disease.}, }
@article {pmid30570854, year = {2018}, author = {Sunar, V and T Dogan, H and Sarici, F and Ates, O and Akin, S and Baspinar, B and Aksoy, S and Altundag, K}, title = {Association between androgen receptor status and prognosis in triple negative breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {23}, number = {5}, pages = {1325-1330}, pmid = {30570854}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Ductal, Breast/metabolism/*secondary/therapy ; Carcinoma, Lobular/metabolism/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptors, Androgen/*metabolism ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/metabolism/*pathology/therapy ; }, abstract = {PURPOSE: Triple negative breast cancer (TNBC) is a heterogeneous disease group with a higher recurrence risk and poorer prognosis. In this study, we aimed to investigate the frequency and prognostic value of androgen receptor (AR) expression in tissues of TNBC patients.<br><br>METHODS: A total of 84 TNBC patients treated between 2000 - 2015 in Hacettepe University Cancer Institute were included and their medical records were analyzed retrospectively. The available paraffin blocks were assessed immunohistochemically to determine AR expression. Tumors with &#x2265;1% nuclear staining were considered AR-positive, while the ones with <1% staining were considered AR-negative. We analyzed the association between AR expression, and clinical-pathologic characteristics and prognosis in TNBC.<br><br>RESULTS: Of the 84 TNBC patients, 25 (29.8%) were AR-positive. The frequency of grade 3 tumors was lower among AR-positive TNBC tumors compared to AR-negative tumors (40 vs 86.4%, p<0.001). In the AR-positive group, invasive ductal carcinoma (IDC) was less prevalent compared to AR-negative group (56 vs 86.4%, p<0.002). However, there were not statistically significant differences between AR positive and negative groups in terms of overall survival (OS) and disease free survival (DFS) (p=0.449, p=0.733, respectively). We found that grade 3 tumors were less frequent in AR-positive TNBC in our study. Nonetheless, we did not detect statistically significant difference in terms of overall survival and disease free survival between AR positive and negative TNBC.<br><br>CONCLUSION: Routine evaluation of AR could contribute to further studies that may enlighten the role of AR targeting therapies in TNBC.}, }
@article {pmid30562218, year = {2019}, author = {Alkhasawneh, A and Nassri, A and John, I}, title = {Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma.}, journal = {The American Journal of dermatopathology}, volume = {41}, number = {7}, pages = {502-504}, doi = {10.1097/DAD.0000000000001322}, pmid = {30562218}, issn = {1533-0311}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Dedifferentiation ; Female ; GATA3 Transcription Factor/metabolism ; Humans ; Keratins/metabolism ; Lymphatic Metastasis ; Melanoma/metabolism/*secondary ; Middle Aged ; Neoplasms, Second Primary/metabolism/*pathology ; Skin Neoplasms/metabolism/*pathology/secondary ; }, abstract = {Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K-mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma.}, }
@article {pmid30558571, year = {2018}, author = {Semango, GP and Charles, RM and Swai, CI and Mremi, A and Amsi, P and Sonda, T and Shao, ER and Mavura, DR and Joosten, LAB and Sauli, E and Nyindo, M}, title = {Prevalence and associated risk factors for Kaposi's sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1258}, pmid = {30558571}, issn = {1471-2407}, support = {001//Tanzania Commission for Science and Technology/ ; }, mesh = {Adolescent ; Adult ; Age Factors ; CD4 Lymphocyte Count ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; HIV Infections/*complications/immunology ; Humans ; Infant ; Infant, Newborn ; Male ; Prevalence ; Referral and Consultation ; Retrospective Studies ; Risk Factors ; Sarcoma, Kaposi/*epidemiology ; Sex Factors ; Tanzania ; Young Adult ; }, abstract = {BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving blood and lymphatic vessels, caused by Human Herpes Virus-8 (HHV-8). KS is an important AIDS-defining tumor with high prevalence in Sub-Saharan Africa, including Tanzania which has high HIV and HHV-8 sero-prevalence. It is critically important to monitor the prevalence of AIDS-defining tumors, such as KS, in the age of HIV/AIDS. We studied the prevalence of KS and associated risk factors among HIV-positive patients at Kilimanjaro Christian Medical Centre (KCMC), a referral hospital in northern Tanzania, over the period from January 2012 to December 2015.<br><br>METHODS: This was a retrospective hospital-based cross-sectional study to determine the prevalence of KS among HIV/AIDS patients between 2012 and 2015. The study included 1100 HIV patients' data which were collected at the Infectious Disease Clinic (IDC) from patients' files. Stata version 13 (StataCorp LP, Texas 77,845 USA) was used for all statistical analyses. The prevalence of KS was calculated across levels of a number of categorical variables. Logistic regression was performed to determine relative risk of KS for all characteristics. We included all variables with p-values &#x2264;10% in the multivariate analysis, including ART use, as this is considered to have an influence on KS. In the multivariate analysis, statistical significance was established based on a two-tailed p-value &#x2264;5%. All patients' notes were kept confidential as per the Helsinki declaration.<br><br>RESULTS: Our results revealed a 4.6% prevalence of KS at KCMC hospital, between January 2012 and December 2015, 51(4.6%) patients were diagnosed with KS out of 1100 HIV-positive patients. The study further revealed that KS in HIV patients was most associated with low CD4 cell count (less than or equal to 200 cells/&#x3bc;l). Moreover, women were more likely than men to diagnosed with KS, with higher odds significantly associated with KS (OR 0.42, p&#x2009;<&#x2009;0.009). Increased age, above 35&#x2009;years, among the HIV seropositive patients was significantly associated with KS (OR 25.67, p&#x2009;<&#x2009;0.007). HIV patients who were none smokers were more likely to suffer from KS compared to HIV smokers (OR 0.41, p&#x2009;<&#x2009;0.010).<br><br>CONCLUSION: KS remains a common malignant vascular tumor commonly associated with HIV/AIDS in Tanzania. Our study highlights the need for continued efforts to combat HIV, as well as associated diseases such as KS. Continued availability of ART (Anti-Retroviral Therapy) to HIV/AIDS patients, and test reagents for CD4 cell count and viral load determination are important measures to alleviate the suffering of these patients. Furthermore, studies to gather more evidence on ART resistance are highly needed to guide treatment choices.}, }
@article {pmid30557036, year = {2019}, author = {Dabarian, AL and Mady, C and Barbosa-Ferreira, JM and Ianni, BM and Hotta, VT and Ramires, FJA and Lopes, HF and Buck, PC and Pessoa, FG and Fonseca, KCB and Nogueira, AR and Fernandes, F}, title = {Dysregulation of insulin levels in Chagas heart disease is associated with altered adipocytokine levels.}, journal = {Canadian journal of physiology and pharmacology}, volume = {97}, number = {2}, pages = {140-145}, doi = {10.1139/cjpp-2018-0349}, pmid = {30557036}, issn = {1205-7541}, mesh = {Adipokines/*blood/metabolism ; Adult ; Autonomic Nervous System/physiopathology ; Cardiomyopathy, Dilated/blood/diagnosis/*metabolism/physiopathology ; Chagas Cardiomyopathy/blood/diagnosis/*metabolism/physiopathology ; Echocardiography, Doppler ; Electrocardiography ; Female ; Heart ; Heart Rate/physiology ; Humans ; Insulin/*blood/metabolism ; Male ; Middle Aged ; }, abstract = {Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 μU/mL) when compared with control (8.0 ± 4.9 μU/mL) and IDC (9.9 ± 5.0 μU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 μg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.}, }
@article {pmid30544169, year = {2019}, author = {Martínez Nicolás, I and Lê Cook, B and Flores, M and Del Olmo Rodriguez, M and Hernández Rodríguez, C and Llamas Sillero, P and Baca-Garcia, E}, title = {The impact of a comprehensive electronic patient portal on the health service use: an interrupted time-series analysis.}, journal = {European journal of public health}, volume = {29}, number = {3}, pages = {413-418}, doi = {10.1093/eurpub/cky257}, pmid = {30544169}, issn = {1464-360X}, mesh = {Ambulatory Care/statistics &amp; numerical data ; Chronic Disease ; Emergency Service, Hospital/statistics &amp; numerical data ; Health Services Research ; Hospitalization/statistics &amp; numerical data ; Humans ; Interrupted Time Series Analysis ; *Patient Portals ; Patient Readmission/statistics &amp; numerical data ; Spain ; *Utilization Review ; }, abstract = {BACKGROUND: There is little empirical research on the potential benefit that electronic patient portals (EPP) can have on the care quality and health outcomes of diverse multi-ethnic international populations. The purpose of this study is to determine the extent to which an EPP was associated with improvements in health service use.<br><br>METHODS: Using a quasi-experimental interrupted time-series approach, we assessed health service use before (April 2012-September 2015) and after (October 2015-December 2016) the implementation of a comprehensive EPP at four hospitals in Madrid, Spain. Primary outcomes were number of outpatient visits, any hospital admission, any 30-day all-cause readmission and any emergency department visit.<br><br>RESULTS: Implementation of the EPP was associated with a significant decline in readmissions. Among patients with chronic heart failure, EPP implementation was associated with a significant decline for all outcome measures, and among patients with COPD, a decline in all outcomes except readmissions. Among patients diagnosed with malignant hematological diseases, no significant changes were identified.<br><br>CONCLUSIONS: EPPs hold promise for reducing hospital readmissions. Certain patient populations with chronic conditions may differentially benefit from portal use depending on their needs for communication with their providers.}, }
@article {pmid30542725, year = {2018}, author = {Shettar, A and Damineni, S and Mukherjee, G and Kondaiah, P}, title = {Gap junction β‑2 expression is negatively associated with the estrogen receptor status in breast cancer tissues and is a regulator of breast tumorigenesis.}, journal = {Oncology reports}, volume = {40}, number = {6}, pages = {3645-3653}, doi = {10.3892/or.2018.6764}, pmid = {30542725}, issn = {1791-2431}, mesh = {Animals ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinogenesis/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Connexin 26 ; Connexins/genetics/*metabolism ; Female ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, Nude ; Receptors, Estrogen/*metabolism ; Up-Regulation ; }, abstract = {Gap junction β‑2 gene (GJB2, also known as connexin 26) is a member of the connexin family which forms gap junction channels. Many connexin genes have been considered to be tumor suppressor genes. However, the overexpression of GJB2 has been found to be associated with a poor prognosis in several human cancers. In our previous microarray study, we revealed the overexpression of GJB2 in breast cancer tissues. Hence, in this study, we investigated the expression of GJB2 in human breast cancer and its role in breast cancer cell proliferation and migration. The RT‑qPCR results revealed the upregulation of the GJB2 gene in invasive ductal carcinoma (P<0.001) of the breast. Immunohistochemical analysis revealed an intense cytoplasmic and membrane staining. We observed that the staining for GJB2 was more intense in the majority of the estrogen receptor (ER)‑negative breast cancer tissues compared to the normal breast tissues (P<0.0001). By contrast, the majority of the ER‑positive breast cancer samples exhibited weak to moderate staining; however, this difference was not statistically significant compared to the normal tisues. The knockdown of GJB2 in human breast cancer cell lines using shRNA led to a significant decrease in the proliferative ability and an increase in the migratory ability of breast cancer cells. In addition, the knockdown of GJB‑2 led to a significant reduction in tumor volume and proliferation (as demonstrated by MIB‑1 staining) in orthotopic xenografts in immunocompromised mice. On the whole, the findings of this study indicate that GJB2 may be an important regulator of breast tumorigenesis.}, }
@article {pmid30524164, year = {2018}, author = {Pusina, S}, title = {Correlation of Serum Levels of Urokinase Activation Plasminogen (uPA) and Its Inhibitor (PAI-1) with Hormonal and HER-2 Status in the Early Invasive Breast Cancer.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {72}, number = {5}, pages = {335-340}, pmid = {30524164}, issn = {1986-5961}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*blood/genetics/pathology ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Plasminogen Activator Inhibitor 1/*blood ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*physiology ; Urokinase-Type Plasminogen Activator/*blood ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is the most common malignant tumor in women. On the list of causes of death immediately after lung cancer. It is a heterogeneous disease, considering the differences in morphological, cytogenetic, molecular, clinical and therapeutic aspects, so that the prognosis in a patient with the same histological grade and pathological status may vary.<br><br>AIM: In this paper we wanted to identify the correlation between the assay of the serum values of uPA-PAI-1 complexes and individual prognostic-predictive parameters, primarily with the status of estrogenic (Er), progesterogenic (PgR) and Her-2 receptors ("human epidermal growth factor).<br><br>MATERIAL AND METHODS: The study was conducted at the Clinic for General and Abdominal Surgery, University Clinical Center of Sarajevo (CCUS), from September 2016 to April 2017. The study included 66 patients, ages 18 to 75, in whom by the needle biopsy preoperatively was pathohistologically verified primary invasive breast cancer.<br><br>RESULTS: Two thirds of the sample were classified as invasive ductal carcinoma, similar to the percentage (68.2%) of pT2 size, and almost half in the grade G3. Lymph node status was negative in 54.5% of respondents, and positive in 31.8% of respondents. Most patients had positive estrogenic (83.3%) and progesterone receptors (62.1%). Almost 80% was Her-2 negative. The blood vessel invasion was present in 56.1%, while the neural invasion was present in less than a third of the sample (30.3%). Median values of uPA-PAI-1 complexes were 1.4 (interquartile range 0.9); almost 70% of the sample was negative for the status analysis of uPA-PAI-1 complex (<1).<br><br>DISCUSSION: A statistically significant difference was determined in the mean values of uPA-PAI-1 complexes in subgroups according to menopausal status, tumor size, histological grade, histological type (invasive ductal carcinoma vs. invasive lobular cancer versus invasive ductal carcinoma vs. invasive lobular cancer), status axillary lymph nodes, Ki67 status (as binary variables), invasion of the blood vessels and neural invasion, as well as subgroups according to the status of expression of hormonal (estrogen and progesterone) receptors.<br><br>CONCLUSION: There is a statistically significant difference in the mean values of the uPA-PAI-1 complex and Her-2 receptor expression. Generally, in perspective, this would be the role played by the uPA/PAI-1 complex in breast cancer, which is that the elevated complex values have a negative prognosis and effect on survival, similar to the negative Her-2 receptor status. Complex uPA/PAI-1 is not a specific serum protein in breast cancer patients and cannot be taken as an individual prognostic-predictive marker for mass pre- or post treatment screening and prediction. Unfortunately, none of the biomarkers are able to independently and fully identify patients of the unknown stage of the disease with better or worse prognosis or to identify cases of more aggressive tumor behavior of the same stage for timely inclusion of adjuvant therapy and reduction of the risk of metastatic disease. The decision on treatment and prognosis should be the result of a combination of all diagnostic, therapeutic, pathohistological and molecular-genetic variables.}, }
@article {pmid30531838, year = {2019}, author = {Pearson, SJ and Roy Sarkar, T and McQueen, CM and Elswood, J and Schmitt, EE and Wall, SW and Scribner, KC and Wyatt, G and Barhoumi, R and Behbod, F and Rijnkels, M and Porter, WW}, title = {ATM-dependent activation of SIM2s regulates homologous recombination and epithelial-mesenchymal transition.}, journal = {Oncogene}, volume = {38}, number = {14}, pages = {2611-2626}, pmid = {30531838}, issn = {1476-5594}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; T32 ES026568/ES/NIEHS NIH HHS/United States ; R01 HD083952/HD/NICHD NIH HHS/United States ; R01 ES025209/ES/NIEHS NIH HHS/United States ; R21 CA190941/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/*genetics ; BRCA1 Protein/genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cadherins/genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics ; Cell Line, Tumor ; DNA Damage/genetics ; DNA Repair/genetics ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Genomic Instability/genetics ; Homologous Recombination/*genetics ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Phosphorylation/genetics ; Rad51 Recombinase/genetics ; }, abstract = {There is increasing evidence that genomic instability is a prerequisite for cancer progression. Here we show that SIM2s, a member of the bHLH/PAS family of transcription factors, regulates DNA damage repair through enhancement of homologous recombination (HR), and prevents epithelial-mesenchymal transitions (EMT) in an Ataxia-telangiectasia mutated (ATM)-dependent manner. Mechanistically, we found that SIM2s interacts with ATM and is stabilized through ATM-dependent phosphorylation in response to IR. Once stabilized, SIM2s interacts with BRCA1 and supports RAD51 recruitment to the site of DNA damage. Loss of SIM2s through the introduction of shSIM2 or the mutation of SIM2s at one of the predicted ATM phosphorylation sites (S115) reduces HR efficiency through disruption of RAD51 recruitment, resulting in genomic instability and induction of EMT. The EMT induced by the mutation of S115 is characterized by a decrease in E-cadherin and an induction of the basal marker, K14, resulting in increased invasion and metastasis. Together, these results identify a novel player in the DNA damage repair pathway and provides a link in ductal carcinoma in situ progression to invasive ductal carcinoma through loss of SIM2s, increased genomic instability, EMT, and metastasis.}, }
@article {pmid30519573, year = {2018}, author = {Son, K and Yu, S and Shin, W and Han, K and Kang, K}, title = {A Simple Guideline to Assess the Characteristics of RNA-Seq Data.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {2906292}, pmid = {30519573}, issn = {2314-6141}, mesh = {Gene Expression ; High-Throughput Nucleotide Sequencing/*statistics &amp; numerical data ; Humans ; *Principal Component Analysis ; RNA/*genetics ; Sequence Analysis, RNA ; Transcriptome/*genetics ; }, abstract = {Next-generation sequencing (NGS) techniques have been used to generate various molecular maps including genomes, epigenomes, and transcriptomes. Transcriptomes from a given cell population can be profiled via RNA-seq. However, there is no simple way to assess the characteristics of RNA-seq data systematically. In this study, we provide a simple method that can intuitively evaluate RNA-seq data using two different principal component analysis (PCA) plots. The gene expression PCA plot provides insights into the association between samples, while the transcript integrity number (TIN) score plot provides a quality map of given RNA-seq data. With this approach, we found that RNA-seq datasets deposited in public repositories often contain a few low-quality RNA-seq data that can lead to misinterpretations. The effect of sampling errors for differentially expressed gene (DEG) analysis was evaluated with ten RNA-seq data from invasive ductal carcinoma tissues and three RNA-seq data from adjacent normal tissues taken from a Korean breast cancer patient. The evaluation demonstrated that sampling errors, which select samples that do not represent a given population, can lead to different interpretations when conducting the DEG analysis. Therefore, the proposed approach can be used to avoid sampling errors prior to RNA-seq data analysis.}, }
@article {pmid30499665, year = {2018}, author = {Okada, K and Moon, HJ and Finney, J and Meier, A and Mure, M}, title = {Extracellular Processing of Lysyl Oxidase-like 2 and Its Effect on Amine Oxidase Activity.}, journal = {Biochemistry}, volume = {57}, number = {51}, pages = {6973-6983}, pmid = {30499665}, issn = {1520-4995}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM110761/GM/NIGMS NIH HHS/United States ; R01 GM113101/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Oxidoreductases/chemistry/genetics/*metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Binding Sites ; Breast Neoplasms/enzymology ; Cell Line ; Collagen Type IV/metabolism ; Female ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Mutagenesis, Site-Directed ; Proprotein Convertases/antagonists &amp; inhibitors/genetics/metabolism ; Protein Domains ; Protein Processing, Post-Translational ; Protein-Lysine 6-Oxidase/chemistry/genetics/metabolism ; RNA, Small Interfering/genetics ; Serine Endopeptidases/genetics/metabolism ; }, abstract = {Overexpression of lysyl oxidase-like 2 (LOXL2) is associated with several hepatic and vascular fibrotic diseases and tumor progression in some aggressive cancers. Secreted LOXL2 promotes extracellular matrix cross-linking by catalyzing the oxidative deamination of peptidyl lysine. A great deal remains to be learned about the post-translational modifications of LOXL2, including whether such modifications modulate enzymatic and disease-promoting activities; such knowledge would inform the development of potential therapies. We discovered that upon secretion in cell culture, LOXL2 undergoes proteolytic processing of the first two of four scavenger receptor cysteine-rich domains at the N-terminus. A similar pattern of processing was also evident in tissue extracts from an invasive ductal carcinoma patient. Processing occurred at [314]Arg-[315]Phe-[316]Arg-[317]Lys↓-[318]Ala-, implicating proprotein convertases. siRNA-mediated knockdown of proprotein convertases (furin, PACE4, and PC5/6), as well as incubation with their recombinant forms, showed that PACE4 is the major protease that acts on extracellular LOXL2. Unlike LOX, which requires cleavage of its propeptide for catalytic activation, cleavage of LOXL2 was not essential for tropoelastin oxidation or for cross-linking of collagen type IV in vitro. However, in the latter case, processing enhanced the extent of collagen cross-linking ∼2-fold at ≤10 nM LOXL2. These results demonstrate an important difference in the regulatory mechanisms for LOX and LOXL2 catalytic activity. Moreover, they pave the way for further studies of potential differential functions of LOXL2 isoforms in fibrosis and tumor progression.}, }
@article {pmid30470306, year = {2018}, author = {Schmidt, SF and Rohm, M and Herzig, S and Berriel Diaz, M}, title = {Cancer Cachexia: More Than Skeletal Muscle Wasting.}, journal = {Trends in cancer}, volume = {4}, number = {12}, pages = {849-860}, doi = {10.1016/j.trecan.2018.10.001}, pmid = {30470306}, issn = {2405-8025}, mesh = {Antineoplastic Agents/pharmacology/*therapeutic use ; Cachexia/etiology/mortality/*physiopathology/prevention &amp; control ; Combined Modality Therapy/methods ; Humans ; Muscle, Skeletal/physiopathology ; Neoplasms/*complications/drug therapy/mortality/physiopathology ; Nutritional Support/*methods ; Paraneoplastic Syndromes/etiology/mortality/*physiopathology/prevention &amp; control ; Quality of Life ; Treatment Outcome ; }, abstract = {Cancer cachexia is a multifactorial condition characterized by body weight loss that negatively affects quality of life and survival of patients with cancer. Despite the clinical relevance, there is currently no defined standard of care to effectively counteract cancer-associated progressive tissue wasting. Skeletal muscle atrophy represents the main manifestation of cancer cachexia. However, cancer cachexia is increasingly seen as a systemic phenomenon affecting and/or influenced by various organs. Here, we describe recent developments elucidating the roles of different tissues as well as tissue crosstalk in this wasting syndrome, including potential links to other cancer-associated morbidities. A more comprehensive understanding of cancer cachexia etiology and heterogeneity may enable the development of intervention strategies to prevent or reverse this devastating condition.}, }
@article {pmid30423024, year = {2019}, author = {Sokol, ES and Feng, YX and Jin, DX and Basudan, A and Lee, AV and Atkinson, JM and Chen, J and Stephens, PJ and Frampton, GM and Gupta, PB and Ross, JS and Chung, JH and Oesterreich, S and Ali, SM and Hartmaier, RJ}, title = {Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {1}, pages = {115-123}, pmid = {30423024}, issn = {1569-8041}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*secondary ; Carcinoma, Lobular/drug therapy/genetics/*secondary ; Drug Resistance, Neoplasm/*genetics ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neurofibromin 1/*genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed.<br><br>PATIENTS AND METHODS: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes.<br><br>RESULTS: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P&#x2009;<&#x2009;0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P&#x2009;<&#x2009;0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%).<br><br>CONCLUSIONS: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.}, }
@article {pmid30412075, year = {2018}, author = {Lee, SJ and Chung, MS and Shin, SJ and Choi, YY}, title = {Correlation of tumor uptake on breast-specific gamma imaging and fluorodeoxyglucose PET/CT with molecular subtypes of breast cancer.}, journal = {Medicine}, volume = {97}, number = {43}, pages = {e12840}, pmid = {30412075}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*secondary ; Female ; Fluorodeoxyglucose F18/*pharmacology ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography/*methods ; Prognosis ; Radiopharmaceuticals/pharmacology ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; }, abstract = {Mechanisms of technetium-99m sesta-methoxyisobutylisonitrile (sestamibi) and F-fluorodeoxyglucose (FDG) uptake by tumor are different. The purpose of this study was to investigate the association between the tumor uptake of these 2 tracers in invasive ductal carcinoma and to examine thecorrelation of uptake of each tracer with prognostic factors and tumor molecular subtypes.A total of 96 patients with invasive ductal carcinoma who underwent preoperative breast-specific gamma imaging and FDG positron-emission tomography/computed tomography were retrospectively enrolled. Tumor-to-background ratio (TBR) of sestamibi and maximum standardized uptake value (SUVmax) of FDG were correlated with each other. Each of them was then compared with prognostic factors and molecular subtypes.In all tumors, there was a moderate positive correlation between TBR and SUVmax (r = 0.520, P < .001). Both TBR and SUVmax were significantly correlated with tumor size, incidence of axillary lymph node metastasis, histologic grade, estrogen receptor, progesterone receptor status, and Ki-67.There is a moderate degree of association between TBR of sestamibi and SUVmax of FDG in the invasive breast cancer. Two imaging indexes showed the similar tendency related with prognostic factors and molecular subtypes. While both TBR and SUVmax were significantly different between luminal A and nonluminal A tumors, neither of them had high enough sensitivity or specificity to obviate pathologic and molecular diagnosis.}, }
@article {pmid30409703, year = {2019}, author = {Wolff, G and Taranko, AE and Meln, I and Weinmann, J and Sijmonsma, T and Lerch, S and Heide, D and Billeter, AT and Tews, D and Krunic, D and Fischer-Posovszky, P and Müller-Stich, BP and Herzig, S and Grimm, D and Heikenwälder, M and Kao, WW and Vegiopoulos, A}, title = {Diet-dependent function of the extracellular matrix proteoglycan Lumican in obesity and glucose homeostasis.}, journal = {Molecular metabolism}, volume = {19}, number = {}, pages = {97-106}, pmid = {30409703}, issn = {2212-8778}, mesh = {Adipocytes/metabolism ; Adipose Tissue/metabolism ; Adipose Tissue, White/metabolism ; Adiposity/drug effects ; Adult ; Animals ; Diet, High-Fat ; Extracellular Matrix/metabolism ; Female ; Glucose/*metabolism ; Homeostasis ; Humans ; Insulin Resistance ; Intra-Abdominal Fat/metabolism ; Liver/metabolism ; Lumican/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/*metabolism ; Proteoglycans/metabolism ; }, abstract = {OBJECTIVE: Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications.<br><br>METHODS: Whole body ablation of Lumican (Lum[-/-]) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling.<br><br>RESULTS: Lumican was found to be particularly enriched in the stromal cells isolated from murine gonadal white adipose tissue. Likewise murine and human visceral fat showed a robust increase in Lumican as compared to fat from the subcutaneous depot. Lumican null female mice exhibited moderately increased fat mass, decreased insulin sensitivity and increased liver triglycerides in a diet-dependent manner. These changes coincided with inflammation in adipose tissue and no overt effects in adipose expandability, i.e. adipocyte formation and hypertrophy. Lumican over-expression in visceral fat and liver resulted in improved insulin sensitivity and glucose clearance.<br><br>CONCLUSIONS: These data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome.}, }
@article {pmid30409127, year = {2018}, author = {Ye, FG and Xia, C and Ma, D and Lin, PY and Hu, X and Shao, ZM}, title = {Nomogram for predicting preoperative lymph node involvement in patients with invasive micropapillary carcinoma of breast: a SEER population-based study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1085}, pmid = {30409127}, issn = {1471-2407}, support = {MOST2016YFC0900300//Ministry of Science and Technology of the People's Republic of China/ ; 81672601//National Natural Science Foundation of China (CN)/ ; 15410724000//Shanghai Committee of Science and Technology Funds/ ; }, mesh = {Aged ; Axilla/pathology ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Papillary/*epidemiology/*pathology ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nomograms ; Odds Ratio ; Population Surveillance ; Preoperative Period ; ROC Curve ; Reproducibility of Results ; Risk Factors ; SEER Program ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. This study was to identify risk factors accounting for IMPC of the breast and to develop a nomogram to preoperatively predict the probability of lymph node involvement.<br><br>METHODS: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation sets. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. A logistic regression model was used to construct the nomogram in the training set and then varified in the validation set. Nomogram performance was quantified with respect to discrimination and calibration using R 3.4.1 software.<br><br>RESULTS: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. Logistic regression analysis indicated larger lesions, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95% confidential interval (CI) 0.692 to 0.777), demonstrating a good prediction performance. Calibration curve for the nomogram was plotted and the slope was close to 1, which demonstrated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, with AUC of 0.748 (95% CI 0.701 to 0.767).<br><br>CONCLUSIONS: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinicalpathologic parameters was established, which could accurately preoperatively predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients.}, }
@article {pmid30407355, year = {2018}, author = {Liu, A and Feng, Y and Chen, B and Li, L and Wu, D and Qian, J and Yang, A}, title = {A case report of metastatic breast cancer initially presenting with esophageal dysphagia.}, journal = {Medicine}, volume = {97}, number = {45}, pages = {e13184}, pmid = {30407355}, issn = {1536-5964}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Deglutition Disorders/*etiology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Esophageal Neoplasms/*secondary/therapy ; Esophagectomy/methods ; Esophagus/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Tomography, X-Ray Computed ; }, abstract = {RATIONALE: Breast cancer metastasis to the esophagus is uncommon. To our knowledge, the present case is the first report of breast cancer with dysphagia as the initial symptom.<br><br>PATIENT CONCERNS: A 62-year-old woman was admitted to our hospital for progressive dysphagia.<br><br>DIAGNOSES: Endoscopic ultrasound-guided fine needle biopsy of the esophageal lesion found poorly differentiated carcinoma, and surgical resection of the breast nodule revealed invasive ductal carcinoma.<br><br>INTERVENTIONS: The patient underwent an esophagectomy, and the immunohistochemistry of surgical specimen was identified as metastatic breast cancer. Then patient was treated with chemotherapy and hormone therapy.<br><br>OUTCOMES: The patient remained symptom-free during 5 months of follow-up examinations.<br><br>LESSONS: This case indicates that metastatic breast cancer to the esophagus should be considered as a cause of esophageal stricture in older women.}, }
@article {pmid30406220, year = {2017}, author = {Cheng, C and Thakur, R and Nair, AR and Sterrett, S and Fridman, G}, title = {Miniature Elastomeric Valve Design for Safe Direct Current Stimulator.}, journal = {IEEE Biomedical Circuits and Systems Conference : healthcare technology : [proceedings]. IEEE Biomedical Circuits and Systems Conference}, volume = {2017}, number = {}, pages = {1-4}, pmid = {30406220}, support = {R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; }, abstract = {For safety reasons, commercial neural implants use charge-balanced biphasic pulses to interact with target neurons using metal electrodes. Short biphasic pulses are used to avoid irreversible electrochemical reactions at the electrode-tissue interfaces. Biphasic pulses are effective at exciting neurons, but quite limited in inhibiting their activity. In contrast, direct current can both excite and inhibit neurons, however delivered to metal electrodes, it causes toxic electrochemical reactions. We recently introduced Safe Direct Current Stimulator (SDCS) technology, which can excite or inhibit neurons without violating the safety criteria. Instead of direct current, SDCS generates an ionic direct current (iDC) from a biphasic input signal using a network of fluidic channels and mechanical valves. A key enabler towards transforming SDCS concept from a benchtop design to an implantable neural prosthesis is the design of a miniature valve. In this work, we present poly-dimethylsiloxane (PDMS) based elastomeric valves, squeeze valve (SV) and plunger valve (PV) capable of being actuated using a shape memory alloy wire.}, }
@article {pmid30388104, year = {2018}, author = {Golan, Y and Alhadeff, R and Glaser, F and Ganoth, A and Warshel, A and Assaraf, YG}, title = {Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter.}, journal = {PLoS computational biology}, volume = {14}, number = {11}, pages = {e1006503}, pmid = {30388104}, issn = {1553-7358}, support = {R35 GM122472/GM/NIGMS NIH HHS/United States ; R01 AI055926/AI/NIAID NIH HHS/United States ; }, mesh = {Cation Transport Proteins/genetics/*metabolism ; Computational Biology/methods ; Deficiency Diseases/metabolism/therapy ; Homeostasis ; Humans ; *Models, Theoretical ; Monte Carlo Method ; Mutagenesis, Site-Directed ; Permeability ; Zinc/deficiency/*metabolism ; }, abstract = {Multiscale modeling provides a very powerful means of studying complex biological systems. An important component of this strategy involves coarse-grained (CG) simplifications of regions of the system, which allow effective exploration of complex systems. Here we studied aspects of CG modeling of the human zinc transporter ZnT2. Zinc is an essential trace element with 10% of the proteins in the human proteome capable of zinc binding. Thus, zinc deficiency or impairment of zinc homeostasis disrupt key cellular functions. Mammalian zinc transport proceeds via two transporter families: ZnT and ZIP; however, little is known about the zinc permeation pathway through these transporters. As a step towards this end, we herein undertook comprehensive computational analyses employing multiscale techniques, focusing on the human zinc transporter ZnT2 and its bacterial homologue, YiiP. Energy calculations revealed a favorable pathway for zinc translocation via alternating access. We then identified key residues presumably involved in the passage of zinc ions through ZnT2 and YiiP, and functionally validated their role in zinc transport using site-directed mutagenesis of ZnT2 residues. Finally, we use a CG Monte Carlo simulation approach to sample the transition between the inward-facing and the outward-facing states. We present our structural models of the inward- and outward-facing conformations of ZnT2 as a blueprint prototype of the transporter conformations, including the putative permeation pathway and participating residues. The insights gained from this study may facilitate the delineation of the pathways of other zinc transporters, laying the foundations for the molecular basis underlying ion permeation. This may possibly facilitate the development of therapeutic interventions in pathological states associated with zinc deficiency and other disorders based on loss-of-function mutations in solute carriers.}, }
@article {pmid30385093, year = {2019}, author = {Shee, K and Muller, KE and Marotti, J and Miller, TW and Wells, WA and Tsongalis, GJ}, title = {Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era: Current and Future Molecular-Based Testing.}, journal = {The American journal of pathology}, volume = {189}, number = {5}, pages = {956-965}, pmid = {30385093}, issn = {1525-2191}, support = {F30 CA216966/CA/NCI NIH HHS/United States ; R01 CA200994/CA/NCI NIH HHS/United States ; R01 CA211869/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Disease Progression ; Female ; Humans ; Neoplasm Invasiveness ; *Precision Medicine ; Prognosis ; }, abstract = {Historically, ductal carcinoma in situ (DCIS) of the breast has been managed aggressively with surgery and radiotherapy because of a risk of progression to invasive ductal carcinoma. However, this treatment paradigm has been challenged by overtreatment concerns and evidence that suggests that DCIS can be stratified according to risk of recurrence or risk of progression to invasive disease. Traditional methods of risk stratification include histologic grade and hormone receptor status. Recent technological advancements have enabled an era of precision medicine, where DCIS can be molecularly analyzed by tools, such as next-generation DNA and RNA sequencing, to identify molecular biomarkers for risk stratification. These findings have led to the development of tools such as the Oncotype DX Breast DCIS Score, a gene expression-based assay with the potential to prevent overtreatment in low-risk disease.}, }
@article {pmid30375263, year = {2018}, author = {Talei, A and Tahmasebi, S and Akrami, M and Zangouri, V and Rezaianzadeh, A and Arasteh, P and Eghbali, T and Hosseini, S}, title = {The Shiraz Breast Cancer Registry (SBCR): study design and primary reports.}, journal = {Personalized medicine}, volume = {15}, number = {6}, pages = {471-479}, doi = {10.2217/pme-2018-0047}, pmid = {30375263}, issn = {1744-828X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology ; Female ; Humans ; Iran/epidemiology ; Male ; Middle Aged ; Neoplasm Staging ; Preliminary Data ; Prognosis ; Registries ; Research Design ; Young Adult ; }, abstract = {AIM: This is a description of the largest breast cancer (BC) registry in Iran, termed the Shiraz Breast Cancer Registry (SBCR).<br><br>METHODS: Data on baseline and clinical characteristics, socioeconomic status, imaging, physical examination, histopathology, treatment and prognosis have been recorded for each individual.<br><br>RESULTS: Overall, 5937 were included in the report. Mean age of first presentation was 49.05&#xa0;&#xb1;&#xa0;11.69&#xa0;years. Mean tumor size was 2.78&#xa0;&#xb1;&#xa0;1.76&#xa0;cm. Most patients had stage 2 (46.9%) and 3 (25.5%) BCs, respectively. Most common type of BC was invasive ductal carcinoma (83.3%), followed by medullary carcinoma (3.8%). Overall, 12.9% were triple negative (HER2-, ER- and PR-).<br><br>CONCLUSION: The study provides an overview on the status of BC's in Iran and a wide opportunity for future studies.}, }
@article {pmid30372658, year = {2019}, author = {Steger, M and Bermejo-Jambrina, M and Yordanov, T and Wagener, J and Brakhage, AA and Pittl, V and Huber, LA and Haas, H and Lass-Flörl, C and Posch, W and Wilflingseder, D}, title = {β-1,3-glucan-lacking Aspergillus fumigatus mediates an efficient antifungal immune response by activating complement and dendritic cells.}, journal = {Virulence}, volume = {10}, number = {1}, pages = {957-969}, pmid = {30372658}, issn = {2150-5608}, mesh = {Aspergillosis/microbiology ; Aspergillus fumigatus/*chemistry/genetics/*immunology ; *Complement Activation ; Cytokines/immunology ; Dendritic Cells/*immunology ; Echinocandins/therapeutic use ; Humans ; Immunity, Innate ; Mutation ; Spores, Fungal/immunology ; THP-1 Cells ; *beta-Glucans ; }, abstract = {Complement system and dendritic cells (DCs) form - beside neutrophils and macrophages - the first line of defense to combat fungal infections. Therefore, we here studied interactions of these first immune elements with Aspergillus fumigatus lacking ß-1,3-glucans (fks1tetOn[rep] under repressed conditions) to mechanistically explain the mode of action of echinocandins in more detail. Echinocandins are cell wall active agents blocking β-glucan synthase, making the A. fumigatus fks1tetOn mutant a good model to study immune-modulatory actions of these drugs. We now demonstrate herein, that complement was activated to significantly higher levels by the fks1-deficient strain compared to its respective wild type. This enhanced covalent linking of complement fragments to the A. fumigatus fks1tetOn[rep] mutant further resulted in enhanced DC binding and internalization of the fungus. Additionally, we found that fks1tetOn[rep] induced a Th1-/Th17-polarizing cytokine profile program in DCs. The effect was essentially dependent on massive galactomannan shedding, since blocking of DC-SIGN significantly reduced the fks1tetOn[rep]-mediated induction of an inflammatory cytokine profile.Our data demonstrate that lack of ß-1,3-glucan, also found under echinocandin therapy, results in improved recognition of Aspergillus fumigatus by complement and DCs and therefore not only directly affects the fungus by its fungistatic actions, but also is likely to exert indirect antifungal mechanisms by strengthening innate host immune mechanisms.Abbreviations: C: complement; CR:complement receptor; DC: dendritic cell; iDC: immature dendritic cell; DC-SIGN: Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; ERK: extracellular signal-regulated kinases; JNK : c-Jun N-terminal kinases; MAPK: mitogen-activated protein kinase; NHS: normal human serum; PRR: pattern recognition receptor; Th :T helper; TLR :Toll-like receptor; WT: wild type.}, }
@article {pmid30371651, year = {2018}, author = {Drucis, K and Brzeziński, M and Gniadek, K}, title = {[Synchronous gastrointestinal stromal tumor of stomach and invasive ductal carcinoma of both breasts].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {45}, number = {268}, pages = {161-163}, pmid = {30371651}, issn = {1426-9686}, mesh = {Breast Neoplasms/*complications/diagnostic imaging/surgery ; Carcinoma, Ductal/*complications/diagnostic imaging/surgery ; Female ; Gastrointestinal Stromal Tumors/*complications/diagnostic imaging/surgery ; Humans ; Mastectomy ; Middle Aged ; Stomach/diagnostic imaging/surgery ; Stomach Neoplasms/*complications/diagnostic imaging/surgery ; }, abstract = {UNLABELLED: Gastrointestinal stromal tumor (GIST), despite the fact that it accounts for less than 5% of all sarcomas, is the most common mesenchymal tumor of the alimentary canal. Synchronous and metachronous stromal tumors are very rare findings. Only a few such cases can be found in the literature, and yet most of them is connected with Von Recklinghausen's disease or Carney's triad in which it is proved a much higher frequency of occurrence of this kind of tumors.<br><br>CASE REPORT: We present a case of 64 years old women, who was diagnosed with invasive ductal carcinoma of both breast due to screening mammography. Patent was qualified to bilateral mastectomy. Perioperative computer tomography scan revealed an additional pathological abnormality situated beyond stomach light, which after resection and immunohistochemistry was found to be a gastrointestinal stromal tumor. This case emphasize the problem of synchronous stromal tumors, the detection of which is often difficult due to nonspecific symptoms. Despite the fact that the most common localization of coexisting tumors is the digestive tract, one should remember about the possibility of occurrence in less frequent locations such as the breast.}, }
@article {pmid30362328, year = {2018}, author = {Abood, RA}, title = {Breast Cancer in Basra Oncology Center: A Clinico- Epidemiological Analysis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {19}, number = {10}, pages = {2943-2946}, pmid = {30362328}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Iraq/epidemiology ; Male ; Middle Aged ; Neoplasm Staging/methods ; Retrospective Studies ; Young Adult ; }, abstract = {Background: Breast cancer is the most common cancer affecting women, and the leading cause of cancer-related deaths. Objective: This study was performed to evaluate clinico-epidemiological features of breast cancer from Iraq during a five-year period. Methodology: This is a retrospective descriptive study. Medical notes and histopathological reports of patients with confirmed diagnosis of breast cancer between January 2011 and December 2015 were reviewed for age, gender, site, laterality, histopathological type, grade of differentiation and TNM stage at diagnosis. Results: A total of 1,000 patients were included in the study. Mean age at diagnosis was 50 years (range 22-85 years), and females constituted 99.2% of cases. Most cases (98.7%) were unilateral and most common (85.5%) histological subtype was invasive ductal carcinoma. Majority of the cases (58%) were moderately differentiated (grade II), wherein 45% belonged to stage II in TNM system, and nearly half (49%) of patients had locally advanced or metastatic cancer. Conclusion: Breast cancer presents at least a decade earlier and at a more advanced stage in Iraqi women when compared to the Western World. Steps for early detection are essential for initiation of prompt therapy and reduction of mortality.}, }
@article {pmid30350269, year = {2019}, author = {Jerevall, PL and Brock, J and Palazzo, J and Wieczorek, T and Misialek, M and Guidi, AJ and Wu, Y and Erlander, MG and Zhang, Y and Schnabel, CA and Goss, PE and Horick, N and Sgroi, DC}, title = {Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score.}, journal = {Breast cancer research and treatment}, volume = {173}, number = {2}, pages = {375-383}, doi = {10.1007/s10549-018-5013-6}, pmid = {30350269}, issn = {1573-7217}, mesh = {Adult ; Age Factors ; Aged ; Breast/pathology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/epidemiology ; Prognosis ; Prospective Studies ; Risk Assessment/methods ; Risk Factors ; Tumor Burden ; }, abstract = {PURPOSE: A recent comparison of the prognostic accuracy of Breast Cancer Index (BCI) and the Recurrence Score (RS) showed that BCI was more precise than RS. BCI identified a subset of RS low and intermediate risk patients with clinically relevant elevated rates of distant recurrences (DR). The current study analyzed the correlation of BCI and RS risk classification to clinical and pathological parameters and further examined the re-categorization between the two risk group indices in a multi-institutional cohort of hormone receptor positive (HR+) breast cancer patients.<br><br>METHODS: 560 women with HR+, lymph node-negative breast cancer who underwent testing with RS as part of their routine clinical care were included in the final analysis. Individual risk was assessed using predefined categories of RS and BCI (Low, Intermediate and High, respectively). Correlations between BCI, RS, and standard clinical-pathological prognostic factors were examined, and re-categorization of risk groups between BCI and RS was analyzed.<br><br>RESULTS: An overall significant association between histological tumor grade and RS or BCI was observed with high-grade tumors more prevalent among RS and BCI high-risk patients. The invasive ductal carcinoma histologic subtype was associated with 98% and 93% of high-risk RS and BCI cases, respectively. The invasive lobular subtype accounted for 0% and 6% of high-risk RS and BCI cases, respectively. A poor agreement between the two biomarker risk group indices was demonstrated with more than 51% of the total cohort stratified differently between BCI and RS. As compared with RS, BCI stratified fewer patients into the intermediate-risk group (29% vs. 39%, BCI and RS, respectively) and more patients into the high-risk group (19% vs. 7%, BCI and RS, respectively). Subsets of both RS low- and intermediate-risk patients were identified by BCI as high risk.<br><br>CONCLUSIONS: In this clinical series, BCI and RS risk groups demonstrated a significant association with histological tumor grade. BCI showed a modest correlation with tumor size and no correlation with age, while RS showed no correlation with tumor size or age. Compared with RS, BCI classifies fewer intermediate risk patients, identifies subsets of low and intermediate RS risk patients as high-risk, and provides distinct individualized risk assessment for patients with early-stage breast cancer.}, }
@article {pmid30339213, year = {2019}, author = {Jacob, T and Bracha, J}, title = {Identification of Signs and Symptoms of Axillary Web Syndrome and Breast Seroma During a Course of Physical Therapy 7 Months After Lumpectomy: A Case Report.}, journal = {Physical therapy}, volume = {99}, number = {2}, pages = {229-239}, doi = {10.1093/ptj/pzy110}, pmid = {30339213}, issn = {1538-6724}, mesh = {Aged ; Axilla/*physiopathology ; Female ; Humans ; Lymphatic Diseases/etiology/*therapy ; Lymphedema/*therapy ; Mastectomy/*adverse effects ; *Physical Therapy Modalities ; Postoperative Complications/etiology ; Seroma/etiology/*therapy ; Syndrome ; }, abstract = {BACKGROUND AND PURPOSE: Axillary web syndrome (AWS) and seroma are common and function-limiting side effects following treatments for breast cancer. Studies of AWS and seroma are rare, and there are no guidelines for physical therapy in these cases.<br><br>CASE DESCRIPTION: After left breast lumpectomy due to invasive ductal carcinoma, a 65-year-old female patient underwent intraoperative radiation therapy and whole breast radiation. Seven months later, during treatment for breast swelling, AWS and breast seroma were identified by a physical therapist certified in lymphedema treatment. Treatment goals were to reduce breast swelling and pain and to improve shoulder movements. Interventions included manual lymph drainage, left arm stretching, and instruction about self-lymphatic-drainage and stretching exercise. Also, a compression bra was ordered, and continued daily activities and physical activity were recommended.<br><br>OUTCOMES: Improvement in shoulder movement, breast swelling, and pain.<br><br>DISCUSSION: Because evidence for treatment guidelines following treatments for breast cancer is lacking, close follow-up for treatment-related complications is recommended. Management should be chosen according to signs and symptoms. Realistic expectations can reduce patient frustration and improve coping strategies and compliance with self-treatment demands. Clinical studies to support these conclusions are required.}, }
@article {pmid30332671, year = {2019}, author = {Kitamura, M and Nakayama, T and Mukaisho, KI and Mori, T and Umeda, T and Moritani, S and Kushima, R and Tani, M and Sugihara, H}, title = {Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {86}, number = {2-3}, pages = {92-101}, doi = {10.1159/000492833}, pmid = {30332671}, issn = {1423-0291}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Comparative Genomic Hybridization ; *DNA Copy Number Variations ; *Disease Progression ; Female ; GATA3 Transcription Factor/genetics ; Humans ; Middle Aged ; Paraffin Embedding ; Tumor Suppressor Protein p53/genetics ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors.<br><br>METHODS: We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering.<br><br>RESULTS: The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters.<br><br>CONCLUSION: Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk.}, }
@article {pmid30325954, year = {2018}, author = {Dhage, S and Ernlund, A and Ruggles, K and Axelrod, D and Berman, R and Roses, D and Schneider, RJ}, title = {A genomic ruler to assess oncogenic transition between breast tumor and stroma.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205602}, pmid = {30325954}, issn = {1932-6203}, support = {T32 CA009161/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast/*metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/surgery ; Cell Transformation, Neoplastic/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genomics ; Humans ; Mastectomy ; Microarray Analysis ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Staging ; RNA, Messenger/metabolism ; Stromal Cells/*metabolism/pathology ; }, abstract = {BACKGROUND: Cancers induce gene expression alterations in stroma surrounding tumors that supports cancer progression. However, it is actually not at all known the extent of altered stromal gene expression enacted by tumors nor the extent to which altered stromal gene expression penetrates the stromal tissue. Presently, post-surgical "tumor-free" stromal tissue is determined to be cancer-free based on solely on morphological normality-a criteria that has not changed in more than 100 years despite the existence of sophisticated gene expression data to the contrary. We therefore investigated the extent to which breast tumors alter stromal gene expression in three dimensions in women undergoing mastectomy with the intent of providing a genomic determination for development of future risk of recurrence criteria, and to inform the need for adjuvant full-breast irradiation.<br><br>METHODS AND FINDINGS: Genome-wide gene expression changes were determined in histopathologically normal breast tissue in 33 women undergoing mastectomy for stage II and III primary invasive ductal carcinoma at serial distances in three dimensions from the tumor. Gene expression was determined by genome-wide mRNA analysis and subjected to metagene mRNA characterization. Tumor-like gene expression signatures in stroma were identified that surprisingly transitioned to a plastic, normalizing homeostatic signature with distance from tumor. Stroma closest to tumor displayed a pronounced tumor-like signature enriched in cancer-promoting pathways involved in disruption of basement membrane, cell migration and invasion, WNT signaling and angiogenesis. By 2 cm from tumor in all dimensions, stromal tissues were in transition, displaying homeostatic and tumor suppressing gene activity, while also expressing cancer supporting pathways.<br><br>CONCLUSIONS: The dynamics of gene expression in the post-tumor breast stroma likely co-determines disease outcome: reversion to normality or transition to transformation in morphologically normal tissue. Our stromal genomic signature may be important for personalizing surgical and adjuvant therapeutic decisions and risk of recurrence.}, }
@article {pmid30306389, year = {2018}, author = {DeVaux, RS and Herschkowitz, JI}, title = {Beyond DNA: the Role of Epigenetics in the Premalignant Progression of Breast Cancer.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {23}, number = {4}, pages = {223-235}, pmid = {30306389}, issn = {1573-7039}, mesh = {Animals ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; DNA/*genetics ; Disease Progression ; Epigenesis, Genetic/*genetics ; Female ; Humans ; }, abstract = {Ductal Carcinoma in Situ (DCIS) is an early breast cancer lesion that is considered a nonobligate precursor to development of invasive ductal carcinoma (IDC). Although only a small subset of DCIS lesions are predicted to progress into a breast cancer, distinguishing innocuous from minacious DCIS lesions remains a clinical challenge. Thus, patients diagnosed with DCIS will undergo surgery with the potential for radiation and hormone therapy. This has led to a current state of overdiagnosis and overtreatment. Interrogating the transcriptome alone has yet to define clear functional determinants of progression from DCIS to IDC. Epigenetic changes, critical for imprinting and tissue specific development, in the incorrect context can lead to global signaling rewiring driving pathological phenotypes. Epigenetic signaling pathways, and the molecular players that interpret and sustain their signals, are critical to understanding the underlying pathology of breast cancer progression. The types of epigenetic changes, as well as the molecular players, are expanding. In addition to DNA methylation, histone modifications, and chromatin remodeling, we must also consider enhancers as well as the growing field of noncoding RNAs. Herein we will review the epigenetic interactions that have been uncovered in early stage lesions that impact breast cancer progression, and how these players may be utilized as biomarkers to mitigate overdiagnosis and overtreatment.}, }
@article {pmid30303137, year = {2018}, author = {Jafarian, AH and Tasbandi, A and Gilan, H and Sheikhi, M and Roshan, NM}, title = {Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {61}, number = {4}, pages = {500-504}, doi = {10.4103/IJPM.IJPM_67_18}, pmid = {30303137}, issn = {0974-5130}, mesh = {Adult ; Aged ; CD4 Antigens/*analysis ; CD8 Antigens/*analysis ; Carcinoma, Ductal, Breast/*immunology/mortality/pathology ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Ki-1 Antigen/*analysis ; Middle Aged ; Prognosis ; Triple Negative Breast Neoplasms/*immunology/mortality/pathology ; }, abstract = {BACKGROUND: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors.<br><br>MATERIALS AND METHODS: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels.<br><br>RESULTS: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes.<br><br>CONCLUSION: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.}, }
@article {pmid30290054, year = {2018}, author = {Gaowa, S and Futamura, M and Tsuneki, M and Kamino, H and Tajima, JY and Mori, R and Arakawa, H and Yoshida, K}, title = {Possible role of p53/Mieap-regulated mitochondrial quality control as a tumor suppressor in human breast cancer.}, journal = {Cancer science}, volume = {109}, number = {12}, pages = {3910-3920}, pmid = {30290054}, issn = {1349-7006}, support = {15ck0106006&#xa0;h0002 (to HA)//AMED/ ; H26-practical-general-001 (to HA)//Ministry of Health, Labour and Welfare for the Practical Research for Innovative Cancer/ ; 23659178 (to HA)//KAKENIHI/ ; 24240117 (to HA)//KAKENIHI/ ; 17K10542 (to MF)//KAKENIHI/ ; 25670169 (to HA)//KAKENIHI/ ; 29-E-1 (to HA), 30-A-3 (to HA)//The National Cancer Center Research and Development Fund/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Caspases/metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; DNA Methylation ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Mitochondria/metabolism ; Mitochondrial Proteins/*genetics/*metabolism ; Mutation ; Promoter Regions, Genetic ; Tumor Suppressor Protein p53/*genetics/*metabolism ; }, abstract = {Mitochondria-eating protein (Mieap), encoded by a p53-target gene, plays an important role in mitochondrial quality control (MQC). Mieap has been reported to have a critical role in tumor suppression in colorectal cancer. Here, we investigated its role as a tumor suppressor in breast cancer. The enforced expression of exogenous Mieap in breast cancer cells induced caspase-dependent apoptosis, with activation of both caspase-3/7 and caspase-9. Immunohistochemistry revealed endogenous Mieap in the cytoplasm in 24/75 (32%) invasive ductal carcinomas (IDC), 15/27 (55.6%) cases of ductal carcinoma in situ (DCIS) and 16/18 (88.9%) fibroadenomas (FA) (IDC vs DCIS; P = 0.0389, DCIS vs FA; P = 0.0234, IDC vs FA; P < 0.0001). In IDC, the Mieap promoter was methylated in 6/46 (13%) cases, whereas p53 was mutated in 6/46 (13%) cases. Therefore, the p53/Mieap-regulated MQC pathway was inactivated in 12/46 IDC (26.1%). Interestingly, all tumors derived from the 12 patients with Mieap promoter methylation or p53 mutations pathologically exhibited more aggressive and malignant breast cancer phenotypes. Impairment of p53/Mieap-regulated MQC pathway resulted in significantly shorter disease-free survival (DFS) (P = 0.021), although p53 status is more prognostic in DFS than Mieap promoter methylation. These results indicate that p53/Mieap-regulated MQC has a critical role in tumor suppression in breast cancer, possibly in part through mitochondrial apoptotic pathway.}, }
@article {pmid30287681, year = {2018}, author = {Ng, CS and Sinha, A and Aniweh, Y and Nah, Q and Babu, IR and Gu, C and Chionh, YH and Dedon, PC and Preiser, PR}, title = {tRNA epitranscriptomics and biased codon are linked to proteome expression in Plasmodium falciparum.}, journal = {Molecular systems biology}, volume = {14}, number = {10}, pages = {e8009}, pmid = {30287681}, issn = {1744-4292}, mesh = {Codon ; Epigenesis, Genetic ; Erythrocytes ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Humans ; Plasmodium falciparum/genetics/*physiology ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Proteomics/methods ; Protozoan Proteins/*genetics/*metabolism ; RNA, Transfer/*metabolism ; }, abstract = {Among components of the translational machinery, ribonucleoside modifications on tRNAs are emerging as critical regulators of cell physiology and stress response. Here, we demonstrate highly coordinated behavior of the repertoire of tRNA modifications of Plasmodium falciparum throughout the intra-erythrocytic developmental cycle (IDC). We observed both a synchronized increase in 22 of 28 modifications from ring to trophozoite stage, consistent with tRNA maturation during translational up-regulation, and asynchronous changes in six modifications. Quantitative analysis of ~2,100 proteins across the IDC revealed that up- and down-regulated proteins in late but not early stages have a marked codon bias that directly correlates with parallel changes in tRNA modifications and enhanced translational efficiency. We thus propose a model in which tRNA modifications modulate the abundance of stage-specific proteins by enhancing translation efficiency of codon-biased transcripts for critical genes. These findings reveal novel epitranscriptomic and translational control mechanisms in the development and pathogenesis of Plasmodium parasites.}, }
@article {pmid30287091, year = {2018}, author = {Schumacher, D and Morgenstern, J and Oguchi, Y and Volk, N and Kopf, S and Groener, JB and Nawroth, PP and Fleming, T and Freichel, M}, title = {Compensatory mechanisms for methylglyoxal detoxification in experimental &amp; clinical diabetes.}, journal = {Molecular metabolism}, volume = {18}, number = {}, pages = {143-152}, pmid = {30287091}, issn = {2212-8778}, mesh = {Aged ; Aldo-Keto Reductases/metabolism ; Animals ; Diabetes Mellitus, Experimental/*metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Female ; Glycation End Products, Advanced/metabolism ; Humans ; Kidney/metabolism ; Lactoylglutathione Lyase/genetics/metabolism ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Pyruvaldehyde/*metabolism ; }, abstract = {OBJECTIVES: The deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one the five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have been shown to metabolize MG; however, the relative contribution of this superfamily to the detoxification of MG in vivo, particularly within the diabetic state, remains unknown.<br><br>METHODS: CRISPR/Cas9-mediated genome editing was used to generate a Glo1 knock-out (Glo1[-/-]) mouse line. Streptozotocin was then applied to investigate metabolic changes under hyperglycemic conditions.<br><br>RESULTS: Glo1[-/-] mice were viable and showed no elevated MG or MG-H1 levels under hyperglycemic conditions. It was subsequently found that the enzymatic efficiency of various oxidoreductases in the liver and kidney towards MG were increased in the Glo1[-/-] mice. The functional relevance of this was supported by the altered distribution of alternative detoxification products. Furthermore, it was shown that MG-dependent AKR activity is a potentially clinical relevant pathway in human patients suffering from diabetes.<br><br>CONCLUSIONS: These data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG.}, }
@article {pmid30276443, year = {2019}, author = {Fortis, SP and Vaxevanis, CK and Mahaira, LG and Sofopoulos, M and Sotiriadou, NN and Dinou, A and Arnogiannaki, N and Stavropoulos-Giokas, C and Thanos, D and Baxevanis, CN and Perez, SA}, title = {Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {68}, number = {1}, pages = {57-70}, doi = {10.1007/s00262-018-2252-7}, pmid = {30276443}, issn = {1432-0851}, support = {Grant GER_1968 (ISPEBREAST)//GSTR/ ; Donation//Haegeman-Goossens family/ ; }, mesh = {Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/classification/*genetics/immunology ; Cytokines/blood ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Leukocytes, Mononuclear/metabolism ; MicroRNAs/blood/*genetics ; Prognosis ; }, abstract = {Breast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23α, miR-146α, miR-155 and miR-181α), in operable BCa patients, with non-metastatic, invasive ductal carcinoma, not receiving neoadjuvant chemotherapy. These miRNAs, known to be involved in both tumor cell progression and immune pathways regulation, were analyzed in relation to circulating cytokines, tumor immune-cell infiltration and established prognostic clinicopathological characteristics. We have identified three different clusters, with overall low (C1), moderate (C2) or high (C3) expression levels of these six circulating miRNAs, which define three distinct groups of non-metastatic BCa patients characterized by different clinicopathological and immune-related characteristics, with possibly different clinical outcomes. Our data provide the proof-of-principle to support the notion that, up- or down-regulation of the same circulating miRNA may reflect different prognosis in BCa. Nonetheless, the prognostic and/or predictive potential of these three "signatures" needs to be further evaluated in larger cohorts of BCa patients with an, at least, 5-year clinical follow-up.}, }
@article {pmid30273605, year = {2019}, author = {Hannafon, BN and Ding, WQ}, title = {Functional Role of miRNAs in the Progression of Breast Ductal Carcinoma in Situ.}, journal = {The American journal of pathology}, volume = {189}, number = {5}, pages = {966-974}, pmid = {30273605}, issn = {1525-2191}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Disease Progression ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Neoplasm Invasiveness ; Prognosis ; }, abstract = {miRNAs are small RNAs that influence gene expression by targeting mRNAs. Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Many of the genetic events required for the invasive progression of DCIS occur at the preinvasive stage, and these events include changes in the expression of miRNAs. Aberrant expression of miRNAs can influence specific oncogenic or tumor-suppressive pathways required for breast cancer progression. miRNAs in DCIS have been shown to influence hormone signaling, cell-cell adhesion, epithelial-to-mesenchymal transition, transforming growth factor β signaling, maintenance of cancer stem cells, and modulation of the extracellular matrix. Additionally, extracellular DCIS miRNAs, such as those found in exosomes, may promote invasive progression by modifying the tumor microenvironment. Here, we review the miRNAs that have been identified in DCIS and how they may contribute to the progression to invasive disease. We also touch on the current state of miRNA therapy development, including the current challenges, and discuss the key future perspectives for research into miRNA function for the purpose of miRNA therapy development for DCIS.}, }
@article {pmid30261528, year = {2018}, author = {Kopf, S and Nawroth, PP}, title = {Diabetic Pulmopathy: A New Clinical Challenge for Diabetology.}, journal = {Experimental and clinical endocrinology &amp; diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association}, volume = {126}, number = {9}, pages = {590-591}, doi = {10.1055/a-0715-2743}, pmid = {30261528}, issn = {1439-3646}, mesh = {*Diabetes Complications/therapy ; Diabetes Mellitus, Type 2/*complications ; Exercise Therapy ; Humans ; Pulmonary Fibrosis/diagnosis/*etiology/therapy ; }, }
@article {pmid30253811, year = {2018}, author = {Abu-Sbeih, H and Ali, FS and Luo, W and Qiao, W and Raju, GS and Wang, Y}, title = {Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis.}, journal = {Journal for immunotherapy of cancer}, volume = {6}, number = {1}, pages = {95}, pmid = {30253811}, issn = {2051-1426}, mesh = {Adult ; Aged ; Antineoplastic Agents, Immunological/*adverse effects/therapeutic use ; Biomarkers ; Biopsy ; Colitis/*diagnosis/*etiology ; Comorbidity ; Disease Management ; *Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*complications/drug therapy/immunology ; Odds Ratio ; Retrospective Studies ; Severity of Illness Index ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICPI) are efficacious treatments for advanced malignancies but can result in immune mediated diarrhea and colitis (IDC). Currently, the guidelines for the treatment of IDC depend only on clinical symptoms. Endoscopic and histologic features of such adverse events are not well studied in a manner that can help to gauge treatment plans. We aimed to characterize endoscopic and histologic features of IDC and to assess their association with clinical outcomes.<br><br>METHODS: Our study included patients who had undergone endoscopy for IDC (1/2010 to 3/2018). Patients with GI infection at time of onset were excluded. High-risk endoscopic features were ulcers deeper than 2&#xa0;mm, larger than 1&#xa0;cm, and extensive colonic involvement. Univariate and multivariate logistic regression were performed to assess the association of endoscopic and histological features with clinical outcomes.<br><br>RESULTS: A total of 182 patients was included; most were white (92%), males (65%) with a mean age of 60&#xa0;years. Median time from ICPI initiation to IDC was 7&#xa0;weeks. Fifty-three percent had grade 3-4 diarrhea, and 32% grade 3-4 colitis. Forty-nine patients had mucosal ulcerations, 66 non-ulcerative inflammation and 67 normal endoscopy. Calprotectin was higher in patients with ulceration (P&#x2009;=&#x2009;0.04). The sensitivity of lactoferrin to detect histologic and endoscopic inflammation was 90% and 70% respectively. Patients who underwent endoscopy earlier than 7&#xa0;days after IDC onset had shorter duration of IDC symptoms and duration of steroid treatment than those who underwent endoscopy after 7&#xa0;days of IDC onset (P&#x2009;=&#x2009;0.026 and P&#x2009;=&#x2009;0.053, respectively). Patients who underwent endoscopy >&#x2009;30&#xa0;days of symptom onset required longer duration of steroids (P&#x2009;=&#x2009;0.02), had more recurrent symptoms (P&#x2009;< 0.01) and received later infliximab/vedolizumab add-on therapy than did those who underwent endoscopy &#x2264;30&#xa0;days (P&#x2009;=&#x2009;0.03). High-risk features were associated with more frequent (P&#x2009;=&#x2009;0.03) and longer duration (P&#x2009;=&#x2009;0.02) hospitalization and infliximab/vedolizumab requirement (P&#x2009;< 0.01). Patients with active histological inflammation had more recurrence (P&#x2009;< 0.01) and repeat endoscopy (P&#x2009;< 0.01). Repeat endoscopy was required in 47 patients. A multivariate logistic regression revealed that longer ICPI treatment was associated with more frequent hospitalizations (OR 1.00; 95%CI 1.00-1.01; P&#x2009;< 0.01) and high-risk endoscopic features were associated with the requirement of infliximab/vedolizumab (OR 3.89; 95%CI 1.68-9.01; P&#x2009;< 0.01).<br><br>CONCLUSION: High risk endoscopic features and active histologic inflammation represent important markers of disease severity with clinical implications and should be used in a timely manner to devise IDC-focused treatment algorithms.}, }
@article {pmid30247211, year = {2018}, author = {Cai, M and Feng, G and Zhang, G}, title = {A Case of Radioactivity Concentrated in Orbital Implant in 99mTc-MDP Bone Scan and SPECT/CT.}, journal = {Clinical nuclear medicine}, volume = {43}, number = {12}, pages = {e453-e454}, doi = {10.1097/RLU.0000000000002277}, pmid = {30247211}, issn = {1536-0229}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Orbital Implants/*adverse effects ; Orbital Neoplasms/*diagnostic imaging/secondary ; Radiopharmaceuticals ; *Single Photon Emission Computed Tomography Computed Tomography ; Technetium Tc 99m Medronate ; }, abstract = {A 27-year-old woman, who has received a hydroxyapatite orbital implant in the right eye due to a trauma 6 years ago, was newly diagnosis with left breast invasive ductal carcinoma. Tc-MDP bone scan showed an increased radiotracer accumulation in the right orbit and SPECT/CT confirmed the focal accumulation at the site of the implant, without any sign of local malignant lesions or orbital infection. Radionuclide imaging could provide certain useful information in diagnosing or differential diagnosing orbital disease.}, }
@article {pmid30236106, year = {2018}, author = {Schultz, S and Bartsch, H and Sotlar, K and Petat-Dutter, K and Bonin, M and Kahlert, S and Harbeck, N and Vogel, U and Seeger, H and Fehm, T and Neubauer, HJ}, title = {Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers.}, journal = {BMC medical genomics}, volume = {11}, number = {1}, pages = {80}, pmid = {30236106}, issn = {1755-8794}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Formaldehyde/chemistry ; *Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Paraffin Embedding ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: The transition from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) is an important step during breast carcinogenesis. Understanding its molecular changes may help to identify high-risk DCIS that progress to IBC. Here, we describe a transcriptomic profiling analysis of matched formalin-fixed and paraffin-embedded (FFPE) DCIS and IBC components of individual breast tumours, containing both tumour compartments. The study was performed to validate progression-associated transcripts detected in an earlier gene profiling project using fresh frozen breast cancer tissue. In addition, FFPE tissues from patients with pure DCIS (pDCIS) were analysed to identify candidate transcripts characterizing DCIS with a high or low risk of progressing to IBC.<br><br>METHODS: Fifteen laser microdissected pairs of DCIS and IBC were profiled by Illumina DASL technology and used for expression validation by qPCR. Differential expression was independently validated using further 25 laser microdissected DCIS/IBC sample pairs. Additionally, laser microdissected epithelial cells from 31 pDCIS were investigated for expression of candidate transcripts using qPCR.<br><br>RESULTS: Multiple statistical calculation methods revealed 1784 mRNAs which are differentially expressed between DCIS and IBC (P&#x2009;<&#x2009;0.05), of which 124 have also been identified in the gene profiling project using fresh frozen breast cancer tissue. Nine mRNAs that had been selected from the gene list obtained using fresh frozen tissues by applying pathway and network analysis (MMP11, GREM1, PLEKHC1, SULF1, THBS2, CSPG2, COL10A1, COL11A1, KRT14) were investigated in tissues from the same 15 microdissected specimens and the 25 independent tissue samples by qPCR. All selected transcripts were also detected in tumour cells from pDCIS. Expression of MMP11 and COL10A1 increased significantly from pDCIS to DCIS of DCIS/IBC mixed tumours.<br><br>CONCLUSION: We confirm differential expression of progression-associated transcripts in FFPE breast cancer samples which might mediate the transition from DCIS to IBC. MMP11 and COL10A1 may characterize pure DCIS with a high risk developing IDC.}, }
@article {pmid30227836, year = {2018}, author = {Jouali, F and Marchoudi, N and Talbi, S and Bilal, B and El Khasmi, M and Rhaissi, H and Fekkak, J}, title = {Detection of PIK3/AKT pathway in Moroccan population with triple negative breast cancer.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {900}, pmid = {30227836}, issn = {1471-2407}, mesh = {Adult ; Aged ; Class I Phosphatidylinositol 3-Kinases/*genetics ; Exons/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Morocco/epidemiology ; Oncogene Protein v-akt/*genetics ; PTEN Phosphohydrolase/*genetics ; Retrospective Studies ; Signal Transduction/genetics ; Triple Negative Breast Neoplasms/epidemiology/*genetics/pathology ; }, abstract = {BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10-20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~ 30%) observed, along with protein loss of PTEN and AKT activation by phosphorylation (pAkt). Therefore, we propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients.<br><br>METHODS: We conducted a retrospective study of 39 patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data.<br><br>RESULTS: All patients were female with a median age of 46&#xa0;years from (34-65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2% of them were grade III SBR. Among the 39, 9 were right sided tumor patients and the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9 and four in exon 20.<br><br>CONCLUSION: The PI3KCA gene is highly activated and plays a crucial role in the pathogenesis of TNBC more, therefore, may be a potential therapeutic target to improve outcomes in patients.}, }
@article {pmid30208271, year = {2018}, author = {Nuñez, NN and Khuu, C and Babu, CS and Bertolani, SJ and Rajavel, AN and Spear, JE and Armas, JA and Wright, JD and Siegel, JB and Lim, C and David, SS}, title = {The Zinc Linchpin Motif in the DNA Repair Glycosylase MUTYH: Identifying the Zn[2+] Ligands and Roles in Damage Recognition and Repair.}, journal = {Journal of the American Chemical Society}, volume = {140}, number = {41}, pages = {13260-13271}, pmid = {30208271}, issn = {1520-5126}, support = {R01 CA067985/CA/NCI NIH HHS/United States ; T32 ES007059/ES/NIEHS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Animals ; Base Sequence ; Binding Sites ; Cysteine/chemistry ; DNA Glycosylases/chemistry/genetics/*metabolism ; Geobacillus stearothermophilus/enzymology ; Humans ; Ligands ; Mice ; Mutation ; Protein Binding ; Sequence Alignment ; Zinc/*metabolism ; }, abstract = {The DNA base excision repair (BER) glycosylase MUTYH prevents DNA mutations by catalyzing adenine (A) excision from inappropriately formed 8-oxoguanine (8-oxoG):A mismatches. The importance of this mutation suppression activity in tumor suppressor genes is underscored by the association of inherited variants of MUTYH with colorectal polyposis in a hereditary colorectal cancer syndrome known as MUTYH-associated polyposis, or MAP. Many of the MAP variants encompass amino acid changes that occur at positions surrounding the two-metal cofactor-binding sites of MUTYH. One of these cofactors, found in nearly all MUTYH orthologs, is a [4Fe-4S][2+] cluster coordinated by four Cys residues located in the N-terminal catalytic domain. We recently uncovered a second functionally relevant metal cofactor site present only in higher eukaryotic MUTYH orthologs: a Zn[2+] ion coordinated by three Cys residues located within the extended interdomain connector (IDC) region of MUTYH that connects the N-terminal adenine excision and C-terminal 8-oxoG recognition domains. In this work, we identified a candidate for the fourth Zn[2+] coordinating ligand using a combination of bioinformatics and computational modeling. In addition, using in vitro enzyme activity assays, fluorescence polarization DNA binding assays, circular dichroism spectroscopy, and cell-based rifampicin resistance assays, the functional impact of reduced Zn[2+] chelation was evaluated. Taken together, these results illustrate the critical role that the "Zn[2+] linchpin motif" plays in MUTYH repair activity by providing for proper engagement of the functional domains on the 8-oxoG:A mismatch required for base excision catalysis. The functional importance of the Zn[2+] linchpin also suggests that adjacent MAP variants or exposure to environmental chemicals may compromise Zn[2+] coordination, and ability of MUTYH to prevent disease.}, }
@article {pmid30185420, year = {2019}, author = {Lee, JY and Schizas, M and Geyer, FC and Selenica, P and Piscuoglio, S and Sakr, RA and Ng, CKY and Carniello, JVS and Towers, R and Giri, DD and de Andrade, VP and Papanastasiou, AD and Viale, A and Harris, RS and Solit, DB and Weigelt, B and Reis-Filho, JS and King, TA}, title = {Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {25}, number = {2}, pages = {674-686}, pmid = {30185420}, issn = {1557-3265}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Breast Carcinoma In Situ/*genetics/*pathology ; Carcinoma, Lobular/*genetics/*pathology ; Clonal Evolution/*genetics ; Disease Progression ; *Genetic Heterogeneity ; *Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Neoplasm Metastasis ; Neoplasm Staging ; Tumor Burden ; Exome Sequencing ; }, abstract = {PURPOSE: Lobular carcinoma in situ (LCIS) is a preinvasive lesion of the breast. We sought to define its genomic landscape, whether intralesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers.Experimental Design: We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24 patients [9 ductal carcinomas in situ (DCIS), 13 invasive lobular carcinomas (ILC), and 5 invasive ductal carcinomas (IDC)]. Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic trees were defined using validated computational methods.<br><br>RESULTS: WES of 43 LCIS lesions revealed a genomic profile similar to that previously reported for ILCs, with CDH1 mutations present in 81% of the lesions. Forty-two percent (18/43) of LCIS were found to be clonally related to synchronous DCIS and/or ILCs, with clonal evolutionary patterns indicative of clonal selection and/or parallel/branched progression. Intralesion genetic heterogeneity was higher among LCIS clonally related to DCIS/ILC than in those nonclonally related to DCIS/ILC. A shift from aging to APOBEC-related mutational processes was observed in the progression from LCIS to DCIS and/or ILC in a subset of cases.<br><br>CONCLUSIONS: Our findings support the contention that LCIS has a repertoire of somatic genetic alterations similar to that of ILCs, and likely constitutes a nonobligate precursor of breast cancer. Intralesion genetic heterogeneity is observed in LCIS and should be considered in studies aiming to develop biomarkers of progression from LCIS to more advanced lesions.}, }
@article {pmid30185184, year = {2018}, author = {Du, JJ and Chen, YF and Peng, Y and Li, XJ and Ma, W}, title = {Calcification of the intervertebral disc and ossification of posterior longitudinal ligament in children.}, journal = {BMC musculoskeletal disorders}, volume = {19}, number = {1}, pages = {316}, pmid = {30185184}, issn = {1471-2474}, support = {81501929//National Natural Science Foundation of China/ ; No. Z161100000116057//Beijing Municipal Science and Technology Commission/ ; }, mesh = {Adolescent ; Calcinosis/*complications/*diagnostic imaging/therapy ; Cervical Vertebrae/*diagnostic imaging ; Child ; Conservative Treatment ; Humans ; Male ; Neck Pain/diagnostic imaging/etiology/therapy ; Ossification of Posterior Longitudinal Ligament/*complications/*diagnostic imaging/therapy ; }, abstract = {BACKGROUND: IDC in children, first reported by Baron in 1924, is very rare. OPLL of the cervical spine mainly affect people ages 50-70 years. The coexistence of IDC and OPLL in children is very rare, only six cases with 3 to 24 months' follow-up were reported to date.<br><br>CASE PRESENTATION: A 6-year-old boy presented with complains of neck pain at July 2007. The boy was treated by conservative treatment and observed up for 9&#xa0;years. Neck pain greatly improved after a one-month conservative treatment and never recur. Laboratory tests revealed elevated ESR and CRP at admission and found nothing abnormal at 19-month and 9-year follow-up. Computed tomography and magnetic resonance imaging revealed IDC at C2/3, C3/4 and OPLL at C3/4 at admission and found minor calcification at C2/3 remained but calcification at C3/4 and OPLL at C3/4 completely disappeared at 19-month and 9-year follow-up. Nineteen months after initial diagnosis, restoration of T2-weighted signal intensity of C2/3 and C3/4 discs was observed through MRI. Loss of T2-weighted signal intensity of C2/3 disc and decrease of T2-weighted signal intensity of C3/4 disc was observed at 9-year follow-up.<br><br>CONCLUSIONS: IDC with OPLL in children is very rare. Conservative treatments are recommended with affirmative short-term and long-term clinical effects. More intensive observation with long-term follow-ups may be needed to warrant the clinical effects.}, }
@article {pmid30183588, year = {2018}, author = {Abdalla, AS and Lazarevska, A and Omer, MM and Tan, E and Asaad, A and Sathananthan, S}, title = {Metastatic Breast Cancer to the Cervix Presenting with Abnormal Vaginal Bleeding During Chemotherapy: A Case Report and Literature Review.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {113}, number = {4}, pages = {564-570}, doi = {10.21614/chirurgia.113.4.564}, pmid = {30183588}, issn = {1221-9118}, mesh = {Antineoplastic Agents/*adverse effects ; Breast Neoplasms/complications/drug therapy/*secondary ; Female ; Humans ; Uterine Cervical Neoplasms/complications/*secondary ; Uterine Hemorrhage/chemically induced/*etiology ; }, abstract = {The most common sites of invasive breast cancer metastasis are the lungs, liver, bones and brain. Less frequent sites include the gastrointestinal tract, pancreas, spleen, thyroid, adrenals, kidneys, heart and female genital tract. The uterus is reported as a rare site for metastasis, and even more so for an isolated metastasis. Other sites of extra-genital sources for uterine metastases include the colon, stomach, pancreas, gallbladder, lung, cutaneous melanoma, urinary bladder and thyroid. The rarity of breast cancer metastasis to the uterine cervix could be explained by the fact that the cervix has a small blood supply and an afferent lymph drainage system alone. It is rare to diagnose a cervical metastasis prior to eliciting the primary breast disease. Invasive lobular carcinoma metastasises to the female reproductive system more frequently than invasive ductal carcinoma. This paper presents a case of breast cancer metastasis to the cervix.}, }
@article {pmid30171046, year = {2019}, author = {Hess, J and Unger, K and Maihoefer, C and Schüttrumpf, L and Wintergerst, L and Heider, T and Weber, P and Marschner, S and Braselmann, H and Samaga, D and Kuger, S and Pflugradt, U and Baumeister, P and Walch, A and Woischke, C and Kirchner, T and Werner, M and Werner, K and Baumann, M and Budach, V and Combs, SE and Debus, J and Grosu, AL and Krause, M and Linge, A and Rödel, C and Stuschke, M and Zips, D and Zitzelsberger, H and Ganswindt, U and Henke, M and Belka, C}, title = {A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {25}, number = {5}, pages = {1505-1516}, doi = {10.1158/1078-0432.CCR-18-0776}, pmid = {30171046}, issn = {1557-3265}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; *Biomarkers, Tumor ; Female ; Head and Neck Neoplasms/*etiology/*mortality/pathology/therapy ; Humans ; Kaplan-Meier Estimate ; Male ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Papillomaviridae ; Papillomavirus Infections/complications ; Prognosis ; Proportional Hazards Models ; *Transcriptome ; Treatment Outcome ; }, abstract = {PURPOSE: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined.<br><br>EXPERIMENTAL DESIGN: We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA-mRNA target network was generated and analyzed.<br><br>RESULTS: For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98-9.88, P < 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40-12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50-6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65-6.04, P < 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88-13.92, P < 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P < 0.001).<br><br>CONCLUSIONS: The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.See related commentary by Clump et al., p. 1441.}, }
@article {pmid30149270, year = {2018}, author = {Yirmiya, K and Djalovski, A and Motsan, S and Zagoory-Sharon, O and Feldman, R}, title = {Stress and immune biomarkers interact with parenting behavior to shape anxiety symptoms in trauma-exposed youth.}, journal = {Psychoneuroendocrinology}, volume = {98}, number = {}, pages = {153-160}, doi = {10.1016/j.psyneuen.2018.08.016}, pmid = {30149270}, issn = {1873-3360}, mesh = {Adolescent ; Adult ; Adverse Childhood Experiences ; Anxiety/*etiology/metabolism/psychology ; Biomarkers/blood ; Child ; Female ; Humans ; Hydrocortisone/analysis ; Hypothalamo-Hypophyseal System ; Immunity, Innate/physiology ; Immunoglobulin A, Secretory ; Male ; Mother-Child Relations/*psychology ; Mothers ; Parenting/*psychology ; Pituitary-Adrenal System ; Saliva/chemistry ; Social Behavior ; Stress Disorders, Post-Traumatic/metabolism ; Stress, Psychological/metabolism ; }, abstract = {The relations between stress, HPA-axis, and the immune system have been extensively studied; however, no study to date addressed the joint contribution of immune and HPA biomarkers to the development of anxiety in youth exposed to chronic trauma as mediated by mother-child interaction patterns. A unique cohort of war-exposed children and their mothers, compared to matched controls, were followed from infancy and the current study reports findings from early adolescence (mean age = 11.66, SD = 1.23; N = 111; exposed = 58 control = 53). Youth and mothers' salivary cortisol (CT) and secretory immunoglobulin (s-IgA) levels were measured three times during a 4-hour lab visit, mother-child interaction patterns were quantified from a joint task, and children's anxiety symptoms diagnosed. Trauma-exposed children had higher levels of CT and s-IgA, exhibited more anxiety symptoms, and showed lower social collaboration with mother during the joint task. Trauma-exposed mothers had higher CT and s-IgA levels and showed less supportive parenting during mother-child interaction. Structural equation modeling defined three bio-behavioral paths by which trauma increases anxiety in youth. While the first path charted a behavioral link from exposure to child anxiety via diminished maternal support, the other two paths described mediated biological paths, one through HPA-axis functioning, the other via the immune system. Paths via the child's HPA and immune system were mediated by the parallel maternal variable. Findings are the first to describe the complex bio-behavioral interplay of stress and immune biomarkers and parenting behavior in shaping to the development of risk and resilience trajectories in youth growing up amidst chronic trauma.}, }
@article {pmid30144784, year = {2018}, author = {Shah, S and Brock, EJ and Jackson, RM and Ji, K and Boerner, JL and Sloane, BF and Mattingly, RR}, title = {Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK/MAPK Activation.}, journal = {Neoplasia (New York, N.Y.)}, volume = {20}, number = {9}, pages = {951-963}, pmid = {30144784}, issn = {1476-5586}, support = {U54 CA193489/CA/NCI NIH HHS/United States ; F31 CA213807/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R25 GM058905/GM/NIGMS NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; R21 CA175931/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Cell Line, Tumor ; Cytoskeleton/metabolism ; Down-Regulation ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; GTPase-Activating Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Immunohistochemistry ; Mitogen-Activated Protein Kinases/metabolism ; Neoplasm Invasiveness ; RNA Interference ; }, abstract = {Diagnosis of breast ductal carcinoma in situ (DCIS) presents a challenge since we cannot yet distinguish those cases that would remain indolent and not require aggressive treatment from cases that may progress to invasive ductal cancer (IDC). The purpose of this study is to determine the role of Rap1Gap, a GTPase activating protein, in the progression from DCIS to IDC. Immunohistochemistry (IHC) analysis of samples from breast cancer patients shows an increase in Rap1Gap expression in DCIS compared to normal breast tissue and IDCs. In order to study the mechanisms of malignant progression, we employed an in vitro three-dimensional (3D) model that more accurately recapitulates both structural and functional cues of breast tissue. Immunoblotting results show that Rap1Gap levels in MCF10.Ca1D cells (a model of invasive carcinoma) are reduced compared to those in MCF10.DCIS (a model of DCIS). Retroviral silencing of Rap1Gap in MCF10.DCIS cells activated extracellular regulated kinase (ERK) mitogen-activated protein kinase (MAPK), induced extensive cytoskeletal reorganization and acquisition of mesenchymal phenotype, and enhanced invasion. Enforced reexpression of Rap1Gap in MCF10.DCIS-Rap1GapshRNA cells reduced Rap1 activity and reversed the mesenchymal phenotype. Similarly, introduction of dominant negative Rap1A mutant (Rap1A-N17) in DCIS-Rap1Gap shRNA cells caused a reversion to nonmalignant phenotype. Conversely, expression of constitutively active Rap1A mutant (Rap1A-V12) in noninvasive MCF10.DCIS cells led to phenotypic changes that were reminiscent of Rap1Gap knockdown. Thus, reduction of Rap1Gap in DCIS is a potential switch for progression to an invasive phenotype. The Graphical Abstract summarizes these findings.}, }
@article {pmid30124442, year = {2018}, author = {Clement, Z and McLeay, W and Hoffmann, C and Shin, P and Kiu, A and Eaton, M}, title = {Role of radiotherapy in women over the age of 65 after breast conserving surgery for breast cancer: A 5-year retrospective study.}, journal = {Breast disease}, volume = {37}, number = {4}, pages = {197-205}, doi = {10.3233/BD-180340}, pmid = {30124442}, issn = {1558-1551}, mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Female ; Humans ; Mammography ; Mastectomy, Segmental/*statistics &amp; numerical data ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND/OBJECTIVE: This study aimed to analyse the local recurrence (LR) and breast cancer related mortality (BCRM) in older women who underwent breast-conserving surgery (BCS) with and without adjuvant radiotherapy (XRT).<br><br>METHODS: This retrospective study included a total of 299 women who underwent BCS for early breast carcinoma, between the years of 2007 and 2011. Predictive risk factors, local recurrence (LR) and breast cancer related mortality (BCRM) were assessed with a mean follow-up period of 84 months.<br><br>RESULTS: Women over the age of 65 in the XRT and No-XRT groups showed similar incidence of LR (5.8% vs 5%, p =&#xa0;0.838). Women over 65 years old with XRT had a higher rate of BCRM (5.8% vs 0%, p =&#xa0;0.05). Resection margins >5&#xa0;mm had a lower rate of BCRM (HR 0.395, p =&#xa0;0.05). Women under the age of 65, invasive ductal carcinoma, grade-3 tumours, HER-2 positive, triple negative, lympho-vascular invasion, axillary lymph node positivity, high breast density on mammography were associated with increased risk of LR and BCRM.<br><br>CONCLUSIONS: XRT in women over the age of 65 did not decrease the risk of LR. Adjuvant XRT in older women should be offered to selective patients with high risk patient and tumour factors.}, }
@article {pmid30110913, year = {2018}, author = {Liu, S and Cruz, ID and Ramos, CC and Taleon, P and Ramasamy, R and Shah, J}, title = {Pilot Study of Immunoblots with Recombinant Borrelia burgdorferi Antigens for Laboratory Diagnosis of Lyme Disease.}, journal = {Healthcare (Basel, Switzerland)}, volume = {6}, number = {3}, pages = {}, pmid = {30110913}, issn = {2227-9032}, abstract = {Accurate laboratory diagnosis of Lyme disease (Lyme borreliosis), caused by the spirochete Borrelia burgdorferi (BB), is difficult and yet important to prevent serious disease. The US Centers for Disease Control and Prevention (CDC) presently recommends a screening test for serum antibodies followed by confirmation with a more specific Western blot (WB) test to detect IgG and IgM antibodies against antigens in whole cell lysates of BB. Borrelia species related to BB cause tick-borne relapsing fever (TBRF). TBRF is increasingly recognized as a health problem in the US and occurs in areas where Lyme disease is prevalent. The two groups of Borrelia share related antigens. We have developed a modified WB procedure termed the Lyme immunoblots (IBs) using recombinant antigens from common strains and species of the BB sensu lato complex for serological diagnosis of Lyme disease. A reference collection of 178 sera from 26 with and 152 patients without Lyme disease were assessed by WB and IB in a blinded manner using either criteria for positive antibody reactions recommended by the CDC or criteria developed in-house. The sensitivity, specificity, positive and negative predictive values obtained with the reference sera suggest that the Lyme IB is superior to the Lyme WB for detection of specific antibodies in Lyme disease. The Lyme IB showed no significant reaction with rabbit antisera produced against two Borrelia species causing TBRF in the US, suggesting that the Lyme IB may be also useful for excluding TBRF.}, }
@article {pmid30110018, year = {2018}, author = {Yildirim, N and Bahceci, A}, title = {Use of pertuzumab and trastuzumab during pregnancy.}, journal = {Anti-cancer drugs}, volume = {29}, number = {8}, pages = {810-813}, doi = {10.1097/CAD.0000000000000658}, pmid = {30110018}, issn = {1473-5741}, mesh = {Adult ; Antibodies, Monoclonal, Humanized/administration &amp; dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/*therapeutic use ; Breast Neoplasms/*drug therapy ; Docetaxel/administration &amp; dosage/adverse effects ; Female ; Fetus/*drug effects ; Humans ; Oligohydramnios/*chemically induced ; Pregnancy ; Pregnancy Complications, Neoplastic/*drug therapy ; Trastuzumab/administration &amp; dosage/adverse effects ; Young Adult ; }, abstract = {Trastuzumab and pertuzumab are monoclonal antibodies used for the treatment of breast cancer. Until now, there have been no reports on the use of pertuzumab during pregnancy and on its potential effects on the fetus. Herein, we present a breast cancer patient who received trastuzumab and pertuzumab treatment during the first 20 weeks of pregnancy. This 22-year-old patient initially diagnosed with invasive ductal carcinoma of the breast was found to be negative for estrogen receptor and progesterone receptor and positive for human epidermal growth factor receptor in the immunohistochemical examination. At the time of diagnosis, she had metastatic lesions and a protocol of docetaxel, trastuzumab, pertuzumab, q21, and zolendronic acid 4 mg every month was started. Following six courses of therapy, she had near-complete response, and, after administration of the same course of treatment for two additional cycles, treatment with pertuzumab plus trastuzumab was continued. While she was being followed-up with remission, a 20-week pregnancy was detected. A fetal ultrasound examination showed oligohydramnios and right renal agenesis. Treatment was stopped, and the fetus was monitored. After 7 weeks of follow-up, fetal growth retardation and anhydramnios were detected. The pregnancy was terminated. Fetal autopsy showed no urinary system pathology, but macroscopic and microscopic hyperplasia of the right adrenal gland was identified. Concomitant use of pertuzumab and trastuzumab during pregnancy may be associated with an unresolved oligohydramnios and/or anhydramnios risk. Extreme caution should be used when these monoclonal antibodies are administered during pregnancy.}, }
@article {pmid30101014, year = {2018}, author = {Yan, L and Dong, X and Xu, H and Huang, J and Wang, W and Huang, L and Wan, Q and Gong, J}, title = {Paraneoplastic cerebellar degeneration associated with breast cancer: A case report and review of the literature.}, journal = {Molecular and clinical oncology}, volume = {9}, number = {2}, pages = {163-167}, pmid = {30101014}, issn = {2049-9450}, abstract = {Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication of cancer characterized by rapid development of cerebellar ataxia. We herein present a case of a 67-year-old female patient with PCD caused by breast cancer. The patient presented with progressively worsening cerebellar deficits that had been misdiagnosed for several months prior to the identification of the anti-Yo autoantibodies in the serum. A whole-body positron emission tomography/computed tomography scan revealed a lesion in the lower outer quadrant of the left breast with slightly increased metabolism. On mammography, a lobulated high-density mass was identified in the left breast. The patient underwent left breast lumpectomy and the histological examination confirmed the presence of an invasive ductal carcinoma. After breast surgery, the patient exhibited marked neurological improvement at the 12-month follow-up. Therefore, it is crucial that clinicians include paraneoplastic neurological syndromes in the differential diagnosis of neurological disorders. The detection of characterized onconeural antibodies in the serum or cerebrospinal fluid may provide guidance in the search for an underlying tumor.}, }
@article {pmid30096623, year = {2018}, author = {Lahav-Kadmiel, Z and Brunstein-Klomek, A}, title = {Bullying victimization and depressive symptoms in adolescence: The moderating role of parent-child conflicts among boys and girls.}, journal = {Journal of adolescence}, volume = {68}, number = {}, pages = {152-158}, doi = {10.1016/j.adolescence.2018.07.014}, pmid = {30096623}, issn = {1095-9254}, mesh = {Adolescent ; Bullying/*psychology ; Child ; Crime Victims/*psychology ; Depression/*etiology ; Family Conflict/*psychology ; Female ; Humans ; Israel ; Male ; *Parent-Child Relations ; Self Report ; Sex Factors ; }, abstract = {INTRODUCTION: The association between bullying victimization and depressive symptoms has been studied extensively over the years. Among the variables studied as having an impact on this association were different characteristics of the parent-child relationship. The current study was the first to specifically examine parent-child conflicts as a moderator in the association between victimization and depressive symptoms among adolescents. In addition, it was the first to examine the roles of the child and parent's gender in this moderation.<br><br>METHODS: 505 7th-9th graders from two schools in two different cities across Israel (mean age&#x202f;=&#x202f;12.736, SD&#x202f;=&#x202f;0.8154) participated in this study. 223 (44.2%) of the participants were male. The participants filled out a battery of self-report questionnaires assessing the different study's variables.<br><br>RESULTS: Significant gender differences were found: among girls, the association between bullying victimization and depressive symptoms was stronger when the level of parent-child conflicts was high, while among boys, it was stronger when the level of conflicts was low.<br><br>CONCLUSIONS: Our results indicate that the psychological outcomes for victims depend on their relationship with their parents. Bullying intervention programs should include the victims' parents. Furthermore, intervention programs should be designed to fit the different needs of girls and boys.}, }
@article {pmid30096287, year = {2018}, author = {Ngara, M and Palmkvist, M and Sagasser, S and Hjelmqvist, D and Björklund, &#xc5;K and Wahlgren, M and Ankarklev, J and Sandberg, R}, title = {Exploring parasite heterogeneity using single-cell RNA-seq reveals a gene signature among sexual stage Plasmodium falciparum parasites.}, journal = {Experimental cell research}, volume = {371}, number = {1}, pages = {130-138}, doi = {10.1016/j.yexcr.2018.08.003}, pmid = {30096287}, issn = {1090-2422}, mesh = {Erythrocytes/*parasitology/pathology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Ontology ; Genetic Heterogeneity ; Humans ; Life Cycle Stages/*genetics ; Molecular Sequence Annotation ; Plasmodium falciparum/*genetics/growth &amp; development/metabolism ; Protozoan Proteins/*genetics/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis ; *Transcriptome ; }, abstract = {The malaria parasite has a complex lifecycle, including several events of differentiation and stage progression, while actively evading immunity in both its mosquito and human hosts. Important parasite gene expression and regulation during these events remain hidden in rare populations of cells. Here, we combine a capillary-based platform for cell isolation with single-cell RNA-sequencing to transcriptionally profile 165 single infected red blood cells (iRBCs) during the intra-erythrocytic developmental cycle (IDC). Unbiased analyses of single-cell data grouped the cells into eight transcriptional states during IDC. Interestingly, we uncovered a gene signature from the single iRBC analyses that can successfully discriminate between developing asexual and sexual stage parasites at cellular resolution, and we verify five, previously undefined, gametocyte stage specific genes. Moreover, we show the capacity of detecting expressed genes from the variable gene families in single parasites, despite the sparse nature of data. In total, the single parasite transcriptomics holds promise for molecular dissection of rare parasite phenotypes throughout the malaria lifecycle.}, }
@article {pmid30094720, year = {2018}, author = {Hashemi-Sadraei, N and Müller-Greven, GM and Abdul-Karim, FW and Ulasov, I and Downs-Kelly, E and Burgett, ME and Lauko, A and Qadan, MA and Weil, RJ and Ahluwalia, MS and Du, L and Prayson, RA and Chao, ST and Budd, TG and Barnholtz-Sloan, J and Nowacki, AS and Keri, RA and Gladson, CL}, title = {Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.}, journal = {Journal of neuro-oncology}, volume = {140}, number = {2}, pages = {237-248}, pmid = {30094720}, issn = {1573-7373}, support = {R01 CA175120/CA/NCI NIH HHS/United States ; R01-CA152883//National Institutes of Health/ ; R01-CA175120//National Institutes of Health/ ; RPC 2010-1070-R1//Cleveland Clinic Foundation/ ; }, mesh = {Adult ; Aged ; Autophagy-Related Proteins ; Biomarkers, Tumor/metabolism ; Brain/metabolism/pathology ; Brain Neoplasms/*metabolism/mortality/*secondary/therapy ; Breast Neoplasms/metabolism/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology/therapy ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Meta-Analysis as Topic ; Microtubule-Associated Proteins/*metabolism ; Middle Aged ; Protein-Tyrosine Kinases/*metabolism ; RNA, Messenger/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer.<br><br>METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining.<br><br>RESULTS: LC3-puncta[+] tumor cells and FIP200/Atg17 expression were detected in greater than 90% of brain metastases but there were considerable intra- and inter-tumor differences in expression levels. High numbers of LC3-puncta[+] tumor cells in brain metastases correlated with a significantly shorter survival time in triple-negative breast cancer. FIP200/Atg17 protein levels were significantly higher in metastases that subsequently recurred following therapy. The percentages of LC3 puncta[+] tumor cells and FIP200/Atg17 protein expression levels, but not mRNA levels, were significantly higher in metastases than primary-BC. Meta-analysis of gene expression datasets revealed a significant correlation between higher FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free survival.<br><br>CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.}, }
@article {pmid30094484, year = {2018}, author = {Tadros, AB and Wen, HY and Morrow, M}, title = {Breast Cancers of Special Histologic Subtypes Are Biologically Diverse.}, journal = {Annals of surgical oncology}, volume = {25}, number = {11}, pages = {3158-3164}, pmid = {30094484}, issn = {1534-4681}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA008748//NIH/NCI Cancer Center Support Grant/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology/surgery ; Carcinoma, Lobular/genetics/metabolism/*pathology/surgery ; Female ; Follow-Up Studies ; Gene Expression Profiling/*methods ; Genomics ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {BACKGROUND/OBJECTIVE: Cancers classified as "special histologic subtypes" are felt to have a good prognosis. We used the 21-gene Oncotype DX Breast Recurrence Score[®] multigene assay to examine prognostic variation within special histologic subtypes. We also examined the Recurrence Score[®] (RS) distribution among the more common ductal (IDC) and lobular (ILC) cancers.<br><br>METHODS: 610,350 tumor specimens examined in the Genomic Health clinical laboratory from 2/2004 to 8/2017 were included. Specimen histology was classified centrally using a single H&amp;E slide and World Health Organization criteria. RS distribution (low&#x2009;<&#x2009;18, intermediate 18-30, and high&#x2009;&#x2265;&#x2009;31) was compared among histologic subtypes.<br><br>RESULTS: Median patient age was 60&#xa0;years (IQR 51-67); 80% were node negative. Most patients had low RS results (59.2%); only 9.5% had high results. The lowest mean RS was seen in the papillary subtype (11); the highest in the IDC group (18.4). Mean RS for all special subtypes was lower than that of IDC patients. When the high RS threshold was decreased from 31 to 25, as used in the TAILORx and RxPONDER trials, the number of high RS-result patients increased from 9.5% to 16.8%. Patients with ILC had a lower mean RS result than patients with IDC, 16.5 versus 18.4.<br><br>CONCLUSION: There is substantial diversity in predicted prognosis among patients with cancers classified as special histologic subtypes, with 12-25% having intermediate RS results and 0.5-9% having high RS results. Pending further definition of the role of chemotherapy for patients with intermediate RS results by TAILORx and RxPONDER, the RS result may help to inform systemic therapy decisions in these patients.}, }
@article {pmid30087348, year = {2018}, author = {Senyilmaz-Tiebe, D and Pfaff, DH and Virtue, S and Schwarz, KV and Fleming, T and Altamura, S and Muckenthaler, MU and Okun, JG and Vidal-Puig, A and Nawroth, P and Teleman, AA}, title = {Dietary stearic acid regulates mitochondria in vivo in humans.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {3129}, pmid = {30087348}, issn = {2041-1723}, support = {SFB1036//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; RG/12/13/29853/BHF_/British Heart Foundation/United Kingdom ; MC_UU_12012/2/MRC_/Medical Research Council/United Kingdom ; SFB1118//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; G0802051/MRC_/Medical Research Council/United Kingdom ; 724286//EC | European Research Council (ERC)/International ; MC_UU_00014/5/MRC_/Medical Research Council/United Kingdom ; BB/H002731/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; G0400192/MRC_/Medical Research Council/United Kingdom ; MC_G0802535/MRC_/Medical Research Council/United Kingdom ; MC_UU_12012/5/MRC_/Medical Research Council/United Kingdom ; RG/18/7/33636/BHF_/British Heart Foundation/United Kingdom ; G0600717/MRC_/Medical Research Council/United Kingdom ; MC_UU_00014/2/MRC_/Medical Research Council/United Kingdom ; MRC_MC_UU_12012/2//Medical Research Council (MRC)/International ; RG/12/13/29853//BHF Centre of Research Excellence, Oxford (BHF Centre of Research Excellence in Oxford)/International ; }, mesh = {Adult ; Beverages ; Carnitine/analogs &amp; derivatives/blood ; Case-Control Studies ; Cross-Over Studies ; Diabetes Mellitus/*metabolism ; Diet ; Fatty Acids/metabolism ; Female ; Humans ; Male ; Middle Aged ; Mitochondria/*metabolism ; Mitochondrial Dynamics ; Musa ; Oxygen/chemistry ; Stearic Acids/*metabolism ; }, abstract = {Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.}, }
@article {pmid30085937, year = {2018}, author = {Zhou, T and Xu, D and Tang, B and Ren, Y and Han, Y and Liang, G and Wang, J and Wang, L}, title = {Expression of programmed death ligand-1 and programmed death-1 in samples of invasive ductal carcinoma of the breast and its correlation with prognosis.}, journal = {Anti-cancer drugs}, volume = {29}, number = {9}, pages = {904-910}, pmid = {30085937}, issn = {1473-5741}, mesh = {Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/*genetics ; Carcinoma, Ductal, Breast/genetics/*pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/*drug effects ; Risk Factors ; Triple Negative Breast Neoplasms/genetics/*pathology ; }, abstract = {The aim of the current study is to investigate programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expressions and to analyze the relationship between the expression of PD-L1 and PD-1 proteins and the molecular type, clinicopathological factors, and prognosis of invasive ductal carcinoma. We enrolled 136 patients with invasive ductal carcinoma of the breast. The expression of PD-L1 in tumor cells and that of PD-1 on paratumor-infiltrating immune cells was detected by immunohistochemistry, and the data were analyzed using SPSS software. The positive expression rates of PD-L1 and PD-1 in triple-negative breast cancer (TNBC) were 47.8 and 43.5%, which were higher than those of other subtypes (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 (P<0.05). The expression of PD-1 in the tumor-infiltrating immune cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 and the histological grade (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of PD-1 in paratumor-infiltrating immune cells (P<0.001). The expression of PD-L1 in tumor cells was found to be an independent prognostic risk factor with the progression-free survival rate for breast invasive ductal carcinoma (P=0.003). These results indicate that PD-L1 and PD-1 were highly expressed in TNBC which suggests that patients with TNBC may benefit from targeted immune therapies to a greater degree than patients with other subtypes. PD-L1 expression is an independent risk factor for breast invasive ductal carcinoma and expression of PD-L1 is expected to be a prognostic factor for breast cancer.}, }
@article {pmid30078647, year = {2018}, author = {Deipolyi, AR and Riedl, CC and Bromberg, J and Chandarlapaty, S and Klebanoff, CA and Sofocleous, CT and Yarmohammadi, H and Brody, LA and Boas, FE and Ziv, E}, title = {Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study.}, journal = {Journal of vascular and interventional radiology : JVIR}, volume = {29}, number = {9}, pages = {1226-1235}, pmid = {30078647}, issn = {1535-7732}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/genetics/pathology ; Clinical Decision-Making ; DNA Mutational Analysis ; Embolization, Therapeutic/adverse effects/*methods ; Female ; Gene Expression Profiling ; Humans ; Liver Neoplasms/*diagnostic imaging/genetics/secondary/*surgery ; Middle Aged ; *Mutation ; New York City ; Patient Selection ; Phosphatidylinositol 3-Kinases/*genetics ; Pilot Projects ; *Positron Emission Tomography Computed Tomography ; Precision Medicine ; Predictive Value of Tests ; Preliminary Data ; Radiopharmaceuticals/*administration &amp; dosage/adverse effects ; Retrospective Studies ; Risk Factors ; Signal Transduction/genetics ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes.<br><br>MATERIALS AND METHODS: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq &#xb1; 1.8) between January 2011 and September 2017 after receiving &#x2265; 3 lines of chemotherapy. Twenty-four underwent genetic profiling with MSK-IMPACT or Sequenom; 26 had positron-emission tomography (PET)/CT imaging before and after treatment. Survival after the first radioembolization and 2-4-month PET/CT imaging response were assessed. Laboratory and imaging features were assessed to determine variables predictive of outcomes. Unpaired Student t tests and Fisher exact tests were used to compare responders and nonresponders categorized by changes in fluorodeoxyglucose avidity. Kaplan-Meier survival analysis was used to determine the impact of predictors on survival after radioembolization.<br><br>RESULTS: Median survival after radioembolization was 11 months (range, 1-49 mo). Most patients (18 of 26; 69%) had complete or partial response based on changes in fluorodeoxyglucose avidity. Imaging response was associated with longer survival (P&#xa0;= .005). Whereas 100% of patients with PI3K pathway mutations showed an imaging response, only 45% of wild-type patients showed a&#xa0;response (P&#xa0;= .01). Median survival did not differ between PI3K pathway wild-type (10.9 mo) and mutant (undefined) patients (P&#xa0;=&#xa0;.50).<br><br>CONCLUSIONS: These preliminary data suggest that genomic profiling may predict which patients with metastatic breast cancer benefit most from radioembolization. PI3K pathway mutations are associated with improved imaging response, which is associated with longer survival.}, }
@article {pmid30071094, year = {2018}, author = {Hong, JH and Ko, YH and Kang, K}, title = {RNA variant identification discrepancy among splice-aware alignment algorithms.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0201822}, pmid = {30071094}, issn = {1932-6203}, mesh = {*Algorithms ; Breast/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Computational Biology/*methods ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; RNA/metabolism ; *RNA Splicing ; Sequence Alignment/*methods ; Sequence Analysis, RNA/*methods ; }, abstract = {Next-generation sequencing (NGS) techniques have been generating various molecular maps, including transcriptomes via RNA-seq. Although the primary purpose of RNA-seq is to quantify the expression level of known genes, RNA variants are also identifiable. However, care must be taken to account for RNA's dynamic nature. In this study, we evaluated the following popular splice-aware alignment algorithms in the context of RNA variant-calling analysis: HISAT2, STAR, STAR (two-pass mode), Subread, and Subjunc. For this, we performed RNA-seq with ten pieces of invasive ductal carcinoma from breast tissue and three pieces of adjacent normal tissue from a single patient. These RNA-seq data were used to evaluate the performance of splice-aware aligners. Surprisingly, the number of common potential RNA editing sites (pRESs) identified by all alignment algorithms was less than 2% of the total. The main cause of this difference was the mapped reads on the splice junctions. In addition, the RNA quality significantly affected the outcome. Therefore, researchers must consider these experimental and bioinformatic features during RNA variant analysis. Further investigations of common pRESs discovered that BDH1, CCDC137, and TBC1D10A transcripts contained a single non-synonymous RNA variant that was unique to breast cancer tissue compared to adjacent normal tissue; thus, further clinical validation is required.}, }
@article {pmid30066839, year = {2018}, author = {Zhu, X and Zeng, Z and Qiu, D and Chen, J}, title = {Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c‑Fos and ATP6V0D2.}, journal = {International journal of molecular medicine}, volume = {42}, number = {4}, pages = {2071-2079}, pmid = {30066839}, issn = {1791-244X}, mesh = {Cell Transdifferentiation/*immunology ; Dendritic Cells/*immunology/pathology ; Humans ; Osteoclasts/*immunology/pathology ; Proto-Oncogene Proteins c-fos/*immunology ; Receptor Activator of Nuclear Factor-kappa B/*immunology ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Signal Transduction/*immunology ; T-Lymphocytes/*immunology/pathology ; Vacuolar Proton-Translocating ATPases/*immunology ; }, abstract = {Osteoimmunological studies have revealed that T cells exert a powerful impact on the formation and activity of osteoclasts and bone remodeling. Evidence demonstrates that immature dendritic cells (iDCs) are more efficient transdifferentiating into osteoclasts (OCs) than monocytes. However, whether Vγ9Vδ2 T (γδ T) cells stimulate or inhibit iDC transdifferentiation into OCs has never been reported. The aim of the present study was to investigate the effects of γδ T cells on this transdifferentiation process. γδ T cells and iDCs were isolated from the peripheral blood of healthy volunteers separately and were co‑cultured with Transwelll inserts, with γδ T cells in the upper chamber and iDCs in the lower chamber. IDCs were treated with macrophage‑colony stimulating factor and receptor activator of nuclear factor‑κB (RANK) ligand. Tartrate resistant acid phosphatase (TRAP) assay and dentine resorption assay were performed to detect OC formation and their resorption capacity, respectively. The mRNA expression of OCs was examined using a microarray and real time‑quantitative polymerase chain reaction to trace the changes during iDC transdifferentiation into OCs. The results demonstrated that γδ T cells significantly inhibited the generation of the TRAP‑positive OCs from iDCs and their resorption capacity. The microarray analysis identified decreased expression level of Fos proto‑oncogene AP‑1 transcription factor subunit (c‑Fos), ATPase H+ transporting V0 subunit d (ATP6V0D2) and cathepsin K when iDCs were co‑cultured with γδ T cells. These genes are associated with OC differentiation, indicating that γδ T cells suppressed iDCs osteoclastogenesis by downregulation of the RANK/c‑Fos/ATP6V0D2 signaling pathway. The present findings provide novel insights into the interactions between human γδ T cells and iDCs, and demonstrate that γδ T cells are capable of inhibiting OC formation and their activity via downregulation of genes associated with OC differentiation.}, }
@article {pmid30066480, year = {2018}, author = {Dodson, A and Parry, S and Ibrahim, M and Bartlett, JM and Pinder, S and Dowsett, M and Miller, K}, title = {Breast cancer biomarkers in clinical testing: analysis of a UK national external quality assessment scheme for immunocytochemistry and in situ hybridisation database containing results from 199 300 patients.}, journal = {The journal of pathology. Clinical research}, volume = {4}, number = {4}, pages = {262-273}, pmid = {30066480}, issn = {2056-4538}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*diagnosis/genetics/metabolism/pathology ; Databases, Factual ; Estrogen Receptor alpha/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Ireland ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; United Kingdom ; }, abstract = {We describe a collated data set of results from clinical testing of breast cancers carried out between 2009 and 2016 in the United Kingdom and Republic of Ireland. More than 199 000 patient biomarker data sets, together with clinicopathological parameters were collected. Our analyses focused on human epidermal growth factor receptor-2 (HER2), oestrogen receptor (ER) and progesterone receptor (PR), with the aim of the study being to provide robust confirmatory evidence on known associations in these biomarkers and to uncover new data on previously undescribed or unconfirmed associations, thus strengthening the evidence-base in clinical breast cancer testing. Overall, 13.1% of tumours were HER2-positive; 10.6% in ER-positive tumours, and 25.5% in ER-negative tumours. Higher rates of HER2 positivity were significantly associated with patient age <56 years versus age ≥56 years, symptomatic versus screen-detected tumours, testing of involved axillary node versus primary breast cancer, invasive ductal carcinoma (not otherwise specified) versus other histological types, higher histological grade, increasing tumour size, increasing nodal involvement, ER-negative versus ER-positive tumour status, PR-negative versus PR-positive tumour status. Where ER status was known, 82.7% of tumours were ER-positive; 80.9% in women age <56 years, and 83.6% in those age ≥56 years (ER-positive cut-off ≥1.0% positive tumour cells or equivalent). Where PR status was known, 64.9% of tumours were PR-positive; 65.8% in women age <56 years, and 64.4% in women age ≥56 years (PR-positive cut off ≥10.0% or equivalent). These analyses of clinical test results provide contemporary benchmarking data for HER2, ER and PR positive rates.}, }
@article {pmid30063890, year = {2018}, author = {Papadopoulos, EI and Papachristopoulou, G and Ardavanis, A and Scorilas, A}, title = {A comprehensive clinicopathological evaluation of the differential expression of microRNA-331 in breast tumors and its diagnostic significance.}, journal = {Clinical biochemistry}, volume = {60}, number = {}, pages = {24-32}, doi = {10.1016/j.clinbiochem.2018.07.008}, pmid = {30063890}, issn = {1873-2933}, mesh = {Adenofibroma/diagnosis/*genetics/pathology ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Carcinoma, Lobular/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; MicroRNAs/*genetics ; Prognosis ; Real-Time Polymerase Chain Reaction ; }, abstract = {OBJECTIVE: MicroRNA-331 (miR-331) has shown regulatory activity against several genes whose expression has been claimed to be deregulated in breast tumors, including that of epidermal growth factor receptor 2 (HER2). Herein, the clinical value of miR-331 expression was investigated by analyzing its levels in breast benign and malignant tumors.<br><br>METHODS: The expression levels of miR-331 were quantified via real-time PCR in 130 malignant and 66 benign breast tissue specimens collected after surgical resection of primary tumors. The generated data were analyzed by applying several statistical tests in order to examine the relationship of miR-331 expression with various established clinicopathological features and survival data of patients.<br><br>RESULTS: Our data showed that miR-331 was overexpressed in malignant breast tumors compared to their benign counterparts both overall (P&#x202f;=&#x202f;0.026) and individually when the subgroups of fibroadenoma and invasive ductal carcinoma were analyzed with each other (P&#x202f;=&#x202f;0.001). ROC curve analysis confirmed the diagnostic value of these variations, providing an AUC value equal to 0.597 (P&#x202f;=&#x202f;0.026) and 0.663 (P&#x202f;=&#x202f;0.001), respectively. Furthermore, miR-331 levels were elevated (P&#x202f;=&#x202f;0.026) in ductal cancerous specimens compared to the lobular ones but failed to correlate with other clinicopathological features or survival data of the breast cancer patients.<br><br>CONCLUSIONS: Our results provide evidence that miR-331 levels might provide valuable information regarding the differential diagnosis of benign and malignant breast tumors but present no prognostic value for breast cancer.}, }
@article {pmid30060783, year = {2018}, author = {Lateef, F and Jamal, S and Nasir, S}, title = {Her-2/neu Oncogene Amplification by Fluorescence In Situ Hybridization and Protein Overexpression on Immunohistochemistry in Breast Cancer.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {28}, number = {8}, pages = {581-585}, doi = {10.29271/jcpsp.2018.08.581}, pmid = {30060783}, issn = {1681-7168}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/*pathology ; Carcinoma, Lobular/*genetics/metabolism/*pathology ; Cross-Sectional Studies ; DNA, Neoplasm/analysis ; Female ; *Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence/*methods ; Middle Aged ; Receptor, ErbB-2/*genetics/metabolism ; }, abstract = {OBJECTIVE: To investigate the concordance and discordance between the test results of Her-2/neu by immunohisto-chemistry (IHC) and flourescence In Situ hybridization (FISH) in breast cancer cases.<br><br>STUDY DESIGN: Descriptive cross-sectional study.<br><br>PLACE AND DURATION OF STUDY: Department of Histopathology, Dr. Ziauddin Hospital, Karachi, from 2011 to 2016.<br><br>METHODOLOGY: Forty-three specimens of invasive ductal carcinoma of breast were evaluated for grade and Her-2/neu status using IHC and FISH methods. Concordance and discordance between their results was determined.<br><br>RESULTS: There is 100% concordance between FISH and IHC in cases scoring 0, 1+ (negative) and 3+ (positive) immunostaining. Tumour cases scoring 2+ immunostaining showed amplification in 69.2% cases. All grade-I tumours were non-amplified on FISH, while most of the grade-III tumours showed Her-2/neu amplification on FISH. There is significant association of Her-2/neu IHC with tumour grade and FISH (p<0.05). A fairly high proportion i.e. 69.7% of cases showed Her-2/neu gene amplification. There was high concordance between Her-2/neu testing on IHC and FISH, (Kappa co-efficient 0.466, p <0.001).<br><br>CONCLUSION: Her-2/neu amplification increases with increasing grade of breast cancer. A high proportion of Her-2/neu gene amplified cases indicates aggressive disease in that area and need for FISH testing on large scale, which is the gold standard for equivocal cases on immunohistochemistry.}, }
@article {pmid30051683, year = {2018}, author = {Solanki, R and Agrawal, N and Ansari, M and Jain, S and Jindal, A}, title = {COX-2 Expression in Breast Carcinoma with Correlation to Clinicopathological Parameters.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {19}, number = {7}, pages = {1971-1975}, pmid = {30051683}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Cyclooxygenase 2/*metabolism ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Prognosis ; }, abstract = {Objective: Breast carcinoma is the most common malignant tumor and the leading cause of carcinoma deaths in women. Its etiology is multifactorial, implicating reproductive factors, hormonal imbalances and genetic predispositions. Studies have shown that Cycloxygenase-2 (COX-2) plays an important role in the carcinogenesis and increased expression has been regarded as a poor prognostic factor. The objective of our study is 1. To study COX-2 expression in normal breast tissue, DCIS and invasive breast cancer. 2. To determine COX-2 expression with clinicopathological prognostic parameters. Methods: Radical mastectomy specimens were studied for COX-2 expression by immunohistochemistry in 50 patients diagnosed as breast carcinoma. COX-2 expression is quantified as IHS Score and separately calculated for normal breast epithelium near the tumor, DCIS and invasive areas. Relationship between COX-2 expression with various clinicopathological parameters was evaluated. Result: The results of our study suggest an association of the expression of COX-2 to the factors associated with poor prognosis in breast cancer, such as larger tumor size, positive lymph node status, higher T stage and N stage and lymphovascular invasion. There was a higher COX-2 expression in the DCIS component as compared to the invasive ductal carcinoma component and the adjoining breast epithelium. Conclusion: Our study established the role of COX-2 in carcinogenesis and its association with adverse prognostic factors.}, }
@article {pmid30050552, year = {2018}, author = {Bai, G and Jenkins, S and Yuan, W and Graef, GL and Ge, Y}, title = {Field-Based Scoring of Soybean Iron Deficiency Chlorosis Using RGB Imaging and Statistical Learning.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {1002}, pmid = {30050552}, issn = {1664-462X}, abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress in soybean that can cause significant biomass and yield reduction. IDC is characterized by stunted growth and yellowing and interveinal chlorosis of early trifoliate leaves. Scoring IDC severity in the field is conventionally done by visual assessment. The goal of this study was to investigate the usefulness of Red Green Blue (RGB) images of soybean plots captured under the field condition for IDC scoring. A total of 64 soybean lines with four replicates were planted in 6 fields over 2 years. Visual scoring (referred to as Field Score, or FS) was conducted at V3-V4 growth stage; and concurrently RGB images of the field plots were recorded with a high-throughput field phenotyping platform. A second set of IDC scores was done on the plot images (displayed on a computer screen) consistently by one person in the office (referred to as Office Score, or OS). Plot images were then processed to remove weeds and extract six color features, which were used to train computer-based IDC scoring models (referred to as Computer Score, or CS) using linear discriminant analysis (LDA) and support vector machine (SVM). The results showed that, in the fields where severe IDC symptoms were present, FS and OS were strongly positively correlated with each other, and both of them were strongly negatively correlated with yield. CS could satisfactorily predict IDC scores when evaluated using FS and OS as the reference (overall classification accuracy > 81%). SVM models appeared to outperform LDA models; and the SVM model trained to predict IDC OS gave the highest prediction accuracy. It was anticipated that coupling RGB imaging from the high-throughput field phenotyping platform with real-time image processing and IDC CS models would lead to a more rapid, cost-effective, and objective scoring pipeline for soybean IDC field screening and breeding.}, }
@article {pmid30033677, year = {2018}, author = {Damin, AP and Pozzer, CL and Farret, TF and Reginatto, AG and Trindade, EN}, title = {Gigantic invasive ductal carcinoma of the breast.}, journal = {The breast journal}, volume = {24}, number = {6}, pages = {1082}, doi = {10.1111/tbj.13087}, pmid = {30033677}, issn = {1524-4741}, mesh = {Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/*pathology/surgery ; Female ; Humans ; Lung Neoplasms/drug therapy/secondary ; Middle Aged ; }, }
@article {pmid30028473, year = {2018}, author = {Gabanti, E and Lilleri, D and Scaramuzzi, L and Zelini, P and Rampino, T and Gerna, G}, title = {Comparison of the T-cell response to human cytomegalovirus (HCMV) as detected by cytokine flow cytometry and QuantiFERON-CMV assay in HCMV-seropositive kidney transplant recipients.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {195-202}, pmid = {30028473}, issn = {1121-7138}, mesh = {Adolescent ; Adult ; Aged ; Cytokines/*physiology ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/blood/*immunology ; Female ; Flow Cytometry ; Humans ; Immunity, Cellular ; Immunoassay/methods ; *Kidney Transplantation ; Male ; Middle Aged ; Sensitivity and Specificity ; T-Lymphocytes/*physiology ; *Transplant Recipients ; Young Adult ; }, abstract = {Human cytomegalovirus (HCMV)-specific T-cell response in kidney transplant recipients (KTR) helps to identify patients at risk for severe infection. To assess the T-cell response, this study compared our in-house developed reference test, based on T-cell (both CD4+ and CD8+) stimulation by autologous HCMV-infected dendritic cells (iDC) and subsequent detection by cytokine flow cytometry (CFC-iDC), with the Quanti-FERON-CMV (QF-CMV) assay. Fifty-three HCMV-seropositive KTR were enrolled. At the DNAemia peak, 33 (62%) had low viral load (LVL, <3x105 DNA copies/mL) self-resolving infection, 19 (36%) high viral load (HVL, >3x105 DNA copies/mL) infection treated with antivirals, and one LVL patient (2%) tissue-invasive disease alone. Both assays showed a delayed recovery of HCMV-specific T-cell immunity in HVL vs LVL patients. Immune reconstitution kinetics did not significantly differ between the two assays in HVL patients. QF-CMV and CFC-iDC showed comparable sensitivities, but QF-CMV had a lower (although not significantly) specificity. Indeed, 7/19 HVL patients (37%) were erroneously considered protected from severe infection by QF-CMV, whereas CFC-iDC misidentified only 3/19 (16%) patients as protected. Although our reference test takes longer to complete, it appears slightly better at predicting patients at risk for severe HCMV infection. Moreover, QF-CMV may provide false negative results with some HLA types.}, }
@article {pmid30026605, year = {2018}, author = {Sen, U and Saxena, H and Khurana, J and Nayak, A and Gupta, A}, title = {Plasmodium falciparum RUVBL3 protein: a novel DNA modifying enzyme and an interacting partner of essential HAT protein MYST.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {10917}, pmid = {30026605}, issn = {2045-2322}, support = {SB/YS/LS-297/2013//Department of Science and Technology, Ministry of Science and Technology (DST)/International ; BT/08/IYBA/2014-4//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; }, mesh = {ATPases Associated with Diverse Cellular Activities/chemistry ; Adenosine Triphosphatases/chemistry/genetics/*metabolism ; Carrier Proteins/chemistry ; Chromatin Assembly and Disassembly ; DNA/*metabolism ; DNA Helicases/chemistry ; Fungal Proteins/chemistry ; Gene Expression Regulation, Developmental ; Histone Acetyltransferases/*metabolism ; Histones/metabolism ; Models, Molecular ; Plasmodium falciparum/chemistry/genetics/*metabolism ; Protein Domains ; Protozoan Proteins/chemistry/genetics/metabolism ; Sequence Homology, Nucleic Acid ; Yeasts/chemistry/metabolism ; }, abstract = {RUVBLs constitute a conserved group of ATPase proteins that play significant role in a variety of cellular processes including transcriptional regulation, cell cycle and DNA damage repair. Three RUVBL homologues, namely, PfRUVBL1, PfRUVBL2 and PfRUVBL3 have been identified in P. falciparum, unlike its eukaryotic counterparts, which have two RUVBL proteins (RUVBL1 &amp; RUVBL2). The present study expands our understanding of PfRUVBL3 protein and thereby basic biology of Plasmodium in general. Here, we have shown that parasite PfRUVBL3 is a true homolog of human/yeast RUVBL2 protein. Our result show that PfRUVBL3 constitutively expresses throughout the stages of intra-erythrocytic cycle (IDC) with varied localization. In addition to ATPase and oligomerization activity, we have for the first time shown that PfRUVBL3 possess DNA cleavage activity which interestingly is dependent on its insertion domain. Furthermore, we have also identified RUVBL3 to be an interacting partner of an essential chromatin remodeling protein PfMYST and together they colocalize with H3K9me1 histone in parasitophorous vacuole during the ring stage of IDC suggesting their potential involvement in chromatin remodeling and gene transcription.}, }
@article {pmid30024024, year = {2019}, author = {Brunstein Klomek, A and Barzilay, S and Apter, A and Carli, V and Hoven, CW and Sarchiapone, M and Hadlaczky, G and Balazs, J and Kereszteny, A and Brunner, R and Kaess, M and Bobes, J and Saiz, PA and Cosman, D and Haring, C and Banzer, R and McMahon, E and Keeley, H and Kahn, JP and Postuvan, V and Podlogar, T and Sisask, M and Varnik, A and Wasserman, D}, title = {Bi-directional longitudinal associations between different types of bullying victimization, suicide ideation/attempts, and depression among a large sample of European adolescents.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {60}, number = {2}, pages = {209-215}, doi = {10.1111/jcpp.12951}, pmid = {30024024}, issn = {1469-7610}, mesh = {Adolescent ; Bullying/*statistics &amp; numerical data ; Crime Victims/*statistics &amp; numerical data ; Depression/*epidemiology ; Europe ; Female ; Humans ; Longitudinal Studies ; Male ; *Suicidal Ideation ; Suicide, Attempted/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: The association between bullying victimization and depression, suicide ideation and suicide attempts has been studied mainly in cross-sectional studies. This study aims to test the bidirectional effect and the chronicity versus sporadic effect of physical, verbal, and relational bullying victimization on suicidal ideation/attempts and depression.<br><br>METHODS: Longitudinal assessments with an interval of 3- and 12-months were performed within a sample of 2,933 adolescents (56.1% females; mean age 14.78, SD&#xa0;=&#xa0;.89) from 10 European countries, participating in the Saving and Empowering Young Lives in Europe (SEYLE) school-based multicenter control sample. Multilevel Structural Equation Models were used, controlling for sociodemographic variables. Victimization was considered chronic when a student was victimized in the first two time points and sporadic when it was reported only at one point but not in another.<br><br>RESULTS: Bidirectional prospective association between all types of victimization and depression were found. Among participants, who reported victimization once (but not twice), physical victimization, but not verbal and relational, was associated with later suicidal ideation and attempts. Chronic victimization of any type increased likelihood for later depression compared with sporadic and no-victimization. Chronic relational victimization increased the likelihood of later suicidal ideation, and chronic physical victimization increased the likelihood for suicidal attempts.<br><br>CONCLUSIONS: The results support the bidirectional effect of victimization and depression and indicate that there are complex longitudinal associations between victimization and suicidal ideation/attempts. Physical victimization may especially carry effect on suicidal risk over time. Interventions should focus on victimization as a cause of distress but also aim to prevent vulnerable adolescents from becoming targets of victimization.}, }
@article {pmid30009102, year = {2018}, author = {Katz, H and Jafri, H and Saad, R and Limjoco, T and Tirona, MT}, title = {Colonic Obstruction from an Unusual Cause: A Rare Case of Metastatic Invasive Ductal Carcinoma to the Colon.}, journal = {Cureus}, volume = {10}, number = {5}, pages = {e2588}, pmid = {30009102}, issn = {2168-8184}, abstract = {Colon metastasis from breast cancer is rare. Gastrointestinal (GI) metastasis is more frequently seen in patients with invasive lobular carcinoma of the breast compared to invasive ductal carcinoma; however, the most common sites of metastasis still remain the lymph nodes, lungs, liver, and bones. We describe a 68-year-old female with a remote history of invasive ductal carcinoma of the breast who presented with abdominal pain and a palpable mass. On imaging, she was found to have a colonic obstruction and underwent a right hemicolectomy that proved to be metastatic invasive ductal carcinoma of the breast.}, }
@article {pmid29985403, year = {2018}, author = {Painter, HJ and Chung, NC and Sebastian, A and Albert, I and Storey, JD and Llinás, M}, title = {Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {2656}, pmid = {29985403}, issn = {2041-1723}, support = {R21 AI133379/AI/NIAID NIH HHS/United States ; }, mesh = {Erythrocytes/parasitology ; Gene Expression Profiling ; Gene Ontology ; Genes, Protozoan/*genetics ; Genome, Protozoan/*genetics ; Humans ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/*genetics/physiology ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/genetics/metabolism ; *Transcription, Genetic ; }, abstract = {Genome-wide analysis of transcription in the malaria parasite Plasmodium falciparum has revealed robust variation in steady-state mRNA abundance throughout the 48-h intraerythrocytic developmental cycle (IDC), suggesting that this process is highly dynamic and tightly regulated. Here, we utilize rapid 4-thiouracil (4-TU) incorporation via pyrimidine salvage to specifically label, capture, and quantify newly-synthesized RNA transcripts at every hour throughout the IDC. This high-resolution global analysis of the transcriptome captures the timing and rate of transcription for each newly synthesized mRNA in vivo, revealing active transcription throughout all IDC stages. Using a statistical model to predict the mRNA dynamics contributing to the total mRNA abundance at each timepoint, we find varying degrees of transcription and stabilization for each mRNA corresponding to developmental transitions. Finally, our results provide new insight into co-regulation of mRNAs throughout the IDC through regulatory DNA sequence motifs, thereby expanding our understanding of P. falciparum mRNA dynamics.}, }
@article {pmid29983888, year = {2018}, author = {Kaymak, A and Sayols, S and Papadopoulou, T and Richly, H}, title = {Role for the transcriptional activator ZRF1 in early metastatic events in breast cancer progression and endocrine resistance.}, journal = {Oncotarget}, volume = {9}, number = {47}, pages = {28666-28690}, pmid = {29983888}, issn = {1949-2553}, abstract = {Breast cancer is one of the most common malignancies among women which is often treated with hormone therapy and chemotherapy. Despite the improvements in detection and treatment of breast cancer, the vast majority of breast cancer patients are diagnosed with metastatic disease either at the beginning of the disease or later during treatment. Still, the molecular mechanisms causing a therapy resistant metastatic breast cancer are still elusive. In the present study we addressed the function of the transcriptional activator ZRF1 during breast cancer progression. We provide evidence that ZRF1 plays an essential role for the early metastatic events in vitro and acts like a tumor suppressor protein during the progression of breast invasive ductal carcinoma into a more advanced stage. Hence, depletion of ZRF1 results in the acquisition of metastatic behavior by facilitating the initiation of the metastatic cascade, notably for cell adhesion, migration and invasion. Furthermore absence of ZRF1 provokes endocrine resistance via misregulation of cell death and cell survival related pathways. Taken together, we have identified ZRF1 as an important regulator of breast cancer progression that holds the potential to be explored for new treatment strategies in the future.}, }
@article {pmid29981615, year = {2018}, author = {Du, R and Zhang, H and Shu, W and Chen, B and Li, Y and Zhang, X and Wu, X and Wang, Z}, title = {Correlation between Ki-67 Expression and Hemodynamics of Contrast-Enhanced Ultrasound in Patients with Breast Infiltrative Ductal Carcinoma.}, journal = {The American surgeon}, volume = {84}, number = {6}, pages = {856-861}, pmid = {29981615}, issn = {1555-9823}, mesh = {Adolescent ; Adult ; Breast Neoplasms/*diagnostic imaging/*metabolism/physiopathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*metabolism/physiopathology ; Cohort Studies ; Contrast Media ; Female ; Hemodynamics ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Regional Blood Flow ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {Breast cancer causes great threats to public health worldwide. The aim of this study was to investigate the correlation between Ki-67 expression and the hemodynamics of contrast-enhanced ultrasound (CEUS) in patients with infiltrative ductal carcinoma (IDC). CEUS was performed on 109 masses in 85 IDC cases before resection. Based on the immunohistochemical staining on the antigen Ki-67, the masses were divided into negative group, weakly positive group, positive group, and strong-positive group. Significant statistical differences were noticed in time to peak, arrive intensity, and peak intensity in the positive groups compared with the negative group. Compared with the positive groups, the negative group showed significant statistical differences in arrive intensity and peak intensity. The antigen Ki-67 was positively correlated with arrived intensity, intensity changes, and rising curve's slope. In contrast, it was negatively correlated with arrived time, time to peak, and continuous time. The hemodynamic parameters of CEUS were correlated with the expression of antigen Ki-67. On this basis, Ki-67 is an effective supplement to the diagnosis of IDC.}, }
@article {pmid29973382, year = {2018}, author = {Bayindir-Buchhalter, I and Wolff, G and Lerch, S and Sijmonsma, T and Schuster, M and Gronych, J and Billeter, AT and Babaei, R and Krunic, D and Ketscher, L and Spielmann, N and Hrabe de Angelis, M and Ruas, JL and Müller-Stich, BP and Heikenwalder, M and Lichter, P and Herzig, S and Vegiopoulos, A}, title = {Cited4 is a sex-biased mediator of the antidiabetic glitazone response in adipocyte progenitors.}, journal = {EMBO molecular medicine}, volume = {10}, number = {8}, pages = {}, pmid = {29973382}, issn = {1757-4684}, mesh = {Adipocytes/*drug effects/metabolism ; Animals ; Diabetes Mellitus, Type 2/*drug therapy/metabolism ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Male ; Mice ; Molecular Targeted Therapy ; PPAR gamma/metabolism ; Rosiglitazone/*therapeutic use ; Sex Factors ; Stem Cells/drug effects/metabolism ; Thermogenesis ; Transcription Factors/biosynthesis/*metabolism ; Transcription, Genetic/drug effects ; Uncoupling Protein 1/biosynthesis ; }, abstract = {Most antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context-specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone-dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta-adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg.}, }
@article {pmid29973218, year = {2018}, author = {Zubeldia-Plazaola, A and Recalde-Percaz, L and Moragas, N and Alcaraz, M and Chen, X and Mancino, M and Fernández-Nogueira, P and Prats de Puig, M and Guzman, F and Noguera-Castells, A and López-Plana, A and Enreig, E and Carbó, N and Almendro, V and Gascón, P and Bragado, P and Fuster, G}, title = {Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis.}, journal = {Breast cancer research : BCR}, volume = {20}, number = {1}, pages = {65}, pmid = {29973218}, issn = {1465-542X}, mesh = {Animals ; Apoptosis/genetics ; Biomarkers, Tumor/*blood/genetics ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*blood/genetics/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Glucocorticoids/*blood ; Heterografts ; Humans ; Laminin/genetics ; Mice ; Myoepithelioma/blood/genetics/pathology ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells.<br><br>METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples.<br><br>RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS.<br><br>CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.}, }
@article {pmid29959495, year = {2018}, author = {Eck, DL and Nguyen, DC and Barnes, LL and Jansen, DA}, title = {Treatment of Breast Animation Deformity in Implant-Based Reconstruction with Selective Nerve Ablation.}, journal = {Aesthetic plastic surgery}, volume = {42}, number = {6}, pages = {1472-1475}, doi = {10.1007/s00266-018-1184-0}, pmid = {29959495}, issn = {1432-5241}, mesh = {Adult ; Breast Implantation/*adverse effects/methods ; *Breast Implants ; Breast Neoplasms/pathology/*surgery ; Denervation/methods ; Esthetics ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/adverse effects/methods ; Mastectomy/methods ; Pectoralis Muscles/*innervation/*surgery ; Peripheral Nerves/*surgery ; Prosthesis Failure ; Reoperation/methods ; Treatment Outcome ; }, abstract = {Breast animation deformity is a known complication of subpectoral implant placement that is usually corrected by repositioning the implant to the prepectoral position. Other less common treatment options include performing the muscle splitting biplanar technique, triple plane technique, neuromodulator injections, and secondary neurotomies via transection of the pectoral muscle. We report a patient with animation deformity successfully treated with direct identification and ablation of the medial and lateral pectoral nerves using selective bipolar electrocautery. The patient is a woman with a history of invasive ductal carcinoma who underwent bilateral mastectomy and breast reconstruction with subpectoral implant placement and autologous fat grafting. Within 1 year of her breast reconstruction, she developed hyperactive pectoralis muscle contraction with resulting distortion of both breasts. Given the disadvantages of repositioning the implant to the prepectoral position and transecting the pectoralis muscles via secondary neurotomy, we chose to directly identify and selectively ablate distal branches of the medial and lateral pectoral nerves. This offers a novel technique for correcting breast animation deformity without transecting the pectoralis muscles, causing muscle atrophy, and preserving the subpectoral implant position.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .}, }
@article {pmid29956094, year = {2018}, author = {Graff-Baker, AN and Orozco, JIJ and Marzese, DM and Salomon, MP and Hoon, DSB and Goldfarb, M}, title = {Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers.}, journal = {Annals of surgical oncology}, volume = {25}, number = {10}, pages = {3082-3087}, doi = {10.1245/s10434-018-6582-7}, pmid = {29956094}, issn = {1534-4681}, mesh = {Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/genetics/pathology/surgery ; Carcinoma, Lobular/genetics/pathology/surgery ; DNA Methylation ; *Epigenomics ; Female ; Follow-Up Studies ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Middle Aged ; Neoplasms, Second Primary/*genetics/pathology/surgery ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy.<br><br>METHODS: RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n&#x2009;=&#x2009;36) and invasive lobular (ILC, n&#x2009;=&#x2009;40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs.<br><br>RESULTS: Differentially expressed genes were identified in IDC SBCs (n&#x2009;=&#x2009;727) and in ILC SBCs (n&#x2009;=&#x2009;261; Wilcoxon's test; P&#x2009;<&#x2009;0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes.<br><br>CONCLUSIONS: Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations.}, }
@article {pmid29954760, year = {2018}, author = {Kase, AM and Menke, D and Tan, W}, title = {Breast cancer metastasis to the bladder: a literature review.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, pmid = {29954760}, issn = {1757-790X}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/drug therapy/*pathology ; *Cancer Survivors ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Cystoscopy ; Estradiol/*analogs &amp; derivatives/therapeutic use ; Fatal Outcome ; Female ; Fulvestrant ; Humans ; Middle Aged ; Receptor, ErbB-2 ; Urinary Bladder Neoplasms/complications/diagnosis/drug therapy/*secondary ; Urinary Bladder, Overactive/*etiology ; }, abstract = {Given the prevalence of breast cancer and the mortality associated with metastatic disease, it is imperative for physicians to not only be aware of common sites but also of rare metastatic destinations such as the bladder. A postmenopausal woman with a medical history of stage 2 invasive ductal carcinoma, oestrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative, in remission for 9 years, presented to her primary care physician with concerns of increased urinary urgency, frequency and incontinence. The patient underwent cystoscopy with biopsy of an area of granulation tissue. Biopsy revealed adenocarcinoma consistent with breast primary. The common sites of metastases from breast cancer are lung, bone and liver. This case is unique where breast cancer was found to metastasise to the bladder. It is important for physicians to consider further investigation when a breast cancer survivor develops urinary symptoms even without haematuria.}, }
@article {pmid29951883, year = {2018}, author = {Finet, JE and Wiggers, GA}, title = {Pharmacologic Management of Cancer Therapeutics-Induced Cardiomyopathy in Adult Cancer Survivors.}, journal = {Current heart failure reports}, volume = {15}, number = {4}, pages = {270-279}, pmid = {29951883}, issn = {1546-9549}, mesh = {Adult ; *Cancer Survivors ; *Cardiomyopathies/chemically induced/drug therapy/epidemiology ; Cardiovascular Agents/*therapeutic use ; Comorbidity ; Global Health ; Heart Failure/*drug therapy/epidemiology ; Humans ; Neoplasms/*drug therapy/epidemiology ; }, abstract = {PURPOSE OF REVIEW: The number of cancer survivors is exponentially increasing worldwide, due to both advances in cancer detection and treatment strategies, as well as the aging and growth of the population. This decrease in cancer mortality has brought forth a concurrent increase of non-ischemic (toxic) dilated cardiomyopathy in the survivor population, also known as cancer therapeutics-induced cardiomyopathy (CTIC). The optimal pharmacological management for this condition is still elusive, and hence, the focus of this work.<br><br>RECENT FINDINGS: Our review of the literature did not identify any prospective randomized clinical trial of CTIC in adult cancer survivors, neither published nor in progress. However, available data seem to suggest that, when managed with standard guideline-derived medical therapy, the outcomes of CTIC are comparable to that of idiopathic dilated cardiomyopathy (IDC). Nonetheless, the evidence behind this strategy is inadequate. Until new information becomes available, pharmacological management of CTIC must parallel that of IDC. However, implementation of such may be hindered by other cancer therapeutics-induced comorbidities and conditioned by the particular effects of heart failure pharmacotherapy on cancer outcomes. This work succinctly reviews these three areas, in the context of adult cancer survivors.}, }
@article {pmid29946183, year = {2018}, author = {Krings, G and Chen, YY}, title = {Genomic profiling of metaplastic breast carcinomas reveals genetic heterogeneity and relationship to ductal carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {31}, number = {11}, pages = {1661-1674}, doi = {10.1038/s41379-018-0081-z}, pmid = {29946183}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; Gene Expression Profiling ; *Genetic Heterogeneity ; Humans ; Metaplasia ; Middle Aged ; Transcriptome ; Triple Negative Breast Neoplasms/*genetics/pathology ; }, abstract = {Metaplastic breast carcinomas comprise a histologically heterogenous group of tumors. Although most are triple (estrogen/progesterone receptor, HER2) negative, these rare tumors are clinicopathologically distinct from other triple negative carcinomas and may be aggressive with worse chemotherapy responses. On the other hand, metaplastic carcinomas are histologically diverse, which is reflected in gene expression differences among subtypes. Whether metaplastic carcinomas are genetically distinct from other triple negative cancers and whether genetic differences underlie histologic subtypes remains poorly understood. We sequenced 408 cancer-related genes in 28 metaplastic carcinomas, including chondroid matrix-producing carcinomas (n = 10), spindle cell carcinomas (n = 5), and carcinomas with squamous (n = 5), mixed spindle/squamous (n = 5), and mixed metaplastic (n = 3) differentiation. Metaplastic carcinomas were highly enriched for PIK3CA/PIK3R1 (61%) and Ras-Map kinase (25%) pathway aberrations compared to other triple negative carcinomas (TCGA dataset 14%, p < 0.001 and 7%, p = 0.005, respectively) and harbored a high frequency of TP53 (64%) and TERT promoter (25%) mutations, but this varied among subtypes. Chondroid-matrix producing carcinomas lacked PI-3 kinase and Ras-Map kinase aberrations and TERT promoter mutations, compared to 100%, 39%, and 39% of non-matrix-producing tumors, respectively. TERT promoter mutations were enriched (47%) in spindle cell carcinomas and tumors with squamous or spindle/squamous differentiation. Spindle cell carcinomas lacked TP53 mutations, in contrast to other subtypes (78%, p = 0.003). Separate analysis of paired ductal carcinoma in situ and metaplastic carcinoma revealed shared clonality in all cases (n = 8). Activating PI-3 kinase and Ras pathway mutations were early events, and inactivating mutations in tumor suppressors including RB1, CDKN2A, and TP53 were associated with invasion in individual cases. Metaplastic components of two tumors showed genetic progression from separately sequenced paired invasive ductal carcinoma. The findings suggest that metaplastic carcinomas are genetically distinct from other triple negative breast cancers and highlight genetic heterogeneity that broadly correlates with histologic subtype. Heterologous elements progress from associated ductal carcinoma.}, }
@article {pmid29943843, year = {2018}, author = {Esmaeili, SA and Mahmoudi, M and Rezaieyazdi, Z and Sahebari, M and Tabasi, N and Sahebkar, A and Rastin, M}, title = {Generation of tolerogenic dendritic cells using Lactobacillus rhamnosus and Lactobacillus delbrueckii as tolerogenic probiotics.}, journal = {Journal of cellular biochemistry}, volume = {119}, number = {9}, pages = {7865-7872}, doi = {10.1002/jcb.27203}, pmid = {29943843}, issn = {1097-4644}, mesh = {Adult ; Case-Control Studies ; Cell Culture Techniques ; Cells, Cultured ; Cytokines/genetics/metabolism ; Dendritic Cells/*cytology/immunology/microbiology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/metabolism ; Interleukin-4/pharmacology ; Lactobacillus delbrueckii/immunology/*physiology ; Lacticaseibacillus rhamnosus/immunology/*physiology ; Lupus Erythematosus, Systemic/immunology/*microbiology ; Male ; Monocytes/*cytology/drug effects/immunology/microbiology ; Probiotics ; }, abstract = {Systemic lupus erythematosus (SLE) concurs with excessive uncontrolled inflammatory immune responses that lead to the loss of immune tolerance. Dendritic cells (DCs) are important and determinant immune cells that regulate immune responses. Tolerogenic DCs with regulatory markers and cytokines could induce regulatory immune cells and responses. Tolerogenic probiotics are capable of producing regulatory DCs from monocytes in in vitro conditions. The purpose of this study was to evaluate the effect of Lactobacillus delbrueckii and Lactobacillus rhamnosus on the production of DCs in an in vitro condition. Peripheral blood mononuclear cells were isolated from the healthy and SLE donors. Monocytes were cultured with optimized concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to produce immature DCs (IDCs). An IDC uptake assay was performed, and IDCs of healthy and SLE donors were divided into three subgroups following 48 hours of treatment with GM-CSF and IL-4, along with L. delbrueckii, L. rhamnosus, and mixed probiotics for the production of tolerogenic DCs. The surface expression of Human Leukocyte Antigen-antigen D Related (HLA-DR), CD86, CD80, CD83, CD1a, and CD14 was analyzed using flow cytometry, and the gene expression levels of indoleamine 2,3-dioxygenase (IDO), IL-10, and IL-12 were measured using real-time polymerase chain reaction. We observed significantly reduced expression of costimulatory molecules and other surface markers in the probiotic-induced mature DCs (MDCs) in both healthy and SLE donor groups in comparison with lipopolysaccharide (LPS)-induced MDCs. In addition, the expression of IDO and IL-10 increased, whereas IL-12 decreased significantly in probiotic-induced MDCs compared with LPS-induced MDCs. IDCs and especially mature tolerogenic DC of SLE patients highly expressed IDO. The results of the current study suggested that live probiotics could modify properties of DCs to modulatory cells, which might contribute to the induction of tolerance and renovation of immune hemostasis.}, }
@article {pmid29941485, year = {2018}, author = {Nagle, AM and Levine, KM and Tasdemir, N and Scott, JA and Burlbaugh, K and Kehm, J and Katz, TA and Boone, DN and Jacobsen, BM and Atkinson, JM and Oesterreich, S and Lee, AV}, title = {Loss of E-cadherin Enhances IGF1-IGF1R Pathway Activation and Sensitizes Breast Cancers to Anti-IGF1R/InsR Inhibitors.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {24}, number = {20}, pages = {5165-5177}, pmid = {29941485}, issn = {1557-3265}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; F31 CA224567/CA/NCI NIH HHS/United States ; R01 CA094118/CA/NCI NIH HHS/United States ; T32 GM008424/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Breast Neoplasms/drug therapy/metabolism/pathology ; Cadherins/genetics/*metabolism ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; *Drug Resistance, Neoplasm ; Drug Synergism ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor I/antagonists &amp; inhibitors/*metabolism ; Mice ; RNA, Small Interfering/genetics ; Receptor, IGF Type 1 ; Receptors, Somatomedin/antagonists &amp; inhibitors/*metabolism ; Signal Transduction/*drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Purpose: Insulin-like growth factor 1 (IGF1) signaling regulates breast cancer initiation and progression and associated cancer phenotypes. We previously identified E-cadherin (CDH1) as a repressor of IGF1 signaling and in this study examined how loss of E-cadherin affects IGF1R signaling and response to anti-IGF1R/insulin receptor (InsR) therapies in breast cancer.Experimental Design: Breast cancer cell lines were used to assess how altered E-cadherin levels regulate IGF1R signaling and response to two anti-IGF1R/InsR therapies. In situ proximity ligation assay (PLA) was used to define interaction between IGF1R and E-cadherin. TCGA RNA-seq and RPPA data were used to compare IGF1R/InsR activation in estrogen receptor-positive (ER+) invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) tumors. ER+ ILC cell lines and xenograft tumor explant cultures were used to evaluate efficacy to IGF1R pathway inhibition in combination with endocrine therapy.Results: Diminished functional E-cadherin increased both activation of IGF1R signaling and efficacy to anti-IGF1R/InsR therapies. PLA demonstrated a direct endogenous interaction between IGF1R and E-cadherin at points of cell-cell contact. Increased expression of IGF1 ligand and levels of IGF1R/InsR phosphorylation were observed in E-cadherin-deficient ER+ ILC compared with IDC tumors. IGF1R pathway inhibitors were effective in inhibiting growth in ER+ ILC cell lines and synergized with endocrine therapy and similarly IGF1R/InsR inhibition reduced proliferation in ILC tumor explant culture.Conclusions: We provide evidence that loss of E-cadherin hyperactivates the IGF1R pathway and increases sensitivity to IGF1R/InsR targeted therapy, thus identifying the IGF1R pathway as a potential novel target in E-cadherin-deficient breast cancers. Clin Cancer Res; 24(20); 5165-77. ©2018 AACR.}, }
@article {pmid29916548, year = {2018}, author = {Lan, VTT and Son, HV and Trang, VL and Trang, NT and Phuong, NT and Toan, NL and Duong, PAT}, title = {Methylation profiles of miR34 gene family in Vietnamese patients suffering from breast and lung cancers.}, journal = {Molecular medicine reports}, volume = {18}, number = {2}, pages = {2476-2484}, doi = {10.3892/mmr.2018.9182}, pmid = {29916548}, issn = {1791-3004}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics/pathology ; DNA Methylation/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/epidemiology/*genetics/pathology ; MicroRNAs/*genetics ; Middle Aged ; Promoter Regions, Genetic ; Vietnam/epidemiology ; }, abstract = {The three genes encoding small non‑coding microRNA (miR)34a, MIR34b and MIR34c act as tumor‑suppressor genes. Their aberrant expressions regulated by DNA methylation have been frequently found in various types of cancer. In the present study, the DNA promoter methylation profiles of the MIR34 gene family were analyzed using the methylation specific polymerase chain reaction in order to clarify their association with breast and lung cancer, non‑cancerous or normal adjacent tissues. The methylation frequency of MIR34a was significantly higher in breast cancer (49.37%) compared with normal adjacent tissues (30.38%). The methylation frequency of MIR34b/c was 59.49 and 62.03% in breast cancer and normal adjacent tissues, respectively. MIR34a methylation showed a significant concordance with that of MIR34b/c only in breast cancer tissue. MIR34a methylation was significantly associated with cancer and the invasive ductal carcinoma type of breast cancer (P=0.015 and P=0.02, respectively). Methylation frequency of MIR34a and MIR34b/c was 48.42 and 56.84% in lung cancer, and 47.22 and 51.39% in pulmonary diseases, respectively. No significant association was observed between the methylation status of MIR34a and MIR34b/c, and the clinicopathological features of lung cancer or with those of non‑cancerous pulmonary diseases. Promoter methylation of MIR34a and MIR34b/c occurs frequently and concomitantly in breast and lung cancer, as well as in pulmonary diseases tissues, but not in breast normal tissues adjacent to tumor. These results of the present study emphasize the involvement of MIR34 methylation in human diseases, including cancer. Furthermore, MIR34a methylation may be a promising marker for a subtype of breast cancer.}, }
@article {pmid29915849, year = {2018}, author = {Linjawi, S and AlGaithy, Z and Sindi, S and Hamdi, N and Linjawi, A and Alharbi, M}, title = {Regulation of Lipocalin-2 oncogene and its impact on gene polymorphisms on breast cancer patients in Jeddah, Saudi Arabia.}, journal = {Saudi medical journal}, volume = {39}, number = {6}, pages = {558-563}, pmid = {29915849}, issn = {1658-3175}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Breast Neoplasms/blood/*genetics ; Carcinoma, Ductal, Breast/blood/*genetics ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Genotype ; Humans ; Lipocalin-2/blood/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Saudi Arabia ; Young Adult ; }, abstract = {OBJECTIVES: To identify the impact of Lipocalin-2 (LCN2) gene polymorphisms on breast cancer patients in western Saudi Arabia.<br><br>METHODS: It is a case control study in which blood samples of participants from Medical Reference Clinics and King Abdulaziz University Hospital in Jeddah, Saudi Arabia have been taken between 2014 and 2016. This study recruited 128 participants (50% control, 50% patients) and used Tetra-Primer amplification-refractory mutation system-polymerase chain reaction method for the detection of missense SNP (rs11556770). The study measured LCN2 plasma protein expression by enzyme-linked immunosorbent assay technique.&#xa0;Results: The results have shown that 100% of the genotypes were normal allele (G/G). In contrast, the&#xa0;plasma level of LCN2 was considerably elevated among patients as compared to control (p=0.001), and higher in invasive ductal carcinoma patients (p=0.001). The LCN2 protein expression in plasma level was significantly elevated among patients, particularly who demonstrated invasive ductal carcinoma.&#xa0;Conclusion: There is no significant relationship between breast cancer patients and LCN2 gene polymorphisms &#xa0; (rs11556770).}, }
@article {pmid29906691, year = {2018}, author = {Sakamoto, S and Tsuruga, Y and Fujii, Y and Shomura, H and Hattori, A and Kazui, K}, title = {Intraductal tubulopapillary neoplasm of the pancreas presenting as recurrent acute pancreatitis: A case report.}, journal = {International journal of surgery case reports}, volume = {48}, number = {}, pages = {122-125}, pmid = {29906691}, issn = {2210-2612}, abstract = {INTRODUCTION: The 2010 World Health Organization classification of intraductal neoplasms of the pancreas includes intraductal tubulopapillary neoplasms (ITPNs) and intraductal papillary mucinous neoplasms, the latter being a rare and new concept. ITPN sometimes cause acute pancreatitis; therefore, distinguishing ITPN from idiopathic acute pancreatitis is important but challenging.<br><br>PRESENTATION OF CASE: We present the case of a 72-year-old male who had recurrent pancreatitis for the past 2 years, his diagnosis was idiopathic acute pancreatitis. He was admitted to our hospital with severe acute pancreatitis and cholangitis due to intrapancreatic bile duct stenosis. After the treatment of cholangitis, contrast-enhanced computed tomography revealed a tumor at the pancreatic head. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis of the main pancreatic duct and distal bile duct, and adenocarcinoma was detected using brush cytology of the bile duct stricture and pancreatic juice. The patient was diagnosed with invasive ductal carcinoma and pancreaticoduodenectomy was performed. Histopathological findings revealed dilation of the pancreatic duct, and proliferation of columnar cells and cuboid epithelial cells in the main pancreatic duct of the pancreatic head. Mucus production was poor, and immunostaining results revealed ITPN. The patient is alive and do not exhibit signs of recurrence for 12 months.<br><br>DISCUSSION: ITPNs can cause acute pancreatitis, which can be challenging to preoperatively diagnose. ITPNs presenting as acute pancreatitis are rare, with reported only 5 cases.<br><br>CONCLUSION: It is important to be keep in mind that there is a possibility of ITPN after diagnosis of idiopathic acute pancreatitis.}, }
@article {pmid29904947, year = {2018}, author = {Dong, C and Liu, Y and Jiang, K and Wang, H and Qu, W and Zhang, C and Liang, R and Gao, Z and Zhao, B and Miao, Q and Shao, S and Wang, L}, title = {The Nogo-B receptor promotes human hepatocellular carcinoma cell growth via the Akt signal pathway.}, journal = {Journal of cellular biochemistry}, volume = {119}, number = {9}, pages = {7738-7746}, pmid = {29904947}, issn = {1097-4644}, support = {R01 HL108938/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Hepatocellular/genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Gene Knockdown Techniques ; Hep G2 Cells ; Humans ; Liver Neoplasms/genetics/metabolism/*pathology ; Male ; Mice ; Neoplasm Transplantation ; Phosphorylation ; Proto-Oncogene Proteins c-akt/*metabolism ; Receptors, Cell Surface/*genetics/*metabolism ; Signal Transduction ; }, abstract = {Nogo-B receptor (NgBR) is a type I receptor with a single transmembrane domain and specifically binds to ligand Nogo-B. A previous study demonstrated that NgBR was highly expressed in human breast invasive ductal carcinoma and promoted epithelial-mesenchymal transition in breast tumor cells. Our recent work found that NgBR expression was associated with a poor prognosis in human patients with hepatocellular carcinoma (HCC). Here, we elucidate that the increased expression of NgBR contributes toward the increased cell growth of human HCC cells both in vitro and in vivo. Cell viability and clonogenic survival analysis results demonstrated that knockdown of NgBR inhibits the cell growth in human HCC cells, which correlates with a reduction in the phosphorylation of Akt levels. Furthermore, overexpression of NgBR by the cotransfected pIRES-NgBR plasmid together with NgBR siRNA in human HCC cells can rescue impaired phosphorylation of Akt levels in NgBR knockdown human HCC cells. In addition, cell viability analyses showed that NgBR overexpression can rescue the cell growth inhibition presented in human HCC NgBR knockdown cells. Taken together, our results suggest that NgBR potentially acts as an oncogene in HCC by increasing Akt activity. Thus, NgBR may represent a new potential diagnostic and therapeutic target for the treatment of HCC.}, }
@article {pmid29889862, year = {2018}, author = {Awungafac, G and Amin, ET and Fualefac, A and Takah, NF and Agyingi, LA and Nwobegahay, J and Ondoa, P and Njukeng, PA}, title = {Viral load testing and the use of test results for clinical decision making for HIV treatment in Cameroon: An insight into the clinic-laboratory interface.}, journal = {PloS one}, volume = {13}, number = {6}, pages = {e0198686}, pmid = {29889862}, issn = {1932-6203}, mesh = {Adult ; Aged ; Anti-Retroviral Agents/pharmacology/*therapeutic use ; Cameroon ; Decision Making ; HIV/drug effects ; HIV Infections/*drug therapy/virology ; Humans ; Middle Aged ; Retrospective Studies ; Treatment Failure ; *Viral Load/drug effects ; Young Adult ; }, abstract = {BACKGROUND: The viral load (VL) in patients receiving antiretroviral therapy (ART) is the best predictor of treatment outcome. The anticipated benefits of VL monitoring depend on the actual uptake of VL test results for clinical decisions. The objective of this study was to assess the uptake and utilization of VL test results for clinical decisions on HIV treatment in Cameroon, from 2013 to 2017.<br><br>METHODS: This was a retrospective cohort analysis of data from files of patients receiving ART at Buea, Limbe, Bamenda and Bafoussam regional hospital HIV treatment centers. A simple random pick of six file blocks was performed in each shelf that corresponded to a year of initiation, and the contents of all selected files were reviewed and the information needed for the study entered a structured questionnaire. The data collected was recorded in Epi Info (version 7.1.5.2), and analyzed using SATA (version 12.1; StataCorp LP).<br><br>RESULTS: Eight hundred and thirty files were reviewed. The mean duration on ART was 39.4&#xb1;12 months. Viral load testing uptake was 24.33% and only one VL test had been done by all patients. Approximately 65% of the patients did the first VL after more than 24 months on ART. The median turnaround (TAT) time for VL testing was 6 days (Interquartile range (IQR) 3-7days). Among 201 patients who did a VL test, 94.55% had VL suppression (&#x2264;1000copies/mm3). Approximately 54% of the patients with virologic failure were switched to a second-line regimen.<br><br>CONCLUSIONS: The uptake of viral load testing is low in North West, South West and West Regions of Cameroon. The current TAT for VL testing is plausible. The rate of switch to second line regimen is low. It is time to strengthen the scale up of VL testing and improve the rate of switch to second-line regimen in Cameroon.}, }
@article {pmid29886591, year = {2018}, author = {Liu, JY and Zou, LP and Wu, HJ and Zhao, ZH and Zhang, ZG}, title = {[Effects of ubiquitin-specific proteases 2-69 on proliferation of breast cancer cells].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {47}, number = {6}, pages = {455-460}, doi = {10.3760/cma.j.issn.0529-5807.2018.06.013}, pmid = {29886591}, issn = {0529-5807}, mesh = {Blotting, Western ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; *Cell Proliferation ; Cyclin D1/metabolism ; Endopeptidases/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; Neoplasm Proteins/genetics/*metabolism ; RNA, Messenger/metabolism ; Transfection ; Tumor Cells, Cultured ; Ubiquitin Thiolesterase ; }, abstract = {Objective: To investigate the expression and significance of ubiquitin-specific proteases 2-69(USP2-69) in invasive ductal carcinoma of breast. Methods: Twenty-four cases of human breast tissue with invasive ductal carcinoma diagnosed at Huanshan Hospital, Fudan University from 2013 to 2015 were collected, and the expression of USP2-69 mRNA and protein was detected by molecular hybridization, Western blot and immunohistochemistry. USP2-69 was over-expressed in cultured human breast cancer cell line MCF-7 by USP2-69 plasmid transfection. The cellular proliferative activity was investigated in vitro. Results: The USP2-69 mRNA and protein were highly expressed in breast invasive ductal carcinoma, compared to adjacent normal tissues (P<0.01). Ki-67 protein expression was also increased in cases with high USP2-69 protein level. Western blot showed significantly higher USP2-69 protein level in cancer tissue compared to the adjacent normal tissue. In the cultured tumor cells, there was increased S phase fraction, cellular proliferation rate, flat positive clones, cyclin D1 expression and decreased p27 expression in USP2-69-transfected MCF-7 cells. Conclusions: USP2-69 is over-expressed in breast invasive ductal carcinoma, and is closely related to proliferation promoting effects. The data provide an important experimental basis for further study on the molecular mechanism of breast cancer cell proliferation.}, }
@article {pmid29884570, year = {2019}, author = {Campo-Sánchez, SM and Camargo-Trillos, J and Calle-Ramírez, JA and Gómez-Wolff, LR and Sánchez-Patiño, LA and García-García, HI}, title = {Colorectal cancer survival at an oncologic center in Colombia. A historic cohort study.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {84}, number = {2}, pages = {174-184}, doi = {10.1016/j.rgmx.2018.04.002}, pmid = {29884570}, issn = {2255-534X}, mesh = {Adenocarcinoma/mortality/therapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Colombia/epidemiology ; Colorectal Neoplasms/*mortality/therapy ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; *Oncology Service, Hospital ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Young Adult ; }, abstract = {INTRODUCTION AND AIMS: In Colombia, cancer of the colon is the third most frequent cancer in relation to incidence and mortality. Five-year survival depends on stage at diagnosis, albeit that rate is not known for the country. The aim of the present study was to characterize the overall survival and disease-free survival rates in an adult population with colorectal cancer treated at an oncology center in Medellín, Colombia.<br><br>MATERIALS AND METHODS: A retrospective cohort study was conducted. The case records of patients with a histologic diagnosis of colorectal cancer, seen within the time frame of 2011 and 2015, were reviewed. The overall survival and disease-free survival curves were calculated using the Kaplan-Meier method.<br><br>RESULTS: A total of 824 (54.9%) patients with cancer of the colon and 676 (45.1%) with cancer of the rectum were treated. Mean patient age was 63.3 years, female sex predominated (56.3%), and 98.1% of the tumors were adenocarcinomas. The majority of the lesions were stage iii (31.9% in the colon and 35.5% in the rectum) at the time of diagnosis. Surgery was the most frequent treatment in the colon (85.2%) and radiotherapy was the most frequent in the rectum (75.4%). Overall survival at the median follow-up (27.3 months) was 66.7% for cancer of the colon and 63.9% for cancer of the rectum. Disease-free survival at the median follow-up (18.6 months in colon and 14.9 in rectum) was 72.5 and 68.9%, respectively.<br><br>CONCLUSIONS: The clinical characteristics and treatment of patients were similar to those found in other studies. Two-year survival was higher than in other Colombian reports and 5-year survival was lower than that observed in developed countries.}, }
@article {pmid29879758, year = {2019}, author = {Choi, CW and Jeong, MH and Park, YS and Son, CH and Lee, HR and Koh, EK}, title = {Combination Treatment of Stereotactic Body Radiation Therapy and Immature Dendritic Cell Vaccination for Augmentation of Local and Systemic Effects.}, journal = {Cancer research and treatment}, volume = {51}, number = {2}, pages = {464-473}, pmid = {29879758}, issn = {2005-9256}, support = {50601-2017//Ministry of Science and Technology/ ; 50595-2018//Ministry of Science and Technology/ ; }, mesh = {Animals ; Antigen Presentation/immunology ; Antigen-Presenting Cells/immunology/metabolism ; Cancer Vaccines/*administration &amp; dosage/*immunology ; Cell Line, Tumor ; Combined Modality Therapy ; Cytokines/metabolism ; Dendritic Cells/*immunology/metabolism ; Disease Models, Animal ; Humans ; Immunotherapy ; Kaplan-Meier Estimate ; Mice ; Neoplasms/*immunology/mortality/pathology/*therapy ; *Radiosurgery/methods ; Tumor Burden ; }, abstract = {PURPOSE: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs).<br><br>METHODS AND MATERIALS: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system.<br><br>RESULTS: Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group.<br><br>CONCLUSION: The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.}, }
@article {pmid29879027, year = {2018}, author = {Yin, L and Li, J and Wei, Y and Ma, D and Sun, Y and Sun, Y}, title = {Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient receiving tamoxifen: A case report and literature review.}, journal = {Medicine}, volume = {97}, number = {23}, pages = {e10900}, pmid = {29879027}, issn = {1536-5964}, mesh = {Antineoplastic Agents, Hormonal/*adverse effects/therapeutic use ; Breast/pathology ; Breast Neoplasms/drug therapy/*pathology ; Endometrial Neoplasms/*pathology ; Endometrium/pathology ; Fatal Outcome ; Female ; Humans ; Laparotomy/methods ; Mastectomy/methods ; Middle Aged ; Ovarian Neoplasms/chemically induced/*pathology ; Ovary/pathology ; Small Cell Lung Carcinoma/chemically induced/*pathology ; Tamoxifen/*adverse effects/therapeutic use ; Tomography, X-Ray Computed ; }, abstract = {RATIONALE: Small cell carcinoma of the ovary (SCCO) is a rare and aggressive extra-pulmonary variant of small cell tumors of uncertain histogenesis. The pathogenesis and optimal treatment of SCCO is unclear. We present a very rare case of a synchronous primary ovarian small cell carcinoma and endometrioid adenocarcinoma of the uterus in a patient after 2 years of tamoxifen treatment for breast cancer. This is the first such report in the English literature.<br><br>PATIENT CONCERNS: A 46-year-old woman had a history of left breast cancer that was treated with a simple mastectomy and sentinel lymph node biopsy in 2013. The post-operative pathology was invasive ductal carcinoma of the left breast. she had been taking tamoxifen for 2 years. The patient underwent an exploratory laparotomy to reduce the tumor burden, improve bowel compression symptoms, and promote defecation in 2015. The post-operative pathology revealed a rare, simultaneous occurrence of two tumors (endometrial adenocarcinoma and SCCO [pulmonary type]).<br><br>DIAGNOSES: Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient.<br><br>INTERVENTIONS: The patient received 3 courses of chemotherapy after operation. The effect was not apparent and the general health status was poor.<br><br>OUTCOMES: The patient died of progressive disease 7 months post-operatively.<br><br>LESSONS: The present case suggests that tamoxifen use might be among many etiologic factors in SCCO development. Despite its rarity, SCCO requires a high degree of attention in clinical work because it is an aggressive tumor that has a poor prognosis.}, }
@article {pmid29875947, year = {2018}, author = {Kharmoum, S and Soughi, M}, title = {[Toxidermy mimicking acute chemotherapy-induced lupus erythematosus].}, journal = {The Pan African medical journal}, volume = {29}, number = {}, pages = {66}, doi = {10.11604/pamj.2018.29.66.6083}, pmid = {29875947}, issn = {1937-8688}, mesh = {Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*adverse effects ; Breast Neoplasms/drug therapy ; Capecitabine/administration &amp; dosage ; Carcinoma, Ductal, Breast/drug therapy ; Docetaxel ; Female ; Humans ; Lichenoid Eruptions/*diagnosis/immunology ; Lupus Erythematosus, Cutaneous/chemically induced/*diagnosis ; Middle Aged ; Skin Diseases/*diagnosis/immunology ; Taxoids/administration &amp; dosage ; }, abstract = {Acute chemotherapy-induced lupus erythematosus (ALE) is rare. A few cases have been reported in the literature criminalizing capecitabine, paclitaxel and docetaxel. We report the case of a 64-year old female patient without a history of autoimmune diseases or of drug allergy followed up for invasive ductal carcinoma in the right breast immediately metastatized to the liver and to the lymph nodes. After AC60 first line chemotherapy regimen (a total of 6 cycles), she was treated with docetaxel at a dose of 100 mg/m[2]. After 5 cycles, she had diffuse erythematous lesions on both hands, forearms, cheeks and on the peribuccal area. She underwent corticosteroid therapy with sun protection and could continue the same chemotherapy until the eighth cycle. Patient's evolution was marked by the progression of the disease. She was treated with capecitabine at a dose of 1250 mg/m[2] twice a day. After six cycles she had erythematosquamous and itchy patches on the face resembling the wings of a butterfly (Panel A, Panel B) with oral ulceration and digital pulpitis (Panel C). This initially suggested acute chemotherapy-induced cutaneous lupus erythematosus. Biopsy suggested lichenoid toxidermia. Immunological assessment was performed to exclude chemotherapy-induced cutaneous lupus erythematosus, which showed anti-native DNA antibodies and negative anti-histone antibodies. Anti-nuclear antibody test is positive at 320; this test may be positive in 50-70% of patients with breast cancer, ENT or lymphoma. In the light of these results the diagnosis of toxidermia was the more likely.}, }
@article {pmid29874679, year = {2018}, author = {Kopf, S and Groener, JB and Kender, Z and Fleming, T and Brune, M and Riedinger, C and Volk, N and Herpel, E and Pesta, D and Szendrödi, J and Wielpütz, MO and Kauczor, HU and Katus, HA and Kreuter, M and Nawroth, PP}, title = {Breathlessness and Restrictive Lung Disease: An Important Diabetes-Related Feature in Patients with Type 2 Diabetes.}, journal = {Respiration; international review of thoracic diseases}, volume = {96}, number = {1}, pages = {29-40}, doi = {10.1159/000488909}, pmid = {29874679}, issn = {1423-0356}, mesh = {Adult ; Aged ; Diabetes Complications/epidemiology ; Diabetes Mellitus, Type 2/*complications ; Dyspnea/epidemiology/*etiology ; Female ; Humans ; Incidence ; Lung Diseases, Interstitial/diagnosis/*etiology ; Male ; Middle Aged ; Prediabetic State/complications ; Respiratory Function Tests ; Tomography, X-Ray Computed ; Walk Test ; }, abstract = {BACKGROUND: Diabetes mellitus is a significant comorbidity of interstitial lung disease (ILD).<br><br>OBJECTIVES: The aim of this study was to investigate the incidence of restrictive lung disease (RLD) and ILD in patients with prediabetes and type 2 diabetes (T2D).<br><br>METHODS: Forty-eight nondiabetics, 68 patients with prediabetes, 29 newly diagnosed T2D, and 110 patients with long-term T2D were examined for metabolic control, diabetes-related complications, breathlessness, and lung function. Five participants with T2D, breathlessness, and RLD underwent multidetector computed tomography (MDCT) and a Six-Minute Walk Test (6MWT). Lung tissue from 4 patients without diabetes and from 3 patients with T2D was histologically examined for presence of pulmonary fibrosis.<br><br>RESULTS: Breathlessness in combination with RLD was significantly increased in patients with prediabetes and T2D (p < 0.01). RLD was found in 9% of patients with prediabetes, in 20% of patients with newly diagnosed T2D, and in 27% of patients with long-term T2D. Thus, patients with long-term T2D had an increased risk of RLD (OR 5.82 [95% CI 1.71-20.5], p < 0.01). RLD was significantly associated with glucose metabolism and albuminuria (p < 0.01); furthermore, presence of nephropathy increased the risk of RLD (OR 8.57 [95% CI 3.4-21.9], p < 0.01) compared to nondiabetics. MDCT revealed ILD in 4 patients, the 6MWT correlated with the extent of ILD, and histological analysis showed fibrosing ILD in patients with T2D.<br><br>CONCLUSIONS: This study demonstrates increased breathlessness and a high prevalence of RLD in patients with T2D, indicating an association between diabetes and fibrosing ILD.}, }
@article {pmid29870876, year = {2018}, author = {Mills, MN and Yang, GQ and Oliver, DE and Liveringhouse, CL and Ahmed, KA and Orman, AG and Laronga, C and Hoover, SJ and Khakpour, N and Costa, RLB and Diaz, R}, title = {Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {98}, number = {}, pages = {48-58}, doi = {10.1016/j.ejca.2018.04.011}, pmid = {29870876}, issn = {1879-0852}, mesh = {Adult ; Aged ; Carcinoma, Adenoid Cystic/*pathology/therapy ; Carcinoma, Ductal, Breast/*parasitology/therapy ; Carcinoma, Lobular/*pathology/therapy ; Databases, Factual/statistics &amp; numerical data ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Prognosis ; Triple Negative Breast Neoplasms/*pathology/therapy ; United States ; }, abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC.<br><br>METHODS: A total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC)&#xa0;or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan-Meier analysis, log-rank testing&#xa0;and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome.<br><br>RESULTS: MBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%)&#xa0;and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p&#xa0;<&#xa0;0.001). TNBC predicted an inferior OS in IDC (p&#xa0;<&#xa0;0.001) and ILC (p&#xa0;<&#xa0;0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%)&#xa0;and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p&#xa0;<&#xa0;0.001). TNBC patients with MBC (HR 1.39, p&#xa0;<&#xa0;0.001), MedBC (HR 0.42, p&#xa0;<&#xa0;0.001)&#xa0;and ACC (HR 0.32, p&#xa0;=&#xa0;0.003) differed significantly in OS when compared to IDC.<br><br>CONCLUSION(S): Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes&#xa0;and thus, has the potential to aid in the development of optimum personalised treatments.}, }
@article {pmid29867980, year = {2018}, author = {Alamri, A and Rahman, R and Zhang, M and Alamri, A and Gounni, AS and Kung, SKP}, title = {Semaphorin-3E Produced by Immature Dendritic Cells Regulates Activated Natural Killer Cells Migration.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {1005}, pmid = {29867980}, issn = {1664-3224}, mesh = {Animals ; Cell Communication/immunology ; Cells, Cultured ; Cytoskeletal Proteins ; Dendritic Cells/*immunology ; Gene Expression Regulation ; Glycoproteins/*genetics/immunology ; Immunity, Innate ; Killer Cells, Natural/*cytology ; *Lymphocyte Activation ; Membrane Proteins/*genetics/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Semaphorins ; Signal Transduction/immunology ; }, abstract = {Natural killer (NK) cells and dendritic cells (DCs) are two innate immune cells that are critical in regulating innate and adaptive immunity. Cellular functions and migratory responses of NK or DC can be further regulated in NK-DC crosstalk that involves multiple cytokine signals and/or direct cell-cell contacts. Semaphorin-3E (Sema-3E) is a member of a large family of Semaphorin proteins that play diverse regulatory functions in different biological systems upon its binding to the cognate receptors. However, possible role(s) of Sema-3E on the regulation of NK-cell functions has not been elucidated. Here, we first demonstrated that DC and NK cells expressed Sema-3E and its receptors, respectively. To formally address the importance of DC-derived Sema-3E in regulating NK-cell migration, we compared in vitro migratory responses of activated NK cells (aNKs) toward different conditioned media of DCs (immature, lipopolysaccharide- or Poly I:C-stimulated) derived from Sema-3E[+/+] or Sema-3E[-/-] mice. We observed that aNKs exhibited enhanced migrations toward the conditioned medium of the immature Sema-3E[-/-] DC, when compared with that of the immature Sema-3E[+/+] DC. Addition of exogenous recombinant Sema-3E to the conditioned medium of the Sema-3E[-/-] immature DC (iDC) abrogated such enhanced NK-cell migration. Our current work revealed a novel role of Sema-3E in limiting NK-cell migrations toward iDC in NK-DC crosstalk.}, }
@article {pmid29860265, year = {2018}, author = {Guo, X and Li, J and Zhang, H and Liu, H and Liu, Z and Wei, X}, title = {Relationship Between ADAMTS8, ADAMTS18, and ADAMTS20 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) Expressions and Tumor Molecular Classification, Clinical Pathological Parameters, and Prognosis in Breast Invasive Ductal Carcinoma.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {24}, number = {}, pages = {3726-3735}, pmid = {29860265}, issn = {1643-3750}, mesh = {ADAMTS Proteins/*biosynthesis/genetics ; Adult ; Aged ; Breast Neoplasms/classification/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/classification/genetics/*metabolism/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptors, Estrogen/metabolism ; Transcriptome ; }, abstract = {BACKGROUND The aim of this study was to investigate the correlations between ADAMTSs expression and breast invasive ductal carcinoma (IDC), and to offer a theoretical basis for novel treatment methods for IDC patients. MATERIAL AND METHODS Non-proliferative catheter of breast fibroadenoma (FA) and IDC were used as the normal control and experimental group, respectively. Immunohistochemical (IHC) staining and Western blot (WB) analysis was used to assess protein expression levels of ADAMTS8, ADAMTS18, and ADAMTS20 in both FA and IDC tissues. The results of IHC, the relationship between the protein expression and the tumor molecular classification, and clinical pathological parameters were all evaluated. RESULTS IHC and WB results showed that the expression of ADAMTS8/18 in IDC samples was higher than in FA samples, while the expression of ADAMTS20 in IDC samples was lower than that in FA samples. According to the results of WB, the level of ADAMTS8 was higher in the HER2+ group than in the HER2- group and FA group. The expression of ADAMTS18 in the HR+ (including ER+ and PR+) group was significantly higher than in the HR- group and FA group. The expression of ADAMTS18 protein was also higher in the Ki67+ group than in the Ki67- group. ADAMTS20 was higher in HER2+ IDC compared with the basal subtype of IDC. CONCLUSIONS ADAMTS8/18/20 levels were not significantly correlated to the molecular subtype of IDC. ADAMTS18/20 was significantly associated with histological grade of IDC. ADAMTS8 may predict poor prognosis results of IDC patients.}, }
@article {pmid29848684, year = {2018}, author = {Rusak, A and Jablonska, K and Piotrowska, A and Grzegrzolka, J and Nowak, A and Wojnar, A and Dziegiel, P}, title = {The Role of CHI3L1 Expression in Angiogenesis in Invasive Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {38}, number = {6}, pages = {3357-3366}, doi = {10.21873/anticanres.12602}, pmid = {29848684}, issn = {1791-7530}, mesh = {Antigens, CD34/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Chitinase-3-Like Protein 1/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic/genetics/*metabolism/pathology ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor C/metabolism ; Vascular Endothelial Growth Factor D/metabolism ; }, abstract = {BACKGROUND/AIM: An increased level of chitinase 3 like 1 protein (CHI3L1) expression is observed in patients with cancer and may have potential prognostic value. The aim of this study was to evaluate the role of CHI3L1 in angiogenesis in invasive ductal breast carcinoma (IDC) (n=110).<br><br>MATERIALS AND METHODS: Immunohistochemistry was used to assess the expression of CHI3L1, CD31, CD34, vascular endothelial growth factor (VEGFA, VEGFC and VEGFD). Real-time polymerase chain reaction and western blot were used to determine the level of CHI3L1 mRNA and protein.<br><br>RESULTS: Immunohistochemistry demonstrated positive correlation between CHI3L1 expression and angiogenesis markers: CD31 (r=0.34, p=0.0003), CD34 (r=0.24, p=0.012), VEGFD (r=0.24, p=0.013). Higher CHI3L1 expression in estrogen receptor-negative (p=0.041) and progesterone receptor-negative (p=0.014) cancer was observed. Higher CHI3L1 expression was reported in cancer tissues in comparison to non-malignant breast lesions.<br><br>CONCLUSION: These results suggest a potential role of CHI3L1 in angiogenesis in IDC and may suggest its involvement in cancer progression.}, }
@article {pmid29804148, year = {2018}, author = {Santangelo, G and Bisecco, A and Trojano, L and Sacco, R and Siciliano, M and d'Ambrosio, A and Della Corte, M and Lavorgna, L and Bonavita, S and Tedeschi, G and Gallo, A}, title = {Cognitive performance in multiple sclerosis: the contribution of intellectual enrichment and brain MRI measures.}, journal = {Journal of neurology}, volume = {265}, number = {8}, pages = {1772-1779}, pmid = {29804148}, issn = {1432-1459}, mesh = {Adolescent ; Adult ; Atrophy ; Brain/*diagnostic imaging ; Cognition Disorders/diagnostic imaging/etiology ; *Cognitive Reserve ; Cross-Sectional Studies ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/complications/*diagnostic imaging/*psychology ; Organ Size ; Young Adult ; }, abstract = {Cognitive reserve (CR) is a construct that originates from the observation of poor correspondence between brain damage and clinical symptoms. The aim of the study was to investigate the association between cognitive reserve (CR), brain reserve (BR) and cognitive functions and to evaluate whether CR might attenuate/moderate the negative impact of brain atrophy and lesion load on cognitive functions in multiple sclerosis (MS). To achieve these aims, ninety-eight relapsing-remitting MS patients underwent the brief repeatable battery of neuropsychological tests and Stroop test (ST). CR was assessed by vocabulary-based estimate of lifetime intellectual enrichment. All patients underwent a 3T MRI to assess T2-lesion load and atrophy measures, including normalized gray matter and white matter (nWMV) volumes. The BR was evaluated by maximal lifetime brain volume expressed by intracranial volume (ICV). Hierarchical regressions were used to investigate whether higher BR and/or CR is related to better cognitive performances after controlling for potentially confounding factors. The ICV was not associated with any cognitive tests. Intellectual enrichment was positively associated with performance on tests assessing memory, attention and information processing speed, verbal fluency and inhibitory control. Significant relationship between nWMV and ST was moderated by intellectual enrichment. In conclusion, the findings suggested that CR seems to mitigate cognitive dysfunction in MS patients and can reduce the negative impact of brain atrophy on inhibitory control, relevant for integrity of instrumental activities of daily living.}, }
@article {pmid29804074, year = {2018}, author = {Schellenberg, AE and Wood, ML and Baniak, N and Hayes, P}, title = {Metastatic ductal carcinoma of the breast to colonic mucosa.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, pmid = {29804074}, issn = {1757-790X}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*secondary ; Colonic Neoplasms/diagnosis/*secondary ; Colonoscopy ; Female ; Humans ; Incidental Findings ; Intestinal Mucosa/pathology ; Rectal Neoplasms/diagnosis/*secondary ; }, abstract = {Breast cancer is the most common malignancy among women, while invasive ductal carcinoma is the most common type of invasive breast cancer. Metastatic spread to the colon and rectum in breast cancer is rare. This report describes a case of a 69-year-old woman with metastatic ductal breast cancer to the rectosigmoid, presenting as an incidental finding on screening colonoscopy. The breast carcinoma was first diagnosed 2 years prior. Colonic biopsies from colonoscopy confirmed metastatic adenocarcinoma consistent with a breast primary. Ultimately her clinical condition worsened as she developed malignant ascites, a small bowel obstruction, and new bone metastases, and the patient succumbed to her illness. Cases of metastatic breast cancer to the gastrointestinal tract have predominantly been lobular breast carcinoma. Increased awareness of colonic metastasis may lead to more accurate diagnosis and earlier systemic treatment.}, }
@article {pmid29802469, year = {2018}, author = {Di Oto, E and Biserni, GB and Varga, Z and Morandi, L and Cucchi, MC and Masetti, R and Foschini, MP}, title = {X chromosome gain is related to increased androgen receptor expression in male breast cancer.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {473}, number = {2}, pages = {155-163}, pmid = {29802469}, issn = {1432-2307}, support = {Fundamentally Oriented Funds for Research - RFO//Universit&#xe0; di Bologna/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Chromosomes, Human, X/genetics ; Gene Amplification ; Genes, X-Linked/*genetics ; Humans ; Male ; Middle Aged ; Receptors, Androgen/biosynthesis/*genetics ; *Sex Chromosome Aberrations ; }, abstract = {X chromosome gain has been previously described in male breast cancer (MBC). Androgen receptor (AR) gene is located on X chromosome. The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia. Cases were tested by fluorescence in situ hybridization (FISH) to assess the X chromosome status and AR amplification. AR expression was studied by immunohistochemistry (IHC). In addition, AR methylation status was assessed.X chromosome gain was observed in 74.7% of invasive duct carcinoma, in 20.6% of in situ duct carcinoma, and in 14.6% of gynecomastia when associated with cancer, while all cases of tumor-free gynecomastia showed wild X chromosome asset. AR gene copy number when increased paralleled the number of X chromosomes. AR IHC expression was observed in 100% of MBC tested. AR gene methylation status revealed low level or absence of methylation.These data suggest that X chromosome can play a role in the neoplastic transformation of male breast epithelium. X chromosome gain is paralleled by AR gene polysomy. Polysomic AR genes show low methylation levels and high AR protein expression on IHC. These data should be taken into consideration for MBC treatment planning.}, }
@article {pmid29772102, year = {2018}, author = {Zhao, J and Sun, G and Liao, B and Zhang, X and Armstrong, CM and Yin, X and Liu, J and Chen, J and Yang, Y and Zhao, P and Tang, Q and Wang, Z and Chen, Z and Li, X and Wei, Q and Li, X and Chen, N and Gao, AC and Shen, P and Zeng, H}, title = {Novel nomograms for castration-resistant prostate cancer and survival outcome in patients with de novo bone metastatic prostate cancer.}, journal = {BJU international}, volume = {122}, number = {6}, pages = {994-1002}, doi = {10.1111/bju.14398}, pmid = {29772102}, issn = {1464-410X}, mesh = {Aged ; Bone Neoplasms/drug therapy/metabolism/*secondary ; Humans ; Male ; Models, Statistical ; *Nomograms ; Prostate-Specific Antigen/analysis ; Prostatic Neoplasms, Castration-Resistant/metabolism/mortality/*pathology ; Survival Analysis ; }, abstract = {OBJECTIVES: To develop nomograms predicting the incidence of castration-resistant prostate cancer (CRPC) and overall survival (OS) for de novo metastatic prostate cancer (PCa).<br><br>PATIENTS AND METHODS: Data from 449 patients with de novo metastatic PCa were retrospectively analysed. Patients were randomly divided into a training (n = 314, 70%) and a validation cohort (n = 135, 30%). Predictive factors were selected using a Cox proportional hazards model and were further used for building predictive models. The outcomes were incidence of CRPC and OS.<br><br>RESULTS: Predictive factors included: Gleason score (GS), intraductal carcinoma of the prostate (IDC-P), Eastern Cooperative Oncology Group status, and alkaline phosphatase, haemoglobin and prostate-specific antigen levels. IDC-P and GS were the strongest prognosticators for both the incidence of CRPC and OS. Nomograms for predicting CRPC and OS had an internal validated concordance index of 0.762 and 0.723, respectively. Based on the &#x3b2; coefficients of the final model, risk classification systems were constructed. For those with favourable, intermediate and poor prognosis, the median time to CRPC was 62.6, 28.0 and 13.0&#xa0;months (P < 0.001), respectively; and the median OS was not reached, 55.0 and 33.0&#xa0;months, respectively (P < 0.001).<br><br>CONCLUSIONS: We developed two novel nomograms to predict the incidence of CRPC and OS for patients with de novo metastatic PCa. These tools may assist in physician decision-making and the designing of clinical trials.}, }
@article {pmid29760696, year = {2018}, author = {Cougoule, C and Lastrucci, C and Guiet, R and Mascarau, R and Meunier, E and Lugo-Villarino, G and Neyrolles, O and Poincloux, R and Maridonneau-Parini, I}, title = {Podosomes, But Not the Maturation Status, Determine the Protease-Dependent 3D Migration in Human Dendritic Cells.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {846}, pmid = {29760696}, issn = {1664-3224}, mesh = {Cell Differentiation ; *Cell Movement ; Cells, Cultured ; Chemokines/immunology ; Dendrites/immunology ; Dendritic Cells/*cytology/enzymology ; Endopeptidases/*metabolism ; Humans ; Macrophages/immunology ; Podosomes/*immunology ; Toll-Like Receptors/immunology ; rho-Associated Kinases/immunology ; }, abstract = {Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo, or in collagen matrices in vitro. However, the mechanisms of 3D migration used by human immature DC (iDC) are still poorly characterized. Here, we reveal that human monocyte-derived DC are able to use two migration modes in 3D. In porous matrices of fibrillar collagen I, iDC adopted the amoeboid migration mode. In dense matrices of gelled collagen I or Matrigel, iDC used the protease-dependent, ROCK-independent mesenchymal migration mode. Upon TLR4 activation by LPS, mDC-LPS lose the capacity to form podosomes and degrade the matrix along with impaired mesenchymal migration. TLR2 activation by Pam3CSK4 resulted in DC maturation, podosome maintenance, and efficient mesenchymal migration. Under all these conditions, when DC used the mesenchymal mode in dense matrices, they formed 3D podosomes at the tip of cell protrusions. Using PGE2, known to disrupt podosomes in DC, we observed that the cells remained in an immature status and the mesenchymal migration mode was abolished. We also observed that, while CCL5 (attractant of iDC) enhanced both amoeboid and mesenchymal migration of iDC, CCL19 and CCL21 (attractants of mDC) only enhanced mDC-LPS amoeboid migration without triggering mesenchymal migration. Finally, we examined the migration of iDC in tumor cell spheroids, a tissue-like 3D environment. We observed that iDC infiltrated spheroids of tumor cells using both migration modes. Altogether, these results demonstrate that human DC adopt the mesenchymal mode to migrate in 3D dense environments, which relies on their capacity to form podosomes independent of their maturation status, paving the way of further investigations on in vivo DC migration in dense tissues and its regulation during infections.}, }
@article {pmid29759595, year = {2018}, author = {Da Ros, L and Moretti, A and Querzoli, P and Pedriali, M and Lupini, L and Bassi, C and Carcoforo, P and Negrini, M and Frassoldati, A}, title = {HER2-Positive Lobular Versus Ductal Carcinoma of the Breast: Pattern of First Recurrence and Molecular Insights.}, journal = {Clinical breast cancer}, volume = {18}, number = {5}, pages = {e1133-e1139}, doi = {10.1016/j.clbc.2018.04.006}, pmid = {29759595}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Immunological/therapeutic use ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Carcinoma, Lobular/drug therapy/genetics/*pathology ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local/epidemiology ; Receptor, ErbB-2 ; Retrospective Studies ; Trastuzumab/therapeutic use ; }, abstract = {BACKGROUND: Infiltrating lobular carcinoma (ILC) represents about 10% of breast cancer and rarely shows overexpression of human epidermal growth factor receptor 2 (HER2). We compared biological and clinical characteristics of HER2-positive ILC versus HER2-positive infiltrating ductal carcinoma (IDC).<br><br>PATIENTS AND METHODS: We retrospectively analyzed the data of 328 patients with HER2-positive pure ductal or lobular breast carcinoma, comparing clinical and biological data at diagnosis as well as outcome between the 2 histologies. A gene-mutation analysis was performed in a subset of patients.<br><br>RESULTS: Two hundred ninety-one patients (88.7%) had IDC and 37 patients (11.3%) ILC. ILC resulted more frequently in multicenter (24.3% vs. 6.5%, P&#xa0;< .0001) and node-positive (54.1% vs. 45%, P&#xa0;=&#xa0;.013) disease of lower proliferative activity (Mib1&#xa0;< 20%: 51.4% vs. 22.3%, P&#xa0;< .0001) and lower histologic grade (grade 3: 32.4% vs. 57.4%, P&#xa0;= .038). Disease recurred in 57 patients (17.4%) and involved the bone in 40% of ILC patients (vs. 17% of IDC patients) and the viscera in 30% of ILC patients (vs. 59.6% of IDC patients). No difference in the recurrence rate between the 2 histologies was observed in patients treated with adjuvant trastuzumab (12.5% of ILC patients and 8.3% of IDC patients). Exploratory molecular analysis revealed a higher frequency of mutations in ILC, with more cases of multiple mutations.<br><br>CONCLUSION: HER2-positive ILC shows different biological behavior than IDC, with a possible higher mutation load. Despite lower proliferation activity and estrogen receptor expression in ILC breast cancer, trastuzumab is clearly an effective therapy for this histologic subtype.}, }
@article {pmid29751292, year = {2018}, author = {Maida, A and Zota, A and Vegiopoulos, A and Appak-Baskoy, S and Augustin, HG and Heikenwalder, M and Herzig, S and Rose, AJ}, title = {Dietary protein dilution limits dyslipidemia in obesity through FGF21-driven fatty acid clearance.}, journal = {The Journal of nutritional biochemistry}, volume = {57}, number = {}, pages = {189-196}, doi = {10.1016/j.jnutbio.2018.03.027}, pmid = {29751292}, issn = {1873-4847}, support = {//CIHR/Canada ; }, mesh = {Animals ; CD36 Antigens/genetics ; Dietary Proteins/*pharmacology ; Dyslipidemias/*diet therapy/etiology/metabolism ; Fatty Acids/*metabolism ; Fibroblast Growth Factors/*metabolism ; Hypertriglyceridemia/diet therapy/etiology ; Lipid Metabolism/drug effects ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Obese ; Non-alcoholic Fatty Liver Disease/diet therapy/etiology ; Obesity/*complications/metabolism ; }, abstract = {Recent studies have demonstrated that dietary protein dilution (PD) can promote metabolic inefficiency and improve glucose metabolism. However, whether PD can promote other aspects of metabolic health, such as improve systemic lipid metabolism, and mechanisms therein remains unknown. Mouse models of obesity, such as high-fat-diet-fed C57Bl/6 N mice, and New Zealand Obese mice were fed normal (i.e., 20%P) and protein-dilute (i.e., 5%EP) diets. FGF21-/- and Cd36-/- and corresponding littermate +/+ controls were also studied to examine gene-diet interactions. Here, we show that chronic PD retards the development of hypertrigylceridemia and fatty liver in obesity and that this relies on the induction of the hepatokine fibroblast growth factor 21 (FGF21). Furthermore, PD greatly enhances systemic lipid homeostasis, the mechanisms by which include FGF21-stimulated, and cluster of differentiation 36 (CD36) mediated, fatty acid clearance by oxidative tissues, such as heart and brown adipose tissue. Taken together, our preclinical studies demonstrate a novel nutritional strategy, as well as highlight a role for FGF21-stimulated systemic lipid metabolism, in combating obesity-related dyslipidemia.}, }
@article {pmid29748110, year = {2018}, author = {Santangelo, G and Vitale, C and Baiano, C and D'Iorio, A and Longo, K and Barone, P and Amboni, M and Conson, M}, title = {Interoceptive processing deficit: A behavioral marker for subtyping Parkinson's disease.}, journal = {Parkinsonism &amp; related disorders}, volume = {53}, number = {}, pages = {64-69}, doi = {10.1016/j.parkreldis.2018.05.001}, pmid = {29748110}, issn = {1873-5126}, mesh = {Aged ; Female ; Gait Disorders, Neurologic/etiology/*physiopathology ; Humans ; Interoception/*physiology ; Male ; Middle Aged ; Parkinson Disease/*classification/complications/*physiopathology ; Postural Balance/*physiology ; Tremor/etiology/*physiopathology ; }, abstract = {BACKGROUND: Non-motor symptoms in Parkinson's disease (PD), such as cognitive, emotional, autonomic and somatosensory alterations, are not ubiquitous but vary between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes of the syndrome. Non-motor phenomena (e.g., anxiety, depression and apathy) have been related to representation of autonomic and somatosensory sensations (interoception), and recent findings suggest interoceptive deficits in PD.<br><br>OBJECTIVES: To test whether interoceptive processing is differently affected in TD and PIGD phenotypes, by assessing both interoceptive accuracy and sensibility in PD patients with TD and PIGD subtypes, and in healthy controls.<br><br>METHODS: Interoceptive accuracy was measured by the heartbeat perception task requiring participants to count their own heartbeats in a given time interval. A time-estimation, control task was also administered asking participants to count the seconds in a set period of time. Interoceptive sensibility was assessed by a questionnaire of subjective interoception. Finally, the patients underwent measures of anxiety, depression, apathy and anhedonia, and impulsive-compulsive disturbances.<br><br>RESULTS: The main results showed reduced interoceptive accuracy and sensibility in TD patients relative to both PIGD patients and healthy controls. Reduced interoceptive accuracy of TD group was a reliable result since their performance on the time estimation control task was comparable to that of both PIGD patients and healthy controls.<br><br>CONCLUSIONS: These findings demonstrate that the behavioural assessment of different aspects of interoceptive processing can provide with a further marker for subtyping patients with PD.}, }
@article {pmid29745077, year = {2018}, author = {Marusa Borgonio-Cuadra, V and Miranda-Duarte, A and Rojas-Toledo, X and Garcia-Hernandez, N and Alfredo Sierra-Ramirez, J and Cardenas-Garcia, M and Elena Hernandez-Caballero, M}, title = {Association between promoter hypermethylation of the DACT2 gene and tumor stages in breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {23}, number = {2}, pages = {361-365}, pmid = {29745077}, issn = {1107-0625}, mesh = {Adaptor Proteins, Signal Transducing ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carrier Proteins/*genetics ; Cell Line, Tumor ; CpG Islands/genetics ; DNA Methylation/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Genetic Association Studies ; Humans ; Middle Aged ; Neoplasm Proteins/*genetics ; Neoplasm Staging ; Promoter Regions, Genetic ; }, abstract = {PURPOSE: Aberrant methylation of CpG islands in the promoter is a hallmark of cancer, leading to transcriptional silencing of tumor suppressor genes. The aim of this work was to evaluate the promoter methylation status of the DACT2 gene in breast cancer (BC) tissue and to analyze its possible effect on tumor type or grade.<br><br>METHODS: CpG island from the DACT2 promoter in region -240 to -14 from transcriptional start site (TSS) were obtained. Through the use of sodium bisulfite DNA conversion analysis, followed by detection with MSP (methylation specific PCR), we analyzed 79 BC and 15 adjacent healthy samples.<br><br>RESULTS: T he c ases a nalyzed w ere i n s tage I (2.5%), I I (38%), or III (59.5%). The most frequent tumor type was invasive ductal carcinoma (71.4%). Methylation analysis comparing tumor tissues with adjacent non-cancerous tissues showed statistical significance. Methylation was observed in 32.9% (26/79) of the samples; no methylation was found in adjacent healthy tissue. DACT2 methylation was associated with tumor stage I-II (p=0.03) and stage III (p=0.004).<br><br>CONCLUSION: An association was found of DACT2 promoter methylation with advanced tumor stages. This gene has been suggested as a potential biomarker, however, more investigation is required to validate this function.}, }
@article {pmid29739984, year = {2018}, author = {Du, T and Zhu, L and Levine, KM and Tasdemir, N and Lee, AV and Vignali, DAA and Houten, BV and Tseng, GC and Oesterreich, S}, title = {Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {7205}, pmid = {29739984}, issn = {2045-2322}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Atlases as Topic ; Breast Neoplasms/diagnosis/genetics/*immunology/metabolism ; Carcinoma, Ductal, Breast/diagnosis/genetics/*immunology/metabolism ; Carcinoma, Lobular/diagnosis/genetics/*immunology/metabolism ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Immune System/immunology/metabolism/pathology ; Immunotherapy/methods ; Lymphatic Metastasis ; Metabolic Networks and Pathways/genetics/*immunology ; Middle Aged ; Neoplasm Proteins/classification/genetics/*immunology/metabolism ; Neoplasm Recurrence, Local/diagnosis/genetics/*immunology/metabolism ; Protein Biosynthesis ; Tumor Escape/genetics ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set. Top pathways that were significantly enriched in ILC were related to immune response. ILC exhibited a higher activity of almost all types of immune cells based on cell type-specific signatures compared to IDC. Conversely, pathways that were less enriched in ILC were related to protein translation and metabolism, which we functionally validated in cell lines. The higher immune activity uncovered in our study highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC. Furthermore, the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.}, }
@article {pmid29733543, year = {2018}, author = {Nahleh, Z and Otoukesh, S and Mirshahidi, HR and Nguyen, AL and Nagaraj, G and Botrus, G and Badri, N and Diab, N and Alvarado, A and Sanchez, LA and Dwivedi, AK}, title = {Disparities in breast cancer: a multi-institutional comparative analysis focusing on American Hispanics.}, journal = {Cancer medicine}, volume = {7}, number = {6}, pages = {2710-2717}, pmid = {29733543}, issn = {2045-7634}, mesh = {Black or African American ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/metabolism/pathology/therapy ; Disease Management ; Ethnicity ; Female ; *Healthcare Disparities ; *Hispanic or Latino ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; }, abstract = {UNLABELLED: Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latino women nationwide. Hispanic women are more likely to be presented with advanced disease and adverse prognosis subtypes. The aim of this study is to describe the clinico- pathological characteristics and disparities in breast cancer in this group at two tertiary care University-based medical centers. After IRB approval, Cancer registry was used to analyze the variables of 3441 patients with breast cancer diagnosed and treated consecutively at two large tertiary University based medical and cancer center database centers in El Paso, TX and Loma Linda, CA between 2005 and 2015. Association between race/ethnicity and cancer type, stage, hormone receptor status and treatment option were investigated. Overall 45.5% of the patients were Hispanic (n: 1566) and those were more likely to be diagnosed at a younger age (57 years) similar to African Americans, more likely to have invasive ductal carcinoma type (82.7%) &amp; triple negative disease (17.1%, 95%CI: 15% to 19%). 58.8% of Hispanics (95%CI: 56% to 61%) have hormone receptor (HR)+ &amp; HER2- as opposed to 71% in non-Hispanic White people. In addition, Hispanic individuals presented with advanced stages of BC (25.3%, 95% CI: 23% to 28%) similar to African American (25.4%), and had a lower proportion of lumpectomy (50%) similar to African American (50%). When compared to African American patients, Hispanic patients had a higher prevalence of triple negative BC (17.11% in Hispanics Versus 13.86% in African American).<br><br>CONCLUSION: Hispanics had significantly higher relative risk of advanced stages at presentation (Relative Risk Ratio (RRR)&#xa0;=&#xa0;2.05, P&#xa0;<&#xa0;0.001), triple negative tumors (RRR&#xa0;=&#xa0;2.64, P&#xa0;<&#xa0;0.0001), HER2&#xa0;+&#xa0;/HR - disease (RRR&#xa0;=&#xa0;1.77, P&#xa0;<&#xa0;0.0001), and less HR+ /HER2- BC (RRR&#xa0;=&#xa0;0.69, P&#xa0;<&#xa0;0.0001). Hispanics and African Americans are diagnosed with breast cancer at a younger age, have a higher prevalence of Triple negative breast cancer, and are diagnosed at more advanced stages of disease. Increasing awareness and targeting minority populations for health promotion interventions, screening and early detection continue to be of paramount importance to reduce the burden of health disparities.}, }
@article {pmid29703057, year = {2018}, author = {Xie, L and Lin, C and Zhang, H and Bao, X}, title = {Second malignancy in young early-stage breast cancer patients with modern radiotherapy: A long-term population-based study (A STROBE-compliant study).}, journal = {Medicine}, volume = {97}, number = {17}, pages = {e0593}, pmid = {29703057}, issn = {1536-5964}, mesh = {Adult ; Age Factors ; Axilla ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Cancer Survivors/*statistics &amp; numerical data ; Carcinoma, Ductal, Breast/*radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lymph Node Excision ; Lymph Nodes/pathology/surgery ; Mastectomy, Segmental ; Neoplasm Staging ; Neoplasms, Second Primary/*epidemiology/etiology ; Radiotherapy, Adjuvant/adverse effects/methods ; Risk Factors ; SEER Program ; Time Factors ; Young Adult ; }, abstract = {Second cancer is a leading cause of death in long-term survivors of younger early-stage breast cancer patients. To date, relationship of age, receipt of radiotherapy (RT), and estimated doses received by target organs have not yet been well elucidated. Using Surveillance, Epidemiology, and End Results database, patients aged 20 to 44, diagnosed with a first primary staging I-IIIA ipsilateral breast invasive ductal carcinoma, underwent surgery during 1988 to 2009 were identified, and those with a second malignancy at ≥1-year follow-up were analyzed to calculate cumulative incidences (CIs) of second malignancy in whole group and each subgroup. Subgroups were dichotomized by surgery type, axillary dissection, and axillary lymph node status. With a median follow-up of 11.8 years, 22,628 women including 1495 patients (6.6%) developing second malignancies (3.7% contralateral breast cancer, 2.9% non-breast second malignancies, and 0.7% high-dose site second malignancies) were identified. Three-dimensional coordinate systems with age at primary diagnosis, time after primary breast cancer diagnosis, and CI of second malignancy as 3 axes, for endpoints including all second malignancy, second primary contralateral breast cancer, and non-breast second malignancy were presented, along with the risk in RT and non-RT groups in overall group and subgroups. Five-, 10-, 15-, and 20-year all second malignancy-free survivals in RT and non-RT groups were 89.5% versus 85.4%, 80.1% versus 75.0%, 72.9% versus 67.9%, and 65.6% versus 61.8% (P < .0001). From the large national dataset, a broad visualized overview of second malignancy risk, including second contralateral breast cancer and non-breast second cancer, suggests generally beneficial therapeutic ratio for radiotherapy in young women with early-stage breast cancer.}, }
@article {pmid29700276, year = {2018}, author = {Rahmani, M and Nili, F and Tabibian, E}, title = {Endometrial Metastasis from Ductal Breast Carcinoma: A Case Report with Literature Review.}, journal = {The American journal of case reports}, volume = {19}, number = {}, pages = {494-499}, pmid = {29700276}, issn = {1941-5923}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Endometrial Neoplasms/*secondary ; Female ; Humans ; Menorrhagia/etiology ; Middle Aged ; Uterine Hemorrhage/etiology ; }, abstract = {BACKGROUND There are few reports of breast cancer cases with uterine metastases; among them, myometrium is more frequently involved than endometrium. The majority of breast cancer metastases to endometrium are lobular type, and there have been only 5 reported cases of ductal type since 1984. Here, we describe a new case of invasive ductal carcinoma with metastases to endometrium and isolated presentation of abnormal uterine bleeding, in addition to reviewing the existing literature on other similar cases. CASE REPORT The patient was a 51-year-old Persian woman with no remarkable past medical or family history of cancer, who presented with a 6-month complaint of menorrhagia to our gynecology clinic. Diagnostic studies including trans-vaginal ultrasonography, pathological examination of endometrial curettage specimen, immunohistochemistry findings, and X-plane and magnetic resonance mammography, and breast core-needle biopsy revealed invasive ductal breast carcinoma as the origin of the endometrial metastasis. CONCLUSIONS Abnormal uterine bleeding in a premenopausal patient should alert clinicians to the possibility of secondary as well as primary neoplasms. It is necessary to differentiate a metastatic tumor from a primary one, since the treatment and prognosis are completely different.}, }
@article {pmid29695771, year = {2018}, author = {Bharti, R and Dey, G and Das, AK and Mandal, M}, title = {Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.}, journal = {British journal of cancer}, volume = {118}, number = {11}, pages = {1442-1452}, pmid = {29695771}, issn = {1532-1827}, mesh = {Animals ; Antigens, CD/metabolism ; Azacitidine/pharmacology ; Breast Neoplasms/blood supply/*metabolism ; Cadherins/metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Chick Embryo ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Human Umbilical Vein Endothelial Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Interleukin-6/*metabolism ; Models, Biological ; Monoamine Oxidase/*metabolism ; Neoplasm Invasiveness ; Receptors, Interleukin-6/*metabolism ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {BACKGROUND: Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis.<br><br>METHODS: We employed various in-vitro and in-vivo techniques and clinical samples.<br><br>RESULTS: We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1&#x3b1; was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen.<br><br>CONCLUSIONS: Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.}, }
@article {pmid29694313, year = {2018}, author = {Vergine, M and Musella, A and Gulotta, E and Frusone, F and De Luca, A and Maceli, F and Libia, A and Benedetti Panici, P and Monti, M}, title = {Paget's disease of the male breast: case report and a point of view from actual literature.}, journal = {Il Giornale di chirurgia}, volume = {39}, number = {2}, pages = {114-117}, pmid = {29694313}, issn = {0391-9005}, mesh = {Aged ; Alzheimer Disease/complications ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms, Male/complications/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Combined Modality Therapy ; *Estrogens ; Humans ; Male ; Mastectomy ; Neoplasms, Hormone-Dependent/complications/drug therapy/*pathology/surgery ; Neoplasms, Multiple Primary/*pathology/surgery ; Nipples/*pathology ; Paget's Disease, Mammary/complications/etiology/*pathology/surgery ; *Progesterone ; Skin Ulcer/etiology ; Tamoxifen/therapeutic use ; }, abstract = {INTRODUCTION: Paget disease of the nipple in man is a very rare breast cancer, and there are not standard procedures or guidelines. In any cases, a Paget's disease could hide an invasive ductal breast cancer.<br><br>CASE DESCRIPTION: We report the case of a 77-years old man affected by Alzheimer's disease, who presented to our attention because of an ulcerated palpable mass in the right nipple. A biopsy of the lesion showed "intra-epidermic proliferation of epitelioid cells, associated with linfo-plasmacellular infiltration of superficial dermis, compatible with Paget's disease (pTis)". We discussed the case in the multidisciplinary meeting and decided to subject the patient to surgery, so a right mastectomy plus sentinel lymph node biopsy (SLNB) were performed. Histo-pathological examination revealed "invasive ductal carcinoma of the breast, associated with a small component of in situ ductal carcinoma and Paget's disease of the nipple with superficial ulceration". Resection margins were free. Sentinel lymph node was negative. Biological features were as follows: ER 95%, PR 60%, Her-2/neu 1+, Ki-67 35%. The patient was discharged in the third post-operative day in good conditions. In the following weeks the patient's healing process was good and free of complications.<br><br>CONCLUSIONS: Clinical recognition of Paget's disease is very important also in man, because it can be the alarm bell for an underlying invasive ductal breast cancer, often more aggressive than in woman.}, }
@article {pmid29692363, year = {2018}, author = {Babaei, R and Schuster, M and Meln, I and Lerch, S and Ghandour, RA and Pisani, DF and Bayindir-Buchhalter, I and Marx, J and Wu, S and Schoiswohl, G and Billeter, AT and Krunic, D and Mauer, J and Lee, YH and Granneman, JG and Fischer, L and Müller-Stich, BP and Amri, EZ and Kershaw, EE and Heikenwälder, M and Herzig, S and Vegiopoulos, A}, title = {Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis.}, journal = {Science signaling}, volume = {11}, number = {527}, pages = {}, doi = {10.1126/scisignal.aai7838}, pmid = {29692363}, issn = {1937-9145}, support = {R01 DK090166/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; }, mesh = {Adipocytes, Beige/*metabolism/pathology ; Adipogenesis/genetics ; Adipose Tissue/*metabolism/pathology ; Animals ; Cell Differentiation/genetics ; Cells, Cultured ; Female ; Gene Expression Profiling ; Humans ; Inflammation/*genetics/metabolism ; Janus Kinases/*genetics/metabolism ; Lipase/genetics/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; STAT3 Transcription Factor/genetics/metabolism ; Signal Transduction/genetics ; Transforming Growth Factor beta/*genetics/metabolism ; }, abstract = {The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as β3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFβ signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGFβ signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.}, }
@article {pmid29686118, year = {2018}, author = {Sheehan, J and Tate, J and Mott, R and Geer, C and Wolfe, R and Strowd, RE and Guzik, A}, title = {Pearls &amp; Oy-sters: The critical role of histopathology in diagnosing cancer-associated necrotizing CNS vasculitis.}, journal = {Neurology}, volume = {90}, number = {17}, pages = {808-811}, doi = {10.1212/WNL.0000000000005350}, pmid = {29686118}, issn = {1526-632X}, mesh = {Aged ; Breast Neoplasms/pathology ; Carcinoma, Squamous Cell/*complications/diagnostic imaging/secondary ; Electroencephalography ; Female ; Humans ; Magnetic Resonance Imaging ; Vasculitis, Central Nervous System/*complications/diagnostic imaging ; }, abstract = {OBJECTIVE: To highlight the importance of a broad differential and histopathologic confirmation in patients with newly diagnosed cancer with brain lesions atypical for CNS metastasis.<br><br>METHODS: We report 2 cases of biopsy-proven CNS vasculitis in patients undergoing treatment for a newly diagnosed nonmetastatic cancer. Comprehensive medical record review was performed to identify the clinical presentation, representative neuroimaging, histopathologic features, and response to treatment.<br><br>RESULTS: Patient 1 presented 1 month into induction therapy of malignant vaginal squamous cell carcinoma (stage 3, T2N1M0) with acute episodic left-sided hemiparesis due to seizure activity progressing to severe encephalopathy. Imaging revealed a right frontoparietal lesion while systemic workup was unrevealing. Biopsy demonstrated necrotizing vasculitis. Patient 2 presented 6 months after diagnosis of right breast invasive ductal carcinoma (stage IIa, T2N0M0, estrogen receptor-positive, progesterone receptor-positive, human epidermal growth factor receptor-2 positive) with subacute bifrontal headaches with associated phonophobia. Imaging showed hyperintense lesions involving the right temporoparietal region and systemic workup was unrevealing. Brain biopsy showed a necrotizing vasculitis. Patient 1 was treated with methyprednisolone and plasmapheresis and patient 2 was treated with prednisone. Both patients showed complete resolution of symptoms shortly after treatment and improvement on imaging.<br><br>CONCLUSIONS: These cases highlight the importance of comprehensive evaluation of new brain lesions in patients with nonmetastatic solid tumors. Characteristics of new brain lesions in patients with cancer that should raise suspicion of diagnoses other than brain metastasis include (1) primary malignancy without regional or distant metastasis, (2) imaging without discrete mass-like enhancement, and (3) cortically based location of lesions not at the gray-white matter junction.}, }
@article {pmid29679553, year = {2018}, author = {Swellam, M and El Magdoub, HM and Hassan, NM and Hefny, MM and Sobeih, ME}, title = {Potential diagnostic role of circulating MiRNAs in breast cancer: Implications on clinicopathological characters.}, journal = {Clinical biochemistry}, volume = {56}, number = {}, pages = {47-54}, doi = {10.1016/j.clinbiochem.2018.04.013}, pmid = {29679553}, issn = {1873-2933}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*blood/diagnosis/metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/metabolism/pathology/secondary ; Diagnosis, Differential ; Early Diagnosis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis/diagnosis/pathology ; MicroRNAs/*blood/metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; RNA, Neoplasm/*blood/metabolism ; *Up-Regulation ; Young Adult ; }, abstract = {BACKGROUND: Circulating miRNAs are stable in body fluids and resembles their levels in cancer tissue/cells. They have been expressed in many cancers among them is breast cancer. Authors aimed to investigate the expression levels of three circulating oncomiRNAs (miRNA-21, miRNA-222 and miRNA-373) in serum samples as a minimally non-invasive method for early detection of breast cancer, and study their relation with clinicopathological characters.<br><br>METHODS: MiRNAs expression levels were determined using quantitative real-time polymerase chain reaction (qPCR) in serum samples from three groups: primary breast cancer patients (n&#x202f;=&#x202f;137), benign breast lesion patients (n&#x202f;=&#x202f;60), and healthy individuals as control group (n&#x202f;=&#x202f;38). Statistical analyses were carried out using SPSS.<br><br>RESULTS: Significant differences were observed between the expression levels of the studied miRNAs in the investigated groups, as their median levels were increased in breast cancer patients followed by benign group patients then the healthy individuals. MiRNA-373 reported the highest diagnostic efficacy as compared to miRNA-21 and miRNA-222 with high area under the curve (AUC equals 0.987). The relation between tested miRNAs and clinicopathological factors revealed significant difference with clinical stages and histological grades. Level of miRNA-21 and miRNA-373 were statistically significantly higher in invasive duct carcinoma (IDC) as compared to non-IDC. Similarly, their levels were increased in lymph node metastasis (P&#x202f;<&#x202f;0.01). MiRNA-222 and miRNA-373 were significantly increased in positive PgR and positive Her-2/neu status, respectively.<br><br>CONCLUSION: Assessment of miRNAs in serum samples can be applied as minimally non-invasive markers for early detection of breast cancer, and as discriminator between different clinicopathological characters.}, }
@article {pmid29676352, year = {2018}, author = {Guleria, P and Srinivas, V and Basannar, D and Dutta, V}, title = {Comparison of lymphangiogenesis, lymphatic invasion, and axillary lymph node metastasis in breast carcinoma.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {61}, number = {2}, pages = {176-180}, doi = {10.4103/IJPM.IJPM_774_16}, pmid = {29676352}, issn = {0974-5130}, mesh = {Aged ; Antibodies, Monoclonal, Murine-Derived/*immunology ; Axilla/pathology ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphangiogenesis/*physiology ; Lymphatic Metastasis/*pathology ; Lymphatic Vessels/pathology ; Mastectomy, Modified Radical ; Middle Aged ; }, abstract = {CONTEXT: Lymphangiogenesis correlates with poor prognosis in Invasive Ductal Carcinoma (IDC) breast. D2-40 antibody, a specific marker for lymphatic endothelium, differentiates lymphatic from vascular endothelium. Therefore, the aims of this study were to estimate lymphangiogenesis using D2-40 antibody and correlate with lymphatic invasion (LI) and axillary lymph node (LN) status and compare lymphatic mean vessel density (LMVD) with Tumor (T) and Node (N) stages and grade of tumor.<br><br>METHODS AND MATERIAL: The study was conducted on fifty consecutive cases of IDC breast who underwent modified radical mastectomy (MRM) from Jan 2009 to March 2011. Hematoxylin-eosin sections and Immunohistochemistry (IHC) slides were studied along with their LN status. LMVD was counted after D2-40 immunostaining (100x magnification) in three hot spots in peritumoral areas and averaged. LI as opposed to vascular invasion (BVI), and LN status for all cases were assessed.<br><br>STATISTICAL ANALYSIS: Statistical analysis was done using SPSS software (version 14.0 for Windows). Pearson's correlations, &#x3c7;[2] tests and Mann-Whitney U test were used.<br><br>RESULTS: Lymphangiogenesis varied from 0 to 58 with mean LMVD of 11. Of 50 cases, five showed no lymphatic vessels in peritumoral areas; of these five, three had positive LNs. 21/50 cases had LI. No statistical significant association was seen between lymphangiogenesis and LI. 34/50 cases had positive LNs. Mean LMVD was higher in patients with N2/N3 stage as compared to N0/N1 stage and was statistically significant (P = 0.013).<br><br>CONCLUSIONS: D2-40 is specific marker for lymphatic endothelium. LI and lymphangiogenesis, as opposed to BVI, are better prognostic indicators in IDC breast.}, }
@article {pmid29672601, year = {2018}, author = {Kassardjian, A and Shintaku, PI and Moatamed, NA}, title = {Expression of immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-L1), in female breast carcinomas.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0195958}, pmid = {29672601}, issn = {1932-6203}, mesh = {Adult ; B7-H1 Antigen/*genetics/metabolism ; *Biomarkers, Tumor ; Breast Neoplasms/*genetics/immunology/metabolism/pathology ; CTLA-4 Antigen/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/immunology/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Female ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; T-Lymphocyte Subsets/immunology/*metabolism ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) have emerged as promising new targets for cancer therapeutics. While tumor expression of PD-L1 has been shown to have objective responses to anti-PD-L1 immunotherapies, the clinical implications of CTLA-4 expression in tumor cells or immune cells in the tumor microenvironment is still controversial. We investigated the expression of CTLA-4 and PD-L1 in human breast tumors and provided a scoring system for the systematic evaluation of CTLA-4 staining.<br><br>METHODS: Immunohistochemical staining for PD-L1 and CTLA-4 expression was performed on a tissue microarray of 102 cores, which included normal and neoplastic breast tissues. Neoplastic cores were divided into four groups: Ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and invasive tubular carcinoma (ITC). PD-L1 and CTLA-4 expressions were scored based on a system which accounted for the percentage and intensity of positivity and results provided in conjunction with available clinical and demographic data.<br><br>RESULTS: Overall, CTLA-4 was over-expressed in 49 of 93 (52.7%) breast tumors. Subcategorically, CTLA-4 was positive in 3 of 8 (37.5%) ductal carcinoma in situ, 40 of 73 (55%) of invasive ductal carcinomas, 4 of 10 (40%) of invasive lobular carcinomas and 2 of 2 (100%) of invasive tubular carcinomas. All 6 normal breast tissues were interpreted as negative for CTLA-4 staining. Only 4.1% of the invasive ductal carcinomas were positive for PD-L1 reactivity and the remaining carcinomas stained negative.<br><br>CONCLUSIONS: This study shows a significant overexpression of CTLA-4 in >50% of breast carcinomas with no such overexpression of CTLA-4 in benign breast tissues. PDL-1 staining is seen in only a small number of invasive ductal carcinomas (4.1%). These findings suggest the need for further investigation of anti-CTLA-4 and anti-PD-L1 immunotherapies and their efficacy in the treatment of breast carcinomas with overexpression of these immune modulators. In addition, the proposed scoring system will facilitate a more systematic correlation between tumor reactivity and clinical outcome which can be applied to all intracytoplasmic tumor markers.}, }
@article {pmid29669935, year = {2018}, author = {Zhu, S and Ward, BM and Yu, J and Matthew-Onabanjo, AN and Janusis, J and Hsieh, CC and Tomaszewicz, K and Hutchinson, L and Zhu, LJ and Kandil, D and Shaw, LM}, title = {IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma.}, journal = {JCI insight}, volume = {3}, number = {8}, pages = {}, pmid = {29669935}, issn = {2379-3708}, support = {F31 CA206378/CA/NCI NIH HHS/United States ; R01 CA142782/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; Humans ; Insulin Receptor Substrate Proteins/*genetics ; Lymph Nodes/pathology ; Middle Aged ; Mutation, Missense/genetics ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Receptor, IGF Type 1 ; Receptors, Somatomedin/*genetics ; Exome Sequencing/methods ; }, abstract = {Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC. IRS2 mutations identified in PILC enhance invasion, revealing a role for this signaling adaptor in the aggressive nature of PILC.}, }
@article {pmid29661250, year = {2018}, author = {Liu, WS and Chan, SH and Chang, HT and Li, GC and Tu, YT and Tseng, HH and Fu, TY and Chang, HY and Liou, HH and Ger, LP and Tsai, KW}, title = {Isocitrate dehydrogenase 1-snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability.}, journal = {Breast cancer research : BCR}, volume = {20}, number = {1}, pages = {25}, pmid = {29661250}, issn = {1465-542X}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Cell Proliferation/genetics ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Isocitrate Dehydrogenase/*genetics ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Signal Transduction/genetics ; Snail Family Transcription Factors/*genetics ; }, abstract = {BACKGROUND: The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown.<br><br>METHODS: In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion.<br><br>RESULTS: The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIF&#x3b1; (hypoxia-inducible factor-1 alpha) and NF&#x3ba;B (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast cancer.<br><br>CONCLUSION: Our findings revealed that a IDH1[low]/Snail[high] molecular signature could serve as an independent biomarker for poor prognosis in breast cancer.}, }
@article {pmid29655534, year = {2018}, author = {Kariminezhad, E and Elektorowicz, M}, title = {Comparison of constant, pulsed, incremental and decremental direct current applications on solid-liquid phase separation in oil sediments.}, journal = {Journal of hazardous materials}, volume = {358}, number = {}, pages = {475-483}, doi = {10.1016/j.jhazmat.2018.04.002}, pmid = {29655534}, issn = {1873-3336}, abstract = {Phase separation of oil wastes can mitigate the effects on the environment, by decreasing the volume of hazardous materials and regenerate energy. This study focused on the advanced electrokinetic method as a treatment technology to treat oil sediments from oil refineries and separate them into their individual phase components. The effects of four types of electrical field on the phase separation of oil sediments from an oil refinery were investigated namely constant direct current (CDC), pulsed direct current (PDC), incremental direct current (IDC) and decremental direct current (DDC). The results showed that the extent and quality of phase separation differed based on the type of electrical current applied, and indicated that different mechanisms such as electroosmosis, electrophoresis, electro-demulsification, and electro-sedimentation might have been involved in the separation process depending on the type of electrical supply. The application of DDC and IDC was found to cause a significant separation of solids by electrophoresis with the movement of almost 70% of solids to the anode of the reactors. The DDC and IDC regimes resulted in the most efficient phase separation of the oil sediments, and even incurred a highly resolved separation of light hydrocarbons at the top anode.}, }
@article {pmid29650905, year = {2018}, author = {Fujimoto, Y and Yamaguchi, K and Ueno, A and Sakurai, R and Nagahisa, Y and Imai, S and Kawamoto, K}, title = {[A Case of HER2-Positive Breast Cancer with Liver Metastases Showing Three Years of Complete Response to Combination Therapy with Trastuzumabplus Pertuzumab].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {45}, number = {3}, pages = {459-461}, pmid = {29650905}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Middle Aged ; Receptor, ErbB-2/analysis ; Recurrence ; Trastuzumab/administration &amp; dosage ; }, abstract = {A 48-year-old woman with severe interstitial pneumonitis was diagnosed with right breast cancer(invasive ductal carcinoma, T1aN1M0, ER+, PgR-, HER2 3+)and underwent modified radical mastectomy.The patient was administered tamoxifen as adjuvant therapy.However, 1 year after the mastectomy, multiple liver metastases were found and the patient received 2 anti-HER2 agents, trastuzumab and pertuzumab.A complete response(CR)was observed with the disappearance of the liver metastases in 7 months.CR was maintained for 2 years after the initiation of treatment, and then, we started trastuzumab monotherapy, which has resulted in long-term disease control.}, }
@article {pmid29621999, year = {2018}, author = {Balekouzou, A and Yin, P and Bekolo, CE and Pamatika, CM and Djeintote, M and Nambei, SW and Ba-Mpoutou, B and Mandjiza, DR and Shu, C and Yin, M and Qing, T and Koffi, B}, title = {Histo-epidemiological profile of breast cancers among women in the Central African Republic: about 174 cases.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {387}, pmid = {29621999}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology/therapy ; Central African Republic/epidemiology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Public Health Surveillance ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer in women worldwide and leading cause of cancer deaths indeveloping countries. There is very limited data on BC in the Central African Republic. The purpose of this study was to describe the epidemiological and histopathological characteristics of BC in Bangui.<br><br>METHODS: This retrospective study reviewed cancer data registries and medical records from the Pathology Unit of the National Laboratory in Bangui and the General Surgery and Gyneacology service from 2003 to 2015. A questionnaire was designed to collect information and data was analysed using descriptive and inferential statistical methods.<br><br>RESULTS: In total, 174 cases of BC were recorded, with an average annual frequency of13.4 cases per year. The age of the women at diagnosis varied from 16 to 90&#xa0;years with a median of 45.5&#xa0;years and InterQuartile range (IQR) 18&#xa0;years. The age group of 45-54&#xa0;years represented the majority of the study population (n&#xa0;=&#x2009;51, 29.3%).About 25.9%ofthe patients were non-educated and 85.6% lived in cities. Over 48 % of the women were housewives with a moderate economic status (n&#xa0;=&#x2009;99, 56.9%). Sixty nine percent of the specimens received at the pathology unit were pieces of breast tumour. Invasive ductal carcinoma (n&#xa0;=&#x2009;113, 64.9%) was the main histological form and most of the tumours were of Grade III (n&#xa0;=&#x2009;14, 46.7%). The only imaging assessment was ultrasound performed in (n&#xa0;=&#x2009;53, 30.4%) women. Surgery was performed in (n&#xa0;=&#x2009;166, 95.4%) patients, while (n&#xa0;=&#x2009;159, 91.4%) received complementary chemotherapy. At the end of the study, 84.5%of the cases had died, 12.1% were alive and 3.4% were considered "lost to follow-up".<br><br>CONCLUSION: BC is an important public health problem and affected most of the younger Central African women. Epidemiological and histological characteristics are more or less common to those described other developing countries. It is imperative to improve the awareness of health care institutions and women on the burden of BC, to carry out early screening of BC, and to strengthen the capacity of women's health care system.}, }
@article {pmid29621845, year = {2018}, author = {Gilbert, B and Naidoo, TL and Redwig, F}, title = {Ins and outs of urinary catheters.}, journal = {Australian journal of general practice}, volume = {47}, number = {3}, pages = {132-136}, doi = {10.31128/AFP-10-17-4362}, pmid = {29621845}, issn = {2208-7958}, mesh = {Catheter-Related Infections/nursing/prevention &amp; control ; Clinical Competence/standards ; Humans ; Urinary Catheterization/*adverse effects/*standards/trends ; Urinary Catheters/adverse effects/standards/trends ; }, abstract = {BACKGROUND: Inserting an indwelling catheter (IDC) is a common medical procedure that is often performed poorly and inappropriately, and can lead to significant morbidity. Although most catheterisations are performed by nursing staff, medical personnel need to be aware of the procedure, products and common IDC complications.<br><br>OBJECTIVE: Current guidelines and literature were reviewed to outline catheterisation indications, catheter types and provide a general understanding of complications associated with IDCs for&amp;nbsp;the general practitioner (GP).<br><br>DISCUSSION: There is evidence that IDCs are often used when not indicated and improperly managed when inserted. IDCs can cause significant morbidity, prolong hospital stay and increase healthcare costs. Infection and traumatic insertion are common complications; advances in catheter design have helped to limit these complications. Most complications are avoidable, do not require specialist input and can be managed by community nurses or GPs. Reviewing indications, adopting proper technique for insertion and defining management strategies can limit complications.}, }
@article {pmid29621776, year = {2018}, author = {Weigand, T and Singler, B and Fleming, T and Nawroth, P and Klika, KD and Thiel, C and Baelde, H and Garbade, SF and Wagner, AH and Hecker, M and Yard, BA and Amberger, A and Zschocke, J and Schmitt, CP and Peters, V}, title = {Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal.}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology}, volume = {46}, number = {2}, pages = {713-726}, doi = {10.1159/000488727}, pmid = {29621776}, issn = {1421-9778}, mesh = {Animals ; Anserine/analysis/chemistry/metabolism ; Carnosine/analysis/*chemistry/*metabolism ; Cell Line ; Cell Survival/drug effects ; Chromatography, High Pressure Liquid ; Glutathione/analysis ; Glutathione Peroxidase/genetics/metabolism ; Glycation End Products, Advanced/chemistry/metabolism ; Humans ; Membrane Glycoproteins/metabolism ; Membrane Transport Proteins/metabolism ; Mice ; Oxidative Stress/drug effects ; Peptide Transporter 1/genetics/metabolism ; Podocytes/cytology/drug effects/metabolism ; Polymers/*chemistry/metabolism ; Pyruvaldehyde/*chemistry/toxicity ; Serum Albumin/chemistry ; Superoxide Dismutase/genetics/metabolism ; Symporters/genetics/metabolism ; }, abstract = {BACKGROUND/AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MG), contribute to diabetic complications. MG-scavenging capacities of carnosine and anserine, which have been shown to mitigate diabetic nephropathy, were evaluated in vitro and in vivo.<br><br>METHODS: MG-induced cell toxicity was characterized by MTT and MG-H1-formation, scavenging abilities by Western Blot and NMR spectroscopies, cellular carnosine transport by qPCR and microplate luminescence and carnosine concentration by HPLC.<br><br>RESULTS: In vitro, carnosine and anserine dose-dependently reduced N-carboxyethyl lysine (CEL) and advanced glycation end products (AGEs) formation. NMR studies revealed the formation of oligo/polymeric products of MG catalyzed by carnosine or anserine. MG toxicity (0.3-1 mM) was dose-dependent for podocytes, tubular and mesangial cells whereas low MG levels (0.2 mM) resulted in increased cell viability in podocytes (143&#xb1;13%, p<0.001) and tubular cells (129&#xb1;3%, p<0.001). Incubation with carnosine/anserine did not reduce MG-induced toxicity, independent of incubation times and across large ranges of MG to carnosine/anserine ratios. Cellular carnosine uptake was low (<0.1% in 20 hours) and cellular carnosine concentrations remained unaffected. The putative carnosine transporter PHT1 along with the taurine transporter (TauT) was expressed in all cell types while PEPT1, PEPT2 and PHT2, also belonging to the proton-coupled oligopeptide transporter (POT) family, were only expressed in tubular cells.<br><br>CONCLUSION: While carnosine and anserine catalyze the formation of MG oligo/polymers, the molar ratios required for protection from MG-induced cellular toxicity are not achievable in renal cells. The effect of carnosine in vivo, to mitigate diabetic nephropathy may therefore be independent upon its ability to scavenge MG and/or carnosine is mainly acting extracellularly.}, }
@article {pmid29602724, year = {2019}, author = {Grimm, LJ and Saha, A and Ghate, SV and Kim, C and Soo, MS and Yoon, SC and Mazurowski, MA}, title = {Relationship between Background Parenchymal Enhancement on High-risk Screening MRI and Future Breast Cancer Risk.}, journal = {Academic radiology}, volume = {26}, number = {1}, pages = {69-75}, doi = {10.1016/j.acra.2018.03.013}, pmid = {29602724}, issn = {1878-4046}, mesh = {Adult ; Aged ; Breast/*diagnostic imaging ; Breast Neoplasms/diagnostic imaging/*epidemiology ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology ; Carcinoma, Lobular/*epidemiology ; Cohort Studies ; Early Detection of Cancer ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; North Carolina/epidemiology ; Parenchymal Tissue/*diagnostic imaging ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {RATIONALE AND OBJECTIVES: To determine if background parenchymal enhancement (BPE) on screening breast magnetic resonance imaging (MRI) in high-risk women correlates with future cancer.<br><br>MATERIALS AND METHODS: All screening breast MRIs (n&#x2009;=&#x2009;1039) in high-risk women at our institution from August 1, 2004, to July 30, 2013, were identified. Sixty-one patients who subsequently developed breast cancer were matched 1:2 by age and high-risk indication with patients who did not develop breast cancer (n&#x2009;=&#x2009;122). Five fellowship-trained breast radiologists independently recorded the BPE. The median reader BPE for each case was calculated and compared between the cancer and control cohorts.<br><br>RESULTS: Cancer cohort patients were high-risk because of a history of radiation therapy (10%, 6 of 61), high-risk lesion (18%, 11 of 61), or breast cancer (30%, 18 of 61); BRCA mutation (18%, 11 of 61); or family history (25%, 15 of 61). Subsequent malignancies were invasive ductal carcinoma (64%, 39 of 61), ductal carcinoma in situ (30%, 18 of 61) and invasive lobular carcinoma (7%, 4of 61). BPE was significantly higher in the cancer cohort than in the control cohort (P&#x2009;=&#x2009;0.01). Women with mild, moderate, or marked BPE were 2.5 times more likely to develop breast cancer than women with minimal BPE (odds ratio&#x2009;=&#x2009;2.5, 95% confidence interval: 1.3-4.8, P&#x2009;=&#x2009;.005). There was fair interreader agreement (&#x3ba;&#x2009;=&#x2009;0.39).<br><br>CONCLUSIONS: High-risk women with greater than minimal BPE at screening MRI have increased risk of future breast cancer.}, }
@article {pmid29599319, year = {2018}, author = {Litwin, M and Szczepańska-Buda, A and Michałowska, D and Grzegrzółka, J and Piotrowska, A and Gomułkiewicz, A and Wojnar, A and Dzięgiel, P and Witkiewicz, W}, title = {Aberrant Expression of PIWIL1 and PIWIL2 and Their Clinical Significance in Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {38}, number = {4}, pages = {2021-2030}, doi = {10.21873/anticanres.12441}, pmid = {29599319}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Argonaute Proteins/*biosynthesis/genetics ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cohort Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; RNA, Messenger/biosynthesis/genetics ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND/AIM: P-Element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) are involved in epigenetic regulation of gene expression in germline cells. Aberrant expression of piRNA and PIWI proteins have been identified in various types of tumour cells. The aim of this study was to evaluate the expression profiles of PIWI-like protein-1, -2 (PIWIL1 and PIWIL2), their immunohistochemical (IHC) characteristics in ductal breast cancer, and determine their correlation with clinicopathological parameters of this type of cancer.<br><br>MATERIALS AND METHODS: Material for IHC studies comprised of 101 invasive ductal carcinoma (IDC) cases and 31 mastopathy tissues. Frozen fragments of paired tissue specimens (tumour and adjacent non-malignant breast tissue) taken from 55 patients with IDC and 18 samples of mastopathy were used for molecular studies using real-time polymerase chain reaction (RT-PCR).<br><br>RESULTS: A statistically significantly higher level of PIWIL1 and PIWIL2 was found in IDC compared to mastopathy samples (p&#x2264;0.0001). Increased expression of PIWIL1 was correlated with increased PIWIL2 expression in breast cancer tissue. Surprisingly, PIWIL1 mRNA was detected only in cancer and mastopathy, but was not found in most normal breast tissues, although it is noteworthy that the PIWIL2 mRNA level was statistically significantly lower in mastopathy and IDC samples compared to normal breast tissues.<br><br>CONCLUSION: Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development.}, }
@article {pmid29579338, year = {2018}, author = {Uemura, MI and French, JT and Hess, KR and Liu, D and Raghav, K and Hortobagyi, GN and Arun, BK and Valero, V and Ueno, NT and Alvarez, RH and Woodward, WA and Debeb, BG and Moulder, SL and Lim, B and Tripathy, D and Ibrahim, NK}, title = {Development of CNS metastases and survival in patients with inflammatory breast cancer.}, journal = {Cancer}, volume = {124}, number = {11}, pages = {2299-2305}, doi = {10.1002/cncr.31336}, pmid = {29579338}, issn = {1097-0142}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Breast/pathology/surgery ; Central Nervous System Neoplasms/*epidemiology/prevention &amp; control/secondary ; Chemotherapy, Adjuvant/methods ; Female ; Follow-Up Studies ; Humans ; Incidence ; Inflammatory Breast Neoplasms/mortality/*pathology/therapy ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/methods ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Taxoids/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Inflammatory breast cancer (IBC) is associated with a poor prognosis and high risk of central nervous system (CNS) metastases.<br><br>METHODS: We retrospectively reviewed stage III-IBC patients compared with noninflammatory invasive ductal carcinoma (NI-IDC) patients treated between January 1, 1984, and December 31, 2011, who began primary treatment within 1 year of diagnosis and had been followed up for at least 1 year before the development of CNS metastasis or death. Cumulative CNS metastasis incidence and post-CNS metastasis overall survival (OS) estimates were computed. Multivariable Cox proportional hazard models explored factors for post-CNS metastasis survival.<br><br>RESULTS: A total of 2323 patients were identified (589-IBC/1734-NI-IDC). Eighty-one IBC patients developed CNS metastasis, versus 154 NI-IDC patients. The 2-, 5-, and 10-year cumulative CNS metastasis incidence rates in IBC and NI-IDC were 9.8%, 15.8%, 17.4% and 6.5%, 10.1%, and 12.7%, respectively. This was significantly different between IBC and NI-IDC patients (P = .0037). Multicovariate competing risk regression models in IBC and NI-IDC patients showed no statistically significant associations with the risk of developing CNS metastasis, except neoadjuvant taxane use in NI-IDC patients (hazard ratio, 0.45; 95% confidence interval, 0.24-0.83; P = .011). The median follow-up was 7.2 years, and the median post-CNS metastasis OS was not significantly different between IBC (7.6 months) and NI-IDC (5.6 months) patients. One hundred ninety patients with CNS metastasis died. HER2-positive patients had better OS, with a median 14.1 versus 4.3 months (P < .0001). Age >50 years (P = .012) but not IBC status was a significant predictor of post-CNS metastasis survival.<br><br>CONCLUSION: IBC patients demonstrated higher CNS metastasis incidence rates but OS following CNS metastases is similar in both groups. HER2 status and age may play prognostic roles. Cancer 2018;124:2299-305. &#xa9; 2018 American Cancer Society.}, }
@article {pmid29551677, year = {2018}, author = {Luo, J and Feng, J and Wen, Q and Qoyawayma, C and Wang, W and Chen, L and Lu, J and Zhan, Y and Xu, L and Zang, H and Fan, S and Chu, S}, title = {Elevated expression of IRS-1 associates with phosphorylated Akt expression and predicts poor prognosis of breast invasive ductal carcinoma.}, journal = {Human pathology}, volume = {79}, number = {}, pages = {9-17}, doi = {10.1016/j.humpath.2018.03.003}, pmid = {29551677}, issn = {1532-8392}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*enzymology/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*enzymology/mortality/pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Insulin Receptor Substrate Proteins/*analysis ; Middle Aged ; Neoplasm Invasiveness ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/*analysis ; Risk Factors ; Time Factors ; Tissue Array Analysis ; Up-Regulation ; }, abstract = {Overexpression of insulin receptor substrate 1 (IRS-1) has been reported to promote cell growth, atypical hyperplasia, and carcinogenesis, and phosphorylated Akt (p-Akt) is certified to be involved in many types of cancers such as breast invasive ductal carcinoma (BIDC). However, the relationship between IRS-1 and Akt, as well as the role of expression of IRS-1 in BIDC, has never been reported. The purpose of this research is to investigate the association between expression of IRS-1 and p-Akt proteins and clinicopathological features of BIDC by immunohistochemistry, as well as the survival status. The results showed that the percentage of either elevated expression of IRS-1 or positive p-Akt expression in BIDC was significantly higher than that in control breast tissue from noncancer patients (P < .001 and P = .001, respectively). Overexpression of IRS-1 was evidently associated with positive expression of p-Akt (r = 0.337, P < .001). Also, positive percentage of p-Akt expression was statistically different among different molecular subtypes of BIDC (highest in luminal B BIDC, P = .009). Furthermore, significantly worse overall survival was found in BIDC patients with high expression of IRS-1 and p-Akt than in patients with low expression (P = .006 and P = .004, respectively). The multivariate Cox proportional hazard regression analysis showed that high expression of IRS-1 and positive expression of p-Akt protein were independent poor prognostic factors for patients with BIDC (P = .022 and P = .046, respectively). In conclusion, we report for the first time that overexpression of IRS-1 protein is associated with expression of p-Akt, and overexpression of IRS-1 and positive expression of p-Akt might be independent biomarkers for poor prognosis in BIDC.}, }
@article {pmid29551588, year = {2018}, author = {Moraru, A and Wiederstein, J and Pfaff, D and Fleming, T and Miller, AK and Nawroth, P and Teleman, AA}, title = {Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes.}, journal = {Cell metabolism}, volume = {27}, number = {4}, pages = {926-934.e8}, doi = {10.1016/j.cmet.2018.02.003}, pmid = {29551588}, issn = {1932-7420}, mesh = {Animals ; Cells, Cultured ; Diabetes Mellitus, Type 2/*metabolism ; Drosophila melanogaster ; Hyperglycemia/metabolism ; Insulin Resistance ; Lactoylglutathione Lyase/genetics ; Obesity/metabolism ; Pyruvaldehyde/*metabolism ; }, abstract = {The molecular causes of type 2 diabetes (T2D) are not well understood. Both type 1 diabetes (T1D) and T2D are characterized by impaired insulin signaling and hyperglycemia. From analogy to T1D, insulin resistance and hyperglycemia are thought to also play causal roles in T2D. Recent clinical studies, however, found that T2D patients treated to maintain glycemia below the diabetes definition threshold (HbA1c < 6.5%) still develop diabetic complications. This suggests additional insulin- and glucose-independent mechanisms could be involved in T2D progression and/or initiation. T2D patients have elevated levels of the metabolite methylglyoxal (MG). We show here, using Drosophila glyoxalase 1 knockouts, that animals with elevated methylglyoxal recapitulate several core aspects of T2D: insulin resistance, obesity, and hyperglycemia. Thus elevated MG could constitute one root cause of T2D, suggesting that the molecular causes of elevated MG warrant further study.}, }
@article {pmid29546577, year = {2018}, author = {Mendler, M and Kopf, S and Groener, JB and Riedinger, C and Fleming, TH and Nawroth, PP and Okun, JG}, title = {Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with type 2 diabetes.}, journal = {Acta diabetologica}, volume = {55}, number = {6}, pages = {585-592}, doi = {10.1007/s00592-018-1130-2}, pmid = {29546577}, issn = {1432-5233}, support = {CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Adenylate Kinase/metabolism ; Adult ; Aged ; Aminoimidazole Carboxamide/*analogs &amp; derivatives/urine ; Animals ; Case-Control Studies ; Cohort Studies ; Diabetes Complications/metabolism/prevention &amp; control/urine ; Diabetes Mellitus, Type 2/complications/metabolism/prevention &amp; control/*urine ; Female ; Humans ; Male ; Middle Aged ; Prediabetic State/pathology/therapy/urine ; Ribonucleotides/*urine ; Risk Factors ; Risk Reduction Behavior ; Signal Transduction/physiology ; }, abstract = {AIMS: 5-Aminoimidazole-4-carboxamide riboside (AICAR) is an endogenous activator of AMPK, a central regulator of energy homeostasis. Loss and/or reduction of AMPK signaling plays an important role in the development of insulin resistance in type 2 diabetes. The loss of AMPK in diabetes could be due to a loss of AICAR. The aim of this study was to characterize urine levels of AICAR in diabetes and determine whether an association exists with respect to late complications, e.g., retinopathy, nephropathy and neuropathy.<br><br>METHODS: Urine AICAR was measured by liquid chromatography tandem mass spectrometry in 223 patients consisting of 5 healthy controls, 63 patients with pre-diabetes, 29 patients with newly diagnosed type 2 diabetes and 126 patients with long-standing type 2 diabetes. For statistical analyses, nonparametric Kruskal-Wallis test, one-way ANOVA and multivariate regression analysis were performed to investigate the associations of urinary AICAR excretion within different groups and different clinical parameters.<br><br>RESULTS: The mean urine AICAR for all 223 patients was 694.7&#x2009;&#xb1;&#x2009;641.1&#xa0;ng/ml. There was no significant difference in urine AICAR between the control and patients with diabetes (592.3&#x2009;&#xb1;&#x2009;345.1 vs. 697.1&#x2009;&#xb1;&#x2009;646.5&#xa0;ng/ml). No association between any of the biochemical and/or clinical parameters measured and urine AICAR was found, with the exception of age of patient (R&#x2009;=&#x2009;-&#xa0;0.34; p&#x2009;<&#x2009;0.01) and estimated glomerular filtration rate (R&#x2009;=&#x2009;0.19; p&#x2009;=&#x2009;0.039). These results were confirmed additionally by linear regression analysis.<br><br>CONCLUSIONS: Clinical diabetes is not associated with a change in endogenous AICAR levels. Loss of AICAR may therefore not be a mechanism by which AMPK signaling is reduced in diabetes.}, }
@article {pmid29538201, year = {2018}, author = {Hsu, CC and Li, WY and Chu, PY}, title = {Salivary duct carcinoma of the supraglottis with a distinct presentation: A case report and literature review.}, journal = {Medicine}, volume = {97}, number = {11}, pages = {e0095}, pmid = {29538201}, issn = {1536-5964}, mesh = {Airway Obstruction/etiology/surgery ; *Carcinoma/pathology/physiopathology/therapy ; Chemoradiotherapy/*methods ; *Cytoreduction Surgical Procedures/instrumentation/methods ; Humans ; *Larynx/pathology/physiopathology/surgery ; Lasers, Gas/therapeutic use ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Salivary Ducts/*pathology ; *Salivary Gland Neoplasms/pathology/physiopathology/therapy ; Salivary Glands, Minor/*pathology ; Treatment Outcome ; }, abstract = {RATIONALE: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. We present the first case of advanced SDC of the minor salivary gland arising from the supraglottis and review the literature on the clinicopathologic characteristics and prognosis of SDC.<br><br>PATIENT CONCERNS: A 59-year-old male patient with progressive difficulty in swallowing and a muffled voice for 2 months.<br><br>DIAGNOSES: The patient was diagnosed with SDC arising from the supraglottis with extensive tumor invasion into the subsites of the larynx and pharynx.<br><br>INTERVENTIONS: Due to impending airway obstruction, the patient underwent CO2 laser debulking surgery. In addition to local disease, lymph node and distant metastases were also noted at diagnosis and concurrent chemoradiation therapy was arranged.<br><br>OUTCOMES: Laryngeal function was preserved and tracheostomy was avoided. The patient has survived for >1 year after the initial diagnosis.<br><br>LESSONS: SDC is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. Here we presented the first case of advanced SDC of the minor salivary gland arising from the supraglottis that was treated with CO2 laser debulking surgery followed by concurrent chemoradiation therapy. Due to their rarity, further studies are required to establish the most effective treatment protocol for advanced SDC.}, }
@article {pmid29528718, year = {2018}, author = {Kizy, S and Huang, JL and Marmor, S and Blaes, A and Yuan, J and Beckwith, H and Tuttle, TM and Hui, JYC}, title = {Distribution of 21-Gene Recurrence Scores Among Breast Cancer Histologic Subtypes.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {142}, number = {6}, pages = {735-741}, doi = {10.5858/arpa.2017-0169-OA}, pmid = {29528718}, issn = {1543-2165}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/classification/epidemiology/*genetics/pathology ; Epidemiological Monitoring ; Female ; Humans ; Logistic Models ; Middle Aged ; Receptor, ErbB-2/*genetics ; Risk Factors ; United States/epidemiology ; Young Adult ; }, abstract = {CONTEXT: - The 21-gene recurrence score (RS) provides a probability of distant recurrence for estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. The utility of RS for rarer histologic subtypes of breast cancer is uncertain.<br><br>OBJECTIVE: - To determine the distribution of RS among various histologic subtypes using a population database.<br><br>DESIGN: - Women between the ages of 18 and 75 with estrogen receptor-positive, HER2-negative breast cancer and known RS results were identified using the Surveillance, Epidemiology, and End Results database. Recurrence scores were categorized into risk groups using both traditional and Trial Assigning Individualized Options for Treatment cutoffs. Multivariable logistic regression was used to determine factors associated with high-risk RS.<br><br>RESULTS: - We identified 45&#x2009;618 patients with stage I to III, estrogen receptor-positive, HER2-negative breast cancer who had RS available. Overall, 3087 (7%) and 6337 (14%) of cancers were classified as high risk based on traditional and Trial Assigning Individualized Options for Treatment RS cutoffs, respectively. The proportion of high-risk RS ranged from 1% (tubular, 2 of 225) to 68% (medullary, 13 of 19) and 4% (tubular, 10 of 225) to 79% (medullary, 15 of 19) for traditional and Trial Assigning Individualized Options for Treatment cutoffs, respectively. Based on multivariable logistic regression (excluding medullary), subtypes other than invasive ductal carcinoma and papillary carcinoma were significantly associated with lower RS. The strongest predictors of a high-risk RS were higher tumor grade and negative progesterone receptor status.<br><br>CONCLUSIONS: - We identified distinct distributions of RS among different histologic subtypes of breast cancer. Excluding medullary carcinoma, histologic subtypes other than invasive ductal carcinoma and papillary carcinoma all predict lower RS.}, }
@article {pmid29522808, year = {2018}, author = {Levy, DA and Mika, R and Radzyminski, C and Ben-Zvi, S and Tibon, R}, title = {Behavioral reconsolidation interference with episodic memory within-subjects is elusive.}, journal = {Neurobiology of learning and memory}, volume = {150}, number = {}, pages = {75-83}, pmid = {29522808}, issn = {1095-9564}, support = {MC_UU_00005/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Cues ; Female ; Humans ; Male ; Memory Consolidation/*physiology ; *Memory, Episodic ; Mental Recall/*physiology ; Photic Stimulation ; Young Adult ; }, abstract = {In studies of behavioral reconsolidation interference, reactivation of a consolidated memory using some form of reminder is followed by the presentation of new information that can cause interference with that memory. Under these conditions, the interference not only impairs retrieval by indirect processes such as cue interference, but supposedly disrupts the original memory trace directly. Almost all studies of behavioral reconsolidation interference in episodic memory in humans have employed between-subjects paradigms, and deduced reminder effects from intrusion errors. Such studies might introduce confounds arising, for example, from differences in retrieval strategies engendered by the pre-test treatments. We therefore set out to examine whether behavioral reconsolidation interference in episodic memory might be demonstrated within-subjects and by direct memory strength rather than intrusion errors. In three separate experiments, we attempted to disrupt reconsolidation of episodic object-picture memory using a reminder + retroactive interference manipulation. We applied the manipulation over three consecutive days, using a forced-choice recognition test without intrusions from interfering learning, keeping all other study and test parameters constant. No effects of reminder-potentiated interference were observed for measures of accuracy, response times, subjective expressions of recollection, or levels of confidence, as substantiated by Bayesian analyses. These results highlight the difficulty of observing clear behavioral reconsolidation interference effects within-subjects in human episodic memory, and provide some indications of what might be boundary conditions for its demonstration.}, }
@article {pmid29516978, year = {2018}, author = {Li, F and Ren, Y and Wang, Z}, title = {Programmed death 1 Ligand 1 expression in breast cancer and its association with patients' clinical parameters.}, journal = {Journal of cancer research and therapeutics}, volume = {14}, number = {1}, pages = {150-154}, doi = {10.4103/jcrt.JCRT_602_17}, pmid = {29516978}, issn = {1998-4138}, mesh = {Adult ; Aged ; B7-H1 Antigen/*genetics/metabolism ; *Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/pathology ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; }, abstract = {OBJECTIVE: To evaluate the expression of programmed death 1 ligand 1 (PD-L1) in the cancer tissues and tumor-adjacent normal tissues of patients with invasive ductal carcinoma of the breast and to analyze the relationship between the expression of PD-L1 and the clinicopathological features of patients.<br><br>MATERIALS AND METHODS: This study included 112 cases of patients with invasive ductal carcinoma of breast who received surgical treatment from March 2012 to February 2016 in Xuzhou Cancer Hospital. The clinical materials of included patients were retrospectively analyzed. The immunohistochemical assay and real-time polymerase chain reaction (PCR) assay were applied to examine the expression of mRNA and protein of PD-L1 in breast cancer specimens of 112 cases and paired tumor-adjacent tissue specimens of 57 cases. The relationship between PD-L1 protein expression and clinicopathological features of patients was analyzed.<br><br>RESULTS: PD-L1 protein was mainly expressed in the cytoplasm. The positive rate of PD-L1 expression in invasive ductal carcinoma was 19.6% (22/112), and the positive rate of PD-L1 expression of tumor-adjacent normal tissues was 3.5% (2/57), indicating that the positive rate of PD-L1 expression of cancerous tissues was significantly higher than that of in tumor-adjacent normal tissues (P < 0.05); the positive expression of PD-L1 was not related with the patients' age, menopause history, family history of breast cancer, tumor size, and location of the tumor (P > 0.05) while it was related with lymph node metastasis, the clinic staging, and histopathological grading (P < 0.05). Real-time PCR was applied to detect the mRNA expression of PD-L1 in breast-invasive ductal carcinoma with the mean &#x394;Ct value of 7.79 &#xb1; 2.25. However, the mRNA expression of PD-L1 in normal tumor-adjacent tissues was of low expression with the mean &#x394;Ct value of 12.37 &#xb1; 3.33. The difference was statistically significant (P< 0.05).<br><br>CONCLUSION: The expression of PD-L1 in breast-invasive ductal carcinoma was significantly increased, and it was related to histological grading, clinical staging, and lymph node metastasis of breast cancer. PD-L1 may be a significant marker for the prognosis of breast cancer patients.}, }
@article {pmid29513137, year = {2018}, author = {Ein-Dor, T and Verbeke, WJMI and Mokry, M and Vrtička, P}, title = {Epigenetic modification of the oxytocin and glucocorticoid receptor genes is linked to attachment avoidance in young adults.}, journal = {Attachment &amp; human development}, volume = {20}, number = {4}, pages = {439-454}, doi = {10.1080/14616734.2018.1446451}, pmid = {29513137}, issn = {1469-2988}, mesh = {Adult ; *Avoidance Learning ; DNA Methylation/genetics ; *Epigenesis, Genetic ; Female ; Humans ; Interpersonal Relations ; Male ; *Object Attachment ; Receptors, Glucocorticoid/*genetics ; Receptors, Oxytocin/*genetics ; Self Report ; Stress, Psychological ; Young Adult ; }, abstract = {Attachment in the context of intimate pair bonds is most frequently studied in terms of the universal strategy to draw near, or away, from significant others at moments of personal distress. However, important interindividual differences in the quality of attachment exist, usually captured through secure versus insecure - anxious and/or avoidant - attachment orientations. Since Bowlby's pioneering writings on the theory of attachment, it has been assumed that attachment orientations are influenced by both genetic and social factors - what we would today describe and measure as gene by environment interaction mediated by epigenetic DNA modification - but research in humans on this topic remains extremely limited. We for the first time examined relations between intra-individual differences in attachment and epigenetic modification of the oxytocin receptor (OXTR) and glucocorticoid receptor (NR3C1) gene promoter in 109 young adult human participants. Our results revealed that attachment avoidance was significantly and specifically associated with increased OXTR and NR3C1 promoter methylation. These findings offer first tentative clues on the possible etiology of attachment avoidance in humans by showing epigenetic modification in genes related to both social stress regulation and HPA axis functioning.}, }
@article {pmid29505681, year = {2018}, author = {Schmitt, FCF and Salgado, E and Friebe, J and Schmoch, T and Uhle, F and Fleming, T and Zemva, J and Kihm, L and Nusshag, C and Morath, C and Zeier, M and Bruckner, T and Mehrabi, A and Nawroth, PP and Weigand, MA and Hofer, S and Brenner, T}, title = {Cell cycle arrest and cell death correlate with the extent of ischaemia and reperfusion injury in patients following kidney transplantation - results of an observational pilot study.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {31}, number = {7}, pages = {751-760}, doi = {10.1111/tri.13148}, pmid = {29505681}, issn = {1432-2277}, mesh = {Biomarkers/blood/urine ; C-Reactive Protein/metabolism ; *Cell Cycle Checkpoints ; *Cell Death ; Cold Ischemia/*adverse effects ; Delayed Graft Function ; Humans ; Keratin-18/blood/urine ; Kidney Transplantation/*adverse effects ; Middle Aged ; Pilot Projects ; Receptor for Advanced Glycation End Products/blood ; Reperfusion Injury/*etiology ; Transplantation Immunology ; }, abstract = {A prolonged cold ischaemia time (CIT) is suspected to be associated with an increased ischaemia and reperfusion injury (IRI) resulting in an increased damage to the graft. In total, 91 patients were evaluated for a delayed graft function within 7 days after kidney transplantation (48 deceased, 43 living donors). Blood and urine samples were collected before, immediately after the operation, and 1, 3, 5, 7 and 10 days later. Plasma and/or urine levels of total keratin 18 (total K18), caspase-cleaved keratin 18 (cc K18), the soluble receptor for advanced glycation end products (sRAGE), tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP7) were measured. As a result of prolonged CIT and increased IRI, deceased donor transplantations were shown to suffer from a more distinct cell cycle arrest and necrotic cell death. Plasmatic total K18 and urinary TIMP-2 and IGFBP7 were therefore demonstrated to be of value for the detection of a delayed graft function (DGF), as they improved the diagnostic performance of a routinely used clinical scoring system. Plasmatic total K18 and urinary TIMP-2 and IGFBP7 measurements are potentially suitable for early identification of patients at high risk for a DGF following kidney transplantation from deceased or living donors.}, }
@article {pmid29495422, year = {2018}, author = {Xu, H and Dorn, GW and Shetty, A and Parihar, A and Dave, T and Robinson, SW and Gottlieb, SS and Donahue, MP and Tomaselli, GF and Kraus, WE and Mitchell, BD and Liggett, SB}, title = {A Genome-Wide Association Study of Idiopathic Dilated Cardiomyopathy in African Americans.}, journal = {Journal of personalized medicine}, volume = {8}, number = {1}, pages = {}, pmid = {29495422}, issn = {2075-4426}, support = {P30 DK072488/DK/NIDDK NIH HHS/United States ; P50 HL077107/HL/NHLBI NIH HHS/United States ; R35 HL135736/HL/NHLBI NIH HHS/United States ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is the most common form of non-ischemic chronic heart failure. Despite the higher prevalence of IDC in African Americans, the genetics of IDC have been relatively understudied in this ethnic group. We performed a genome-wide association study to identify susceptibility genes for IDC in African Americans recruited from five sites in the U.S. (662 unrelated cases and 1167 controls). The heritability of IDC was calculated to be 33% (95% confidence interval: 19-47%; p = 6.4 × 10[-7]). We detected association of a variant in a novel intronic locus in the CACNB4 gene meeting genome-wide levels of significance (p = 4.1 × 10[-8]). The CACNB4 gene encodes a calcium channel subunit expressed in the heart that is important for cardiac muscle contraction. This variant has not previously been associated with IDC in any racial group. Pathway analysis, based on the 1000 genes most strongly associated with IDC, showed an enrichment for genes related to calcium signaling, growth factor signaling, neuronal/neuromuscular signaling, and various types of cellular level signaling, including gap junction and cAMP signaling. Our results suggest a novel locus for IDC in African Americans and provide additional insights into the genetic architecture and etiology.}, }
@article {pmid29483434, year = {2018}, author = {Ishizuka, M and Tsubota, Y and Ueda, A and Sueoka, N and Yoshikawa, K and Yamamoto, D}, title = {[Local Control by Mastectomy in Advanced Breast Cancer with Liver Metastasis after Chemotherapy, Radiotherapy, and Hyperthermia - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {45}, number = {2}, pages = {321-323}, pmid = {29483434}, issn = {0385-0684}, mesh = {Biopsy, Needle ; Breast Neoplasms/pathology/*therapy ; Chemoradiotherapy ; Female ; Fever ; Humans ; Liver Neoplasms/secondary/*therapy ; Mastectomy ; Middle Aged ; }, abstract = {Advanced breast cancer has a poor prognosis compared to early breast cancer; however, quality of life and radical operation can be improved in some case by using multidisciplinary treatment. A 54-year-old woman was examined at the hospital because of an enlarging tumor in the left breast. She was aware of a lump for 3 years. Results of the initial examination indicated invasive ductal carcinoma with liver metastasis. She first received chemotherapy(AC followed by weekly paclitaxel). After 4 courses of weekly paclitaxel, computed tomography revealed axillary lymph nodes involved in the axillary vein. Operation was difficult and conversion therapy was administered. The patient underwent radiotherapy, hyperthermia, and hormone therapy. After 1 year from the start of hormone therapy, the metastasis had disappeared and the patient underwent operation in our unit. Eight months after operation, no recurrence was observed.}, }
@article {pmid29480844, year = {2018}, author = {Wang, X and Jin, M and Ye, Q and Wang, M and Hu, Y and Yang, Y and Yang, J and Cai, J}, title = {Solitary duodenum metastasis from breast cancer with 8 years' latency: A case report.}, journal = {Medicine}, volume = {97}, number = {2}, pages = {e9550}, pmid = {29480844}, issn = {1536-5964}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diagnosis, Differential ; Duodenal Neoplasms/drug therapy/pathology/*secondary/surgery ; Female ; Humans ; Middle Aged ; }, abstract = {RATIONALE: Advanced breast cancer frequently metastasizes to the lungs, liver, and bones. Metastatic involvement of the duodenal bulb is extremely rare and difficult to detect by endoscopy.<br><br>PATIENT CONCERNS: A 51-year-old menopausal woman presented with abdominal fullness and obstructive symptoms, and was diagnosed with adenocarcinoma in the duodenal bulb. The patient had undergone modified radical mastectomy of the left breast for infiltrating ductal carcinoma (IDC) 8 years previously.<br><br>DIAGNOSIS: Metastatic infiltration of the duodenal bulb originating from IDC was proven histologically and immunohistochemically.<br><br>INTERVENTIONS: She received chemotherapy with docetaxel and capecitabine followed by hormone maintenance therapy with letrozole after operation.<br><br>OUTCOMES: After treatment, the patient recovered well. She is currently being followed up.<br><br>LESSONS: Patients with known breast cancer history with the IDC histological type and presenting with nonspecific abdominal symptoms or signs, such as abdominal fullness, nausea, and vomiting, should undergo endoscopy with histopathological examination in order to detect possible gastrointestinal metastasis of the primary breast tumor. This report intends to alert people to heed this type of breast cancer metastasis and not treat it as a primary gastrointestinal tumor.}, }
@article {pmid29475895, year = {2018}, author = {Rhone, P and Ruszkowska-Ciastek, B and Bielawski, K and Brkic, A and Zarychta, E and Góralczyk, B and Roszkowski, K and Rość, D}, title = {Comprehensive analysis of haemostatic profile depending on clinicopathological determinants in breast cancer patients.}, journal = {Bioscience reports}, volume = {38}, number = {2}, pages = {}, pmid = {29475895}, issn = {1573-4935}, mesh = {Aged ; Breast Neoplasms/*blood/pathology ; Female ; Humans ; Lipoproteins/blood ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/*blood ; Plasminogen Activator Inhibitor 1/blood ; Thromboplastin/metabolism ; Tissue Plasminogen Activator/blood ; }, abstract = {Thrombosis is one of the leading causes of mortality in cancer patients. The aim of the study was to evaluate the concentrations and activities of selected haemostatic parameters in the plasma of patients diagnosed with breast cancer (BrCa) and to make an attempt at finding associations with their levels and selected clinicopathological factors; clinical classification, histological grading, and molecular subtype of BrCa. The study involved 145 Caucasian ethnicity women. Eighty-five women aged 45-66 with primary BrCa without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary BrCa, without previous radiotherapy and chemotherapy. The control group consisted of 60, post-menopausal women, aged 45-68. Haemostatic profile expressed by concentrations and activities of tissue factor (TF) and its inhibitor (TFPI) as well as concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured applying immunoassay techniques. A significantly higher concentration of PAI-1 was noted in patients with BrCa localized in the left breast. We observed significantly lower activity of TFPI and significantly higher concentration of PAI-1 in the group of patients with invasive ductal carcinoma as compared with invasive lobular carcinoma. A significantly higher concentration of t-PA in patients with pT2 BrCa in relation to pT1 cases was noted. Based on comprehensive analysis of haemostatic profile depending on clinicopathological features, we suggest that haemostatic parameters play crucial roles in invasion and metastases of malignant tumours.}, }
@article {pmid29471435, year = {2018}, author = {Desmedt, C and Salgado, R and Fornili, M and Pruneri, G and Van den Eynden, G and Zoppoli, G and Rothé, F and Buisseret, L and Garaud, S and Willard-Gallo, K and Brown, D and Bareche, Y and Rouas, G and Galant, C and Bertucci, F and Loi, S and Viale, G and Di Leo, A and Green, AR and Ellis, IO and Rakha, EA and Larsimont, D and Biganzoli, E and Sotiriou, C}, title = {Immune Infiltration in Invasive Lobular Breast Cancer.}, journal = {Journal of the National Cancer Institute}, volume = {110}, number = {7}, pages = {768-776}, pmid = {29471435}, issn = {1460-2105}, mesh = {Breast Neoplasms/diagnosis/*immunology/metabolism/*pathology ; Carcinoma, Lobular/diagnosis/*immunology/metabolism/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Lymphocyte Count ; Lymphocytes, Tumor-Infiltrating/metabolism/*pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.<br><br>METHODS: We considered two patient series with TIL data: a multicentric retrospective series (n&#x2009;=&#x2009;614) and the BIG 02-98 study (n&#x2009;=&#x2009;149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n&#x2009;=&#x2009;159) and IDC (n&#x2009;=&#x2009;468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n&#x2009;=&#x2009;98) and IDC (n&#x2009;=&#x2009;388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided.<br><br>RESULTS: TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with young age, lymph node involvement, and high proliferative tumors. In the univariate analysis, high TIL levels were associated with worse prognosis in the retrospective and BIG 02-98 lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition.<br><br>CONCLUSIONS: This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.}, }
@article {pmid29470686, year = {2018}, author = {Fukuda, J and Tanaka, S and Ishida, N and Ioka, T and Ikezawa, K and Takakura, R and Nakao, M and Ohkawa, K and Katayama, K and Nagata, S}, title = {A case of stage IA pancreatic ductal adenocarcinoma accompanied with focal pancreatitis demonstrated by contrast-enhanced ultrasonography.}, journal = {Journal of medical ultrasonics (2001)}, volume = {45}, number = {4}, pages = {617-622}, pmid = {29470686}, issn = {1613-2254}, mesh = {Carcinoma, Pancreatic Ductal/complications/*diagnostic imaging/pathology/surgery ; *Contrast Media ; Early Diagnosis ; Female ; Humans ; *Microbubbles ; Middle Aged ; Neoplasm Staging ; Pancreas/diagnostic imaging/pathology ; Pancreatic Neoplasms/complications/*diagnostic imaging/pathology/surgery ; Pancreatitis/complications/*diagnostic imaging/pathology ; Tomography, X-Ray Computed ; *Ultrasonography ; }, abstract = {A patient with slight dilatation of the main pancreatic duct was followed-up with ultrasonography every 6 months as a high-risk case of pancreatic cancer. Twelve years later, a faint hypoechoic area 13 mm in diameter was first detected on the body of the pancreas. Contrast-enhanced ultrasonography revealed a well-demarcated hypoenhanced area 8 mm in diameter and a hyperenhanced area with an unclear margin. The former was suspected to be a small pancreatic cancer lesion, and the latter to be focal pancreatitis accompanying cancer. However, contrast-enhanced dynamic CT did not suggest any tumor, diagnosis of adenocarcinoma was confirmed with pancreatic juice cytology through endoscopic retrograde pancreatography. Surgical resection was performed, and the lesion was pathologically diagnosed as invasive ductal carcinoma as follows: pTS1 (1.0 cm), infiltrative type (pT1), stage IA. When comparing the images from contrast-enhanced ultrasonography with the pathological findings, the hypoenhanced area corresponded to ductal adenocarcinoma, and the hyperenhanced area to focal pancreatitis. Contrast-enhanced ultrasonography was able to reveal detailed information on the focal lesion in the pancreas, and it was effective for the early diagnosis of pancreatic cancer.}, }
@article {pmid29461494, year = {2018}, author = {Seimon, RV and Wild-Taylor, AL and Gibson, AA and Harper, C and McClintock, S and Fernando, HA and Hsu, MSH and Luz, FQD and Keating, SE and Johnson, NA and Grieve, SM and Markovic, TP and Caterson, ID and Byrne, NM and Sainsbury, A}, title = {Less Waste on Waist Measurements: Determination of Optimal Waist Circumference Measurement Site to Predict Visceral Adipose Tissue in Postmenopausal Women with Obesity.}, journal = {Nutrients}, volume = {10}, number = {2}, pages = {}, pmid = {29461494}, issn = {2072-6643}, mesh = {*Adiposity ; Aged ; Anthropometry/*methods ; Female ; Humans ; Intra-Abdominal Fat/*diagnostic imaging/physiopathology ; *Magnetic Resonance Imaging ; Middle Aged ; Obesity/*diagnosis/diagnostic imaging/physiopathology ; *Postmenopause ; Predictive Value of Tests ; Reproducibility of Results ; *Waist Circumference ; }, abstract = {With obesity being a leading cause of preventable death, it is vital to understand how best to identify individuals with greater risk of metabolic disease, especially those with high visceral adipose tissue (VAT). This study aimed to determine whether three commonly used waist circumference (WC) measurement sites could provide accurate estimations of VAT, as determined by magnetic resonance imaging (MRI), which is a gold standard for measuring VAT, in postmenopausal women with obesity. VAT volume was measured by MRI of the total abdomen in 97 women aged 57.7 ± 0.4 years (mean ± SEM), mean body mass index 34.5 ± 0.2 kg/m[2]. WC was measured at the midpoint between the lowest rib and the iliac crest (WCmid), the narrowest point of the torso (WCnarrow), and at the level of the umbilicus (WCumbilicus). WC differed significantly according to measurement site, with WCnarrow (102.1 ± 0.7 cm) < WCmid (108.3 ± 0.7 cm) < WCumbilicus (115.7 ± 0.8 cm) (p < 0.001). WCmid, WCnarrow and WCumbilicus were all significantly correlated with VAT, as measured by MRI (r = 0.581, 0.563 and 0.390, respectively; p < 0.001 for all), but the relationships between WCmid or WCnarrow and VAT determined by MRI were stronger than for WCumbilicus. Measurement of either WCmid or WCnarrow provides valid estimates of VAT in postmenopausal women with obesity, with WCnarrow being favoured in light of its greater ease and speed of measurement in this population.}, }
@article {pmid29436376, year = {2018}, author = {Yu, BH and Tang, SX and Xu, XL and Cheng, YF and Bi, R and Shui, RH and Tu, XY and Lu, HF and Zhou, XY and Yang, WT}, title = {Breast carcinoma in sclerosing adenosis: a clinicopathological and immunophenotypical analysis on 206 lesions.}, journal = {Journal of clinical pathology}, volume = {71}, number = {6}, pages = {546-553}, doi = {10.1136/jclinpath-2017-204751}, pmid = {29436376}, issn = {1472-4146}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/genetics ; Biopsy ; Breast Carcinoma In Situ/*chemistry/genetics/pathology/surgery ; Breast Neoplasms/*chemistry/genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/genetics/pathology/surgery ; Carcinoma, Lobular/*chemistry/genetics/pathology/surgery ; Diagnostic Errors ; Female ; Fibrocystic Breast Disease/*chemistry/genetics/pathology/surgery ; Humans ; *Immunohistochemistry ; Immunophenotyping/*methods ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Phenotype ; Predictive Value of Tests ; Reproducibility of Results ; Retrospective Studies ; *Sclerosis ; Tumor Burden ; }, abstract = {AIMS: To fully elucidate the clinicopathological features of breast carcinoma in sclerosing adenosis (SA-BC).<br><br>METHODS: Clinical and histological characteristics of 206 SA-BCs from 180 patients were retrospectively evaluated. Immunohistochemical phenotype was examined. The clinicopathological relevance of the topographical pattern of SA-BCs was analysed.<br><br>RESULTS: Overall, up to 46 patients (25.6%) had contralateral cancer, either SA associated or not. Of 99 cases who underwent core needle biopsy (CNB), 36 were underestimated as adenosis or atypical ductal hyperplasia at CNB, 5 invasive cases were misinterpreted as in situ carcinomas, whereas 4 ductal carcinoma in situ (DCIS) cases were overdiagnosed as invasive carcinoma. Microscopically, 163 tumours were in situ, including 136 DCIS, 19 lobular carcinomas in situ (LCIS) and 8 mixed DCIS/LCIS; of these carcinomas in situ (CIS), 37 had microinvasion. The DCIS group exhibited low, intermediate and high grades in 53.7%, 34.6% and 11.8% of cases, respectively, mostly with solid (43.4%) or cribriform (41.9%) pattern. Forty out of 43 invasive cases were invasive ductal carcinoma (IDC), mostly DCIS predominant. Immunophenotypically, luminal A phenotype was identified in 55.1%, 63.2% and 45.0% of DCIS, LCIS and IDC cases, respectively. Topographical type A group (carcinoma being entirely confined to SA, n=176) was characterised by smaller size, less invasiveness, lower grade and more frequency of luminal A immunophenotype compared with type B group (&#x2265; 50% but not all of the carcinomatous lesion being located in SA, n=30) (all P<0.05).<br><br>CONCLUSIONS: CIS, especially non-high-grade DCIS, represents the most common variant of SA-BC, and luminal A is the most predominant immunophenotype. CNB assessment might be challenging in some SA-BCs. The topographical pattern has great clinicopathological relevance. Careful evaluation of the contralateral breast and long-term follow-up for patients with SA-BC is necessary given its high prevalence of bilaterality.}, }
@article {pmid29422258, year = {2018}, author = {Papachristopoulou, G and Papadopoulos, EI and Nonni, A and Rassidakis, GZ and Scorilas, A}, title = {Expression Analysis of miR-29b in Malignant and Benign Breast Tumors: A Promising Prognostic Biomarker for Invasive Ductal Carcinoma With a Possible Histotype-Related Expression Status.}, journal = {Clinical breast cancer}, volume = {18}, number = {4}, pages = {305-312.e3}, doi = {10.1016/j.clbc.2017.11.007}, pmid = {29422258}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology/therapy ; Carcinoma, Ductal, Breast/genetics/*pathology/therapy ; Carcinoma, Lobular/genetics/pathology/therapy ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Prognosis ; ROC Curve ; Survival Analysis ; }, abstract = {BACKGROUND: Aberrations in microRNA levels seem to provide valuable information regarding breast cancer prognosis and therapy. In this study, we sought to analyze miR-29b expression in breast tumors and thus explore its clinical value.<br><br>MATERIALS AND METHODS: One hundred twenty-one malignant and 56 benign breast tissue specimens were collected and subjected to extraction of total RNA, which was polyadenylated and reverse transcribed to cDNA. Subsequently, a highly sensitive quantitative real-time polymerase chain reaction protocol was developed and miR-29b levels, estimated via the comparative CT method, were finally subjected to comprehensive statistical analysis.<br><br>RESULTS: MiR-29b levels did not differ between the analyzed benign and malignant breast tissue specimens, but were found to be significantly (P&#xa0;= .010) decreased in invasive ductal adenocarcinomas compared with their lobular counterparts, albeit receiver operating characteristics curve analysis did not verify the latter correlation. Additionally, miR-29b expression was elevated in samples with positive estrogen receptor status (P&#xa0;= .021) in the overall population, whereas it was negatively correlated (P&#xa0;= .035) with primary tumor staging in the ductal subset and increased in poorly-differentiated tumors of lobular origin (P&#xa0;= .041). Furthermore, Kaplan-Meier and Cox regression analyses showed that patients with ductal carcinoma and elevated miR-29b levels had a significantly longer disease-free survival (P&#xa0;= .010) and a lower risk to relapse (hazard ratio&#xa0;= 0.35, 95% confidence interval, 0.15-0.81; P&#xa0;= .014).<br><br>CONCLUSION: Our results provide evidence that miR-29b levels constitute a promising biomarker of favorable prognosis for patients with invasive ductal breast carcinoma and imply that its expression status might be affected by the histological origin of breast malignancy.}, }
@article {pmid29416801, year = {2018}, author = {More, TH and RoyChoudhury, S and Christie, J and Taunk, K and Mane, A and Santra, MK and Chaudhury, K and Rapole, S}, title = {Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples.}, journal = {Oncotarget}, volume = {9}, number = {2}, pages = {2678-2696}, pmid = {29416801}, issn = {1949-2553}, abstract = {Invasive ductal carcinoma (IDC) is the most common type of breast cancer and the leading cause of breast cancer related mortality. In the present study, metabolomic profiles of 72 tissue samples and 146 serum samples were analysed using targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM/MS) and untargeted gas chromatography mass spectrometry (GC-MS) approaches. Combination of univariate and multivariate statistical treatment identified significant alterations of 42 and 32 metabolites in tissue and serum samples of IDC, respectively when compared to control. Some of the metabolite changes from tissue were also reflected in serum, indicating a bi-directional interaction of metabolites in IDC. Additionally, 8 tissue metabolites and 9 serum metabolites showed progressive change from control to benign to IDC suggesting their possible role in malignant transformation. We have identified a panel of three metabolites viz. tryptophan, tyrosine, and creatine in tissue and serum, which could be useful in screening of IDC subjects from both control and benign. The metabolomic alterations in IDC showed perturbations in purine and pyrimidine metabolism, amino sugar metabolism, amino acid metabolism, fatty acid biosynthesis etc. Comprehensively, this study provides valuable insights into metabolic adaptations of IDC, which can help to identify diagnostic markers as well as potential therapeutic targets.}, }
@article {pmid29403520, year = {2018}, author = {Waters, BM and Amundsen, K and Graef, G}, title = {Gene Expression Profiling of Iron Deficiency Chlorosis Sensitive and Tolerant Soybean Indicates Key Roles for Phenylpropanoids under Alkalinity Stress.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {10}, pmid = {29403520}, issn = {1664-462X}, abstract = {Alkaline soils comprise 30% of the earth and have low plant-available iron (Fe) concentration, and can cause iron deficiency chlorosis (IDC). IDC causes soybean yield losses of $260 million annually. However, it is not known whether molecular responses to IDC are equivalent to responses to low iron supply. IDC tolerant and sensitive soybean lines provide a contrast to identify specific factors associated with IDC. We used RNA-seq to compare gene expression under combinations of normal pH (5.7) or alkaline pH (7.7, imposed by 2.5 mM bicarbonate, or pH 8.2 imposed by 5 mM bicarbonate) and normal (25 μM) or low (1 μM) iron conditions from roots of these lines. Thus, we were able to treat pH and Fe supply as separate variables. We also noted differential gene expression between IDC sensitive and tolerant genotypes in each condition. Classical iron uptake genes, including ferric-chelate reductase (FCR) and ferrous transporters, were upregulated by both Fe deficiency and alkaline stress, however, their gene products did not function well at alkaline pH. In addition, genes in the phenylpropanoid synthesis pathway were upregulated in both alkaline and low Fe conditions. These genes lead to the production of fluorescent root exudate (FluRE) compounds, such as coumarins. Fluorescence of nutrient solution increased with alkaline treatment, and was higher in the IDC tolerant line. Some of these genes also localized to previously identified QTL regions associated with IDC. We hypothesize that FluRE become essential at alkaline pH where the classical iron uptake system does not function well. This work could result in new strategies to screen for IDC tolerance, and provide breeding targets to improve crop alkaline stress tolerance.}, }
@article {pmid29394825, year = {2017}, author = {Goto, W and Kashiwagi, S and Asano, Y and Takada, K and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Bladder Metastasis from Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {44}, number = {12}, pages = {1933-1935}, pmid = {29394825}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal/drug therapy/*secondary ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Urinary Bladder Neoplasms/drug therapy/*secondary ; }, abstract = {A 64-year-old woman visited hospital with a chief complaint of a nodule at the left neck skin. Skin biopsy revealed adenocarcinoma, and the diagnosis was skin metastasis of unknown primary origin. Positron emission tomography and computed tomography showed multiple bone and lymph node metastasis, left breast tumor, bladder tumor, and hydronephrosis. A needle biopsy of breast revealed invasive ductal carcinoma, and transurethral biopsy of bladder revealed adenocarcinoma. The findings were similar to those for the breast and the expression pattern of estrogen-receptor was the same. We diagnosed her with breast cancer and bladder metastasis. We administered systemic chemotherapy, however she died 10 days later. Bladder metastasis of breast cancer is rarely encountered in clinical practice and is often accompanied by life threatening symptoms. Careful histopathological examinations and rapid systemic chemotherapy are significant.}, }
@article {pmid29394824, year = {2017}, author = {Goto, W and Kashiwagi, S and Asano, Y and Takada, K and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Breast Cancer Associated with Dermatitis That Was Difficult to Differentiate from Dermatomyositis].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {44}, number = {12}, pages = {1930-1932}, pmid = {29394824}, issn = {0385-0684}, mesh = {Breast Neoplasms/*complications/pathology ; Dermatitis/*diagnosis/*etiology ; Dermatomyositis/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; }, abstract = {A 46-year-old woman visited our hospital with a chief complaint of a mass in the right breast. Breast ultrasonography revealed a hypoechoic area with an indistinct border on the right breast, and right axillary lymph node swelling. A core needle biopsy revealed invasive ductal carcinoma, and the diagnosis was right breast cancer, cT2N2M0, Stage III A, HER2-enriched type. We administered 4 courses of FEC followed by weekly paclitaxel plus trastuzumab. After the treatment, she had eruption and erythema on the face, precordium and forearm. Though dermatomyositis associated cancer was suspected, a definite diagnosis was not made. However, skin symptoms were improved significantly after mastectomy, suggesting that she had dermatomyositis. For the skin symptom during breast cancer treatment, the examination should be made with the possibility of the adverse effect of chemotherapy and dermatomyositis associated cancer.}, }
@article {pmid29394793, year = {2017}, author = {Katsumori, T and Ohshima, H and Hamaguchi, H and Yamamoto, S and Tsukamoto, Y and Iwanaga, T and Ohkawara, S}, title = {[A Case of Long-Term Survival of Breast Cancer with Lymph Node and Liver Metastases Treated with Sequential Anti-HER2 Drugs, Chemotherapy, and Endocrine Therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {44}, number = {12}, pages = {1838-1840}, pmid = {29394793}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/therapy ; Chemoradiotherapy ; Endocrine System ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2/*antagonists &amp; inhibitors ; }, abstract = {A 50s-year-old woman underwent left partial mastectomy with axillary lymphadenectomy for breast cancer. Histological examination indicated invasive ductal carcinoma, pT1c, pN0, Stage I , ly(+), ER(+), PgR(+). She received adjuvant therapy with tamoxifen and 50 Gy of irradiation to the residual breast. Four years after mastectomy, she was found to have left Rotter lymph node metastasis; then, anastrozole was administered instead of tamoxifen. Nine months later, she was found to have liver metastasis. Immunohistostaining revealed that the breast cancer was HER2-positive; she received AC followed by paclitaxel(PTX)with trastuzumab(T), and achieved complete response(CR). Subsequently, abdominal, cervical lymph node, and liver metastases appeared. Letrozole followed by lapatinib with capecitabine, FEC100, PTX with T, eribulin, S-1, docetaxel with pertuzumab and T, everolimus with exemestane, bevacizumab, and PTX were then administered, resulting in long-term disease control. Sixteen years after mastectomy, she receives outpatient chemotherapy in performance status 1 state.}, }
@article {pmid29394713, year = {2017}, author = {Waraya, M and Hayashi, K and Oshida, S and Yamamoto, K and Hosoya, S and Habiro, T and Inukai, M and Kosaka, Y and Sengoku, N and Watanabe, M}, title = {[A Case Report of Ipsilateral Nipple Skin Recurrence].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {44}, number = {12}, pages = {1595-1597}, pmid = {29394713}, issn = {0385-0684}, mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*secondary/*surgery ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy, Segmental ; Nipples/*pathology/surgery ; Recurrence ; }, abstract = {We report our experience with a patient with breast cancer who showed recurrence in the nipple skin 5 years and 10 months after a breast-preserving surgery. The patient was a woman, and was 65-years old at the time of initial surgery. Breast-preserving surgery and axillary lymph-node dissection were performed for left breast cancer. Invasive ductal carcinoma of the breast(pT3N0M0)was triple-negative, and the patient postoperatively received adjuvant chemotherapy. Left breast pain developed 5 years and 6 months after surgery. Computed tomography showed no evidence of recurrence, and the symptoms resolved after treatment with non-steroidal anti-inflammatory drugs(NSAIDs). After 3 months, however, the left nipple had enlarged to about 1.5 cm, and the surrounding skin was red and painful. Treatment with NSAIDs was thus resumed. After 1 week, redness of the nipple skin and pain were improved. However, the nipple had enlarged to twice its normal size. Nipple skin biopsy was subsequently performed, and revealed adenocarcinoma invading the skin. Left axillary lymph-node metastasis was suspected, but there was no evidence of metastasis to other sites or recurrence. Conservative total mastectomy with axillary lymph-node dissection was thus performed. The histopathological diagnosis was the recurrence of invasive ductal carcinoma, arising mainly in the reticular layer of the dermis. Chemotherapy was administered postoperatively. There has been no evidence of recurrence as of 1 year after surgery.}, }
@article {pmid29394534, year = {2017}, author = {Inoue, T and Shimomura, A and Sugimoto, T and Wakamiya, S and Chou, U and Fujiwara, A and Uchikoshi, F and Watanabe, T and Kitamura, N}, title = {[Local Control of Advanced Breast Cancer with Giant Ulcer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {44}, number = {12}, pages = {1062-1064}, pmid = {29394534}, issn = {0385-0684}, mesh = {Biopsy ; Breast Neoplasms/complications/pathology/*therapy ; Carcinoma, Ductal/complications/*therapy ; Chemoradiotherapy ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Ulcer/*etiology ; }, abstract = {This study reports the treatment and local control of advanced breast cancer with a giant ulcer. A 53-year-old woman presented with a large left breast tumor and an associated giant ulcer, with massive exudates, bleeding, and an offensive odor. Histopathological examination revealed an invasive ductal carcinoma(Luminal B type). Computed tomography(CT) showed multiple metastases to the lymph nodes, lungs, liver and bones. The patient received chemotherapy with a combina- tion of paclitaxel(PTX 90mg/m / 2)and bevacizumab(BEV 10 mg/kg). After 4 courses of chemotherapy, there was a significant reduction in the tumor size, the discharge of exudates and bleeding as well as lumbago and femoral pain. High CEA and CA15-3 levels had been normalized and CT showed a remarkable decrease in metastases. Compared to the tumor itself, the ulcer associated with it had shown a smaller decrease in size, and there was the possibility of perforation in the thin chest wall. Suspecting these outcomes to the adverse events of BEV, its use was discontinued, and starting with course 5 of chemothera- py, we administrated only PTX(90mg/m2). Subsequently, the ulcer showed obvious granulation and was infected. CT of the chest prior to the second course of PTX revealed pleurisy, pneumonia and atelectasis. Following the administration of antibiotics, while infection in the ulcer had subsided, pleurisy and pneumonia continued, with increased right pleural effusion, which finally required drainage. We had to discontinue the administration of PTX. BEV, although effective as first-line therapy, has the adverse effect of slowing wound healing. Therefore, even though the combination therapy of BEV and PTX is markedly effective for systemic therapy, it should be altered for local wound healing as in this case.}, }
@article {pmid29378343, year = {2018}, author = {Enríquez-Marulanda, A and Beltrán-Osorio, LD and Escobar, LA and Granados, AM and Velásquez-Lasprilla, F and Orozco, JL}, title = {Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration Manifesting as Acute Cerebellitis with Posterior Cranial Fossa Hypertension.}, journal = {World neurosurgery}, volume = {112}, number = {}, pages = {117-122}, doi = {10.1016/j.wneu.2018.01.105}, pmid = {29378343}, issn = {1878-8769}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Cranial Fossa, Posterior/*pathology/surgery ; Craniotomy/*methods ; Female ; Humans ; Intracranial Hypertension/*etiology/pathology/surgery ; Middle Aged ; Paraneoplastic Cerebellar Degeneration/*complications/pathology/surgery ; }, abstract = {BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a rare complication of some malignant cancers. It is most commonly described in women with gynecologic or breast malignancies; however, there have been reports in other types of cancers. Symptoms include ataxia, dysarthria, and tremors, which could be the first manifestations of an underlying malignancy.<br><br>CASE DESCRIPTION: A 50-year-old woman had an acute PCD with anti-Yo antibodies from an underlying breast invasive ductal carcinoma. She presented with intracranial hypertension in the posterior cranial fossa that required an emergent decompressive craniectomy.<br><br>CONCLUSIONS: PCD is an uncommon disease that may manifest initially as posterior cranial fossa hypertension and subsequent acute hydrocephalus owing to diffuse cerebellar swelling. To our knowledge, this is the first described case of an anti-Yo PCD that has manifested as acute posterior cranial fossa hypertension owing to diffuse cerebellar edema. Early diagnosis and treatment should be pursued to improve long-term outcomes.}, }
@article {pmid29373327, year = {2018}, author = {D'heygere, E and Meulemans, J and Vander Poorten, V}, title = {Salivary duct carcinoma.}, journal = {Current opinion in otolaryngology &amp; head and neck surgery}, volume = {26}, number = {2}, pages = {142-151}, doi = {10.1097/MOO.0000000000000436}, pmid = {29373327}, issn = {1531-6998}, mesh = {Disease-Free Survival ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Rare Diseases ; Receptor, ErbB-2/genetics ; Receptors, Androgen/genetics ; Risk Assessment ; Salivary Ducts/*pathology/surgery ; Salivary Gland Neoplasms/*genetics/mortality/pathology/*surgery ; Survival Rate ; }, abstract = {PURPOSE OF REVIEW: The review puts new information on geno- and phenotype of salivary duct carcinoma (SDC) in the perspective of the updated 2017 WHO classification.<br><br>RECENT FINDINGS: The proportion of SDC is increasing. This may be because of a true rise in incidence, but certainly to better diagnostic tests and changed WHO definitions. In this light, a substantial proportion of carcinoma expleomorphic adenoma is now attributed to the category of SDC. 'Low-grade SDC' and 'SDC in-situ' of the former WHO classification, are now named low-grade and high-grade intraductal carcinoma (IDC), respectively. Recent series quantify biologic aggressiveness: perineural growth, vascular invasion, and extracapsular extension in lymph node metastasis are each observed in two out of three patients with SDC. Most patients die within 3 years, but once 5-year disease-free survival is reached, further disease activity is exceptional. The typical molecular biological profile with high human epidermal growth factor receptor 2 and androgen receptor expression is increasingly successfully exploited in clinical trials for advanced SDC.<br><br>SUMMARY: The aggressive SDC is increasingly diagnosed. Despite intensive combined surgery and radiation therapy, many patients recur, for whom new bullets, targeting the molecular biological mechanisms, are the subject of ongoing clinical trials.}, }
@article {pmid29373286, year = {2018}, author = {Sachdeva, R and Schlotterer, A and Schumacher, D and Matka, C and Mathar, I and Dietrich, N and Medert, R and Kriebs, U and Lin, J and Nawroth, P and Birnbaumer, L and Fleming, T and Hammes, HP and Freichel, M}, title = {TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation.}, journal = {Molecular metabolism}, volume = {9}, number = {}, pages = {156-167}, pmid = {29373286}, issn = {2212-8778}, mesh = {Animals ; Cells, Cultured ; Diabetic Retinopathy/genetics/*metabolism ; Female ; Lactoylglutathione Lyase/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pyruvaldehyde/blood/*metabolism ; Retina/metabolism ; TRPC Cation Channels/*genetics/metabolism ; }, abstract = {OBJECTIVE: Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6[-/-] compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy.<br><br>METHODS: We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types. Chronic hyperglycemia was induced by Streptozotocin (STZ) treatment. To assess the development of diabetic retinopathy, vasoregression, pericyte loss, and thickness of individual retinal layers were analyzed. Plasma and cellular methylglyoxal (MG) levels, as well as Glyoxalase 1 (GLO1) enzyme activity and protein expression, were measured in WT and Trpc1/4/5/6[-/-] cells or tissues. MG-evoked toxicity in cells of both genotypes was compared by MTT assay.<br><br>RESULTS: We find that Trpc1/4/5/6[-/-] mice are protected from hyperglycemia-evoked vasoregression determined by the formation of acellular capillaries and pericyte drop-out. In addition, Trpc1/4/5/6[-/-] mice are resistant to the STZ-induced reduction in retinal layer thickness. The RCS metabolite methylglyoxal, which represents a key mediator for the development of diabetic retinopathy, was significantly reduced in plasma and red blood cells (RBCs) of STZ-treated Trpc1/4/5/6[-/-] mice compared to controls. GLO1 is the major MG detoxifying enzyme, and its activity and protein expression were significantly elevated in Trpc1/4/5/6-deficient cells, which led to significantly increased resistance to MG toxicity. GLO1 activity was also increased in retinal extracts from Trpc1/4/5/6[-/-] mice. The TRPCs investigated here are expressed at different levels in endothelial and glial cells of the retina.<br><br>CONCLUSION: The protective phenotype in diabetic retinopathy observed in Trpc1/4/5/6[-/-] mice is suggestive of a predominant action of TRPCs in M&#xfc;ller cells and microglia because of their central position in the retention of a proper homoeostasis of the neurovascular unit.}, }
@article {pmid29367511, year = {2017}, author = {Sakamoto, N and Ueda, S and Mizoguchi, H and Kawahara, I and Kobayashi, T and Hamaguchi, M and Yoshikawa, M}, title = {[SIGNIFICANCE OF INTRADUCTAL CARCINOMA OF THE PROSTATE IN POST-OPERATIVE BIOCHEMICAL RECURRENCE].}, journal = {Nihon Hinyokika Gakkai zasshi. The japanese journal of urology}, volume = {108}, number = {1}, pages = {5-11}, doi = {10.5980/jpnjurol.108.5}, pmid = {29367511}, issn = {0021-5287}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*diagnosis/*etiology ; Predictive Value of Tests ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/pathology/*surgery ; Time Factors ; }, abstract = {(Objective) We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy specimens. (Materials and methods) We evaluated 441 patients treated with radical prostatectomy and analyzed data on IDC-P, lymph node metastases, Gleason score, seminal vesicle invasion, extraprostatic extension, surgical margin, total cancer volume, and zonal origin of dominant cancer focus in radical prostatectomy specimens. The median follow-up was 50 months (range 6-164 months). (Results) We identified IDC-P in 112 cases (25.4%). The five-year biochemical progression-free survival rate in patients with IDC-P was significantly lower than for those without IDC-P (35.8% vs 69.6%; p<0.0001). In a univariate analysis, IDC-P (p<0.0001), lymph node metastases (p=0.0022), Gleason score (p<0.0001), seminal vesicle invasion (p<0.0001), extraprostatic extension (p<0.0001), surgical margin (p<0.0001) and total cancer volume (p<0.0001) were significantly associated with the biochemical progression-free survival. In a multivariate analysis, Gleason score (p<0.0001), IDC-P (p=0.0002), seminal vesicle invasion (p=0.0011), extraprostatic extension (p=0.0012), surgical margin (p=0.0019) and lymph node metastases (p=0.0402) were significantly associated with biochemical progression-free survival. (Conclusions) The presence of IDC-P is an independent factor of biochemical recurrence in prostate cancer patients treated with radical prostatectomy. We therefore recommend that the presence of IDC-P in radical prostatectomy specimens be reported.}, }
@article {pmid29362505, year = {2018}, author = {Hand, BN and Krause, JS and Simpson, KN}, title = {Polypharmacy and adverse drug events among propensity score matched privately insured persons with and without spinal cord injury.}, journal = {Spinal cord}, volume = {56}, number = {6}, pages = {591-597}, pmid = {29362505}, issn = {1476-5624}, support = {UL1 TR001450/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Drug-Related Side Effects and Adverse Reactions/*epidemiology ; Female ; Humans ; Insurance, Health ; Likelihood Functions ; Male ; Middle Aged ; Odds Ratio ; *Polypharmacy ; Propensity Score ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Spinal Cord Injuries/drug therapy/*epidemiology ; United States/epidemiology ; Young Adult ; }, abstract = {STUDY DESIGN: Retrospective quasi-experimental design.<br><br>OBJECTIVES: To compare the incidence of adverse drug events (ADEs) between persons with and without spinal cord injury (SCI), while controlling for all potential and available risk factors.<br><br>SETTING: A commercially available claims dataset consisting of ~170 million patient cases in the United States between 2012 and 2013.<br><br>METHODS: Participants (aged 18-64 years) included 2779 persons with polypharmacy and traumatic or non-traumatic SCI and 2779 propensity score-matched persons with polypharmacy without SCI. The cohorts were matched using demographic variables including number of concomitant prescriptions, comorbidities, hospital admissions, age, gender, and geographic region. Inpatient and outpatient claims records containing 395 distinct IDC-9 codes indicative of ADEs were extracted. Incidence and frequency of ADEs were compared between groups using logistic and Poisson regression, respectively.<br><br>RESULTS: Persons with SCI were significantly more likely to experience an ADE than matched controls (Odds Ratio&#x2009;=&#x2009;1.45, p&#x2009;<&#x2009;0.0001). Among persons with ADEs (n&#x2009;=&#x2009;1552), individuals with SCI experienced fewer ADEs over time than matched controls (Incidence Rate Ratio&#x2009;=&#x2009;0.91, p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSIONS: While persons with SCI and polypharmacy are at a greater risk for experiencing an ADE, their medical care after an ADE may be better managed than that of a matched control population. There may be a need for practice guidelines that facilitate proactive identification of persons with SCI at the highest risk of ADE. Steps may then be taken to mitigate risk, in contrast to current practice trends that appear to take a reactive approach after an ADE has occurred.}, }
@article {pmid29362351, year = {2018}, author = {Sakagami, M and Hirano, T and Suzuki, S and Adachi, K and Kubota, H and Hara, Y and Enomoto, K and Tomita, R and Fujisaki, S and Sakurai, K}, title = {[A Case of Advanced Breast Cancer with Liver Metastasis Successfully Treated with Multi-Disciplinary].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {45}, number = {1}, pages = {190-192}, pmid = {29362351}, issn = {0385-0684}, mesh = {Adult ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Carcinoma, Ductal/*drug therapy/*secondary/surgery ; Combined Modality Therapy ; Female ; Humans ; Liver Neoplasms/*drug therapy/*secondary ; Neoplasm Staging ; Treatment Outcome ; }, abstract = {We report a case of advanced breast cancer with liver metastasis(T2N1M1, Stage IV)achieving a significant improvement of QOL by multi-disciplinary therapy. The patient was 37-year-old woman who had breast lump and axillary lymph nodes swelling with liver metastasis. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma, negative for estrogen receptor and progesterone receptor, and positive for HER2/neu protein expression. The Ki-67 positive cell index was 40%. She received 16 courses of DOC plus HER plus PER(docetaxel 75mg/m / 2, trastuzumab 6 mg/kg, pertu- zumab 450mg/body, and received 4 courses of EC(epirubicin 90mg/m / 2, cyclophosphamide 600 mg/m2). The breast lesion and liver metastatic lesion disappeared after chemotherapy. We checked up whole body. There was no metastatic lesion. Therefore, we diagnosed a clinical complete response. We performed muscle preserving mastectomy and axillary lymph nodes dissection. The pathological diagnosis from resected specimens were pathological complete response. The surgical margin was negative. She was started the endocrine therapy by tamoxifen(20mg/day). Three years after surgery, she was well without metastases. Multi-disciplinary therapy can improve patient QOL and the clinical outcomes in Stage IV advanced breast cancer.}, }
@article {pmid29360854, year = {2018}, author = {Dolka, I and Czopowicz, M and Gruk-Jurka, A and Wojtkowska, A and Sapierzyński, R and Jurka, P}, title = {Diagnostic efficacy of smear cytology and Robinson's cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0191595}, pmid = {29360854}, issn = {1932-6203}, mesh = {Animals ; Biopsy ; Dog Diseases/*diagnosis/pathology ; Dogs ; Female ; Mammary Neoplasms, Animal/*diagnosis/pathology ; *Neoplasm Metastasis ; Sensitivity and Specificity ; Survival Analysis ; }, abstract = {Cytology is a simple, rapid, and inexpensive method used for pre-operative diagnosis of canine mammary tumors (CMTs) in veterinary practice. Studies related to human breast cancer showed the Robinson's grading system-established for invasive ductal carcinoma, not otherwise specified (IDC, NOS) and used on cytological material-to not only closely correspond to the histopathological grading but also be helpful in assessing prognosis and selecting most suitable treatments before surgery. The objectives of this study were: to evaluate the accuracy of cytological diagnosis and cytological Robinson's grading system compared to the histopathological examination of CMTs; to compare of cytological features and cytomorphometric parameters with tumor behavior, as well as cytological and histological grading; and to determine an association of the Robinson's grading system and cytological background details with metastases, and patients' survival. We report substantial diagnostic accuracy in detecting simple types and high grade tumors. Cytological diagnosis of tumor behavior showed relatively low sensitivity and specificity compared to human studies, and this might be caused by the heterogeneous morphology of CMTs. The presence of mucosecretory material and extracellular matrix was not significantly associated with tumor behavior. We report a positive correlation between both grading systems and cytological features (included in Robinson's grading), the presence of necrotic debris, inflammation, and red blood cells. A negative correlation was determined only for the presence of extracellular matrix. The univariate and multivariate analyses confirmed a significantly higher risk of developing metastasis and shorter overall survival for dogs with tumors of grade 2 or 3 on cytology. In addition, these tumors were the most common cause of CMT-related deaths in dogs. Taken together, our findings suggest that the Robinson's method of cytological grading applied for malignant CMTs evaluated in cytological smears regardless of tumor type can be adapted to veterinary cytology. Additionally, some background features seem to aid malignancy assessment.}, }
@article {pmid29358028, year = {2018}, author = {Santangelo, G and Garramone, F and Baiano, C and D'Iorio, A and Piscopo, F and Raimo, S and Vitale, C}, title = {Personality and Parkinson's disease: A meta-analysis.}, journal = {Parkinsonism &amp; related disorders}, volume = {49}, number = {}, pages = {67-74}, doi = {10.1016/j.parkreldis.2018.01.013}, pmid = {29358028}, issn = {1873-5126}, mesh = {Adult ; Aged ; Aged, 80 and over ; Avoidance Learning/*physiology ; *Character ; Exploratory Behavior/*physiology ; *Extraversion, Psychological ; Female ; Humans ; Male ; Middle Aged ; Neuroticism/*physiology ; Parkinson Disease/complications/*physiopathology ; Personality Disorders/etiology/*physiopathology ; }, abstract = {INTRODUCTION: Personality changes are considered pre-motor features of Parkinson's disease (PD). Cross-sectional studies revealed that PD patients were more introvert, apprehensive, and cautious than healthy subjects (HS), whereas other studies failed to disclose these behavioural traits. Some studies found mixed results concerning Novelty Seeking (NS) and Harm Avoidance (HA) profiles in PD patients. To better clarify the personality profile in PD we performed a meta-analysis on studies exploring such topic according to both Cloninger's Psychobiological Model (PM) and Big Five Model (BFM) METHODS: The meta-analysis included 17 studies evaluating the personality in PD patients compared with HS. The outcomes were the dimensions of the temperament and character of the PM and personality traits of BFM. Effect sizes from data reported in the primary studies were computed using Hedges'g unbiased approach. Heterogeneity among the studies and publication bias were assessed. Meta-regressions were conducted with age at evaluation, gender, schooling, and type of personality trait tools as moderators.<br><br>RESULTS: As for PM, PD patients scored higher on HA and lower on NS than HS. No difference was found on Reward Dependence, Perseverance/Persistence and on character level. As for BFM, higher levels of Neuroticism, but lower levels of Openness and Extraversion were associated with PD.<br><br>DISCUSSION: The personality profile in PD is characterized by high Neuroticism and HA, and by low Openness, Extraversion and NS. The personality profile delineated in the present study on PD patients seems to reflect the premorbid one and might contribute to development and persistence of affective disorders.}, }
@article {pmid29356019, year = {2018}, author = {Shalaby, N and Al-Ebraheem, A and Le, D and Cornacchi, S and Fang, Q and Farrell, T and Lovrics, P and Gohla, G and Reid, S and Hodgson, N and Farquharson, M}, title = {Time-resolved fluorescence (TRF) and diffuse reflectance spectroscopy (DRS) for margin analysis in breast cancer.}, journal = {Lasers in surgery and medicine}, volume = {50}, number = {3}, pages = {236-245}, doi = {10.1002/lsm.22795}, pmid = {29356019}, issn = {1096-9101}, mesh = {Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/surgery ; Female ; Humans ; *Margins of Excision ; Mastectomy ; Reproducibility of Results ; *Spectrometry, Fluorescence ; }, abstract = {PURPOSE: One of the major problems in breast cancer surgery is defining surgical margins and establishing complete tumor excision within a single surgical procedure. The goal of this work is to establish instrumentation that can differentiate between tumor and normal breast tissue with the potential to be implemented in vivo during a surgical procedure.<br><br>METHODS: A time-resolved fluorescence and reflectance spectroscopy (tr-FRS) system is used to measure fluorescence intensity and lifetime as well as collect diffuse reflectance (DR) of breast tissue, which can subsequently be used to extract optical properties (absorption and reduced scatter coefficient) of the tissue. The tr-FRS data obtained from patients with Invasive Ductal Carcinoma (IDC) whom have undergone lumpectomy and mastectomy surgeries is presented. A preliminary study was conducted to determine the validity of using banked pre-frozen breast tissue samples to study the fluorescence response and optical properties. Once the validity was established, the tr-FRS system was used on a data-set of 40 pre-frozen matched pair cases to differentiate between tumor and normal breast tissue. All measurements have been conducted on excised normal and tumor breast samples post surgery.<br><br>RESULTS: Our results showed the process of freezing and thawing did not cause any significant differences between fresh and pre-frozen normal or tumor breast tissue. The tr-FRS optical data obtained from 40 banked matched pairs showed significant differences between normal and tumor breast tissue.<br><br>CONCLUSION: The work detailed in the main study showed the tr-FRS system has the potential to differentiate malignant from normal breast tissue in women undergoing surgery for known invasive ductal carcinoma. With further work, this successful outcome may result in the development of an accurate intraoperative real-time margin assessment system. Lasers Surg. Med. 50:236-245, 2018. &#xa9; 2018 Wiley Periodicals, Inc.}, }
@article {pmid29353241, year = {2018}, author = {Jabs, M and Rose, AJ and Lehmann, LH and Taylor, J and Moll, I and Sijmonsma, TP and Herberich, SE and Sauer, SW and Poschet, G and Federico, G and Mogler, C and Weis, EM and Augustin, HG and Yan, M and Gretz, N and Schmid, RM and Adams, RH and Gröne, HJ and Hell, R and Okun, JG and Backs, J and Nawroth, PP and Herzig, S and Fischer, A}, title = {Inhibition of Endothelial Notch Signaling Impairs Fatty Acid Transport and Leads to Metabolic and Vascular Remodeling of the Adult Heart.}, journal = {Circulation}, volume = {137}, number = {24}, pages = {2592-2608}, doi = {10.1161/CIRCULATIONAHA.117.029733}, pmid = {29353241}, issn = {1524-4539}, mesh = {Adaptor Proteins, Signal Transducing ; Angiopoietins/genetics/metabolism ; Animals ; CD36 Antigens/genetics/metabolism ; Calcium-Binding Proteins ; Endothelium, Vascular/cytology/*metabolism ; Fatty Acid-Binding Proteins/genetics/metabolism ; Fatty Acids/genetics/*metabolism ; Glucose/genetics/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; Mice ; Mice, Transgenic ; Myocardium/*metabolism ; Myocytes, Cardiac/metabolism ; Neovascularization, Physiologic ; Receptors, Notch/genetics/*metabolism ; Ribosomal Protein S6 Kinases/genetics/metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases/genetics/metabolism ; *Vascular Remodeling ; }, abstract = {BACKGROUND: Nutrients are transported through endothelial cells before being metabolized in muscle cells. However, little is known about the regulation of endothelial transport processes. Notch signaling is a critical regulator of metabolism and angiogenesis during development. Here, we studied how genetic and pharmacological manipulation of endothelial Notch signaling in adult mice affects endothelial fatty acid transport, cardiac angiogenesis, and heart function.<br><br>METHODS: Endothelial-specific Notch inhibition was achieved by conditional genetic inactivation of Rbp-j&#x3ba; in adult mice to analyze fatty acid metabolism and heart function. Wild-type mice were treated with neutralizing antibodies against the Notch ligand Delta-like 4. Fatty acid transport was studied in cultured endothelial cells and transgenic mice.<br><br>RESULTS: Treatment of wild-type mice with Delta-like 4 neutralizing antibodies for 8 weeks impaired fractional shortening and ejection fraction in the majority of mice. Inhibition of Notch signaling specifically in the endothelium of adult mice by genetic ablation of Rbp-j&#x3ba; caused heart hypertrophy and failure. Impaired heart function was preceded by alterations in fatty acid metabolism and an increase in cardiac blood vessel density. Endothelial Notch signaling controlled the expression of endothelial lipase, Angptl4, CD36, and Fabp4, which are all needed for fatty acid transport across the vessel wall. In endothelial-specific Rbp-j&#x3ba;-mutant mice, lipase activity and transendothelial transport of long-chain fatty acids to muscle cells were impaired. In turn, lipids accumulated in the plasma and liver. The attenuated supply of cardiomyocytes with long-chain fatty acids was accompanied by higher glucose uptake, increased concentration of glycolysis intermediates, and mTOR-S6K signaling. Treatment with the mTOR inhibitor rapamycin or displacing glucose as cardiac substrate by feeding a ketogenic diet prolonged the survival of endothelial-specific Rbp-j&#x3ba;-deficient mice.<br><br>CONCLUSIONS: This study identifies Notch signaling as a novel regulator of fatty acid transport across the endothelium and as an essential repressor of angiogenesis in the adult heart. The data imply that the endothelium controls cardiomyocyte metabolism and function.}, }
@article {pmid29350308, year = {2018}, author = {Ory, V and Kietzman, WB and Boeckelman, J and Kallakury, BV and Wellstein, A and Furth, PA and Riegel, AT}, title = {The PPARγ agonist efatutazone delays invasive progression and induces differentiation of ductal carcinoma in situ.}, journal = {Breast cancer research and treatment}, volume = {169}, number = {1}, pages = {47-57}, pmid = {29350308}, issn = {1573-7217}, support = {P30CA051008//National Cancer Institute/ ; RO1CA205632//National Institutes of Health/ ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA205632/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; CA009686//T32 Training Grant in Tumor Biology/ ; R01 CA112176/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Neoplasm Invasiveness/genetics/pathology ; PPAR gamma/*genetics ; Thiazolidinediones/*administration &amp; dosage ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion of the breast considered a precursor of invasive ductal carcinoma. This study aimed to determine whether activated PPARγ acts as a tumor suppressor in human DCIS progression.<br><br>METHODS: We utilized the high-affinity PPAR&#x3b3; agonist, efatutazone, to activate endogenous PPAR&#x3b3; in a well-defined model for the progression of basal (triple negative) DCIS, MCFDCIS cells, cultured under 2D and 3D conditions. We studied the effects of activated PPAR&#x3b3; on DCIS progression in MCFDCIS xenograft and C3(1)/Tag transgenic mice treated with 30&#xa0;mg/kg of efatutazone.<br><br>RESULTS: In vitro, efatutazone did not alter the MCFDCIS cell proliferation but induced phenotypic and gene expression changes, indicating that activated PPAR&#x3b3; is able to differentiate MCFDCIS cells into more luminal and lactational-like cells. In addition, MCFDCIS tumorsphere formation in 3D was reduced by PPAR&#x3b3; activation. In vivo, efatutazone-treated MCFDCIS tumors exhibited fat deposition along with upregulation of PPAR&#x3b3; responsive genes in both epithelial and stromal compartments, suggesting features of milk-producing mammary epithelial cell differentiation. The efatutazone-treated lesions were less invasive with fewer CD44+/p63+ basal progenitor cells. PPAR&#x3b3; activation downregulated Akt phosphorylation in these tumors, although the ERK pathway remained unchanged. Similar trends in gene expression changes consistent with lactational and luminal cell differentiation were observed in the C3(1)/Tag mouse model after efatutazone treatment.<br><br>CONCLUSIONS: Our data suggest that activation of the PPAR&#x3b3; pathway differentiates DCIS lesions and may be a useful approach to delay DCIS progression.}, }
@article {pmid29349758, year = {2018}, author = {Feinberg, J and Wetstone, R and Greenstein, D and Borgen, P}, title = {Is DCIS Overrated?.}, journal = {Cancer treatment and research}, volume = {173}, number = {}, pages = {53-72}, doi = {10.1007/978-3-319-70197-4_5}, pmid = {29349758}, issn = {0927-3042}, mesh = {Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/mortality/pathology/*therapy ; Female ; Gene Expression Profiling ; Humans ; Neoplasm Invasiveness ; }, abstract = {Ductal carcinoma in situ (DCIS), the noninvasive form of breast cancer (BC), comprises just over 20% of breast cancer cases diagnosed each year in the USA. Most patients are treated with local excision of the disease followed by whole breast radiation therapy. Total mastectomy is not an uncommon approach, and total mastectomy with a contralateral risk-reducing mastectomy has been on the rise in the past decade. In estrogen receptor-positive disease, patients are often offered endocrine ablative therapy with a selective estrogen receptor modulator or an aromatase inhibitor as both treatment and prevention. Local regional treatment options have no impact upon ultimate overall survival. Long-term survival rates are higher in patients with DCIS than with any other form of the disease. Are these strikingly high success rates a testament to effective treatment strategies or is there a significant subset of DCIS that was unlikely to ever progress to invasive ductal carcinoma? DCIS was not seen in the US prior to the advent of screening mammography. When compared to other countries, the USA has the highest utilization of screening mammography and the incidence rate of DCIS. Other lines of evidence include autopsy series examining the breast tissue of women who died of other causes, missed-diagnosis series and current retrospective reviews of DCIS, all align in support of the concept of DCIS as indolent in the majority of cases [3-14]. The evidence suggests that both patient and physician misconceptions about DCIS have led to overdiagnosis and over-treatment of DCIS. Recently, a gene expression profiling tool (12 gene assay, Oncotype DCIS) has emerged that shows considerable promise in predicting class in DCIS patients.}, }
@article {pmid29345622, year = {2018}, author = {Valero, A and Navarro, AM and Del Cuvillo, A and Alobid, I and Benito, JR and Colás, C and de Los Santos, G and Fernández Liesa, R and García-Lliberós, A and González-Pérez, R and Izquierdo-Domínguez, A and Jurado-Ramos, A and Lluch-Bernal, MM and Montserrat Gili, JR and Mullol, J and Puiggròs Casas, A and Sánchez-Hernández, MC and Vega, F and Villacampa, JM and Armengot-Carceller, M and Dordal, MT and , }, title = {Position paper on nasal obstruction: evaluation and treatment.}, journal = {Journal of investigational allergology &amp; clinical immunology}, volume = {28}, number = {2}, pages = {67-90}, doi = {10.18176/jiaci.0232}, pmid = {29345622}, issn = {1018-9068}, mesh = {Animals ; Humans ; Nasal Cavity/drug effects ; Nasal Obstruction/*drug therapy ; Quality of Life ; Rhinomanometry/methods ; Rhinometry, Acoustic/methods ; }, abstract = {Nasal obstruction (NO) is defined as the subjective perception of discomfort or difficulty in the passage of air through the nostrils. It is a common reason for consultation in primary and specialized care and may affect up to 30%-40% of the population. It affects quality of life (especially sleep) and lowers work efficiency. The aim of this document is to agree on how to treat NO, establish a methodology for evaluating and diagnosing it, and define an individualized approach to its treatment. NO can be unilateral or bilateral, intermittent or persistent and may be caused by local or systemic factors, which may be anatomical, inflammatory, neurological, hormonal, functional, environmental, or pharmacological in origin. Directed study of the medical history and physical examination are key for diagnosing the specific cause. NO may be evaluated using subjective assessment tools (visual analog scale, symptom score, standardized questionnaires) or by objective estimation (active anterior rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow). Although there is little correlation between the results, they may be considered complementary and not exclusive. Assessing the impact on quality of life through questionnaires standardized according to the underlying disease is also advisable. NO is treated according to its cause. Treatment is fundamentally pharmacological (topical and/or systemic) when the etiology is inflammatory or functional. Surgery may be necessary when medical treatment fails to complement or improve medical treatment or when other therapeutic approaches are not possible. Combinations of surgical techniques and medical treatment may be necessary.}, }
@article {pmid29345290, year = {2018}, author = {Nowak, A and Grzegrzółka, J and Kmiecik, A and Piotrowska, A and Matkowski, R and Dzięgiel, P}, title = {Role of nestin expression in angiogenesis and breast cancer progression.}, journal = {International journal of oncology}, volume = {52}, number = {2}, pages = {527-535}, doi = {10.3892/ijo.2017.4223}, pmid = {29345290}, issn = {1791-2423}, mesh = {Breast Neoplasms/*blood supply/metabolism/pathology ; Carcinoma, Ductal, Breast/*blood supply/metabolism/pathology ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic ; Nestin/genetics/*metabolism ; SOXF Transcription Factors/metabolism ; Triple Negative Breast Neoplasms/blood supply/metabolism/pathology ; }, abstract = {Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis. Immunohistochemical (IHC) analyses were carried out on 124 cases of invasive ductal carcinoma (IDC) of the breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34, SOX-18 and Ki‑67. We evaluated nestin expression in tumour and endothelial cells, Ki‑67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our results demonstrated that nestin expression in tumour cells correlated with the area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also found a positive correlation between nestin-expressing vessels and SOX-18-expressing vessels. Our results are consistent with those of previous studies, in which nestin expression in endothelial cells was shown to be strongly associated with triple-negative subtype, poorly differentiated G3 tumours, a higher proliferation index and a shorter overall survival. Nestin expression was also examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA‑MB‑231 and BO2 cells) representing a different level of tumour aggressiveness and reflecting histological grade. A higher nestin protein level was observed in more aggressive MDA‑MB‑231 and BO2 cells than in MCF-7 and SK-BR-3 cells.}, }
@article {pmid29336321, year = {2018}, author = {Yahia, R and Zaoui, C and Derbale, W and Boudi, H and Chebloune, Y and Sahraoui, T and Elkebir, FZ}, title = {[Epstein Barr virus and invasive mammary carcinomas: EBNA, EBERs and molecular profile in a population of West Algeria].}, journal = {Annales de biologie clinique}, volume = {76}, number = {1}, pages = {75-80}, doi = {10.1684/abc.2017.1312}, pmid = {29336321}, issn = {1950-6112}, mesh = {Adult ; Algeria/epidemiology ; Breast Neoplasms/complications/epidemiology/genetics/*virology ; Carcinoma, Ductal, Breast/complications/epidemiology/genetics/*virology ; Enzyme-Linked Immunosorbent Assay ; Epstein-Barr Virus Infections/*diagnosis/epidemiology ; Epstein-Barr Virus Nuclear Antigens/analysis/*isolation &amp; purification/metabolism ; Female ; Herpesvirus 4, Human/genetics/*isolation &amp; purification/metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Molecular Typing/methods ; RNA, Viral/genetics/*isolation &amp; purification/metabolism ; }, abstract = {Breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr virus (EBV) is a widely studied candidate virus. The objective of this study is to determine the association of EBV infection with infiltrating ductal carcinomas (IDC). This descriptive study was carried out in the laboratory of developmental biology and differentiation, from 2012 to 2014. Of 39 cases, we determined the clinicopathological characteristics of the population. Of the 23 cases of IDC, we implemented the techniques Elisa, immunohistochemistry and in situ hybridization. To determine the serological profile, overexpression of onco-proteins EBNA-1, HER2, the mitotic index Ki67 and detection of the presence of the viral genome. The mean age is 57.40±4, SBR II predominates with 70%, pN+ (27%), RE+ (58%), RP+ (52%), HER2 (81%), Luminal A (34%), Luminal B (14%), HER2 (24%), and triple negative (28%). The serological profile of IgG VCA + in IgG EBNA-1 (87%), EBNA-1 P79 (82%) with a positive relationship between the IgG EBNA-1 and EBNA-1 P79 serology profile (p=0.001), HER2 (p=0.003) and with the molecular profile (p=0.051), EBNA-1 overexpression in (13%). The viral genome (EBER) is found in the tumors 43% representing an inverse relationship with the overexpression of Ki67 and a positive relationship with the overexpression of HER2. In our study we found an association with the presence of the EBV virus and the IDC studied.}, }
@article {pmid29327767, year = {2017}, author = {Darouich, S and El Amine El Hadj, O and Betaieb, I and Goucha, A and Dhiab, T and Rahal, K and Gamoudi, A and El May, A}, title = {Triple negative breast cancer: A clinico-epidemiological and histopronostic study of 90 cases.}, journal = {La Tunisie medicale}, volume = {95}, number = {1}, pages = {37-44}, pmid = {29327767}, issn = {0041-4131}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/*pathology/therapy ; Female ; Humans ; Incidence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/pathology/therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/diagnosis/*epidemiology/*pathology/therapy ; Tunisia/epidemiology ; }, abstract = {PURPOSE: The aim of this study was to describe the clinico-epidemiological and histopronostic characteristics of triple negative breast cancer (TNBC) and to evaluate the therapeutic results in tunisian women.<br><br>METHODS: We reported the results of a retrospective study including 90 patients treated for TNBC between Junuary 2008 and December 2009 in the Salah Azaiz Institute of Tunis.<br><br>RESULTS: TNBCoccured in 14% of diagnosed breast cancers. The mean age at diagnosis was 53.67 years. Family history of breast cancer was reported in 10% of cases.The majority of tumors were classified as T2 (41%) and associated with invasive ductal carcinoma histological type (99%) and SBR grade-II (54%). Tumor lymph node metastases were detected in 44% of patients.Among operated patients, 46% of patients underwent conservative surgery and 54% radical surgery. Chemotherapy and postoperative radiotherapy were given in97% and 80%of patients, respectively. After a median follow-up of 33.51 months, 61% of patients remained free of disease, 12% hadloco-regional recurrence, 9% had disease progression during chemotherapy and 21% developed systemic disease.<br><br>CONCLUSION: TNBC diagnosis is often made in the advanced stage and has a tendency to recur after treatment. The variable responseto chemotherapy is due to the molecular tumor heterogeneity. The development of targeted therapies is necessary to improve outcome of chemoresistant TNBC.}, }
@article {pmid29307488, year = {2018}, author = {Casasent, AK and Schalck, A and Gao, R and Sei, E and Long, A and Pangburn, W and Casasent, T and Meric-Bernstam, F and Edgerton, ME and Navin, NE}, title = {Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing.}, journal = {Cell}, volume = {172}, number = {1-2}, pages = {205-217.e12}, pmid = {29307488}, issn = {1097-4172}, support = {R01 CA169244/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Movement ; *Clonal Evolution ; Exome ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Sequence Analysis, DNA ; Single-Cell Analysis ; }, abstract = {Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections. We applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions in addition to exome sequencing. Our data reveal a direct genomic lineage between in situ and invasive tumor subpopulations and further show that most mutations and copy number aberrations evolved within the ducts prior to invasion. These results support a multiclonal invasion model, in which one or more clones escape the ducts and migrate into the adjacent tissues to establish the invasive carcinomas.}, }
@article {pmid29299933, year = {2018}, author = {Aydin, H and Guner, B and Esen Bostanci, I and Bulut, ZM and Aribas, BK and Dogan, L and Gulcelik, MA}, title = {Is there any relationship between adc values of diffusion-weighted imaging and the histopathological prognostic factors of invasive ductal carcinoma?.}, journal = {The British journal of radiology}, volume = {91}, number = {1084}, pages = {20170705}, pmid = {29299933}, issn = {1748-880X}, mesh = {Breast Neoplasms/*diagnostic imaging/*pathology/therapy ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology/therapy ; Contrast Media ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Gadolinium DTPA ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness/*diagnostic imaging/*pathology ; Neoplasm Staging ; Organometallic Compounds ; Prognosis ; Prospective Studies ; }, abstract = {OBJECTIVE: MRI is being used increasingly as a modality that can provide important information about breast cancer. Diffusion-weighted imaging (DWI) is an imaging technique from which apparent diffusion coefficient (ADC) values can be calculated in addition to obtaining important structural information which cannot be obtained from other imaging studies. We did not find any significant relationships between ADC values and prognostic factors, but did provide some explanations for conflicting results in the literature.<br><br>METHODS: The ADC results of 61&#xa0;females with invasive ductal carcinomas were evaluated. DWI was performed and ADC values were calculated from the area in which restriction of diffusion was the highest in ADC mapping. B value was 500 and region of interest (ROI) was designated between 49&#xa0;and&#xa0;100&#xa0;mm[2]. Calculations were performed automatically by the device. Tissue samples were obtained for prognostic factor evaluation. The relationships between ADC and prognostic factors were investigated. Comparisons between groups were made with one-way ANOVA and Kruskal Wallis test. Pairwise comparisons were made with Dunn's test. Analyses of categorical variables were made with Chi-square test.<br><br>RESULTS: We found a weak negative correlation between ADC and Ki-67 values (r = -0.279; p = 0.029). When we compared ADC values in regard to tumour type, we found no significant differences for tumour grade, Ki-67 positivity, estrogen receptor&#xa0;positivity, progesterone receptor&#xa0;positivity, C-erb B2, lymphovascular invasion and ductal carcinoma in situ or lobular carcinoma in situ&#xa0;component. On a side note, we found that mean ADC values decreased as tumour grade increased; however, this was not statistically significant.<br><br>CONCLUSION: The literature contains studies that report conflicting results which may be caused by differences in B values, ROI area and magnetic field strength. Multicentre studies and systematic reviews of these findings may produce crucial data for the use of DWI in breast cancer. Advances in knowledge: To determine if any significant relationship exists between DWI findings and prognostic factors of breast cancer.}, }
@article {pmid29295717, year = {2018}, author = {Böttcher, R and Kweldam, CF and Livingstone, J and Lalonde, E and Yamaguchi, TN and Huang, V and Yousif, F and Fraser, M and Bristow, RG and van der Kwast, T and Boutros, PC and Jenster, G and van Leenders, GJLH}, title = {Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {8}, pmid = {29295717}, issn = {1471-2407}, support = {03O-402//Center for Translational Molecular Medicine/International ; #RS2014-01//Movember Foundation/International ; New Investigator Award//CIHR/Canada ; New Investigator Award//Terry Fox Research Institute/International ; }, mesh = {Adenocarcinoma/*genetics/pathology ; Aged ; Biomarkers, Tumor/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; *DNA Copy Number Variations ; Follow-Up Studies ; *Genomic Instability ; Genomics/*methods ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/*genetics/pathology ; }, abstract = {BACKGROUND: Invasive cribriform and intraductal carcinoma (CR/IDC) is associated with adverse outcome of prostate cancer patients. The aim of this study was to determine the molecular aberrations associated with CR/IDC in primary prostate cancer, focusing on genomic instability and somatic copy number alterations (CNA).<br><br>METHODS: Whole-slide images of The Cancer Genome Atlas Project (TCGA, N&#xa0;=&#x2009;260) and the Canadian Prostate Cancer Genome Network (CPC-GENE, N&#xa0;=&#x2009;199) radical prostatectomy datasets were reviewed for Gleason score (GS) and presence of CR/IDC. Genomic instability was assessed by calculating the percentage of genome altered (PGA). Somatic copy number alterations (CNA) were determined using Fisher-Boschloo tests and logistic regression. Primary analysis were performed on TCGA (N&#x2009;=&#x2009;260) as discovery and CPC-GENE (N&#x2009;=&#x2009;199) as validation set.<br><br>RESULTS: CR/IDC growth was present in 80/260 (31%) TCGA and 76/199 (38%) CPC-GENE cases. Patients with CR/IDC and &#x2265; GS 7 had significantly higher PGA than men without this pattern in both TCGA (2.2 fold; p&#xa0;=&#x2009;0.0003) and CPC-GENE (1.7 fold; p&#xa0;=&#x2009;0.004) cohorts. CR/IDC growth was associated with deletions of 8p, 16q, 10q23, 13q22, 17p13, 21q22, and amplification of 8q24. CNAs comprised a total of 1299 gene deletions and 369 amplifications in the TCGA dataset, of which 474 and 328 events were independently validated, respectively. Several of the affected genes were known to be associated with aggressive prostate cancer such as loss of PTEN, CDH1, BCAR1 and gain of MYC. Point mutations in TP53, SPOP and FOXA1were also associated with CR/IDC, but occurred less frequently than CNAs.<br><br>CONCLUSIONS: CR/IDC growth is associated with increased genomic instability clustering to genetic regions involved in aggressive prostate cancer. Therefore, CR/IDC is a pathologic substrate for progressive molecular tumour derangement.}, }
@article {pmid29290072, year = {2018}, author = {Kalisya, LM and Bake, JF and Bigabwa, R and Rothstein, DH and Cairo, SB}, title = {Operations for Suspected Neoplasms in a Resource-Limited Setting: Experience and Challenges in the Eastern Democratic of Congo.}, journal = {World journal of surgery}, volume = {42}, number = {7}, pages = {1913-1918}, pmid = {29290072}, issn = {1432-2323}, mesh = {Adult ; Child ; Democratic Republic of the Congo ; Female ; *Health Resources ; Humans ; Male ; Middle Aged ; Neoplasms/*surgery ; Retrospective Studies ; }, abstract = {INTRODUCTION: Surgery is an essential component of a functional health system, with surgical conditions accounting for nearly 11-15% of world disability. While communicable diseases continue to burden low- and low-middle-income countries, non-communicable diseases, such as cancer, are an important cause of morbidity and mortality worldwide. Preliminary data on malignancies in low- and middle-income countries, specifically in Africa, suggest a higher mortality compared to other regions of the world, a difference partially explained by limited availability of screening and early detection systems as well as poorer access to treatment.<br><br>OBJECTIVE: To evaluate the diagnosed tumor burden in the Eastern Democratic Republic of Congo (DRC) and review literature on existing and suspected barriers to accessing appropriate oncologic care.<br><br>METHODS: This is a retrospective study carried out at Healthcare, Education, community Action, and Leadership development Africa, a 197-bed tertiary referral hospital, in the Province of North Kivu, along the eastern border of the DRC from 2012 to 2015. Patient charts were reviewed for diagnoses of presumed malignancy with biopsy results.<br><br>RESULTS: A total of 252 cases of suspected cancer were reviewed during the study period; 39.7% were men. The average age of patients was 43&#xa0;years. Amongst adult patients, the most common presenting condition involved breast lesions with 5.8% diagnosis of fibrocystic breast changes and 2.9% invasive ductal carcinoma of the breast. 37.3% of female patients had lesions involving the cervix or uterus. The most common diagnosis amongst male adults was prostate disease (16.7% of men). For pediatric patients, the most common diagnoses involved bone and/or cartilage (27.3%) followed by skin and soft tissue lesions (20.0%). All patients underwent surgical resection of lesions; some patients were advised to travel out of country for chemotherapy and radiation for which follow-up data are unavailable.<br><br>CONCLUSION: Adequate and timely treatment of malignancy in the DRC faces a multitude of challenges. Access to surgical services for diagnosis and management as well as chemotherapeutic agents is prohibitively limited. Increased collaboration with local clinicians and remote specialist consultants is needed to deliver subspecialty care in resource-poor settings.}, }
@article {pmid29286468, year = {2017}, author = {Hidmark, AS and Nawroth, PP and Fleming, T}, title = {Analysis of Immune Cells in Single Sciatic Nerves and Dorsal Root Ganglion from a Single Mouse Using Flow Cytometry.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {130}, pages = {}, pmid = {29286468}, issn = {1940-087X}, mesh = {Animals ; Flow Cytometry/*methods ; Ganglia, Spinal/*cytology/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Regeneration/*physiology ; Sciatic Nerve/*cytology/*immunology ; }, abstract = {Nerve-resident immune cells in the peripheral nervous system (PNS) are essential to maintaining neuronal integrity in a healthy nerve. The immune cells of the PNS are affected by injury and disease, affecting the nerve function and the capacity for regeneration. Neuronal immune cells are commonly analyzed by immunofluorescence (IF). While IF is essential for determining the location of the immune cells in the nerve, IF is only semi-quantitative and the method is limited to the number of markers that can be analyzed simultaneously and the degree of surface expression. In this study, flow cytometry was used for quantitative analysis of leukocyte infiltration into sciatic nerves or dorsal root ganglions (DRGs) of individual mice. Single cell analysis was performed using DAPI and several proteins were analyzed simultaneously for either surface or intracellular expression. Both sciatic nerves from one mouse that were treated according to this protocol generated ≥ 30,000 single nucleated events. The proportion of leukocytes in the sciatic nerves, determined by expression of CD45, was approximately 5% of total cell content in the sciatic nerve and approximately 5-10% in the DRG. Although this protocol focuses primarily on the immune cell population within the PNS, the flexibility of flow cytometry to measure a number of markers simultaneously means that the other cells populations present within the nerve, such as Schwann cells, pericytes, fibroblasts, and endothelial cells, can also be analyzed using this method. This method therefore provides a new means for studying systemic effects on the PNS, such as neurotoxicology and genetic models of neuropathy or in chronic diseases, such as diabetes.}, }
@article {pmid29281999, year = {2017}, author = {Mercogliano, MF and Inurrigarro, G and De Martino, M and Venturutti, L and Rivas, MA and Cordo-Russo, R and Proietti, CJ and Fernández, EA and Frahm, I and Barchuk, S and Allemand, DH and Figurelli, S and Deza, EG and Ares, S and Gercovich, FG and Cortese, E and Amasino, M and Guzmán, P and Roa, JC and Elizalde, PV and Schillaci, R}, title = {Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {895}, pmid = {29281999}, issn = {1471-2407}, support = {IDB/PICT 2012-382//Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/International ; PID 2012-066//Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/International ; IDB/PICT 2012-668//Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/International ; IDB/PICT 2012 1017//Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/International ; #20//Instituto Nacional del C&#xe1;ncer (AR)/International ; 1819/03//Consejo Nacional de Investigaciones Cient&#xed;ficas y T&#xe9;cnicas (AR)/International ; PIP 2012 059//Consejo Nacional de Investigaciones Cient&#xed;ficas y T&#xe9;cnicas/International ; BOD/2016//Universidad Cat&#xf3;lica de C&#xf3;rdoba/International ; }, mesh = {Adult ; Aged ; Antineoplastic Agents, Immunological ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*mortality/pathology ; Carcinoma, Papillary/drug therapy/metabolism/*mortality/pathology ; Case-Control Studies ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Mucin-4/*metabolism ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/antagonists &amp; inhibitors/immunology/*metabolism ; Retrospective Studies ; Survival Rate ; Trastuzumab/*pharmacology ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC.<br><br>METHODS: We retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry.<br><br>RESULTS: IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression and tumor size and inversely correlated with patient's age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio&#x2009;=&#x2009;2.6; 95%, confidence interval 1.1-6.1, P&#x2009;=&#x2009;0.0340). MUC4, a glycoprotein associated with metastasis, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma.<br><br>CONCLUSION: In HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently monitored and/or receive additional therapies.}, }
@article {pmid29281012, year = {2018}, author = {Perdijk, O and van Neerven, RJJ and Meijer, B and Savelkoul, HFJ and Brugman, S}, title = {Induction of human tolerogenic dendritic cells by 3'-sialyllactose via TLR4 is explained by LPS contamination.}, journal = {Glycobiology}, volume = {28}, number = {3}, pages = {126-130}, pmid = {29281012}, issn = {1460-2423}, mesh = {Animals ; Dendritic Cells/drug effects/*immunology ; Humans ; Immune Tolerance/drug effects/*immunology ; Lipopolysaccharides/*analysis/*immunology ; Milk, Human/chemistry ; NF-kappa B/metabolism ; Oligosaccharides/*immunology/pharmacology ; Toll-Like Receptor 4/immunology/*metabolism ; }, abstract = {The human milk oligosaccharide 3'-sialyllactose (3'SL) has previously been shown to activate murine dendritic cells (DC) in a Toll-like receptor (TLR) 4-mediated manner ex vivo. In this study we aimed to investigate whether 3'SL has similar immunomodulatory properties on human DC. 3'SL was shown to induce NF-κB activation via human TLR4. However, LPS was detected in the commercially obtained 3'SL from different suppliers. After the removal of LPS from 3'SL, we studied its ability to modify DC differentiation in vitro. In contrast to LPS and 3'SL, LPS-free 3'SL did not induce functional and phenotypical changes on immature DC (iDC). iDC that were differentiated in the presence of LPS or 3'SL showed a semi-mature phenotype (i.e., fewer CD83+CD86+ DC), produced IL-10 and abrogated IL-12p70 and tumor necrosis factor-alpha levels upon stimulation with several TLR ligands. Differentiation into these tolerogenic DC was completely abrogated by LPS removal from 3'SL. In contrast to previous reports in mice, we found that LPS-free 3'SL does not activate NF-κB via human TLR4. In conclusion, removing LPS from (oligo)saccharide preparations is necessary to study their potential immunomodulatory function.}, }
@article {pmid29276992, year = {2018}, author = {Levav, I and Klomek, AB}, title = {A review of epidemiologic studies on suicide before, during, and after the Holocaust.}, journal = {Psychiatry research}, volume = {261}, number = {}, pages = {35-39}, doi = {10.1016/j.psychres.2017.12.042}, pmid = {29276992}, issn = {1872-7123}, mesh = {Austria/epidemiology ; Concentration Camps/trends ; Epidemiologic Studies ; Germany/epidemiology ; Holocaust/*psychology/trends ; Humans ; Israel/epidemiology ; Jews/*psychology ; Suicide/*psychology/trends ; Survivors/psychology ; *World War II ; }, abstract = {The available literature on the risk of suicides related to the Holocaust (1939-1945) and its aftermath differs in its time periods, in the countries investigated, and in the robustness of its sources. Reliable information seems to indicate that the risk of suicide for Jews in Nazi Germany and Austria during the pre-war period (1933-1939) was elevated, while information on suicide during the internment in the concentration camps is fraught with problems. The latter derives from the Nazis' decision to hide the statistics on the inmates' causes of death, and from the prevailing life conditions that impeded separation between self-inflicted death and murder. Reliable studies conducted in Israel among refugees who entered pre-state Israel, 1939-1945, and post-World War II survivors reaching Israel (1948 on), show a mixed picture: suicide rates among the former were higher than comparison groups, while the latter group shows evidence of resilience.}, }
@article {pmid29275106, year = {2018}, author = {Inoue, Y and Yamashita, N and Kitao, H and Tanaka, K and Saeki, H and Oki, E and Oda, Y and Tokunaga, E and Maehara, Y}, title = {Clinical Significance of the Wild Type p53-Induced Phosphatase 1 Expression in Invasive Breast Cancer.}, journal = {Clinical breast cancer}, volume = {18}, number = {4}, pages = {e643-e650}, doi = {10.1016/j.clbc.2017.11.008}, pmid = {29275106}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Copy Number Variations ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Mutation ; Neoplasm Staging ; Prognosis ; Protein Phosphatase 2C/genetics/*metabolism ; Tumor Suppressor Protein p53/genetics ; }, abstract = {BACKGROUND: Wild type p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase magnesium dependent 1 delta (PPM1D), inhibits p53. PPM1D amplification has been reported in breast cancer. Breast cancer can sometimes develop without a tumor protein 53 (TP53) mutation. In these cases, the p53 pathway might be disrupted by alternative mechanisms, and Wip1 is reported to be a key molecule involved.<br><br>MATERIALS AND METHODS: Primary invasive ductal carcinoma specimens were obtained from 201 cases, for which archival tissue samples for immunohistochemistry were available. We evaluated Wip1 and p21 protein expression (201 cases), Wip1 mRNA expression (63 cases), PPM1D DNA copy number (71 cases) and TP53 status (36 cases) using available samples among the 201 cases, and analyzed their relationships with clinicopathological factors and prognosis.<br><br>RESULTS: The nuclear expression of Wip1 protein was positive in 21 cases (10.4%). The PPM1D DNA copy number was significantly correlated with Wip1 protein expression. All cases with PPM1D amplification by single-nucleotide polymorphism comparative genomic hybridization array showed positive nuclear Wip1 expression. Wip1 protein expression was positively correlated with p21 expression. The tumors with positive Wip1 and negative p21 expression showed the poorest prognosis among all tumor types.<br><br>CONCLUSION: The protein expression of Wip1 might be regulated by PPM1D amplification, independent of TP53 status. Positive Wip1 and negative p21 expression was associated with the poorest prognosis and suggests the loss of p53 function.}, }
@article {pmid29262562, year = {2017}, author = {Li, J and Sun, L and Xu, F and Xiao, J and Jiao, W and Qi, H and Shen, C and Shen, A}, title = {Characterization of plasma proteins in children of different Mycobacterium tuberculosis infection status using label-free quantitative proteomics.}, journal = {Oncotarget}, volume = {8}, number = {61}, pages = {103290-103301}, pmid = {29262562}, issn = {1949-2553}, abstract = {Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an infectious disease found worldwide. Children infected with MTB are more likely to progress to active TB (ATB); however, the molecular mechanism behind this process has long been a mystery. We employed the label-free quantitative proteomic technology to identify and characterize differences in plasma proteins between ATB and latent TB infection (LTBI) in children. To detect differences that are indicative of MTB infection, we first selected proteins whose expressions were markedly different between the ATB and LTBI groups and the control groups (inflammatory disease control (IDC) and healthy control (HC) groups). A total of 521 proteins differed (> 1.5-fold or < 0.6-fold) in the LTBI group, and 318 proteins in the ATB group when compared with the control groups. Of these, 49 overlapping proteins were differentially expressed between LTBI and ATB. Gene Ontology (GO) analysis revealed most proteins had a cellular and organelle distribution. The MTB infection status was mainly related to differences in binding, cellular and metabolic processes. XRCC4, PCF11, SEMA4A and ATP11A were selected and further verified by qPCR and western blot. At the mRNA level, the expression of XRCC4, PCF11and SEMA4A presented an increased trend in ATB group compare with LTBI. At the protein level, the expression of all these proteins by western blot in ATB/LTBI was consistent with the trends from proteomic detection. Our results provide important data for future mechanism studies and biomarker selection for MTB infection in children.}, }
@article {pmid29249796, year = {2017}, author = {Farran, Y and Padilla, O and Chambers, K and Philipovskiy, A and Nahleh, Z}, title = {Atypical Presentation of Radiation-Associated Breast Angiosarcoma: A Case Report and Review of Literature.}, journal = {The American journal of case reports}, volume = {18}, number = {}, pages = {1347-1350}, pmid = {29249796}, issn = {1941-5923}, mesh = {Aged ; Breast Neoplasms/*etiology/pathology/radiotherapy ; Carcinoma, Ductal, Breast/radiotherapy ; Female ; Hemangiosarcoma/*etiology/pathology ; Humans ; *Neoplasms, Radiation-Induced ; Pigmentation Disorders/*etiology/pathology ; Radiotherapy, Adjuvant/*adverse effects ; }, abstract = {BACKGROUND Radiation-associated breast angiosarcoma is a rare clinical entity that is thought to be increasing in incidence. CASE REPORT Here we present the case of a 67-year-old female with a history of left breast invasive ductal carcinoma who received breast conserving surgery and radiation therapy eight years ago. She then presented with a painless mild skin discoloration of the left breast that had been present for over one year. Mammograms and ultrasounds were normal. A punch biopsy and a subsequent excisional biopsy revealed the diagnosis of angiosarcoma. The patient was treated with mastectomy and had no subsequent recurrences. CONCLUSIONS The long-term clinical surveillance for all patients who receive breast conservation surgery is recommended and a high degree of suspicion should be exercised in view of potential atypical presentations of this disease.}, }
@article {pmid29246496, year = {2018}, author = {Hannafon, BN and Ding, WQ}, title = {miRNAs as Biomarkers for Predicting the Progression of Ductal Carcinoma in Situ.}, journal = {The American journal of pathology}, volume = {188}, number = {3}, pages = {542-549}, pmid = {29246496}, issn = {1525-2191}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Humans ; MicroRNAs/genetics/*metabolism ; }, abstract = {Ductal carcinoma in situ (DCIS) is defined as a proliferation of neoplastic cells within the duct of the mammary gland that have not invaded into the surrounding stroma. DCIS is considered a precursor to invasive ductal carcinoma (IDC); however, approximately half of DCIS may progress to IDC, if left untreated. Current research has shown that the genomic and transcriptomic changes are present in DCIS before the emergence of invasive disease, indicating that the malignant nature of the DCIS is defined before invasion. However, important questions remain surrounding the specific changes and processes required for malignant progression and identification of prognostic indicators of aggressiveness. miRNAs are small regulatory RNAs that can modulate gene expression by complementary binding to target mRNAs and inducing translational repression and/or mRNA degradation. In the past decade, research has shown that miRNA expression is dysregulated in IDC and that these changes are already present at the DCIS stage. Therefore, changes in miRNA expression may provide the necessary information to identify a clinical indicator of the aggressiveness of DCIS. Herein, we review the miRNA signatures identified in DCIS, describe how these signatures may be used to predict the aggressiveness of DCIS, and discuss future perspectives for DCIS biomarker discovery.}, }
@article {pmid29230302, year = {2017}, author = {Gharia, B and Seegobin, K and Maharaj, S and Marji, N and Deutch, A and Zuberi, L}, title = {Letrozole-induced hepatitis with autoimmune features: a rare adverse drug reaction with review of the relevant literature.}, journal = {Oxford medical case reports}, volume = {2017}, number = {11}, pages = {omx074}, pmid = {29230302}, issn = {2053-8855}, abstract = {While aromatase inhibitors (AIs) have been known to cause minor elevations in liver enzymes, severe hepatotoxicity is rare. To the best of our knowledge, this is the first reported case of Letrozole-induced hepatitis with autoimmune features. A 70-year-old female with estrogen positive, invasive ductal carcinoma of the breast, presented with jaundice 3 months after starting letrozole. Hepatic transaminases were markedly elevated and her ANA and anti-smooth muscle antibody was positive. Liver biopsy featured drug-induced hepatitis. After stopping letrozole, liver tests trended back to normal within 3 weeks. She scored 9 for Roussel-Uclaf Causality Assessment Method (RUCAM). Over the last 10 years, there have been reported cases of drug-induced hepatitis secondary to AIs. We anticipate that there will be more widespread use of AIs based on recommendations from the TEXT, SOFT and extended AI trials. Therefore, physicians must be aware of this rare but life-threatening complication.}, }
@article {pmid29227474, year = {2018}, author = {Lehmann, LH and Jebessa, ZH and Kreusser, MM and Horsch, A and He, T and Kronlage, M and Dewenter, M and Sramek, V and Oehl, U and Krebs-Haupenthal, J and von der Lieth, AH and Schmidt, A and Sun, Q and Ritterhoff, J and Finke, D and Völkers, M and Jungmann, A and Sauer, SW and Thiel, C and Nickel, A and Kohlhaas, M and Schäfer, M and Sticht, C and Maack, C and Gretz, N and Wagner, M and El-Armouche, A and Maier, LS and Londoño, JEC and Meder, B and Freichel, M and Gröne, HJ and Most, P and Müller, OJ and Herzig, S and Furlong, EEM and Katus, HA and Backs, J}, title = {A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway.}, journal = {Nature medicine}, volume = {24}, number = {1}, pages = {62-72}, pmid = {29227474}, issn = {1546-170X}, mesh = {Animals ; Epigenesis, Genetic ; Gene Transfer Techniques ; Heart Failure/genetics/*metabolism ; Hexosamines/*biosynthesis ; Histone Deacetylases/genetics/*metabolism ; Mice ; Mice, Knockout ; *Myocardial Contraction ; Myocardium/enzymology ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/metabolism ; Physical Conditioning, Animal ; Proteolysis ; Stromal Interaction Molecule 1/metabolism ; }, abstract = {The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure.}, }
@article {pmid29217299, year = {2018}, author = {Zahorchak, AF and Macedo, C and Hamm, DE and Butterfield, LH and Metes, DM and Thomson, AW}, title = {High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.}, journal = {Cellular immunology}, volume = {323}, number = {}, pages = {9-18}, pmid = {29217299}, issn = {1090-2163}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; R34 AI123033/AI/NIAID NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; }, mesh = {B7-2 Antigen/*immunology ; B7-H1 Antigen/*immunology ; Cell Differentiation/immunology ; Dendritic Cells/cytology/*immunology ; Humans ; Interleukin-10/immunology ; Lymphocyte Activation ; Monocytes/immunology ; Organ Transplantation/methods ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology ; }, abstract = {Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naïve and memory allogeneic CD4[+] and CD8[+] T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8[+] T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway.}, }
@article {pmid29215790, year = {2018}, author = {Carrascal, MA and Silva, M and Ramalho, JS and Pen, C and Martins, M and Pascoal, C and Amaral, C and Serrano, I and Oliveira, MJ and Sackstein, R and Videira, PA}, title = {Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation.}, journal = {Molecular oncology}, volume = {12}, number = {5}, pages = {579-593}, pmid = {29215790}, issn = {1878-0261}, support = {P01 HL107146/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; E-Selectin/genetics/*metabolism ; Female ; Fucose/analogs &amp; derivatives/pharmacology ; Fucosyltransferases/*antagonists &amp; inhibitors ; Humans ; Ligands ; MAP Kinase Signaling System/drug effects ; Middle Aged ; Neoplasm Invasiveness ; Oligosaccharides/*metabolism ; Primary Cell Culture ; Sialyl Lewis X Antigen ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism ; }, abstract = {Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLe[X][/A]), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLe[X][/A] , to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E-selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E-selectin and anti-sLe[X][/A] antibodies in both IDC tissue and cell lines, and expression of α-1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the 'CF1_T cell line'. Treatment with 2-fluorofucose (2-FF), a fucosylation inhibitor, completely abrogated its sLe[X][/A] expression and dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal-regulating protein kinases 1 and 2 and p38 mitogen-activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.}, }
@article {pmid29211399, year = {2018}, author = {Arribillaga, LC and Ledesma, M and Montedoro, A and Pisano, F and Bengió, RG}, title = {OAB score: a clinical model that predicts the probability of presenting overactive detrusor in the urodynamic study.}, journal = {International braz j urol : official journal of the Brazilian Society of Urology}, volume = {44}, number = {2}, pages = {348-354}, pmid = {29211399}, issn = {1677-6119}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Urinary Bladder, Overactive/*diagnosis/physiopathology ; Urodynamics/*physiology ; }, abstract = {PURPOSE: To create a predictive model of involuntary detrusor contraction (IDC) to improve the diagnostic accuracy of overactive detrusor (OAD), associating overactive bladder (OAB) symptoms with other clinical parameters in the female population.<br><br>MATERIALS AND METHODS: A total of 727 women were studied retrospectively. In all of them, urodynamic study was conducted for urogynecological causes. Demographics information, personal history, symptoms, physical exam, a 3-day frequency/volume chart and urinary culture, were collected in all patients and they subsequently underwent uroflowmetry and urodynamic studies. A logistic regression model was performed in order to determine independent predictors of presence of IDC. Odd ratio (OR) estimation was used to assign a score to each one of the significant variables (p&#x2264;0.05) in the logistic regression model. We performed a ROC curve in order to determine the predictive ability of the score in relation to the presence of OAD.<br><br>RESULTS: presence of OAD was evident in 210 women (29%). In the logistic regression analysis, independent predictors of OAD were urgency, urgency incontinence, nocturia, absence of SUI symptoms, diabetes mellitus, reduction of vaginal trophism and bladder capacity below 150 mL. The probability of IDC diagnosis increases as the score raises (Score 0: 4% until Score &#x2265;10: 88%). Sensitivity was 71% and specificity 72%. The area under the curve of OAB score was 0.784 (p>0.001).<br><br>CONCLUSIONS: OAB score is a clinical tool that shows higher diagnostic accuracy than OAB symptoms alone to predict overactive detrusor.}, }
@article {pmid29209551, year = {2017}, author = {Yetkin, G and Celayir, F and Akgun, IE and Ucak, R}, title = {Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma.}, journal = {Case reports in surgery}, volume = {2017}, number = {}, pages = {7048149}, pmid = {29209551}, issn = {2090-6900}, abstract = {A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.}, }
@article {pmid29206714, year = {2018}, author = {Khanlari, M and Schally, AV and Block, NL and Nadji, M}, title = {Expression of GHRH-R, a Potentially Targetable Biomarker, in Triple-negative Breast Cancer.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {26}, number = {1}, pages = {1-5}, doi = {10.1097/PAI.0000000000000622}, pmid = {29206714}, issn = {1533-4058}, mesh = {Biomarkers, Tumor/*genetics ; *Drug Delivery Systems ; Female ; Humans ; Receptors, Neuropeptide/*genetics/metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/*genetics/metabolism ; Triple Negative Breast Neoplasms/*diagnosis/*genetics ; }, abstract = {PURPOSE: Growth hormone-releasing hormone (GHRH) has been shown to modify the growth behavior of many cancers, including breast. GHRH is produced by tumor cells, acts in an autocrine/paracrine manner, and requires the presence of GHRH receptor (GHRH-R) on the tumor cells to exert its effects. GHRH activity can be effectively blocked by synthetic antagonists of its receptor and hence, the expression of GHRH-R by tumor cells could serve as a predictor of response to GHRH-R antagonist therapy. In this study, we investigated the expression of GHRH-R in triple-negative breast cancers (TNBC). As TNBCs are morphologically and immunophenotypically heterogenous, the staining results were also correlated with the histologic subtypes of these tumors.<br><br>MATERIALS AND METHODS: On the basis of histomorphology and immunophenotype, 134 cases of primary TNBCs were further subdivided into medullary, metaplastic, apocrine, and invasive ductal carcinomas of no special type (IDC-NST). Immunohistochemistry for GHRH-R was performed on paraffin sections and the staining results were assessed semiquantitatively as negative, low expression, moderate, and high expression.<br><br>RESULTS: Of the 134 TNBCs, 85 were classified as IDC-NST, 25 as metaplastic, 16 as medullary, and 8 as apocrine carcinoma. Overall, positive reaction for GHRH-R was seen in 77 (57%) of tumors including 66 (77.6%) of IDC-NST. All medullary carcinomas were negative for GHRH-R and, with the exception of 1 case with low expression, none of the metaplastic carcinomas expressed GHRH-R (P<0.005).<br><br>CONCLUSIONS: A considerable number of TNBCs are positive for GHRH-R as a predictor of potential response to anti-GHRH-R treatment. This expression however, varies considerably between histologic subtypes of triple-negative breast cancers. Although most medullary and metaplastic carcinomas do not express GHRH-R, three fourths of the IDC-NST show a positive reaction. Testing for GHRH-R expression is therefore advisable if anti-GHRH-R therapy is being considered.}, }
@article {pmid29195137, year = {2018}, author = {Rezende, F and Moll, F and Walter, M and Helfinger, V and Hahner, F and Janetzko, P and Ringel, C and Weigert, A and Fleming, I and Weissmann, N and Kuenne, C and Looso, M and Rieger, MA and Nawroth, P and Fleming, T and Brandes, RP and Schröder, K}, title = {The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.}, journal = {Redox biology}, volume = {15}, number = {}, pages = {12-21}, pmid = {29195137}, issn = {2213-2317}, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Aorta/metabolism/pathology ; Diabetes Mellitus, Experimental/*genetics/metabolism/pathology ; Endothelial Cells/metabolism ; Gene Expression ; Humans ; Lymphocytes/metabolism/pathology ; Mice ; Mice, Knockout ; NADP/metabolism ; NADPH Oxidases/*genetics/metabolism ; Protein Binding ; Proteins/*genetics ; Reactive Oxygen Species/metabolism ; }, abstract = {AIM: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.<br><br>RESULTS: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.<br><br>INNOVATION AND CONCLUSION: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.}, }
@article {pmid29189723, year = {2017}, author = {Giroud, M and Scheideler, M}, title = {Long Non-Coding RNAs in Metabolic Organs and Energy Homeostasis.}, journal = {International journal of molecular sciences}, volume = {18}, number = {12}, pages = {}, pmid = {29189723}, issn = {1422-0067}, mesh = {Adipose Tissue/metabolism ; Animals ; Energy Metabolism/genetics/physiology ; Gene Expression Regulation ; Homeostasis ; Humans ; Muscle, Skeletal/metabolism ; Pancreas/metabolism ; RNA, Long Noncoding/genetics/*metabolism ; }, abstract = {Single cell organisms can surprisingly exceed the number of human protein-coding genes, which are thus not at the origin of the complexity of an organism. In contrast, the relative amount of non-protein-coding sequences increases consistently with organismal complexity. Moreover, the mammalian transcriptome predominantly comprises non-(protein)-coding RNAs (ncRNA), of which the long ncRNAs (lncRNAs) constitute the most abundant part. lncRNAs are highly species- and tissue-specific with very versatile modes of action in accordance with their binding to a large spectrum of molecules and their diverse localization. lncRNAs are transcriptional regulators adding an additional regulatory layer in biological processes and pathophysiological conditions. Here, we review lncRNAs affecting metabolic organs with a focus on the liver, pancreas, skeletal muscle, cardiac muscle, brain, and adipose organ. In addition, we will discuss the impact of lncRNAs on metabolic diseases such as obesity and diabetes. In contrast to the substantial number of lncRNA loci in the human genome, the functionally characterized lncRNAs are just the tip of the iceberg. So far, our knowledge concerning lncRNAs in energy homeostasis is still in its infancy, meaning that the rest of the iceberg is a treasure chest yet to be discovered.}, }
@article {pmid29174251, year = {2017}, author = {Dalal, J and Katekhaye, V and Jain, R}, title = {Effect of ferric carboxymaltose on hospitalization and mortality outcomes in chronic heart failure: A meta-analysis.}, journal = {Indian heart journal}, volume = {69}, number = {6}, pages = {736-741}, pmid = {29174251}, issn = {2213-3763}, mesh = {*Anemia, Iron-Deficiency/drug therapy/etiology/mortality ; Ferric Compounds/*administration &amp; dosage ; Global Health ; *Heart Failure/complications/mortality/therapy ; Hospitalization/*trends ; Humans ; Infusions, Intravenous ; Maltose/administration &amp; dosage/*analogs &amp; derivatives ; Prospective Studies ; *Quality of Life ; }, abstract = {INTRODUCTION: Iron administration especially intravenous iron therapy is associated with improvements in exercise capacity and quality of life in patients with chronic heart failure (CHF). Our aim was to assess effect of ferric carboxymaltose (FCM) on hospitalization and mortality outcomes in CHF.<br><br>MATERIALS AND METHODS: A literature search across PUBMED, Google Scholar and trials database www.clinicaltrials.gov was conducted to search for randomized controlled trials (till August 2016) comparing FCM to placebo in CHF with or without anaemia. Published human studies in English language which reported data on mortality and hospitalization rates were included. Primary outcome was rates of HF hospitalizations and secondary outcomes were hospitalization due to any cardiovascular (CV) cause, death due to worsening HF and any CV death.<br><br>RESULTS: From 17 studies identified, two were included in final analysis (n=760; 455 in FCM and 305 in placebo arms). We observed significantly lower rates of hospitalization for worsening HF in FCM arm [Risk Ratio (RR) 0.34, 95% confidence interval (CI) 0.19, 0.59, p=0.0001] as well as for any CV hospitalizations [RR 0.49, 95% CI 0.35, 0.70; p<0.0001] (figure). No heterogeneity in studies was seen for these two outcomes (I[2]=0%, p>0.05). No significant treatment effect with FCM was noted in mortality from worsening HF (RR 0.41, 95% CI 0.02, 7.36; p=0.55) or any CV death (RR 0.80, 95% CI 0.40, 1.57; p=0.51).<br><br>CONCLUSION: FCM reduces hospitalization rates in CHF but may not reduce mortality outcome. This finding needs further evaluation in a large, prospective, randomized controlled trial.}, }
@article {pmid29172216, year = {2018}, author = {Deprez, PH and Garces Duran, R and Moreels, T and Furneri, G and Demma, F and Verbeke, L and Van der Merwe, SW and Laleman, W}, title = {The economic impact of using single-operator cholangioscopy for the treatment of difficult bile duct stones and diagnosis of indeterminate bile duct strictures.}, journal = {Endoscopy}, volume = {50}, number = {2}, pages = {109-118}, doi = {10.1055/s-0043-121268}, pmid = {29172216}, issn = {1438-8812}, mesh = {Adult ; Aged ; Cholangiopancreatography, Endoscopic Retrograde/*economics/methods ; Cholestasis/diagnosis/etiology/*surgery ; Cost-Benefit Analysis ; Female ; Follow-Up Studies ; Gallstones/complications/diagnosis/*surgery ; Humans ; Male ; Middle Aged ; *Models, Economic ; Retrospective Studies ; Severity of Illness Index ; }, abstract = {BACKGROUND AND STUDY AIM: Conventional endoscopic retrograde cholangiopancreatography (ERCP) combines endoscopy and radiography to diagnose and treat pathological conditions of the bile duct. The aim of the present analysis was to evaluate the clinical and economic impact of the use of single-operator intraductal cholangioscopy (IDC), which allows for direct visualization of the bile duct, as an alternative to ERCP for the treatment of difficult bile duct stones and the diagnosis of bile duct strictures.<br><br>PATIENTS AND METHODS: The clinical and economic consequences of single-operator IDC use were evaluated using two decision-tree models, one for management of difficult-to-remove stones and one for stricture diagnosis. A hospital perspective was adopted. Data to populate the models were derived from two Belgian hospitals that specialize in endoscopic procedures of the bile duct. Overall, the examined population consisted of 62 patients with difficult stones and 49 patients with indeterminate strictures.<br><br>RESULTS: In the model for difficult stone management, the use of IDC determined a decrease in the number of procedures (-&#x200a;27&#x200a;% relative reduction) and costs (-&#x200a;&#x20ac;73&#x2005;000;&#x200a;-&#x200a;11&#x200a;% relative reduction) when compared with ERCP. In the model for stricture diagnosis, the use of IDC determined a decrease in the number of procedures (-&#x200a;31&#x200a;% relative reduction) and costs (-&#x200a;&#x20ac;13&#x2005;000;&#x200a;-&#x200a;5&#x200a;% relative variation) when compared with ERCP.<br><br>CONCLUSIONS: The single-operator IDC system performed better than ERCP for the treatment of difficult bile duct stones and the diagnosis of bile duct strictures, and reduced the overall expenditure in hospitals in Belgium.}, }
@article {pmid29164828, year = {2019}, author = {Koren, D and Rothschild-Yakar, L and Lacoua, L and Brunstein-Klomek, A and Zelezniak, A and Parnas, J and Shahar, G}, title = {Attenuated psychosis and basic self-disturbance as risk factors for depression and suicidal ideation/behaviour in community-dwelling adolescents.}, journal = {Early intervention in psychiatry}, volume = {13}, number = {3}, pages = {532-538}, doi = {10.1111/eip.12516}, pmid = {29164828}, issn = {1751-7893}, support = {//University of Haifa/International ; //Israel Science Foundation/International ; }, mesh = {Adolescent ; Depressive Disorder/*diagnosis/psychology ; Depressive Disorder, Major/diagnosis/psychology ; *Ego ; Female ; Humans ; Independent Living/psychology ; Male ; Pilot Projects ; Prodromal Symptoms ; Psychotic Disorders/*diagnosis/psychology ; Risk Factors ; Self-Injurious Behavior/diagnosis/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND AND AIMS: Adolescents at clinical high risk (CHR) for psychosis, as defined by the presence of attenuated psychosis symptoms (APS), exhibit increased levels of suicidal ideation and behaviour. However, no research thus far has examined the link between basic self-disturbances (SDs), an established marker for CHR, and suicidality/self-harm in this population. The goal of this pilot study was to assess the association between SD, depression and suicidal ideation and behaviour among non-help-seeking adolescents from the community.<br><br>METHOD: A total of 100 community-dwelling adolescents (age range: 13-16) were assessed using the Examination of Anomalous Self-experience, Prodromal Questionnaire, Structured Interview for Prodromal Syndromes, Mood and Anxiety Symptom Questionnaire and the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The K-SADS was used to derive a binary diagnosis of unipolar depression, as well as to measure suicidal ideation and behaviour and self-harm.<br><br>RESULTS: In a multiple regression analysis, SD accounted for variance in depressive symptoms and suicidality/self-harm over and above that accounted for by APS. Moreover, SD accounted for variance in suicidality/self-harm over and above that accounted for by depression symptoms.<br><br>CONCLUSIONS: These pilot results suggest that SD might be a unique dimension of vulnerability to depression and suicidality/self-harm in adolescence. Also, they encourage assessment of SD as part of a suicide risk assessment, particularly in the context of risk for subsequent psychosis.}, }
@article {pmid29155474, year = {2018}, author = {Gilboa, Y and Frenkel, TI and Schlesinger, Y and Rousseau, S and Hamiel, D and Achiron, R and Perlman, S}, title = {Visual biofeedback using transperineal ultrasound in second stage of labor.}, journal = {Ultrasound in obstetrics &amp; gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology}, volume = {52}, number = {1}, pages = {91-96}, doi = {10.1002/uog.18962}, pmid = {29155474}, issn = {1469-0705}, mesh = {Adult ; *Biofeedback, Psychology ; Delivery, Obstetric/*methods ; Female ; Head/*diagnostic imaging/embryology ; Humans ; Infant, Newborn ; Labor Stage, Second/*physiology ; Perineum/*diagnostic imaging ; Pregnancy ; Pregnancy Outcome ; Prospective Studies ; Self Report ; *Ultrasonography/methods ; }, abstract = {OBJECTIVE: To assess the obstetric and psychological effects of visual biofeedback by transperineal ultrasound (TPU) during the second stage of labor.<br><br>METHODS: This was a prospective, single-center observational study of low-risk nulliparous women with epidural analgesia undergoing vaginal delivery. Visual biofeedback using TPU was provided to 26 women during the second stage of labor. Pushing efficacy was assessed by the change in the angle of progression (AoP) at rest and during pushing efforts, before and after biofeedback. Obstetric outcomes included incidence of perineal tearing, mode of delivery and length of second stage of labor. Psychological outcomes were assessed by self-reported measures obtained during the postnatal hospital stay and included measures of perceived control and maternal satisfaction with childbirth, as well as level of maternal feelings of connectedness with the newborn. Obstetric and psychological results were compared with those of a control group of 69 women who received standard obstetric coaching from midwives.<br><br>RESULTS: Pushing efficacy increased significantly following visual biofeedback by TPU (P&#x2009;=&#x2009;0.01), as indicated by a significantly lower delta AoP before (mean, 22.2&#xb0; (95% CI, 13.9-31.7&#xb0;)) compared with after (mean, 35.2&#xb0; (95% CI, 25.9-45.3&#xb0;)) biofeedback. A significant association was found between visual biofeedback and an intact perineum following delivery (P&#x2009;=&#x2009;0.03). No significant differences were found between the two groups with regard to mode of delivery or length of the second stage. Feelings of maternal connectedness with the newborn were significantly stronger (P&#x2009;=&#x2009;0.003) in women who received visual biofeedback than in those who did not. However, perceived control during childbirth and maternal satisfaction with childbirth did not differ significantly between the biofeedback and control groups.<br><br>CONCLUSIONS: This pilot study suggests that biofeedback using TPU may serve as a complementary tool to coached maternal pushing during the second stage of labor, with obstetric as well as psychological benefits. Further studies are required to confirm our findings and define the optimal duration of the intervention. Copyright &#xa9; 2017 ISUOG. Published by John Wiley &amp; Sons Ltd.}, }
@article {pmid29154888, year = {2017}, author = {Hou, N and Wen, Y and Yuan, X and Xu, H and Wang, X and Li, F and Ye, B}, title = {Activation of Yap1/Taz signaling in ischemic heart disease and dilated cardiomyopathy.}, journal = {Experimental and molecular pathology}, volume = {103}, number = {3}, pages = {267-275}, pmid = {29154888}, issn = {1096-0945}, support = {R01 HL072166/HL/NHLBI NIH HHS/United States ; R01 HL111480/HL/NHLBI NIH HHS/United States ; R01 HL122793/HL/NHLBI NIH HHS/United States ; }, mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Cardiomyopathies/genetics/pathology ; Cardiomyopathy, Dilated/*genetics/pathology ; DNA-Binding Proteins/*genetics ; Humans ; Mice ; Muscular Dystrophies/genetics/pathology ; Myocardial Ischemia/*genetics/pathology ; Nuclear Proteins/*genetics ; Phosphoproteins/*genetics ; Signal Transduction/genetics ; TEA Domain Transcription Factors ; Transcription Factors/*genetics ; YAP-Signaling Proteins ; }, abstract = {Genetic manipulation of key components of the evolutionally conserved Hippo pathway has shown that the precise control of these signaling molecules is critical to cardiac development and response to stresses. However, how this pathway is involved in the progression of cardiac dysfunction in different heart diseases remains unclear. We investigated the expressional levels and subcellular localization of Yap1, Taz, and Tead1 and determined Hippo target gene expression in failing human hearts with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (IDC) and mouse desmin-related cardiomyopathy (DES). Our results demonstrated that Yap1, Taz, and Tead1 were significantly increased in failing human and DES hearts compared with the non-failing controls (NFH) or wild type (WT) mouse hearts at both mRNA and protein levels. Interestingly, adult human and mouse hearts had more Taz than Yap1 by mRNA and protein expression and their increases in diseased hearts were proportional and did not change Yap1/Taz ratio. Yap1, Taz, and Tead1 were accumulated in the nuclear fraction and cardiomyocyte nuclei of diseased hearts. The ratio of Yap1 phosphorylated at serine 127 (human) or serine 112 (mouse) to the total Yap1 (pYap1/Yap1) was significantly lower in the nuclear fraction of diseased hearts than that in normal controls. More importantly, Hippo downstream targets Ankrd1, Ctgf, and Cyr61 were transcriptionally elevated in the diseased hearts. These results suggest that Yap1/Taz signaling is activated in human and mouse dysfunctional hearts. Further investigation with relevant animal models will determine whether this pathway is a potential target for preventing and reversing abnormal remodeling during the progression of different cardiac disorders.}, }
@article {pmid29146271, year = {2018}, author = {Co, M and Kwong, A and Shek, T}, title = {Factors affecting the under-diagnosis of atypical ductal hyperplasia diagnosed by core needle biopsies - A 10-year retrospective study and review of the literature.}, journal = {International journal of surgery (London, England)}, volume = {49}, number = {}, pages = {27-31}, doi = {10.1016/j.ijsu.2017.11.005}, pmid = {29146271}, issn = {1743-9159}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/methods/*statistics &amp; numerical data ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma in Situ/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Carcinoma, Lobular/pathology ; Diagnostic Errors ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {INTRODUCTION: Due to the possibility of underestimation, surgical excision is usually offered to patients with atypical ductal hyperplasia (ADH) diagnosed with core needle biopsy (CNB). Here we review the 10-year data of patients with ADH diagnosed by CNB, aiming to identify the factors associated with under-diagnosis.<br><br>METHODS: Retrospective review of database from 1st Jan 2005 to 31st Dec 2014 was performed; patients with ADH diagnosed by CNB were identified. Diagnosis upgrade rate and its risk factors were evaluated.<br><br>RESULTS: 104 patients were found to have ADH on CNB, 101 patients received excisional biopsy while 3 patients refused operation. 34 patients had ductal carcinoma in situ (DCIS) after excision, 6 had invasive ductal carcinoma, 1 had lobular carcinoma in situ and 1 had angiosarcoma. CNB under-diagnosed up to 41.6% of malignant lesions. Breast mass on presentation and suspicious mammograms (BIRADS &#x2265; 4) are associated with diagnosis upgrade (P&#xa0;=&#xa0;0.0005, 0.0001). Literature review of 39 studies between 1997 and 2017 revealed 3125 excision procedures performed for ADH diagnosed by CNB, the pooled median diagnosis upgrade rate was 25% (Range 4-54%).<br><br>CONCLUSION: We recommend excision in all patients with ADH diagnosed by CNB, especially in patients with suspicious mammographic features.}, }
@article {pmid29142588, year = {2017}, author = {Mwakigonja, AR and Lushina, NE and Mwanga, A}, title = {Characterization of hormonal receptors and human epidermal growth factor receptor-2 in tissues of women with breast cancer at Muhimbili National Hospital, Dar es salaam, Tanzania.}, journal = {Infectious agents and cancer}, volume = {12}, number = {}, pages = {60}, pmid = {29142588}, issn = {1750-9378}, abstract = {BACKGROUND: Breast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu) expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH).<br><br>METHODS: A cross-sectional study of female breast post-modified radical mastectomy (MRM)/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January-December 2013). Tissue blocks having poor morphology, without tumor, secondary tumors, cases outside the study period and male patients were excluded. Routine staining was done followed by immunohistochemistry for estrogen (ER), and progesterone (PgR) receptors and HER2. Data analyzed using Statistical Package for Social Sciences (SPSS).<br><br>RESULTS: A total of 218 cases were confirmed to be carcinoma including 70 meeting inclusion criteria. Age at diagnosis ranged 18-75&#xa0;years and mean age was 48.36&#xa0;years. Majority (64.3%) were in the 36-55&#xa0;years age-group. Histologically, most (88.6%) women had invasive ductal carcinoma including 43.1% of intermediate grade. A great majority (78%) were stage three. Due to logistical constrains, 75.7% (n&#xa0;=&#xa0;53/70) cases where immunostained for hormones including 43.4% (ER+), 26.4% (PgR+), and 28% (ER+/PgR+). Furthermore, 65.7% (n&#xa0;=&#xa0;46/70) cases were immunostained for HER-2 and 15.2% (n&#xa0;=&#xa0;7/46) were positive, 45.6% were triple negative (ER-,PgR-,HER2-), 23.9% (ER+,PgR+,HER2-) or luminal B, 2.2% (ER+,PgR-,HER2+),13% (ER-,PgR-,HER2+) and 15% (ER+,PgR-,HER2-) with none being triple positive.<br><br>CONCLUSIONS: Hormonal receptors and HER2 expression at MNH appears to be comparable to previous Africans/African Americans reports but not with studies among Caucasians and the current proportion of triple negative breast carcinomas (TNBC) is higher than in a previous Tanzanian report and majority are luminal. HER2 over-expression is relatively common. It is strongly recommended that receptor status assessment be made routine for breast cancer patients at MNH.}, }
@article {pmid29873455, year = {2017}, author = {Mileski, M and Ayala, L and Campuzano, E and Joy, A and Ornelas, S and Ortiz, M and Saenz, J}, title = {Quality of Life Considerations During Cancer Treatment in Invasive Ductal Carcinoma Patients: A Systemic Review.}, journal = {The ABNF journal : official journal of the Association of Black Nursing Faculty in Higher Education, Inc}, volume = {28}, number = {1}, pages = {9-13}, pmid = {29873455}, issn = {1046-7041}, mesh = {Female ; Humans ; *Breast Neoplasms/psychology/therapy ; *Carcinoma, Ductal, Breast/psychology/therapy ; *Quality of Life ; }, abstract = {Breast cancer is the number two leading cause of death in women all over the world and is often associated with poor quality of life (QOL). The positive and negative QOL factors influence the overall health and well-being of those affected with invasive ductal carcinoma (IDC). This literature review was structured to identify and understand both the positive and negative QOL factors throughout breast cancer treatment, as well as post breast cancer treatment. Systemic searches were done of three databases to gather data in breast cancer treatment from 2010-2015. Results identified the positive and negative factors associated with the QOL in relation to breast cancer treatment. The most prevalent positive QOL factors included patient expectations, decreased side effects, and increased survival rate. The most prevalent negative QOL factors included treatment, specific side effects and decreased quality of life. This review may guide healthcare professionals in incorporating new practices and identifying the best regimen to improving QOL. The positive and negative QOL factors, in relation to treatment, are important because they help healthcare professionals understand how those factors impact the overall health and well-being of individuals with IDC.}, }
@article {pmid29787025, year = {2016}, author = {Kasap, E and Gene, M and Sahin, N and Sivrikoz, ON}, title = {Mayer-Rokitansky-Kuster-Hauser syndrome accompanied by invasive ductal carcinoma: a case report.}, journal = {European journal of gynaecological oncology}, volume = {37}, number = {5}, pages = {744-746}, pmid = {29787025}, issn = {0392-2936}, mesh = {46, XX Disorders of Sex Development/*complications/pathology ; Adult ; Breast Neoplasms/*etiology/pathology ; Carcinoma, Ductal, Breast/*etiology/pathology ; Congenital Abnormalities/pathology ; Female ; Humans ; Mullerian Ducts/*abnormalities/pathology ; }, abstract = {Milllerian agenesis and the absence of organs of Millerian canal origin are referred to as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Invasive ductal carcinoma constitutes 47-75% of all breast carcinomas and is the most common type. The authors report the first case of invasive ductal carcinoma associated with MRKH syndrome in the literature to their knowledge. A 25-year-old woman with a palpable mass in her right breast for three months presented to the presented clinic. On physical examination a mobile, firm mass measuring 2x2 cm was detected in right breast, at a region close to axilla. A fine needle aspiration biopsy from the lesion revealed malignant cells and thus a segmental mastectomy operation was performed. All genital tract and endocrinological system should be thoroughly examined before administering hormone replacement therapy to patients presenting with primary amenorrhea.The co-occurrence MRKH syndrome of with invasive ductal carcinoma is regarded as coincidental. Confirming the absence of a common etiology, however, requires further genetic studies.}, }
@article {pmid29147419, year = {2015}, author = {Budimir, I and Sabol Pusic, M and Nikolic, M and Dorosulic, Z and Ljubicic, N and Stajduhar, E and Mise, I and Vazdar, L and Sarcevic, B}, title = {Obstructive Jaundice as an Uncommon Manifestation of Metastatic Breast Cancer.}, journal = {World journal of oncology}, volume = {6}, number = {1}, pages = {297-300}, pmid = {29147419}, issn = {1920-454X}, abstract = {Invasive ductal carcinoma is the most common type of breast cancer and accounts for about 70-85% of all invasive breast carcinomas. It primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain. Most of breast cancer recurrence occurs within the first 5 years of diagnosis, particularly for ER negative disease. Gastrointestinal tract involvement is very rare and is detected in only 10% of all the cases, and it usually derives from lobular breast cancer rather than the much more common cell type of ductal breast cancer. Early diagnosis is very important because it enables prompt and adequate choice of treatment and improves patient's long-term prognosis. In this report we describe an unusual case of obstructive jaundice caused by metastases from invasive ductal breast cancer to the lymph nodes of the hepatoduodenal ligament with extramural compression of the distal common bile duct and tumor invasion to the lumen of the duct. Our goal is to emphasize possible diagnostic pitfalls and increase the clinical awareness and the importance of intensive follow-up in patients with breast cancer, even years after the initial diagnosis.}, }
@article {pmid31159098, year = {1996}, author = {Yu, FY and Chu, FS}, title = {Production and Characterization of Antibodies against Fumonisin B1.}, journal = {Journal of food protection}, volume = {59}, number = {9}, pages = {992-997}, doi = {10.4315/0362-028X-59.9.992}, pmid = {31159098}, issn = {1944-9097}, abstract = {Polyclonal antibodies against fumonisin B1 (FmB1) were produced in rabbits after immunizing the animals with either FmBl-keyhole limpet hemocyanin (KLH) or FmB1 bovine serum albumin (BSA). A direct competitive enzyme-linked immunosorbent assay (dc-ELISA) and an indirect competitive ELISA (idc-ELISA) were used for the characterization of the antibodies and for analysis of the toxin in corn samples. The antibody titers in the serum of rabbits immunized with FmBl-KLH were considerably higher than in those immunized with FmBl-BSA. The antibodies from the rabbits immunized with FmBl-KLH were further characterized. The concentrations causing 50% inhibition of binding of FmB1-horseradish peroxidase (HRP) to the antibodies by FmB1, FmB2 and FmB3 in the ELISA were found to be 0.45, 0.72, and 25 ng/ml, respectively. The detection limit of FmBl, based on 95% confidence at 5% of inhibition of binding of FmBl-HRP conjugate, in buffer of the dc-ELISA was found to be 0.05 ng/ml. In the presence of a matrix such as corn, the detection limit was less than 50 ppb. The overall analytical recoveries of FmBl (50 to 1,000 ng/g) added to the ground corn and then extracted with CH3CN/H2O (1/1, vol/vol) with cleanup and without cleanup in the dc ELISA were found to be 70.5 and 85.9%, respectively. A good correlation was found between the FmBl levels in 2 starch and 10 naturally contaminated corn samples analyzed by the dc-ELISA and the high-pressure liquid chromatography (HPLC) method. The correlation coefficients between ELISA and HPLC were found to be 0.955 (y [ELISA] = 1.3 1x [HPLC] + 77 ppb; P < 0.001) and 0.811 (y = 1.13x + 34 ppb; P < 0.01) for the sample without and with cleanup treatment, respectively.}, }
@article {pmid29142206, year = {2017}, author = {Wang, CQ and Li, Y and Huang, BF and Zhao, YM and Yuan, H and Guo, D and Su, CM and Hu, GN and Wang, Q and Long, T and Wang, Y and Tang, CH and Li, X}, title = {EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {15654}, pmid = {29142206}, issn = {2045-2322}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carrier Proteins/*genetics ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; ErbB Receptors/genetics ; Female ; Gefitinib/administration &amp; dosage ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Microfilament Proteins/*genetics ; Middle Aged ; *Molecular Targeted Therapy ; Neoplasm Recurrence, Local/drug therapy/genetics/pathology ; Progression-Free Survival ; Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology ; }, abstract = {Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.}, }
@article {pmid29131529, year = {2017}, author = {Yang, LP and Sun, HF and Zhao, Y and Chen, MT and Zhang, N and Jin, W}, title = {Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study.}, journal = {Cancer medicine}, volume = {6}, number = {12}, pages = {2867-2875}, pmid = {29131529}, issn = {2045-7634}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Carcinoma, Lobular/mortality/*secondary/therapy ; Chi-Square Distribution ; Disease Progression ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; Young Adult ; }, abstract = {The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534-0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (P = 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS.}, }
@article {pmid29126758, year = {2017}, author = {Helal, DS and El-Guindy, DM}, title = {Maspin expression and subcellular localization in invasive ductal carcinoma of the breast: Prognostic significance and relation to microvessel density.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {29}, number = {4}, pages = {177-183}, doi = {10.1016/j.jnci.2017.09.002}, pmid = {29126758}, issn = {2589-0409}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*genetics/*metabolism ; Carcinoma, Ductal, Breast/diagnosis/*genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neovascularization, Pathologic/genetics/metabolism ; Prognosis ; Protein Transport ; Serpins/*genetics/*metabolism ; Tumor Burden ; }, abstract = {Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor. The expression of maspin was evaluated immunohistochemically in 45 IDC cases. The positive rate of maspin expression was 73.3%. Maspin positivity was significantly related to higher tumor grade (p value = 0.041), nodal metastasis (p value = 0.044), perineural invasion (p value = 0.047), and high CD34+MVD (p value = 0.002). Nuclear maspin was detected in 36.6% whereas cytoplasmic maspin was detected in 63.4% of maspin positive cases. A significant inverse relationship was observed between nuclear maspin and high tumor grade (p value = 0.016), and nodal metastasis (p value = 0.047). These results suggest that maspin expression has a prognostic role in breast cancer. Maspin expression is related to increased angiogenesis. Subcellular localization of maspin can strongly affect cancer prognosis. Cytoplasmic maspin relates to poor prognostic parameters whereas nuclear maspin relates to good prognostic ones.}, }
@article {pmid29090670, year = {2018}, author = {Gurzu, S and Banias, L and Bara, T and Feher, I and Bara, T and Jung, I}, title = {The Epithelial-Mesenchymal Transition Pathway in Two Cases with Gastric Metastasis Originating from Breast Carcinoma, One with a Metachronous Primary Gastric Cancer.}, journal = {Recent patents on anti-cancer drug discovery}, volume = {13}, number = {1}, pages = {118-124}, doi = {10.2174/2212798409666171101121108}, pmid = {29090670}, issn = {2212-3970}, mesh = {Aged ; Breast Neoplasms/diagnosis/*metabolism ; Epithelial-Mesenchymal Transition/*physiology ; Female ; Humans ; Neoplasms, Second Primary/diagnosis/*metabolism/secondary ; Stomach Neoplasms/diagnosis/*metabolism/secondary ; }, abstract = {BACKGROUND: Metastases to the stomach are extremely rare and the metastatic pathway is not well understood.<br><br>OBJECTIVE: To present two unusual gastric metastases and a review of the literature regarding the pathway of Epithelial Mesenchymal Transition (EMT) in the metastatic cells.<br><br>METHOD: The clinicopathological aspects of the two cases were presented in the light of the most recent patents. Data about patents were obtained from the online databases PubMed, World Intellectual Property Organization (WIPO) and Google patents.<br><br>RESULTS: In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, &#x3b2;-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed. In the second case, a 67-year-old female with invasive ductal carcinoma of the breast, which benefited from chemotherapy and mastectomy, presented a metachronous gastric adenocarcinoma with collision-type metastatic breast ductal carcinoma. The aggressiveness of the GC cells was induced through the E-cadherin/maspin pathway, while the CD44-related stem-like properties of the tumor cells induced the aggressiveness of ductal carcinoma.<br><br>CONCLUSION: In females with breast cancer, a possible metastasis in the stomach should be taken into account. Maspin and VSIG1 are not involved in breast cancer histogenesis. The Wnt/&#x3b2;-catenin signaling is not involved in the lobular carcinoma progression. The CD44/HER2 positivity in ductal carcinoma cells might indicate high risk of distant metastasis and low response to chemotherapy.}, }
@article {pmid29084692, year = {2017}, author = {Chen, K and Wang, CQ and Fan, YQ and Xie, YS and Yin, ZF and Xu, ZJ and Zhang, HL and Cao, JT and Wang, Y and Gao, L}, title = {Model design for screening effective Antihyperlipidemic drugs using zebrafish system.}, journal = {Pakistan journal of pharmaceutical sciences}, volume = {30}, number = {5}, pages = {1697-1707}, pmid = {29084692}, issn = {1011-601X}, mesh = {Animals ; Atorvastatin/pharmacology ; Biomarkers/blood ; Cholesterol/blood ; Diet, High-Fat ; Disease Models, Animal ; Drug Discovery/*methods ; Ezetimibe/pharmacology ; Fenofibrate/pharmacology ; *High-Throughput Screening Assays ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Hyperlipidemias/blood/*drug therapy/etiology ; Hypolipidemic Agents/*pharmacology ; Lipid Metabolism/*drug effects ; Male ; Triglycerides/blood ; Zebrafish/*blood ; }, abstract = {The purpose of this paper was to explore a new method for screening lipid-lowering drugs in zebrafish models. The suitable drug concentrations of atorvastatin (ATV), fenofibrate (FEF) and ezetimibe (EZE) were first determined. Then, the serum cholesterol and triglyceride levels were detected in high-fat diet (HFD)-fed zebrafish. The HFD zebrafish models were constructed and the effects of drugs on them were observed by Oil red O staining and fluorescence labeling. Statistical analyses among groups were conducted using SPSS software. The lowest drug concentration (LDC) and the highest (HDC) of ATV, FEF and EZE were 0.3 μM/37.0μM, 1.2μM/3.5μM, and 6.3 μM/26.4μM, respectively, while, the intermediate (IDC) was, in order, 18.5μM, 1.8μM, 13.2μM. The cholesterol and triglyceride levels in HFD-fed zebrafish were increased after 7 weeks fat feeding (p<0.05). Moreover, the levels of triglyceride were significantly decreased after LDC of ATV and FEF treated (p<0.05), but not that of EZE. While, the cholesterol levels were reduced in three groups (p<0.05). Moreover, the 5 dpf high-fat zebrafish model was established successfully and maintained stably for 24h. ATV produced effects in a concentration-dependent manner, while only IDC and HDC of FEF and EZE made effects on this model. Intravascular cholesterol levels were significantly increased after HCD treatment and decreased after drug treated. The high-fat zebrafish model induced by HFD-fed was available and successful, besides, the Oil red O staining may be an available and rapid method for screening lipid-lowering drugs.}, }
@article {pmid29076877, year = {2018}, author = {Skálová, A and Stenman, G and Simpson, RHW and Hellquist, H and Slouka, D and Svoboda, T and Bishop, JA and Hunt, JL and Nibu, KI and Rinaldo, A and Vander Poorten, V and Devaney, KO and Steiner, P and Ferlito, A}, title = {The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas.}, journal = {The American journal of surgical pathology}, volume = {42}, number = {2}, pages = {e11-e27}, doi = {10.1097/PAS.0000000000000980}, pmid = {29076877}, issn = {1532-0979}, mesh = {Biomarkers, Tumor/*genetics ; Biopsy ; Carcinoma/*genetics/pathology/therapy ; Diagnosis, Differential ; Gene Fusion ; Genetic Predisposition to Disease ; Humans ; *Molecular Diagnostic Techniques ; Mutation ; Neoplasm Grading ; Phenotype ; Predictive Value of Tests ; Salivary Gland Neoplasms/*genetics/pathology/therapy ; Translocation, Genetic ; }, abstract = {Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.}, }
@article {pmid29072365, year = {2017}, author = {Chen, H and Wu, K and Wang, M and Wang, F and Zhang, M and Zhang, P}, title = {Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.}, journal = {Cancer medicine}, volume = {6}, number = {12}, pages = {2775-2786}, pmid = {29072365}, issn = {2045-7634}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/*mortality/secondary/therapy ; Carcinoma, Papillary/chemistry/*mortality/secondary/therapy ; Chi-Square Distribution ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Propensity Score ; Proportional Hazards Models ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; }, abstract = {There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P < 0.001, 95% CI: 0.293-0.572) and OS (HR = 0.497, P < 0.001, 95% CI: 0.387-0.637). In subgroup analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation.}, }
@article {pmid29069648, year = {2017}, author = {Huang, R and Han, J and Liang, X and Sun, S and Jiang, Y and Xia, B and Niu, M and Li, D and Zhang, J and Wang, S and Wei, W and Liu, Q and Zheng, W and Zhang, G and Song, Y and Panga, D}, title = {Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit β-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer.}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology}, volume = {43}, number = {6}, pages = {2212-2225}, doi = {10.1159/000484300}, pmid = {29069648}, issn = {1421-9778}, mesh = {Androgen Receptor Antagonists/*pharmacology/therapeutic use ; Anilides/*pharmacology/therapeutic use ; Animals ; Apoptosis/drug effects ; Breast Neoplasms/drug therapy/mortality/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Down-Regulation/drug effects ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Nitriles/*pharmacology/therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; Receptors, Androgen/chemistry/*genetics/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Signal Transduction/drug effects ; Tosyl Compounds/*pharmacology/therapeutic use ; Transcription, Genetic/*drug effects ; Transplantation, Heterologous ; beta Catenin/genetics/*metabolism ; }, abstract = {BACKGROUND/AIMS: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment.<br><br>METHODS: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer.<br><br>RESULTS: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/&#x3b2;-catenin signaling and inhibited the growth of AR+/ER- breast cancer.<br><br>CONCLUSION: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.}, }
@article {pmid29065116, year = {2017}, author = {Picillo, M and Pivonello, R and Santangelo, G and Pivonello, C and Savastano, R and Auriemma, R and Amboni, M and Scannapieco, S and Pierro, A and Colao, A and Barone, P and Pellecchia, MT}, title = {Serum IGF-1 is associated with cognitive functions in early, drug-naïve Parkinson's disease.}, journal = {PloS one}, volume = {12}, number = {10}, pages = {e0186508}, pmid = {29065116}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cognition Disorders/*blood/complications ; Female ; Humans ; Insulin-Like Growth Factor I/*metabolism ; Male ; Middle Aged ; Parkinson Disease/blood/*complications ; }, abstract = {OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) since the early stages and many patients eventually develop dementia. Yet, occurrence of dementia in PD is unpredictable. Evidence supports the hypothesis that insulin-like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to evaluate the relationship between serum IGF-1 levels and neuropsychological scores in a large cohort of drug-naïve PD patients during the earliest stages of the disease.<br><br>METHODS: Serum IGF-1 levels were determined in 405 early, drug-na&#xef;ve PD patients and 191 healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). The association between serum IGF-1 levels and neuropsychological scores was evaluated with linear regression analysis.<br><br>RESULTS: IGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile was a predictor of lower performances at the Semantic Fluency task (&#x3b2; = -3.46, 95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (&#x3b2; = -2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test Retention (&#x3b2; = -0.05, 95%CI: -0.09 to -0.009, p = 0.019).<br><br>CONCLUSIONS: Lower serum IGF-1 levels are associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory in a large cohort of early PD patients. Follow-up studies are warranted to assess if IGF-1 is related to the development of dementia in PD.}, }
@article {pmid29056512, year = {2017}, author = {Rios Garcia, M and Steinbauer, B and Srivastava, K and Singhal, M and Mattijssen, F and Maida, A and Christian, S and Hess-Stumpp, H and Augustin, HG and Müller-Decker, K and Nawroth, PP and Herzig, S and Berriel Diaz, M}, title = {Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence.}, journal = {Cell metabolism}, volume = {26}, number = {6}, pages = {842-855.e5}, doi = {10.1016/j.cmet.2017.09.018}, pmid = {29056512}, issn = {1932-7420}, mesh = {Acetyl-CoA Carboxylase/genetics/*metabolism ; Acetylation ; Animals ; Breast Neoplasms/*metabolism/*pathology ; Disease Models, Animal ; Female ; HEK293 Cells ; Humans ; Leptin/metabolism ; Lung Neoplasms/*secondary ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/metabolism/*pathology ; Tissue Array Analysis ; }, abstract = {Breast tumor recurrence and metastasis represent the main causes of cancer-related death in women, and treatments are still lacking. Here, we define the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player in breast cancer metastasis. ACC1 phosphorylation was increased in invading cells both in murine and human breast cancer, serving as a point of convergence for leptin and transforming growth factor (TGF) β signaling. ACC1 phosphorylation was mediated by TGFβ-activated kinase (TAK) 1, and ACC1 inhibition was indispensable for the elevation of cellular acetyl-CoA, the subsequent increase in Smad2 transcription factor acetylation and activation, and ultimately epithelial-mesenchymal transition and metastasis induction. ACC1 deficiency worsened tumor recurrence upon primary tumor resection in mice, and ACC1 phosphorylation levels correlated with metastatic potential in breast and lung cancer patients. Given the demonstrated effectiveness of anti-leptin receptor antibody treatment in halting ACC1-dependent tumor invasiveness, our work defines a "metabolocentric" approach in metastatic breast cancer therapy.}, }
@article {pmid29052527, year = {2017}, author = {Chen, HR and Wu, YT and Yu, QB and Yang, YY and Wei, YX and Li, HY and Wu, KN and Kong, LQ}, title = {Negative genic switch of HER-2 in the primary tumor instead of the synchronous metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary HER2-positive breast cancer.}, journal = {World journal of surgical oncology}, volume = {15}, number = {1}, pages = {189}, pmid = {29052527}, issn = {1477-7819}, mesh = {Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Biopsy, Large-Core Needle ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/secondary/therapy ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymph Nodes/*pathology/surgery ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/*methods ; Receptor, ErbB-2/antagonists &amp; inhibitors/*genetics ; Trastuzumab/therapeutic use ; }, abstract = {BACKGROUND: A few retrospective studies have indicated that neoadjuvant chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary tumor. Little is known about the status of HER-2 gene of the synchronous nodal metastases when that of the residual tumor undergoes negative conversion in a neoadjuvant setting.<br><br>CASE PRESENTATION: We describe a female patient with left breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary tumor instead of the synchronous nodal lesions after NAC. Core needle biopsy showed invasive ductal carcinoma with HER2 immunohistochemistry (IHC) (2+) and amplified HER-2 gene determined by fluorescence in situ hybridization (FISH). Then, the patient underwent 4&#xa0;cycles of anthracycline- and taxane-based NAC and subsequent left modified radical mastectomy. Postoperative pathology showed invasive ductal carcinoma involving 4 of 12 surgically excised axillary lymph nodes with HER2 IHC (1+) and FISH negative (HER2 gene not amplified) in the residual tumor of the breast specimen. Due to the negative genic switch of HER2 after NAC, the patient rejected to accept trastuzumab. Under the patient's consent, the synchronous nodal lesions were further investigated and showed HER2 IHC(-) but FISH positive (HER-2 gene amplified). Therefore, the patient agreed to accept adjuvant trastuzumab treatment every 3&#xa0;weeks for 1&#xa0;year.<br><br>CONCLUSIONS: We propose further assessment of HER2 gene in the synchronous nodal metastases, especially when negative genic switch of HER-2 occurs in the primary tumor after NAC in order to tailor the systemic regimens for breast cancer patients.}, }
@article {pmid29045292, year = {2018}, author = {Bennett, JA and Young, RH and Chuang, AY and Lerwill, MF}, title = {Ovarian Metastases of Breast Cancers With Signet Ring Cells: A Report of 17 Cases Including 14 Krukenberg Tumors.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {37}, number = {6}, pages = {507-515}, doi = {10.1097/PGP.0000000000000462}, pmid = {29045292}, issn = {1538-7151}, mesh = {Adenocarcinoma/*secondary ; Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Carcinoma, Signet Ring Cell/*secondary ; Female ; Humans ; Krukenberg Tumor/*secondary ; Middle Aged ; Ovarian Neoplasms/*secondary ; }, abstract = {Krukenberg tumor, defined as metastatic adenocarcinoma to the ovary containing at least 10% signet ring cells, usually arises from the stomach but can also originate from other sites. We reviewed 17 metastatic breast carcinomas to the ovary with signet ring cells to potentially identify features indicative of mammary origin as opposed to other possible primary sites. The patients ranged from 41 to 76 (mean, 53.6) yr. Fourteen had a prior history of invasive breast carcinoma (invasive ductal carcinoma, 4; invasive lobular carcinoma, 3; adenocarcinoma not otherwise specified, 3; carcinoma with ductal and lobular features, 2; and unspecified carcinoma, 2) and metastases were identified 2 to 284 (mean, 79) mo after the original diagnosis. Three patients had no known history of invasive breast carcinoma: 1 was subsequently diagnosed with invasive lobular carcinoma, 1 had suspicious bilateral breast masses identified on imaging, and 1 was lost to follow-up. Bilateral ovarian metastases were present in 87%, and the tumors ranged from 3.8 to 19 (mean, 8) cm. Microscopically the ovarian architecture was effaced in 71% by discrete tumor lobules separated by striking edema. The tumors exhibited a variety of histologic patterns: nests were most common (88%), followed by cords (82%), diffuse sheets (82%), single cells (71%), small clusters (41%), glands (29%), and follicle-like cysts (12%). Signet ring cells comprised 2% to 70% (mean, 33%) of the tumors, with 14 cases meeting the criteria for Krukenberg tumor. Signet ring cells were most frequently observed within diffuse sheets (71%) and cords (65%). Tumor cells arranged in nests, cords, and diffuse sheets are typical of Krukenberg tumor of breast origin, and the patterns recapitulate those seen in primary breast carcinomas. Features characteristic of gastrointestinal origin, such as extracellular mucin, intestinal-type glands, dirty necrosis, microcysts, and goblet cell carcinoid-like foci, were absent. The overall morphologic picture in cases of ovarian spread of breast cancer with signet ring cells is usually strongly suggestive of mammary origin. The diagnosis can be further supported by the clinical history and immunohistochemical evaluation.}, }
@article {pmid29043464, year = {2018}, author = {Mordang, JJ and Gubern-Mérida, A and Bria, A and Tortorella, F and Mann, RM and Broeders, MJM and den Heeten, GJ and Karssemeijer, N}, title = {The importance of early detection of calcifications associated with breast cancer in screening.}, journal = {Breast cancer research and treatment}, volume = {167}, number = {2}, pages = {451-458}, pmid = {29043464}, issn = {1573-7217}, support = {KUN 2012-5577//KWF Kankerbestrijding/International ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*complications/pathology ; Calcinosis/complications/*diagnosis/pathology ; *Early Diagnosis ; Female ; Humans ; Mammography ; Mass Screening ; Middle Aged ; }, abstract = {PURPOSE: The aim of this study was to assess how often women with undetected calcifications in prior screening mammograms are subsequently diagnosed with invasive cancer.<br><br>METHODS: From a screening cohort of 63,895 women, exams were collected from 59,690 women without any abnormalities, 744 women with a screen-detected cancer and a prior negative exam, 781 women with a false positive exam based on calcifications, and 413 women with an interval cancer. A radiologist identified cancer-related calcifications, selected by a computer-aided detection system, on mammograms taken prior to screen-detected or interval cancer diagnoses. Using this ground truth and the pathology reports, the sensitivity for calcification detection and the proportion of lesions with visible calcifications that developed into invasive cancer were determined.<br><br>RESULTS: The screening sensitivity for calcifications was 45.5%, at a specificity of 99.5%. A total of 68.4% (n&#xa0;=&#xa0;177) of cancer-related calcifications that could have been detected earlier were associated with invasive&#xa0;cancer when diagnosed.<br><br>CONCLUSIONS: Screening sensitivity for detection of malignant calcifications is low. Improving the detection of these early signs of cancer is important, because the majority of lesions with detectable calcifications that are not recalled immediately but detected as interval cancer or in the next screening round are invasive at the time of diagnosis.}, }
@article {pmid29037500, year = {2017}, author = {Siciliano, M and Trojano, L and De Micco, R and De Mase, A and Garramone, F and Russo, A and Tedeschi, G and Tessitore, A}, title = {Motor, behavioural, and cognitive correlates of fatigue in early, de novo Parkinson disease patients.}, journal = {Parkinsonism &amp; related disorders}, volume = {45}, number = {}, pages = {63-68}, doi = {10.1016/j.parkreldis.2017.10.004}, pmid = {29037500}, issn = {1873-5126}, mesh = {Aged ; Anxiety/epidemiology/etiology ; Apathy ; Cognitive Dysfunction/epidemiology/etiology ; Fatigue/epidemiology/*etiology/*psychology ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications ; Prevalence ; Sleep Wake Disorders/epidemiology/etiology ; }, abstract = {INTRODUCTION: Fatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.<br><br>METHODS: Eighty-one consecutive de novo PD patients (64% men; mean age 65.73&#xa0;&#xb1;&#xa0;8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score&#xa0;&#x2265;&#xa0;8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.<br><br>RESULTS: Twelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p&#xa0;= 0.04), "episodic anxiety" subscale of PAS (p&#xa0;=&#xa0;0.005), and "cognitive apathy" subscale of AES (p&#xa0;=&#xa0;0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p&#xa0;= 0.745).<br><br>CONCLUSION: In a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.}, }
@article {pmid29026955, year = {2018}, author = {Watson, L and Dunn, D and Fraser-Kirk, G}, title = {Indolent Rib Osteomyelitis Following Breast Implant Reconstruction: An Unusual Case and Review of the Literature.}, journal = {Aesthetic plastic surgery}, volume = {42}, number = {2}, pages = {447-450}, doi = {10.1007/s00266-017-0975-z}, pmid = {29026955}, issn = {1432-5241}, mesh = {Anti-Bacterial Agents/therapeutic use ; Australia ; Breast Implantation/*adverse effects/methods ; Breast Implants/*adverse effects ; Breast Neoplasms/pathology/*surgery ; Device Removal ; Female ; Follow-Up Studies ; Humans ; Mastectomy/methods ; Middle Aged ; Osteomyelitis/drug therapy/*etiology/physiopathology ; Prosthesis-Related Infections/diagnosis/microbiology/*surgery ; Rare Diseases ; Ribs/*microbiology/pathology ; Risk Assessment ; Treatment Outcome ; }, abstract = {UNLABELLED: Rib osteomyelitis is an infrequently occurring but important complication of breast implant surgery. Although prosthetic or surgical site infection (SSI) and rib osteomyelitis as separate entities are well described in the literature, only five cases of rib or sternal osteomyelitis related to implant placement have been reported globally. Historically patients who experience this complication have not demonstrated an identifiable prevalence of the traditional risk factors associated with SSI or rib osteomyelitis. This report describes the sequence of clinical manifestations of an unusual case of breast implants complicated by rib osteomyelitis. A 56-year-old female underwent mastectomy and insertion of tissue expanders for bilateral invasive ductal carcinoma following which the tissue expanders became infected in the early postoperative period and were subsequently removed. The patient underwent successful expander insertion and subsequent implant exchange surgery several years later and enjoyed an uncomplicated recovery from this. Following nipple reconstruction more than 12 months after successful implant placement, she presented with Staphylococcus epidermidis bacteremia and a left-sided clinical peri-implant infection. Upon removal of her implant, an intraoperative discovery of rib necrosis/osteomyelitis was made for which she was treated. To provide context, the literature was reviewed for other reported cases of rib osteomyelitis following breast implant surgery. This patient, in combination with others reported in the literature, emphasises the diagnostic difficulties posed by this condition as a result of its low incidence and variable or absent clinical features.<br><br>LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .}, }
@article {pmid28993866, year = {2018}, author = {Stuebs, F and Heidemann, S and Caliebe, A and Mundhenke, C and Arnold, N}, title = {CDH1 mutation screen in a BRCA1/2-negative familial breast-/ovarian cancer cohort.}, journal = {Archives of gynecology and obstetrics}, volume = {297}, number = {1}, pages = {147-152}, doi = {10.1007/s00404-017-4551-1}, pmid = {28993866}, issn = {1432-0711}, mesh = {Adult ; Antigens, CD/*metabolism ; BRCA1 Protein/*metabolism ; BRCA2 Protein/*metabolism ; Breast Neoplasms/*genetics/pathology ; Cadherins/*metabolism ; Cohort Studies ; Early Detection of Cancer ; Female ; Genetic Predisposition to Disease ; Humans ; Mutation ; Ovarian Neoplasms/*genetics/pathology ; }, abstract = {PURPOSE: Mutations in the CDH1 gene are linked both to diffuse gastric cancer and invasive lobular carcinoma (ILC). A high mutation rate is found in families fulfilling the diagnostic criteria for hereditary diffuse gastric cancer. Aim of this study was to clarify whether or not there is a significant contribution of CDH1 mutations in hereditary breast-/ovarian cancer (HBOC).<br><br>METHODS: Ninety-seven unrelated probands fulfilling the diagnostic criteria for HBOC (96 affected, 1 unaffected) but tested negative for pathogenic BRCA1/2 mutations were screened for CDH1 mutations by denaturing high performance liquid chromatography (DHPLC) and subsequent Sanger sequencing of suspicious and positive DHPLC results.<br><br>RESULTS: In total, we found two potentially pathogenic CDH1 alterations, c.1774G&#xa0;>&#xa0;A, pAla592Thr, and c.2512 A&#xa0;>&#xa0;G, p.Ser838Gly, classified as variants of unknown significance according to ClinVar. In addition, we detected a high number of known CDH1 polymorphisms (n&#xa0;=&#xa0;62), some of them more frequent in patients with lobular (55%) than in those with invasive ductal carcinoma (27%).<br><br>CONCLUSION: Although none of the probands studied carried a clearly pathogenic CDH1 mutation, CDH1 could be considered a potential breast cancer gene, esp. for ILC worth including it in the NGS (next generation sequencing) HBOC panel.}, }
@article {pmid28982860, year = {2017}, author = {Grzegrzolka, J and Wojtyra, P and Biala, M and Piotrowska, A and Gomulkiewicz, A and Rys, J and Podhorska-Okolow, M and Dziegiel, P}, title = {Correlation Between Expression of Twist and Podoplanin in Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {37}, number = {10}, pages = {5485-5493}, doi = {10.21873/anticanres.11978}, pmid = {28982860}, issn = {1791-7530}, mesh = {Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/genetics/mortality/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/mortality/surgery ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Membrane Glycoproteins/*analysis/genetics ; Middle Aged ; Nuclear Proteins/*analysis/genetics ; Proportional Hazards Models ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Stromal Cells/chemistry/pathology ; Time Factors ; Treatment Outcome ; Twist-Related Protein 1/*analysis/genetics ; Up-Regulation ; }, abstract = {BACKGROUND/AIM: As a result of activation of transcription factors engaged in epithelial-mesenchymal transition (EMT), such as Twist, inhibition of epithelial markers and an increased expression of mesenchymal markers are observed. One of the specific markers of cancer-associated fibroblasts is podoplanin (PDPN) - a mucin-type membrane glycoprotein. The aim of this work was to study the localisation and intensity of expression of Twist and PDPN on the mRNA and protein level in cases of invasive ductal breast carcinoma (IDC), and its association with patients' clinico-pathological data.<br><br>MATERIALS AND METHODS: The study included archival material in a form of 80 paraffin IDC blocks and 11 IDC fragments frozen in liquid nitrogen. Immunohistochemical expression of Twist and PDPN was evaluated using light microscope and semiquantitative scale for evaluation of nuclear expression or immunoreactive scale (IRS) for evaluation of cytoplasmic expression. Material was isolated from frozen IDC fragments using laser micro-dissection (from cancer and stromal cells, separately) and was used to perform real-time PCR.<br><br>RESULTS: Twist expression was higher in stromal cells in comparison to cancer cells. Analysis of patients' survival rate showed, that higher expression of Twist in cancer cells was associated with shorter overall survival time and shorter event-free survival time. The expression of PDPN was also higher in stromal cells in comparison with cancer cells. In addition, positive correlation was observed between expression of Twist and PDPN in stromal cells of IDC (r=0.267; p<0.05).<br><br>CONCLUSION: The relationship between the higher expression of Twist in both cancer and stromal cells and shorter patients' survival indicates Twist as a potential useful prognostic marker in IDC. Positive correlation of Twist and PDPN expression may indicate the role of PDPN in EMT in IDC.}, }
@article {pmid28977635, year = {2017}, author = {Kumar, V and Fleming, T and Terjung, S and Gorzelanny, C and Gebhardt, C and Agrawal, R and Mall, MA and Ranzinger, J and Zeier, M and Madhusudhan, T and Ranjan, S and Isermann, B and Liesz, A and Deshpande, D and Häring, HU and Biswas, SK and Reynolds, PR and Hammes, HP and Peperkok, R and Angel, P and Herzig, S and Nawroth, PP}, title = {Homeostatic nuclear RAGE-ATM interaction is essential for efficient DNA repair.}, journal = {Nucleic acids research}, volume = {45}, number = {18}, pages = {10595-10613}, pmid = {28977635}, issn = {1362-4962}, mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/*metabolism ; Cell Nucleus/enzymology/metabolism ; Cellular Senescence ; DNA/metabolism ; DNA Breaks, Double-Stranded ; *DNA Repair ; DNA Repair Enzymes/metabolism ; DNA-Binding Proteins/metabolism ; Homeostasis ; Lung/physiopathology ; MRE11 Homologue Protein ; Mice, Inbred C57BL ; Mice, Knockout ; Pulmonary Fibrosis/genetics/physiopathology ; Receptor for Advanced Glycation End Products/genetics/*metabolism ; Reperfusion Injury/genetics/metabolism ; Signal Transduction ; }, abstract = {The integrity of genome is a prerequisite for healthy life. Indeed, defects in DNA repair have been associated with several human diseases, including tissue-fibrosis, neurodegeneration and cancer. Despite decades of extensive research, the spatio-mechanical processes of double-strand break (DSB)-repair, especially the auxiliary factor(s) that can stimulate accurate and timely repair, have remained elusive. Here, we report an ATM-kinase dependent, unforeseen function of the nuclear isoform of the Receptor for Advanced Glycation End-products (nRAGE) in DSB-repair. RAGE is phosphorylated at Serine376 and Serine389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response. nRAGE preferentially co-localized with the MRE11 nuclease subunit of the MRN complex and orchestrates its nucleolytic activity to the ATR kinase signaling. This promotes efficient RPA2S4-S8 and CHK1S345 phosphorylation and thereby prevents cellular senescence, IPF and carcinoma formation. Accordingly, loss of RAGE causatively linked to perpetual DSBs signaling, cellular senescence and fibrosis. Importantly, in a mouse model of idiopathic pulmonary fibrosis (RAGE-/-), reconstitution of RAGE efficiently restored DSB-repair and reversed pathological anomalies. Collectively, this study identifies nRAGE as a master regulator of DSB-repair, the absence of which orchestrates persistent DSB signaling to senescence, tissue-fibrosis and oncogenesis.}, }
@article {pmid28974441, year = {2017}, author = {Kim, YY and Lee, S and Kim, MJ and Kang, BC and Dhakal, H and Choi, YA and Park, PH and Choi, H and Shin, TY and Choi, HG and Kwon, TK and Khang, D and Kim, SH}, title = {Tyrosol attenuates lipopolysaccharide-induced acute lung injury by inhibiting the inflammatory response and maintaining the alveolar capillary barrier.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {109}, number = {Pt 1}, pages = {526-533}, doi = {10.1016/j.fct.2017.09.053}, pmid = {28974441}, issn = {1873-6351}, mesh = {Acute Lung Injury/*drug therapy/etiology/genetics/*immunology ; Animals ; Cyclooxygenase 2/genetics/immunology ; Cytokines/genetics/immunology ; Humans ; Interleukin-6/genetics/immunology ; Lipopolysaccharides/adverse effects ; Lung/immunology/pathology ; Male ; Mice ; Mice, Inbred BALB C ; NF-kappa B/genetics/immunology ; Nitric Oxide Synthase Type II/genetics/immunology ; Phenylethyl Alcohol/administration &amp; dosage/*analogs &amp; derivatives ; Pulmonary Alveoli/drug effects/immunology ; Signal Transduction/drug effects ; }, abstract = {Acute lung injury (ALI) is a life-threatening disease characterized by increased pulmonary vascular permeability because of alveolar capillary barrier dysfunction and increased immune responses. This study determined the anti-inflammatory effect of tyrosol on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms of action. BALB/c mice were orally administered with tyrosol (0.1, 1, and 10 mg/kg) 1 h before an intratracheal injection of LPS (25 μg/50 μL). Oral treatment with tyrosol inhibited lung vascular permeability, histopathological changes, wet/dry lung weight ratio, and pulmonary vascular cell infiltration. The LPS-induced imbalance in the activity of enzymes, such as superoxide dismutase and myeloperoxidase, was regulated by tyrosol. Pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, were reduced by tyrosol in bronchoalveolar lavage fluid and lung tissue. The activation of inflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated-IκBα, was suppressed by the presence of tyrosol in the lung tissue. In addition, tyrosol attenuated the production of NO, the expression of pro-inflammatory cytokines, the expression of iNOS and COX-2, and the nuclear translocation of nuclear factor-κB in LPS-stimulated RAW 264.7 macrophages. These results suggested that tyrosol is a potential therapeutic agent for treating inflammatory lung diseases.}, }
@article {pmid28967088, year = {2017}, author = {Cavalieri, S and Stathis, A and Fabbri, A and Sonzogni, A and Perrone, F and Tamborini, E and Pelosi, G and de Braud, F and Platania, M}, title = {Uncommon somatic mutations in metastatic NUT midline carcinoma.}, journal = {Tumori}, volume = {103}, number = {Suppl. 1}, pages = {e5-e8}, doi = {10.5301/tj.5000685}, pmid = {28967088}, issn = {2038-2529}, mesh = {Adult ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/secondary ; DCC Receptor/genetics ; DNA-Binding Proteins/genetics ; Fatal Outcome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; *Mutation ; Neoplasm Proteins ; Nuclear Proteins/*genetics ; Oncogene Proteins/*genetics ; Phosphoproteins/genetics ; RNA Splicing Factors/genetics ; }, abstract = {INTRODUCTION:: NUT midline carcinoma (NMC) is a rare and aggressive epithelial cancer arising from median organs. It is driven by chromosomal translocation t(15;19) involving the rearrangement of NUT (nuclear protein in testis) and BRD4 (bromodomain 4) genes leading to fusion oncoprotein BRD4-NUT.<br><br>CASE PRESENTATION:: We report the case of a woman who was previously treated with induction chemotherapy, surgery, radiotherapy and adjuvant trastuzumab for HER-2 positive invasive ductal carcinoma of the breast. After 6 months of follow-up a lung nodule appeared. A biopsy showed an adenocarcinoma fetal type/lung blastoma, so a left inferior lobectomy was performed: NMC harboring BRD4-NUT rearrangement was diagnosed. After 9 months of follow-up, bone and soft tissue metastases occurred, so the patient was given radiotherapy. Next-generation sequencing technology identified somatic mutations in deleted in colorectal cancer (DCC), mixed lineage leukemia protein 3 (MLL3), and splicing factor 3B subunit 1 (SF3B1) genes in NMC cells from both primitive cancer and metastases. The patient was treated with the experimental BRD4 inhibitor for 10 months, until the disease progressed to the lung and bone. After spinal cord compression, the patient was offered palliative radiotherapy to bone and eventually died aged 39 years.<br><br>CONCLUSIONS:: To the best of our knowledge, our case is the first DCC, MLL3, and SF3B1 mutated NUT midline carcinoma reported in the literature. If these mutations were confirmed to play a role in this neoplasm, clinical trials analyzing targeted therapies should be considered, eg. colorectal cancer-like chemotherapies for DCC mutations, hypomethylating agents for MLL3 mutations or SF3B1 inhibitors in case of specific somatic mutations.}, }
@article {pmid28954989, year = {2017}, author = {Nozoe, T and Nozoe, E and Kono, M and Ohga, T and Ezaki, T}, title = {Further evidence to demonstrate the significance of serum appearance of anti-p53 antibody as a marker for progressive potential in invasive ductal carcinoma of the breast.}, journal = {The journal of medical investigation : JMI}, volume = {64}, number = {3.4}, pages = {241-244}, doi = {10.2152/jmi.64.241}, pmid = {28954989}, issn = {1349-6867}, mesh = {Adult ; Aged ; Antibodies/*blood ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*pathology ; Carcinoma, Ductal, Breast/blood/*pathology ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Tumor Suppressor Protein p53/*immunology ; }, abstract = {BACKGROUND: Serum appearance of anti-p53 antibody (p53Ab) has been reported as an indicator for progressive potential of human tumor tumors including breast cancer. But its significance in breast cancer has not been discussed fully.<br><br>METHODS: Relationship between serum appearance of p53Abs and representative data accounting for progressive potential in breast cancer, nuclear grade (NG), triple negative cancer, and the cumulative score based on these two data (TGS) was investigated among 129 women with invasive ductal carcinoma (IDC) of the breast, who had been treated with surgical resection.<br><br>RESULTS: There was a significant correlation between appearance of p53Abs and recurrence of the tumors (P = 0.035). Significant correlation of serum appearance of p53Abs with negative expression of ER (P = 0.011), the proportion of TNBC (P = 0.013), NG (P = 0.017), and TGS (P = 0.0005).<br><br>CONCLUSIONS: Preoperative serum appearance of p53Abs can be correlated with pathological nuclear grade, incidence of triple negative breast cancer, and TGS. These results might demonstrate more powerful significance of serum appearance of p53Abs as an indicator of progressive potential in IDC of the breast. J. Med. Invest. 64: 241-244, August, 2017.}, }
@article {pmid28942323, year = {2018}, author = {Nawroth, PP and Bendszus, M and Pham, M and Jende, J and Heiland, S and Ries, S and Schumann, C and Schmelz, M and Schuh-Hofer, S and Treede, RD and Kuner, R and Oikonomou, D and Groener, JB and Kopf, S}, title = {The Quest for more Research on Painful Diabetic Neuropathy.}, journal = {Neuroscience}, volume = {387}, number = {}, pages = {28-37}, doi = {10.1016/j.neuroscience.2017.09.023}, pmid = {28942323}, issn = {1873-7544}, mesh = {Animals ; *Biomedical Research ; Diabetic Neuropathies/*complications/diagnosis/drug therapy ; Disease Progression ; Humans ; Pain/*complications ; }, abstract = {A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made.}, }
@article {pmid28938000, year = {2017}, author = {Suchanski, J and Tejchman, A and Zacharski, M and Piotrowska, A and Grzegrzolka, J and Chodaczek, G and Nowinska, K and Rys, J and Dziegiel, P and Kieda, C and Ugorski, M}, title = {Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.}, journal = {PloS one}, volume = {12}, number = {9}, pages = {e0184970}, pmid = {28938000}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Cancer-Associated Fibroblasts/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line ; Cell Movement/*physiology ; Coculture Techniques ; Disease Progression ; Endothelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Glycoproteins/genetics/*metabolism ; Middle Aged ; Neoplasm Invasiveness/physiopathology ; RNA, Messenger/metabolism ; }, abstract = {In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such podoplanin-mediated effects can affect tube formation by endothelial cells and participate in their pathological properties in the tumor context. Our experimental data were supported by clinical studies. First, when IDC and DCIS were analyzed by immunohistochemistry according to the presence of podoplanin-expressing cells, the numbers of cancer-associated fibroblasts with high expression of this glycoprotein were significantly higher in IDC than in DCIS cases. Second, using immunofluorescence, the co-localization of PDPN-positive CAFs with blood vessels stained with antibody directed against CD34 was observed in tumor stroma of IDC samples.}, }
@article {pmid28935545, year = {2018}, author = {Stires, H and Heckler, MM and Fu, X and Li, Z and Grasso, CS and Quist, MJ and Lewis, JA and Klimach, U and Zwart, A and Mahajan, A and Győrffy, B and Cavalli, LR and Riggins, RB}, title = {Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.}, journal = {Molecular and cellular endocrinology}, volume = {471}, number = {}, pages = {105-117}, pmid = {28935545}, issn = {1872-8057}, support = {U54 CA149147/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*drug effects/genetics ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic/drug effects ; Glutamic Acid/metabolism ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Mitogen-Activated Protein Kinase Kinases/antagonists &amp; inhibitors/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Mutation/genetics ; Protein Kinase Inhibitors/pharmacology ; Receptors, Estrogen/metabolism ; Receptors, Metabotropic Glutamate/*metabolism ; *Signal Transduction/drug effects ; Tamoxifen/*pharmacology ; Transcriptome/drug effects/genetics ; Exome Sequencing ; }, abstract = {Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.}, }
@article {pmid28934992, year = {2017}, author = {Plonczak, AM and DiMarco, AN and Dina, R and Gujral, DM and Palazzo, FF}, title = {Breast cancer metastases to the thyroid gland - an uncommon sentinel for diffuse metastatic disease: a case report and review of the literature.}, journal = {Journal of medical case reports}, volume = {11}, number = {1}, pages = {269}, pmid = {28934992}, issn = {1752-1947}, mesh = {Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma/diagnosis/*secondary/surgery ; Carcinoma, Papillary/diagnosis ; Chemotherapy, Adjuvant ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*pathology ; Mastectomy ; Middle Aged ; Neck Dissection ; Radiotherapy, Adjuvant ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/diagnosis/*secondary/surgery ; Thyroidectomy ; }, abstract = {BACKGROUND: Metastases to the thyroid are rare. The most common primary cancer to metastasize to the thyroid is renal cell carcinoma, followed by malignancies of the gastrointestinal tract, lungs, and skin, with breast cancer metastases to the thyroid being rare. Overall, the outcomes in malignancies that have metastasized to the thyroid are poor. There are no prospective studies addressing the role of surgery in metastatic disease of the thyroid. Isolated thyroidectomy has been proposed as a local disease control option to palliate and prevent the potential morbidity of tumor extension related to the airway. Here, we present a case of a patient with breast cancer metastases to the thyroid gland and discuss the role of thyroidectomy in the context of the current literature.<br><br>CASE PRESENTATION: A 62-year-old Afro-Caribbean woman was diagnosed as having bilateral breast carcinoma in 2004, for which she underwent bilateral mastectomy. The pathology revealed multifocal disease on the right, T2N0(0/20)M0 grade 1 and 2 invasive ductal carcinoma, and on the left side, T3N1(2/18)M0 grade 1 invasive ductal carcinoma. Surgery was followed by adjuvant chemotherapy and regional radiotherapy. The disease was under control on hormonal therapy until 2016, when she developed cervical lymphadenopathy. The fine-needle aspiration cytology of the thyroid was reported as papillary thyroid cancer; and the fine-needle biopsy of the left lateral nodal disease was more suggestive of breast malignancy. She underwent a total thyroidectomy and a clearance of the central compartment lymph nodes and a biopsy of the lateral nodal disease. The histopathological analysis was consistent with metastatic breast cancer in the thyroid and lymph nodes with no evidence of a primary thyroid malignancy.<br><br>CONCLUSIONS: A past history of a malignancy elsewhere should raise the index of suspicion of metastatic disease in patients presenting with thyroid lumps with or without cervical lymphadenopathy. Detection of metastases to the thyroid generally indicates poor prognosis, obviating the need of surgery in an already compromised patient. An empirical thyroidectomy should be considered in select patients for local disease control.}, }
@article {pmid28906374, year = {2017}, author = {Golmohammadi, R and Namazi, MJ and Going, JJ and Derakhshan, MH}, title = {A single nucleotide polymorphism in codon F31I and V57I of the AURKA gene in invasive ductal breast carcinoma in Middle East.}, journal = {Medicine}, volume = {96}, number = {37}, pages = {e7933}, pmid = {28906374}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aurora Kinase A/*genetics ; Breast Neoplasms/*genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*genetics/mortality/*pathology ; Case-Control Studies ; Codon ; Female ; Humans ; Iran ; Middle Aged ; Neoplasm Invasiveness ; *Polymorphism, Single Nucleotide ; Prognosis ; Survival Rate ; Young Adult ; }, abstract = {Although few studies have suggested a carcinogenic role for polymorphism of F31I and V57I codons of AURKA gene in invasive ductal carcinoma, contradictory results from different populations mandates regional investigations. We aimed to determine polymorphisms of F31I and V57I codons of AURKA gene and their association with cancer prognosis in patients compared with controls in an eastern population of Iran.A case-control study was conducted on specimens from 100 patients and 100 age- and gender-matched controls. DNA was extracted and the codons F31I and V57I were amplified. The different genotypes were analyzed by PCR-RFLP and electrophoresis.In codon F31I, the frequency of Phe/Ile was 70% and 82% in patients and healthy controls respectively, whereas (Ile/Ile) was 30% in patients and 18% in healthy (P = .047). Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048). No association was observed between SNPs of either F31I or V57I genotypes and histological grades. However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran. Determination of allelic polymorphism of those codons will help to understand background genetic predisposition and could have prognostic value in management of breast cancer in the target population.}, }
@article {pmid28902360, year = {2017}, author = {Ratajczak-Wielgomas, K and Grzegrzolka, J and Piotrowska, A and Matkowski, R and Wojnar, A and Rys, J and Ugorski, M and Dziegiel, P}, title = {Expression of periostin in breast cancer cells.}, journal = {International journal of oncology}, volume = {51}, number = {4}, pages = {1300-1310}, doi = {10.3892/ijo.2017.4109}, pmid = {28902360}, issn = {1791-2423}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Adhesion Molecules/*genetics/*metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Tumor Burden ; Up-Regulation ; }, abstract = {Periostin (POSTN) is a protein involved in multiple processes important for cancer development, both at the stage of cancer initiation and progression, as well as metastasis. The aim of this study was to determine the expression of POSTN in the cells of non-invasive ductal breast carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to correlate it with clinicopathological data. Immunohistochemical studies (IHC) were conducted on 21 cases of fibrocystic breast change (FC), 44 cases of DCIS and 92 cases of IDC. POSTN expression at mRNA (real-time PCR) and protein level (western blot analysis) was also confirmed in selected breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231 and BO2). Statistically significant higher level of POSTN expression in IDC and DCIS cancer cells compared to FC was noted. Also, the level of POSTN expression in the cytoplasm of IDC cells was shown to increase with the increasing degree of tumour malignancy (G) and significantly higher expression of POSTN was observed in each degree of tumour malignancy (G) relative to FC. Statistically significant higher POSTN expression was observed in tumours with estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) phenotypes in comparison to estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) cases, as well as significant negative correlation between POSTN expression in cancer cells and expression of ER and PR (p<0.05). Additionally, statistically significant differences in POSTN expression were shown between particular breast cancer cell lines, both at mRNA and protein level. Observed POSTN expression was the lowest in the case of MCF-7, and the highest in MDA-MB-231 and BO2 of the most aggressive potential clinically corresponding to G3 tumours. POSTN expression in the cytoplasm of IDC cancer cells may play an important role in cancer transformation mechanism.}, }
@article {pmid28901319, year = {2017}, author = {Tan, R and Wang, L and Song, J and Li, J and He, T}, title = {Expression and significance of Twist, estrogen receptor, and E-cadherin in human breast cancer cells and tissues.}, journal = {Journal of cancer research and therapeutics}, volume = {13}, number = {4}, pages = {707-714}, doi = {10.4103/jcrt.JCRT_1396_16}, pmid = {28901319}, issn = {1998-4138}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis ; Nuclear Proteins/*genetics ; Receptors, Estrogen/*genetics ; Twist-Related Protein 1/*genetics ; }, abstract = {OBJECTIVES: Breast cancer is one of the most common malignancies in women, and the tumor cells' invasion and metastasis is the main cause of death. Recent reports showed that Twist, a transcription factor, plays multiple roles in breast cancer initiation, progress, and metastasis. However, the underlying mechanisms of Twist in tumor invasion and metastasis of breast cancer still remain unclear. Here, we examined the correlation between Twist, E-cadherin, and estrogen receptor (ER) in promoting invasion and metastasis in breast cancer cells and tissues.<br><br>MATERIALS AND METHODS: The mRNA and protein expression of Twist, E-cadherin, and ER in breast cancer cell lines (MCF-7, MDA-MB-435, MDA-MB-231, and ZR-75-30) and human invasive ductal carcinoma (IDC) tissues from 32 patients were detected by reverse transcription-polymerase chain reaction and immunohistochemistry (IHC), respectively.<br><br>RESULTS: Expression of Twist in cells with high ability of invasion and metastasis was higher than that in MCF-7 cell line which has low ability of invasion and metastasis, while the expression of ER and E-cadherin was much more higher in MCF-7 cell line than in other cells. IHC showed that the expression rate of Twist in IDC tissues and adjacent tissues was 84.38% and 31.25% and the positive expression of E-cadherin and ER was 21.88% and 40.63% in IDC tissues and 81.25% and 84.38% in adjacent tissues, respectively. Interestingly, overexpression of Twist promoted cellular invasion and metastasis and decreased the expression of E-cadherin, ER, AKT, and p-AKT in HEK-293 cells.<br><br>CONCLUSIONS: Taken together, these findings demonstrated that Twist was upregulated in high invasion and metastasis cell lines as well as IDC tissues companioned with downregulated expression of E-cadherin and ER, which provides important clues for the deeper study of breast cancer.}, }
@article {pmid28899737, year = {2017}, author = {Cao, L and Sun, PL and Yao, M and Jia, M and Gao, H}, title = {Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues.}, journal = {Human pathology}, volume = {68}, number = {}, pages = {166-174}, doi = {10.1016/j.humpath.2017.08.032}, pmid = {28899737}, issn = {1532-8392}, mesh = {Adaptor Proteins, Signal Transducing/*analysis ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Carcinoma/*chemistry/mortality/secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Phosphoproteins/*analysis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Transcription Factors ; YAP-Signaling Proteins ; }, abstract = {The transcriptional co-activator YES-associated protein (YAP) has been reported to act as both an oncogene and tumor suppressor in breast cancers. In this study, we evaluated YAP expression immunohistochemically in 324 breast cancer tissues and correlated the expression with clinicopathological findings and patient survival data. Additionally, we reviewed the literature to clarify the role of YAP in breast cancer. We detected YAP, estrogen receptor, progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) expression and a Ki67 labeling index >20% in 53.4%, 49.0%, 45.0%, 28.3%, and 57.4% of invasive ductal carcinoma tissues, respectively. YAP is mainly localized within the tumor cell nuclei, and its expression was associated with the PR status and luminal A subtype. YAP expression also inversely correlated with the HER2 and Ki67 levels and lymph node metastasis. Kaplan-Meier curves revealed associations of YAP expression with favorable disease-free survival (DFS) and overall survival in patients with luminal A breast cancer and with favorable DFS association among patients with invasive ductal carcinoma, luminal B (HER2-), and luminal B (HER2+) breast cancers. A multivariate Cox analysis revealed that YAP expression and PR status were independent favorable predictors of DFS and overall survival, respectively, among patients with breast cancer, whereas tumor-node-metastasis stage and an old age were independent predictors of a poor DFS. Our results, together with the literature review findings, suggest that YAP could be a prognostic marker in patients with breast cancer.}, }
@article {pmid28891551, year = {2017}, author = {Olarinoye-Akorede, SA and Silas, BT}, title = {Mondor's disease of the breast in a Nigerian woman previously treated for invasive ductal carcinoma in the contralateral breast: A case report.}, journal = {Nigerian journal of clinical practice}, volume = {20}, number = {8}, pages = {1040-1043}, doi = {10.4103/njcp.njcp_354_16}, pmid = {28891551}, issn = {1119-3077}, mesh = {Breast/diagnostic imaging ; Breast Neoplasms/*complications ; Carcinoma, Ductal, Breast/*complications ; Female ; Humans ; Middle Aged ; Nigeria ; Pain/etiology ; Thrombophlebitis/*complications/*diagnostic imaging ; }, abstract = {Mondor's disease is a self-limiting sclerosing angitis mostly affecting the superficial veins of the breast and chest wall. It is seldom diagnosed, and its etiology and epidemiology are speculative. However, numerous predisposing factors including breast cancer have been postulated. In Nigerian literature, only two cases have been documented to the best of our knowledge. This report is aimed at reminding breast specialists to include it as a diagnostic consideration in patients presenting with a breast lump in the appropriate clinical setting. Its imaging features are also highlighted because it may be incorrectly overlooked as mere ductal dilatation. We present the case of a 60-year-old woman who complained of a painful cordlike lesion in her right breast. Mondor's disease was diagnosed based on the clinical and radiological findings. She had also been previously treated for invasive ductal breast carcinoma in the contralateral breast. Mondor's disease is usually a benign entity, which may resolve spontaneously. On the other hand, it may also be the sole presenting symptom or clue of a breast malignancy; hence, a need for increased awareness.}, }
@article {pmid28869838, year = {2017}, author = {Turczyk, L and Kitowska, K and Mieszkowska, M and Mieczkowski, K and Czaplinska, D and Piasecka, D and Kordek, R and Skladanowski, AC and Potemski, P and Romanska, HM and Sadej, R}, title = {FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells.}, journal = {Neoplasia (New York, N.Y.)}, volume = {19}, number = {10}, pages = {791-804}, pmid = {28869838}, issn = {1476-5586}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/genetics/metabolism/pathology ; Cell Line, Tumor ; Estrogen Receptor alpha/*metabolism ; Female ; Fibroblast Growth Factors/metabolism ; Fibroblasts/drug effects ; Gene Expression ; Gene Knockout Techniques ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Proteolysis ; Receptor, ErbB-2/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/genetics/*metabolism ; Selective Estrogen Receptor Modulators/*pharmacology ; Signal Transduction/*drug effects ; Tamoxifen/*pharmacology ; }, abstract = {Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.}, }
@article {pmid28865741, year = {2017}, author = {Greenhouse, I and Babushkin, F and Finn, T and Shimoni, Z and Aliman, M and Ben-Ami, R and Cohen, R}, title = {Long-term outcomes of inappropriate antibiotic therapy for upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a retrospective cohort study.}, journal = {Diagnostic microbiology and infectious disease}, volume = {89}, number = {3}, pages = {222-229}, doi = {10.1016/j.diagmicrobio.2017.07.011}, pmid = {28865741}, issn = {1879-0070}, mesh = {Aged ; Cohort Studies ; Drug Prescriptions/standards ; Drug Resistance, Bacterial ; *Enterobacteriaceae/enzymology ; Enterobacteriaceae Infections/*drug therapy ; Humans ; Retrospective Studies ; Treatment Outcome ; Urinary Tract Infections/drug therapy/*microbiology ; *beta-Lactamases/biosynthesis/metabolism ; }, abstract = {BACKGROUND: To evaluate the short- and long-term outcomes of different antimicrobial treatment options for upper urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.<br><br>METHODS: We retrospectively analyzed patients with a first episode of febrile UTI and positive urine culture with ESBL-producing E. coli or K. pneumoniae during 2012-2015. We compared outcomes among patients who received: (1) definitive treatment with a carbapenem (CP), (2) a microbiologically appropriate intravenous non-carbapenem agent (NCA), (3) a non-appropriate antimicrobial (NAA), and (4) an intravenous NAA followed by an oral NCA (NAA-PO).<br><br>RESULTS: The majority of patients received empirical therapy with NAA (165/178, 93%), and definitive treatment with NCA (n=43), NAA (n=50), and NAA-PO (n=59). The NCA group had significantly higher SIRS score than the NAA-PO group (2.18 versus 1.76, P=0.018), but no differences were found between the NCA and NAA groups (2.18 and 1.92, P=0.15). Clinical cure at discharge from the index hospitalization was high (97-100%) in all 3 groups. The NCA group had longer length of stay as compared with the NAA-PO and NAA groups (8.7days versus 5.39 and 5.24days, P<0.0001) and a lower rate of early (48-72h) improvement (79% versus 96-100%, P=0.0002). Among re-admitted patients, re-admission with ESBL-related bloodstream infection was significantly higher in the NAA group as compared to the NAA-PO and NCA groups (33% versus 4% and 0%, respectively, P=0.02). Death rate within 60days was also higher in the NAA and NCA groups as compared with the NAA-PO group (P=0.048).<br><br>CONCLUSIONS: Inappropriate antimicrobial therapy for febrile non-bacteremic UTI with ESBL-producing enterobacteriaceae is associated with favorable short-term outcomes, but also with a long-term risk of relapsed bacteremic UTI. Definitive treatment with appropriate carbapenem-sparing antimicrobial agents effectively prevents late relapses.}, }
@article {pmid28862125, year = {2017}, author = {Stroescu, C and Gilca, I and Chirita, D and Poenaru, R and Puşcaşu, A and Pescaru, D and Birceanu, A and Niţipir, C and Copcă, N}, title = {Solitary Adrenal Metastases from Breast Invasive Ductal Carcinoma.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {112}, number = {4}, pages = {473-476}, doi = {10.21614/chirurgia.112.4.473}, pmid = {28862125}, issn = {1221-9118}, mesh = {Adrenal Gland Neoplasms/*secondary/surgery ; *Adrenalectomy ; Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Neoplasm Invasiveness ; Treatment Outcome ; }, abstract = {The usual neoplastic dissease involving suprarenal glands are adrenal metastaes. The majority of suprarenal metastatic disease arise from lung cancer, followed by the stomach and colon cancer, oesophagus, the liver/bile ducts cancer and renal cell carcinoma. Invasive mammary carcinoma usually spreads to the bones, lungs, lymph nodes, liver and the brain. Adrenal gland metastases from invasive no special type carcinoma represents an extremly low rate number of cases. We discuss about a 66 year old patient who presented with a solitary adrenal metastases from triple negative breast invasive carcinoma. The patient underwent total left adrenalectomy in June 2016. No further adjuvants therapies were performed. At the time of writing the patient is in good condition, without any evidence of recurrence. The role of surgical and adjuvant therapy in treating adrenal metastases after breast cancer in survival rate will be determined in future studies.}, }
@article {pmid28860708, year = {2017}, author = {Li, A and Li, Y and Ge, L and Li, P and Li, W}, title = {Onychomadesis associated with chemotherapy: case report and mini literature review.}, journal = {Drug design, development and therapy}, volume = {11}, number = {}, pages = {2373-2376}, pmid = {28860708}, issn = {1177-8881}, mesh = {Aged ; Albumins/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*adverse effects ; Breast Neoplasms/therapy ; Capecitabine/administration &amp; dosage ; Carcinoma, Ductal, Breast/therapy ; Female ; Follow-Up Studies ; Humans ; Nail Diseases/*chemically induced/pathology/therapy ; Paclitaxel/administration &amp; dosage ; }, abstract = {The side effects of chemotherapy drugs have increased in recent years, and some side effects can lead to onychomadesis. A 72-year-old woman who was diagnosed with an invasive ductal carcinoma of the right breast underwent a modified radical mastectomy in April 2015, followed by chemotherapy with capecitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Subsequently, the patient experienced palmoplantar redness, pain, onycholysis, a transparent serous exudate, and onychomadesis. The chemotherapy was discontinued, and the patient was treated with oral vitamin B6, a polymyxin ointment, and a high-energy red light. The palmoplantar redness and pain were alleviated after 1 month. However, although her fingernails improved, dysesthesia symptoms remained, and all her toenails exhibited defects or deformities at a 24-month follow-up. The symptoms of this disorder should be recognized by dermatologists.}, }
@article {pmid28844697, year = {2017}, author = {Hamada, Y and Nakayama, Y}, title = {Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {17}, number = {6}, pages = {951-955}, doi = {10.1016/j.pan.2017.08.006}, pmid = {28844697}, issn = {1424-3911}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*pathology ; Female ; Humans ; Liver/pathology ; Liver Neoplasms/*secondary ; Lung Neoplasms ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Pancreatic Neoplasms/*pathology ; }, abstract = {BACKGROUND: Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors.<br><br>METHODS: Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters <2&#xa0;cm. The follow-up period of the 20 patients with smaller tumors was 1-24 years.<br><br>RESULTS: The small-tumor group (n&#xa0;=&#xa0;20) included 11 men and 9 women, aged 51-80 years. Five died of liver metastasis (LM group, n&#xa0;=&#xa0;5) and 15 patients (non-LM group, n&#xa0;=&#xa0;15) were either alive without recurrence (n&#xa0;=&#xa0;11) or died of peritonitis carcinomatosa following local recurrence, subarachnoid hemorrhage, primary lung cancer, or old age (n&#xa0;=&#xa0;1 for each cause of death). The LM and non-LM groups did not significantly differ in numbers of venous invasion by the carcinoma in IDCP and non-IDCP area of the pancreas. However, median numbers of invaded veins in the area of IDCP and percentage of invaded vein/total number of vein in IDCP area were significantly higher in the LM group.<br><br>CONCLUSION: Among patients with small IDCP tumors, the LM group showed more aggressive venous invasion by IDPC. Patients in whom &#x2265;60% of veins were invaded by IDCP should be prepared for LM.}, }
@article {pmid28843709, year = {2018}, author = {Karnik, T and Kimler, BF and Fan, F and Tawfik, O}, title = {PD-L1 in breast cancer: comparative analysis of 3 different antibodies.}, journal = {Human pathology}, volume = {72}, number = {}, pages = {28-34}, doi = {10.1016/j.humpath.2017.08.010}, pmid = {28843709}, issn = {1532-8392}, mesh = {Antibodies, Monoclonal/immunology/*therapeutic use ; B7-H1 Antigen/*immunology ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*drug therapy/immunology ; Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology ; Immunohistochemistry/methods ; Lung Neoplasms/*drug therapy/immunology/pathology ; Treatment Outcome ; }, abstract = {The interaction of programmed cell death-1 and its ligand-1 (PD-L1) serves as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of 3 different PD-L1 antibodies (Ventana SP263, Dako 22C3, and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic, and 46 distantly metastatic diseases. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor, progesterone receptor, HER2, Ki67, molecular type, and triple-negative status. There was excellent agreement between the 3 antibodies, with highly significant κ values (P≤.001). PD-L1 expression was more likely to be associated with higher tumor grade and estrogen receptor-negative, progesterone receptor-negative, triple-negative, and highly proliferative tumors (P<.001). When we studied PD-L1 expression at 0, 1%-9%, 10%-49%, and ≥50% cutoff points by the 3 antibodies, there were 20 discordant cases between the antibodies. Sixteen were of inconsequential impact as far as low and high PD-L1 expression. The 4 differences between antibodies did exhibit an interesting pattern of expression, where there was a general agreement between the BioCare and Ventana antibodies with consistently higher PD-L1 expression compared with the Dako antibody. Given the high concordance, it is not surprising that all 3 antibodies demonstrated the same associations with all pathologic and clinical parameters studied. Standardization studies to identify reliable biomarkers that help in patient selection for immune therapy to improve the risk-benefit ratio for these drugs are still needed.}, }
@article {pmid28830512, year = {2017}, author = {Gupta, AP and Zhu, L and Tripathi, J and Kucharski, M and Patra, A and Bozdech, Z}, title = {Histone 4 lysine 8 acetylation regulates proliferation and host-pathogen interaction in Plasmodium falciparum.}, journal = {Epigenetics &amp; chromatin}, volume = {10}, number = {1}, pages = {40}, pmid = {28830512}, issn = {1756-8935}, mesh = {Acetylation ; *Cell Proliferation ; Chromatin/metabolism ; Erythrocytes/parasitology ; Histones/*metabolism ; *Host-Parasite Interactions ; Humans ; Open Reading Frames ; Plasmodium falciparum/*genetics/pathogenicity ; Promoter Regions, Genetic ; *Protein Processing, Post-Translational ; Protozoan Proteins/*metabolism ; }, abstract = {BACKGROUND: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (IDC) of P. falciparum.<br><br>RESULTS: Using a dominant-negative transgenic approach, we showed that acetylations of histone H4 play a direct role in transcription. Specifically, these histone modifications mediate an inverse transcriptional relationship between the factors of cell proliferation and host-parasite interaction. Out of the four H4 acetylations, H4K8ac is likely the rate-limiting, regulatory step, which modulates the overall dynamics of H4 posttranslational modifications. H4K8ac exhibits maximum responsiveness to HDAC inhibitors and has a highly dynamic distribution pattern along the genome of P. falciparum during the IDC. Moreover, H4K8ac functions mainly in the euchromatin where its occupancy shifts from intergenic regions located upstream of 5' end of open reading frame into the protein coding regions. This shift is directly or indirectly associated with transcriptional activities at the corresponding genes. H4K8ac is also active in the heterochromatin where it stimulates expression of the main antigenic gene family (var) by its presence in the promoter region.<br><br>CONCLUSIONS: Overall, we demonstrate that H4K8ac is a potential major regulator of chromatin-linked transcriptional changes during P. falciparum life cycle which is associated not only with euchromatin but also with heterochromatin environment. This is potentially a highly significant finding that suggests a regulatory connection between growth and parasite-host interaction both of which play a major role in malaria parasite virulence.}, }
@article {pmid28826004, year = {2017}, author = {Zemva, J and Fink, CA and Fleming, TH and Schmidt, L and Loft, A and Herzig, S and Knieß, RA and Mayer, M and Bukau, B and Nawroth, PP and Tyedmers, J}, title = {Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux.}, journal = {Redox biology}, volume = {13}, number = {}, pages = {674-686}, pmid = {28826004}, issn = {2213-2317}, mesh = {Amino Acid Transport Systems/metabolism ; *Energy Metabolism ; Glucose/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; *Hormesis ; Pyruvaldehyde/*metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; }, abstract = {Energy production is inevitably linked to the generation of toxic metabolites, such as reactive oxygen and carbonyl species, known as major contributors to ageing and degenerative diseases. It remains unclear how cells can adapt to elevated energy flux accompanied by accumulating harmful by-products without taking any damage. Therefore, effects of a sudden rise in glucose concentrations were studied in yeast cells. This revealed a feedback mechanism initiated by the reactive dicarbonyl methylglyoxal, which is formed non-enzymatically during glycolysis. Low levels of methylglyoxal activate a multi-layered defence response against toxic metabolites composed of prevention, detoxification and damage remission. The latter is mediated by the protein quality control system and requires inducible Hsp70 and Btn2, the aggregase that sequesters misfolded proteins. This glycohormetic mechanism enables cells to pre-adapt to rising energy flux and directly links metabolic to proteotoxic stress. Further data suggest the existence of a similar response in endothelial cells.}, }
@article {pmid28801774, year = {2017}, author = {Escórcio-Dourado, CS and Martins, LM and Simplício-Revoredo, CM and Sampaio, FA and Tavares, CB and da Silva-Sampaio, JP and Borges, US and Alves-Ribeiro, FA and Lopes-Costa, PV and Lima-Dourado, JC and da Silva, BB}, title = {Bcl-2 antigen expression in luminal A and triple-negative breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {34}, number = {9}, pages = {161}, pmid = {28801774}, issn = {1559-131X}, mesh = {Adult ; Antigens/metabolism ; Biomarkers, Tumor/immunology/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/*immunology/metabolism ; Triple Negative Breast Neoplasms/*immunology/*pathology ; }, abstract = {Biomarkers for the prognosis of breast cancer have been routinely used in clinical practice, including the expression of hormone receptors, Ki-67 and HER-2. More recently, Bcl-2 has been recognized as an important prognostic factor in breast cancer, although controversies persist with respect to the significance of its expression. The aim of the present study was to evaluate Bcl-2 antigen expression in luminal A and triple-negative breast cancer. Sixty women with invasive ductal carcinoma were included in the study and divided into two groups: Group A (luminal A) and Group B (triple-negative), with 30 cases in each group. Immunohistochemistry was performed on tissue sections to evaluate Bcl-2 antigen expression. Fisher's exact test was used to compare the proportions of cases with cells expressing Bcl-2 between the two subtype cancer groups, with statistical significance being established at p < 0.05. The number of cases with cells expressing Bcl-2 in Groups A and B was 26 (86.7%) and 12 (40.0%), respectively (p < 0.0003). In the present study, the expression of the anti-apoptotic protein Bcl-2 was greater in luminal A breast cancer tissue samples compared to triple-negative breast cancer.}, }
@article {pmid28797564, year = {2017}, author = {D'Iorio, A and Vitale, C and Piscopo, F and Baiano, C and Falanga, AP and Longo, K and Amboni, M and Barone, P and Santangelo, G}, title = {Impact of anxiety, apathy and reduced functional autonomy on perceived quality of life in Parkinson's disease.}, journal = {Parkinsonism &amp; related disorders}, volume = {43}, number = {}, pages = {114-117}, doi = {10.1016/j.parkreldis.2017.08.003}, pmid = {28797564}, issn = {1873-5126}, mesh = {*Activities of Daily Living ; Anxiety/diagnosis/*etiology ; Apathy/*physiology ; Cognition Disorders/diagnosis/etiology ; Female ; Humans ; Male ; Neuropsychological Tests ; Parkinson Disease/*complications/*psychology ; Psychiatric Status Rating Scales ; Quality of Life/*psychology ; Severity of Illness Index ; Statistics as Topic ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: Parkinson's disease (PD) is characterized by a wide spectrum of non-motor symptoms that may impact negatively on the activities of the patient's daily life and reduce Health-related quality of life (HRQoL). The present study explored the impact of specific non-motor symptoms on the HRQoL in PD.<br><br>METHODS: Eighty-four outpatients underwent the Montreal Cognitive Assessment (MoCA) assessing global functioning and several questionnaires to assess depression, apathy, impulse control disorders (ICD), anxiety, anhedonia and functional impact of cognitive impairment. The perceived QoL was assessed by Parkinson's Disease Questionnaire (PDQ-8). The PD sample was divided into patients with high and low HRQoL around the median of PDQ-8 and compared on clinical features, cognitive and neuropsychiatric variables. A linear regression analysis, in which the global functioning, apathy, depression, anxiety, anhedonia, ICD and the functional autonomy scores were entered as independent variables and PDQ-8 score as dependent variable, was applied.<br><br>RESULTS: Patients with lower HRQoL were more depressed, apathetic, anxious and showed more severe reduction of functional autonomy and global functioning than patients with high HRQoL. The regression analysis revealed that higher level of anxiety, executive apathy and more reduced functional autonomy were significantly associated with higher score on PDQ-8.<br><br>CONCLUSIONS: The finding indicated that anxiety, apathy associated with impaired planning, attention and organization (i.e., executive apathy evaluated by the Dimensional Apathy Scale) and reduced functional autonomy contribute significantly to reduce the HRQoL in PD. Therefore, early identification and management of these neuropsychiatric symptoms should be relevant to preserve HRQoL in PD.}, }
@article {pmid28793265, year = {2017}, author = {Niopek, K and Üstünel, BE and Seitz, S and Sakurai, M and Zota, A and Mattijssen, F and Wang, X and Sijmonsma, T and Feuchter, Y and Gail, AM and Leuchs, B and Niopek, D and Staufer, O and Brune, M and Sticht, C and Gretz, N and Müller-Decker, K and Hammes, HP and Nawroth, P and Fleming, T and Conkright, MD and Blüher, M and Zeigerer, A and Herzig, S and Berriel Diaz, M}, title = {A Hepatic GAbp-AMPK Axis Links Inflammatory Signaling to Systemic Vascular Damage.}, journal = {Cell reports}, volume = {20}, number = {6}, pages = {1422-1434}, doi = {10.1016/j.celrep.2017.07.023}, pmid = {28793265}, issn = {2211-1247}, mesh = {AMP-Activated Protein Kinase Kinases ; Animals ; Atherosclerosis/etiology/*metabolism/pathology ; Cell Line ; Cells, Cultured ; Cholesterol/metabolism ; GA-Binding Protein Transcription Factor/chemistry/*metabolism ; Hepatocytes/*metabolism ; Hypercholesterolemia/complications/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Protein Kinases/*metabolism ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Reactive Oxygen Species/metabolism ; *Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Increased pro-inflammatory signaling is a hallmark of metabolic dysfunction in obesity and diabetes. Although both inflammatory and energy substrate handling processes represent critical layers of metabolic control, their molecular integration sites remain largely unknown. Here, we identify the heterodimerization interface between the α and β subunits of transcription factor GA-binding protein (GAbp) as a negative target of tumor necrosis factor alpha (TNF-α) signaling. TNF-α prevented GAbpα and β complex formation via reactive oxygen species (ROS), leading to the non-energy-dependent transcriptional inactivation of AMP-activated kinase (AMPK) β1, which was identified as a direct hepatic GAbp target. Impairment of AMPKβ1, in turn, elevated downstream cellular cholesterol biosynthesis, and hepatocyte-specific ablation of GAbpα induced systemic hypercholesterolemia and early macro-vascular lesion formation in mice. As GAbpα and AMPKβ1 levels were also found to correlate in obese human patients, the ROS-GAbp-AMPK pathway may represent a key component of a hepato-vascular axis in diabetic long-term complications.}, }
@article {pmid28791367, year = {2017}, author = {Zheng, T and Wang, A and Hu, D and Wang, Y}, title = {Molecular mechanisms of breast cancer metastasis by gene expression profile analysis.}, journal = {Molecular medicine reports}, volume = {16}, number = {4}, pages = {4671-4677}, pmid = {28791367}, issn = {1791-3004}, mesh = {Breast Neoplasms/*genetics/immunology/metabolism/*pathology ; Cell Adhesion/genetics ; Computational Biology/methods ; Databases, Genetic ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Molecular Sequence Annotation ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Protein Interaction Mapping ; Protein Interaction Maps ; *Transcriptome ; }, abstract = {Metastasis is the main cause of breast cancer‑related mortalities. The present study aimed to uncover the relevant molecular mechanisms of breast cancer metastasis and to explore potential biomarkers that may be used for prognosis. Expression profile microarray data GSE8977, which contained 22 stroma samples (15 were from normal breast and 7 were from invasive ductal carcinoma tumor samples), were obtained from the Gene Expression Omnibus database. Following data preprocessing, differentially expressed genes (DEGs) were selected based on analyses conducted using the linear models for microarray analysis package from R and Bioconductor software. The resulting data were used in subsequent function and pathway enrichment analyses, as well as protein‑protein interaction (PPI) network and subnetwork analyses. Transcription factors (TFs) and tumor‑associated genes were also identified among the DEGs. A total of 234 DEGs were identified, which were enriched in immune response, cell differentiation and cell adhesion‑related functions and pathways. Downregulated DEGs included TFs, such as the proto‑oncogene SPI1, pre‑B‑cell leukemia homeobox 3 (PBX3) and lymphoid enhancer‑binding factor 1 (LEF1), as well as tumor suppressors (TSs), such as capping actin protein, gelsolin like (CAPG) and tumor protein p53‑inducible nuclear protein 1 (TP53INP1). Upregulated DEGs also included TFs and tumor suppressors, consisting of transcription factor 7‑like 2 (TCF7L2) and pleiomorphic adenoma gene‑like 1 (PLAGL1). DEGs that were identified at the hub nodes in the PPI network and the subnetwork were epidermal growth factor receptor (EGFR) and spleen‑associated tyrosine kinase (SYK), respectively. Several genes crucial in the metastasis of breast cancer were identified, which may serve as potential biomarkers, many of which were associated with cell adhesion, proliferation or immune response, and may influence breast cancer metastasis by regulating these function or pathways.}, }
@article {pmid28778029, year = {2017}, author = {Watanabe, M and Matsuoka, R and Ichimura, Y and Takagaki, T and Iitsuka, Y}, title = {Papillotubular carcinoma with an invasive micropapillary carcinoma component of the breast, characterized by a rapid increase in size due to intra-tumoral hemorrhage: A case report.}, journal = {International journal of surgery case reports}, volume = {38}, number = {}, pages = {189-191}, pmid = {28778029}, issn = {2210-2612}, abstract = {INTRODUCTION: Rapidly enlarging mammary tumors, including invasive breast tumors, are clinically rare. Invasive micropapillary carcinoma (IMPC) of the breast is known to have aggressive behavior and poor clinical course compared to invasive ductal carcinoma.<br><br>CASE PRESENTATION: An 87-year-old woman presented with a rapidly enlarging tumor of the right breast over the course of 3 weeks. Ultrasonography and computed tomography of the chest revealed a giant tumor located on the right chest wall, with heterogeneous parenchymal components and several cystic lesions. Emergency mastectomy was performed because of rapid tumor enlargement complicated by hemorrhage. Histopathological diagnosis confirmed a papillotubular invasive ductal carcinoma with an IMPC component. Tumor cells were negative for estrogen and progesterone receptors, and the human epidermal growth factor receptor 2 score was 2+.<br><br>DISCUSSION: There has been only one report of breast carcinoma with rapid enlargement caused by spontaneous intratumoral hemorrhage to date. IMPC is associated with a high incidence of axillary lymph node metastases, frequent local recurrence, and a poor clinical outcome. In the present case, the specific breast cancer type can be considered as potential factors responsible for hemorrhage induction within the tumor that further enhanced rapid tumor growth.<br><br>CONCLUSION: IMPC is a rare, clinically aggressive variant of invasive ductal carcinoma. Owing to its aggressive clinical behaviors, surgeons should readily recognize the morphology of IMPC.}, }
@article {pmid28765906, year = {2017}, author = {Wang, J and Song, L and Yang, S and Zhang, W and Lu, P and Li, S and Li, H and Wang, L}, title = {HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.}, journal = {Molecular medicine reports}, volume = {16}, number = {4}, pages = {4634-4642}, pmid = {28765906}, issn = {1791-3004}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/*genetics/*mortality/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Protein Serine-Threonine Kinases/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; }, abstract = {Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma‑not otherwise specified (IDC‑NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC‑NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC‑NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC‑NOS were detected using immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1‑positive, and 100 out of 148 (67.6%) were ER‑positive. Of the latter, 28% (28/100) were HPK1‑positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=‑0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC‑NOS tissues were PR‑ or HER2‑positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor‑node‑metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER‑positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC‑NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC‑NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.}, }
@article {pmid28755148, year = {2017}, author = {Meng, F and Liu, B and Xie, G and Song, Y and Zheng, X and Qian, X and Li, S and Jia, H and Zhang, X and Zhang, L and Yang, YL and Fu, L}, title = {Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast.}, journal = {Breast cancer research and treatment}, volume = {166}, number = {2}, pages = {383-392}, doi = {10.1007/s10549-017-4407-1}, pmid = {28755148}, issn = {1573-7217}, mesh = {Adult ; Aged ; Antigens, Neoplasm/*genetics/*metabolism ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Papillary/genetics/*metabolism ; Cell Adhesion Molecules/metabolism ; Chromosomes, Human, Pair 8/genetics ; Female ; GPI-Linked Proteins/genetics/metabolism ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Proteins/*genetics/*metabolism ; Prognosis ; Survival Analysis ; *Up-Regulation ; }, abstract = {PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied.<br><br>METHODS: Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC-NST, and 56 ILC samples using immunohistochemical analysis.<br><br>RESULTS: PSCA gene amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC-NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9% (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples, respectively. The concordant&#xa0;rate&#xa0;of the immunohistochemistry and&#xa0;FISH&#xa0;data was 85.2%. PSCA gene amplification highly correlated with its protein overexpression (rs&#xa0;=&#xa0;0.687, P&#xa0;<&#xa0;0.001), suggesting that gene amplification is an important mechanism involved in PSCA overexpression. Our univariate analysis showed that the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS) compared to PSCA-negative IMPC patients (P&#xa0;=&#xa0;0.003). Our multivariate analysis confirmed the worse DFS in PSCA-positive IMPC patients (P&#xa0;=&#xa0;0.022).<br><br>CONCLUSIONS: Our results indicate that PSCA may be an attractive target in the 8q24 amplicon and that it may serve as a molecular marker of metastasis and recurrence in IMPC. The differential expression of PSCA may be associated with cell adhesion. Detection of PSCA protein and gene amplification may help manage and predict the prognosis of IMPC patients.}, }
@article {pmid28732472, year = {2017}, author = {Kulkarni, S and Jadhav, S and Khopkar, P and Sane, S and Londhe, R and Chimanpure, V and Dhilpe, V and Ghate, M and Yelagate, R and Panchal, N and Rahane, G and Kadam, D and Gaikwad, N and Rewari, B and Gangakhedkar, R}, title = {GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.}, journal = {BMC infectious diseases}, volume = {17}, number = {1}, pages = {506}, pmid = {28732472}, issn = {1471-2334}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Antiretroviral Therapy, Highly Active ; Case-Control Studies ; HIV Infections/*drug therapy/*virology ; *HIV-1/genetics/pathogenicity ; Humans ; India ; Point-of-Care Systems ; Real-Time Polymerase Chain Reaction/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Viral Load/*methods ; }, abstract = {BACKGROUND: Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings.<br><br>METHODS: A systematic validation of the GeneXpert&#xae; HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (<40 to >5&#xa0;L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure.<br><br>RESULTS: The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r&#xa0;=&#xa0;0.886) was statistically significant (p&#xa0;<&#xa0;0.01), the linear regression showed a moderate fit (R[2]&#xa0;=&#xa0;0.784) and differences were within limits of agreement. Reproducibility showed an average variation of 4.15 and 3.52% while Lower limit of detection (LLD) and Upper limit of detection (ULD) were 42 and 1,740,000 copies/ml respectively. The misclassification rates for three viral load cut offs were not statistically different (p&#xa0;=&#xa0;0.736). All seronegative samples were negative and viral loads of the stored samples showed a good fit (R[2]&#xa0;=&#xa0;0.896 to 0.982).<br><br>CONCLUSION: The viral load results of GeneXpert HIV-1 Quant assay compared well with Abbott HIV-1&#xa0;m2000 Real Time PCR; suggesting its use as a Point of care assay for viral load estimation in resource limited settings. Its ease of performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.}, }
@article {pmid28730339, year = {2017}, author = {Santiago, L and Adrada, BE and Huang, ML and Wei, W and Candelaria, RP}, title = {Breast cancer neoplastic seeding in the setting of image-guided needle biopsies of the breast.}, journal = {Breast cancer research and treatment}, volume = {166}, number = {1}, pages = {29-39}, doi = {10.1007/s10549-017-4401-7}, pmid = {28730339}, issn = {1573-7217}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnostic imaging/metabolism/mortality/*pathology ; Female ; Humans ; Image-Guided Biopsy ; Mammography ; Neoplasm Grading ; Neoplasm Seeding ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; Triple Negative Breast Neoplasms/diagnostic imaging/metabolism/mortality/pathology ; }, abstract = {PURPOSE: To identify clinicopathologic, technical, and imaging features associated with neoplastic seeding (NS) following image-guided needle breast biopsy.<br><br>METHODS: We performed an institutional review board-approved retrospective review of patients presenting with a new diagnosis of breast cancer or suspicious breast findings requiring biopsy with subsequent diagnosis of NS. The time from biopsy to NS diagnosis was calculated. Histology, grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, T category, and N category were recorded. Biopsy guidance method, needle gauge, and number of passes were reviewed in addition to the mammographic and sonographic features of the primary tumors and the NS.<br><br>RESULTS: Eight cases of NS were identified in 4010 patients. The mean time from biopsy to NS diagnosis was 60.8&#xa0;days. The most frequent histology was invasive ductal carcinoma (7/8). Six cases were grade 3 (75.0%). Five primary breast cancers were ER, PR, and HER2 negative (62.5%). Seven patients underwent biopsy with ultrasound guidance. Multiple-insertion, non-coaxial ultrasound-guided core-needle biopsy was done in 6 cases. Mammographic presentation of NS was focal asymmetry (3/7 cases), mass (1/7), calcifications only (1/7), or occult (2/7). Sonographic presentation of NS was most often a mass (7/8) with irregular shape (5/7) and without circumscribed margins (6/7) and was occult in 1 case (1/8). NS distribution was subdermal and intradermal.<br><br>CONCLUSION: High-grade, triple-negative breast cancers and multiple-insertion, non-coaxial biopsies may be risk factors for NS. NS should be suspected on the basis of the superficial and linear pattern of disease progression in these patients.}, }
@article {pmid28726282, year = {2017}, author = {Horikawa, H and Umegaki-Arao, N and Funakoshi, T and Amagai, M and Tanaka, M}, title = {Dermoscopy of pigmented invasive ductal carcinoma mimicking basal cell carcinoma.}, journal = {The Australasian journal of dermatology}, volume = {58}, number = {4}, pages = {326-327}, doi = {10.1111/ajd.12671}, pmid = {28726282}, issn = {1440-0960}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Basal Cell/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/secondary ; *Dermoscopy ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Nipples ; Skin Neoplasms/*diagnostic imaging/pathology/secondary ; Skin Pigmentation ; }, }
@article {pmid28719381, year = {2018}, author = {Oliveira, RV and Souza, VB and Souza, PC and Soares, FA and Vassallo, J and Rocha, RM and Schenka, AA}, title = {Detection of Putative Stem-cell Markers in Invasive Ductal Carcinoma of the Breast by Immunohistochemistry: Does It Improve Prognostic/Predictive Assessments?.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {26}, number = {10}, pages = {760-768}, pmid = {28719381}, issn = {1533-4058}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Brazil ; Breast Neoplasms/metabolism/mortality/pathology ; *Carcinoma, Ductal, Breast/metabolism/mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Risk Factors ; Survival Rate ; }, abstract = {INTRODUCTION: Experimental evidences from the last 2 decades supports the existence of a special type of neoplastic cell with stem-like features [cancer stem cell (CSC)] and their role in the pathophysiology and therapeutic resistance of breast cancer. However, their clinical value in human breast cancer has not been fully determined.<br><br>MATERIALS AND METHODS: An immunohistochemistry panel of 10 putative CSC markers (CD34, C-KIT, CD10, SOX-2, OCT 3/4, p63, CD24, CD44, CD133, and ESA/EPCAM) was applied to 74 cases of breast cancer, followed in a Regional Cancer Center of Minas Gerais State, Brazil, from 2004 to 2006. Possible associations between CSC markers and classic variables of clinicopathologic relevance were investigated.<br><br>RESULTS: The most frequently positive CSC markers were CD44, CD24, CD133, and ESA (the others were present in <15% of the cases). Two CSC profiles were defined: CD24/CD44 (CSC-1) and CD133/ESA (CSC-2). CSC-1 was significantly associated to patients older than 40 years, tumors of <2.0 cm in diameter, early clinical stages (P<0.05), and increased death risk of 4 times (P=0.03; 95% confidence interval, 1.09-14.41). CSC-2 was related to increased relapse risk of 3.75 times (P=0.04; 95% confidence interval, 1.02-13.69).<br><br>CONCLUSION: The detection of the most frequently positive CSC markers by immunohistochemistry is of clinicopathologic and prognostic relevance.}, }
@article {pmid28717182, year = {2017}, author = {Bjørklund, SS and Panda, A and Kumar, S and Seiler, M and Robinson, D and Gheeya, J and Yao, M and Alnæs, GIG and Toppmeyer, D and Riis, M and Naume, B and Børresen-Dale, AL and Kristensen, VN and Ganesan, S and Bhanot, G}, title = {Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {5568}, pmid = {28717182}, issn = {2045-2322}, mesh = {*Alternative Splicing ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cohort Studies ; Databases, Genetic ; Exons ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Sequence Analysis, RNA/methods ; }, abstract = {Cancer cells can have different patterns of exon usage of individual genes when compared to normal tissue, suggesting that alternative splicing may play a role in shaping the tumor phenotype. The discovery and identification of gene variants has increased dramatically with the introduction of RNA-sequencing technology, which enables whole transcriptome analysis of known, as well as novel isoforms. Here we report alternative splicing and transcriptional events among subtypes of invasive ductal carcinoma in The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Alternative exon usage was widespread, and although common events were shared among three subtypes, ER+ HER2-, ER- HER2-, and HER2+, many events on the exon level were subtype specific. Additional RNA-seq analysis was carried out in an independent cohort of 43 ER+ HER2- and ER- HER2- primary breast tumors, confirming many of the exon events identified in the TCGA cohort. Alternative splicing and transcriptional events detected in five genes, MYO6, EPB41L1, TPD52, IQCG, and ACOX2 were validated by qRT-PCR in a third cohort of 40 ER+ HER2- and ER- HER2- patients, showing that these events were truly subtype specific.}, }
@article {pmid28710742, year = {2018}, author = {Avnon, A and Orkaby, N and Hadas, A and Berger, U and Brunstein Klomek, A and Fennig, S}, title = {Inpatient weight curve trajectory as a prognostic factor among adolescents with anorexia nervosa: a preliminary report.}, journal = {Eating and weight disorders : EWD}, volume = {23}, number = {5}, pages = {645-651}, pmid = {28710742}, issn = {1590-1262}, mesh = {Adolescent ; Anorexia Nervosa/physiopathology/*therapy ; Body Mass Index ; Body Weight/*physiology ; Child ; Female ; Humans ; *Inpatients ; Male ; Patient Discharge ; Prognosis ; Recurrence ; Risk Factors ; Treatment Outcome ; Weight Gain/*physiology ; }, abstract = {OBJECTIVE: To investigate the predictive value of weight restoration trajectories for relapse within the first year after discharge from inpatient treatment among adolescents with AN.<br><br>METHODS: Forty four inpatient adolescents (5 boys, 39 girls) aged 11-18 (M 14.85, SD 1.87) diagnosed with anorexia were assessed at admission and discharge from a general hospital inpatient ward. Re-hospitalizations within 1&#xa0;year of discharge were recorded. Factors assessed included 1/BMI at admission, 2/BMI at discharge, 3/percent from target weight (PFTW) at discharge, 4/length of hospitalization, and 5/a weight restoration trajectory measuring weight drops during inpatient weight restoration (rates of negative cubic variation in body weight (NCV).<br><br>RESULTS: Logistic regression indicated that negative cubic variation rates (NCV) predicted re-hospitalization. PFTW was found only marginally significant.<br><br>CONCLUSION: Variations in weight restoration during inpatient treatment may be used to identify patients at risk for relapse. NCV can alert clinicians to initiate early relapse prevention interventions before discharge. Level of Evidence Level III, cohort study.}, }
@article {pmid28709865, year = {2017}, author = {Wan, G and Tian, L and Yu, Y and Li, F and Wang, X and Li, C and Deng, S and Yu, X and Cai, X and Zuo, Z and Cao, F}, title = {Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer.}, journal = {Biochemical and biophysical research communications}, volume = {491}, number = {1}, pages = {104-111}, doi = {10.1016/j.bbrc.2017.07.053}, pmid = {28709865}, issn = {1090-2104}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/*mortality/pathology ; China/epidemiology ; Female ; Fucosyltransferases/*metabolism ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prevalence ; Prognosis ; Receptor, Notch1/*metabolism ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Up-Regulation ; }, abstract = {PURPOSE: The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer.<br><br>MATERIAL AND METHODS: Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter.<br><br>RESULTS: Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p&#xa0;<&#xa0;0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p&#xa0;=&#xa0;0.005 for Pofut1, p&#xa0;<&#xa0;0.001 for N1IC, p&#xa0;=&#xa0;0.017 for Slug), advanced stage(p&#xa0;=&#xa0;0.039 for Pofut1, p&#xa0;=&#xa0;0.025 for N1IC) and higher histological grade(p&#xa0;=&#xa0;0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r&#xa0;=&#xa0;0.244, p&#xa0;=&#xa0;0.001; r&#xa0;=&#xa0;0.374, p&#xa0;<&#xa0;0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r&#xa0;=&#xa0;0.496, p&#xa0;<&#xa0;0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome.<br><br>CONCLUSION: Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer.}, }
@article {pmid28702871, year = {2018}, author = {Hirayama, K and Kono, H and Nakata, Y and Akazawa, Y and Wakana, H and Fukushima, H and Fujii, H}, title = {Expression of podoplanin in stromal fibroblasts plays a pivotal role in the prognosis of patients with pancreatic cancer.}, journal = {Surgery today}, volume = {48}, number = {1}, pages = {110-118}, pmid = {28702871}, issn = {1436-2813}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*genetics/mortality/*pathology ; Disease-Free Survival ; Female ; Fibroblasts/*metabolism/*pathology ; *Gene Expression ; Humans ; Lymphatic Metastasis ; Male ; Membrane Glycoproteins/*genetics/*metabolism ; Middle Aged ; Pancreatic Neoplasms/*genetics/mortality/*pathology ; Prognosis ; Proportional Hazards Models ; Risk Factors ; }, abstract = {PURPOSE: To investigate the role of podoplanin (PDPN) expression in invasive ductal carcinoma of the pancreas (IDCP) in humans.<br><br>METHODS: Tumor samples were obtained from 95 patients with IDCP. Immunohistochemical staining was done to evaluate the expression of PDPN in cancer tissues.<br><br>RESULTS: PDPN was detected predominantly in stromal fibroblasts, stained with &#x3b1;-smooth muscle actin. The cutoff value of PDPN-positive areas was calculated according to a histogram. There was no significant difference in clinicopathologic factors between patients with high vs. those with low PDPN expression. The high PDPN group showed significantly poorer disease-free and disease-specific survival rates than the low PDPN group. Among patients from the high PDPN group, those with lymph node metastases and those with a tumor larger than 20&#xa0;cm in diameter had significantly poorer prognoses than similar patients from the low PDPN group. Multivariate Cox proportional hazards analysis indicated that a high expression of PDPN was an independent risk factor for disease-specific survival.<br><br>CONCLUSIONS: PDPN expression in cancer-related fibrotic tissues is associated with a poor prognosis, especially in patients with large tumors or lymph node metastases.}, }
@article {pmid28700421, year = {2018}, author = {Xing, D and Jenson, EG and Zwick, CA and Rodriguez, FJ and Kurman, RJ}, title = {Atypical Proliferative (Borderline) Serous Tumor in the Brain: A Case Report.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {37}, number = {1}, pages = {52-56}, doi = {10.1097/PGP.0000000000000389}, pmid = {28700421}, issn = {1538-7151}, mesh = {Biomarkers, Tumor/metabolism ; Biopsy ; Brain/pathology ; Brain Neoplasms/diagnostic imaging/pathology/*secondary ; Breast Neoplasms/*pathology/surgery ; Cell Proliferation ; Cystadenocarcinoma, Serous/diagnostic imaging/pathology/*secondary/surgery ; Cystadenofibroma/diagnostic imaging/*pathology/surgery ; Diagnosis, Differential ; Encephalomalacia/diagnostic imaging/pathology/surgery ; Epithelial Cells/pathology ; Fallopian Tubes/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Ovarian Neoplasms/*pathology/surgery ; Salpingo-oophorectomy ; }, abstract = {A 59-year-old woman with a remote history of invasive ductal carcinoma of the breast was found on a follow-up computed tomography scan of her brain to have a 1-cm lesion in the right frontal lobe in 2008. In the ensuing years, before her current admission, multiple imaging studies of the brain revealed that the lesion was stable and it was, therefore, interpreted as a small area of encephalomalacia related to a thrombosed cortical vein, a cavernoma, or treated metastatic breast cancer. In 2013, the patient underwent a bilateral salpingo-oophorectomy for ovarian tumors that were diagnosed as bilateral serous cystadenofibromas. A partial omentectomy showed no evidence of implants. In June 2016, the brain lesion was completely excised and diagnosed as an atypical proliferative (borderline) serous tumor. Immunohistochemical staining demonstrated that the tumor cells were immunoreactive for Pax8, WT-1, ER, and CK-7 and negative for Gata-3, PR, TTF-1, CDX-2, Napsin A, and CK-20, which was consistent with that diagnosis. We present a brief review of possible mechanisms to account for this unusual presentation and speculate that the most likely one is exfoliation of fallopian tube epithelial cells into the peritoneal cavity, which then gain access to lymphatics resulting in cells implanting in the brain and subsequently progressing to an atypical proliferative (borderline) serous tumor.}, }
@article {pmid28693516, year = {2017}, author = {Sun, X and Zuo, K and Huang, D and Yu, B and Cheng, Y and Yang, W}, title = {Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report.}, journal = {Diagnostic pathology}, volume = {12}, number = {1}, pages = {52}, pmid = {28693516}, issn = {1746-1596}, mesh = {Biomarkers, Tumor/metabolism ; Breast/pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Lobular/*secondary ; Female ; Humans ; Immunohistochemistry/methods ; Middle Aged ; Pancreatic Neoplasms/*secondary ; Receptors, Progesterone ; }, abstract = {BACKGROUND: Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare.<br><br>CASE PRESENTATION: We report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast.<br><br>CONCLUSIONS: To the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.}, }
@article {pmid28681371, year = {2017}, author = {Kumaki, N and Okamatsu, C and Tokuda, Y and Nakamura, N}, title = {Breast Cancer in Patients of Rheumatoid Arthritis with Methotrexate Therapy Mimicking Histopathological Changes after Neoadjuvant Chemotherapy.}, journal = {The Tokai journal of experimental and clinical medicine}, volume = {42}, number = {2}, pages = {104-108}, pmid = {28681371}, issn = {2185-2243}, mesh = {Aged ; Antirheumatic Agents/*therapeutic use ; Arthritis, Rheumatoid/complications/*drug therapy ; Breast/*pathology ; Breast Neoplasms/complications/*pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/complications/*pathology/*therapy ; *Chemotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy ; Methotrexate/*therapeutic use ; Middle Aged ; *Neoadjuvant Therapy ; }, abstract = {Two breast cancer patients with a history of treatment for long-term rheumatoid arthritis (RA) had histological findings similar to histological changes seen in resected mammary gland specimens following neoadjuvant chemotherapy (NAC). The first patient was a 64-year-old woman who visited our hospital after feeling a lump in her left breast. The second patient was a 68-year-old woman who visited our hospital for an indentation in her left nipple. They were diagnosed with breast cancer following detailed examinations and underwent mastectomy. Both patients had a history of RA and were being treated with Methotrexate. The histological diagnoses of these patients were invasive ductal carcinoma, but frequent dispersal of cancer cell nests, stromal fibrosis, elastosis, edema and inflammatory cell infiltration were seen. Fibrosis was also found in the dissected lymph node. These histological findings were extremely similar to changes that occur in the mammary gland tissue after NAC; however, these patients had not undergone NAC. Methotrexate, which was being administered as an anti-rheumatic drug to the two patients, might have played a role similar to that of metronomic chemotherapy, which involves the continuous use of low-dose anti-cancer drugs, resulting in histological changes similar to those seen after NAC.}, }
@article {pmid28671041, year = {2017}, author = {Liu, B and Xiong, J and Liu, G and Wu, J and Wen, L and Zhang, Q and Zhang, C}, title = {High expression of Rac1 is correlated with partial reversed cell polarity and poor prognosis in invasive ductal carcinoma of the breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {39}, number = {7}, pages = {1010428317710908}, doi = {10.1177/1010428317710908}, pmid = {28671041}, issn = {1423-0380}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Polarity ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; *Prognosis ; rac1 GTP-Binding Protein/*biosynthesis/genetics ; }, abstract = {The change of cell polarity is usually associated with invasion and metastasis. Partial reverse cell polarity in IDC-NOS may play a role in lymphatic tumor spread. Rac1 is a kind of polarity related protein. It plays an important role in invasion and metastasis in tumors. We here investigated the expression of Rac1 and partial reverse cell polarity status in breast cancer and evaluated their value for prognosis in breast cancer. The association of the expression of Rac1 and MUC-1 with clinicopathological parameters and prognostic significance was evaluated in 162 cases of IDC-NOS paraffin-embedded tissues by immunohistochemical method. The Rac1 messenger RNA expression was measured by real-time polymerase chain reaction in 30 breast cancer patients, which was divided into two groups of partial reverse cell polarity and no partial reverse cell polarity. We found that lymph node metastasis of partial reverse cell polarity patients was higher than no partial reverse cell polarity patients (Z = -4.030, p = 0.000). Rac1 was upregulated in partial reverse cell polarity group than no partial reverse cell polarity group (Z = -3.164, p = 0.002), and there was correlationship between the expression of Rac1 and partial reverse cell polarity status (rs = 0.249, p = 0.001). The level of Rac1 messenger RNA expression in partial reverse cell polarity group was significantly higher compared to no partial reverse cell polarity group (t = -2.527, p = 0.017). Overexpression of Rac1 and partial reverse cell polarity correlates with poor prognosis of IDC-NOS patients (p = 0.011). Partial reverse cell polarity and lymph node metastasis remained as independent predictors for poor disease-free survival of IDC-NOS (p = 0.023, p = 0.046). Our study suggests that partial reverse cell polarity may lead to poor prognosis of breast cancer. Overexpression of Rac1 may lead to polarity change in IDC-NOS of the breast. Therefore, Rac1 could be a therapeutic target for breast cancer.}, }
@article {pmid28661760, year = {2017}, author = {Curigliano, G and Criscitiello, C}, title = {Maximizing the Clinical Benefit of Anthracyclines in Addition to Taxanes in the Adjuvant Treatment of Early Breast Cancer.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {35}, number = {23}, pages = {2600-2603}, doi = {10.1200/JCO.2017.72.5960}, pmid = {28661760}, issn = {1527-7755}, mesh = {Anthracyclines/administration &amp; dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Breast Neoplasms/pathology/*therapy ; Bridged-Ring Compounds/administration &amp; dosage ; Carcinoma, Ductal, Breast/secondary/*therapy ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; *Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Radiotherapy, Adjuvant ; Taxoids/administration &amp; dosage ; }, abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A healthy 56-year-old postmenopausal woman discovered a palpable mass at the one o'clock position of the left breast. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer that measured 3.5 cm. There was extensive lymphovascular invasion. Pathology review indicated a poorly differentiated, grade 3 invasive ductal carcinoma and ductal carcinoma in situ (largest focus, 3.5 cm). The margins were negative. Two of the 11 axillary lymph nodes contained metastatic carcinoma. Immunohistochemical studies previously obtained on the core biopsy indicated that the tumor was positive for estrogen receptor expression (50%), negative for progesterone receptor expression, and had a Ki-67 score of 60%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. Our multidisciplinary tumor board recommended adjuvant chemotherapy, postmastectomy radiation therapy, and endocrine therapy. A 52-year-old postmenopausal woman presented with a palpable mass of the right breast. An initial core biopsy confirmed carcinoma in the breast. She underwent quadrantectomy and axillary node dissection. The final pathology report disclosed a moderately differentiated invasive ductal carcinoma (diameter, 2.5 cm). The margins were negative. None of the three sentinel lymph nodes contained metastatic carcinoma. Immunohistochemical studies showed that the tumor was positive for estrogen receptor expression (90%) and for progesterone receptor expression (40%) and had a Ki-67 score of 20%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. A genomic assay was obtained and suggested an intermediate to high risk of recurrence. Her past medical history was notable for hypertension and moderately overweight status (body mass index, 39 kg/m[2]). Our multidisciplinary tumor board recommended adjuvant chemotherapy, postsurgical radiation therapy, and endocrine therapy.}, }
@article {pmid28658335, year = {2017}, author = {Aquino, RGF and Vasques, PHD and Cavalcante, DIM and Oliveira, ALS and Oliveira, BMK and Pinheiro, LGP}, title = {Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {44}, number = {2}, pages = {163-170}, doi = {10.1590/0100-69912017002010}, pmid = {28658335}, issn = {1809-4546}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology/*secondary ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {OBJECTIVE: to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma.<br><br>METHODS: this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Cear&#xe1;, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-Bloom-Richadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases.<br><br>RESULTS: the mean patients'age was 56.81 years &#xb1; 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm &#xb1; 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and p<0.0001).<br><br>CONCLUSION: elevated mitotic indexes, tumors with a diameter greater than 2cm and the presence of angiolymphatic invasion were individuallyassociatedwith the occurrence of axillary metastases.}, }
@article {pmid28652380, year = {2017}, author = {Gil Del Alcazar, CR and Huh, SJ and Ekram, MB and Trinh, A and Liu, LL and Beca, F and Zi, X and Kwak, M and Bergholtz, H and Su, Y and Ding, L and Russnes, HG and Richardson, AL and Babski, K and Min Hui Kim, E and McDonnell, CH and Wagner, J and Rowberry, R and Freeman, GJ and Dillon, D and Sorlie, T and Coussens, LM and Garber, JE and Fan, R and Bobolis, K and Allred, DC and Jeong, J and Park, SY and Michor, F and Polyak, K}, title = {Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.}, journal = {Cancer discovery}, volume = {7}, number = {10}, pages = {1098-1115}, pmid = {28652380}, issn = {2159-8290}, support = {F32 CA156991/CA/NCI NIH HHS/United States ; R35 CA197623/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; }, mesh = {B7-H1 Antigen/genetics ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*immunology ; CD3 Complex/genetics ; Carcinoma, Ductal, Breast/genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*immunology ; Disease Progression ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Leukocyte Common Antigens/genetics ; Receptor, ErbB-2/genetics ; T-Lymphocytes/*immunology ; Tumor Microenvironment ; }, abstract = {To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45[+]CD3[+] T cells demonstrated a decrease in CD8[+] signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB[+]CD8[+] T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2[+] breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047.}, }
@article {pmid28647915, year = {2017}, author = {Kizy, S and Huang, JL and Marmor, S and Tuttle, TM and Hui, JYC}, title = {Impact of the 21-gene recurrence score on outcome in patients with invasive lobular carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {165}, number = {3}, pages = {757-763}, doi = {10.1007/s10549-017-4355-9}, pmid = {28647915}, issn = {1573-7217}, mesh = {Adolescent ; Adult ; Aged ; *Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Carcinoma, Lobular/*genetics/*mortality/pathology ; Female ; *Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Young Adult ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) of the breast has unique clinicopathologic characteristics, compared to invasive ductal carcinoma. The role of the 21-gene Recurrence Score (RS) has not been clearly defined for ILC. We sought to determine the prognostic value of RS and the impact of adjuvant chemotherapy on long-term survival in patients with ILC.<br><br>METHODS: Utilizing the Surveillance, Epidemiology and End Results database from 2004 to 2013, we identified records of women aged 18-74&#xa0;years, diagnosed with estrogen receptor (ER)-positive ILC (stage I to III) with RS available. We categorized patients into risk groups based on the traditional RS cutoffs and into those of the Trial Assigning Individualized Options for Treatment (TAILORx). Five-year breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and Cox proportional hazards models.<br><br>RESULTS: Of the 7316 women included, 21% were in the low-risk; 71%, intermediate-risk; and 8%, high-risk groups as per TAILORx RS cutoffs. The 5-year BCSS was 99% in the low-risk, 99% in the intermediate-risk, and 96% in the high-risk groups. A high-risk RS as per TAILORx cutoff was independently associated with increased mortality (hazard ratio [HR] of death 2.37, 95% confidence interval [CI] 1.14-4.95) when compared to a low-risk RS. In both the high-risk and intermediate-risk groups, adjuvant chemotherapy was not significantly associated with the HR of death (high-risk, HR 1.14, 95% CI 0.55-2.38; intermediate-risk, HR 1.08, 95% CI 0.62-1.87).<br><br>CONCLUSION: For patients with ER-positive ILC, 8% were in the high-risk and 72% were in the intermediate-risk groups as per the TAILORx RS cutoffs. In the high-risk group, the RS predicted a lower 5-year BCSS. Adjuvant chemotherapy did not seem to confer a survival benefit for either the intermediate- or the high-risk cohorts.}, }
@article {pmid28633434, year = {2017}, author = {Singh, DK and Gholamalamdari, O and Jadaliha, M and Ling Li, X and Lin, YC and Zhang, Y and Guang, S and Hashemikhabir, S and Tiwari, S and Zhu, YJ and Khan, A and Thomas, A and Chakraborty, A and Macias, V and Balla, AK and Bhargava, R and Janga, SC and Ma, J and Prasanth, SG and Lal, A and Prasanth, KV}, title = {PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes.}, journal = {Carcinogenesis}, volume = {38}, number = {10}, pages = {966-975}, pmid = {28633434}, issn = {1460-2180}, support = {R01 GM088252/GM/NIGMS NIH HHS/United States ; R01 GM099669/GM/NIGMS NIH HHS/United States ; R01 GM123314/GM/NIGMS NIH HHS/United States ; R01 HG007352/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Breast Neoplasms/*genetics/mortality/*pathology ; Cell Cycle/*genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chromatin/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Oncogenes ; Promoter Regions, Genetic ; RNA Polymerase II/genetics/metabolism ; Tissue Array Analysis ; Transcription Factors/*genetics/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; }, abstract = {Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.}, }
@article {pmid28631956, year = {2017}, author = {Siciliano, M and Santangelo, G and Trojsi, F and Di Somma, C and Patrone, M and Femiano, C and Monsurrò, MR and Trojano, L and Tedeschi, G}, title = {Coping strategies and psychological distress in caregivers of patients with Amyotrophic Lateral Sclerosis (ALS).}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {18}, number = {5-6}, pages = {367-377}, doi = {10.1080/21678421.2017.1285316}, pmid = {28631956}, issn = {2167-9223}, mesh = {*Adaptation, Psychological ; Adult ; Aged ; Amyotrophic Lateral Sclerosis/*psychology/*therapy ; Caregivers/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Quality of Life/psychology ; Stress, Psychological/*psychology/*therapy ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) causes distress in caregivers. The present study aims to examine the association between coping strategies and psychological distress in caregivers of ALS patients.<br><br>METHODS: Coping strategies were assessed in 96 ALS informal caregivers by means of the Coping Inventory for Stressful Situations. Data about caregivers' demographic characteristics, levels of burden, depression and anxiety (psychological distress) were also gathered by standardised questionnaires. Patients' clinical, cognitive and behavioural disturbances were evaluated by ALS specific assessment tools.<br><br>RESULTS: Sequential logistic regression analysis showed that emotion-oriented coping strategy was significantly associated with high levels of depressive (p&#x2009;<&#x2009;0.01) and anxiety (p&#x2009;<&#x2009;0.05) symptoms and high levels of burden (p&#x2009;<&#x2009;0.05), after controlling for all other variables. Moreover, a significant relationship of patients' functional dependence levels with burden experienced by caregivers was observed. No relationships were detected between task-oriented and avoidance-oriented coping strategies and caregivers' levels of psychological distress.<br><br>CONCLUSIONS: The present study supported the mediating effects of coping strategies on intensity of burden, depression and anxiety experienced by ALS caregivers. These findings suggest that interventions aimed at reducing utilisation of maladaptive coping strategies may improve well-being in ALS caregivers, and, possibly, management of symptoms in ALS patients.}, }
@article {pmid28628772, year = {2017}, author = {Carbognin, L and Sperduti, I and Fabi, A and Dieci, MV and Kadrija, D and Griguolo, G and Pilotto, S and Guarneri, V and Zampiva, I and Brunelli, M and Orvieto, E and Nortilli, R and Fiorio, E and Parolin, V and Manfrin, E and Caliò, A and Nisticò, C and Pellini, F and Scarpa, A and Pollini, GP and Conte, P and Tortora, G and Bria, E}, title = {Prognostic impact of proliferation for resected early stage 'pure' invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation.}, journal = {Breast (Edinburgh, Scotland)}, volume = {35}, number = {}, pages = {21-26}, doi = {10.1016/j.breast.2017.06.005}, pmid = {28628772}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/*pathology ; Carcinoma, Lobular/*immunology/*pathology ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Analysis ; }, abstract = {INTRODUCTION: The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage 'pure' invasive lobular carcinoma (ILC).<br><br>METHODS: Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well.<br><br>RESULTS: Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p&#xa0;=&#xa0;0.007) and 79.4% and 69.2% (p&#xa0;=&#xa0;0.03) for patients with Ki67&#xa0;&#x2264;&#xa0;4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p&#xa0;=&#xa0;0.02, DFS was 84.0% and 52.6%, p&#xa0;=&#xa0;0.0003, for patients with Ki67&#xa0;&#x2264;&#xa0;14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap.<br><br>CONCLUSIONS: Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology.}, }
@article {pmid28625415, year = {2018}, author = {de Zárraga Mata, C and Thomas Salom, G and Vilella Martorell, A and Salvà Ramonell, F and Maura Oliver, &#xc1;L and Dolz Abadía, C}, title = {Gastric metastatic extension of invasive ductal carcinoma of the breast with atypical endoscopic presentation.}, journal = {Gastroenterologia y hepatologia}, volume = {41}, number = {5}, pages = {304-305}, doi = {10.1016/j.gastrohep.2017.04.006}, pmid = {28625415}, issn = {0210-5705}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary/therapy ; Chemoradiotherapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; *Gastroscopy ; Humans ; Image-Guided Biopsy ; Incidental Findings ; Lymphatic Metastasis ; Mastectomy, Segmental ; Stomach Neoplasms/*diagnostic imaging/therapy ; }, }
@article {pmid28623240, year = {2017}, author = {Vegiopoulos, A and Rohm, M and Herzig, S}, title = {Adipose tissue: between the extremes.}, journal = {The EMBO journal}, volume = {36}, number = {14}, pages = {1999-2017}, pmid = {28623240}, issn = {1460-2075}, mesh = {Adipokines ; Adipose Tissue/*pathology ; Animals ; Atrophy/pathology/physiopathology ; *Energy Metabolism ; Homeostasis ; Humans ; *Lipid Metabolism ; Obesity/pathology/physiopathology ; }, abstract = {Adipose tissue represents a critical component in healthy energy homeostasis. It fulfills important roles in whole-body lipid handling, serves as the body's major energy storage compartment and insulation barrier, and secretes numerous endocrine mediators such as adipokines or lipokines. As a consequence, dysfunction of these processes in adipose tissue compartments is tightly linked to severe metabolic disorders, including obesity, metabolic syndrome, lipodystrophy, and cachexia. While numerous studies have addressed causes and consequences of obesity-related adipose tissue hypertrophy and hyperplasia for health, critical pathways and mechanisms in (involuntary) adipose tissue loss as well as its systemic metabolic consequences are far less understood. In this review, we discuss the current understanding of conditions of adipose tissue wasting and review microenvironmental determinants of adipocyte (dys)function in related pathophysiologies.}, }
@article {pmid28618949, year = {2017}, author = {Zhao, HY and Han, Y and Wang, J and Yang, LH and Zheng, XY and Du, J and Wu, GP and Wang, EH}, title = {IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {39}, number = {6}, pages = {1010428317705769}, doi = {10.1177/1010428317705769}, pmid = {28618949}, issn = {1423-0380}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal/*genetics/pathology/surgery ; Cyclin D1/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Prognosis ; Proto-Oncogene Proteins c-myc/genetics ; Survival Analysis ; Wnt Signaling Pathway/genetics ; beta Catenin/genetics ; ras GTPase-Activating Proteins/*genetics ; }, abstract = {IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.}, }
@article {pmid28615042, year = {2017}, author = {Darekar, A and Lamontagne, A and Fung, J}, title = {Locomotor circumvention strategies are altered by stroke: I. Obstacle clearance.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {14}, number = {1}, pages = {56}, pmid = {28615042}, issn = {1743-0003}, support = {MOP- 77548//Canadian Institutes of Health Research/International ; }, mesh = {Adult ; Aged ; Female ; Gait ; Humans ; *Locomotion ; Male ; Middle Aged ; Orientation ; Paresis/etiology/physiopathology ; Psychomotor Performance ; Stroke/*psychology ; Stroke Rehabilitation/methods ; User-Computer Interface ; Walking ; }, abstract = {BACKGROUND: Functional locomotion requires the ability to adapt to environmental challenges such as the presence of stationary or moving obstacles. Difficulties in obstacle circumvention often lead to restricted community ambulation in individuals with stroke. The objective of this study was to contrast obstacle circumvention strategies between post-stroke (n = 12) and healthy individuals (n = 12) performing locomotor and perceptuomotor (joystick navigation) tasks with different obstacle approaches.<br><br>METHODS: Participants walked and navigated with a joystick towards a central target, in a virtual environment simulating a large room, while avoiding an obstacle that either remained stationary at the pre-determined point of intersection or moved from head-on or diagonally 30&#xb0; left/right. The outcome measures included dynamic clearance (DC), instantaneous distance from obstacle at crossing (IDC), number of collisions and preferred side of circumvention. These measures were compared between groups (stroke vs. healthy), obstacle parameter (stationary vs. moving head-on) and direction of approach (left/paretic vs. right/non-paretic).<br><br>RESULTS: DC was significantly larger when circumventing a moving obstacle that approached head-on as compared to a stationary obstacle for both groups during both tasks, while not significantly different in either diagonal approach in either group. IDC was smaller in the stroke group while walking and larger in both groups during joystick navigation when avoiding moving as compared to stationary obstacle. IDC was significantly larger in the stroke group compared to controls for diagonal approaches during walking, wherein two different strategies emerged amongst individuals with stroke: circumventing to the same (Vsame n&#xa0;=&#xa0;6) or opposite (Vopp n&#xa0;=&#xa0;4) side of obstacle approach. This behavior was not seen in the perceptuomotor task, wherein post-stroke participants circumvented to opposite side of the obstacle approach as seen in healthy participants. In the locomotor task, the Vsame subgroup that had greater functional limitations used larger DC as compared to the Vopp subgroup and healthy individuals. The remaining two individuals with stroke collided with obstacles in >50% trials of either obstacle approach. The underlying mechanisms for collision were however different for both individuals.<br><br>CONCLUSION: Avoidance strategies in individuals with stroke can vary depending on the individual locomotor capabilities and obstacle characteristics.}, }
@article {pmid28592128, year = {2017}, author = {Li, J and Zhang, X and Zheng, L and Liu, Y}, title = {Association of nuclear FOXP3 expression with low Ki67 index and better prognosis in patients with breast invasive ductal carcinoma.}, journal = {Neoplasma}, volume = {64}, number = {5}, pages = {754-761}, doi = {10.4149/neo_2017_514}, pmid = {28592128}, issn = {0028-2685}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Female ; Forkhead Transcription Factors/genetics/*metabolism ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*metabolism ; Prognosis ; }, abstract = {Recent studies have provided clear evidence that some types of human cancer cells expressed Forkhead Box Protein 3 (FOXP3). However, the presence and role of FOXP3 in breast cancer are still contradictory up to now. In this study, we detected the expression of FOXP3 protein by immunohistochemistry in 123 cases of breast invasive ductal carcinoma. It exhibited that the subcellular localization of FOXP3 expression in breast cancer cells is heterogeneous. In nucleus, FOXP3 expression ratio was 47.97% (59/123) and the nuclear FOXP3 expression was significantly associated with lower Ki67 index (P=0.041), negative vessel tumor embolus (P=0.024). It was also significantly correlated with the molecular subtypes of breast cancer (P=0.002), displaying the highest ratio in the Luminal A subtype (68.18%). Kaplan-Meier analysis indicated that high nuclear FOXP3 expression was associated with better overall survival (OS) (94.92% vs. 82.81%, P=0.022) and disease-free survival (DFS) (91.53% vs. 76.56%, P=0.026). Moreover, nuclear FOXP3 represented an independent prognostic factor for OS (P =0.033) in multivariate analysis. However, in cytoplasm, FOXP3 expression ratio was 63.41% (78/123) and no statistic prognostic significance was found. Thus, our data demonstrated that nuclear FOXP3 expression correlated with low Ki-67 index and better outcome in breast invasive ductal carcinoma, indicating that FOXP3 acted as a potential prognostic marker for breast cancer.}, }
@article {pmid28591263, year = {2017}, author = {Rodrigues, FT and Klemig, LR and Cardozo, MRP and Alves, PC and Aguiar, VM and Lessa, CS}, title = {Myiasis associated with an invasive ductal carcinoma of the left breast: case study.}, journal = {Revista do Instituto de Medicina Tropical de Sao Paulo}, volume = {59}, number = {}, pages = {e35}, pmid = {28591263}, issn = {1678-9946}, mesh = {Adult ; Animals ; Antiparasitic Agents/therapeutic use ; Breast Neoplasms/*complications/parasitology ; Carcinoma, Ductal/*complications/parasitology ; Female ; Humans ; Ivermectin/therapeutic use ; Larva ; Myiasis/*complications/diagnosis/drug therapy ; }, abstract = {Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis.}, }
@article {pmid28576605, year = {2017}, author = {Siciliano, M and De Micco, R and Trojano, L and De Stefano, M and Baiano, C and Passaniti, C and De Mase, A and Russo, A and Tedeschi, G and Tessitore, A}, title = {Cognitive impairment is associated with Hoehn and Yahr stages in early, de novo Parkinson disease patients.}, journal = {Parkinsonism &amp; related disorders}, volume = {41}, number = {}, pages = {86-91}, doi = {10.1016/j.parkreldis.2017.05.020}, pmid = {28576605}, issn = {1873-5126}, mesh = {Aged ; Cognition Disorders/*diagnosis/*etiology ; Executive Function ; Female ; Humans ; Male ; Mental Recall ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*complications ; *Severity of Illness Index ; Statistics, Nonparametric ; }, abstract = {INTRODUCTION: The relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages.<br><br>METHODS: Forty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II.<br><br>RESULTS: Patients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p&#xa0;=&#xa0;0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p&#xa0;<&#xa0;0.0001), 10 points Clock Drawing Test (p&#xa0;=&#xa0;0.002), and Rey-Osterrieth Complex Figure&#xa0;Test -copy (p&#xa0;<&#xa0;0.0001). ORs of having cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II.<br><br>CONCLUSION: In de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI.}, }
@article {pmid28567703, year = {2017}, author = {Baglia, ML and Malone, KE and Tang, MC and Li, CI}, title = {Alcohol Intake and Risk of Breast Cancer by Histologic Subtype and Estrogen Receptor Status Among Women Aged 55 to 74 Years.}, journal = {Hormones &amp; cancer}, volume = {8}, number = {4}, pages = {211-218}, pmid = {28567703}, issn = {1868-8500}, support = {R01 CA105041/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; *Alcohol Drinking/adverse effects ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/*etiology/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Population Surveillance ; Receptors, Estrogen/*metabolism ; Risk ; SEER Program ; Socioeconomic Factors ; }, abstract = {Previous studies suggest that alcohol consumption and risk of breast cancer may differ by histologic subtype and hormone receptor status, though results are not entirely consistent. In this population-based case-control study, we evaluated the association between alcohol consumption and risk of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and invasive ductal-lobular carcinoma (IDLC) overall and by estrogen receptor (ER) status, among women aged 55-74 years of age. Using polytomous regression, associations between current alcohol consumption, overall and by type of alcohol, and breast cancer risk were evaluated in 891 controls and 905 IDC, 567 ILC, and 489 IDLC cases. Current alcohol use was moderately associated with risk of ILC (odds ratio = 1.25, 95% confidence interval 0.99, 1.58) with a positive dose-response relationship based on average number of drinks per week consumed (P trend = 0.0005). When further stratified by ER status, alcohol use was positively associated with risk of ER+ ILC (P trend = 0.002) and ER+ IDC (P trend = 0.02), but inversely associated with risk of ER-IDC (P trend = 0.01). No association between alcohol and risk of IDLC tumors was observed. While the link between alcohol consumption and breast cancer risk is well established, our results suggest that the increased risk associated with alcohol is largely limited to ER+ ILC and ER+ IDC. Thus, avoiding or moderating alcohol consumption may be one way that women can lower their risks of these forms of breast cancer.}, }
@article {pmid28567637, year = {2017}, author = {Lambein, K and Van Bockstal, M and Vandemaele, L and Van den Broecke, R and Cocquyt, V and Geenen, S and Denys, H and Libbrecht, L}, title = {Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {471}, number = {5}, pages = {575-587}, pmid = {28567637}, issn = {1432-2307}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Disease Progression ; Female ; Gene Amplification ; Humans ; Middle Aged ; Receptor, ErbB-2/*genetics ; }, abstract = {Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.}, }
@article {pmid28561207, year = {2017}, author = {Rice, GI and Kitabayashi, N and Barth, M and Briggs, TA and Burton, ACE and Carpanelli, ML and Cerisola, AM and Colson, C and Dale, RC and Danti, FR and Darin, N and De Azua, B and De Giorgis, V and De Goede, CGL and Desguerre, I and De Laet, C and Eslahi, A and Fahey, MC and Fallon, P and Fay, A and Fazzi, E and Gorman, MP and Gowrinathan, NR and Hully, M and Kurian, MA and Leboucq, N and Lin, JS and Lines, MA and Mar, SS and Maroofian, R and Martí-Sanchez, L and McCullagh, G and Mojarrad, M and Narayanan, V and Orcesi, S and Ortigoza-Escobar, JD and Pérez-Dueñas, B and Petit, F and Ramsey, KM and Rasmussen, M and Rivier, F and Rodríguez-Pombo, P and Roubertie, A and Stödberg, TI and Toosi, MB and Toutain, A and Uettwiller, F and Ulrick, N and Vanderver, A and Waldman, A and Livingston, JH and Crow, YJ}, title = {Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease.}, journal = {Neuropediatrics}, volume = {48}, number = {3}, pages = {166-184}, pmid = {28561207}, issn = {1439-1899}, support = {309449/ERC_/European Research Council/International ; K12 NS001692/NS/NINDS NIH HHS/United States ; MR/M501803/1/MRC_/Medical Research Council/United Kingdom ; TRF-2016-09-002/DH_/Department of Health/United Kingdom ; }, mesh = {Adenosine Deaminase/*genetics ; Adolescent ; Adult ; Autoimmune Diseases of the Nervous System/diagnostic imaging/*genetics/*immunology ; Biomarkers/metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interferon Type I/*metabolism ; Male ; Mutation ; Nervous System Malformations/diagnostic imaging/*genetics/*immunology ; Phenotype ; RNA-Binding Proteins/*genetics ; Young Adult ; }, abstract = {We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi-Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64-25.71) compared with controls (median: 0.93, IQR: 0.57-1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context.}, }
@article {pmid28560596, year = {2017}, author = {Petruolo, OA and Pilewskie, M and Patil, S and Barrio, AV and Stempel, M and Wen, HY and Morrow, M}, title = {Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy.}, journal = {Annals of surgical oncology}, volume = {24}, number = {9}, pages = {2556-2562}, pmid = {28560596}, issn = {1534-4681}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*drug therapy/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary/surgery ; Carcinoma, Lobular/*drug therapy/metabolism/secondary/surgery ; Chemotherapy, Adjuvant ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR).<br><br>OBJECTIVE: The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC.<br><br>METHODS: Patients with stage I-III ER+, HER2- breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP).<br><br>RESULTS: From 2007 to 2016, 402 ER+/HER2- cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II-III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients (p&#xa0;<&#xa0;0.0001). Patients with ILC initially ineligible for BCS (n&#xa0;=&#xa0;56) were less likely to downstage than those with invasive ductal carcinoma (IDC; n&#xa0;=&#xa0;183, 16 vs. 48%, p&#xa0;&#x2264;&#xa0;0.0001), with a similar trend in the axilla (p&#xa0;=&#xa0;0.086). The rates of BCS eligibility after NAC were highest in PR-/HP patients (62%) and lowest in PR+/non-HP patients (29%) [p&#xa0;=&#xa0;0.005]. In the axilla, nodal pCR among cN+ patients (n&#xa0;=&#xa0;301) ranged from 0 to 35% (p&#xa0;<&#xa0;0.0001) within these groups, and was most frequent in PR-/HP patients.<br><br>CONCLUSIONS: ER+/HER2- patients most likely to benefit from NAC are those with PR- and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared with IDC. The use of these criteria can assist in defining the initial treatment approach.}, }
@article {pmid28554530, year = {2017}, author = {Hidmark, A and Spanidis, I and Fleming, TH and Volk, N and Eckstein, V and Groener, JB and Kopf, S and Nawroth, PP and Oikonomou, D}, title = {Electrical Muscle Stimulation Induces an Increase of VEGFR2 on Circulating Hematopoietic Stem Cells in Patients With Diabetes.}, journal = {Clinical therapeutics}, volume = {39}, number = {6}, pages = {1132-1144.e2}, doi = {10.1016/j.clinthera.2017.05.340}, pmid = {28554530}, issn = {1879-114X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Count ; Diabetes Mellitus/blood/metabolism/*therapy ; *Electric Stimulation Therapy ; Female ; Hematopoietic Stem Cells/*metabolism ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; Vascular Endothelial Growth Factor Receptor-2/*metabolism ; Young Adult ; }, abstract = {PURPOSE: External electric muscle stimulation (EMS) of the thigh muscles was found to reduce pain resulting from diabetic neuropathy (DN), a vascular complication of diabetes. This study investigated circulating hematopoietic stem cells (HSCs) after EMS treatment. Impaired function of HSCs and the subpopulation endothelial progenitor cells (EPCs), important for neovascularization and endothelial repair, has been associated with DN.<br><br>METHODS: Twenty-four patients with painful DN were treated 3 times with EMS over a period of 1 week. Blood samples were collected before and after the first EMS treatment. Before a fourth treatment, neuropathic pain was evaluated and a third blood sample was collected. Cells were used for flow cytometry.<br><br>FINDINGS: Patients with painful DN reported that the pain decreased after 3 times of 1-hour treatments with EMS (Neuropathy Symptom Score: from 8 to 6, P = 0.001; Neuropathy Disability Score: from 5.5 to 5, P = 0.027, n = 24). At the end of the study, diastolic blood pressure had decreased from 80 to 70 mm Hg (P = 0.043), and plasma adrenaline and noradrenaline metabolites metanephrine and normetanephrine were reduced (both P &#x2264; 0.01; n = 21). A single EMS treatment caused an immediate and transient decrease in the frequency of CD34[+] HSCs in circulation (-20%; P < 0.001; n = 27). In 9 of the patients with DN, the proportion of HSCs expressing vascular endothelial growth factor receptor 2 (VEGFR2; defining the HSCs as EPCs) increased by 36% (P = 0.011) after EMS treatment. Proteins required for binding to endothelium (junctional adhesion molecule A and CD31), homing toward hypoxic tissue (C-X-C chemokine receptor type 4), and endothelial differentiation (CD31) were increased on HSCs immediately after EMS treatment. An increased frequency of VEGFR2 expression was also observed on HSCs of 6 healthy control volunteers (34%; P = 0.046) after EMS treatment, but not after sham treatment.<br><br>IMPLICATIONS: Three EMS treatments decreased symptoms of pain caused by DN and reduced diastolic blood pressure and biomarkers of stress. A single EMS treatment increased molecules mediating attachment and differentiation on the surface of HSCs in circulation. We hypothesize that the EMS-induced increase in surface attachment molecules on the HSCs caused the HSCs to leave circulation and that EMS treatment improves the function of HSCs and EPCs in vivo.}, }
@article {pmid28543784, year = {2017}, author = {Chaudhuri, RK and Bojanowski, K}, title = {Improvement of hydration and epidermal barrier function in human skin by a novel compound isosorbide dicaprylate.}, journal = {International journal of cosmetic science}, volume = {39}, number = {5}, pages = {518-526}, doi = {10.1111/ics.12405}, pmid = {28543784}, issn = {1468-2494}, mesh = {Administration, Topical ; Aquaporin 3/metabolism ; Body Water ; Cadherins/genetics ; Caprylates/administration &amp; dosage/*pharmacology ; Cell Differentiation/drug effects ; Emollients/administration &amp; dosage ; Epidermis/*drug effects/metabolism ; Glycerol/administration &amp; dosage ; Humans ; Hyaluronan Receptors/metabolism ; Keratinocytes/cytology/drug effects ; Oligonucleotide Array Sequence Analysis ; Placebos ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; Up-Regulation/drug effects ; Water/metabolism ; }, abstract = {OBJECTIVE: The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin.<br><br>METHODS: The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo.<br><br>RESULTS: IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin.<br><br>CONCLUSION: Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing.}, }
@article {pmid28541858, year = {2017}, author = {Jean-Louis, CJ and Masdon, J and Smith, B and Battles, O and Dale, P}, title = {The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.}, journal = {The American surgeon}, volume = {83}, number = {5}, pages = {482-485}, pmid = {28541858}, issn = {1555-9823}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Carcinoma In Situ/*epidemiology/pathology/therapy ; Breast Neoplasms/*epidemiology/*pathology/therapy ; Carcinoma, Lobular/*epidemiology/pathology/therapy ; Female ; Humans ; Incidence ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*epidemiology/pathology/therapy ; Retrospective Studies ; Risk Factors ; }, abstract = {For years, lobular carcinoma In Situ (LCIS) has been considered a high-risk marker for developing breast cancer. It is well known that ductal carcinoma In Situ is a precursor for the development of invasive ductal carcinoma, and ductal carcinoma In Situ is reported to be present in invasive ductal carcinoma in at least 40 per cent of cases. A similar relationship between LCIS and invasive lobular carcinoma (ILC) remains in question. This study evaluates the incidence of synchronous LCIS and ILC at our institution. This is a retrospective review of our tumor registry database of women diagnosed with LCIS or ILC from 2000 to 2014. Pathology reports were evaluated to determine the incidence of pure ILC and mixed ILC/LCIS. Those with both LCIS/ILC (mixed group) and those with pure ILC (pure group) were compared for age, surgical intervention, lymph node involvement, tumor size, nuclear grade, and margins between these two groups. A total of 182 women were identified with LCIS, ILC, or mixed LCIS and ILC. There were 76 subjects with pure ILC and 90 with mixed LCIS and ILC. The median and age range for each group were 63.6 (range: 40-97) for the mixed and 64.1 (range: 40-86) for pure groups. Tumor size was evaluated for each group and the median tumor size was 2.5 cm (range: 0.1-7.0cm) for the mixed group and 3.0 cm (range: 0.5-12.5 cm) for the pure group. Nodal involvement was present in 35.23 per cent of the mixed group and 46.3 per cent in the pure group. Surgical treatment for each group was similar, with mastectomy being the preferred surgical option over breast conservation therapy in the mixed and pure groups, 67.07 and 64.71 per cent, respectively. Presently, LCIS is considered a marker, or risk factor, for development of future breast cancer. This retrospective study does identify a strong relationship, 54 per cent, between LCIS and ILC at diagnosis. This high percentage of concurrent LCIS and ILC in surgical/pathological specimens supports the notion that LCIS may in fact have a precursory role in development of invasive lobular carcinoma of the breast. Additional studies to further investigate this relationship between LCIS and ILC, including genomic analysis, are presently underway.}, }
@article {pmid28532133, year = {2017}, author = {Elyasinia, F and Keramati, MR and Ahmadi, F and Rezaei, S and Ashouri, M and Parsaei, R and Yaghoubi, M and Elyasinia, F and Aboutorabi, A and Kaviani, A}, title = {Neutrophil-Lymphocyte Ratio in Different Stages of Breast Cancer.}, journal = {Acta medica Iranica}, volume = {55}, number = {4}, pages = {228-232}, pmid = {28532133}, issn = {1735-9694}, mesh = {Adult ; Aged ; Blood Platelets ; Breast Neoplasms/*pathology ; Cross-Sectional Studies ; Female ; Humans ; Inflammation/*pathology ; Iran ; Lymphocytes/*metabolism/pathology ; Middle Aged ; Neoplasm Staging ; Neutrophils/*metabolism ; Prognosis ; }, abstract = {Despite many advances in the treatment of breast cancer, it is still the second most common cause of death in women in the United States. It has been shown that inflammation plays a major role in the treatment of these cancers and inflammatory factors enhance tumor growth, invasion, metastasis, and vascularization. In this study, we would like to analyze peripheral blood neutrophil-lymphocyte ratio (NLR) in breast cancer patients and its correlation with disease staging. This cross-sectional analytic study was conducted in Imam Hospital, affiliated with Tehran University of Medical Sciences; a total of 195 female patients with breast cancer met the inclusion criteria. All of the patients had a complete blood count with leukocyte differential performed before chemotherapy. Medical records including pathology reports were also available. Data for all patients were collected prior to any surgical intervention. Exclusion criteria included clinical evidence of active infection, presence of hematological disorders, acute as well as chronic inflammatory or autoimmune diseases, or prior steroid therapy. Higher platelet count was significantly associated with the higher stage. The stage was not associated with the hemoglobin level. There was no association between the tumor size and age of patients with NLR. There was a significant relationship between NLR and IDC. There was a significant relationship between IDC and NLRs of less than 8.1 and greater than 3.3. There was a significant relationship between NLR and vascular invasion. There was no association between NLR and estrogen receptor and HER2. There was no significant relationship between the PLR and the cancer stage. In this study, NLR showed a significant relation with the disease staging. As the NLR increases the stage increases as well. Therefore, this ratio may be helpful in the preoperative evaluation of patients with breast cancer.}, }
@article {pmid28531310, year = {2017}, author = {Lu, XM and Batugedara, G and Lee, M and Prudhomme, J and Bunnik, EM and Le Roch, KG}, title = {Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.}, journal = {Nucleic acids research}, volume = {45}, number = {13}, pages = {7825-7840}, pmid = {28531310}, issn = {1362-4962}, support = {R01 AI106775/AI/NIAID NIH HHS/United States ; S10 OD016290/OD/NIH HHS/United States ; }, mesh = {Animals ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; *Genes, Protozoan ; Humans ; Malaria, Falciparum/blood/parasitology ; Plasmodium falciparum/*genetics/growth &amp; development/pathogenicity ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/*genetics/metabolism ; Sequence Analysis, RNA ; Transcription, Genetic ; }, abstract = {Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P. falciparum. Our findings indicate that the majority of genes are transcribed simultaneously during the trophozoite stage of the IDC and that only a small subset of genes is subject to differential transcriptional timing. RNA polymerase II is engaged with promoter regions prior to this transcriptional burst, suggesting that Pol II pausing plays a dominant role in gene regulation. In addition, we found that the overall transcriptional program during gametocyte differentiation is surprisingly similar to the IDC, with the exception of relatively small subsets of genes. Results from this study suggest that further characterization of the molecular players that regulate stage-specific gene expression and Pol II pausing will contribute to our continuous search for novel antimalarial drug targets.}, }
@article {pmid28512126, year = {2017}, author = {Lo, PK and Zhang, Y and Yao, Y and Wolfson, B and Yu, J and Han, SY and Duru, N and Zhou, Q}, title = {Tumor-associated myoepithelial cells promote the invasive progression of ductal carcinoma in situ through activation of TGFβ signaling.}, journal = {The Journal of biological chemistry}, volume = {292}, number = {27}, pages = {11466-11484}, pmid = {28512126}, issn = {1083-351X}, support = {R01 CA157779/CA/NCI NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Line, Tumor ; Epithelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Mice ; Mice, Nude ; MicroRNAs/metabolism ; Myeloid Cells/*metabolism/pathology ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Neoplasm Transplantation ; RNA, Neoplasm/metabolism ; *Signal Transduction ; Transforming Growth Factor beta/*metabolism ; }, abstract = {The normal myoepithelium has a tumor-suppressing nature and inhibits the progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC). Conversely, a growing number of studies have shown that tumor-associated myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of tumor-associated myoepithelial cells in the DCIS-to-IDC development remains undefined. To address this, we explored the role of tumor-associated myoepithelial cells in the DCIS-to-IDC progression. We developed a direct coculture system to study the cell-cell interactions between DCIS cells and tumor-associated myoepithelial cells. Coculture studies indicated that tumor-associated myoepithelial cells promoted the invasive progression of a DCIS cell model in vitro, and mechanistic studies revealed that the interaction with DCIS cells stimulated tumor-associated myoepithelial cells to secrete TGFβ1, which subsequently contributed to activating the TGFβ/Smads pathway in DCIS cells. We noted that activation of the TGFβ signaling pathway promoted the epithelial-mesenchymal transition, basal-like phenotypes, stemness, and invasiveness of DCIS cells. Importantly, xenograft studies further demonstrated that tumor-associated myoepithelial cells enhanced the DCIS-to-IDC progression in vivo Furthermore, we found that TGFβ-mediated induction of oncogenic miR-10b-5p expression and down-regulation of RB1CC1, a miR-10b-5p-targeted tumor-suppressor gene, contributed to the invasive progression of DCIS. Our findings provide the first experimental evidence to directly support the paradigm that altered DCIS-associated myoepithelial cells promote the invasive progression of DCIS into IDC via TGFβ signaling activation.}, }
@article {pmid28511883, year = {2017}, author = {Chua, MLK and Lo, W and Pintilie, M and Murgic, J and Lalonde, E and Bhandari, V and Mahamud, O and Gopalan, A and Kweldam, CF and van Leenders, GJLH and Verhoef, EI and Hoogland, AM and Livingstone, J and Berlin, A and Dal Pra, A and Meng, A and Zhang, J and Orain, M and Picard, V and Hovington, H and Bergeron, A and Lacombe, L and Fradet, Y and Têtu, B and Reuter, VE and Fleshner, N and Fraser, M and Boutros, PC and van der Kwast, TH and Bristow, RG}, title = {A Prostate Cancer "Nimbosus": Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies.}, journal = {European urology}, volume = {72}, number = {5}, pages = {665-674}, doi = {10.1016/j.eururo.2017.04.034}, pmid = {28511883}, issn = {1873-7560}, support = {//CIHR/Canada ; }, mesh = {Adenocarcinoma/*genetics/mortality/pathology/therapy ; Biomarkers, Tumor/*genetics ; Disease Progression ; Disease-Free Survival ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; *Genomic Instability ; Humans ; Kaplan-Meier Estimate ; Male ; Neoplasm Invasiveness ; Netherlands ; New York City ; Ontario ; Phenotype ; Proportional Hazards Models ; Prostatic Neoplasms/*genetics/mortality/pathology/therapy ; Quebec ; RNA, Long Noncoding/*genetics ; Risk Factors ; Time Factors ; Transcriptome ; Treatment Outcome ; Tumor Hypoxia ; }, abstract = {BACKGROUND: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent unfavorable subpathologies in localized prostate cancer. We recently showed that IDC shares a clonal ancestry with the adjacent glandular adenocarcinoma.<br><br>OBJECTIVE: We investigated for the co-occurrence of "aggression" factors, genomic instability and hypoxia, and performed gene expression profiling of these tumors.<br><br>A total of 1325 men were treated for localized prostate cancer from four academic institutions (University Health Network, CHU de Qu&#xe9;bec-Universit&#xe9; Laval, Memorial Sloan Kettering Cancer Center [MSKCC], and Erasmus Medical Center). Pathological specimens were centrally reviewed. Gene copy number and expression, and intraprostatic oxygenation were assessed.<br><br>IDC/CA was separately assessed for biochemical relapse risk in the Canadian and MSKCC cohorts. Both cohorts were pooled for analyses on metastasis.<br><br>RESULTS AND LIMITATION: Presence of IDC/CA independently predicted for increased risks of biochemical relapse (HRCanadian 2.17, p<0.001; HRMSKCC 2.32, p=0.0035) and metastasis (HRpooled 3.31, p<0.001). IDC/CA+ cancers were associated with an increased percentage of genome alteration (PGA [median] 7.2 vs 3.0, p<0.001), and hypoxia (64.0% vs 45.5%, p=0.17). Combinatorial genomic-pathological indices offered the strongest discrimination for metastasis (C-index 0.805 [clinical+IDC/CA+PGA] vs 0.786 [clinical+IDC/CA] vs 0.761 [clinical]). Profiling of mRNA abundance revealed that long noncoding RNA, SChLAP1, was the only gene expressed at >3-fold higher (p<0.0001) in IDC/CA+ than in IDC/CA- tumors, independently corroborated by increased SChLAP1 RNA in situ hybridization signal. Optimal treatment intensification for IDC/CA+ prostate cancer requires prospective testing.<br><br>CONCLUSIONS: The poor outcome associated with IDC and CA subpathologies is associated with a constellation of genomic instability, SChLAP1 expression, and hypoxia. We posit a novel concept in IDC/CA+ prostate cancer, "nimbosus" (gathering of stormy clouds, Latin), which manifests as increased metastatic capacity and lethality.<br><br>PATIENT SUMMARY: A constellation of unfavorable molecular characteristics co-occur with intraductal and cribriform subpathologies in prostate cancer. Modern imaging for surveillance and treatment intensification trials should be considered in this adverse subgroup.}, }
@article {pmid28506312, year = {2017}, author = {Sameni, M and Cavallo-Medved, D and Franco, OE and Chalasani, A and Ji, K and Aggarwal, N and Anbalagan, A and Chen, X and Mattingly, RR and Hayward, SW and Sloane, BF}, title = {Pathomimetic avatars reveal divergent roles of microenvironment in invasive transition of ductal carcinoma in situ.}, journal = {Breast cancer research : BCR}, volume = {19}, number = {1}, pages = {56}, pmid = {28506312}, issn = {1465-542X}, support = {R01 CA131990/CA/NCI NIH HHS/United States ; R01 DK110314/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*genetics/pathology ; Cancer-Associated Fibroblasts/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-6/*genetics ; Mice ; Neoplasm Invasiveness/genetics/pathology ; Plasminogen Activator Inhibitor 1/*genetics ; Proteome/genetics ; Receptors, Urokinase Plasminogen Activator/*genetics ; Tissue Array Analysis ; Tumor Microenvironment/genetics ; Urokinase-Type Plasminogen Activator/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC.<br><br>METHODS: We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression.<br><br>RESULTS: Our results show that MEPs suppress tumor formation by DCIS cells in vivo even in the presence of CAFs. In the in vitro MAME model, MEPs reduce the size of 3D DCIS structures and their degradation of extracellular matrix. We further show that the tumor-suppressive effects of MEPs on DCIS are linked to inhibition of urokinase plasminogen activator (uPA)/urokinase plasminogen activator receptor (uPAR)-mediated proteolysis by plasminogen activator inhibitor 1 (PAI-1) and that they can lessen the tumor-promoting effects of CAFs by attenuating interleukin 6 (IL-6) signaling pathways.<br><br>CONCLUSIONS: Our studies using MAME are, to our knowledge, the first to demonstrate a divergent interplay between MEPs and CAFs within the DCIS tumor microenvironment. We show that the tumor-suppressive actions of MEPs are mediated by PAI-1, uPA and its receptor, uPAR, and are sustained even in the presence of the CAFs, which themselves enhance DCIS tumorigenesis via IL-6 signaling. Identifying tumor microenvironmental regulators of DCIS progression will be critical for defining a robust and predictive molecular signature for clinical use.}, }
@article {pmid28484924, year = {2017}, author = {Turner-Ivey, B and Smith, EL and Rutkovsky, AC and Spruill, LS and Mills, JN and Ethier, SP}, title = {Development of mammary hyperplasia, dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3.}, journal = {Breast cancer research and treatment}, volume = {164}, number = {2}, pages = {349-358}, pmid = {28484924}, issn = {1573-7217}, support = {P30 CA138313/CA/NCI NIH HHS/United States ; R01 CA100724/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Ductal, Breast/genetics/*pathology ; Cell Transformation, Neoplastic/genetics/*pathology ; Female ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Hyperplasia ; Lactation ; Mammary Neoplasms, Experimental/genetics/*pathology ; Mice ; Mice, Transgenic ; Neoplasm Grading ; Nuclear Proteins/*genetics ; Promoter Regions, Genetic ; }, abstract = {PURPOSE: NSD3 has been implicated as a candidate driver oncogene from the 8p11-p12 locus, and we have previously published evidence for its amplification and overexpression in human breast cancer. This aim of this study was to further characterize the transforming function of NSD3 in vivo.<br><br>METHODS: We generated a transgenic mouse model in which NSD3 gene expression was driven by the MMTV promoter and expressed in mammary epithelium of FVB mice. Mammary glands were fixed and whole mounts were stained with carmine to visualize gland structure. Mammary tumors were formalin-fixed, and paraffin embedded (FFPE) tumors were stained with hematoxylin and eosin.<br><br>RESULTS: Pups born to transgenic females were significantly underdeveloped compared to pups born to WT females due to a lactation defect in transgenic female mice. Whole mount analysis of the mammary glands of transgenic female mice revealed a profound defect in functional differentiation of mammary gland alveoli that resulted in the lactation defect. We followed parous and virgin NSD3 transgenic and control mice to 50&#xa0;weeks of age and observed that several NSD3 parous females developed mammary tumors. Whole mount analysis of the mammary glands of tumor-bearing mice revealed numerous areas of mammary hyperplasia and ductal dysplasia. Histological analysis showed that mammary tumors were high-grade ductal carcinomas, and lesions present in other mammary glands exhibited features of alveolar hyperplasia, ductal dysplasia, and carcinoma in situ.<br><br>CONCLUSIONS: Our results are consistent with our previous studies and demonstrate that NSD3 is a transforming breast cancer oncogene.}, }
@article {pmid28481705, year = {2017}, author = {Poppe, MM and Agarwal, JP}, title = {Breast Reconstruction With Postmastectomy Radiation: Choices and Tradeoffs.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {35}, number = {22}, pages = {2467-2470}, doi = {10.1200/JCO.2017.72.7388}, pmid = {28481705}, issn = {1527-7755}, mesh = {*Breast Implants ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/secondary/surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mammaplasty/methods ; Mastectomy ; Middle Aged ; Neoplasms, Multiple Primary/pathology/*radiotherapy/surgery ; Radiotherapy, Adjuvant ; Rectus Abdominis/transplantation ; *Surgical Flaps ; Transplantation, Autologous ; }, abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old premenopausal woman presented with multifocal cancer in the right breast, with lesions at 1:00 and 4:00, the largest measuring approximately 3 cm on exam, and multiple palpable right axillary lymph nodes. A core biopsy confirmed invasive ductal carcinoma, grade 2 of 3, that was estrogen receptor positive, progesterone receptor positive, and HER2 negative. Fine needle aspiration of a right axillary node confirmed metastatic carcinoma. A positron emission tomography (PET)/ computed tomography done before starting chemotherapy demonstrated an absence of metastatic disease with expected avidity in two separate breast masses and multiple conglomerated 1-2 cm level I and II axillary lymph nodes. She received neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide, followed by paclitaxel, and had a complete clinical response with resolution of the breast and axillary masses on exam. A repeat PET/computed tomography demonstrated reduced size of the breast and axillary disease, and no significant residual PET avidity. Her breast surgeon recommended a right mastectomy with axillary node dissection. As part of her multidisciplinary treatment plan, she consulted with two plastic surgeons to discuss reconstruction options. Plastic Surgeon A advised placement of an implant at the time of mastectomy while Surgeon B contrasted the pros and cons of an autologous transverse rectus abdominis muscle flap reconstruction with an implant based reconstruction. Surgeon B believed that autologous reconstruction would yield the best long-term cosmetic outcome. Before making her surgery decision, the patient consulted with a radiation oncologist to discuss the effect radiation may have on her reconstruction outcome.}, }
@article {pmid28480663, year = {2017}, author = {Lee, SJ and Choi, YY and Kim, C and Chung, MS}, title = {Correlations between Tumor to Background Ratio on Breast-Specific Gamma Imaging and Prognostic Factors in Breast Cancer.}, journal = {Journal of Korean medical science}, volume = {32}, number = {6}, pages = {1031-1037}, pmid = {28480663}, issn = {1598-6357}, mesh = {Adult ; Aged ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Female ; *Gamma Rays ; Humans ; Ki-67 Antigen/genetics/metabolism ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Technetium Tc 99m Sestamibi/chemistry ; }, abstract = {The purpose of this study was to investigate the correlations between tumor-to-background ratio (TBR) obtained from breast-specific gamma imaging (BSGI) and the prognostic factors of breast cancer. Sixty-seven patients with invasive ductal carcinoma who underwent preoperative BSGI were enrolled. The BSGI images were visually scored from 1 to 5 according to a breast imaging reporting and data system (BIRADS). The TBR results obtained from positive BSGI images were compared according to the following prognostic factors: tumor size; axillary lymph node metastasis; nuclear grade (NG); histologic grade (HG); subtype; Ki-67; and the expression profile of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Among 67 images, 60 were classified as a positive finding (sensitivity 89.6%). A higher TBR value was significantly correlated with tumor size ≥ 2 cm (P = 0.001), axillary lymph node metastasis (P = 0.007), high HG (P = 0.029), negative PR status (P = 0.036), and Ki-67 ≥ 14% (P = 0.007). The TBR showed a significant difference between the luminal A and non-luminal A subtypes (P = 0.007). On multivariate analysis, TBR had a high correlation with tumor size ≥ 2 cm, axillary lymph node metastasis, and negative PR status (P = 0.003, 0.048, and 0.030, respectively). A high TBR on BSGI was significantly correlated with poor prognostic factors of breast cancer. Luminal A subtype, a breast cancer subtype with more favorable prognosis, was associated with a low TBR on BSGI.}, }
@article {pmid28475000, year = {2017}, author = {Wang, Y and Shen, H and Yin, Q and Zhang, T and Liu, Z and Zhang, W and Niu, Y}, title = {Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {39}, number = {5}, pages = {1010428317699754}, doi = {10.1177/1010428317699754}, pmid = {28475000}, issn = {1423-0380}, mesh = {Aged ; Animals ; Apoptosis/drug effects ; Breast Neoplasms/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Middle Aged ; NIMA-Related Kinases/biosynthesis/*genetics ; Paclitaxel/*administration &amp; dosage ; Xenograft Model Antitumor Assays ; }, abstract = {NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues. NIMA-related kinase 2B was lowly expressed in the precancerous cells, MCF-10A and MCF-10AT, and it was highly expressed in carcinomatous cells, MCF-10DCIS.com and MCF-10CA1a. The upregulation of NIMA-related kinase 2B can introduce the growth of MCF-10AT cells, knockdown of NIMA-related kinase 2B could remarkably inhibit cell proliferation in MCF-10DCIS.com and MCF-10 CA1a cells. Comparing the volume of the xenografts in nude mouse, we found that the tumors treated by NIMA-related kinase 2B small interfering RNA associated with paclitaxel were the smallest among all the groups. Expression of NIMA-related kinase 2B messenger RNA was associated with higher histological grades, positive lymph node, and high Ki67 index (>20%). The partial response rates were 75.0% in NIMA-related kinase 2B negative (NIMA-related kinase 2B-) patients and 15.8% in NIMA-related kinase 2B++ patients. The progressive disease rates were 10.0% in NIMA-related kinase 2B- patients and 52.6% in NIMA-related kinase 2B++ patients (p = 0.002). Our findings suggested that NIMA-related kinase 2B could play a role in the development and progression of breast cancer. Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer.}, }
@article {pmid28463676, year = {2017}, author = {Martiniuc, A and Dumitraşcu, T and Pavel, M and Stroescu, C}, title = {Simultaneous Breast and Liver Surgery in a Patient with Stage IV Triple Positive Breast Cancer - A Case Report.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {112}, number = {2}, pages = {165-171}, doi = {10.21614/chirurgia.112.2.165}, pmid = {28463676}, issn = {1221-9118}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology/*surgery/therapy ; Carcinoma, Ductal, Breast/metabolism/*secondary/*surgery/therapy ; Chemotherapy, Adjuvant/methods ; Female ; *Hepatectomy/methods ; Humans ; Liver Neoplasms/metabolism/*secondary/*surgery/therapy ; *Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; }, abstract = {UNLABELLED: Introduction: In the modern context of multimodal treatment strategies for cancer patients with systemic disease, the dogma that surgery has a limited role is becoming less and less valid. Although a "œcurative" approach is not possible for the majority of the cases, however, some patients with limited systemic disease and favorable tumor biology could benefit from an aggressive combined cytotoxic and surgical strategy.<br><br>CASE REPORT: A 48-year-old patient was diagnosed with an invasive ductal carcinoma with the immunohistochemistry positive for estrogen and progesterone receptors, positive Her2 and three liver metastases. After nine cycles of chemotherapy, a favorable tumor response was identified at the level of the primary tumor as well as for the liver lesions: two of the metastases have disappeared, and the third one decreased in dimensions. The patient was operated in our unit, a lumpectomy together with a level II axillary lymph nodes dissection and a non-anatomic resection of the segment V of the liver was performed. Conclusions: A subgroup of patients with stage IV breast cancer with limited liver metastases and no extrahepatic disease might benefit from an aggressive combined cytotoxic and surgical strategy regarding disease control and overall survival.}, }
@article {pmid28462850, year = {2017}, author = {El-Naby, NEH and Hassan Mohamed, H and Mohamed Goda, A and El Sayed Mohamed, A}, title = {Epstein-Barr virus infection and breast invasive ductal carcinoma in Egyptian women: A single center experience.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {29}, number = {2}, pages = {77-82}, doi = {10.1016/j.jnci.2017.02.002}, pmid = {28462850}, issn = {2589-0409}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/genetics/virology ; Carcinoma, Ductal/complications/*epidemiology/genetics/virology ; Egypt/epidemiology ; Epstein-Barr Virus Infections/complications/*epidemiology/genetics/virology ; Female ; Herpesvirus 4, Human/*pathogenicity ; Humans ; Middle Aged ; }, abstract = {BACKGROUND: A controversy of the role of Epstein-Barr virus (EBV) infection in breast carcinomas has been reported in the literature.<br><br>OBJECTIVES: We carried on this research to explore possible association between EBV infection and breast invasive ductal carcinoma (IDC) in Egyptian women attending our center.<br><br>STUDY DESIGN: This study carried out at Sohag university hospital on 84 paraffin embedded samples of breast tissue, of them 42 breast IDC as the case group and 42 breast fibroadenomas as the control group. Nested PCRand immunohistochemistry (IHC) done separately for all samples to identify the Epstein-Barr nuclear antigen-1 (EBNA-1) gene and EBV latent membrane protein-1 (LMP-1) respectively, in breast cancer cells and controls.<br><br>RESULTS: Specimen considered positive when both (EBNA-1) gene and LMP-1 were detected using PCR and IHC separately for the same sample, this was achieved by 10/42 (23.81%) of breast IDC (case group) and 6/42 (14.29%) of breast fibro-adenomas (control group) (P-value=0.4). Nodal involvement was the only parameter that demonstrated a significant statistical relationship with EBV presence in cancerous tissue with p-value=0.003.<br><br>CONCLUSION: Our research could not find a significant statistical association between EBV infection and breast IDC in Egyptian women attending our center, but, there might be an association between the existence of EBV and tumor aggressiveness.}, }
@article {pmid28434924, year = {2017}, author = {Mori, K and Takeda, M and Kodama, Y and Kiyokawa, H and Yasojima, H and Mizutani, M and Otani, Y and Morikawa, N and Masuda, N and Mano, M}, title = {Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ.}, journal = {Human pathology}, volume = {64}, number = {}, pages = {145-155}, doi = {10.1016/j.humpath.2017.04.004}, pmid = {28434924}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/surgery ; Chi-Square Distribution ; Decision Support Techniques ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Logistic Models ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Predictive Value of Tests ; ROC Curve ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, "tumor thickness," extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor "thickness" was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions.}, }
@article {pmid28434900, year = {2017}, author = {Hirai, E and Sarukawa, S and Yamamoto, K and Okamoto, M}, title = {Breast Cancer in a Pectoralis Major Myocutaneous Flap Used for the Reconstruction of Tongue Cancer: A Case Report.}, journal = {Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons}, volume = {75}, number = {7}, pages = {1569.e1-1569.e7}, doi = {10.1016/j.joms.2017.03.035}, pmid = {28434900}, issn = {1531-5053}, mesh = {Aged ; Breast Neoplasms/*etiology ; Female ; Humans ; Muscle Neoplasms/*etiology ; Myocutaneous Flap/*adverse effects ; Neoplasms, Second Primary/*etiology ; Tongue Neoplasms/*surgery ; }, abstract = {Breast cancers are the most common cancers in women. However, breast cancer occurring in a pectoralis major myocutaneous flap is extremely rare. This article describes a case of breast cancer occurring in such a flap used for reconstruction of the tongue in a 72-year-old woman. Follow-up computed tomogram depicted a slowly growing mass in the flap. Thirty-nine months postoperatively, a fine-needle aspiration biopsy specimen taken from the lesion suggested glandular carcinoma. The patient was diagnosed with breast cancer in the neck area of the flap and tumor excision was performed. Histologic examination of the excised tumor showed tumor cells arranged in cords, with tubular and cribriform carcinomas near the pectoral muscle with adipose tissue. The cytoplasm was abundant and eosinophilic. Thus, the patient was diagnosed with invasive ductal carcinoma in the pectoralis major flap. Sequential radiotherapy was performed to the neck with a total radiation dose of 50 Gy. Furthermore, the patient received oral anastrozole 1 mg daily as systemic adjuvant therapy for the receptor-positive breast malignancy. One year after surgery, the patient was alive with no evidence of disease. Including this case, only 2 cases of breast cancer in a pectoralis major myocutaneous flap used for reconstruction in the head and neck region have been reported.}, }
@article {pmid28432480, year = {2017}, author = {Song, BI and Kim, HW and Won, KS}, title = {Predictive Value of [18]F-FDG PET/CT for Axillary Lymph Node Metastasis in Invasive Ductal Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {24}, number = {8}, pages = {2174-2181}, doi = {10.1245/s10434-017-5860-0}, pmid = {28432480}, issn = {1534-4681}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multimodal Imaging/*methods ; Neoplasm Invasiveness ; Positron Emission Tomography Computed Tomography/*methods ; Prognosis ; ROC Curve ; *Radiopharmaceuticals ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: This study assessed whether primary tumor maximum standardized uptake value (pSUVmax) measured by [18]F-fluoro-2-deoxy-D-glucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) could improve the prediction of axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC).<br><br>METHODS: In this study, 128 IDC patients who underwent pretreatment [18]F-FDG PET/CT and surgical resection of primary tumor with sentinel lymph node biopsy, ALN dissection, or both were analyzed. All the patients were classified as five molecular subtypes. The optimal cutoff values of pSUVmax for all the patients and each molecular subtype for the prediction of ALN metastasis were determined using receiver operating characteristic (ROC) analysis. Furthermore, the prognostic accuracy of ALN metastasis was assessed using c-statistics.<br><br>RESULTS: The findings showed ALN metastasis in 52 patients (40.6%). The [18]F-FDG PET/CT procedure had a sensitivity of 48.1% and a specificity of 94.7% for ALN metastasis. In the ROC analysis of pSUVmax for ALN metastasis, the optimal cutoff value was 3.9 for all the patients, 2.8 for the luminal A subtype, 3.3 for the luminal B (human epidermal growth factor receptor 2 [HER2]-negative) subtype, 5.3 for the luminal B (HER2-positive) subtype, 12.7 for the HER2-positive subtype, and 11.5 for the triple-negative subtype. A predictive ALN metastasis model using nodal [18]F-FDG uptake finding gave a c-statistic of 0.714, and a model combination of nodal [18]F-FDG uptake finding with pSUVmax of all the patients gave a c-statistic of 0.736 (P&#xa0;=&#xa0;0.3926). However, the combination of nodal the [18]F-FDG uptake finding with the pSUVmax of each molecular subtype gave a c-statistic of 0.791 (P&#xa0;=&#xa0;0.0047).<br><br>CONCLUSIONS: Combining the pSUVmax of each molecular subtype with the nodal [18]F-FDG uptake finding can improve the prediction of ALN metastasis in IDC.}, }
@article {pmid28431271, year = {2017}, author = {Li, Y and Gao, D and Tu, M and Luo, YZ and Deng, ZH}, title = {Investigation of pathology malpractice claims in China from 2002-2015.}, journal = {Journal of forensic and legal medicine}, volume = {48}, number = {}, pages = {30-34}, doi = {10.1016/j.jflm.2017.04.005}, pmid = {28431271}, issn = {1878-7487}, mesh = {China ; Compensation and Redress/legislation &amp; jurisprudence ; Humans ; Malpractice/*legislation &amp; jurisprudence ; Medical Errors ; Pathology, Clinical/*legislation &amp; jurisprudence ; Retrospective Studies ; }, abstract = {OBJECTIVE: To examine pathology-related medical claims in China and identify the most common errors to result in such claims.<br><br>METHOD: A retrospective analysis was performed of 71 forensic evaluation reports carried out in two Chinese institutes of forensic medicine between 2002 and 2015 due to suspicion of medical malpractice. The judicial outcomes of each case were also reviewed when available.<br><br>RESULTS: Of 71 cases, 54 cases had judicial outcomes. The most frequently claimed events were false-negative diagnoses of skin cancer, invasive ductal carcinoma of the breast, and osteosarcoma; and false positive diagnoses of uterine cervical squamous cell carcinoma, gastric carcinoma, and soft tissue carcinoma. The most common cause of error (82%, 56 of 68) was pathological misinterpretation. Plaintiffs in most cases (89%, 48 of 54) received compensation.<br><br>CONCLUSION: Our data are in agreement with other findings regarding the most frequent medical malpractice allegations related to pathology. Addressing the issues at the root of these claims would lead to a decline in the number of medical errors. Quality assurance programs and good pathologist-clinician communication may decrease the risk of litigation.}, }
@article {pmid28430808, year = {2017}, author = {El Guerrab, A and Cayre, A and Kwiatkowski, F and Privat, M and Rossignol, JM and Rossignol, F and Penault-Llorca, F and Bignon, YJ}, title = {Quantification of hypoxia-related gene expression as a potential approach for clinical outcome prediction in breast cancer.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0175960}, pmid = {28430808}, issn = {1932-6203}, mesh = {Breast Neoplasms/genetics/*pathology ; *Cell Hypoxia ; Female ; *Gene Expression ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies ; }, abstract = {Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by "hypoxia inducible factors" that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression. Gene expression was quantified by RT-qPCR in a retrospective series of 32 patients with invasive ductal carcinoma. Data were analyzed in relation to classical clinicopathological criteria and relapse occurrence. Coordinated overexpression of selected genes was observed in high-grade and HER2+ tumors. Hierarchical cluster analysis of gene expression significantly segregated relapsed patients (p = 0.008, Chi2 test). All genes (except one) were up-regulated and six markers were significantly expressed in tumors from recurrent patients. The expression of this 6-gene set was used to develop a basic algorithm for identifying recurrent patients according to a risk score of relapse. Analysis of Kaplan-Meier relapse-free survival curves allowed the definition of a threshold score of 2 (p = 0.021, Mantel-Haenszel test). The risk of recurrence was increased by 40% in patients with a high score. In addition to classical prognostic factors, we showed that hypoxic markers have potential prognostic value for outcome and late recurrence prediction, leading to improved treatment decision-making for patients with early-stage invasive breast cancer. It will be necessary to validate the clinical relevance of this prognostic approach through independent studies including larger prospective patient cohorts.}, }
@article {pmid28430349, year = {2018}, author = {Xu, Y and Lan, S and Zheng, Q}, title = {Prognostic significance of infiltrating immune cell subtypes in invasive ductal carcinoma of the breast.}, journal = {Tumori}, volume = {104}, number = {3}, pages = {196-201}, doi = {10.5301/tj.5000624}, pmid = {28430349}, issn = {2038-2529}, mesh = {B-Lymphocytes/immunology/metabolism/pathology ; Biomarkers/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology ; CD8-Positive T-Lymphocytes/immunology/metabolism/pathology ; Carcinoma, Ductal/*immunology/metabolism/*pathology ; Female ; Forkhead Transcription Factors/metabolism ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; T-Lymphocytes, Regulatory/immunology/metabolism/pathology ; }, abstract = {PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis.<br><br>MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low).<br><br>RESULTS: Kaplan-Meier survival analysis showed (a) for all patients that high tumor-infiltrating CD8+ and CD20+ B lymphocytes, low tumor-infiltrating FOXP3+ regulatory T cells (Tregs), and CD68+ macrophages all increased OS and DFS (p<0.05); (b) for both the 35 ER-negative and 45 lymph-node-negative patients, high CD8+ cytotoxic T lymphocytes (CTLs) increased OS and DFS (p<0.05). Multivariate analysis of OS and DFS showed that for all patients high CD8+ CTLs and low FOXP3+ Tregs were related to good OS and DFS (p<0.05).<br><br>CONCLUSION: High numbers of tumor-infiltrating CD8+ and low numbers of FOXP3+ T lymphocytes both could function as potential independent prognostic markers for invasive ductal breast carcinoma.}, }
@article {pmid28425682, year = {2017}, author = {Degrate, L and Bernasconi, DP and Meroni, P and Garancini, M and Macchini, D and Romano, F and Uggeri, F and Gianotti, L}, title = {Mild acute biliary pancreatitis: the timing of cholecystectomy should not exceed index admission.}, journal = {Minerva chirurgica}, volume = {72}, number = {5}, pages = {383-390}, doi = {10.23736/S0026-4733.17.07356-4}, pmid = {28425682}, issn = {1827-1626}, mesh = {Acute Disease ; Aged ; *Cholecystectomy, Laparoscopic/methods ; Female ; Gallstones/complications/diagnosis/*surgery ; Humans ; Italy ; Male ; Middle Aged ; Pancreatitis/*diagnosis/etiology ; *Patient Selection ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Laparoscopic cholecystectomy (LC) to treat mild biliary acute pancreatitis (MBAP) during index admission is recommended. However, the optimal surgical timing is controversial, considering that patients are actually often discharged from hospital and readmitted for elective cholecystectomy. Moreover, previous studies showed an uneven patients' stratification for pancreatitis severity. The aim of this study was to determine the outcome of patients homogenously categorizedfor MBAP according to the newest pancreatitis classifications, undergoing cholecystectomy with different timing.<br><br>METHODS: We retrospectively identified all patients undergoing cholecystectomy from 2008 to 2015 for MBAP, according to the 2012 Revision of the Atlanta Classification and the Determinant-Based Classification of Acute Pancreatitis, and stratified them in two groups: index cholecystectomy (IC) and interval-delayed cholecystectomy (IDC, after at least 4 weeks).<br><br>RESULTS: One hundred and three patients were analyzed. IC was performed in 40 patients (38.8%) while IDC in 63 patients (61.2%). The two groups were similar in comorbidities and pancreatitis severity at admission. There were no differences for conversion rate, operation length, total length of hospitalization and overall complication rates. However, IDC patients had a 33.3% rate of re-hospitalization for recurrent biliary-pancreatic events while waiting for the elective procedure and showed a higher rate of acute cholecystitis at histological diagnosis than IC (11.1% vs. 0%, P=0.041).<br><br>CONCLUSIONS: Among patients affected by MBAP, homogenously assessed following the new acute pancreatitis severity scores, the performance of cholecystectomy during the index admission is the best treatment option in order to avoid further undesired hospitalizations for recurrent biliary/pancreatic events while waiting for surgery.}, }
@article {pmid28422303, year = {2017}, author = {Tang, B and Han, CT and Gan, HL and Zhang, GM and Zhang, CZ and Yang, WY and Shen, Y and Zhu, Y and Ye, DW}, title = {Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.}, journal = {The Prostate}, volume = {77}, number = {9}, pages = {984-989}, doi = {10.1002/pros.23354}, pmid = {28422303}, issn = {1097-0045}, mesh = {Aged ; Biopsy/methods/statistics &amp; numerical data ; *Carcinoma, Ductal/epidemiology/pathology ; China/epidemiology ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Prostate/*pathology ; *Prostatic Neoplasms/epidemiology/pathology ; Risk Factors ; Smoking/*epidemiology ; Statistics as Topic ; }, abstract = {OBJECTIVE: To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men.<br><br>PATIENTS AND METHODS: We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence.<br><br>RESULTS: A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group&#x2009;&#x2265;&#x2009;4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR&#x2009;=&#x2009;1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR&#x2009;=&#x2009;0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR&#x2009;=&#x2009;1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR&#x2009;=&#x2009;2.29, 95%CI: 1.14-4.59).<br><br>CONCLUSION: Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa.}, }
@article {pmid28422090, year = {2017}, author = {Wu, Q and Ding, X and Li, J and Sun, S and Zhu, S and Wu, J and Liu, Q and Yao, F and Sun, S}, title = {Surgical treatment in Paget's disease with invasive ductal carcinoma: an observational study based on SEER.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {45510}, pmid = {28422090}, issn = {2045-2322}, mesh = {Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Humans ; Paget's Disease, Mammary/complications/*pathology/*surgery ; Prognosis ; Survival Analysis ; Treatment Outcome ; }, abstract = {The aim is to analyse the clinical presentation, treatment and outcomes in patients with Paget's disease with invasive ductal carcinoma (PD-IDC), with special emphasis on the role of surgical treatment. Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, we investigated the differences in characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM) between patients with PD-IDC and those with invasive ductal carcinoma (IDC). Compared with IDC group, patients with PD-IDC had a better prognosis and lower mortality in adjusted analyses. In the multivariate analysis of cases with PD-IDC, history of ALND was significantly associated with OS while Her2 status were associated with BCSM. Further, subgroup analysis demonstrated no difference between surgical treatment subgroups for either OS or BCSM. The results demonstrated that PD-IDC appears to alter the association between prognosis and Her2 status. Meanwhile, breast-conserving surgery with radiotherapy may be a feasible treatment alternative and sentinel lymph node biopsy should be considered as an appropriate treatment for patients with PD-IDC.}, }
@article {pmid28416734, year = {2017}, author = {Coulson, R and Liew, SH and Connelly, AA and Yee, NS and Deb, S and Kumar, B and Vargas, AC and O'Toole, SA and Parslow, AC and Poh, A and Putoczki, T and Morrow, RJ and Alorro, M and Lazarus, KA and Yeap, EFW and Walton, KL and Harrison, CA and Hannan, NJ and George, AJ and Clyne, CD and Ernst, M and Allen, AM and Chand, AL}, title = {The angiotensin receptor blocker, Losartan, inhibits mammary tumor development and progression to invasive carcinoma.}, journal = {Oncotarget}, volume = {8}, number = {12}, pages = {18640-18656}, pmid = {28416734}, issn = {1949-2553}, mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Angiotensin II Type 1 Receptor Blockers/*therapeutic use ; Animals ; Biopsy ; Breast Neoplasms/*pathology ; Carcinogenesis/metabolism ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemically induced/*drug therapy/immunology/pathology ; Cell Proliferation/drug effects ; *Disease Progression ; Female ; Humans ; Immunohistochemistry ; Interleukin-6/metabolism ; Losartan/*therapeutic use ; Mammary Neoplasms, Experimental/chemically induced/*drug therapy/immunology/pathology ; Medroxyprogesterone Acetate/toxicity ; Mice ; Neoplasm Invasiveness ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; Receptor, Angiotensin, Type 1/*metabolism ; Renin-Angiotensin System/drug effects ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Tumor Burden/drug effects ; Tumor Necrosis Factor-alpha/metabolism ; Up-Regulation ; }, abstract = {Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis. However, there is no evidence, so far, of the functional contribution of AT1R to breast tumorigenesis. We explored the potential therapeutic benefit of ARB in a carcinogen-induced mouse model of breast cancer and clarified the mechanisms associated with its success.Mammary tumors were induced with 7,12-dimethylbenz[α]antracene (DMBA) and medroxyprogesterone acetate (MPA) in female wild type mice and the effects of the ARB, Losartan treatment assessed in a preventative setting (n = 15 per group). Tumor histopathology was characterised by immunohistochemistry, real-time qPCR to detect gene expression signatures, and tumor cytokine levels measured with quantitative bioplex assays. AT1R was detected with radiolabelled ligand binding assays in fresh frozen tumor samples.We showed that therapeutic inhibition of AT1R, with Losartan, resulted in a significant reduction in tumor burden; and no mammary tumor incidence in 20% of animals. We observed a significant reduction in tumor progression from DCIS to invasive cancer with Losartan treatment. This was associated with reduced tumor cell proliferation and a significant reduction in IL-6, pSTAT3 and TNFα levels. Analysis of tumor immune cell infiltrates, however, demonstrated no significant differences in the recruitment of lymphocytes or tumour-associated macrophages in Losartan or vehicle-treated mammary tumors.Analysis of AT1R expression with radiolabelled ligand binding assays in human breast cancer biopsies showed high AT1R levels in 30% of invasive ductal carcinomas analysed. Furthermore, analysis of the TCGA database identified that high AT1R expression to be associated with luminal breast cancer subtype.Our in vivo data and analysis of human invasive ductal carcinoma samples identify the AT1R is a potential therapeutic target in breast cancer, with the availability of a range of well-tolerated inhibitors currently used in clinics. We describe a novel signalling pathway critical in breast tumorigenesis, that may provide new therapeutic avenues to complement current treatments.}, }
@article {pmid28414329, year = {2017}, author = {Fischer, K and Ruiz, HH and Jhun, K and Finan, B and Oberlin, DJ and van der Heide, V and Kalinovich, AV and Petrovic, N and Wolf, Y and Clemmensen, C and Shin, AC and Divanovic, S and Brombacher, F and Glasmacher, E and Keipert, S and Jastroch, M and Nagler, J and Schramm, KW and Medrikova, D and Collden, G and Woods, SC and Herzig, S and Homann, D and Jung, S and Nedergaard, J and Cannon, B and Tschöp, MH and Müller, TD and Buettner, C}, title = {Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.}, journal = {Nature medicine}, volume = {23}, number = {5}, pages = {623-630}, pmid = {28414329}, issn = {1546-170X}, support = {R01 DK017844/DK/NIDDK NIH HHS/United States ; R03 DK082724/DK/NIDDK NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; R01 AI093637/AI/NIAID NIH HHS/United States ; R01 DK099222/DK/NIDDK NIH HHS/United States ; R37 DK017844/DK/NIDDK NIH HHS/United States ; R56 DK083658/DK/NIDDK NIH HHS/United States ; 340345/ERC_/European Research Council/International ; R01 AA023416/AA/NIAAA NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Adipocytes/drug effects/*metabolism ; Adipose Tissue/drug effects/*metabolism ; Adipose Tissue, Brown/drug effects/metabolism ; Adipose Tissue, White/drug effects/metabolism ; Animals ; Blotting, Western ; Body Composition/immunology ; Catecholamines/metabolism ; Cell Differentiation ; Culture Media, Conditioned ; Energy Metabolism/genetics ; Flow Cytometry ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Interleukin-4/immunology/pharmacology ; Macrophages/drug effects/*immunology ; Mice ; Mice, Knockout ; Norepinephrine/*metabolism ; Receptors, Adrenergic, beta-3/*metabolism ; Receptors, Cell Surface/genetics ; Thermogenesis/genetics/*immunology ; Tyrosine 3-Monooxygenase/*genetics ; Uncoupling Protein 1/genetics ; }, abstract = {Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1[-/-] and interleukin-4 receptor-α double-negative (Il4ra[-/-]) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.}, }
@article {pmid28413435, year = {2017}, author = {San, TH and Fujisawa, M and Fushimi, S and Yoshimura, T and Ohara, T and Soe, L and Min, NW and Kyaw, O and Yang, X and Matsukawa, A}, title = {Low prevalence of human mammary tumor virus (HMTV) in breast cancer patients from Myanmar.}, journal = {Infectious agents and cancer}, volume = {12}, number = {}, pages = {20}, pmid = {28413435}, issn = {1750-9378}, abstract = {BACKGROUND: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse mammary tumor virus (MMTV), one of the causal agents of murine mammary tumors. HMTV (MMTV-like) sequences were reported to be present in human breast cancers from several populations with a prevalence range of 0-78%; however, the prevalence of HMTV in breast cancers from Myanmar remains unknown.<br><br>METHODS: Fifty-eight breast cancer samples from Myanmar women were examined in this study. DNA was isolated from formalin-fixed paraffin-embedded specimens, and HMTV envelope sequences were detected by semi-nested PCR. The sequence of the PCR products was also confirmed.<br><br>RESULTS: Only 1.7% (1 of 58) of the breast cancers were positive for HMTV, and the sequence of PCR products was 98.9% identical to the reference HMTV sequence (GenBank accession No. AF243039). The tumor with HMTV was grade III invasive ductal carcinoma, 7.0&#xa0;cm in size with lymph node metastasis (T3, N1, M0).<br><br>CONCLUSIONS: We, for the first time, investigated the presence of HMTV in Myanmar breast cancer patients. In accordance with other Asian studies, the prevalence of HMTV in Myanmar was quite low, supporting the hypothesis that Asian breast cancers have different etiologies than in Western countries, where HMTV is more prevalent.}, }
@article {pmid28412522, year = {2017}, author = {Amri, EZ and Scheideler, M}, title = {Small non coding RNAs in adipocyte biology and obesity.}, journal = {Molecular and cellular endocrinology}, volume = {456}, number = {}, pages = {87-94}, doi = {10.1016/j.mce.2017.04.009}, pmid = {28412522}, issn = {1872-8057}, mesh = {Adipocytes, Brown/*metabolism/pathology ; Adipocytes, White/*metabolism/pathology ; Adipogenesis/genetics ; Adipose Tissue/metabolism/pathology ; Animals ; Biomarkers/metabolism ; Energy Intake/genetics ; Gene Expression Regulation ; Humans ; MicroRNAs/*genetics/metabolism ; Obesity/diagnosis/*genetics/metabolism/pathology ; RNA, Small Nucleolar/*genetics/metabolism ; RNA, Transfer/*genetics/metabolism ; }, abstract = {Obesity has reached epidemic proportions world-wide and constitutes a substantial risk factor for hypertension, type 2 diabetes, cardiovascular diseases and certain cancers. So far, regulation of energy intake by dietary and pharmacological treatments has met limited success. The main interest of current research is focused on understanding the role of different pathways involved in adipose tissue function and modulation of its mass. Whole-genome sequencing studies revealed that the majority of the human genome is transcribed, with thousands of non-protein-coding RNAs (ncRNA), which comprise small and long ncRNAs. ncRNAs regulate gene expression at the transcriptional and post-transcriptional level. Numerous studies described the involvement of ncRNAs in the pathogenesis of many diseases including obesity and associated metabolic disorders. ncRNAs represent potential diagnostic biomarkers and promising therapeutic targets. In this review, we focused on small ncRNAs involved in the formation and function of adipocytes and obesity.}, }
@article {pmid28410206, year = {2017}, author = {Fu, S and Cheng, J and Wei, C and Yang, L and Xiao, X and Zhang, D and Stewart, MD and Fu, J}, title = {Development of diagnostic SCAR markers for genomic DNA amplifications in breast carcinoma by DNA cloning of high-GC RAMP-PCR fragments.}, journal = {Oncotarget}, volume = {8}, number = {27}, pages = {43866-43877}, pmid = {28410206}, issn = {1949-2553}, mesh = {Adult ; Aged ; Base Composition ; Base Sequence ; *Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/genetics ; Cloning, Molecular ; DNA Primers ; Dipeptidases/genetics ; Female ; GPI-Linked Proteins/genetics ; *Gene Amplification ; *Genomics/methods ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger/genetics ; Random Amplified Polymorphic DNA Technique ; Sequence Analysis, DNA ; }, abstract = {Cancer is genetically heterogeneous regarding to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers, including DNA markers, is used in determining genomic instability, molecular subtype determination and disease prognosis, and estimating sensitivity to different drugs in clinical practice. In a previous study, we developed highly effective DNA markers using improved random amplified polymorphic DNA (RAPD) with high-GC primers, which is a valuable approach for the genetic authentication of medicinal plants. In this study, we applied this effective DNA marker technique to generate genetic fingerprints that detect genomic alterations in human breast cancer tissues and then developed sequence-characterized amplified region (SCAR) markers. Three SCAR markers (BC10-1, BC13-4 and BC31-2) had high levels of genomic DNA amplification in breast cancer. The PHKG2 and RNF40 genes are either overlapping or close to the sequences of SCAR marker BC13-4, while SCAR marker BC10-1 is in the intron and overlap the DPEP1 gene, suggesting that alterations in the expression of these genes could contribute to cancer progression. Screening of breast cancer cell lines showed that the mRNA expression levels for the PHKG2 and DPEP1 were lower in non-tumorigenic mammary epithelial cell MCF10A, but elevated in other cell lines. The DPEP1 mRNA level in invasive ductal carcinoma specimens was significantly higher than that of the adjacent normal tissues in women. Taken together, high-GC RAMP-PCR provides greater efficacy in measuring genomic DNA amplifications, deletion or copy number variations. Furthermore, SCAR markers BC10-1 and BC13-4 might be useful diagnostic markers for breast cancer carcinomas.}, }
@article {pmid28403836, year = {2017}, author = {Fu, G and Wang, G and Dai, X}, title = {An adaptive threshold determination method of feature screening for genomic selection.}, journal = {BMC bioinformatics}, volume = {18}, number = {1}, pages = {212}, pmid = {28403836}, issn = {1471-2105}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/genetics ; Computer Simulation ; Genome, Plant ; Genome-Wide Association Study ; Genomics ; *Models, Genetic ; Phenotype ; Plant Breeding ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Although the dimension of the entire genome can be extremely large, only a parsimonious set of influential SNPs are correlated with a particular complex trait and are important to the prediction of the trait. Efficiently and accurately selecting these influential SNPs from millions of candidates is in high demand, but poses challenges. We propose a backward elimination iterative distance correlation (BE-IDC) procedure to select the smallest subset of SNPs that guarantees sufficient prediction accuracy, while also solving the unclear threshold issue for traditional feature screening approaches.<br><br>RESULTS: Verified through six simulations, the adaptive threshold estimated by the BE-IDC performed uniformly better than fixed threshold methods that have been used in the current literature. We also applied BE-IDC to an Arabidopsis thaliana genome-wide data. Out of 216,130 SNPs, BE-IDC selected four influential SNPs, and confirmed the same FRIGIDA gene that was reported by two other traditional methods.<br><br>CONCLUSIONS: BE-IDC accommodates both the prediction accuracy and the computational speed that are highly demanded in the genomic selection.}, }
@article {pmid28401771, year = {2018}, author = {Brück, N and Koskivuo, I and Boström, P and Saunavaara, J and Aaltonen, R and Parkkola, R}, title = {Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.}, journal = {Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society}, volume = {107}, number = {1}, pages = {14-22}, doi = {10.1177/1457496917701669}, pmid = {28401771}, issn = {1799-7267}, mesh = {Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/mortality/*surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/mortality/*surgery ; Disease-Free Survival ; Female ; Finland ; Hospitals, University ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/*methods ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/pathology/surgery ; Preoperative Care/methods ; Prognosis ; Prospective Studies ; Risk Assessment ; Statistics, Nonparametric ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma.<br><br>MATERIAL AND METHODS: A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms.<br><br>RESULTS: In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group (p&#x2009;=&#x2009;0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group (p&#x2009;=&#x2009;0.202). The mean interval between referral and first surgical procedure was 34&#x2009;days in the magnetic resonance imaging group and 21&#x2009;days in the control group (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Preoperative magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.}, }
@article {pmid28400203, year = {2017}, author = {Desmedt, C and Zoppoli, G and Sotiriou, C and Salgado, R}, title = {Transcriptomic and genomic features of invasive lobular breast cancer.}, journal = {Seminars in cancer biology}, volume = {44}, number = {}, pages = {98-105}, doi = {10.1016/j.semcancer.2017.03.007}, pmid = {28400203}, issn = {1096-3650}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; Genome, Human ; Genomics ; Humans ; Neoplasm Invasiveness/*genetics/pathology ; Prognosis ; Transcriptome/*genetics ; }, abstract = {Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance.}, }
@article {pmid28395915, year = {2017}, author = {Abel, S and Renz, P and Trombetta, M and Cowher, M and Day Werts, E and Julian, TB and Wegner, R}, title = {Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?.}, journal = {Practical radiation oncology}, volume = {7}, number = {3}, pages = {167-172}, doi = {10.1016/j.prro.2016.10.018}, pmid = {28395915}, issn = {1879-8519}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*radiotherapy/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Radiodermatitis/*etiology ; Radiotherapy/*adverse effects/*methods ; Retrospective Studies ; Thoracic Wall ; Treatment Failure ; }, abstract = {PURPOSE: Postmastectomy chest wall radiation therapy has historically used bolus to increase dose at the skin surface. Despite the theoretical benefits of bolus, the clinical implications of locoregional tumor control, cosmesis, and the incidence of radiodermatitis are less well characterized. We hypothesized that treatment in the presence or absence of bolus results in equivalent chest wall recurrence rates, but its presence results in more severe acute dermatologic toxicity.<br><br>METHODS AND MATERIALS: Locally advanced breast cancer patients undergoing chest wall radiation therapy were retrospectively reviewed from 2005 to 2015 (n = 106; 53 with bolus, 53 without). Outcomes including local failure, acute skin toxicity, and treatment interruptions were recorded. Median age was 59 years (range, 28-91) and median follow-up was 34 months. Histology was invasive ductal carcinoma (73%), invasive lobular carcinoma (20%), inflammatory (6%), and neuroendocrine (1%). Fifty-nine percent were T3/T4 primary tumors and 29.2% had clinical/pathologic skin involvement. Node-positive patients accounted for 80.2%. Chemotherapy was administered in 84.0%. All patients had 3-dimensional conformal radiation therapy and received a median dose of 61Gy (range, 50-63 Gy).<br><br>RESULTS: Local failure was 6.6% (n = 7) overall, with 4 failures in the bolus group and 3 in the no bolus group. No pathological factors were associated with local failure. Acute grade 2 and 3 skin toxicities (37 vs 22) and treatment interruptions (20 vs 3) were more common in the bolus group (P < .05). Mean treatment interruption (14.5 vs 5 days) was longer for patients receiving bolus. Patients undergoing treatment interruption were more likely to fail locally than patients not requiring a treatment interruption (17.4% vs 3.6%, P = .0322).<br><br>CONCLUSIONS: Bolus omission in adjuvant chest wall radiation therapy may be a reasonable approach to avoid acute skin toxicity and treatment interruptions while preserving local control; however, further study will be needed to reach a definitive conclusion.}, }
@article {pmid28391968, year = {2017}, author = {Barzilay, S and Brunstein Klomek, A and Apter, A and Carli, V and Wasserman, C and Hadlaczky, G and Hoven, CW and Sarchiapone, M and Balazs, J and Kereszteny, A and Brunner, R and Kaess, M and Bobes, J and Saiz, P and Cosman, D and Haring, C and Banzer, R and Corcoran, P and Kahn, JP and Postuvan, V and Podlogar, T and Sisask, M and Varnik, A and Wasserman, D}, title = {Bullying Victimization and Suicide Ideation and Behavior Among Adolescents in Europe: A 10-Country Study.}, journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine}, volume = {61}, number = {2}, pages = {179-186}, doi = {10.1016/j.jadohealth.2017.02.002}, pmid = {28391968}, issn = {1879-1972}, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Bullying/*statistics &amp; numerical data ; Crime Victims/*statistics &amp; numerical data ; Europe ; Female ; Humans ; Male ; Prevalence ; Protective Factors ; Self Report ; Suicide/*statistics &amp; numerical data ; Surveys and Questionnaires ; }, abstract = {PURPOSE: To examine risk and protective factors moderating the associations between three types of bullying victimization (physical, verbal, and relational bullying) with suicide ideation/attempts in a large representative sample of European adolescents.<br><br>METHODS: We analyzed cross-sectional data on 11,110 students (mean age&#xa0;= 14.9, standard deviation&#xa0;= .89) recruited from 168 schools in 10 European Union countries involved in the Saving and Empowering Young Lives in Europe study. A self-report questionnaire was used to measure victimization types, depression, anxiety, parental and peer support, and suicide ideation and attempts. For each outcome, we applied hierarchical nonlinear models controlling for sociodemographics.<br><br>RESULTS: Prevalence of victimization was 9.4% physical, 36.1% verbal, and 33.0% relational. Boys were more likely to be physically and verbally victimized, whereas girls were more prone to relational victimization. Physical victimization was associated with suicide ideation, and relational victimization was associated with suicide attempts. Other associations between victimization and suicidality (ideation/attempts) were identified through analysis of interactions with additional risk and protective factors. Specifically, verbal victimization was associated with suicide ideation among adolescents with depression who perceived low parental support. Similarly, low peer support increased the associations between verbal victimization and suicide ideation. Verbal victimization was associated with suicide attempts among adolescents with anxiety who perceived low parental support.<br><br>CONCLUSIONS: Findings support the development of prevention strategies for adolescent victims of bullying who may be at elevated risk for suicide ideation/behavior, by taking into account gender, the type of bullying, symptomatology, and availability of interpersonal support.}, }
@article {pmid28391236, year = {2017}, author = {Weis, S and Hagel, S and Schmitz, RP and Scherag, A and Brunkhorst, FM and Forstner, C and Löffler, B and Pletz, MW}, title = {Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.}, journal = {BMJ open}, volume = {7}, number = {4}, pages = {e013976}, pmid = {28391236}, issn = {2044-6055}, mesh = {Administration, Intravenous ; Anti-Bacterial Agents/therapeutic use ; Clinical Protocols ; Cluster Analysis ; *Counseling/methods ; Cross-Over Studies ; Germany/epidemiology ; Humans ; Patient Education as Topic ; Program Evaluation ; Quality Assurance, Health Care ; Referral and Consultation ; *Staphylococcal Infections/drug therapy/epidemiology/prevention &amp; control ; Staphylococcus aureus/*drug effects ; Telephone ; }, abstract = {INTRODUCTION: Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question.<br><br>METHODS AND ANALYSIS: SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90&#x2005;days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC.<br><br>ETHICS AND DISSEMINATION: We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media.<br><br>TRIAL REGISTRATION NUMBER: DRKS00010135.}, }
@article {pmid28388580, year = {2017}, author = {Lian, K and Ma, C and Hao, C and Li, Y and Zhang, N and Chen, YH and Liu, S}, title = {TIPE3 protein promotes breast cancer metastasis through activating AKT and NF-κB signaling pathways.}, journal = {Oncotarget}, volume = {8}, number = {30}, pages = {48889-48904}, pmid = {28388580}, issn = {1949-2553}, mesh = {Adult ; Aged ; Animals ; Biomarkers, Tumor ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics/metabolism ; Disease Models, Animal ; Female ; Gene Expression ; Heterografts ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Middle Aged ; NF-kappa B/*metabolism ; Neoplasm Metastasis ; Neoplasm Staging ; Proto-Oncogene Proteins c-akt/*metabolism ; *Signal Transduction ; Tumor Burden ; }, abstract = {TIPE3 (TNFAIP8L3) is the transfer protein of phosphoinositide second messengers that promote cancer. Its role in breast cancer has not been evaluated. We report here that TIPE3 protein was significantly upregulated in human breast cancer tissues as compared with adjacent non-tumor tissues from the same patients. The level of TIPE3 protein in invasive ductal carcinoma was significant higher than that in ductal carcinoma in situ (DCIS), and the level of TIPE3 in lymphatic metastasized carcinoma was higher than that in invasive ductal carcinoma from the same patients. Additionally, the level of TIPE3 protein was positively correlated with the level of human epidermal growth factor receptor 2 (HER-2), and TIPE3 expression was significantly higher in high-invasive breast cancer cell lines than that in low-invasive cell lines. Importantly, TIPE3 knockdown in breast cancer cells inhibited cell proliferation, migration, and invasion in vitro, whereas TIPE3 overexpression had the opposite effect. In mice, TIPE3 expression significantly promoted the metastasis of breast cancer cells. TIPE3 expression also increased the level of MMP2 and uPA, and the activation of the AKT and NF-κB signaling pathways. These results demonstrate that TIPE3 may promote breast cancer growth and metastasis through AKT and NF-κB, and may serve as a potential biomarker for breast cancer metastasis.}, }
@article {pmid28385191, year = {2017}, author = {Hidmark, AS and Nawroth, PP and Fleming, T}, title = {STZ causes depletion of immune cells in sciatic nerve and dorsal root ganglion in experimental diabetes.}, journal = {Journal of neuroimmunology}, volume = {306}, number = {}, pages = {76-82}, doi = {10.1016/j.jneuroim.2017.03.008}, pmid = {28385191}, issn = {1872-8421}, mesh = {Animals ; Antibiotics, Antineoplastic/toxicity ; Antigens, CD/metabolism ; Cytokines/metabolism ; Diabetes Mellitus, Experimental/chemically induced/*pathology/*physiopathology ; Disease Models, Animal ; Flow Cytometry ; Ganglia, Spinal/drug effects/*pathology ; Hyperalgesia/etiology ; Intercellular Adhesion Molecule-1/metabolism ; Leukocytes/pathology ; Macrophages/drug effects/pathology ; Mice ; Mice, Inbred C57BL ; Sciatic Nerve/drug effects/*pathology ; Streptozocin/toxicity ; Time Factors ; }, abstract = {Streptozotocin (STZ) treatment, a common model for inducing diabetes in rodent models, induces thermal hyperalgesia and neuronal toxicity independently of hyperglycemia by oxidizing and activating TRPA1 and TRPV1. Following treatment with STZ, CD45[+] immune cells were found to be depleted in sciatic nerve (SN) and DRG in mice, prior to hyperglycemia. Macrophages were also lost in DRG and NFκB-p65-activation was increased in SN macrophages. Immune cells were significantly reduced in both SN and DRG up to three weeks, post-treatment. Loss of PNS-resident macrophages in response to STZ-mediated toxicity may affect the regenerative capacity of the nerve in response to further injury caused by diabetes.}, }
@article {pmid28382159, year = {2017}, author = {Lee, HT and Liu, SP and Lin, CH and Lee, SW and Hsu, CY and Sytwu, HK and Hsieh, CH and Shyu, WC}, title = {A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke.}, journal = {Theranostics}, volume = {7}, number = {4}, pages = {855-875}, pmid = {28382159}, issn = {1838-7640}, mesh = {Animals ; Chemokines, CXC/*metabolism ; Dendritic Cells/immunology ; Humans ; *Lymphocyte Activation ; Rats, Sprague-Dawley ; Stroke/*physiopathology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Inflammatory processes have a detrimental role in the pathophysiology of ischemic stroke. However, little is known about the endogenous anti-inflammatory mechanisms in ischemic brain. Here, we identify CXCL14 as a critical mediator of these mechanisms. CXCL14 levels were upregulated in the ischemic brains of humans and rodents. Moreover, hypoxia inducible factor-1α (HIF-1α) drives hypoxia- or cerebral ischemia (CI)-dependent CXCL14 expression via directly binding to the CXCL14 promoter. Depletion of CXCL14 inhibited the accumulation of immature dendritic cells (iDC) or regulatory T cells (Treg) and increased the infarct volume, whereas the supplementation of CXCL14 had the opposite effects. CXCL14 promoted the adhesion, migration, and homing of circulating CD11c[+] iDC to the ischemic tissue via the upregulation of the cellular prion protein (PrP[C]), PECAM-1, and MMPs. The accumulation of Treg in ischemic areas of the brain was mediated through a cooperative effect of CXCL14 and iDC-secreted IL-2-induced Treg differentiation. Interestingly, CXCL14 largely promoted IL-2-induced Treg differentiation. These findings indicate that CXCL14 is a critical immunomodulator involved in the stroke-induced inflammatory reaction. Passive CXCL14 supplementation provides a tractable path for clinical translation in the improvement of stroke-induced neuroinflammation.}, }
@article {pmid28375214, year = {2017}, author = {Gallet, R and Violle, C and Fromin, N and Jabbour-Zahab, R and Enquist, BJ and Lenormand, T}, title = {The evolution of bacterial cell size: the internal diffusion-constraint hypothesis.}, journal = {The ISME journal}, volume = {11}, number = {7}, pages = {1559-1568}, pmid = {28375214}, issn = {1751-7370}, mesh = {Bacteria/*cytology/*genetics ; *Biological Evolution ; *Cell Size ; }, abstract = {Size is one of the most important biological traits influencing organismal ecology and evolution. However, we know little about the drivers of body size evolution in unicellulars. A long-term evolution experiment (Lenski's LTEE) in which Escherichia coli adapts to a simple glucose medium has shown that not only the growth rate and the fitness of the bacterium increase over time but also its cell size. This increase in size contradicts prominent 'external diffusion' theory (EDC) predicting that cell size should have evolved toward smaller cells. Among several scenarios, we propose and test an alternative 'internal diffusion-constraint' (IDC) hypothesis for cell size evolution. A change in cell volume affects metabolite concentrations in the cytoplasm. The IDC states that a higher metabolism can be achieved by a reduction in the molecular traffic time inside of the cell, by increasing its volume. To test this hypothesis, we studied a population from the LTEE. We show that bigger cells with greater growth and CO2 production rates and lower mass-to-volume ratio were selected over time in the LTEE. These results are consistent with the IDC hypothesis. This novel hypothesis offers a promising approach for understanding the evolutionary constraints on cell size.}, }
@article {pmid28365833, year = {2017}, author = {Truin, W and Roumen, RMH and Siesling, S and van de Vijver, KK and Tjan-Heijnen, VCG and Voogd, AC}, title = {Estrogen and progesterone receptor expression levels do not differ between lobular and ductal carcinoma in patients with hormone receptor-positive tumors.}, journal = {Breast cancer research and treatment}, volume = {164}, number = {1}, pages = {133-138}, pmid = {28365833}, issn = {1573-7217}, mesh = {Aged ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/pathology ; Carcinoma, Lobular/*diagnosis/genetics/pathology ; Diagnosis, Differential ; Estrogens/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Netherlands ; Progesterone/genetics ; Receptors, Estrogen/*genetics ; Receptors, Progesterone/*genetics ; Treatment Outcome ; }, abstract = {BACKGROUND: Differences in estrogen (ER) and progesterone (PR) expression between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) could be an underlying reason for the difference in chemo-sensitivity and response to hormonal therapy between ILC and IDC. The aim of this study was to investigate the differences in ER and PR expression levels between postmenopausal patients with hormonal receptor-positive ILC and IDC.<br><br>METHODS: We included all ER and/or PR receptor-positive ILC and IDC, diagnosed between January 2011 and December 2013 from the population-based Netherlands Cancer Registry. A semi-quantitative classification was used to analyze differences in ER/PR expression, which consisted of three ER expression classes: 10-69, 70-89, and &#x2265;90%. Differences in ER and PR expression levels between IDC and ILC were analyzed according to age group, tumor size, axillary nodal status, grade, and HER2 status.<br><br>RESULTS: In total, 26,339 ER and/or PR-positive breast cancers were included in the study, of which 17% were ILC and 83% IDC. In patients with IDC, 86% of the tumors showed an ER expression level of 90% or more, compared to 84% in those with ILC. In both IDC and ILC a PR expression level of 90% or more was observed in 54% of the tumors. In postmenopausal patients aged 50-69&#xa0;years no significant differences could be observed in ER and PR expression levels between ILC and IDC.<br><br>CONCLUSION: Patients with ER and PR-positive ILC and IDC have similar quantitative ER and PR expression profiles, implicating that ER/PR expression is unlikely to be a confounding factor in studies concerning chemo-sensitivity of ILC and IDC.}, }
@article {pmid28355358, year = {2017}, author = {Carrara, GF and Scapulatempo-Neto, C and Abrahão-Machado, LF and Brentani, MM and Nunes, JS and Folgueira, MA and Vieira, RA}, title = {Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {72}, number = {3}, pages = {134-142}, pmid = {28355358}, issn = {1980-5322}, mesh = {Adult ; Breast Neoplasms/*drug therapy/pathology/*surgery ; Carcinoma/*drug therapy/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Recurrence, Local/*etiology ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Survival Analysis ; Time Factors ; Treatment Outcome ; Tumor Burden ; }, abstract = {OBJECTIVE:: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer.<br><br>METHODS:: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival.<br><br>RESULTS:: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01).<br><br>CONCLUSIONS:: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.}, }
@article {pmid28353289, year = {2017}, author = {Masferrer, L and Garre-Olmo, J and Caparrós, B}, title = {Factor structure and concurrent construct validity of ICG among bereaved substance users.}, journal = {Actas espanolas de psiquiatria}, volume = {45}, number = {2}, pages = {47-55}, pmid = {28353289}, issn = {1578-2735}, mesh = {Cross-Sectional Studies ; Female ; *Grief ; Humans ; Male ; Middle Aged ; Patient Health Questionnaire ; Psychometrics ; Reproducibility of Results ; Substance-Related Disorders/*etiology/*psychology ; }, abstract = {BACKGROUND: It is important to understand the repercussions of Complicated Grief (CG) symptoms in addictions. There are no studies to date which have examined the psychometric properties of any test of bereavement among people with substance use disorder (SUD). Participants with SUD can have a different experience of bereavement from other people and therefore could respond differently to the usual instruments which assess CG symptomatology.<br><br>METHOD: This study aims to establish the psychometric properties of the Spanish adaption of the Inventory of Complicated Grief (ICG) in a sample of 196 bereaved drug dependent patients.<br><br>RESULTS: Results indicate that the internal consistency of the Spanish ICG was high (Cronbach&#8217;s alpha=0.922). The Spanish IDC shows good psychometric properties and it is a useful tool to discriminate adaptive reactions to symptomatology of complicated grief. Four factors were identified: discomfort, non-acceptance, loneliness-isolation and presence of deceased. Those factors showed a good internal reliability (minimum Cronbach&#8217;s alpha=0.78).<br><br>CONCLUSIONS: The results of the current study confirm the multidimensionality of CG&#8217;s symptomatology construct.}, }
@article {pmid28342640, year = {2017}, author = {Porter, LH and Lawrence, MG and Ilic, D and Clouston, D and Bolton, DM and Frydenberg, M and Murphy, DG and Pezaro, C and Risbridger, GP and Taylor, RA}, title = {Systematic Review Links the Prevalence of Intraductal Carcinoma of the Prostate to Prostate Cancer Risk Categories.}, journal = {European urology}, volume = {72}, number = {4}, pages = {492-495}, doi = {10.1016/j.eururo.2017.03.013}, pmid = {28342640}, issn = {1873-7560}, mesh = {Carcinoma/*epidemiology/pathology/therapy ; Cell Proliferation ; Humans ; Male ; Neoplasm Grading ; Prevalence ; Prostatic Neoplasms/*epidemiology/pathology/therapy ; Risk Assessment ; Risk Factors ; }, abstract = {UNLABELLED: Intraductal carcinoma of the prostate (IDC-P) is associated with poor prognosis. While it is often regarded as a rare pathology, the prevalence of IDC-P remains unclear, with variable reports from small and disparate patient populations. To determine how common IDC-P is across the spectrum of prostate cancer, we conducted a systematic review correlating IDC-P prevalence with prostate cancer risk. Electronic searches of the OVID Medline, PubMed, and Scopus literature databases identified 38 patient cohorts in 24 articles, which were divided between four prostate cancer risk categories (low, moderate, high, and recurrent or metastatic disease). This review, which included radical prostatectomy and prostate biopsy specimens from >7000 patients, revealed an unexpectedly high rate of IDC-P. The IDC-P prevalence increased from 2.1% in low-risk patient cohorts to 23.1%, 36.7%, and 56.0% in moderate-risk, high-risk, and metastatic or recurrent disease risk categories, respectively (p<0.0001). IDC-P was also highly prevalent in tumours following androgen deprivation therapy or chemotherapy (60%). Contrary to common perceptions, this study demonstrates a strong association between IDC-P prevalence and aggressive prostate cancer, with a significantly higher frequency in high-risk disease. Greater recognition and systematic reporting of IDC-P may improve patient risk stratification.<br><br>PATIENT SUMMARY: Prostate cancer can grow within ducts of the prostate, as well as in prostate tissue. By reviewing all reports describing prostate cancer growing within ducts, we found that it occurs more commonly than many scientists and clinicians appreciate, especially in aggressive prostate cancers. We conclude that there should be more awareness of this pattern of prostate cancer.}, }
@article {pmid28331761, year = {2017}, author = {Külahcı, &#xd6; and Esen, HH and Asut, E and Güngör, S}, title = {Association of ICAM-1, VCAM-1, CYCLIN D1 and Cathepsin D with Clinicopathological Parameters in Breast Carcinoma; an Immunohistochemical Study.}, journal = {The journal of breast health}, volume = {13}, number = {1}, pages = {5-9}, pmid = {28331761}, issn = {1306-0945}, abstract = {OBJECTIVE: Breast carcinoma is the most common malignant tumor detected in women. The hypothesis that increased levels of adhesion molecules and Cathepsin D affect cancerous cells moving away the primary tumor and contributes to migration of the cancerous cell and may cause remote organ metastases is defended. The aim of the present study was to search the association of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), Cyclin D1, cathepsin D immunohistochemically with clinicopathological parameters in the patients diagnosed with invasive ductal breast carcinoma.<br><br>MATERIALS AND METHODS: The pathological slides of 153 patients diagnosed with invasive ductal carcinoma were evaluated retrospectively. Three groups were created. Group 1 consisted of patients with positive lymph node metastasis and extranodal tumor invasion; Group 2 consisted of patients with positive axillary lymph node metastasis and negative extranodal tumor invasion and Group 3 consisted of the patients with negative axillary lymph node metastasis. In all groups, 20 paraffin blocks belonging to the primary tumor in the breast were stained by ICAM-1, VCAM-1, Cyclin D1 and Cathepsin D. Findings were examined by comparing with clinicopathological parameters.<br><br>RESULTS: The highest number of metastatic axillary lymph nodes and the highest rate of cathepsin D staining were statistically found in the cases with positive axillary lymph node metastasis and extranodal tumor invasion. CerbB2 was negative in the cases with negative ICAM-1 whereas estrogen receptor and progesterone receptor were positive in the cases with positive VCAM-1.<br><br>CONCLUSION: The present study reveals significant results for the patients diagnosed with invasive ductal carcinoma through breast biopsy especially before mastectomy in terms of increased number of metastatic axillary lymph nodes and extranodal tumor invasion by immunohistochemical Cathepsin D stain without any additional invasive intervention. Results of the present study may contribute to monitoring and treatment of the patients in the future.}, }
@article {pmid28326638, year = {2017}, author = {Mizukawa, K and Kobayashi, T and Yamada, N and Hirota, T}, title = {Intervertebral disc calcification with ossification of the posterior longitudinal ligament.}, journal = {Pediatrics international : official journal of the Japan Pediatric Society}, volume = {59}, number = {5}, pages = {622-624}, doi = {10.1111/ped.13243}, pmid = {28326638}, issn = {1442-200X}, mesh = {Calcinosis/complications/*diagnostic imaging ; Cervical Vertebrae/*diagnostic imaging ; Child ; Female ; Humans ; Ossification of Posterior Longitudinal Ligament/complications/*diagnostic imaging ; *Tomography, X-Ray Computed ; }, abstract = {A 6-year-old girl presented to hospital with a 4 day history of increasing neck pain. White blood cell count was normal with slightly raised C-reactive protein. The patient had a limited range of neck movement, and experienced enhanced pain with neck extension. X-ray and cervical computed tomography (CT) confirmed the diagnosis of cervical intervertebral disc calcification (IDC) and IDC with ossification of the posterior longitudinal ligament (OPLL), respectively. The symptoms improved after approximately 1 week following rest and oral acetaminophen. X-ray 6 months after onset confirmed the disappearance of the calcification. IDC is often reported in children, but IDC with OPLL is extremely rare and has not been previously reported in Japan. We believe that IDC with or without OPLL in children has a good prognosis when treated conservatively.}, }
@article {pmid28325697, year = {2017}, author = {Sulaj, A and Kopf, S and Gröne, E and Gröne, HJ and Hoffmann, S and Schleicher, E and Häring, HU and Schwenger, V and Herzig, S and Fleming, T and Nawroth, PP and von Bauer, R}, title = {ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy.}, journal = {Journal of diabetes and its complications}, volume = {31}, number = {6}, pages = {1058-1065}, doi = {10.1016/j.jdiacomp.2017.01.002}, pmid = {28325697}, issn = {1873-460X}, mesh = {Adult ; Aged ; Antigens, CD/analysis/*blood/physiology ; Biomarkers/*blood ; Case-Control Studies ; Cell Adhesion Molecules, Neuronal/analysis/*blood/physiology ; Diabetes Mellitus, Type 2/*blood/*complications/diagnosis ; Diabetic Nephropathies/blood/*diagnosis/etiology ; Disease Progression ; Female ; Fetal Proteins/analysis/*blood/physiology ; Humans ; Kidney/physiopathology ; Male ; Middle Aged ; Prognosis ; }, abstract = {BACKGROUND &amp; AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN.<br><br>METHODS: A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA. Expression of ALCAM and S100B in kidney histology from patients with DN was determined by immunohistochemistry. Cell expression of ALCAM and S100B was analyzed through confocal immunofluorescence microscopy.<br><br>RESULTS: Serum concentration of sALCAM was increased in diabetic patients with DN compared to non-diabetic (59.85&#xb1;14.99ng/ml vs. 126.88&#xb1;66.45ng/ml, P<0.0001). Moreover sALCAM correlated positively with HbA1c (R=0.31, P<0.0001), as well as with the stages of chronic kidney disease and negatively correlated with eGFR (R=-0.20, P<0.05). In diabetic patients with normal albuminuria sALCAM was increased compared to patients with DN (126.88&#xb1;66.45ng/ml vs. 197.50&#xb1;37.17ng/ml, P<0.0001). In diabetic patients, ALCAM expression was significantly upregulated in both the glomeruli and tubules (P<0.001). ALCAM expression in the glomeruli correlated with presence of sclerosis (R=0.25, P<0.001) and localized mainly in the podocytes supporting the hypothesis that membrane bound ALCAM drives diabetic nephropathy and thus explaining sALCAM decrease in diabetic patients with DN. The expression of S100B was increased significantly in the glomeruli of diabetic patients (P<0.001), but not in the tubules. S100B was as well localized in the podocytes.<br><br>CONCLUSIONS: This study identifies for the first time ALCAM as a potential mediator in the late complications of diabetes in the kidney.}, }
@article {pmid28301465, year = {2017}, author = {Chao, LF and Singh, M and Thompson, J and Yates, JR and Hagstrom, KA}, title = {An SMC-like protein binds and regulates Caenorhabditis elegans condensins.}, journal = {PLoS genetics}, volume = {13}, number = {3}, pages = {e1006614}, pmid = {28301465}, issn = {1553-7404}, support = {P41 GM103533/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/*genetics/metabolism ; Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/embryology/*genetics/growth &amp; development ; Caenorhabditis elegans Proteins/classification/*genetics/metabolism ; Chromosomal Proteins, Non-Histone/genetics/metabolism ; DNA-Binding Proteins/*genetics/metabolism ; Gene Expression Regulation, Developmental ; Meiosis/genetics ; Microscopy, Confocal ; Mitosis/genetics ; Multiprotein Complexes/*genetics/metabolism ; Mutation ; Nuclear Proteins/genetics/metabolism ; Phylogeny ; Protein Binding ; Protein Subunits/genetics/metabolism ; Sequence Homology, Amino Acid ; X Chromosome/genetics ; }, abstract = {Structural Maintenance of Chromosomes (SMC) family proteins participate in multisubunit complexes that govern chromosome structure and dynamics. SMC-containing condensin complexes create chromosome topologies essential for mitosis/meiosis, gene expression, recombination, and repair. Many eukaryotes have two condensin complexes (I and II); C. elegans has three (I, II, and the X-chromosome specialized condensin IDC) and their regulation is poorly understood. Here we identify a novel SMC-like protein, SMCL-1, that binds to C. elegans condensin SMC subunits, and modulates condensin functions. Consistent with a possible role as a negative regulator, loss of SMCL-1 partially rescued the lethal and sterile phenotypes of a hypomorphic condensin mutant, while over-expression of SMCL-1 caused lethality, chromosome mis-segregation, and disruption of condensin IDC localization on X chromosomes. Unlike canonical SMC proteins, SMCL-1 lacks hinge and coil domains, and its ATPase domain lacks conserved amino acids required for ATP hydrolysis, leading to the speculation that it may inhibit condensin ATPase activity. SMCL-1 homologs are apparent only in the subset of Caenorhabditis species in which the condensin I and II subunit SMC-4 duplicated to create the condensin IDC- specific subunit DPY-27, suggesting that SMCL-1 helps this lineage cope with the regulatory challenges imposed by evolution of a third condensin complex. Our findings uncover a new regulator of condensins and highlight how the duplication and divergence of SMC complex components in various lineages has created new proteins with diverse functions in chromosome dynamics.}, }
@article {pmid28296665, year = {2018}, author = {Boufelli, G and Giannotti, MA and Ruiz, CA and Barros, N and Chala, LF and Maesaka, JY and Goncalves, R and Bresciani, BH and Vianna, P and Soares, JM and Baracat, EC and Filassi, JR}, title = {Papillomas of the breast: factors associated with underestimation.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {27}, number = {4}, pages = {310-314}, pmid = {28296665}, issn = {1473-5709}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Papillary/*diagnosis/diagnostic imaging/surgery ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Mammography/*methods ; Middle Aged ; Prognosis ; Risk Assessment/*methods ; Risk Factors ; Ultrasonography, Mammary/*methods ; }, abstract = {The distinction between benign and malignant papilloma of the breast through percutaneous needle biopsy can be difficult because of limited samples; the underestimation rate can be up to 25%. The aim of this study is to identify clinical and histological factors associated with underestimation, invasive ductal carcinoma, or ductal in-situ carcinoma (DCIS) of the breast found in surgical specimens from papillary lesions. This may contribute toward selection of patients for a follow-up strategy without the need for surgical excision. From a database of 3563 patients, we identified 85 with intraductal papilloma between 2007 and 2013 who had undergone breast-imaging studies, percutaneous needle biopsy, and surgical resection of the lesion. Central papillomas normally present with a palpable mass, whereas peripheral papillomas generally do not have clinical manifestations (microcalcifications); both central and peripheral papillomas were related to atypical lesions, 13.5 and 15.4%, respectively. Among the 59 cases of central papillomas, there were four cases of underestimation, three DCIS and one invasive ductal carcinoma (6.8%). Among the 26 cases of peripheral papillomas, there was one case of DCIS (3.8%), with a total underestimation rate of 5.8%; all underestimated lesions measured more than 1 cm. The median size was 11 mm at mammography and 19 mm at ultrasound. Our data suggest that lesions less than 1 cm in size, without atypia and concordant imaging and clinical findings, may not require surgical resection.}, }
@article {pmid28292037, year = {2016}, author = {Khalil, AI and Bendahhou, K and Mestaghanmi, H and Saile, R and Benider, A}, title = {[Breast cancer in Morocco: phenotypic profile of tumors].}, journal = {The Pan African medical journal}, volume = {25}, number = {}, pages = {74}, pmid = {28292037}, issn = {1937-8688}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*pathology/therapy ; Breast Neoplasms, Male/epidemiology/*pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/*pathology/therapy ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Neoplasm Staging ; Phenotype ; Young Adult ; }, abstract = {Breast cancer is most common in women and it is among the leading causes of cancer related deaths. The curability of this type of tumor is increasing thanks to screening programs and treatment advances which have certainly enhanced patient survival. But challenges remain, particularly in respect of phenotypic instability of cancer cells. The aim of this study was to analyse the phenotypic profile of breast cancer in patients treated at Mohammed VI Cancer Treatment Center over the years 2013-2014. We conducted a cross-sectional study over a two-year period, including the cases of breast cancer treated in our Center. Data were collected from patients medical records and analyzed using Epi Info software. 1277 patients were treated in our Center. 99.5% were females, mean age 50.20 ± 11.34 years. The most common histological type was invasive ductal carcinoma (80.7% of cases). It was diagnosed at an early stage (56,9%). The most common molecular phenotype was luminal A (41.4% of cases). Luminal B, HER2 and triple negatives occurred in 10.4%, 6.3%, 11.2% of cases respectively. The study of tumor phenotype in patients with breast cancer helps clinician make treatment choice and policy makers implement programs against this disease.}, }
@article {pmid28291966, year = {2017}, author = {Miyazaki, T and Ohishi, Y and Miyasaka, Y and Oda, Y and Aishima, S and Ozono, K and Abe, A and Nagai, E and Nakamura, M and Oda, Y}, title = {Molecular Characteristics of Pancreatic Ductal Adenocarcinomas with High-Grade Pancreatic Intraepithelial Neoplasia (PanIN) Are Different from Those without High-Grade PanIN.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {84}, number = {4}, pages = {192-201}, doi = {10.1159/000455194}, pmid = {28291966}, issn = {1423-0291}, mesh = {Aged ; Carcinoma in Situ/*complications ; Carcinoma, Pancreatic Ductal/complications/*genetics/metabolism/*pathology ; Humans ; Middle Aged ; Pancreas/metabolism/pathology ; Pancreatic Neoplasms/complications/*genetics/metabolism/pathology ; Prognosis ; Proto-Oncogene Proteins p21(ras)/*genetics ; Smad4 Protein/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {AIMS: We reported that pancreatic ductal adenocarcinomas (PDACs) without high-grade pancreatic intraepithelial neoplasia (PanIN) in the vicinity had worse prognoses than PDACs with high-grade PanIN. However, the molecular characteristics of PDACs with and without high-grade PanIN have not been compared. The aim of this study is to clarify the molecular characteristics of PDACs with and without high-grade PanIN.<br><br>METHOD AND RESULTS: We reviewed all of a consecutive series of 100 patients with PDACs and divided them into 2 groups: the PDACs with PanIN-2 or PanIN-3 in the background (the PanIN-high group, n = 60) and the PDACs without PanIN-2 or PanIN-3 in the background (the PanIN-low group, n = 40). We evaluated the p53, p16, and SMAD4 expressions in the invasive ductal carcinoma (IDC) components by immunohistochemical staining. KRAS mutation was also analyzed in 80 tumors. The PanIN-low group showed significantly more frequent "high p53 expression" and "loss of SMAD4 expression" than the PanIN-high group (p = 0.048 and p = 0.019, respectively). Loss of p16 expression was not significantly different between the groups. The rate of KRAS wild type was significantly higher in the PanIN-low group than the PanIN-high group (p = 0.024).<br><br>CONCLUSIONS: Our results demonstrated that the molecular characteristics in the PDACs with high-grade PanIN were different from those in the PDACs without high-grade PanIN. PDACs without high-grade PanIN may develop via a pathway other than the PanIN-carcinoma sequence.}, }
@article {pmid28291131, year = {2017}, author = {Konstantinova, AM and Shelekhova, KV and Imyanitov, EN and Iyevleva, A and Kacerovska, D and Michal, M and Kazakov, DV}, title = {Study of Selected BRCA1, BRCA2, and PIK3CA Mutations in Benign and Malignant Lesions of Anogenital Mammary-Like Glands.}, journal = {The American Journal of dermatopathology}, volume = {39}, number = {5}, pages = {358-362}, doi = {10.1097/DAD.0000000000000725}, pmid = {28291131}, issn = {1533-0311}, mesh = {Aged ; Aged, 80 and over ; Anus Neoplasms/genetics/pathology ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Biopsy, Needle ; Class I Phosphatidylinositol 3-Kinases/*genetics ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Mammary Glands, Human/pathology ; Middle Aged ; Mutation ; Paget Disease, Extramammary/*genetics/*pathology ; Prognosis ; Retrospective Studies ; Risk Assessment ; Vulvar Neoplasms/genetics/pathology ; }, abstract = {Anogenital mammary-like glands (AGMLGs) are nowadays considered a normal component of the anogenital area. Lesions involving AGMLGs are histopathologically very similar to their mammary counterparts, but the information on molecular biological mechanisms in these vulvar/perianal tumors is scarce. Mutations in the PI3K-AKT cascade have been found in hidradenoma papilliferum. The authors studied selected BRCA1, BRCA2, and PIK3CA mutations in series of benign and malignant neoplasms thought to be associated with AGMLGs, including 9 cases of primary extramammary Paget disease, 3 different cases of mammary-type carcinoma (adenoid cystic like, tubulolobular, and invasive ductal like), and 5 cases of hidradenoma papilliferum. No BRCA mutation was detected, whereas 3 neoplasms yielded PIK3CA mutation, including extramammary Paget disease, mammary-type invasive ductal carcinoma, and tubulolobular carcinoma. Our study expands the spectrum of lesions of AGMLGs harboring mutations in genes encoding the PI3K-AKT cascade. Further studies of the whole BRCA1 and BRCA2 genes using a larger cohort are needed to clarify their role in the pathogenesis of AGMLG lesions.}, }
@article {pmid28274688, year = {2017}, author = {Li, X and Lu, P and Li, B and Zhang, W and Yang, R and Chu, Y and Luo, K}, title = {Interleukin 2 and interleukin 10 function synergistically to promote CD8[+] T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {87}, number = {}, pages = {1-7}, pmid = {28274688}, issn = {1878-5875}, mesh = {Breast Neoplasms/immunology/*pathology ; CD4 Antigens/metabolism ; CD4-Positive T-Lymphocytes/*cytology/*drug effects/immunology ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Synergism ; Female ; Humans ; Interleukin-10/*pharmacology ; Interleukin-2/*pharmacology ; Interleukin-2 Receptor alpha Subunit/metabolism ; Middle Aged ; T-Lymphocytes, Regulatory/*cytology/*drug effects/immunology/metabolism ; }, abstract = {The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8[+] T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8[+] T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8[+] T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8[+] T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8[+] T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8[+] T cells but could significantly enhance IL-2-mediated promotion of CD8[+] T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8[+] T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4[+]CD25[+] regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8[+] T cells, an effect suppressible by CD4[+]CD25[+] Treg cells.}, }
@article {pmid28272456, year = {2017}, author = {Zhang, J and Naik, HS and Assefa, T and Sarkar, S and Reddy, RV and Singh, A and Ganapathysubramanian, B and Singh, AK}, title = {Computer vision and machine learning for robust phenotyping in genome-wide studies.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {44048}, pmid = {28272456}, issn = {2045-2322}, mesh = {*Artificial Intelligence ; Genome-Wide Association Study/*methods ; Image Processing, Computer-Assisted ; *Machine Learning ; Phenotype ; Quantitative Trait Loci ; Soybeans/*genetics/metabolism ; Stress, Physiological ; }, abstract = {Traditional evaluation of crop biotic and abiotic stresses are time-consuming and labor-intensive limiting the ability to dissect the genetic basis of quantitative traits. A machine learning (ML)-enabled image-phenotyping pipeline for the genetic studies of abiotic stress iron deficiency chlorosis (IDC) of soybean is reported. IDC classification and severity for an association panel of 461 diverse plant-introduction accessions was evaluated using an end-to-end phenotyping workflow. The workflow consisted of a multi-stage procedure including: (1) optimized protocols for consistent image capture across plant canopies, (2) canopy identification and registration from cluttered backgrounds, (3) extraction of domain expert informed features from the processed images to accurately represent IDC expression, and (4) supervised ML-based classifiers that linked the automatically extracted features with expert-rating equivalent IDC scores. ML-generated phenotypic data were subsequently utilized for the genome-wide association study and genomic prediction. The results illustrate the reliability and advantage of ML-enabled image-phenotyping pipeline by identifying previously reported locus and a novel locus harboring a gene homolog involved in iron acquisition. This study demonstrates a promising path for integrating the phenotyping pipeline into genomic prediction, and provides a systematic framework enabling robust and quicker phenotyping through ground-based systems.}, }
@article {pmid28264146, year = {2017}, author = {Yao, X and Gan, Y and Chang, E and Hibshoosh, H and Feldman, S and Hendon, C}, title = {Visualization and tissue classification of human breast cancer images using ultrahigh-resolution OCT.}, journal = {Lasers in surgery and medicine}, volume = {49}, number = {3}, pages = {258-269}, pmid = {28264146}, issn = {1096-9101}, support = {DP2 HL127776/HL/NHLBI NIH HHS/United States ; }, mesh = {Biopsy, Needle ; Breast/*diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology/*surgery ; Cross-Sectional Studies ; Female ; Humans ; *Imaging, Three-Dimensional ; Immunohistochemistry ; In Vitro Techniques ; Mastectomy/methods ; Reference Values ; Sampling Studies ; Tomography, Optical Coherence/*methods ; }, abstract = {BACKGROUND AND OBJECTIVE: Breast cancer is one of the most common cancers, and recognized as the third leading cause of mortality in women. Optical coherence tomography (OCT) enables three dimensional visualization of biological tissue with micrometer level resolution at high speed, and can play an important role in early diagnosis and treatment guidance of breast cancer. In particular, ultra-high resolution (UHR) OCT provides images with better histological correlation. This paper compared UHR OCT performance with standard OCT in breast cancer imaging qualitatively and quantitatively. Automatic tissue classification algorithms were used to automatically detect invasive ductal carcinoma in ex vivo human breast tissue.<br><br>Human breast tissues, including non-neoplastic/normal tissues from breast reduction and tumor samples from mastectomy specimens, were excised from patients at Columbia University Medical Center. The tissue specimens were imaged by two spectral domain OCT systems at different wavelengths: a home-built ultra-high resolution (UHR) OCT system at 800&#x2009;nm (measured as 2.72&#x2009;&#x3bc;m axial and 5.52&#x2009;&#x3bc;m lateral) and a commercial OCT system at 1,300&#x2009;nm with standard resolution (measured as 6.5&#x2009;&#x3bc;m axial and 15&#x2009;&#x3bc;m lateral), and their imaging performances were analyzed qualitatively. Using regional features derived from OCT images produced by the two systems, we developed an automated classification algorithm based on relevance vector machine (RVM) to differentiate hollow-structured adipose tissue against solid tissue. We further developed B-scan based features for RVM to classify invasive ductal carcinoma (IDC) against normal fibrous stroma tissue among OCT datasets produced by the two systems. For adipose classification, 32 UHR OCT B-scans from 9 normal specimens, and 28 standard OCT B-scans from 6 normal and 4 IDC specimens were employed. For IDC classification, 152 UHR OCT B-scans from 6 normal and 13 IDC specimens, and 104 standard OCT B-scans from 5 normal and 8 IDC specimens were employed.<br><br>RESULTS: We have demonstrated that UHR OCT images can produce images with better feature delineation compared with images produced by 1,300&#x2009;nm OCT system. UHR OCT images of a variety of tissue types found in human breast tissue were presented. With a limited number of datasets, we showed that both OCT systems can achieve a good accuracy in identifying adipose tissue. Classification in UHR OCT images achieved higher sensitivity (94%) and specificity (93%) of adipose tissue than the sensitivity (91%) and specificity (76%) in 1,300&#x2009;nm OCT images. In IDC classification, similarly, we achieved better results with UHR OCT images, featured an overall accuracy of 84%, sensitivity of 89% and specificity of 71% in this preliminary study.<br><br>CONCLUSION: In this study, we provided UHR OCT images of different normal and malignant breast tissue types, and qualitatively and quantitatively studied the texture and optical features from OCT images of human breast tissue at different resolutions. We developed an automated approach to differentiate adipose tissue, fibrous stroma, and IDC within human breast tissues. Our work may open the door toward automatic intraoperative OCT evaluation of early-stage breast cancer. Lasers Surg. Med. 49:258-269, 2017. &#xa9; 2017 Wiley Periodicals, Inc.}, }
@article {pmid28240310, year = {2017}, author = {Sowrirajan, B and Saito, Y and Poudyal, D and Chen, Q and Sui, H and DeRavin, SS and Imamichi, H and Sato, T and Kuhns, DB and Noguchi, N and Malech, HL and Lane, HC and Imamichi, T}, title = {Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47[phox].}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {43441}, pmid = {28240310}, issn = {2045-2322}, support = {HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Cell Differentiation/drug effects ; Dendritic Cells/cytology/*drug effects/immunology ; Gene Expression Regulation ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Interleukins/*pharmacology ; Macrophage Activation/drug effects ; Macrophage Colony-Stimulating Factor/pharmacology ; Macrophages/cytology/*drug effects/immunology ; NADPH Oxidases/*genetics/immunology ; Phosphorylation/drug effects ; Primary Cell Culture ; Signal Transduction ; Superoxide Dismutase/genetics/immunology ; Superoxides/immunology/*metabolism ; }, abstract = {Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ROS) generating activity during differentiation of monocytes to macrophages. In this study, we further investigated the mechanism of the enhanced potential for ROS generation by IL-27. Real time PCR, western blot and knock down assays demonstrate that IL-27 is able to enhance the potential of superoxide production not only during differentiation but also in terminally differentiated-macrophages and immature dendritic cells (iDC) in association with the induction of p47[phox], a cytosolic component of the ROS producing enzyme, NADPH oxidase, and the increase in amounts of phosphorylated p47[phox] upon stimulation. We also demonstrate that IL-27 is able to induce extracellular superoxide dismutase during differentiation of monocytes but not in terminal differentiated macrophages. Since ROS plays an important role in a variety of inflammation, our data demonstrate that IL-27 is a potent regulator of ROS induction and may be a novel therapeutic target.}, }
@article {pmid28224328, year = {2017}, author = {Santangelo, G and Lagravinese, G and Battini, V and Chiorri, C and Siciliano, M and Abbruzzese, G and Vitale, C and Barone, P}, title = {The Parkinson's Disease-Cognitive Rating Scale (PD-CRS): normative values from 268 healthy Italian individuals.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {38}, number = {5}, pages = {845-853}, pmid = {28224328}, issn = {1590-3478}, mesh = {Adult ; Age Factors ; Aged ; Cognition Disorders/*diagnosis/*etiology ; Educational Status ; Female ; Healthy Volunteers ; Humans ; Italy ; Male ; Middle Aged ; *Neuropsychological Tests ; Parkinson Disease/*complications ; Reference Values ; Severity of Illness Index ; Young Adult ; }, abstract = {The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a cognitive screening battery that includes subtests to assess cortical and subcortical functions. It is a valid screening tool for mild cognitive impairment (MCI) in Parkinson's disease (PD) and is recommended for diagnosing PD-MCI-Level I. Until now, no study has provided population-based norms for the Italian population. The aim of the present study was to collect normative values in a sample of Italian healthy subjects. Two hundred and sixty-eight (125 men) participants of different ages (age range 30-79 years) and educational levels (from primary school to university) underwent the PD-CRS. Regression-based norming was used to explore the influence of demographic variables (age, education level, and gender) on PD-CRS total score, frontal-subcortical and instrumental-cortical sub-scores, and score achieved on each task of the PD-CRS. Multiple linear regression analysis revealed that age and education significantly predicted the total score, the two sub-scores and the score on each task of the PD-CRS. No significant effect of gender was found. From the derived linear equations, a correction grid for raw scores was developed. Inferential cut-off scores, estimated using a non-parametric technique, were 71.25 for PD-CRS total score and 46.25 and 20.17 for frontal-subcortical and instrumental-cortical sub-score, respectively. Since the use of adjusted scores is more informative when they are standardized, we have converted adjusted scores into equivalent scores. The present study provides normative data for the PD-CRS, being useful and recommended by Movement Disorders Society task force to identify PD-MCI-Level I, at several stages of the disease.}, }
@article {pmid28214265, year = {2017}, author = {Picillo, M and Santangelo, G and Erro, R and Cozzolino, A and Amboni, M and Vitale, C and Barone, P and Pellecchia, MT}, title = {Association between dopaminergic dysfunction and anxiety in de novo Parkinson's disease.}, journal = {Parkinsonism &amp; related disorders}, volume = {37}, number = {}, pages = {106-110}, doi = {10.1016/j.parkreldis.2017.02.010}, pmid = {28214265}, issn = {1873-5126}, mesh = {Aged ; Anxiety/diagnostic imaging/*etiology ; Chi-Square Distribution ; Cohort Studies ; Cross-Sectional Studies ; Dopamine/*metabolism ; Dopamine Plasma Membrane Transport Proteins/*metabolism ; Female ; Humans ; International Cooperation ; Male ; Middle Aged ; Parkinson Disease/*complications/diagnostic imaging/*metabolism ; Psychiatric Status Rating Scales ; Statistics as Topic ; Tomography, Emission-Computed, Single-Photon ; }, abstract = {OBJECTIVES: To explore the relationships between nigrostriatal dysfunction and neuropsychiatric symptoms (including anxiety, depression and apathy) in a large cohort of newly diagnosed, drug-naïve Parkinson disease (PD) patients compared to a cohort of healthy controls (HC).<br><br>METHODS: This is a cross-sectional analysis of the Parkinson's Progression Markers Initiative (PPMI) cohort at baseline, including 405 PD patients and 187 HC. Nigrostriatal degeneration was evaluated by means of SPECT DAT scan. Relationships between neuropsychiatric symptoms and DAT uptakes were analysed by means of stepwise multiple regression analysis.<br><br>RESULTS: In the PD group, lower DAT uptake in the right caudate was associated with higher STAI trait subscore (&#x3b2;&#xa0;=&#xa0;-2.939, 95%CI:&#xa0;-4.634 to&#xa0;-1.254, p&#xa0;=&#xa0;0.001). Depression and apathy scores were not related with DAT uptakes. No associations were found in the HC group.<br><br>CONCLUSIONS: Our cross-sectional analysis of the PPMI data shows that lower caudate DAT uptake is associated with higher level of anxiety. The data strengthens the relationship between dopaminergic dysfunction and neuropsychiatric symptoms in early PD.}, }
@article {pmid28207532, year = {2017}, author = {Zhong, J and Lei, J and Jiang, K and Li, Z and Gong, R and Zhu, J}, title = {Synchronous papillary thyroid carcinoma and breast ductal carcinoma: A rare case report and literature review.}, journal = {Medicine}, volume = {96}, number = {7}, pages = {e6114}, pmid = {28207532}, issn = {1536-5964}, mesh = {Breast Neoplasms/*complications/pathology/surgery ; Carcinoma/*complications/pathology/surgery ; Carcinoma, Ductal, Breast/*complications/pathology/surgery ; Carcinoma, Papillary ; Female ; Humans ; Lymph Node Excision ; Mastectomy ; Middle Aged ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/*complications/pathology/surgery ; Thyroidectomy ; }, abstract = {BACKGROUND: The incidences of both thyroid cancer and breast cancer have been rising in recent years; however, it is very rare to find a single person with both of these cancers. Only a few cases of synchronous thyroid and breast cancer have been published, and even fewer cases have been reported in older patients (>60 years).<br><br>CASE SUMMARY: The current study presents a case of synchronous papillary thyroid carcinoma and breast ductal carcinoma in an elderly patient. The patient first underwent a mastectomy and axillary lymphadenectomy in our department, followed by a total thyroidectomy and lymphadenectomy of the left lateral region of the neck 1 month later. Postoperative pathological examination identified invasive ductal carcinoma of the breast and papillary carcinoma of the thyroid. Over almost half a year of follow-up, the patient has exhibited no evidence of recurrence or metastasis, as demonstrated by careful ultrasound examinations. Herein, we not only report this case but also present a systematic review of the causes, diagnosis, and treatment of synchronous breast and thyroid cancer.<br><br>CONCLUSION: Although synchronous primary tumors of the thyroid and breast are very rare, they remain a possibility; therefore, more attention should be paid to these cases.}, }
@article {pmid28198519, year = {2017}, author = {Jeong, YJ and Jung, JW and Cho, YY and Park, SH and Oh, HK and Kang, S}, title = {Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT.}, journal = {Nuclear medicine review. Central &amp; Eastern Europe}, volume = {20}, number = {1}, pages = {32-38}, doi = {10.5603/NMR.a2016.0043}, pmid = {28198519}, issn = {1644-4345}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnostic imaging/*metabolism/mortality ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Middle Aged ; Molecular Imaging/methods ; Positron Emission Tomography Computed Tomography/methods/statistics &amp; numerical data ; Prevalence ; Radiopharmaceuticals/pharmacokinetics ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Tumor Hypoxia ; }, abstract = {BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed.<br><br>MATERIAL AND METHODS: Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.<br><br>RESULTS: pSUVmax was significantly higher in patients with HIF-1a expression &#x2265; 2 compared to patients with HIF-1a expression < 2 (5.2 &#xb1; 4.5 vs. 3.7 &#xb1; 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 &#xb1; 4.4 vs. 4.1 &#xb1; 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001).<br><br>CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell.}, }
@article {pmid28188401, year = {2017}, author = {Walter, H}, title = {[Research domain criteria (RDoC) : Psychiatric research as applied cognitive neuroscience].}, journal = {Der Nervenarzt}, volume = {88}, number = {5}, pages = {538-548}, pmid = {28188401}, issn = {1433-0407}, mesh = {Biomedical Research/*organization &amp; administration ; Cognitive Neuroscience/*methods/*organization &amp; administration ; *Diagnostic and Statistical Manual of Mental Disorders ; Germany ; *Models, Organizational ; Patient Care Team/*organization &amp; administration ; Psychiatry/*organization &amp; administration ; Research Design ; }, abstract = {BACKGROUND: Just before the official launch of the DSM-5 in 2013, the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health was made public and is becoming increasingly more important in psychiatric research.<br><br>OBJECTIVE: The aim of this paper is to clarify the conceptual approach of RDoC, to systematically discuss limitations, to present exemplary RDoC-based studies and to consider the relevance of the RDoC concepts for clinicians and scientists.<br><br>MATERIAL AND METHODS: The is a&#xa0;qualitative introduction and review article with a critical discussion.<br><br>RESULTS AND DISCUSSION: The RDoC initiative was not conceived as an alternative diagnostic manual to DSM-5 or IDC-10/11 for use in clinical practice. It is a&#xa0;new systematic framework for psychiatric research based on the most recent results of cognitive neuroscience and aims to map mental disorders dimensionally and transdiagnostically. Despite some weaknesses, it is currently the most elaborated and scientifically grounded approach for multidisciplinary research on mental disorders. In contrast to the purely symptom-based DSM and ICD approaches, which are agnostic with respect to the pathogenesis of mental diseases, the explicit aim of the RDoC initiative is to systematize biological knowledge about risk factors and causes of mental disorders; therefore, it has a&#xa0;much greater potential to develop new and individualized therapeutic strategies based on disease mechanisms.}, }
@article {pmid28173783, year = {2017}, author = {Effi, AB and Aman, NA and Koui, BS and Koffi, KD and Traoré, ZC and Kouyate, M}, title = {Immunohistochemical determination of estrogen and progesterone receptors in breast cancer: relationship with clinicopathologic factors in 302 patients in Ivory Coast.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {115}, pmid = {28173783}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*metabolism ; Cote d'Ivoire ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Prospective Studies ; Receptors, Estrogen/*analysis/genetics ; Receptors, Progesterone/*analysis/genetics ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous and a hormone-dependent disease. The detection of the estrogen receptor (ER) and progesterone receptor (PgR) is crucial for prognostic evaluation and treatment choice of breast cancer for clinical practice. The purpose of this study was to evaluate the expression of the hormonal receptors, their distribution, and their correlation with clinicopathologic prognostic parameters for the improvement of the patients' treatment in Ivory Coast.<br><br>METHODS: The 20-month prospective study included 302 patients who were diagnosed with primary invasive breast carcinomas at the Central Laboratory in Abidjan. The paraffin-embedded blocks of these patients were examined by immunohistochemistry to assess the ER and PgR status. The one-way analysis of variance and Chi-Square Test were used to analyze the data.<br><br>RESULTS: The mean age of patients at diagnosis was 48&#x2009;&#xb1;&#x2009;11&#xa0;years. The majority of the women were premenopausal in 180 cases (59.9%). The predominant histologic type was invasive ductal carcinoma not otherwise specified (IDC NOS) in 247 cases (82%). Tumor grade 2 was more frequent in 166 cases (55%). Among 302 patients, 169 (56%) and 154 (49%) expressed ER and PgR respectively. The ER+PgR+ group with 131 cases (43%) was predominant, followed by 116 cases (38%) of ER-PgR-. The expression of ER and PgR was correlated with the age of the patients (p&#x2009;=&#x2009;0.026) and the tumor grade (p&#x2009;=&#x2009;0.0004). However, there was not statistically significant correlation between ER/PgR and the menopausal status of patients (p&#x2009;=&#x2009;0.149), nor between ER/PgR and the histologic type (p&#x2009;=&#x2009;0.523).<br><br>CONCLUSION: The ER+PgR+ and ER-PgR- are the most common subgroups in women with breast cancer in Ivory Coast. The hormonal receptor status is associated with the age and the histologic grade in breast cancer patients. The systematic use of hormonal treatment should be reevaluated. A further study should be done to investigate the reasons of high rate of ER-PgR- in breast cancer patients in Ivory Coast.}, }
@article {pmid28169235, year = {2016}, author = {Rohilla, M and Bal, A and Singh, G and Joshi, K}, title = {Prediction of heterogeneity in breast cancer immunophenotype at ductal carcinoma in situ stage?.}, journal = {Journal of cancer research and therapeutics}, volume = {12}, number = {4}, pages = {1249-1256}, doi = {10.4103/0973-1482.199541}, pmid = {28169235}, issn = {1998-4138}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Carcinoma In Situ/*diagnosis/genetics/*metabolism ; Breast Neoplasms/*diagnosis/genetics/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; *Immunophenotyping ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Tumor Burden ; Young Adult ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) is considered a heterogeneous lesion at the molecular level. However, there is a paucity of literature about the existence of molecular subtypes in DCIS which can predict their biological behavior at the preinvasive stage.<br><br>MATERIALS AND METHODS: Precise prevalence of molecular subtypes of pure DCIS and DCIS component of infiltrating duct carcinoma (IDC) was evaluated using immunohistochemistry and correlated with known prognostic factors.<br><br>RESULTS: DCIS cases were classified as luminal A (46.6% in each group), luminal B (pure DCIS 20% and DCIS component of IDC 13.3%), HER2 overexpressing, basal and nonbasal (pure DCIS 3.3% and 26.6% and DCIS component of IDC 3.3% and 33.3%, respectively), and triple negative, nonbasal (pure DCIS and DCIS component of IDC 3.3% each). The molecular phenotype of DCIS correlated well with that of the coexisting IDC.<br><br>CONCLUSIONS: This study demonstrated molecular heterogeneity in DCIS; however, similar molecular phenotypes were seen in the coexisting IDC suggesting that DCIS is a precursor lesion and can predict phenotype of the invasive component. This also suggests that the invasiveness of DCIS is not dependent solely on the molecular character of the tumor epithelial cells, but factors such as tumor microenvironment may play a role.}, }
@article {pmid28167700, year = {2017}, author = {Zhang, X and Ivanova, A and Vandepoele, K and Radomiljac, J and Van de Velde, J and Berkowitz, O and Willems, P and Xu, Y and Ng, S and Van Aken, O and Duncan, O and Zhang, B and Storme, V and Chan, KX and Vaneechoutte, D and Pogson, BJ and Van Breusegem, F and Whelan, J and De Clercq, I}, title = {The Transcription Factor MYB29 Is a Regulator of ALTERNATIVE OXIDASE1a.}, journal = {Plant physiology}, volume = {173}, number = {3}, pages = {1824-1843}, pmid = {28167700}, issn = {1532-2548}, mesh = {Antimycin A/pharmacology ; Arabidopsis/enzymology/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Cell Nucleus/genetics/metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Plant/drug effects/*genetics ; Gene Ontology ; Gene Regulatory Networks ; Immunoblotting ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/*genetics/metabolism ; Mutation ; Oxidoreductases/*genetics/metabolism ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {Plants sense and integrate a variety of signals from the environment through different interacting signal transduction pathways that involve hormones and signaling molecules. Using ALTERNATIVE OXIDASE1a (AOX1a) gene expression as a model system of retrograde or stress signaling between mitochondria and the nucleus, MYB DOMAIN PROTEIN29 (MYB29) was identified as a negative regulator (regulator of alternative oxidase1a 7 [rao7] mutant) in a genetic screen of Arabidopsis (Arabidopsis thaliana). rao7/myb29 mutants have increased levels of AOX1a transcript and protein compared to wild type after induction with antimycin A. A variety of genes previously associated with the mitochondrial stress response also display enhanced transcript abundance, indicating that RAO7/MYB29 negatively regulates mitochondrial stress responses in general. Meta-analysis of hormone-responsive marker genes and identification of downstream transcription factor networks revealed that MYB29 functions in the complex interplay of ethylene, jasmonic acid, salicylic acid, and reactive oxygen species signaling by regulating the expression of various ETHYLENE RESPONSE FACTOR and WRKY transcription factors. Despite an enhanced induction of mitochondrial stress response genes, rao7/myb29 mutants displayed an increased sensitivity to combined moderate light and drought stress. These results uncover interactions between mitochondrial retrograde signaling and the regulation of glucosinolate biosynthesis, both regulated by RAO7/MYB29. This common regulator can explain why perturbation of the mitochondrial function leads to transcriptomic responses overlapping with responses to biotic stress.}, }
@article {pmid28165048, year = {2017}, author = {Johanning, GL and Malouf, GG and Zheng, X and Esteva, FJ and Weinstein, JN and Wang-Johanning, F and Su, X}, title = {Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {41960}, pmid = {28165048}, issn = {2045-2322}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P50 CA100632/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Basal Cell/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Databases, Factual ; Endogenous Retroviruses/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Viral ; Genome, Human ; Humans ; Viral Envelope Proteins/*genetics ; }, abstract = {Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus. Expression of the HERV-K envelope gene (env) was highly significantly increased in basal tumors in comparison with the also-upregulated expression of other HERV-K genes. Analysis of reverse-phase protein array data indicated that increased expression of HERV-K is associated with decreased mutation of H-Ras (wild-type). Our results show elevation of HERV-K expression exclusively in the basal subtype of IDC breast cancer (as opposed to the other subtypes) and suggest HERV-K as a possible target for cancer vaccines or immunotherapy against this highly aggressive form of breast cancer.}, }
@article {pmid28162815, year = {2017}, author = {Roobol, MJ and Verbeek, JFM and van der Kwast, T and Kümmerlin, IP and Kweldam, CF and van Leenders, GJLH}, title = {Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator for Initial Prostate Biopsy by Incorporating the 2014 International Society of Urological Pathology Gleason Grading and Cribriform growth.}, journal = {European urology}, volume = {72}, number = {1}, pages = {45-51}, doi = {10.1016/j.eururo.2017.01.033}, pmid = {28162815}, issn = {1873-7560}, mesh = {Adenocarcinoma/mortality/*pathology/therapy ; Aged ; Area Under Curve ; Biopsy ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology/therapy ; Clinical Decision-Making ; *Decision Support Techniques ; Humans ; Logistic Models ; Male ; Middle Aged ; *Mobile Applications ; Multivariate Analysis ; *Neoplasm Grading ; Patient Selection ; Predictive Value of Tests ; Prostatic Neoplasms/mortality/*pathology/therapy ; ROC Curve ; Reproducibility of Results ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; Unnecessary Procedures ; }, abstract = {BACKGROUND: The survival rate for men with International Society of Urological Pathology (ISUP) grade 2 prostate cancer (PCa) without invasive cribriform (CR) and intraductal carcinoma (IDC) is similar to that for ISUP grade 1. If updated into the European Randomized Study of Screening for Prostate Cancer (ERSPC Rotterdam) risk calculator number 3 (RC3), this may further improve upfront selection of men who need a biopsy.<br><br>OBJECTIVE: To improve the number of possible biopsies avoided, while limiting undiagnosed clinically important PCa by applying the updated RC3 for risk-based patient selection.<br><br>The RC3 is based on the first screening round of the ERSPC Rotterdam, which involved 3616 men. In 2015, histopathologic slides for PCa cases (n=885) were re-evaluated. Low-risk (LR) PCa was defined as ISUP grade 1 or 2 without CR/IDC. High-risk (HR) PCa was defined as ISUP grade 2 with CR/IDC and PCa with ISUP grade&#x2265;3.<br><br>We updated the RC3 using multinomial logistic regression analysis, including data on age, PSA, digital rectal examination, and prostate volume, for predicting LR and HR PCa. Predictive accuracy was quantified using receiver operating characteristic analysis and decision curve analysis.<br><br>RESULTS AND LIMITATIONS: Men without PCa could effectively be distinguished from men with LR PCa and HR PCa (area under the curve 0.70, 95% confidence interval [CI] 0.68-0.72 and 0.92, 95% CI 0.90-0.94). At a 1% risk threshold, the updated calculator would lead to a 34% reduction in unnecessary biopsies, while only 2% of HR PCa cases would be undiagnosed.<br><br>CONCLUSIONS: A relatively simple risk stratification tool augmented with a highly sensitive contemporary pathologic biopsy classification would result in a considerable decrease in unnecessary prostate biopsies and overdiagnosis of potentially indolent disease.<br><br>PATIENT SUMMARY: We improved a well-known prostate risk calculator with a new pathology classification system that better reflects disease burden. This new risk calculator allows individualized prediction of the chance of having (potentially aggressive) biopsy-detectable prostate cancer and can guide shared decision-making when considering prostate biopsy.}, }
@article {pmid28153863, year = {2017}, author = {Ng, CKY and Piscuoglio, S and Geyer, FC and Burke, KA and Pareja, F and Eberle, CA and Lim, RS and Natrajan, R and Riaz, N and Mariani, O and Norton, L and Vincent-Salomon, A and Wen, YH and Weigelt, B and Reis-Filho, JS}, title = {The Landscape of Somatic Genetic Alterations in Metaplastic Breast Carcinomas.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {23}, number = {14}, pages = {3859-3870}, pmid = {28153863}, issn = {1557-3265}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Cadherins/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Metaplasia/*genetics/pathology ; Mutation ; Nuclear Proteins/genetics ; PTEN Phosphohydrolase/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Proto-Oncogene Proteins c-akt/genetics ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/genetics ; Transcription Factors/genetics ; Triple Negative Breast Neoplasms/*genetics/pathology ; Tumor Suppressor Protein p53/genetics ; Exome Sequencing ; Wnt Signaling Pathway/genetics ; }, abstract = {Purpose: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of breast cancer, predominantly of triple-negative phenotype, and characterized by the presence of malignant cells showing squamous and/or mesenchymal differentiation. We sought to define the repertoire of somatic genetic alterations and the mutational signatures of MBCs.Experimental Design: Whole-exome sequencing was performed in 35 MBCs, with 16, 10, and 9 classified as harboring chondroid, spindle, and squamous metaplasia as the predominant metaplastic component. The genomic landscape of MBCs was compared with that of triple-negative invasive ductal carcinomas of no special type (IDC-NST) from The Cancer Genome Atlas. Wnt and PI3K/AKT/mTOR pathway activity was assessed using a qPCR assay.Results: MBCs harbored complex genomes with frequent TP53 (69%) mutations. In contrast to triple-negative IDC-NSTs, MBCs more frequently harbored mutations in PIK3CA (29%), PIK3R1 (11%), ARID1A (11%), FAT1 (11%), and PTEN (11%). PIK3CA mutations were not found in MBCs with chondroid metaplasia. Compared with triple-negative IDC-NSTs, MBCs significantly more frequently harbored mutations in PI3K/AKT/mTOR pathway-related (57% vs. 22%) and canonical Wnt pathway-related (51% vs. 28%) genes. MBCs with somatic mutations in PI3K/AKT/mTOR or Wnt pathway-related genes displayed increased activity of the respective pathway.Conclusions: MBCs are genetically complex and heterogeneous, and are driven by a repertoire of somatic mutations distinct from that of triple-negative IDC-NSTs. Our study highlights the genetic basis and the importance of PI3K/AKT/mTOR and Wnt pathway dysregulation in MBCs and provides a rationale for the metaplastic phenotype and the reported responses to PI3K/AKT/mTOR inhibitors in these tumors. Clin Cancer Res; 23(14); 3859-70. ©2017 AACR.}, }
@article {pmid28133686, year = {2017}, author = {Uçar, FM and Açar, B}, title = {Neutrophil to lymphocyte ratio predicts appropriate therapy in idiopathic dilated cardiomyopathy patients with primary prevention implantable cardioverter defibrillator.}, journal = {Saudi medical journal}, volume = {38}, number = {2}, pages = {143-148}, pmid = {28133686}, issn = {1658-3175}, mesh = {Cardiac Pacing, Artificial/methods ; Cardiomyopathy, Dilated/diagnostic imaging/immunology/*therapy ; *Defibrillators, Implantable/statistics &amp; numerical data ; Echocardiography ; Female ; Humans ; *Leukocyte Count ; *Lymphocyte Count ; Male ; Middle Aged ; *Neutrophils ; Primary Prevention ; Retrospective Studies ; }, abstract = {OBJECTIVES: To investigate whether an inflammatory marker of neutrophil to lymphocyte ratio (NLR) predicts appropriate implantable cardioverter defibrillator (ICD) therapy (shock or anti tachycardia pacing) in idiopathic dilated cardiomyopathy (IDC) patients.<br><br>METHODS: We retrospectively examined IDC patients (mean age: 58.3 &#xb1; 11.8 years, 81.5% male) with ICD who admitted to outpatient clinic for pacemaker control at 2 tertiary care hospitals in Ankara and Edirne, Turkey from January 2013-2015. All ICDs were implanted for primary prevention. Hematological and biochemical parameters were measured prior procedure.&#xa0;Results: Over a median follow-up period of 43 months (Range 7-125), 68 (33.1%) patients experienced appropriate ICD therapy. The NLR was increased in patients that received appropriate therapy (4.39 &#xb1; 2.94 versus 2.96 &#xb1; 1.97, p less than&#xa0;0.001).To identify independent risk factors for appropriate therapy, a multivariate linear regression model was conducted and age (&#x3b2;=0.163, p=0.013), fasting glucose (&#x3b2;=0.158, p=0.017), C-reactive protein (CRP) (&#x3b2;=0.289, p less than&#xa0;0.001) and NLR (&#x3b2;=0.212, p less than&#xa0;0.008) were found to be independent risk factors for appropriate ICD therapy.&#xa0;Conclusions: Before ICD implantation by using NLR and CRP, arrhythmic episodes may be predictable and better antiarrhythmic medical therapy optimization may protect these IDC patients from unwanted events.}, }
@article {pmid28133285, year = {2016}, author = {Watanabe, M and Enomoto, K and Sakurai, K}, title = {[Primary Breast Cancer in a Man].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {12}, pages = {2249-2251}, pmid = {28133285}, issn = {0385-0684}, mesh = {*Adenocarcinoma, Scirrhous/diagnostic imaging/secondary/surgery ; Aged ; Axilla/pathology ; Biopsy, Large-Core Needle ; Breast Neoplasms, Male/diagnostic imaging/*pathology/surgery ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Mammography ; Mastectomy ; Neoplasm Invasiveness ; }, abstract = {A 76-year-old man noticed a tumor under his right nipple. Mammography revealed an irregularly shaped nodule in the right breast. Ultrasonography showed a 20mm irregularly shaped nodule in the central area. MRI showed an 18mm irregularly shaped nodule in the central area with skin invasion. On core needle biopsy, the tumor was diagnosed as an invasive ductal carcinoma of the right breast. The patient underwent a mastectomy and axillary lymph node dissection. Histopathologically, the patient was diagnosed with invasive ductal carcinoma(scirrhous carcinoma). The tumor was positive for both ER and PgR, and the HER2 score was 1. The Ki-67 index was 20-30%. Male breast carcinoma accounts for approximately 1.0% of all breast carcinomas. The most common complaint is elastic, hard nodules with no pain. Postoperative therapy for male breast cancer is similar to that for female cancer. This patient underwent a mastectomy and lymph node dissection. After surgery, tamoxifen was administered as adjuvant therapy. There has been no evidence of recurrence for 4 months after the surgery.}, }
@article {pmid28133282, year = {2016}, author = {Asano, Y and Kashiwagi, S and Goto, W and Takada, K and Morisaki, T and Takashima, T and Noda, S and Onoda, N and Ohsawa, M and Hirakawa, K and Ohira, M}, title = {[Pathological Complete Response Obtained by Eribulin Chemotherapy in a Case of Advanced Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {12}, pages = {2240-2242}, pmid = {28133282}, issn = {0385-0684}, mesh = {Adult ; Biopsy, Fine-Needle ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Female ; Furans/*therapeutic use ; Humans ; Ketones/*therapeutic use ; Lymphatic Metastasis ; Neoadjuvant Therapy ; }, abstract = {A goal for treating advanced disease is prolonging survival while maintaining a good quality of life(QOL). Eribulin chemotherapy may be suitable for this purpose. We report a case of advanced breast cancer with pathological complete response (pCR)obtained by eribulin chemotherapy. The patient was a 43-year-old woman who complained of a right mammary mass. A tumor measuring approximately 3 cm was palpated, and breast cancer was detected via ultrasound examination. Core needle biopsy indicated invasive ductal carcinoma based on histopathological findings. A metastasis to the supraclavicular lymph node was observed and was found to be malignant via fine-needle aspiration cytology. The patient was diagnosed with advanced breast cancer cT2N3M0, stage III C, Luminal B like. She underwent primary systemic therapy with 6 cycles of eribulin. The patient exhibited a clinical complete response to eribulin chemotherapy. Thereafter, a right mastectomy with level 3 axillary lymph node dissection was performed. Pathological diagnosis of the surgical specimen was pCR. At present, 3 years after surgery, the patient has no recurrence.}, }
@article {pmid28133210, year = {2016}, author = {Tokunou, K and Yamamoto, T and Yamamoto, H and Kamei, R and Kitamura, Y and Ando, S}, title = {[A Case of Male Hereditary Breast Cancer Involving a Sentinel Lymph Node Biopsy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {12}, pages = {2026-2028}, pmid = {28133210}, issn = {0385-0684}, mesh = {Antineoplastic Agents, Hormonal/therapeutic use ; BRCA2 Protein/genetics ; Breast Neoplasms/drug therapy/genetics/*pathology/surgery ; Breast Neoplasms, Male/drug therapy/genetics/*pathology/surgery ; Combined Modality Therapy ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Sentinel Lymph Node Biopsy ; Tamoxifen/therapeutic use ; Treatment Outcome ; }, abstract = {We report a rare case of male hereditary breast cancer in which a sentinel lymph node biopsy was performed. A 62-yearold man was admitted to our hospital because of a palpable tumor in his right breast. Both his younger sister and daughter had had breast cancer. Genetic testing revealed a morbid mutation in the BRCA2 gene. The tumor was palpated to an elastic hard mass and had a clear border in the right DCE area. We performed a core needle biopsy and diagnosed invasive ductal carcinoma, specifically, cT1cN0cM0, cStage I hereditary breast cancer. The patient underwent mastectomy and a sentinel lymph node biopsy. Nine days later, tamoxifen therapy was initiated. There has been no sign of recurrence during the 9 months after the operation.}, }
@article {pmid28108967, year = {2017}, author = {Inoue, M and Nakagomi, H and Nakada, H and Furuya, K and Ikegame, K and Watanabe, H and Omata, M and Oyama, T}, title = {Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {24}, number = {5}, pages = {667-672}, doi = {10.1007/s12282-017-0753-4}, pmid = {28108967}, issn = {1880-4233}, mesh = {Adult ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology/secondary ; Carcinoma, Lobular/drug therapy/mortality/*pathology/secondary ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*epidemiology/pathology/secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/mortality/*pathology ; Peritoneal Neoplasms/*epidemiology/pathology/secondary ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial.<br><br>METHODS: We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor-node-metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC. We then selected the patients in the ER[+] or PR[+]/HER2[-] subtype specifically and compared sites of recurrence, and the survival curve starting from the point of development of metastatic disease.<br><br>RESULTS: The clinical stage was significantly higher in the ILC patients than in the IDC (p&#xa0;=&#xa0;0.001). The mean (&#xb1;SD) of DFS for the ILC and IDC patients was 2.6&#xa0;&#xb1;&#xa0;0.6 and 2.4&#xa0;&#xb1;&#xa0;0.3&#xa0;years, respectively, with no significant difference (p&#xa0;=&#xa0;0.18). However, the hormone receptor status was same between both groups; the rate of HER2 positivity was significantly lower in the ILC group (0%) than in the IDC group (16.2%) (p&#xa0;=&#xa0;0.05). In ER[+] or PR[+]/HER2[-] subtype, the mean DFS for the ILC and IDC was 2.9&#xa0;&#xb1;&#xa0;0.6 and 3.1&#xa0;&#xb1;&#xa0;0.3&#xa0;years, and the median survival time after the recurrence for ILC and IDC patients was 4.2&#xa0;&#xb1;&#xa0;0.7 and 5.6&#xa0;&#xb1;&#xa0;0.7&#xa0;years, respectively, with no significant difference (p&#xa0;=&#xa0;0.77). The frequency of lung metastases was significantly lower in the ILC group (6.3%) than in the IDC group (53.7%) (p&#xa0;<&#xa0;0.01), while the frequency of peritoneal metastases was significantly higher in the ILC group (68.8%) than in the IDC group (1%) (p&#xa0;=&#xa0;0.00). Of note, the prognosis after the diagnosis of peritoneal metastases was poor, with a median survival time of 19&#xa0;&#xb1;&#xa0;9&#xa0;months and resistance to hormone therapy.<br><br>CONCLUSIONS: The extremely high rate (68.8%) of peritoneal metastases was observed in long-term follow-up for the metastatic breast cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.}, }
@article {pmid28104032, year = {2017}, author = {Hong, J and Chen, XS and Wu, JY and Huang, O and Zhu, L and He, JR and Fang, Q and Chen, WG and Li, YF and Shen, KW}, title = {[Analysis of the factors influencing adjuvant chemotherapy decisions for triple negative breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {39}, number = {1}, pages = {39-43}, doi = {10.3760/cma.j.issn.0253-3766.2017.01.008}, pmid = {28104032}, issn = {0253-3766}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Ductal, Breast/*drug therapy/pathology/secondary ; Chemotherapy, Adjuvant/statistics &amp; numerical data ; Consensus ; Cyclophosphamide/administration &amp; dosage ; *Decision Making ; Docetaxel ; Epirubicin/administration &amp; dosage ; Female ; Fluorouracil/administration &amp; dosage ; Humans ; Middle Aged ; Paclitaxel/administration &amp; dosage ; Patient Care Team/statistics &amp; numerical data ; Platinum Compounds/administration &amp; dosage ; Retrospective Studies ; Taxoids/administration &amp; dosage ; Treatment Outcome ; Triple Negative Breast Neoplasms/*drug therapy/pathology ; }, abstract = {Objective: To analyze adjuvant chemotherapy decisions for triple negative breast cancer (TNBC), and explore the influencing factors in the multidisciplinary treatment (MDT) modality. Methods: A retrospective analysis was performed. The cases with invasive TNBC who underwent surgery and MDT discussion for adjuvant treatment in Ruijin Hospital, from April 2013 to June 2015, were recruited. The patients' clinicopathological characteristics were analyzed and adjuvant treatment suggestions from MDT were obtained. Here the chemotherapy decision alteration was defined as a disagreement in chemotherapy or not, or inconsistence in regimens between the attending doctor and the multidisciplinary team. Results: A total of 194 patients aged ≤70 years old were enrolled in the multidisciplinary discussion, and 187 patients (96.4%) were suggested to receive chemotherapy. When compared the opinions of the attending doctor to suggestions of the multidisciplinary team, we found that the percentage of chemotherapy decision alteration reached 22.7% (39/172), of which 94.9% (37/39) were inconsistence in chemotherapy regimens. There were 119 patients who were recommended to receive epirubicin plus cyclophosphamide (EC) followed by docetaxel (T) or weekly paclitaxel (wP) regimens. Before the announcement of results for the E1199 trial, EC-T accounted for 62.5% (55/88), and EC-wP accounted for 37.5% (33/88) for this group of patients. After that, the proportion of EC-T was decreased to 22.6% (7/31) and proportion of EC-wP increased to 77.4%(24/31) (P<0.001). In addition, a total of 20 patients were suggested to receive platinum based chemotherapy. The proportions were 9.3% in cases with invasive ductal carcinoma, and 33.3% in cases with metaplastic carcinoma, respectively (P=0.016). Conclusions: The adjuvant chemotherapy decision for TNBC patients is altered in 22.7% of the patients after MDT discussion. After the announcement of SABCS E1199 results, more patients are suggested to receive EC followed by weekly paclitaxel. There is a lack of detailed evidence for platinum based adjuvant chemotherapy for TNBC, and more patients with metaplastic carcinoma receive platinum based adjuvant chemotherapy.}, }
@article {pmid28097781, year = {2017}, author = {Felts, JL and Zhu, J and Han, B and Smith, SJ and Truica, CI}, title = {An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular Breast Cancer.}, journal = {The breast journal}, volume = {23}, number = {6}, pages = {677-686}, doi = {10.1111/tbj.12751}, pmid = {28097781}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/genetics/*mortality/pathology ; Carcinoma, Lobular/genetics/*mortality/pathology ; Cohort Studies ; Disease-Free Survival ; Female ; Gene Expression Profiling/economics/*methods ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local/genetics/*mortality/pathology ; Neoplasm Staging ; Pennsylvania ; Registries ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {The Oncotype DX breast cancer assay (Genomic Health, Redwood City, CA) is increasingly being used to guide treatment decisions for patients with early stage, hormone-positive, Her-2-negative breast cancer. The utility of the Oncotype DX in decision making for treatment of invasive lobular carcinoma (ILC) has not been investigated as the results reported by Genomic Health are largely in a population with invasive ductal carcinoma (IDC). The authors hypothesized that the Oncotype DX recurrence score (RS) distribution for ILC is different than that for IDC. We performed a retrospective analysis of early stage breast cancer patients treated at Penn State Cancer Institute from 2001 to 2011 and identified 102 patients with ILC. We also pulled RS data from our institution's prospective registry of consecutive patients with early stage IDC treated during the same time period. Median follow-up was 55 months. We found that the RS distribution for ILC differed significantly from that of IDC (p = 0.024). We also found a statistically significant difference in the RS distribution between the pure ILC and pleomorphic ILC subtypes (p = 0.027). The Oncotype DX RS distribution in ILC is unique, differing significantly from that in ductal carcinoma. Consequently, the clinical usefulness and cost-effectiveness of the Oncotype DX in guiding treatment for ILC should be further investigated.}, }
@article {pmid28087477, year = {2017}, author = {Xiao, M and Xu, Q and Lou, C and Qin, Y and Ning, X and Liu, T and Zhao, X and Jia, S and Huang, Y}, title = {Overexpression of TNFAIP8 is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma.}, journal = {Human pathology}, volume = {62}, number = {}, pages = {40-49}, doi = {10.1016/j.humpath.2016.12.020}, pmid = {28087477}, issn = {1532-8392}, mesh = {Apoptosis Regulatory Proteins/*analysis/genetics ; Biomarkers, Tumor/*analysis/genetics ; Blotting, Western ; Breast Neoplasms/*chemistry/genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/secondary/surgery ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Logistic Models ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Odds Ratio ; Proportional Hazards Models ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Treatment Outcome ; Up-Regulation ; }, abstract = {Tumor necrosis factor α-induced protein 8 (TNFAIP8), a transcription factor nuclear factor κB-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time polymerase chain reaction (PCR) and Western blot analysis in 20 fresh IDC tissues and immunohistochemical analysis in 351 paraffin-embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 messenger RNA and protein were up-regulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P=.001), advanced TNM stage (P<.001), high histologic grade (P<.001), molecular subtype (P<.001), and postoperative recurrence (P<.001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95% confidence interval, 1.167-2.832; P=.008). Moreover, Kaplan-Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than did those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic factor for overall survival and disease-free survival in IDC (P=.041 and P=.020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC.}, }
@article {pmid28067867, year = {2017}, author = {Taylor, RA and Fraser, M and Livingstone, J and Espiritu, SM and Thorne, H and Huang, V and Lo, W and Shiah, YJ and Yamaguchi, TN and Sliwinski, A and Horsburgh, S and Meng, A and Heisler, LE and Yu, N and Yousif, F and Papargiris, M and Lawrence, MG and Timms, L and Murphy, DG and Frydenberg, M and Hopkins, JF and Bolton, D and Clouston, D and McPherson, JD and van der Kwast, T and Boutros, PC and Risbridger, GP and Bristow, RG}, title = {Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {13671}, pmid = {28067867}, issn = {2041-1723}, mesh = {Aged ; BRCA2 Protein/deficiency/*genetics ; Carcinoma, Ductal/*genetics/metabolism/pathology/surgery ; DNA Mutational Analysis ; Epigenesis, Genetic ; Evolution, Molecular ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Genomic Instability ; *Germ-Line Mutation ; Heterozygote ; Humans ; Male ; Mediator Complex/*genetics/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prostate/metabolism/pathology/surgery ; Prostatectomy ; Prostatic Neoplasms/*genetics/metabolism/pathology/surgery ; Protein Isoforms/genetics/metabolism ; Retrospective Studies ; Whole Genome Sequencing ; }, abstract = {Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.}, }
@article {pmid28062852, year = {2017}, author = {Diaz-Vera, J and Palmer, S and Hernandez-Fernaud, JR and Dornier, E and Mitchell, LE and Macpherson, I and Edwards, J and Zanivan, S and Norman, JC}, title = {A proteomic approach to identify endosomal cargoes controlling cancer invasiveness.}, journal = {Journal of cell science}, volume = {130}, number = {4}, pages = {697-711}, pmid = {28062852}, issn = {1477-9137}, support = {MR/P01058X/1/MRC_/Medical Research Council/United Kingdom ; C596/A12935/CRUK_/Cancer Research UK/United Kingdom ; C596/A18277/CRUK_/Cancer Research UK/United Kingdom ; C596/A17196/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Amino Acids/metabolism ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Endosomes/*metabolism ; Female ; Gene Knockdown Techniques ; Humans ; Intracellular Membranes/metabolism ; Isotope Labeling ; Models, Biological ; Neoplasm Grading ; Neoplasm Invasiveness ; Neuropilin-2/metabolism ; Protein Binding ; Protein Transport ; Proteomics/*methods ; R-SNARE Proteins/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Estrogen/metabolism ; SNARE Proteins/metabolism ; Survival Analysis ; rab GTP-Binding Proteins/genetics/metabolism ; }, abstract = {We have previously shown that Rab17, a small GTPase associated with epithelial polarity, is specifically suppressed by ERK2 (also known as MAPK1) signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this, are unknown. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to a highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp8 is associated with Rab17 at late endosomes. Reduced levels of Vamp8 promote transition between ductal carcinoma in situ (DCIS) and a more invasive phenotype. We developed an unbiased proteomic approach to elucidate the complement of receptors that redistributes between endosomes and the plasma membrane, and have pin-pointed neuropilin-2 (NRP2) as a key pro-invasive cargo of Rab17- and Vamp8-regulated trafficking. Indeed, reduced Rab17 or Vamp8 levels lead to increased mobilisation of NRP2-containing late endosomes and upregulated cell surface expression of NRP2. Finally, we show that NRP2 is required for the basement membrane disruption that accompanies the transition between DCIS and a more invasive phenotype.}, }
@article {pmid28041875, year = {2017}, author = {Khan, A and Dellago, H and Terlecki-Zaniewicz, L and Karbiener, M and Weilner, S and Hildner, F and Steininger, V and Gabriel, C and Mück, C and Jansen-Dürr, P and Hacobian, A and Scheideler, M and Grillari-Voglauer, R and Schosserer, M and Grillari, J}, title = {SNEV[hPrp19/hPso4] Regulates Adipogenesis of Human Adipose Stromal Cells.}, journal = {Stem cell reports}, volume = {8}, number = {1}, pages = {21-29}, pmid = {28041875}, issn = {2213-6711}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Adipogenesis/*genetics ; Adipose Tissue/*cytology ; Animals ; Caenorhabditis elegans ; Cell Differentiation/*genetics ; DNA Damage ; DNA Repair Enzymes/*genetics/metabolism ; Gene Expression ; Gene Knockdown Techniques ; Humans ; Insulin/metabolism ; Nuclear Proteins/*genetics/metabolism ; Oxidative Stress ; PPAR gamma/metabolism ; RNA Splicing Factors/*genetics/metabolism ; Stromal Cells/*cytology/*metabolism ; }, abstract = {Aging is accompanied by loss of subcutaneous adipose tissue. This may be due to reduced differentiation capacity or deficiency in DNA damage repair (DDR) factors. Here we investigated the role of SNEV[hPrp19/hPso4], which was implicated in DDR and senescence evasion, in adipogenic differentiation of human adipose stromal cells (hASCs). We showed that SNEV is induced during adipogenesis and localized both in the nucleus and in the cytoplasm. Knockdown of SNEV perturbed adipogenic differentiation and led to accumulation of DNA damage in hASCs upon oxidative stress. In addition, we demonstrated that SNEV is required for fat deposition in Caenorhabditis elegans. Consequently, we tested other DDR factors and found that WRN is also required for adipogenesis in both models. These results demonstrate that SNEV regulates adipogenesis in hASCs and indicate that DDR capacity in general might be a pre-requisite for this process.}, }
@article {pmid28032317, year = {2017}, author = {Kim, GJ and Lee, JY and Choi, HG and Kim, SY and Kim, E and Shim, SH and Nam, JW and Kim, SH and Choi, H}, title = {Cinnamomulactone, a new butyrolactone from the twigs of Cinnamomum cassia and its inhibitory activity of matrix metalloproteinases.}, journal = {Archives of pharmacal research}, volume = {40}, number = {3}, pages = {304-310}, doi = {10.1007/s12272-016-0877-7}, pmid = {28032317}, issn = {1976-3786}, mesh = {4-Butyrolactone/*analogs &amp; derivatives/chemistry/pharmacology ; Arthritis, Rheumatoid/enzymology ; Cell Survival/drug effects ; Cinnamomum/*chemistry ; Dexamethasone/pharmacology ; Fibroblasts/drug effects ; Humans ; Interleukin-1beta/biosynthesis/genetics ; Matrix Metalloproteinase 1/biosynthesis/genetics ; Matrix Metalloproteinase 3/biosynthesis/genetics ; Matrix Metalloproteinase Inhibitors/chemistry/*pharmacology ; Plant Extracts/chemistry/pharmacology ; Plant Stems/chemistry ; Spectrophotometry, Ultraviolet ; Tumor Necrosis Factor-alpha/pharmacology ; }, abstract = {Cinnamomum cassia (Lauraceae) has long been used as one of the most frequently used traditional oriental medicines for the treatment of gastritis, diabetes, blood circulation disturbance and inflammatory diseases. Cinnamomulactone (1), a new butyrolactone was isolated from the twigs of C. cassia together with nine known compounds, coumarin (2), trans-cinnamic acid (3), cinnamaldehyde (4), 2-hydroxycinnamaldehyde (5), 2-methoxycinnamaldehyde (6), 2-hydroxy-cinnamyl alcohol (7), benzoic acid (8), (+)-syringaresinol (9) and phenethyl (E)-3-[4-methoxyphenyl]-2-propenoate (10). The planar structure of 1 was elucidated on the basis of spectroscopic data analysis and its configurations were determined by coupling constant ([3] J HH) analysis and a comparison with specific rotation data of related compounds on the literatures. The structures of known compounds were confirmed by the comparison of their spectroscopic data to the reported values. Compound 10 was isolated for the first time from this plant. Compounds 1, 2, 4, and 9 showed inhibitory activity against matrix metalloproteinases (MMPs) gene expression. Among them, compound 1 has been revealed to suppress the gene expression of MMP-3 and interleukin (IL)-1β as well as MMP-1 in tumor necrosis factor (TNF)-α stimulated rheumatoid arthritis synovial fibroblasts.}, }
@article {pmid28031185, year = {2017}, author = {Zhu, L and Ding, Y and Chen, CY and Wang, L and Huo, Z and Kim, S and Sotiriou, C and Oesterreich, S and Tseng, GC}, title = {MetaDCN: meta-analysis framework for differential co-expression network detection with an application in breast cancer.}, journal = {Bioinformatics (Oxford, England)}, volume = {33}, number = {8}, pages = {1121-1129}, pmid = {28031185}, issn = {1367-4811}, support = {R01 CA190766/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Computational Biology/*methods ; Computer Simulation ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Genes, Neoplasm ; Humans ; Receptors, Estrogen/metabolism ; Sample Size ; }, abstract = {MOTIVATION: Gene co-expression network analysis from transcriptomic studies can elucidate gene-gene interactions and regulatory mechanisms. Differential co-expression analysis helps further detect alterations of regulatory activities in case/control comparison. Co-expression networks estimated from single transcriptomic study is often unstable and not generalizable due to cohort bias and limited sample size. With the rapid accumulation of publicly available transcriptomic studies, co-expression analysis combining multiple transcriptomic studies can provide more accurate and robust results.<br><br>RESULTS: In this paper, we propose a meta-analytic framework for detecting differentially co-expressed networks (MetaDCN). Differentially co-expressed seed modules are first detected by optimizing an energy function via simulated annealing. Basic modules sharing common pathways are merged into pathway-centric supermodules and a Cytoscape plug-in (MetaDCNExplorer) is developed to visualize and explore the findings. We applied MetaDCN to two breast cancer applications: ER+/ER- comparison using five training and three testing studies, and ILC/IDC comparison with two training and two testing studies. We identified 20 and 4 supermodules for ER+/ER- and ILC/IDC comparisons, respectively. Ranking atop are 'immune response pathway' and 'complement cascades pathway' for ER comparison, and 'extracellular matrix pathway' for ILC/IDC comparison. Without the need for prior information, the results from MetaDCN confirm existing as well as discover novel disease mechanisms in a systems manner.<br><br>R package 'MetaDCN' and Cytoscape App 'MetaDCNExplorer' are available at http://tsenglab.biostat.pitt.edu/software.htm .<br><br>CONTACT: ctseng@pitt.edu.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid28027219, year = {2017}, author = {Myckatyn, TM and Wagner, IJ and Mehrara, BJ and Crosby, MA and Park, JE and Qaqish, BF and Moore, DT and Busch, EL and Silva, AK and Kaur, S and Ollila, DW and Lee, CN}, title = {Cancer Risk after Fat Transfer: A Multicenter Case-Cohort Study.}, journal = {Plastic and reconstructive surgery}, volume = {139}, number = {1}, pages = {11-18}, pmid = {28027219}, issn = {1529-4242}, support = {K07 CA154850/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/*adverse effects/*methods ; *Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*etiology ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Subcutaneous Fat/*transplantation ; }, abstract = {BACKGROUND: Fat transfer is an increasingly popular method for refining postmastectomy breast reconstructions. However, concern persists that fat transfer may promote disease recurrence. Adipocytes are derived from adipose-derived stem cells and express adipocytokines that can facilitate active breast cancer cells in laboratory models. The authors sought to evaluate the association between fat transfer to the reconstructed breast and cancer recurrence in patients diagnosed with local or regional invasive breast cancers.<br><br>METHODS: A multicenter, case-cohort study was performed. Eligible patients from four centers (Memorial Sloan Kettering, M. D. Anderson Cancer Center, Alvin J. Siteman Cancer Center, and the University of Chicago) were identified by each site's institutional tumor registry or cancer data warehouse. Eligibility criteria were as follows: mastectomy with immediate breast reconstruction between 2006 and 2011, age older than 21 years, female sex, and incident diagnosis of invasive ductal carcinoma (stage I, II, or III). Cases consisted of all recurrences during the study period, and controls consisted of a 30 percent random sample of the study population. Cox proportional hazards regression was used to evaluate for association between fat transfer and time to recurrence in bivariate and multivariate models.<br><br>RESULTS: The time to disease recurrence unadjusted hazard ratio for fat transfer was 0.99 (95 percent CI, 0.56 to 1.7). After adjustment for age, body mass index, stage, HER2/Neu receptor status, and estrogen receptor status, the hazard ratio was 0.97 (95 percent CI, 0.54 to 1.8).<br><br>CONCLUSION: In this population of breast cancer patients who had mastectomy with immediate reconstruction, fat transfer was not associated with a higher risk of cancer recurrence.<br><br>Therapeutic, III.}, }
@article {pmid28018301, year = {2016}, author = {Li, J and Sun, L and Xu, F and Qi, H and Shen, C and Jiao, W and Xiao, J and Li, Q and Xu, B and Shen, A}, title = {Screening and Identification of APOC1 as a Novel Potential Biomarker for Differentiate of Mycoplasma pneumoniae in Children.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {1961}, pmid = {28018301}, issn = {1664-302X}, abstract = {Background: Although Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal. Proteomics is increasingly being used to study the biomarkers of infectious diseases. Methods: Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups. Selected proteins that can distinguish MPP from HC and IDC were further validated by enzyme-linked immunosorbent assay (ELISA). Results: After multivariate analyses, 27 potential plasma biomarkers were identified to be expressed differently among child MPP, HC, and IDC groups. Among these proteins, SERPINA3, APOC1, ANXA6, KNTC1, and CFLAR were selected for ELISA verification. SERPINA3, APOC1, and CFLAR levels were significantly different among the three groups and the ratios were consistent with the trends of proteomics results. A comparison of MPP patients and HC showed APOC1 had the largest area under the curve (AUC) of 0.853, with 77.6% sensitivity and 81.1% specificity. When APOC1 levels were compared between MPP and IDC patients, it also showed a relatively high AUC of 0.882, with 77.6% sensitivity and 85.3% specificity. Conclusion: APOC1 is a potential biomarker for the rapid and noninvasive diagnosis of MPP in children. The present finding may offer new insights into the pathogenesis and biomarker selection of MPP in children.}, }
@article {pmid28008158, year = {2017}, author = {Chen, QX and Li, JJ and Wang, XX and Lin, PY and Zhang, J and Song, CG and Shao, ZM}, title = {Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database.}, journal = {Oncotarget}, volume = {8}, number = {4}, pages = {6206-6215}, pmid = {28008158}, issn = {1949-2553}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Carcinoma, Adenoid Cystic/chemistry/mortality/secondary/*therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/secondary/*therapy ; Cell Differentiation ; Chi-Square Distribution ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Propensity Score ; Proportional Hazards Models ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/chemistry/mortality/pathology/*therapy ; United States/epidemiology ; Young Adult ; }, abstract = {Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients.}, }
@article {pmid27988039, year = {2017}, author = {Bobbo, M and Pinamonti, B and Merlo, M and Stolfo, D and Iorio, A and Ramani, F and Barbati, G and Carriere, C and Massa, L and Poli, S and Scapol, S and Gigli, M and Di Lenarda, A and Sinagra, G}, title = {Comparison of Patient Characteristics and Course of Hypertensive Hypokinetic Cardiomyopathy Versus Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {119}, number = {3}, pages = {483-489}, doi = {10.1016/j.amjcard.2016.10.014}, pmid = {27988039}, issn = {1879-1913}, mesh = {Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Amiodarone/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Anti-Arrhythmia Agents/therapeutic use ; Cardiomyopathies/etiology/physiopathology/therapy ; Cardiomyopathy, Dilated/*physiopathology/therapy ; Cause of Death ; Disease Progression ; Female ; Heart Failure/etiology/*physiopathology/therapy ; Heart Transplantation ; Heart-Assist Devices ; Humans ; Hypertension/complications ; Hypertrophy, Left Ventricular/etiology/*physiopathology/therapy ; Male ; Middle Aged ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Mortality ; Retrospective Studies ; Stroke Volume ; Tachycardia, Ventricular/epidemiology ; Ventricular Dysfunction, Left/etiology/*physiopathology/therapy ; Ventricular Fibrillation/epidemiology ; Ventricular Remodeling ; }, abstract = {Hypertensive hypokinetic cardiomyopathy (HHC) is defined by left ventricular (LV) systolic dysfunction with a history of systemic hypertension as the only possible cause. Although commonly encountered in clinical practice, its characterization and differences with true idiopathic dilated cardiomyopathy (IDC) are lacking. The aim of this study was to characterize the clinical instrumental features and the natural history of HHC. We analyzed the data of 4,191 patients referred to our center for newly diagnosed LV systolic dysfunction from 2005 to 2010. Of them, 310 presented idiopathic LV systolic dysfunction (LV ejection fraction <50%): 136 (44%) had a history of systemic hypertension and were defined HHC. The remaining 174 patients were considered IDC. Compared with patients with IDC, those with HHC were older (63 ± 11 vs 47 ± 14 years, p <0.001), with worse comorbidity profile, higher blood pressure, and increased LV mass. During follow-up, patients with HHC showed earlier and higher proportion of LV reverse remodeling (46% vs 21% at 6 months' follow-up). Moreover, they had a better long-term survival free from cardiovascular death/ventricular assist device/heart transplant/malignant ventricular arrhythmias (5.1 vs 12.6 in HHC and IDC, p = 0.03). Indeed, their mortality was mainly driven by noncardiovascular causes (at 10 years 9.6% vs 1.7% in HHC and IDC, p <0.001). In conclusion, HHC has a high prevalence among patients with "idiopathic" LV dysfunction. The natural history of patients with HHC is characterized by a rapid response to optimal therapy for heart failure, a favorable cardiovascular outcome, and a relevant incidence of noncardiovascular events.}, }
@article {pmid27979331, year = {2017}, author = {Loft, A and Forss, I and Mandrup, S}, title = {Genome-Wide Insights into the Development and Function of Thermogenic Adipocytes.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {28}, number = {2}, pages = {104-120}, doi = {10.1016/j.tem.2016.11.005}, pmid = {27979331}, issn = {1879-3061}, mesh = {Adipocytes/*metabolism ; Adipogenesis/genetics/*physiology ; Adipose Tissue, Brown/metabolism ; Animals ; High-Throughput Nucleotide Sequencing ; Humans ; Thermogenesis/genetics/*physiology ; }, abstract = {Brown and brown-like adipocytes are specialized adipocytes with a high capacity to convert metabolic energy to heat. This function is not only eminent in supporting organismal thermogenesis, but may also have potential in the fight against obesity. The latter has spurred a massive interest in understanding the development and regulation of these thermogenic adipocytes. Here, we review how genome-wide studies based on next-generation sequencing have provided insight into how the chromatin and transcriptional landscapes are established in thermogenic adipocytes and how thermogenic signals can change the genomic programming of white adipocytes. Furthermore, we discuss how the integration of genomic data can be used to discover novel transcriptional pathways that may be modulated as part of therapeutic strategies for the treatment of obesity.}, }
@article {pmid27956549, year = {2017}, author = {Morgenstern, J and Fleming, T and Schumacher, D and Eckstein, V and Freichel, M and Herzig, S and Nawroth, P}, title = {Loss of Glyoxalase 1 Induces Compensatory Mechanism to Achieve Dicarbonyl Detoxification in Mammalian Schwann Cells.}, journal = {The Journal of biological chemistry}, volume = {292}, number = {8}, pages = {3224-3238}, pmid = {27956549}, issn = {1083-351X}, mesh = {Aldehyde Reductase/*metabolism ; Animals ; Cells, Cultured ; Gene Deletion ; Gene Knockout Techniques ; Glycation End Products, Advanced/*metabolism ; Lactoylglutathione Lyase/genetics/*metabolism ; Mice ; Oxidative Stress ; Pyruvaldehyde/*metabolism ; Schwann Cells/cytology/*metabolism ; }, abstract = {The glyoxalase system is a highly specific enzyme system existing in all mammalian cells that is responsible for the detoxification of dicarbonyl species, primarily methylglyoxal (MG). It has been implicated to play an essential role in preventing the increased formation of advanced glycation end products under certain pathological conditions. We have established the first glyoxalase 1 knock-out model (GLO1[-/-]) in mammalian Schwann cells using the CRISPR/Cas9 technique to investigate compensatory mechanisms. Neither elevated concentrations of MG nor associated protein modifications were observed in GLO1[-/-] cells. Alternative detoxification of MG in GLO1[-/-] is achieved by increased catalytic efficiency of aldose reductase toward hemithioacetal (product of glutathione and MG), which is most likely caused by S-nitrosylation of aldose reductase. The hemithioacetal is mainly converted into lactaldehyde, which is paralleled by a loss of reduced glutathione. Inhibition of aldose reductase in GLO1[-/-] cells is associated with an increased sensitivity against MG, elevated intracellular MG levels, associated modifications, as well as increased oxidative stress. Our data suggest that aldose reductase can compensate for the loss of GLO1. This might be of clinical importance within the context of neuronal diseases caused by an impaired glyoxalase system and elevated levels of dicarbonyl species, such as MG.}, }
@article {pmid27928699, year = {2017}, author = {Eaton, AA and Pesce, CE and Murphy, JO and Stempel, MM and Patil, SM and Brogi, E and Hudis, CA and El-Tamer, M}, title = {Estimating the OncotypeDX score: validation of an inexpensive estimation tool.}, journal = {Breast cancer research and treatment}, volume = {161}, number = {3}, pages = {435-441}, pmid = {27928699}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Female ; Gene Expression Profiling/*methods/standards ; Genetic Testing/*methods/standards ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Reproducibility of Results ; Risk Factors ; Young Adult ; }, abstract = {BACKGROUND: OncotypeDX, a multi-gene expression assay, has been incorporated into clinical practice as a prognostic and predictive tool. However, its use in resource-constrained international healthcare systems is limited. Here we develop and validate a simplified model using clinicopathologic criteria to predict OncotypeDX score.<br><br>METHODS: Patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive and HER2-negative invasive ductal carcinoma for whom the OncotypeDX test was successfully performed between 09/2008 and 12/2011 were retrospectively identified. Tumor size, nuclear and histologic grade, lymphovascular invasion, and ER and PR status were extracted from pathology reports. Data were split into a training dataset comprising women tested 09/2008-04/2011, and a validation dataset comprising women tested 04/2011-12/2011. Using the training dataset, linear regression analysis was used to identify factors associated with OncotypeDX score, and to create a simplified risk score and identify risk cutoffs.<br><br>RESULTS: Estrogen and progesterone receptors, tumor size, nuclear and histologic grades, and lymphovascular involvement were independently associated with OncotypeDX. The full model explained 39% of the variation in the test data, and the simplified risk score and cutoffs assigned 57% of patients in the test data to the correct risk category (OncotypeDX score&#xa0;<18, 18-30, >30). 41% of patients were predicted to have OncotypeDX score&#xa0;<18, of these 83, 16, and 2% had true scores of&#xa0;<18, 18-30, and&#xa0;>30, respectively.<br><br>CONCLUSIONS: Awaiting an inexpensive test that is prognostic and predictive, our simplified tool allows clinicians to identify a fairly large group of patients (41%) with very low chance of having high-risk disease (2%).}, }
@article {pmid27924790, year = {2017}, author = {Li, BK and Chen, BS and Xin, YH and Liu, CX and Zheng, SB and Xu, YW and Li, HL and Zou, Y and Li, LP}, title = {Can the lower urinary tract storage symptoms be completely resolved after plasmakinetic enucleation of the prostate?.}, journal = {Asian journal of andrology}, volume = {19}, number = {6}, pages = {655-658}, pmid = {27924790}, issn = {1745-7262}, mesh = {Aged ; Humans ; Lower Urinary Tract Symptoms/etiology/physiopathology/*surgery ; Male ; Middle Aged ; Prostate/physiopathology/*surgery ; Prostatic Hyperplasia/complications/physiopathology/*surgery ; Quality of Life ; Transurethral Resection of Prostate/*methods ; Treatment Outcome ; Urodynamics/physiology ; }, abstract = {The aim of this study was to determine whether the lower urinary tract storage symptoms of benign prostatic obstruction (BPO) could be completely resolved after plasmakinetic enucleation of the prostate (PKEP) and the possible predictors of persistent symptoms. Two hundred and sixty-seven cases of BPO performed PKEP from July 2008 to June 2009 were retrospectively analyzed. Five-year postoperative data were collected and compared with the preoperative data. According to the urodynamic results, the patients were divided into involuntary detrusor contraction (IDC) group (n = 95) and no IDC group (n = 172) preoperatively; the patients with IDC were divided into IDC-persistent group (n = 33) and IDC-resolved group (n = 62) after PKEP. The predictors of persistent IDC were analyzed. Compared with the preoperative data, the 5-year postoperative data showed that the IDC rate was lower (P = 0.000), Overactive Bladder Symptom Score (OABSS) was lower (P = 0.000), maximum cystometric capacity (MCC) was larger (P = 0.000), Prostate volume (PV) was smaller (P = 0.000), and prostate-specific antigen (PSA) was lower (P = 0.000). Compared with the no IDC group, the IDC group showed that the age was older (P = 0.016), MCC was smaller (P = 0.004), PSA was higher (P = 0.016), and Chronic Inflammation rate was higher (P = 0.004). Compared with IDC-resolved group after PKEP, IDC-persistent group showed that the age was older (P = 0.019), MCC was smaller (P = 0.000), PSA was higher (P = 0.013), and Chronic Inflammation rate was higher (P = 0.032). The present study shows that the storage symptoms are still needed to be focused on after PKEP. The advanced patient age, MCC, PSA, and chronic inflammation may be the important clinical predictors of persistent IDC.}, }
@article {pmid27923458, year = {2016}, author = {Scheideler, M}, title = {MicroRNAs in adipocyte formation and obesity.}, journal = {Best practice &amp; research. Clinical endocrinology &amp; metabolism}, volume = {30}, number = {5}, pages = {653-664}, doi = {10.1016/j.beem.2016.11.009}, pmid = {27923458}, issn = {1878-1594}, mesh = {Adipocytes, Brown/cytology/*metabolism ; Animals ; Energy Metabolism ; Humans ; MicroRNAs/*genetics/metabolism ; Obesity/*genetics/metabolism ; }, abstract = {The worldwide epidemic of obesity demands novel and more effective therapeutic approaches. Fat cells are at the core of energy metabolism trying either to cope with a positive energy balance by hypertrophy and hyperplasia of energy storing white adipocytes or to counteract obesity by the induction of non-shivering thermogenesis in energy combusting brite/brown adipocytes. However, the comprehensive regulatory network of adipocyte formation remains to be elucidated. MicroRNAs are an emerging class of important regulatory determinants in many biological processes and diseases, including adipocyte formation and obesity. In this review, microRNAs governing the formation of white, brite and brown adipocytes as well as candidates with impact on obesity are overviewed, concluded with recommendations for further research that considers prerequisites for successful therapeutic applications.}, }
@article {pmid27916938, year = {2016}, author = {Pehserl, AM and Ress, AL and Stanzer, S and Resel, M and Karbiener, M and Stadelmeyer, E and Stiegelbauer, V and Gerger, A and Mayr, C and Scheideler, M and Hutterer, GC and Bauernhofer, T and Kiesslich, T and Pichler, M}, title = {Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {17}, number = {12}, pages = {}, pmid = {27916938}, issn = {1422-0067}, mesh = {Animals ; Caco-2 Cells ; Cell Cycle Checkpoints/drug effects ; Colorectal Neoplasms/*drug therapy/genetics/pathology ; Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*biosynthesis/genetics ; Mutation ; Niacinamide/administration &amp; dosage/*analogs &amp; derivatives ; Phenylurea Compounds/*administration &amp; dosage ; Proto-Oncogene Proteins p21(ras)/genetics ; Sorafenib ; }, abstract = {MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle-arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies.}, }
@article {pmid27909910, year = {2016}, author = {Berriel Diaz, M and Herzig, S and Schafmeier, T}, title = {Biological Mechanisms for the Effect of Obesity on Cancer Risk: Experimental Evidence.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {208}, number = {}, pages = {219-242}, doi = {10.1007/978-3-319-42542-9_12}, pmid = {27909910}, issn = {0080-0015}, mesh = {Adipokines/*metabolism ; Adipose Tissue/*metabolism/physiopathology ; Adiposity ; Animals ; Biomarkers, Tumor/*metabolism ; Cell Transformation, Neoplastic/*metabolism/pathology ; Energy Metabolism ; Gastrointestinal Microbiome ; Humans ; Inflammation Mediators/metabolism ; Neoplasms/*etiology/metabolism/pathology ; Obesity/*complications/metabolism/physiopathology ; Risk Factors ; Signal Transduction ; }, abstract = {Multiple epidemiological studies demonstrated that overweight and obesity significantly increase the risk of several types of cancer. As the prevalence of obesity is dramatically rising, it is expected that it will represent one of the major lifestyle-associated risk factors for cancer development in the near future. Numerous recent studies expanded knowledge about key players and pathways, which are deregulated in the obese state and potentially promote cancer initiation, progression and aggressiveness via remote and local effects. These players include (but are not limited to) insulin/IGF, adipokines and inflammatory signaling molecules as well as metabolites. Nevertheless, the detailed mechanisms linking obesity and malignant transformation at the systemic, cellular and molecular level still demand further investigation. Additionally, dysfunctional molecular metabolic pathways appear to be specific for distinct cancer entities, thereby yet precluding definition of a common principle. This chapter will present an overview of the current knowledge of molecular nodes linking obesity and cancer and will briefly touch upon potential therapy options addressing metabolic cancer etiologies.}, }
@article {pmid27903648, year = {2017}, author = {Pfaff, DH and Fleming, T and Nawroth, P and Teleman, AA}, title = {Evidence Against a Role for the Parkinsonism-associated Protein DJ-1 in Methylglyoxal Detoxification.}, journal = {The Journal of biological chemistry}, volume = {292}, number = {2}, pages = {685-690}, pmid = {27903648}, issn = {1083-351X}, support = {P40 OD018537/OD/NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cell Survival ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Nerve Tissue Proteins/genetics/*metabolism ; Protein Deglycase DJ-1 ; Pyruvaldehyde/*pharmacokinetics/*toxicity ; }, abstract = {Methylglyoxal (MG) is a reactive metabolite that forms adducts on cysteine, lysine and arginine residues of proteins, thereby affecting their function. Methylglyoxal is detoxified by the Glyoxalase system, consisting of two enzymes, Glo1 and Glo2, that act sequentially to convert MG into d-lactate. Recently, the Parkinsonism-associated protein DJ-1 was described in vitro to have glyoxalase activity, thereby detoxifying the MG metabolite, or deglycase activity, thereby removing the adduct formed by MG on proteins. Since Drosophila is an established model system to study signaling, neurodegeneration, and metabolic regulation in vivo, we asked whether DJ-1 contributes to MG detoxification in vivo Using both DJ-1 knockdown in Drosophila cells in culture, and DJ-1β knock-out flies, we could detect no contribution of DJ-1 to survival to MG challenge or to accumulation of MG protein adducts. Furthermore, we provide data suggesting that the previously reported deglycation activity of DJ-1 can be ascribed to a TRIS buffer artifact.}, }
@article {pmid27900579, year = {2017}, author = {Saito, R and Miki, Y and Hata, S and Ishida, T and Suzuki, T and Ohuchi, N and Sasano, H}, title = {Aryl hydrocarbon receptor induced intratumoral aromatase in breast cancer.}, journal = {Breast cancer research and treatment}, volume = {161}, number = {3}, pages = {399-407}, doi = {10.1007/s10549-016-4063-x}, pmid = {27900579}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aromatase/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Estrogens/biosynthesis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Ligands ; MCF-7 Cells ; Middle Aged ; Receptors, Aryl Hydrocarbon/*metabolism ; }, abstract = {PURPOSE: Aryl hydrocarbon receptor (AhR) inhibits estrogen receptor (ER) pathway, which may suppress estrogen-dependent cell proliferation. However, the correlation between AhR stimulation and intratumoral estrogen synthesis, especially through aromatase, has not been reported to date. In the present study, we examined this correlation in breast cancer cells.<br><br>METHODS: We examined AhR and aromatase immunoreactivity in 29 patients with invasive ductal carcinoma. We performed in vitro studies using three breast carcinoma cell lines, MCF-7, T47D, and MDA-MB-231.<br><br>RESULTS: AhR stimulation induced the mRNA expression of the aromatase gene in vitro in three breast carcinoma cell lines, and increased estrogen synthesis in MCF-7 cell line. Results of microarray analysis showed that AhR-induced aromatase expression was associated with BRCA1 induction. Analysis of patients with breast cancer showed a significant positive correlation between intratumoral AhR and aromatase status. We also compared the effects of AhR stimulation on the induction of intratumoral estrogen synthesis and inhibition of the ER signaling pathway, because AhR exerts contradictory effects on estrogen action in breast carcinoma cells. AhR-induced aromatase expression persisted for a significantly longer duration than AhR-induced ER pathway inhibition. Moreover, breast carcinoma cells treated with an AhR agonist tended to show earlier cell proliferation after removing the agonist than cells not treated with the AhR agonist.<br><br>CONCLUSION: The results of the present study suggest that AhR stimulates estrogen-dependent progression of breast carcinoma by inducing aromatase expression under some conditions. These results provide new insights on the possible roles of environmental toxins in breast cancer development.}, }
@article {pmid27890770, year = {2017}, author = {Woulfe, KC and Siomos, AK and Nguyen, H and SooHoo, M and Galambos, C and Stauffer, BL and Sucharov, C and Miyamoto, S}, title = {Fibrosis and Fibrotic Gene Expression in Pediatric and Adult Patients With Idiopathic Dilated Cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {23}, number = {4}, pages = {314-324}, pmid = {27890770}, issn = {1532-8414}, support = {R21 HL097123/HL/NHLBI NIH HHS/United States ; T35 HL007715/HL/NHLBI NIH HHS/United States ; T32 HL007171/HL/NHLBI NIH HHS/United States ; R01 HL126928/HL/NHLBI NIH HHS/United States ; R01 HL107715/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; }, mesh = {Age Factors ; Cardiomyopathy, Dilated/*complications ; Child ; Female ; Fibrosis ; Galectin 3/analysis ; Gene Expression Profiling ; *Heart Failure/etiology/metabolism/pathology ; *Heart Ventricles/metabolism/pathology ; Humans ; Interleukin-1/analysis ; Male ; Matrix Metalloproteinase 2/analysis ; MicroRNAs/*genetics ; Middle Aged ; *Myocardium/metabolism/pathology ; Signal Transduction ; Statistics as Topic ; Tissue Inhibitor of Metalloproteinases/analysis ; }, abstract = {BACKGROUND: Although fibrosis seems to be prognostic for adverse outcomes in adults with idiopathic dilated cardiomyopathy (IDC), little is known about the prevalence and development of fibrosis in pediatric IDC hearts. We hypothesized that there is less activation of fibrosis at a molecular level in pediatric IDC hearts than in failing adult hearts.<br><br>METHODS AND RESULTS: Pediatric hearts were analyzed histologically to determine the prevalence of fibrosis. Left ventricular tissue from adult and pediatric IDC hearts and adult and pediatric nonfailing (NF) hearts were subjected to quantitative reverse-transcription polymerase chain reaction to study the expression of important mRNAs that affect fibrosis. We found age-specific differences between IDC and NF hearts in the regulation of noncoding galectin-3, Corin, matrix metalloproteinase (MMP) 2, MMP-9, tissue inhibitor of metalloproteinase (TIMP) 2, and TIMP-3. We also found markers that were similarly altered in both adult and pediatric IDC hearts (interleukin-1 receptor-like 1 receptor, TIMP-1, and TIMP-4). Finally, microRNAs 29a-c were significantly decreased in the pediatric IDC patients.<br><br>CONCLUSIONS: Pediatric IDC patients demonstrate age-specific differences in the molecular pathways implicated in fibrosis in the adult heart. At the ultrastructural level the unique gene expression pattern appears to limit fibrosis in the failing pediatric heart.}, }
@article {pmid27886676, year = {2016}, author = {Kawashima, H and Ariizumi, T and Saijo, Y and Moriyama, M and Umezu, H and Ikeda, Y and Ogose, A and Endo, N}, title = {Chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast.}, journal = {Cancer genetics}, volume = {209}, number = {11}, pages = {501-505}, doi = {10.1016/j.cancergen.2016.10.005}, pmid = {27886676}, issn = {2210-7762}, mesh = {Breast Neoplasms/*genetics/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*genetics/radiotherapy ; *Chromosome Aberrations ; Cytogenetic Analysis ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Myoepithelioma/*genetics/radiotherapy/surgery ; Neoplasm Recurrence, Local/genetics/radiotherapy ; Neoplasms, Second Primary/genetics/radiotherapy ; }, abstract = {Myoepithelial carcinoma of the breast is an extremely rare tumor composed entirely of malignant spindle cells with myoepithelial differentiation. The majority of previously reported cases have mainly described the clinicopathological features of the disease, and few have presented cytogenetic data. We herein present the case of a 48-year-old woman who was admitted with a left-sided breast lump in the inner upper quadrant that was initially diagnosed as a myoepithelioma with potentially malignant disorder. At 12 months after resection, she complained about a newly developed solid mass in the subareolar region of the ipsilateral breast that was diagnosed as an invasive ductal carcinoma. In addition, 16 months after the initial admission, a re-growing remnant lesion recurred in the inner upper quadrant and was ultimately diagnosed as a myoepithelial carcinoma. Lymph node metastasis of the myoepithelial carcinoma was also observed in her left axillary region 11 months after local recurrence. A cytogenetic analysis showed recurring specific chromosomal alterations both in the locally recurrent and in the lymph-node metastatic lesion: 48, XX, t(5;18)(q13;q23),del(6)(q?),+14. + mar1. To our knowledge, this is the first published report of clonal chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast.}, }
@article {pmid27866023, year = {2017}, author = {Takagi, H and Ando, T and Umemoto, T and , }, title = {Direct and adjusted indirect comparisons of perioperative mortality after sutureless or rapid-deployment aortic valve replacement versus transcatheter aortic valve implantation.}, journal = {International journal of cardiology}, volume = {228}, number = {}, pages = {327-334}, doi = {10.1016/j.ijcard.2016.11.253}, pmid = {27866023}, issn = {1874-1754}, mesh = {Aortic Valve Stenosis/diagnostic imaging/mortality/*surgery ; Cardiac Catheterization/methods ; Female ; Humans ; Male ; *Patient Safety ; Prognosis ; Randomized Controlled Trials as Topic ; Survival Analysis ; }, abstract = {OBJECTIVES: To determine which procedure, aortic valve replacement (AVR) with a sutureless or rapid-deployment prosthesis (SL-AVR) or transcatheter aortic valve implantation (TAVI), achieves better perioperative survival for severe aortic stenosis (AS), we conducted direct-comparison meta-analyses (DC-MAs) and an adjusted indirect-comparison meta-analysis (IDC-MA).<br><br>METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through April 2016. Eligible studies were randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. We performed a DC-MA-[A] of SL-AVR versus TAVI, a DC-MA-[B] of SL-AVR versus conventional AVR (C-AVR), and a DC-MA-[C] TAVI versus C-AVR. Then, we computed a IDC-MA-[A'] of TAVI versus SL-AVR from the results of the DC-MA-[B] and the DC-MA-[C].<br><br>RESULTS: We identified 6 RCTs and 30 PSM studies enrolling a total of 15,887 patients. The 3 DC-MAs demonstrated significantly lower perioperative (30-day or in-hospital) all-cause mortality after SL-AVR than after TAVI (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.28 to 0.80; p=0.005) and no significant differences between SL-AVR and C-AVR (OR, 1.07; 95% CI, 0.60 to 1.94; p=0.81) and between TAVI and C-AVR (1.07; 95% CI, 0.90 to 1.27; p=0.45). The computed IDC-MA-[A'] indicated no significant difference in mortality between SL-AVR and TAVI (1.01; 95% CI, 0.54 to 1.86). Combining the results of the DC-MA-[A] and IDC-MA [A'] showed significantly lower mortality after SL-AVR than after TAVI (OR, 0.65; 95% CI, 0.44 to 0.97; p=0.03).<br><br>CONCLUSIONS: For patients with severe AS, SL-AVR may achieve better perioperative survival than TAVI.}, }
@article {pmid27864119, year = {2017}, author = {Dai, H and Gallagher, D and Schmitt, S and Pessetto, ZY and Fan, F and Godwin, AK and Tawfik, O}, title = {Role of miR-139 as a surrogate marker for tumor aggression in breast cancer.}, journal = {Human pathology}, volume = {61}, number = {}, pages = {68-77}, doi = {10.1016/j.humpath.2016.11.001}, pmid = {27864119}, issn = {1532-8392}, mesh = {Biomarkers, Tumor/classification/*genetics ; Biopsy ; Breast Neoplasms/blood/*genetics/mortality/pathology ; Carcinoma, Ductal, Breast/blood/*genetics/mortality/pathology ; Cell Proliferation ; Disease Progression ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; MicroRNAs/blood/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Phenotype ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Survival Analysis ; Tumor Burden ; }, abstract = {MicroRNAs are non-protein coding molecules that play a key role in oncogenesis, tumor progression, and metastasis in many types of malignancies including breast cancer. In the current study, we studied the expression of microRNA-139-5p (miR-139) in invasive ductal carcinoma (IDC) of the breast and correlated its expression with tumor grade, molecular subtype, hormonal status, human epidermal growth factor receptor 2 status, proliferation index, tumor size, lymph node status, patient's age, and overall survival in 74 IDC cases. In addition, we compared and correlated miR-139 expression in 18 paired serum and tissue samples from patients with IDC to assess its value as a serum marker. Our data showed that miR-139 was down-regulated in all tumor tissue samples compared with control. More pronounced down-regulation was seen in tumors that were higher grade, estrogen receptor negative, progesterone receptor negative, more proliferative, or larger in size (P < .05). Although not statistically significant, lower miR-139 level was frequently associated with human epidermal growth factor receptor 2 overexpression. In addition, significantly lower miR-139 tissue level was seen in patients who were deceased (P = .027), although older age (>50 years) and positive local nodal disease did not adversely affect miR-139 expression. In contrast, serum miR-139 profile of the patients appeared similar to that of normal control. In conclusion, our study demonstrated that down-regulation of miR-139 was associated with aggressive tumor behavior and disease progression in breast cancer. miR-139 may serve as a risk assessment biomarker in tailoring treatment options.}, }
@article {pmid27862063, year = {2016}, author = {Tasharrofi, B and Soudyab, M and Nikpayam, E and Iranpour, M and Mirfakhraie, R and Sarrafzadeh, S and Geranpayeh, L and Azargashb, E and Sayad, A and Ghafouri-Fard, S}, title = {Comparative expression analysis of hypoxia-inducible factor-alpha and its natural occurring antisense in breast cancer tissues and adjacent noncancerous tissues.}, journal = {Cell biochemistry and function}, volume = {34}, number = {8}, pages = {572-578}, doi = {10.1002/cbf.3230}, pmid = {27862063}, issn = {1099-0844}, mesh = {Adolescent ; Adult ; Breast Neoplasms/*genetics ; Child ; Demography ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism ; Middle Aged ; RNA, Antisense/*genetics/metabolism ; }, abstract = {Hypoxia-inducible factors (HIFs) have been shown to be upregulated in tumor tissues and linked with tumor progression and metastasis in breast cancer. Among regulatory mechanisms for HIF expression is a natural occurring antisense named aHIF, which has been shown to be overexpressed in breast cancer and influence the level of the HIF-1α transcript. In the present study, we analyzed the expression of HIF-1α and aHIF in breast cancer tissues versus adjacent noncancer tissues (ANCTs) in relation with the clinical and biological behavior of the tumors. aHIF has been shown to be expressed in 67.4% of invasive ductal carcinoma samples, while none of ANCTs showed its expression. HIF-1α has been expressed in all of tumors and 90% of ANCTs. Comparison of HIF-1α expression level between tumor and ANCT tissues showed a total upregulation in tumor samples. No statistically significant association has been found between the level of HIF-1α expression in tumor samples and clinicopathologic and demographic characteristics such as age, tumor size, estrogen receptor status, progesterone receptor status, HER2/neu expression level, lymph node status, histological grade, and stage except for a weak correlation between HIF-1α expression and Ki-67 status. Besides, we could not detect any significant correlation between relative expression of HIF-1α and aHIF in tumor samples. Collectively, these data suggest that aHIF overexpression can be used as a potential biomarker in breast cancer. However, further studies are needed for the evaluation of its mechanism of action in regulation of HIF-1α expression in different pathological conditions. HIF-1α overexpression results in the upregulation of several genes that participated in cancer-associated pathways such as proliferation, angiogenesis, and glucose metabolism. We showed that HIF-1α is upregulated in breast tumor samples compared with adjacent noncancerous tissues. Its expression has been associated with Ki-67 status. Its natural occurring antisense is only expressed in tumor tissues. Thus, it can be used as a potential biomarker in breast cancer.}, }
@article {pmid27861897, year = {2017}, author = {Casasent, AK and Edgerton, M and Navin, NE}, title = {Genome evolution in ductal carcinoma in situ: invasion of the clones.}, journal = {The Journal of pathology}, volume = {241}, number = {2}, pages = {208-218}, pmid = {27861897}, issn = {1096-9896}, support = {R01 CA169244/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma in Situ/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics ; Disease Progression ; Female ; *Genomics ; Humans ; }, abstract = {Ductal carcinoma in situ (DCIS) is the most frequently diagnosed early-stage breast cancer. Only a subset of patients progress to invasive ductal carcinoma (IDC), and this presents a formidable clinical challenge for determining which patients to treat aggressively and which patients to monitor without therapeutic intervention. Understanding the molecular and genomic basis of invasion has been difficult to study in DCIS cancers due to several technical obstacles, including low tumour cellularity, lack of fresh-frozen tissues, and intratumour heterogeneity. In this review, we discuss the role of intratumour heterogeneity in the progression of DCIS to IDC in the context of three evolutionary models: independent lineages, evolutionary bottlenecks, and multiclonal invasion. We examine the evidence in support of these models and their relevance to the diagnosis and treatment of patients with DCIS. We also discuss how emerging technologies, such as single-cell sequencing, STAR-FISH, and imaging mass spectrometry, are likely to provide new insights into the evolution of this enigmatic disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.}, }
@article {pmid27856072, year = {2017}, author = {Gesser-Edelsburg, A and Walter, N and Shir-Raz, Y and Sassoni Bar-Lev, O and Rosenblat, S}, title = {The behind-the-scenes activity of parental decision-making discourse regarding childhood vaccination.}, journal = {American journal of infection control}, volume = {45}, number = {3}, pages = {267-271}, doi = {10.1016/j.ajic.2016.10.009}, pmid = {27856072}, issn = {1527-3296}, mesh = {Adult ; Attitude to Health ; *Decision Making ; Female ; Humans ; Male ; Medication Adherence/*psychology ; Middle Aged ; Parents/*psychology ; *Patient Acceptance of Health Care ; Surveys and Questionnaires ; Vaccination/*psychology ; }, abstract = {BACKGROUND: Vaccine compliance has long been a cause for concern for health authorities throughout the world. However very little effort has been made to examine parental discourse during the decision-making process.<br><br>METHODS: An online survey was conducted (N&#x2009;=&#x2009;437) to examine predictors of parents' attitudes regarding childhood vaccination.<br><br>RESULTS: Hesitant parents were 4 times more likely to conduct intrafamily discussion regarding vaccination compared with provaccination parents (Exp[B]&#x2009;=&#x2009;4.26). There were no significant differences between hesitant and antivaccination parents with respect to intrafamily discussion. Hesitant parents were also 4 times more likely than provaccination parents to report intrafamily disagreements regarding vaccination (Exp[B]&#x2009;=&#x2009;4.27). They were also twice as likely as antivaccination parents to express disagreements regarding vaccination within their families (Exp[B]&#x2009;=&#x2009;2.33). Likewise, Jewish parents were significantly more likely to define themselves as vaccination-hesitant, whereas Muslim parents were significantly more likely to be provaccination.<br><br>CONCLUSIONS: To improve the way health organizations communicate information about vaccines and increase parental trust in immunization programs, we should not only look at the level of understanding, perceptions, and biases of different groups, but also thoroughly examine parents' decision-making processes and the discourse during this process. We must communicate risk to all groups, including the provaccination group, to improve parents' decision making and the process of informed consent.}, }
@article {pmid27847402, year = {2016}, author = {Dyachenko, L and Havrysh, K and Lytovchenko, A and Dosenko, I and Antoniuk, S and Filonenko, V and Kiyamova, R}, title = {Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades.}, journal = {Disease markers}, volume = {2016}, number = {}, pages = {5128720}, pmid = {27847402}, issn = {1875-8630}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/*blood/genetics/immunology ; Autoantibodies/*blood ; Base Sequence ; Biomarkers, Tumor/*blood/immunology ; Breast Neoplasms/blood/*immunology/pathology ; Carcinoma, Ductal, Breast/blood/immunology/pathology ; Carcinoma, Lobular/blood/immunology/pathology ; Carcinoma, Medullary/blood/immunology/pathology ; Case-Control Studies ; DNA-Binding Proteins/*blood/genetics/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Gene Library ; Humans ; Middle Aged ; Molecular Chaperones ; Neoplasm Grading ; Neoplasm Staging ; Nuclear Pore Complex Proteins/blood/genetics/immunology ; Oncogene Proteins/*blood/genetics/immunology ; Prognosis ; RNA-Binding Proteins/blood/genetics/immunology ; Young Adult ; }, abstract = {Purpose. To investigate a frequency of antibody response to SEREX-identified medullary breast carcinoma autoantigens ZRF1 and KRR1 in sera of breast cancer patients taking into account clinical and molecular characteristics of tumors for opening of new perspectives in creation of minimally invasive immunological tests for cancer diagnostics. Methods. Enzyme-linked immunosorbent assay and bioinformatics analysis. Results. Increased frequency of antibody response was found in sera of breast cancer patients to ZRF and KRR1 antigens. The antibody response to these antigens was higher in sera of patients with invasive ductal carcinoma than in sera of patients with other histological types of breast tumors. Moreover, more frequent antibody response to ZRF antigen was found in sera of patients with less aggressive tumors. The sequence analysis of ZRF1 antigen SEREX clones obtained from cDNA libraries of different tumors demonstrates that they encode different protein isoforms. Conclusion. Tumor-associated antigens KRR1 and ZRF1 and their cognate autoantibodies could be considered as potential molecular markers of breast cancer which need to be further investigated.}, }
@article {pmid27842678, year = {2016}, author = {Seithe, T and Braun, J and Wolf, M and Vahldiek, J and Wolny, D and Auer, J and Pociej, J and Heine, O and Hamm, B and de Bucourt, M}, title = {Diagnostic efficacy and safety of gadoteric acid MR mammography in 1537 patients.}, journal = {European journal of radiology}, volume = {85}, number = {12}, pages = {2281-2287}, doi = {10.1016/j.ejrad.2016.10.013}, pmid = {27842678}, issn = {1872-7727}, mesh = {Administration, Intravenous ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/*diagnostic imaging ; Breast Neoplasms/diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging ; *Contrast Media/administration &amp; dosage/adverse effects ; Deglutition Disorders/chemically induced ; Early Detection of Cancer ; Exanthema/chemically induced ; Female ; Humans ; Image Enhancement/methods ; Magnetic Resonance Imaging/*methods ; Male ; *Meglumine/administration &amp; dosage/adverse effects ; Middle Aged ; *Organometallic Compounds/administration &amp; dosage/adverse effects ; Product Surveillance, Postmarketing ; Safety ; Tachycardia/chemically induced ; Urticaria/chemically induced ; Young Adult ; }, abstract = {OBJECTIVES: To perform a large-scale multicenter post-marketing surveillance study for analyzing diagnostic effectiveness and safety of intravenous (IV) gadoteric acid (Dotarem[®]) in magnetic resonance (MR) mammography under daily practice conditions.<br><br>MATERIALS AND METHODS: Patients underwent high-resolution MR mammography with gadoteric acid in 15 German centers. Radiologists used a standardized questionnaire to report data including patient demographics and medical history, characteristics of MR examination and results in terms of diagnosis and safety for the patient.<br><br>RESULTS: A total of 1537 patients were examined. In 99.2% of all patients, a diagnosis was established. In 91.6% of all patients, image quality was excellent or good. Histopathological examinations were performed for 232 of 1537 patients (15.1%) with invasive ductal carcinoma being the most frequent diagnosis (109 patients, 47.0%). Based on histopathology as the standard of reference, IV gadoteric acid-enhanced MR mammography confirmed diagnoses of invasive ductal carcinoma in 93.5% of the patients. Adverse drug reactions occurred in 5 of 1537 patients (0.3%) and were classified as serious in one case (tachycardia, dysphagia, urticaria, rash). All patients with adverse drug reactions fully recovered after the examination.<br><br>CONCLUSION: This noninterventional surveillance study shows IV gadoteric acid to be a safe and effective contrast agent for use in MR mammography.}, }
@article {pmid27840910, year = {2016}, author = {Gomulkiewicz, A and Jablonska, K and Pula, B and Grzegrzolka, J and Borska, S and Podhorska-Okolow, M and Wojnar, A and Rys, J and Ambicka, A and Ugorski, M and Zabel, M and Dziegiel, P}, title = {Expression of metallothionein 3 in ductal breast cancer.}, journal = {International journal of oncology}, volume = {49}, number = {6}, pages = {2487-2497}, doi = {10.3892/ijo.2016.3759}, pmid = {27840910}, issn = {1791-2423}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Female ; Fibrocystic Breast Disease/*pathology ; Humans ; Immunohistochemistry ; MCF-7 Cells ; Metallothionein 3 ; Middle Aged ; Nerve Tissue Proteins/biosynthesis/genetics/*metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {Metallothionein 3 (MT-3) has the ability to regulate the growth of nerve cells, but the significance of MT-3 expression outside the central nervous system and its participation in carcinogenesis have not yet been clarified. The aim of our study was to investigate the expression of MT-3 in ductal breast cancer and to determine its relationship with well-defined clinicopathological factors in this type of tumor. The study was conducted on 134 cases of invasive ductal breast carcinoma (IDC), 42 samples of non-malignant breast tissue (NMBT), and 26 cases of mastopathy. Moreover, selected breast cancer cell lines (MCF-7, SKBR-3, MDA-MB-231, BO2) and normal human breast epithelial cells (hTERT-HME1) were used. The expression of MT-3 was examined on the protein level using immunohistochemistry and on the mRNA level using real-time PCR. It was shown that the MT-3 protein in cells of IDC and mastopathy appeared in the cytoplasm as well as in the cell nuclei. Both the cytoplasmic and nuclear expression of MT-3 was significantly lower in IDC than in the mastopathies (p<0.0001 and p<0.001). However, no significant correlation was demonstrated between the level of MT-3 protein and the studied clinicopathological factors. The mRNA expression of MT-3 in IDC was also lower than in non‑malignant breast tissue (p<0.0001). Furthermore, in the cases of IDC with lymph node metastasis, the level of MT-3 mRNA was significantly lower than in the cases without metastasis (p=0.0199). The expression of MT-3 mRNA in breast cancer cell lines was significantly lower than in the normal human breast epithelial cell line (p<0.001). These results suggest that MT-3 may play a role in the malignant transformation of breast epithelial cells and in tumor progression.}, }
@article {pmid27837608, year = {2016}, author = {Panagiotopoulos, N and Lagoudianakis, E and Pappas, A and Filis, K and Salemis, N and Manouras, A and Kontzoglou, K and Zografos, G}, title = {Lymphovascular infiltration in the tumor bed is a useful marker of biological behavior in breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {21}, number = {5}, pages = {1082-1089}, pmid = {27837608}, issn = {1107-0625}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Blood Vessels/chemistry/*pathology ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Lymphatic Vessels/chemistry/*pathology ; Mastectomy ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Proportional Hazards Models ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; }, abstract = {PURPOSE: Tumor cells can metastasize by entering existing vessels or new vessels actively recruited into the primary tumor. Invasion of the lymphatics and blood vessels in the periphery of the tumor seems to be a prerequisite step in the metastatic process. The aim of this study was to correlate peripheral lymphatic vessel infiltration (PLI) and peripheral blood vessel infiltration (PVI) in a cohort of patients with invasive ductal carcinoma of the breast with various other prognostic parameters and outcome.<br><br>METHODS: The study population consisted of 236 female patients with invasive ductal breast carcinomas, who had been operated between 2011 and 2013. The registered data included age at diagnosis, histological subtype, tumor size, TNM stage, histological grade, estrogen (ER) and progesterone receptors (PR), HER-2, p53, and PLI and PVI.<br><br>RESULTS: Pathological examination revealed that 22.5% of the patients had PVI and 37.3% had PLI at the tumor front. PVI correlated with younger age (p<0.05), higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05), higher N stage (p<0.05) and positive Ki67 expression (p<0.05). Similarly, PLI correlated with higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05) and higher N stage (p<0.05). Statistical analysis did not reveal significant correlation between the presence of tumor blood and lymphatic vessels with infiltration in overall (OS) and disease-free survival (DFS).<br><br>CONCLUSIONS: PLI and PVI are important markers of worse clinical outcome as shown by their association with other established factors, but no association with recurrence and survival could be proven.}, }
@article {pmid27837296, year = {2017}, author = {Timbrell, S and Al-Himdani, S and Shaw, O and Tan, K and Morris, J and Bundred, N}, title = {Comparison of Local Recurrence After Simple and Skin-Sparing Mastectomy Performed in Patients with Ductal Carcinoma In Situ.}, journal = {Annals of surgical oncology}, volume = {24}, number = {4}, pages = {1071-1076}, pmid = {27837296}, issn = {1534-4681}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Margins of Excision ; Mastectomy, Simple/*methods ; Middle Aged ; *Neoplasm Recurrence, Local/etiology ; Neoplasm, Residual ; Organ Sparing Treatments ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) is increasing with the use of screening mammography, and approximately 30% of all women diagnosed with DCIS are treated by mastectomy. There is increasing use of a skin-sparing mastectomy (SSM) approach to surgically excise DCIS as this facilitates immediate breast reconstruction. The rates of locoregional recurrence (LRR) after simple mastectomy performed for pure DCIS are historically reported as 1%; however, international data suggest that LRR after SSM may be higher.<br><br>METHODS: To determine our rates of LRR and compare the effect of the type of mastectomy performed, we undertook a retrospective review of all patients who underwent a mastectomy for pure DCIS at our institution between 2000 and 2010.<br><br>RESULTS: In total, 199 patients underwent a mastectomy for pure DCIS (with eight local recurrences), all of which were invasive ductal carcinoma. The recurrences all occurred after SSM, which was associated with a higher 5-year LRR of 5.9% (5/102) compared with 0% in the simple mastectomy group (0/97; p&#xa0;=&#xa0;0.012), log-rank. Univariate analysis showed the two factors that predicted the risk of recurrence were a young age at mastectomy and close or involved margins.<br><br>CONCLUSIONS: These data highlight the importance of achieving clear margins, especially in young women with estrogen receptor-negative DCIS who have a higher risk of invasive recurrence. Women undergoing a mastectomy for DCIS should be counseled as to the importance of achieving clear margins and the potential increased need for further excision, post-mastectomy radiotherapy and post-reconstruction mammography in order to prevent LRR after SSM.}, }
@article {pmid27835573, year = {2016}, author = {Sang, J and Yi, D and Tang, X and Zhang, Y and Huang, T}, title = {The associations between mast cell infiltration, clinical features and molecular types of invasive breast cancer.}, journal = {Oncotarget}, volume = {7}, number = {49}, pages = {81661-81669}, pmid = {27835573}, issn = {1949-2553}, mesh = {Age Factors ; Breast Neoplasms/chemistry/classification/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/classification/*pathology/therapy ; Carcinoma, Lobular/chemistry/*pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Lymphatic Metastasis ; Mast Cells/chemistry/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Risk Factors ; Tumor Burden ; }, abstract = {Associations between mast cell infiltration and the clinical features and known molecular profile of breast cancer remain unclear. The distribution difference of mast cell was evaluated, in 219 patients with no special type of invasive carcinoma, using sorts of age, max diameter of cancer, histological type, lymph node metastasis as well as the expressions of estrogen receptor (ER), progestogen receptor (PR), human epidermal growth factor receptor 2 (HER-2) and nuclear protein Ki67. The mast cell density (MCD) in patients younger than 50 years old was significantly higher than that in patients with age ≥ 50. The MCD in ER or PR positive patients was significantly higher than MCD in ER or PR negative patients. The MCD in patients with Ki67 ≤ 14% was also significantly higher than MDC in patients with Ki67 > 14%. The MCD of patients with invasive ductal carcinoma was significantly higher than MCD of patients with invasive lobular carcinoma. No significant distribution difference of MCD was found to be associated with max diameter of cancer, lymph node metastasis and HER-2. Further analysis found that MDC was significantly higher in patients after neo-adjuvant chemotherapy. The distribution difference of mast cell widely exists in patients with distinct clinical features, the role of mast cell in breast cancer need further research with detailed and reasonable classification to clarify.}, }
@article {pmid27827363, year = {2016}, author = {Ekim Üstünel, B and Friedrich, K and Maida, A and Wang, X and Krones-Herzig, A and Seibert, O and Sommerfeld, A and Jones, A and Sijmonsma, TP and Sticht, C and Gretz, N and Fleming, T and Nawroth, PP and Stremmel, W and Rose, AJ and Berriel-Diaz, M and Blüher, M and Herzig, S}, title = {Control of diabetic hyperglycaemia and insulin resistance through TSC22D4.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {13267}, pmid = {27827363}, issn = {2041-1723}, mesh = {Animals ; Blood Glucose/*metabolism ; Cell Line ; Diabetes Mellitus, Type 2/blood/*genetics ; Female ; Gene Expression Regulation ; Humans ; Hyperglycemia/blood/*genetics ; Insulin Resistance/*genetics ; Lipocalins/genetics/metabolism ; Liver/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Transcription Factors/*genetics/metabolism ; }, abstract = {Obesity-related insulin resistance represents the core component of the metabolic syndrome, promoting glucose intolerance, pancreatic beta cell failure and type 2 diabetes. Efficient and safe insulin sensitization and glucose control remain critical therapeutic aims to prevent diabetic late complications Here, we identify transforming growth factor beta-like stimulated clone (TSC) 22 D4 as a molecular determinant of insulin signalling and glucose handling. Hepatic TSC22D4 inhibition both prevents and reverses hyperglycaemia, glucose intolerance and insulin resistance in diabetes mouse models. TSC22D4 exerts its effects on systemic glucose homeostasis-at least in part-through the direct transcriptional regulation of the small secretory protein lipocalin 13 (LCN13). Human diabetic patients display elevated hepatic TSC22D4 expression, which correlates with decreased insulin sensitivity, hyperglycaemia and LCN13 serum levels. Our results establish TSC22D4 as a checkpoint in systemic glucose metabolism in both mice and humans, and propose TSC22D4 inhibition as an insulin sensitizing option in diabetes therapy.}, }
@article {pmid27825140, year = {2017}, author = {Lu, DG and Ma, YM and Zhu, AJ and Han, YW}, title = {An early biomarker and potential therapeutic target of RUNX 3 hypermethylation in breast cancer, a system review and meta-analysis.}, journal = {Oncotarget}, volume = {8}, number = {13}, pages = {22166-22174}, pmid = {27825140}, issn = {1949-2553}, mesh = {Animals ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/*genetics ; Core Binding Factor Alpha 3 Subunit/*genetics ; *DNA Methylation ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; }, abstract = {Runt-related transcription factor 3 (RUNX3) methylation plays an important role in the carcinogenesis of breast cancer (BC). However, the association between RUNX3 hypermethylation and significance of BC remains under investigation. The purpose of this study is to perform a meta-analysis and literature review to evaluate the clinicopathological significance of RUNX3 hypermethylation in BC. A comprehensive literature search was performed in Medline, Web of Science, EMBASE, Cochrane Library Database, CNKI and Google scholar. A total of 10 studies and 747 patients were included for the meta-analysis. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were evaluated and summarized respectively. RUNX3 hypermethylation was significantly correlated with the risk of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), OR was 50.37, p < 0.00001 and 22.66, p < 0.00001 respectively. Interestingly, the frequency of RUNX3 hypermethylation increased in estrogen receptor (ER) positive BC, OR was 12.12, p = 0.005. High RUNX3 mRNA expression was strongly associated with better relapse-free survival (RFS) in BC patients. In summary, RUNX3 methylation could be a promising early biomarker for the diagnosis of BC. High RUNX3 mRNA expression is correlated to better RFS in BC patients. RUNX3 could be a potential therapeutic target for the development of personalized therapy.}, }
@article {pmid27822759, year = {2016}, author = {Autenshlyus, AI and Kunts, TA and Karpukhina, KV and Mikhaylova, ES and Varaksin, NA and Marinkin, IO and Lyakhovich, VV}, title = {Cytokine pattern of the breast tumor supernatant.}, journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections}, volume = {470}, number = {1}, pages = {247-248}, pmid = {27822759}, issn = {1608-3105}, mesh = {Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Cell Fractionation ; Cytokines/*immunology ; Female ; Fibroadenoma/*immunology ; Humans ; Inflammation Mediators/*immunology ; Tumor Cells, Cultured ; Tumor Microenvironment/*immunology ; }, abstract = {Cytokine production was evaluated in supernatants of cultured tumor cells that were obtained by biopsy of the breast invasive ductal carcinoma (IDC) and breast fibroadenoma (FA) and grown in vitro. In the IDC supernatants, the concentrations of pro-inflammatory (pro-oncogenic) cytokines IL-17, IL-18, and IFNγ and of IL-1 receptor antagonist were significantly higher than in the FA cell supernatants. The concentrations of anti-inflammatory cytokine IL-10 and MCP-1 protein in supernatants of IDC cells were significantly lower than those determined in FA supernatants.}, }
@article {pmid27613186, year = {2016}, author = {Ilahi, NE and Anwar, S and Noreen, M and Hashmi, SN and Murad, S}, title = {Detection of human papillomavirus-16 DNA in archived clinical samples of breast and lung cancer patients from North Pakistan.}, journal = {Journal of cancer research and clinical oncology}, volume = {142}, number = {12}, pages = {2497-2502}, pmid = {27613186}, issn = {1432-1335}, mesh = {Adult ; Aged ; Breast Neoplasms/complications/epidemiology/*virology ; DNA, Viral/*isolation &amp; purification ; Female ; Human papillomavirus 16/genetics/*isolation &amp; purification ; Humans ; Lung Neoplasms/complications/epidemiology/*virology ; Middle Aged ; Pakistan/epidemiology ; Papillomavirus Infections/*complications/epidemiology/genetics ; Prevalence ; Registries ; Retrospective Studies ; }, abstract = {PURPOSE: Over the past few decades, human papillomavirus (HPV) has been recorded as a key player in the development of various genital cancers, most notably cervical cancer. It has also been associated with some non-genital cancers. A subset of oropharyngeal cancers are known to be caused by HPV. Its aetiological involvement has been suggested for breast and lung cancer as well. However, reports regarding the HPV DNA detection vary widely from different parts of the world. Due to scarcity of local data in this regard, the current study aimed at retrospective detection of HPV presence in the archival samples of breast and lung cancer patients from north part of the country.<br><br>METHODS: A total of 55 formalin-fixed paraffin-embedded tissue sections of invasive ductal carcinoma of breast&#xa0;(n&#xa0;=&#xa0;46) and lung (n&#xa0;=&#xa0;9) were collected for this study. Genotyping for HPV16 and 18 was carried out through PCR.<br><br>RESULTS: HPV16 DNA was found in both breast and lung carcinoma samples with the prevalence rate of 17 and 11&#xa0;%, respectively. An interesting association&#xa0;was found between ER/PR (Oestrogen/Progesterone receptor) and HER2/Neu (Human epidermal growth factor receptor-2) positivity with HPV occurrence in breast tumours.<br><br>CONCLUSION: Current study shows the presence of HPV16 DNA in archived clinical biopsy sections from breast and lung cancers (17, 11&#xa0;%), respectively. A positive correlation of HPV16 presence was found with ER/PR and HER2-positive breast cancers. These initial findings warrant further investigation in order to determine HPV prevalence and aetiological role in local cancers, especially in ER/PR/HER2-positive breast cancers on a larger scale.}, }
@article {pmid27785066, year = {2016}, author = {Meng, L and Xu, Y and Xu, C and Zhang, W}, title = {Biomarker discovery to improve prediction of breast cancer survival: using gene expression profiling, meta-analysis, and tissue validation.}, journal = {OncoTargets and therapy}, volume = {9}, number = {}, pages = {6177-6185}, pmid = {27785066}, issn = {1178-6930}, abstract = {PURPOSE: Breast cancer is the leading cause of cancer death worldwide in women. The molecular mechanism for human breast cancer is unknown. Gene microarray has been widely used in breast cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis survival. So far, the valuable multigene signatures in clinical practice are unclear, and the biological importance of individual genes is difficult to detect, as the described signatures virtually do not overlap. Early prognosis of this disease, breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS), is vital in breast surgery.<br><br>METHODS: Thus, this study reports gene expression profiling in large breast cancer cohorts from Gene Expression Omnibus, including GSE29044 (N=138) and GSE10780 (N=185) test series and four independent validation series GSE21653 (N=266), GSE20685 (N=327), GSE26971 (N=276), and GSE12776 (N=204). Significantly differentially expressed genes in human breast IDC and breast DCIS were detected by transcriptome microarray analysis.<br><br>RESULTS: We created a set of three genes (MAMDC2, TSHZ2, and CLDN11) that were significantly correlated with disease-free survival of breast cancer patients using a univariate Cox regression model (significance level P<0.01) in a meta-analysis. Based on the risk score of the three genes, the test series patients could be separated into low-risk and high-risk groups with significantly different survival times. This signature was validated in the other three cohorts. The prognostic value of this three-gene signature was confirmed in the internal validation series and another four independent breast cancer data sets. The prognostic impact of one of the three genes, CLDN11, was confirmed by immunohistochemistry. CLDN11 was significantly overexpressed in human breast IDC as compared with normal breast tissues and breast DCIS.<br><br>CONCLUSION: Using novel gene expression profiling together with a meta-analysis validation approach, we have identified a three-gene signature with independent prognostic impact. Furthermore, CLDN11 may offer a biomarker to predict prognosis as well as a new target for prognostic and therapeutic intervention for human breast IDC.}, }
@article {pmid26642960, year = {2016}, author = {Endo, Y and Dong, Y and Kondo, N and Yoshimoto, N and Asano, T and Hato, Y and Nishimoto, M and Kato, H and Takahashi, S and Nakanishi, R and Toyama, T}, title = {HER2 mutation status in Japanese HER2-positive breast cancer patients.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {23}, number = {6}, pages = {902-907}, doi = {10.1007/s12282-015-0659-y}, pmid = {26642960}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Asian People/genetics ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*drug therapy/*genetics/pathology ; Female ; Humans ; Middle Aged ; *Mutation ; Receptor, ErbB-2/antagonists &amp; inhibitors/*genetics/metabolism ; Trastuzumab/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Human epidermal growth factor receptor 2 (HER2) gene amplification/overexpression is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-HER2 agents. HER2 somatic mutations have been reported, and these may influence the effect of HER2-targeted drugs.<br><br>METHODS: Here, we sought HER2 mutations in a group of 135 Japanese breast cancer patients with HER2-positive tumors. We analyzed HER2 mutations by direct Sanger sequencing of two major areas, the extracellular domain at position 309-310 and the kinase domain between 755 and 781.<br><br>RESULTS: Two patients with the HER2 somatic mutation S310F in the extracellular domain were found in this series. One patient with the S310F mutation had a node-negative invasive ductal carcinoma classified as HER2 2+ by the HercepTest and fluorescence in situ hybridization (FISH) positive, and which was estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative. Another patient with the S310F mutation had an apocrine carcinoma with seven lymph nodes positive for metastasis, classified as HER2 3+ by the HercepTest, but which was FISH-negative, as well as ER-negative and PgR-negative. Both patients had received adjuvant single-agent trastuzumab therapy, and had no local recurrence or distant metastasis for five and three years after surgery, respectively.<br><br>CONCLUSIONS: Our data show that HER2 mutations are rare in HER2-positive Japanese breast cancer patients. The two mutations found in this study were identical, S310F. We suggest that in vitro experiments to determine whether the S310F mutation could be involved in resistance to anti-HER2 drugs are worthwhile in future.}, }
@article {pmid27781130, year = {2016}, author = {Paiva, C and Garcia, J and Silva, C and Araújo, A and Araújo, A and Santos, MD}, title = {Single Jejunum Metastasis from Breast Cancer Arising Twelve Years after the Initial Treatment.}, journal = {Case reports in oncological medicine}, volume = {2016}, number = {}, pages = {8594652}, pmid = {27781130}, issn = {2090-6706}, abstract = {Metastatic involvement of gastrointestinal tract from breast cancer is a rare event. We report the case of a 61-year-old woman presenting with bowel obstruction, related to metastasis of a primary breast cancer she had 12 years earlier (a triple-negative invasive ductal carcinoma treated with surgery and chemotherapy). Bowel obstruction was caused by a 20-centimeter tumor in the jejunum, involving also the transverse colon. The patient underwent en bloc resection of tumor with jejunum and transverse bowel segment and received adjuvant chemotherapy with carboplatin and paclitaxel. Twenty months later, she was alive without disease recurrence.}, }
@article {pmid27776915, year = {2017}, author = {Mendler, M and Riedinger, C and Schlotterer, A and Volk, N and Fleming, T and Herzig, S and Nawroth, PP and Morcos, M}, title = {Reduction in ins-7 gene expression in non-neuronal cells of high glucose exposed Caenorhabditis elegans protects from reactive metabolites, preserves neuronal structure and head motility, and prolongs lifespan.}, journal = {Journal of diabetes and its complications}, volume = {31}, number = {2}, pages = {304-310}, doi = {10.1016/j.jdiacomp.2016.09.014}, pmid = {27776915}, issn = {1873-460X}, mesh = {Animals ; Behavior, Animal ; Caenorhabditis elegans/enzymology/growth &amp; development/*metabolism ; Caenorhabditis elegans Proteins/agonists/*antagonists &amp; inhibitors/genetics/*metabolism ; Feedback, Physiological ; *Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Gene Knockout Techniques ; Glucose/*poisoning ; Glycation End Products, Advanced/metabolism ; Lactoylglutathione Lyase/antagonists &amp; inhibitors/genetics/*metabolism ; Longevity ; Mutation ; Neuroprotection ; Osmolar Concentration ; *Oxidative Stress ; Peptide Hormones/agonists/*antagonists &amp; inhibitors/genetics/metabolism ; RNA Interference ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/antagonists &amp; inhibitors/genetics/*metabolism ; Survival Analysis ; }, abstract = {BACKGROUND: Glucose derived metabolism generates reactive metabolites affecting the neuronal system and lifespan in C. elegans. Here, the role of the insulin homologue ins-7 and its downstream effectors in the generation of high glucose induced neuronal damage and shortening of lifespan was studied.<br><br>RESULTS: In C. elegans high glucose conditions induced the expression of the insulin homologue ins-7. Abrogating ins-7 under high glucose conditions in non-neuronal cells decreased reactive oxygen species (ROS)-formation and accumulation of methylglyoxal derived advanced glycation endproducts (AGEs), prevented structural neuronal damage and normalised head motility and lifespan. The restoration of lifespan by decreased ins-7 expression was dependent on the concerted action of sod-3 and glod-4 coding for the homologues of iron-manganese superoxide dismutase and glyoxalase 1, respectively.<br><br>CONCLUSIONS: Under high glucose conditions mitochondria-mediated oxidative stress and glycation are downstream targets of ins-7. This impairs the neuronal system and longevity via a non-neuronal/neuronal crosstalk by affecting sod-3 and glod-4, thus giving further insight into the pathophysiology of diabetic complications.}, }
@article {pmid27633896, year = {2016}, author = {Ratajczak-Wielgomas, K and Grzegrzolka, J and Piotrowska, A and Gomulkiewicz, A and Witkiewicz, W and Dziegiel, P}, title = {Periostin expression in cancer-associated fibroblasts of invasive ductal breast carcinoma.}, journal = {Oncology reports}, volume = {36}, number = {5}, pages = {2745-2754}, doi = {10.3892/or.2016.5095}, pmid = {27633896}, issn = {1791-2431}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis/genetics ; Cancer-Associated Fibroblasts/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating ; Cell Adhesion/genetics ; Cell Adhesion Molecules/*biosynthesis/genetics ; Cell Proliferation ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; }, abstract = {Periostin (POSTN) is a secreted cell adhesion glycoprotein that plays an important role in proliferation, adhesion and migration processes, as well as in regulation of mechanisms related to epithelial-mesenchymal transition (EMT). It also plays a key role in angio- and lymphangiogenesis and in formation of distant metastases. The aim of this work was to determine expression of POSTN in invasive ductal breast carcinoma (IDC) and in non-invasive ductal carcinoma in situ (DCIS) and to correlate its expression with clinicopathological parameters. Material for immunohistochemical studies (IHC) comprise of 70 IDC cases, 44 DCIS cases and 21 cases of fibrocystic change (FC). Frozen (-80˚C) fragments of tumours taken from 41 patients with IDC were used for molecular studies (real-time PCR), including 11 cases of IDC subjected to laser capture microdissection (LCM). POSTN expression was shown mainly in tumour stromal cells, i.e. cancer-associated fibroblasts (CAFs). Statistically significant higher level of POSTN expression in CAFs in IDC as compared to FC (p<0.0001) was observed. Additionally, statistically elevated expression level of POSTN in CAFs in IDC relative to DCIS (p<0.0001) and significantly increased expression of POSTN in CAFs in DCIS in comparison to FC (p=0.0158) was also shown. High level of POSTN expression in CAFs in IDC (>8 IRS points) was significantly correlated with tumour malignancy grade (G) (p=0.0070). Moreover, higher POSTN expression by CAFs was associated with patient shorter overall survival. Significant increase of POSTN expression on mRNA and protein level in CAFs in IDC with the growing malignancy grade of the tumours (G) was shown. Furthermore, with the use of LCM method, statistically significant higher expression of mRNA POSTN in stromal cells relative to cancer cells (p<0.001) was noted. POSTN might be a factor playing an important role in the mechanism of IDC progression.}, }
@article {pmid27775181, year = {2017}, author = {Kaya, Z and Akkiprik, M and Karabulut, S and Peker, I and Gullu Amuran, G and Ozmen, T and Gulluoglu, BM and Kaya, H and Ozer, A}, title = {Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.}, journal = {Journal of clinical laboratory analysis}, volume = {31}, number = {5}, pages = {}, pmid = {27775181}, issn = {1098-2825}, mesh = {Breast/*chemistry ; Breast Neoplasms/chemistry/*epidemiology/*genetics/mortality ; Cohort Studies ; DNA Methylation ; Female ; Humans ; Insulin-Like Growth Factor Binding Proteins/*genetics ; Middle Aged ; Survival Analysis ; Telomere/chemistry/*genetics ; Turkey ; }, abstract = {BACKGROUND: Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL.<br><br>METHODS: Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting.<br><br>RESULTS: Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters.<br><br>CONCLUSION: These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.}, }
@article {pmid27406466, year = {2016}, author = {El-Hage, A and Ruel, C and Afif, W and Wissanji, H and Hogue, JC and Desbiens, C and Leblanc, G and Poirier, &#xc9;}, title = {Metastatic pattern of invasive lobular carcinoma of the breast-Emphasis on gastric metastases.}, journal = {Journal of surgical oncology}, volume = {114}, number = {5}, pages = {543-547}, doi = {10.1002/jso.24362}, pmid = {27406466}, issn = {1096-9098}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Canada ; Carcinoma, Lobular/epidemiology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms/epidemiology/*secondary ; }, abstract = {BACKGROUND AND OBJECTIVES: Breast invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have different metastatic patterns, but the exact pattern of metastases from ILC is poorly known. This study aimed to determine the frequency of ILC metastases in atypical locations, with an emphasis on gastric metastases.<br><br>METHODS: Patients with ILC treated at the Saint-Sacrement Hospital (Quebec City, Canada) and the Maisonneuve-Rosemont Hospital (Montreal, Canada) between January 2003 and December 2009 were retrospectively reviewed. Demographic, clinical, and follow-up data were retrieved from the medical charts. Metastases that were diagnosed during follow-up were recorded.<br><br>RESULTS: Among the 481 patients with ILC, 74 (15.4%) were diagnosed with metastases after a median follow-up of 46 months. Among these 74 patients, 41.9% had metastases in atypical sites. Five patients were diagnosed with histologically confirmed gastric metastases of ILC.<br><br>CONCLUSION: Metastases of breast ILC to atypical sites might be more frequent than previously reported. Clinicians should keep a high level of suspicion when a patient with a history of ILC develops digestive symptoms. It is important to differentiate metastases from a primary GI tumor by using immunohistochemical markers. J. Surg. Oncol. 2016;114:543-547. &#xa9; 2016 Wiley Periodicals, Inc.}, }
@article {pmid27760942, year = {2016}, author = {Matsuoka, A and Hirano, A and Hattori, A and Ogura, K and Inoue, H and Yukawa, H and Sakaguchi, S and Tanaka, N and Kodera, A and Kamimura, M and Naritaka, Y and Shimizu, T}, title = {[Ethinylestradiol Following Everolimus plus Exemestane Was Effective in Postmenopausal Endocrine-Responsive Metastatic Breast Cancer - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {10}, pages = {1219-1222}, pmid = {27760942}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Estrogen Replacement Therapy ; Ethinyl Estradiol/administration &amp; dosage ; Everolimus/administration &amp; dosage ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymph Node Excision ; Mastectomy ; Postmenopause ; }, abstract = {A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin.Then, estrogen therapy with ethinylestradiol(EE2)was started in December 2013.T he pleural effusion disappeared and the liver metastases were reduced.After 11 months of progression-free survival(PFS), regrowth of the liver metastases was seen.Thus, everolimus plus exemestane was administered, and approximately 8 months of PFS was obtained.Therefore, both EE2 and everolimus are effective therapy even for heavily pretreated metastatic breast cancer.}, }
@article {pmid27760180, year = {2016}, author = {Fu, J and Wu, L and Jiang, M and Li, D and Jiang, T and Hong, Z and Wang, F and Li, S}, title = {Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer.}, journal = {PloS one}, volume = {11}, number = {10}, pages = {e0164921}, pmid = {27760180}, issn = {1932-6203}, mesh = {Adenocarcinoma, Mucinous/*epidemiology/metabolism/mortality ; Aged ; Analysis of Variance ; Breast Neoplasms/*epidemiology/metabolism/mortality ; Carcinoma, Ductal, Breast/*epidemiology/metabolism/mortality ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptors, Estrogen/*metabolism ; Risk Factors ; SEER Program ; Survival Analysis ; }, abstract = {BACKGROUND: The features related to the prognosis of patients with mucinous breast cancer (MBC) remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes.<br><br>METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify 139611 women with resectable breast cancer from 1990 to 2007. Survival curves were generated using Kaplan-Meier methods. The 5-year and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Based on Cox models, a nomogram was constructed to predict the probabilities of CSS for an individual patient. The competing risk regression model was used to analyse the specific survival of patients with MBC.<br><br>RESULTS: There were 136569 (97.82%) infiltrative ductal cancer (IDC) patients and 3042 (2.18%) MBC patients. Patients with MBC had less lymph node involvement, a higher frequency of well-differentiated lesions, and more estrogen receptor (ER)-positive tumors. Patients with MBC had significantly higher 5 and10-year CSS rates (98.23 and 96.03%, respectively) than patients with IDC (91.44 and 85.48%, respectively). Univariate and multivariate analyses showed that MBC was an independent factor for better prognosis. As for patients with MBC, the event of death caused by another disease exceeded the event of death caused by breast cancer. A competing risk regression model further showed that lymph node involvement, poorly differentiated grade and advanced T-classification were independent factors of poor prognosis in patients with MBC. The Nomogram can accurately predict CSS with a high C-index (0.816). Risk scores developed from the nomogram can more accurately predict the prognosis of patients with MBC (C-index = 0.789) than the traditional TNM system (C-index = 0.704, P< 0.001).<br><br>CONCLUSIONS: Patients with MBC have a better prognosis than patients with IDC. Nomograms could help clinicians make more informed decisions in clinical practice. The competing risk regression model, as a more rational model, is recommended for use in the survival analysis of patients with MBC in the future.}, }
@article {pmid27219913, year = {2016}, author = {Santangelo, G and Sacco, R and Siciliano, M and Bisecco, A and Muzzo, G and Docimo, R and De Stefano, M and Bonavita, S and Lavorgna, L and Tedeschi, G and Trojano, L and Gallo, A}, title = {Anxiety in Multiple Sclerosis: psychometric properties of the State-Trait Anxiety Inventory.}, journal = {Acta neurologica Scandinavica}, volume = {134}, number = {6}, pages = {458-466}, doi = {10.1111/ane.12564}, pmid = {27219913}, issn = {1600-0404}, mesh = {Adult ; Anxiety/epidemiology/etiology/*psychology ; Depression/epidemiology/etiology/psychology ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/complications/*psychology ; *Neuropsychological Tests ; Prevalence ; *Psychiatric Status Rating Scales ; Psychometrics ; Reference Values ; Sex Characteristics ; }, abstract = {OBJECTIVE: The aims of the present study were to examine psychometric properties of the Spielberger State-Trait Anxiety Inventory (STAI-Y-1 and STAI-Y-2, respectively) in a Multiple Sclerosis (MS) population and to identify a cut-off score to detect those MS patients with high level of state and/or trait anxiety who could be more vulnerable to development of depression and/or cognitive defects.<br><br>MATERIAL AND METHODS: The STAI-Y-1 and STAI-Y-2 was completed by a group of patients (n = 175) affected by MS and a group of healthy subjects (n = 150) matched for age, educational level, and gender. In MS patients internal consistency, divergent and discriminant validities were evaluated. Construct validity was examined by exploratory factor analysis for each scale.<br><br>RESULTS: There was no missing data, no floor or ceiling effects for both scales. The two scales showed high internal consistency, good divergent, and Known-groups validities. To identify high levels of state and trait anxiety in a patient with MS, we proposed three gender specific screening cut-off values (1, 1.5, 2 SD) for the STAI-Y-1 and the STAI-Y-2.<br><br>CONCLUSIONS: The findings showed that the STAI-Y-1 and the STAI-Y-2 are a valid tool for clinical use in MS patients and can be useful to measure the severity of anxiety and to identify those patients with high anxiety to introduce them in specific non-pharmacological intervention.}, }
@article {pmid27755404, year = {2017}, author = {Sakamoto, Y and Fujita, S and Adachi, M and Sakamoto, H and Naruse, T and Yanamoto, S and Ikeda, T and Umeda, M}, title = {Carcinoma Ex Pleomorphic Adenoma of the Tongue: Difficulty in Diagnosis Between Metastasis of Breast Cancer and Salivary Tumor.}, journal = {The Journal of craniofacial surgery}, volume = {28}, number = {2}, pages = {e182-e185}, doi = {10.1097/SCS.0000000000003136}, pmid = {27755404}, issn = {1536-3732}, mesh = {Adenocarcinoma/*diagnosis/etiology/pathology ; Adenoma, Pleomorphic/complications/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Diagnosis, Differential ; Female ; Glossectomy ; Humans ; Middle Aged ; Neoplasms, Second Primary/*diagnosis/etiology/pathology ; Salivary Gland Neoplasms/complications/*pathology ; Tongue Neoplasms/*diagnosis/etiology/pathology ; }, abstract = {Carcinoma ex pleomorphic adenoma (CEPA) is a carcinoma that shows histologic evidence of arising in or from a benign pleomorphic adenoma. Carcinoma ex pleomorphic adenoma often occurs in parotid glands, but is extremely rarely in the tongue. A 53-year-old Japanese woman was referred to the Department of Oral and Maxillofacial Surgery, Nagasaki University Hospital, because of tumor of the right dorsum tongue. She had a history of surgery of breast cancer (invasive ductal carcinoma) and it was disseminated to the lung and bone. Macroscopic examination revealed an oval tumor with a smooth mucosal surface of 10 mm in diameter in the right dorsum tongue. A clinical diagnosis was metastasis from breast cancer or primary salivary gland tumor. Histologic diagnosis of the biopsy specimen was CEPA. She underwent partial glossectomy under general anesthesia. The final diagnosis of surgical materials was CEPA based on the differential diagnosis from breast carcinoma. She is alive bearing disseminated breast carcinoma without recurrence of CEPA at 6 months after glossectomy.}, }
@article {pmid27727404, year = {2016}, author = {Gabanti, E and Bruno, F and Scaramuzzi, L and Mangione, F and Zelini, P and Gerna, G and Lilleri, D}, title = {Predictive value of human cytomegalovirus (HCMV) T-cell response in the control of HCMV infection by seropositive solid-organ transplant recipients according to different assays and stimuli.}, journal = {The new microbiologica}, volume = {39}, number = {4}, pages = {247-258}, pmid = {27727404}, issn = {1121-7138}, mesh = {Adult ; Aged ; Antigens, Viral ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cytomegalovirus Infections/*immunology/*prevention &amp; control ; Enzyme-Linked Immunospot Assay ; Female ; Humans ; Male ; Middle Aged ; Organ Transplantation/*adverse effects ; Predictive Value of Tests ; T-Lymphocytes/*physiology ; Young Adult ; }, abstract = {Human cytomegalovirus (HCMV) is still the most common viral infection in solid-organ transplant recipients (SOTR). Our study aimed to identify the predictive values of the T-cell response able to protect from HCMV disease, according to different assays. Viral DNA was determined by real-time PCR. The T-cell immune response to HCMV infection was investigated in SOTR according to the following assays and stimuli: cytokine flow cytometry (CFC) after peripheral blood mononuclear cell (PBMC) stimulation with autologous HCMV-infected dendritic cells (iDC) vs three ELISPOT assays using PBMCs stimulated with: 1. HCMV-infected cell lysate (iCL); 2. a pool of 34 epitopic peptides (PP) from different HCMV proteins; 3. a commercial pp65 peptide pool (CPM). ELISPOT results were normalized to T-cell counts. Overall, 51 SOTR were enrolled: 29 (57%) had low viral load (LVL) self-resolving infections, 19 (37%) high viral load (HVL) infections treated with antiviral drugs, and 3 (6%) tissue-invasive disease (TID). At DNAemia peak, ROC analysis showed that CFC-iDC CD4+ and the ELISPOT-iCL assays yielded overlapping area under the curve (AUC) results. The time needed to reconstitute protective T-cell immunity in SOTR with HVL infections was significantly longer with each assay compared to LVL infections. Using the CFC-iDC assay as a reference test (requiring 7 days to complete), the 24h ELISPOT-iCL assay provides similar results in terms of protection prediction from HCMV infection.}, }
@article {pmid27720394, year = {2016}, author = {Nogués, L and Reglero, C and Rivas, V and Salcedo, A and Lafarga, V and Neves, M and Ramos, P and Mendiola, M and Berjón, A and Stamatakis, K and Zhou, XZ and Lu, KP and Hardisson, D and Mayor, F and Penela, P}, title = {G Protein-coupled Receptor Kinase 2 (GRK2) Promotes Breast Tumorigenesis Through a HDAC6-Pin1 Axis.}, journal = {EBioMedicine}, volume = {13}, number = {}, pages = {132-145}, pmid = {27720394}, issn = {2352-3964}, support = {R01 CA167677/CA/NCI NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Apoptosis/genetics ; Breast Neoplasms/genetics/*metabolism/mortality/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival/genetics ; Cell Transformation, Neoplastic/*metabolism ; Disease Models, Animal ; Female ; G-Protein-Coupled Receptor Kinase 2/genetics/*metabolism ; Gene Expression ; Histone Deacetylase 6 ; Histone Deacetylases/genetics/*metabolism ; Humans ; Mice, Transgenic ; Models, Biological ; NIMA-Interacting Peptidylprolyl Isomerase/*metabolism ; Prognosis ; RNA Interference ; RNA, Small Interfering/genetics ; *Signal Transduction ; Tumor Burden ; }, abstract = {In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6) leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators. Interestingly, a correlation between GRK2 expression and Pin1 levels and de-acetylation status is detected in breast cancer patients. Activation of the HDAC6-Pin1 axis underlies the positive effects of GRK2 on promoting growth factor signaling, cellular proliferation and anchorage-independent growth in both luminal and basal breast cancer cells. Enhanced GRK2 levels promote tumor growth in mice, whereas GRK2 down-modulation sensitizes cells to therapeutic drugs and abrogates tumor formation. Our data suggest that GRK2 acts as an important onco-modulator by strengthening the functionality of key players in breast tumorigenesis such as HDAC6 and Pin1.}, }
@article {pmid27718416, year = {2016}, author = {Fives, C and O'Neill, CJ and Murphy, R and Corrigan, MA and O'Sullivan, MJ and Feeley, L and Bennett, MW and O'Connell, F and Browne, TJ}, title = {When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted.}, journal = {Breast (Edinburgh, Scotland)}, volume = {30}, number = {}, pages = {125-129}, doi = {10.1016/j.breast.2016.09.006}, pmid = {27718416}, issn = {1532-3080}, mesh = {Adult ; Aftercare ; Aged ; Biopsy, Large-Core Needle ; Breast Carcinoma In Situ/complications/diagnostic imaging/pathology/*therapy ; Breast Neoplasms/complications/diagnostic imaging/pathology/*therapy ; Cohort Studies ; Disease Management ; Female ; Fibroadenoma/complications/diagnostic imaging/pathology/*therapy ; Humans ; Hyperplasia ; Mammography ; *Mastectomy, Segmental ; Middle Aged ; Retrospective Studies ; *Watchful Waiting ; }, abstract = {BACKGROUND: The diagnosis and management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) remains controversial. Current management options after a core needle biopsy (CNB) with lobular neoplasia (LN) incorporating both ALH and LCIS include excision biopsy or careful clinical and radiologic follow up.<br><br>METHODS: A retrospective analysis of the surgical database at Cork University Hospital was performed to identify all core needle biopsies from January 1st 2010 to 31st December 2013 with a diagnosis of FA who subsequently underwent surgical excision biopsy. All cases with associated LN including ALH and classical LCIS were selected. We excluded cases with coexistent ductal carcinoma in situ (DCIS), invasive carcinoma, LN associated with necrosis, pleomorphic lobular carcinoma in situ (PLCIS) or lesions which would require excision in their own right (papilloma, radial scar, atypical ductal hyperplasia (ADH) or flat epithelial atypia (FEA)). Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded.<br><br>RESULTS: 2878 consecutive CNB with a diagnosis of FA were identified. 25 cases had a diagnosis of concomitant ALH or classical LCIS. Our study cohort consisted of 21 women with a mean age 53 years (age range 41-70 years). The core biopsy diagnosis was of LCIS and FA in 16 cases and ALH and FA in 5 cases. On excision biopsy, a FA was confirmed in all 21 cases. In addition to the FA, residual LCIS was present in 14 cases with residual ALH in 2 cases. One of the twenty-one cases (4.8%) was upgraded to invasive ductal carcinoma on excision.}, }
@article {pmid27708222, year = {2016}, author = {Elias, EV and de Castro, NP and Pineda, PH and Abuázar, CS and Bueno de Toledo Osorio, CA and Pinilla, MG and da Silva, SD and Camargo, AA and Silva, WA and E Ferreira, EN and Brentani, HP and Carraro, DM}, title = {Epithelial cells captured from ductal carcinoma in situ reveal a gene expression signature associated with progression to invasive breast cancer.}, journal = {Oncotarget}, volume = {7}, number = {46}, pages = {75672-75684}, pmid = {27708222}, issn = {1949-2553}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Disease Progression ; Epithelial Cells/metabolism ; Female ; Gene Expression Profiling ; Genetic Association Studies ; Humans ; Neoplasm Staging ; Reproducibility of Results ; *Transcriptome ; }, abstract = {Breast cancer biomarkers that can precisely predict the risk of progression of non-invasive ductal carcinoma in situ (DCIS) lesions to invasive disease are lacking. The identification of molecular alterations that occur during the invasion process is crucial for the discovery of drivers of transition to invasive disease and, consequently, biomarkers with clinical utility. In this study, we explored differences in gene expression in mammary epithelial cells before and after the morphological manifestation of invasion, i.e., early and late stages, respectively. In the early stage, epithelial cells were captured from both pre-invasive lesions with distinct malignant potential [pure DCIS as well as the in situ component that co-exists with invasive breast carcinoma lesions (DCIS-IBC)]; in the late stage, epithelial cells were captured from the two distinct morphological components of the same sample (in situ and invasive components). Candidate genes were identified using cDNA microarray and rapid subtractive hybridization (RaSH) cDNA libraries and validated by RT-qPCR assay using new samples from each group. These analyses revealed 26 genes, including 20 from the early and 6 from the late stage. The expression profile based on the 20 genes, marked by a preferential decrease in expression level towards invasive phenotype, discriminated the majority of DCIS samples. Thus, this study revealed a gene expression signature with the potential to predict DCIS progression and, consequently, provides opportunities to tailor treatments for DCIS patients.}, }
@article {pmid27692597, year = {2016}, author = {den Boer, SL and Rizopoulos, D and du Marchie Sarvaas, GJ and Backx, AP and Ten Harkel, AD and van Iperen, GG and Rammeloo, LA and Tanke, RB and Boersma, E and Helbing, WA and Dalinghaus, M}, title = {Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children.}, journal = {The American journal of cardiology}, volume = {118}, number = {11}, pages = {1723-1729}, doi = {10.1016/j.amjcard.2016.08.053}, pmid = {27692597}, issn = {1879-1913}, mesh = {Acute Disease ; Adolescent ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/mortality ; Child ; Child, Preschool ; Chronic Disease ; Death, Sudden, Cardiac/*epidemiology ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Natriuretic Peptide, Brain/*blood ; Netherlands/epidemiology ; Peptide Fragments/*blood ; Prognosis ; Retrospective Studies ; *Risk Assessment ; Risk Factors ; Survival Rate/trends ; }, abstract = {N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.}, }
@article {pmid27689969, year = {2016}, author = {Vaidya, JS and Wenz, F and Bulsara, M and Tobias, JS and Joseph, DJ and Saunders, C and Brew-Graves, C and Potyka, I and Morris, S and Vaidya, HJ and Williams, NR and Baum, M}, title = {An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial).}, journal = {Health technology assessment (Winchester, England)}, volume = {20}, number = {73}, pages = {1-188}, doi = {10.3310/hta20730}, pmid = {27689969}, issn = {2046-4924}, support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; }, abstract = {BACKGROUND: Based on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed - the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies.<br><br>OBJECTIVE: To compare TARGIT within a risk-adapted approach with whole-breast external beam radiotherapy (EBRT) over several weeks.<br><br>DESIGN: The TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a pragmatic, prospective, international, multicentre, non-inferiority, non-blinded, randomised (1&#x2009;:&#x2009;1 ratio) clinical trial. Originally, randomisation occurred before initial lumpectomy (prepathology) and, if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added in which randomisation occurred after initial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but which needed a reoperation to reopen the wound to give TARGIT as a delayed procedure. The risk-adapted approach meant that, in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised in the real world.<br><br>SETTING: Thirty-three centres in 11 countries.<br><br>PARTICIPANTS: Women who were aged &#x2265;&#x2009;45 years with unifocal invasive ductal carcinoma preferably &#x2264;&#x2009;3.5&#x2009;cm in size.<br><br>INTERVENTIONS: TARGIT within a risk-adapted approach and whole-breast EBRT.<br><br>MAIN OUTCOME MEASURES: The primary outcome measure was absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary outcome measures included toxicity and breast cancer-specific and non-breast-cancer mortality.<br><br>RESULTS: In total, 3451 patients were recruited between March 2000 and June 2012. The following values are 5-year Kaplan-Meier rates for TARGIT compared with EBRT. There was no statistically significant difference in local recurrence between TARGIT and EBRT. TARGIT was non-inferior to EBRT overall [TARGIT 3.3%, 95% confidence interval (CI) 2.1% to 5.1% vs. EBRT 1.3%, 95% CI 0.7% to 2.5%; p&#x2009;=&#x2009;0.04; Pnon-inferiority&#x2009;=&#x2009;0.00000012] and in the prepathology stratum (n&#x2009;=&#x2009;2298) when TARGIT was given concurrently with lumpectomy (TARGIT 2.1%, 95% CI 1.1% to 4.2% vs. EBRT 1.1%, 95% CI 0.5% to 2.5%; p&#x2009;=&#x2009;0.31; Pnon-inferiority&#x2009;=&#x2009;0.0000000013). With delayed TARGIT postpathology (n&#x2009;=&#x2009;1153), the between-group difference was larger than 2.5% and non-inferiority was not established for this stratum (TARGIT 5.4%, 95% CI 3.0% to 9.7% vs. EBRT 1.7%, 95% CI 0.6% to 4.9%; p&#x2009;=&#x2009;0.069; Pnon-inferiority&#x2009;=&#x2009;0.06640]. The local recurrence-free survival was 93.9% (95% CI 90.9% to 95.9%) when TARGIT was given with lumpectomy compared with 92.5% (95% CI 89.7% to 94.6%) for EBRT (p&#x2009;=&#x2009;0.35). In a planned subgroup analysis, progesterone receptor (PgR) status was found to be the only predictor of outcome: hormone-responsive patients (PgR positive) had similar 5-year local recurrence with TARGIT during lumpectomy (1.4%, 95% CI 0.5% to 3.9%) as with EBRT (1.2%, 95% CI 0.5% to 2.9%; p&#x2009;=&#x2009;0.77). Grade 3 or 4 radiotherapy toxicity was significantly reduced with TARGIT. Overall, breast cancer mortality was much the same between groups (TARGIT 2.6%, 95% CI 1.5% to 4.3% vs. EBRT 1.9%, 95% CI 1.1% to 3.2%; p&#x2009;=&#x2009;0.56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1.4%, 95% CI 0.8% to 2.5% vs. 3.5%, 95% CI 2.3% to 5.2%; p&#x2009;=&#x2009;0.0086), attributable to fewer deaths from cardiovascular causes and other cancers, leading to a trend in reduced overall mortality in the TARGIT arm (3.9%, 95% CI 2.7% to 5.8% vs. 5.3%, 95% CI 3.9% to 7.3%; p&#x2009;=&#x2009;0.099]. Health economic analyses suggest that TARGIT was statistically significantly less costly than EBRT, produced similar quality-adjusted life-years, had a positive incremental net monetary benefit that was borderline statistically significantly different from zero and had a probability of >&#x2009;90% of being cost-effective. There appears to be little uncertainty in the point estimates, based on deterministic and probabilistic sensitivity analyses. If TARGIT were given instead of EBRT in suitable patients, it might potentially reduce costs to the health-care providers in the UK by &#xa3;8-9.1 million each year. This does not include environmental, patient and societal costs.<br><br>LIMITATIONS: The number of local recurrences is small but the number of events for local recurrence-free survival is not as small (TARGIT 57 vs. EBRT 59); occurrence of so few events (<&#x2009;3.5%) also implies that both treatments are effective and any difference is unlikely to be large. Not all 3451 patients were followed up for 5 years; however, more than the number of patients required to answer the main trial question (n&#x2009;=&#x2009;585) were followed up for >&#x2009;5 years.<br><br>CONCLUSIONS: For patients with breast cancer (women who are aged &#x2265;&#x2009;45 years with hormone-sensitive invasive ductal carcinoma that is up to 3.5&#x2009;cm in size), TARGIT concurrent with lumpectomy within a risk-adapted approach is as effective as, safer than and less expensive than postoperative EBRT.<br><br>FUTURE WORK: The analyses will be repeated with longer follow-up. Although this may not change the primary result, the larger number of events may confirm the effect on overall mortality and allow more detailed subgroup analyses. The TARGeted Intraoperative radioTherapy Boost (TARGIT-B) trial is testing whether or not a tumour bed boost given intraoperatively (TARGIT) boost is superior to a tumour bed boost given as part of postoperative EBRT.<br><br>TRIAL REGISTRATION: Current Controlled Trials ISRCTN34086741 and ClinicalTrials.gov NCT00983684.<br><br>FUNDING: University College London Hospitals (UCLH)/University College London (UCL) Comprehensive Biomedical Research Centre, UCLH Charities, Ninewells Cancer Campaign, National Health and Medical Research Council and German Federal Ministry of Education and Research (BMBF). From September 2009 this project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 73. See the NIHR Journals Library website for further project information.}, }
@article {pmid27689750, year = {2016}, author = {Na, N and Luo, Y and Zhao, D and Yang, S and Hong, L and Li, H and Miao, B and Qiu, J}, title = {Prolongation of kidney allograft survival regulated by indoleamine 2, 3-dioxygenase in immature dendritic cells generated from recipient type bone marrow progenitors.}, journal = {Molecular immunology}, volume = {79}, number = {}, pages = {22-31}, doi = {10.1016/j.molimm.2016.09.005}, pmid = {27689750}, issn = {1872-9142}, mesh = {Allografts/immunology ; Animals ; Blotting, Western ; Dendritic Cells/enzymology/*immunology ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Graft Survival ; Hematopoietic Stem Cells/enzymology/immunology ; Immune Tolerance/*immunology ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*immunology/metabolism ; *Kidney Transplantation ; Lymphocyte Culture Test, Mixed ; Male ; Rats ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology/*immunology ; }, abstract = {Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance. In this study, BN rat recipients were pre-injected with donor renal alloantigen-treated recipient iDCs before kidney transplantation. The renal allograft exhibited a lighter renal rejection response, prolonged graft survival time, and an increasing content of CD4[+]CD25[+]Foxp3[+] regulatory T cells (Tregs). Additionally, up-regulated secretion of Th2 cytokines were found in recipient sera post-transplantation. Transfection of si-IDO1 RNA into renal-antigen-treated recipient iDCs reversed these changes, which suggested that IDO channel signaling may be involved in iDC-induced allograft immunotolerance. These results suggested that iDC-induced and IDO-mediated allograft immunotolerance might be a potentially feasible tactic to prolong allograft survival, in addition to immunosuppressive drugs.}, }
@article {pmid27688086, year = {2016}, author = {Wang, D and Fu, L and Shah, W and Zhang, J and Yan, Y and Ge, X and He, J and Wang, Y and Li, X}, title = {Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in invasive ductal carcinoma of breast.}, journal = {Pathology, research and practice}, volume = {212}, number = {12}, pages = {1151-1156}, doi = {10.1016/j.prp.2016.09.009}, pmid = {27688086}, issn = {1618-0631}, mesh = {Breast Neoplasms/genetics/pathology/*virology ; Carcinoma, Ductal, Breast/genetics/pathology/*virology ; DNA, Viral/*genetics ; Female ; Human Papillomavirus DNA Tests ; Humans ; Middle Aged ; Oncogenes/*genetics ; Papillomaviridae/*genetics ; Papillomavirus Infections/virology ; }, abstract = {BACKGROUND AND AIMS: The causative role of high risk human papillomavirus (HR-HPV) in breast cancer development is controversial, though a number of reports have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies to date have focused primarily on viral DNA rather than the viral transcription. The aim of this study was to investigate the presence of HR-HPV in breast cancer tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization (ISH).<br><br>METHODS: One hundred and forty six (146) cases of breast invasive ductal carcinoma(IDC) and 83 cases of benign breast lesions were included in the study. Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18 and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7 assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC).<br><br>RESULTS: HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731).<br><br>CONCLUSIONS: HR-HPVs certainly exist in breast cancer tissue with less active transcription, which implies that the causal role of HPV in breast cancer development need further study.}, }
@article {pmid27683971, year = {2017}, author = {Detremerie, C and Timmermans, F and De Pauw, M and Gheeraert, P and Hemelsoet, D and Toeback, J and Bové, T and Vandecasteele, E}, title = {Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma.}, journal = {Acta clinica Belgica}, volume = {72}, number = {4}, pages = {268-273}, doi = {10.1080/17843286.2016.1219012}, pmid = {27683971}, issn = {2295-3337}, mesh = {Aged ; Breast Neoplasms/*complications/*diagnosis ; Carcinoma, Ductal, Breast/*complications/*diagnosis ; Endocarditis, Non-Infective/diagnostic imaging/*etiology ; Female ; Humans ; Stroke/diagnostic imaging/*etiology ; }, abstract = {We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.}, }
@article {pmid27682634, year = {2016}, author = {Pellecchia, MT and Savastano, R and Moccia, M and Picillo, M and Siano, P and Erro, R and Vallelunga, A and Amboni, M and Vitale, C and Santangelo, G and Barone, P}, title = {Lower serum uric acid is associated with mild cognitive impairment in early Parkinson's disease: a 4-year follow-up study.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {123}, number = {12}, pages = {1399-1402}, pmid = {27682634}, issn = {1435-1463}, mesh = {Aged ; Cognitive Dysfunction/*blood/diagnostic imaging/*etiology ; Female ; Humans ; Italy ; Logistic Models ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/blood/*complications/diagnostic imaging ; Severity of Illness Index ; Tomography, X-Ray Computed ; Uric Acid/*metabolism ; }, abstract = {Cognitive deficits are common in Parkinson's disease (PD) and many patients eventually develop dementia; however, its occurrence is unpredictable. Serum uric acid (UA) has been proposed as a biomarker of PD, both in the preclinical and clinical phase of the disease. The aim of this pilot study was to evaluate relationships between baseline serum UA levels and occurrence of mild cognitive impairment (MCI) at 4-year follow-up in a cohort of early PD patients. Early PD patients, not presenting concomitant diseases, cognitive impairment or treatment possibly interfering with UA levels, underwent neuropsychological testing at baseline and 4-year follow-up. UA levels were determined in serum at baseline. MCI was found in 23 out of 42 PD patients completing 4-year follow-up. Patients presenting MCI had significantly higher age at onset and lower Frontal Assessment Battery scores at baseline as compared with patients cognitively intact. Logistic regression analysis showed that both serum UA levels (OR = 0.54, p = 0.044) and age (OR = 1.16, p = 0.009) contribute to the occurrence of MCI at 4-year follow-up. Our pilot study suggests that lower levels of serum UA in the early disease stages are associated to the later occurrence of MCI. These results need to be confirmed by further studies on larger samples.}, }
@article {pmid27670952, year = {2017}, author = {Firat, D and Ozturk, G and Demirbas, E and Idiz, O and Isik, A and Eken, H}, title = {Auto-Amputation of the Breast; a Rare Case Caused by Invasive Ductal Carcinoma.}, journal = {The breast journal}, volume = {23}, number = {1}, pages = {102-103}, doi = {10.1111/tbj.12696}, pmid = {27670952}, issn = {1524-4741}, mesh = {Aged ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Thorax/diagnostic imaging ; Tomography, X-Ray Computed ; }, }
@article {pmid27668497, year = {2016}, author = {Lee, HS and Ha, JY and Choi, W and Yoon, KC}, title = {Bilateral Corneal Epithelial Lesions Associated with Paclitaxel.}, journal = {Optometry and vision science : official publication of the American Academy of Optometry}, volume = {93}, number = {10}, pages = {1333-1336}, doi = {10.1097/OPX.0000000000000945}, pmid = {27668497}, issn = {1538-9235}, abstract = {PURPOSE: An antineoplastic drug, paclitaxel, is widely used in small cell lung cancer, breast cancer, and ovarian cancer. We report a case of bilateral, vision-impairing corneal epithelial lesions that developed in a patient receiving paclitaxel monotherapy for breast cancer.<br><br>CASE REPORT: A 45-year-old woman presented with a 1-month history of bilateral visual disturbances. She had been receiving paclitaxel chemotherapy after modified radical mastectomy for invasive ductal carcinoma in her left breast. Best-corrected visual acuity was 20/100 in the right eye and 20/40 in the left eye. Slit-lamp examination revealed irregular triangular corneal lesions in both eyes. The lesions extended to the center of the cornea involving the visual axis and showed late staining with fluorescein dye. The lesions resolved 5 months after discontinuation of paclitaxel chemotherapy, and best-corrected visual acuity was restored to 20/20 in both eyes.<br><br>CONCLUSIONS: Microtubule-stabilizing chemotherapeutic drugs such as paclitaxel can cause visually significant corneal lesions, and these lesions appear to be reversible with discontinuation of the drug. This case highlights the need for regular ophthalmologic examinations for the detection of this reversible adverse ocular reaction.}, }
@article {pmid27630343, year = {2016}, author = {Do, SI and Yoon, G and Kim, HS and Kim, K and Lee, H and Do, IG and Kim, DH and Chae, SW and Sohn, JH}, title = {Increased Brahma-related Gene 1 Expression Predicts Distant Metastasis and Shorter Survival in Patients with Invasive Ductal Carcinoma of the Breast.}, journal = {Anticancer research}, volume = {36}, number = {9}, pages = {4873-4882}, doi = {10.21873/anticanres.11051}, pmid = {27630343}, issn = {1791-7530}, mesh = {Adult ; Aged ; Biomarkers, Tumor/biosynthesis/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Helicases/biosynthesis/*genetics ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Nuclear Proteins/biosynthesis/*genetics ; Prognosis ; Transcription Factors/biosynthesis/*genetics ; }, abstract = {BACKGROUND: Previous studies have demonstrated aberrant Brahma-related gene 1 (BRG1) expression in various tumor types. Increased BRG1 expression has recently been shown to correlate with aggressive oncogenic behavior in many different types of human cancer. However, the role of BRG1 in breast cancer development and progression is not fully understood.<br><br>MATERIALS AND METHODS: We evaluated BRG1 expression in 224 patients with invasive ductal carcinoma (IDC) of the breast using tissue microarray samples and immunohistochemistry. We also investigated whether BRG1 expression status is associated with clinicopathological characteristics and outcomes of patients with IDC.<br><br>RESULTS: Among the 224 patients with IDC, 37.5% (84/224) exhibited high BRG1 expression. IDC exhibited significantly higher BRG1 expression compared to ductal carcinoma in situ (p=0.009) and normal breast tissue (p=0.005). High BRG1 expression in IDC significantly correlated with higher histological grade (p=0.035) and presence of distant metastasis (p=0.002). Furthermore, high BRG1 expression was an independent factor for predicting distant metastasis (relative risk=4.079; p=0.007). In addition, high BRG1 expression predicted shorter overall (p=0.011) and recurrence-free (p=0.003) survival in patients with IDC. In particular, BRG1 had a significant prognostic value in predicting recurrence-free survival of patients with IDC with lymph node metastasis or stage III disease.<br><br>CONCLUSION: BRG1 is involved in the progression and metastasis of breast cancer and can serve as a novel biomarker predictive of distant metastasis and patient outcomes.}, }
@article {pmid27628551, year = {2016}, author = {Hamaoka, A and Matsuda, T and Konishi, E and Taguchi, T}, title = {[A Case of Luminal-HER2 Advanced Breast Cancer with Liver Metastasis Showed Pathological Complete Response to the Therapy with Pertuzumab plus Trastuzumab plus Docetaxel].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {9}, pages = {1097-1100}, pmid = {27628551}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/surgery ; Combined Modality Therapy ; Docetaxel ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phenobarbital/analysis/metabolism ; Receptor, ErbB-2/analysis/metabolism ; Taxoids/administration &amp; dosage ; Trastuzumab/administration &amp; dosage ; Treatment Outcome ; }, abstract = {A 56-year-old woman noticed a mass on her left breast and visited our hospital. An irregular mass of 3 cm with associated axillary lymphadenopathy was detected under the nipple of the left breast. After further evaluations, the diagnosis was an invasive ductal carcinoma(scirrhous carcinoma)ofLuminal -HER2 type with liver metastases(cT4bN1M1, Stage IV). Treatment was initiated with a combination ofpertuzumab, trastuzumab, and docetaxel(PTD). The primary tumor showed a clinical complete response, and the liver metastases and the axillary lymph node metastases showed a partial response. Docetaxel was excluded after the 8th cycle because the patient experienced severe edema. After 15 cycles of therapy, the primary tumor was resected, and pathological examination revealed a pathological complete response ofthe primary lesion. Thus, PTD combination therapy is effective for Stage IV metastatic breast cancer ofthe Luminal-HER2 type.}, }
@article {pmid27625208, year = {2016}, author = {Hidalgo, IH and Fleming, T and Eckstein, V and Herzig, S and Nawroth, PP and Tyedmers, J}, title = {Characterization of aggregate load and pattern in living yeast cells by flow cytometry.}, journal = {BioTechniques}, volume = {61}, number = {3}, pages = {137-148}, doi = {10.2144/000114452}, pmid = {27625208}, issn = {1940-9818}, mesh = {Flow Cytometry/*methods ; Green Fluorescent Proteins/analysis/chemistry/genetics/metabolism ; High-Throughput Screening Assays ; Peptide Termination Factors/analysis/chemistry/genetics/metabolism ; *Protein Aggregates ; Recombinant Fusion Proteins/analysis/chemistry/genetics/metabolism ; Saccharomyces cerevisiae/*chemistry/cytology/metabolism ; Saccharomyces cerevisiae Proteins/analysis/chemistry/genetics/metabolism ; }, abstract = {Protein aggregation is both a hallmark of and a driving force for a number of diseases. It is therefore important to identify the nature of these aggregates and the mechanism(s) by which the cell counteracts their detrimental properties. Currently, the study of aggregation in vivo is performed primarily using fluorescently tagged versions of proteins and analyzing the aggregates by fluorescence microscopy. While this strategy is considered the gold standard, it has several limitations, particularly with respect to its suitability for high-throughput screening (HTS). Here, using a GFP fusion of the well-characterized yeast prion amyloid protein [PSI+], we demonstrate that flow cytometry, which utilizes the same physical principles as fluorescence microscopy, can be used to determine the aggregate load and pattern in live and fixed yeast cells. Furthermore, our approach can easily be applied to high-throughput analyses such as screenings with a yeast deletion library.}, }
@article {pmid27589880, year = {2017}, author = {Jay, AM and Hamame, AS and Dul, C and Wesen, C}, title = {Breast Cancer in a 19-Year-Old Female Adolescent Identified with Li-Fraumeni Syndrome.}, journal = {Journal of pediatric and adolescent gynecology}, volume = {30}, number = {1}, pages = {e5-e6}, doi = {10.1016/j.jpag.2016.08.011}, pmid = {27589880}, issn = {1873-4332}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Humans ; Li-Fraumeni Syndrome/*genetics ; *Tumor Suppressor Protein p53 ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is rare in adolescents. In one study, breast carcinoma accounted for 0.02% of breast masses surgically removed in young women. We report a case of breast cancer in a 19-year-old woman who was found to have Li-Fraumeni Syndrome.<br><br>CASE: The patient presented with a new, hard, nonmobile lump in the right breast which prompted her to seek medical attention. A biopsy identified invasive ductal carcinoma. Genetic testing showed a p53 mutation associated with Li-Fraumeni syndrome.<br><br>SUMMARY AND CONCLUSION: Although breast masses in young women are mostly benign, one must entertain the possibility of more serious conditions when a breast mass is identified with concerning medical or physical findings. Genetic testing might be informative for such patients.}, }
@article {pmid27576528, year = {2016}, author = {Calhoun, BC and Portier, B and Wang, Z and Minca, EC and Budd, GT and Lanigan, C and Tubbs, RR and Morrison, LE}, title = {MET and PTEN gene copy numbers and Ki-67 protein expression associate with pathologic complete response in ERBB2-positive breast carcinoma patients treated with neoadjuvant trastuzumab-based therapy.}, journal = {BMC cancer}, volume = {16}, number = {1}, pages = {695}, pmid = {27576528}, issn = {1471-2407}, mesh = {Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Area Under Curve ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Chemotherapy, Adjuvant/methods ; Female ; Gene Dosage ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Ki-67 Antigen/biosynthesis ; Middle Aged ; Neoadjuvant Therapy/methods ; PTEN Phosphohydrolase/genetics ; Prognosis ; Proto-Oncogene Proteins c-met/genetics ; ROC Curve ; Receptor, ErbB-2 ; Sensitivity and Specificity ; Trastuzumab/*therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy for breast cancer is associated with improved prognosis in aggressive tumor subtypes, including ERBB2- positive tumors. Recent adoption of pCR as a surrogate endpoint for clinical trials in early stage breast cancer in the neoadjuvant setting highlights the need for biomarkers that, alone or in combination, help predict the likelihood of response to treatment.<br><br>METHODS: Biopsy specimens from 29 patients with invasive ductal carcinoma treated with trastuzumab-based therapy prior to definitive resection and pathologic staging were evaluated by dual color bright field in situ hybridization (dual ISH) using probes for MET, TOP2A, PTEN, and PIK3CA genes, each paired with centromeric probes to their respective chromosomes (chromosomes 7, 17, 10, and 3). Ki-67 expression was assessed by immunohistochemistry (IHC). Various parameters describing copy number alterations were evaluated for each gene and centromere probe to identify the optimal parameters for clinical relevance. Combinations of ISH parameters and IHC expression for Ki-67 were also evaluated.<br><br>RESULTS: Of the four genes and their respective chromosomes evaluated by ISH, two gene copy number parameters provided statistically significant associations with pCR: MET gain or loss relative to chromosome 7 (AUC&#x2009;=&#x2009;0.791, sensitivity&#x2009;=&#x2009;92&#xa0;% and specificity&#x2009;=&#x2009;67&#xa0;% at optimal cutoff, p&#x2009;=&#x2009;0.0032) and gain of PTEN (AUC&#x2009;=&#x2009;0.674, sensitivity&#x2009;=&#x2009;38&#xa0;% and specificity&#x2009;=&#x2009;100&#xa0;% at optimal cutoff, p&#x2009;=&#x2009;0.039). Ki-67 expression was also found to associate significantly with pCR (AUC&#x2009;=&#x2009;0.726, sensitivity&#x2009;=&#x2009;100&#xa0;% and specificity&#x2009;=&#x2009;42&#xa0;% at optimal cutoff, p&#x2009;=&#x2009;0.0098). Combining gain or loss of MET relative to chromosome 7 with Ki-67 expression further improved the association with pCR (AUC&#x2009;=&#x2009;0.847, sensitivity&#x2009;=&#x2009;92&#xa0;% and specificity&#x2009;=&#x2009;83&#xa0;% at optimal cutoffs, p&#x2009;=&#x2009;0.0006).<br><br>CONCLUSIONS: An immunogenotypic signature of low complexity comprising MET relative copy number and Ki-67 expression generated by dual ISH and IHC may help predict pCR in ERBB2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. These findings require validation in additional patient cohorts.}, }
@article {pmid27571348, year = {2016}, author = {Rohm, M and Schäfer, M and Laurent, V and Üstünel, BE and Niopek, K and Algire, C and Hautzinger, O and Sijmonsma, TP and Zota, A and Medrikova, D and Pellegata, NS and Ryden, M and Kulyte, A and Dahlman, I and Arner, P and Petrovic, N and Cannon, B and Amri, EZ and Kemp, BE and Steinberg, GR and Janovska, P and Kopecky, J and Wolfrum, C and Blüher, M and Berriel Diaz, M and Herzig, S}, title = {An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice.}, journal = {Nature medicine}, volume = {22}, number = {10}, pages = {1120-1130}, pmid = {27571348}, issn = {1546-170X}, mesh = {AMP-Activated Protein Kinases/*metabolism/pharmacology ; Adipocytes, White/*drug effects/metabolism ; Adipose Tissue, White/*drug effects/metabolism ; Animals ; Apoptosis Regulatory Proteins/*drug effects/metabolism ; Cachexia/etiology/*metabolism ; Cells, Cultured ; In Vitro Techniques ; Lipid Metabolism/*drug effects ; Lipogenesis/drug effects ; Lipolysis/drug effects ; Mice ; Neoplasms/complications/*metabolism ; Peptide Fragments/*pharmacology ; Thermogenesis/drug effects ; Uncoupling Protein 1/drug effects/metabolism ; }, abstract = {Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.}, }
@article {pmid27571158, year = {2016}, author = {Barone, P and Santangelo, G and Amboni, M and Pellecchia, MT and Vitale, C}, title = {Pisa syndrome in Parkinson's disease and parkinsonism: clinical features, pathophysiology, and treatment.}, journal = {The Lancet. Neurology}, volume = {15}, number = {10}, pages = {1063-1074}, doi = {10.1016/S1474-4422(16)30173-9}, pmid = {27571158}, issn = {1474-4465}, mesh = {Aged ; Aged, 80 and over ; *Dystonia/etiology/physiopathology/therapy ; Female ; Humans ; Male ; Middle Aged ; Parkinsonian Disorders/*complications ; *Spinal Curvatures/etiology/physiopathology/therapy ; }, abstract = {Pisa syndrome is defined as a reversible lateral bending of the trunk with a tendency to lean to one side. It is a frequent and often disabling complication of Parkinson's disease, and has also been described in several atypical forms of parkinsonism and in neurodegenerative and psychiatric disorders after drug exposure and surgical procedures. Although no consistent diagnostic criteria for Pisa syndrome are available, most investigations have adopted an arbitrary cutoff of at least 10° of lateral flexion for the diagnosis of the syndrome. Pathophysiological mechanisms underlying Pisa syndrome have not been fully explained. One hypothesis emphasises central mechanisms, whereby Pisa syndrome is thought to be caused by alterations in sensory-motor integration pathways; by contrast, a peripheral hypothesis emphasises the role of anatomical changes in the musculoskeletal system. Furthermore, several drugs are reported to induce Pisa syndrome, including antiparkinsonian drugs. As Pisa syndrome might be reversible, clinicians need to be able to recognise this condition early to enable prompt management. Nevertheless, further research is needed to determine optimum treatment strategies.}, }
@article {pmid27569097, year = {2016}, author = {Arfaoui, A and Douik, H and Kablouti, G and Chaaben, A and Handiri, N and Zid, Z and Ouni, N and Zouiouch, F and Ayari, F and Mamoghli, T and Bouassida, J and Harzallah, L and Guemira, F}, title = {MDM2 344T&gt;A polymorphism; could it be a predictive marker of anthracycline resistance?.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {21}, number = {3}, pages = {732-739}, pmid = {27569097}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/*therapeutic use ; Breast Neoplasms/*drug therapy/genetics ; Drug Resistance, Neoplasm ; Female ; Genes, p53 ; Humans ; Middle Aged ; *Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins c-mdm2/*genetics ; }, abstract = {PURPOSE: To find a possible association between the Mouse Double Minute 2(MDM2) 344T>A, alone and in combination with p53 72 Arg/Pro polymorphism, and resistance to anthracycline-based chemotherapy of breast cancer in Tunisia.<br><br>METHODS: This study enrolled 542 patients with invasive ductal carcinoma (IDC) treated with anthracycline-based chemotherapy. Genomic DNA was isolated from whole blood, using the phenol chloroform method. Anthracycline response was scored according to the World Health Organization (WHO). MDM2 344T>A polymorphism was genotyped using real time polymerase chain reaction (RT-PCR) with the TaqMan method. Data was statistically analyzed using the x2 test.<br><br>RESULTS: Response was evaluated in 400 patients, of whom a quarter was found to be resistant to chemotherapy. Genetic data revealed that resistance to anthracycline-based chemotherapy did not seem to be correlated with 344T>A polymorphism in the studied population. Also, no significant association was found between the single nucleotide polymorphism (SNP) 344T>A status and clinicopathologic parameters (p>0.05 for all comparisons). Moreover, analysis of p53 rs1042522 and MDM2 rs1196333 combination showed no significant association between these two genetic variants and anthracycline resistance (p=0.2).<br><br>CONCLUSIONS: Our findings provide no evidence indicating that SNP 344 T>A may affect response to anthracycline-based chemotherapy. However, the results obtained from the combination of SNPs 344T>A of MDM2 and 72 Arg/Pro of p53, do not support the hypothesis of the prominent role of common p53 and MDM2 variations in the genetic mechanisms of chemotherapy resistance in breast cancer.}, }
@article {pmid27562113, year = {2016}, author = {Li, Z and Liu, Q and Piao, J and Hua, F and Wang, J and Jin, G and Lin, Z and Zhang, Y}, title = {Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast.}, journal = {BMC cancer}, volume = {16}, number = {1}, pages = {681}, pmid = {27562113}, issn = {1471-2407}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*genetics/mortality/*pathology ; Cell Line, Tumor ; Disease Progression ; Female ; *Gene Expression ; Guanine Nucleotide Exchange Factors/*genetics/metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; }, abstract = {BACKGROUND: T-lymphoma invasion and metastasis-inducing protein 1 (Tiam1) has been implicated in tumor occurrence and progression. Recent studies have shown that high expression levels of Tiam1 protein appear to be associated with the progression of numerous human tumors. This study attempted to explore the role of Tiam1 protein in tumor progression and the prognostic evaluation of breast cancer.<br><br>METHODS: The localization of the Tiam1 protein was determined in the MDA-MB-231 breast cancer cell line using immunofluorescence (IF) staining. In addition, a total of 283 breast tissue samples, including 153 breast cancer tissues, 67 ductal carcinoma in situ (DCIS) and 63 adjacent non-tumor breast tissues, were analyzed by immunohistochemical (IHC) staining of the Tiam1 protein. The correlation between Tiam1 expression and clinicopathological characteristics was evaluated by Chi-square test and Fisher's exact tests. Disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier method. Additionally, univariate and multivariate analyses were performed by the Cox proportional hazards regression models.<br><br>RESULTS: Tiam1 protein showed a mainly cytoplasmic staining pattern in breast cancer cells; however, nuclear staining was also observed. Tiam1 protein expression was significantly higher in breast cancers (42.5&#xa0;%, 65/153) and DCIS (40.3&#xa0;%, 27/67) than in adjacent non-tumor tissues (12.7&#xa0;%, 8/63). In addition, Tiam1 associated with tumor stage and Ki-67 expression, but negatively correlated with receptor tyrosine-protein kinase erbB-2 (Her2) expression. Moreover, survival analyses showed that DFS and 10-year OS rates were significantly lower in breast cancer patients with high Tiam1 expression than those with low Tiam1 expression. Univariate analysis suggested that molecular types, clinical stage, Her2 expression levels and Tiam1 expression levels were also significantly associated with DFS and 10-year OS rates of breast cancer patients. Furthermore, multivariate analysis suggested that Tiam1 expression is a significant independent prognostic factor along with tumor stage in patients with breast cancer.<br><br>CONCLUSIONS: Tiam1 expression is frequently up-regulated in breast cancer. Tiam1 expression correlated with clinicopathological parameters, suggesting that it may be a useful prognostic biomarker and potential therapeutic target for patients with breast cancer.}, }
@article {pmid27556047, year = {2016}, author = {Zhang, L and Xia, CQ}, title = {PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells.}, journal = {Journal of immunology research}, volume = {2016}, number = {}, pages = {2419621}, pmid = {27556047}, issn = {2314-7156}, mesh = {Adoptive Transfer ; Animals ; B7-H1 Antigen/*metabolism ; Graft Survival/immunology ; *Immune Tolerance/radiation effects ; Isoantigens/*immunology ; Lymphocyte Activation/immunology ; Mice ; Programmed Cell Death 1 Receptor/*metabolism ; Protein Binding ; Skin Transplantation ; T-Lymphocyte Subsets/immunology/metabolism ; *Ultraviolet Rays ; }, abstract = {Our previous study demonstrated that transfusion of ultraviolet B-irradiated immature dendritic cells (UVB-iDCs) induced alloantigen-specific tolerance between two different strains of mice. Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been suggested to play an important role in maintaining immune tolerance. In the present study, we seek to address whether PD-1/PD-L1 plays a role in the maintenance of UVB-iDC-induced tolerance. We first observe that the UVB-iDC-induced alloantigen-specific tolerance can be maintained for over 6 weeks. Supporting this, at 6 weeks after tolerance induction completion, alloantigen-specific tolerance is still able to be transferred to syngeneic naïve mice through adoptive transfer of CD4+ T cells. Furthermore, skin transplantation study shows that the survival of allogeneic grafts is prolonged in those tolerant recipients. Further studies show that PD-1/PD-L1 interaction is essential for maintaining the induced tolerance as blockade of PD-1/PD-L1 by anti-PD-L1 antibodies largely breaks the tolerance at both cellular and humoral immunological levels. Importantly, we show that PD-1/PD-L1 interaction in tolerant mice is also essential for controlling alloantigen-responding T cells, which have never experienced alloantigens. The above findings suggest that PD-1/PD-L1 plays a crucial role in maintaining immune tolerance induced by UVB-iDCs, as well as in actively controlling effector T cells specific to alloantigens.}, }
@article {pmid27550996, year = {2016}, author = {Zwack, PJ and De Clercq, I and Howton, TC and Hallmark, HT and Hurny, A and Keshishian, EA and Parish, AM and Benkova, E and Mukhtar, MS and Van Breusegem, F and Rashotte, AM}, title = {Cytokinin Response Factor 6 Represses Cytokinin-Associated Genes during Oxidative Stress.}, journal = {Plant physiology}, volume = {172}, number = {2}, pages = {1249-1258}, pmid = {27550996}, issn = {1532-2548}, mesh = {Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Chlorophyll/chemistry/metabolism ; Cytokinins/*metabolism ; Fluorescence ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant/drug effects/*genetics ; Gene Ontology ; Hydrogen Peroxide/pharmacology ; Mutation ; Oxidants/pharmacology ; *Oxidative Stress ; Plant Leaves/genetics/metabolism ; Plants, Genetically Modified ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Seedlings/genetics/metabolism ; Transcription Factors/*genetics/metabolism ; Two-Hybrid System Techniques ; }, abstract = {Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6-dependent genes and establishes a novel connection between cytokinin and oxidative stress response.}, }
@article {pmid27533259, year = {2016}, author = {Gaui, EN and Klein, CH and Oliveira, GM}, title = {Proportional Mortality due to Heart Failure and Ischemic Heart Diseases in the Brazilian Regions from 2004 to 2011.}, journal = {Arquivos brasileiros de cardiologia}, volume = {107}, number = {3}, pages = {230-238}, pmid = {27533259}, issn = {1678-4170}, mesh = {Adolescent ; Adult ; Age Distribution ; Age Factors ; Aged ; Aged, 80 and over ; Brazil/epidemiology ; Cause of Death ; Child ; Child, Preschool ; Chronic Disease ; Female ; Heart Failure/*mortality ; Humans ; Infant ; Male ; Middle Aged ; Myocardial Ischemia/*mortality ; Risk Factors ; Sex Distribution ; Sex Factors ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND:: Heart failure (HF) and ischemic heart diseases (IHD) are important causes of death in Brazil.<br><br>OBJECTIVE:: To assess proportional mortality (PM) due to HF and IHD as underlying causes stratified by sex and age groups in the Brazilian geoeconomic regions from 2004 to 2011.<br><br>METHODS:: Data from death certificates were obtained in the DATASUS site under the following International Statistical Classification of Diseases and Related Health Problems codes, 10th Revision: 1) from chapter IX: I20 to I24 for acute IHD, I25 for chronic IHD, and I50 for HF; and 2) from chapter XVIII, for ill-defined causes (IDC).<br><br>RESULTS:: Proportional mortality due to HF increased with age in both sexes and all regions, the highest percentages being found among elderly women. Among men, the highest percentages were observed in the West-Central region up to the ninth decade, but, among the eldest individuals, the highest percentages were identified in the Southern region. Among women, the regions did not differ up to the age group of 70-79 years, although the West-Central region took the lead from 50 to 79 years; however, from the age of 80 years on, the Southern region showed the highest PM due to HF. Proportional mortality due to acute IHD in all Brazilian regions and in both sexes increased up to the age group of 60-69 years, from which it decreased. Among men, the Southeastern region had the highest percentages in the age group of 50-59 years, while women had lower PM due to acute IHD than men in all regions. In both sexes, PM due to chronic IHD increased with age in the Southern and Southeastern regions, which did not happen in the others, while the Southern region had the highest rate of all regions for all age groups.<br><br>CONCLUSIONS:: Regional differences were more prominent at more advanced ages, especially when deaths due to IDC were excluded.<br><br>FUNDAMENTO:: Insufici&#xea;ncia card&#xed;aca (IC) e doen&#xe7;as isqu&#xea;micas do cora&#xe7;&#xe3;o (DIC) s&#xe3;o importantes causas de morte no Brasil.<br><br>OBJETIVO:: Avaliar a mortalidade proporcional (MP) por IC e DIC, como causas b&#xe1;sicas, estratificada por sexo e faixa et&#xe1;ria nas regi&#xf5;es brasileiras de 2004 a 2011.<br><br>M&#xc9;TODOS:: As informa&#xe7;&#xf5;es das declara&#xe7;&#xf5;es de &#xf3;bito foram obtidas no site do DATASUS, codificadas conforme a Classifica&#xe7;&#xe3;o Estat&#xed;stica Internacional de Doen&#xe7;as e Problemas Relacionados &#xe0; Sa&#xfa;de, 10&#xaa; Revis&#xe3;o: 1) do Cap&#xed;tulo IX: I20 a I24 para DIC aguda, I25 para DIC cr&#xf4;nica, e I50 para IC; e 2) do Cap&#xed;tulo XVIII, para causas mal definidas (CMD).<br><br>RESULTADOS:: A MP por IC aumentou com a idade nos dois sexos e em todas as regi&#xf5;es, as mais altas porcentagens sendo encontradas entre as mulheres mais idosas. Entre os homens, as mais altas porcentagens foram observadas na regi&#xe3;o Centro-Oeste at&#xe9; a nona d&#xe9;cada; entre os mais idosos, por&#xe9;m, as mais altas porcentagens foram identificadas na regi&#xe3;o Sul. Entre as mulheres, as regi&#xf5;es n&#xe3;o diferiram at&#xe9; a faixa et&#xe1;ria de 70-79 anos, embora a regi&#xe3;o Centro-Oeste tenha liderado dos 50 aos 79 anos; entretanto, a partir dos 80 anos, a regi&#xe3;o Sul apresentou a mais alta MP por IC. Em todas as regi&#xf5;es brasileiras e nos dois sexos, a MP por DIC aguda aumentou at&#xe9; a faixa et&#xe1;ria de 60-69 anos, a partir da qual diminuiu. Entre os homens, a regi&#xe3;o Sudeste apresentou as mais altas porcentagens na faixa et&#xe1;ria de 50-59 anos, enquanto as mulheres tiveram menor MP por DIC aguda em compara&#xe7;&#xe3;o aos homens em todas as regi&#xf5;es. Nos dois sexos, a MP por DIC cr&#xf4;nica aumentou com a idade nas regi&#xf5;es Sul e Sudeste, mas n&#xe3;o nas demais, enquanto a regi&#xe3;o Sul apresentou a mais alta MP entre todas as regi&#xf5;es para todas as faixas et&#xe1;rias.<br><br>CONCLUS&#xd5;ES:: Diferen&#xe7;as regionais foram mais marcantes nas idades mais avan&#xe7;adas, especialmente quando exclu&#xed;das as mortes por CMD.}, }
@article {pmid27521604, year = {2016}, author = {Lee, JH and Kim, JE and Kim, BG and Han, HH and Kang, S and Cho, NH}, title = {STAT3-induced WDR1 overexpression promotes breast cancer cell migration.}, journal = {Cellular signalling}, volume = {28}, number = {11}, pages = {1753-1760}, doi = {10.1016/j.cellsig.2016.08.006}, pmid = {27521604}, issn = {1873-3913}, mesh = {Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Line, Tumor ; *Cell Movement ; Female ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; Humans ; Microfilament Proteins/genetics/*metabolism ; Neoplasm Invasiveness ; Promoter Regions, Genetic/genetics ; Protein Binding ; STAT3 Transcription Factor/*metabolism ; Survival Analysis ; Up-Regulation ; }, abstract = {WD repeat domain 1 (WDR1), a protein that assists cofilin-mediated actin filament disassembly, is overexpressed in the invading front of invasive ductal carcinoma (IDC), but its implication of overexpression and how to be regulated have not been studied. In our study, we demonstrated that STAT3 bound to the 5' upstream sequence (-1971 to -1964), a putative promoter region, of WDR1 gene, and its activation induced WDR1 overexpression in breast cancer cells. The exogenous overexpression of WDR1 increased the migration of MDA-MB-231, which was attenuated by WDR1 knockdown. In the analysis of breast cancer patients, WDR1 overexpression was associated with a shorter distant metastasis-free survival (DMFS), more specifically in basal-like tumors.}, }
@article {pmid27521488, year = {2016}, author = {Georgiou, GP and Provatopoulou, X and Kalogera, E and Siasos, G and Menenakos, E and Zografos, GC and Gounaris, A}, title = {Serum resistin is inversely related to breast cancer risk in premenopausal women.}, journal = {Breast (Edinburgh, Scotland)}, volume = {29}, number = {}, pages = {163-169}, doi = {10.1016/j.breast.2016.07.025}, pmid = {27521488}, issn = {1532-3080}, mesh = {Adiponectin/blood ; Adult ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*etiology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leptin/blood ; Logistic Models ; Middle Aged ; Premenopause/*blood ; Resistin/*blood ; Risk Factors ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: Adipokines have been suggested as potential mediators linking obesity and breast cancer. Resistin is the least-studied adipokine with diverse findings regarding its association with disease development and progression. The present study aimed to determine resistin serum levels in breast cancer in relation to the histological type of disease and to investigate their association with breast cancer risk.<br><br>METHODS: The study included 216 women, of which 163 were diagnosed with breast cancer (58 with IDC, 52 with DCIS and 53 with LN) and 53 were healthy. Serum levels of resistin, leptin and adiponectin were quantitatively determined in duplicates by ELISA. Differences in resistin levels among patient groups were evaluated with Kruskal-Wallis and Mann-Whitney tests. The association of resistin with breast cancer risk was evaluated by multiple logistic regression analysis.<br><br>RESULTS: Resistin levels varied between histological types of breast cancer (p&#xa0;=&#xa0;0.044). Significant differences in serum resistin were observed in IDC patients compared to those with DCIS and to controls (p&#xa0;<&#xa0;0.014 and p&#xa0;<&#xa0;0.03, respectively). Decreased levels of resistin, adiponectin and leptin were observed in premenopausal patients. Resistin was associated with a reduced risk for ductal carcinoma only in premenopausal women (OR: 0.364, 95% CI: 0.154-0.862, p&#xa0;<&#xa0;0.022).<br><br>CONCLUSION: Our findings indicate that resistin levels were inversely related to breast cancer risk in premenopausal women, supporting a protective role of resistin for these patients. Further advances in adipokine research may lead to tangible benefits for overweight/obese women at an increased risk for breast cancer.}, }
@article {pmid27517320, year = {2016}, author = {Fu, Z and Chen, S and Liu, S and Han, S and Gao, X and Li, D and Li, D}, title = {DcR3 gene polymorphisms are associated with sporadic breast infiltrating ductal carcinoma in Northeast Chinese women.}, journal = {Oncotarget}, volume = {7}, number = {36}, pages = {57970-57977}, pmid = {27517320}, issn = {1949-2553}, mesh = {Adult ; Alleles ; Asian People/genetics ; Breast Neoplasms/ethnology/*genetics/pathology ; Carcinoma, Ductal, Breast/ethnology/*genetics/pathology ; Case-Control Studies ; China ; Female ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Lymphatic Metastasis ; Middle Aged ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, Tumor Necrosis Factor, Member 6b/*genetics ; }, abstract = {Decoy Receptor 3 (DcR3), also called TNFRSF6β, is a member of the tumor necrosis factor receptor superfamily and is a soluble receptor for FasL. DcR3 is overexpressed in cancers and contributes to tumorigenesis through immune suppression and promotion of angiogenesis. We found that DcR3 is overexpressed in breast infiltrating ductal carcinoma (IDC) cells as compared with normal controls. We also conducted a case-control study analyzing associations of DcR3 polymorphisms with breast IDC risk. Subjects included 531 females with breast IDC and 592 age-matched healthy controls. Four DcR3 single nucleotide polymorphism loci with minor frequencies of more than 5% (rs3208008, rs41309931, rs2297441 and rs1291207) were genotyped using polymerase chain reaction restriction fragment length polymorphism and sequencing. Our results revealed significant differences in rs41309931genotypes and alleles (P < 0.01). Based on Haploview software analysis, the haplotype block Ars3208008 Grs41309931 Grs2297441 Ars1291207 exhibited the highest frequency, but, haplotype blocks Ars3208008 Trs41309931 Grs2297441 Ars1291207 and Crs3208008 Grs41309931 Grs2297441 Ars1291207 were associated with breast IDC risk. This study also detected associations between DcR3 gene polymorphisms and the clinicopathological features of breast IDC, including lymph node metastasis and C-erbB2, P53, estrogen receptor and progesterone receptor status. These data indicate that DcR3 gene polymorphisms are associated with sporadic breast IDC risk in Northeast Chinese females.}, }
@article {pmid27510020, year = {2016}, author = {Baloch, AH and Khosa, AN and Bangulzai, N and Shuja, J and Naseeb, HK and Jan, M and Marghazani, IB and Kakar, M and Baloch, DM and Cheema, AM and Ahmad, J}, title = {Novel Nonsense Variants c.58C&gt;T (p.Q20X) and c.256G&gt;T (p.E85X) in the CHEK2 Gene Identified in Breast Cancer Patients from Balochistan.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {7}, pages = {3623-3626}, pmid = {27510020}, issn = {2476-762X}, mesh = {Adult ; Breast Neoplasms/*genetics ; Checkpoint Kinase 2/*genetics ; Exons/genetics ; Female ; Genetic Predisposition to Disease/genetics ; Humans ; Middle Aged ; Mutation/*genetics ; Pakistan ; }, abstract = {Breast cancer is very common and the leading cause of cancer deaths among women globally. Hereditary cases account for 510% of the total burden and CHEK2, which plays crucial role in response to DNA damage to promote cell cycle arrest and repair or induce apoptosis, is considered as a moderate penetrance breast cancer risk gene. Our objective in the current study was to analyze mutations in related to breast cancer. A total of 271 individuals including breast cancer patients and normal subjects were enrolled and all 14 exons of CHEK2 were amplified and sequenced. The majority of the patients (>95%) were affected with invasive ductal carcinoma (IDC), 52.1% were diagnosed with grade III tumors and 56.2% and 27.5% with advanced stages III and IV. Two novel nonsense variants i.e. c.58C>T (P.Q20X) and c.256G>T (p.E85X) at exon 1 and 2 in two breast cancer patients were identified, both novel and not reported elsewhere.}, }
@article {pmid27503013, year = {2016}, author = {Li, SN and Zhang, XL and Cai, GL and Lin, RW and Jiang, H and Chen, JZ and Xu, B and Huang, W}, title = {Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy.}, journal = {Chinese medical journal}, volume = {129}, number = {16}, pages = {1904-1911}, pmid = {27503013}, issn = {2542-5641}, mesh = {Aged ; Cardiomyopathy, Dilated/pathology/*physiopathology ; Electrocardiography ; Female ; Heart Failure/pathology/physiopathology ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC.<br><br>METHODS: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality.<br><br>RESULTS: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90&#xb0; died compared to 31 of 193 patients with QRS-T angles &#x2264;90&#xb0; (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 &#xb1; 53.4&#xb0; vs. 107.2 &#xb1; 54.4&#xb0;, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class.<br><br>CONCLUSIONS: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.}, }
@article {pmid27483711, year = {2016}, author = {Ursaru, M and Jari, I and Gheorghe, L and Naum, AG and Scripcariu, V and Negru, D}, title = {BILATERAL BREAST CANCER: DIAGNOSIS AND PROGNOSIS.}, journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi}, volume = {120}, number = {2}, pages = {316-320}, pmid = {27483711}, issn = {0048-7848}, mesh = {Adult ; Breast Neoplasms/*diagnosis/mortality/surgery ; Carcinoma, Ductal, Breast/*diagnosis/mortality/surgery ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*diagnosis/mortality/surgery ; Neoplasm Staging ; Neoplasms, Multiple Primary/*diagnosis/mortality/surgery ; Neoplasms, Second Primary/*diagnosis/mortality/surgery ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIM: To assess bilateral breast cancer patients, initially diagnosed with stage II unilateral breast cancer.<br><br>MATERIAL AND METHODS: 113 patients with stage 0-II breast cancer diagnosed between 1983 and 2011 were assessed. Of these, 8 patients had bilateral breast cancer: 7 patients with metachronous bilateral breast cancer and 1 patient with synchronous breast cancer. Breast ultrasound, mammography, computed tomography and magnetic resonance imaging were used to diagnose recurrence, loco regional and distant metastasis.<br><br>RESULTS: Age at diagnosis ranged from 37 to 59 years, with a maximum age incidence in the 4th decade (age between: 31-40 years). The average time interval between the two breast cancers was 8.125 years. The most common histological type was invasive ductal carcinoma. All eight patients with bilateral breast cancer had at least one type of recurrence/metastasis, mostly in the liver, and statistically the pleuropulmonary and liver metastases were the most frequent causes of death.<br><br>CONCLUSIONS: Patients in the 4th decade diagnosed with unilateral breast cancer are at risk of developing bilateral breast cancer. In metachronous breast cancer, the time interval between the detection of the second breast cancer and death is directly proportional to the time interval between the two breast cancers. TASTASES, DEATH.}, }
@article {pmid27479041, year = {2016}, author = {Sabiani, L and Houvenaeghel, G and Heinemann, M and Reyal, F and Classe, JM and Cohen, M and Garbay, JR and Giard, S and Charitansky, H and Chopin, N and Rouzier, R and Daraï, E and Coutant, C and Azuar, P and Gimbergues, P and Villet, R and Tunon de Lara, C and Lambaudie, E}, title = {Breast cancer in young women: Pathologic features and molecular phenotype.}, journal = {Breast (Edinburgh, Scotland)}, volume = {29}, number = {}, pages = {109-116}, doi = {10.1016/j.breast.2016.07.007}, pmid = {27479041}, issn = {1532-3080}, mesh = {Adult ; *Age Factors ; Breast Neoplasms/chemistry/drug therapy/*pathology ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; France ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/etiology ; *Phenotype ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Risk Factors ; }, abstract = {PURPOSE: Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications.<br><br>METHODS: We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected.<br><br>RESULTS: 5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients &#x2264;35 years old. Triple negative and HER2 tumors were predominantly found in patients &#x2264;35 (22.2% and 22.1%, p&#xa0;<&#xa0;0.01). A young age &#x2264;40 years (p&#xa0;<&#xa0;0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or &#x2264;35 years (p&#xa0;<&#xa0;0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age &#x2264;35 (p&#xa0;<&#xa0;0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p&#xa0;<&#xa0;0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p&#xa0;<&#xa0;0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p&#xa0;<&#xa0;0.01).<br><br>CONCLUSION: Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.}, }
@article {pmid27460667, year = {2016}, author = {Fu, L and Luo, S and Cai, S and Hong, W and Guo, Y and Wu, J and Liu, T and Zhao, C and Li, F and Huang, H and Huang, M and Wang, J}, title = {Identification of LAMP2 Mutations in Early-Onset Danon Disease With Hypertrophic Cardiomyopathy by Targeted Next-Generation Sequencing.}, journal = {The American journal of cardiology}, volume = {118}, number = {6}, pages = {888-894}, doi = {10.1016/j.amjcard.2016.06.037}, pmid = {27460667}, issn = {1879-1913}, mesh = {Adolescent ; Age of Onset ; Blotting, Western ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Hypertrophic/*genetics/metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Codon, Nonsense ; Female ; Fluorescent Antibody Technique ; Genotype ; Glycogen Storage Disease Type IIb/*genetics/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Lysosomal-Associated Membrane Protein 2/*genetics/metabolism ; Male ; Muscle, Skeletal/metabolism ; *Mutation ; Myocardium/metabolism ; Phenotype ; Sequence Analysis, DNA ; Wolff-Parkinson-White Syndrome/genetics ; }, abstract = {Danon disease is an X-linked disorder with the clinical triad of cardiomyopathy, skeletal myopathy, and mental retardation. Early diagnosis of this disease remains a challenge, especially in the pediatric population. In this study, we developed a targeted panel-based next generation sequencing pipeline to identify mutations by sequencing of selected candidate genes in 136 pediatric patients with either hypertrophic cardiomyopathy (HC) or idiopathic dilated cardiomyopathy (IDC). This led to the identification of lysosome-associated membrane protein 2 (LAMP2) mutations in 4 of the 64 (6%) probands with HC, including 3 novel nonsense mutations (p.Q240X, p.S250X, and p.G22X). No LAMP2 mutation was detected in the other 72 probands with IDC. All 4 probands and one additional affected family member (2 men and 3 women) had an early-onset age and presented either HC alone or combined with Wolff-Parkinson-White syndrome and skeletal myopathy. Immunofluorescence staining and Western blot analysis revealed absent LAMP2 expression in both cardiac and skeletal muscle samples of the first proband and severely decreased LAMP2 expression in the skeletal muscle samples of the second proband. In conclusion, cardiomyopathy in the patients with Danon disease may occur during early childhood and tend to be HC rather than IDC in both affected men and women. Therefore, Danon disease should be considered as one of the leading causes of unexplained ventricular hypertrophy in pediatric patients. The inclusion of LAMP2 gene in cardiomyopathy genetic screening panels may contribute to early diagnosis of Danon disease.}, }
@article {pmid27453513, year = {2016}, author = {Merlo, M and Anzini, M and Bussani, R and Artico, J and Barbati, G and Stolfo, D and Gigli, M and Muça, M and Naso, P and Ramani, F and Di Lenarda, A and Pinamonti, B and Sinagra, G}, title = {Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {118}, number = {6}, pages = {895-900}, doi = {10.1016/j.amjcard.2016.05.063}, pmid = {27453513}, issn = {1879-1913}, mesh = {Adult ; Cardiomyopathy, Dilated/*etiology/mortality/surgery ; Cohort Studies ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Mortality ; Multivariate Analysis ; Myocarditis/*complications ; Prognosis ; Proportional Hazards Models ; Protective Factors ; Risk Factors ; Ventricular Dysfunction, Left/*etiology/mortality/surgery ; }, abstract = {Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC.}, }
@article {pmid27435300, year = {2017}, author = {Monica, MA and Baccarini, P and Cucchi, MC and Lacava, N and Foschini, MP}, title = {Endobronchial Pagetoid Spread of a Breast Carcinoma Metastatic to the Lung.}, journal = {International journal of surgical pathology}, volume = {25}, number = {1}, pages = {83-86}, doi = {10.1177/1066896916660619}, pmid = {27435300}, issn = {1940-2465}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology ; Bronchi/pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*secondary ; Neoplasm Invasiveness/*pathology ; }, abstract = {A case of endobronchial pagetoid spread of a breast carcinoma metastatic to the lung is described. A 73-year-old woman underwent wedge lung resection after the cytological diagnosis of lung metastasis from ductal invasive breast carcinoma. The breast carcinoma had been surgically removed 6 years previously; at the time of diagnosis it was a T1N0, grade 3 invasive ductal carcinoma, with HER-2 amplification. The lung metastasis measured 1,9 cm and showed the same histology and biological profile of the primary tumor. In addition, numerous neoplastic cells, with large cytoplasm and atypical nuclei, appear to spread along the mucosa of the bronchi adjacent to the metastatic lesion as well as that of the main lobar bronchus, intermingled with the columnar ciliated cells. The neoplastic elements were negative for TTF-1 and strongly HER-2 positive; these features appeared consistent with endobronchial pagetoid spread by the metastatic breast carcinomatous cells.}, }
@article {pmid27430170, year = {2016}, author = {Liu, L and Li, D and Chen, S and Zhao, R and Pang, D and Li, D and Fu, Z}, title = {B7-H4 expression in human infiltrating ductal carcinoma‑associated macrophages.}, journal = {Molecular medicine reports}, volume = {14}, number = {3}, pages = {2135-2142}, doi = {10.3892/mmr.2016.5510}, pmid = {27430170}, issn = {1791-3004}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/immunology/*metabolism/*pathology ; Carcinoma, Ductal, Breast/immunology/*metabolism/*pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Interleukin-10/metabolism ; Interleukin-6/metabolism ; Macrophages/immunology/*metabolism/pathology ; Middle Aged ; Neoplasm Staging ; Phenotype ; Tumor Microenvironment ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/genetics/*metabolism ; }, abstract = {B7-H4 is a co‑inhibitory molecule of the B7 family, which is expressed on antigen‑presenting cells (APCs) and is able to limit the T‑cell immune response. Macrophages act as professional APCs and are important for immunoregulation of the tumor microenvironment in breast cancer. In order to identify the association between the presence of B7‑H4 on macrophages and infiltrating ductal carcinoma (IDC), the present study investigated the expression of B7‑H4 on macrophages with different polarizations. The expression levels of B7‑H4 in IDC tissues were determined using immunohistochemistry, and the expression of B7‑H4 on macrophages in the breast IDC microenvironment were determined using western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression levels of interleukin (IL)‑6 and IL‑10 were detected in IDC tissues and the supernatants of polarized macrophages using an enzyme‑linked immunosorbent assay and RT‑qPCR. The present study demonstrated that B7‑H4 was overexpressed in IDC tissues and macrophages. In vitro, M1 and M2 macrophages exhibited different expression levels of B7‑H4. IL‑6 and ‑10 exhibited higher expression in the IDC tissues compared with in distal pericarcinomatous tissues. In conclusion, B7‑H4 exhibited overexpression in IDC tissues and cultured macrophage cells. Furthermore, M2 macrophages exhibited higher expression levels of B7‑H4 compared with the M1 subtype. In addition, IL‑6 and ‑10 may be associated with B7‑H4 expression on macrophages of different polarizations in the IDC microenvironment.}, }
@article {pmid27415582, year = {2016}, author = {Laudanski, K and Zawadka, M and Lapko, N}, title = {The Ability of Precursory Monocytes (MO) to Differentiate Varies Among Individuals But Is Stable Over Time.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {22}, number = {}, pages = {2463-2470}, pmid = {27415582}, issn = {1643-3750}, mesh = {Adult ; Antigens, CD1/immunology ; Cell Differentiation/immunology ; Cells, Cultured ; Dendritic Cells/cytology/immunology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology ; Humans ; Interleukin-4/immunology ; Lymphocyte Culture Test, Mixed ; Macrophage Colony-Stimulating Factor/immunology ; Macrophages/cytology/immunology ; Male ; Middle Aged ; Monocytes/*cytology/immunology ; T-Lymphocytes/cytology/immunology ; }, abstract = {BACKGROUND The ability to generate dendritic cells (DCs) from precursory monocytes (MOs) was a breakthrough in the field of immunology. However, it is unknown whether the ability of MOs to differentiate into immature DCs (iDCs) differs across subjects or is time dependent. Given that the study of immune system function is gaining recognition in the field of clinical medicine, it is important to know how certain immunologic features vary over time. MATERIAL AND METHODS This study investigates how much individuals' MO-to-iDC differentiation potential changes over time. We estimated this potential by measuring the expression of an iDC marker (CD1a), cytokine secretion (interleukin [IL]-12p70), and the ability of IL-4 and granulocyte macrophage colony-stimulating factor (GM-CSF) differentiation MOs to stimulate T cells. We collected MOs obtained from different subjects (n=17) at least 1 month apart. Furthermore, we investigated several variables (expression for cytokine receptors, timing, and emergence of DC-related transcriptional factor PU.1). RESULTS The ability of MOs to become DCs under the influence of IL-4 and GM-CSF varied greatly between individuals (range of CD1a expression, 20-80%) but was stable over time (change of CD1a expression between sampling, ~5%). A similar pattern emerged when production of IL-12p70 was analyzed. The ability to stimulate T cells was variable and depended on the T-cell source. The ability of MOs to become iDCs was not linked to the surface expression of receptors for IL-4 and GM-CSF but rather to the activation of PU.1 in the precursory MO. It took 5 days for all committed MOs to become iDCs under in vitro influence of IL-4 and GM-CSF. CONCLUSIONS We concluded that the potential of MO to become iDC is an individual feature and depends on activation of PU.1.}, }
@article {pmid27404457, year = {2016}, author = {Lumachi, F and Basso, SM and Camozzi, V and Tozzoli, R and Spaziante, R and Ermani, M}, title = {Bone turnover markers in women with early stage breast cancer who developed bone metastases. A prospective study with multivariate logistic regression analysis of accuracy.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {460}, number = {}, pages = {227-230}, doi = {10.1016/j.cca.2016.07.005}, pmid = {27404457}, issn = {1873-3492}, mesh = {Aged ; Alkaline Phosphatase/analysis ; Biomarkers, Tumor/analysis ; Bone Neoplasms/diagnosis/*secondary ; *Bone Remodeling ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Case-Control Studies ; Female ; Humans ; Logistic Models ; Middle Aged ; Peptide Fragments/analysis ; Postmenopause ; Procollagen/analysis ; Prospective Studies ; Tartrate-Resistant Acid Phosphatase/analysis ; }, abstract = {BACKGROUND: The skeleton is the most common site of metastasis for breast cancer and the periodic measurement of circulating bone turnover markers (BTMs) can be useful. The aim of this study was to prospectively evaluate the diagnostic accuracy of a panel of BTMs in the early detection of bone metastases (BMs).<br><br>METHODS: We reviewed the medical records of 297 postmenopausal women with early stage luminal-type invasive ductal carcinoma (IDC). Twenty-six patients who developed isolated BMs during follow-up and 24 randomly selected controls were studied. The two groups were matched according to age, final disease staging, and follow-up. All patients underwent periodic measurement of total and bone-specific (BSAP) alkaline phosphatase, CTX, ICTP, osteocalcin, NTX, PINP, and TRACP5b.<br><br>RESULTS: Only BSAP, CTX, PINP, and TRACP5b were significantly (p<0.05) associated with the group, and the logistic regression analysis excluded CTX from the model. The AUC (ROC curve) for TRACP5b alone, which was the most accurate marker, and for the combination of BSAP+PINP+TRACP5b was 0.784 (95% CI: 0.651-0.916) and 0.889 (95% CI: 0.798-0.981), respectively.<br><br>CONCLUSION: According to our results, the measurement of these three markers together should be performed in all postmenopausal patients with luminal-type IDC, when an early diagnosis of BMs is required.}, }
@article {pmid27401634, year = {2016}, author = {Divatia, MK and Ro, JY}, title = {Intraductal Carcinoma of the Prostate Gland: Recent Advances.}, journal = {Yonsei medical journal}, volume = {57}, number = {5}, pages = {1054-1062}, pmid = {27401634}, issn = {1976-2437}, mesh = {Carcinoma, Acinar Cell/chemistry/*diagnosis/pathology ; Carcinoma, Ductal/chemistry/*diagnosis/pathology ; Carcinoma, Transitional Cell/chemistry/*diagnosis/pathology ; Diagnosis, Differential ; Humans ; Male ; Neoplasm Grading ; Prostatic Intraepithelial Neoplasia/chemistry/*diagnosis/pathology ; Prostatic Neoplasms/chemically induced/*diagnosis/*pathology ; Tumor Burden ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is characterized by prostatic carcinoma involving ducts and/or acini. The presence of IDC-P is usually associated with a high-grade Gleason score, large tumor volume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion. When present, IDC-P is associated with worse outcomes, regardless of treatment status. IDC-P is included in a broader diagnostic category of atypical cribriform lesions of the prostate gland. This category of lesions also includes high-grade prostatic intraepithelial neoplasia (HGPIN), urothelial carcinoma involving prostatic ducts or acini, and prostatic ductal adenocarcinoma, amongst other intraductal proliferations. Differentiating between these entities is important as they have differing therapeutic and prognostic implications for patients, although differential diagnosis thereof is not always straightforward. The present review discusses IDC-P in regards to its morphological characteristics, molecular features, and clinical outcomes. Given the current state of knowledge, the presence of IDC-P should be evaluated and documented correctly in both radical prostatectomy and needle biopsy specimens, and the clinical implications thereof should be taken into consideration during treatment and follow up.}, }
@article {pmid27401580, year = {2016}, author = {Turner, RB and Valcarlos, E and Won, R and Chang, E and Schwartz, J}, title = {Impact of Infectious Diseases Consultation on Clinical Outcomes of Patients with Staphylococcus aureus Bacteremia in a Community Health System.}, journal = {Antimicrobial agents and chemotherapy}, volume = {60}, number = {10}, pages = {5682-5687}, pmid = {27401580}, issn = {1098-6596}, mesh = {Adult ; Aged ; Bacteremia/*drug therapy/mortality ; Cohort Studies ; Community Health Services ; Female ; Hospitals ; Humans ; Male ; Middle Aged ; Mortality ; Oregon ; Quality of Health Care ; Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/*drug therapy/mortality ; Staphylococcus aureus/*pathogenicity ; Treatment Outcome ; }, abstract = {Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited settings such as community hospitals are available. This retrospective cohort study evaluated the adherence to quality-of-care indicators and the clinical outcomes for SAB in a five-hospital community health system (range of 95 to 272 available beds per hospital), for patients with versus without infectious diseases consultation (IDC). IDC was provided if requested by the attending physician. The primary outcome was the incidence of treatment failure, defined as 30-day in-hospital death or 90-day SAB recurrence. Other outcomes included adherence to quality-of-care indicators. A total of 473 adult patients with SAB were included, with 369 (78%) receiving IDC. We identified substantial differences in baseline characteristics between the IDC group and the no-IDC group, including greater incidences of complicated bacteremia and intravenous drug users in the IDC group, with similar rates of severe illness (measured by Pitt bacteremia scores). Adherence to quality-of-care indicators was greater for patients with IDC (P < 0.001). After adjustment for other predicting variables, IDC was associated with a lower rate of treatment failure (adjusted odds ratio, 0.42 [95% confidence interval, 0.20 to 0.86]; P = 0.018). IDC provided better quality of care and better clinical outcomes for patients with SAB who were treated at small, resource-limited, community hospitals.}, }
@article {pmid27383477, year = {2016}, author = {Sopik, V and Iqbal, J and Sun, P and Narod, SA}, title = {Impact of a prior diagnosis of DCIS on survival from invasive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {158}, number = {2}, pages = {385-393}, doi = {10.1007/s10549-016-3894-9}, pmid = {27383477}, issn = {1573-7217}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/epidemiology ; Carcinoma, Ductal, Breast/*diagnosis/epidemiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology ; Child ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; SEER Program ; Survival Analysis ; Young Adult ; }, abstract = {A diagnosis of invasive breast cancer after DCIS can be described as a new primary cancer or as a local invasive recurrence. It is of interest to determine if, among women with early-stage breast cancer, a past history of DCIS influences survival. We retrieved the records of 306,249 women diagnosed with stage I or stage II breast cancer between 2004 and 2012, in the surveillance, epidemiology, and end results registries database, of whom 5395 had a previous diagnosis of DCIS. For each patient, we extracted information on the year of diagnosis, age at diagnosis, tumor size, nodal status, grade, estrogen receptor status, type of surgery (lumpectomy/mastectomy), use of radiotherapy (no/yes), prior DCIS (no/yes), cause of death, and follow-up time. For each case with prior DCIS, we recorded information on the year of diagnosis of DCIS, laterality of DCIS, and treatments received for DCIS. We matched 3979 patients with a prior DCIS to 3979 patients without a prior DCIS, according to the various prognostic features of the invasive cancer. We estimated the risk of death from breast cancer for patients with invasive ductal carcinoma, with and without a prior diagnosis of DCIS. We identified 306,249 women with stage I/II breast cancer, of whom 2335 had a prior ipsilateral DCIS and 3060 had a prior contralateral DCIS. Breast cancer-specific survival at 9 years was 94.6 % for patients with a prior DCIS (ipsilateral or contralateral) and was 95.2 % for patients with no prior DCIS (p = 0.32). In a matched analysis (3979 matched pairs), the hazard ratio for death from breast cancer for patients with a prior ipsilateral DCIS, compared to patients with no prior DCIS, was 0.91 (95 % CI = 0.49-1.68; p = 0.75). A prior diagnosis of ipsilateral DCIS does not impact upon the prognosis of women with early-stage invasive breast cancer. This suggests that primary breast cancers and local invasive recurrences following DCIS are similar conditions and should be treated in the same way.}, }
@article {pmid27376491, year = {2016}, author = {Koca, &#x130; and Özgür, A and Er, M and Gümüş, M and Açikalin Coşkun, K and Tutar, Y}, title = {Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis.}, journal = {European journal of medicinal chemistry}, volume = {122}, number = {}, pages = {280-290}, doi = {10.1016/j.ejmech.2016.06.032}, pmid = {27376491}, issn = {1768-3254}, mesh = {Adenosine Triphosphatases/antagonists &amp; inhibitors ; Adenosine Triphosphate/metabolism ; Antineoplastic Agents/chemical synthesis/chemistry/pharmacology ; Bone Neoplasms/pathology/*secondary ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; *Drug Design ; HSP90 Heat-Shock Proteins/*antagonists &amp; inhibitors/chemistry ; Humans ; Hydrolysis/drug effects ; Molecular Docking Simulation ; Protein Conformation, beta-Strand ; Thiourea/*chemical synthesis/chemistry/*pharmacology ; }, abstract = {Invasive ductal carcinoma is the most common breast malignancies tumors and has tendency to bone metastases. Many oncogenic client proteins involved in formation of metastatic pathways. Stabilization, regulation, and maintenance of these oncogenic client proteins are provided with Heat Shock Protein 90 (Hsp90). Hsp90 perform these processes through its ATP binding and subsequent hydrolysis energy. Therefore, designing Hsp90 inhibitors is a novel cancer treatment method. However, many Hsp90 inhibitors have solubility problems and showed adverse effects in clinical trials. Thus, we designed and synthesized novel pyrimidinyl acyl thiourea derivatives to selectively inhibit Hsp90 alpha in human invasive ductal breast (MCF-7) and human bone osteosarcoma (Saos-2) cell lines. In vitro experiments showed that the compounds inhibited cell proliferation, ATP hydrolysis, and exhibited cytotoxic effect on these cancer cell lines. Further, gene expression was analyzed by microarray studies on MCF-7 cell lines. Several genes that play vital roles in breast cancer pathogenesis displayed altered gene expression in the presence of a selected pyrimidinyl acyl thiourea compound. Molecular docking studies were also performed to determine interaction between Hsp90 ATPase domain and pyrimidinyl acyl thiourea derivatives. The results indicated that the compounds are able to interact with Hsp90 ATP binding pocket and inhibit ATPase function. The designed compounds powerfully inhibit Hsp90 by an average of 1 μM inhibition constant. And further, the compounds perturb Hsp90 N terminal domain proper orientation and ATP may not provide required conformational change for Hsp90 function as evidenced by in silico experiments. Therefore, the designed compounds effectively inhibited both invasive ductal breast carcinoma and bone metastasis. Pyrimidinyl acyl thiourea derivatives may provide a drug template for effective treatment of invasive ductal breast carcinoma and its bone metastasis as well as new therapeutic perspective for drug design.}, }
@article {pmid27374087, year = {2016}, author = {Duru, N and Gernapudi, R and Lo, PK and Yao, Y and Wolfson, B and Zhang, Y and Zhou, Q}, title = {Characterization of the CD49f+/CD44+/CD24- single-cell derived stem cell population in basal-like DCIS cells.}, journal = {Oncotarget}, volume = {7}, number = {30}, pages = {47511-47525}, pmid = {27374087}, issn = {1949-2553}, support = {R01 CA157779/CA/NCI NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/etiology/*pathology ; CD24 Antigen/*analysis ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Cell Line, Tumor ; Cell Movement ; DNA Methylation ; Female ; Humans ; Hyaluronan Receptors/*analysis ; Integrin alpha6/*analysis ; Mice ; Neoplastic Stem Cells/*pathology ; Octamer Transcription Factor-3/physiology ; SOXB1 Transcription Factors/physiology ; }, abstract = {The molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f+/CD44+/CD24- surface markers, we characterized the aggressive clones that have enhanced self-renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non-aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f+/CD44+/CD24- DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition.}, }
@article {pmid27362268, year = {2016}, author = {Gertz, EM and Chowdhury, SA and Lee, WJ and Wangsa, D and Heselmeyer-Haddad, K and Ried, T and Schwartz, R and Schäffer, AA}, title = {FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe.}, journal = {PloS one}, volume = {11}, number = {6}, pages = {e0158569}, pmid = {27362268}, issn = {1932-6203}, support = {R01 CA140214/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; *Databases, Genetic ; Female ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Ploidies ; Uterine Cervical Neoplasms/*genetics/pathology ; }, abstract = {Advances in fluorescence in situ hybridization (FISH) make it feasible to detect multiple copy-number changes in hundreds of cells of solid tumors. Studies using FISH, sequencing, and other technologies have revealed substantial intra-tumor heterogeneity. The evolution of subclones in tumors may be modeled by phylogenies. Tumors often harbor aneuploid or polyploid cell populations. Using a FISH probe to estimate changes in ploidy can guide the creation of trees that model changes in ploidy and individual gene copy-number variations. We present FISHtrees 3.0, which implements a ploidy-based tree building method based on mixed integer linear programming (MILP). The ploidy-based modeling in FISHtrees includes a new formulation of the problem of merging trees for changes of a single gene into trees modeling changes in multiple genes and the ploidy. When multiple samples are collected from each patient, varying over time or tumor regions, it is useful to evaluate similarities in tumor progression among the samples. Therefore, we further implemented in FISHtrees 3.0 a new method to build consensus graphs for multiple samples. We validate FISHtrees 3.0 on a simulated data and on FISH data from paired cases of cervical primary and metastatic tumors and on paired breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Tests on simulated data show improved accuracy of the ploidy-based approach relative to prior ploidyless methods. Tests on real data further demonstrate novel insights these methods offer into tumor progression processes. Trees for DCIS samples are significantly less complex than trees for paired IDC samples. Consensus graphs show substantial divergence among most paired samples from both sets. Low consensus between DCIS and IDC trees may help explain the difficulty in finding biomarkers that predict which DCIS cases are at most risk to progress to IDC. The FISHtrees software is available at ftp://ftp.ncbi.nih.gov/pub/FISHtrees.}, }
@article {pmid27358153, year = {2016}, author = {Alessio, C and Scali, E and Manti, F and Amoruso, GF and Marchese, S and Riga, B and Bottoni, U and Tamburrini, O}, title = {An unusual case of mammary Paget’s disease in a woman with psoriasis.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {30}, number = {2}, pages = {589-592}, pmid = {27358153}, issn = {0393-974X}, mesh = {Breast Neoplasms/*etiology ; Female ; Humans ; Middle Aged ; Paget's Disease, Mammary/*etiology ; Psoriasis/*complications ; }, abstract = {Mammary Paget’s disease (MPD) is a malignant breast tumor, which is characterized by intraepidermal infiltration from malignant glandular epithelial cells. Often it may include an underlying ductal carcinoma in situ or an invasive ductal carcinoma. Clinically it appears as an erythematous patch, moist or crusted, with or without desquamation that in some cases becomes ulcerated, causing infiltration and inversion of the nipple. We report the clinical case of a 60-year-old woman, treated in our department for psoriasis, presenting with erythema of nipple and areola with nipple erosion, ulceration and poor secretion. Suspecting Paget’s disease of the nipple, radiological exams (mammography and breast MRI) were performed. A biopsy for histological examination was carried out and confirmed the diagnosis of mammary Paget’s disease. MPD is sometimes difficult to diagnose both clinically and radiologically, therefore it is important to distinguish from other conditions: in literature MPD is reported in differential diagnosis with psoriasis given its similar clinical features, and in some cases MPD has been treated with topical and systemic steroids due to a wrong diagnosis. However, the concomitance, in the same individual, of mammary Paget’s disease and psoriasis has never been described.}, }
@article {pmid27355204, year = {2016}, author = {Winn, JS and Baker, MG and Fanous, IS and Slack-Davis, JK and Atkins, KA and Dillon, PM}, title = {Lobular Breast Cancer and Abdominal Metastases: A Retrospective Review and Impact on Survival.}, journal = {Oncology}, volume = {91}, number = {3}, pages = {135-142}, doi = {10.1159/000447264}, pmid = {27355204}, issn = {1423-0232}, mesh = {Abdominal Neoplasms/*secondary/therapy ; Age Factors ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/*pathology/therapy ; Breast Neoplasms, Male/pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Carcinoma, Lobular/*secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Male ; Mastectomy, Segmental ; Middle Aged ; *Neoplasm Recurrence, Local/etiology ; Neoplasm Staging ; Neoplasm, Residual ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: The predominant breast cancer subtypes, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), have similar recurrence and survival rates but differing patterns of metastatic recurrence.<br><br>METHODS: A retrospective review of breast cancers treated at an academic medical center from 1999 to 2012 was performed. Demographic, pathologic, treatment, and follow-up data were collected for 179 ILC and 358 IDC patients (1:2 stage-matched). The median follow-up was 4.7 years.<br><br>RESULTS: The baseline characteristics were similar in the two groups. ILC was more likely to be hormone-receptor-positive/HER2-negative and mammographically occult. The number of surgical resections, breast conservation rate, systemic treatment, and taxane use was similar between the groups. The overall recurrence rate was the same. ILC recurred more often in the abdominal cavity (24.3% in ILC vs. 4.1% in IDC, p = 0.001). The disease-free survival and overall survival were equal. On multivariate analysis, age, stage of disease, hormone receptor status, and systemic therapy were associated with survival, but histology was not.<br><br>CONCLUSIONS: Compared to ductal breast cancers, lobular breast cancers recur more often in the abdominal cavity. Both ILC and IDC have comparable surgical and medical treatment outcomes and survival. Our data suggest that enhanced surveillance and imaging might be useful in ILC.}, }
@article {pmid27353975, year = {2016}, author = {Timpano, H and Chan Ho Tong, L and Gautier, V and Lalucque, H and Silar, P}, title = {The PaPsr1 and PaWhi2 genes are members of the regulatory network that connect stationary phase to mycelium differentiation and reproduction in Podospora anserina.}, journal = {Fungal genetics and biology : FG &amp; B}, volume = {94}, number = {}, pages = {1-10}, doi = {10.1016/j.fgb.2016.06.006}, pmid = {27353975}, issn = {1096-0937}, mesh = {Fungal Proteins/genetics ; *Gene Expression Regulation, Fungal ; *Gene Regulatory Networks ; Genetic Complementation Test ; Mutation ; Mycelium/*genetics/growth &amp; development ; Phosphorylation ; Podospora/*genetics/growth &amp; development ; }, abstract = {In filamentous fungi, entrance into stationary phase is complex as it is accompanied by several differentiation and developmental processes, including the synthesis of pigments, aerial hyphae, anastomoses and sporophores. The regulatory networks that control these processes are still incompletely known. The analysis of the "Impaired in the development of Crippled Growth (IDC)" mutants of the model filamentous ascomycete Podospora anserina has already yielded important information regarding the pathway regulating entrance into stationary phase. Here, the genes affected in two additional IDC mutants are identified as orthologues of the Saccharomyces cerevisiae WHI2 and PSR1 genes, known to regulate stationary phase in this yeast, arguing for a conserved role of these proteins throughout the evolution of ascomycetes.}, }
@article {pmid27333920, year = {2016}, author = {Onodera, Y and Takagi, K and Miki, Y and Takayama, K and Shibahara, Y and Watanabe, M and Ishida, T and Inoue, S and Sasano, H and Suzuki, T}, title = {TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation.}, journal = {Cancer medicine}, volume = {5}, number = {8}, pages = {1973-1982}, pmid = {27333920}, issn = {2045-7634}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Breast Neoplasms/*metabolism/*mortality/pathology ; Carrier Proteins/genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gonadal Steroid Hormones/metabolism ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Tumor Suppressor Proteins/genetics/metabolism ; }, abstract = {Transforming acidic coiled-coil protein 2 (TACC2) belongs to TACC family proteins and involved in a variety of cellular processes through interactions with some molecules involved in centrosomes/microtubules dynamics. Mounting evidence suggests that TACCs is implicated in the progression of some human malignancies, but significance of TACC2 protein in breast carcinoma is still unknown. Therefore, in this study, we examined the clinical significance of TACC2 in breast carcinoma and biological functions by immunohistochemistry and in vitro experiments. Immunohistochemistry for TACC2 was performed in 154 cases of invasive ductal carcinoma. MCF-7 and MDA-MB-453 breast carcinoma cell lines were transfected with small interfering RNA (siRNA) for TACC2, and subsequently, cell proliferation, 5-Bromo-2'-deoxyuridine (BrdU), and invasion assays were performed. TACC2 immunoreactivity was detected in 78 out of 154 (51%) breast carcinoma tissues, and it was significantly associated with Ki-67 LI. The immunohistochemical TACC2 status was significantly associated with increased incidence of recurrence and breast cancer-specific death of the patients, and multivariate analyses demonstrated TACC2 status as an independent prognostic factor for both disease-free and breast cancer-specific survival. Subsequent in vitro experiments showed that TACC2 significantly increased the proliferation activity of MCF-7 and MDA-MB-453. These results suggest that TACC2 plays an important role in the cell proliferation of breast carcinoma and therefore immunohistochemical TACC2 status is a candidate of worse prognostic factor in breast cancer cases.}, }
@article {pmid27323669, year = {2016}, author = {Gautheron, J and Vucur, M and Schneider, AT and Severi, I and Roderburg, C and Roy, S and Bartneck, M and Schrammen, P and Diaz, MB and Ehling, J and Gremse, F and Heymann, F and Koppe, C and Lammers, T and Kiessling, F and Van Best, N and Pabst, O and Courtois, G and Linkermann, A and Krautwald, S and Neumann, UP and Tacke, F and Trautwein, C and Green, DR and Longerich, T and Frey, N and Luedde, M and Bluher, M and Herzig, S and Heikenwalder, M and Luedde, T}, title = {The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11869}, pmid = {27323669}, issn = {2041-1723}, support = {208237/ERC_/European Research Council/International ; }, mesh = {Adipocytes/enzymology/pathology ; Adipose Tissue, White/*enzymology/pathology ; Animals ; Apoptosis/genetics ; Body Mass Index ; Caspase 8/genetics/metabolism ; Choline/metabolism ; Choline Deficiency/enzymology/etiology/*genetics/pathology ; Diet, High-Fat ; Gene Expression Regulation ; Glucose Intolerance/enzymology/etiology/*genetics/pathology ; Homeostasis ; Humans ; Inflammation ; Insulin/metabolism ; Insulin Resistance ; Intra-Abdominal Fat/*enzymology/pathology ; Male ; Mice ; Necrosis/*enzymology/genetics/pathology ; Obesity/enzymology/etiology/*genetics/pathology ; Receptor-Interacting Protein Serine-Threonine Kinases/*genetics/metabolism ; }, abstract = {Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet. Genetic inactivation of Ripk3 promotes increased Caspase-8-dependent adipocyte apoptosis and WAT inflammation, associated with impaired insulin signalling in WAT as the basis for glucose intolerance. Similarly to mice, in visceral WAT of obese humans, RIPK3 is overexpressed and correlates with the body mass index and metabolic serum markers. Together, these findings provide evidence that RIPK3 in WAT maintains tissue homeostasis and suppresses inflammation and adipocyte apoptosis, suggesting that systemic targeting of necroptosis might be associated with the risk of promoting insulin resistance in obese patients.}, }
@article {pmid27306813, year = {2016}, author = {Terasawa, R and Iwamoto, M and Tanaka, S and Kimura, K and Takahashi, Y and Fujioka, H and Sato, N and Kawaguchi, K and Ikari, A and Maezawa, S and Tominaga, T and Matsuda, J and Umezaki, N and Uchiyama, K}, title = {[A Case of Squamous Cell Carcinoma of the Breast].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {6}, pages = {749-752}, pmid = {27306813}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Squamous Cell/*diagnosis/therapy ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Fatal Outcome ; Female ; Humans ; Recurrence ; Thoracic Wall/*pathology ; }, abstract = {Squamous cell carcinoma(SCC)of the breast is a rare disease. We encountered a case of SCC of the breast that relapsed in the early postoperative period and rapidly progressed thereafter. A 38-year-old woman visited our hospital presenting with a tumor in the left breast consisting of a 5-cm mass with an irregularly sharped wall. Fine needle biopsy examination showed squamous cell carcinoma. A modified radical mastectomy by Auchincloss's method was performed on the left breast. SCC was confirmed by histological examination. Two months later, local recurrence on the chest wall was found during adjuvant chemotherapy. Thereafter, the disease rapidly progressed, and finally, the patient died of respiratory failure caused by lung metastasis. The prognosis of SCC of the breast is recognized as being more unfavorable than that of invasive ductal carcinoma. We should develop an effective chemotherapeutic strategy for this disease.}, }
@article {pmid27284958, year = {2016}, author = {Ross, JS and Gay, LM and Wang, K and Ali, SM and Chumsri, S and Elvin, JA and Bose, R and Vergilio, JA and Suh, J and Yelensky, R and Lipson, D and Chmielecki, J and Waintraub, S and Leyland-Jones, B and Miller, VA and Stephens, PJ}, title = {Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: An emerging opportunity for anti-HER2 targeted therapies.}, journal = {Cancer}, volume = {122}, number = {17}, pages = {2654-2662}, doi = {10.1002/cncr.30102}, pmid = {27284958}, issn = {1097-0142}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/drug therapy/*genetics/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/secondary ; Carcinoma, Lobular/drug therapy/genetics/secondary ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic/drug effects ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; *Molecular Targeted Therapy ; Mutation/*genetics ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/drug therapy/*genetics/pathology ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/antagonists &amp; inhibitors/*genetics ; }, abstract = {BACKGROUND: Activating, nonamplification ERBB2 mutations (ERBB2mut) are not detected by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but are detected by DNA sequencing and may predict clinical responses to human epidermal growth factor receptor (HER2)-targeted therapy. The authors queried 5605 advanced/metastatic breast cancers (mBC) to uncover the frequency of ERBB2mut genomic alterations. Clinical responses to anti-HER2 therapeutics were identified.<br><br>METHODS: DNA was extracted from 40&#x2009;&#xb5;m of formalin-fixed paraffin-embedded (FFPE) sections. Comprehensive genomic profiling (CGP) was used to evaluate up to 315 genes (592&#xd7; mean coverage depth). Results were analyzed for base substitutions, short indels, copy number changes, and selected rearrangements.<br><br>RESULTS: Of 5605 cases, 698 (12.5%) featured ERBB2 alterations, including 596 (10.6%) ERBB2 amplifications (ERBB2amp) and 138 (2.4%) ERBB2mut; 38 cases (0.7%) had co-occurring ERBB2amp and ERBB2mut. ERBB2mut predominantly affected the kinase (124 cases; 90%) or extracellular (15 cases; 11%) domains. Both primary BC (52 cases; 38%) and metastatic site biopsies (86 cases; 62%) were found to harbor ERBB2mut, which were distributed across carcinoma not otherwise specified (NOS) (69 cases; 50%), invasive ductal carcinoma (IDC) (40 cases; 29%), invasive lobular carcinoma (ILC) (27 cases; 20%), and mucinous mBC (2 cases; 1%). Genes commonly coaltered with ERBB2 were tumor protein 53 (TP53) (49%); phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (42%); cadherin 1, type 1 (CDH1) (37%); MYC (17%); and cyclin D1 protein (CCND1) (16%). CDH1 mutations were enriched in ERBB2mut mBC (P<0.0006) and associated with recurrent mBC. Selected patients with ERBB2mut, without ERBB2amp, who responded to anti-HER2 targeted therapies are presented herein.<br><br>CONCLUSIONS: Within this large series, 1.8% of cases harbored ERBB2mut, which are undetectable by standard-of-care IHC or FISH tests. Metastatic BC driven by ERBB2mut respond to anti-HER2 targeted therapies, and expanding clinical trials designed to detect ERBB2mut by CGP and optimize targeted treatments are warranted. Cancer 2016. &#xa9; 2016 American Cancer Society. Cancer 2016;122:2654-2662. &#xa9; 2016 American Cancer Society.}, }
@article {pmid27279334, year = {2016}, author = {Shen, S and Wang, Y and Wang, C and Wu, YN and Xing, Y}, title = {SURVIV for survival analysis of mRNA isoform variation.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11548}, pmid = {27279334}, issn = {2041-1723}, support = {R01 GM088342/GM/NIGMS NIH HHS/United States ; R01 GM105431/GM/NIGMS NIH HHS/United States ; }, mesh = {*Alternative Splicing ; Breast Neoplasms/*etiology/mortality ; Carcinoma, Ductal, Breast/*etiology/mortality ; Humans ; Models, Statistical ; *RNA Isoforms ; *Survival Analysis ; }, abstract = {The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations to clinical outcomes. Here we report a statistical method SURVIV (Survival analysis of mRNA Isoform Variation), designed for identifying mRNA isoform variation associated with patient survival time. A unique feature and major strength of SURVIV is that it models the measurement uncertainty of mRNA isoform ratio in RNA-seq data. Simulation studies suggest that SURVIV outperforms the conventional Cox regression survival analysis, especially for data sets with modest sequencing depth. We applied SURVIV to TCGA RNA-seq data of invasive ductal carcinoma as well as five additional cancer types. Alternative splicing-based survival predictors consistently outperform gene expression-based survival predictors, and the integration of clinical, gene expression and alternative splicing profiles leads to the best survival prediction. We anticipate that SURVIV will have broad utilities for analysing diverse types of mRNA isoform variation in large-scale clinical RNA-seq projects.}, }
@article {pmid27267193, year = {2016}, author = {Desmond, BL and Blattner, CM and Young Iii, J}, title = {Generalized morphea as the first sign of breast carcinoma: a case report.}, journal = {Dermatology online journal}, volume = {22}, number = {2}, pages = {}, pmid = {27267193}, issn = {1087-2108}, mesh = {Breast Neoplasms/*complications/diagnosis ; Carcinoma, Ductal, Breast/*complications/diagnosis ; Female ; Humans ; Middle Aged ; Paraneoplastic Syndromes/*complications/pathology ; Scleroderma, Localized/*complications/pathology ; }, abstract = {Generalized morphea is a rare idiopathic form of scleroderma that literally means "hard skin." Morphea is usually considered an isolated event that is not associated with malignancy. However, case reports of lung, hematologic, and breast cancer occurring simultaneously with large plaque morphea have caused dermatologists to question whether a work-up for malignancy is appropriate. We highlight a case of generalized morphea that preceded invasive ductal carcinoma of the breast and provide a discussion about the possible paraneoplastic origin of generalized morphea and systemic sclerosis (SSc).}, }
@article {pmid27258056, year = {2016}, author = {Ahuja, S and Makkar, P and Gupta, S and Vigoda, I}, title = {Paraneoplastic syndrome and underlying breast cancer: a worsening rash despite initiation of chemotherapy.}, journal = {The Journal of community and supportive oncology}, volume = {14}, number = {5}, pages = {229-231}, doi = {10.12788/jcso.0186}, pmid = {27258056}, issn = {2330-7749}, abstract = {Skin may show the first clinical evidence of systemic disease and can be the first clue to malignancy in 1% of cases. Dermatomyositis is an immunologically mediated inflammatory myopathy characterized by proximal muscle weakness, muscle inflammation, and characteristic skin findings. It has an incidence of 1 in 100,000 patients. In 15%-30% cases of dermatomyositis, an underlying malignancy is the cause of paraneoplastic syndrome. Ovarian and breast cancer in women and lung cancer in men are the most common malignancies associated with dermatomyositis. Here we report the case of a 55-year-old postmenopausal woman who initially presented with a facial rash. She was treated for chemical dermatitis without resolution of symptoms and was subsequently found to have dermatomyositis associated with stage IV invasive ductal carcinoma of the breast. In most cases, the skin changes resolve after treatment for the underlying malignancy has been initiated, but in this case of paraneoplastic dermatomyositis, the rash worsened with initiation of treatment for underlying breast cancer.}, }
@article {pmid27255575, year = {2017}, author = {Bond, SE and Boutlis, CS and Jansen, SG and Miyakis, S}, title = {Discontinuation of peri-operative gentamicin use for indwelling urinary catheter manipulation in orthopaedic surgery.}, journal = {ANZ journal of surgery}, volume = {87}, number = {11}, pages = {E199-E203}, doi = {10.1111/ans.13642}, pmid = {27255575}, issn = {1445-2197}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Antibiotic Prophylaxis/standards ; Arthroplasty/*adverse effects ; Australia/epidemiology ; Bacteremia/drug therapy/prevention &amp; control ; Bacteriuria/drug therapy/prevention &amp; control ; Catheters, Indwelling/adverse effects/microbiology/*standards ; Device Removal/adverse effects/standards ; Female ; Gentamicins/administration &amp; dosage/*therapeutic use ; Humans ; Male ; Middle Aged ; New South Wales/epidemiology ; Orthopedic Procedures/*adverse effects ; Perioperative Care/*standards ; Practice Patterns, Physicians'/standards ; Retrospective Studies ; Surgical Wound Infection/prevention &amp; control ; Urinary Catheters/*microbiology ; }, abstract = {BACKGROUND: Gentamicin has historically been used prior to insertion and removal of indwelling urinary catheters (IDCs) around elective joint replacement surgery to prevent infection; however, this indication is not recognized in the Australian Therapeutic Guidelines: Antibiotic and the paradigm for safe use of gentamicin has shifted.<br><br>METHODS: The antimicrobial stewardship team of a 500 bed tertiary regional hospital performed a retrospective clinical study of gentamicin IDC prophylaxis around total hip and knee arthroplasties. Results were presented to the orthopaedic surgeons. A literature review identified no guidelines to support gentamicin prophylaxis and only a very low risk of bacteraemia associated with IDC insertion/removal in patients with established bacteriuria. Consensus was reached with the surgeons to discontinue this practice. Subsequent prospective data collection was commenced to determine effectiveness, with weekly feedback to the Department Head of Orthopaedics.<br><br>RESULTS: Data from 137 operations pre-intervention (6 months) were compared with 205 operations post-intervention (12 months). The median patient age was 72 years in both groups. Following the intervention, reductions in gentamicin use were demonstrated for IDC insertion (59/137 (42%) to 4/205 (2%), P < 0.01) and removal (39/137 (28%) to 6/205 (3%), P < 0.01). No gentamicin use was observed during the final 40 weeks of the post-intervention period. There were no significant differences between the groups for pre-operative bacteriuria, surgical site infections or acute kidney injury.<br><br>CONCLUSION: A collaborative approach using quality improvement methodology can lead to an evidence-based reappraisal of established practice. Regular rolling audits and timely feedback were useful in sustaining change.}, }
@article {pmid27209064, year = {2016}, author = {Roggenbuck, D and Borghi, MO and Somma, V and Büttner, T and Schierack, P and Hanack, K and Grossi, C and Bodio, C and Macor, P and von Landenberg, P and Boccellato, F and Mahler, M and Meroni, PL}, title = {Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers.}, journal = {Arthritis research &amp; therapy}, volume = {18}, number = {1}, pages = {111}, pmid = {27209064}, issn = {1478-6362}, mesh = {Adult ; Aged ; Antibodies, Antiphospholipid/*analysis ; Antiphospholipid Syndrome/*diagnosis/immunology ; Diagnosis, Differential ; Female ; Humans ; Immunoassay/*methods ; Infections/diagnosis/immunology ; Male ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)).<br><br>METHODS: Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (&#x3b2;2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-&#x3b2;2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human &#x3b2;2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human &#x3b2;2GPI or after CL-micelle absorption.<br><br>RESULTS: Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM a&#xdf;2GPI and aCL. Anti-CL and anti-&#xdf;2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and &#xdf;2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL)&#x2009;+&#x2009;samples than in patients with APS. HumoAb against domain 1 recognized &#x3b2;2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-&#x3b2;2GPI humoAbs.<br><br>CONCLUSIONS: The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.}, }
@article {pmid27208304, year = {2016}, author = {Van Aken, O and De Clercq, I and Ivanova, A and Law, SR and Van Breusegem, F and Millar, AH and Whelan, J}, title = {Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases.}, journal = {Plant physiology}, volume = {171}, number = {3}, pages = {2150-2165}, pmid = {27208304}, issn = {1532-2548}, mesh = {Antimycin A/pharmacology ; Arabidopsis/drug effects/*physiology ; Arabidopsis Proteins/genetics/metabolism ; Chloroplasts/drug effects/*physiology ; Energy Metabolism/genetics ; Fluoroacetates/pharmacology ; Gene Expression Regulation, Plant/drug effects ; Mitochondria/drug effects/*physiology ; Mitochondrial Proteins/genetics ; Plants, Genetically Modified ; Signal Transduction/drug effects ; Stress, Physiological/*physiology ; Transcription Factors/genetics/metabolism ; }, abstract = {Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control.}, }
@article {pmid27184932, year = {2016}, author = {Desai, K and Nair, MG and Prabhu, JS and Vinod, A and Korlimarla, A and Rajarajan, S and Aiyappa, R and Kaluve, RS and Alexander, A and Hari, PS and Mukherjee, G and Kumar, RV and Manjunath, S and Correa, M and Srinath, BS and Patil, S and Prasad, MS and Gopinath, KS and Rao, RN and Violette, SM and Weinreb, PH and Sridhar, TS}, title = {High expression of integrin β6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers.}, journal = {Cancer medicine}, volume = {5}, number = {8}, pages = {2000-2011}, pmid = {27184932}, issn = {2045-7634}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*metabolism/mortality/pathology ; Female ; Gene Amplification ; Gene Expression ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Integrin beta Chains/*genetics ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Receptor, ErbB-2/genetics/*metabolism ; *Signal Transduction ; rac GTP-Binding Proteins/*metabolism ; }, abstract = {Integrin αvβ6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin β6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αvβ6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens (N = 460) for the expression of integrin β6 (ITGB6) mRNA by qPCR. In addition, we have examined a subset (N = 147) for the expression of αvβ6 integrin by immunohistochemistry (IHC). The expression levels of members of Rho-Rac pathway including downstream genes (ACTR2, ACTR3) and effector proteinases (MMP9, MMP15) were estimated by qPCR in the HER2+ subset (N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+HER2- and triple negative (TNBC) subtypes (P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho-Rac pathway (P-values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease-free survival compared to the group with lower ITGB6 levels (HR = 2.9 (0.9-8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node-positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho-Rac pathway through increased expression of MMP9 and MMP15.}, }
@article {pmid27173185, year = {2016}, author = {Oliveira, NC and Gomig, TH and Milioli, HH and Cordeiro, F and Costa, GG and Urban, CA and Lima, RS and Cavalli, IJ and Ribeiro, EM}, title = {Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.}, journal = {Genetics and molecular research : GMR}, volume = {15}, number = {2}, pages = {}, doi = {10.4238/gmr.15027701}, pmid = {27173185}, issn = {1676-5680}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Proteome/*genetics/metabolism ; }, abstract = {Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.}, }
@article {pmid27161340, year = {2016}, author = {Zalsman, G and Shoval, G and Mansbach-Kleinfeld, I and Farbstein, I and Kanaaneh, R and Lubin, G and Apter, A}, title = {Maternal versus adolescent reports of suicidal behaviors: a nationwide survey in Israel.}, journal = {European child &amp; adolescent psychiatry}, volume = {25}, number = {12}, pages = {1349-1359}, pmid = {27161340}, issn = {1435-165X}, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Depressive Disorder/psychology ; Female ; *Health Surveys/standards ; Humans ; Israel/epidemiology ; Male ; Mothers/*psychology ; Prevalence ; Residence Characteristics ; Risk Factors ; *Self Report/standards ; Stress Disorders, Post-Traumatic/epidemiology/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; }, abstract = {Community and nationwide surveys on adolescent suicidal behaviors using clinical interviews are not abundant. Rates of self-reported suicide attempts in community samples vary greatly between 1 and 20 %. In general, adolescent and parental agreement in child psychiatry practice is low, and their agreement with regard to suicidal behavior is unknown. The current study assesses the rates of suicidal ideation and behaviors as well as the rate of agreement between adolescents and their mothers in a representative nationwide sample. The survey included a representative and randomized community sample of 14- to 17-year-old adolescents (n = 957), and their mothers who were interviewed using the Development and Well-Being Assessment Inventory (DAWBA). The prevalence of suicidal ideation and self-initiated behaviors was 4.9 and 1.9 %, respectively. The concordance between mothers' and adolescents' reporting on ideation was low (7.3 %). There was no concordance between mothers' and adolescents' reports of suicidal acts. Adolescents reported self-initiated behaviors nearly three times more frequently than their mothers. Paternal unemployment, care by welfare agencies and having a psychiatric disorder, specifically depression or post-traumatic stress disorder, was associated with a higher risk for both suicidal ideation and attempts. In this nationwide community study, by evaluating information gathered by clinical interviews, it was found that the lifetime rates of suicidal ideation were moderate. The rates of suicide attempts were lower than have been previously reported. The concordance between the reports of adolescents and their mothers was low for ideation and nonexistent for attempts. Thus, clinicians should interview adolescents separately from their mothers regarding their suicidality.}, }
@article {pmid27156133, year = {2016}, author = {Santos, CS and Carvalho, SM and Leite, A and Moniz, T and Roriz, M and Rangel, AO and Rangel, M and Vasconcelos, MW}, title = {Effect of tris(3-hydroxy-4-pyridinonate) iron(III) complexes on iron uptake and storage in soybean (Glycine max L.).}, journal = {Plant physiology and biochemistry : PPB}, volume = {106}, number = {}, pages = {91-100}, doi = {10.1016/j.plaphy.2016.04.050}, pmid = {27156133}, issn = {1873-2690}, mesh = {Biomass ; Chlorophyll/metabolism ; FMN Reductase/metabolism ; Ferric Compounds/*pharmacology ; Gene Expression Regulation, Plant/drug effects ; Iron/*metabolism ; Iron Chelating Agents/chemistry/pharmacology ; Ligands ; Lipid Peroxidation/drug effects ; Malondialdehyde/metabolism ; Minerals/metabolism ; Plant Development/drug effects ; Plant Diseases ; Plant Leaves/drug effects/metabolism ; Plant Proteins/genetics/metabolism ; Plant Roots/metabolism ; Plant Shoots/drug effects/metabolism ; Pyridines/*pharmacology ; Soybeans/drug effects/genetics/*metabolism ; Spectrum Analysis ; }, abstract = {Iron deficiency chlorosis (IDC) is a serious environmental problem affecting the growth of several crops in the world. The application of synthetic Fe(III) chelates is still one of the most common measures to correct IDC and the search for more effective Fe chelates remains an important issue. Herein, we propose a tris(3-hydroxy-4-pyridinonate) iron(III) complex, Fe(mpp)3, as an IDC corrector. Different morphological, biochemical and molecular parameters were assessed as a first step towards understanding its mode of action, compared with that of the commercial fertilizer FeEDDHA. Plants treated with the pyridinone iron(III) complexes were significantly greener and had increased biomass. The total Fe content was measured using ICP-OES and plants treated with pyridinone complexes accumulated about 50% more Fe than those treated with the commercial chelate. In particular, plants supplied with compound Fe(mpp)3 were able to translocate iron from the roots to the shoots and did not elicit the expression of the Fe-stress related genes FRO2 and IRT1. These results suggest that 3,4-HPO iron(III) chelates could be a potential new class of plant fertilizing agents.}, }
@article {pmid27153443, year = {2017}, author = {Chatterjee, D and Bal, A and Das, A and Kohli, PS and Singh, G and Mittal, BR}, title = {Invasive Duct Carcinoma of the Breast With Dominant Signet-Ring Cell Differentiation: A Microsatellite Stable Tumor With Aggressive Behavior.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {25}, number = {10}, pages = {720-724}, doi = {10.1097/PAI.0000000000000366}, pmid = {27153443}, issn = {1533-4058}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Signet Ring Cell/*diagnosis/pathology ; DNA-Binding Proteins/genetics ; Female ; Humans ; Immunohistochemistry ; Microsatellite Repeats/genetics ; Middle Aged ; MutS Homolog 2 Protein/genetics ; Prognosis ; }, abstract = {AIMS: Invasive duct carcinoma, no special type (IDC, NST), of the breast with signet-ring cell differentiation is uncommon. This study was undertaken to describe the clinicopathologic characteristics of IDC, NST, with dominant signet-ring cell differentiation, and look for microsatellite instability in these tumors.<br><br>METHODS: Cases of IDC, NST, with dominant signet-ring cell differentiation, diagnosed over the past 2 years, were retrieved. Detailed clinical and pathologic analyses were performed. Immunohistochemistry was performed for estrogen receptor, progesterone receptors, Her-2 neu, Ki-67, E-cadherin, CK7, and CK20. Microsatellite instability was examined using immunohistochemistry for the 4 mismatch repair proteins: MLH1, MSH2, MSH6, and PMS2.<br><br>RESULTS: Of the total 1646 cases of IDC, NST, only 5 cases showed dominant signet-ring cells (ranging from 70% to 100%) and strong E-cadherin positivity and were diagnosed as IDC, NST, with dominant signet-ring cell differentiation. The age ranged from 32 to 65 years. Two cases were of histologic grade 3 and the remaining cases were grade 2 tumors. Four patients had T2 tumor and 1 had T3 tumor. All cases had axillary lymph node metastasis and distant metastasis was present in 1 case. All cases were microsatellite stable.<br><br>CONCLUSIONS: Signet-ring cell differentiation in IDC, NST, is rare and associated with a high histologic grade. Lymph node metastasis and distant metastasis are common, indicating an aggressive clinical behavior. Thus, they should be recognized separately as they may warrant aggressive management. However, these are microsatellite-stable tumors in contrast to signet-ring cell tumors of other organs.}, }
@article {pmid27146735, year = {2016}, author = {Krishnamurthy, J and Kumar, PS}, title = {Significance of prognostic indicators in infiltrating duct carcinoma breast: Scenario in developing country.}, journal = {Indian journal of cancer}, volume = {53}, number = {1}, pages = {34-38}, doi = {10.4103/0019-509X.180834}, pmid = {27146735}, issn = {1998-4774}, mesh = {Adult ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Developing Countries ; Female ; Humans ; Middle Aged ; Prognosis ; }, abstract = {CONTEXT: Carcinoma of the breast is one of the most common malignant tumors and is the most common cause of death from cancers in females. Early diagnosis and assessing the prognosis for each patient is essential for a better therapeutic plan and management.<br><br>AIMS: To evaluate the significance of various prognostic indicators of breast carcinoma by correlating with Nottingham modification of Scarff Bloom-Richardson's grading system (NMBGS).<br><br>MATERIALS AND METHODS: Eighty four patients who underwent mastectomy for breast carcinoma at a tertiary care centre in South India over a period of 2 years have been evaluated to note the importance of the various prognostic factors correlating them with NMBGS.<br><br>STATISTICAL ANALYSIS: A Chi-square test was used to determine possible association between the various prognostic factors.<br><br>RESULTS: Eighty percent of the tumors were infiltrating ductal carcinoma (IDC), and it is seen that the larger tumor size, higher histopathological grade, increased lymphovascular invasion, lymphnode metastasis, tumor necrosis, microvessel density, estrogen and progesterone receptor negativity, and HER-2/neu positivity were associated with higher grade of tumor.<br><br>CONCLUSIONS: The traditional morphological factors including the histological type, grade, tumor size, lymphovascular invasion, lymph node status, presence of necrosis, stromal reaction, and microvascular density (MVD) count are relatively simple but robust prognostic factors to assess, while the hormonal and genetic status not only have prognostic value but are useful predictive marker for adjuvant chemotherapy. Hence, the status of these various prognostic factors should form the basis of all routine histopathological reports in cases of breast cancer for better management.}, }
@article {pmid27145402, year = {2016}, author = {Tessitore, A and Giordano, A and De Micco, R and Caiazzo, G and Russo, A and Cirillo, M and Esposito, F and Tedeschi, G}, title = {Functional connectivity underpinnings of fatigue in "Drug-Naïve" patients with Parkinson's disease.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {31}, number = {10}, pages = {1497-1505}, doi = {10.1002/mds.26650}, pmid = {27145402}, issn = {1531-8257}, mesh = {Aged ; Cerebral Cortex/diagnostic imaging/*physiopathology ; Connectome/*methods ; Fatigue/diagnostic imaging/etiology/*physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parkinson Disease/complications/diagnostic imaging/*physiopathology ; }, abstract = {INTRODUCTION: Fatigue is a common problem in PD either in the early or later stage of the disease. Using resting-state functional MRI, we investigated the functional correlates of fatigue in a cohort of "drug-naïve" patients with PD.<br><br>METHODS: MRI at 3Tesla was collected in 40 patients with PD, 20 with and 20 without fatigue, and 20 matched healthy controls. Presence and the severity of fatigue were defined based on the 16-item Parkinson fatigue scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting state networks between patients subgroups and healthy controls. In addition, we used voxel-based morphometry to test whether between-group functional changes were related to structural differences.<br><br>RESULTS: Distressing fatigue was associated with a decreased connectivity in the supplementary motor area within the sensorimotor network and an increased connectivity in the prefrontal and posterior cingulate cortices within the default mode network (P < 0.05 corrected). Fatigue severity was correlated with both sensorimotor and default mode networks connectivity changes. Voxel-based morphometry analysis did not reveal any significant volume differences between all patients with PD and healthy controls and between patients with PD with and without fatigue (P < 0.05; family-wise error).<br><br>CONCLUSIONS: Our findings revealed that primary PD-related fatigue is associated with an altered default mode network and sensorimotor network connectivity in drug-na&#xef;ve patients. We hypothesize that these divergent motor and cognitive networks connectivity changes and their adaptive or maladaptive functional outcome may play a prominent role in the pathophysiology of fatigue in PD. &#xa9; 2016 International Parkinson and Movement Disorder Society.}, }
@article {pmid27125354, year = {2016}, author = {Yao, M and Yu, E and Staggs, V and Fan, F and Cheng, N}, title = {Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {29}, number = {8}, pages = {810-823}, pmid = {27125354}, issn = {1530-0285}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology/therapy ; Calcium-Binding Proteins/analysis ; Carcinoma, Ductal, Breast/*chemistry/pathology/therapy ; Carcinoma, Lobular/*chemistry/pathology/therapy ; Chemokine CCL2/*analysis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Risk Factors ; S100 Calcium-Binding Protein A4 ; Stromal Cells/*chemistry/pathology ; Time Factors ; Tissue Array Analysis ; Treatment Outcome ; Tumor Burden ; Tumor Microenvironment ; Up-Regulation ; }, abstract = {Despite advances in treatment, up to 30% of breast cancer patients experience disease recurrence accompanied by more aggressive disease and poorer prognosis. Treatment of breast cancer is complicated by the presence of multiple breast cancer subtypes, including: luminal, Her2 overexpressing, and aggressive basal-like breast cancers. Identifying new biomarkers specific to breast cancer subtypes could enhance the prediction of patient prognosis and contribute to improved treatment strategies. The microenvironment influences breast cancer progression through expression of growth factors, angiogenic factors and other soluble proteins. In particular, chemokine C-C ligand 2 (CCL2) regulates macrophage recruitment to primary tumors and signals to cancer cells to promote breast tumor progression. Here we employed a software-based approach to evaluate the prognostic significance of CCL2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1 (Fsp1), a mesenchymal marker. Immunohistochemistry analysis of tissue microarrays revealed that CCL2 significantly correlated with Fsp1 expression in the stroma and tumor epithelium of invasive ductal carcinoma. In the overall cohort of invasive ductal carcinomas (n=427), CCL2 and Fsp1 expression in whole tissues, stroma and epithelium were inversely associated with cancer stage and tumor size. When factoring in molecular subtype, stromal CCL2 was observed to be most highly expressed in basal-like breast cancers. By Cox regression modeling, stromal CCL2, but not epithelial CCL2, expression was significantly associated with decreased recurrence-free survival. Furthermore, stromal CCL2 (HR=7.51 P=0.007) was associated with a greater hazard than cancer stage (HR=2.45, P=0.048) in multivariate analysis. These studies indicate that stromal CCL2 is associated with decreased recurrence-free survival in patients with basal-like breast cancer, with important implications on the use of stromal markers for predicting patient prognosis.}, }
@article {pmid27116366, year = {2016}, author = {Dobbs, JL and Shin, D and Krishnamurthy, S and Kuerer, H and Yang, W and Richards-Kortum, R}, title = {Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.}, journal = {International journal of cancer}, volume = {139}, number = {5}, pages = {1140-1149}, doi = {10.1002/ijc.30160}, pmid = {27116366}, issn = {1097-0215}, mesh = {Adipocytes/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal/*pathology ; Carcinoma, Ductal, Breast/immunology/pathology ; Female ; Humans ; *Microscopy, Confocal/methods ; *Tumor Microenvironment ; }, abstract = {Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions.}, }
@article {pmid27097912, year = {2016}, author = {Costello, LC and Zou, J and Franklin, RB}, title = {In situ clinical evidence that zinc levels are decreased in breast invasive ductal carcinoma.}, journal = {Cancer causes &amp; control : CCC}, volume = {27}, number = {6}, pages = {729-735}, pmid = {27097912}, issn = {1573-7225}, support = {R01 CA079903/CA/NCI NIH HHS/United States ; R01 CA093443/CA/NCI NIH HHS/United States ; R01 DK042839/DK/NIDDK NIH HHS/United States ; R01 DK076763/DK/NIDDK NIH HHS/United States ; }, mesh = {Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Case-Control Studies ; Chelating Agents ; Dithizone ; Female ; Humans ; Zinc/*metabolism ; }, abstract = {PURPOSE: Altered zinc levels in malignant cells versus their normal cells have important implications in the development and progression of several cancers. Prostate, pancreatic, and hepatocellular carcinomas exhibit consistent marked zinc decrease in situ in the malignant cells, and other cancers (such as kidney, lung, and thyroid) also exhibit decreased tissue zinc levels. However, zinc levels are increased in breast cancer tissue compared to breast normal tissue, and the contemporary dominant view is that zinc is increased in invasive ductal carcinoma. This has important implications regarding the role and effects of zinc in breast malignancy compared to other cancers, which caused us to initiate this study to either confirm or challenge the contemporary view of an increased zinc level in the invasive ductal malignant cells.<br><br>METHODS: We employed dithizone staining of breast tissue sections and tissue cores to determine the relative in situ cellular zinc levels specifically in the invasive ductal malignant cells as compared to normal ductal epithelium. This approach had not been employed in any of the reported breast studies.<br><br>RESULTS: The results revealed that the zinc levels are consistently and markedly decreased in the ductal malignant cells as compared with higher prominent zinc levels in the normal ductal epithelium. Decreased zinc is evident in Grade 1 well-differentiated malignancy and in Grade 2 and Grade 3 carcinomas. Among the twenty-five cancer cases in this study, none exhibited increased zinc in the invasive ductal carcinoma compared to the zinc level in the normal ductal epithelium.<br><br>CONCLUSIONS: The decreased zinc levels in breast invasive ductal carcinoma is consistent with prostate, pancreatic, and liver carcinomas in which the decrease in zinc is a required event in the development of malignancy to prevent cytotoxicity that would result from the higher zinc levels in the normal cells. This new understanding requires a redirection in elucidating the mechanisms and factors regarding the regulation of zinc in breast cancer, its potential translational applications as possible biomarkers, and for treatment of breast invasive ductal carcinoma.}, }
@article {pmid27092808, year = {2017}, author = {Giarenis, I and Zacchè, M and Robinson, D and Cardozo, L}, title = {Is there any association between urodynamic variables and severity of overactive bladder in women with idiopathic detrusor overactivity?.}, journal = {Neurourology and urodynamics}, volume = {36}, number = {3}, pages = {780-783}, doi = {10.1002/nau.23023}, pmid = {27092808}, issn = {1520-6777}, mesh = {Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Severity of Illness Index ; Urinary Bladder/*physiopathology ; Urinary Bladder, Neurogenic/complications/diagnosis/*physiopathology ; Urinary Bladder, Overactive/complications/diagnosis/*physiopathology ; Urinary Incontinence/diagnosis/etiology/*physiopathology ; Urodynamics/*physiology ; }, abstract = {AIMS: The lack of a validated detrusor overactivity (DO) severity tool limits the clinical value of urodynamics in the management of patients with overactive bladder syndrome (OAB). The aim of this study, was to identify urodynamic variables that correlate with validated OAB severity measures.<br><br>METHODS: This was a cross-sectional study enrolling consecutive women with idiopathic DO. The 24&#x2009;hr urgency episodes and the score of the Incontinence Impact (II) domain of the King's Health Questionnaire (KHQ) were used to assess the severity of OAB.<br><br>RESULTS: The study enrolled 299 women with idiopathic DO. The cystometric capacity, compliance, and the threshold volume for the first involuntary detrusor contraction (IDC) showed a statistically significant negative correlation with the II domain of the KHQ and the 24&#x2009;hr urgency episodes. There was a statistically significant positive correlation between the amplitude of first IDC and the OAB severity measures, but only borderline for the amplitude of the highest IDC. There were no statistically significant differences between women with and without leakage per urethram during a detrusor contraction.<br><br>CONCLUSIONS: Cystometric capacity, compliance (measured in ml/cm H2 O), threshold volume, and amplitude of the first IDC could be routinely documented in everyday clinical practice. The measures more commonly used for describing the severity of DO, such as leakage per urethram during a detrusor contraction and amplitude of the highest detrusor contraction, have a limited role confirming the complicated interaction between the detrusor muscle, the urethral sphincter, and the pelvic floor in women. Neurourol. Urodynam. 36:780-783, 2017. &#xa9; 2016 Wiley Periodicals, Inc.}, }
@article {pmid27080531, year = {2016}, author = {Chabot, V and Martin, L and Meley, D and Sensebé, L and Baron, C and Lebranchu, Y and Dehaut, F and Velge-Roussel, F}, title = {Unexpected impairment of TNF-α-induced maturation of human dendritic cells in vitro by IL-4.}, journal = {Journal of translational medicine}, volume = {14}, number = {}, pages = {93}, pmid = {27080531}, issn = {1479-5876}, mesh = {Biomarkers/metabolism ; CD4-Positive T-Lymphocytes/drug effects ; Cell Differentiation/*drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Chemokines/pharmacology ; Dendritic Cells/*cytology/drug effects/metabolism ; Humans ; Interleukin-12/metabolism ; Interleukin-4/metabolism ; Lymphocyte Activation/drug effects ; RNA, Messenger/genetics/metabolism ; Receptors, CCR7/genetics/metabolism ; Th1 Cells/drug effects ; Tumor Necrosis Factor-alpha/*pharmacology ; }, abstract = {BACKGROUND: An efficient strategy for programming dendritic cells (DCs) for cancer immunotherapy is the optimization of their maturation so that they can efficiently stimulate cancer-specific T cell responses. Interleukin (IL)-4 has appeared as an essential cytokine, widely used in vitro with granulocyte macrophage-colony stimulating factor (GM-CSF) to differentiate monocytes into immature DCs (iDC) and to prevent macrophage formation. Conflicting data have been published regarding the effect of IL-4 on functional DC maturation. To further understand IL-4's effects on DC maturation and function in vitro, we choose the most commonly used maturation factor tumor necrosis factor (TNF)-α.<br><br>METHODS: Human monocyte-derived iDC were treated for 48 h with GM-CSF and TNF-&#x3b1; in the presence (IL-4(+)-DC) or absence (IL-4(-)-DC) of IL-4 and functions of both DC populations were compared.<br><br>RESULTS: On mixed lymphocyte reaction assay, IL-4(+)-DC were less potent than IL-4(-)-DC at inducing the proliferation of allogeneic CD4(+) T cells and the proportion of activated T cells expressing CD69 and/or CD25 was smaller. Interleukin-4 reduced the cell-surface expression of TNF-&#x3b1;-induced DC maturation markers CD83, CD86, HLA-DR and CD25 and generated a heterogeneous population of DCs. IL-4(+)-DC secreted less IL-12 and more IL-10 than IL-4(-)-DC following activation by soluble CD40L, and IL-4(+)-DC-activated T cells secreted lesser amounts of T helper (Th) 1 cytokines (IL-2 and interferon-&#x3b3;). Importantly, IL-4 impaired the in vitro migratory capacity of DCs in response to CCL21 and CCL19 chemokines. This effect was related to reduced expression of CCR7 at both mRNA and protein levels.<br><br>CONCLUSION: Interleukin-4 used with GM-CSF and TNF-&#x3b1; during the maturation of DCs in vitro impaired DC functions and disturbed the maturation effect of TNF-&#x3b1;. Finally, our study reinforces the view that the quality of the DC maturation stimulus, which regulates DC migration and cytokine production, may be a decisive feature of the immunogenicity of DCs.}, }
@article {pmid27067853, year = {2016}, author = {Ooe, A and Suganuma, Y}, title = {[Breast Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine Monotherapy after Failure of Combination Therapy Comprising Bevacizumab and Paclitaxel].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {3}, pages = {349-351}, pmid = {27067853}, issn = {0385-0684}, mesh = {Aged ; Antimetabolites, Antineoplastic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration &amp; dosage ; Breast Neoplasms/*drug therapy/*pathology ; Capecitabine/*therapeutic use ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Paclitaxel/administration &amp; dosage ; Salvage Therapy ; }, abstract = {We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients.}, }
@article {pmid27050973, year = {2016}, author = {Zhao, L and Zhang, QY and Luan, X and Huang, X and Zhao, S and Zhao, H}, title = {Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma.}, journal = {Genetics and molecular research : GMR}, volume = {15}, number = {1}, pages = {}, doi = {10.4238/gmr.15017464}, pmid = {27050973}, issn = {1676-5680}, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Enhancer of Zeste Homolog 2 Protein/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Middle Aged ; Prognosis ; Receptor, Notch1/genetics/*metabolism ; }, abstract = {We determined whether the coexpression of Notch1 and EZH2 influences the progression and prognosis of breast invasive ductal carcinoma. Using the χ(2) test, a significant difference was found between high and low expression of Notch1 in terms of lymph node, hormone receptor, and p53 expression (P < 0.05). Moreover, a significant difference was found between high and low expression of EZH2 in terms of tumor size, histologic grade, hormone receptor, and expression of Ki67 (P < 0.05). Using Pearson correlation analysis, we found a significant positive correlation between Notch1 and EZH2 expression in the tissue samples of breast invasive ductal carcinoma (P = 0.038). High Notch1 and EZH2 expression was associated with poor progression-free survival compared with low expression (PNotch1 = 0.000, 40.3 vs 48.9 months; PEZH2 = 0.000, 40.2 vs 49.9 months). Moreover, we found that high Notch1 and EZH2 expression was associated with poor overall survival compared with low expression (PNotch1 = 0.000, 51.2 vs 56.2 months; PEZH2 = 0.002, 51.7 vs 56.4 months). In conclusion, Notch1 and EZH2 coexpression contributes to the progression and prognosis of breast invasive ductal carcinoma.}, }
@article {pmid27041335, year = {2016}, author = {Lim, ST and Choi, JE and Kim, SJ and Kim, HA and Kim, JY and Park, HK and Suh, YJ}, title = {Prognostic implication of the tumor location according to molecular subtypes in axillary lymph node-positive invasive ductal cancer in a Korean population.}, journal = {Breast cancer research and treatment}, volume = {156}, number = {3}, pages = {473-483}, doi = {10.1007/s10549-016-3771-6}, pmid = {27041335}, issn = {1573-7217}, mesh = {Adult ; Axilla ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/genetics ; Registries ; Republic of Korea ; Retrospective Studies ; }, abstract = {Previous studies have not considered the axillary lymph node status when investigating the prognostic role of tumor location according to each molecular subtype. The present study aimed to investigate the prognostic implication of tumor location according to each molecular subtype in Korean invasive ductal carcinoma (IDC) patients with axillary lymph node metastasis. Data from 7856 Korean IDC women with axillary lymph node metastasis were retrospectively analyzed. According to tumor location, patients were divided into the following groups: upper-outer quadrant, lower-outer quadrant, upper-inner quadrant, lower-inner quadrant (LIQ), and central group. Overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated according to tumor location and molecular subtype. A subgroup analysis based on tumor size categorization was also performed. The patients' mean age was 47.97 ± 9.64 years, and the median follow-up time was 90 months. The LIQ group showed significantly worse prognosis in OS and BCSS (76.4 and 83.3 %, respectively) compared with the other groups, which was only significant in human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative (TN) subtypes. In the subgroup analysis according to tumor size, the LIQ group showed a significantly worse prognosis in OS and BCSS compared with the other groups, in HER2 and TN subtypes, and only in patients with more than T2 stage. In Korean IDC patients with axillary lymph node metastasis, LIQ tumor location was associated with poor prognosis among those with HER2 and TN molecular subtypes and especially in those with more than T2 stage.}, }
@article {pmid27039751, year = {2016}, author = {Yadav, P and Mir, R and Nandi, K and Javid, J and Masroor, M and Ahmad, I and Zuberi, M and Kaza, R and Jain, S and Khurana, N and Ray, PC and Saxena, A}, title = {The C609T (Pro187Ser) Null Polymorphism of the NQO1 Gene Contributes Significantly to Breast Cancer Susceptibility in North Indian Populations: a Case Control Study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {3}, pages = {1215-1219}, doi = {10.7314/apjcp.2016.17.3.1215}, pmid = {27039751}, issn = {2476-762X}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Genetic Predisposition to Disease ; Genotype ; Humans ; India/epidemiology ; Middle Aged ; NAD(P)H Dehydrogenase (Quinone)/*genetics ; Neoplasm Grading ; Neoplasm Staging ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide/*genetics ; Prognosis ; Risk Factors ; }, abstract = {BACKGROUND: Worldwide, breast cancer is the most common cancer among women and is a leading cause of cancer death. In the present study, we investigated the NQO1 C609T genotypic and allelic distribution in north Indian breast cancer patients.<br><br>MATERIALS AND METHODS: The genotypic distribution of the NQ01 C609T polymorphism was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and 100 healthy controls using allele specific PCR (AS-PCR).<br><br>RESULTS: A lower frequency of the CC genotype was found in breast cancer patients (24%) than in the controls. On the other hand, TT genotype frequency was also found to be higher in female healthy controls (32%) than the female breast cancer patients (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%, 56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not find any significant correlation between the NQO1 C609T polymorphism and age group, grading, menopausal status and distant metastasis. A less significant association was found between the NQ01 C609T polymorphism and the stage of breast cancer (X2=5.931, P=0.05).<br><br>CONCLUSIONS: The present study shows a strong association between NQO1 C609T polymorphism with the breast cancer risk in the north Indian breast cancer patients so that possible use as a risk factor should be further explored.}, }
@article {pmid27032379, year = {2016}, author = {Wieczorek, E and Galicki, M and Tomasik, B and Krol, M and Jablonska, E and Fendler, W and Gromadzinska, J and Morawiec, Z and Wasowicz, W and Reszka, E}, title = {Expression of MMP and TIMP mRNA in peripheral blood leukocytes of patients with invasive ductal carcinoma of the breast.}, journal = {The International journal of biological markers}, volume = {31}, number = {3}, pages = {e309-16}, doi = {10.5301/jbm.5000203}, pmid = {27032379}, issn = {1724-6008}, mesh = {Breast Neoplasms/blood/*genetics/metabolism ; Carcinoma, Ductal, Breast/blood/*genetics/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leukocytes/cytology/*metabolism ; Matrix Metalloproteinases/biosynthesis/*genetics/metabolism ; Middle Aged ; RNA, Messenger/*biosynthesis/blood/genetics ; Tissue Inhibitor of Metalloproteinase-1/biosynthesis/*genetics/metabolism ; }, abstract = {PURPOSE: An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) appears critical for tumor progression and metastasis. This study aimed to determine whether gene expression of MMP1, MMP2, MMP9, TIMP1 and TIMP3 and the MMP/TIMP expression ratio in peripheral blood leukocytes (PBLs) and the MMP1 and TIMP1 contents or MMP1/TIMP1 ratio in plasma were associated with clinicopathological characteristics in invasive ductal carcinoma (IDC) of the breast.<br><br>MATERIALS AND METHODS: Blood samples were collected from women newly diagnosed with IDC who had not received prior treatment (n = 102). Gene expression in PBLs was analyzed by quantitative real-time polymerase chain reaction. Concentrations of MMP1 and TIMP1 in plasma were measured using ELISA.<br><br>RESULTS: In univariate analysis the expression levels of MMP2 and TIMP1 mRNA were significantly higher in premenopausal compared to postmenopausal patients (p<0.001 and p = 0.014, respectively). MMP2 mRNA expression negatively correlated with age (p<0.001, r = -0.43). We found that the MMP2/TIMP3 expression ratio was significantly higher in women after menopause (p = 0.007). The MMP2/TIMP1 expression ratio was higher in human epidermal growth factor receptor 2 (HER2)-positive patients (p = 0.022). Low-grade tumors had significantly lower MMP1/TIMP1 and MMP2/TIMP1 expression ratios (p = 0.047 and p = 0.048, respectively). TIMP1 plasma concentration was significantly higher in small tumors compared with T2-T3 tumors (p = 0.013).<br><br>CONCLUSIONS: These findings reveal an important association between tumor characteristics and expression ratios of MMP1/TIMP1 and MMP2/TIMP1 in PBLs and TIMP1 concentration in plasma. Menopausal status may influence the mRNA expression levels of MMP2 and TIMP1 as well as the MMP2/TIMP3 expression ratio in IDC of the breast.}, }
@article {pmid27022189, year = {2016}, author = {Lau, SS and Cheung, PS and Wong, TT and Ma, MK and Kwan, WH}, title = {Comparison of clinical and pathological characteristics between screen-detected and self-detected breast cancers: a Hong Kong study.}, journal = {Hong Kong medical journal = Xianggang yi xue za zhi}, volume = {22}, number = {3}, pages = {202-209}, doi = {10.12809/hkmj154575}, pmid = {27022189}, issn = {1024-2708}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology/therapy ; *Breast Self-Examination ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/*pathology/therapy ; Early Detection of Cancer/statistics &amp; numerical data ; Female ; Hong Kong ; Humans ; Logistic Models ; Lymph Nodes/pathology ; Mammography ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is the leading cause of death of Hong Kong women with increasing incidence. This study aimed to determine any prognostic differences between screen-detected and self-detected cases of breast cancer in a cohort of Hong Kong patients.<br><br>METHODS: This was a case series with internal comparison carried out in a private hospital in Hong Kong. Approximately 3000 cases of Chinese patients diagnosed with ductal carcinoma in situ or invasive breast cancer were reviewed.<br><br>RESULTS: The screen-detected group showed better pathological characteristics than the self-detected group. Number of lymph nodes involved, invasive tumour size, and tumour grade were more favourable in the screen-detected group. There was also a lower proportion of patients with pure invasive ductal carcinoma and mastectomy in the screen-detected group.<br><br>CONCLUSION: This study provides indirect evidence that women in the local population may gain clinical benefit from regular breast cancer screening. The findings need to be validated in a representative population of Hong Kong women.}, }
@article {pmid27014949, year = {2016}, author = {Cenarro, A and Etxebarria, A and de Castro-Orós, I and Stef, M and Bea, AM and Palacios, L and Mateo-Gallego, R and Benito-Vicente, A and Ostolaza, H and Tejedor, T and Martín, C and Civeira, F}, title = {The p.Leu167del Mutation in APOE Gene Causes Autosomal Dominant Hypercholesterolemia by Down-regulation of LDL Receptor Expression in Hepatocytes.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {101}, number = {5}, pages = {2113-2121}, doi = {10.1210/jc.2015-3874}, pmid = {27014949}, issn = {1945-7197}, mesh = {Adult ; Apolipoproteins E/*genetics/metabolism ; Case-Control Studies ; DNA Mutational Analysis ; Down-Regulation/*genetics ; Female ; Hepatocytes/*metabolism ; Humans ; Hyperlipoproteinemia Type II/*genetics/metabolism ; Male ; Middle Aged ; *Mutation ; Receptors, LDL/*genetics/metabolism ; }, abstract = {CONTEXT: The p.Leu167del mutation in the APOE gene has been associated with hyperlipidemia.<br><br>OBJECTIVES: Our objective was to determine the frequency of p.Leu167del mutation in APOE gene in subjects with autosomal dominant hypercholesterolemia (ADH) in whom LDLR, APOB, and PCSK9 mutations had been excluded and to identify the mechanisms by which this mutant apo E causes hypercholesterolemia.<br><br>DESIGN: The APOE gene was analyzed in a case-control study.<br><br>SETTING: The study was conducted at a University Hospital Lipid Clinic.<br><br>Two groups (ADH, 288 patients; control, 220 normolipidemic subjects) were included.<br><br>INTERVENTION: We performed sequencing of APOE gene and proteomic and cellular experiments.<br><br>MAIN OUTCOME MEASURE: To determine the frequency of the p.Leu167del mutation and the mechanism by which it causes hypercholesterolemia.<br><br>RESULTS: In the ADH group, nine subjects (3.1%) were carriers of the APOE c.500_502delTCC, p.Leu167del mutation, cosegregating with hypercholesterolemia in studied families. Proteomic quantification of wild-type and mutant apo E in very low-density lipoprotein (VLDL) from carrier subjects revealed that apo E3 is almost a 5-fold increase compared to mutant apo E. Cultured cell studies revealed that VLDL from mutation carriers had a significantly higher uptake by HepG2 and THP-1 cells compared to VLDL from subjects with E3/E3 or E2/E2 genotypes. Transcriptional down-regulation of LDLR was also confirmed.<br><br>CONCLUSIONS: p.Leu167del mutation in APOE gene is the cause of hypercholesterolemia in the 3.1% of our ADH subjects without LDLR, APOB, and PCSK9 mutations. The mechanism by which this mutation is associated to ADH is that VLDL carrying the mutant apo E produces LDLR down-regulation, thereby raising plasma low-density lipoprotein cholesterol levels.}, }
@article {pmid27007655, year = {2016}, author = {Jin, B and Wu, BW and Wen, ZC and Shi, HM and Zhu, J}, title = {HLA-DR3 antigen in the resistance to idiopathic dilated cardiomyopathy.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {49}, number = {4}, pages = {e5131}, pmid = {27007655}, issn = {1414-431X}, mesh = {Biopsy ; Cardiomyopathy, Dilated/*genetics/pathology ; Case-Control Studies ; Genetic Predisposition to Disease ; HLA-DR3 Antigen/*genetics ; Humans ; Myocardium/pathology ; Polymorphism, Genetic ; Risk Factors ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC.}, }
@article {pmid26980443, year = {2016}, author = {Fujikawa, Y and Roma, LP and Sobotta, MC and Rose, AJ and Diaz, MB and Locatelli, G and Breckwoldt, MO and Misgeld, T and Kerschensteiner, M and Herzig, S and Müller-Decker, K and Dick, TP}, title = {Mouse redox histology using genetically encoded probes.}, journal = {Science signaling}, volume = {9}, number = {419}, pages = {rs1}, doi = {10.1126/scisignal.aad3895}, pmid = {26980443}, issn = {1937-9145}, mesh = {Animals ; HEK293 Cells ; Humans ; Mice ; Mice, Nude ; Molecular Imaging/*methods ; Molecular Probes/genetics/*metabolism ; Oxidation-Reduction ; *Transgenes ; }, abstract = {Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation.}, }
@article {pmid26975010, year = {2016}, author = {Dong, A and Wang, Y and Lu, J and Zuo, C}, title = {Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT.}, journal = {Clinical nuclear medicine}, volume = {41}, number = {7}, pages = {543-557}, pmid = {26975010}, issn = {1536-0229}, mesh = {Breast/metabolism ; Breast Diseases/*diagnostic imaging/metabolism ; Breast Neoplasms/diagnostic imaging ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Male ; Positron Emission Tomography Computed Tomography/*methods ; Radiopharmaceuticals/*pharmacokinetics ; }, abstract = {Interpretation of F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging.}, }
@article {pmid26972027, year = {2016}, author = {Mata-Cantero, L and Azkargorta, M and Aillet, F and Xolalpa, W and LaFuente, MJ and Elortza, F and Carvalho, AS and Martin-Plaza, J and Matthiesen, R and Rodriguez, MS}, title = {New insights into host-parasite ubiquitin proteome dynamics in P. falciparum infected red blood cells using a TUBEs-MS approach.}, journal = {Journal of proteomics}, volume = {139}, number = {}, pages = {45-59}, doi = {10.1016/j.jprot.2016.03.004}, pmid = {26972027}, issn = {1876-7737}, mesh = {*Erythrocytes/metabolism/parasitology ; Host-Parasite Interactions/*physiology ; Humans ; Malaria, Falciparum/*metabolism ; Plasmodium falciparum/*physiology ; Proteome/*metabolism ; Protozoan Proteins/*metabolism ; Ubiquitin/*metabolism ; }, abstract = {UNLABELLED: Malaria, caused by Plasmodium falciparum (P. falciparum), ranks as one of the most baleful infectious diseases worldwide. New antimalarial treatments are needed to face existing or emerging drug resistant strains. Protein degradation appears to play a significant role during the asexual intraerythrocytic developmental cycle (IDC) of P. falciparum. Inhibition of the ubiquitin proteasome system (UPS), a major intracellular proteolytic pathway, effectively reduces infection and parasite replication. P. falciparum and erythrocyte UPS coexist during IDC but the nature of their relationship is largely unknown. We used an approach based on Tandem Ubiquitin-Binding Entities (TUBEs) and 1D gel electrophoresis followed by mass spectrometry to identify major components of the TUBEs-associated ubiquitin proteome of both host and parasite during ring, trophozoite and schizont stages. Ring-exported protein (REX1), a P. falciparum protein located in Maurer's clefts and important for parasite nutrient import, was found to reach a maximum level of ubiquitylation in trophozoites stage. The Homo sapiens (H. sapiens) TUBEs associated ubiquitin proteome decreased during the infection, whereas the equivalent P. falciparum TUBEs-associated ubiquitin proteome counterpart increased. Major cellular processes such as DNA repair, replication, stress response, vesicular transport and catabolic events appear to be regulated by ubiquitylation along the IDC P. falciparum infection.<br><br>BIOLOGICAL SIGNIFICANCE: In this work we analyze for the first time the interconnection between Plasmodium and human red blood cells ubiquitin-regulated proteins in the context of infection. We identified a number of human and Plasmodium proteins whose ubiquitylation pattern changes during the asexual infective stage. We demonstrate that ubiquitylation of REX1, a P. falciparum protein located in Maurer's clefts and important for parasite nutrient import, peaks in trophozoites stage. The ubiquitin-proteome from P. falciparum infected red blood cells (iRBCs) revealed a significant host-parasite crosstalk, underlining the importance of ubiquitin-regulated proteolytic activities during the intraerythrocytic developmental cycle (IDC) of P. falciparum. Major cellular processes defined from gene ontology such as DNA repair, replication, stress response, vesicular transport and catabolic events appear to be regulated by ubiquitylation along the IDC P. falciparum infection. Given the importance of ubiquitylation in the development of infectious diseases, this work provides a number of potential drug-target candidates that should be further explored.}, }
@article {pmid26971121, year = {2016}, author = {Sun, H and Li, K and Shen, S}, title = {A study of the role of Notch1 and JAG1 gene methylation in development of breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {33}, number = {4}, pages = {35}, pmid = {26971121}, issn = {1559-131X}, mesh = {Adolescent ; Adult ; Aged ; Breast Diseases/genetics/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; CpG Islands ; DNA Methylation ; Female ; Humans ; Hyperplasia/pathology ; Jagged-1 Protein/*genetics/metabolism ; Lymphatic Metastasis/pathology ; Middle Aged ; Receptor, Notch1/*genetics/metabolism ; Young Adult ; }, abstract = {This study is to explore the roles of gene methylation of Notch1 and JAG1 in development of invasive ductal carcinoma of breast. Quantitative analysis the DNA methylation levels of Notch1 and JAG1 gene by the MassARRAY method in invasive ductal carcinoma of breast (IDC; n = 89), atypical ductal hyperplasia of breast (ADH; n = 11), and ordinary ductal hyperplasia of breast (UDH; n = 20). The expressions of JAG1 and Notch1 protein in four breast tissues were detected by immunohistochemistry SP method. (1) Positive expression rates of Notch1 protein in IDC and DCIS were 88.7 % (79/89) and 70.0 % (14/20), respectively, which were significantly higher than the levels in ADH (36.0 %, 4/11) and UDH (25.0 %, 5/20; P < 0.05). Notch1 protein expression was significant positively correlated with lymph node metastasis, pathological grades, and TNM stages of IDC. (2) Positive expression rates of JAG1 protein in IDC and DCIS were 89.9 % (80/89) and 75.0 % (15/20), respectively, which were significantly higher than those of ADH (45.0 %, 5/11) and UDH (30.0 %, 6/20; P < 0.05). JAG1 protein expression was significant positive correlation with lymph node metastasis, pathological grades and TNM stages of IDC. There is an overall hypomethylation alteration of Notch1 and JAG gene in IDC, with corresponding over-expression of Notch1 and JAG1 protein. This inverse correlation shows that the alteration of protein expression results from hypomethylation oncogene Notch1 and JAG1, and this change may play an important role in occurrence and progression of breast cancer.}, }
@article {pmid26950599, year = {2016}, author = {Stephen, HM and Khoury, RJ and Majmudar, PR and Blaylock, T and Hawkins, K and Salama, MS and Scott, MD and Cosminsky, B and Utreja, NK and Britt, J and Conway, RE}, title = {Epigenetic suppression of neprilysin regulates breast cancer invasion.}, journal = {Oncogenesis}, volume = {5}, number = {3}, pages = {e207}, pmid = {26950599}, issn = {2157-9024}, abstract = {In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer.}, }
@article {pmid26943913, year = {2016}, author = {Takagi, M and Miki, Y and Miyashita, M and Hata, S and Yoda, T and Hirakawa, H and Sagara, Y and Rai, Y and Ohi, Y and Tamaki, K and Ishida, T and Suzuki, T and Ouchi, N and Sasano, H}, title = {Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.}, journal = {Breast cancer research and treatment}, volume = {156}, number = {1}, pages = {45-55}, doi = {10.1007/s10549-016-3739-6}, pmid = {26943913}, issn = {1573-7217}, mesh = {17-Hydroxysteroid Dehydrogenases/metabolism ; Adult ; Aged ; Aged, 80 and over ; Aromatase/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Lobular/genetics/*metabolism/pathology ; Estrogens/*biosynthesis ; Female ; Forkhead Transcription Factors/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Repressor Proteins/genetics ; Sulfatases/metabolism ; Sulfotransferases/metabolism ; }, abstract = {The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.}, }
@article {pmid26939875, year = {2016}, author = {Kweldam, CF and Kümmerlin, IP and Nieboer, D and Verhoef, EI and Steyerberg, EW and van der Kwast, TH and Roobol, MJ and van Leenders, GJ}, title = {Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {29}, number = {6}, pages = {630-636}, pmid = {26939875}, issn = {1530-0285}, mesh = {Adenocarcinoma/mortality/*pathology/therapy ; Aged ; Biopsy ; Chi-Square Distribution ; Disease-Free Survival ; Europe ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Predictive Value of Tests ; Proportional Hazards Models ; Prostatic Neoplasms/mortality/*pathology/therapy ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {Invasive cribriform and intraductal carcinoma in radical prostatectomy specimens have been associated with an adverse clinical outcome. Our objective was to determine the prognostic value of invasive cribriform and intraductal carcinoma in pre-treatment biopsies on time to disease-specific death. We pathologically revised the diagnostic biopsies of 1031 patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993-2000). Ninety percent of all patients (n=923) had received active treatment, whereas 10% (n=108) had been followed by watchful waiting. The median follow-up was 13 years. Patients who either had invasive cribriform growth pattern or intraductal carcinoma were categorized as CR/IDC+. The outcome was disease-specific survival. Relationships with outcome were analyzed using multivariable Cox regression and log-rank analysis. In total, 486 patients had Gleason score 6 (47%) and 545 had ≥7 (53%). The 15-year disease-specific-survival probabilities were 99% in Gleason score 6 (n=486), 94% in CR/IDC- Gleason score ≥7 (n=356) and 67% in CR/IDC+ Gleason score ≥7 (n=189). CR/IDC- Gleason score 3+4=7 patients did not have statistically different survival probabilities from those with Gleason score 6 (P=0.30), while CR/IDC+ Gleason score 3+4=7 patients did (P<0.001). In multivariable analysis, CR/IDC+ status was independently associated with a poorer disease-specific survival (HR 2.6, 95% CI 1.4-4.8, P=0.002). We conclude that CR/IDC+ status in prostate cancer biopsies is associated with a worse disease-specific survival. Our findings indicate that men with biopsy CR/IDC- Gleason score 3+4=7 prostate cancer could be candidates for active surveillance, as these patients have similar survival probabilities to those with Gleason score 6.}, }
@article {pmid26904685, year = {2016}, author = {Wu, Y and Gu, Y and Guo, S and Dai, Q and Zhang, W}, title = {Expressing Status and Correlation of ARID1A and Histone H2B on Breast Cancer.}, journal = {BioMed research international}, volume = {2016}, number = {}, pages = {7593787}, pmid = {26904685}, issn = {2314-6141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Chromatin/genetics ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Histones/*biosynthesis/genetics ; Humans ; Middle Aged ; Mutation ; Nuclear Proteins/*biosynthesis/genetics ; Prognosis ; Transcription Factors/*biosynthesis/genetics ; }, abstract = {ARID1A is one of the important cancer-related genes and regulates transcription of certain genes by altering chromatin structure. Inactivated mutations and decreased expression of ARID1A gene have been reported in several kinds of cancer. Histone H2B is a major component of chromatin and encoded by HIST1H2BE. The goal of the study is to evaluate expressing status of ARID1A and H2B as well as their correlation on breast cancer. Gene expression profiles of ARID1A and H2B on Oncomine database are analyzed. Tissue microarray of breast cancer was used for examination of ARID1A and H2B expression by immunohistochemistry. As a result, the disagreement of ARID1A expression was found, while HIST1H2BE expression is elevated in 4 out of 5 datasets on Oncomine database. There were 15 cases (20%) of breast cancers that were positive for ARID1A. Fifty-eight out of 75 cases of breast cancer (77.3%) were highly expressed for H2B protein and 17 cases (22.7%) were low expressed for H2B protein. All cases with ARID1A expression are overlapped with H2B high expression. Among 15 cases with ARID1A and H2B coexpression, 13 are invasive ductal carcinoma and 2 are mucinous carcinoma. Our results indicate that ARID1A gene may be involved in carcinogenesis of some subtypes of breast cancer.}, }
@article {pmid26897954, year = {2015}, author = {Matsuoka, S and Ishii, T and Miyazawa, S and Mizutani, T and Ito, K and Kamimura, S and Matsumoto, N and Moriyama, M and Takayama, T}, title = {Utility of Partial Splenic Embolization for Hypersplenism using Guglielmi Detachable Coils.}, journal = {Hepato-gastroenterology}, volume = {62}, number = {139}, pages = {683-687}, pmid = {26897954}, issn = {0172-6390}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Embolization, Therapeutic/adverse effects/*instrumentation ; Equipment Design ; Female ; Humans ; Hypersplenism/blood/diagnosis/etiology/*therapy ; Liver Cirrhosis/complications ; Male ; Middle Aged ; Platelet Count ; *Splenic Artery ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: We examined the utility of partial splenic embolization (PSE) using a Guglielmi Detachable Coil (GDC) comparing its safety and therapeutic efficacy with those of conventional metallic coils (IDC).<br><br>METHODOLOGY: The GDC group comprised 8 patients who were subjected to embolization using a GDC in combination with an IDC, and the IDC group comprised 13 patients. Treatment factors were evaluated by the total number of coils used. We assessed the mean C-reactive protein (CRP) and the increased rate of platelet counts, 2 weeks after treatment.<br><br>RESULTS: The rate of increase in platelet counts at 2 weeks after PSE was 2.47 in the GDC group and 3.18 in the IDC group (p = 0.076). The mean CRP levels were 3.0 in the GDC group and 5.9 in the IDC group (p = 0.14). The mean number of coils were 5.3 in the GDC group and 15.3 in the IDC group and this difference was statistically significant (p = 0.0008).<br><br>CONCLUSION: A GDC is excellent in terms of stability and allows the operator to conduct embolization of hypersplenism in an accurate and reliable manner. In summary, use of a GDC for hypersplenism reduced the total number of coils required for successful treatment.}, }
@article {pmid26886800, year = {2016}, author = {Kuhlwilm, M and Gronau, I and Hubisz, MJ and de Filippo, C and Prado-Martinez, J and Kircher, M and Fu, Q and Burbano, HA and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Rudan, P and Brajkovic, D and Kucan, &#x17d; and Gušic, I and Marques-Bonet, T and Andrés, AM and Viola, B and Pääbo, S and Meyer, M and Siepel, A and Castellano, S}, title = {Ancient gene flow from early modern humans into Eastern Neanderthals.}, journal = {Nature}, volume = {530}, number = {7591}, pages = {429-433}, pmid = {26886800}, issn = {1476-4687}, support = {R01 GM102192/GM/NIGMS NIH HHS/United States ; GM102192/GM/NIGMS NIH HHS/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; }, mesh = {Altitude ; Animals ; Bayes Theorem ; Chromosomes, Human, Pair 21/genetics ; Croatia/ethnology ; Gene Flow/*genetics ; Genome, Human/genetics ; Genomics ; Haplotypes/genetics ; Heterozygote ; Humans ; Hybridization, Genetic/genetics ; Neanderthals/*genetics ; Phylogeny ; Population Density ; Siberia ; Spain/ethnology ; Time Factors ; }, abstract = {It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.}, }
@article {pmid26884359, year = {2016}, author = {Petridis, C and Brook, MN and Shah, V and Kohut, K and Gorman, P and Caneppele, M and Levi, D and Papouli, E and Orr, N and Cox, A and Cross, SS and Dos-Santos-Silva, I and Peto, J and Swerdlow, A and Schoemaker, MJ and Bolla, MK and Wang, Q and Dennis, J and Michailidou, K and Benitez, J and González-Neira, A and Tessier, DC and Vincent, D and Li, J and Figueroa, J and Kristensen, V and Borresen-Dale, AL and Soucy, P and Simard, J and Milne, RL and Giles, GG and Margolin, S and Lindblom, A and Brüning, T and Brauch, H and Southey, MC and Hopper, JL and Dörk, T and Bogdanova, NV and Kabisch, M and Hamann, U and Schmutzler, RK and Meindl, A and Brenner, H and Arndt, V and Winqvist, R and Pylkäs, K and Fasching, PA and Beckmann, MW and Lubinski, J and Jakubowska, A and Mulligan, AM and Andrulis, IL and Tollenaar, RA and Devilee, P and Le Marchand, L and Haiman, CA and Mannermaa, A and Kosma, VM and Radice, P and Peterlongo, P and Marme, F and Burwinkel, B and van Deurzen, CH and Hollestelle, A and Miller, N and Kerin, MJ and Lambrechts, D and Floris, G and Wesseling, J and Flyger, H and Bojesen, SE and Yao, S and Ambrosone, CB and Chenevix-Trench, G and Truong, T and Guénel, P and Rudolph, A and Chang-Claude, J and Nevanlinna, H and Blomqvist, C and Czene, K and Brand, JS and Olson, JE and Couch, FJ and Dunning, AM and Hall, P and Easton, DF and Pharoah, PD and Pinder, SE and Schmidt, MK and Tomlinson, I and Roylance, R and García-Closas, M and Sawyer, EJ}, title = {Genetic predisposition to ductal carcinoma in situ of the breast.}, journal = {Breast cancer research : BCR}, volume = {18}, number = {1}, pages = {22}, pmid = {26884359}, issn = {1465-542X}, support = {CA54281/CA/NCI NIH HHS/United States ; CA128978/CA/NCI NIH HHS/United States ; R01 CA176785/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; UM1 CA164920/CA/NCI NIH HHS/United States ; C12292/A11174/CRUK_/Cancer Research UK/United Kingdom ; C5047/A10692/CRUK_/Cancer Research UK/United Kingdom ; R01 CA128978/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; C5047/A15007/CRUK_/Cancer Research UK/United Kingdom ; R01 CA132839/CA/NCI NIH HHS/United States ; U19 CA148065/CA/NCI NIH HHS/United States ; C1281/A12014/CRUK_/Cancer Research UK/United Kingdom ; C8197/A16565/CRUK_/Cancer Research UK/United Kingdom ; 10119/CRUK_/Cancer Research UK/United Kingdom ; 10124/CRUK_/Cancer Research UK/United Kingdom ; CA116201/CA/NCI NIH HHS/United States ; P30 CA016056-32/CA/NCI NIH HHS/United States ; /CAPMC/CIHR/Canada ; CA63464/CA/NCI NIH HHS/United States ; C490/A10124/CRUK_/Cancer Research UK/United Kingdom ; U01 CA116167/CA/NCI NIH HHS/United States ; C5047/A8384/CRUK_/Cancer Research UK/United Kingdom ; C1287/A 10710/CRUK_/Cancer Research UK/United Kingdom ; CA116167/CA/NCI NIH HHS/United States ; CA176785/CA/NCI NIH HHS/United States ; U19 CA148537/CA/NCI NIH HHS/United States ; R01 CA116167/CA/NCI NIH HHS/United States ; C1287/A12014/CRUK_/Cancer Research UK/United Kingdom ; R01 CA063464/CA/NCI NIH HHS/United States ; R01 CA054281/CA/NCI NIH HHS/United States ; U01 CA063464/CA/NCI NIH HHS/United States ; 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; U19 CA148112/CA/NCI NIH HHS/United States ; U01 CA098758/CA/NCI NIH HHS/United States ; CA132839/CA/NCI NIH HHS/United States ; CA098758/CA/NCI NIH HHS/United States ; MC_PC_14105/MRC_/Medical Research Council/United Kingdom ; C1287/A10118/CRUK_/Cancer Research UK/United Kingdom ; U01 CA164973/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cyclin D1/*genetics ; Female ; *Genetic Association Studies ; Genotype ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Proteins/genetics ; Polymorphism, Single Nucleotide ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci.<br><br>METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip.<br><br>RESULTS: Most (67&#xa0;%) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P&#x2009;<&#x2009;5.0x10(-8).<br><br>CONCLUSION: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.}, }
@article {pmid26876209, year = {2016}, author = {Kim, DY and Helfman, DM}, title = {Loss of MLCK leads to disruption of cell-cell adhesion and invasive behavior of breast epithelial cells via increased expression of EGFR and ERK/JNK signaling.}, journal = {Oncogene}, volume = {35}, number = {34}, pages = {4495-4508}, pmid = {26876209}, issn = {1476-5594}, mesh = {Actin Cytoskeleton/metabolism ; Breast/*pathology ; Breast Neoplasms/enzymology/*pathology ; Cell Adhesion ; Cell Aggregation ; Cell Line, Tumor ; Cell Movement ; Cells, Cultured ; Epithelial Cells/pathology ; ErbB Receptors/*physiology ; Female ; Humans ; MAP Kinase Signaling System/*physiology ; Myosin-Light-Chain Kinase/*physiology ; Neoplasm Invasiveness ; RNA, Small Interfering/genetics ; }, abstract = {Myosin light chain kinase (MLCK) expression is downregulated in breast cancer, including invasive ductal carcinoma compared with ductal breast carcinoma in situ and metastatic breast tumors. However, little is known about how loss of MLCK expression contributes to tumor progression. MLCK is a component of the actin cytoskeleton and its known role is the phosphorylation of the regulatory light chain of myosin II. To gain insights into the role of MLCK in breast cancer, we perturbed its function using small interfering RNA (siRNA) or pharmacological inhibition in untransformed breast epithelial cells (MCF10A). Loss of MLCK by siRNAs led to increased cell migration and invasion, disruption of cell-cell adhesions and enhanced formation of focal adhesions at the leading edge of migratory cells. In addition, downregulation of MLCK cooperated with HER2 in MCF10A cells to promote cell migration and invasion and low levels of MLCK is associated with a poor prognosis in HER2-positive breast cancer patients. Associated with these altered migratory behaviors were increased expression of epidermal growth factor receptor and activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways in MLCK downregulated MCF10A cells. By contrast, inhibition of the kinase function of MLCK using pharmacological agents inhibited cell migration and invasion, and did not affect cellular adhesions. Our results show that loss of MLCK contributes to the migratory properties of epithelial cells resulting from changes in cell-cell and cell-matrix adhesions, and increased epidermal growth factor receptor signaling. These findings suggest that decreased expression of MLCK may have a critical role during tumor progression by facilitating the metastatic potential of tumor cells.}, }
@article {pmid26864079, year = {2016}, author = {Gulvin, J and Aboulafia, DM}, title = {Squamous Cell Cancer of Unknown Primary and Primary Breast Cancer in an HIV-Infected Woman: The Importance of Cancer Screening for People Living with HIV/AIDS.}, journal = {Journal of the International Association of Providers of AIDS Care}, volume = {15}, number = {3}, pages = {194-200}, doi = {10.1177/2325957416629550}, pmid = {26864079}, issn = {2325-9574}, mesh = {*Breast Neoplasms/complications/diagnostic imaging ; *Carcinoma, Squamous Cell/complications/diagnostic imaging/secondary ; Early Detection of Cancer ; Female ; Groin/diagnostic imaging/pathology ; HIV Infections/*complications ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Middle Aged ; Papillomavirus Infections ; }, abstract = {People living with HIV/AIDS (PLWHA) are surviving longer, with an increased risk of cancer. Cancer screening strategies in PLWHA are lacking. We describe the case of a woman with a history of AIDS, who had a nondetectable viral load on treatment. She is an activist, promoting HIV care, but had not undergone routine screening for breast, cervical, or colonic neoplasia. She presented with a left groin mass, which on biopsy proved to be a p16 immuno-histochemical positive squamous cell carcinoma. Anal and cervicovaginal examinations did not show invasive cancer, although high-resolution anoscopy identified high-grade anal dysplasia. A mammogram followed by magnetic resonance imaging showed invasive ductal carcinoma. Her breast cancer was treated with lumpectomy, adjuvant brachytherapy and chemotherapy. The left groin tumor was treated with chemo-radiation. Herein, we also review medical literature concerning anal, cervical, breast, colorectal, and lung cancer screening for PLWHA, which is important for our aging population of PLWHA.}, }
@article {pmid26858037, year = {2016}, author = {Zhu, L and Mok, S and Imwong, M and Jaidee, A and Russell, B and Nosten, F and Day, NP and White, NJ and Preiser, PR and Bozdech, Z}, title = {New insights into the Plasmodium vivax transcriptome using RNA-Seq.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {20498}, pmid = {26858037}, issn = {2045-2322}, support = {093956//Wellcome Trust/United Kingdom ; }, mesh = {Chromosomes/genetics/metabolism ; *High-Throughput Nucleotide Sequencing ; Humans ; Plasmodium vivax/*genetics/metabolism ; RNA, Protozoan/biosynthesis/*genetics ; Transcriptome/*physiology ; }, abstract = {Historically seen as a benign disease, it is now becoming clear that Plasmodium vivax can cause significant morbidity. Effective control strategies targeting P. vivax malaria is hindered by our limited understanding of vivax biology. Here we established the P. vivax transcriptome of the Intraerythrocytic Developmental Cycle (IDC) of two clinical isolates in high resolution by Illumina HiSeq platform. The detailed map of transcriptome generates new insights into regulatory mechanisms of individual genes and reveals their intimate relationship with specific biological functions. A transcriptional hotspot of vir genes observed on chromosome 2 suggests a potential active site modulating immune evasion of the Plasmodium parasite across patients. Compared to other eukaryotes, P. vivax genes tend to have unusually long 5' untranslated regions and also present multiple transcription start sites. In contrast, alternative splicing is rare in P. vivax but its association with the late schizont stage suggests some of its significance for gene function. The newly identified transcripts, including up to 179 vir like genes and 3018 noncoding RNAs suggest an important role of these gene/transcript classes in strain specific transcriptional regulation.}, }
@article {pmid26843058, year = {2016}, author = {Pare, R and Shin, JS and Lee, CS}, title = {Increased expression of senescence markers p14(ARF) and p16(INK4a) in breast cancer is associated with an increased risk of disease recurrence and poor survival outcome.}, journal = {Histopathology}, volume = {69}, number = {3}, pages = {479-491}, doi = {10.1111/his.12948}, pmid = {26843058}, issn = {1365-2559}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; *Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p16/analysis/*biosynthesis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local/mortality/pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Tissue Array Analysis ; Tumor Suppressor Protein p14ARF/analysis/*biosynthesis ; }, abstract = {AIMS: Breast cancer is a hormonally driven disease. Cellular senescence is an age-related irreversible cell cycle arrest at the G1 phase upon induction. The aim of this study was to characterize the expression patterns of the senescence markers p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) during breast cancer progression in a large patient cohort.<br><br>METHODS AND RESULTS: We conducted a retrospective study of 1080 patients with invasive ductal carcinoma, no special type, over an 11-year period. We performed immunohistochemical staining on tissue microarrays that included normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma tissue from each patient. Invasive ductal carcinomas showed higher expression of p14(ARF) and p16(INK4a) but lower expression of p21(WAF1/Cip1) than non-malignant tissues. There were significant correlations of normal, benign, preinvasive and malignant tissues with p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) expression (P < 0.05). Univariate comparison showed a correlation between high p16(INK4a) expression and poor survival (P = 0.000) and an increased risk of relapse (P = 0.000), whereas high p14(ARF) expression correlated only with an increased risk of relapse (P = 0.038). Multivariate analysis showed p16(INK4a) to be an important prognostic factor for overall survival (P = 0.011) and disease-free survival (P = 0.004), with p14(ARF) also being a significant prognostic factor for disease-free survival (P = 0.043). Moreover, patients showing both high p16(INK4a) expression and and high p14(ARF) expression had an adjusted three-fold increased risk of disease recurrence (P < 0.05) and a two-fold increased risk of all-cause-related death (P < 0.05).<br><br>CONCLUSIONS: These finding suggest p16(INK4a) expression and p14(ARF) expression may play an important role in the progression of proliferative breast tissue to invasive cancer, and may be useful as prognostic factors.}, }
@article {pmid26838218, year = {2016}, author = {Moazzezy, N and Ebrahimi, F and Sisakht, MM and Yahyazadeh, H and Bouzari, S and Oloomi, M}, title = {Relationship between erb-B2 mRNA Expression in Blood and Tissue of Invasive Ductal Carcinoma Breast Cancer Patients and Clinicopathological Characteristics of the Tumors.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {1}, pages = {249-254}, doi = {10.7314/apjcp.2016.17.1.249}, pmid = {26838218}, issn = {2476-762X}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/metabolism ; Breast Neoplasms/blood/*genetics/metabolism/*pathology ; Carcinoma, Ductal/blood/*genetics/metabolism/*pathology ; Cell Line, Tumor ; Female ; Humans ; Lymph Nodes/metabolism/pathology ; Middle Aged ; Prognosis ; RNA, Messenger/blood/*genetics/metabolism ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Young Adult ; }, abstract = {Molecular detection methods such as RT-PCR for detecting breast cancer-associated gene expression in the peripheral blood have the potential to modify breast cancer (BC) staging and therapy. In this regard, we evaluated the potential of erb-B2 molecular marker in BC detection and analyzed the expression of erb-B2 mRNA in the peripheral blood and fresh tissue samples of 50 pretreated female BC patients and 50 healthy females by reverse transcription-PCR (RT-PCR) method. We also assessed the correlation of erb-B2 mRNA marker positivity in peripheral blood and tumor tissue samples with clinical and pathological factors in BC patients in order to evaluate its prognostic value. It was shown that there is a significant difference between healthy females and BC patients with expression of the erb-B2 molecular marker (p<0.01). A significant difference between the expression of erb-B2 in the peripheral blood and tissue samples of BC patients (p<0.01) and the frequency of circulating erb-B2 mRNA expression in peripheral blood and in tissue was detected by RT-PCR. No correlation was found between erb-B2 mRNA expression in blood or tumor tissue samples and lymph node, tumor grade, tumor stage, tumor size, patient's age, ki67, estrogen receptor (ER), progesterone receptor (PGR), P53, and HER-2 status. However, in a small subset of 31 BC patients we found that expression of erb-B2 in peripheral blood or in both peripheral blood and tumor tissue was directly correlated with lympho-vascular invasion and perineural invasion as poor prognostic features. The highest rates of erb-B2 expression in peripheral blood or tumor tissue were in the ER and PR negative and HER-2 positive group. This study suggests that the application of the RT-PCR and immunohistochemical methods for erb-B2 molecular marker detection would provide a higher detection rate, especially in early stage BC.}, }
@article {pmid26829374, year = {2016}, author = {Annacontini, L and Ciancio, F and Parisi, D and Innocenti, A and Portincasa, A}, title = {Management of nipple-areolar complex complications in skin-sparing mastectomy with prosthetic reconstruction A case report.}, journal = {Annali italiani di chirurgia}, volume = {87}, number = {ePub}, pages = {}, pmid = {26829374}, issn = {2239-253X}, mesh = {Breast Neoplasms/pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Female ; Humans ; Mammaplasty/*adverse effects/methods ; *Mastectomy, Subcutaneous/adverse effects/methods ; Middle Aged ; *Negative-Pressure Wound Therapy/methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Nipples/*blood supply ; Prostheses and Implants ; Surgical Wound/*etiology/*therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION AND OBJECCTIVES: Venous congestion of the NAC (Nipple-Areola Complex) is not an uncommon complication of Skin-Reducing Mastectomy (SRM). The correct and prompt evaluation of the NAC's vitality in the first hours after surgery is important for the survival of the same, in fact the possibility of early intervention allows avoiding the use of invasive and radicals techniques to the advantage of simpler rapid procedures.<br><br>MATERIALS AND METHODS: DM, 57yr, multiple invasive ductal carcinoma of the right breast, underwent a SRM and immediate reconstruction with implant in August 2014 In the immediate post-operative appeared a venous stasis of the NAC. Treatment started with Negative Pressure Wound Therapy (NWPT) through VAC-Systems to 75 mmHg.<br><br>RESULTS: The use of the VAC-Therapy was in total 12 days and allowed the partial rescue of the NAC (85%). the vacuum pump is put into a portable bag so the patient's mobility is not limited.<br><br>DISCUSSION: NWPT permitted a rapid resolution of NAC's complication in SRM in order to guarantee an optimal timing for the start of adjuvant chemotherapy. The VAC-Therapy is a cost effective and simple to use in cases of suffering venous NAC in patients undergoing breast surgery.<br><br>KEY WORDS: NAC, NWPT, Skin-Reducing Mastectomy, VAC-Therapy.}, }
@article {pmid26826418, year = {2016}, author = {Mardekian, SK and Bombonati, A and Palazzo, JP}, title = {Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions.}, journal = {Human pathology}, volume = {49}, number = {}, pages = {114-123}, doi = {10.1016/j.humpath.2015.11.003}, pmid = {26826418}, issn = {1532-8392}, mesh = {Animals ; Biomarkers, Tumor/analysis/*genetics ; Biopsy ; Breast Neoplasms/chemistry/*genetics/pathology/therapy ; Carcinoma/chemistry/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*genetics/pathology/therapy ; Disease Progression ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Mastectomy ; Molecular Diagnostic Techniques ; Neoplasm Recurrence, Local ; Phenotype ; Predictive Value of Tests ; Reproducibility of Results ; Treatment Outcome ; }, abstract = {Ductal carcinoma in situ (DCIS) of the breast is a lesion characterized by significant heterogeneity, in terms of morphology, immunohistochemical staining, molecular signatures, and clinical expression. For some patients, surgical excision provides adequate treatment, but a subset of patients will experience recurrence of DCIS or progression to invasive ductal carcinoma (IDC). Recent years have seen extensive research aimed at identifying the molecular events that characterize the transition from normal epithelium to DCIS and IDC. Tumor epithelial cells, myoepithelial cells, and stromal cells undergo alterations in gene expression, which are most important in the early stages of breast carcinogenesis. Epigenetic modifications, such as DNA methylation, together with microRNA alterations, play a major role in these genetic events. In addition, tumor proliferation and invasion is facilitated by the lesional microenvironment, which includes stromal fibroblasts and macrophages that secrete growth factors and angiogenesis-promoting substances. Characterization of DCIS on a molecular level may better account for the heterogeneity of these lesions and how this manifests as differences in patient outcome and response to therapy. Molecular assays originally developed for assessing likelihood of recurrence in IDC are recently being applied to DCIS, with promising results. In the future, the classification of DCIS will likely incorporate molecular findings along with histologic and immunohistochemical features, allowing for personalized prognostic information and therapeutic options for patients with DCIS. This review summarizes current data regarding the molecular characterization of DCIS and discusses the potential clinical relevance.}, }
@article {pmid26823905, year = {2015}, author = {Huo, Z and Gao, Y and Yu, Z and Zuo, W and Zhang, Y}, title = {Metastasis of breast cancer to renal cancer: report of a rare case.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {11}, pages = {15417-15421}, pmid = {26823905}, issn = {1936-2625}, mesh = {Adult ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*secondary/surgery ; Carcinoma, Renal Cell/chemistry/*pathology ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; Kidney Neoplasms/chemistry/*pathology/secondary ; Mastectomy, Modified Radical ; Neoplasms, Multiple Primary/chemistry/*pathology/surgery ; Nephrectomy ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {Tumor-to-tumor metastasis (TTM) is a rare phenomenon. We present a case of an invasive ductal carcinoma (IDC) of the breast metastasizing to a clear cell renal cell carcinoma (RCC). Breast cancer (BC) metastasis to the RCC is rarely reported, especially in resected kidney tumor. In several cases reported, IDC was the exclusively histologic type of BC metastasized to RCC. It seems that the different molecular type of IDC doesn't affect the metastatic tendencies to RCC. TTM was an indicator of diffuse disease. For any patient with a history of breast cancer, especially with multi-organs metastasis, resection of kidney tumor should be carefully considered.}, }
@article {pmid26813772, year = {2016}, author = {Saita, C and Goto, R and Aruga, T and Idera, N and Honda, Y and Horiguchi, K and Miyamoto, H and Horiguchi, S and Yamashita, T and Kuroi, K}, title = {Invasive papillary carcinoma treated with neoadjuvant endocrine therapy in which pathological complete response was achieved.}, journal = {BMC research notes}, volume = {9}, number = {}, pages = {46}, pmid = {26813772}, issn = {1756-0500}, mesh = {Aged, 80 and over ; Antineoplastic Agents, Hormonal/*therapeutic use ; Aromatase Inhibitors/*therapeutic use ; Breast Neoplasms/genetics/metabolism/pathology/*therapy ; Carcinoma, Papillary/genetics/metabolism/pathology/*therapy ; Female ; Gene Expression ; Humans ; Letrozole ; Neoadjuvant Therapy/methods ; Nitriles/*therapeutic use ; Postmenopause ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Treatment Outcome ; Triazoles/*therapeutic use ; }, abstract = {BACKGROUND: Invasive papillary carcinoma is a rare type of invasive ductal carcinoma. Neoadjuvant endocrine therapy is now considered as an optional therapy for postmenopausal women with hormone receptor-positive breast cancers, including invasive papillary carcinoma.<br><br>CASE PRESENTATION: We discuss the case of an 83-year-old postmenopausal Japanese female with hormone receptor-positive invasive papillary carcinoma who started treatment with an aromatase inhibitor and achieved pathological complete response after 12 months of endocrine treatment.<br><br>CONCLUSION: Appropriate drugs and durations of neoadjuvant endocrine treatment have yet to be established. Continuing therapy with an aromatase inhibitor until the best clinical response is achieved may represent one of the best strategies in neoadjuvant endocrine therapy.}, }
@article {pmid26807730, year = {2016}, author = {Korsten, H and Ziel-van der Made, AC and van Weerden, WM and van der Kwast, T and Trapman, J and Van Duijn, PW}, title = {Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice.}, journal = {PloS one}, volume = {11}, number = {1}, pages = {e0147500}, pmid = {26807730}, issn = {1932-6203}, mesh = {Adenocarcinoma/chemistry/genetics/pathology ; Animals ; Apoptosis/genetics ; Biomarkers ; Biomarkers, Tumor ; Cadherins/analysis ; Carcinoma/chemistry/*genetics/pathology ; Carcinosarcoma/chemistry/genetics/pathology ; Cellular Senescence/genetics ; Disease Progression ; Epithelial Cells/chemistry ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Inflammation/genetics ; Keratins/analysis ; Male ; Mesoderm/chemistry ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Neoplasm Proteins/analysis ; Neovascularization, Pathologic/genetics/pathology ; PTEN Phosphohydrolase/*deficiency ; Prostatic Hyperplasia/genetics/pathology ; Prostatic Neoplasms/chemistry/classification/*genetics/pathology ; RNA, Messenger/biosynthesis/genetics ; RNA, Neoplasm/biosynthesis/genetics ; Stromal Cells/chemistry ; }, abstract = {Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m) developed at older age (>10m) into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC), adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK), and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7-8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1) and tumor class 2 (TC2). TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E-Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma/intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well-defined PSA-Cre;Pten-loxP/loxP prostate tumor model, histopathological, molecular and biological heterogeneity occurred during later stages of tumor development.}, }
@article {pmid26805359, year = {2015}, author = {Noguchi, K and Tomimaru, Y and Eguchi, H and Ogawa, H and Yamada, D and Tomokuni, A and Noda, T and Asaoka, T and Wada, H and Kawamoto, K and Goto, K and Marubashi, S and Nagano, H and Mori, M and Doki, Y}, title = {[Three Resected Cases of Metachronous Pancreatic Cancer Successfully Treated with Repeated Pancreatectomy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {42}, number = {12}, pages = {2346-2348}, pmid = {26805359}, issn = {0385-0684}, mesh = {Aged ; Biopsy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/drug therapy/secondary ; Male ; Middle Aged ; Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; Recurrence ; }, abstract = {Repeated pancreatectomy for metachronous pancreatic cancer has rarely been reported. We report 3 cases with metachronous pancreatic ductal carcinoma that developed after pancreatectomy for the first pancreatic cancer. They were successfully resected by removal of the remnant pancreas. In all 3 cases, the cancers in the remnant pancreas were treated with repeated pancreatectomy. The histological margin of the first pancreatic resection was cancer-free in all the cases. Furthermore, the second cancer tissue contained carcinoma lesions in situ adjacent to invasive ductal carcinoma. Based on these findings, the 3 patients were diagnosed with metachronous pancreatic cancers.}, }
@article {pmid26805179, year = {2015}, author = {Kakimoto, M and Nakata, T and Imaizumi, K and Hirano, T and Murata, T and Okuno, K and Hoshino, M and Matsuyama, T and Goto, H and Koshiishi, H and Yoshimura, T and Osanai, T and Suzuki, K}, title = {[Subclavian Artery Hemorrhage Related to Everolimus in a Patient with Recurrent Breast Cancer--A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {42}, number = {12}, pages = {1806-1808}, pmid = {26805179}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Everolimus/administration &amp; dosage/*adverse effects ; Fatal Outcome ; Female ; Hemorrhage/*chemically induced ; Humans ; Mastectomy, Segmental ; Middle Aged ; Recurrence ; *Subclavian Artery ; }, abstract = {A 53-year-old woman underwent breast-conserving surgery for right breast cancer (invasive ductal carcinoma, T1cN0M0, ly+, stage ⅠA, ER+, PR+, HER2-) 5 years previously. During treatment with tamoxifen, massive recurrence in the axillary lymph nodes was found. First- through fourth-line chemotherapy were tried, but they all failed. Everolimus and exemestane were administered, resulting in rapid shrinking of the tumor, but the patient developed sudden severe bleeding from the subclavian artery. Hemostasis was achieved with artery stenting. The patient also developed a thoracic duct-cutaneous fistula. The patient died from tumor regrowth 6.5 months after her first everolimus treatment. Treating tumors involving major vessels with everolimus can cause severe bleeding after rapid shrinking of the tumor.}, }
@article {pmid26805172, year = {2015}, author = {Sato, Y and Okishiro, M and Ohneda, Y and Motoyama, Y and Ishida, T and Morimoto, Y and Kusama, H and Matsushita, K and Hashimoto, T and Kimura, K and Naito, A and Murakami, K and Katsura, Y and Nitta, K and Ohmura, Y and Kagawa, Y and Takeno, A and Sakisaka, H and Taniguchi, H and Egawa, C and Takeda, Y and Kato, T and Tamura, S and Takatsuka, Y and Goto, T and Nagano, T and Nakatsuka, S}, title = {[A Case of Peritoneal Metastasis of Breast Cancer Diagnosed by Laparoscopic-Assisted Right Hemicolectomy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {42}, number = {12}, pages = {1785-1787}, pmid = {26805172}, issn = {0385-0684}, mesh = {Adenocarcinoma/*surgery ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy/*pathology/*surgery ; Carcinoma, Ductal/drug therapy/*surgery ; Colectomy ; Female ; Humans ; Laparoscopy ; Peritoneal Neoplasms/*secondary/*surgery ; Recurrence ; Tamoxifen/therapeutic use ; Tegafur/therapeutic use ; Uracil/therapeutic use ; }, abstract = {The patient was an 86-year-old woman. She underwent right breast-conserving surgery and sentinel lymph node biopsy for breast cancer in August 2006. The pathological diagnosis was invasive ductal carcinoma, T1N0M0, Stage Ⅰ, ER (+), PgR (-), HER2 (-). She was treated with tamoxifen for 5 years as adjuvant therapy and showed no signs of recurrence. In November 2014, CA15-3 was elevated and an accumulation of FDG in the right paracolic sulcus was observed on PET-CT. Peritoneal metastasis of breast cancer was suspected, and an operation was performed for a definitive diagnosis. During the operation, the tumor was seen on the paracolic sulcus, and laparoscopic-assisted right hemicolectomy was performed. A poorly differentiated adenocarcinoma was diagnosed by pathological examination, and immunostaining results were as follows: CK7(+), CK20(-), mammaglobin (-), GCDFP-15 (-), ER (-), PgR (-), and HER2 (-). Because there was no original lesion other than the breast cancer, the tumor was diagnosed as a metastasis of breast cancer. The frequency of peritoneal metastasis of breast cancer is low. In this case, pathological diagnosis was necessary for a definitive diagnosis. A change of subtype was also confirmed, and the treatment strategy was decided appropriately. Surgical resection should be considered for peritoneal metastasis of breast cancer when the operation can be performed safely.}, }
@article {pmid26805170, year = {2015}, author = {Takaoka, A and Nakagawa, T and Ogawa, N and Hayashi, M and Park, S and Iseki, H and Bei, Y}, title = {[HER2-Positive T1a Breast Cancer Metastatic to the Liver and Brain in a Patient Who Died Four Years and Three Months after Mastectomy--A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {42}, number = {12}, pages = {1779-1781}, pmid = {26805170}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary/*therapy ; Breast Neoplasms/chemistry/pathology/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/secondary/*therapy ; Mastectomy ; Middle Aged ; Receptor, ErbB-2/analysis ; }, abstract = {The prognosis of patients with T1a breast cancer is generally good, with a 5-year overall survival rate of 95%. However, HER2 overexpression is a risk factor for recurrence. A 46-year-old woman with left breast cancer underwent a total breast resection. The resected specimen showed invasive ductal carcinoma (T1a, NX, MX, g, ly0, v0, ER [-], PgR [-], HER2 [3+], Ki-67 20%). The patient did not receive adjuvant chemotherapy based on treatment guidelines. Nine months after the mastectomy, multiple liver metastases and severe acute hepatic insufficiency were found. The patient received chemotherapy with trastuzumab and paclitaxel, and a complete response was observed with disappearance of the liver metastases. One year and 11 months after the mastectomy, multiple brain metastases appeared. The patient received whole brain radiation therapy, Gamma Knife radiosurgery, and Cyber Knife radiosurgery. However, the brain metastasis could not be controlled, and the patient died 4 years and 3 months after mastectomy. HER2 positive T1a breast cancer should be observed carefully, and treatment with trastuzumab should be considered.}, }
@article {pmid26805079, year = {2015}, author = {Kanada, Y and Matsuzaki, H and Kobayashi, H and Suzuki, K and Sawada, H and Senba, Y and Yoshioka, T and Note, H and Sato, Y and Miyazaki, A and Natsume, T and Tanaka, H and Maruyama, T}, title = {[A Case of Locally-Advanced Breast Cancer with Liver Metastasis, Treated with Mastectomy of the Primary Tumor after Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {42}, number = {12}, pages = {1509-1511}, pmid = {26805079}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Cyclophosphamide/administration &amp; dosage ; Epirubicin/administration &amp; dosage ; Estrogen Replacement Therapy ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Mastectomy ; Neoplasm Staging ; Tamoxifen/therapeutic use ; }, abstract = {The patient was a 39-year-old woman who was referred to our hospital with suspicion of locally-advanced breast cancer. After several tests, she received a diagnosis of cT4bN1M1 (liver), Stage Ⅳbreast cancer. The liver metastasis was located in S4, and was 1 cm in size. Core needle biopsy was performed on the breast tumor; the pathological diagnosis was invasive ductal carcinoma (scirrhous carcinoma), nuclear Grade (NG) 3, and HER2-positive. She received epirubicin plus cyclophosphamide (EC) followed by docetaxel (DOC) plus pertuzumab (PER) plus trastuzumab (HER). After chemotherapy, the liver metastasis and axillary lymph node metastases had disappeared on imaging findings, showing a complete response (CR), but the primary breast tumor remained, showing a partial response (PR). She underwent mastectomy and axillary lymph node dissection for local control. After surgery, no metastases including liver metastases were seen on CT. The patient is currently receiving tamoxifen and anti-HER2 therapy.}, }
@article {pmid26804549, year = {2016}, author = {Fardmanesh, H and Shekari, M and Movafagh, A and Alizadeh Shargh, S and Poursadegh Zonouzi, AA and Shakerizadeh, S and Poursadegh Zonouzi, A and Hosseinzadeh, A}, title = {Upregulation of the double-stranded RNA binding protein DGCR8 in invasive ductal breast carcinoma.}, journal = {Gene}, volume = {581}, number = {2}, pages = {146-151}, doi = {10.1016/j.gene.2016.01.033}, pmid = {26804549}, issn = {1879-0038}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; RNA-Binding Proteins/*genetics ; *Up-Regulation ; }, abstract = {High-throughput experimental studies have indicated that the miRNAome is globally downregulated in various types of malignancy, and dysregulation of miRNAs processing component(s) is one possible mechanism for this phenomenon. Despite the progression in identifying cellular functions of Digeorge Syndrome Critical Region 8 (DGCR8) in miRNAs biogenesis, the role of altered expression of DGCR8 in the pathogenesis of invasive ductal breast carcinoma (IDC) has not yet been fully investigated. The objective of the present study was to evaluate DGCR8 mRNA expression in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissues using quantitative real-time PCR and to assess the value of clinicopathological parameters on its expression. Our findings revealed that DGCR8 mRNA expression is upregulated in more than two-thirds of the cancerous specimens (68.66%) when compared to adjacent non-neoplastic tissue. This difference is statistically significant (P<0.05). We found that DGCR8 mRNA levels were increased in the high-grade and metastatic compared with those of both low-grade and non-metastatic. We demonstrated that there is not significant correlation between DGCR8 mRNA expression levels and clinicopathological parameters. In conclusion, our study suggested that upregulation of DGCR8 may be involved in tumorigenesis and aggressiveness of IDC and may serve as future therapeutic target.}, }
@article {pmid26775637, year = {2016}, author = {Ghandour, RA and Giroud, M and Vegiopoulos, A and Herzig, S and Ailhaud, G and Amri, EZ and Pisani, DF}, title = {IP-receptor and PPARs trigger the conversion of human white to brite adipocyte induced by carbaprostacyclin.}, journal = {Biochimica et biophysica acta}, volume = {1861}, number = {4}, pages = {285-293}, doi = {10.1016/j.bbalip.2016.01.007}, pmid = {26775637}, issn = {0006-3002}, mesh = {Adipocytes, Brown/*drug effects/metabolism ; Adipocytes, White/*drug effects/metabolism ; Adipogenesis/*drug effects ; Anti-Obesity Agents/*pharmacology ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dose-Response Relationship, Drug ; Energy Metabolism/drug effects ; Enzyme Activation ; Epoprostenol/*analogs &amp; derivatives/pharmacology ; Humans ; Infant ; Ion Channels/genetics/metabolism ; Male ; Mitochondrial Proteins/genetics/metabolism ; PPAR alpha/*agonists/genetics/metabolism ; PPAR gamma/*agonists/metabolism ; Phenotype ; RNA Interference ; Receptors, Epoprostenol ; Receptors, Prostaglandin/*agonists/metabolism ; Signal Transduction/drug effects ; Thermogenesis/drug effects ; Time Factors ; Transfection ; Uncoupling Protein 1 ; }, abstract = {Brite adipocytes recently discovered in humans are of considerable importance in energy expenditure by converting energy excess into heat. This property could be useful in the treatment of obesity, and nutritional aspects are relevant to this important issue. Using hMADS cells as a human cell model which undergoes a white to a brite adipocyte conversion, we had shown previously that arachidonic acid, the major metabolite of the essential nutrient Ω6-linoleic acid, plays a major role in this process. Its metabolites PGE2 and PGF2 alpha inhibit this process via a calcium-dependent pathway, whereas in contrast carbaprostacyclin (cPGI2), a stable analog of prostacyclin, activates white to brite adipocyte conversion. Herein, we show that cPGI2 generates via its cognate cell-surface receptor IP-R, a cyclic AMP-signaling pathway involving PKA activity which in turn induces the expression of UCP1. In addition, cPGI2 activates the pathway of nuclear receptors of the PPAR family, i.e. PPARα and PPARγ, which act separately from IP-R to up-regulate the expression of key genes involved in the function of brite adipocytes. Thus dual pathways are playing in concert for the occurrence of a browning process of human white adipocytes. These results make prostacyclin analogs as a new class of interesting molecules to treat obesity and associated diseases.}, }
@article {pmid26775353, year = {2015}, author = {Qin, XJ and Gao, ZG and Huan, JL and Pan, XF and Zhu, L}, title = {Protein kinase D1 inhibits breast cancer cell invasion via regulating matrix metalloproteinase expression.}, journal = {European journal of gynaecological oncology}, volume = {36}, number = {6}, pages = {690-693}, pmid = {26775353}, issn = {0392-2936}, mesh = {Breast Neoplasms/enzymology/*pathology ; Cell Line, Tumor ; Female ; Humans ; Matrix Metalloproteinase 2/analysis ; Matrix Metalloproteinase 9/analysis ; Neoplasm Invasiveness ; Protein Kinase C/genetics/*physiology ; }, abstract = {PURPOSE: This study aimed to explore the role of protein kinase D1 (PKD1) in breast cancer invasion.<br><br>MATERIALS AND METHODS: The relative expression of PKD1mRNA and protein in human invasive breast cancer tissue samples and normal samples, as well as breast cancer cell lines, were detected. Constitutively-active PKD1 and PKD1 specific shRNA were expressed in the MD-MB-231 and MCF-7 cells, respectively. The role of PKD1 in the invasive behavior of breast cancer cell line was evaluated by matrix metalloproteinase (MMP) expression.<br><br>RESULTS: The results showed that PKD1, as a serine/threonine kinase, is downregulated significantly in invasive ductal carcinoma and metastatic invasive ductal carcinoma tissue than the normal tissue and the low expression of PKD1 is also found in breast cancer cell line MD-MB-231. The MMP2 and MMP9 expression in PKD1 constitutively-active MD-MB-231 cells and MCF-7 knockdown cells were decreased and increased respectively.<br><br>CONCLUSION: The authors confirmed that PKD1 was downregulated in invasive breast cancer. PKD1 can negatively regulate the MMP expression and may serve as a potential therapeutic target.}, }
@article {pmid26774154, year = {2016}, author = {Sobic Saranovic, D and Stojiljkovic, M and Susnjar, S and Odalovic, S and Artiko, V and Pavlovic, S and Grozdic-Milojevic, I and Obradovic, V}, title = {Metabolic activity of breast cancer metastatic lesions on positron emission tomography/computed tomography: comparison with histological and biological characteristics of primary tumor.}, journal = {Neoplasma}, volume = {63}, number = {2}, pages = {313-321}, doi = {10.4149/219_150813N440}, pmid = {26774154}, issn = {0028-2685}, mesh = {Bone Neoplasms/metabolism/secondary ; Breast Neoplasms/*diagnostic imaging/*pathology ; Energy Metabolism/*physiology ; Female ; Fluorodeoxyglucose F18/*metabolism ; Glucose/*metabolism ; Humans ; Ki-67 Antigen/metabolism ; Liver Neoplasms/metabolism/secondary ; Lymph Nodes/metabolism ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Multimodal Imaging ; *Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals/*metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Higher intensity of FDG uptake on PET/CT in primary tumor is seen in patients with IDC compared to ILC, also in high grade tumours, tumours with negative ER and higher Ki67 values, while data are inconsistent in case of relation between primary tumor's PgR and HER2 expression with its metabolic activity levels. On account of the lack of studies that include research of breast cancer metastatic lesion metabolism level and its relation to tumor histology and biology, our goal was to investigate the association of metastatic lesions' glucose metabolism level on PET/CT with different histological and biological characteristics of primary tumor. In a total number of N=100 patients, highest SUVmax values for each patient were used in testing difference between metastatic metabolic activity in patients with different tumor histology, grade, ER, PgR and HER2 status, subtype, as well in testing relation of Ki67 index to metastasis' metabolism level. In testing difference between histological types of breast cancer, SUVmax values were also compared separately for each specific anatomical site (regional and distant lymph nodes, bones and liver). No difference was found regarding metastatic SUVmax values in patients with primary IDC (n=55, median SUVmax 9.70) and ILC (n=34, median SUVmax 7.20) independently of anatomic site, and for each of analysed sites separately. No difference was found as well between SUVmax detected in metastasis in patients with different grade (grade II: n=58, median SUVmax 7.70; grade III: n=12, median SUVmax 10.20), ER (59 positive, median SUVmax 8.50; 22 negative, median SUVmax 8.05), PgR (55 positive, median SUVmax 8.50; 23 negative, median SUVmax 7.80), and HER2 (14 positive, median SUVmax 6.84; 51 negative, median SUVmax 8.63) expression in primary tumor, and between patients with different tumor subtype. Ki67 was also not associated with tumor metastatic SUVmax values (n=11, rs = -0.21, p=0.53). We conclude that there is no association of primary breast cancer histological type, grade, ER, PgR, HER2 and Ki67 expression with metabolic activity in metastasis detected on PET/CT.}, }
@article {pmid26769139, year = {2016}, author = {Thompson, E and Taube, JM and Elwood, H and Sharma, R and Meeker, A and Warzecha, HN and Argani, P and Cimino-Mathews, A and Emens, LA}, title = {The immune microenvironment of breast ductal carcinoma in situ.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {29}, number = {3}, pages = {249-258}, pmid = {26769139}, issn = {1530-0285}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*immunology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*immunology/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Tissue Array Analysis ; Tumor Microenvironment/*immunology ; Young Adult ; }, abstract = {The host immune response has a key role in breast cancer progression and response to therapy. However, relative to primary invasive breast cancers, the immune milieu of breast ductal carcinoma in situ (DCIS) is less understood. Here, we profile tumor infiltrating lymphocytes and expression of the immune checkpoint ligand programmed death ligand 1 (PD-L1) in 27 cases of DCIS with known estrogen receptor (ER), progesterone receptor, and human epidermal growth factor 2 (HER-2) expression using tissue microarrays. Twenty-four cases were pure DCIS and three had associated invasive ductal carcinoma. Tumors were stained by immunohistochemistry for PD-L1, as well as the lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20. The expression of PD-L1 by DCIS carcinoma cells and tumor infiltrating lymphocytes was determined, and the average tumor infiltrating lymphocytes per high power field were manually scored. None of the DCIS cells expressed PD-L1, but 81% of DCIS lesions contained PD-L1+ tumor infiltrating lymphocytes. DCIS with moderate-diffuse tumor infiltrating lymphocytes was more likely to have PD-L1+ tumor infiltrating lymphocytes (P=0.004). Tumor infiltrating lymphocytes with high levels of PD-L1 expression (>50% cells) were seen only in triple-negative DCIS (P=0.0008), and PD-L1-tumor infiltrating lymphocytes were seen only in ER+/HER-2-DCIS (P=0.12). The presence of PD-L1+ tumor infiltrating lymphocytes was associated with a younger mean patient age (P=0.01). Further characterization of the DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention.}, }
@article {pmid26744317, year = {2016}, author = {Riku, M and Inaguma, S and Ito, H and Tsunoda, T and Ikeda, H and Kasai, K}, title = {Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis.}, journal = {Oncotarget}, volume = {7}, number = {5}, pages = {5690-5701}, pmid = {26744317}, issn = {1949-2553}, mesh = {Apoptosis ; Blotting, Western ; Breast/metabolism/*pathology ; Breast Neoplasms/genetics/metabolism/*pathology ; Carboxypeptidases/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; Case-Control Studies ; Cell Proliferation ; Cell Transformation, Neoplastic/*genetics/pathology ; Cells, Cultured ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Receptors, CXCR4/genetics/metabolism ; Repressor Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcriptional Activation ; Zinc Finger Protein GLI1/genetics/*metabolism ; }, abstract = {Although breast cancer is one of the most common malignancies, the molecular mechanisms underlying its development and progression are not fully understood. To identify key molecules involved, we screened publicly available microarray datasets for genes differentially expressed between breast cancers and normal mammary glands. We found that three of the genes predicted in this analysis were differentially expressed among human mammary tissues and cell lines. Of these genes, we focused on the role of the zinc-finger homeobox protein TSHZ2, which is down-regulated in breast cancer cells. We found that TSHZ2 is a nuclear protein harboring a bipartite nuclear localization signal, and we confirmed its function as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. Through comprehensive screening, we identified TSHZ2-suppressing genes such as AEBP1 and CXCR4, which are conversely up-regulated by GLI1, the downstream transcription factor of Hedgehog signaling. We found that GLI1 forms a ternary complex with CtBP2 in the presence of TSHZ2 and that the transcriptional activity of GLI1 is suppressed by TSHZ2 in a CtBP-dependent manner. Indeed, knockdown of TSHZ2 increases the expression of AEBP1 and CXCR4 in TSHZ2-expressing immortalized mammary duct epithelium. Concordantly, immunohistochemical staining of mammary glands revealed that normal duct cells expresses GLI1 in the nucleus along with TSHZ2 and CtBP2, whereas invasive ductal carcinoma cells, which does not express TSHZ2, show the increase in the expression of AEBP1 and CXCR4 and in the cytoplasmic localization of GLI1. Thus, we propose that down-regulation of TSHZ2 is crucial for mammary tumorigenesis via the activation of GLI1.}, }
@article {pmid26740749, year = {2015}, author = {Makki, J}, title = {Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance.}, journal = {Clinical medicine insights. Pathology}, volume = {8}, number = {}, pages = {23-31}, pmid = {26740749}, issn = {1179-5557}, abstract = {Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality, with an incidence of >1,000,000 cases occurring worldwide annually. It is one of the most common human neoplasms, accounting for approximately one-quarter of all cancers in females worldwide and 27% of cancers in developed countries with a Western lifestyle. They exhibit a wide scope of morphological features, different immunohistochemical profiles, and unique histopathological subtypes that have specific clinical course and outcome. Breast cancers can be classified into distinct subgroups based on similarities in the gene expression profiles and molecular classification.}, }
@article {pmid26729235, year = {2016}, author = {Michaut, M and Chin, SF and Majewski, I and Severson, TM and Bismeijer, T and de Koning, L and Peeters, JK and Schouten, PC and Rueda, OM and Bosma, AJ and Tarrant, F and Fan, Y and He, B and Xue, Z and Mittempergher, L and Kluin, RJ and Heijmans, J and Snel, M and Pereira, B and Schlicker, A and Provenzano, E and Ali, HR and Gaber, A and O'Hurley, G and Lehn, S and Muris, JJ and Wesseling, J and Kay, E and Sammut, SJ and Bardwell, HA and Barbet, AS and Bard, F and Lecerf, C and O'Connor, DP and Vis, DJ and Benes, CH and McDermott, U and Garnett, MJ and Simon, IM and Jirström, K and Dubois, T and Linn, SC and Gallagher, WM and Wessels, LF and Caldas, C and Bernards, R}, title = {Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {18517}, pmid = {26729235}, issn = {2045-2322}, support = {102696/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics/*metabolism/mortality ; Carcinoma, Lobular/diagnosis/*genetics/*metabolism ; Cluster Analysis ; DNA-Binding Proteins/genetics/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Profiling ; *Genomics/methods ; Humans ; Immunohistochemistry ; Mutation Rate ; Polymorphism, Single Nucleotide ; Prognosis ; *Proteome ; Proteomics ; Reproducibility of Results ; Transcription Factors/genetics/metabolism ; *Transcriptome ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.}, }
@article {pmid26721716, year = {2016}, author = {Wang, L and Lyu, S and Wang, S and Shen, H and Niu, F and Liu, X and Liu, J and Niu, Y}, title = {Loss of FAT1 during the progression from DCIS to IDC and predict poor clinical outcome in breast cancer.}, journal = {Experimental and molecular pathology}, volume = {100}, number = {1}, pages = {177-183}, doi = {10.1016/j.yexmp.2015.12.012}, pmid = {26721716}, issn = {1096-0945}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology/therapy ; Disease Progression ; Female ; Humans ; Immunohistochemistry/methods ; Middle Aged ; Receptors, Estrogen/metabolism ; Treatment Outcome ; beta Catenin/metabolism ; }, abstract = {FAT1 and β-catenin are important tumor regulatory factors. The aim of this study was to detect the possible disparity in their expression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) and to explore its correlation with clinicopathological factors. We used immunohistochemistry to detect protein expression of FAT1 and β-catenin in breast cancer tissues from 113 cases of DCIS and 149 cases of IDC. As compared with DCIS, expression of FAT1 and β-catenin were significantly decreased in IDC (P<0.05). In addition, our study also revealed a correlation between their expression and some clinicopathological factors. We found that FAT1 expression was associated with nuclear grade and comedonecrosis (P<0.05) in DCIS, whereas FAT1 expression showed significant variation with histological grade and LN status (P<0.05) in IDC. Similar associations were observed in the β-catenin subgroup. Furthermore, expressions of FAT1 and β-catenin were correlated with each other in DCIS and IDC (P<0.05). FAT1(-), β-catenin(-), or FAT1(-)/β-catenin(-) may indicate worse DFS and OS in breast cancer (P<0.05). This study suggests that loss of FAT1 and β-catenin are associated with breast cancer progression, aggressive behavior, and poor prognosis. FAT1 alone or together with β-catenin might be a valuable biomarker in predicting the prognosis of patients with breast cancer.}, }
@article {pmid28330128, year = {2016}, author = {Paryan, M and Tavakoli, R and Rad, SMAH and Feizi, N and Kamani, F and Mostafavi, E and Mohammadi-Yeganeh, S}, title = {Over-expression of NOTCH1 as a biomarker for invasive breast ductal carcinoma.}, journal = {3 Biotech}, volume = {6}, number = {1}, pages = {58}, pmid = {28330128}, issn = {2190-572X}, abstract = {Breast cancer is the leading cause of cancer-related death in women worldwide. Invasive ductal carcinoma (IDC) is the most frequent invasive form of breast cancer followed by metastasis. There is no accepted marker for distinguishing this form from other less aggressive forms of breast cancer. Therefore, finding new markers especially molecularly detectable ones are noteworthy. It has been shown that NOTCH1 has been overexpressed in the patients with breast cancer, but no study has investigated the expression of NOTCH1 and its correlation with other molecular and hormonal markers of breast cancer so far. In the current study, 20 breast cancer tissues and 20 matched adjacent normal breast tissue from breast cancer patients were obtained and categorized in two groups: patients with IDC and patient with other types of breast cancer. Gene expression analysis using real-time PCR showed that the NOTCH1 gene was significantly overexpressed in patients with IDC. We also found a slight correlation between NOTCH1 overexpression and p53 accumulation in the cancerous cells confirmed by Immunohistochemistry (IHC). This results showed that it is possible to introduce NOTCH1 expression as a novel biomarker of IDC, alone or preferably accompanied by IHC of p53. We also can design new therapeutic agents targeting NOTCH1 expression for inhibition of metastasis in ductal breast carcinoma.}, }
@article {pmid26715212, year = {2016}, author = {Nakagawa, S and Miki, Y and Miyashita, M and Hata, S and Takahashi, Y and Rai, Y and Sagara, Y and Ohi, Y and Hirakawa, H and Tamaki, K and Ishida, T and Watanabe, M and Suzuki, T and Ohuchi, N and Sasano, H}, title = {Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets.}, journal = {Breast cancer research and treatment}, volume = {155}, number = {1}, pages = {65-75}, doi = {10.1007/s10549-015-3668-9}, pmid = {26715212}, issn = {1573-7217}, mesh = {Actins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Angiogenesis Inducing Agents/metabolism ; Antigens, CD34/metabolism ; Biomarkers ; Breast Neoplasms/genetics/*metabolism/*pathology/therapy ; Carcinoma, Lobular/genetics/*metabolism/*pathology/therapy ; Cell Cycle Proteins/metabolism ; Female ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor I/genetics/metabolism ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic/genetics/metabolism ; Nestin/metabolism ; Receptor, IGF Type 1/genetics/metabolism ; Tumor Burden ; *Tumor Microenvironment/genetics ; }, abstract = {Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.}, }
@article {pmid26688682, year = {2015}, author = {Grebić, D and Tomašić, AM}, title = {Sporadic Case of Breast Angiosarcoma as a Complication of Radiotherapy Following Breast-Conserving Surgery for Invasive Ductal Breast Cancer.}, journal = {Breast care (Basel, Switzerland)}, volume = {10}, number = {5}, pages = {336-338}, pmid = {26688682}, issn = {1661-3791}, abstract = {BACKGROUND: Angiosarcomas are highly aggressive and malignant blood vessel tumors. Rarely, angiosarcomas develop in the breast following conservative therapy, namely radiotherapy.<br><br>CASE REPORT: A 70-year-old female patient presented with dark purple discoloration of the skin of the right breast. 6 years earlier, the patient had undergone conservative surgery for invasive ductal carcinoma of the right breast. According to the breast-conserving surgery protocol, the patient had been treated with radiotherapy to the residual breast tissue. The patient's annual mammograms and ultrasound findings were normal. The skin lesion was superficially localized mostly at the border between the upper and lower medial quadrants of the breast (between 2 and 4 o'clock) and above the areola. The borders were uneven; the dimensions were 7 cm &#xd7; 4 cm. The mammogram was classified as Breast Imaging Report and Data System (BI-RADS) 2. Ultrasound examination showed a well-vascularized structure, although the etiology was unclear. A tissue biopsy revealed angiosarcoma. The patient underwent radical simplex mastectomy. Following surgery, the patient underwent chemotherapy. Tests excluded metastases for a follow-up period of 5 years.<br><br>CONCLUSION: Angiosarcomas that develop after radiotherapy following breast-conserving surgery are sporadic, but it is important to take this possible incident into consideration during treatment.}, }
@article {pmid26684357, year = {2016}, author = {Dai, K and Qin, F and Zhang, H and Liu, X and Guo, C and Zhang, M and Gu, F and Fu, L and Ma, Y}, title = {Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy.}, journal = {Oncotarget}, volume = {7}, number = {4}, pages = {4770-4784}, pmid = {26684357}, issn = {1949-2553}, support = {R03 AA020101/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*metabolism ; Bone Morphogenetic Protein Receptors, Type I/*metabolism ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Bridged-Ring Compounds/administration &amp; dosage ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*secondary ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Taxoids/administration &amp; dosage ; }, abstract = {Bone morphogenetic protein receptor type IB (BMPRIB) is one osteogenesis factor, which function in breast cancer has been rarely explored until recently. In the clinical study presented here, involving a cohort of 368 invasive ductal carcinoma (IDC) patients, we identified that patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal B subtype. We also provided the first piece of evidence that low level of BMPRIB was a promoting factor for breast cancer patients to develop bone metastasis, but not lung, liver or brain. The first of its kind, we reported that patients with high expression of BMPRIB exhibited favorable prognosis by a retrospective analysis consisting of 168 patients treated with TE (taxane and anthracycline) regimens. And the patients with high expression of BMPRIB were more sensitive to TE regimens in the detection of 32 paired pre-neoadjuvant and post-neoadjuvant specimens. Overall, our study concluded that low expression of BMPRIB indicated poor prognosis of breast cancer and was insensitive to taxane-anthracycline chemotherapy. Our findings also lay a foundation to help clinicians improve identification of patients for TE regimens by BMPRIB in the era of precision medicine.}, }
@article {pmid26680994, year = {2016}, author = {Fan, Z and Silva, P and Gronau, I and Wang, S and Armero, AS and Schweizer, RM and Ramirez, O and Pollinger, J and Galaverni, M and Ortega Del-Vecchyo, D and Du, L and Zhang, W and Zhang, Z and Xing, J and Vilà, C and Marques-Bonet, T and Godinho, R and Yue, B and Wayne, RK}, title = {Worldwide patterns of genomic variation and admixture in gray wolves.}, journal = {Genome research}, volume = {26}, number = {2}, pages = {163-173}, pmid = {26680994}, issn = {1549-5469}, support = {R00 HG005846/HG/NHGRI NIH HHS/United States ; R00HG005846/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Dogs/*genetics ; Female ; Genome ; Hybridization, Genetic ; Male ; Markov Chains ; Models, Genetic ; Phylogeny ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Sequence Analysis, DNA ; Wolves/*genetics ; }, abstract = {The gray wolf (Canis lupus) is a widely distributed top predator and ancestor of the domestic dog. To address questions about wolf relationships to each other and dogs, we assembled and analyzed a data set of 34 canine genomes. The divergence between New and Old World wolves is the earliest branching event and is followed by the divergence of Old World wolves and dogs, confirming that the dog was domesticated in the Old World. However, no single wolf population is more closely related to dogs, supporting the hypothesis that dogs were derived from an extinct wolf population. All extant wolves have a surprisingly recent common ancestry and experienced a dramatic population decline beginning at least ∼30 thousand years ago (kya). We suggest this crisis was related to the colonization of Eurasia by modern human hunter-gatherers, who competed with wolves for limited prey but also domesticated them, leading to a compensatory population expansion of dogs. We found extensive admixture between dogs and wolves, with up to 25% of Eurasian wolf genomes showing signs of dog ancestry. Dogs have influenced the recent history of wolves through admixture and vice versa, potentially enhancing adaptation. Simple scenarios of dog domestication are confounded by admixture, and studies that do not take admixture into account with specific demographic models are problematic.}, }
@article {pmid26679836, year = {2016}, author = {Ben-David, BM and Durham, NA and van Lieshout, PH}, title = {The Linguistic Acoustic ThreaT Effect (LATTE): Screening tool for the impact of semantic threat in speech processing after a brain injury.}, journal = {Brain injury}, volume = {30}, number = {2}, pages = {237-239}, doi = {10.3109/02699052.2015.1091506}, pmid = {26679836}, issn = {1362-301X}, mesh = {Adolescent ; Brain Injuries/*complications ; Female ; Humans ; Linguistics ; Male ; Semantics ; Speech/*physiology ; Young Adult ; }, }
@article {pmid26670275, year = {2015}, author = {Serina, P and Riley, I and Stewart, A and Flaxman, AD and Lozano, R and Mooney, MD and Luning, R and Hernandez, B and Black, R and Ahuja, R and Alam, N and Alam, SS and Ali, SM and Atkinson, C and Baqui, AH and Chowdhury, HR and Dandona, L and Dandona, R and Dantzer, E and Darmstadt, GL and Das, V and Dhingra, U and Dutta, A and Fawzi, W and Freeman, M and Gamage, S and Gomez, S and Hensman, D and James, SL and Joshi, R and Kalter, HD and Kumar, A and Kumar, V and Lucero, M and Mehta, S and Neal, B and Ohno, SL and Phillips, D and Pierce, K and Prasad, R and Praveen, D and Premji, Z and Ramirez-Villalobos, D and Rampatige, R and Remolador, H and Romero, M and Said, M and Sanvictores, D and Sazawal, S and Streatfield, PK and Tallo, V and Vadhatpour, A and Wijesekara, N and Murray, CJ and Lopez, AD}, title = {A shortened verbal autopsy instrument for use in routine mortality surveillance systems.}, journal = {BMC medicine}, volume = {13}, number = {}, pages = {302}, pmid = {26670275}, issn = {1741-7015}, mesh = {Adult ; Cause of Death ; Child, Preschool ; Developing Countries ; *Epidemiological Monitoring ; Humans ; Infant, Newborn ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach.<br><br>METHODS: We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates.<br><br>RESULTS: The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively.<br><br>CONCLUSIONS: We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand-held electronic tablets and analyzed using Tariff 2.0. The length of a VA questionnaire was shortened by almost 50% without a significant drop in performance. The shortened VAI developed reduces the burden of time and resources required for data collection and analysis of cause of death data in civil registration systems.}, }
@article {pmid26652003, year = {2015}, author = {Hein, AM and Rosenthal, SB and Hagstrom, GI and Berdahl, A and Torney, CJ and Couzin, ID}, title = {The evolution of distributed sensing and collective computation in animal populations.}, journal = {eLife}, volume = {4}, number = {}, pages = {e10955}, pmid = {26652003}, issn = {2050-084X}, mesh = {Animals ; *Behavior, Animal ; Biological Evolution ; Fishes/*physiology ; Models, Biological ; *Social Behavior ; }, abstract = {Many animal groups exhibit rapid, coordinated collective motion. Yet, the evolutionary forces that cause such collective responses to evolve are poorly understood. Here, we develop analytical methods and evolutionary simulations based on experimental data from schooling fish. We use these methods to investigate how populations evolve within unpredictable, time-varying resource environments. We show that populations evolve toward a distinctive regime in behavioral phenotype space, where small responses of individuals to local environmental cues cause spontaneous changes in the collective state of groups. These changes resemble phase transitions in physical systems. Through these transitions, individuals evolve the emergent capacity to sense and respond to resource gradients (i.e. individuals perceive gradients via social interactions, rather than sensing gradients directly), and to allocate themselves among distinct, distant resource patches. Our results yield new insight into how natural selection, acting on selfish individuals, results in the highly effective collective responses evident in nature.}, }
@article {pmid26644140, year = {2015}, author = {Serina, P and Riley, I and Stewart, A and James, SL and Flaxman, AD and Lozano, R and Hernandez, B and Mooney, MD and Luning, R and Black, R and Ahuja, R and Alam, N and Alam, SS and Ali, SM and Atkinson, C and Baqui, AH and Chowdhury, HR and Dandona, L and Dandona, R and Dantzer, E and Darmstadt, GL and Das, V and Dhingra, U and Dutta, A and Fawzi, W and Freeman, M and Gomez, S and Gouda, HN and Joshi, R and Kalter, HD and Kumar, A and Kumar, V and Lucero, M and Maraga, S and Mehta, S and Neal, B and Ohno, SL and Phillips, D and Pierce, K and Prasad, R and Praveen, D and Premji, Z and Ramirez-Villalobos, D and Rarau, P and Remolador, H and Romero, M and Said, M and Sanvictores, D and Sazawal, S and Streatfield, PK and Tallo, V and Vadhatpour, A and Vano, M and Murray, CJ and Lopez, AD}, title = {Improving performance of the Tariff Method for assigning causes of death to verbal autopsies.}, journal = {BMC medicine}, volume = {13}, number = {}, pages = {291}, pmid = {26644140}, issn = {1741-7015}, mesh = {Autopsy/*methods ; *Cause of Death ; Female ; Humans ; Male ; }, abstract = {BACKGROUND: Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method.<br><br>METHODS: This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database.<br><br>RESULTS: For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in analyses without HCE.<br><br>CONCLUSIONS: Tariff 2.0 addresses the main shortcomings of the application of the Tariff Method to analyze data from VAs in community settings. It provides an estimation of COD from VAs with better performance at the individual and population level than the previous version of this method, and it is publicly available for use.}, }
@article {pmid26643230, year = {2015}, author = {Street, P and Thompson, J and Bailey, M}, title = {Management of urinary catheters following hip fracture.}, journal = {Australasian journal on ageing}, volume = {34}, number = {4}, pages = {241-246}, doi = {10.1111/ajag.12166}, pmid = {26643230}, issn = {1741-6612}, mesh = {Aged ; Aged, 80 and over ; *Catheters, Indwelling ; Chi-Square Distribution ; Dementia/complications ; Device Removal ; Female ; Guideline Adherence ; *Health Services for the Aged/standards ; Hip Fractures/complications/diagnosis/*therapy ; Humans ; Logistic Models ; Male ; Medical Audit ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Patient Discharge ; Practice Guidelines as Topic ; Prognosis ; Residential Facilities ; Retrospective Studies ; Risk Factors ; Urinary Catheterization/adverse effects/*instrumentation/standards ; *Urinary Catheters ; }, abstract = {AIM: To examine current practices and factors associated with outcomes of urinary catheter removal ('trial of void' or TOV) in patients following hip fracture.<br><br>METHOD: Retrospective file audit of patients discharged over a three-year period with a diagnosis of recent hip fracture.<br><br>RESULTS: There were 133 TOVs in 310 patients. Of the 78 TOVs occurring in the aged care rehabilitation hospital, 50% were successful. Adherence to the hospital's TOV guideline was documented infrequently. TOV outcome was not related to interval since catheter insertion, constipation or inability to mobilise. Multivariate analysis showed that dementia was independently associated with the presence of an in-dwelling catheter (IDC) on discharge and that patients discharged with an IDC had a higher probability of residential care placement.<br><br>CONCLUSIONS: Practices in managing TOVs are inconsistent. No potentially modifiable predictors of TOV success were identified. The presence of an IDC has implications for discharge destination.}, }
@article {pmid26628432, year = {2016}, author = {Kim, YS and Chang, JM and Moon, HG and Lee, J and Shin, SU and Moon, WK}, title = {Residual Mammographic Microcalcifications and Enhancing Lesions on MRI After Neoadjuvant Systemic Chemotherapy for Locally Advanced Breast Cancer: Correlation with Histopathologic Residual Tumor Size.}, journal = {Annals of surgical oncology}, volume = {23}, number = {4}, pages = {1135-1142}, doi = {10.1245/s10434-015-4993-2}, pmid = {26628432}, issn = {1534-4681}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Calcinosis/chemically induced/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/metabolism/pathology ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Magnetic Resonance Imaging/*methods ; Mammography ; Middle Aged ; Neoadjuvant Therapy/*adverse effects ; Neoplasm Staging ; Neoplasm, Residual/chemically induced/*diagnosis/diagnostic imaging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Young Adult ; }, abstract = {PURPOSE: To evaluate the accuracy of residual microcalcifications on mammogram (MG) in predicting the extent of the residual tumor after neoadjuvant systemic treatment (NST) in patients with locally advanced breast cancer and to evaluate factors affecting the accuracy of MG microcalcifications using magnetic resonance imaging (MRI) as a reference.<br><br>METHODS: The patients who underwent NST and showed suspicious microcalcifications on MG comprised our study population. Clinicopathologic and imaging (MG, MRI) findings were investigated. Agreement between image findings and pathology was assessed and factors affecting the discrepancy were analyzed.<br><br>RESULTS: Among 207 patients, 196 had residual invasive ductal carcinoma or ductal carcinoma-in-situ (mean size, 3.78&#xa0;cm). The overall agreement of residual microcalcifications on MG predicting residual tumor extents was lower than MRI in all tumor subtypes (intraclass correlation coefficient [ICC]&#xa0;=&#xa0;0.368 and 0.723, p&#xa0;<&#xa0;0.0001). The agreement of residual MG microcalcifications and pathology was highest in HR(+)/HER2(+) tumors and lowest in the triple-negative tumors (ICC&#xa0;=&#xa0;0.417 and 0.205, respectively). Multivariate linear regression analysis revealed that a size discrepancy between microcalcifications and histopathology was correlated with molecular subtype (p&#xa0;=&#xa0;0.005). In HR(+)/HER2(-) and triple-negative subtypes, the mean extents of residual microcalcification were smaller than residual cancer, and overestimation of tumor extent was more frequent in HR(+)/HER2(+) and HR(-)/HER2(+) tumors.<br><br>CONCLUSIONS: The extent of microcalcifications on MG after NST showed an overall lower correlation with the extent of the pathologic residual tumor than enhancing lesions on MRI. The accuracy of residual tumor evaluation after NST with MG and MRI is affected by their molecular subtype.}, }
@article {pmid26621543, year = {2016}, author = {Ruszczyk, M and Zirpoli, G and Kumar, S and Bandera, EV and Bovbjerg, DH and Jandorf, L and Khoury, T and Hwang, H and Ciupak, G and Pawlish, K and Schedin, P and Masso-Welch, P and Ambrosone, CB and Hong, CC}, title = {Breast cancer risk factor associations differ for pure versus invasive carcinoma with an in situ component in case-control and case-case analyses.}, journal = {Cancer causes &amp; control : CCC}, volume = {27}, number = {2}, pages = {183-198}, pmid = {26621543}, issn = {1573-7225}, support = {U58 DP003931/DP/NCCDPHP CDC HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; 5U58DP003931-02/DP/NCCDPHP CDC HHS/United States ; P30 CA072720/CA/NCI NIH HHS/United States ; R01 CA169175/CA/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; K22 CA138563/CA/NCI NIH HHS/United States ; N01PC-2013-00021/PC/NCI NIH HHS/United States ; R03 CA17106/CA/NCI NIH HHS/United States ; R03 CA171061/CA/NCI NIH HHS/United States ; R01 CA185623/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Feeding/*statistics &amp; numerical data ; Breast Neoplasms/*epidemiology/pathology ; Carcinoma, Ductal, Breast/*epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/pathology ; Case-Control Studies ; Female ; Humans ; Logistic Models ; Middle Aged ; Multivariate Analysis ; Obesity/*epidemiology ; Odds Ratio ; Overweight/epidemiology ; *Reproductive History ; Risk Factors ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) is diagnosed with or without a ductal carcinoma in situ (DCIS) component. Previous analyses have found significant differences in tumor characteristics between pure IDC lacking DCIS and mixed IDC with DCIS. We will test our hypothesis that pure IDC represents a form of breast cancer with etiology and risk factors distinct from mixed IDC/DCIS.<br><br>METHODS: We compared reproductive risk factors for breast cancer risk, as well as family and smoking history between 831 women with mixed IDC/DCIS (n = 650) or pure IDC (n = 181), and 1,620 controls, in the context of the Women's Circle of Health Study (WCHS), a case-control study of breast cancer in African-American and European-American women. Data on reproductive and lifestyle factors were collected during interviews, and tumor characteristics were abstracted from pathology reports. Case-control and case-case analyses were conducted using unconditional logistic regression.<br><br>RESULTS: Most risk factors were similarly associated with pure IDC and mixed IDC/DCIS. However, among postmenopausal women, risk of pure IDC was lower in women with body mass index (BMI) 25 to <30 [odds ratio (OR) 0.66; 95 % confidence interval (CI) 0.35-1.23] and BMI &#x2265; 30 (OR 0.33; 95 % CI 0.18-0.67) compared to women with BMI < 25, with no associations with mixed IDC/DCIS. In case-case analyses, women who breastfed up to 12 months (OR 0.55; 95 % CI 0.32-0.94) or longer (OR 0.47; 95 % CI 0.26-0.87) showed decreased odds of pure IDC than mixed IDC/DCIS compared to those who did not breastfeed.<br><br>CONCLUSIONS: Associations with some breast cancer risk factors differed between mixed IDC/DCIS and pure IDC, potentially suggesting differential developmental pathways. These findings, if confirmed in a larger study, will provide a better understanding of the developmental patterns of breast cancer and the influence of modifiable risk factors, which in turn could lead to better preventive measures for pure IDC, which have worse disease prognosis compared to mixed IDC/DCIS.}, }
@article {pmid26617852, year = {2015}, author = {Chen, Y and Song, J and Jiang, Y and Yu, C and Ma, Z}, title = {Predictive value of CD44 and CD24 for prognosis and chemotherapy response in invasive breast ductal carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {9}, pages = {11287-11295}, pmid = {26617852}, issn = {1936-2625}, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy/immunology/pathology/surgery ; CD24 Antigen/*analysis ; Carcinoma, Ductal, Breast/*drug therapy/*immunology/secondary/surgery ; Chemotherapy, Adjuvant ; Child ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Hyaluronan Receptors/*analysis ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Phenotype ; Predictive Value of Tests ; Proportional Hazards Models ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Cells with unique phenotypes and stem cell-like properties have been found to exist in breast cancer. The aim of the present study was to study the relationship of CD24, CD44, CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor phenotypes' with clinico-pathological features, chemotherapy response and with prognosis.<br><br>METHODS: The study included paraffin-embedded tissues of 140 primary and secondary invasive ductal carcinoma samples. All the patients received routine chemotherapy. Expression of CD24, CD44, ER, PR, and Her2 were assayed immunohistochemically. We applied double-staining immunohistochemistry for the detection of CD44(+)/CD24(-/low), CD44(+)/CD24 (+), CD44(-)/CD24(-) and CD44(-)/CD24(+) cells. The association between the proportions of CD44(+)/CD24(-/low) and CD44(-)/CD24(+) and clinicopathological features, chemotherapy response and with prognosis of these patients was evaluated.<br><br>RESULTS: CD24 expression was not significantly associated with tumor characteristics, but was significantly associated with poor prognostic variables including ER-, PR-, HER2(+) and triple negative (TN) phenotype; There was no association of CD44 with nodal status, age or HER2 expression. In the correlation analysis, CD24 expression was positively associated with chemotherapy response (P = 0.018), however, CD44 expression was not associated with pathological response to chemotherapy When both markers are considered, the CD44(+)/CD24(-) phenotype had the poor prognosis. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement, recurrent or metastatic tumors and ER/PR status. High CD44(+)/CD24(-) phenotype had poor response to chemotherapy. The median disease-free survival (DFS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 19.8 &#xb1; 2.6 months and 31.7 &#xb1; 4.2 months, and the median overall survival (OS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 33.5 &#xb1; 2.8 months and 51.4 &#xb1; 3.9 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44(+)/CD24(-/low) tumor cells was strongly correlated with DFS and OS. However, the CD44(-)/CD24(+), CD44(+)/CD24(+), CD44(-)/CD24 (-) phenotype had no relation with prognosis.<br><br>CONCLUSION: There was significant correlation between CD44(+)/CD24(-/low) tumor cell prevalence and tumor metastasis, prognosis and chemotherapy response. The CD44(+)/CD24(-) phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.}, }
@article {pmid26613509, year = {2016}, author = {Skazik-Voogt, C and Kühler, K and Ott, H and Czaja, K and Zwadlo-Klarwasser, G and Merk, HF and Amann, PM and Baron, JM}, title = {Myeloid human cell lines lack functional regulation of aryl hydrocarbon receptor-dependent phase I genes.}, journal = {ALTEX}, volume = {33}, number = {1}, pages = {37-46}, doi = {10.14573/altex.1502041}, pmid = {26613509}, issn = {1868-8551}, mesh = {Aryl Hydrocarbon Receptor Nuclear Translocator/*metabolism ; Cell Line ; Cytochrome P-450 CYP1A1/*genetics/metabolism ; Cytochrome P-450 CYP1B1/metabolism ; Dendritic Cells ; Dermatitis, Contact ; *Gene Expression Regulation/drug effects ; Humans ; Langerhans Cells ; Monocytes ; *Myeloid Cells ; RNA, Messenger/metabolism ; Receptors, Aryl Hydrocarbon/genetics/*metabolism ; }, abstract = {Primary dendritic cells and myeloid cell lines are used to assess the skin sensitization hazard in in vitro approaches. The aryl hydrocarbon receptor (AhR) modulates expression of CYP enzymes which play a significant role in the bioactivation of various xenobiotics. These studies revealed a strong constitutive expression of the AhR in primary human monocytes, monocyte-derived immature dendritic cells (iDC) and cord blood-derived Langerhans cells (LC). In contrast, mRNA and protein expression of AhR was hardly detectable in the cell lines THP-1 and MUTZ-3. U937 cells and MUTZ-3-derived dendritic (MUTZ-DC) or Langerhans cells (MUTZ-LC) showed about half the expression of AhR compared to iDC. Incubation of cells with the specific AhR-inducer benzo[a]anthracene resulted in an upregulation of CYP and IL-1β mRNA expression in primary monocytes and iDC. CYP1A1 but not CYP1B1 and IL-1β expression was increased by benzo[a]anthracene in these cell lines except for U937 cells. AhR-independent CYP genes were not regulated by benzo[a]anthracene. Constitutive mRNA expression of other non AhR-dependent CYP enzymes was higher in some of the cell lines compared to the corresponding primary cells. This study demonstrates significant differences in expression and regulation of phase I genes in cell lines currently used for in vitro skin sensitization hazard assessment compared to primary cells. Additional studies are required regarding the combination of cutaneous xenobiotic metabolizing enzymes and APC-sensitization for the development of valid in vitro models for skin sensitization assessment.}, }
@article {pmid26612847, year = {2016}, author = {Coyne, JD}, title = {Gynecomastia With Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ Associated With Invasive Breast Carcinoma in a Male Patient on Antiretroviral Therapy: A Case Report.}, journal = {International journal of surgical pathology}, volume = {24}, number = {2}, pages = {139-141}, doi = {10.1177/1066896915608437}, pmid = {26612847}, issn = {1940-2465}, mesh = {Adult ; Antiretroviral Therapy, Highly Active ; Breast Neoplasms, Male/complications/*pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*pathology ; Gynecomastia/*etiology ; *HIV Infections ; Humans ; Male ; }, abstract = {Breast carcinoma in males is rare although a 4-fold increased incidence is reported in HIV-infected men. Herein we report a case of invasive breast carcinoma in a HIV-positive man on antiretroviral therapy. The carcinoma was associated with features of florid gynecomastia, atypical ductal hyperplasia, ductal carcinoma in situ, and columnar cell change. This combination of morphological changes has not previously been reported in the context of male breast carcinoma and their etiopathological associations are discussed.}, }
@article {pmid26610382, year = {2015}, author = {Swain, SM and Nunes, R and Yoshizawa, C and Rothney, M and Sing, AP}, title = {Quantitative Gene Expression by Recurrence Score in ER-Positive Breast Cancer, by Age.}, journal = {Advances in therapy}, volume = {32}, number = {12}, pages = {1222-1236}, pmid = {26610382}, issn = {1865-8652}, mesh = {Adult ; Age Factors ; Aged ; Breast Neoplasms/*genetics/mortality/*pathology ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/mortality/*pathology ; Neoplasm Staging ; Receptors, Estrogen/*metabolism ; }, abstract = {INTRODUCTION: Breast cancer in young women (<50 years) has been associated with an increased risk of recurrence and decreased survival compared with patients older than 50. The objective of this analysis was to determine, from a large database of patients with early-stage breast cancer, if the Recurrence Score(®) result (Oncotype DX(®), Genomic Health, Inc, Redwood City, CA, USA) provided clinically meaningful differences in predicted risk of recurrence in younger-compared with older-patients.<br><br>METHODS: Tumor samples from patients with estrogen receptor (ER)-positive breast cancers that were successfully processed in the Genomic Health central lab between June 2004 and December 2013 for Recurrence Score and quantitative gene expression of ER, progesterone receptor (PR), and Her/2neu, were included. Descriptive statistics were used to describe the distribution of scores by age group: <40, 40-49, 50-59, 60-69, and &#x2265;70 years, nodal status, and histologic subtype.<br><br>RESULTS: Specimens from 394,031 patients [3.3% (n = 13,029) aged <40 years; 15.6% (n = 61,643) aged &#x2265;70 years] were included; 81.6% of patients had invasive ductal carcinoma. Nodal status was specified for 362,001 patients (87.0% negative). Median Recurrence Score results were similar across risk groups. Low (<18)- and high (&#x2265;31)- risk Recurrence Score results were seen in 58.5% and 8.5% of patients, respectively. A greater proportion of patients aged <40 (14.1%) than &#x2265;70 (8.8%) years had a high-risk score. ER expression increased as a function of age and PR single-gene and invasion gene group expression were similar across age groups.<br><br>CONCLUSION: These data indicate that in patients with ER-positive breast cancer, age alone does not reflect the underlying individual tumor biology, suggesting that the Recurrence Score result may add potentially useful information for personalized treatment decisions.<br><br>FUNDING: Genomic Health, Inc.}, }
@article {pmid26599012, year = {2015}, author = {Mu, QJ and Li, HL and Yao, Y and Liu, SC and Yin, CG and Ma, XZ}, title = {Chromodomain Helicase/ATPase DNA-Binding Protein 1-Like Gene (CHD1L) Expression and Implications for Invasion and Metastasis of Breast Cancer.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0143030}, pmid = {26599012}, issn = {1932-6203}, mesh = {Adult ; Aged ; Animals ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Helicases/antagonists &amp; inhibitors/*biosynthesis/genetics ; DNA-Binding Proteins/antagonists &amp; inhibitors/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Mice ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Proteins/*biosynthesis ; RNA, Small Interfering ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L), also known as ALC1 (amplified in liver cancer 1 gene), is a new oncogene amplified in many solid tumors. Whether this gene plays a role in invasion and metastasis of breast cancer is unknown.<br><br>METHODS: Immunohistochemistry was performed to detect the expression of CHD1L in patients with invasive ductal carcinoma and normal mammary glands. Chemotaxis, wound healing, and Transwell invasion assays were also performed to examine cell migration and invasion. Western blot analysis was conducted to detect the expression of CHD1L, MMP-2, MMP-9, pAkt/Akt, pARK5/ARK5, and pmTOR/mTOR. Moreover, ELISA was carried out to detect the expression levels of MMP-2 and MMP-9. Nude mice xenograft model was used to detect the invasion and metastasis of breast cancer cell lines.<br><br>RESULTS: CHD1L overexpression was observed in 112 of 268 patients (41.8%). This overexpression was associated with lymph node metastasis (P = 0.008), tumor differentiation (P = 0.020), distant metastasis (P = 0.026), MMP-2 (P = 0.035), and MMP-9 expression (P = 0.022). In the cell experiment, reduction of CHD1L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1L knockdown via siRNA suppressed EGF-induced pAkt, pARK5, and pmTOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.<br><br>CONCLUSIONS: CHD1L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ARK5/mTOR/MMP signaling pathway. This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer.}, }
@article {pmid26597811, year = {2015}, author = {Lappalainen, AK and Mäki, K and Laitinen-Vapaavuori, O}, title = {Estimate of heritability and genetic trend of intervertebral disc calcification in Dachshunds in Finland.}, journal = {Acta veterinaria Scandinavica}, volume = {57}, number = {}, pages = {78}, pmid = {26597811}, issn = {1751-0147}, mesh = {Animals ; Calcinosis/diagnostic imaging/genetics/prevention &amp; control/*veterinary ; Dog Diseases/diagnostic imaging/*genetics/pathology/prevention &amp; control ; Dogs ; Female ; Finland ; Intervertebral Disc/*pathology ; Intervertebral Disc Degeneration/diagnostic imaging/genetics/prevention &amp; control/*veterinary ; Male ; Mass Screening/*veterinary ; Radiography ; }, abstract = {BACKGROUND: Intervertebral disc disease (IDD) is a hereditary condition particularly common in Dachshunds. The breed is predisposed to early intervertebral disc degeneration and intervertebral disc calcification (IDC). When calcified, these severely degenerated discs are visible in spinal radiographs. Since the number of calcified discs (NCD) is associated with IDD, spinal radiography can be utilized in screening programmes in attempts to diminish the incidence of IDD in Dachshunds. Our aims were to estimate the heritability and genetic trend of NCD in Dachshunds in Finland and to explore the effect of age at the time of radiographic screening. Since the NCD has a highly skewed distribution, a log-transformed NCD (lnNCD) was also used as an analysed trait. The variance components for both traits were estimated, using the restricted maximum likelihood method. The fixed effects of breed variant, sex, as well as year of screening and the random effects of litter and animal were included in the model. The genetic trends in the NCD and lnNCD were assessed from the estimated breeding values (EBVs) of individual dogs by comparing the mean EBV of dogs born in different years. The breeding values were estimated, using the best linear unbiased prediction animal model. The pedigree in the genetic analyses included a total of 9027 dogs, of which 1567 showed results for NCDs.<br><br>RESULTS: The heritability estimates of the NCD and lnNCD in Dachshunds were high (0.53 and 0.45, respectively). Small genetic improvements were seen as the mean EBVs increased from 100 to 104 and 105 over a 15-year period. The gain in the entire Dachshund population in Finland may differ from that observed, since less than 10 % of the Dachshunds registered have a screening result for NCD. Age at the time of the screening did not significantly affect the NCD or lnNCD.<br><br>CONCLUSIONS: We recommend systematic radiographic screening for IDC in Dachshunds and adopting EBVs as a tool for selecting breeding dogs. Age at the time of the radiographic screening may not be as important as previously suggested.}, }
@article {pmid26588055, year = {2016}, author = {Tan, X and Fu, Y and Chen, L and Lee, W and Lai, Y and Rezaei, K and Tabbara, S and Latham, P and Teal, CB and Man, YG and Siegel, RS and Brem, RF and Fu, SW}, title = {miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer.}, journal = {Oncotarget}, volume = {7}, number = {1}, pages = {293-307}, pmid = {26588055}, issn = {1949-2553}, support = {R21 CA159103/CA/NCI NIH HHS/United States ; 1R21 CA159103/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/pharmacology ; Blotting, Western ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Cycle/drug effects/genetics ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Cisplatin/pharmacology ; *Down-Regulation ; Epirubicin/pharmacology ; Epithelial-Mesenchymal Transition/*genetics ; Fluorouracil/pharmacology ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/*genetics/metabolism ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; MicroRNAs/*genetics ; Microscopy, Confocal ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. cDNA microarray data revealed that differentially expressed genes when miR-671-5p was transfected are associated with cell proliferation, invasion, cell cycle, and EMT. These data indicate that miR-671-5p functions as a tumor suppressor miRNA in breast cancer by directly targeting FOXM1. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management.}, }
@article {pmid26581728, year = {2015}, author = {Ayal, S and Gino, F and Barkan, R and Ariely, D}, title = {Three Principles to REVISE People's Unethical Behavior.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {10}, number = {6}, pages = {738-741}, doi = {10.1177/1745691615598512}, pmid = {26581728}, issn = {1745-6924}, mesh = {Humans ; *Morals ; Motivation ; *Public Policy ; Self Concept ; *Social Behavior ; *Social Control, Informal ; United States ; }, abstract = {Dishonesty and unethical behavior are widespread in the public and private sectors and cause immense annual losses. For instance, estimates of U.S. annual losses indicate $1 trillion paid in bribes, $270 billion lost due to unreported income, and $42 billion lost in retail due to shoplifting and employee theft. In this article, we draw on insights from the growing fields of moral psychology and behavioral ethics to present a three-principle framework we call REVISE. This framework classifies forces that affect dishonesty into three main categories and then redirects those forces to encourage moral behavior. The first principle, reminding, emphasizes the effectiveness of subtle cues that increase the salience of morality and decrease people's ability to justify dishonesty. The second principle, visibility, aims to restrict anonymity, prompt peer monitoring, and elicit responsible norms. The third principle, self-engagement, increases people's motivation to maintain a positive self-perception as a moral person and helps bridge the gap between moral values and actual behavior. The REVISE framework can guide the design of policy interventions to defeat dishonesty.}, }
@article {pmid26576347, year = {2015}, author = {Ataei-Kachouei, M and Nadaf, J and Akbari, MT and Atri, M and Majewski, J and Riazalhosseini, Y and Garshasbi, M}, title = {Double Heterozygosity of BRCA2 and STK11 in Familial Breast Cancer Detected by Exome Sequencing.}, journal = {Iranian journal of public health}, volume = {44}, number = {10}, pages = {1348-1352}, pmid = {26576347}, issn = {2251-6085}, abstract = {BACKGROUND: Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of dominantly inherited familial breast cancers; still a big part of genetic component is unknown. The aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance.<br><br>METHODS: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. Sanger sequencing was applied for validation and segregation analysis of mutations.<br><br>RESULTS: Here, we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to heterozygous frame shift mutation rs80359352 in BRCA2 gene as the first report in Iranian patients in association with a novel missense SNP of STK11 (p.S422G). These mutations are inherited from their normal father.<br><br>CONCLUSION: Despite apparent recessive pattern of inheritance a dominant gene (here BRCA2) can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of BRCA2 mutations.}, }
@article {pmid26566041, year = {2015}, author = {Li, CZ and Li, CC and Lin, MC and Chih-Chuan, H and Chen, NF and Chen, CL and Tang, CT}, title = {A Clinical Pitfall: Optimal Management of Single Dural-based Metastatic Carcinoma of the Breast Mimicking Meningioma.}, journal = {The neurologist}, volume = {20}, number = {5}, pages = {93-95}, doi = {10.1097/NRL.0000000000000059}, pmid = {26566041}, issn = {2331-2637}, mesh = {Brain Neoplasms/diagnosis/*secondary/therapy ; Breast Neoplasms/*pathology/surgery ; Carcinoma/*pathology/surgery ; Female ; Fluorodeoxyglucose F18/metabolism ; Humans ; Magnetic Resonance Imaging ; Meningeal Neoplasms/*physiopathology ; Meningioma/*physiopathology ; Middle Aged ; Positron-Emission Tomography ; }, abstract = {Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma.}, }
@article {pmid26564123, year = {2016}, author = {Moccia, M and Erro, R and Picillo, M and Santangelo, G and Spina, E and Allocca, R and Longo, K and Amboni, M and Palladino, R and Assante, R and Pappatà, S and Pellecchia, MT and Barone, P and Vitale, C}, title = {A Four-Year Longitudinal Study on Restless Legs Syndrome in Parkinson Disease.}, journal = {Sleep}, volume = {39}, number = {2}, pages = {405-412}, pmid = {26564123}, issn = {1550-9109}, mesh = {Adult ; Age of Onset ; Aged ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Female ; Humans ; Incidence ; Logistic Models ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/*complications/diagnosis/drug therapy/*epidemiology ; Prevalence ; Random Allocation ; Restless Legs Syndrome/*complications/diagnosis/*epidemiology/physiopathology ; Sleep Wake Disorders/complications ; Surveys and Questionnaires ; Tomography, Emission-Computed, Single-Photon ; }, abstract = {STUDY OBJECTIVES: Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data.<br><br>METHODS: One hundred nine newly diagnosed, drug-na&#xef;ve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability.<br><br>RESULTS: RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88).<br><br>CONCLUSIONS: RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.}, }
@article {pmid26552553, year = {2015}, author = {Sánchez-Borque, P and Rubio, JM and Benezet-Mazuecos, J and Quiñones, MA and Farré, J}, title = {Atrial fibrillation with Wolff-Parkinson-White syndrome in epilepsy: A potentially fatal combination.}, journal = {Seizure}, volume = {32}, number = {}, pages = {1-3}, doi = {10.1016/j.seizure.2015.08.002}, pmid = {26552553}, issn = {1532-2688}, mesh = {Adult ; Atrial Fibrillation/*complications/physiopathology ; Electrocardiography/methods ; Epilepsy/*complications/physiopathology ; Female ; Humans ; Seizures/complications/physiopathology ; Video Recording/methods ; Wolff-Parkinson-White Syndrome/*complications/physiopathology ; }, }
@article {pmid26546077, year = {2016}, author = {Azagra, R and Zwart, M and Aguyé, A and Martín-Sánchez, JC and Casado, E and Díaz-Herrera, MA and Moriña, D and Cooper, C and Díez-Pérez, A and Dennison, EM and , }, title = {Fracture experience among participants from the FROCAT study: what thresholding is appropriate using the FRAX tool?.}, journal = {Maturitas}, volume = {83}, number = {}, pages = {65-71}, doi = {10.1016/j.maturitas.2015.10.002}, pmid = {26546077}, issn = {1873-4111}, support = {19583/ARC_/Arthritis Research UK/United Kingdom ; MC_U147585827/MRC_/Medical Research Council/United Kingdom ; MC_U147585819/MRC_/Medical Research Council/United Kingdom ; MC_UP_A620_1014/MRC_/Medical Research Council/United Kingdom ; 19583/VAC_/Versus Arthritis/United Kingdom ; MC_UU_12011/1/MRC_/Medical Research Council/United Kingdom ; G0400491/MRC_/Medical Research Council/United Kingdom ; MC_U147585824/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; *Algorithms ; Female ; Humans ; Middle Aged ; Osteoporotic Fractures/*epidemiology ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Spain/epidemiology ; }, abstract = {OBJECTIVE: To perform an external validation of FRAX algorithm thresholds for reporting level of risk of fracture in Spanish women (low < 5%; intermediate ≥ 5% and < 7.5%; high ≥ 7.5%) taken from a prospective cohort "FRIDEX".<br><br>METHODS: A retrospective study of 1090 women aged &#x2265; 40 and &#x2264; 90 years old obtained from the general population (FROCAT cohort). FRAX was calculated with data registered in 2002. All fractures were validated in 2012. Sensitivity analysis was performed.<br><br>RESULTS: When analyzing the cohort (884) excluding current or past anti osteoporotic medication (AOM), using our nominated thresholds, among the 621 (70.2%) women at low risk of fracture, 5.2% [CI95%: 3.4-7.6] sustained a fragility fracture; among the 99 at intermediate risk, 12.1% [6.4-20.2]; and among the 164 defined as high risk, 15.9% [10.6-24.2]. Sensitivity analysis against model risk stratification FRIDEX of FRAX Spain shows no significant difference. By including 206 women with AOM, the sensitivity analysis shows no difference in the group of intermediate and high risk and minimal differences in the low risk group.<br><br>CONCLUSIONS: Our findings support and validate the use of FRIDEX thresholds of FRAX when discussing the risk of fracture and the initiation of therapy with patients.}, }
@article {pmid26543228, year = {2016}, author = {Hart, PC and Ratti, BA and Mao, M and Ansenberger-Fricano, K and Shajahan-Haq, AN and Tyner, AL and Minshall, RD and Bonini, MG}, title = {Caveolin-1 regulates cancer cell metabolism via scavenging Nrf2 and suppressing MnSOD-driven glycolysis.}, journal = {Oncotarget}, volume = {7}, number = {1}, pages = {308-322}, pmid = {26543228}, issn = {1949-2553}, support = {R01 DK044525/DK/NIDDK NIH HHS/United States ; R01 HL071626/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Caveolin 1/*genetics/metabolism ; Cell Line ; *Glycolysis ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Kelch-Like ECH-Associated Protein 1 ; MCF-7 Cells ; Mammary Neoplasms, Animal/genetics/metabolism ; Mice ; Microscopy, Confocal ; NF-E2-Related Factor 2/genetics/*metabolism ; Prognosis ; Protein Binding ; RNA Interference ; Superoxide Dismutase/genetics/*metabolism ; Survival Analysis ; }, abstract = {Aerobic glycolysis is an indispensable component of aggressive cancer cell metabolism. It also distinguishes cancer cells from most healthy cell types in the body. Particularly for this reason, targeting the metabolism to improve treatment outcomes has long been perceived as a potentially valuable strategy. In practice, however, our limited knowledge of why and how metabolic reprogramming occurs has prevented progress towards therapeutic interventions that exploit the metabolic peculiarities of tumors. We recently described that in breast cancer, MnSOD upregulation is both necessary and sufficient to activate glycolysis. Here, we focused on determining the molecular mechanisms of MnSOD upregulation. We found that Caveolin-1 (Cav-1) is a central component of this mechanism due to its suppressive effects of NF-E2-related factor 2 (Nrf2), a transcription factor upstream of MnSOD. In transformed MCF10A(Er/Src) cells, Cav-1 loss preceded the activation of Nrf2 and its induction of MnSOD expression. Consistently, with previous observations, MnSOD expression secondary to Nrf2 activation led to an increase in the glycolytic rate dependent on mtH2O2 production and the activation of AMPK. Moreover, rescue of Cav-1 expression in a breast cancer cell line (MCF7) suppressed Nrf2 and reduced MnSOD expression. Experimental data were reinforced by epidemiologic nested case-control studies showing that Cav-1 and MnSOD are inversely expressed in cases of invasive ductal carcinoma, with low Cav-1 and high MnSOD expression being associated with lower 5-year survival rates and molecular subtypes with poorest prognosis.}, }
@article {pmid26511818, year = {2016}, author = {Chang, JS and Lee, J and Kim, HJ and Kim, KH and Yun, M and Kim, SI and Keum, KC and Suh, CO and Kim, YB}, title = {(18)F-FDG/PET May Help to Identify a Subgroup of Patients with T1-T2 Breast Cancer and 1-3 Positive Lymph Nodes Who Are at a High Risk of Recurrence after Mastectomy.}, journal = {Cancer research and treatment}, volume = {48}, number = {2}, pages = {508-517}, pmid = {26511818}, issn = {2005-9256}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology/radiotherapy ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnostic imaging/*pathology/radiotherapy ; *Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/prevention &amp; control ; *Positron-Emission Tomography ; Risk Assessment ; Risk Factors ; Tumor Burden ; }, abstract = {PURPOSE: The purpose of this study is to assess the utility of positron emission tomography (PET) for predicting recurrence among patients with T1-T2/N1 breast cancer who were treated with mastectomy.<br><br>MATERIALS AND METHODS: Of 712 consecutive patients with T1-T2/N1 breast cancer treated during 2003-2012, 109 had undergone preoperative (18)F-fluorodeoxyglucose/PET and were included. Metabolic (maximum standardized uptake value [SUVmax]), volumetric (metabolic tumor volume [MTV]), and combined (total lesion glycolysis [TLG]) indices were measured. The resulting values were analyzed and compared with clinical outcome.<br><br>RESULTS: At the median follow-up of 46.7 months, the 3-year relapse-free survival (RFS) rate was 95.2%. SUVmax (area under curve, 0.824) was more useful than MTV or TLG as a means of identifying patients at high risk for any recurrence. In multivariate analysis, SUVmax remained an independent risk factor for RFS (p=0.006). Using the method of Contal and O'Quigley, a SUVmax threshold of 5.36 showed the best predictive performance. The PET-based high-risk group (&#x2265; 5.36 in either breast or nodes) had more T1c-T2, high-grade, hormone-receptor negative, and invasive ductal carcinoma tumors than the low-risk group (< 5.36 in both breast and nodes). The prognosis was much worse when high SUVmax (&#x2265; 5.36) was detected in nodes (p < 0.001). In the no-radiotherapy cohort, the PET-based high-risk group had increased risk of locoregional recurrence when compared to the low-risk group (p=0.037).<br><br>CONCLUSION: High SUVmax on preoperative PET showed association with elevated risk of locoregional recurrence and any recurrence. Pre-treatment PET may improve assessments of recurrence risk and clarify indications for post-mastectomy radiotherapy in this subset of patients.}, }
@article {pmid26505860, year = {2016}, author = {Ni, J and Tang, P}, title = {An Unusual Bone Metastasis Mimicking SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis) Syndrome on Bone Scintigraphy.}, journal = {Clinical nuclear medicine}, volume = {41}, number = {2}, pages = {173-175}, doi = {10.1097/RLU.0000000000001061}, pmid = {26505860}, issn = {1536-0229}, mesh = {Acquired Hyperostosis Syndrome/*diagnostic imaging ; Bone Neoplasms/*diagnostic imaging/secondary ; Breast Neoplasms/diagnostic imaging/*pathology ; Diagnostic Errors ; Female ; Humans ; Middle Aged ; Radionuclide Imaging ; }, abstract = {The costosternoclavicular region is not a common bone metastasis site, and symmetrical involvement is even rarer. Increased tracer uptake in the manubrium and sternoclavicular joints usually gives the typical "bull-horn" appearance seen in SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis). Herein, we report a case of a 47-year-old woman with a history of invasive ductal carcinoma who had undergone left radical mastectomy 3 years earlier and presented with typical increased tracer uptake in the bilateral sternocostoclavicular region resembling the so-called bull horn. The final diagnosis of metastasis from breast cancer was made histopathologically following biopsy.}, }
@article {pmid26503945, year = {2016}, author = {Podo, F and Santoro, F and Di Leo, G and Manoukian, S and de Giacomi, C and Corcione, S and Cortesi, L and Carbonaro, LA and Trimboli, RM and Cilotti, A and Preda, L and Bonanni, B and Pensabene, M and Martincich, L and Savarese, A and Contegiacomo, A and Sardanelli, F}, title = {Triple-Negative versus Non-Triple-Negative Breast Cancers in High-Risk Women: Phenotype Features and Survival from the HIBCRIT-1 MRI-Including Screening Study.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {22}, number = {4}, pages = {895-904}, doi = {10.1158/1078-0432.CCR-15-0459}, pmid = {26503945}, issn = {1557-3265}, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/*diagnosis/genetics/mortality/therapy ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Middle Aged ; Mutation ; Phenotype ; Risk ; Treatment Outcome ; Triple Negative Breast Neoplasms/*diagnosis/genetics/mortality/therapy ; }, abstract = {PURPOSE: To compare phenotype features and survival of triple-negative breast cancers (TNBC) versus non-TNBCs detected during a multimodal annual screening of high-risk women.<br><br>EXPERIMENTAL DESIGN: Analysis of data from asymptomatic high-risk women diagnosed with invasive breast cancer during the HIBCRIT-1 study with median 9.7-year follow-up.<br><br>RESULTS: Of 501 enrolled women with BRCA1/2 mutation or strong family history (SFH), 44 were diagnosed with invasive breast cancers: 20 BRCA1 (45%), 9 BRCA2 (21%), 15 SFH (34%). Magnetic resonance imaging (MRI) sensitivity (90%) outperformed that of mammography (43%, P < 0.001) and ultrasonography (61%, P = 0.004). The 44 cases (41 screen-detected; 3 BRCA1-associated interval TNBCs) comprised 14 TNBCs (32%) and 30 non-TNBCs (68%), without significant differences for age at diagnosis, menopausal status, prophylactic oophorectomy, or previous breast cancer. Of 14 TNBC patients, 11 (79%) were BRCA1; of the 20 BRCA1 patients, 11 (55%) had TNBC; and of 15 SFH patients, 14 (93%) had non-TNBCs (P = 0.007). Invasive ductal carcinomas (IDC) were 86% for TNBCs versus 43% for non-TNBCs (P = 0.010), G3 IDCs 71% versus 23% (P = 0.006), size 16 &#xb1; 5 mm versus 12 &#xb1; 6 mm (P = 0.007). TNBC patients had more frequent ipsilateral mastectomy (79% vs. 43% for non-TNBCs, P = 0.050), contralateral prophylactic mastectomy (43% vs. 10%, P = 0.019), and adjuvant chemotherapy (100% vs. 44%, P < 0.001). The 5-year overall survival was 86% &#xb1; 9% for TNBCs versus 93% &#xb1; 5% (P = 0.946) for non-TNBCs; 5-year disease-free survival was 77% &#xb1; 12% versus 76% &#xb1; 8% (P = 0.216).<br><br>CONCLUSIONS: In high-risk women, by combining an MRI-including annual screening with adequate treatment, the usual reported gap in outcome between TNBCs and non-TNBCs could be reduced.}, }
@article {pmid26491255, year = {2015}, author = {Su, Y and Wang, X and Li, J and Xu, J and Xu, L}, title = {The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review.}, journal = {Drug design, development and therapy}, volume = {9}, number = {}, pages = {5439-5445}, pmid = {26491255}, issn = {1177-8881}, mesh = {Acid Anhydride Hydrolases/*genetics/metabolism ; Animals ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*drug therapy/enzymology/*genetics/pathology ; Carcinoma, Ductal, Breast/*drug therapy/enzymology/*genetics/pathology ; Chi-Square Distribution ; DNA Methylation/*drug effects ; Drug Discovery/*methods ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *Molecular Targeted Therapy ; Neoplasm Proteins/*genetics/metabolism ; Neoplasm Staging ; Odds Ratio ; Risk Factors ; Signal Transduction/drug effects ; }, abstract = {FHIT is a bona fide tumor-suppressor gene and its loss contributes to tumorigenesis of epithelial cancers including breast cancer (BC). However, the association and clinicopathological significance between FHIT promoter hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate the clinicopathological significance of FHIT methylation in BC. A detailed literature search was performed in PubMed, EMBASE, Web of Science, and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds ratios with 95% corresponding confidence intervals were calculated. A total of seven relevant articles were available for meta-analysis, which included 985 patients. The frequency of FHIT hypermethylation was significantly increased in invasive ductal carcinoma compared to benign breast disease, the pooled odds ratio was 8.43, P<0.00001. The rate of FHIT hypermethylation was not significantly different between stage I/II and stage III/IV, odds ratio was 2.98, P=0.06. In addition, FHIT hypermethylation was not significantly associated with ER and PR status. FHIT hypermethylation was not significantly correlated with premenopausal and postmenopausal patients with invasive ductal carcinoma. In summary, our meta-analysis indicated that the frequency of FHIT hypermethylation was significantly increased in BC compared to benign breast disease. The rate of FHIT hypermethylation in advanced stages of BC was higher than in earlier stages; however, the difference was not statistically significant. Our data suggested that FHIT methylation could be a diagnostic biomarker of BC carcinogenesis. FHIT is a potential drug target for development of demethylation treatment for patients with BC.}, }
@article {pmid26489549, year = {2015}, author = {Takayanagi, H and Hayami, R and Tsuneizumi, M and Nakagami, K}, title = {[Thrombophlebitis in an Elderly Japanese Woman Treated with Tamoxifen for Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {42}, number = {10}, pages = {1203-1205}, pmid = {26489549}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Antineoplastic Agents, Hormonal/*adverse effects/therapeutic use ; Biopsy ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy ; Female ; Humans ; Neoplasm Staging ; Tamoxifen/*adverse effects/therapeutic use ; Thrombophlebitis/*chemically induced/diagnostic imaging ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {In this study, we report the rare case of an elderly woman who developed thrombophlebitis after being treated with tamoxifen for breast cancer. She visited our department with a lump in her left breast. She underwent core needle biopsy, and she was diagnosed with breast cancer (invasive ductal carcinoma, ER- and PgR-positive, HER2-negative). We chose hormonal therapy because surgical treatment was deemed too invasive considering her general status. She was administered tamoxifen (20 mg/day) instead of an aromatase inhibitor in consideration of her osteoporosis. Six months after initiating tamoxifen therapy, she exhibited swelling in her left leg. Computed tomography and ultrasound revealed thrombophlebitis in her left femoral vein. She stopped taking tamoxifen and started warfarin potassium as thrombolytic therapy, after which thrombophlebitis was relieved. Advanced age may be a risk factor for thrombophlebitis associated with tamoxifen treatment; therefore, precautions should be taken accordingly.}, }
@article {pmid26481274, year = {2015}, author = {Ballard, AJ}, title = {Epstein-Barr virus infection is equally distributed across the invasive ductal and invasive lobular forms of breast cancer.}, journal = {Pathology, research and practice}, volume = {211}, number = {12}, pages = {1003-1005}, doi = {10.1016/j.prp.2015.09.017}, pmid = {26481274}, issn = {1618-0631}, mesh = {Breast Neoplasms/*pathology/*virology ; Carcinoma, Ductal, Breast/pathology/*virology ; Carcinoma, Lobular/pathology/*virology ; Epstein-Barr Virus Infections/*complications ; Female ; Humans ; Immunohistochemistry ; Tissue Array Analysis ; }, abstract = {The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer is still unclear, although a growing body of evidence supports a link. The aim of this study was to investigate if EBV infection was more prevalent in invasive ductal carcinoma or invasive lobular carcinoma. An immunohistochemical marker for EBV (Epstein-Barr virus nuclear antigen 1 (EBNA1) clone E1-2.5) was applied to a tissue micro array section. The tissue micro array contained 80 cases of invasive ductal carcinoma, and 80 cases of invasive lobular carcinoma. Each case was scored as positive or negative for nuclear expression of EBNA1 in tumor cells using standard light microscopy. EBNA1 staining was evident in the tumor cells of 63 cases (39.4% of tumor cases). By tumor type (ductal/lobular) EBV infection was noted in 34 (42.5%) cases of invasive ductal carcinoma and 29 (36.2%) cases of invasive lobular carcinoma, this difference was not found to be significant (P=0.518). This study indicates that EBV infection is equally distributed across the ductal and lobular tumor types.}, }
@article {pmid26475094, year = {2015}, author = {Di Oto, E and Monti, V and Cucchi, MC and Masetti, R and Varga, Z and Foschini, MP}, title = {X chromosome gain in male breast cancer.}, journal = {Human pathology}, volume = {46}, number = {12}, pages = {1908-1912}, doi = {10.1016/j.humpath.2015.08.008}, pmid = {26475094}, issn = {1532-8392}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Chromosomes, Human, X/*genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; }, abstract = {Male breast cancer (MBC) is an uncommon disease whose molecular profile is not well known. X chromosome gain has been described as a marker of aggressive behavior in female breast cancer. The aim of this study is to investigate the role of the X chromosome in male breast cancer. Twenty cases of male breast invasive ductal carcinoma were retrieved and compared with 10 cases of gynecomastia. Cases were tested by fluorescence in situ hybridization to assess a cytogenetic profile for the X chromosome. The X chromosome status was compared with histopathologic features and stage at presentation. All MBC cases harbored an X chromosome gain (100%) in a variable percentage of neoplastic cells, ranging from 31% to 85% (mean, 59%). On the contrary, all cases of gynecomastia showed wild X chromosome asset. The patients' age at surgery and tumor grading showed a statistically significant correlation (P = .0188-.04), with the percentages of neoplastic cells showing an X chromosome gain. These data suggest that this X chromosome gain plays a role in the neoplastic transformation of male breast epithelial cells.}, }
@article {pmid26474389, year = {2015}, author = {Aswad, L and Yenamandra, SP and Ow, GS and Grinchuk, O and Ivshina, AV and Kuznetsov, VA}, title = {Genome and transcriptome delineation of two major oncogenic pathways governing invasive ductal breast cancer development.}, journal = {Oncotarget}, volume = {6}, number = {34}, pages = {36652-36674}, pmid = {26474389}, issn = {1949-2553}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cohort Studies ; Female ; Genome, Human ; Humans ; Middle Aged ; Prognosis ; Transcriptome ; }, abstract = {Invasive ductal carcinoma (IDC) is a major histo-morphologic type of breast cancer. Histological grading (HG) of IDC is widely adopted by oncologists as a prognostic factor. However, HG evaluation is highly subjective with only 50%-85% inter-observer agreements. Specifically, the subjectivity in the assignment of the intermediate grade (histologic grade 2, HG2) breast cancers (comprising ~50% of IDC cases) results in uncertain disease outcome prediction and sub-optimal systemic therapy. Despite several attempts to identify the mechanisms underlying the HG classification, their molecular bases are poorly understood.We performed integrative bioinformatics analysis of TCGA and several other cohorts (total 1246 patients). We identified a 22-gene tumor aggressiveness grading classifier (22g-TAG) that reflects global bifurcation in the IDC transcriptomes and reclassified patients with HG2 tumors into two genetically and clinically distinct subclasses: histological grade 1-like (HG1-like) and histological grade 3-like (HG3-like). The expression profiles and clinical outcomes of these subclasses were similar to the HG1 and HG3 tumors, respectively. We further reclassified IDC into low genetic grade (LGG = HG1+HG1-like) and high genetic grade (HGG = HG3-like+HG3) subclasses. For the HG1-like and HG3-like IDCs we found subclass-specific DNA alterations, somatic mutations, oncogenic pathways, cell cycle/mitosis and stem cell-like expression signatures that discriminate between these tumors. We found similar molecular patterns in the LGG and HGG tumor classes respectively.Our results suggest the existence of two genetically-predefined IDC classes, LGG and HGG, driven by distinct oncogenic pathways. They provide novel prognostic and therapeutic biomarkers and could open unique opportunities for personalized systemic therapies of IDC patients.}, }
@article {pmid26472289, year = {2015}, author = {Ressl, N and Oberndorfer, S}, title = {Multiple calcified brain metastases in a man with invasive ductal breast cancer.}, journal = {BMJ case reports}, volume = {2015}, number = {}, pages = {}, pmid = {26472289}, issn = {1757-790X}, mesh = {Brain Neoplasms/*pathology/*secondary ; Breast Neoplasms, Male/*pathology ; Calcinosis/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Humans ; Male ; Middle Aged ; }, abstract = {We report a case of a 52-year-old Caucasian man with invasive ductal carcinoma of the breast. One year after initial diagnosis, he developed a generalised epileptic seizure and neuroimaging showed multiple, calcified intracerebral lesions. Owing to these atypical cerebral imaging findings, comprehensive serological and cerebrospinal fluid analysis was conducted and a latent toxoplasmosis was suspected. In order to distinguish between metastases and an infectious disease, a cerebral biopsy was performed, which verified brain metastases. The patient received whole-brain radiotherapy. The last cerebral CT scan, 18 months later showed stable disease. Calcification of brain metastases in patients with breast cancer is very rare. Owing to their non-characteristic radiological appearance with a lack of contrast enhancement, diagnosis of metastases can be difficult. Infectious diseases should be considered within the diagnostic work up. Owing to possible pitfalls, we recommend a widespread differential diagnostic work up in similar cases, and even in cases with a confirmed primary tumour.}, }
@article {pmid26466985, year = {2016}, author = {Di Rosa, M and Tibullo, D and Saccone, S and Distefano, G and Basile, MS and Di Raimondo, F and Malaguarnera, L}, title = {CHI3L1 nuclear localization in monocyte derived dendritic cells.}, journal = {Immunobiology}, volume = {221}, number = {2}, pages = {347-356}, doi = {10.1016/j.imbio.2015.09.023}, pmid = {26466985}, issn = {1878-3279}, mesh = {Adipokines/genetics/*immunology ; Amino Acid Sequence ; Cell Differentiation ; Cell Nucleus/drug effects/*metabolism ; Chitinase-3-Like Protein 1 ; Dendritic Cells/cytology/drug effects/*immunology ; Gene Expression Regulation ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Lectins/genetics/*immunology ; Macrophages/cytology/drug effects/*immunology ; Models, Molecular ; Molecular Sequence Data ; Monocytes/cytology/drug effects/*immunology ; Primary Cell Culture ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Signal Transduction ; }, abstract = {Chitinase-3-like-1 protein (CHI3L1) is a glycosyl hydrolase (GH) highly expressed in a variety of inflammatory diseases at infectious and non-infectious etiology. CHI3L1 is produced by a wide variety of cells including monocyte-derived macrophages cell lines such as polarized M1 and M2 type macrophages, osteoclasts and Kupffer cells. In this study we have examined the expression of CHI3L1 during the differentiation and maturation of dendritic cells. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) through a combination of factors and cytokines. Our result showed, for the first time, that CHI3L1 is expressed during the process of differentiation and maturation of dendritic cells in time dependent manner. Furthermore, the CHI3L1 is evenly distributed in cytoplasm and in the nucleus of both the iDCs and mDCs. These results suggest that CHI3L1 may play crucial role in the DCs immunoresponse.}, }
@article {pmid26463438, year = {2016}, author = {Gayarre, J and Kamieniak, MM and Cazorla-Jiménez, A and Muñoz-Repeto, I and Borrego, S and García-Donas, J and Hernando, S and Robles-Díaz, L and García-Bueno, JM and Ramón Y Cajal, T and Hernández-Agudo, E and Heredia Soto, V and Márquez-Rodas, I and Echarri, MJ and Lacambra-Calvet, C and Sáez, R and Cusidó, M and Redondo, A and Paz-Ares, L and Hardisson, D and Mendiola, M and Palacios, J and Benítez, J and García, MJ}, title = {The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients.}, journal = {Journal of gynecologic oncology}, volume = {27}, number = {1}, pages = {e7}, pmid = {26463438}, issn = {2005-0399}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis/genetics ; Carcinoma, Ovarian Epithelial ; Cystadenocarcinoma, Serous/*genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Proteins/biosynthesis/genetics ; Neoplasms, Glandular and Epithelial/*genetics/metabolism/pathology ; Ovarian Neoplasms/*genetics/metabolism/pathology ; Prognosis ; Transcription Factors/biosynthesis/*genetics ; Tumor Cells, Cultured ; }, abstract = {OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.<br><br>METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and &#x2264; median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays.<br><br>RESULTS: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells.<br><br>CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.}, }
@article {pmid26451490, year = {2015}, author = {Ciriello, G and Gatza, ML and Beck, AH and Wilkerson, MD and Rhie, SK and Pastore, A and Zhang, H and McLellan, M and Yau, C and Kandoth, C and Bowlby, R and Shen, H and Hayat, S and Fieldhouse, R and Lester, SC and Tse, GM and Factor, RE and Collins, LC and Allison, KH and Chen, YY and Jensen, K and Johnson, NB and Oesterreich, S and Mills, GB and Cherniack, AD and Robertson, G and Benz, C and Sander, C and Laird, PW and Hoadley, KA and King, TA and ,  and Perou, CM}, title = {Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.}, journal = {Cell}, volume = {163}, number = {2}, pages = {506-519}, pmid = {26451490}, issn = {1097-4172}, support = {P50-CA58223-09A1/CA/NCI NIH HHS/United States ; R00 CA166228/CA/NCI NIH HHS/United States ; K22 LM011931/LM/NLM NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U24 CA143848/CA/NCI NIH HHS/United States ; F30 CA192725/CA/NCI NIH HHS/United States ; U24 CA143867/CA/NCI NIH HHS/United States ; K99 CA166228/CA/NCI NIH HHS/United States ; P50 CA058223/CA/NCI NIH HHS/United States ; R01 CA180006/CA/NCI NIH HHS/United States ; U24 CA143858/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cadherins/chemistry/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Lobular/*genetics/metabolism/*pathology ; Female ; Hepatocyte Nuclear Factor 3-alpha/chemistry/genetics/metabolism ; Humans ; Models, Molecular ; Mutation ; Oligonucleotide Array Sequence Analysis ; Oncogene Protein v-akt/metabolism ; Transcriptome ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.}, }
@article {pmid26440364, year = {2015}, author = {Cheng, YS and Seibert, O and Klöting, N and Dietrich, A and Straßburger, K and Fernández-Veledo, S and Vendrell, JJ and Zorzano, A and Blüher, M and Herzig, S and Berriel Diaz, M and Teleman, AA}, title = {PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis.}, journal = {PLoS genetics}, volume = {11}, number = {10}, pages = {e1005561}, pmid = {26440364}, issn = {1553-7404}, mesh = {AMP-Activated Protein Kinases/genetics ; Animals ; Dietary Carbohydrates/metabolism ; Energy Metabolism/*genetics ; Glucose/metabolism ; Hepatocytes/metabolism ; Humans ; Insulin Resistance/genetics ; Lipid Metabolism/*genetics ; Lipogenesis/genetics ; Liver/metabolism ; Mice ; Obesity/*genetics/pathology ; Protein Phosphatase 2/*genetics ; Sterol Regulatory Element Binding Protein 1/genetics ; }, abstract = {In mammals, the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids. In particular, when dietary carbohydrates are in excess, the liver converts them to lipids via de novo lipogenesis. The molecular checkpoints regulating the balance between carbohydrate and lipid homeostasis, however, are not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as a novel modulator of liver metabolism in postprandial physiology. Inactivation of PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance and insulin sensitivity, but elevated circulating triglyceride levels. We show that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1 activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic patients, and correlate with obesity and insulin resistance in these subjects. In sum, our data suggest that hepatic PPP2R5C represents an important factor in the functional wiring of energy metabolism and the maintenance of a metabolically healthy state.}, }
@article {pmid26438270, year = {2015}, author = {Kim, TS and Kang, YJ and Kim, JY and Lee, S and Lee, WJ and Sohn, Y and Lee, HW}, title = {Up-regulated S100 calcium binding protein A8 in Plasmodium-infected patients correlates with CD4(+)CD25(+)Foxp3 regulatory T cell generation.}, journal = {Malaria journal}, volume = {14}, number = {}, pages = {385}, pmid = {26438270}, issn = {1475-2875}, mesh = {Adult ; CD4 Antigens/analysis ; Calgranulin A/*blood ; Enzyme-Linked Immunosorbent Assay ; Forkhead Transcription Factors/analysis ; Humans ; Immune Evasion ; Interleukin-2 Receptor alpha Subunit/analysis ; Malaria, Vivax/*immunology ; Plasmodium vivax/*immunology/physiology ; Serum/chemistry ; T-Lymphocyte Subsets/chemistry/*immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/chemistry/*immunology ; }, abstract = {BACKGROUND: The pro-inflammatory S100 calcium binding protein A8 (S100A8) is elevated in the serum of patients with Plasmodium falciparum malaria, but its function in Plasmodium vivax malaria is not yet clear. This function was investigated in P. vivax-infected patients in this study.<br><br>METHODS: The level of S100A8 in the serum was measured with ELISA. Full amino acids of S100A8 were synthesized to verify the functions for maturation of immature dendritic cell (iDC) and evaluation of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) generation by mature DC (mDC).<br><br>RESULTS: A higher amount of S100A8 was detected in vivax-infected patients (141.2 &#xb1; 61.849 ng/ml, n = 40) compared with normal control group (48.1 &#xb1; 27.384 ng/ml, n = 40). The level of S100A8 did not coincide with that of anti-malarial antibody measured by indirect fluorescent antibody test (IFAT) using parasite-infected red blood cells as antigen. Programmed death-ligand 1 (PD-L1) was up-regulated on the surface of iDCs following treatment with synthetic S100A8, not with synthetic MSP-1, AMA-1 and CSP, as compared to the expression seen for non-treated iDCs. The addition of red blood cells of infected patients to iDCs also elevated their surface expression of CD86. However, the serum levels of S100A8 decreased with increase in parasitaemia. DCs matured by sera containing S100A8 generated Treg cells from na&#xef;ve T cells. The ratio of Treg cells generated was inversely proportional to the concentration of S100A8 in sera.<br><br>CONCLUSIONS: Treg cells suppress the activity of cytotoxic T cells, which kill malaria parasites; therefore, the up-regulation of S100A8 in malaria patients may contribute to pathogen immune escape or tolerance.}, }
@article {pmid26437542, year = {2015}, author = {Claimon, A and Chuthapisith, S and Samarnthai, N and Pusuwan, P}, title = {Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {98}, number = {8}, pages = {828-832}, pmid = {26437542}, issn = {0125-2208}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis/*secondary ; Carcinoma, Neuroendocrine/*diagnosis/*secondary ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed ; }, abstract = {The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor}, }
@article {pmid26425077, year = {2015}, author = {Huang, R and Ding, P and Yang, F}, title = {Clinicopathological significance and potential drug target of CDH1 in breast cancer: a meta-analysis and literature review.}, journal = {Drug design, development and therapy}, volume = {9}, number = {}, pages = {5277-5285}, pmid = {26425077}, issn = {1177-8881}, mesh = {Antigens, CD ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/drug therapy/*genetics/metabolism/mortality/pathology ; Cadherins/*genetics/metabolism ; Carcinoma, Ductal, Breast/drug therapy/*genetics/metabolism/mortality/pathology ; Chi-Square Distribution ; *DNA Methylation ; Drug Design ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Molecular Targeted Therapy ; Odds Ratio ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Risk Factors ; Treatment Outcome ; }, abstract = {CDH1, as a tumor suppressor gene, contributes sporadic breast cancer (BC) progression. However, the association between CDH1 hypermethylation and BC, and its clinicopathological significance remains unclear. We conducted a meta-analysis to investigate the relationship between the CDH1 methylation profile and the major clinicopathological features. A detailed literature was searched through the electronic databases PubMed, Web of Science™, and EMBASE™ for related research publications. The data were extracted and assessed by two reviewers independently. Odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated and summarized respectively. The frequency of CDH1 methylation was significantly higher in invasive ductal carcinoma than in normal breast tissues (OR =5.83, 95% CI 3.76-9.03, P<0.00001). CDH1 hypermethylation was significantly higher in estrogen receptor (ER)-negative BC than in ER-positive BC (OR =0.62, 95% CI 0.43-0.87, P=0.007). In addition, we found that the CDH1 was significantly methylated in HER2-negative BC than in HER2-positive BC (OR =0.26, 95% CI 0.15-0.44, P<0.00001). However, CDH1 methylation frequency was not associated with progesterone receptor (PR) status, or with grades, stages, or lymph node metastasis of BC patients. Our results indicate that CDH1 hypermethylation is a potential novel drug target for developing personalized therapy. CDH1 hypermethylation is strongly associated with ER-negative and HER2-negative BC, respectively, suggesting CDH1 methylation status could contribute to the development of novel therapeutic approaches for the treatment of ER-negative or HER2-negative BC with aggressive tumor biology.}, }
@article {pmid26410088, year = {2015}, author = {Yang, JZ and Wang, ZX and Ma, LH and Shen, XB and Sun, Y and Hu, DW and Sun, LX}, title = {The organochlorine pesticides residues in the invasive ductal breast cancer patients.}, journal = {Environmental toxicology and pharmacology}, volume = {40}, number = {3}, pages = {698-703}, doi = {10.1016/j.etap.2015.07.007}, pmid = {26410088}, issn = {1872-7077}, mesh = {Adipose Tissue/*chemistry ; Adult ; Aged ; Breast Neoplasms/*blood/metabolism/pathology ; Carcinoma, Ductal, Breast/*blood/metabolism/pathology ; Chlorobenzenes/blood ; Dichlorodiphenyl Dichloroethylene/blood ; Female ; Hexachlorocyclohexane/blood ; Humans ; Hydrocarbons, Chlorinated/*toxicity ; Middle Aged ; Receptors, Estrogen/metabolism ; }, abstract = {Investigation of organochlorine pesticides residues (important environmental contamination causing malignant transformation) in breast cancer patients is valuable to understanding their roles in breast cancer. 75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of β-HCH and PCTA were higher in IDC than those in both controls (both p<0.05), and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of β-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of β-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC (all p<0.05). The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.}, }
@article {pmid26408705, year = {2015}, author = {Ozturk, T and Kucukhuseyin, O and Eronat, AP and Tuzuner, MB and Daglar-Aday, A and Saygili, N and Kisakesen, HI and Seyhan, F and Velidedeoğlu, M and Calay, Z and Ilvan, &#x15e; and Yilmaz-Aydoğan, H and Ozturk, O and Isbir, T}, title = {Preliminary Study: Prominent miRNAs of Breast Malignant Tissues Compared to Normal Tissues in Turkish Patients with Breast Cancer.}, journal = {Anticancer research}, volume = {35}, number = {10}, pages = {5425-5432}, pmid = {26408705}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/*pathology ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; MicroRNAs/*genetics ; Middle Aged ; Turkey ; }, abstract = {miRNA involvement has been observed in almost every type of cancer, including breast cancer. The etiology of abnormal expression of miRNAs in cancer is still not clearly understood. In order to obtain insight into miRNA de-regulation in breast cancer, we analyzed expression levels of five breast cancer-related miRNAs, miRNA21, miRNA155, miRNA19a, miRNA17-5p and let7a miRNA, in both malignant and neighboring non-tumoral paraffin-embedded tissues of 47 patients with invasive ductal breast cancer. The targeted miRNAs, and a reference snRNA, U6, were analyzed by real-time polymerase chain reaction. let7a Levels were significantly lower in patients with lymphatic invasion than in those without (p=0.047). miR21 was down-regulated in 93.3% of patients with necrosis [p=0.017 (Fisher's exact test (FE))], while at least one oncogenic miRNA was up-regulated in 87.3% of the patients with invasive ductal carcinoma [p=0.009 (FE)]. In addition, tumor-suppressor miRNA was down-regulated or unaltered in 65.8% of the patients with tumor grade 2 or 3 and in all with grade 1 [p=0.047 (FE)]. Based on this preliminary study, we suggest that these miRNAs, especially let7a and miRNA21, might be useful markers in follow-up of breast cancer and in prognosis.}, }
@article {pmid26404623, year = {2015}, author = {Nestal de Moraes, G and Delbue, D and Silva, KL and Robaina, MC and Khongkow, P and Gomes, AR and Zona, S and Crocamo, S and Mencalha, AL and Magalhães, LM and Lam, EW and Maia, RC}, title = {FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance.}, journal = {Cellular signalling}, volume = {27}, number = {12}, pages = {2496-2505}, doi = {10.1016/j.cellsig.2015.09.013}, pmid = {26404623}, issn = {1873-3913}, support = {A12011/CRUK_/Cancer Research UK/United Kingdom ; BBS/B/03785/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Antibiotics, Antineoplastic/pharmacology ; Base Sequence ; Binding Sites ; Breast Neoplasms/drug therapy/metabolism/mortality ; Cell Survival ; Docetaxel ; Doxorubicin/pharmacology ; *Drug Resistance, Neoplasm ; Female ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/*physiology ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Inhibitor of Apoptosis Proteins/genetics/*metabolism ; Kaplan-Meier Estimate ; MCF-7 Cells ; Middle Aged ; Prognosis ; Promoter Regions, Genetic ; Protein Binding ; Survivin ; Taxoids/pharmacology ; X-Linked Inhibitor of Apoptosis Protein/genetics/*metabolism ; }, abstract = {Drug resistance is a major hurdle for successful treatment of breast cancer, the leading cause of deaths in women throughout the world. The FOXM1 transcription factor is a potent oncogene that transcriptionally regulates a wide range of target genes involved in DNA repair, metastasis, cell invasion, and migration. However, little is known about the role of FOXM1 in cell survival and the gene targets involved. Here, we show that FOXM1-overexpressing breast cancer cells display an apoptosis-resistant phenotype, which associates with the upregulation of expression of XIAP and Survivin antiapoptotic genes. Conversely, FOXM1 knockdown results in XIAP and Survivin downregulation as well as decreased binding of FOXM1 to the promoter regions of XIAP and Survivin. Consistently, FOXM1, XIAP, and Survivin expression levels were higher in taxane and anthracycline-resistant cell lines when compared to their sensitive counterparts and could not be downregulated in response to drug treatment. In agreement with our in vitro findings, we found that FOXM1 expression is significantly associated with Survivin and XIAP expression in samples from patients with IIIa stage breast invasive ductal carcinoma. Importantly, patients co-expressing FOXM1, Survivin, and nuclear XIAP had significantly worst overall survival, further confirming the physiological relevance of the regulation of Survivin and XIAP by FOXM1. Together, these findings suggest that the overexpression of FOXM1, XIAP, and Survivin contributes to the development of drug-resistance and is associated with poor clinical outcome in breast cancer patients.}, }
@article {pmid26401837, year = {2015}, author = {Wolmer, L and Hamiel, D and Versano-Eisman, T and Slone, M and Margalit, N and Laor, N}, title = {Preschool Israeli Children Exposed to Rocket Attacks: Assessment, Risk, and Resilience.}, journal = {Journal of traumatic stress}, volume = {28}, number = {5}, pages = {441-447}, doi = {10.1002/jts.22040}, pmid = {26401837}, issn = {1573-6598}, mesh = {Child ; Child, Preschool ; Diagnostic and Statistical Manual of Mental Disorders ; Explosive Agents ; Female ; Humans ; Interviews as Topic ; Israel/epidemiology ; Life Change Events ; Male ; Mothers/*psychology ; Multivariate Analysis ; *Resilience, Psychological ; Stress Disorders, Post-Traumatic/diagnosis/etiology/*psychology ; Terrorism/*psychology ; }, abstract = {Preschool children are among the most vulnerable populations to adversity. This study described the effects of 4 weeks of daily exposure to rocket attacks on children living on Israel's southern border. Participants enrolled in this study were 122 preschool children (50% boys) between the ages 3 and 6 years from 10 kindergartens. We assessed mothers' report of children's symptoms according to the DSM-IV and alternative criteria resembling the DSM-5 criteria for posttraumatic stress disorder (PTSD), general adaptation, traumatic exposure, and stressful life events 3 months after the war. The prevalence of PTSD was lower when the diagnosis was derived from the DSM-IV (4%) than from the DSM-5 criteria (14%). Mothers of children with 4 or more stressful life events reported more functional impairment in social, occupational, and other important areas of functioning compared to children with 0 or 1 stressful life event. Children with more severe exposure showed more severe symptoms and mothers had more concerns about the child's functioning (η(p)(2) = .09-.25). Stressful life events and exposure to traumatic experiences accounted for 32% of the variance in PTSD and 19% of the variance in the adaptation scale. Results were explored in terms of risk and resilience factors.}, }
@article {pmid26400100, year = {2015}, author = {Qin, F and Zhang, H and Ma, L and Liu, X and Dai, K and Li, W and Gu, F and Fu, L and Ma, Y}, title = {Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {14430}, pmid = {26400100}, issn = {2045-2322}, support = {R03 AA020101/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Brain Neoplasms/*metabolism/mortality/*secondary ; Breast Neoplasms/*metabolism/mortality/*pathology ; Carcinoma in Situ/genetics ; Carcinoma, Ductal, Breast/genetics/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Middle Aged ; Nerve Tissue Proteins/genetics/*metabolism ; Prognosis ; Proportional Hazards Models ; Receptors, Immunologic/genetics/*metabolism ; }, abstract = {Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.}, }
@article {pmid26396924, year = {2015}, author = {Usmani, A and Shoro, AA and Memon, Z and Hussain, M and Rehman, R}, title = {Diagnostic, prognostic and predictive value of MicroRNA-21 in breast cancer patients, their daughters and healthy individuals.}, journal = {American journal of cancer research}, volume = {5}, number = {8}, pages = {2484-2490}, pmid = {26396924}, issn = {2156-6976}, abstract = {MicroRNA-21 (miR-21) located on 17q23.1 expressed in breast cancer has anti-apoptotic ability and causes tumor cell growth. It is also involved in functions such as signal transduction pathways effecting normal cell growth and differentiation. The primary objective of the study was to identify presence of miR-21 in the serum levels of stage III invasive ductal carcinoma patients and compare its expression with age matched healthy individuals and daughters of index cases. The secondary objective was to evaluate the significance of serum miR-21 gene expression with histologically proven estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) proteins. A total of 132 subjects were recruited: 50 (cases) of stage III invasive ductal carcinoma patients who had not undergone any chemotherapy or surgery were randomly picked with exclusion of females with other types of breast carcinoma. Age-matched, 50 healthy individuals (control A) were selected by purposive sampling after confirmation of no palpable lump/s in their breasts together with 32 daughters of index cases (control B). Serum tests were run on Real Time quantitative Reverse Transcription PCR, threshold cycle was determined and fold change calculated.Normality of continuous variables was assessed by Shapiro-Wilk's test, groups compared by student t-test, Mann-Whitney test and Fisher exact test, P-value ≤ 0.05 was considered significant. We observed that miR-21 was significantly higher in cases as compared to control A and B (P = 0.001) however control B showed significant gene expression as compared to control A (P = 0.001). The cases were also divided as positive or negative for ER, PR and HER2. High expression of miR-21 in females with stage III invasive ductal carcinoma had been calculated as compared to its age matched healthy subjects. It was observed that triple negative cases showed a greater expression of gene as compared to other groups (P = 0.001). Expression of miR-21 in daughters of the cases was significantly higher as compared to healthy controls but lesser than females with invasive intraductal carcinoma. This result strengthens the concept of inheritability of disease with prediction of miR-21 as a potentially strong diagnostic and prognostic biomarker of breast cancer.}, }
@article {pmid26394603, year = {2015}, author = {Padovese, V and Racalbuto, V and Barnabas, GA and Morrone, A}, title = {Operational research on the correlation between skin diseases and HIV infection in Tigray region, Ethiopia.}, journal = {International journal of dermatology}, volume = {54}, number = {10}, pages = {1169-1174}, doi = {10.1111/ijd.12809}, pmid = {26394603}, issn = {1365-4632}, mesh = {Adult ; Candidiasis, Oral/epidemiology ; Case-Control Studies ; Condylomata Acuminata/epidemiology ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; HIV Infections/diagnosis/*epidemiology ; Hair Diseases/epidemiology ; Herpes Zoster/epidemiology ; Humans ; Leukoplakia, Hairy/epidemiology ; Male ; Prevalence ; Prurigo/epidemiology ; Skin Diseases/*epidemiology ; Tongue Diseases/epidemiology ; }, abstract = {BACKGROUND: In Ethiopia, skin diseases are among the leading causes of outpatient attendance to primary health service. Correlation of skin diseases and HIV has long been recognized and used to guide medical management in resource-limited settings. Therefore, this study aims to assess the correlation of skin diseases and HIV infection, to estimate epidemiological distribution in the study area, and to provide health workers of skin indicators for HIV early detection.<br><br>METHODS: The operational research was designed as a case-control study and carried out in three intervention districts of Tigray region; baseline and final data on skin diseases and HIV were compared with those of three control districts matched for population size, density, and environmental characteristics. Health workers of intervention districts were trained on skin diseases/STIs diagnosis and treatment. Data were collected from study and control districts and then analyzed at the Italian Dermatological Centre (IDC) in Mekele.<br><br>RESULTS: In the research period, a total of 1044 HIV positive patients were detected. Disorders of skin and mucous membranes statistically related with HIV (P < 0.05) were tongue papillary atrophy (80%), oral hairy leukoplakia (69%), herpes zoster (66%), oral candidiasis (50%), pruritic papular eruption (43%), condylomata acuminata (38%), and telogen effluvium (27%).<br><br>CONCLUSIONS: The high frequency of oral disorders and telogen effluvium is not described in literature and may be indicative for case detection. Operational research offers significant gains on health service delivery and outcomes at relatively low cost and in a short timeframe.}, }
@article {pmid26392358, year = {2015}, author = {Moelans, CB and Vlug, EJ and Ercan, C and Bult, P and Buerger, H and Cserni, G and van Diest, PJ and Derksen, PW}, title = {Methylation biomarkers for pleomorphic lobular breast cancer - a short report.}, journal = {Cellular oncology (Dordrecht)}, volume = {38}, number = {5}, pages = {397-405}, pmid = {26392358}, issn = {2211-3436}, mesh = {Adaptor Proteins, Signal Transducing/genetics ; Analysis of Variance ; BRCA1 Protein/genetics ; Biomarkers, Tumor/classification/*genetics ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Lobular/diagnosis/*genetics ; Cluster Analysis ; *DNA Methylation ; DNA-Binding Proteins/genetics ; Diagnosis, Differential ; Female ; Humans ; Logistic Models ; Multiplex Polymerase Chain Reaction/methods ; MutL Protein Homolog 1 ; Nuclear Proteins/genetics ; Promoter Regions, Genetic/genetics ; ROC Curve ; Tumor Protein p73 ; Tumor Suppressor Proteins/classification/genetics ; }, abstract = {BACKGROUND: Pleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC.<br><br>METHODS: We performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases.<br><br>RESULTS: We found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different.<br><br>CONCLUSION: This is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC.}, }
@article {pmid26384318, year = {2015}, author = {Elsarraj, HS and Hong, Y and Valdez, KE and Michaels, W and Hook, M and Smith, WP and Chien, J and Herschkowitz, JI and Troester, MA and Beck, M and Inciardi, M and Gatewood, J and May, L and Cusick, T and McGinness, M and Ricci, L and Fan, F and Tawfik, O and Marks, JR and Knapp, JR and Yeh, HW and Thomas, P and Carrasco, DR and Fields, TA and Godwin, AK and Behbod, F}, title = {Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion.}, journal = {Breast cancer research : BCR}, volume = {17}, number = {}, pages = {128}, pmid = {26384318}, issn = {1465-542X}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; P20 RR016475/RR/NCRR NIH HHS/United States ; HD02528/HD/NICHD NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM103326/GM/NIGMS NIH HHS/United States ; R21 CA185460/CA/NCI NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; P20 GM103418/GM/NIGMS NIH HHS/United States ; 1R21CA185460-01/CA/NCI NIH HHS/United States ; U01 CA084955/CA/NCI NIH HHS/United States ; U01CA113916/CA/NCI NIH HHS/United States ; U01 CA113916/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Disease Progression ; Epithelial-Mesenchymal Transition/genetics ; Female ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Proteins/*genetics ; Neoplasm Recurrence, Local/genetics/pathology ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Transcription Factors ; Transcription, Genetic/genetics ; Transcriptome/*genetics ; Up-Regulation/genetics ; Wnt Proteins/genetics ; beta Catenin/genetics ; }, abstract = {INTRODUCTION: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized.<br><br>METHODS: Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers.<br><br>RESULTS: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification.<br><br>CONCLUSION: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC.}, }
@article {pmid26381749, year = {2015}, author = {Roque, M and Duarte, I and Fouto, O and Távora, I}, title = {Invasive Ductal Carcinoma of the Breast in a Complex Cyst.}, journal = {The breast journal}, volume = {21}, number = {6}, pages = {683-684}, doi = {10.1111/tbj.12505}, pmid = {26381749}, issn = {1524-4741}, mesh = {Adult ; Breast Cyst/complications/*diagnosis ; Breast Neoplasms/complications/*diagnosis ; Carcinoma, Ductal, Breast/complications/*diagnosis ; Female ; Humans ; Mammography ; Ultrasonography, Mammary ; }, }
@article {pmid26376021, year = {2015}, author = {Wong, SM and Freedman, RA and Sagara, Y and Stamell, EF and Desantis, SD and Barry, WT and Golshan, M}, title = {The effect of Paget disease on axillary lymph node metastases and survival in invasive ductal carcinoma.}, journal = {Cancer}, volume = {121}, number = {24}, pages = {4333-4340}, doi = {10.1002/cncr.29687}, pmid = {26376021}, issn = {1097-0142}, mesh = {Axilla ; Breast Neoplasms/complications/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/complications/metabolism/*pathology/therapy ; Chemotherapy, Adjuvant ; Databases, Factual ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Paget's Disease, Mammary/complications/metabolism/*pathology/therapy ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; SEER Program ; Tumor Burden ; }, abstract = {BACKGROUND: The objective of this study was to examine the effect of Paget disease (PD) on axillary lymph node metastases and survival in patients who had concomitant invasive ductal carcinoma (PD-IDC).<br><br>METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women who were diagnosed with PD-IDC from 2000 to 2011, comparing baseline demographic and tumor characteristics with those who were diagnosed with IDC alone during the same period. Multivariable logistic regression was used to examine the association of PD-IDC with axillary lymph node metastasis, and breast cancer-specific survival and overall survival were compared between the PD-IDC and IDC groups using the Kaplan-Meier method and Cox proportional hazards regression.<br><br>RESULTS: The study cohort included 1102 patients with PD-IDC and 302,242 controls with IDC alone. PD-IDC tumors were more likely to be centrally located (26.9% vs 5.5%; P&#x2009;<&#x2009;.001), high grade (63.5% vs 40.3%; P&#x2009;<&#x2009;.001), >2 cm in greatest dimension (47.1% vs 35.7%; P&#x2009;<&#x2009;.001), and estrogen/progesterone receptor-negative (45.2% vs 22.1%; P&#x2009;<&#x2009;.001). In adjusted analyses, patients with PD-IDC had higher odds of axillary lymph node metastasis (odds ratio, 1.83; P&#x2009;<&#x2009;.001). The unadjusted 10-year breast cancer-specific and overall survival rates were lower for the PD-IDC group compared with the IDC-alone group, although, after adjusting for disease stage, tumor characteristics, and local therapy, no significant differences in mortality risk were observed between the 2 groups (hazard ratio, 0.91; P&#x2009;=&#x2009;.24).<br><br>CONCLUSIONS: PD-IDC is associated with an increased risk of axillary lymph node metastasis, but not with inferior survival, compared with IDC alone after adjustment for other disease factors.}, }
@article {pmid26373617, year = {2016}, author = {Zheng, B and Ohuchida, K and Chijiiwa, Y and Zhao, M and Mizuuchi, Y and Cui, L and Horioka, K and Ohtsuka, T and Mizumoto, K and Oda, Y and Hashizume, M and Nakamura, M and Tanaka, M}, title = {CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression.}, journal = {Molecular carcinogenesis}, volume = {55}, number = {11}, pages = {1560-1572}, doi = {10.1002/mc.22409}, pmid = {26373617}, issn = {1098-2744}, mesh = {CD146 Antigen/genetics/metabolism ; Cancer-Associated Fibroblasts/cytology/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Coculture Techniques ; Disease Progression ; *Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; NF-kappa B/metabolism ; Neoplasm Invasiveness ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Tumor Cells, Cultured ; }, abstract = {Cancer-associated fibroblasts (CAFs) are heterogeneous cell populations that influence tumor initiation and progression. CD146 is a cell membrane protein whose expression has been implicated in multiple human cancers. CD146 expression is also detected in pancreatic cancer stroma; however, the role it plays in this context remains unclear. This study aimed to clarify the function and significance of CD146 expression in pancreatic cancer. We performed immunohistochemical staining to investigate the prevalence of CD146 expression in stromal fibroblasts in pancreatic cancer. We also examined the influence of CD146 on CAF-mediated tumor invasion and migration and CAF activation using CD146 small interfering RNA or overexpression plasmids in primary cultures of CAFs derived from pancreatic cancer tissues. CD146 expression in CAFs was associated with high-grade pancreatic intraepithelial neoplasia and low histological grade invasive ductal carcinoma of the pancreas, while patients with low CD146 expression had a poorer prognosis. Blocking CD146 expression in CAFs significantly enhanced tumor cell migration and invasion in a co-culture system. CD146 knockdown also promoted CAF activation, possibly by inducing the production of pro-tumorigenic factors through modulation of NF-κB activity. Consistently, overexpression of CD146 in CAFs inhibited migration and invasion of co-cultured cancer cells. Finally, CD146 expression in CAFs was reduced by interaction with cancer cells. Our findings suggest that decreased CD146 expression in CAFs promotes pancreatic cancer progression. © 2015 Wiley Periodicals, Inc.}, }
@article {pmid26359561, year = {2016}, author = {Makis, W and Robinson, D and McEwan, AJ and Riauka, TA}, title = {Chest X-ray Artifact Caused by Bilateral 99mTc-Antimony Trisulfite Injection for Sentinel Node Imaging in a Patient With Breast Cancer.}, journal = {Clinical nuclear medicine}, volume = {41}, number = {4}, pages = {319-320}, doi = {10.1097/RLU.0000000000000967}, pmid = {26359561}, issn = {1536-0229}, mesh = {Antimony/administration &amp; dosage/*adverse effects ; Artifacts ; Breast Neoplasms/*diagnostic imaging ; Female ; Humans ; Lymph Nodes/*diagnostic imaging ; Middle Aged ; Radiopharmaceuticals/administration &amp; dosage/*adverse effects ; Technetium Compounds/administration &amp; dosage/*adverse effects ; }, abstract = {A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 μSv).}, }
@article {pmid26358115, year = {2016}, author = {Chikman, B and Davidson, T and Kais, H and Jeroukhimov, I and Leshno, A and Sandbank, J and Halevy, A and Lavy, R}, title = {Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?.}, journal = {Familial cancer}, volume = {15}, number = {1}, pages = {41-47}, pmid = {26358115}, issn = {1573-7292}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/genetics ; Carcinoma, Ductal, Breast/epidemiology/genetics ; Carcinoma, Lobular/*epidemiology/genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Humans ; Incidence ; Middle Aged ; Pedigree ; Retrospective Studies ; Stomach Neoplasms/*epidemiology/genetics ; }, abstract = {CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, <50 and ≥50 years. One thousand one hundred and sixty-seven patients with IDC and ILC entered the study. A family history of malignancies was reported in 21.6 % of patients with IDC as opposed to 37.8 % of patients with ILC (P < 0.001). A history of gastric cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P < 0.008. A family history of breast cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.}, }
@article {pmid26353381, year = {2016}, author = {Catanzaro, D and Shackney, SE and Schaffer, AA and Schwartz, R}, title = {Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {13}, number = {4}, pages = {643-655}, pmid = {26353381}, issn = {1557-9964}, support = {R01 AI076318/AI/NIAID NIH HHS/United States ; R01 CA140214/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Breast Neoplasms/diagnosis/*genetics/*physiopathology ; Carcinoma, Ductal/diagnosis/*genetics/*physiopathology ; Clonal Evolution ; Cluster Analysis ; Computational Biology/*methods ; Female ; Humans ; Models, Genetic ; }, abstract = {Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.}, }
@article {pmid26349603, year = {2015}, author = {Omran, OM and Al Sheeha, M}, title = {Cytoskeletal Focal Adhesion Proteins Fascin-1 and Paxillin Are Predictors of Malignant Progression and Poor Prognosis in Human Breast Cancer.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {34}, number = {3}, pages = {201-212}, doi = {10.1615/jenvironpatholtoxicoloncol.2015013663}, pmid = {26349603}, issn = {2162-6537}, mesh = {Adult ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/*genetics/pathology ; Carrier Proteins/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Microfilament Proteins/*genetics/metabolism ; Middle Aged ; Paxillin/*genetics/metabolism ; Prognosis ; }, abstract = {Breast cancer is a major health problem in both developing and developed countries. The incremental motility of malignant cells is a critical step in their migration, invasion, and metastasis and is regulated by the reorganization of the actin cytoskeleton and regulation of focal adhesion. Fascin-1 and paxillin are essential components of these cellular structures. In cancer, the expression level of fascin-1 and paxillin can vary depending on cell type. However, its precise role in breast cancer of Saudi women has not been evaluated in any published study. We investigated fascin-1 and paxillin expression in breast carcinoma, and we have related these results to the established prognostic factors. We studied 100 breast carcinoma specimens. Immunohistochemical analyses for fascin-1 and paxillin were conducted on paraffin sections of breast tissues using the avidin-biotin peroxidase method. Fascin-1 and paxillin were expressed in 58% and 43% of infiltrating duct carcinoma (IDC) cases. There was a statistically significant correlation between fascin-1 and paxillin expression with each of the following: tumor grade, clinical stage, lymph-node metastasis grade, and HER2 expression. Furthermore, there was a significant correlation between fascin-1 expression with paxillin immunostaining but no such association with PR or ER status. Increased fascin-1 and paxillin expression in IDC cells and their correlation with poor prognostic factors support their strong correlation with tumor progression, invasion, and metastasis in human breast cancer, indicating that these markers can be used as a target for the development of novel therapies.}, }
@article {pmid26347357, year = {2015}, author = {Harrison, K and Hoad, G and Scott, P and Simpson, L and Horgan, GW and Smyth, E and Heys, SD and Haggarty, P}, title = {Breast cancer risk and imprinting methylation in blood.}, journal = {Clinical epigenetics}, volume = {7}, number = {1}, pages = {92}, pmid = {26347357}, issn = {1868-7075}, abstract = {BACKGROUND: Altered DNA methylation of imprinted genes has been implicated in a range of cancers. Imprinting is established early in development, and some are maintained throughout the life course in multiple tissues, providing a plausible mechanism linking known early life factors to cancer risk. This study investigated methylation status of seven imprinted differentially methylated regions-PLAGL1/ZAC1, H19-ICR1, IGF2-DMR2, KvDMR-ICR2, RB1, SNRPN-DMR1 and PEG3-in blood samples from 189 women with the most common type of invasive breast cancer (invasive ductal carcinoma-IDC), 41 women with in situ breast cancer (ductal carcinoma in situ-DCIS) and 363 matched disease-free controls.<br><br>RESULTS: There was no evidence that imprinted gene methylation levels varied with age (between 25 and 87&#xa0;years old), weight or height. Higher PEG3 methylation was associated with an elevated risk of IDC (odds ratio (OR) 1.065; 95&#xa0;% confidence interval (CI) 1.002, 1.132; p&#x2009;=&#x2009;0.042) and DCIS (OR 1.139; 95&#xa0;% CI 1.027, 1.263; p&#x2009;=&#x2009;0.013). The effect was stronger when in situ and invasive breast cancer were combined (OR 1.079; 95&#xa0;% CI 1.020, 1.142; p&#x2009;=&#x2009;0.008). DCIS breast cancer risk increased with higher KvDMR-ICR2 methylation (OR 1.395; 95&#xa0;% CI 1.190, 1.635; p&#x2009;<&#x2009;0.001) and lower PLAGL1/ZAC1 methylation (OR 0.905; 95&#xa0;% CI 0.833, 0.982; p&#x2009;=&#x2009;0.017). In a combined model, only KvDMR-ICR2 methylation remained significantly&#xa0;associated.<br><br>CONCLUSIONS: These findings may help to improve our understanding of the aetiology of breast cancer and the importance of early life factors in particular. Imprinting methylation status also has the potential to contribute to the development of improved screening and treatment strategies for women with, or at risk of, breast cancer.}, }
@article {pmid26336132, year = {2015}, author = {Döppler, H and Bastea, L and Borges, S and Geiger, X and Storz, P}, title = {The phosphorylation status of VASP at serine 322 can be predictive for aggressiveness of invasive ductal carcinoma.}, journal = {Oncotarget}, volume = {6}, number = {30}, pages = {29740-29752}, pmid = {26336132}, issn = {1949-2553}, support = {P50 CA116201/CA/NCI NIH HHS/United States ; R01 GM086435/GM/NIGMS NIH HHS/United States ; CA116201-03DR4/CA/NCI NIH HHS/United States ; GM086435/GM/NIGMS NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal/genetics/*metabolism/pathology ; Cell Adhesion Molecules/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; Cell Movement/genetics ; Disease Progression ; HeLa Cells ; Humans ; Immunoblotting ; Immunohistochemistry ; Kaplan-Meier Estimate ; Microfilament Proteins/genetics/*metabolism ; Microscopy, Confocal ; Mutation ; Neoplasm Invasiveness ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Prognosis ; Protein Kinase D2 ; Protein Kinases/genetics/metabolism ; Serine/genetics/*metabolism ; Tissue Array Analysis ; }, abstract = {Vasodilator-stimulated phosphoprotein (VASP) signaling is critical for dynamic actin reorganization processes that define the motile phenotype of cells. Here we show that VASP is generally highly expressed in normal breast tissue and breast cancer. We also show that the phosphorylation status of VASP at S322 can be predictive for breast cancer progression to an aggressive phenotype. Our data indicate that phosphorylation at S322 is gradually decreased from normal breast to DCIS, luminal/ER+, HER2+ and basal-like/TN phenotypes. Similarly, the expression levels of PKD2, the kinase that phosphorylates VASP at this site, are decreased in invasive ductal carcinoma samples of all three groups. Overall, the phosphorylation status of this residue may serve as an indicator of aggressiveness of breast tumors.}, }
@article {pmid26331372, year = {2016}, author = {Haffner, MC and Weier, C and Xu, MM and Vaghasia, A and Gürel, B and Gümüşkaya, B and Esopi, DM and Fedor, H and Tan, HL and Kulac, I and Hicks, J and Isaacs, WB and Lotan, TL and Nelson, WG and Yegnasubramanian, S and De Marzo, AM}, title = {Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.}, journal = {The Journal of pathology}, volume = {238}, number = {1}, pages = {31-41}, pmid = {26331372}, issn = {1096-9896}, support = {P50 CA058236/CA/NCI NIH HHS/United States ; R01 CA183965/CA/NCI NIH HHS/United States ; P30CA006973/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; R01CA183965/CA/NCI NIH HHS/United States ; R01 CA070196/CA/NCI NIH HHS/United States ; P50CA58236/CA/NCI NIH HHS/United States ; P50CA058236/CA/NCI NIH HHS/United States ; R01CA070196/CA/NCI NIH HHS/United States ; T32 GM008752/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenocarcinoma/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Cell Line, Tumor ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Neoplasm Invasiveness ; Oncogene Proteins, Fusion/genetics ; PTEN Phosphohydrolase/genetics ; Prostatic Intraepithelial Neoplasia/genetics/*pathology ; Prostatic Neoplasms/genetics/*pathology ; Trans-Activators/genetics ; Transcriptional Regulator ERG ; }, abstract = {Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2-ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for intraductal carcinoma adjacent to invasive adenocarcinoma. These findings represent a potentially undervalued indicator of pre-existing invasive prostate cancer and have significant implications for prostate cancer diagnosis and risk stratification.}, }
@article {pmid26329827, year = {2015}, author = {Webster, BL and Rabone, M and Pennance, T and Emery, AM and Allan, F and Gouvras, A and Knopp, S and Garba, A and Hamidou, AA and Mohammed, KA and Ame, SM and Rollinson, D and Webster, JP}, title = {Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium.}, journal = {Parasites &amp; vectors}, volume = {8}, number = {}, pages = {432}, pmid = {26329827}, issn = {1756-3305}, support = {104958/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cost-Benefit Analysis ; *Genetic Variation ; Genetics, Population ; Humans ; Larva/classification/genetics ; *Microsatellite Repeats ; Multiplex Polymerase Chain Reaction/*methods ; Niger ; Schistosoma haematobium/*classification/*genetics/isolation &amp; purification ; Schistosomiasis haematobia/parasitology ; Tanzania ; Time Factors ; Urinary Tract Infections/parasitology ; }, abstract = {BACKGROUND: Human urogenital schistosomiasis caused by Schistosoma haematobium is widely distributed across Africa and is increasingly targeted for control and regional elimination. The development of new high-throughput, cost-effective molecular tools and approaches are needed to monitor and evaluate the impact of control programs on the parasite populations. Microsatellite loci are genetic markers that can be used to investigate how parasite populations change over time and in relation to external influences such as control interventions.<br><br>FINDINGS: Here, 18 existing S. haematobium microsatellite loci were optimised to enable simultaneous amplification across two novel multiplex microsatellite PCR's, each containing nine loci. Methods were developed for the cost effective and rapid processing and microsatellite analysis of S. haematobium larval stages stored on Whatman-FTA cards and proved robust on miracidia and cercariae collected from Zanzibar and Niger.<br><br>CONCLUSION: The development of these novel and robust multiplex microsatellite assays, in combination with an improved protocol to elute gDNA from Whatman-FTA fixed schistosome larval stages, enables the high-throughput population genetic analysis of S. haematobium. The molecular resources and protocols described here advance the way researchers can perform multi locus-based population genetic analyses of S. haematobium as part of the evaluation and monitoring of schistosomiasis control programmes.}, }
@article {pmid26329135, year = {2016}, author = {Zhang, Z and Atwell, LL and Farris, PE and Ho, E and Shannon, J}, title = {Associations between cruciferous vegetable intake and selected biomarkers among women scheduled for breast biopsies.}, journal = {Public health nutrition}, volume = {19}, number = {7}, pages = {1288-1295}, pmid = {26329135}, issn = {1475-2727}, support = {P01 CA090890/CA/NCI NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; UL1TR000128/TR/NCATS NIH HHS/United States ; R21 CA132236/CA/NCI NIH HHS/United States ; R21 CA132236-01A2/CA/NCI NIH HHS/United States ; P30 ES000210/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers/blood/urine ; Biopsy ; Body Mass Index ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Cell Proliferation/physiology ; Creatinine/urine ; *Diet ; Double-Blind Method ; Female ; Histone Deacetylases/metabolism ; Humans ; Isothiocyanates/blood/urine ; Ki-67 Antigen/genetics/metabolism ; Life Style ; Linear Models ; Middle Aged ; Multivariate Analysis ; Nutrition Assessment ; Socioeconomic Factors ; Sulfoxides ; *Vegetables ; }, abstract = {OBJECTIVE: To examine the relationship between dietary cruciferous vegetable intake and selected tumour biomarkers for histone acetylation (H3K9ac, H3K18ac, HDAC3 and HDAC6), proliferation (Ki-67) and cell-cycle regulation (p21) from breast tissue.<br><br>DESIGN: The study used baseline data of women recruited to participate in a clinical trial of sulforaphane supplement. Dietary cruciferous vegetable intake was collected through a validated Arizona Cruciferous Vegetable Intake Questionnaire. Breast tissue was obtained from biopsy samples. Spearman correlations were calculated between intake of specific cruciferous vegetables and biomarkers. Tissue biomarkers were log2-transformed to obtain approximate normality. Linear regression analyses were conducted to examine associations between cruciferous vegetable intake and biomarkers adjusting for age and use of non-steroidal anti-inflammatory drugs. False discovery rate (FDR) was used to account for multiple comparisons.<br><br>SETTING: Clinical trial baseline.<br><br>SUBJECTS: Fifty-four women who had abnormal mammogram findings and were scheduled for breast biopsy.<br><br>RESULTS: Mean intake of total cruciferous vegetables from all food sources was 81&#xb7;7 (sd 57&#xb7;3) g/d. Mean urinary total sulforaphane metabolites was 0&#xb7;08 (sd 0&#xb7;07) &#xb5;m/mm creatinine. Total cruciferous vegetable intake was inversely associated with Ki-67 protein expression in breast ductal carcinoma in situ (DCIS) tissue (&#x3b2;=-0&#xb7;004; se=0&#xb7;001; FDR q value=0&#xb7;03), but not in benign or invasive ductal carcinoma (IDC) tissue. No association was found for other biomarkers measured (HDAC3, HDAC6, H3K9, H3K18 and p21) in all tissues examined (benign, DCIS and IDC).<br><br>CONCLUSIONS: The present study sought to provide additional evidence for the potential role of sulforaphane in histone acetylation and cell proliferation. Here, we report that total cruciferous vegetable intake is associated with decreased cell proliferation in breast DCIS tissue.}, }
@article {pmid26323933, year = {2015}, author = {Zhu, MZ and Yu, XF and He, XM and Feng, WL and Fan, JH and Li, J and Xu, F and Tang, ZH and Zhang, BN and Qiao, YL and Zheng, S and Yang, HJ}, title = {Clinicopathological features of invasive lobular carcinoma of the breast: A nationwide multicenter study in China.}, journal = {Journal of cancer research and therapeutics}, volume = {11 Suppl 1}, number = {}, pages = {C89-94}, doi = {10.4103/0973-1482.163851}, pmid = {26323933}, issn = {1998-4138}, mesh = {Adult ; Biomarkers ; Breast Neoplasms/*epidemiology/metabolism/*pathology ; Carcinoma, Lobular/*epidemiology/metabolism/*pathology ; China/epidemiology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: To analyze the clinicopathological features of invasive lobular carcinoma (ILC) and compare them with invasive ductal carcinoma (IDC), hoping to find the fact of ILC in China and assist the decision makers with proper individualized treatment.<br><br>MATERIALS AND METHODS: A nationwide multicenter retrospective study was performed. A total of 4211 primary breast cancer cases were randomly selected from 1999 to 2008 in seven regions of China. ILC cases were compared with IDC by clinicopathological features and molecular subtypes.<br><br>RESULTS: A total of 135 (3.2%) ILC and 3471 (82.4%) IDC cases were included for analysis. The age, tumor size, menopausal state, family history, nodal status, and stage of ILC were similar to that of IDC. ILC was more likely to be positive for estrogen receptor (65.5% vs. 57.7%) and progesterone receptor (64.7% vs. 58.5%), and less likely to overexpress human epidermal growth factor receptor-2 (17.3% vs. 23.6%). Even though, these differences are not significant, the proportion of luminal A type of ILC is significantly larger than that of IDC (54.8% vs. 42.7%; P < 0.05).<br><br>CONCLUSION: ILC has a larger proportion of luminal A type compared with IDC. Larger sample size study for better known of molecular subtypes of ILC is needed in future to individualize the treatment decision.}, }
@article {pmid26321244, year = {2015}, author = {do Nascimento, JC and Ferreira, Sde A and Vasconcelos, JL and da Silva-Filho, JL and Barbosa, BT and Bezerra, MF and Rocha, CR and Beltrão, EI}, title = {Fut3 role in breast invasive ductal carcinoma: Investigating its gene promoter and protein expression.}, journal = {Experimental and molecular pathology}, volume = {99}, number = {3}, pages = {409-415}, doi = {10.1016/j.yexmp.2015.08.015}, pmid = {26321244}, issn = {1096-0945}, mesh = {Brazil ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Female ; Fucosyltransferases/*genetics/metabolism ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Immunohistochemistry/methods ; Lewis X Antigen/metabolism ; *Promoter Regions, Genetic ; }, abstract = {Fucosylated glycans synthesized by α1,3/4-fucosyltransferase (FUT3) enzyme play an important role in breast cancer prognosis and metastasis, being involved in the binding of circulating tumor cells to the endothelium and being related to tumor stage, metastatic potential and chemoresistance. Despite the pro-tumor action of this enzyme, studies have demonstrated its role in natural killer-induced cytotoxicity through the recognition of sialyl Lewis X by C-type lectin receptors and through extrinsic apoptosis pathway triggered by Apo2L-TRAIL. This study aimed to investigate the expression pattern of FUT3 in invasive breast carcinoma (IDC) from patients of Pernambuco state, Northeast of Brazil, and genotype FUT3 promoter region to identify possible SNPs that could be associated with variations in FUT3 expression. Immunohistochemistry assay was used to access the FUT3 expression in normal (n=11) and tumor tissues (n=85). DNA sequencing was performed to genotype the FUT3 promoter region in patients with IDC (n=109) and healthy controls (n=110). Our results demonstrated that the absence of FUT3 enzyme is related to breast's IDC. The non-expression of FUT3 was more frequent in larger lesions and also in HER2 negative IDC tumors. Genomic analysis showed that two variations localized in FUT3 promoter region are possibly associated with IDC. Our results suggest that minor allele T of SNP rs73920070 (-6933 C>T) confers protection whereas minor allele T of SNP rs2306969 (-6951 C>T) triggers to susceptibility to IDC in the population of Pernambuco state, Northeast of Brazil.}, }
@article {pmid26320758, year = {2016}, author = {Ben-David, BM and Icht, M}, title = {Voice Changes in Real Speaking Situations During a Day, With and Without Vocal Loading: Assessing Call Center Operators.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {30}, number = {2}, pages = {247.e1-11}, doi = {10.1016/j.jvoice.2015.04.002}, pmid = {26320758}, issn = {1873-4588}, mesh = {Acoustics ; Adolescent ; Adult ; Case-Control Studies ; Female ; Habits ; Humans ; Life Style ; Male ; Occupational Diseases/diagnosis/etiology/*physiopathology ; *Occupational Health ; *Occupations ; Risk Factors ; *Speech Acoustics ; Speech Production Measurement ; Surveys and Questionnaires ; *Telephone ; Time Factors ; Voice Disorders/diagnosis/etiology/*physiopathology ; *Voice Quality ; Workload ; Young Adult ; }, abstract = {OBJECTIVES: Occupational-related vocal load is an increasing global problem with adverse personal and economic implications. We examined voice changes in real speaking situations during a single day, with and without vocal loading, aiming to identify an objective acoustic index for vocal load over a day.<br><br>METHODS: Call center operators (CCOs, n&#xa0;=&#xa0;27) and age- and gender-matched students (n&#xa0;=&#xa0;25) were recorded at the beginning and at the end of a day, with (CCOs) and without (students) vocal load. Speaking and reading voice samples were analyzed for fundamental frequency (F0), sound pressure level (SPL), and their variance (F0 coefficient of variation [F0 CV], SPL CV). The impact of lifestyle habits on voice changes was also estimated.<br><br>RESULTS AND CONCLUSIONS: The main findings revealed an interaction, with F0 rise at the end of the day for the students but not for the CCOs. We suggest that F0 rise is a typical phenomenon of a day of normal vocal use, whereas vocal loading interferes with this mechanism. In addition, different lifestyle profiles of CCOs and controls were observed, as the CCOs reported higher incidence of dehydrating behaviors (eg, smoking, caffeine). Yet, this profile was not linked with voice changes. In sum, we suggest that F0 rise over a day can potentially serve as an index for typical voice use. Its lack thereof can hint on consequent voice symptoms and complaints.}, }
@article {pmid26319586, year = {2016}, author = {Liu, W and Tang, C and Liu, L and Zhu, QS and Huang, LF}, title = {Cervical intervertebral disc calcification with extreme lateral herniation in a child: T2-weighted signal intensity of the involved disc can be restored to normal.}, journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery}, volume = {32}, number = {4}, pages = {749-752}, pmid = {26319586}, issn = {1433-0350}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Calcinosis/*complications/diagnostic imaging/drug therapy ; Child ; Female ; Humans ; Imaging, Three-Dimensional ; Intervertebral Disc Degeneration/*complications/diagnostic imaging/drug therapy ; Longitudinal Studies ; Magnetic Resonance Imaging ; Tomography Scanners, X-Ray Computed ; }, abstract = {PURPOSE: The purpose of this case report is to present a very atypical case of cervical intervertebral disc calcification (IDC) with extreme lateral herniated calcification in a child. This is the first ever reported case in which T2-weighted signal intensity of the involved disc was restored to normal after a 2-year follow-up.<br><br>METHODS: A 10-year-old girl presented with neck pain and right upper limb numbness for 2 months. The initial computed tomography (CT) images on admission showed calcified nucleus pulposus with extreme lateral herniated calcification at the C6-C7 level. Meanwhile, T2-weighted magnetic resonance imaging (MRI) revealed decreased signal intensity of the involved disc. The patient was treated conservatively with nonsteroidal anti-inflammatory drugs and jaw-occipital belt traction for 2 weeks. The cervical CT and MRI scans were repeated at 2-year follow-up.<br><br>RESULTS: Her clinical symptoms were completely resolved after 2 weeks. At 2-year follow-up, CT and MRI images demonstrated that calcification was completely absorbed and T2-weighted signal intensity of the C6-C7 disc was restored back to normal.<br><br>CONCLUSION: Cervical IDC combined with extreme lateral herniated calcification is extremely rare in children. The recovery of signal intensity of intervertebral disc on MRI may provide further support to the feasibility of conservative treatment of IDC.}, }
@article {pmid26319120, year = {2015}, author = {Buas, MF and Rho, JH and Chai, X and Zhang, Y and Lampe, PD and Li, CI}, title = {Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study.}, journal = {Breast cancer research and treatment}, volume = {153}, number = {2}, pages = {445-454}, pmid = {26319120}, issn = {1573-7217}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; U01CA152637/CA/NCI NIH HHS/United States ; HHSN268201100046C/HL/NHLBI NIH HHS/United States ; HHSN268201100003C/WH/WHI NIH HHS/United States ; T32 CA009168/CA/NCI NIH HHS/United States ; HHSN271201100004C/AG/NIA NIH HHS/United States ; HHSN268201100002C/WH/WHI NIH HHS/United States ; U01 CA152746/CA/NCI NIH HHS/United States ; U01 CA152637/CA/NCI NIH HHS/United States ; T32CA009168/CA/NCI NIH HHS/United States ; HHSN268201100001C/WH/WHI NIH HHS/United States ; HHSN268201100004C/WH/WHI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/*metabolism ; Breast Neoplasms/blood/*diagnosis/*metabolism ; Carcinoma, Ductal, Breast/blood/*diagnosis/*metabolism ; Case-Control Studies ; Computational Biology/methods ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Proteome ; Proteomics/methods ; ROC Curve ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Risk Factors ; }, abstract = {Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for ~45 % of invasive breast cancer (BC) diagnoses in the U.S. Despite reductions in BC mortality attributable to mammography screening and adjuvant hormonal therapy, an important challenge remains the development of clinically useful blood-based biomarkers for risk assessment and early detection. The objective of this study was to identify novel protein markers for ER+/PR+ ductal BC. A nested case-control study was conducted within the Women's Health Initiative observational study. Pre-clinical plasma specimens, collected up to 12.5 months before diagnosis from 121 cases and 121 matched controls, were equally divided into training and testing sets and interrogated using a customized antibody array targeting >2000 proteins. Statistically significant differences (P < 0.05) in matched case versus control signals were observed for 39 candidates in both training and testing sets, and four markers (CSF2, RYBP, TFRC, ITGB4) remained significant after Bonferroni correction (P < 2.03 × 10(-5)). A multivariate modeling procedure based on elastic net regression with Monte Carlo cross-validation achieved an estimated AUC of 0.75 (SD 0.06). Most candidates did not overlap with those described previously for triple-negative BC, suggesting sub-type specificity. Gene set enrichment analyses identified two GO gene sets as upregulated in cases-microtubule cytoskeleton and response to hormone stimulus (P < 0.05, q < 0.25). This study has identified a pool of novel candidate plasma protein biomarkers for ER+/PR+ ductal BC using pre-diagnostic biospecimens. Further validation studies are needed to confirm these candidates and assess their potential clinical utility for BC risk assessment/early detection.}, }
@article {pmid26316122, year = {2015}, author = {Gordon, N and Skinner, AM and Pommier, RF and Schillace, RV and O'Neill, S and Peckham, JL and Muller, P and Condron, ME and Donovan, C and Naik, A and Hansen, J and Pommier, SJ}, title = {Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism.}, journal = {Stem cell research &amp; therapy}, volume = {6}, number = {1}, pages = {157}, pmid = {26316122}, issn = {1757-6512}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Cells, Cultured ; Female ; *Glycolysis ; Humans ; MCF-7 Cells ; Neoplastic Stem Cells/*metabolism ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; *Transcriptome ; }, abstract = {INTRODUCTION: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response.<br><br>METHODS: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test.<br><br>RESULTS: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression.<br><br>CONCLUSIONS: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.}, }
@article {pmid26285240, year = {2015}, author = {Shih, J and Bashir, B and Gustafson, KS and Andrake, M and Dunbrack, RL and Goldstein, LJ and Boumber, Y}, title = {Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.}, journal = {Journal of the National Comprehensive Cancer Network : JNCCN}, volume = {13}, number = {8}, pages = {947-952}, pmid = {26285240}, issn = {1540-1413}, support = {R01 GM084453/GM/NIGMS NIH HHS/United States ; }, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Brain Neoplasms/diagnosis/secondary/therapy ; Breast Neoplasms/diagnosis/drug therapy/*genetics ; Female ; *Gene Amplification ; Genetic Testing ; Humans ; Lung Neoplasms/diagnosis/therapy ; *Mutation ; Neoplasm Staging ; Neoplasms, Second Primary ; Radiography, Thoracic ; Radiosurgery ; Receptor, ErbB-2/*genetics ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.}, }
@article {pmid26271144, year = {2015}, author = {Wang, X and Hu, B and Shen, H and Zhou, H and Xue, X and Chen, Y and Chen, S and Han, Y and Yuan, B and Zhao, H and Zhi, Q and Kuang, Y}, title = {Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {75}, number = {}, pages = {218-225}, doi = {10.1016/j.biopha.2015.07.038}, pmid = {26271144}, issn = {1950-6007}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Disease Progression ; Enhancer of Zeste Homolog 2 Protein ; Female ; Humans ; Kaplan-Meier Estimate ; Neoplasm Staging ; Odds Ratio ; Polycomb Repressive Complex 2/*analysis ; Risk Factors ; Treatment Outcome ; Up-Regulation ; }, abstract = {The polycomb group protein enhancer of zeste homolog 2 (EZH2) is regarded as a tightly linking oncogene in many types of cancer. However, the prognostic role of EZH2 in breast cancer (BC) still remains controversial. Our study aimed to evaluate the clinical and prognostic relevance of EZH2 in BC patients based on published studies. 11 studies totally containing 2330 patients (1052 EZH2-positive and 1278 EZH2-negative) were included in our meta-analysis. Our data showed that EZH2 over-expression was significantly associated with estrogen receptor (ER) negativity [OR=0.227, 95% CI=0.174-0.297, P=0.000], progesterone receptor (PR) negativity [OR=0.454, 95% CI=0.300-0.687, P=0.000], human epidermal growth factor receptor type 2 (HER-2) positivity [OR=1.846, 95% CI=1.366-2.496, P=0.000], invasive ductal cancer (IDC) [OR=2.237, 95% CI=1.489-3.361, P=0.000], race (Caucasian) [OR=0.707, 95% CI=0.522-0.957, P=0.025], high histological grade [OR=3.177, 95% CI=2.012-5.014, P=0.000] and triple-negative status (TNBCs) [OR=5.380, 95% CI=1.065-27.187, P=0.042], which led to a poor OS rate in BC [RR=2.193, 95% CI=1.495-3.217, P=0.000]. In conclusion, EZH2 participated in the progression of BC as a putative factor, and over-expression of EZH2 was distinctly correlated with a poor patient survival. EZH2 may serve as a prognostic biomarker and target in BC patients.}, }
@article {pmid26268905, year = {2016}, author = {Rominger, M and Berg, D and Frauenfelder, T and Ramaswamy, A and Timmesfeld, N}, title = {Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer?.}, journal = {European radiology}, volume = {26}, number = {5}, pages = {1457-1465}, pmid = {26268905}, issn = {1432-1084}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Multivariate Analysis ; Retrospective Studies ; Tumor Burden ; }, abstract = {OBJECTIVES: To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer.<br><br>MATERIALS AND METHODS: MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path-TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors.<br><br>RESULTS: Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In-Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In-Plane with Path-Diameter was 86% (97/113), overestimation 9% (10/113) and underestimation 5% (6/113); BI-RADS mass lesions were overestimated in 7% (6/81) versus 41% (13/32) for non-mass enhancements. On multivariate analysis only BI-RADS lesion type significantly influenced MRI-pathology concordance (p&#x2009;<&#x2009;0.001). 2/59 (3%) ILC did not enhance.<br><br>CONCLUSION: Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non-mass enhancement significantly predicted discordance.<br><br>KEY POINTS: &#x2022; Execution and scope of MRI and histopathological size measurements influence concordance rate. &#x2022; Non-mass like enhancement predicts discordance. &#x2022; Additional high-risk lesions in proximity of tumour do not cause measurement discordance. &#x2022; Low percentage of ILC do not enhance at all.}, }
@article {pmid26255059, year = {2015}, author = {Rane, SU and Mirza, H and Grigoriadis, A and Pinder, SE}, title = {Selection and evolution in the genomic landscape of copy number alterations in ductal carcinoma in situ (DCIS) and its progression to invasive carcinoma of ductal/no special type: a meta-analysis.}, journal = {Breast cancer research and treatment}, volume = {153}, number = {1}, pages = {101-121}, doi = {10.1007/s10549-015-3509-x}, pmid = {26255059}, issn = {1573-7217}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Chromosome Aberrations ; Chromosome Mapping ; Computational Biology ; *DNA Copy Number Variations ; Disease Progression ; Female ; Humans ; Molecular Sequence Annotation ; Neoplasm Invasiveness ; Neurophysins/genetics ; Protein Precursors/genetics ; Signal Transduction ; Vasopressins/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) is a pre-invasive malignancy detected with an increasing frequency through screening mammography. One of the primary aims of therapy is to prevent local recurrence, as in situ or as invasive carcinoma, the latter arising in half of the recurrent cases. Reliable biomarkers predictive of its association with recurrence, particularly as invasive disease, are however lacking. In this study, we perform a meta-analysis of 26 studies which report somatic copy number aberrations (SCNAs) in 288 cases of 'pure' DCIS and 328 of DCIS associated with invasive carcinoma, along with additional unmatched cases of 145 invasive carcinoma of ductal/no special type (IDC) and 50 of atypical ductal hyperplasia (ADH). SCNA frequencies across the genome were calculated at cytoband resolution (UCSC genome build 19) to maximally utilize the available information in published literature. Fisher's exact test was used to identify significant differences in the gain-loss distribution in each cytoband in different group comparisons. We found synchronous DCIS to be at a more advanced stage of genetic aberrations than pure DCIS and was very similar to IDC. Differences in gains and losses in each disease process (i.e. invasive or in situ) at each cytoband were used to infer evidence of selection and conservation for each cytoband and to define an evolutionary conservation scale (ECS) as a tool to identify and distinguish driver SCNA from the passenger SCNA. Using ECS, we have identified aberrations that show evidence of selection from the early stages of neoplasia (i.e. in ADH and pure DCIS) and persist in IDC; we postulate these to be driver aberrations and that their presence may predict progression to invasive disease.}, }
@article {pmid26253945, year = {2015}, author = {Tsai, KW and Li, GC and Chen, CH and Yeh, MH and Huang, JS and Tseng, HH and Fu, TY and Liou, HH and Pan, HW and Huang, SF and Chen, CC and Chang, HY and Ger, LP and Chang, HT}, title = {Reduction of global 5-hydroxymethylcytosine is a poor prognostic factor in breast cancer patients, especially for an ER/PR-negative subtype.}, journal = {Breast cancer research and treatment}, volume = {153}, number = {1}, pages = {219-234}, doi = {10.1007/s10549-015-3525-x}, pmid = {26253945}, issn = {1573-7217}, mesh = {5-Methylcytosine/analogs &amp; derivatives ; Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics/*mortality/pathology ; Cytosine/*analogs &amp; derivatives/metabolism ; *DNA Methylation ; DNA-Binding Proteins/genetics/metabolism ; Dioxygenases ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Mixed Function Oxygenases ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Protein Transport ; Proto-Oncogene Proteins/genetics/metabolism ; Receptors, Estrogen/deficiency ; Receptors, Progesterone/deficiency ; Risk Factors ; Survival Analysis ; Young Adult ; }, abstract = {DNA methylation at the 5 position of cytosine (5 mC) is an epigenetic hallmark in cancer. The 5 mC can be converted to 5-hydroxymethylcytosine (5 hmC) through a ten-eleven-translocation (TET). We investigated the impact of 5 mC, 5 hmC, TET1, and TET2 on tumorigenesis and prognosis of breast cancer. Immunohistochemistry was used to assess the levels of 5 mC, 5 hmC, TET1, and TET2 in the corresponding tumor adjacent normal (n = 309), ductal carcinoma in situ (DCIS, n = 120), and invasive ductal carcinoma (IDC, n = 309) tissues for 309 breast ductal carcinoma patients. 5 mC, 5 hmC, TET1-n, and TET2-n were significantly decreased during DCIS and IDC progression. In IDC, the decrease of 5 hmC was correlated with the cytoplasmic mislocalization of TET1 (p < 0.001) as well as poor disease-specific survival (DSS) (adjusted hazard ratio [AHR] 1.95, p = 0.003) and disease-free survival (DFS) (AHR 1.91, p = 0.006). The combined decrease of 5 mC and 5 hmC was correlated with worse DSS (AHR 2.19, p = 0.008) and DFS (AHR 1.99, p = 0.036). Stratification analysis revealed that the low level of 5 mC was associated with poor DSS (AHR 1.89, p = 0.044) and DFS (AHR 2.02, p = 0.035) for the ER/PR-positive subtype. Conversely, the low level of 5 hmC was associated with worse DSS (AHR 2.77, p = 0.002) and DFS (AHR 2.69, p = 0.006) for the ER/PR-negative subtype. The decreases of 5 mC, 5 hmC, TET1-n, and TET2-n were biomarkers of tumor development. The global reduction of 5 hmC was a poor prognostic factor for IDC, especially for ER/PR-negative subtype.}, }
@article {pmid26242364, year = {2015}, author = {McEvoy, MP and Coopey, SB and Mazzola, E and Buckley, J and Belli, A and Polubriaginof, F and Merrill, AL and Tang, R and Garber, JE and Smith, BL and Gadd, MA and Specht, MC and Guidi, AJ and Roche, CA and Hughes, KS}, title = {Breast Cancer Risk and Follow-up Recommendations for Young Women Diagnosed with Atypical Hyperplasia and Lobular Carcinoma In Situ (LCIS).}, journal = {Annals of surgical oncology}, volume = {22}, number = {10}, pages = {3346-3349}, doi = {10.1245/s10434-015-4747-1}, pmid = {26242364}, issn = {1534-4681}, mesh = {Adult ; Breast/*pathology ; Breast Neoplasms/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; *Continuity of Patient Care ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/pathology ; Mammography ; Neoplasm Invasiveness ; Neoplasm Staging ; Precancerous Conditions/*pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {BACKGROUND: The risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population.<br><br>METHODS: A retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed. Patient characteristics, pathology and follow-up were determined from chart review.<br><br>RESULTS: We identified 58 young women with atypical breast lesions. Median age at diagnosis was 31 years (range 19-34). 34 patients had ADH, 11 had ALH, 8 had LCIS, and 5 had severe ADH. 7 (12%) patients developed breast cancer. The median follow-up was 86 months (range 1-298). Median time to cancer diagnosis was 90 months (range 37-231). 4 cancers were on the same side, 3 were contralateral. 4 were IDC, 1 was ILC, and 2 were DCIS. Cancer was detected by screening mammogram in 4 patients, 2 by clinical exam, and 1 unknown. In the entire cohort, 26 (45%) patients had screening mammograms as part of their follow up, 12 patients had only clinical follow up, and 20 had no additional follow up. 13 patients required subsequent biopsies.<br><br>CONCLUSION: Young women with atypical breast lesions are at a markedly increased risk for developing breast cancer and should be followed closely. Based on our findings, we recommend close clinical follow-up, MRI starting at age 25 through age 29, and screening mammograms for those over 30 in this high-risk group of patients.}, }
@article {pmid26233575, year = {2015}, author = {Broch, K and Murbræch, K and Andreassen, AK and Hopp, E and Aakhus, S and Gullestad, L}, title = {Contemporary Outcome in Patients With Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {116}, number = {6}, pages = {952-959}, doi = {10.1016/j.amjcard.2015.06.022}, pmid = {26233575}, issn = {1879-1913}, mesh = {Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiac Resynchronization Therapy ; Cardiomyopathy, Dilated/complications/*therapy ; Cardiotonic Agents/therapeutic use ; Cohort Studies ; Death, Sudden, Cardiac/etiology/*prevention &amp; control ; Defibrillators, Implantable ; Digitoxin/therapeutic use ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Exercise Test ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Oxygen Consumption ; Prospective Studies ; Stroke Volume ; Treatment Outcome ; Ventricular Dysfunction, Left/complications/*therapy ; }, abstract = {Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines.}, }
@article {pmid26229954, year = {2015}, author = {Panisello-Tafalla, A and Clua-Espuny, JL and Gil-Guillen, VF and González-Henares, A and Queralt-Tomas, ML and López-Pablo, C and Lucas-Noll, J and Lechuga-Duran, I and Ripolles-Vicente, R and Carot-Domenech, J and López, MG}, title = {Results from the Registry of Atrial Fibrillation (AFABE): Gap between Undiagnosed and Registered Atrial Fibrillation in Adults--Ineffectiveness of Oral Anticoagulation Treatment with VKA.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {134756}, pmid = {26229954}, issn = {2314-6141}, mesh = {Administration, Oral ; Adult ; Aged ; Anticoagulants/administration &amp; dosage/*therapeutic use ; Atrial Fibrillation/*diagnosis/*drug therapy/epidemiology ; Female ; Humans ; Male ; Prevalence ; *Registries ; Risk Factors ; Spain/epidemiology ; Survival Analysis ; Vitamin K/*antagonists &amp; inhibitors ; }, abstract = {OBJECTIVE: This study aimed to examine the effectiveness of the use of oral anticoagulation (OAC) medication, recommended by national guidelines for stroke prevention but reportedly underused in AF patients with moderate to high stroke risk.<br><br>METHOD: A multicentre and cross-sectional study of undiagnosed AF among out-of-hospital patients over 60 years old was carried out, visiting 3,638 patients at primary health centres or at home for AF diagnosis using the IDC-10 classification. The main outcome measures were CHA&#x2082;DS&#x2082;VASC, HAS-BLED scores, cardiovascular comorbidity, pharmacological information, TTR, and SAMe-TT2R2 scores.<br><br>RESULTS: The main findings were undiagnosed AF in 26.44% of cases; 31.04% registered with AF but not using OAC despite 95.6% having a CHA&#x2082;DS&#x2082;VASC &#x2265; 2 score; a risk of bleeding in important subgroups using OAC without indication (37.50% CHA&#x2082;DS&#x2082;VASC < 2 score); the use of OAC with TTR < 60% (33.1%), of whom 47.6% had a HAS-BLED score &#x2265;3. Thus, 35.4% of the expected AF prevalence achieved an optimal time in the therapeutic range.<br><br>CONCLUSIONS: The expected AF prevalence was 10.9% (n 5267), but the registered prevalence was 7.5% (n 3638). Only 35.04% (CI = 95%, 33.7-36.3) of AF patients treated with vitamin K antagonists (VKAs) achieve the goal of TTR > 60%.}, }
@article {pmid26214623, year = {2015}, author = {Abu Rabi, Z and Zoranovic, T and Milovanovic, J and Todorovic-Rakovic, N and Nikolic-Vukosavljevic, D}, title = {Breast cancer in postmenopausal patients: Impact of age.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {20}, number = {3}, pages = {723-729}, pmid = {26214623}, issn = {1107-0625}, mesh = {Age Factors ; Aged ; *Aging ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/secondary/*therapy ; Chemotherapy, Adjuvant ; Disease Progression ; Disease-Free Survival ; Estrogen Antagonists/therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; *Postmenopause ; Receptors, Estrogen/analysis/drug effects ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; Tamoxifen/therapeutic use ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: We analyzed the significance of age together with other classic prognostic parameters on the course of breast cancer in postmenopausal patients.<br><br>METHODS: Our study included 151 postmenopausal patients with primary breast cancer, of which 55% received adjuvant tamoxifen therapy and 45% did not receive any kind of therapy. Probabilities of disease-free interval (DFI) were estimated using the Kaplan-Meier method and were compared by the log-rank test. A p value<0.05 was considered as statistically significant.<br><br>RESULTS: In the tamoxifen-treated subgroup, patients with estrogen receptor (ER) or progesterone receptor (PR) concentration&#x2265;5 fmol/mg had favorable course of disease (p<0.01, p<0.04), respectively. Patients&#x2265;66 years of age had a worse disease course compared to those<66 years. Also, patients&#x2265;66 years with pT1 tumors had a worse disease course compared to those<66 years and pT1 tumors. This result was repeated in other groups as well. In pT2 (&#x2265;2 cm), ER-positive, PR-positive and invasive ductal carcinoma (IDC) subgroups, patients&#x2265;66 years always had a worse disease course compared to patients<66 years. In the untreated subgroup, patients with ER&#x2265;52 fmol/mg (p<0.01), tumors&#x2265;2 cm (p<0.01), IDC (p<0.01) type or &#x2265;56 years (p<0.04) had statistically more recurrences. Among patients&#x2265;56 years, those with ER-positive or pT2 tumors had shorter DFI compared to ER-negative or pT1. Positive correlation between ER, PR and age of patients was also shown in this subgroup (p<0.03, p<0.02).<br><br>CONCLUSION: Age of patients, ER and PR are significant prognostic factors in the tamoxifen-treated subgroup. In the untreated subgroup relevant prognostic parameters are age, tumor size, histological type and ER. The above prognostic factors retained their value in the long-term follow up in both the investigated subgroups of patients.}, }
@article {pmid26208902, year = {2015}, author = {Benevides, L and da Fonseca, DM and Donate, PB and Tiezzi, DG and De Carvalho, DD and de Andrade, JM and Martins, GA and Silva, JS}, title = {IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.}, journal = {Cancer research}, volume = {75}, number = {18}, pages = {3788-3799}, pmid = {26208902}, issn = {1538-7445}, support = {R01 AI103542/AI/NIAID NIH HHS/United States ; R21 AI083948/AI/NIAID NIH HHS/United States ; I083948-01//PHS HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/chemistry/immunology/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/immunology/mortality/*secondary ; Chemotaxis, Leukocyte/*physiology ; Cytokines/biosynthesis/genetics/metabolism ; Disease Progression ; Disease-Free Survival ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-17/analysis/antagonists &amp; inhibitors/immunology/*physiology ; Lymphocytes, Tumor-Infiltrating/*immunology/metabolism ; Mammary Neoplasms, Experimental/immunology/pathology ; Mice ; Mice, Inbred BALB C ; Neoplasm Proteins/analysis/antagonists &amp; inhibitors/immunology/*physiology ; Neutrophils/*immunology/metabolism ; Prognosis ; Th17 Cells/immunology ; }, abstract = {The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors.}, }
@article {pmid26204115, year = {2015}, author = {Son, SH and Lee, SW and Jeong, SY and Song, BI and Chae, YS and Ahn, BC and Lee, J}, title = {Whole-Body Metabolic Tumor Volume, as Determined by (18)F-FDG PET/CT, as a Prognostic Factor of Outcome for Patients With Breast Cancer Who Have Distant Metastasis.}, journal = {AJR. American journal of roentgenology}, volume = {205}, number = {4}, pages = {878-885}, doi = {10.2214/AJR.14.13906}, pmid = {26204115}, issn = {1546-3141}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; Neoplasm Metastasis/*diagnostic imaging ; *Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Risk Factors ; *Tomography, X-Ray Computed ; Tumor Burden ; }, abstract = {OBJECTIVE: This study was performed to evaluate the prognostic relevance of PET parameters measured by (18)F-FDG PET/CT in patients with invasive ductal carcinoma of the breast (IDC) who had distant metastasis at the time of initial diagnosis.<br><br>MATERIALS AND METHODS: Forty women with IDC who had distant metastasis at the time of initial diagnosis and who underwent FDG PET/CT before receiving treatment were enrolled in the study. Clinicopathologic parameters and metabolic PET parameters, including the maximum standardized uptake value (SUVmax) of the primary tumor (pSUVmax), the SUVmax of the axillary lymph node (nSUVmax), the highest SUVmax of whole malignant lesions (wSUVmax), the whole-body (WB) metabolic tumor volume (MTV), and WB total lesion glycolysis (TLG), were analyzed to determine their usefulness in predicting overall survival (OS). Univariate and multivariate analyses were performed with the use of Kaplan-Meier and Cox proportional hazards models.<br><br>RESULTS: Twenty-one of the 40 patients (52.5%) died during follow-up (mean follow-up, 36.4 months; range, 0.8-71.4 months). Nonsurvivors had a statistically significantly higher mean (&#xb1; SD) WB MTV than did survivors (424.0 &#xb1; 683.9 vs 92.1 &#xb1; 96.3 cm(3); p = 0.0430). T category, performance of palliative surgery, presence of visceral metastasis, wSUVmax, WB MTV, and WB TLG were identified by univariate analysis as prognostic factors for OS, whereas age, N category, hormone receptor status, status, triple-negative breast cancer status (defined as a tumor for which estrogen receptor, progesterone receptor, and ERBB2 statuses were all negative), pSUVmax, and nSUVmax were not. Multivariate analysis revealed that only WB MTV independently predicted OS (hazard ratio, 4.10; 95% CI, 1.17-14.31; p = 0.0280).<br><br>CONCLUSION: The WB MTV value, as determined by FDG PET/CT performed before treatment, was found to be an independent prognostic factor for OS in patients with IDC who had distant metastasis at the time of initial diagnosis.}, }
@article {pmid26195469, year = {2015}, author = {Yoon, PD and Chalasani, V and Woo, HH}, title = {Systematic review and meta-analysis on management of acute urinary retention.}, journal = {Prostate cancer and prostatic diseases}, volume = {18}, number = {4}, pages = {297-302}, pmid = {26195469}, issn = {1476-5608}, mesh = {5-alpha Reductase Inhibitors/therapeutic use ; Acute Disease ; Adrenergic alpha-1 Receptor Antagonists/therapeutic use ; Disease Management ; Humans ; Male ; Odds Ratio ; Prostatectomy/methods ; Prostatic Hyperplasia/complications ; Treatment Outcome ; Urinary Catheterization/methods ; Urinary Retention/*diagnosis/etiology/*therapy ; }, abstract = {BACKGROUND: Acute urinary retention (AUR) is a common urological emergency. In this article, we review the current literature and present a structured summary in management of AUR.<br><br>METHODS: A systematic review was conducted using the keywords 'acute AND retention AND urin*' within the title in search engines including Medline, EMBASE and EBM Review. The obtained literature was manually reviewed by the primary author (PDY) and was further refined by confining the subject to management of AUR. Exclusion criteria included paediatric and female population studies, case reports, reviews, surveys, economical assessment and articles on AUR in prostate cancer and post-operative patients.<br><br>RESULTS: Total of 54 articles met our inclusion and exclusion criteria. The trial without catheter (TWOC) post-immediate catheterisation is widely practiced although there remains a significant variability in terms of type and duration of catheterisation required, use of concurrent medical therapy or post-catheterisation management. Our systematic review and subsequent meta-analysis has shown superiority of &#x3b1;1-adrenergic receptor blockers over placebo in achieving successful voiding in patients with AUR. Suprapubic catheter (SPC) is an alternative to urethral catheterisation (indwelling catheter (IDC)) and may provide several advantages. Clean intermittent self-catheterisation may be a safe and useful option for patients with AUR until their definitive management. The overall long-term outcome of in-and-out catheterisation remains promising in selected patients. Surgery is an end point in patients with unsuccessful TWOC as well as in those with significant lower urinary tract symptoms post-successful TWOC.<br><br>CONCLUSIONS: We recommend use of &#x3b1;1-adrenergic receptor blockers before TWOC and discourage emergency operative management. Use of SPC over IDC in AUR is debatable. Duration of catheterisation is controversial but <3 days is a safe option in avoiding catheterisation-related complications. Although TURP remains the current gold standard, there has been an emergence of newer operative management utilising laser techniques.}, }
@article {pmid26193775, year = {2016}, author = {Aires, L and Silva, G and Martins, C and Marques, E and Lagoa, MJ and Ribeiro, JC and Rêgo, C and Nascimento, H and Pereira, PR and Santos-Silva, A and Belo, L and Mota, J}, title = {Exercise intervention and cardiovascular risk factors in obese children. Comparison between obese youngsters taking part in a physical activity school-based programme with and without individualised diet counselling: the ACORDA project.}, journal = {Annals of human biology}, volume = {43}, number = {3}, pages = {183-190}, doi = {10.3109/03014460.2015.1059889}, pmid = {26193775}, issn = {1464-5033}, mesh = {Adolescent ; Body Composition ; Body Height ; Body Weight ; Cardiovascular Diseases/*epidemiology/*etiology ; Child ; *Counseling ; *Diet ; Exercise/*physiology ; Female ; Humans ; Male ; Obesity/complications/*epidemiology ; Risk Factors ; *Schools ; }, abstract = {AIM: To determine the effects of a school-based exercise intervention programme on cardiovascular risk factors, including body fat (BF), metabolic profile and physical activity (PA) in children with and without individualised dietary counselling approach (IDC and WIDC).<br><br>SUBJECTS AND METHODS: Forty-six overweight children from 6-16 years old (25 girls, 54.3%; age&#x2009;=&#x2009;10.3&#x2009;&#xb1;&#x2009;2.8) of six schools took part in an 8-month interdisciplinary, school-based intervention programme. All children were engaged in PA classes, but only one group was exposed to individualised counselling. Blood pressure (BP), lipids and lipoproteins, accelerometer-based PA, percentage of body fat (%BF) and trunk fat (%TF) measures were taken before and after intervention. General Linear Model (Repeated Measures ANOVA) adjusted for age, maturation and height change was used to analyse the longitudinal effect of individualised counselling between two evaluations in each group.<br><br>RESULTS: Favourable changes were observed for %BF, %TF, systolic BP and total cholesterol in the IDC group. Subjects WIDC only increased light and moderate-vigorous PA. In IDC, significant effects for time * group interactions were found for systolic BP, total cholesterol and LDL-cholesterol, indicating that counselling might add favourable changes in these markers, beyond those explained by PA and growth.<br><br>CONCLUSION: School-based interventions can contribute to counteracting obesity in youth, particularly when individualised dietary counselling is provided. Therefore, the link between schools and professional counselling should be strengthened to ensure consolidated changes towards healthy behaviours.}, }
@article {pmid26179699, year = {2016}, author = {Cui, M and Wang, Q and Chen, G}, title = {Serum metabolomics analysis reveals changes in signaling lipids in breast cancer patients.}, journal = {Biomedical chromatography : BMC}, volume = {30}, number = {1}, pages = {42-47}, doi = {10.1002/bmc.3556}, pmid = {26179699}, issn = {1099-0801}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Breast Neoplasms/*blood/pathology ; Chromatography, High Pressure Liquid ; Disease Progression ; Female ; Humans ; Lipids/*blood ; Mass Spectrometry ; Metabolomics/*methods ; Middle Aged ; Pilot Projects ; }, abstract = {Breast cancer is the most commonly diagnosed cancer and one of the leading causes of cancer death among women worldwide. It is a biologically variable disease with different molecular subtypes, risk factors, clinical behaviors and responses to treatment. Better understanding of the molecular changes associated with each subtype is essential for identifying new therapeutic targets and markers for the monitoring of treatment responses. In this pilot study, mass spectrometry-based metabolic profiling was performed to characterize the changes in serum profiles of patients with invasive ductal carcinoma (IDC) - the most common type of breast cancer. Serum samples from 20 IDC patients and 20 age- and gender-matched healthy subjects were analyzed and 15 differentially expressed metabolites were identified. These metabolites are involved in several metabolic pathways such as sphingolipid metabolism, phospholipid metabolism and fatty acid β-oxidation. Among these, two classes of signaling lipids, lysophosphatidylethanolamine and ceramide, may play an important role in IDC development and progression. This study demonstrates metabolic profiling as a promising tool for finding disease biomarkers and our findings provide new directions for further mechanistic studies on the pathology of IDC.}, }
@article {pmid26179530, year = {2015}, author = {Morita, S and Onaya, H and Kishi, Y and Hiraoka, N and Arai, Y}, title = {Multiple Intraglandular Metastases in a Patient with Invasive Ductal Carcinoma of the Pancreas.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {54}, number = {14}, pages = {1753-1756}, doi = {10.2169/internalmedicine.54.3819}, pmid = {26179530}, issn = {1349-7235}, mesh = {Carcinoma, Pancreatic Ductal/complications/*diagnosis/pathology/surgery ; Cholangiopancreatography, Endoscopic Retrograde ; Flank Pain/etiology ; Humans ; Jaundice/etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasms, Second Primary/complications/*diagnosis/pathology/surgery ; Pancreas/*pathology ; Pancreatectomy/methods ; Pancreatic Neoplasms/complications/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; }, abstract = {A 56-year-old man was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the head of the pancreas, with three other tumors detected in the body and tail. Magnetic resonance imaging showed similar enhancement patterns and signal intensities in all four lesions. The patient underwent total pancreatectomy based on a preoperative diagnosis of multiple invasive ductal carcinomas. Histopathologically, the lesion in the pancreatic head was considered to be the primary lesion, while the others were diagnosed as metastases. This is a rare case of pancreatic cancer with intraglandular metastases. The possibility of this differential diagnosis should thus be considered when imaging shows multiple hypovascular lesions in the pancreas.}, }
@article {pmid26175196, year = {2015}, author = {Campagna, L and Gronau, I and Silveira, LF and Siepel, A and Lovette, IJ}, title = {Distinguishing noise from signal in patterns of genomic divergence in a highly polymorphic avian radiation.}, journal = {Molecular ecology}, volume = {24}, number = {16}, pages = {4238-4251}, doi = {10.1111/mec.13314}, pmid = {26175196}, issn = {1365-294X}, mesh = {Animals ; Bayes Theorem ; Female ; Gene Flow ; Genetic Loci ; *Genetic Speciation ; Genetics, Population ; Genomics ; Male ; Models, Genetic ; Passeriformes/classification/*genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; South America ; *Sympatry ; }, abstract = {Recently diverged taxa provide the opportunity to search for the genetic basis of the phenotypes that distinguish them. Genomic scans aim to identify loci that are diverged with respect to an otherwise weakly differentiated genetic background. These loci are candidates for being past targets of selection because they behave differently from the rest of the genome that has either not yet differentiated or that may cross species barriers through introgressive hybridization. Here we use a reduced-representation genomic approach to explore divergence among six species of southern capuchino seedeaters, a group of recently radiated sympatric passerine birds in the genus Sporophila. For the first time in these taxa, we discovered a small proportion of markers that appeared differentiated among species. However, when assessing the significance of these signatures of divergence, we found that similar patterns can also be recovered from random grouping of individuals representing different species. A detailed demographic inference indicates that genetic differences among Sporophila species could be the consequence of neutral processes, which include a very large ancestral effective population size that accentuates the effects of incomplete lineage sorting. As these neutral phenomena can generate genomic scan patterns that mimic those of markers involved in speciation and phenotypic differentiation, they highlight the need for caution when ascertaining and interpreting differentiated markers between species, especially when large numbers of markers are surveyed. Our study provides new insights into the demography of the southern capuchino radiation and proposes controls to distinguish signal from noise in similar genomic scans.}, }
@article {pmid26165857, year = {2015}, author = {Allen, MD and Jones, LJ}, title = {The role of inflammation in progression of breast cancer: Friend or foe? (Review).}, journal = {International journal of oncology}, volume = {47}, number = {3}, pages = {797-805}, doi = {10.3892/ijo.2015.3075}, pmid = {26165857}, issn = {1791-2423}, mesh = {Biomarkers, Tumor/*immunology ; Breast Neoplasms/*drug therapy/immunology/*pathology ; Disease Progression ; Female ; Humans ; Immunotherapy/methods ; Prognosis ; Tumor Microenvironment/drug effects ; }, abstract = {There is a growing interest in the role of the microenvironment in cancer, however, it has been known for over one hundred years that the immune system plays a prominent role in cancer. Recent decades have revealed more and more data on how our own host response to cancer cells can help or hinder progression of the disease. Despite all this work it is surprising how little is known about the role of the immune system in human breast cancer development, as compared to other cancers. Recent successes of PD-1 blockade in treating multiple cancers, and new developments with other immune targets such as CTLA-4 and CSF-1 inhibitors, highlight that it is becoming ever more important that we understand the complexity of the immune and inflammatory systems in the development and progression of breast cancer. With this knowledge it may be possible to not only target therapy but also more accurately predict those patients that truly need it. This review summarises some of the most significant findings for the role of the immune system and inflammatory response in breast cancer progression. Focusing on how the inflammatory microenvironment may be involved in the progression of pre-invasive ductal carcinoma in situ to invasive breast cancer. It will also discuss the use of immune markers as diagnostic and prognostic tools and summarise the state of the art of immune-therapeutics in breast cancer treatment.}, }
@article {pmid26163605, year = {2015}, author = {Payandeh, M and Sadeghi, M and Sadeghi, E and Aeinfar, M}, title = {Clinicopathology Figures and Long-term Effects of Tamoxifen Plus Radiation on Survival of Women with Invasive Ductal Carcinoma and Triple Negative Breast Cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {16}, number = {12}, pages = {4863-4867}, doi = {10.7314/apjcp.2015.16.12.4863}, pmid = {26163605}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Carcinoma, Ductal, Breast/*mortality/*secondary/therapy ; Chemoradiotherapy/*mortality ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; Survival Rate ; Tamoxifen/*therapeutic use ; Triple Negative Breast Neoplasms/*mortality/*pathology/therapy ; Young Adult ; }, abstract = {BACKGROUND: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports.<br><br>MATERIALS AND METHODS: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results.<br><br>RESULTS: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively.<br><br>CONCLUSIONS: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.}, }
@article {pmid26154605, year = {2015}, author = {Walker, CG and Solis-Trapala, I and Holzapfel, C and Ambrosini, GL and Fuller, NR and Loos, RJ and Hauner, H and Caterson, ID and Jebb, SA}, title = {Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.}, journal = {PloS one}, volume = {10}, number = {7}, pages = {e0131681}, pmid = {26154605}, issn = {1932-6203}, support = {MC_EX_G0701642/2/MRC_/Medical Research Council/United Kingdom ; P60 DK020541/DK/NIDDK NIH HHS/United States ; G0701642/MRC_/Medical Research Council/United Kingdom ; MC_U105960389/MRC_/Medical Research Council/United Kingdom ; U105960389/MRC_/Medical Research Council/United Kingdom ; P30 DK020541/DK/NIDDK NIH HHS/United States ; }, mesh = {Biomarkers/*metabolism ; Diabetes Mellitus, Type 2/*genetics ; Diet ; Dietary Fats/pharmacology ; Female ; *Genetic Predisposition to Disease ; Humans ; *Life Style ; Male ; Markov Chains ; Middle Aged ; *Models, Biological ; Quantitative Trait, Heritable ; Regression Analysis ; Risk Factors ; Weight Loss ; }, abstract = {The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention.}, }
@article {pmid26153395, year = {2015}, author = {Santangelo, G and Trojano, L and Barone, P and Vitale, C}, title = {Cortical thickness in Parkinsonians with impulse control disorders: A comment.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {30}, number = {9}, pages = {1293}, doi = {10.1002/mds.26262}, pmid = {26153395}, issn = {1531-8257}, mesh = {Cerebral Cortex/*pathology ; Disruptive, Impulse Control, and Conduct Disorders/*complications/*pathology ; Female ; Humans ; Male ; Parkinson Disease/*complications ; }, }
@article {pmid26152288, year = {2015}, author = {Dallol, A and Buhmeida, A and Merdad, A and Al-Maghrabi, J and Gari, MA and Abu-Elmagd, MM and Elaimi, A and Assidi, M and Chaudhary, AG and Abuzenadah, AM and Nedjadi, T and Ermiah, E and Alkhayyat, SS and Al-Qahtani, MH}, title = {Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {12}, pages = {9677-9683}, pmid = {26152288}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Line, Tumor ; CpG Islands ; DNA Methylation/genetics ; Epigenesis, Genetic ; Female ; Fibroblast Growth Factors/*biosynthesis/genetics ; Gene Expression Regulation, Neoplastic ; Glucuronidase/*genetics ; Humans ; Klotho Proteins ; Middle Aged ; Promoter Regions, Genetic ; Receptor, Fibroblast Growth Factor, Type 4/*biosynthesis/genetics ; }, abstract = {Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context.}, }
@article {pmid26125904, year = {2015}, author = {Ramos, FS and Serino, LT and Carvalho, CM and Lima, RS and Urban, CA and Cavalli, IJ and Ribeiro, EM}, title = {PDIA3 and PDIA6 gene expression as an aggressiveness marker in primary ductal breast cancer.}, journal = {Genetics and molecular research : GMR}, volume = {14}, number = {2}, pages = {6960-6967}, doi = {10.4238/2015.June.26.4}, pmid = {26125904}, issn = {1676-5680}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Protein Disulfide-Isomerases/*genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; }, abstract = {Changes in the expression of the protein disulfide isomerase genes PDIA3 and PDIA6 may increase endoplasmic reticulum stress, leading to cellular instability and neoplasia. We evaluated the expression of PDIA3 and PDIA6 in invasive ductal carcinomas. Using reverse transcription-quantitative polymerase chain reaction, we compared the mRNA expression level in 45 samples of invasive ductal carcinoma with that in normal breast samples. Increased expression of the PDIA3 gene in carcinomas (P = 0.0009) was observed. In addition, PDIA3 expression was increased in tumors with lymph node metastasis (P = 0.009) and with grade III (P < 0.02). The PDIA6 gene showed higher expression levels in the presence of lymph node metastasis (U = 99.00, P = 0.0476) and lower expression for negative hormone receptors status (P = 0.0351). Our results suggest that alterations in PDIA3/6 expression levels may be involved in the breast carcinogenic process and should be further investigated as a marker of aggressiveness.}, }
@article {pmid26125737, year = {2015}, author = {Zhao, LH and Liu, HG}, title = {Immunohistochemical detection and clinicopathological significance of JARID1B/KDM5B and P16 expression in invasive ductal carcinoma of the breast.}, journal = {Genetics and molecular research : GMR}, volume = {14}, number = {2}, pages = {5417-5426}, doi = {10.4238/2015.May.22.11}, pmid = {26125737}, issn = {1676-5680}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p16/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/*biosynthesis/genetics ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Staging ; Nuclear Proteins/*biosynthesis/genetics ; Repressor Proteins/*biosynthesis/genetics ; }, abstract = {The aims of this study were to investigate the expression of the H3K4 demethylase, jumonji AT-rich interactive domain 1B (JARID1B/KDM5B) and of p16 (multiple tumor suppressor gene MTS1) in breast cancer tissue and determine its clinicopathological significance. JARID1B/KDM5B and P16 protein expression in 176 resected breast cancer specimens and adjacent normal breast tissue was detected by the streptavidin-peroxidase (S-P) immunohistochemical method. The TNM staging grade was assigned according to the World Health Organization (2012) breast classification system. The positive staining rate of JARID1B/KDM5B and p16 protein in cancer tissue was 74.43 and 35.8%, respectively. JARID1B/KDM5B protein expression was positively associated with T grade, Bloom and Richardson (B&amp;R) score and axillary lymph node metastasis (P < 0.05). p16 protein expression was negatively associated with T grade, B&amp;R score, and axillary lymph node metastasis (P < 0.05). JARID1B/KDM5B and p16 protein expression in breast cancer and adjacent normal breast tissue were negatively correlated (r = -0.303, P < 0.001). The data demonstrated that protein expression of p16 and JARID1B/KDM5B is negatively correlated in invasive ductal carcinoma of the breast.}, }
@article {pmid26124343, year = {2015}, author = {Grzegrzolka, J and Biala, M and Wojtyra, P and Kobierzycki, C and Olbromski, M and Gomulkiewicz, A and Piotrowska, A and Rys, J and Podhorska-Okolow, M and Dziegiel, P}, title = {Expression of EMT Markers SLUG and TWIST in Breast Cancer.}, journal = {Anticancer research}, volume = {35}, number = {7}, pages = {3961-3968}, pmid = {26124343}, issn = {1791-7530}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Gene Expression/genetics ; Humans ; Middle Aged ; Nuclear Proteins/*genetics ; RNA, Messenger/genetics ; Snail Family Transcription Factors ; Stromal Cells/metabolism ; Transcription Factors/*genetics ; Twist-Related Protein 1/*genetics ; }, abstract = {BACKGROUND: The epithelial-mesenchymal transition (EMT) has been observed in progression of in situ breast cancer to the invasive form and might be initiated by snail family zinc finger 2 (SLUG) and twist family bHLH transcription factor 1 (TWIST) protein overexpression. During this phenomenon, cells lose their epithelial phenotype and acquire mesenchymal features. The aim of the study was to examine the association of EMT markers SLUG and TWIST with clinicopathological data and the possibility of using these proteins as prognostic markers of breast cancer.<br><br>MATERIALS AND METHODS: Immunohistochemical analysis (IHC) of SLUG and TWIST expression was performed on archival paraffin samples of 19 cases with fibrocystic breast changes (control group), 148 cases of invasive ductal breast cancer (IDC) and 26 of invasive lobular breast cancer (ILC). Laser capture microdissection for isolation of cells from 17 frozen samples of IDC was employed and subsequently SLUG and TWIST mRNA expression in cancer and stromal cells was detected separately by real-time polymerase chain reaction.<br><br>RESULTS: SLUG and TWIST expression in IDC was significant higher in stromal cells regardless of the method of quantification used (p<0.001 for SLUG mRNA, and p<0.0001 for SLUG IHC, TWIST IHC and TWIST mRNA expression). Positive correlation of SLUG and TWIST protein and mRNA expression was observed in stromal cells of IDC (r=0.347; p<0.0001 and r=0.704; p<0.01, respectively). Expression of TWIST protein in IDC was higher in cancer cells of cases with shorter event-free survival period, as well as in stromal cells of cases with shorter overall survival period (p<0.05 for both).<br><br>CONCLUSION: Stromal cells could play a role in the regulation of EMT in breast cancer.}, }
@article {pmid26112049, year = {2015}, author = {Romaniuk, A and Lуndіn, M}, title = {Immune microenvironment as a factor of breast cancer progression.}, journal = {Diagnostic pathology}, volume = {10}, number = {}, pages = {79}, pmid = {26112049}, issn = {1746-1596}, mesh = {B-Lymphocytes/*immunology/pathology ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/*immunology/pathology ; Carcinoma, Ductal, Breast/chemistry/*immunology/pathology ; Estrogen Receptor alpha/analysis ; Female ; HSP90 Heat-Shock Proteins/analysis ; Humans ; Immunohistochemistry ; Inflammation/*immunology/metabolism/pathology ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Progesterone/analysis ; Triple Negative Breast Neoplasms/chemistry/immunology/pathology ; Tumor Microenvironment/*immunology ; }, abstract = {BACKGROUND: The rate of progression of the disease depends on various factors and the tumor microenvironment takes not the last place among them. One part of researchers argues that the presence of tumor-infiltrating leukocytes serves as a favorable marker of the disease. There exists a completely different point of view on the matter. The investigation of the effects of the inflammatory infiltration on the course of breast cancer process.<br><br>METHODS: We found a pronounced inflammatory infiltration in the tumor microenvironment in 24 cases. Nineteen cases of IDC without inflammatory infiltration were used as a control group. Immunohistochemical reaction showed expression of ER&#x3b1;, PR, HER2/neu, E-cadherin, Hsp90&#x3b1;, Bcl-2, CD3, CD79&#x3b1;, S100 and Myeloperoxidase receptors. Mathematical calculations were done using Microsoft Excel 2010 with 12.0.5 Attestat option.<br><br>RESULTS: We have determined five variants of immune microenvironment: interstitial, trabecular, nodular, diffuse and mixed. We have established a direct correlation between the expression of ER&#x3b1; and PR and indirect correlation between the receptors of steroid hormones and HER2/neo in both groups of breast cancer. HER2/neo positive tumors in 100% of cases were accompanied by the presence of heat shock proteins. There was a combination of Bcl-2 presence with the steroid receptors expression in 90 % of cases. There was found the indirect correlation between the presence of B lymphocytes and expression of steroid receptors.<br><br>CONCLUSIONS: The presence of B lymphocytes in an inflammatory infiltrate leads to the disappearance of estrogen receptors and progesterone receptors. It provokes the accumulation of Hsp90 in a cell. It contributes to the stabilization of HER2/neu receptors and most proteins that promote tumor progression.<br><br>VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1362330168161694.}, }
@article {pmid26097589, year = {2015}, author = {Lv, ZD and Zhang, L and Liu, XP and Jin, LY and Dong, Q and Li, FN and Wang, HB and Kong, B}, title = {NKD1 down-regulation is associated with poor prognosis in breast invasive ductal carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {4}, pages = {4015-4021}, pmid = {26097589}, issn = {1936-2625}, support = {CDP 13-005/HX/HSRD VA/United States ; }, mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology/therapy ; Calcium-Binding Proteins ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/therapy ; Carrier Proteins/genetics/*metabolism ; Cell Line, Tumor ; *Cell Movement ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Receptors, Estrogen/metabolism ; Risk Factors ; Time Factors ; Transfection ; Treatment Outcome ; Young Adult ; }, abstract = {As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression and clinicopathological significance of NKD1 in patients with breast cancer is still unclear. The aim of this study was to evaluate NKD1 expression in breast cancer and to investigate the question of whether reduced expression of NKD1 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of NKD1 and relevance with clinicopathological factors in the breast invasive ductal carcinoma. Reduction of NKD1 was significantly correlated with lymph node metastasis, histological grade and ER expression in breast cancer. Patients with negative NKD1 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive NKD1 expression. This interpretation is in keeping with the results obtained from our in vitro experiments on MDA-MB-231 cells, we demonstrated that upregulation of NKD1 expression by infect with an adenovirus containing a NKD1 vector significantly reduced the migration of breast cancer cells. These data suggest that NKD1 plays an important role in invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.}, }
@article {pmid26080617, year = {2015}, author = {Luo, Y and Tanabe, E and Kitayoshi, M and Nishiguchi, Y and Fujiwara, R and Matsushima, S and Sasaki, T and Sasahira, T and Chihara, Y and Nakae, D and Fujii, K and Ohmori, H and Kuniyasu, H}, title = {Expression of MAS1 in breast cancer.}, journal = {Cancer science}, volume = {106}, number = {9}, pages = {1240-1248}, pmid = {26080617}, issn = {1349-7006}, mesh = {Animals ; Apoptosis/genetics ; Carcinoma, Ductal, Breast/drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cisplatin/pharmacology ; ErbB Receptors/genetics ; Female ; Humans ; Immunohistochemistry/methods ; Lymphatic Metastasis/genetics/pathology ; MCF-7 Cells ; Mice ; Proto-Oncogene Mas ; Proto-Oncogene Proteins/*genetics ; Receptors, G-Protein-Coupled/*genetics ; Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology ; }, abstract = {MAS1 is a receptor for angiotensin 1-7 (A1-7), which is derived from angiotensin II (A-II) by the action of angiotensin converting enzyme (ACE) 2. MAS1 induces anti-A-II phenotypes, such as vessel dilation and depression of blood pressure. Using immunohistochemistry, we examined the role of MAS1 in 132 cases of invasive ductal carcinoma (IDC) of the breast. While benign mammary tissues expressed MAS1 at high levels, MAS1 expression was attenuated in all IDC, especially in scirrhous IDC. The decrease in MAS1 expression was associated with tumor growth, lymph node metastasis, and grade. MAS1 expression was inversely associated with the proliferation index and epidermal growth factor receptor and human epidermal growth factor receptor-2 expression. Of the 132 cases, 12 (9.1%) were triple-negative breast cancer (TNBC) cases. All TNBC cases (the 12 cases and the additional 36 cases using a tissue array) expressed MAS1. Using the TNBC cell lines 4T1 and MDA-MB-468, which expresses MAS1, we found that cell growth, anti-apoptotic survival and invasion were suppressed by MAS1 activation with A1-7 treatment and enhanced by MAS1 knockdown. In contrast, synergic effect was found between tamoxifen and A1-7 in a luminal A breast cancer cell line, MCF-7. Combination treatment with cisplatin, an ACE2 activator, and an A-II type 1 receptor blocker showed synergic effects on tumor growth inhibition of 4T1 tumors in a syngeneic mouse model. These findings suggest that MAS1 might act as an inhibitory regulator of breast cancer and may be a possible molecular target for this malignancy.}, }
@article {pmid26076803, year = {2015}, author = {Poursadegh Zonouzi, AA and Nejatizadeh, A and Rahmati-Yamchi, M and Fardmanesh, H and Shakerizadeh, S and Poursadegh Zonouzi, A and Nejati-Koshki, K and Shekari, M}, title = {Dysregulated expression of Dicer in invasive ductal breast carcinoma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {32}, number = {7}, pages = {203}, pmid = {26076803}, issn = {1559-131X}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma/*genetics/pathology ; DEAD-box RNA Helicases/*genetics ; Down-Regulation/*genetics ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; MicroRNAs/genetics ; Middle Aged ; Ribonuclease III/*genetics ; }, abstract = {Several lines of evidence suggest that the global down-regulation of the microRNAome (miRNAome) involved in pathogenesis of various malignancies. Impaired microRNAs processing pathway is one possible mechanism for global down-regulation of the miRNAome. Dicer is a key enzyme in miRNA processing pathway, and dysregulation of its expression has been suggested as a possible cause of miRNAome alterations observed in various cancers. However, Dicer mRNA expression in invasive ductal breast carcinoma (IDC) has not been investigated in depth. Therefore, this study aimed to evaluate the mRNA expression of Dicer in IDC and also to assess the correlation of its expression with clinicopathological parameters including age, histological grade, tumor size and lymph node metastasis. We investigated the expression of the Dicer in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissue by quantitative real-time PCR using validated reference genes. In addition, the possible impact of clinicopathological characteristics on Dicer expression levels was analyzed. Our results showed that Dicer mRNA expression is down-regulated in slightly more than half (51.43 %) of the tumor specimens when compared to adjacent non-neoplastic tissue. Comparison of the Dicer expression level between tumor and matched adjacent non-neoplastic tissue showed that there is no statistical significant differences between them (P = 0.425). We also found that Dicer mRNA expression in IDC samples was not correlated with clinicopathological features. In conclusion, our findings provide additional evidence to support the hypothesis that Dicer expression down-regulated in breast cancer. This study suggested that the decreased expression of Dicer may be potential underlying mechanism in pathogenesis of IDC.}, }
@article {pmid26076065, year = {2015}, author = {Khani, F and Epstein, JI}, title = {Prostate Biopsy Specimens With Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes.}, journal = {The American journal of surgical pathology}, volume = {39}, number = {10}, pages = {1383-1389}, doi = {10.1097/PAS.0000000000000465}, pmid = {26076065}, issn = {1532-0979}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/secondary/*surgery ; Disease Progression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; *Prostatectomy ; Prostatic Neoplasms/chemistry/*pathology/*surgery ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Although intraductal carcinoma of the prostate (IDC-P) is typically present on biopsies in which there is also invasive prostate carcinoma of Gleason pattern 4 or 5 and an associated unfavorable outcome, there are limited studies on IDC-P in needle core biopsies or transurethral resections (TURP) with only a concomitant low-grade invasive component. There are differing opinions on incorporating IDC-P into the Gleason score in such cases. The aim of this study was to investigate clinical outcomes and radical prostatectomy (RP) findings in patients with Gleason 3+3=6 and IDC-P on biopsy or TURP. We identified 73 patients in our consult files (2001 to 2014) who had IDC-P and Gleason score 6 carcinoma on biopsy or TURP with no invasive higher Gleason grade component. Clinical follow-up information was available in 62 patients. Treatment was RP in 14 patients, radiation therapy in 31 patients, androgen deprivation therapy in 1 patient, and cryotherapy in 1 patient. Four patients were found to have metastatic disease at the time of diagnosis and were treated with chemotherapy. Eleven patients underwent active surveillance after diagnosis, of which 6 were eventually treated for progressive disease. The 14 RP specimens were centrally reviewed, and 86% had extensive IDC-P present. The Gleason grades in these 14 RP cases were 3+3=6 in 21%, 3+4=7 in 36%, 4+3=7 in 29%, and 4+4=8 in 14%. Pathologic stage was pT2 in 36%, pT3a in 36%, and pT3b in 28%. After 3 years, there was a 20% actuarial rate of disease progression in men who underwent either RP or radiation therapy. In summary, most men with IDC-P on biopsy/TURP have aggressive tumors, even when the invasive tumor on biopsy is Gleason score 6. As a minority of men may only have Gleason 6 invasive cancer at RP and a favorable prognosis, we recommend that IDC-P on biopsy/TURP be reported separately and not assigned a Gleason score.}, }
@article {pmid26074415, year = {2015}, author = {Dittmar, L and Mohr, E and Kleist, C and Ehser, S and Demirdizen, H and Sandra-Petrescu, F and Hundemer, M and Opelz, G and Terness, P}, title = {Immunosuppressive properties of mitomycin C-incubated human myeloid blood cells (MIC) in vitro.}, journal = {Human immunology}, volume = {76}, number = {7}, pages = {480-487}, doi = {10.1016/j.humimm.2015.06.008}, pmid = {26074415}, issn = {1879-1166}, mesh = {Apoptosis/drug effects ; Cells, Cultured ; Dendritic Cells/drug effects ; Humans ; Immunosuppressive Agents/*pharmacology ; Mitomycin/*pharmacology ; Monocytes/cytology/drug effects/radiation effects ; Myeloid Cells/*drug effects ; T-Lymphocytes/immunology ; }, abstract = {Previous animal studies showed that donor-derived blood cells treated with mitomycin C (MMC) prolong allograft survival when injected into recipients. This model was effective with whole blood, peripheral blood mononuclear cells (PBMC) (monocytes being the active cell subpopulation) or dendritic cells. In view of a potential clinical application, we study now the immunosuppressive properties of human myeloid cells in vitro. Mature dendritic cells (generated from naïve monocytes) or monocytes treated with mitomycin C do not or only weakly inhibit allogeneic T cells in vitro, whereas cells in an early differentiation state between monocytes and DC exert suppressive activity when treated with MMC. In contrast, DC generated from MMC-treated monocytes show the morphology and phenotype of early immature DC (iDC) and suppress T-cell responses. It is known that untreated monocytes injected into a recipient encounter a cytokine milieu which differentiates them to stimulatory DC. In our in vitro experiment MMC-treated monocytes cultured in a DC-maturing milieu transform themselves into suppressive early iDC. This reproduces a process which takes place when administering MMC-monocytes to a recipient. In conclusion, human MMC-DC or MMC-monocytes are not or only weakly suppressive in vitro. When MMC-monocytes are differentiated to DC the resulting cells become suppressive.}, }
@article {pmid26070712, year = {2015}, author = {Stoy, C and Sundaram, A and Rios Garcia, M and Wang, X and Seibert, O and Zota, A and Wendler, S and Männle, D and Hinz, U and Sticht, C and Muciek, M and Gretz, N and Rose, AJ and Greiner, V and Hofmann, TG and Bauer, A and Hoheisel, J and Berriel Diaz, M and Gaida, MM and Werner, J and Schafmeier, T and Strobel, O and Herzig, S}, title = {Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy.}, journal = {EMBO molecular medicine}, volume = {7}, number = {8}, pages = {1048-1062}, pmid = {26070712}, issn = {1757-4684}, mesh = {Animals ; Carcinoma, Pancreatic Ductal/*pathology ; Gene Expression Profiling ; Humans ; Mice ; Pancreatic Neoplasms/*pathology ; Survival Analysis ; Transducin/deficiency/*metabolism ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here, we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI3 kinase signaling which in turn could rescue TBL1 deficiency-dependent phenotypes. TBL1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo. As TBL1 mRNA levels were also found to correlate with PI3 kinase levels and overall survival in a cohort of human PDAC patients, TBL1 was identified as a checkpoint in the malignant behavior of pancreatic cancer and its expression may serve as a novel molecular target in the treatment of human PDAC.}, }
@article {pmid26070507, year = {2015}, author = {Jazayeri, SB and Saadat, S and Ramezani, R and Kaviani, A}, title = {Incidence of primary breast cancer in Iran: Ten-year national cancer registry data report.}, journal = {Cancer epidemiology}, volume = {39}, number = {4}, pages = {519-527}, doi = {10.1016/j.canep.2015.04.016}, pmid = {26070507}, issn = {1877-783X}, mesh = {Adult ; Breast Neoplasms/*epidemiology ; Breast Neoplasms, Male/*epidemiology ; Female ; Humans ; Incidence ; Iran/epidemiology ; Male ; Middle Aged ; Registries ; }, abstract = {Breast cancer is the leading type of malignancy and the leading cause of cancer-related deaths in women worldwide. The screening programs and advances in the treatment of patients with breast cancer have led to an increase in overall survival. Cancer registry systems play an important role in providing basic data for research and the monitoring of the cancer status. In this study, the results of the 10-year national cancer registry (NCR) of Iran in breast cancer are reviewed. NCR database records were searched for primary breast cancer records according to ICD-O-3 coding and the cases were reviewed. A total of 52,068 cases were found with the coding of primary breast cancer. Females constituted 97.1% of the cases. Breast cancer was the leading type of cancer in Iranian females, accounting for 24.6% of all cancers. The mean age of the women with breast cancer was 49.6 years (95%CI 49.5-49.6). Most of the cases (95.7%) were registered as having invasive pathologies (behavior code 3). The most common morphology of primary breast cancer was invasive ductal carcinoma (ICD-O 8500/3) followed by invasive lobular carcinoma (ICD-O 8520/3) with relative frequencies of 77.8% and 5.2%, respectively. The average annual crude incidence of primary breast cancer in females was 22.6 (95%CI 22.1-23.1) per 100,000 females, with an age-standardized rate (ASR) of 27.4 (95%CI 22.5-35.9). There were no data on survival, staging or immunohistochemical marker(s) of the breast-cancer-registered cases. The incidence of breast cancer in Iran is lower than in low-middle-income neighboring countries. The NCR data registry of breast cancer is not accurate in monitoring the effect of screening programs or determining the current status of breast cancer in Iran. Screening programs of breast cancer in Iran have failed to enhance the detection of the patients with in situ lesion detection. A quality breast cancer registry and a screening program for breast cancer are both needed.}, }
@article {pmid26039396, year = {2014}, author = {Silva, FX and Katz, L and Souza, AS and Amorim, MM}, title = {Mammography in asymptomatic women aged 40-49 years.}, journal = {Revista de saude publica}, volume = {48}, number = {6}, pages = {931-939}, pmid = {26039396}, issn = {1518-8787}, mesh = {Adult ; Biopsy ; Brazil ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Cross-Sectional Studies ; Early Detection of Cancer ; Female ; Humans ; Mammography/*statistics &amp; numerical data ; Mass Screening/*methods ; Middle Aged ; Risk Factors ; }, abstract = {OBJECTIVE To assess findings of mammography of and interventions resulting from breast cancer screening in women aged 40-49 years with no increased risk (typical risk) of breast cancer. METHODS This cross-sectional study evaluated women aged 40-49 years who underwent mammography screening in a mastology reference center in Recife, PE, Northeastern Brazil, between January 2010 and October 2011. Women with breast-related complaints, positive findings in the physical examination, or high risk of breast cancer were excluded. RESULTS The 1,000 mammograms performed were classified into the following Breast Imaging-Reporting and Data System (BI-RADS) categories BI-RADS 0, 232; BI-RADS 1, 294; BI-RADS 2, 294; BI-RADS 3, 16; BI-RADS 4A, 2; BI-RADS 5, 1. There was one case of grade II invasive ductal carcinoma and various interventions, including 469 ultrasound scans, 53 referrals to mastologists, 11 cytological examinations, and 8 biopsies. CONCLUSIONS Mammography screening in women aged 40-49 years with typical risk of breast cancer led to the performance of other interventions. However, it also resulted in increased costs without demonstrable efficacy in decreasing mortality.}, }
@article {pmid26033922, year = {2015}, author = {Bochicchio, GV and Hipszer, BR and Magee, MF and Bergenstal, RM and Furnary, AP and Gulino, AM and Higgins, MJ and Simpson, PC and Joseph, JI}, title = {Multicenter Observational Study of the First-Generation Intravenous Blood Glucose Monitoring System in Hospitalized Patients.}, journal = {Journal of diabetes science and technology}, volume = {9}, number = {4}, pages = {739-750}, pmid = {26033922}, issn = {1932-2968}, mesh = {Adult ; Aged ; Automation ; Blood Glucose/*analysis ; Calibration ; Catheterization ; Equipment Design ; Female ; Hospitalization ; Humans ; Infusion Pumps, Implantable ; Infusions, Intravenous/instrumentation/methods ; *Insulin Infusion Systems ; Male ; Middle Aged ; Monitoring, Physiologic/*instrumentation/*methods ; Patient Safety ; Prospective Studies ; Reproducibility of Results ; United States ; }, abstract = {BACKGROUND: Current methods of blood glucose (BG) monitoring and insulin delivery are labor intensive and commonly fail to achieve the desired level of BG control. There is great clinical need in the hospital for a user-friendly bedside device that can automatically monitor the concentration of BG safely, accurately, frequently, and reliably.<br><br>METHODS: A 100-patient observation study was conducted at 6 US hospitals to evaluate the first generation of the Intravenous Blood Glucose (IVBG) System (Edwards Lifesciences LLC &amp; Dexcom Inc). Device safety, accuracy, and reliability were assessed. A research nurse sampled blood from a vascular catheter every 4 hours for &#x2264; 72 hours and BG concentration was measured using the YSI 2300 STAT Plus Analyzer (YSI Life Sciences). The IVBG measurements were compared to YSI measurements to calculate point accuracy.<br><br>RESULTS: The IVBG systems logged more than 5500 hours of operation in 100 critical care patients without causing infection or inflammation of a vein. A total of 44135 IVBG measurements were performed in 100 patients with 30231 measurements from the subset of 75 patients used for accuracy analysis. In all, 996 IVBG measurements were time-matched with reference YSI measurements. These pairs had a mean absolute difference (MAD) of 11.61 mg/dl, a mean absolute relative difference (MARD) of 8.23%, 93% met 15/20% accuracy defined by International Organization for Standardization 15197:2003 standard, and 93.2% were in zone A of the Clarke error grid. The IVBG sensors were exposed to more than 200 different medications with no observable effect on accuracy.<br><br>CONCLUSIONS: The IVBG system is an automated and user-friendly glucose monitoring system that provides accurate and frequent BG measurements with great potential to improve the safety and efficacy of insulin therapy and BG control in the hospital, potentially leading to improved clinical outcomes.}, }
@article {pmid26026464, year = {2015}, author = {Di Rosa, M and Tibullo, D and Cambria, D and Distefano, G and Saccone, S and Di Raimondo, F and Malaguarnera, L}, title = {Chitotriosidase Expression during Monocyte-Derived Dendritic Cells Differentiation and Maturation.}, journal = {Inflammation}, volume = {38}, number = {6}, pages = {2082-2091}, pmid = {26026464}, issn = {1573-2576}, mesh = {*Cell Differentiation ; Cells, Cultured ; Cytoplasm/enzymology ; Dendritic Cells/*enzymology/immunology ; Gene Expression Regulation, Enzymologic ; Hexosaminidases/genetics/*metabolism ; Humans ; Monocytes/*enzymology/immunology ; Phenotype ; RNA, Messenger/metabolism ; Signal Transduction ; Time Factors ; }, abstract = {The chitotriosidase (CHIT-1) is a glycosyl hydrolase (GH), which has been found highly expressed in activated macrophages and in different monocyte-derived cell lines such as Kupffer cells and osteoclasts, as well is differently produced in diverse stages of macrophage polarization (M1 and M2). Recent finding suggests that CHIT-1 plays a crucial role in innate and acquired immunity. Dendritic cells (DCs) are a complex group of cells that play a critical role in immune response. The aim of this study was to investigate the presence of CHIT-1 during the differentiation and maturation of DCs. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs). Our results showed, for the first time, that CHIT-1 is expressed during the process of differentiation and maturation of DCs in a time-dependent manner. We found that CHIT1 is evenly distributed in cytoplasm of both the iDCs and mDCs. Additionally, a significantly increased expression of CHIT1 mRNA and protein was observed in mature DCs. These results suggest that CHIT-1 play an important role in the DCs immunoresponse.}, }
@article {pmid26024935, year = {2015}, author = {Hoefgen, HR and Merritt, DF}, title = {Invasive Ductal Carcinoma in a 46,XY Partial Androgen Insensitivity Syndrome Patient on Hormone Therapy.}, journal = {Journal of pediatric and adolescent gynecology}, volume = {28}, number = {4}, pages = {e95-7}, doi = {10.1016/j.jpag.2014.08.005}, pmid = {26024935}, issn = {1873-4332}, mesh = {Androgen-Insensitivity Syndrome/blood/*diagnosis/etiology ; Breast Neoplasms/blood/*complications/drug therapy ; Carcinoma, Ductal/blood/*complications/drug therapy ; Female ; Follow-Up Studies ; Hormone Replacement Therapy/*adverse effects ; Humans ; Infant, Newborn ; Male ; }, abstract = {BACKGROUND: The hormonal management of patients with androgen insensitivity can be challenging.<br><br>CASE: An illustrative case is presented of a newborn with ambiguous genitalia who was raised female. She was diagnosed as 46,XY Disorder of Sexual Development with partial androgen insensitivity. To induce puberty, conjugated equine estrogens were administered beginning at age 12. At age 13, she instead began taking combined oral contraceptives for maternal concerns about height and continued taking them for social reasons. Invasive ductal carcinoma was diagnosed at age 27, and the patient was treated with chemotherapy, radiation therapy, bilateral mastectomies, and endocrine therapy.<br><br>SUMMARY AND CONCLUSION: The current literature is reviewed, and hormonal management and other risks for breast cancer are discussed.}, }
@article {pmid26017877, year = {2015}, author = {Fulga, V and Rudico, L and Balica, AR and Cimpean, AM and Saptefrati, L and Raica, M}, title = {Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile?.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {66}, number = {1}, pages = {30-37}, doi = {10.5114/pjp.2015.51150}, pmid = {26017877}, issn = {1233-9687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*chemistry/classification/*pathology ; Carcinoma, Ductal, Breast/*chemistry/classification/*secondary ; Cell Differentiation ; Female ; Humans ; Immunohistochemistry ; *Immunophenotyping ; Lymph Nodes/*chemistry/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phenotype ; Retrospective Studies ; }, abstract = {In the present study we compared the immunophenotypic subtypes of breast ductal invasive carcinomas with their ipsilateral, axillary lymph node metastasis. The ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal growth factor receptor 2), and CK5 (cytokeratin 5) status and the proliferation marker Ki-67 were determined by immunohistochemistry on specimens from 43 women. All selected cases were diagnosed as invasive breast carcinomas, of no special type (NST), G2 grade of differentiation. The most frequently encountered subtype at both sites was luminal B. We determined that tumor profile evaluated by surrogate markers is not stable during the metastatic process. The total rate of shifted cases was 23.26% (10 cases), and the highest rate of shifting (6.98%) was encountered from luminal B/Ki-67 to luminal A subtype. In five cases, the subtype shifted to a poorer one according to prognosis. These data support the hypothesis that breast cancer is a heterogeneous disease, with substantial variability of cellular components within each category, a statement applicable to invasive breast carcinomas of NST type too. The receptor profile of this carcinoma, indicated by surrogate markers, is not stable throughout the metastatic process.}, }
@article {pmid26004371, year = {2015}, author = {Chung, YR and Kim, H and Park, SY and Park, IA and Jang, JJ and Choe, JY and Jung, YY and Im, SA and Moon, HG and Lee, KH and Suh, KJ and Kim, TY and Noh, DY and Han, W and Ryu, HS}, title = {Distinctive role of SIRT1 expression on tumor invasion and metastasis in breast cancer by molecular subtype.}, journal = {Human pathology}, volume = {46}, number = {7}, pages = {1027-1035}, doi = {10.1016/j.humpath.2015.03.015}, pmid = {26004371}, issn = {1532-8392}, mesh = {Adult ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*enzymology/genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/mortality/*secondary ; *Cell Movement ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; MCF-7 Cells ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; RNA Interference ; Retrospective Studies ; Sirtuin 1/genetics/*metabolism ; Tissue Array Analysis ; Transfection ; Triple Negative Breast Neoplasms/enzymology/pathology ; }, abstract = {The aim of this study was to evaluate silent mating type information regulation 2 homolog 1 (SIRT1) expression levels by subtype and evaluate its predictive power of axillary lymph node metastasis (LNM) and its association with clinical outcome. A total of 427 patients diagnosed with invasive ductal carcinoma were chosen, immunohistochemical staining for SIRT1 expression was performed on tissue microarrays, and in vitro experiments with each intrinsic subtype of human breast cancer cell line were carried out. Increased expression of SIRT1 in hormone receptor-positive breast cancer and HER2 breast cancer subtype significantly correlated with lower risks of LNM. On the contrary, in triple-negative breast cancer, increased SIRT1 expression was more frequently observed in LNM-positive subgroup than LNM-negative subgroup. Combination of statistically significant, independent parameters including SIRT1 revealed predictive performance for LNM with area under the curve of 0.602, 0.587, and 0.726 for hormone receptor-positive breast cancer, HER2 breast cancer, and triple-negative breast cancer subtype, respectively. Inhibition of SIRT1 expression with small interfering RNA suppressed tumor invasion in MDA-MB-231, specifically. This is the first study to examine SIRT1 expression in breast cancer by subtype, and we have observed the potentially different role of SIRT1 gene having tumor-suppressive or tumor-promoting influence depending on the subtype; thus, different associations between SIRT1 expression and prognosis by subtype should be considered in its target therapy.}, }
@article {pmid25998492, year = {2015}, author = {Ben-Zvi, S and Soroker, N and Levy, DA}, title = {Parietal lesion effects on cued recall following pair associate learning.}, journal = {Neuropsychologia}, volume = {73}, number = {}, pages = {176-194}, doi = {10.1016/j.neuropsychologia.2015.05.009}, pmid = {25998492}, issn = {1873-3514}, mesh = {Acoustic Stimulation ; Adult ; Aged ; Aged, 80 and over ; Association Learning/*physiology ; Auditory Perception/physiology ; Brain Mapping ; Cues ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mental Recall/*physiology ; Middle Aged ; Neuropsychological Tests ; Parietal Lobe/pathology/physiology/*physiopathology ; Photic Stimulation ; Stroke/pathology/*physiopathology ; Tomography, X-Ray Computed ; Visual Perception/physiology ; Young Adult ; }, abstract = {We investigated the involvement of the posterior parietal cortex in episodic memory in a lesion-effects study of cued recall following pair-associate learning. Groups of patients who had experienced first-incident stroke, generally in middle cerebral artery territory, and exhibited damage that included lateral posterior parietal regions, were tested within an early post-stroke time window. In three experiments, patients and matched healthy comparison groups executed repeated study and cued recall test blocks of pairs of words (Experiment 1), pairs of object pictures (Experiment 2), or pairs of object pictures and environmental sounds (Experiment 3). Patients' brain CT scans were subjected to quantitative analysis of lesion volumes. Behavioral and lesion data were used to compute correlations between area lesion extent and memory deficits, and to conduct voxel-based lesion-symptom mapping. These analyses implicated lateral ventral parietal cortex, especially the angular gyrus, in cued recall deficits, most pronouncedly in the cross-modal picture-sound pairs task, though significant parietal lesion effects were also found in the unimodal word pairs and picture pairs tasks. In contrast to an earlier study in which comparable parietal lesions did not cause deficits in item recognition, these results indicate that lateral posterior parietal areas make a substantive contribution to demanding forms of recollective retrieval as represented by cued recall, especially for complex associative representations.}, }
@article {pmid25981591, year = {2015}, author = {Lajus, TB and Sales, RM}, title = {CDH1 germ-line missense mutation identified by multigene sequencing in a family with no history of diffuse gastric cancer.}, journal = {Gene}, volume = {568}, number = {2}, pages = {215-219}, doi = {10.1016/j.gene.2015.05.035}, pmid = {25981591}, issn = {1879-0038}, mesh = {Adult ; Aged ; Antigens, CD ; Breast Neoplasms/*genetics ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics ; DNA Mutational Analysis ; Female ; Genetic Testing ; Germ-Line Mutation ; Humans ; Male ; Mutation, Missense ; Stomach Neoplasms/*genetics ; }, abstract = {Germ-line mutation in CDH1 gene is associated with high risk for Hereditary Diffuse Gastric Cancer (HDGC) and Infiltrative Lobular Carcinoma (ILC). Although somatic CDH1 mutations were also detected in ILC with a frequency ranging from 10 to 56%, CDH1 alterations in more frequent infiltrative ductal carcinoma (IDC) appear to be rare, and no association with germ-line CDH1 mutation and IDC has been established. Here we report the case of a woman diagnosed with IDC at 39years of age, presenting extensive familial history of cancer at multiple sites with early-age onset and with no case of HDGC. Deep sequencing have revealed CDH1 missense mutation c.1849G>A (p.Ala617Thr) in heterozygous and four BRCA2 single nucleotide polymorphism in homozygosis. In this family, the mutation c.1849G>A in the CDH1 gene is not related to HDGC nor ILC. Therefore, here we highlight that multigene analysis is important to detect germ-line mutations and genetic variants in patients with cancers at multiple sites in the family, even if inconclusive genetic counseling can be offered, since hereafter, medical awareness will be held.}, }
@article {pmid25980321, year = {2016}, author = {Truin, W and Vugts, G and Roumen, RM and Maaskant-Braat, AJ and Nieuwenhuijzen, GA and van der Heiden-van der Loo, M and Tjan-Heijnen, VC and Voogd, AC}, title = {Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in Invasive Lobular Versus Ductal Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {23}, number = {1}, pages = {51-57}, pmid = {25980321}, issn = {1534-4681}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/metabolism/secondary/*surgery ; Carcinoma, Lobular/drug therapy/metabolism/secondary/*surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: This study was conducted to determine the impact of neoadjuvant chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed for patients with invasive lobular breast carcinoma (ILC) and invasive ductal carcinoma (IDC).<br><br>METHODS: Female patients with a diagnosis of ILC or IDC in The Netherlands between July 2008 and December 2012 were identified through the population-based Netherlands Cancer Registry.<br><br>RESULTS: A total of 466 ILC patients received NAC compared with 3622 IDC patients. Downstaging by NAC was seen in 49.7&#xa0;% of the patients with ILC and in 69.6&#xa0;% of the patients with IDC, and a pathologic complete response (pCR) was observed in 4.9 and 20.2&#xa0;% of these patients, respectively (P&#xa0;<&#xa0;0.0001). Breast-conserving surgery was performed for 24.4&#xa0;% of the patients with ILC receiving NAC versus 39.4&#xa0;% of the patients with IDC. In the ILC group, 8.2&#xa0;% of the patients needed surgical reinterventions after BCS due to tumor-positive resection margins compared with 3.4&#xa0;% of the patients with IDC (P&#xa0;<&#xa0;0.0001). Lobular histology was independently associated with a higher mastectomy rate (odds ratio 1.91; 95&#xa0;% confidence interval 1.49-2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more often when NAC was administered in ILC as well as IDC.<br><br>CONCLUSION: The patients with ILC receiving NAC were less likely to experience a pCR and less likely to undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for ILC patients was lower than for patients receiving surgery without NAC. However, despite the high number to treating in order to achieve BCS, a small subset of ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.}, }
@article {pmid25971426, year = {2015}, author = {Dashevsky, BZ and Goldman, DA and Parsons, M and Gönen, M and Corben, AD and Jochelson, MS and Hudis, CA and Morrow, M and Ulaner, GA}, title = {Appearance of untreated bone metastases from breast cancer on FDG PET/CT: importance of histologic subtype.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {42}, number = {11}, pages = {1666-1673}, pmid = {25971426}, issn = {1619-7089}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*diagnosis/diagnostic imaging/*secondary ; Breast Neoplasms/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; *Multimodal Imaging ; Neoplasm Grading ; *Positron-Emission Tomography ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {PURPOSE: To determine if the histology of a breast malignancy influences the appearance of untreated osseous metastases on FDG PET/CT.<br><br>METHODS: This retrospective study was performed under IRB waiver. Our Hospital Information System was screened for breast cancer patients who presented with osseous metastases, who underwent FDG PET/CT prior to systemic therapy or radiotherapy from 2009 to 2012. Patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or mixed ductal/lobular (MDL) histology were included. Patients with a history of other malignancies were excluded. PET/CT was evaluated, blinded to histology, to classify osseous metastases on a per-patient basis as sclerotic, lytic, mixed lytic/sclerotic, or occult on CT, and to record SUVmax for osseous metastases on PET.<br><br>RESULTS: Following screening, 95 patients who met the inclusion criteria (74 IDC, 13 ILC, and 8 MDL) were included. ILC osseous metastases were more commonly sclerotic and demonstrated lower SUVmax than IDC metastases. In all IDC and MDL patients with osseous metastases, at least one was FDG-avid. For ILC, all patients with lytic or mixed osseous metastases demonstrated at least one FDG-avid metastasis; however, in only three of seven patients were sclerotic osseous metastases apparent on FDG PET.<br><br>CONCLUSION: The histologic subtype of breast cancer affects the appearance of untreated osseous metastases on FDG PET/CT. In particular, non-FDG-avid sclerotic osseous metastases were more common in patients with ILC than in patients with IDC. Breast cancer histology should be considered when interpreting non-FDG-avid sclerotic osseous lesions on PET/CT, which may be more suspicious for metastases (rather than benign lesions) in patients with ILC.}, }
@article {pmid25955408, year = {2015}, author = {Morikawa, A and Takeuchi, T and Kito, Y and Saigo, C and Sakuratani, T and Futamura, M and Yoshida, K}, title = {Expression of beclin-1 in the microenvironment of invasive ductal carcinoma of the breast: correlation with prognosis and the cancer-stromal interaction.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0125762}, pmid = {25955408}, issn = {1932-6203}, mesh = {Apoptosis Regulatory Proteins/antagonists &amp; inhibitors/genetics/*metabolism ; Beclin-1 ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cells, Cultured ; Coculture Techniques ; Cytokines/metabolism ; Discoidin Domain Receptors ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Interleukin-10 Receptor beta Subunit/metabolism ; Interleukin-1beta/genetics/metabolism ; Lymphatic Metastasis ; MCF-7 Cells ; Membrane Proteins/antagonists &amp; inhibitors/genetics/*metabolism ; Mesenchymal Stem Cells/cytology/metabolism ; Neoplasm Recurrence, Local ; Prognosis ; RNA Interference ; RNA, Small Interfering/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Receptors, Cytokine/metabolism ; Receptors, Mitogen/genetics/metabolism ; Tumor Microenvironment ; }, abstract = {We examined the pathobiological properties of beclin-1, which is a key regulator of autophagosome formation in invasive ductal carcinoma of the breast, with a particular focus on the cancer microenvironment. Immunohistochemistry demonstrated that cancer cells and stromal mesenchymal cells expressed beclin-1 in 68 and 38 of 115 invasive ductal cancers, respectively. Expression of beclin-1 in cancer or stromal cells alone did not correlate with patient prognosis. In contrast, loss of beclin-1 in cancer cells and overexpression in stromal mesenchymal cells was associated with local cancer recurrence, postoperative lymph node metastasis, and a poor disease-free survival rate. A comprehensive gene expression analysis was performed on a co-culture of breast cancer cells and mesenchymal stromal cells, that latter of which either expressed beclin-1 or was depleted of beclin-1 by siRNA. Notably, siRNA-mediated downregulation of beclin-1 in mesenchymal cells co-cultured with breast cancer cells decreased the levels of various pro-inflammatory cytokines, their receptors, and collagen receptors. Quantitative reverse transcription polymerase chain reaction analysis confirmed that reduction of stromal beclin-1 expression decreased the expression of IL-1β and collagen receptor discoidin domain receptor 2 (DDR2). Microenvironmental IL-1β is believed to play an important role in tumor invasion. Recent work has also indicated that overexpression of DDR2 contributes to breast cancer invasion and lymph node metastasis. Taken together, these findings indicate beclin-1 expression in the stroma might be important for shaping the breast cancer microenvironment and thus could be a potent molecular target in patients with invasive ductal carcinoma of the breast.}, }
@article {pmid25955205, year = {2015}, author = {Gutierrez, DA and Muralidhar, S and Feyerabend, TB and Herzig, S and Rodewald, HR}, title = {Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance.}, journal = {Cell metabolism}, volume = {21}, number = {5}, pages = {678-691}, doi = {10.1016/j.cmet.2015.04.013}, pmid = {25955205}, issn = {1932-7420}, mesh = {Animals ; Gene Deletion ; Hematopoiesis ; *Insulin Resistance ; Male ; Mast Cells/immunology/metabolism/*pathology ; Metabolic Syndrome/genetics ; Mice ; Mice, Inbred C57BL ; Obesity/*genetics/immunology/pathology ; Stem Cell Factor/*genetics/immunology ; Transcriptome ; }, abstract = {Obesity, insulin resistance, and related pathologies are associated with immune-mediated chronic inflammation. Kit mutant mice are protected from diet-induced obesity and associated co-morbidities, and this phenotype has previously been attributed to their lack of mast cells. We performed a comprehensive metabolic analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell-deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob) background) models of obesity. Our results show that mast cell deficiency, in the absence of Kit mutations, plays no role in the regulation of weight gain or insulin resistance. Moreover, we provide evidence that the metabolic phenotype observed in Kit mutant mice, while independent of mast cells, is immune regulated. Our data underscore the value of definitive mast cell deficiency models to conclusively test the involvement of this enigmatic cell in immune-mediated pathologies and identify Kit as a key hematopoietic factor in the pathogenesis of metabolic syndrome.}, }
@article {pmid25953261, year = {2015}, author = {Jiang, G and Zhang, X and Zhang, Y and Wang, L and Fan, C and Xu, H and Miao, Y and Wang, E}, title = {A novel biomarker C6orf106 promotes the malignant progression of breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {10}, pages = {7881-7889}, pmid = {25953261}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Biomarkers, Tumor/genetics/*metabolism ; Blotting, Western ; Breast/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism/*secondary ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Movement ; *Cell Proliferation ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/antagonists &amp; inhibitors/genetics/*metabolism ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Triple Negative Breast Neoplasms/genetics/metabolism/*pathology ; Tumor Cells, Cultured ; }, abstract = {C6orf106 (chromosome 6 open reading frame 106) is a recently discovered protein encoded by the 6th chromosome. Though many proteins encoded by chromosome 6 are reportedly related to cancer, schizophrenia, autoimmunity and many other diseases, the function of C6orf106 was not well demonstrated so far. As measured by immunohistochemical staining, C6orf106 was positive in normal breast duct myoepithelial cells (92.31 %, 72/78), but negative in normal breast duct glandular epithelial cells (3.85 %, 3/78). In breast ductal carcinoma in situ, C6orf106 showed weakly or moderately positive (77.97 %, 46/59), but it was significantly strongly positive in invasive ductal carcinoma (79.57 %, 148/186). The expression intensity of C6orf106 seemed increased significantly along with the malignancy of breast cancer (p < 0.001). Additionally, C6orf106 expression was significantly correlated with TNM stage (p = 0.001 and p = 0.004) and lymph node metastasis (p = 0.018 and p = 0.025) of the overall and the triple-negative breast cancer, respectively. Consistently, we found that the interference of C6orf106 was able to inhibit cell proliferation and invasion of two triple-negative breast cancer cell lines, MDA-MB-231 and BT-549, accompanied by the decrease of cyclin A2, cyclin B1, c-myc, and N-cadherin and the increase of E-cadherin. Collectively, these results indicate that C6orf106 may promote tumor progression in the invasive breast cancer, particularly in triple-negative breast cancer, and C6orf106 might serve as a novel therapeutic target of breast cancer, especially for triple-negative breast cancer.}, }
@article {pmid25948818, year = {2015}, author = {Alissafi, T and Hatzioannou, A and Ioannou, M and Sparwasser, T and Grün, JR and Grützkau, A and Verginis, P}, title = {De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the accumulation of inflammatory dendritic cells in draining lymph nodes.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {194}, number = {12}, pages = {5812-5824}, doi = {10.4049/jimmunol.1500111}, pmid = {25948818}, issn = {1550-6606}, mesh = {Animals ; Autoantigens/*immunology ; Autoimmunity ; Chemotaxis/immunology ; Cluster Analysis ; Dendritic Cells/*immunology ; Disease Models, Animal ; Disease Progression ; Encephalomyelitis, Autoimmune, Experimental/genetics/immunology/metabolism ; Female ; Forkhead Transcription Factors/metabolism ; Gene Expression Profiling ; Immune Tolerance ; Inflammation/genetics/*immunology/metabolism ; Interleukin-10/metabolism ; Lymph Nodes/*immunology ; Lymphocyte Depletion ; Mice ; Mice, Knockout ; Myelin-Oligodendrocyte Glycoprotein/administration &amp; dosage/immunology ; Peptide Fragments/administration &amp; dosage/immunology ; Receptors, CCR7/genetics/metabolism ; Signal Transduction ; T-Cell Antigen Receptor Specificity/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; }, abstract = {Foxp3(+) regulatory T cell (Treg)-based immunotherapy holds promise for autoimmune diseases. However, this effort has been hampered by major caveats, including the low frequency of autoantigen-specific Foxp3(+) Tregs and lack of understanding of their molecular and cellular targets, in an unmanipulated wild-type (WT) immune repertoire. In this study, we demonstrate that infusion of myelin in WT mice results in the de novo induction of myelin-specific Foxp3(+) Tregs in WT mice and amelioration of experimental autoimmune encephalomyelitis. Myelin-specific Foxp3(+) Tregs exerted their effect both by diminishing Ag-bearing inflammatory dendritic cell (iDC) recruitment to lymph nodes and by impairing their function. Transcriptome analysis of ex vivo-isolated Treg-exposed iDCs showed significant enrichment of transcripts involved in functional properties of iDCs, including chemotaxis-related genes. To this end, CCR7 expression by iDCs was significantly downregulated in tolerant mice and this was tightly regulated by the presence of IL-10. Collectively, our data demonstrate a novel model for deciphering the Ag-specific Foxp3(+) Treg-mediated mechanisms of tolerance and delineate iDCs as a Foxp3(+) Treg cellular target in unmanipulated mice.}, }
@article {pmid25940209, year = {2015}, author = {Di Bonito, M and Cantile, M and Cerrone, M and Liguori, G and Botti, G}, title = {Synchronous Pleomorphic Adenoma and Invasive Ductal Carcinoma in Distinct Breasts.}, journal = {The breast journal}, volume = {21}, number = {4}, pages = {428-430}, doi = {10.1111/tbj.12426}, pmid = {25940209}, issn = {1524-4741}, mesh = {Adenoma, Pleomorphic/*pathology/surgery ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasms, Multiple Primary/*pathology ; Parotid Neoplasms/*pathology ; }, }
@article {pmid25931358, year = {2015}, author = {Dopheide, JF and Zeller, GC and Kuhlmann, M and Girndt, M and Sester, M and Sester, U}, title = {Differentiation of Monocyte Derived Dendritic Cells in End Stage Renal Disease is Skewed Towards Accelerated Maturation.}, journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University}, volume = {24}, number = {2}, pages = {257-266}, doi = {10.17219/acem/40463}, pmid = {25931358}, issn = {1899-5276}, mesh = {Age Factors ; Aged ; Biomarkers/metabolism ; Case-Control Studies ; *Cell Differentiation/drug effects ; Cells, Cultured ; Dendritic Cells/drug effects/*immunology/metabolism ; Female ; GPI-Linked Proteins/immunology/metabolism ; Humans ; Kidney Failure, Chronic/*immunology/therapy ; Lipopolysaccharide Receptors/immunology/metabolism ; Lipopolysaccharides/pharmacology ; Male ; Middle Aged ; Monocytes/drug effects/*immunology/metabolism ; Phenotype ; Receptors, IgG/immunology/metabolism ; Renal Dialysis ; Time Factors ; }, abstract = {BACKGROUND: Dendritic cells (DC) play an important role in the induction of immune responses. Patients with end stage renal disease (ESRD) suffer from chronic inflammation, leading to a secondary, uremic immunodeficiency associated with alterations in monocyte subpopulations with increased proinflammatory capacities.<br><br>OBJECTIVES: The aim of this study was to examine, under isolated conditions, whether alterations in monocyte subpopulations may affect in vitro maturation of dendritic cells (DC) in patients with ESRD, thus allowing us to draw conclusions for the situation in vivo.<br><br>MATERIAL AND METHODS: Monocytes from 30 patients undergoing hemodialysis (HD) and 15 healthy volunteers were enriched from peripheral blood leukocytes, differentiated into immature DC (iDC) in medium containing IL-4 and GM-CSF, and were induced with LPS to differentiate into mature DC (mDC). Monocyte subpopulations and DC maturation stages were phenotypically characterized using flow-cytometry.<br><br>RESULTS: Although phenotypically indistinguishable, the number of both iDC and mDC that were generated from uremic monocytes was significantly higher compared to those from healthy controls (p=0.02 and p=0.03, respectively). This was associated with an increased number of CD14+ CD16+ monocytes (p=0.02) and by a higher maturation efficiency of mDC in patients (p=0.04).<br><br>CONCLUSIONS: A high percentage of CD14+ CD16+ monocytes in patients with ESRD is associated with an increased propensity to differentiate into DC. This indicates that chronic inflammation may substantiate the biased consistence of monocyte subpopulations leading to profound alteration in DC generation and maturation in ESRD.}, }
@article {pmid25928089, year = {2015}, author = {Katanov, C and Lerrer, S and Liubomirski, Y and Leider-Trejo, L and Meshel, T and Bar, J and Feniger-Barish, R and Kamer, I and Soria-Artzi, G and Kahani, H and Banerjee, D and Ben-Baruch, A}, title = {Regulation of the inflammatory profile of stromal cells in human breast cancer: prominent roles for TNF-α and the NF-κB pathway.}, journal = {Stem cell research &amp; therapy}, volume = {6}, number = {1}, pages = {87}, pmid = {25928089}, issn = {1757-6512}, mesh = {Blotting, Western ; Bone Marrow Cells/cytology ; Breast Neoplasms/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Chemokine CCL2/analysis ; Chemokine CCL5/analysis ; Culture Media, Conditioned/pharmacology ; Female ; Fibroblasts/cytology/*metabolism ; Humans ; Interleukin-1beta/pharmacology ; Interleukin-8/analysis ; JNK Mitogen-Activated Protein Kinases/antagonists &amp; inhibitors/genetics/metabolism ; MCF-7 Cells ; Mesenchymal Stem Cells/cytology/*drug effects/metabolism ; NF-kappa B/*metabolism ; RNA Interference ; Signal Transduction ; Transcription Factor RelA/antagonists &amp; inhibitors/genetics/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism/*pharmacology ; Up-Regulation/drug effects ; }, abstract = {INTRODUCTION: Breast cancer progression is promoted by stromal cells that populate the tumors, including cancer-associated fibroblasts (CAFs) and mesenchymal stem/stromal cells (MSCs). The activities of CAFs and MSCs in breast cancer are integrated within an intimate inflammatory tumor microenvironment (TME) that includes high levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Here, we identified the impact of TNF-α and IL-1β on the inflammatory phenotype of CAFs and MSCs by determining the expression of inflammatory chemokines that are well-characterized as pro-tumorigenic in breast cancer: CCL2 (MCP-1), CXCL8 (IL-8) and CCL5 (RANTES).<br><br>METHODS: Chemokine expression was determined in breast cancer patient-derived CAFs by ELISA and in patient biopsies by immunohistochemistry. Chemokine levels were determined by ELISA in (1) human bone marrow-derived MSCs stimulated by tumor conditioned media (Tumor CM) of breast tumor cells (MDA-MB-231 and MCF-7) at the end of MSC-to-CAF-conversion process; (2) Tumor CM-derived CAFs, patient CAFs and MSCs stimulated by TNF-&#x3b1; (and IL-1&#x3b2;). The roles of AP-1 and NF-&#x3ba;B in chemokine secretion were analyzed by Western blotting and by siRNAs to c-Jun and p65, respectively. Migration of monocytic cells was determined in modified Boyden chambers.<br><br>RESULTS: TNF-&#x3b1; (and IL-1&#x3b2;) induced the release of CCL2, CXCL8 and CCL5 by MSCs and CAFs generated by prolonged stimulation of MSCs with Tumor CM of MDA-MB-231 and MCF-7 cells. Patient-derived CAFs expressed CCL2 and CXCL8, and secreted CCL5 following TNF-&#x3b1; (and IL-1&#x3b2;) stimulation. CCL2 was expressed in CAFs residing in proximity to breast tumor cells in biopsies of patients diagnosed with invasive ductal carcinoma. CCL2 release by TNF-&#x3b1;-stimulated MSCs was mediated by TNF-RI and TNF-RII, through the NF-&#x3ba;B but not via the AP-1 pathway. Exposure of MSCs to TNF-&#x3b1; led to potent CCL2-induced migration of monocytic cells, a process that may yield pro-cancerous myeloid infiltrates in breast tumors.<br><br>CONCLUSIONS: Our novel results emphasize the important roles of inflammation-stroma interactions in breast cancer, and suggest that NF-&#x3ba;B may be a potential target for inhibition in tumor-adjacent stromal cells, enabling improved tumor control in inflammation-driven malignancies.}, }
@article {pmid25927974, year = {2015}, author = {Shenker, NS and Flower, KJ and Wilhelm-Benartzi, CS and Dai, W and Bell, E and Gore, E and El Bahrawy, M and Weaver, G and Brown, R and Flanagan, JM}, title = {Transcriptional implications of intragenic DNA methylation in the oestrogen receptor alpha gene in breast cancer cells and tissues.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {337}, pmid = {25927974}, issn = {1471-2407}, support = {13086/CRUK_/Cancer Research UK/United Kingdom ; //Medical Research Council/United Kingdom ; A13086//Cancer Research UK/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cell Line, Tumor ; DNA Methylation ; Epigenesis, Genetic ; Estrogen Receptor alpha/*genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Glands, Human/metabolism ; Milk, Human/cytology ; *Promoter Regions, Genetic ; Sequence Analysis, DNA ; Transcription, Genetic ; }, abstract = {BACKGROUND: DNA methylation variability regions (MVRs) across the oestrogen receptor alpha (ESR1) gene have been identified in peripheral blood cells from breast cancer patients and healthy individuals. In contrast to promoter methylation, gene body methylation may be important in maintaining active transcription. This study aimed to assess MVRs in ESR1 in breast cancer cell lines, tumour biopsies and exfoliated epithelial cells from expressed breast milk (EBM), to determine their significance for ESR1 transcription.<br><br>METHODS: DNA methylation levels in eight MVRs across ESR1 were assessed by pyrosequencing bisulphite-converted DNA from three oestrogen receptor (ER)-positive and three ER-negative breast cancer cell lines. DNA methylation and expression were assessed following treatment with DAC (1 &#x3bc;M), or DMSO (controls). ESR1 methylation levels were also assayed in DNA from 155 invasive ductal carcinoma biopsies provided by the Breast Cancer Campaign Tissue Bank, and validated with DNA methylation profiles from the TCGA breast tumours (n = 356 ER-pos, n = 109 ER-neg). DNA methylation was profiled in exfoliated breast epithelial cells from EBM using the Illumina 450 K (n = 36) and pyrosequencing in a further 53 donor samples. ESR1 mRNA levels were measured by qRT-PCR.<br><br>RESULTS: We show that ER-positive cell lines had unmethylated ESR1 promoter regions and highly methylated intragenic regions (median, 80.45%) while ER-negative cells had methylated promoters and lower intragenic methylation levels (median, 38.62%). DAC treatment increased ESR1 expression in ER-negative cells, but significantly reduced methylation and expression of ESR1 in ER-positive cells. The ESR1 promoter was unmethylated in breast tumour biopsies with high levels of intragenic methylation, independent of ER status. However, ESR1 methylation in the strongly ER-positive EBM DNA samples were very similar to ER-positive tumour cell lines.<br><br>CONCLUSION: DAC treatment inhibited ESR1 transcription in cells with an unmethylated ESR1 promoter and reduced intragenic DNA methylation. Intragenic methylation levels correlated with ESR1 expression in homogenous cell populations (cell lines and exfoliated primary breast epithelial cells), but not in heterogeneous tumour biopsies, highlighting the significant differences between the in vivo tumour microenvironment and individual homogenous cell types. These findings emphasise the need for care when choosing material for epigenetic research and highlights the presence of aberrant intragenic methylation levels in tumour tissue.}, }
@article {pmid25921169, year = {2015}, author = {Sushma, C and Prasad, S and Devi, R and Murthy, S and Rao, Ts and Naidu, C}, title = {High Frequency of Codon 12 but not Codon 13 and 61 K-ras Gene Mutations in Invasive Ductal Carcinoma of Breast in a South Indian Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {16}, number = {8}, pages = {3505-3508}, doi = {10.7314/apjcp.2015.16.8.3505}, pmid = {25921169}, issn = {2476-762X}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Codon ; Female ; Genetic Predisposition to Disease ; Humans ; India ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins p21(ras) ; Sequence Analysis, DNA ; White People/*genetics ; ras Proteins/*genetics ; }, abstract = {BACKGROUND: Ras genes are thought to play an important role in human cancer since they have been found to be activated frequently in several types of tumors including breast cancer, where the overall incidence of K-RAS oncogene activation is 0-10%. Evaluation of K-RAS gene not only for mutational frequency but also for mutation types in this downstream signaling gene pathway is necessary to determine the mechanisms of action. The present study was conducted to test the hypothesis that K-RAS activation is involved in breast cancer risk of south Indian population.<br><br>MATERIALS AND METHODS: A total of 70 paired pathologically confirmed tumor and non-tumor tissues from the same breast cancer patients were analysed for most common K-RAS mutations of codon 12,13 and 61 by polymerase chain reaction followed by restriction digestion and direct nucleotide sequencing method.<br><br>RESULTS: We found that a high rate of homozygous and heterozygous mutations of codon 12, but not codon 13 and 61, may influence the invasive ductal carcinoma of breast risk in this study.<br><br>CONCLUSIONS: Our study indicated that only codon 12 may be involved in initiating breast carcinogenesis in India.}, }
@article {pmid25916980, year = {2015}, author = {Kamrava, M and Kuske, RR and Anderson, B and Chen, P and Hayes, J and Quiet, C and Wang, PC and Veruttipong, D and Snyder, M and Jeffrey Demanes, D}, title = {Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.}, journal = {Annals of surgical oncology}, volume = {22 Suppl 3}, number = {}, pages = {S404-11}, doi = {10.1245/s10434-015-4563-7}, pmid = {25916980}, issn = {1534-4681}, mesh = {Adult ; *Brachytherapy ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/pathology/*radiotherapy ; Carcinoma, Intraductal, Noninfiltrating/pathology/*radiotherapy ; Carcinoma, Lobular/pathology/*radiotherapy ; Catheterization/*methods ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasm Staging ; Prognosis ; Radiotherapy Dosage ; *Registries ; Retrospective Studies ; Survival Rate ; }, abstract = {PURPOSE: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation with interstitial multicatheter brachytherapy by a cooperative group of institutions.<br><br>METHODS: From 1992 to 2013, a total of 1356 patients were treated with breast-conserving surgery and adjuvant accelerated partial breast irradiation using interstitial multicatheter brachytherapy. A total of 1131 patients had >1 year of data available to assess oncologic and cosmesis outcomes. Median age was 59 years old (range 22-90 years). Histologies treated included 1005 (73 %) invasive ductal carcinoma and 240 (18 %) ductal carcinoma-in situ. T stages were 18 % Tis, 75 % T1, and 8 % &#x2265;T2. Nodal status was 73 % N0 and 6 % N1a. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was positive in 83, 70, and 6 %, respectively. Cox multivariate analysis for local control was performed using histology, age, estrogen receptor status, tumor size, grade, margin, and nodal status.<br><br>RESULTS: The mean (SD) follow-up was 6.9 years (4.3). The 10-year actuarial risk (95 % confidence interval) of an ipsilateral breast tumor recurrence was 7.6 % (5.6-10.1). Other 10-year actuarial risks (95 % confidence interval) were regional failure 2.3 % (1.4-3.7), distant metastasis 3.8 % (2.5-5.7), cause-specific survival 96.3 % (94.2-97.6), overall survival 86.5 (83.0-89.3), and new contralateral cancers 4.6 % (3.0-6.9). On multivariate analysis, high grade (hazard ratio 2.81) and positive margin status (hazard ratio 18.42) were the only two significant variables associated with an increased risk of local recurrence. Physician-reported cosmesis was excellent/good in 84 % (98 of 116) of patients with >5 years of follow-up.<br><br>CONCLUSIONS: This is the largest report of outcomes with interstitial breast brachytherapy. This treatment resulted in excellent long-term local control and cosmesis outcomes.}, }
@article {pmid25911756, year = {2015}, author = {Miki, H and Nakahashi-Oda, C and Sumida, T and Shibuya, A}, title = {Involvement of CD300a Phosphatidylserine Immunoreceptor in Aluminum Salt Adjuvant-Induced Th2 Responses.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {194}, number = {11}, pages = {5069-5076}, doi = {10.4049/jimmunol.1402915}, pmid = {25911756}, issn = {1550-6606}, mesh = {Adjuvants, Immunologic/*pharmacology ; Alum Compounds/*pharmacology ; Animals ; Antibodies, Neutralizing/administration &amp; dosage/immunology ; Apoptosis/immunology ; Asthma/genetics/immunology/therapy ; Bronchoalveolar Lavage Fluid/cytology/immunology ; Dendritic Cells/immunology ; Eosinophils/immunology ; Immunoglobulin E/blood ; Inflammation/immunology ; Interleukin-4/biosynthesis ; Lymphocyte Activation/drug effects/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin/*pharmacology ; Phosphatidylserines/antagonists &amp; inhibitors ; Receptors, Immunologic/biosynthesis/genetics/*immunology ; Respiratory Hypersensitivity/genetics/*immunology/prevention &amp; control ; Th2 Cells/*immunology ; }, abstract = {Aluminum salt (alum) has been widely used for vaccinations as an adjuvant. Alum not only enhances immunogenicity but also induces Th2 cell immune responses. However, the mechanisms of how alum enhances Th2 cell immune responses have been controversial. In an experimental allergic airway inflammation model, in which alum in conjunction with OVA Ag was i.p. injected for immunization, we found that apoptotic cells and inflammatory dendritic cells (iDC) expressing CD300a, an inhibitory immunoreceptor for phosphatidylserine (PS), significantly increased in number in the peritoneal cavity after the immunization. In contrast, apoptotic cells and iDCs were scarcely observed in the peritoneal cavity after injection of OVA alone. In CD300a-deficient mice, eosinophil infiltration in bronchoalveolar lavage fluid, serum IgE levels, and airway hyperreactivity were significantly decreased after immunization with alum plus OVA compared with wild-type mice. In vitro, iDCs purified from CD300a-deficient mice after the immunization induced significantly less IL-4 production from OT-II naive CD4(+) T cells after coculture with OVA Ag. CD300a expressed on iDCs bound PS on apoptotic cells in the peritoneal cavity after injection of OVA plus alum. Blocking CD300a interaction with PS by injection of a neutralizing anti-CD300a Ab resulted in inhibition of the development of allergic airway inflammation. These results suggest that CD300a is involved in alum-induced Th2 skewing.}, }
@article {pmid25909142, year = {2015}, author = {Popovska, S and Damianova, P and Tomov, S and Dineva, T and Ivanov, I}, title = {[Case of encapsulated solid papillary carcinoma with triple-negative and basal-like phenotype occurred in pregnant woman with review of the literature].}, journal = {Akusherstvo i ginekologiia}, volume = {54}, number = {2}, pages = {50-56}, pmid = {25909142}, issn = {0324-0959}, mesh = {Adult ; BRCA1 Protein/analysis/genetics ; BRCA2 Protein/analysis/genetics ; Breast/*pathology ; Breast Neoplasms/diagnosis/genetics/*pathology ; Carcinoma, Papillary/diagnosis/genetics/*pathology ; Female ; Humans ; Mutation ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnosis/genetics/*pathology ; Tumor Suppressor Protein p53/analysis ; }, abstract = {The term breast cancer in pregnant women is used when the disease has been diagnosed during pregnancy or within first 12 months after delivery. The frequency of this type of breast cancer is about 7% of all cases in reproductive period. We present a case of breast cancer that occurred in pregnant 35 year old woman. We performed histological and immunohistochemical tests of excised tumor formation. We did not find sufficient evidence of both carcinoma in situ and invasive ductal carcinoma. The lesion was consisted with encapsulated/intracystic carcinoma, solid papillary variant with a low degree of differentiation-G3. Young age of patient, receptor status of the tumor the characteristic morphology of hereditary cancer, the presence of inflammatory infiltrates intratumorally, absence of reaction to IHC protein product of the tumor suppressor gene BRCA1 in combination with a positive p53 IHC makes this case suitable for genetic testing of BRCA1/BRCA2 susceptibility genes. The case is interesting because of the rarity of the histological variant, the young age of the patient, the combination with BC and pregnancy and the triple-negative phenotype.}, }
@article {pmid25908223, year = {2015}, author = {del Molino, F and Gonzalez, I and Saperas, E}, title = {[Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].}, journal = {Gastroenterologia y hepatologia}, volume = {38}, number = {8}, pages = {501-510}, doi = {10.1016/j.gastrohep.2015.02.014}, pmid = {25908223}, issn = {0210-5705}, mesh = {Administration, Oral ; Antithrombins/administration &amp; dosage/*adverse effects/pharmacokinetics/therapeutic use ; Blood Coagulation Factors/therapeutic use ; Blood Transfusion ; *Endoscopy, Digestive System/adverse effects ; Factor Xa Inhibitors/administration &amp; dosage/adverse effects/pharmacokinetics/therapeutic use ; Gastrointestinal Hemorrhage/*chemically induced/drug therapy/etiology/therapy ; Hemostatics/therapeutic use ; Humans ; Plasma Substitutes/therapeutic use ; Practice Guidelines as Topic ; Renal Dialysis ; Thrombophilia/drug therapy ; }, abstract = {New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed.}, }
@article {pmid25900029, year = {2015}, author = {Zhifu, Y and Mingli, J and Shuang, C and Fan, W and Zhenkun, F and Wangyang, C and Lin, Z and Guangxiao, L and Yashuang, Z and Dianjun, L}, title = {SNP-SNP interactions of immunity related genes involved in the CD28/B7 pathway with susceptibility to invasive ductal carcinoma of the breast.}, journal = {Gene}, volume = {566}, number = {2}, pages = {217-222}, doi = {10.1016/j.gene.2015.04.044}, pmid = {25900029}, issn = {1879-0038}, mesh = {Algorithms ; Breast Neoplasms/genetics/*immunology ; CD28 Antigens/*immunology ; Carcinoma, Ductal, Breast/genetics/*immunology ; Cross-Over Studies ; Female ; *Genetic Predisposition to Disease ; Haplotypes ; Humans ; Immunity/*genetics ; *Polymorphism, Single Nucleotide ; }, abstract = {To explore the interactions among immunity related genes and the risk of breast cancer (BC), 376 invasive ductal carcinoma (IDC) of the breast cases and 366 healthy controls were selected into our study. Twenty single nucleotide polymorphisms (SNPs) of five immunological genes in the CD28/B7 pathway were genotyped. Overall, five SNPs filtered by the Relief F algorithm were rs733618, rs11889031, rs4553808, rs4675374 and rs10754339. The best model of multifactor dimensionality reduction (MDR) contained rs733618 and rs11889031. The high risk genotype combination contributed to increasing risk of breast cancer (odds ratio (OR), 4.36; 95% confidence interval (CI); 3.15-6.02). The information gain (IG) value of these two SNPs was 8.07%, presented the strongest interaction effect. Five significant multiplicative interactions and seven significant combining effects were found among the filtered SNPs. Moreover, the filtered SNPs were still stable in the groups of ER(+), PR(+), CerbB2(-) and lymph node (LN) involvement positive with the best models including rs733618 and rs11889031. The most frequent haplotype was TACC which significantly increased breast cancer risk (OR, 1.80; 95% CI, 1.43-2.25). These results suggested that interactions among cytotoxic T lymphocyte antigen-4 (CTLA4), inducible co-stimulator (ICOS) and B7H4 might play critical roles on the risk of breast cancer.}, }
@article {pmid25899545, year = {2015}, author = {Amboni, M and Stocchi, F and Abbruzzese, G and Morgante, L and Onofrj, M and Ruggieri, S and Tinazzi, M and Zappia, M and Attar, M and Colombo, D and Simoni, L and Ori, A and Barone, P and Antonini, A and , }, title = {Prevalence and associated features of self-reported freezing of gait in Parkinson disease: The DEEP FOG study.}, journal = {Parkinsonism &amp; related disorders}, volume = {21}, number = {6}, pages = {644-649}, doi = {10.1016/j.parkreldis.2015.03.028}, pmid = {25899545}, issn = {1873-5126}, mesh = {Aged ; Aged, 80 and over ; Antiparkinson Agents/administration &amp; dosage/therapeutic use ; Female ; *Freezing Reaction, Cataleptic ; *Gait ; Gait Disorders, Neurologic/classification/*epidemiology/physiopathology ; Humans ; Levodopa/administration &amp; dosage/therapeutic use ; Male ; Middle Aged ; Parkinson Disease/drug therapy/*physiopathology/psychology ; Prevalence ; Quality of Life/*psychology ; Risk Factors ; Self Report ; Severity of Illness Index ; Surveys and Questionnaires ; }, abstract = {Freezing of Gait (FOG) is a common and disabling symptom in patients with Parkinson disease (PD). The relationship between FOG and dopaminergic medication is complex. The aim of the present study was to estimate the prevalence of self-reported FOG, its associated clinical features, and its relationship with wearing-off in a wide PD population. This is an observational multicenter study of 634 consecutive non-demented PD patients. Patients were identified either as freezers or non-freezers based on item-3 of the Freezing of Gait-Questionnaire. FOG was then classified as on, off and onoff freezing based on its relationship with wearing-off. Patients were assessed with Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, 8-item Parkinson's disease Questionnaire, Mini-Mental State Examination. Data from 593 patients were analyzed, 325 (54.3%) were freezers of whom 200 (61.6%) experienced FOG only during off state (off-freezers), 6 (1.8%) only during on state and 119 (36.6%) either in on and off states or independently of dopaminergic response-related symptoms (onoff-freezers). Overall, freezers vs non-freezers had longer disease duration, more advanced disease and greater disability. Moreover, freezers more frequently reported wearing-off and experienced worse quality of life. Onoff-freezers vs off-freezers were older, more severely disabled, less likely to experience wearing-off, treated with lower levodopa equivalent daily dose and with poorer cognitive performance. Self-reported FOG is mainly recognizable in advanced PD and is associated with more disability and worse quality of life. Onoff-FOG may represent the result of under-treatment or rather interpretable as a distinct clinical entity.}, }
@article {pmid25893606, year = {2015}, author = {Zhou, X and Wang, S and Wang, Z and Feng, X and Liu, P and Lv, XB and Li, F and Yu, FX and Sun, Y and Yuan, H and Zhu, H and Xiong, Y and Lei, QY and Guan, KL}, title = {Estrogen regulates Hippo signaling via GPER in breast cancer.}, journal = {The Journal of clinical investigation}, volume = {125}, number = {5}, pages = {2123-2135}, pmid = {25893606}, issn = {1558-8238}, mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/physiology ; Animals ; Breast Neoplasms/genetics/metabolism/*physiopathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*physiopathology ; Cell Division ; Cell Movement ; Cell Transformation, Neoplastic ; Estrogens/pharmacology/*physiology ; Female ; GTP-Binding Protein alpha Subunits, Gq-G11/antagonists &amp; inhibitors/genetics/physiology ; Gene Expression Regulation, Neoplastic ; Hippo Signaling Pathway ; Humans ; Intracellular Signaling Peptides and Proteins ; Mice ; Mice, Inbred BALB C ; Neoplasm Proteins/*physiology ; Neoplasms, Hormone-Dependent/genetics/metabolism/*physiopathology ; Phospholipase C beta/physiology ; Phosphoproteins/physiology ; Phosphorylation ; Protein Kinase C/physiology ; Protein Processing, Post-Translational ; Protein Serine-Threonine Kinases/analysis/antagonists &amp; inhibitors/metabolism/*physiology ; RNA Interference ; Receptors, Estrogen/drug effects/*physiology ; Receptors, G-Protein-Coupled/drug effects/*physiology ; Serine-Threonine Kinase 3 ; Signal Transduction/*physiology ; Transcription Factors/physiology ; Transcription, Genetic ; Tumor Suppressor Proteins/analysis/*physiology ; YAP-Signaling Proteins ; rho-Associated Kinases/physiology ; }, abstract = {The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.}, }
@article {pmid25893590, year = {2015}, author = {Zhang, H and Li, Y and Moran, MS and Haffty, BG and Yang, Q}, title = {Predictive factors of nipple involvement in breast cancer: a systematic review and meta-analysis.}, journal = {Breast cancer research and treatment}, volume = {151}, number = {2}, pages = {239-249}, doi = {10.1007/s10549-015-3385-4}, pmid = {25893590}, issn = {1573-7217}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*mortality ; Female ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Nipples/*pathology ; Prognosis ; Risk Factors ; Tumor Burden ; }, abstract = {Nipple-sparing mastectomy (NSM) provides a cosmetic and psychological benefit for patients, but concerns on nipple involvement (NI) of tumor continue to persist. Several studies have reported factors for predicting NI, but the results were inconsistent and uncomprehensive, making patient selection difficult. The aim of the systematic review was to pool the published data to further discern factors associated with NI. A literature review was conducted of PubMed database, following the PRISMA guidelines. Relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effect or fix-effect model. Publication bias and Chi-square test were also calculated. From 1978 to 2014, 27 clinical studies with 7971 patients met the inclusion criteria. Predictive factors suggest higher rates of NI including the following: tumor-to-nipple distance (TND) ≤ 2.5 cm (3.65, 1.42-9.33); positive lymph node status (2.09, 1.71-2.57); stage III or IV disease (2.41, 1.93-3.00); tumor size > 5 cm (2.42, 1.95-3.02); estrogen receptor (ER)-negative status (1.19, 1.01-1.40); progesterone receptor (PR)-negative status (1.52, 1.25-1.84); HER-positive status (1.76, 1.46-2.12); patients with ductal carcinoma in situ (DCIS) compared with invasive ductal carcinoma (1.55, 1.16-2.08). Due to the statistical heterogeneity detected with certain parameters, further investigations to confirm their association with NI will be needed. Patients with one or more risk factors such as centrally located tumors; higher tumor stage; large tumors; ER-negative/PR-negative/HER-positive status and associated DCIS have higher risk of NI. Taking these factors into consideration comprehensively may help with decision-making process for NSM.}, }
@article {pmid25890786, year = {2015}, author = {Sugiyama, M and Hasebe, T and Shimada, H and Takeuchi, H and Shimizu, K and Shimizu, M and Yasuda, M and Ueda, S and Shigekawa, T and Osaki, A and Saeki, T}, title = {Grading system for blood vessel tumor emboli of invasive ductal carcinoma of the breast.}, journal = {Human pathology}, volume = {46}, number = {6}, pages = {906-916}, doi = {10.1016/j.humpath.2015.03.001}, pmid = {25890786}, issn = {1532-8392}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/diagnosis ; Neoplasms, Vascular Tissue/*pathology/secondary ; Neoplastic Cells, Circulating/pathology ; Prognosis ; }, abstract = {We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast.}, }
@article {pmid25890610, year = {2015}, author = {Debi, U and Thulkar, S and Sharma, S and Sharma, MC and Seenu, V and Deo, SV and Agarwal, S and Hari, S}, title = {Role of directional vacuum assisted breast biopsy in previously equivocal biopsies for breast masses suspicious for malignancy.}, journal = {The Malaysian journal of pathology}, volume = {37}, number = {1}, pages = {25-33}, pmid = {25890610}, issn = {0126-8635}, mesh = {Biomarkers, Tumor/analysis ; Biopsy, Large-Core Needle/*methods ; Breast Neoplasms/chemistry/*pathology/secondary/surgery ; Breast Neoplasms, Male/chemistry/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Male ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Reproducibility of Results ; Vacuum ; }, abstract = {UNLABELLED: Among percutaneous biopsy techniques, the vacuum assisted breast biopsy (VAB) obtains large tissue samples to alleviate some of the limitations associated with conventional percutaneous biopsy techniques. We aimed to determine the efficacy of VAB in previous equivocal biopsies using the mammotome device.<br><br>MATERIALS AND METHODS: A prospective non-randomized efficacy study was planned and executed on 43 patients (42 women, 1 man) whose previous FNAC and/or CNB of breast masses yielded inconclusive results or were suspicious for cancer.<br><br>RESULTS: VAB revealed malignancy in 31 (72%) of the 43 patients. Among them, 23 were diagnosed as infiltrative ductal carcinoma (IDC) on VAB, 20 underwent surgery and the final histopathological diagnosis was the same in 19 of them. One patient showed ductal carcinoma-in-situ (DCIS) only in the surgical specimen. Other malignancies included infiltrating lobular carcinoma (ILC) in 5 patients and one each of DCIS, non- Hodgkin lymphoma (NHL) and metastasis from lung cancer. Benign lesions were detected in 12 (28%) patients. These included 8 fibroadenomas, 2 fibrocystic disease and 1 each of mastitis and breast abscess. Four patients with fibroadenoma underwent surgical excision.}, }
@article {pmid25889325, year = {2015}, author = {Han, Z and Chen, Z and Zheng, R and Cheng, Z and Gong, X and Wang, D}, title = {Clinicopathological significance of CD133 and CD44 expression in infiltrating ductal carcinoma and their relationship to angiogenesis.}, journal = {World journal of surgical oncology}, volume = {13}, number = {}, pages = {56}, pmid = {25889325}, issn = {1477-7819}, mesh = {AC133 Antigen ; Adult ; Aged ; Antigens, CD ; Breast Neoplasms/blood supply/metabolism/*pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/*secondary ; Female ; Follow-Up Studies ; Glycoproteins ; Humans ; Hyaluronan Receptors ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplastic Stem Cells/metabolism/*pathology ; Neovascularization, Pathologic/metabolism/*pathology ; Peptides ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the leading cause of cancer death in females worldwide, and the majority type is infiltrating ductal carcinoma (IDC). Most of IDC patients died of metastasis and recurrence. Cancer stem cells (CSCs) are defined with the ability to be self-renewal and potentially promote proliferation and formation of tumors. CSCs are related to angiogenesis and are important targets in new cancer treatment strategies. In this study, we purposed to investigate on expression and clinical significances of CSCs marked by CD133 and CD44 in IDC and their relationship to angiogenesis.<br><br>METHODS: The specimens of IDC from 325 Chinese patients with follow-up were analyzed for CD133, CD44, CD82, and CD34 protein expression by immunohistochemical staining. The Pearson chi-square test and t test were used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time in these patients with IDC was analyzed by univariate and multivariate analyses.<br><br>RESULTS: In IDC tissues, positive rates of 48.6%, 53.8%, and 42.2% were obtained for CD133, CD44, and CD82 protein, respectively; the mean score of microvessel density (MVD) was 20.5&#x2009;&#xb1;&#x2009;7.0 in IDC group. And there was a significant difference between the two groups. There was a positive relationship between the expression of CD133, CD44, and the score of MVD and the grades of tumor, lymph node metastasis, tumor-node-metastasis (TNM) stages (all P&#x2009;<&#x2009;0.05); and the expression of CD82 was negatively related to grades of tumor, lymph node metastasis, and TNM stages (all P&#x2009;<&#x2009;0.05). The overall mean survival time of the patients with CD133, CD44, and the score of MVD (&#x2265;21) positive expression was lower than that of patients with negative expression. The overall mean survival time of patients of CD82-positive expression was longer than that of patients of the negative expression group. The positive expression of CD133 and CD82, and TNM stages were independent prognostic factors of IDC (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: CSCs, angiogenesis, and aberrant expression of CD82 may be involved in the initiation, development, metastasis, and recurrence. It is suggested that CSCs, angiogenesis, and CD82 be possible as a therapeutic marker for anti-tumor therapy.}, }
@article {pmid25888835, year = {2015}, author = {Nakahori, R and Takahashi, R and Akashi, M and Tsutsui, K and Harada, S and Matsubayashi, RN and Nakagawa, S and Momosaki, S and Akagi, Y}, title = {Breast carcinoma originating from a silicone granuloma: a case report.}, journal = {World journal of surgical oncology}, volume = {13}, number = {}, pages = {72}, pmid = {25888835}, issn = {1477-7819}, mesh = {Aged ; Breast Implants/*adverse effects ; Breast Neoplasms/*etiology/pathology ; Carcinoma, Ductal, Breast/*etiology/pathology ; Female ; Granuloma, Foreign-Body/*etiology ; Humans ; Prognosis ; Silicones/*adverse effects ; }, abstract = {Breast carcinoma rarely occurs in cases of foreign body granulomas following liquid silicone injection. Although the Food and Drug Administration (FDA) banned the use of all silicone injection products in 1992, liquid silicone injection for breast augmentation continues to be performed illegally. We herein report a case of breast carcinoma following liquid silicone injection in a 67-year-old female.A total of 45 years after liquid silicone injection, the patient had felt a breast mass in the right breast. Mammography showed a smooth mass that retracted the right nipple. Due to the presence of a marked acoustic shadow caused by the granulomas, evaluating the mass on ultrasonography was difficult. However, magnetic resonance imaging (MRI) showed a lobulated mass under the right nipple. The mass exhibited low signal intensity (SI) on T1-weighted images and intermingled high and low SI on T2-weighted images. Heterogeneous early enhancement with central low intensity was noted on dynamic contrast-enhanced MRI. Several oval-shaped low SI structures in the adipose tissue and disruption of the pectoralis major muscle were also observed. We diagnosed the patient with invasive ductal carcinoma based on a stereotactic-guided Mammotome® (a vacuum-assisted biopsy system manufactured by DEVICOR MEDICAL JAPAN, Tokyo, Japan) biopsy and subsequently performed mastectomy and axillary lymph node dissection (with a positive result for the sentinel node biopsy). Histologically, invasive ductal carcinoma was observed in the silicone granuloma.The development of foreign body granulomas following breast augmentation usually makes it difficult to detect breast cancer; thus, various devices are required to confirm the histological diagnosis of breast lesions. The stereotactic-guided Mammotome® biopsy system may be an effective device for diagnosing breast cancer developing in the augmented breast.}, }
@article {pmid25886372, year = {2015}, author = {Liu, D and Zhang, L and Li, Z and Zhang, X and Wu, Y and Yang, H and Min, B and Zhang, X and Ma, D and Lu, Y}, title = {Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer's disease.}, journal = {BMC neurology}, volume = {15}, number = {}, pages = {14}, pmid = {25886372}, issn = {1471-2377}, mesh = {Aged ; Alzheimer Disease/*physiopathology ; Case-Control Studies ; Cognitive Dysfunction/*physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nerve Fibers/*pathology ; Retina/*pathology ; Tomography, Optical Coherence ; Vision Disorders/etiology ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and patients often have visual disorders. Mild cognitive impairment (MCI) is characterized by a memory deficit when compared with those of a similar age and education level which could indicate an earlier onset of AD. The aim of this study is to measure the changes of the retinal nerve fiber layer (RNFL) thickness of AD and MCI patients in comparison with the normal age controls.<br><br>METHODS: The RNFL thickness was assessed using optical coherence tomography (OCT) in patients with MCI, AD (mild, moderate and severe) and the age matched controls.<br><br>RESULTS: The thickness of RNFL in the superior quadrant and total mean values are gradually and significantly decreased from MCI to severe AD when compared to that in the controls. There is also a significant reduction of the retinal nerve fiber layer in the inferior quadrant in severe AD patients.<br><br>CONCLUSIONS: Our data indicate that the retinal nerve fiber layer degeneration is paralleled with dementia progression. Owing to its non-invasive and cost effective nature, monitoring RNFL thickness may have a value in assessing disease progression and the efficacy of any treatments.}, }
@article {pmid25881005, year = {2015}, author = {Toyoshima, M and Iwahashi, H and Shima, T and Hayasaka, A and Kudo, T and Makino, H and Igeta, S and Matsuura, R and Ishigaki, N and Akagi, K and Sakurada, J and Suzuki, H and Yoshinaga, K}, title = {Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.}, journal = {Journal of medical case reports}, volume = {9}, number = {}, pages = {47}, pmid = {25881005}, issn = {1752-1947}, mesh = {Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology ; Carcinoma, Lobular/diagnosis/*secondary/therapy ; Carrier Proteins/analysis ; Combined Modality Therapy ; Female ; Glycoproteins/analysis ; Humans ; Leiomyoma/therapy ; Membrane Transport Proteins ; Middle Aged ; Nitriles/therapeutic use ; Triazoles/therapeutic use ; Uterine Neoplasms/*secondary/therapy ; }, abstract = {INTRODUCTION: Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma.<br><br>CASE PRESENTATION: A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue.<br><br>CONCLUSION: We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.}, }
@article {pmid25880415, year = {2015}, author = {Tancioni, I and Miller, NL and Uryu, S and Lawson, C and Jean, C and Chen, XL and Kleinschmidt, EG and Schlaepfer, DD}, title = {FAK activity protects nucleostemin in facilitating breast cancer spheroid and tumor growth.}, journal = {Breast cancer research : BCR}, volume = {17}, number = {}, pages = {47}, pmid = {25880415}, issn = {1465-542X}, support = {R01 CA087038/CA/NCI NIH HHS/United States ; CA180769/CA/NCI NIH HHS/United States ; R01 CA102310/CA/NCI NIH HHS/United States ; CA102310/CA/NCI NIH HHS/United States ; R01 CA180769/CA/NCI NIH HHS/United States ; F32 CA159558/CA/NCI NIH HHS/United States ; 1F32CA159558/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Enzyme Activation ; Female ; Focal Adhesion Protein-Tyrosine Kinases/antagonists &amp; inhibitors/genetics/*metabolism ; GTP-Binding Proteins/*metabolism ; Humans ; Mice ; Nuclear Proteins/*metabolism ; Nucleophosmin ; Protein Kinase Inhibitors/pharmacology ; Protein Transport ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Sirolimus/pharmacology ; Spheroids, Cellular ; Tumor Burden/drug effects/genetics ; Tumor Cells, Cultured ; Tumor Stem Cell Assay ; }, abstract = {INTRODUCTION: Focal adhesion kinase (FAK) controls cell growth and survival downstream of integrin-matrix receptors. Upon adhesion loss or FAK inhibition, FAK can translocate to the nucleus. The nucleolus is a non-membrane nuclear structure that regulates ribosome biogenesis and cell proliferation. Nucleostemin (NS), a nucleolar-localized protein, modulates cell cycle progression, stemness, and three-dimensional tumor spheroid formation. The signaling pathways that regulate NS levels in tumors remain undefined.<br><br>METHODS: Human breast carcinoma cells were evaluated for growth in culture (adherent and anchorage-independent spheroid) and as orthotopic tumors. FAK signaling was evaluated by pharmacological FAK inhibitor addition (PF-271, IC50~0.1 &#x3bc;M) and by small hairpin RNA (shRNA) knockdown followed by re-expression of FAK wildtype (WT) or a kinase-dead (KD, K454R) FAK point mutant. Immunoblotting was used to evaluate FAK, NS, nucleolar phosphoprotein B23, and nucleolin levels. Total and phosphospecific antibody imunoblotting were used to detect changes in FAK, Akt kinase (Akt also known as protein kinase B), and 4E-binding protein 1 (4E-BP1) phosphorylation, a translation repressor protein and target of the mammalian target of rapamycin (mTOR) complex. Immunohistochemical, co-immunoprecipitation, and cellular fractionation analyses were used to evaluate FAK association with nucleoli.<br><br>RESULTS: Pharmacological (0.1 &#x3bc;M PF-271) or genetic inhibition of FAK activity prevents MDA-MB-231 and 4T1L breast carcinoma growth as spheroids and as orthotopic tumors. FAK inhibition triggers proteasome-mediated decreased NS levels but no changes in other nucleolar proteins such as B23 (nucleophosmin) or nucleolin. Active FAK was associated with purified nucleoli of anchorage-independent cells and present within nucleoli of human invasive ductal carcinoma tumor samples. FAK co-immunoprecipitated with B23 that binds NS and a complex between FAK, NS, Akt, and mTOR was detected. Constitutively-active Akt kinase promoted tumor spheroid growth, stabilized NS levels, and promoted pS65 4E-BP1 phosphorylation in the presence of inhibited FAK. Rapamycin lowered NS levels and inhibited pS65 4E-BP1 phosphorylation in cells with activated Akt-mTOR signaling.<br><br>CONCLUSIONS: FAK signaling occurs in the nucleolus, active FAK protects NS, and Akt-mTOR pathway regulates NS protein stability needed for breast carcinoma spheroid and tumor growth.}, }
@article {pmid25880352, year = {2015}, author = {Benezet-Mazuecos, J and Iglesias, JA and Rubio, JM and Farré, J}, title = {Anodal Stimulation in Biventricular Pacing: Unrecognized and Misinterpreted Phenomenon.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {38}, number = {12}, pages = {1485-1488}, doi = {10.1111/pace.12650}, pmid = {25880352}, issn = {1540-8159}, mesh = {Aged, 80 and over ; Cardiac Resynchronization Therapy/*adverse effects/*methods ; Diagnosis, Differential ; Diagnostic Errors/*prevention &amp; control ; Electric Injuries/*diagnosis/*etiology/prevention &amp; control ; Heart Failure/complications/*prevention &amp; control ; Humans ; }, }
@article {pmid25880075, year = {2015}, author = {Bae, SY and Kim, S and Lee, JH and Lee, HC and Lee, SK and Kil, WH and Kim, SW and Lee, JE and Nam, SJ}, title = {Poor prognosis of single hormone receptor- positive breast cancer: similar outcome as triple-negative breast cancer.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {138}, pmid = {25880075}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/drug therapy/genetics/*metabolism/*mortality/pathology ; Female ; Follow-Up Studies ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Risk Factors ; Survival Analysis ; Triple Negative Breast Neoplasms/drug therapy/genetics/mortality ; Young Adult ; }, abstract = {BACKGROUND: Response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PR) status. Generally, hormone receptor-positive (HR+) breast cancers have favorable prognosis. In order to understand the exact clinical characteristics and prognosis of single HR-positive breast cancer (ER + PR- tumors and ER-PR+ tumors), we compared these tumors to double HR+ tumors as well as HR- negative tumors (ER-PR-).<br><br>METHODS: We examined the clinical and biological features of 6,980 women with invasive ductal carcinoma, and these patients were stratified according to ER and PR expression as double HR+ (ER + PR+), single HR+ (ER + PR- and ER-PR+) and double HR-negative (HR-, ER-PR-) tumors.<br><br>RESULTS: In this study, 571 (8.2%) cases were single HR+ tumors, of which 90 (1.3%) were ER-PR+ tumors and 481 (6.9%) were ER + PR- tumors. Our multivariate analysis showed that in patients without HER2 overexpression ER + PR- tumors were associated with an increased risk of recurrence and death compared with ER + PR+ tumors, with a hazard ratio of 2.12 for disease-free survival (DFS) and 4.79 for overall survival (OS). In patients without HER2 overexpression ER-PR+ tumors had increased risk of recurrence and death compared with ER + PR+ tumor, with a hazard ratio of 4.19 for DFS and 7.22 for OS. In contrast, in patients with HER2 overexpression, the difference in survival between single HR+ tumors and double HR+ HR- tumors was not statistically significant. In patients without HER2 overexpression the DFS and OS of ER + PR- and ER-PR+ tumors were not significantly different from those of ER-PR- tumors.<br><br>CONCLUSION: We have identified clinically and biologically distinct features of single HR+ tumors (ER-PR+ and ER + PR-) through comparison with both ER + PR+ and ER-PR- tumors. These differences were only significant in HER2- tumors, not in HER2+ tumors. Single HR+ tumors without HER2 overexpression (ER + PR-HER2- or ER-PR + HER2-) were associated with poorer survival than ER + PR + HER2- tumors, and had comparable poor survival to ER-PR-HER2- tumors (triple-negative breast cancer).}, }
@article {pmid25852060, year = {2015}, author = {Borges, S and Perez, EA and Thompson, EA and Radisky, DC and Geiger, XJ and Storz, P}, title = {Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101.}, journal = {Molecular cancer therapeutics}, volume = {14}, number = {6}, pages = {1306-1316}, pmid = {25852060}, issn = {1538-8514}, support = {CA116201/CA/NCI NIH HHS/United States ; GM086435/GM/NIGMS NIH HHS/United States ; R01 CA140182/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; CA140182/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; R01 GM086435/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Cell Line, Tumor ; Cell Movement/drug effects/genetics ; Cell Proliferation/drug effects/genetics ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/metabolism/prevention &amp; control/secondary ; Lymphatic Metastasis ; MCF-7 Cells ; Mice, Inbred NOD ; Mice, SCID ; Microscopy, Confocal ; Neoplasm Invasiveness ; Protein Kinase C/*antagonists &amp; inhibitors/genetics/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Pyrimidines/*pharmacology ; RNA Interference ; Receptors, Estrogen/metabolism ; Tumor Burden/drug effects/genetics ; Xenograft Model Antitumor Assays ; }, abstract = {Invasive ductal carcinomas (IDC) of the breast are associated with altered expression of hormone receptors (HR), amplification or overexpression of HER2, or a triple-negative phenotype. The most aggressive cases of IDC are characterized by a high proliferation rate, a great propensity to metastasize, and their ability to resist to standard chemotherapy, hormone therapy, or HER2-targeted therapy. Using progression tissue microarrays, we here demonstrate that the serine/threonine kinase protein kinase D3 (PKD3) is highly upregulated in estrogen receptor (ER)-negative (ER(-)) tumors. We identify direct binding of the ER to the PRKD3 gene promoter as a mechanism of inhibition of PKD3 expression. Loss of ER results in upregulation of PKD3, leading to all hallmarks of aggressive IDC, including increased cell proliferation, migration, and invasion. This identifies ER(-) breast cancers as ideal for treatment with the PKD inhibitor CRT0066101. We show that similar to a knockdown of PKD3, treatment with this inhibitor targets all tumorigenic processes in vitro and decreases growth of primary tumors and metastasis in vivo. Our data strongly support the development of PKD inhibitors for clinical use for ER(-) breast cancers, including the triple-negative phenotype.}, }
@article {pmid25850931, year = {2015}, author = {Sutton, EJ and Oh, JH and Dashevsky, BZ and Veeraraghavan, H and Apte, AP and Thakur, SB and Deasy, JO and Morris, EA}, title = {Breast cancer subtype intertumor heterogeneity: MRI-based features predict results of a genomic assay.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {42}, number = {5}, pages = {1398-1406}, pmid = {25850931}, issn = {1522-2586}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cohort Studies ; Contrast Media ; Female ; Gadolinium DTPA ; Gene Expression/genetics ; Genomics/*methods ; Humans ; Image Enhancement ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Retrospective Studies ; }, abstract = {PURPOSE: To investigate the association between a validated, gene-expression-based, aggressiveness assay, Oncotype Dx RS, and morphological and texture-based image features extracted from magnetic resonance imaging (MRI).<br><br>MATERIALS AND METHODS: This retrospective study received Internal Review Board approval and need for informed consent was waived. Between 2006-2012, we identified breast cancer patients with: 1) ER+, PR+, and HER2- invasive ductal carcinoma (IDC); 2) preoperative breast MRI; and 3) Oncotype Dx RS test results. Extracted features included morphological, histogram, and gray-scale correlation matrix (GLCM)-based texture features computed from tumors contoured on pre- and three postcontrast MR images. Linear regression analysis was performed to investigate the association between Oncotype Dx RS and different clinical, pathologic, and imaging features. P&#x2009;<&#x2009;0.05 was considered statistically significant.<br><br>RESULTS: Ninety-five patients with IDC were included with a median Oncotype Dx RS of 16 (range: 0-45). Using stepwise multiple linear regression modeling, two MR-derived image features, kurtosis in the first and third postcontrast images and histologic nuclear grade, were found to be significantly correlated with the Oncotype Dx RS with P&#x2009;=&#x2009;0.0056, 0.0005, and 0.0105, respectively. The overall model resulted in statistically significant correlation with Oncotype Dx RS with an R-squared value of 0.23 (adjusted R-squared&#x2009;=&#x2009;0.20; P&#x2009;=&#x2009;0.0002) and a Spearman's rank correlation coefficient of 0.49 (P&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: A model for IDC using imaging and pathology information correlates with Oncotype Dx RS scores, suggesting that image-based features could also predict the likelihood of recurrence and magnitude of chemotherapy benefit.}, }
@article {pmid25848941, year = {2015}, author = {Dossus, L and Benusiglio, PR}, title = {Lobular breast cancer: incidence and genetic and non-genetic risk factors.}, journal = {Breast cancer research : BCR}, volume = {17}, number = {}, pages = {37}, pmid = {25848941}, issn = {1465-542X}, mesh = {Breast Neoplasms/*epidemiology/*etiology ; Carcinoma, Lobular/*epidemiology/*etiology ; Environment ; Female ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Humans ; Incidence ; Risk Factors ; }, abstract = {While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004, reflecting among other causes the decreasing use of menopausal hormone therapy, and these variations were stronger for invasive lobular than for invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly associated with early menarche, late menopause and late age at first birth. As for genetic risk factors, four high-penetrance genes are tested in clinical practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2, TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion protein, is of special interest as mutations are associated with invasive lobular carcinoma, but never with ductal carcinoma. It was initially known as the main susceptibility gene for gastric cancer of the diffuse type, but the excess of breast cancers of the lobular type in CDH1 families led researchers to identify it also as a susceptibility gene for invasive lobular carcinoma. The risk of invasive lobular carcinoma is high in female mutation carriers, as about 50% are expected to develop the disease. Carriers must therefore undergo intensive breast cancer screening, with, for example, yearly magnetic resonance imaging and mammogram starting at age 30 years.}, }
@article {pmid25845386, year = {2015}, author = {Lin, CS and Chang, SC and Ou, LH and Chen, CM and Hsieh, SS and Chung, YP and King, KL and Lin, SL and Wei, YH}, title = {Mitochondrial DNA alterations correlate with the pathological status and the immunological ER, PR, HER-2/neu, p53 and Ki-67 expression in breast invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {33}, number = {6}, pages = {2924-2934}, doi = {10.3892/or.2015.3887}, pmid = {25845386}, issn = {1791-2431}, mesh = {Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Cell Proliferation ; DNA Copy Number Variations/genetics ; DNA, Mitochondrial/*genetics ; Estrogen Receptor alpha/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/*biosynthesis/genetics ; Middle Aged ; Mutation ; Prognosis ; Receptor, ErbB-2/*biosynthesis/genetics ; Receptors, Progesterone/*biosynthesis/genetics ; Tumor Suppressor Protein p53/*biosynthesis/genetics ; }, abstract = {We analyzed the changes in mitochondrial DNA (mtDNA) copy numbers and the shifting of mtDNA D310 sequence variations (D310 mutation) with their relationships to pathological status and the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2/neu), tumor-suppressor protein p53 and cellular proliferation protein Ki-67 in breast invasive ductal carcinoma (BIDC), respectively. Fifty-one paraffin-embedded BIDCs and their paired non-cancerous breast tissues were dissected for DNA extraction. The mtDNA copy number and mtDNA D310 sequence variations were determined by quantitative real-time polymerase chain reaction (q-PCR) and PCR-based direct sequencing, respectively. The expression levels of ER, PR, HER-2/neu, p53 and Ki-67 were determined by immunohistochemical (IHC) staining. Compared to the paired non-cancerous breast tissues, 24 (47.1%) BIDCs had elevated mtDNA copy numbers and 29 (56.9%) harbored mtDNA D310 mutations. Advanced T-status (p=0.056), negative-ER (p=0.005), negative-PR (p=0.007), positive-p53 (p=0.050) and higher Ki-67 (p=0.004) expressions were related to a higher mtDNA copy ratio. In addition, advanced T-status (p=0.019) and negative-HER-2/neu expression (p=0.061) were associated with mtDNA D310 mutations. In conclusion, higher mtDNA copy ratio and D310 mutations may be relevant biomarkers correlated with pathological T-status and the expression levels of ER, PR, HER-2/neu, p53 and Ki-67 in BIDCs.}, }
@article {pmid25837163, year = {2015}, author = {Cha, YJ and Jung, WH and Cho, NH and Koo, JS}, title = {Expression of sarcosine metabolism-related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma.}, journal = {Yonsei medical journal}, volume = {56}, number = {3}, pages = {598-607}, pmid = {25837163}, issn = {1976-2437}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Phenotype ; Proportional Hazards Models ; Regression Analysis ; Retrospective Studies ; Sarcosine/genetics/*metabolism ; Tissue Array Analysis ; }, abstract = {PURPOSE: The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results.<br><br>MATERIALS AND METHODS: Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)].<br><br>RESULTS: The sarcosine metabolic phenotype differed between ILC and IDC (p<0.001). In IDC, sarcosine metabolic phenotype was distributed as null type (61.7%)>low sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC.<br><br>CONCLUSION: Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.}, }
@article {pmid25833969, year = {2015}, author = {Fuller, NR and Caterson, ID and Sainsbury, A and Denyer, G and Fong, M and Gerofi, J and Baqleh, K and Williams, KH and Lau, NS and Markovic, TP}, title = {The effect of a high-egg diet on cardiovascular risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) study-a 3-mo randomized controlled trial.}, journal = {The American journal of clinical nutrition}, volume = {101}, number = {4}, pages = {705-713}, doi = {10.3945/ajcn.114.096925}, pmid = {25833969}, issn = {1938-3207}, mesh = {Aged ; Blood Glucose/metabolism ; Body Mass Index ; Cardiovascular Diseases/*diet therapy/*prevention &amp; control ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Diabetes Mellitus, Type 2/*diet therapy ; *Diet ; *Eggs ; Fatty Acids, Monounsaturated/administration &amp; dosage/blood ; Fatty Acids, Unsaturated/administration &amp; dosage/blood ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Nutritional Status ; Obesity/blood/diet therapy ; Overweight/blood/diet therapy ; Prospective Studies ; Risk Factors ; Satiation ; Surveys and Questionnaires ; Treatment Outcome ; Triglycerides/blood ; }, abstract = {BACKGROUND: Previously published research that examined the effects of high egg consumption in people with type 2 diabetes (T2D) produced conflicting results leading to recommendations to limit egg intake. However, people with T2D may benefit from egg consumption because eggs are a nutritious and convenient way of improving protein and micronutrient contents of the diet, which have importance for satiety and weight management.<br><br>OBJECTIVE: In this randomized controlled study, we aimed to determine whether a high-egg diet (2 eggs/d for 6 d/wk) compared with a low-egg diet (<2 eggs/wk) affected circulating lipid profiles, in particular high-density lipoprotein (HDL) cholesterol, in overweight or obese people with prediabetes or T2D.<br><br>DESIGN: A total of 140 participants were randomly assigned to one of the 2 diets as part of a 3-mo weight maintenance study. Participants attended the clinic monthly and were instructed on the specific types of foods and quantities to be consumed.<br><br>RESULTS: There was no significant difference in the change in HDL cholesterol from screening to 3 mo between groups; the mean difference (95% CI) between high- and low-egg groups was +0.02 mmol/L (-0.03, 0.08 mmol/L; P = 0.38). No between-group differences were shown for total cholesterol, low-density lipoprotein cholesterol, triglycerides, or glycemic control. Both groups were matched for protein intake, but the high-egg group reported less hunger and greater satiety postbreakfast. Polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) intakes significantly increased from baseline in both groups.<br><br>CONCLUSIONS: High egg consumption did not have an adverse effect on the lipid profile of people with T2D in the context of increased MUFA and PUFA consumption. This study suggests that a high-egg diet can be included safely as part of the dietary management of T2D, and it may provide greater satiety. This trial was registered at the Australia New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12612001266853.}, }
@article {pmid25831047, year = {2015}, author = {Kim, SY and Jung, SH and Kim, MS and Baek, IP and Lee, SH and Kim, TM and Chung, YJ and Lee, SH}, title = {Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.}, journal = {Oncotarget}, volume = {6}, number = {10}, pages = {7597-7607}, pmid = {25831047}, issn = {1949-2553}, mesh = {Adult ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Female ; Gene Dosage/*genetics ; Genomics ; Humans ; Middle Aged ; Sequence Analysis, DNA/*methods ; }, abstract = {Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.}, }
@article {pmid25820821, year = {2015}, author = {Asiaf, A and Ahmad, ST and Malik, AA and Aziz, SA and Rasool, Z and Masood, A and Zargar, MA}, title = {Protein expression and methylation of MGMT, a DNA repair gene and their correlation with clinicopathological parameters in invasive ductal carcinoma of the breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {8}, pages = {6485-6496}, pmid = {25820821}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Methylation/*genetics ; DNA Modification Methylases/biosynthesis/*genetics ; DNA Repair Enzymes/biosynthesis/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Promoter Regions, Genetic ; Tumor Suppressor Proteins/biosynthesis/*genetics ; }, abstract = {Epigenetic mechanisms such as DNA methylation are being increasingly recognized to play an important role in cancer and may serve as a cancer biomarker. The aim of this study was to evaluate the promoter methylation status of MGMT (O6-methylguanine-DNA methyltransferase) and a possible correlation with the expression of MGMT and standard clinicopathological parameters in invasive ductal breast carcinoma patients (IDC) of Kashmir. Methylation-specific PCR was carried out to investigate the promoter methylation status of MGMT in breast tumors paired with the corresponding normal tissue samples from 128 breast cancer patients. The effect of promoter methylation on protein expression in the primary breast cancer and adjacent normal tissues was evaluated by immunohistochemistry (n = 128) and western blotting (n = 30). The frequency of tumor hypermethylation was 39.8 % and a significant difference in methylation frequency among breast tumors were found (p < 0.001) when compared with the corresponding normal tissue. Immunohistochemical analysis showed no detectable expression of MGMT in 68/128 (53.1 %) tumors. MGMT promoter methylation mediated gene silencing was associated with loss of its protein expression (rs = -0.285, p = 0.001, OR = 3.38, 95 % CI = 1.59-7.17). A significant correlation was seen between loss of MGMT and lymph node involvement (p = 0.030), tumor grade (p < 0.0001), loss of estrogen receptors (ER; p = 0.021) and progesterone receptors (PR) (p = 0.016). Also, MGMT methylation was found to be associated with tumor grade (p = 0.011), tumor stage (p = 0.009), and loss of ER (p = 0.003) and PR receptors (p = 0.009). To our knowledge, our findings, for the first time, in Kashmiri population, indicate that MGMT is aberrantly methylated in breast cancer and promoter hypermethylation could be attributed to silencing of MGMT gene expression in breast cancer. Our data suggests that MGMT promoter hypermethylation could have a potential function as molecular biomarker of breast oncogenesis. Also, based on their predictive value of response to therapy, the immunohistochemical evaluation and interpretation of MGMT may also help in future to establish therapeutic strategies for patients with breast cancer.}, }
@article {pmid25818033, year = {2015}, author = {Oger, AS and Boukerrou, M and Cutuli, B and Campion, L and Rousseau, E and Bussières, E and Raro, P and Classe, JM}, title = {[Male breast cancer: prognostic factors, diagnosis and treatment: a multi-institutional survey of 95 cases].}, journal = {Gynecologie, obstetrique &amp; fertilite}, volume = {43}, number = {4}, pages = {290-296}, doi = {10.1016/j.gyobfe.2015.02.010}, pmid = {25818033}, issn = {1769-6682}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*diagnosis/pathology/*therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/therapy ; Chemotherapy, Adjuvant ; Humans ; Lymphatic Metastasis/pathology ; Male ; Mastectomy ; Middle Aged ; Obesity/complications ; Prognosis ; Radiotherapy, Adjuvant ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVES: The optimal treatment for male breast cancer is not known because male breast cancer is a rare disease. It represents as little as 0.6% of all breast cancers and less than 1% of human cancers. The aim was to analyze the clinical, histological and therapeutic characteristics of 95 men cared for breast cancer between 2000 and 2010 in four hospitals, and determine predictors of poor prognosis to improve care of male breast cancer.<br><br>METHODS: This study is a multi-institutional survey, retrospective, involving four French institutions: Cancer Institute of the West (ICO), Reunion Island South hospital group, the hospital group of Dax, and the Bergoni&#xe9; Institute. All carcinomas in situ or invasive breast occurred in male patients were included. An analysis of clinical, histological and therapeutic features was performed. Statistical analysis of our study focused on the overall survival of patients and specific method of Kaplan-Meier, enabling search for predictors of poor prognosis.<br><br>RESULTS: The mean age was 65 years. Thirty-seven percent of patients were overweight or obese. It was in 88% of cases of palpable tumor whose average size was 26.29mm. Ninety patients, none had a lesion palpable T0, 44% T1 tumors, 38% T2 tumors, 3% had a T3 tumors, and finally 10% T4 tumors. The histological type was the most common invasive ductal carcinoma (87%). He found a similar proportion of patients with or without lymph node involvement. N+ patients, capsular rupture was observed in 29% of cases. Receptor positivity was found, estrogen in 95% of cases and progesterone in 83% of cases. Additional irradiation was performed in 75% of patients and chemotherapy in 37% of patients. Overall survival was 79.2% at five years and 70.8% at ten years. Age, tumor size and histological capsular rupture are factors that significantly influence the overall survival and specific.<br><br>CONCLUSION: Male breast cancer is a different pathology of breast cancer in women. The majority of recommendations suggest treating men who are diagnosed with breast cancer, using the guidelines applied to postmenopausal women treatments. There is no study based on male population that has evaluated these treatment modalities in terms of impact on survival. The diagnosis is usually made at later stages, and tumor size is often greater. Histological characteristics also differ. However, the treatment is almost identical.}, }
@article {pmid25816287, year = {2015}, author = {Rebollo, MP and Mohammed, KA and Thomas, B and Ame, S and Ali, SM and Cano, J and Escalada, AG and Bockarie, MJ}, title = {Cessation of mass drug administration for lymphatic filariasis in Zanzibar in 2006: was transmission interrupted?.}, journal = {PLoS neglected tropical diseases}, volume = {9}, number = {3}, pages = {e0003669}, pmid = {25816287}, issn = {1935-2735}, support = {G1001337/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Child ; Communicable Disease Control/*methods ; Disease Eradication/methods/*statistics &amp; numerical data ; Elephantiasis, Filarial/*drug therapy/*epidemiology/*transmission ; Humans ; Indian Ocean Islands/epidemiology ; Male ; Surveys and Questionnaires ; Tanzania/epidemiology ; }, abstract = {BACKGROUND: Lymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4-6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped.<br><br>In line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS) in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded.<br><br>CONCLUSIONS: Our findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.}, }
@article {pmid25809301, year = {2015}, author = {Calandrella, D and Romito, LM and Elia, AE and Del Sorbo, F and Bagella, CF and Falsitta, M and Albanese, A}, title = {Causes of withdrawal of duodenal levodopa infusion in advanced Parkinson disease.}, journal = {Neurology}, volume = {84}, number = {16}, pages = {1669-1672}, doi = {10.1212/WNL.0000000000001500}, pmid = {25809301}, issn = {1526-632X}, mesh = {Aged ; Antiparkinson Agents/administration &amp; dosage/*adverse effects ; Duodenum/surgery ; Female ; Humans ; Infusion Pumps, Implantable/*adverse effects ; Infusions, Parenteral/*adverse effects ; Levodopa/administration &amp; dosage/*adverse effects ; Male ; Middle Aged ; Parkinson Disease/*drug therapy ; }, abstract = {OBJECTIVE: We performed a real-life observation of patients with Parkinson disease (PD) who received duodenal levodopa infusion (DLI) to determine which adverse events caused treatment discontinuation and when such events occurred.<br><br>METHODS: All consecutive patients with PD treated at the Carlo Besta Neurological Institute were included. The patients were evaluated at baseline and after DLI at regular intervals. Their motor condition was assessed and adverse events were recorded.<br><br>RESULTS: Thirty-five patients with PD (15 men and 20 women) were included. They received DLI implants between October 2007 and September 2013. Four patients died of causes unrelated to the procedure. At the end of the study, 21 patients (60%) were still on treatment. DLI provided efficacious motor control in all patients. Discontinuation was most frequently caused by device- or infusion-related adverse events. Ten patients of the remaining 31 discontinued DLI. There were 2 main causes of withdrawal: stoma infection (4 patients), and worsening of dyskinesias not manageable with infusion reduction (3 patients). In most patients, discontinuations occurred during the first year after implant. Risk of discontinuation was related to age at implant, but no other demographic or clinical variables.<br><br>CONCLUSIONS: We identified 2 main causes leading to DLI withdrawal during the first year postimplant and suggest adopting measures to prevent such occurrences. Elderly patients are at higher risk of treatment discontinuation.}, }
@article {pmid25804795, year = {2015}, author = {Wang, T and Ma, Y and Wang, L and Liu, H and Chen, M and Niu, R}, title = {Strong adverse effect of epidermal growth factor receptor 2 overexpression on prognosis of patients with invasive lobular breast cancer: a comparative study with invasive ductal breast cancer in Chinese population.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {8}, pages = {6113-6124}, pmid = {25804795}, issn = {1423-0380}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*biosynthesis/genetics ; }, abstract = {The data on the outcome of breast invasive lobular carcinoma (ILC) are conflicting. In addition, the prognostic effect of molecular subtypes on ILC remains unclear. In this study, the clinicopathological and prognostic data between 269 ILC and 816 invasive ductal carcinoma (IDC) cases in a Chinese population were extensively compared, with a median follow-up time of 7.8 years. Compared with the IDC group, ILC tumors had more lymph node invasion, hormonal receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity. ILC patients showed overall survival (OS) and recurrence/metastasis-free survival (RFS) rates similar to those of IDC patients but exhibited worse disease-free survival (DFS) rate because of the higher rate of contralateral breast cancer (BC). Further analysis showed that OS, RFS, and DFS were similar between ILC and IDC patients in the subgroups of luminal A and triple-negative BC with HER2 negativity but were worse in ILC patients than those in IDC patients in the subgroups of luminal B and HER2 overexpression with positive HER2 expression. Multivariate analysis indicated HER2 positivity as an independent risk factor for OS, RFS, and DFS of ILC patients, which increased the risk in the ILC group than that in IDC group. The interaction of HER2 and ILC was also defined as an independent risk factor for OS, RFS, and DFS of the entire population. In conclusion, overexpression of HER2 exhibited stronger negative effect on the prognosis of ILC patients than that in IDC patients, suggesting that treatment targeting HER2 is crucial for this BC subgroup.}, }
@article {pmid25791599, year = {2015}, author = {Karbiener, M and Scheideler, M}, title = {Microarray analysis of small non-coding RNAs.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1296}, number = {}, pages = {161-171}, doi = {10.1007/978-1-4939-2547-6_15}, pmid = {25791599}, issn = {1940-6029}, mesh = {Microarray Analysis/*methods ; Nucleic Acid Hybridization/methods ; Oligonucleotide Probes/genetics ; RNA, Small Untranslated/*genetics ; Transition Temperature ; }, abstract = {Microarray technology has evolved to efficiently profile the expression of RNAs. However, analysis of small non-coding RNAs (ncRNAs) is challenging due to their short length and highly divergent sequences with large variation in GC content leading to very different hybridization properties. To overcome these challenges, LNA-modified oligonucleotides have been used to enhance and normalize the melting temperature (Tm) of capture probes, which allows sensitive profiling of small ncRNAs regardless of their sequence. Here, we describe the isolation and labeling of small non-coding RNAs, as well as their hybridization to microarrays with LNA-modified oligonucleotide probes using a semi-automated hybridization device.}, }
@article {pmid25784697, year = {2015}, author = {Leonhardt, I and Spielberg, S and Weber, M and Albrecht-Eckardt, D and Bläss, M and Claus, R and Barz, D and Scherlach, K and Hertweck, C and Löffler, J and Hünniger, K and Kurzai, O}, title = {The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity.}, journal = {mBio}, volume = {6}, number = {2}, pages = {e00143}, pmid = {25784697}, issn = {2150-7511}, mesh = {Adaptive Immunity/*drug effects ; Candida albicans/*physiology ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/drug effects/immunology ; Farnesol/*metabolism ; Gene Expression Profiling ; Humans ; Immunologic Factors/*metabolism ; Monocytes/drug effects/immunology ; Neutrophils/drug effects/immunology ; *Quorum Sensing ; Virulence Factors/*metabolism ; }, abstract = {UNLABELLED: Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and macrophage inflammatory protein 1 alpha [MIP-1α]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance.<br><br>IMPORTANCE: Farnesol is a quorum-sensing molecule which controls morphological plasticity of the pathogenic yeast Candida albicans. As such, it is a major mediator of intraspecies communication. Here, we investigated the impact of farnesol on human innate immune cells known to be important for fungal clearance and protective immunity. We show that farnesol is able to enhance inflammation by inducing activation of neutrophils and monocytes. At the same time, farnesol impairs differentiation of monocytes into immature dendritic cells (iDC) by modulating surface phenotype, cytokine release and migrational behavior. Consequently, iDC generated in the presence of farnesol are unable to induce proper T cell responses and fail to secrete Th1 promoting interleukin 12 (IL-12). As farnesol induced down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, desensitization to GM-CSF could potentially explain transcriptional reprofiling of iDC effector molecules. Taken together, our data show that farnesol can also mediate Candida-host communication and is able to act as a virulence factor.}, }
@article {pmid25783336, year = {2015}, author = {Kushnir, J and Djerassi, R and Sofer, T and Kushnir, T}, title = {Threat perception, anxiety and noncompliance with preoperative fasting instructions among mothers of children attending elective same day surgery.}, journal = {Journal of pediatric surgery}, volume = {50}, number = {5}, pages = {869-874}, doi = {10.1016/j.jpedsurg.2014.08.018}, pmid = {25783336}, issn = {1531-5037}, mesh = {Adult ; *Ambulatory Surgical Procedures ; Anxiety/*epidemiology/etiology ; Child ; Child, Preschool ; *Elective Surgical Procedures ; *Fasting ; Female ; Humans ; Incidence ; Israel/epidemiology ; Male ; Mothers/*psychology ; *Patient Compliance ; Preoperative Care/*methods ; }, abstract = {PURPOSE: The current study examined possible links between threat perception, anxiety, conscientiousness and parental noncompliance with preoperative fasting instructions for their children.<br><br>METHODS: 100 mothers of children about to undergo an ambulatory elective surgery were divided to two equal groups based on compliance/noncompliance with pre surgery fasting requirements. Logistic regression analysis was preformed to predict compliance/noncompliance. In addition a logistic model estimating the effect of anxiety and conscientiousness levels, and their interaction, on the probability of fasting was performed.<br><br>RESULTS: Mothers who did not comply with fasting requirements perceived the procedure as more threatening, were more anxious and had lower conscientiousness levels. Additionally, mother's anxiety prior to surgery mediated the association between mothers' threat perception and compliance. Finally, conscientiousness moderated the anxiety and compliance association so that high conscientiousness levels reduced the effect of anxiety, elevating the likelihood of anxious mothers to comply with fasting guidelines.<br><br>CONCLUSIONS: Based on these findings we recommend medical staff to make significant efforts to identify highly anxious parents as early as possible during the preoperative process. Innovative assessment and intervention tools should be developed in order to conduct a smooth medical operation and reduce the chance of unnecessary and costly surgery cancelation.}, }
@article {pmid25771081, year = {2015}, author = {Sorin, T and Fyad, JP and Delay, E and Rouanet, P and Rimareix, F and Houpeau, JL and Classe, JM and Garrido, I and Tunon De Lara, C and Dauplat, J and Bendavid, C and Houvenaeghel, G and Clough, KB and Sarfati, I and Leymarie, N and Trudel, M and Salleron, J and Guillemin, F and Oldrini, G and Brix, M and Dolivet, G and Simon, E and Verhaeghe, JL and Marchal, F}, title = {Occult cancer in specimens of reduction mammaplasty aimed at symmetrization. A multicentric study of 2718 patients.}, journal = {Breast (Edinburgh, Scotland)}, volume = {24}, number = {3}, pages = {272-277}, doi = {10.1016/j.breast.2015.02.033}, pmid = {25771081}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/secondary/surgery ; Carcinoma, Lobular/*epidemiology/secondary/surgery ; Female ; Humans ; Incidence ; Mammaplasty/*statistics &amp; numerical data ; Mastectomy, Segmental ; Middle Aged ; Neoplasms, Unknown Primary/*epidemiology ; Retrospective Studies ; }, abstract = {Women who have undergone surgical treatment for breast cancer often benefit from a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the contralateral breast unaffected by the initial cancer. In our 7-year multicentric study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017). 35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical specimens were correctly oriented. En bloc resection and orientation of surgical specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be proposed as an option when margins are invaded. The histological distribution of the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%, invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%.}, }
@article {pmid25769963, year = {2015}, author = {Cassinello, F and Prieto, I and del Olmo, M and Rivas, S and Strichartz, GR}, title = {Cancer surgery: how may anesthesia influence outcome?.}, journal = {Journal of clinical anesthesia}, volume = {27}, number = {3}, pages = {262-272}, doi = {10.1016/j.jclinane.2015.02.007}, pmid = {25769963}, issn = {1873-4529}, mesh = {Anesthesia/*methods ; Anesthetics, Local/pharmacology ; Apoptosis ; Cell Movement ; Cell Proliferation ; Disease Progression ; Humans ; Neoplasms/mortality/pathology/*surgery ; Substance P/physiology ; Voltage-Gated Sodium Channels/drug effects ; }, abstract = {OBJECTIVE: To review the published literature regarding the effects of anesthesia on cancer surgery to prevent tumor cell proliferation/migration or induce apoptosis.<br><br>BACKGROUND: Surgery is the main treatment for potentially curable solid tumors, but most cancer-related deaths in patients who have received previous surgical treatment are caused by metastatic disease. There is increasing evidence that anesthetic technique has the potential to affect long-term outcome after cancer surgery.<br><br>METHODS: This work reviews the English published literature that was obtained by performing a search of the PubMed database up to January 2014. We selected articles that provided evidence or reviewed the possible actions of anesthetics on cancer cells or the influence of anesthesia in recurrence/outcome.<br><br>RESULTS: Inhaled anesthetics induce immunosuppression and activate inflammatory cascade activation, whereas propofol has a protective action. Opioids might promote cancer recurrence and metastasis. In vitro and in vivo studies have demonstrated that local anesthetics inhibit proliferation and migration of cancer cells and induce apoptosis.<br><br>CONCLUSIONS: Anesthesiologists should follow current best clinical practice and include all strategies that effectively decrease pain and attenuate stress. Regional anesthesia and multimodal analgesia, adding anti-inflammatory drugs, play an unquestionable role in the control of perioperative pain and may improve recurrence-free survival.}, }
@article {pmid25759617, year = {2014}, author = {Basaran, D and Turgal, M and Beksac, K and Ozyuncu, O and Aran, O and Beksac, MS}, title = {Pregnancy-associated breast cancer: clinicopathological characteristics of 20 cases with a focus on identifiable causes of diagnostic delay.}, journal = {Breast care (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {355-359}, pmid = {25759617}, issn = {1661-3791}, abstract = {BACKGROUND: The primary objective of this study was to evaluate the clinicopathological characteristics of patients with pregnancy-associated breast cancer (PABC), with a special focus on diagnostic delays and the identifiable causes of diagnostic delays.<br><br>PATIENTS AND METHODS: Clinicopathological data of patients treated for PABC between 2003 and 2012 at Hacettepe University Hospital was retrospectively reviewed.<br><br>RESULTS: 20 patients with PABC were included. The pathological examination revealed predominance of invasive ductal carcinoma (80%), grade III tumors (65%) and advanced-stage (III-IV) disease (75%). In 8 patients (40%), there was a diagnostic delay between occurrence of the presenting symptoms and the initiation of breast mass workup. For these 8 patients, the main identifiable causes of diagnostic delay were the attribution of disease-related symptoms to pregnancy or lactation in 5 (63%) and negligence of symptoms in 2 (25%).<br><br>CONCLUSIONS: PABC mostly presents with advanced-stage disease, and there can be a substantial diagnostic delay before these patients receive treatment. Preconceptional, gestational and postpartum examination of women of reproductive age should include a thorough breast examination and should provide adequate information regarding the physiological changes in breast tissue and the possible pathological symptoms.}, }
@article {pmid25752197, year = {2015}, author = {Simpson, K and Jones, RE and Grimstead, JW and Hills, R and Pepper, C and Baird, DM}, title = {Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.}, journal = {Molecular oncology}, volume = {9}, number = {6}, pages = {1186-1193}, pmid = {25752197}, issn = {1878-0261}, support = {C17199/A13490//Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/genetics/*metabolism/*mortality/pathology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Survival Rate ; Telomere/genetics/*metabolism ; *Telomere Homeostasis ; }, abstract = {Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.}, }
@article {pmid25751500, year = {2015}, author = {Son, CH and Bae, JH and Lee, HR and Shin, DY and Yang, K and Park, YS}, title = {Enhanced dendritic cell-based immunotherapy using low-dose cyclophosphamide and CD25-targeted antibody for transplanted Lewis lung carcinoma cells.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {38}, number = {3}, pages = {107-115}, doi = {10.1097/CJI.0000000000000068}, pmid = {25751500}, issn = {1537-4513}, mesh = {Animals ; Antibodies, Monoclonal/*administration &amp; dosage ; Antineoplastic Agents/*administration &amp; dosage ; Apoptosis/drug effects/radiation effects ; Carcinoma, Lewis Lung/*immunology/mortality/pathology/therapy ; Cell Line, Tumor ; Combined Modality Therapy ; Cyclophosphamide/*administration &amp; dosage ; Cytotoxicity, Immunologic/drug effects/radiation effects ; Dendritic Cells/*immunology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Immunophenotyping ; Immunosuppressive Agents/administration &amp; dosage ; Immunotherapy ; Interleukin-2 Receptor alpha Subunit/*antagonists &amp; inhibitors ; Male ; Mice ; Phenotype ; Radiation ; Spleen/immunology ; T-Lymphocytes, Regulatory/drug effects/immunology/metabolism/radiation effects ; Th1 Cells/drug effects/immunology/metabolism/radiation effects ; Tumor Microenvironment/drug effects/immunology/radiation effects ; }, abstract = {Regulatory T cells (Tregs) is one of the main obstacles to the success of cancer immunotherapy. The effect of dendritic cell (DC)-based immunotherapy can be attenuated by immune suppressive functions of Tregs. We used a CD25-targeted antibody and low-dose cyclophosphamide (CTX) as immunomodulators to increase the antitumor effect of intratumoral injection of immature DCs into the irradiated tumor cells (IR/iDC). CTX or CD25-targeted antibody alone showed a significant reduction in the number of Tregs within the tumor microenvironment. When they are combined with IR/iDC, the number of Tregs was further reduced. Although IR/IDC showed strong antitumor effects such as reduction in tumor growth, increase in Th1 immune response, and improvement of survival, the therapeutic effect was further improved by combining treatments with immunomodulators. CTX and CD25-targeted antibody showed no significant difference in tumor growth when combined with IR/iDC, but CTX further increased the number of interferon (IFN)-γ-secreting T cells, cytotoxicity, and survival rate. Although irradiation induced depletion of T lymphocytes, administration of DCs recovered this depletion. Particularly, the lymphocytes were more significantly increased when CTX and IR/iDC were combined. Low-dose CTX has already been used as an immunomodulator in clinical trials, and it offers several advantages, including convenience, low-cost, and familiarity to clinicians. However, CD25-targeted antibody cannot only deplete Tregs, but also may affect IL-2-dependent effector T lymphocytes. Therefore, CTX is an effective means to inhibit Tregs, and an effective immunomodulatory agent for multimodality therapy such as combination treatment of conventional cancer therapy and immunotherapy.}, }
@article {pmid25750340, year = {2015}, author = {Arfaoui, A and Douik, H and Kablouti, G and Chaaben, AB and Handiri, N and Zid, Z and Ouni, N and Zouiouch, F and Ayari, F and Mamoughli, T and Bouassida, J and Abazza, H and Harzallaha, L and Guemira, F}, title = {Role of p53 Codon72 SNP in breast cancer risk and anthracycline resistance.}, journal = {Anticancer research}, volume = {35}, number = {3}, pages = {1763-1769}, pmid = {25750340}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/*therapeutic use ; Breast Neoplasms/drug therapy/etiology/*genetics ; Case-Control Studies ; *Codon ; *Drug Resistance, Neoplasm ; Female ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {BACKGROUND/AIM: We undertook a case-control and a case-case study to examine the possible association of p53 codon72 polymorphism with the breast cancer risk and resistance to anthracycline-based chemotherapy.<br><br>PATIENTS AND METHODS: Case-control study: This study enrolled 175 patients with breast cancer treated at the Salah Aziez Institute and 159 healthy Tunisian women (matched for age, ethnicity and origin), used as a control, with no clinical evidence of any neoplastic disorder. Case-Case study: 400 breast cancer patients, with invasive ductal carcinoma (IDC) treated with anthracycline based-chemotherapy. Genomic DNA was isolated from whole-blood leucocytes using the phenol-chloroform method. Anthracycline response was scored according to the World Health Organization (WHO) criteria. P53 codon72 polymorphism was genotyped using real-time polymerase chain reaction (RT-PCR) with the TaqMan method. Data were statistically analyzed using the Chi-square test.<br><br>RESULTS: Clinical data revealed that among the 400 patients, one quarter was resistant to chemotherapy treatment. Genetic data revealed that the p53 Arg72Pro genotype was found to be greatly associated with breast cancer risk (p<0.001), as well as tumor site (p=0.046). However, resistance to anthracycline-based chemotherapy does not seem to be correlated with p53 codon72 polymorphism in our population. Also, the distribution of tumor size, lymph node involvement and tumor grade was not significantly different among the polymorphic variants.<br><br>CONCLUSION: We conclude that p53 codon72 polymorphism is involved in susceptibility to developing breast cancer. It may be a factor of progression when breast sites are taken into account. However, there is no evidence indicating that Arg72Pro SNP may influence response to anthracycline-based chemotherapy.}, }
@article {pmid25736840, year = {2015}, author = {Cherbal, F and Gaceb, H and Mehemmai, C and Saiah, I and Bakour, R and Rouis, AO and Boualga, K and Benbrahim, W and Mahfouf, H}, title = {Distribution of molecular breast cancer subtypes among Algerian women and correlation with clinical and tumor characteristics: a population-based study.}, journal = {Breast disease}, volume = {35}, number = {2}, pages = {95-102}, doi = {10.3233/BD-150398}, pmid = {25736840}, issn = {1558-1551}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Algeria ; Black People ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; Cohort Studies ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*metabolism/pathology ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. Molecular classification of breast cancer is an important factor for prognosis and clinical outcome. There are limited data regarding molecular breast cancer subtypes among Algerian women. The objective of the present study was to analyze the proportion and distribution of molecular subtypes and to determine their associations with some clinical and tumor characteristics: age at diagnosis, menopausal status, histological type and histological grade.<br><br>MATERIALS AND METHODS: The study population included 3014 female breast cancers. We analyzed breast cancers from cancer registries of academic medical oncology service of public hospital of Rouiba, anticancer center of Blida, and anticancer center of Batna. Breast cancers were diagnosed between 2008 and 2013. Molecular subtype classification was done based on immunohistochemical surrogates for ER (Estrogen receptor), PR (Progesterone receptor) and HER2 (human epidermal growth factor receptor-2) status obtained from medical records for 3014 breast cancer patients. Breast cancer subtypes definitions were as follow: Luminal A (ER+ and/or PR+, HER2-), Luminal B (ER+ and/or PR+, HER2+), TNBC (ER-, PR - , HER2-), HER2+ (ER-, PR-, HER2+). Molecular subtypes were correlated with the clinicopathological characteristics of the tumors.<br><br>RESULTS: The mean age at diagnosis cancer was 48.5 years. Proportions of the luminal A, TNBC, luminal B and HER2+ breast cancer subtypes were 50.59%, 20.80%, 19.67% and 8.92%, respectively. We noted a significant difference in the distribution of age at diagnosis among the four cancer subtypes (P= 0.004). Luminal A, Luminal B, TNBC and HER2+ subtypes were significantly different by premenopausal and postmenopausal status (P= 0.01). Invasive Ductal Carcinoma was the most common histological type in all breast cancer subtypes. Tumors with histological grade 2 and 3 were more common in patients for the four breast cancer subtypes.<br><br>CONCLUSIONS: For the first time, we report the distribution of molecular breast cancer subtypes and their associations with some clinicopathological characteristics in a large cohort of Algerian women. In our current study, the median age of diagnosis for all breast cancer subtypes was younger than the average age in Europe and America. Luminal A was the most common sub- type in our patients followed by TNBC. The proportion of luminal A subtype was lesser than reported in white women with breast cancer in Europe and America. The proportion of TNBC subtype in Algerian women was higher compared with Caucasian women of European ancestry. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for Algerian breast cancer patients.}, }
@article {pmid25731466, year = {2014}, author = {Miyazawa, K and Yoshioka, S and Shiobara, M and Wakatsuki, K and Kataoka, M and Arai, S and Yamazaki, K}, title = {[Long-term survival following postoperative combined modality therapy for pancreatic cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {41}, number = {12}, pages = {2190-2192}, pmid = {25731466}, issn = {0385-0684}, mesh = {Aged ; Carcinoma, Ductal/*therapy ; Catheter Ablation ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/secondary/therapy ; Pancreatectomy ; Pancreatic Neoplasms/pathology/*therapy ; Recurrence ; Time Factors ; }, abstract = {A 69-year-old woman with back pain underwent distal pancreatectomy with left adrenectomy for advanced pancreatic cancer pathologically diagnosed as poorly differentiated invasive ductal carcinoma with retroperitoneal and perineural invasion, pT3N0M0, Stage III. The patient received adjuvant chemotherapy with S-1 for 6 months. However, 3 years after surgery, computed tomography (CT) revealed para-aorticlymph node (LN) recurrence. Treatment with gemcitabine (GEM) was begun and continued for 3 years. Following progression of the LN recurrence 5 and half years after surgery, administration of radiotherapy reduced diarrhea and back pain. Supportive care combined with radio-frequency ablation(RFA)was provided for multiple liver metastasis 5 years 7 months after surgery. The patient died due to gastrointestinal hemorrhage 6 years after surgery. We report long-term postoperative survival of a patient with recurrent pancreatic cancer following combined modality therapy.}, }
@article {pmid25731396, year = {2014}, author = {Hayashi, K and Oshida, S and Nemoto, K and Habiro, T and Sengoku, N and Tanino, H and Watanabe, M}, title = {[Determination of treatment strategies for a 43-year-old single woman with Stage IV breast cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {41}, number = {12}, pages = {1981-1984}, pmid = {25731396}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/drug therapy/*secondary ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy ; Female ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; }, abstract = {The patient was a 43-year-old single woman. Her family history included schizophrenia in her mother and manic-depression in her father. Remicade® (infliximab) had been administered for 3 years to treat rheumatoid arthritis. The patient initially presented to our hospital with dyspnea. Computed tomography revealed left-sided breast cancer associated with multiple bone tumors and multiple pulmonary nodules. A poorly mobile mass with an ulcer was found in left breast. Core-needle biopsy and fluorescent in situ hybridization (FISH)revealed an invasive ductal carcinoma that was positive for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2, 2 +). The clinical diagnosis was Stage IV T4bN3M1 cancer (metastases to the lungs, liver, and bone). Because of the presence of bone metastasis, the patient was admitted and she received complete bed rest as supportive therapy. However, the patient decided to receive treatment on an outpatient basis after carefully discussing the following points: 1) treatment of pulmonary metastasis with dyspnea should receive priority; 2) anticancer agents not causing nausea were required; 3) the risk of bone fractures as a complication (spinal cord injury); 4) how she wanted to spend the limited time available with her family; and 5) how the patient wanted to.}, }
@article {pmid25731395, year = {2014}, author = {Yabe, N and Murai, S and Kunugi, C and Nakadai, J and Oto, I and Yoshikawa, T and Kitasato, K and Shimizu, H and Nakamura, A and Masuda, A and Miyazaki, Y and Ohashi, M and Jinno, H and Kitagawa, Y}, title = {[Synchronous male bladder cancer and breast cancer - a case report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {41}, number = {12}, pages = {1978-1980}, pmid = {25731395}, issn = {0385-0684}, mesh = {*Adenocarcinoma, Scirrhous/drug therapy/secondary/surgery ; Aged ; *Breast Neoplasms/drug therapy/pathology/surgery ; *Breast Neoplasms, Male/drug therapy/pathology/surgery ; Humans ; Lymphatic Metastasis ; Male ; *Neoplasms, Multiple Primary/drug therapy/surgery ; Sentinel Lymph Node Biopsy ; *Urinary Bladder Neoplasms/drug therapy/pathology/surgery ; }, abstract = {A 74-year-old man complained of blood in his urine over a 1-week period beginning in early October 2013, and was examined in the urology department of our hospital. A thorough examination revealed bladder cancer, and surgery was planned after two cycles of preoperative gemcitabine plus cisplatin chemotherapy. A chest computed tomography (CT) performed to evaluate the response to chemotherapy revealed a mass in the right breast. The patient had previously complained about the same site, and mammography and ultrasonography had suggested the possibility of a malignant mammary gland tumor. The results of aspiration cytology were Class V, and based on that finding, a diagnosis of cancer of the right breast was made. In February 2014, we performed a mastectomy, while preserving the pectoral muscles, along with sentinel node biopsy, total cystectomy, urethrectomy, pelvic lymph node dissection, and ureteroileal anastomosis. The histopathological diagnosis of the right breast tumor was invasive ductal carcinoma[scirrhous carcinoma, ly (+), v (-), g (+), f (+), s (+), nuclear grade 1=atypia 2+mitosis 1, EIC (-), ICT (-), NCAT (-)]. A micrometastatic tumor measuring approximately 1mm was observed in the sentinel lymph node. The breast disease was classified as pT1N1mi(sn)M0, Stage IIA, and the tumor was ER (+), PgR (+), HER2/neu (2+), and FISH (-). The bladder cancer was diagnosed as urothelial carcinoma, non-papillary, invasive G2>G3, pT2a; no pelvic lymph node metastases were detected, and it was classified as pT2aN0M0, Stage II. Synchronous male breast cancer and bladder cancer is a very rare condition, and we report the case with a review of the literature.}, }
@article {pmid25731387, year = {2014}, author = {Tsubota, Y and Sueoka, N and Yamamoto, D}, title = {[A complete response following treatment with Paclitaxel and bevacizumab for metastatic breast cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {41}, number = {12}, pages = {1954-1956}, pmid = {25731387}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/secondary ; Combined Modality Therapy ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Paclitaxel/administration &amp; dosage ; Remission Induction ; }, abstract = {A 60-year-old woman with left breast cancer underwent partial mastectomy and sentinel lymph node biopsy. Pathological examination revealed an invasive ductal carcinoma that was ER (+), PgR (-), HER2 (-), and node positive (1/1). She received adjuvant chemotherapy with doxorubicin and cyclophosphamide (AC), followed by weekly paclitaxel (PTX). After receiving radiation therapy, she was administered an aromatase inhibitor for 5 years. Six months after completion of therapy, she found a hard lymph node in the left infraclavicular area. Fine needle aspiration cytology of the lymph node indicated metastatic breast cancer. Fulvestrant was administered but disease progression was observed after 3 months. Systemic chemotherapy with PTX and bevacizumab (Bev) was begun. After 3 cycles of chemotherapy, computed tomography (CT) scan revealed a complete response (CR). After 6 cycles of chemotherapy, the CR has been maintained.}, }
@article {pmid25731373, year = {2014}, author = {Sakurai, K and Fujisaki, S and Nagashima, S and Maeda, T and Tomita, R and Suzuki, S and Hara, Y and Hirano, T and Enomoto, K and Amano, S}, title = {[Usefulness of reductive surgery for elderly advanced breast cancer with bone metastases - a case report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {41}, number = {12}, pages = {1912-1914}, pmid = {25731373}, issn = {0385-0684}, mesh = {Adenocarcinoma, Mucinous/drug therapy/secondary/*surgery ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/*drug therapy/secondary ; Breast Neoplasms/drug therapy/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/secondary/*surgery ; Combined Modality Therapy ; Female ; Humans ; }, abstract = {We report the case of an elderly, advanced breast cancer patient with multiple bone metastases. Breast reduction surgery was useful for this patient. The patient was an 81-year-old woman who had a breast lump. A core needle biopsy for breast cancer led to a diagnosis of invasive ductal carcinoma. The mucinous carcinoma was estrogen receptor (ER) nd progesterone receptor (PgR) positive and HER2/neu negative. Due to patient complications, it was not possible to treat with chemotherapy. The patient was administrated aromatase inhibitors (AI) and zoledronic acid hydrate. However, the AI treatment was not effective, and so she was administered toremifene. Toremifene treatment was effective for 6 months, after which she received fulvestrant. Fulvestrant treatment maintained stable disease (SD)for 14 months. After 14 months of fulvestrant treatment, serum concentrations of the tumor markers CA15-3, CEA, and BCA225 increased. We therefore decided to perform surgical breast reduction surgery. The pathological diagnosis from the surgically resected specimen was mucinous carcinoma, positive for ER and HER2, and negative for PgR. After surgery, serum concentrations of the tumor markers decreased. Following surgery, the patient was administrated lapatinib plus denosumab plus fulvestrant. The patient remains well, without bone metastases, 2 years and 6 months after surgery.}, }
@article {pmid25731362, year = {2014}, author = {Kakimoto, M and Nakata, T and Imaizumi, K and Hirano, T and Yamamoto, Y and Chikatani, K and Hoshino, M and Matsuyama, T and Motoyama, K and Goto, H and Yoshimura, T and Koshiishi, H and Tsuruta, K}, title = {[A case of locally recurrent breast cancer difficult to differentiate from nodular fasciitis].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {41}, number = {12}, pages = {1881-1883}, pmid = {25731362}, issn = {0385-0684}, mesh = {Aged ; Breast Neoplasms/complications/pathology/*therapy ; Carcinoma, Ductal, Breast/complications/*therapy ; Combined Modality Therapy ; Fasciitis/*etiology ; Fatal Outcome ; Female ; Humans ; Neoplasm Recurrence, Local ; }, abstract = {Breast-conserving surgery was performed on a 78-year-old woman for left breast cancer 5 years previously (invasive ductal carcinoma, T1cN2M0, stage IIIA, ER[+], PR[-], HER2[-]). Chemotherapy, radiotherapy, and hormonal therapy were administered. A left subclavian tumor was detected, and an excisional biopsy was performed. Histological examination showed spindle cells, different from primary breast cancer histology, and nodular fasciitis was diagnosed negative cytokeratin and vimentin immunostaining results. After 12 months, a mass had developed in the same region, and reoperation was performed for resection. Similar spindle cells were observed, but they tested positive for cytokeratin. Carcinoma was diagnosed and thought to be locally recurrent breast cancer. Despite postoperative chemotherapy, the patient experienced bone and lung metastasis and a third local recurrence. She died 13 months following the last surgery. Recurrent breast cancer sometimes displays different histology from the initial cancer, and mimics stromal tumors in certain cases.}, }
@article {pmid25721482, year = {2015}, author = {Stolfo, D and Merlo, M and Pinamonti, B and Poli, S and Gigli, M and Barbati, G and Fabris, E and Di Lenarda, A and Sinagra, G}, title = {Early improvement of functional mitral regurgitation in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {115}, number = {8}, pages = {1137-1143}, doi = {10.1016/j.amjcard.2015.01.549}, pmid = {25721482}, issn = {1879-1913}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/diagnosis/*physiopathology ; Echocardiography, Doppler, Color ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging, Cine ; Male ; Middle Aged ; Mitral Valve Insufficiency/diagnosis/etiology/*physiopathology ; Prognosis ; *Recovery of Function ; Retrospective Studies ; Time Factors ; Ventricular Function, Left/*physiology ; Ventricular Remodeling/*physiology ; }, abstract = {The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 ± 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation.}, }
@article {pmid25714914, year = {2015}, author = {Mbongue, JC and Nicholas, DA and Zhang, K and Kim, NS and Hamilton, BN and Larios, M and Zhang, G and Umezawa, K and Firek, AF and Langridge, WH}, title = {Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0118562}, pmid = {25714914}, issn = {1932-6203}, support = {DK-99-013/DK/NIDDK NIH HHS/United States ; S10 RR027643/RR/NCRR NIH HHS/United States ; R25 GM060507/GM/NIGMS NIH HHS/United States ; 1S10RR027643/RR/NCRR NIH HHS/United States ; P20 MD006988/MD/NIMHD NIH HHS/United States ; 5P20MD006988/MD/NIMHD NIH HHS/United States ; }, mesh = {Cell Differentiation ; Cholera Toxin/genetics/*immunology ; Cluster Analysis ; Dendritic Cells/cytology/*immunology/*metabolism ; Gene Expression Profiling ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*biosynthesis/genetics ; Monocytes/cytology/metabolism ; NF-kappa B/metabolism ; Proinsulin/genetics/*immunology ; Proteome ; Proteomics ; Signal Transduction ; Vaccines, Subunit/genetics/*immunology ; }, abstract = {Dendritic cells (DC) interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1). Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines) showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention of type 1 diabetes autoimmunity.}, }
@article {pmid25714366, year = {2015}, author = {Medrikova, D and Sijmonsma, TP and Sowodniok, K and Richards, DM and Delacher, M and Sticht, C and Gretz, N and Schafmeier, T and Feuerer, M and Herzig, S}, title = {Brown adipose tissue harbors a distinct sub-population of regulatory T cells.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0118534}, pmid = {25714366}, issn = {1932-6203}, mesh = {Adipose Tissue, Brown/*immunology/metabolism/pathology ; Animals ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Inflammation/genetics/immunology/metabolism ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; Mice ; Phenotype ; Spleen/cytology/immunology/metabolism ; T-Lymphocyte Subsets/*immunology/metabolism ; T-Lymphocytes, Regulatory/*immunology/metabolism ; }, abstract = {Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT). Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.}, }
@article {pmid25713171, year = {2015}, author = {Cohen-Chen, S and Crisp, RJ and Halperin, E}, title = {Perceptions of a changing world induce hope and promote peace in intractable conflicts.}, journal = {Personality &amp; social psychology bulletin}, volume = {41}, number = {4}, pages = {498-512}, pmid = {25713171}, issn = {1552-7433}, mesh = {Adult ; *Conflict, Psychological ; Female ; *Hope ; Humans ; Male ; Negotiating/*psychology ; *Social Perception ; Young Adult ; }, abstract = {The importance of hope in promoting conciliatory attitudes has been asserted in the field of conflict resolution. However, little is known about conditions inducing hope, especially in intractable conflicts, where reference to the outgroup may backfire. In the current research, five studies yielded convergent support for the hypothesis that hope for peace stems from a general perception of the world as changing. In Study 1, coders observed associations between belief in a changing world, hope regarding peace, and support for concessions. Study 2 revealed the hypothesized relations using self-reported measures. Studies 3 and 4 established causality by instilling a perception of the world as changing (vs. unchanging) using narrative and drawing manipulations. Study 5 compared the changing world message with a control condition during conflict escalation. Across studies, although the specific context was not referred to, the belief in a changing world increased support for concessions through hope for peace.}, }
@article {pmid25708664, year = {2015}, author = {Yıldız, N and Alkan, H and Sarsan, A and Alkan, S}, title = {The effects of repeated filling cystometries on cystometric variables in spinal cord-injured patients with overactive detrusor, who utilize different type of urine drainage methods.}, journal = {Spinal cord}, volume = {53}, number = {8}, pages = {625-629}, pmid = {25708664}, issn = {1476-5624}, mesh = {Adult ; Aged ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Spinal Cord Injuries/*complications ; Treatment Outcome ; Urinary Bladder, Overactive/*etiology/*therapy ; Urinary Catheterization/*methods ; Young Adult ; }, abstract = {STUDY DESIGN: Cross-sectional study.<br><br>OBJECTIVES: Our aim was to compare the effects of repeated cystometric measurements in spinal cord injury (SCI) patients with neurogenic detrusor overactivity (NDO) who use indwelling catheters (IDC) or intermittent catheterization (IC).<br><br>SETTING: Turkey.<br><br>METHODS: A total of 20 SCI patients with NDO, 9 patients on IC and 11 on IDC for at least two consecutive months were included. After emptying the bladder, first involuntary detrusor contraction volume (1stIDCV), cystometric bladder capacity (CC), bladder compliance and maximum detrusor pressure (MPdet) were assessed by filling it with sterile physiological saline at room temperature at a continuous rate of 30&#x2009;ml&#x2009;min(-1). The bladder was re-emptied after the process and a second filling cystometry was performed in the same way.<br><br>RESULTS: When all study population were taken into account, 1stIDCV and CC measures were significantly increased in the second cystometry compared with the first cystometry (P=0.001 and P=0.022, respectively), whereas there was no statistically significant difference on bladder compliance and MPdet measures between the first and the repeated cystometry. There was no statistically significant difference on 1stIDCV, CC and bladder compliance measures between the first and the repeated cystometries for IC group, whereas there was statistically significant increase on these measures in the IDC group (P=0.003, P=0.008 and P=0.022, respectively). In addition there was no statistically significant difference on MP(det) measures between the first and the repeated cystometries for both the urine drainage methods. When IC and IDC groups were compared according to mean values of differences in 1stIDCV, CC and bladder compliance measures between the two cystometries, the IDC group had a statistically significant increase in all parameters when compared with the IC group in the second cystometry performed (P=0.001, P=0.003 and P=0.048, respectively).<br><br>CONCLUSION: Repeated cystometric measurements in SCI patients with NDO lead to an increase in 1stIDCV and CC. However, when the type of urine drainage method is taken into account, although repeated filling cystometry leads to an increase in 1stIDCV, MCC and bladder compliance in patients with IDC, it does not cause a difference in patients on IC.}, }
@article {pmid25697711, year = {2015}, author = {Moccia, M and Picillo, M and Erro, R and Allocca, R and Barone, P and Vitale, C}, title = {Diagnosis and treatment of restless legs syndrome in progressive supranuclear palsy.}, journal = {Journal of the neurological sciences}, volume = {350}, number = {1-2}, pages = {103-104}, doi = {10.1016/j.jns.2015.01.025}, pmid = {25697711}, issn = {1878-5883}, mesh = {Dopamine Agents/therapeutic use ; Humans ; Male ; Middle Aged ; Restless Legs Syndrome/complications/*diagnosis/*therapy ; Supranuclear Palsy, Progressive/complications/*diagnosis/*therapy ; Treatment Outcome ; }, abstract = {Restless legs syndrome (RLS) has only been recently investigated in a small cohort of progressive supranuclear palsy (PSP) patients and it has been reported to have variable prevalence (among 3.7-58%). However little is known about its management. Here, we report a case of severe RLS occurring during the course of PSP. Diagnostic issues and therapeutic approaches are discussed.}, }
@article {pmid25691085, year = {2015}, author = {Abouharb, S and Moulder, S}, title = {Metaplastic breast cancer: clinical overview and molecular aberrations for potential targeted therapy.}, journal = {Current oncology reports}, volume = {17}, number = {3}, pages = {431}, pmid = {25691085}, issn = {1534-6269}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/*therapeutic use ; *Breast Neoplasms/drug therapy/genetics/pathology/secondary ; *Carcinoma/drug therapy/genetics/pathology/secondary ; Diagnosis, Differential ; Female ; Humans ; Molecular Targeted Therapy/*methods ; Prognosis ; *Rare Diseases/drug therapy/genetics/pathology ; }, abstract = {Metaplastic breast cancer is a rare subtype of invasive mammary carcinoma, with an aggressive behavior and usually poor outcome. Responses to systemic chemotherapy are suboptimal compared to patients with standard invasive ductal carcinoma. Limited data are available in regards to best treatment modalities, including chemotherapy. This review gives an overview of metaplastic breast cancer and its clinical and pathologic characteristics, in addition to treatment strategies, clinical trials, and future directions.}, }
@article {pmid25658358, year = {2015}, author = {Matsuda, Y and Ishiwata, T and Izumiyama-Shimomura, N and Hamayasu, H and Fujiwara, M and Tomita, K and Hiraishi, N and Nakamura, K and Ishikawa, N and Aida, J and Takubo, K and Arai, T}, title = {Gradual telomere shortening and increasing chromosomal instability among PanIN grades and normal ductal epithelia with and without cancer in the pancreas.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0117575}, pmid = {25658358}, issn = {1932-6203}, mesh = {Carcinoma in Situ/genetics/metabolism/*pathology ; Chromosomal Instability/*genetics ; Epithelium/metabolism/*pathology ; Humans ; Pancreas/metabolism/*pathology ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Telomere/genetics/*pathology ; *Telomere Shortening ; }, abstract = {A large body of evidence supports a key role for telomere dysfunction in carcinogenesis due to the induction of chromosomal instability. To study telomere shortening in precancerous pancreatic lesions, we measured telomere lengths using quantitative fluorescence in situ hybridization in the normal pancreatic duct epithelium, pancreatic intraepithelial neoplasias (PanINs), and cancers. The materials employed included surgically resected pancreatic specimens without cancer (n = 33) and with invasive ductal carcinoma (n = 36), as well as control autopsy cases (n = 150). In comparison with normal ducts, telomere length was decreased in PanIN-1, -2 and -3 and cancer. Furthermore, telomeres were shorter in cancer than in PanIN-1 and -2. Telomere length in cancer was not associated with histological type, lesion location, or cancer stage. PanINs with or without cancer showed similar telomere lengths. The incidences of atypical mitosis and anaphase bridges, which are morphological characteristics of chromosomal instability, were negatively correlated with telomere length. The telomeres in normal duct epithelium became shorter with aging, and those in PanINs or cancers were shorter than in age-matched controls, suggesting that telomere shortening occurs even when histological changes are absent. Our data strongly suggest that telomere shortening occurs in the early stages of pancreatic carcinogenesis and progresses with precancerous development. Telomere shortening and chromosomal instability in the duct epithelium might be associated with carcinogenesis of the pancreas. Determination of telomere length in pancreatic ductal lesions may be valuable for accurate detection and risk assessment of pancreatic cancer.}, }
@article {pmid25648466, year = {2015}, author = {Boland, MR and Prichard, RS and Daskalova, I and Lowery, AJ and Evoy, D and Geraghty, J and Rothwell, J and Quinn, CM and O'Doherty, A and McDermott, EW}, title = {Axillary nodal burden in primary breast cancer patients with positive pre-operative ultrasound guided fine needle aspiration cytology: management in the era of ACOSOG Z011.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {41}, number = {4}, pages = {559-565}, doi = {10.1016/j.ejso.2015.01.011}, pmid = {25648466}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology/surgery ; Breast Neoplasms, Male/pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Image-Guided Biopsy ; *Lymph Node Excision ; Lymph Nodes/diagnostic imaging/*pathology/*surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Preoperative Care ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Tumor Burden ; Ultrasonography, Interventional ; Young Adult ; }, abstract = {INTRODUCTION: Recent years have seen a dramatic shift to more conservative management of the axilla in patients with a positive sentinel lymph node biopsy (SLNB). Identification of nodal disease with positive pre-operative ultrasound guided axillary fine needle aspiration cytology (AUS/FNAC) may represent a higher axillary disease burden mandating an axillary clearance and thus an upfront SLNB may be avoided. The aims of this study were to quantify nodal burden in patients with positive pre-operative AUS/FNAC and identify patients who may have been able to avoid an axillary clearance (ALND) based on ACOSOG Z011 criteria.<br><br>METHODS: A retrospective review of a prospectively maintained database identified patients with positive pre-operative AUS/FNAC between 2007 and 2012. Core biopsies were excluded. Demographic and tumour characteristics were analysed. Eligibility for ACOSOG Z011 criteria was assessed and patients who may have avoided ALND were identified.<br><br>RESULTS: 432 patients were identified with positive AUS/FNAC. 85 patients were excluded leaving 347 for analysis. Median age was 56 years (22-87), median tumour size was 25 mm (1.5 mm-150 mm) and median tumour pathology was grade 3 (50%) and invasive ductal carcinoma (82%). Median number of nodes removed at ALND was 23 (1-55) with a median number of positive nodes being 4 (1-47). 134 (39%) patients had &#x2264;2 positive nodes identified on ALND making them eligible for the ACOSOG Z011 study. When other ACOSOG Z011 exclusion factors were applied only 27 (7.8%) patients may have avoided ALND.<br><br>CONCLUSIONS: Nodal positivity on AUS/FNAC is associated with higher axillary disease burden. Few patients would satisfy ACOSOG/Z011 criteria and avoid ALND making an upfront SLNB unnecessary.}, }
@article {pmid25645984, year = {2015}, author = {Cao, YW and Wan, GX and Sun, JP and Cui, XB and Hu, JM and Liang, WH and Zheng, YQ and Li, WQ and Li, F}, title = {Implications of the Notch1-Snail/Slug-epithelial to mesenchymal transition axis for lymph node metastasis in infiltrating ductal carcinoma.}, journal = {The Kaohsiung journal of medical sciences}, volume = {31}, number = {2}, pages = {70-76}, doi = {10.1016/j.kjms.2014.11.008}, pmid = {25645984}, issn = {2410-8650}, mesh = {Antigens, CD/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Receptor, Notch1/*metabolism ; Snail Family Transcription Factors ; Transcription Factors/*metabolism ; }, abstract = {Emerging evidence suggests that activation of the Notch1 signaling pathway inducing epithelial to mesenchymal transition (EMT) mediated by Snail/Slug promotes invasion and metastasis of breast cancer cells in vitro. However, the implication of the Notch1-Snail/Slug-EMT axis in breast cancer patients remains unclear. A total of 200 formalin-fixed paraffin-embedded samples of invasive ductal carcinoma (IDC), and 37 adjacent non-neoplastic tissue (ANNT) samples from patients who had not been treated with neoadjuvant therapy were examined. Expression of Notch1, Slug, Snail, E-cadherin, N-cadherin, and vimentin was determined by immunohistochemistry on tissue microarrays (TMAs). The correlation between protein expression and clinicopathological characteristics of breast cancer patients was also evaluated. Results showed that a significantly high percentage of cases with high expression of Notch1 (74%, 148/200), Slug (36%, 72/200), Snail (62%, 124/200), and N-cadherin (77%, 153/200) and a low percentage of cases with high expression of E-cadherin (27%, 54/200) were observed in IDC compared to those in ANNTs. High Notch1, Slug, Snail, and N-cadherin expression and low E-cadherin expression in patients with IDC were significantly correlated with lymph node metastasis. In addition, correlation analysis results revealed that high Notch1 expression was significantly associated with high Slug, Snail, and N-cadherin expression and low E-cadherin expression in IDC. Furthermore, a high Snail expression was significantly associated with low E-cadherin expression, and a high Slug expression was found to be significantly associated with increased N-cadherin expression in patients with IDC. Hence, our study suggested that the Notch1-Snail/Slug-EMT axis may be implicated in the lymph node metastasis affecting patients with IDC.}, }
@article {pmid25644728, year = {2014}, author = {Moschetta, M and Telegrafo, M and Cornacchia, I and Vincenti, L and Ranieri, V and Cirili, A and Rella, L and Stabile Ianora, AA and Angelelli, G}, title = {PIP breast implants: rupture rate and correlation with breast cancer.}, journal = {Il Giornale di chirurgia}, volume = {35}, number = {11-12}, pages = {274-278}, pmid = {25644728}, issn = {0391-9005}, mesh = {Adult ; *Breast Implants ; Breast Neoplasms/*diagnosis/*epidemiology/etiology ; Female ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Prospective Studies ; *Prosthesis Failure ; }, abstract = {AIM: To evaluate the incidence of Poly Implant Prosthése (PIP) rupture as assessed by magnetic resonance imaging (MRI), the prevalence of the detected signs and the potential correlation with breast carcinoma.<br><br>PATIENTS AND METHODS: 67 patients with silicone breast implants and clinical indications for breast MRI were evaluated for a total of 125 implants: 40 (32%) PIP in 21 patients and 85 non-PIP in 46 patients (68%), the latest considered as control group. A 1.5-T MR imaging device was used in order to assess implant integrity with dedicated sequences and in 6 cases a dynamic study was performed for characterizing breast lesions. Two radiologists with more than 5 years' experience in the field of MRI evaluated in consensus all MR images searching for the presence of clear signs of intra or extra-capsular implant rupture.<br><br>RESULTS: 20/40 (50%) PIP implants presented signs of intra-capsular rupture: linguine sign in 20 cases (100%), tear-drop sign in 6 (30%). In 12/20 cases (60%), MRI signs of extra-capsular rupture were detected. In the control group, an intra-capsular rupture was diagnosed in 12/85 cases (14%) associated with extra-capsular one in 5/12 cases (42%). Among the six cases with suspected breast lesions, in 2/21 patients with PIP implants (10%) a breast carcinoma was diagnosed (mucinous carcinoma, n=1; invasive ductal carcinoma, n=1). In 4/46 patients (9%) with non-PIP implants, an invasive ductal carcinoma was diagnosed.<br><br>CONCLUSION: The rupture rate of PIP breast implants is significantly higher than non-PIP (50% vs 14%). MRI represents the most accurate imaging tool for evaluating breast prostheses and the linguine sign is the most common MRI sign to be searched. The incidence of breast carcinoma does not significantly differ between the PIP and non-PIP implants and a direct correlation with breast cancer can not been demonstrated.}, }
@article {pmid25640082, year = {2015}, author = {Li, L and Wang, K and Sun, X and Wang, K and Sun, Y and Zhang, G and Shen, B}, title = {Parameters of dynamic contrast-enhanced MRI as imaging markers for angiogenesis and proliferation in human breast cancer.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {21}, number = {}, pages = {376-382}, pmid = {25640082}, issn = {1643-3750}, mesh = {Adult ; Aged ; Antigens, CD/metabolism ; Biomarkers/metabolism ; Breast Neoplasms/*diagnosis/metabolism/*pathology ; Cell Proliferation ; Contrast Media/*chemistry ; Endoglin ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neovascularization, Pathologic/*pathology ; Permeability ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Prognosis ; Receptors, Cell Surface/metabolism ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy and the leading cause of cancer death in women worldwide; however, early diagnosis has been difficult due to its complex pathological structure. This study evaluated the value of morphological examination in conjunction with dynamic contrast-enhanced MRI (DCE-MRI) for more precise diagnosis of breast cancer, as well as their correlation with angiogenesis and proliferation biomarkers.<br><br>MATERIAL/METHODS: DCE-MRI parameters (including Ktrans: volume transfer coefficient reflecting vascular permeability, Kep: flux rate constant, Ve: extracellular volume ratio reflecting vascular permeability, and ADC: apparent diffusion coefficient) were obtained from 124 patients with breast cancer (124 lesions). Microvessel density (MVD) was evaluated by the immunohistochemical analysis of tumor vessels for CD31 and CD105 expression. The proliferation was assessed by analyzing Ki67.<br><br>RESULTS: Ktrans values were in the order of: malignant lesions>benign lesions>normal glands. Similar results were observed for Kep. The opposite changes were seen with Ve. Ktrans and Kep values were significantly higher in invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) than in mammary ductal dysplasia (MDD; ANOVA followed by Dunnett's test). In sharp contrast, ADC values were lower in IDC and DCIS than in MDD, and Ve was not significantly different among the three groups. The data from MIP (maximum intensity projection) showed that benign breast lesions had no or only one blood vessel, whereas malignant lesions had two or more blood vessels. In addition, expression of CD105 and Ki67, the commonly recognized markers for angiogenesis and proliferation, respectively, were closely correlated with MRI parameters as revealed by Pearson analysis.<br><br>CONCLUSIONS: Determination of Ktrans, Kep and ADC values permits estimation of tumor angiogenesis and proliferation in breast cancer and DCE-MRI parameters can be used as imaging biomarkers to predict patient prognosis and the biologic aggressiveness of the tumor.}, }
@article {pmid25620480, year = {2014}, author = {Hua, X and Huang, X and Liao, Z and Xian, Q and Yu, L}, title = {[Changes of fibroblast immunophenotype and their clinical significance in stromal remodeling of breast tumors].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {36}, number = {11}, pages = {834-838}, pmid = {25620480}, issn = {0253-3766}, mesh = {Breast ; Breast Neoplasms/immunology/*pathology ; Carcinoma in Situ ; Carcinoma, Ductal, Breast ; Carcinoma, Intraductal, Noninfiltrating ; Endopeptidases ; Fibroblasts/*immunology ; Gelatinases/metabolism ; Humans ; Hyperplasia ; Immunohistochemistry ; Immunophenotyping ; Membrane Proteins/metabolism ; Serine Endopeptidases/metabolism ; }, abstract = {OBJECTIVE: To evaluate the immunophenotype conversion of fibroblasts and its clinical significance in the process of breast tumor stromal remodeling.<br><br>METHODS: CD34, FAP-&#x3b1;, p63 and a-SMA were detected by immunohistochemistry in 273 breast biopsies, including 60 normal breast tissues, 46 atypical ductal hyperplasia (ADH), 60 ductal carcinoma in situ (DCIS), 47 DCIS microinvasive carcinoma (DCIS-MI) and 60 invasive ductal carcinoma (IDC).<br><br>RESULTS: The positive expression rates of CD34, FAP-&#x3b1; and &#x3b1;-SMA in the stromal fibroblasts of normal breast tissues were 93.3%, 6.7% and 18.3%, respectively. Those in the stromal fibroblasts of ADH tissues were 95.7%, 4.3% and 10.9%, respectively. Those in the stromal fibroblasts of DCIS tissues were 95.0%, 8.3% and 15.0%, respectively. Those in the IDC tissues were 35.0%, 85.0% and 93.3%, respectively. The expressions of CD34, &#x3b1;-SMA and FAP-&#x3b1; in the stromal fibroblasts of normal, ASH and DCIS breast tissues did not show significant differences (&#x3c7;(2) = 1.142, P = 0.896). The main immunophenotype of stromal fibroblasts in the tumor-host interface at the invasive front of ADH and DCIS lesions was CD34(+)&#x3b1;-SMA(+)FAP-&#x3b1;(+). There were statistically significant differences in the expression of CD34, &#x3b1;-SMA and FAP-&#x3b1; between IDC and ADH, DCIS and normal breast tissues (&#x3c7;(2) = 8.351, P < 0.001). The immunophenotype of stromal fibroblasts in the IDC and DCIS-MI breast tissues was CD34(-) &#x3b1;-SMA(+) FAP-&#x3b1;(+).<br><br>CONCLUSIONS: Immunophenotype conversion from CD34(+) &#x3b1;-SMA(-) FAP-&#x3b1;(-) to CD34(-) &#x3b1;-SMA(+)FAP-&#x3b1;(+) may be a sensitive indicator to judge whether DCIS has microinvasion. Detection of the immunophenotype conversion of stromal fibroblasts may be helpful to determine the presence of microinvasion, and to improve the diagnostic accuracy rate of DCIS.}, }
@article {pmid25604797, year = {2015}, author = {Braunstein, LZ and Brock, JE and Chen, YH and Truong, L and Russo, AL and Arvold, ND and Harris, JR}, title = {Invasive lobular carcinoma of the breast: local recurrence after breast-conserving therapy by subtype approximation and surgical margin.}, journal = {Breast cancer research and treatment}, volume = {149}, number = {2}, pages = {555-564}, doi = {10.1007/s10549-015-3273-y}, pmid = {25604797}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Lobular/*pathology/radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retreatment ; Risk Factors ; Time Factors ; Tumor Burden ; Young Adult ; }, abstract = {Invasive lobular carcinoma (ILC) typically presents at a later stage than invasive ductal carcinoma (IDC) and poses unique radiographic and surgical challenges. However, current principles of breast-conserving therapy (BCT) do not distinguish between histologic subtypes, raising uncertainty about the optimal approach for patients with ILC. We studied 998 BCT patients from 1998-2007, comprised 74 % IDC, 8 % ILC, and 18 % with mixed ILC/IDC. In light of recent guidelines addressing surgical margins, specimens were assessed for margin width and biologic subtype. The Kaplan-Meier method and Cox proportional hazards models were used to analyze effects of patient and disease characteristics on local recurrence (LR). At a median of 119 months, 45 patients had an isolated LR. 10-year LR was 5.5 % for patients with IDC, 4.4 % for ILC, and 1.2 % for mixed histology (p = 0.08). The majority of ILC cases had luminal A biologic subtype (91.1 %), and analysis among all luminal A cases revealed 10-year LR of 2.6 % for IDC, 3.4 % for ILC, and 0 % for mixed tumors (p = 0.12). Patients with ILC were more likely to have initially positive surgical margins (45.0 vs 17.5 %; p < 0.001) resulting in more frequent re-excision (57.1 % vs 40.4 %; p = 0.02), though final margins were similar between ILC and IDC (p = 0.88). No LR was observed among ILC or mixed histology patients with margins <2 mm (n = 28). On multivariate analysis, histologic subtype was not associated with LR (p = 0.52). Modern approaches confer similarly favorable LR rates for ILC, IDC, and mixed histology breast cancers despite inherent histologic differences. Patients with ILC did not require more extensive surgical margins than those with IDC.}, }
@article {pmid25598690, year = {2015}, author = {Choi, JW and Moon, WJ and Choi, N and Roh, HG and Kim, MY and Kim, NR and Moon, SG and Chung, HW and Lim, SD and Yang, JH}, title = {Charcoal-induced granuloma that mimicked a nodal metastasis on ultrasonography and FDG-PET/CT after neck dissection.}, journal = {Korean journal of radiology}, volume = {16}, number = {1}, pages = {196-200}, pmid = {25598690}, issn = {2005-8330}, mesh = {Breast Neoplasms/pathology/surgery/therapy ; Carcinoma/*pathology/surgery/therapy ; Cervix Uteri/diagnostic imaging/pathology ; Charcoal/toxicity ; Female ; Fluorodeoxyglucose F18 ; Granuloma/*diagnosis/pathology ; Humans ; Lymph Nodes/diagnostic imaging/*surgery ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Positron-Emission Tomography ; Radiopharmaceuticals ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Charcoal can be used for preoperative localization of metastatic lymph nodes in the neck. Charcoal remains stable without causing foreign body reactions during as hort period. However, foreign body reactions may develop if charcoal is left in situ for more than 6 months. We reported a case of charcoal granuloma mimicking local recurrence on fluorodeoxyglucose-positron emission tomography/computed tomography and ultrasonography in a 47-year-old woman who had cervical lymph node dissection due to metastatic invasive ductal carcinoma of the breast.}, }
@article {pmid25585858, year = {2015}, author = {Bas, R and Vallverdú, M and Valencia, JF and Voss, A and de Luna, AB and Caminal, P}, title = {Evaluation of acceleration and deceleration cardiac processes using phase-rectified signal averaging in healthy and idiopathic dilated cardiomyopathy subjects.}, journal = {Medical engineering &amp; physics}, volume = {37}, number = {2}, pages = {195-202}, doi = {10.1016/j.medengphy.2014.12.001}, pmid = {25585858}, issn = {1873-4030}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/diagnosis/*physiopathology ; Case-Control Studies ; Death, Sudden, Cardiac ; *Deceleration ; Feasibility Studies ; Female ; Follow-Up Studies ; Heart/*physiology/*physiopathology ; Humans ; Male ; Middle Aged ; Risk Assessment ; *Signal Processing, Computer-Assisted ; Sleep ; Wakefulness ; }, abstract = {The aim of the present study was to investigate the suitability of the Phase-Rectified Signal Averaging (PRSA) method for improved risk prediction in cardiac patients. Moreover, this technique, which separately evaluates acceleration and deceleration processes of cardiac rhythm, allows the effect of sympathetic and vagal modulations of beat-to-beat intervals to be characterized. Holter recordings of idiopathic dilated cardiomyopathy (IDC) patients were analyzed: high-risk (HR), who suffered sudden cardiac death (SCD) during the follow-up; and low-risk (LR), without any kind of cardiac-related death. Moreover, a control group of healthy subjects was analyzed. PRSA indexes were analyzed, for different time scales T and wavelet scales s, from RR series of 24 h-ECG recordings, awake periods and sleep periods. Also, the behavior of these indexes from simulated data was analyzed and compared with real data results. Outcomes demonstrated the PRSA capacity to significantly discriminate healthy subjects from IDC patients and HR from LR patients on a higher level than traditional temporal and spectral measures. The behavior of PRSA indexes agrees with experimental evidences related to cardiac autonomic modulations. Also, these parameters reflect more regularity of the autonomic nervous system (ANS) in HR patients.}, }
@article {pmid25585381, year = {2015}, author = {Yang, M and Tang, M and Ma, X and Yang, L and He, J and Peng, X and Guo, G and Zhou, L and Luo, N and Yuan, Z and Tong, A}, title = {AP-57/C10orf99 is a new type of multifunctional antimicrobial peptide.}, journal = {Biochemical and biophysical research communications}, volume = {457}, number = {3}, pages = {347-352}, doi = {10.1016/j.bbrc.2014.12.115}, pmid = {25585381}, issn = {1090-2104}, mesh = {Amino Acid Sequence ; Antimicrobial Cationic Peptides/chemistry/*genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; Colorectal Neoplasms/genetics/metabolism/pathology ; Conserved Sequence ; DNA, Neoplasm/metabolism ; DNA-Binding Proteins/chemistry/*genetics/*metabolism ; Humans ; Molecular Sequence Data ; Recombinant Proteins/genetics/metabolism ; Sequence Homology, Amino Acid ; Tissue Distribution ; Tumor Suppressor Proteins/chemistry/genetics/metabolism ; }, abstract = {Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune response that provides host defence at skin and mucosal surfaces. Here, we report the identification and characterization of a new type human AMPs, termed AP-57 (Antimicrobial Peptide with 57 amino acid residues), which is also known as C10orf99 (chromosome 10 open reading frame 99). AP-57 is a short basic amphiphilic peptide with four cysteines and a net charge +14 (MW = 6.52, PI = 11.28). The highest expression of AP-57 were detected in the mucosa of stomach and colon through immunohistochemical assay. Epithelium of skin and esophagus show obvious positive staining and strong positive staining were also observed in some tumor and/or their adjacent tissues, such as esophagus cancer, hepatocellular carcinoma, squamous cell carcinoma and invasive ductal carcinoma. AP-57 exhibited broad-spectrum antimicrobial activities against Gram-positive Staphylococcus aureus, Actinomyce, and Fungi Aspergillus niger as well as mycoplasma and lentivirus. AP-57 also exhibited DNA binding capacity and specific cytotoxic effects against human B-cell lymphoma Raji. Compared with other human AMPs, AP-57 has its distinct characteristics, including longer sequence length, four cysteines, highly cationic character, cell-specific toxicity, DNA binding and tissue-specific expressing patterns. Together, AP-57 is a new type of multifunctional AMPs worthy further investigation.}, }
@article {pmid25583208, year = {2015}, author = {Bursle, EC and Dyer, J and Looke, DF and McDougall, DA and Paterson, DL and Playford, EG}, title = {Risk factors for urinary catheter associated bloodstream infection.}, journal = {The Journal of infection}, volume = {70}, number = {6}, pages = {585-591}, doi = {10.1016/j.jinf.2015.01.001}, pmid = {25583208}, issn = {1532-2742}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Australia/epidemiology ; Bacteremia ; Case-Control Studies ; Catheter-Related Infections/drug therapy/*epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors ; Urinary Catheterization/*adverse effects ; Urinary Catheters/*adverse effects ; Urinary Tract Infections/drug therapy/*epidemiology ; }, abstract = {OBJECTIVES: Urinary catheter associated bloodstream infection (UCABSI) causes significant morbidity, mortality and healthcare costs. We aimed to define the risk factors for UCABSI.<br><br>METHODS: A case-control study was conducted at two Australian tertiary hospitals. Patients with urinary source bloodstream infection associated with an indwelling urinary catheter (IDC) were compared to controls with an IDC who did not develop urinary source bloodstream infection.<br><br>RESULTS: There were 491 controls and 67 cases included in the analysis. Independent statistically significant risk factors for the development of UCABSI included insertion of the catheter in operating theatre, chronic kidney disease, age-adjusted Charlson comorbidity index, accurate urinary measurements as reason for IDC insertion and dementia. IDCs were inserted for valid reasons in nearly all patients, however an appropriate indication at 48 h post-insertion was found in only 44% of patients. Initial empiric antibiotics were deemed inappropriate in 23 patients (34%).<br><br>CONCLUSION: To our knowledge, this is the first study to look specifically at the risk factors for bloodstream infection in urinary catheterised patients. Several risk factors were identified. IDC management and empiric management of UCABSI could be improved and is likely to result in a decreased incidence of infection and its complications.}, }
@article {pmid25574147, year = {2014}, author = {Yano, H and Nakayama, N and Morimitsu, K and Futamura, M and Ohe, N and Miwa, K and Shinoda, J and Iwama, T}, title = {Changes in protein level in the cerebrospinal fluid of a patient with cerebral radiation necrosis treated with bevacizumab.}, journal = {Clinical Medicine Insights. Oncology}, volume = {8}, number = {}, pages = {153-157}, pmid = {25574147}, issn = {1179-5549}, abstract = {A 32-year-old woman underwent surgeries and radiation therapy for astrocytoma. She developed symptomatic radiation necrosis in the lesion, which caused hydrocephalus. She initially underwent ventricular drainage, because the protein level in the cerebrospinal fluid (CSF) was 787 mg/dL, which was too high for shunt surgery. Because she also had breast cancer, which was pathologically diagnosed as an invasive ductal carcinoma, standard bevacizumab therapy in combination with paclitaxel every 2 weeks was selected. Interestingly, after 2 days, the agents had dramatically reduced the CSF protein level. However, it returned to approximately the initial level within 2 weeks. After two courses of this regimen, a ventriculoperitoneal shunt was placed. After 10 courses of this regimen, the CSF protein level decreased to 338 mg/dL, which is less than half of the initial level. Long-term administration of bevacizumab might decrease leakage of protein from the vessels around the ventriculus.}, }
@article {pmid25571972, year = {2015}, author = {Vogel, S and Börger, V and Peters, C and Förster, M and Liebfried, P and Metzger, K and Meisel, R and Däubener, W and Trapp, T and Fischer, JC and Gawaz, M and Sorg, RV}, title = {Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death.}, journal = {Cell death and differentiation}, volume = {22}, number = {7}, pages = {1219-1230}, pmid = {25571972}, issn = {1476-5403}, mesh = {Animals ; *Apoptosis ; Chemotaxis ; Dendritic Cells/*physiology ; HMGB1 Protein/*metabolism ; Hepatocyte Growth Factor/*metabolism ; Humans ; Inflammation ; Male ; Mesenchymal Stem Cells/*physiology ; Mice ; Monocytes/*physiology ; Myocytes, Cardiac/metabolism/physiology ; *Necrosis ; Neurons/metabolism/physiology ; Regeneration ; }, abstract = {Tissue damage due to apoptotic or necrotic cell death typically initiates distinct cellular responses, leading either directly to tissue repair and regeneration or to immunological processes first, to clear the site, for example, of potentially damage-inducing agents. Mesenchymal stem cells (MSC) as well as immature dendritic cells (iDC) and monocytes migrate to injured tissues. MSC have regenerative capacity, whereas monocytes and iDC have a critical role in inflammation and induction of immune responses, including autoimmunity after tissue damage. Here, we investigated the influence of apoptotic and necrotic cell death on recruitment of MSC, monocytes and iDC, and identified hepatocyte growth factor (HGF) and the alarmin high mobility group box 1 (HMGB1) as key factors differentially regulating these migratory responses. MSC, but not monocytes or iDC, were attracted by apoptotic cardiomyocytic and neuronal cells, whereas necrosis induced migration of monocytes and iDC, but not of MSC. Only apoptotic cell death resulted in HGF production and HGF-mediated migration of MSC towards the apoptotic targets. In contrast, HMGB1 was predominantly released by the necrotic cells and mediated recruitment of monocytes and iDC via the receptor of advanced glycation end products. Moreover, necrotic cardiomyocytic and neuronal cells caused an HMGB1/toll-like receptor-4-dependent inhibition of MSC migration towards apoptosis or HGF, while recruitment of monocytes and iDC by necrosis or HMGB1 was not affected by apoptotic cells or HGF. Thus, the type of cell death differentially regulates recruitment of either MSC or monocytes and iDC through HGF and HMGB1, respectively, with a dominant, HMGB1-mediated role of necrosis in determining tropism after tissue injury.}, }
@article {pmid27386035, year = {2015}, author = {Adeniji-Sofoluwe, AT and Obajimi, GO and Obajimi, MO}, title = {Pregnancy related breast diseases in a developing African country: Initial Sonographic Evaluation.}, journal = {The Pan African medical journal}, volume = {20}, number = {}, pages = {239}, pmid = {27386035}, issn = {1937-8688}, mesh = {Adult ; Breast Diseases/diagnosis/*epidemiology/pathology ; Breast Feeding ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology ; Female ; Humans ; Lactation ; Nigeria/epidemiology ; Nipple Discharge ; Pregnancy ; Pregnancy Complications/diagnosis/*epidemiology/pathology ; Pregnancy Complications, Neoplastic/diagnosis/*epidemiology/pathology ; Retrospective Studies ; Risk Factors ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {Benign diseases are more common than malignant diseases in pregnant and lactating women. Fibroadenomas are the most commonly identified benign breast tumour in pregnant and lactating women. Pregnancy related breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at 1 in 3000 to 1 in 10 000 pregnancies. Several reproductive factors like age at menarche, age at menopause, age at full-term pregnancy, parity, age at any birth and spacing of pregnancies, breast feeding, characteristics of the menstrual cycle, infertility, spontaneous and induced abortions, characteristics of the menstrual cycle and infertility are some of the factors that have been incriminated as risk factors for breast cancer. We sought to describe the predominant breast pattern, sonographic array of pregnancy related breast diseases in women referred to the breast imaging unit in the department of Radiology at the University College Hospital, Ibadan south west Nigeria. Socio-demographic characteristics in these women were also evaluated. Archived images were reviewed and documented and data was analysed with SPSS version 17 and presented with descriptives. In this descriptive study, we retrospectively retrieved the sonomammographic records of 21 women (pregnant or lactating) referred to and imaged in the department of radiology, University college hospital Ibadan, between 2006 and 2013. Diagnostic breast sonograms performed by MO and ATS; Consultant radiologists with 7-10 years' experience utilized a 7-10 MHz transducer of the General electric GE Logiq P5 machine for the scans. Twenty-one women with ages between 22-42 years (Mean 31.4 ± 5.4 SD) pregnant or lactating were referred to the radiology department for sonomammographic evaluation. Majority of the women were in the 3rd decade. Referral was mainly (11) by family Physicians from the general outpatient clinic, 5 were self-referred, 2 from radiotherapy department, 2 from obstetrics and gynaecology department and 1 from the surgical outpatient clinic. Nineteen (89.5%) were lactating and breastfeeding while 2 (10.5%) were pregnant. Nipple discharge (89.5%) was the predominant presenting complaint in the study. They were all married with the majority attaining menarche at age 14.6 ± 2.1 SD years. Most of the women were multi-parous 17(89.5%) and possessed higher level of Education 17 (81.0%). Twenty (96.0%) women had no previous breast disease while only 1 (4.0%) woman had a positive family history of breast cancer. They weighed between 44-102 kg (mean 69.84 kg ± 15.33 SD). Their mean height was 159.8 cm. Waist hip ratio was between 0.69-0.93 (Mean 0.83). The heterogeneous fibroglandular pattern was predominant in 15 (71.4%) women. Final BIRADS assessment of 2 was most frequent (11/21) 52.4% while 19.0% were assigned to BIRADS categories 0 and 1 (4/21). Histological diagnosis of Invasive ductal carcinoma was made in the 3 women with final BIRADS of 5 breast diseases found in most pregnant and lactating women were benign. It is important to note that malignant breast lesions can also occur in this group of women who may assume that the changes noted in their breast are due to lactation.}, }
@article {pmid25527452, year = {2015}, author = {Huang, KT and Tan, D and Chen, KE and Walker, AM}, title = {Blockade of estrogen-stimulated proliferation by a constitutively-active prolactin receptor having lower expression in invasive ductal carcinoma.}, journal = {Cancer letters}, volume = {358}, number = {2}, pages = {152-160}, doi = {10.1016/j.canlet.2014.12.031}, pmid = {25527452}, issn = {1872-7980}, mesh = {Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Estradiol/metabolism/pharmacology ; Estrogens/*metabolism/pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasm Invasiveness ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Receptors, Prolactin/chemistry/genetics/*metabolism ; }, abstract = {A comprehensive understanding of prolactin's (PRL's) role in breast cancer is complicated by disparate roles for alternatively-spliced PRL receptors (PRLR) and crosstalk between PRL and estrogen signaling. Among PRLRs, the short form 1b (SF1b) inhibits PRL-stimulated cell proliferation. In addition to ligand-dependent PRLRs, constitutively-active varieties, missing the S2 region of the extracellular domain (ΔS2), naturally occur. Expression analysis of the ΔS2 version of SF1b (ΔS2SF1b) showed higher expression in histologically-normal contiguous tissue versus invasive ductal carcinoma. To determine the function of ΔS2SF1b, a T47D breast cancer line with inducible expression was produced. Induction of ΔS2SF1b blocked estrogen-stimulated cell proliferation. Unlike intact SF1b, induction of ΔS2SF1b had no effect on PRL-mediated activation of Stat5a. However induction inhibited estrogen's stimulatory effects on serine-118 phosphorylation of estrogen receptor α, serine-473 phosphorylation of Akt, serine-9 phosphorylation of GSK3β, and c-myc expression. In addition, induction of ΔS2SF1b increased expression of the cell cycle-inhibiting protein, p21. Thus, increased expression of ΔS2SF1b, such as we demonstrate occurs with the selective PRLR modulator, S179D PRL, would create a physiological state in which estrogen-stimulated proliferation was inhibited, but differentiative responses to PRL were maintained.}, }
@article {pmid25523328, year = {2014}, author = {Lappalainen, AK and Vaittinen, E and Junnila, J and Laitinen-Vapaavuori, O}, title = {Intervertebral disc disease in Dachshunds radiographically screened for intervertebral disc calcifications.}, journal = {Acta veterinaria Scandinavica}, volume = {56}, number = {1}, pages = {89}, pmid = {25523328}, issn = {1751-0147}, mesh = {Animals ; Calcinosis/diagnostic imaging/epidemiology/etiology/*veterinary ; Dog Diseases/diagnostic imaging/*epidemiology/etiology ; Dogs ; Finland/epidemiology ; Intervertebral Disc Degeneration/diagnostic imaging/epidemiology/etiology/*veterinary ; Intervertebral Disc Displacement/diagnostic imaging/epidemiology/etiology/*veterinary ; Mass Screening/veterinary ; Radiography ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Intervertebral disc disease (IDD) is a very common neurological disease, Dachshunds being the breed most often affected. In this breed, IDD has a hereditary background and is associated with intervertebral disc calcification (IDC), an indicator of severe intervertebral disc degeneration. In Finland, spinal radiography is used, when screening for IDC before breeding Dachshunds. We evaluated the association between IDC and IDD in Finnish Dachshunds radiographically screened for IDC. A questionnaire was sent to owners of 193 radiographically screened Dachshunds aged at least ten years. Clinical signs indicative of IDD were compared with IDC grade (grade 0 = no calcifications, grade 1 = 1 - 2 calcifications, grade 2 = 3 - 4 calcifications and grade 3 = 5 or more calcifications) and with age at the time of the radiographic examination. The diagnosis of IDD was confirmed by a veterinarian.<br><br>RESULTS: IDD was common in the study population with 31% of dogs being affected. IDD and IDC were clearly connected (P&#x2009;<&#x2009;0.001); IDD was rare in dogs with no calcifications (grade 0) and common in dogs with severe IDC (grade 3). The IDC grade was strongly positively associated with frequency of back pain periods (P&#x2009;<&#x2009;0.001), and dogs with IDC grade 3 had frequent periods of pain. Reluctance to jump onto a sofa had a strong positive association with back pain. No association existed between age of the dog at the time of the radiographic examination and clinical signs indicative of IDD.<br><br>CONCLUSIONS: Radiographically detected IDC and IDD are common in Finnish Dachshunds and are strongly associated with one another. Spinal radiography is an appropriate screening tool for breeders attempting to diminish IDC and IDD in Dachshunds. A breeding program that screens dogs and selects against IDC can be expected to reduce the occurrence of IDD in future. Twenty-four to 48 months of age is a suitable age for screening.}, }
@article {pmid25518541, year = {2014}, author = {Andjelić-Dekić, N and Božović-Spasojević, I and Milošević, S and Matijašević, M and Karadžić, K}, title = {A rare case of isolated adrenal metastasis of invasive ductal breast carcinoma.}, journal = {Srpski arhiv za celokupno lekarstvo}, volume = {142}, number = {9-10}, pages = {597-601}, doi = {10.2298/sarh1410597a}, pmid = {25518541}, issn = {0370-8179}, mesh = {Adrenal Gland Neoplasms/drug therapy/*secondary ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; Trastuzumab/therapeutic use ; }, abstract = {INTRODUCTION: Isolated adrenal metastases of invasive ductal breast carcinoma are extremely rare. We report a case with isolated left adrenal metastases, verified three years after diagnosed breast carcinoma.<br><br>CASE OUTLINE: A 58-year-old female patient with a right breast tumor, clinically staged as IIIA (T2N2M0) started neoadjuvant anthracycline chemotherapy after biopsy which revealed invasive ductal breast carcinoma. Immunohistochemical findings of tumor biopsy showed hormonal steroid receptors for estrogen and progesterone negative, and human epidermal growth factor receptor 2 (HER2) positive. After 4 cycles of chemotherapy and partial tumor regression the patient underwent radical mastectomy. Definite histopathological analysis confirmed the diagnosis of invasive ductal carcinoma. The patient continued treatment with adjuvant chemotherapy to cumulative dose of anthracyclines, postoperative radiotherapy and adjuvant trastuzumab for one year. Three years later abdominal computerized tomography showed tumor in the left adrenal gland as the only metastatic site. Left adrenalectomy was performed and histopathological finding confirmed breast cancer metastases. Postoperatively, the patient received 6 cycles of docetaxel with trastuzumab and continued trastuzumab until disease progression. One year after left adrenalectomy control abdominal computerized tomography showed a right adrenal tumor with retroperitoneal lymphadenopathy. Treatment with capecitabine was continued for one year, but eventually she developed brain metastasis causing lethal outcome.<br><br>CONCLUSION: In order to better understand metastatic pathways of invasive ductal breast carcinoma, publications of individual patient cases diagnosed with rare metastatic sites should be encouraged. This might improve our understanding of metastatic behavior of breast cancer and stimulate further clinical research.}, }
@article {pmid25493218, year = {2014}, author = {Wazir, U and Mokbel, K}, title = {Emerging gene-based prognostic tools in early breast cancer: First steps to personalised medicine.}, journal = {World journal of clinical oncology}, volume = {5}, number = {5}, pages = {795-799}, pmid = {25493218}, issn = {2218-4333}, abstract = {Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor (ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.}, }
@article {pmid25486426, year = {2015}, author = {Chen, C and Wang, X and Xiong, X and Liu, Q and Huang, Y and Xu, Q and Hu, J and Ge, G and Ling, K}, title = {Targeting type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis.}, journal = {Oncogene}, volume = {34}, number = {35}, pages = {4635-4646}, pmid = {25486426}, issn = {1476-5594}, support = {R01 CA149039/CA/NCI NIH HHS/United States ; R01 DK090038/DK/NIDDK NIH HHS/United States ; R01 DK099160/DK/NIDDK NIH HHS/United States ; 1R01CA149039-01A1/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; ErbB Receptors/metabolism ; Female ; Gene Knockdown Techniques ; Lung Neoplasms/*enzymology/secondary ; Mammary Neoplasms, Experimental/*enzymology/pathology ; Mice, Inbred BALB C ; Neoplasm Invasiveness ; Phosphotransferases (Alcohol Group Acceptor)/*genetics/metabolism ; Protein Processing, Post-Translational ; RNA, Small Interfering/genetics ; }, abstract = {Most deaths from breast cancer are caused by metastasis, a complex behavior of cancer cells involving migration, invasion, survival and microenvironment manipulation. Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) regulates focal adhesion assembly and its phosphorylation at Y639 is critical for cell migration induced by EGF. However, the role of this lipid kinase in tumor metastasis remains unclear. Here we report that PIPKIγ is vital for breast cancer metastasis. Y639 of PIPKIγ can be phosphorylated by stimulation of EGF and hepatocyte growth factor (HGF), two promoting factors for breast cancer progression. Histological analysis revealed elevated Y639 phosphorylation of PIPKIγ in invasive ductal carcinoma lesions and suggested a positive correlation with tumor grade. Orthotopically transplanted PIPKIγ-depleted breast cancer cells showed substantially reduced growth and metastasis, as well as suppressed expression of multiple genes related to cell migration and microenvironment manipulation. Re-expression of wild-type PIPKIγ in PIPKIγ-depleted cells restored tumor growth and metastasis, reinforcing the importance of PIPKIγ in breast cancer progression. Y639-to-F or a kinase-dead mutant of PIPKIγ could not recover the diminished metastasis in PIPKIγ-depleted cancer cells, suggesting that Y639 phosphorylation and lipid kinase activity are both required for development of metastasis. Further analysis with in vitro assays indicated that depleting PIPKIγ inhibited cell proliferation, MMP9 secretion and cell migration and invasion, lending molecular mechanisms for the eliminated cancer progression. These results suggest that PIPKIγ, downstream of EGF and/or HGF receptor, participates in breast cancer progression from multiple aspects and deserves further studies to explore its potential as a therapeutic target.}, }
@article {pmid25481753, year = {2015}, author = {Yasaka, R and Ohba, K and Schwinghamer, MW and Fletcher, J and Ochoa-Corona, FM and Thomas, JE and Ho, SYW and Gibbs, AJ and Ohshima, K}, title = {Phylodynamic evidence of the migration of turnip mosaic potyvirus from Europe to Australia and New Zealand.}, journal = {The Journal of general virology}, volume = {96}, number = {Pt 3}, pages = {701-713}, doi = {10.1099/jgv.0.000007}, pmid = {25481753}, issn = {1465-2099}, mesh = {Australia ; Biological Evolution ; Brassicaceae/*virology ; Europe ; Genome, Viral ; Molecular Sequence Data ; Mosaic Viruses/genetics/*isolation &amp; purification ; New Zealand ; Phylogeny ; Phylogeography ; Plant Diseases/*virology ; Reassortant Viruses ; Time Factors ; }, abstract = {Turnip mosaic virus (TuMV) is a potyvirus that is transmitted by aphids and infects a wide range of plant species. We investigated the evolution of this pathogen by collecting 32 isolates of TuMV, mostly from Brassicaceae plants, in Australia and New Zealand. We performed a variety of sequence-based phylogenetic and population genetic analyses of the complete genomic sequences and of three non-recombinogenic regions of those sequences. The substitution rates, divergence times and phylogeographical patterns of the virus populations were estimated. Six inter- and seven intralineage recombination-type patterns were found in the genomes of the Australian and New Zealand isolates, and all were novel. Only one recombination-type pattern has been found in both countries. The Australian and New Zealand populations were genetically different, and were different from the European and Asian populations. Our Bayesian coalescent analyses, based on a combination of novel and published sequence data from three non-recombinogenic protein-encoding regions, showed that TuMV probably started to migrate from Europe to Australia and New Zealand more than 80 years ago, and that distinct populations arose as a result of evolutionary drivers such as recombination. The basal-B2 subpopulation in Australia and New Zealand seems to be older than those of the world-B2 and -B3 populations. To our knowledge, our study presents the first population genetic analysis of TuMV in Australia and New Zealand. We have shown that the time of migration of TuMV correlates well with the establishment of agriculture and migration of Europeans to these countries.}, }
@article {pmid25478233, year = {2014}, author = {Mirmalek, SA and Hajilou, M and Salimi Tabatabaee, SA and Parsa, Y and Yadollah-Damavandi, S and Parsa, T}, title = {Prevalence of HER-2 and Hormone Receptors and P53 Mutations in the Pathologic Specimens of Breast Cancer Patients.}, journal = {International journal of breast cancer}, volume = {2014}, number = {}, pages = {564308}, pmid = {25478233}, issn = {2090-3170}, abstract = {Prognostic factors are in interest for breast cancer as the second cause of malignancy deaths. Some have predictive values as human epidermal growth factor receptor-2 (HER-2) and estrogen receptor (ER). To access the incidence of HER2 and its relations to other factors, like age, pathology, ER, progesterone receptor (PR), and P53, 2000 pathologic blocks from 2750 total samples have been selected from 2011 to 2013 in Cancer Institute of Tehran. Incidence of HER2, ER, PR, and P53 was; 58.5%, 33.4%, 43.3%, and 65.4%, respectively. Invasive ductal carcinoma was the most pathologic type (82.2%) and 60%-70% positive HER2 and P53 had negative ER and PR (poor prognosis). The peak age of incidence of breast cancer was perimenopausal age group (46-55 years). Our cases had more positive HER2 and P53 and less positive PR and ER compared to other studies. High perimenopausal incidence as another finding assures the importance of breast cancer screening in these age groups.}, }
@article {pmid25476558, year = {2015}, author = {Singh, TP and Blume, ED and Alexander, PM and Gauvreau, K}, title = {Association of hemodynamic profiles with wait-list mortality in children listed for heart transplantation with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {115}, number = {2}, pages = {243-248}, doi = {10.1016/j.amjcard.2014.10.030}, pmid = {25476558}, issn = {1879-1913}, mesh = {Adolescent ; Cardiomyopathy, Dilated/mortality/physiopathology/*surgery ; Cause of Death/trends ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; *Heart Transplantation ; Humans ; Infant ; Male ; Pulmonary Wedge Pressure/physiology ; Retrospective Studies ; Risk Assessment/*methods ; Risk Factors ; Survival Rate/trends ; Time Factors ; United States/epidemiology ; Waiting Lists/*mortality ; }, abstract = {The prognostic significance of intracardiac hemodynamics in children with advanced heart failure is unknown. The purpose of this study was to describe hemodynamic profiles in children with idiopathic dilated cardiomyopathy (IDC) listed for heart transplant (HT) and to assess their association with wait-list mortality. We identified all US children <18 years with IDC listed for HT during 2000 to 2010 with available pulmonary capillary wedge pressure (PCWP) and cardiac index (CIx) data. We excluded children on ventilator or mechanical support at listing. CIx >2.2 L/min/m(2) (warm) and PCWP >18 mm Hg (wet) were used to define 4 hemodynamic profiles: warm-dry, warm-wet, cold-dry, and cold-wet. The primary end point was death on the wait-list or becoming too sick to transplant. Of 476 children analyzed, 248 (52%) children had PCWP >18 mm Hg and 300 (63%) had CIx >2.2 L/min/m(2). Overall, 36% children were warm-dry, 27% were warm-wet, 12% were cold-dry, and 25% were cold-wet; 32 (6.7%) children reached the primary end point. In adjusted analysis, cold-dry (hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.1, 11.5) and cold-wet (HR 3.2, 95% CI 1.2, 8.6) children were at higher risk of wait-list death versus warm-dry children, whereas warm-wet children were not (HR 2.3, 95% CI 0.8, 6.6). All groups were equally likely to receive HT and had similar 1-year post-transplant survival. In conclusion, in children with IDC listed for HT, those with low cardiac output at evaluation are at higher risk of wait-list mortality. Defining hemodynamic profiles may improve risk stratification of children with IDC listed for HT.}, }
@article {pmid25466398, year = {2015}, author = {Alberti, N and Bechade, D and Dupuis, F and Crombe, A and Neuville, A and Debled, M and Palussiere, J and Buy, X and Perez, JT and Desjardin, M and Frulio, N and Kind, M}, title = {Hepar lobatum carcinomatosum associated with liver metastases from breast cancer: report of five cases.}, journal = {Diagnostic and interventional imaging}, volume = {96}, number = {1}, pages = {73-78}, doi = {10.1016/j.diii.2014.11.003}, pmid = {25466398}, issn = {2211-5684}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Liver Neoplasms/*pathology/*secondary ; Middle Aged ; }, abstract = {BACKGROUNDS AND AIMS: Hepar lobatum carcinomatosum (HLC) is an exceptional acquired hepatic distortion which consists in irregularly lobulated hepatic contours seen in patients with known liver metastases, usually from breast carcinoma. We aimed to describe and analyze five similar cases of HLC resulting from metastatic mammary carcinoma in the liver and associated with rapid hepatic failure.<br><br>METHODS: Five cases of HLC were investigated. Medical (including blood liver tests), radiological and histological data (2 cases) were collected and retrospectively analyzed. All patients were followed up for metastatic invasive ductal carcinoma of the breast and had a common pattern of treatment with combination of targeted therapies (bevacizumab, AVASTIN) and chemotherapy (paclitaxel, TAXOL).<br><br>RESULTS: All the patients showed rapid hepatic failure after a mean of 9 courses of bevacizumab/paclitaxel. In all cases, liver imaging revealed liver capsule retraction and an irregular lobular margin. An apparent tumor regression of all liver metastases was showed in two cases. Biopsies were consistent with sinusoidal obstruction syndrome (SOS) and, surprisingly, no tumoral cells were found.<br><br>CONCLUSION: Although rare, such an unusual pattern of liver metastasis may mimick acute cirrhosis and cause rapid hepatic failure in patients, despite possible apparent tumor regression on imaging. The etiology of this pathology is unclear, and may involve multiple pathogenic factors. Direct or indirect vascular injury plays an important role in the development of HLC.}, }
@article {pmid25459069, year = {2015}, author = {Yu, JI and Choi, DH and Huh, SJ and Ahn, SJ and Lee, JS and Shin, KH and Kwon, Y and Kim, YB and Suh, CO and Kim, JH and Cho, J and Kim, IA and Lee, JH and Park, W}, title = {Unique characteristics and failure patterns of metaplastic breast cancer in contrast to invasive ductal carcinoma: a retrospective multicenter case-control study (KROG 13-07).}, journal = {Clinical breast cancer}, volume = {15}, number = {2}, pages = {e105-15}, doi = {10.1016/j.clbc.2014.10.002}, pmid = {25459069}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local/*mortality ; Prognosis ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/mortality/*pathology ; Young Adult ; }, abstract = {BACKGROUND: This retrospective study was performed to investigate the need for management modification in MBC according to evaluation of characteristics and failure patterns compared with IDC.<br><br>PATIENTS AND METHODS: We performed this multicenter study taking MBC and randomly assigned IDC cases matched for age (&#xb1; 3 years), pathologic stage (T and N), locoregional treatment methods (surgery with or without radiation therapy), and period of treatment (&#xb1; 6 months) that occurred from January 1999 to November 2011 in the 6 institutions of the Korean Radiation Oncology Group.<br><br>RESULTS: A total of 144 female MBC patients were enrolled. The median follow-up was 51 months (range, 1-186 months). The rates of positivity for estrogen receptor (P < .001), progesterone receptor (P < .001), and HER2 (P = .007) were significantly lower in MBC patients. During follow-up, recurrence developed in 22 (15.3%) MBC and 6 (4.2%) IDC patients (P = .002). The median time to recurrence of MBC and IDC was 15 months and 24 months, respectively. Most instances of recurrence in MBC developed in the triple-negative (TN) subgroup (TN-MBC). In particular, locoregional recurrence developed exclusively in the TN-MBC subgroup. In the TN-MBC subgroup, the number of risk factors (pT2-3, N1-3) was related to significant differences in overall survival (P = .001) and recurrence-free survival (P < .001).<br><br>CONCLUSION: The MBC patients had a higher rate of TN, poorer differentiation, and a higher recurrence rate than did the IDC patients. Considering the unique characteristics and failure patterns, it is necessary to modify the current management guidelines for MBC.}, }
@article {pmid25457635, year = {2014}, author = {Xia, HJ and He, BL and Wang, CY and Zhang, HL and Ge, GZ and Zhang, YX and Lv, LB and Jiao, JL and Chen, C}, title = {PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {50}, number = {18}, pages = {3230-3242}, doi = {10.1016/j.ejca.2014.10.012}, pmid = {25457635}, issn = {1879-0852}, mesh = {9,10-Dimethyl-1,2-benzanthracene ; Animals ; Carcinogens ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Papillary/genetics ; *Disease Models, Animal ; Estrogens/metabolism ; Female ; Mammary Glands, Animal/metabolism ; Mammary Neoplasms, Animal/chemically induced/*genetics ; Mammary Neoplasms, Experimental/chemically induced/*genetics ; Medroxyprogesterone Acetate ; Mutation/*genetics ; PTEN Phosphohydrolase/*genetics ; Papilloma, Intraductal/genetics ; Phosphatidylinositol 3-Kinase/*genetics ; Progesterone/metabolism ; Random Allocation ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tupaiidae ; }, abstract = {Tree shrew has increasingly become an attractive experimental animal model for human diseases, particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. However, neither normal mammary glands nor breast tumours have been well characterised in the Chinese tree shrew (Tupaia belangeri chinensis). In this study, normal mammary glands from four different developmental stages and 18 spontaneous breast tumours were analysed. Haematoxylin and eosin (H&amp;E) staining and immunohistochemistry (IHC) showed that normal mammary gland morphology and structures of tree shrews were quite similar to those found in humans. Spontaneous breast tumours of tree shrews were identified as being intraductal papilloma, papillary carcinoma, and invasive ductal carcinoma with or without lung metastasis. To further analyse breast cancer tumours among tree shrews, 40 3-4 month-old female tree shrews were orally administrated 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil thrice, and then, 15 of these DMBA administrated tree shrews were implanted with medroxyprogesterone acetate (MPA) pellets. DMBA was shown to induce breast tumours (12%) while the addition of MPA increased the tumour incidence (50%). Of these, three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma (IDC). The PTEN/PIK3CA (phosphatase and tensin homologue/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), but not TP53 and GATA3, genes are frequently mutated in breast tumours, and the PTEN/PIK3CA gene mutation status correlated with the expression of pAKT in tree shrew breast tumours. These results suggest that tree shrews may be a promising animal model for a subset of human breast cancers with PTEN/PIK3CA gene mutations.}, }
@article {pmid25455606, year = {2014}, author = {Bozorgmehr, M and Moazzeni, SM and Salehnia, M and Sheikhian, A and Nikoo, S and Zarnani, AH}, title = {Menstrual blood-derived stromal stem cells inhibit optimal generation and maturation of human monocyte-derived dendritic cells.}, journal = {Immunology letters}, volume = {162}, number = {2 Pt B}, pages = {239-246}, doi = {10.1016/j.imlet.2014.10.005}, pmid = {25455606}, issn = {1879-0542}, mesh = {Adult ; Antigens, Differentiation/immunology ; Cell Differentiation/*immunology ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology/*immunology ; Female ; Humans ; Interleukin-10/immunology ; Interleukin-6/immunology ; *Menstruation ; Mesenchymal Stem Cells/cytology/*immunology ; Monocytes/cytology/*immunology ; }, abstract = {INTRODUCTION: Menstrual blood stromal stem Cells (MenSCs) have shown promising potential for future clinical settings. Nonetheless, data regarding their interaction with immune cells is still scarce. Here, we investigated whether MenSCs could affect the generation and/or maturation of human blood monocyte-derived dendritic cells (DCs).<br><br>MATERIALS AND METHODS: MenSCs were isolated from menstrual blood of normal women through culture of adherent mononuclear cells. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) in the presence or absence of MenSCs. Monocyte-derived cells were assessed for the percentage of monocyte-, iDC-, and mDC-specific markers as well as the expression of costimulatory molecules. IL-6 and IL-10 levels were also determined in supernatants of MenSC-monocytes cocultures.<br><br>RESULTS: Optimal phenotypic differentiation of monocytes into iDCs was inhibited upon coculture with MenSCs. Moreover, higher levels of IL-6 and IL-10 were detected in these settings. Even though addition of MenSCs to iDC cultures could not prevent iDC maturation, coculture of MenSCs with monocytes from the beginning of differentiation process could effectively hinder generation of fully mature DCs.<br><br>CONCLUSION: This is the first study to address the inhibitory impact of MenSCs on generation and maturation of DCs. IL-6 and IL-10 could be partly held responsible for this effect. Given the central roles of DCs in regulation of immune responses, these results highlight the importance of further research on the potential modulatory impacts of MenSCs, as rather easily accessible and expandable stem cells, on the immune system-related cells.}, }
@article {pmid25445919, year = {2015}, author = {Wahler, J and So, JY and Cheng, LC and Maehr, H and Uskokovic, M and Suh, N}, title = {Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {148}, number = {}, pages = {148-155}, pmid = {25445919}, issn = {1879-1220}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; R03CA172827/CA/NCI NIH HHS/United States ; K22CA133105/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis/drug effects ; Biomarkers, Tumor/genetics/*metabolism ; Blotting, Western ; Breast/*drug effects/metabolism/pathology ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Humans ; Neoplastic Stem Cells/*drug effects/metabolism/pathology ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Spheroids, Cellular/drug effects ; Tumor Cells, Cultured ; Vitamin D/*pharmacology ; Vitamins/*pharmacology ; }, abstract = {Breast cancer stem cells (BCSCs) are a subset of tumor cells that are believed to be the cells responsible for the establishment and maintenance of tumors. Moreover, BCSCs are suggested to be the main cause of progression to metastasis and recurrence of cancer because of their tumor-initiating abilities and resistance to conventional therapies. Ductal carcinoma in situ (DCIS) is an early precursor in breast carcinogenesis which progresses to invasive ductal carcinoma (IDC). We have previously reported that a vitamin D compound, BXL0124, inhibits the progression of DCIS to IDC. In the present study we sought to determine whether this effect was mediated through an influence on BCSCs. In MCF10DCIS cells treated with vitamin D compounds (1α25(OH)2D3 or BXL0124), the breast cancer stem cell-like population, identified by the CD44(+)/CD24(-/low) and CD49f(+)/CD24(-/low) subpopulations, was reduced. To determine the effects of vitamin D compounds on cancer stem cell activity, the MCF10DCIS mammosphere cell culture system, which enriches for mammary progenitor cells and putative BCSCs, was utilized. Untreated MCF10DCIS mammospheres showed a disorganized and irregular shape. When MCF10DCIS cells were treated with 1α25(OH)2D3 or BXL0124, the mammospheres that formed exhibited a more organized, symmetrical and circular shape, similar to the appearance of spheres formed by the non-malignant, normal mammary epithelial cell line, MCF10A. The mammosphere forming efficiency (MFE) was significantly decreased upon treatment with 1α25(OH)2D3 or BXL0124, indicating that these compounds have an inhibitory effect on mammosphere development. Treatment with 1α25(OH)2D3 or BXL0124 repressed markers associated with the stem cell-like phenotype, such as CD44, CD49f, c-Notch1, and pNFκB. Furthermore, 1α25(OH)2D3 and BXL0124 reduced the expression of pluripotency markers, OCT4 and KLF-4 in mammospheres. This study suggests that vitamin D compounds repress the breast cancer stem cell-like population, potentially contributing to their inhibition of breast cancer. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.}, }
@article {pmid25435991, year = {2015}, author = {Liu, L and Shi, J and Mao, F and Wei, J and Fu, D and Zhang, J}, title = {Synchronous primary cancers of the thyroid and breast: A case report and review of the literature.}, journal = {Oncology letters}, volume = {9}, number = {1}, pages = {351-354}, pmid = {25435991}, issn = {1792-1074}, abstract = {The current report presents the case of a 41-year-old female exhibiting synchronous primary cancers of the thyroid and breast. Pathological examination of a tissue sample following biopsy identified papillary carcinoma of the thyroid and invasive ductal carcinoma of the breast to provide a definitive diagnosis of synchronous primary tumors. The patient underwent a modified radical mastectomy and total thyroidectomy. Following regular adjuvant chemotherapy with cyclophosphamide (800 mg), doxorubicin (100 mg) and paclitaxel (120 mg), once every three weeks for 3.5 months, oral levothyroxine and endocrinotherapy was recommended. Two years after the initial diagnosis, the patient was healthy with no disease recurrence. To the best of our knowledge, no association has been identified between the etiology and diagnoses of the two synchronous primary tumors. Thus, the aim of the current report was to improve the understanding of synchronous primary tumors of the thyroid and breast by presenting a review of the associated literature regarding breast and thyroid cancer. The mechanisms of synchronous neoplasms have only recently been elucidated, however, misdiagnosis is common. Clinicians are, therefore, advised to carefully examine patients with thyroid or breast cancer to avoid an incorrect or misdiagnosis. Furthermore, the present report aims to provide a reference for the cancer database, since the majority of analyses of rare diseases are derived from case reports. To improve the understanding of synchronous primary cancers of the thyroid and breast, an analysis of recent studies regarding the underlying mechanisms of synchronous primary cancers was also undertaken.}, }
@article {pmid25433206, year = {2015}, author = {Huang, B and Warner, M and Gustafsson, J&#xc5;}, title = {Estrogen receptors in breast carcinogenesis and endocrine therapy.}, journal = {Molecular and cellular endocrinology}, volume = {418 Pt 3}, number = {}, pages = {240-244}, doi = {10.1016/j.mce.2014.11.015}, pmid = {25433206}, issn = {1872-8057}, mesh = {Breast Neoplasms/*drug therapy/metabolism/pathology ; Drug Resistance, Neoplasm ; Estrogen Receptor alpha/*metabolism ; Estrogen Receptor beta/*metabolism ; Estrogens/*therapeutic use ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Recurrence, Local/drug therapy/metabolism ; Signal Transduction ; Tamoxifen/*therapeutic use ; }, abstract = {Excessive exposure to estrogen has long been associated with an increased risk for developing breast cancer and anti-estrogen therapy is the gold standard of care in the treatment of estrogen receptor (ER) α-positive breast cancers. However, there are several mysteries concerning both anti-estrogen, tamoxifen, and estrogen. The most important of these are: (1) some ERα-positive breast cancers do not respond to tamoxifen; (2) some ERα-negative breast cancers do respond to tamoxifen; (3) initial or acquired resistance to tamoxifen occurs with recurrent tumors; (4) estrogen can cause marked tumor regression in long-term tamoxifen-resistant ERα-positive breast cancer. These mysteries indicate that we do not know enough about estrogen signaling to understand the effects of targeting these receptors in cancer. The discovery of ERβ, the second estrogen receptor, has added another level of complexity to estrogen signaling. This review summarizes recent publications and makes an updated portrait of ERα and ERβ in breast carcinogenesis and endocrine cancer therapy.}, }
@article {pmid25424886, year = {2015}, author = {Lacaze, I and Lalucque, H and Siegmund, U and Silar, P and Brun, S}, title = {Identification of NoxD/Pro41 as the homologue of the p22phox NADPH oxidase subunit in fungi.}, journal = {Molecular microbiology}, volume = {95}, number = {6}, pages = {1006-1024}, doi = {10.1111/mmi.12876}, pmid = {25424886}, issn = {1365-2958}, mesh = {Amino Acid Sequence ; Cytochrome b Group/metabolism ; Endoplasmic Reticulum/*enzymology ; Genome, Fungal ; Mutation ; Mycelium/ultrastructure ; NADPH Oxidases/chemistry/*genetics/*metabolism ; Phylogeny ; Podospora/*enzymology/genetics ; Sequence Analysis, DNA ; Superoxides/metabolism ; Vacuoles/*enzymology ; }, abstract = {NADPH oxidases (Nox) are membrane complexes that produce O2(-). Researches in mammals, plants and fungi highlight the involvement of Nox-generated ROS in cell proliferation, differentiation and defense. In mammals, the core enzyme gp91(phox)/Nox2 is associated with p22(phox) forming the flavocytochrome b558 ready for activation by a cytosolic complex. Intriguingly, no homologue of the p22(phox) gene has been found in fungal genomes, questioning how the flavoenzyme forms. Using whole genome sequencing combined with phylogenetic analysis and structural studies, we identify the fungal p22(phox) homologue as being mutated in the Podospora anserina mutant IDC(509). Functional studies show that the fungal p22(phox), PaNoxD, acts along PaNox1, but not PaNox2, a second fungal gp91(phox) homologue. Finally, cytological analysis of functional tagged versions of PaNox1, PaNoxD and PaNoxR shows clear co-localization of PaNoxD and PaNox1 and unravel a dynamic assembly of the complex in the endoplasmic reticulum and in the vacuolar system.}, }
@article {pmid25421310, year = {2015}, author = {Buijs, JT and Matula, KM and Cheung, H and Kruithof-de Julio, M and van der Mark, MH and Snoeks, TJ and Cohen, R and Corver, WE and Mohammad, KS and Jonkers, J and Guise, TA and van der Pluijm, G}, title = {Spontaneous bone metastases in a preclinical orthotopic model of invasive lobular carcinoma; the effect of pharmacological targeting TGFβ receptor I kinase.}, journal = {The Journal of pathology}, volume = {235}, number = {5}, pages = {745-759}, pmid = {25421310}, issn = {1096-9896}, support = {U01 CA143057/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Bone Neoplasms/enzymology/genetics/*secondary ; Breast Neoplasms/chemically induced/enzymology/genetics/*pathology ; Carcinoma, Lobular/chemically induced/enzymology/genetics/*secondary ; Cdh1 Proteins/deficiency/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Female ; Mammary Neoplasms, Experimental/chemically induced/enzymology/genetics/*pathology ; Mice, Knockout ; Neoplasm Micrometastasis ; Protein Kinase Inhibitors/*toxicity ; Protein Serine-Threonine Kinases/*antagonists &amp; inhibitors/metabolism ; Pteridines/*toxicity ; Receptor, Transforming Growth Factor-beta Type I ; Receptors, Transforming Growth Factor beta/*antagonists &amp; inhibitors/metabolism ; Signal Transduction/drug effects ; Time Factors ; Transfection ; Tumor Burden/drug effects ; Tumor Suppressor Protein p53/deficiency/genetics ; }, abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most frequently occurring histological subtypes of breast cancer, accounting for 80-90% and 10-15% of the total cases, respectively. At the time of diagnosis and surgical resection of the primary tumour, most patients do not have clinical signs of metastases, but bone micrometastases may already be present. Our aim was to develop a novel preclinical ILC model of spontaneous bone micrometastasis. We used murine invasive lobular breast carcinoma cells (KEP) that were generated by targeted deletion of E-cadherin and p53 in a conditional K14cre;Cdh1((F/F));Trp53((F/F)) mouse model of de novo mammary tumour formation. After surgical resection of the growing orthotopically implanted KEP cells, distant metastases were formed. In contrast to other orthotopic breast cancer models, KEP cells readily formed skeletal metastases with minimal lung involvement. Continuous treatment with SD-208 (60 mg/kg per day), an orally available TGFβ receptor I kinase inhibitor, increased the tumour growth at the primary site and increased the number of distant metastases. Furthermore, when SD-208 treatment was started after surgical resection of the orthotopic tumour, increased bone colonisation was also observed (versus vehicle). Both our in vitro and in vivo data show that SD-208 treatment reduced TGFβ signalling, inhibited apoptosis, and increased proliferation. In conclusion, we have demonstrated that orthotopic implantation of murine ILC cells represent a new breast cancer model of minimal residual disease in vivo, which comprises key steps of the metastatic cascade. The cancer cells are sensitive to the anti-tumour effects of TGFβ. Our in vivo model is ideally suited for functional studies and evaluation of new pharmacological intervention strategies that may target one or more steps along the metastatic cascade of events.}, }
@article {pmid25418428, year = {2015}, author = {Cavallo Marincola, B and Pediconi, F and Anzidei, M and Miglio, E and Di Mare, L and Telesca, M and Mancini, M and D'Amati, G and Monti, M and Catalano, C and Napoli, A}, title = {High-intensity focused ultrasound in breast pathology: non-invasive treatment of benign and malignant lesions.}, journal = {Expert review of medical devices}, volume = {12}, number = {2}, pages = {191-199}, doi = {10.1586/17434440.2015.986096}, pmid = {25418428}, issn = {1745-2422}, mesh = {Breast/*pathology ; Breast Neoplasms/*diagnostic imaging/pathology/*therapy ; Female ; High-Intensity Focused Ultrasound Ablation/*methods ; Humans ; Magnetic Resonance Spectroscopy ; Treatment Outcome ; Ultrasonography ; }, abstract = {Breast neoplasms are one of the leading causes of morbidity and mortality in women. Even if surgery is the treatment of choice, other forms of less invasive radical treatment are desirable. High-intensity focused ultrasound is already established as a valid non-invasive technique that ensures tumor ablation in various organs. The use of ultrasound or magnetic resonance guidance allows having some advantages such as the capability to treat tumors in moving organs or the possibility to have a real-time monitoring of the temperature increase. The aim of this paper is to report the use of high-intensity focused ultrasound technique with ultrasound and magnetic resonance guidance for the ablation of breast tumors, including both benign and malignant lesions.}, }
@article {pmid25415740, year = {2014}, author = {Maglione, KD and Margolies, L and Jaffer, S and Szabo, J and Schmidt, H and Weltz, C and Sonnenblick, EB}, title = {Breast cancer in male-to-female transsexuals: use of breast imaging for detection.}, journal = {AJR. American journal of roentgenology}, volume = {203}, number = {6}, pages = {W735-40}, doi = {10.2214/AJR.14.12723}, pmid = {25415740}, issn = {1546-3141}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/*etiology ; Female ; Humans ; Male ; Mammography/*methods ; Middle Aged ; *Transgender Persons ; Transsexualism/*complications/*diagnostic imaging ; }, abstract = {OBJECTIVE: The purposes of this article are to describe two cases of breast cancer in male-to-female transsexuals and to review eight cases previously reported in the literature.<br><br>CONCLUSION: Breast cancer occurs in male-to-female transsexuals who receive high doses of exogenous estrogen and develop breast tissue histologically identical to that of a biologically female breast. This exposure to estrogen results in increased risk of breast cancer. The first patient described is a male-to-female transsexual with screening-detected ductal carcinoma in situ and a family history of breast cancer. The other patient is a male-to-female transsexual with invasive ductal carcinoma that was occult on diagnostic digital mammographic and ultrasound findings but visualized on digital breast tomosynthesis and breast MR images. The analysis of the eight previously reported cases showed that breast cancer in male-to-female transsexuals occurs at a younger age and is more frequently estrogen receptor negative than breast cancer in others born biologically male. Screening for breast cancer in male-to-female transsexuals should be undertaken for those with additional risk factors (e.g., family history, BRCA2 mutation, Klinefelter syndrome) and should be available to those who desire screening, preferably in a clinical trial.}, }
@article {pmid25410489, year = {2015}, author = {Kim, HJ and Im, SA and Keam, B and Ham, HS and Lee, KH and Kim, TY and Kim, YJ and Oh, DY and Kim, JH and Han, W and Jang, IJ and Kim, TY and Park, IA and Noh, DY}, title = {ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy.}, journal = {Cancer science}, volume = {106}, number = {1}, pages = {86-93}, pmid = {25410489}, issn = {1349-7006}, mesh = {ATP Binding Cassette Transporter, Subfamily B/genetics ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/drug therapy/*genetics/mortality ; Carcinoma, Ductal, Breast/drug therapy/*genetics/mortality ; Chemotherapy, Adjuvant ; Cytochrome P-450 CYP3A/genetics ; Docetaxel ; Doxorubicin/administration &amp; dosage ; Female ; Gene Frequency ; Genetic Association Studies ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Neoadjuvant Therapy ; Polymorphism, Single Nucleotide ; Prognosis ; Proportional Hazards Models ; Taxoids/administration &amp; dosage ; }, abstract = {Expression of the adenosine triphosphate-binding cassette B1 (ABCB1) transporter and P-glycoprotein are associated with resistance to anticancer drugs. The purpose of this study was to investigate the role of single nucleotide polymorphism in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant chemotherapy. Stage II/III breast cancer patients were treated with three cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy. The polymorphisms of ABCB1 and CYP3A were genotyped. The correlation of polymorphism of ABCB1, CYP3A, and clinical outcomes was analyzed. Among the 216 patients, ABCB1 3435TT genotype had a longer overall survival (OS). than CC/CT. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non-triple negative phenotype and initial operable stage were significantly associated with a lower death risk. ABCB1 3435TT genotype had a higher AUC than CC/CT for docetaxel. These higher AUCs in the C3435TT was associated with increased toxicities of neutropenia and diarrhea. This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer OS. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. This study results provides valuable information on individualized therapy according to genotypes.}, }
@article {pmid25404445, year = {2014}, author = {Iqbal, J and Shafi, AA and Alharthi, BN}, title = {Neoadjuvant chemotherapy in locally advanced breast cancer.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {24}, number = {11}, pages = {845-848}, pmid = {25404445}, issn = {1681-7168}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Hormones/therapeutic use ; Humans ; *Mastectomy ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Recurrence, Local/epidemiology/therapy ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; Saudi Arabia/epidemiology ; Severity of Illness Index ; Survival Analysis ; Survival Rate ; Treatment Outcome ; }, abstract = {OBJECTIVE: To assess the response to Neoadjuvant Chemotherapy (NAC) in Locally Advanced Breast Cancer (LABC) in terms of pathological response, overall survival and feasibility of breast conservation surgery.<br><br>STUDY DESIGN: Case series.<br><br>PLACE AND DURATION OF STUDY: King Fahad Medical City (KFMC), Riyadh, from January 2009 to July 2012.<br><br>METHODOLOGY: All patients of LABC who received NAC and underwent surgery were included. All these patients received the GORG001 regimen (FEC+Docetaxal+Cisplatin+/-Herceptin). After chemotherapy patients were offered surgery either Modified Radical Mastectomy (MRM) or Breast Conservation Surgery (BCS) +Radiotherapy. Patients were then followed to exclude local or distant metastasis. RESULTS were described in percentage.<br><br>RESULTS: The median age at the time of diagnosis was 46.8 years. While complete response was achieved in 24 (44.4%) patients, 14 (25.9%) of the patients had partial response and 16 (29.6%) progressed clinically. Surgery was performed in these patients after NAC. Forty (74%) patients had MRM, 14 (25.9%) had BCS; all had axillary lymph node dissection. Invasive ductal carcinoma accounted for 92% of cases. Vascular invasion was present in 12 (22%) of the patients. Estrogen / progesterone receptor positivity was 61%. Thirty nine percent of the patients were Her2 positive. On an average, follow-up of 4 - 51 months in the MRM group, one patient had resection margin (deep) positive and was treated with adjuvant therapy. While in the BCS group after 3 - 26 months of follow-up, one patient had resection margin positive (medial margin) and underwent MRM, while no patient had local or distant metastasis in both the groups.<br><br>CONCLUSION: NAC caused down staging of disease in LABC making more conservative surgery feasible. BCC should be considered as an option for treatment of LABC, however, longer follow-up is recommended.}, }
@article {pmid25400746, year = {2014}, author = {Lv, ZD and Kong, B and Liu, XP and Dong, Q and Niu, HT and Wang, YH and Li, FN and Wang, HB}, title = {CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {10}, pages = {6671-6678}, pmid = {25400746}, issn = {1936-2625}, mesh = {Animals ; Breast Neoplasms/genetics/immunology/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/genetics/immunology/*metabolism/mortality/secondary ; *Cell Proliferation ; Chemokine CXCL12/genetics/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; MCF-7 Cells ; Mice, Nude ; Middle Aged ; Neoplasm Invasiveness ; Signal Transduction ; Time Factors ; Transfection ; Tumor Burden ; }, abstract = {Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of CXCL12 and relevance with clinicopathological factors in the invasive ductal carcinoma. Reduction of CXCL12 was significantly correlated with tumor size, lymph node metastasis, TNM stage and Her-2 expression in breast cancer. Patients with negative CXCL12 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive CXCL12 expression. In addition, we demonstrated that upregulation of CXCL12 expression by infection with an adenovirus containing a CXCL12 vector significantly inhibited cell growth and reduced the migration of breast cancer cells. Furthermore, animal studies revealed that nude mice injected with the Ad-CXCL12 cell lines featured a lighter weight than the control cell lines. These data suggest that CXCL12 plays an important role in cell growth and invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.}, }
@article {pmid25394563, year = {2015}, author = {Liu, Y and Liu, T and Sun, Q and Niu, M and Jiang, Y and Pang, D}, title = {Downregulation of Ras GTPase‑activating protein 1 is associated with poor survival of breast invasive ductal carcinoma patients.}, journal = {Oncology reports}, volume = {33}, number = {1}, pages = {119-124}, doi = {10.3892/or.2014.3604}, pmid = {25394563}, issn = {1791-2431}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*metabolism/mortality ; Carcinoma, Ductal, Breast/*metabolism/mortality ; Disease-Free Survival ; Down-Regulation ; Female ; Gene Expression ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; p120 GTPase Activating Protein/genetics/*metabolism ; }, abstract = {Ras GTPase‑activating protein 1 (RASA1) functions to inactivate Ras‑GTPase and inhibit the mitogenic signal. Reduction or loss of RASA1 expression occurs during human cancer development and progression. This study investigated RASA1 expression in normal and breast cancer tissue specimens to determine the association with prognosis of breast cancer patients. Two sets of patient samples (45 fresh tissues and 373 paraffin‑embedded tissues) were analyzed for RASA1 expression using RT‑qPCR and immunohisto-chemistry. The results showed that the expression of RASA1 mRNA was lower in breast cancer tissues than in the corresponding normal tissues (P<0.001). Additionally, RASA1 expression was reduced in 60.6% (226/373) of breast cancer tissues. The reduced RASA1 expression was significantly associated with tumor lymph node metastasis (P=0.002), advanced TNM stages (P=0.017), estrogen receptor (ER) expression (P=0.002), Ki‑67 (P=0.009), higher histological grade (P<0.001), and triple‑negative breast cancer (P=0.041). Moreover, the reduced RASA1 expression was associated with shorter disease‑free survival (P=0.036) and overall survival (P<0.001) of breast cancer patients. RASA1 expression, together with tumor lymph‑node metastasis, TNM stage, Her‑2 expression, and triple‑negative breast cancer were independent factors in predicting survival of breast cancer patients. In conclusion, RASA1 expression is frequently reduced in breast cancer tissues, and the reduced RASA1 expression is associated with breast cancer progression and poor survival and disease‑free survival of patients.}, }
@article {pmid25391703, year = {2014}, author = {Yanagihara, K and Takei, H and Iida, S and Yamashita, K and Kurita, T and Iwamoto, M and Saegusa, H and Uchida, E}, title = {Grade 4 epistaxis in a woman with metastatic breast cancer treated with bevacizumab: a case report.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {81}, number = {5}, pages = {333-336}, doi = {10.1272/jnms.81.333}, pmid = {25391703}, issn = {1347-3409}, mesh = {Adult ; Angiogenesis Inhibitors/*adverse effects ; Antibodies, Monoclonal, Humanized/administration &amp; dosage/*adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*secondary ; Epistaxis/*chemically induced ; Female ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Paclitaxel/administration &amp; dosage ; Severity of Illness Index ; }, abstract = {We describe a 39-year-old woman with metastatic breast cancer who had grade 4 epistaxis induced by bevacizumab. The patient visited our outpatient clinic with complaints of a lump in her right breast, fatigue, dyspnea, abdominal distention, appetite loss, and weight loss of 10 kg over 1 year. Liver dysfunction was detected, with elevated levels of aspartate aminotransferase (271 IU/L), alanine aminotransferase (100 IU/L), alkaline phosphatase (4,205 IU/L), total bilirubin (2.7 mg/dL), and direct bilirubin (2.1 mg/dL). A secondary liver tumor that occupied most of the liver volume was found, and bone metastasis, ascites, and pleural effusion were also discovered. The Eastern Cooperative Oncology Group performance status was 2. A core needle biopsy of the right breast tumor revealed invasive ductal carcinoma of the breast (nuclear grade 1) that was positive for estrogen receptor and progesterone receptor and negative for human epidermal growth factor receptor 2 overexpression and had a high Ki-67 score. We chose combination chemotherapy with paclitaxel (80 mg/m(2) on days 1, 8, and 15) and bevacizumab (10 mg/kg on days 1 and 15) for 28 days (1 cycle). After completion of the first cycle of chemotherapy, the ascites and pleural effusion decreased, and the metastatic liver tumor shrank. The performance status improved from 2 to 1. On day 3 of the third cycle of chemotherapy, however, she began having persistent epistaxis. On day 6, she lost consciousness and was transported to the emergency room of our hospital. The hemoglobin level was 5.6 g/dL. Blood transfusion and endoscopic hemostasis were immediately started. Bevacizumab was discontinued, and paclitaxel alone was continued; after this change, epistaxis did not recur.}, }
@article {pmid25385074, year = {2014}, author = {Wong, H and Lau, S and Cheung, P and Wong, TT and Parker, A and Yau, T and Epstein, RJ}, title = {Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {826}, pmid = {25385074}, issn = {1471-2407}, mesh = {Adult ; Australia ; Breast Neoplasms/*chemistry/*pathology ; Carcinoma, Ductal, Breast/*chemistry/*secondary ; Carcinoma, Lobular/*chemistry/*secondary ; Cell Proliferation ; Chemotherapy, Adjuvant ; Female ; Hong Kong ; Humans ; Ki-67 Antigen/analysis ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Tumor Burden ; }, abstract = {BACKGROUND: Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity.<br><br>METHODS: The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed.<br><br>RESULTS: Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC tumors failed to demonstrate any such inverse relationship (p >0.6).<br><br>CONCLUSION: These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.}, }
@article {pmid25379017, year = {2014}, author = {Scheiber, MN and Watson, PM and Rumboldt, T and Stanley, C and Wilson, RC and Findlay, VJ and Anderson, PE and Watson, DK}, title = {FLI1 expression is correlated with breast cancer cellular growth, migration, and invasion and altered gene expression.}, journal = {Neoplasia (New York, N.Y.)}, volume = {16}, number = {10}, pages = {801-813}, pmid = {25379017}, issn = {1476-5586}, support = {P01 CA078582/CA/NCI NIH HHS/United States ; P30 CA138313/CA/NCI NIH HHS/United States ; P01CA78582/CA/NCI NIH HHS/United States ; P30 CA 138313/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Neoplasms, Experimental/genetics/pathology ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mice, Transgenic ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Protein c-fli-1/*genetics/metabolism ; Proto-Oncogene Proteins c-ets/genetics ; }, abstract = {ETS factors have been shown to be dysregulated in breast cancer. ETS factors control the expression of genes involved in many biological processes, such as cellular proliferation, differentiation, and apoptosis. FLI1 is an ETS protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of FLI1 in epithelial-derived cancers. Using data mining, we show that loss of FLI1 expression is associated with shorter survival and more aggressive phenotypes of breast cancer. Gain and loss of function cellular studies indicate the inhibitory effect of FLI1 expression on cellular growth, migration, and invasion. Using Fli1 mutant mice and both a transgenic murine breast cancer model and an orthotopic injection of syngeneic tumor cells indicates that reduced Fli1 contributes to accelerated tumor growth. Global expression analysis and RNA-Seq data from an invasive human breast cancer cell line with over expression of either FLI1 and another ETS gene, PDEF, shows changes in several cellular pathways associated with cancer, such as the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways. This study demonstrates a novel role for FLI1 in epithelial cells. In addition, these results reveal that FLI1 down-regulation in breast cancer may promote tumor progression.}, }
@article {pmid25373614, year = {2014}, author = {Rai, R and Zhu, L and Chen, H and Gupta, AP and Sze, SK and Zheng, J and Ruedl, C and Bozdech, Z and Featherstone, M}, title = {Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {959}, pmid = {25373614}, issn = {1471-2164}, mesh = {Antibodies, Monoclonal/pharmacology ; Binding Sites/genetics ; Chromatin Immunoprecipitation ; Cluster Analysis ; Computational Biology ; Erythrocytes/parasitology ; Gene Dosage ; *Genome, Protozoan ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; Malaria, Falciparum/*parasitology ; Molecular Sequence Annotation ; Phosphorylation ; Plasmodium falciparum/*genetics/*metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Subunits/antagonists &amp; inhibitors ; RNA Polymerase II/antagonists &amp; inhibitors/chemistry/*metabolism ; RNA, Messenger/genetics ; Transcription, Genetic ; Transcriptional Activation ; }, abstract = {BACKGROUND: Over the course of its intraerythrocytic developmental cycle (IDC), the malaria parasite Plasmodium falciparum tightly orchestrates the rise and fall of transcript levels for hundreds of genes. Considerable debate has focused on the relative importance of transcriptional versus post-transcriptional processes in the regulation of transcript levels. Enzymatically active forms of RNAPII in other organisms have been associated with phosphorylation on the serines at positions 2 and 5 of the heptad repeats within the C-terminal domain (CTD) of RNAPII. We reasoned that insight into the contribution of transcriptional mechanisms to gene expression in P. falciparum could be obtained by comparing the presence of enzymatically active forms of RNAPII at multiple genes with the abundance of their associated transcripts.<br><br>RESULTS: We exploited the phosphorylation state of the CTD to detect enzymatically active forms of RNAPII at most P. falciparum genes across the IDC. We raised highly specific monoclonal antibodies against three forms of the parasite CTD, namely unphosphorylated, Ser5-P and Ser2/5-P, and used these in ChIP-on-chip type experiments to map the genome-wide occupancy of RNAPII. Our data reveal that the IDC is divided into early and late phases of RNAPII occupancy evident from simple bi-phasic RNAPII binding profiles. By comparison to mRNA abundance, we identified sub-sets of genes with high occupancy by enzymatically active forms of RNAPII and relatively low transcript levels and vice versa. We further show that the presence of active and repressive histone modifications correlates with RNAPII occupancy over the IDC.<br><br>CONCLUSIONS: The simple early/late occupancy by RNAPII cannot account for the complex dynamics of mRNA accumulation over the IDC, suggesting a major role for mechanisms acting downstream of RNAPII occupancy in the control of gene expression in this parasite.}, }
@article {pmid25368291, year = {2014}, author = {Klopfer, K and Delahunt, B and Adamson, M and Samaratunga, H}, title = {Value of uroplakin III in distinguishing variants of primary bladder urothelial carcinoma from malignancy metastatic to the urinary bladder.}, journal = {Anticancer research}, volume = {34}, number = {11}, pages = {6779-6784}, pmid = {25368291}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Giant Cell/metabolism/*secondary ; Carcinoma, Large Cell/metabolism/*secondary ; Carcinoma, Papillary/metabolism/*secondary ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Urinary Bladder Neoplasms/metabolism/*pathology ; Uroplakin III/*metabolism ; }, abstract = {BACKGROUND: Urothelial carcinoma (UC) variants can be difficult to differentiate from carcinoma metastatic to the bladder.<br><br>MATERIALS AND METHODS: We examined immunostaining for uroplakin III in 43 cases of primary bladder UC variants including micropapillary UC (n=19), nested variant of UC (n=2), pleomorphic giant-cell carcinoma (n=8), plasmacytoid UC (n=4), lymphoepithelioma-like carcinoma (n=2), large cell undifferentiated carcinoma (n=2), UC with abundant myxoid stroma (n=3) and lipid cell variant (n=3) and in 11 tumors from other organs metastatic to the bladder. These tumors included invasive ductal carcinoma of the breast (n=2), colorectal adenocarcinoma (n=4), endometrioid adenocarcinoma (n=1) and serous papillary carcinoma of the uterus (n=1) melanoma (n=1), embryonal carcinoma of the testis (n=1), and renal clear cell carcinoma (n=1).<br><br>RESULTS: Out of the 43 UC variants, 35 (81%) were positive for uroplakin III, including micropapillary, lipid cell variant and UC with abundant myxoid stroma. Pleomorphic giant cell carcinoma, plasmacytoid UC and nested variant of UC were less commonly positive. Of the 11 metastatic tumors, six were found to be positive for uropIakin III: metastatic colorectal adenocarcinoma, clear cell carcinoma of the kidney and embryonal carcinoma of testis.<br><br>CONCLUSION: UP III Positivity for uroplakin III is not found only in primary bladder UC variants, but in some tumors that have metastatized to the bladder. Staining for uroplakin III alone should not be taken as evidence of UC.}, }
@article {pmid25360699, year = {2014}, author = {Ma, FJ and Liu, ZB and Hu, X and Ling, H and Li, S and Wu, J and Shao, ZM}, title = {Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients.}, journal = {PloS one}, volume = {9}, number = {10}, pages = {e111639}, pmid = {25360699}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Myeloid Differentiation Factor 88/*metabolism ; Prognosis ; Toll-Like Receptor 4/*metabolism ; }, abstract = {PURPOSE: Breast cancer remains a major cause of death in women worldwide, and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment. Chronic inflammation is often related to the occurrence and growth of various malignancies. This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response: myeloid differentiation primary response 88 (MyD88) and Toll-like receptor 4 (TLR4).<br><br>METHODS: We analyzed data from 205 breast invasive ductal carcinoma (IDC) patients who were treated at the Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, from 2002 to 2006. Overall survival (OS) and disease-free survival (DFS) were compared.<br><br>RESULTS: In total, 152 patients (74.15%) were disease-free without relapse or metastasis, whereas 53 (25.85%) patients developed recurrence or metastasis. A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001). Patients with high expression were more likely to experience death and recurrence/metastasis events (p<0.05). Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels (log-rank test: p<0.001). Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test: p<0.001). In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663-6.641; p&#x200a;=&#x200a;0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546-13.098; p&#x200a;=&#x200a;0.006).<br><br>CONCLUSIONS: TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer. Therefore, TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy.}, }
@article {pmid25357113, year = {2014}, author = {Jorns, JM and Thomas, DG and Healy, PN and Daignault, S and Vickery, TL and Snider, JE and Mardis, ER and Davies, SR and Ellis, MJ and Visscher, DW}, title = {Estrogen receptor expression is high but is of lower intensity in tubular carcinoma than in well-differentiated invasive ductal carcinoma.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {138}, number = {11}, pages = {1507-1513}, pmid = {25357113}, issn = {1543-2165}, support = {P30 CA091842/CA/NCI NIH HHS/United States ; T32 CA083654/CA/NCI NIH HHS/United States ; P30 CA91842/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/genetics/*metabolism/*pathology ; Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cell Differentiation ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Middle Aged ; Molecular Typing ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {CONTEXT: Tubular carcinoma (TC) is a rare, luminal A subtype of breast carcinoma with excellent prognosis, for which adjuvant chemotherapy is usually contraindicated.<br><br>OBJECTIVE: To examine the levels of estrogen receptor (ER) and progesterone receptor expression in cases of TC and well-differentiated invasive ductal carcinoma as compared to normal breast glands and to determine if any significant differences could be detected via molecular testing.<br><br>DESIGN: We examined ER and progesterone receptor via immunohistochemistry in tubular (N = 27), mixed ductal/tubular (N = 16), and well-differentiated ductal (N = 27) carcinomas with comparison to surrounding normal breast tissue. We additionally performed molecular subtyping of 10 TCs and 10 ductal carcinomas via the PAM50 assay.<br><br>RESULTS: Although ER expression was high for all groups, TC had statistically significantly lower ER staining percentage (ER%) (P = .003) and difference in ER expression between tumor and accompanying normal tissue (P = .02) than well-differentiated ductal carcinomas, with mixed ductal/tubular carcinomas falling between these 2 groups. Mean ER% was 79%, 87%, and 94%, and mean tumor-normal ER% differences were 13.6%, 25.9%, and 32.6% in tubular, mixed, and ductal carcinomas, respectively. Most tumors that had molecular subtyping were luminal A (9 of 10 tubular and 8 of 10 ductal), and no significant differences in specific gene expression between the 2 groups were identified.<br><br>CONCLUSIONS: Tubular carcinoma exhibited decreased intensity in ER expression, closer to that of normal breast parenchyma, likely as a consequence of a high degree of differentiation. Lower ER% expression by TC may represent a potential pitfall when performing commercially available breast carcinoma prognostic assays that rely heavily on ER-related gene expression.}, }
@article {pmid25355267, year = {2014}, author = {Qing, Z and Zou, W and Luo, J and Wen, Q and Fan, S}, title = {[p53 protein expression in HER2-negative breast invasive ductal carcinoma].}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {39}, number = {10}, pages = {1016-1022}, doi = {10.11817/j.issn.1672-7347.2014.10.005}, pmid = {25355267}, issn = {1672-7347}, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Prognosis ; Receptor, ErbB-2 ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {OBJECTIVE: To determine the expression of p53 and its clinical significance in HER2-negative breast invasive ductal carcinoma (BIDC).<br><br>METHODS: The expression of p53, ER and PR in the HER2-negative BIDC was detected by immunohistochemistry and the results were analyzed by SPSS10.0 software packet, chi-square test, spearman's correlation analysis, Kaplan-Meier survival curves and Cox regression analysis.<br><br>RESULTS: The positive expression of p53 protein in BIDC with pathological grade III was significantly higher than that with grade I (P<0.05), but there was no significant correlation between the expression of p53 and age, clinical stage, or lymph node metastasis status in the BIDC. The positive expression of p53 protein in BIDC with ER-positive was significantly lower than that with ER-negative (P<0.01). The positive expression of p53 protein was significantly lower in BIDC with common expression of ER and PR than that with negative expression of ER or PR (P<0.05). The HER2-negative BIDC patients with p53-positive expression had a lower 5 year survival than those with p53-negative expression.<br><br>CONCLUSION: The positive expression of p53 protein might have significant prognostic value and is an independent prognostic marker in HER2 -negative BIDC.}, }
@article {pmid25344624, year = {2014}, author = {Riobó Serván, P and Sierra Poyatos, R and Soldo Rodríguez, J}, title = {Low and no calorie sweeteners (LNCS); myths and realities.}, journal = {Nutricion hospitalaria}, volume = {30 Suppl 2e}, number = {}, pages = {49-55}, doi = {10.3305/nh.2014.30.sup2e.8288}, pmid = {25344624}, issn = {1699-5198}, mesh = {Diabetes Mellitus/prevention &amp; control ; *Energy Intake ; Humans ; Neoplasms/chemically induced ; Obesity/prevention &amp; control ; *Sweetening Agents/adverse effects ; }, abstract = {Since their introduction in the market, there has been much debate regarding the health effects of low and no calorie sweetners (LNCS). Therefore, through this review, we aim to establish scientific information about the most commonly used LNCS by the food industry. Key questions about uses, safety, and weight control are reviewed. Scientific evidence revised concludes that LNCS available on the market are safe and no epidemiological relationship has been established with the development of non-communicable diseases, including different kind of cancer in humans. Also, LCNS combined with physical activity and a healthy lifestyle can play a significant role in weight loss and the maintenance of a healthy weight. But non nutritive sweeteners will be helpful only as long as people don't eat additional calories later as compensation. Even more, LNCS represent an additional instrument in the dietary treatment of people with diabetes for metabolic control, without avoiding sweet taste.}, }
@article {pmid25343550, year = {2014}, author = {Hu, A and Sun, M and Yan, D and Chen, K}, title = {Clinical significance of mTOR and eIF4E expression in invasive ductal carcinoma.}, journal = {Tumori}, volume = {100}, number = {5}, pages = {541-546}, doi = {10.1700/1660.18176}, pmid = {25343550}, issn = {2038-2529}, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Adult ; Aged ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Carrier Proteins/metabolism ; Cell Cycle Proteins ; Eukaryotic Initiation Factor-4E/*metabolism ; Eukaryotic Initiation Factors/metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Molecular Targeted Therapy ; Phosphoproteins/metabolism ; Prognosis ; Protein Transport ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {AIMS AND BACKGROUND: Mammalian target of rapamycin (mTOR) is one of the serine-threonine protein kinases and plays an important regulatory role in cell growth. Eukaryotic translation initiation factor 4E (eIF4E) and 4E binding protein (4EBP) are the downstream proteins of mTOR signaling pathway and are the most efficient speed regulator of eukaryotic mRNA translation. The aim of the study was to investigate the clinical significance of mTOR, eIF4E and 4EBPs expression in invasive ductal carcinoma.<br><br>METHODS: Fresh biopsy specimens of invasive ductal carcinoma tissues and normal breast tissues were collected from 45 patients with breast cancer. The expressions of mTOR, eIF4E and 4EBPs in specimens were detected by an immunohistochemical SP method, and the relationship of mTOR, eIF4E and 4EBPS expressions and of their expressions with tumor metastasis were analyzed.<br><br>RESULTS: Expressions of mTOR, eIF4E and 4EBPs in invasive ductal carcinoma were significantly higher than in normal breast tissue (P <0.05). mTOR expression was positively correlated with eIF4E and 4EBP expression in invasive ductal carcinoma (P <0.05). The positive rates of mTOR, eIF4E and 4EBPs in patients with lymph node metastasis were significantly higher than in patients without lymph node metastasis (P <0.05).<br><br>CONCLUSIONS: Increased expressions of mTOR and eIF4E in invasive ductal carcinoma may be correlated with the occurrence and metastasis of breast cancer.}, }
@article {pmid25339043, year = {2014}, author = {Wan Abdul Rahman, WF and Fauzi, MH and Jaafar, H}, title = {Expression of DNA methylation marker of paired-like homeodomain transcription factor 2 and growth receptors in invasive ductal carcinoma of the breast.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {19}, pages = {8441-8445}, doi = {10.7314/apjcp.2014.15.19.8441}, pmid = {25339043}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Cross-Sectional Studies ; *DNA Methylation ; Female ; Follow-Up Studies ; Homeodomain Proteins/*metabolism ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2).<br><br>METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH).<br><br>RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).<br><br>CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.}, }
@article {pmid25337201, year = {2014}, author = {Ren, J and Chen, QC and Jin, F and Wu, HZ and He, M and Zhao, L and Yu, ZJ and Yao, WF and Mi, XY and Wang, EH and Wei, MJ}, title = {Overexpression of Rsf-1 correlates with pathological type, p53 status and survival in primary breast cancer.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {9}, pages = {5595-5608}, pmid = {25337201}, issn = {1936-2625}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality/pathology/surgery ; Carcinoma/*chemistry/mortality/pathology/surgery ; Chi-Square Distribution ; Chromatin Assembly and Disassembly ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Nuclear Proteins/*analysis ; Predictive Value of Tests ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies ; Risk Factors ; Time Factors ; Trans-Activators/*analysis ; Treatment Outcome ; Tumor Burden ; Tumor Suppressor Protein p53/*analysis ; Up-Regulation ; Young Adult ; }, abstract = {AIM: The incidence of breast cancer in developing countries still increasing, to identify novel molecular markers associated with carcinogenesis and prognosis of breast cancer still being implemented. The largest subunit of Remodeling and spacing factor (RSF), Rsf-1, mediates ATPase-dependent chromatin remodeling. Its oncogenic properties have been demonstrated in certain carcinomas. The aim of this study was to examine the prognostic value of Rsf-1 in patients with primary breast carcinoma.<br><br>METHODS: A total of 537 patients with primary breast cancer, and 54 with benign breast hyperplasia, were performed resection surgery in the same period were enrolled. Rsf-1 immunoexpression was retrospectively assessed by immunohistochemistry (IHC). As well as, it relationship with clinicopathological factors and patient survival (LRFS, DFS and OS) was investigated.<br><br>RESULTS: Compared with benign breast hyperplasia tissues, higher percentage of Rsf-1 positive expression was detected in malignant breast carcinomas. Based on IHC staining extent &#xd7; intensity scores and ROC analysis, 278 of 526 cancers (52.9%) had high-expression (cut-off values 2.5) of Rsf-1, which correlated significantly to pathologic subtypes of breast cancer (DCIS vs. IDC, P < 0.001; ILC vs. IDC, P = 0.036), bigger tumor size (P = 0.030), higher TNM stage (P = 0.044), and p53-positive expression. In addition, there was a trend that high-expression of Rsf-1 associated with younger age (P = 0.053). We further prove that combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) was correlated with the bigger tumor size (P = 0.018), and higher TNM stage (P = 0.024). Kaplan-Meier survival analysis showed that Rsf-1 high-expression and combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) exhibited a significant correlation with poor overall survival of patients with primary breast cancer, and no association has been identified in relation to LRFS or DFS. Especially, Univariate and multivariate survival analysis demonstrated Rsf-1 expression is an independent prognostic parameter for the overall survival of patients with breast cancer.<br><br>CONCLUSIONS: High-expression of Rsf-1 is associated with pathologic subtypes of breast cancer, aggressive phenotype, p53 positive and poor clinical outcome, which confers tumor aggressiveness through chromatin remodeling, and targeting Rsf-1 gene and the pathway it related may provide new therapeutic avenues for treating breast cancer.}, }
@article {pmid25327792, year = {2014}, author = {Wang, X and Zheng, X and Lin, X and Shi, Y and He, Y and Chen, G}, title = {[Methylation of Runx3 promoter in different breast lesions].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {43}, number = {7}, pages = {447-450}, pmid = {25327792}, issn = {0529-5807}, mesh = {Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/*metabolism ; Core Binding Factor Alpha 3 Subunit/genetics/*metabolism ; *DNA Methylation ; Female ; Fibroadenoma/*metabolism ; Humans ; Neoplasm Proteins/*metabolism ; Promoter Regions, Genetic ; }, abstract = {OBJECTIVE: To investigate the methylation status of Runx3 promoter and Runx3 expression in breast lesion tissues.<br><br>METHODS: One hundred and fourteen breast lesions, including 35 cases of fibroadenoma, 39 cases of intraductal carcinoma, 40 cases of invasive ductal carcinoma, and 33 cases of normal breast tissue from Fabruary 2010 to August 2012 were included in this study. Runx3 protein expression was assessed by immunohistochemical SP method; whereas methylation of Runx3 promoter was assessed by high resolution melting (HRM) analysis.<br><br>RESULTS: Runx3 protein was mainly expressed in the cytoplasm of ductal epithelial cells. The expression rates of Runx3 in normal breast tissue, fibroadenoma, ductal carcinoma in situ, invasive ductal carcinoma were 87.9% (29/33), 85.7% (30/35), 53.8% (21/39), and 40.0% (16/40) respectively. The methylation rates of Runx3 promoter were 12.1% (4/33), 20.0% (7/35), 46.2% (18/39), and 57.5% (23/40), respectively. Correlation analysis between promoter methylation and protein expression of Runx3 in different breast tissue showed the r value in normal breast tissue, fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma was -0.431 (P = 0.012), -0.408 (P = 0.015), -0.589 (P = 0.000) and -0.743 (P = 0.000) respectively.<br><br>CONCLUSIONS: Runx3 protein expression shows a downward trend in ductal carcinoma in situ and invasive ductal carcinoma, meanwhile its promoter methylation increases significantly. The methylation of Runx3 promoter may be one of the important factors in the occurrence and development of breast cancer.}, }
@article {pmid25307858, year = {2015}, author = {Zhao, T and Liao, B and Yao, J and Liu, J and Huang, R and Shen, P and Peng, Z and Gui, H and Chen, X and Zhang, P and Zhu, Y and Li, X and Wei, Q and Zhou, Q and Zeng, H and Chen, N}, title = {Is there any prognostic impact of intraductal carcinoma of prostate in initial diagnosed aggressively metastatic prostate cancer?.}, journal = {The Prostate}, volume = {75}, number = {3}, pages = {225-232}, doi = {10.1002/pros.22906}, pmid = {25307858}, issn = {1097-0045}, mesh = {Adenocarcinoma/*secondary ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Carcinoma, Ductal/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/*pathology ; Prognosis ; Prostatic Neoplasms/*pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of prostate (IDC-P) was usually found to be co-exist with conventional aggressive prostate adenocarcinoma. The presence of IDC-P was considered as an adverse pathological factor, which was associated with high Gleason score, large prostate volume and accelerated disease progression. However, no any information is available on the presence of IDC-P diagnosed by needle biopsy in patients with metastatic prostate cancer. We investigated the incidence and prognostic value of intraductal carcinoma of prostate (IDC-P) in initial diagnosed metastatic prostate cancer.<br><br>METHODS: We included 278 patients with initial diagnosed metastatic prostate cancer treated between 2008 and 2011, all the pathological diagnosis were from ultrasonic-guided transperineal needle biopsy. IDC-P was strictly defined according to Epstein's criteria. Analyzed factors included age, Eastern Cooperative Oncology Group (ECOG) score, clinical T staging, Gleason scores, baseline prostate specific antigen (PSA), alkaline phosphatase (ALP), hemoglobin (HGB), PSA normalization, and the presence of IDC-P.<br><br>RESULTS: Totally, IDC-P was found in 57/278 (20.5%) cases. Univariate analysis showed that, compared with cases without IDC-P, cases with IDC-P was definitely associated with much shorter CRPC-free survival (CFS) time (46.05&#x2009;&#xb1;&#x2009;1.39 vs. 22.98&#x2009;&#xb1;&#x2009;1.80 months, P&#x2009;=&#x2009;0.000) and OS time (50.38&#x2009;&#xb1;&#x2009;1.18 vs. 36.43&#x2009;&#xb1;&#x2009;2.10 months, P&#x2009;=&#x2009;0.000). Multivariate analysis showed that the presence of IDC-P was the only independent prognostic factor associated with poor CFS (HR&#x2009;=&#x2009;4.886, P&#x2009;=&#x2009;0.011) and OS (HR&#x2009;=&#x2009;1.945, P&#x2009;=&#x2009;0.020). Further sub-analysis showed, even among patients with higher Gleason score (&#x2265;8) (n&#x2009;=&#x2009;158), IDC-P was still significantly and inversely associated with CFS and OS (the median CFS time: 40 versus 22 months; P&#x2009;=&#x2009;0.000; the median OS time: 54 vs. 36 months, P&#x2009;=&#x2009;0.000). Again, Cox's regression model confirmed that only the presence of IDC-P was still not only an independent prognostic factor predicting shorter time of CRPC (HR&#x2009;=&#x2009;4.031, P&#x2009;=&#x2009;0.035), but also for poorer OS (HR&#x2009;=&#x2009;2.499, P&#x2009;=&#x2009;0.006).<br><br>CONCLUSIONS: The presence of IDC-P in initial diagnosed metastatic prostate cancer, even among patients with more aggressive pattern, was firstly found to be significantly and independently associated with earlier occurrence of CRPC and poorer OS. We recommended the presence of IDC-P should be a routine record in pathological report of clinical diagnosis and other potential therapeutic regimen might be added to intervene in the integrated therapy as early as possible. Prostate 75:225-232, 2015. &#xa9; 2014 Wiley Periodicals, Inc.}, }
@article {pmid25306216, year = {2014}, author = {Volinia, S and Nuovo, G and Drusco, A and Costinean, S and Abujarour, R and Desponts, C and Garofalo, M and Baffa, R and Aeqilan, R and Maharry, K and Sana, ME and Di Leva, G and Gasparini, P and Dama, P and Marchesini, J and Galasso, M and Manfrini, M and Zerbinati, C and Corrà, F and Wise, T and Wojcik, SE and Previati, M and Pichiorri, F and Zanesi, N and Alder, H and Palatini, J and Huebner, KF and Shapiro, CL and Negrini, M and Vecchione, A and Rosenberg, AL and Croce, CM and Garzon, R}, title = {Pluripotent stem cell miRNAs and metastasis in invasive breast cancer.}, journal = {Journal of the National Cancer Institute}, volume = {106}, number = {12}, pages = {}, pmid = {25306216}, issn = {1460-2105}, support = {P30 CA016058/CA/NCI NIH HHS/United States ; U01 CA154200/CA/NCI NIH HHS/United States ; U01 CA166905/CA/NCI NIH HHS/United States ; U01 CA152758/CA/NCI NIH HHS/United States ; }, mesh = {Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*secondary ; Female ; Humans ; Lymphatic Metastasis ; MicroRNAs/*analysis ; *Neoplastic Stem Cells ; *Pluripotent Stem Cells ; }, abstract = {BACKGROUND: The purpose of this study is to determine whether microRNA for pluripotent stem cells are also expressed in breast cancer and are associated with metastasis and outcome.<br><br>METHODS: We studied global microRNA profiles during differentiation of human embryonic stem cells (n =26) and in breast cancer patients (n = 33) and human cell lines (n = 35). Using in situ hybridization, we then investigated MIR302 expression in 318 untreated breast cancer patients (test cohort, n = 22 and validation cohort, n = 296). In parallel, using next-generation sequencing data from breast cancer patients (n = 684), we assessed microRNA association with stem cell markers. All statistical tests were two-sided.<br><br>RESULTS: In healthy tissues, the MIR302 (high)/MIR203 (low) asymmetry was exclusive for pluripotent stem cells. MIR302 was expressed in a small population of cancer cells within invasive ductal carcinoma, but not in normal breast (P < .001). Furthermore, MIR302 was expressed in the tumor cells together with stem cell markers, such as CD44 and BMI1. Conversely, MIR203 expression in 684 breast tumors negatively correlated with CD44 (Spearman correlation, Rho = -0.08, P = .04) and BMI1 (Rho = -0.11, P = .004), but positively correlated with differentiation marker CD24 (Rho = 0.15, P < .001). Primary tumors with lymph node metastasis had cancer cells showing scattered expression of MIR302 and widespread repression of MIR203. Finally, overall survival was statistically significantly shorter in patients with MIR302-positive cancer cells (P = .03).<br><br>CONCLUSIONS: In healthy tissues the MIR302(high)/MIR203(low) asymmetry was characteristic of embryonic and induced pluripotency. In invasive ductal carcinoma, the MIR302/MIR203 asymmetry was associated with stem cell markers, metastasis, and shorter survival.}, }
@article {pmid25299107, year = {2014}, author = {Huan, JL and Gao, X and Xing, L and Qin, XJ and Qian, HX and Zhou, Q and Zhu, L}, title = {Screening for key genes associated with invasive ductal carcinoma of the breast via microarray data analysis.}, journal = {Genetics and molecular research : GMR}, volume = {13}, number = {3}, pages = {7919-7925}, doi = {10.4238/2014.September.29.5}, pmid = {25299107}, issn = {1676-5680}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal/*genetics ; Female ; *Genes, Neoplasm ; *Genetic Predisposition to Disease ; Humans ; Oligonucleotide Array Sequence Analysis ; }, abstract = {The aim of this study was to identify key genes related to invasive ductal carcinoma (IDC) of the breast by analyzing gene expression data with bioinformatic tools. Microarray data set GSE31138 was downloaded from Gene Expression Omnibus, including 3 breast cancer tissue samples and 3 normal controls. Differentially expressed genes (DEGs) between breast cancer and normal control were screened out (FDR < 0.05 and |logFC| > 2). Coexpression between genes was examined with String, and a network was then constructed. Relevant pathways and diseases were retrieved with KOBAS. A total of 56 DEGs were obtained in the IDC of the breast compared with normal controls. A gene coexpression network including 27 pairs of genes was constructed and all the genes in the network were upregulated. Further study indicated that most of the genes in the coexpression network were enriched in ECM-receptor interaction (COL4A2, FN1, and HMMR) and nucleotide excision repair (CETN2 and PCNA) pathways, and that the most significantly related disease was autoimmune lymphoproliferative syndromes. A number of DEGs were acquired through comparative analysis of gene expression data. These findings are beneficial in promoting the understanding of the molecular mechanisms in breast cancer. More importantly, some key genes were revealed via gene coexpression network analysis, which could be potential biomarkers for IDC of the breast.}, }
@article {pmid25296604, year = {2014}, author = {Ross, M and Hadzikadic Gusic, L and Dabbs, DJ and Kelley, J and Diego, E}, title = {Simultaneous breast and axillary recurrence in a patient with a history of breast cancer and ipsilateral upper extremity melanoma: challenges in diagnosis and management.}, journal = {Tumori}, volume = {100}, number = {4}, pages = {136e-9e}, doi = {10.1700/1636.17928}, pmid = {25296604}, issn = {2038-2529}, mesh = {Adult ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Arm ; Axilla ; Breast Neoplasms/diagnosis/*therapy ; Capecitabine ; Carcinoma, Ductal, Breast/*diagnosis/*therapy ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/therapy ; Chemotherapy, Adjuvant ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Female ; Fluorouracil/administration &amp; dosage/analogs &amp; derivatives ; Humans ; Interferons/administration &amp; dosage ; *Lymph Node Excision ; Mammaplasty ; *Mastectomy, Segmental/methods ; Mastectomy, Simple ; Melanoma/*secondary ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/*therapy ; Neoplasms, Multiple Primary/*diagnosis/pathology/*therapy ; Patient Care Team ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/pathology/*therapy ; Skin Neoplasms/*pathology ; Trastuzumab ; }, abstract = {BACKGROUND: Nodal patterns of spread for breast cancer and melanoma have been extensively studied in the literature. The phenomenon of upper extremity melanoma and ipsilateral breast cancer has been previously reported. We describe a rare case of a simultaneous locoregional recurrence of both malignancies.<br><br>CASE REPORT: A patient with a previous diagnosis of stage 1A melanoma of the left upper extremity at age 29 developed left breast invasive ductal carcinoma 1 year later. The patient underwent a wide local excision with negative margins for the melanoma and a partial mastectomy with axillary dissection followed by chemotherapy and radiation therapy for her breast cancer. Five years later she was diagnosed with a dual recurrence while 36 weeks pregnant.<br><br>CONCLUSIONS: Regular follow-up according to the NCCN guidelines is critical in diagnosing a recurrence of malignancy. Pathologic analysis is paramount in dictating management strategies in rare cases of dual recurrence.}, }
@article {pmid25287760, year = {2015}, author = {Abomaray, FM and Al Jumah, MA and Kalionis, B and AlAskar, AS and Al Harthy, S and Jawdat, D and Al Khaldi, A and Alkushi, A and Knawy, BA and Abumaree, MH}, title = {Human Chorionic Villous Mesenchymal Stem Cells Modify the Functions of Human Dendritic Cells, and Induce an Anti-Inflammatory Phenotype in CD1+ Dendritic Cells.}, journal = {Stem cell reviews and reports}, volume = {11}, number = {3}, pages = {423-441}, pmid = {25287760}, issn = {2629-3277}, mesh = {Antigens, CD1/metabolism ; Cell Differentiation/drug effects/*genetics ; Cell Proliferation/genetics ; Chorionic Villi/metabolism ; Coculture Techniques ; Dendritic Cells/*cytology/metabolism ; Female ; Gene Expression Regulation, Developmental ; Granulocyte-Macrophage Colony-Stimulating Factor/administration &amp; dosage ; Humans ; Interleukin-4/administration &amp; dosage ; Mesenchymal Stem Cells/*cytology/metabolism ; Monocytes/*cytology/metabolism ; Placenta/cytology/metabolism ; Pregnancy ; }, abstract = {BACKGROUND: Mesenchymal stem cells derived from the chorionic villi of human term placenta (pMSCs) have drawn considerable interest because of their multipotent differentiation potential and their immunomodulatory capacity. These properties are the foundation for their clinical application in the fields of stem cell transplantation and regenerative medicine. Previously, we showed that pMSCs induce an anti-inflammatory phenotype in human macrophages. In this study, we determined whether pMSCs modify the differentiation and maturation of human monocytes into dendritic cells (DCs). The consequences on dendritic function and on T cell proliferation were also investigated.<br><br>METHODS: Interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF) were used to stimulate the differentiation of monocytes into immature dendritic cells (iDCs), which were subsequently co-cultured with pMSCs. Lipopolysaccharide (LPS) was used to induce maturation of iDCs into mature dendritic cells (mDCs). Flow cytometry and enzyme-linked immunosorbent assays (ELISA) were used to quantify the effect pMSC co-culturing on DC differentiation using CD1a, a distinctive marker of DCs, as well as other molecules important in the immune functions of DCs. The phagocytic activity of iDCs co-cultured with pMSCs, and the effects of iDCs and mDC stimulation on T cell proliferation, were also investigated.<br><br>RESULTS: Monocyte differentiation into iDCs was inhibited when co-cultured with pMSCs and maturation of iDCs by LPS treatment was also prevented in the presence of pMSCs as demonstrated by reduced expression of CD1a and CD83, respectively. The inhibitory effect of pMSCs on iDC differentiation was dose dependent. In addition, pMSC co-culture with iDCs and mDCs resulted in both phenotypic and functional changes as shown by reduced expression of costimulatory molecules (CD40, CD80, CD83 and CD86) and reduced capacity to stimulate CD4(+) T cell proliferation. In addition, pMSC co-culture increased the surface expression of major histocompatibility complex (MHC-II) molecules on iDCs but decreased MHC-II expression on mDCs. Moreover, pMSC co-culture with iDCs or mDCs increased the expression of immunosuppressive molecules [B7H3, B7H4, CD273, CD274 and indoleamine-pyrrole 2,3-dioxygenase (IDO). Additionally, the secretion of IL-12 and IL-23 by iDCs and mDCs co-cultured with pMSCs was decreased. Furthermore, pMSC co-culture with mDCs decreased the secretion of IL-12 and INF-&#x3b3; whilst increasing the secretion of IL-10 in a T cell proliferation experiment. Finally, pMSC co-culture with iDCs induced the phagocytic activity of iDCs.<br><br>CONCLUSIONS: We have shown that pMSCs have an inhibitory effect on the differentiation, maturation and function of DCs, as well as on the proliferation of T cells, suggesting that pMSCs can control the immune responses at multiple levels.}, }
@article {pmid25287438, year = {2015}, author = {Adrada, BE and Huo, L and Lane, DL and Arribas, EM and Resetkova, E and Yang, W}, title = {Histopathologic correlation of residual mammographic microcalcifications after neoadjuvant chemotherapy for locally advanced breast cancer.}, journal = {Annals of surgical oncology}, volume = {22}, number = {4}, pages = {1111-1117}, doi = {10.1245/s10434-014-4113-8}, pmid = {25287438}, issn = {1534-4681}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Breast Neoplasms/diagnostic imaging/drug therapy/*pathology ; Calcinosis/chemically induced/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/drug therapy/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/drug therapy/*pathology ; Carcinoma, Lobular/diagnostic imaging/drug therapy/*pathology ; Female ; Follow-Up Studies ; Humans ; Mammography ; Middle Aged ; Neoadjuvant Therapy/*adverse effects ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasm, Residual/chemically induced/diagnostic imaging/*pathology ; Prognosis ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: This study was designed to determine the histopathologic correlation at surgery of residual mammographic calcifications in patients after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC).<br><br>METHODS: This single-institution, retrospective study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability act compliant. Women with LABC who underwent NAC between January 1, 2004 and December 31, 2008 and had mammography performed before and after NAC available for review were included in this study. The extent of microcalcifications associated with cancer before and after the completion of NAC was correlated with histopathology and biomarker status.<br><br>RESULTS: Of 494 patients who met the inclusion criteria, 106 demonstrated microcalcifications on pre-, post-chemotherapy, or both sets of mammograms and were included in this study. Of 106 women, 31 (29 %) had invasive ductal carcinoma (IDC) and 60 (57 %) had both IDC and ductal carcinoma in situ (DCIS). Microcalcifications decreased or remained stable in 76 (72 %) patients after completion of NAC. Correlation of microcalcifications with histopathology after NAC showed that 43 (40.6 %) patients had tumors associated with benign pathology. Of 32 patients with pathologic complete response, calcifications were associated with DCIS in 9 (9 %) and benign findings in 21 (22 %). The proportion of residual malignant calcifications was higher in ER+ versus ER- patients after NAC.<br><br>CONCLUSIONS: The extent of calcifications on mammography following NAC does not correlate with the extent of residual disease in up to 22 % of women; this information may impact surgical planning in subsets of women with breast cancer.}, }
@article {pmid25271877, year = {2015}, author = {Barbosa, OV and Reiriz, AB and Boff, RA and Oliveira, WP and Rossi, L}, title = {Angiosarcoma in previously irradiated breast in patient with Li-Fraumeni syndrome. A case report.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {133}, number = {2}, pages = {151-153}, pmid = {25271877}, issn = {1806-9460}, mesh = {Adult ; Breast Neoplasms/etiology/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/*radiotherapy ; Female ; Genes, p53 ; Genetic Predisposition to Disease ; Hemangiosarcoma/*etiology/pathology ; Humans ; Li-Fraumeni Syndrome/*genetics/pathology ; *Neoplasms, Radiation-Induced/pathology ; Radiotherapy, Adjuvant/adverse effects ; }, abstract = {CONTEXT: Li-Fraumeni syndrome is a rare disease with an autosomal dominant inheritance pattern and high penetrance that defines a 50% chance of developing cancer before the age of 30 years, including cases of breast sarcoma. Patients with this syndrome who require radiotherapy have an increased risk of developing secondary malignancies including angiosarcomas.<br><br>CASE REPORT: This was a case report on a female patient with Li-Fraumeni syndrome. In October 2005, she was diagnosed with invasive ductal carcinoma of the right breast and underwent sectorectomy. She then received chemotherapy and adjuvant radiotherapy. Trastuzumab and tamoxifen were also part of the treatment. She recently sought care at our hospital, complaining of hyperemia and nodulation in the right breast, and underwent surgical resection that revealed epithelioid angiosarcoma.<br><br>CONCLUSIONS: When genetic predisposition due to Li-Fraumeni syndrome is documented, the therapy should be adapted so as to minimize the risk. Thus, conservative surgical treatments should be avoided and mastectomy without radiation should be prioritized. In cases in which use of radiotherapy is justified, patients should be followed up intensively.}, }
@article {pmid25270118, year = {2014}, author = {Pacheco-Velázquez, SC and Gallardo-Pérez, JC and Aguilar-Ponce, JL and Villarreal, P and Ruiz-Godoy, L and Pérez-Sánchez, M and Marín-Hernández, A and Ruiz-García, E and Meneses-García, A and Moreno-Sánchez, R and Rodríguez-Enríquez, S}, title = {Identification of a metabolic and canonical biomarker signature in Mexican HR+/HER2-, triple positive and triple-negative breast cancer patients.}, journal = {International journal of oncology}, volume = {45}, number = {6}, pages = {2549-2559}, doi = {10.3892/ijo.2014.2676}, pmid = {25270118}, issn = {1791-2423}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Estrogen Receptor alpha/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis ; Mexico ; Middle Aged ; Prognosis ; *Proteomics ; Proto-Oncogene Proteins c-myc/biosynthesis ; Receptor, ErbB-2/*genetics ; Retrospective Studies ; Triple Negative Breast Neoplasms/diagnosis/*genetics/pathology ; }, abstract = {Infiltrating ductal breast cancer (IDC) is the principal tumor associated-malignancy in Mexican women. In IDC, the development of intermittent hypoxia leads to an adaptive response coordinated by the transcriptional factor HIF-1α. In the present pilot, retrospective/cross-sectional study, the HIF-1α expression was analyzed in 102 tru-cut biopsies from female patients (51 ± 12 years) without previous clinical treatment and compared to 31 normal breast biopsies. The 102 IDC samples corresponded to 56% of HER2-/HR+; 8% of HER2+/HR-; 22% of triple positive (HER2+/HR+); and 14% of triple negative (TN, HER2-/HR-) subtypes. To assess HIF-1α functionality, proteomic and kinetic analysis of glycolytic as well as mitochondrial enzymes, were determined. Validation of HIF-1α as cancer biomarker was assessed by determining the contents of the commonly used biomarkers c-MYC, Ki67, and H- and K-RAS, as well as metastatic and autophagy proteins. Proteomic analysis revealed that HIF-1α, c-MYC, HER2 and COXIV contents were significantly increased in all IDC subtypes vs. normal tissue. The contents and activities of glycolytic proteins were similar between normal and IDC samples, except for HER2-/HR+ where a substantial increase of HKII was observed. Significant increase in 2OGDH and E-cadherin was detected for TN samples vs. other IDC subtypes and for normal samples. These results clearly indicated that HIF-1α + COXIV + c-MYC (+ HER2 for HER2+ subtype) may be useful to depict a breast cancer metabolic marker pattern for diagnosis, whereas the contents of HIF-1α + c-MYC + 2OGDH + E-cadherin may be an alternative useful and reliable signature for TN subtype cancer prognosis.}, }
@article {pmid25261651, year = {2014}, author = {Petekkaya, I and Aksoy, S and Roach, EC and Okoh, AK and Gecmez, G and Gezgen, G and Isler, DC and Dogan, E and Babacan, T and Sarici, F and Petekkaya, E and Altundag, K}, title = {Impact of inflammatory markers on the prognosis of patients with operable breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {19}, number = {3}, pages = {673-680}, pmid = {25261651}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Sedimentation ; Breast Neoplasms/blood/*mortality ; C-Reactive Protein/analysis ; Female ; Ferritins/blood ; Humans ; Inflammation/*complications ; L-Lactate Dehydrogenase/blood ; Middle Aged ; Prognosis ; Serum Albumin/analysis ; beta 2-Microglobulin/blood ; }, abstract = {PURPOSE: To investigate the effect of inflammatory markers on the prognosis of patients with operable breast cancer.<br><br>METHODS: This study was conducted on breast cancer patients followed up between December 2009 and December 2012 at the Division of Medical Oncology, Department of Internal Medicine, Hacettepe University Medical School. A total of 704 patients with stages I to III disease whose inflammatory markers were assessed at the time of diagnosis were included the study. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, ferritin, &#x3b2;2 microglobulin (&#x3b2;2-M), and lactate dehydrogenase (LDH) levels were evaluated as inflammatory markers.<br><br>RESULTS: The median age at diagnosis was 50 years (range 25-92). Of the patients 42.8% were premenopausal and 48.2 % postmenopausal. Invasive ductal carcinoma was the most common histology (76.5 %). Serum ferritin, LDH, &#x3b2;2-M, ESR, and CRP were higher than the normal values in 1.0, 4.3, 9.5, 32.4 and 36.4 % of the patients, respectively. Serum albumin levels were lower than the normal values in 1.7 % of the patients. The median patient follow-up period was 22 months (range 3-227). During follow-up, metastatic disease developed in 31 patients (4.4%) and 11 patients (1.56%) died due to disease progression. Two-year overall survival (OS) and disease free survival (DFS) rates were not statistically different among patients with normal and abnormal values with respect to albumin, ferritin, LDH, &#x3b2;2-M, CRP, and ESR.<br><br>CONCLUSION: Our study is the first study to investigate the effect of inflammatory markers on the prognosis of operable breast cancer patients. We showed that inflammatory markers such as ESR, CRP, ferritin, &#x3b2;2-M, albumin and LDH have no effect on prognosis.}, }
@article {pmid25260852, year = {2015}, author = {Moccia, M and Mosca, L and Erro, R and Cervasio, M and Allocca, R and Vitale, C and Leonardi, A and Caranci, F and Del Basso-De Caro, ML and Barone, P and Penco, S}, title = {Hypomorphic NOTCH3 mutation in an Italian family with CADASIL features.}, journal = {Neurobiology of aging}, volume = {36}, number = {1}, pages = {547.e5-11}, doi = {10.1016/j.neurobiolaging.2014.08.021}, pmid = {25260852}, issn = {1558-1497}, mesh = {Adult ; Aged ; Animals ; CADASIL/*genetics ; *Codon, Nonsense ; Exons/genetics ; Female ; Humans ; Italy ; Male ; Mice ; Middle Aged ; RNA, Messenger ; Receptor, Notch3 ; Receptors, Notch/*genetics ; Signal Transduction/genetics/physiology ; Young Adult ; }, abstract = {The cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is because of NOTCH3 mutations affecting the number of cysteine residues. In this view, the role of atypical NOTCH3 mutations is still debated. Therefore, we investigated a family carrying a NOTCH3 nonsense mutation, with dominantly inherited recurrent cerebrovascular disorders. Among 7 family members, 4 received a clinical diagnosis of CADASIL. A heterozygous truncating mutation in exon 3 (c.307C>T, p.Arg103X) was found in the 4 clinically affected subjects and in one 27-year old lady, only complaining of migraine with aura. Magnetic resonance imaging scans found typical signs of small-vessel disease in the 4 affected subjects, supporting the clinical diagnosis. Skin biopsies did not show the typical granular osmiophilic material, but only nonspecific signs of vascular damage, resembling those previously described in Notch3 knockout mice. Interestingly, messenger RNA (mRNA) analysis supports the hypothesis of an atypical NOTCH3 mutation, suggesting a nonsense-mediated mRNA decay. In conclusion, the present study broadens the spectrum of CADASIL mutations, and, therefore, opens new insights about Notch3 signaling.}, }
@article {pmid25257596, year = {2015}, author = {Zhang, M and Zhou, J and Wang, J and Zhou, Q and Fang, J and Zhou, C and Chen, W}, title = {Superparamagnetic iron oxide labeling limits the efficacy of rabbit immature dendritic cell vaccination by decreasing their antigen uptake ability in a lysosome-dependent manner.}, journal = {Biotechnology letters}, volume = {37}, number = {2}, pages = {289-298}, doi = {10.1007/s10529-014-1681-4}, pmid = {25257596}, issn = {1573-6776}, mesh = {Animals ; Aspirin ; Autophagy/drug effects ; Cell Survival/drug effects ; Dendritic Cells/*drug effects/metabolism ; Lysosomes/*drug effects/metabolism ; Magnetite Nanoparticles/*chemistry/toxicity ; Rabbits ; Vaccination ; }, abstract = {Immature dendritic cells (iDCs) are for cell transplantation; however, no method has yet been developed for in vivo monitoring the transplanted iDCs. We have explored the feasibility of using superparamagnetic iron oxide (SPIO) labeling and magnetic resonance imaging for in vivo tracking of transplanted iDCs and determined the effects of SPIO labeling on iDC vaccination. With up to 50 μg Fe/ml, SPIO effectively labeled the iDCs without affecting their growth. At or above 100 μg Fe/ml, SPIO caused considerable damage to iDCs. SPIO labeling resulted in autophagosome formation and decreased the uptake of oxidized low density lipoprotein (ox-LDL), an exogenous antigen, by iDCs. SPIO and ox-LDL both localized to the lysosomes, and this competition for lysosomes could be partially responsible for the decreased ox-LDL phagocytic capacity of iDCs due to SPIO labeling.}, }
@article {pmid25252956, year = {2014}, author = {Ellegård, R and Crisci, E and Burgener, A and Sjöwall, C and Birse, K and Westmacott, G and Hinkula, J and Lifson, JD and Larsson, M}, title = {Complement opsonization of HIV-1 results in decreased antiviral and inflammatory responses in immature dendritic cells via CR3.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {193}, number = {9}, pages = {4590-4601}, pmid = {25252956}, issn = {1550-6606}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Complement System Proteins/*immunology ; Dendritic Cells/*immunology/*metabolism/virology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Profiling ; HIV Infections/genetics/*immunology/metabolism ; HIV-1/*immunology ; Humans ; Immunity, Innate/genetics ; Inflammation/genetics/immunology/metabolism ; Interferon Regulatory Factor-1/metabolism ; Interferon Regulatory Factor-3/metabolism ; Macrophage-1 Antigen/*metabolism ; Models, Biological ; NF-kappa B/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Phosphorylation ; Protein Transport ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; Toll-Like Receptor 8/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; src-Family Kinases/metabolism ; }, abstract = {Immature dendritic cells (iDCs) in genital and rectal mucosa may be one of the first cells to come into contact with HIV-1 during sexual transmission of virus. HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab-opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-β, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1β, IL-6, and TNF-α, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-κB pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.}, }
@article {pmid25231588, year = {2014}, author = {Gabanti, E and Bruno, F and Fornara, C and Bernuzzi, S and Lilleri, D and Gerna, G}, title = {Polyfunctional analysis of human cytomegalovirus (HCMV)-specific CD4(+) and CD8 (+) memory T-cells in HCMV-seropositive healthy subjects following different stimuli.}, journal = {Journal of clinical immunology}, volume = {34}, number = {8}, pages = {999-1008}, pmid = {25231588}, issn = {1573-2592}, mesh = {Adult ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*chemistry ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/*immunology ; Flow Cytometry ; Healthy Volunteers ; Humans ; Immunization ; *Immunologic Memory ; Middle Aged ; }, abstract = {PURPOSE: Following primary human cytomegalovirus (HCMV) infection, both humoral and T-cell-mediated immune responses develop in immunocompetent subjects. However, while antibodies may be measured by different methodologies, the T-cell-mediated response remains to be analyzed in its polyfunctional aspects, in view of defining (following different stimuli) the optimal assay to monitor the HCMV-specific T-cell response in HCMV-seropositive subjects.<br><br>METHODS: In a group of 30 HCMV-seropositive adults, T-cell response revealed by the HCMV-infected dendritic cell (iDC) stimulus was compared with those given by the HCMV-infected cell lysate (iCL), and by a 34-peptide pool (PP).<br><br>RESULTS: All HCMV-seropositive subjects showed presence of both HCMV-specific CD4(+) and CD8(+) T-cells in peripheral blood following iDC stimulation. One subject did not respond to PP. As compared to iDC, the number of HCMV-specific stimulated T-cells/&#x3bc;l blood was slightly lower for iCL (P&#x2009;=&#x2009;0.195) and significantly lower for PP (P&#x2009;=&#x2009;0.001). Polyfunctional analysis of the T-cell response indicated that the lower number of CD4(+) T-cells stimulated by iCL was due to the bifunctional (IFN-&#x3b3;(+) TNF-&#x3b1;(+)) and CD40L-negative T-cell reduction, while the reduction in specific PP-stimulated CD8(+) T-cells was attributable to the reduction in tri-(IFN-&#x3b3;(+) TNF-&#x3b1;(+) IL2(+)), bi-(IFN-&#x3b3;(+) TNF-&#x3b1;(+)) and mono-(IFN-&#x3b3;(+)) functional T-cells. In addition, 15/30 (50&#xa0;%) subjects showed a CD4(+) cross-response to PP, and 11/30 (37&#xa0;%) a CD8(+) cross-response to iCL.<br><br>CONCLUSIONS: HCMV-specific stimulus given by iDC is not significantly different from that of iCL on CD4(+) and is significantly superior to that of PP on CD8+ T-cells. However, iCL may contribute significantly to CD8(+), and PP to CD4(+) T-cell stimulation.}, }
@article {pmid25230850, year = {2014}, author = {Zheng, L and Zhou, B and Meng, X and Zhu, W and Zuo, A and Wang, X and Jiang, R and Yu, S}, title = {A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer.}, journal = {International journal of oncology}, volume = {45}, number = {6}, pages = {2241-2249}, pmid = {25230850}, issn = {1791-2423}, mesh = {Animals ; Biomarkers, Tumor/biosynthesis ; Breast Neoplasms/*genetics/pathology ; Cyclin D1/biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Mammary Neoplasms, Animal/*genetics/pathology ; Mice ; Proto-Oncogene Proteins c-myc/biosynthesis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Vascular Endothelial Growth Factor A/biosynthesis ; }, abstract = {Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study was to characterize the spontaneous mammary tumor model. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and muscle tissue. Metastatic spread through blood vessel into liver and lungs was observed by hematoxylin eosin staining. No estrogen receptor (ER) or progesterone receptor (PR) immunoreactivity was detected in their associated malignant tumors, human epidermal growth factor receptor-2 (HER-2) protein weak expression was found by immunohistochemistry. High expression of vascular endothelial growth factor (VEGF), moderate or high expression of c-Myc and cyclin D1 were observed in tumor sections at different stages (2, 4, 6 and 8 weeks after cancer being found) when compared with that of the normal mammary glands. The result showed that the model is of an invasive ductal carcinoma. Remarkably in the mouse model, ER and PR-negative and HER2 weak positivity are observed. The high or moderate expressions of breast cancer markers (VEGF, c-Myc and cyclin D1) in mammary cancer tissue change at different stages. To our knowledge, this is the first report of a spontaneous mammary model displaying colony-strain, outbred mice. This model will be an attractive tool to understand the biology of anti-hormonal breast cancer in women.}, }
@article {pmid25230018, year = {2014}, author = {Yoda, T and McNamara, KM and Miki, Y and Takagi, M and Rai, Y and Ohi, Y and Sagara, Y and Tamaki, K and Hirakawa, H and Ishida, T and Suzuki, T and Ohuchi, N and Sasano, H}, title = {Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.}, journal = {Cancer science}, volume = {105}, number = {11}, pages = {1503-1509}, pmid = {25230018}, issn = {1349-7006}, mesh = {3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics/metabolism ; Adult ; Aged ; Aged, 80 and over ; Androgens/*metabolism ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Lobular/genetics/*metabolism/*pathology ; Estradiol Dehydrogenases/genetics/metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Tumor Burden ; }, abstract = {Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen-responsive environment, the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1) in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. Androgen receptor prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (P = 0.0053) and nuclear grade (P = 0.0290), and significantly associated with better overall survival of the patients (P = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (P < 0.0001) and intratumoral 17βHSD2 was inversely correlated with tumor size in ILC (P = 0.0075). These correlations suggest one protective mode of androgen action could be through modulation of estrogen metabolism. Results of our present study indicated that androgen-producing enzymes could play pivotal protective roles in AR-enriched ILC cases.}, }
@article {pmid25228385, year = {2014}, author = {Tan, X and Peng, J and Fu, Y and An, S and Rezaei, K and Tabbara, S and Teal, CB and Man, YG and Brem, RF and Fu, SW}, title = {miR-638 mediated regulation of BRCA1 affects DNA repair and sensitivity to UV and cisplatin in triple-negative breast cancer.}, journal = {Breast cancer research : BCR}, volume = {16}, number = {5}, pages = {435}, pmid = {25228385}, issn = {1465-542X}, support = {R21 CA159103/CA/NCI NIH HHS/United States ; 1R21 CA159103-01/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/*pharmacology ; BRCA1 Protein/*genetics/metabolism ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin/*pharmacology ; DNA Repair ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*physiology ; Neoplasm Invasiveness ; RNA Interference ; Triple Negative Breast Neoplasms/drug therapy/*genetics/metabolism/pathology ; Ultraviolet Rays ; }, abstract = {INTRODUCTION: Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targets BRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment.<br><br>METHODS: Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal epithelial and invasive ductal carcinoma (IDC) cells, and total RNA was isolated. Several breast cancer cell lines were used for the functional analysis. miR-638 target genes were identified by TARGETSCAN-VERT 6.2 and miRanda. The expression of miR-638 and its target genes was analyzed by real-time qRT-PCR and Western blotting. Dual-luciferase reporter assay was employed to confirm the specificity of miR-638 target genes. The biological function of miR-638 was analyzed by MTT chemosensitivity, matrigel invasion and host cell reactivation assays.<br><br>RESULTS: The expression of miR-638 was decreased in IDC tissue samples compared to their adjacent normal controls. The decreased miR-638 expression was more prevalent in non-TNBC compared with TNBC cases. miR-638 expression was significantly downregulated in breast cancer cell lines compared to the immortalized MCF-10A epithelial cells. BRCA1 was predicted as one of the direct targets of miR-638, which was subsequently confirmed by dual-luciferase reporter assay. Forced expression of miR-638 resulted in a significantly reduced proliferation rate as well as decreased invasive ability in TNBC cells. Furthermore, miR-638 overexpression increased sensitivity to DNA-damaging agents, ultraviolet (UV) and cisplatin, but not to 5-fluorouracil (5-FU) and epirubicin exposure in TNBC cells. Host cell reactivation assays showed that miR-638 reduced DNA repair capability in post UV/cisplatin-exposed TNBC cells. The reduced proliferation, invasive ability, and DNA repair capabilities are associated with downregulated BRCA1 expression.<br><br>CONCLUSIONS: Our findings suggest that miR-638 plays an important role in TNBC progression via BRCA1 deregulation. Therefore, miR-638 might serve as a potential prognostic biomarker and therapeutic target for breast cancer.}, }
@article {pmid25227964, year = {2014}, author = {Kryh, CG and Pietersen, CA and Rahr, HB and Christensen, RD and Wamberg, P and Lautrup, MD}, title = {Re-resection rates and risk characteristics following breast conserving surgery for breast cancer and carcinoma in situ: A single-centre study of 1575 consecutive cases.}, journal = {Breast (Edinburgh, Scotland)}, volume = {23}, number = {6}, pages = {784-789}, doi = {10.1016/j.breast.2014.08.011}, pmid = {25227964}, issn = {1532-3080}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms/pathology/*surgery ; Carcinoma in Situ/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Cohort Studies ; Denmark ; Female ; Humans ; *Mastectomy, Segmental ; Neoadjuvant Therapy ; Reoperation ; Risk Factors ; }, abstract = {OBJECTIVES: To examine the frequency of re-resections and describe risk characteristics: invasive carcinoma or carcinoma in situ (CIS), palpability of the lesion, and neoadjuvant chemotherapy.<br><br>RESULTS: 1703 breast conserving surgeries were performed: 1575 primary breast conserving surgeries (BCS), and 128 diagnostic excisions (DE). 176 BCS (11.2% [9.6; 12.7]) and 100 DE had inadequate margins indicating re-resection. The overall re-resection rate was 16.2% [14.5; 18.0]. 10.3% of invasive carcinoma BCS patients, and 28.6% CIS patients underwent re-resection (relative risk (RR) 2.8 [1.9; 4.1]). Invasive lobular carcinoma (ilc) had an RR of re-resection of 2.5 [1.7; 3.8], compared with invasive ductal carcinoma (idc).<br><br>CONCLUSION: Overall 11.2% of the BCS patients needed a re-resection. For isolated CIS (28.6%), RR of re-resection was almost three times as high compared to invasive carcinoma (10.3%). Ilc had an RR of re-resection of 2.5 compared to idc. Palpability and neoadjuvant chemotherapy did not significantly influence the risk of re-resection.}, }
@article {pmid25225893, year = {2014}, author = {Mamidi, S and Lee, RK and Goos, JR and McClean, PE}, title = {Genome-wide association studies identifies seven major regions responsible for iron deficiency chlorosis in soybean (Glycine max).}, journal = {PloS one}, volume = {9}, number = {9}, pages = {e107469}, pmid = {25225893}, issn = {1932-6203}, mesh = {Alleles ; Chromosome Mapping ; Disease Resistance/genetics ; Epistasis, Genetic ; Genes, Plant ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Genotype ; *Iron Deficiencies ; Linkage Disequilibrium ; Molecular Sequence Annotation ; Phenotype ; Plant Diseases/*genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Soybeans/*genetics/*metabolism ; }, abstract = {Iron deficiency chlorosis (IDC) is a yield limiting problem in soybean (Glycine max (L.) Merr) production regions with calcareous soils. Genome-wide association study (GWAS) was performed using a high density SNP map to discover significant markers, QTL and candidate genes associated with IDC trait variation. A stepwise regression model included eight markers after considering LD between markers, and identified seven major effect QTL on seven chromosomes. Twelve candidate genes known to be associated with iron metabolism mapped near these QTL supporting the polygenic nature of IDC. A non-synonymous substitution with the highest significance in a major QTL region suggests soybean orthologs of FRE1 on Gm03 is a major gene responsible for trait variation. NAS3, a gene that encodes the enzyme nicotianamine synthase which synthesizes the iron chelator nicotianamine also maps to the same QTL region. Disease resistant genes also map to the major QTL, supporting the hypothesis that pathogens compete with the plant for Fe and increase iron deficiency. The markers and the allelic combinations identified here can be further used for marker assisted selection.}, }
@article {pmid25224685, year = {2015}, author = {Ganoth, A and Merimi, KC and Peer, D}, title = {Overcoming multidrug resistance with nanomedicines.}, journal = {Expert opinion on drug delivery}, volume = {12}, number = {2}, pages = {223-238}, doi = {10.1517/17425247.2015.960920}, pmid = {25224685}, issn = {1744-7593}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; *Drug Delivery Systems ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Nanomedicine ; Nanoparticles ; Neoplasms/*drug therapy/pathology ; }, abstract = {INTRODUCTION: Cancer remains the leading cause of death worldwide. Numerous therapeutic strategies that include smart biological treatments toward specific cellular pathways are being developed. Yet, inherent and acquired multidrug resistance (MDR) to chemotherapeutic drugs remains the major obstacle in effective cancer treatments.<br><br>AREAS COVERED: Herein, we focused on an implementation of nanoscale drug delivery strategies (nanomedicines) to treat tumors that resist MDR. Specifically, we briefly discuss the MDR phenomenon and provide structural and functional characterization of key proteins that account for MDR. We next describe the strategies to target tumors using nanoparticles and provide a mechanistic overview of how changes in the influx:efflux ratio result in overcoming MDR.<br><br>EXPERT OPINION: Various strategies have been applied in preclinical and clinical settings to overcome cancer MDR. Among them are the use of chemosensitizers that aim to sensitize the cancer cells to chemotherapeutic treatment and the use of nanomedicines as delivery vehicles that can increase the influx of drugs into cancer cells. These strategies can enhance the therapeutic response in resistant tumors by bypassing efflux pumps or by increasing the nominal amounts of therapeutic payloads into the cancer cells at a given time point.}, }
@article {pmid25224155, year = {2014}, author = {Li, J and Zhang, Y and Zhang, W and Gao, Y and Jia, S and Guo, J}, title = {Contrast enhanced computed tomography is indicative for angiogenesis pattern and display prognostic significance in breast cancer.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {672}, pmid = {25224155}, issn = {1471-2407}, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*diagnostic imaging/mortality/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Female ; Humans ; Immunohistochemistry ; Microvessels/pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Neovascularization, Pathologic/*diagnostic imaging ; Prognosis ; Risk Factors ; Survival Analysis ; *Tomography, X-Ray Computed/methods ; }, abstract = {BACKGROUND: The Prognostic value of microvessel density in cancer remains unclear. Recent studies have suggested that the uneven distribution of microvessels in tumours caused the variation in sample selection which led to different prognostic outcome. The enhancement pattern of Contrast-enhanced computed tomography (CECT) is determined in part by the microvessel distribution in solid tumors. Therefore, survival analysis of tumors grouping by the enhancement pattern and the pattern of microvessel distribution is important.<br><br>METHODS: Survival analysis grouped by the tumor enhancement pattern and the microvessel distribution was carried out in 255 patients with invasive ductal carcinoma.<br><br>RESULTS: There were significant differences in overall survival (OS) and disease-free survival (DFS) among the homogeneous, heterogeneous and peripheral enhancement groups. There were significant differences between OS and DFS groups with uniform and uneven distributions of microvessels.<br><br>CONCLUSIONS: The distribution of microvessels in a tumor is a potential prognostic indicator in patients with breast cancer, and can be assessed by CECT prior the operation.}, }
@article {pmid25209856, year = {2014}, author = {Kondo, Y and Kikuchi, T and Esteban, JC and Kumaki, N and Ogura, G and Inomoto, C and Hirabayashi, K and Kajiwara, H and Sakai, A and Sugimoto, R and Otsuru, M and Okami, K and Tsukinoki, K and Nakamura, N}, title = {Intratumoral heterogeneity of HER2 protein and amplification of HER2 gene in salivary duct carcinoma.}, journal = {Pathology international}, volume = {64}, number = {9}, pages = {453-459}, doi = {10.1111/pin.12195}, pmid = {25209856}, issn = {1440-1827}, mesh = {Adenocarcinoma/genetics/*metabolism/pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Child ; Child, Preschool ; Gene Amplification ; *Gene Expression Regulation, Neoplastic ; Genetic Heterogeneity ; Humans ; Immunohistochemistry ; In Situ Hybridization/methods ; Male ; Middle Aged ; Receptor, ErbB-2/genetics/*metabolism ; Retrospective Studies ; Salivary Gland Neoplasms/genetics/*metabolism/pathology ; Young Adult ; }, abstract = {Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands, and accounts for 1-3% of all malignant salivary gland tumors, resembling morphologically invasive ductal carcinoma (IDC) of the breast. In contrast to IDC of the breast and gastric carcinoma (GC), the study of human epidermal growth factor receptor 2 (HER2) in SDC has not progressed. Therefore, we investigated the relationship between HER2 protein expression and amplification of the HER2 gene, and compared them in terms of intratumoral heterogeneity (ITH) in 13 cases of SDC using immunohistochemistry and dual color in situ hybridization. We found seven cases with protein overexpression (53.8%) and five cases with gene amplification (38.5%) in accordance with ASCO/CAP guidelines. ITH of HER2 protein expression was seen in seven cases (53.8%). Interestingly, the ratio of the HER2 gene showed homogenous distribution with or without the presence of ITH of HER2 protein expression. SDC tends to have more ITH of HER2 protein similarly to GC, in contrast to IDC of the breast. ITH of HER2 protein in SDC has no heterogeneity of the HER2 gene amplification. The mechanism of HER2 protein expression in SDC might proceed through a more complex pathway relative to that of IDC of the breast.}, }
@article {pmid25205656, year = {2014}, author = {List, T and Casi, G and Neri, D}, title = {A chemically defined trifunctional antibody-cytokine-drug conjugate with potent antitumor activity.}, journal = {Molecular cancer therapeutics}, volume = {13}, number = {11}, pages = {2641-2652}, doi = {10.1158/1535-7163.MCT-14-0599}, pmid = {25205656}, issn = {1538-8514}, mesh = {Animals ; Antibodies/chemistry/immunology/*pharmacology ; CHO Cells ; Cell Line, Tumor ; Cricetinae ; Cricetulus ; Cytokines/chemistry/immunology/*pharmacology ; Disease Models, Animal ; Female ; Humans ; Immunotoxins/*chemistry/immunology/*pharmacology ; Male ; Mice ; Neoplasms/*drug therapy/immunology ; }, abstract = {The combination of immunostimulatory agents with cytotoxic drugs is emerging as a promising approach for potentially curative tumor therapy, but advances in this field are hindered by the requirement of testing individual combination partners as single agents in dedicated clinical studies, often with suboptimal efficacy. Here, we describe for the first time a novel multipayload class of targeted drugs, the immunocytokine-drug conjugates (IDC), which combine a tumor-homing antibody, a cytotoxic drug, and a proinflammatory cytokine in the same molecular entity. In particular, the IL2 cytokine and the disulfide-linked maytansinoid DM1 microtubular inhibitor could be coupled to the F8 antibody, directed against the alternatively spliced EDA domain of fibronectin, in a site-specific manner, yielding a chemically defined product with selective tumor-homing performance and potent anticancer activity in vivo, as tested in two different immunocompetent mouse models.}, }
@article {pmid25202063, year = {2014}, author = {Pula, B and Olbromski, M and Owczarek, T and Ambicka, A and Witkiewicz, W and Ugorski, M and Rys, J and Zabel, M and Dziegiel, P and Podhorska-Okolow, M}, title = {Nogo-B receptor expression correlates negatively with malignancy grade and ki-67 antigen expression in invasive ductal breast carcinoma.}, journal = {Anticancer research}, volume = {34}, number = {9}, pages = {4819-4828}, pmid = {25202063}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/mortality/*pathology ; Cell Line, Transformed ; Cell Line, Tumor ; Female ; Fibroblasts/metabolism ; Follow-Up Studies ; Gene Expression ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Prognosis ; Receptors, Cell Surface/genetics/*metabolism ; }, abstract = {BACKGROUND: Nogo-B receptor (NgBR) has been shown to be involved in endothelial cell chemotaxis and morphogenesis. However, few studies analyzing its expression in cancer cells have been performed.<br><br>MATERIALS AND METHODS: We examined NgBR expression in 233 patients with invasive ductal breast carcinoma (IDC) and corresponding non-malignant breast tissues (NMBT) on mRNA (real-time polymerase chain reaction) and protein levels (immunohistochemistry; IHC and western-blot analysis). NgBR expression was found also analyzed in breast cancer cell lines of varying invasiveness.<br><br>RESULTS: NgBR expression was increased in IDC compared to NMBT on the mRNA (p=0.0007) and protein level (p=0.018). NgBR expression decreased significantly with IDC malignancy grade and correlated negatively with the Ki-67 antigen expression (r=-0.18; p=0.0005). High NgBR mRNA expression was associated with estrogen receptor negativity (p=0.0023) and the triple-negative phenotype of the tumors (p=0.0129).<br><br>CONCLUSION: NgBR may be involved in IDC development, however, its role in its progression requires further research.}, }
@article {pmid25192983, year = {2015}, author = {Chu, J and Wang, T and Pei, S and Yin, Z}, title = {Surgical treatment for idiopathic intervertebral disc calcification in a child: case report and review of the literature.}, journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery}, volume = {31}, number = {1}, pages = {123-127}, pmid = {25192983}, issn = {1433-0350}, mesh = {Adolescent ; Calcinosis/*complications/*surgery ; Decompression, Surgical/*methods ; Humans ; Intervertebral Disc/*surgery ; Intervertebral Disc Degeneration/*complications/*surgery ; Male ; }, abstract = {PURPOSE: Intervertebral disc calcification (IDC) is rare in children. Conservative treatment has been recommended for the majority of cases. We describe surgical treatment of a case of IDC with progressive neurological impairment and review the literature relevant to this rare entity and its management.<br><br>METHODS: A 16-year-old boy presented with sudden onset of severe neck pain, radiating into his left shoulder. Three months later, he developed neurological symptoms and signs with a progressive motor and sensory loss of his left upper limb.<br><br>RESULTS: Anterior cervical corpectomy with fusion and instrumentation was performed. Neurologic deficits completely resolved within 1 week. After 1-year follow-up, radiological images showed solid fusion and no further compression.<br><br>CONCLUSION: Surgical decompression should be recommended for cases with acutely progressive and severe neurological impairments in IDC and a good result can be obtained. When surgery is needed, anterior decompression is usually used in cervical lesion, while in thoracic and lumbar area, posterior approach is suggested.}, }
@article {pmid25192706, year = {2014}, author = {Chen, L and Malone, KE and Li, CI}, title = {Bra wearing not associated with breast cancer risk: a population-based case-control study.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {23}, number = {10}, pages = {2181-2185}, pmid = {25192706}, issn = {1538-7755}, support = {R01 CA085913/CA/NCI NIH HHS/United States ; R01CA 85913/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/*epidemiology ; Carcinoma/*epidemiology ; Case-Control Studies ; Clothing/*adverse effects ; Female ; Humans ; Middle Aged ; Risk Factors ; United States/epidemiology ; }, abstract = {Despite the widespread use of bras among U.S. women and concerns in the lay media that bra wearing may increase breast cancer risk, there is a scarcity of credible scientific studies addressing this issue. The goal of the study was to evaluate the relationship between various bra-wearing habits and breast cancer risk among postmenopausal women. We conducted a population-based case-control study of breast cancer in the Seattle-Puget Sound metropolitan area that compared 454 invasive ductal carcinoma (IDC) cases and 590 invasive lobular carcinoma (ILC) cases diagnosed between 2000 and 2004 with 469 control women between 55 to 74 years of age. Information on bra-wearing habits and other breast cancer risk factors was collected from study participants through in-person interviews. Multivariate adjusted odds ratios (OR) and their associated 95% confidence intervals (CI) were estimated using polytomous logistic regression. No aspect of bra wearing, including bra cup size, recency, average number of hours/day worn, wearing a bra with an underwire, or age first began regularly wearing a bra, was associated with risks of either IDC or ILC. Our results did not support an association between bra wearing and increased breast cancer risk among postmenopausal women.}, }
@article {pmid25176936, year = {2014}, author = {De Castro-Orós, I and Cenarro, A and Tejedor, MT and Baila-Rueda, L and Mateo-Gallego, R and Lamiquiz-Moneo, I and Pocoví, M and Civeira, F}, title = {Common genetic variants contribute to primary hypertriglyceridemia without differences between familial combined hyperlipidemia and isolated hypertriglyceridemia.}, journal = {Circulation. Cardiovascular genetics}, volume = {7}, number = {6}, pages = {814-821}, doi = {10.1161/CIRCGENETICS.114.000522}, pmid = {25176936}, issn = {1942-3268}, mesh = {Adaptor Proteins, Signal Transducing/genetics ; Adult ; Age Factors ; Alleles ; Apolipoprotein A-V ; Apolipoproteins A/genetics ; Blood Glucose/analysis ; Body Mass Index ; Female ; Gene Frequency ; *Genetic Variation ; Genotype ; Humans ; Hyperlipidemia, Familial Combined/*genetics/pathology ; Hypertriglyceridemia/*genetics/pathology ; Lipoprotein Lipase/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Sex Factors ; Triglycerides/blood ; }, abstract = {BACKGROUND: The majority of hypertriglyceridemias are diagnosed as familial combined hyperlipidemia (FCHL) and primary isolated hypertriglyceridemias. The contribution of common genetic variants in primary hypertriglyceridemias and the genetic difference between FCHL and isolated hypertriglyceridemias have not been thoroughly examined.<br><br>METHODS AND RESULTS: This study involved 580 patients with hypertriglyceridemias and 403 controls. Of the 37 single nucleotide polymorphisms examined, 12 located in 10 genes showed allelic and genotype frequency differences between hypertriglyceridemias and controls. The minor alleles of APOE, APOA5, GALNTN2, and GCKR variants were positively correlated with plasma triglycerides, whereas minor alleles of ADIPOR2, ANGPTL3, LPL, and TRIB1 polymorphisms were inversely associated. Body mass index, glucose, sex, rs328 and rs7007797 in LPL, rs662799 and rs3135506 in APOA5, and rs1260326 in GCKR explained 36% of the variability in plasma triglycerides, 7.3% of which was attributable to the genetic variables. LPL, GCKR, and APOA5 polymorphisms fit dominant, recessive, and additive inheritance models, respectively. Variants more frequently identified in isolated hypertriglyceridemias were rs7412 in APOE and rs1800795 in IL6; rs2808607 in CYP7A1 and rs3812316 and rs17145738 in MLXIPL were more frequent in FCHL. The other 32 single nucleotide polymorphisms presented similar frequencies between isolated hypertriglyceridemias and FCHL.<br><br>CONCLUSIONS: Common genetic variants found in LPL, APOA5, and GCKR are associated with triglycerides levels in patients with primary hypertriglyceridemias. FCHL and isolated hypertriglyceridemias are probably trace to an accumulation of genetic variants predisposing to familial and sporadic hypertriglyceridemias or to hypertriglyceridemias and hypercholesterolemia in case of FCHL.}, }
@article {pmid25173099, year = {2015}, author = {Zhao, B and Xu, B and Hu, W and Song, C and Wang, F and Liu, Z and Ye, M and Zou, H and Miao, QR}, title = {Comprehensive proteome quantification reveals NgBR as a new regulator for epithelial-mesenchymal transition of breast tumor cells.}, journal = {Journal of proteomics}, volume = {112}, number = {}, pages = {38-52}, pmid = {25173099}, issn = {1876-7737}, support = {R01 HL108938/HL/NHLBI NIH HHS/United States ; R01HL108938/HL/NHLBI NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Cell Line, Tumor ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; Neoplasm Proteins/genetics/*metabolism ; Proteome/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; }, abstract = {UNLABELLED: Nogo-B receptor (NgBR) is a type I receptor and specifically binds to ligand Nogo-B. Our previous work has shown that NgBR is highly expressed in human breast invasive ductal carcinoma. Here, comprehensive proteome quantification was performed to examine the alteration of protein expression profile in MDA-MB-231 breast tumor cells after knocking down NgBR using lentivirus-mediated shRNA approach. Among a total of 1771 proteins feasibly quantified, 994 proteins were quantified in two biological replicates with RSD <50%. There are 122 proteins significantly down-regulated in NgBR knockdown MDA-MB-231 breast tumor cells, such as vimentin and S100A4, well-known markers for mesenchymal cells, and CD44, a stemness indicator. The decrease of vimentin, S100A4 and CD44 protein expression levels was further confirmed by Western blot analysis. MDA-MB-231 cells are typical breast invasive ductal carcinoma cells showing mesenchymal phenotype. Cell morphology analysis demonstrates NgBR knockdown in MDA-MB-231 cells results in reversibility of epithelial-mesenchymal transition (EMT), which is one of the major mechanisms involved in breast cancer metastasis. Furthermore, we demonstrated that NgBR knockdown in MCF-7 cells significantly prevented the TGF-β-induced EMT process as determined by the morphology change, and staining of E-cadherin intercellular junction as well as the decreased expression of vimentin.<br><br>BIOLOGICAL SIGNIFICANCE: Our previous publication showed that NgBR is highly expressed in human breast invasive ductal carcinoma. However, the roles of NgBR and NgBR-mediated signaling pathway in breast tumor cells are still unclear. Here, we not only demonstrated that the quantitative proteomics analysis is a powerful tool to investigate the global biological function of NgBR, but also revealed that NgBR is involved in the transition of breast epithelial cells to mesenchymal stem cells, which is one of the major mechanisms involved in breast cancer metastasis. These findings provide new insights for understanding the roles of NgBR in regulating breast epithelial cell transform during the pathogenesis of breast cancer.}, }
@article {pmid25171226, year = {2014}, author = {Samikkannu, T and Rao, KV and Ding, H and Agudelo, M and Raymond, AD and Yoo, C and Nair, MP}, title = {Immunopathogenesis of HIV infection in cocaine users: role of arachidonic acid.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e106348}, pmid = {25171226}, issn = {1932-6203}, support = {R25 MH080663/MH/NIMH NIH HHS/United States ; DA 025576/DA/NIDA NIH HHS/United States ; R01 DA034547/DA/NIDA NIH HHS/United States ; DA034547/DA/NIDA NIH HHS/United States ; R37 DA025576/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Arachidonic Acid/*blood ; Cells, Cultured ; Cocaine/*adverse effects ; Cyclooxygenase 2/metabolism ; Dendritic Cells/*immunology ; Dinoprostone/blood ; Drug Users ; Female ; Gene Expression Regulation/drug effects ; HIV Infections/blood/*immunology/pathology ; Humans ; Intramolecular Oxidoreductases/blood ; Male ; Middle Aged ; Prostaglandin D2/*analogs &amp; derivatives/blood ; Prostaglandin-E Synthases ; }, abstract = {Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE2), thromboxane A2 receptor (TBXA2R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), 14-3-3 ζ/δ and 5-lipoxygenase (5-LOX) mediated induction of IDC immune dysfunctions in cocaine using HIV positive patients. The plasma levels of AA, PGE2, 15d-PGJ2, 14-3-3 ζ/δ and IDC intracellular COX-2 and 5-LOX expression were assessed in cocaine users, HIV positive patients, HIV positive cocaine users and normal subjects. Results showed that plasma concentration levels of AA, PGE2 and COX-2, TBXA2R and 5-LOX in IDCs of HIV positive cocaine users were significantly higher whereas 15d-PGJ2 and 14-3-3 ζ/δ were significantly reduced compared to either HIV positive subjects or cocaine users alone. This report demonstrates that AA metabolites are capable of mediating the accelerative effects of cocaine on HIV infection and disease progression.}, }
@article {pmid25154392, year = {2015}, author = {Risbridger, GP and Taylor, RA and Clouston, D and Sliwinski, A and Thorne, H and Hunter, S and Li, J and Mitchell, G and Murphy, D and Frydenberg, M and Pook, D and Pedersen, J and Toivanen, R and Wang, H and Papargiris, M and Lawrence, MG and Bolton, DM}, title = {Patient-derived xenografts reveal that intraductal carcinoma of the prostate is a prominent pathology in BRCA2 mutation carriers with prostate cancer and correlates with poor prognosis.}, journal = {European urology}, volume = {67}, number = {3}, pages = {496-503}, doi = {10.1016/j.eururo.2014.08.007}, pmid = {25154392}, issn = {1873-7560}, mesh = {Aged ; Animals ; BRCA2 Protein/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics/mortality/*pathology/surgery ; Genetic Predisposition to Disease ; Heredity ; Heterografts ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; *Mutation ; Neoplasm Transplantation ; Pedigree ; Phenotype ; Proportional Hazards Models ; Prostatectomy ; Prostatic Neoplasms/*genetics/mortality/*pathology/surgery ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathologic entity associated with aggressive prostate cancer (PCa). PCa patients carrying a breast cancer 2, early onset (BRCA2) germline mutation exhibit highly aggressive tumours with poor prognosis.<br><br>OBJECTIVE: To investigate the presence and implications of IDC-P in men with a strong family history of PCa who either carry a BRCA2 pathogenic mutation or do not carry the mutation (BRCAX).<br><br>Patient-derived xenografts (PDXs) were generated from three germline BRCA2 mutation carriers and one BRCAX patient. Specimens were examined for histologic evidence of IDC-P. Whole-genome copy number analysis (WG-CNA) was performed on IDC-P from a primary and a matched PDX specimen.<br><br>The incidence of IDC-P and association with overall survival for BRCA2 and BRCAX patients were determined using Kaplan-Meier analysis.<br><br>RESULTS AND LIMITATIONS: PDXs from BRCA2 tumours showed increased incidence of IDC-P compared with sporadic PCa (p=0.015). WG-CNA confirmed that the genetic profile of IDC-P from a matched (primary and PDX) BRCA2 tumour was similar. The incidence of IDC-P was significantly increased in BRCA2 carriers (42%, n=33, p=0.004) but not in BRCAX patients (25.8%, n=62, p=0.102) when both groups were compared with sporadic cases (9%, n=32). BRCA2 carriers and BRCAX patients with IDC-P had significantly worse overall and PCa-specific survival compared with BRCA2 carriers and BRCAX patients without IDC-P (hazard ratio [HR]: 16.9, p=0.0064 and HR: 3.57, p=0.0086, respectively).<br><br>CONCLUSIONS: PDXs revealed IDC-P in patients with germline BRCA2 mutations or BRCAX classification, identifying aggressive tumours with poor survival even when the stage and grade of cancer at diagnosis were similar. Further studies of the prognostic significance of IDC-P in sporadic PCa are warranted.<br><br>PATIENT SUMMARY: Intraductal carcinoma of the prostate is common in patients with familial prostate cancer and is associated with poor outcomes. This finding affects genetic counselling and identifies patients in whom earlier multimodality treatment may be required.}, }
@article {pmid25149281, year = {2014}, author = {Moran Lauter, AN and Peiffer, GA and Yin, T and Whitham, SA and Cook, D and Shoemaker, RC and Graham, MA}, title = {Identification of candidate genes involved in early iron deficiency chlorosis signaling in soybean (Glycine max) roots and leaves.}, journal = {BMC genomics}, volume = {15}, number = {}, pages = {702}, pmid = {25149281}, issn = {1471-2164}, mesh = {Binding Sites ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Homeostasis ; *Iron Deficiencies ; Multigene Family ; Plant Diseases/*genetics ; Plant Leaves/*genetics/metabolism ; Plant Roots/*genetics/metabolism ; Protein Binding ; *Signal Transduction ; Soybeans/*genetics/*metabolism ; Stress, Physiological ; Time Factors ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Iron is an essential micronutrient for all living things, required in plants for photosynthesis, respiration and metabolism. A lack of bioavailable iron in soil leads to iron deficiency chlorosis (IDC), causing a reduction in photosynthesis and interveinal yellowing of leaves. Soybeans (Glycine max (L.) Merr.) grown in high pH soils often suffer from IDC, resulting in substantial yield losses. Iron efficient soybean cultivars maintain photosynthesis and have higher yields under IDC-promoting conditions than inefficient cultivars.<br><br>RESULTS: To capture signaling between roots and leaves and identify genes acting early in the iron efficient cultivar Clark, we conducted a RNA-Seq study at one and six hours after replacing iron sufficient hydroponic media (100&#xa0;&#x3bc;M iron(III) nitrate nonahydrate) with iron deficient media (50&#xa0;&#x3bc;M iron(III) nitrate nonahydrate). At one hour of iron stress, few genes were differentially expressed in leaves but many were already changing expression in roots. By six hours, more genes were differentially expressed in the leaves, and a massive shift was observed in the direction of gene expression in both roots and leaves. Further, there was little overlap in differentially expressed genes identified in each tissue and time point.<br><br>CONCLUSIONS: Genes involved in hormone signaling, regulation of DNA replication and iron uptake utilization are key aspects of the early iron-efficiency response. We observed dynamic gene expression differences between roots and leaves, suggesting the involvement of many transcription factors in eliciting rapid changes in gene expression. In roots, genes involved iron uptake and development of Casparian strips were induced one hour after iron stress. In leaves, genes involved in DNA replication and sugar signaling responded to iron deficiency. The differentially expressed genes (DEGs) and signaling components identified here represent new targets for soybean improvement.}, }
@article {pmid25147131, year = {2014}, author = {Bhattacharya-Ghosh, B and Bozkurt, S and Rutten, MC and van de Vosse, FN and Díaz-Zuccarini, V}, title = {An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.}, journal = {Computers in biology and medicine}, volume = {53}, number = {}, pages = {141-153}, doi = {10.1016/j.compbiomed.2014.06.013}, pmid = {25147131}, issn = {1879-0534}, mesh = {Calcium/metabolism ; Cardiomyopathy, Dilated/*physiopathology ; Computational Biology ; *Computer Simulation ; Heart/physiology ; Humans ; *Models, Cardiovascular ; Muscle Proteins/metabolism ; *Myocardium/chemistry/cytology/metabolism ; Ventricular Pressure/physiology ; }, abstract = {Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.}, }
@article {pmid25124574, year = {2014}, author = {Chim-ong, A and Thawornkuno, C and Chavalitshewinkoon-Petmitr, P and Punyarit, P and Petmitr, S}, title = {SLC35B2 expression is associated with a poor prognosis of invasive ductal breast carcinoma.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {15}, pages = {6065-6070}, doi = {10.7314/apjcp.2014.15.15.6065}, pmid = {25124574}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast/metabolism ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/secondary ; Carcinoma, Lobular/genetics/secondary ; DNA-Binding Proteins/*genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Membrane Transport Proteins/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasms/*drug therapy/pathology ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfate Transporters ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women worldwide, including Thailand, and is a major cause of mortality and morbidity, despite advances in diagnosis and treatment. Novel gene expression in breast cancer is a focus in searches for prognostic biomarkers and new therapeutic targets.<br><br>MATERIALS AND METHODS: The mRNA expression of novel B4GALT4, SLC35B2, and WDHD1 genes in breast cancer were examined in invasive ductal breast carcinoma (IDC) patients using quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR).<br><br>RESULTS: Among these genes, increased expression of SLC35B2 mRNA was significantly associated with TNM stage III+IV of IDC (p<0.001). Hence, up-regulation of SLC35B2 may serve as a prognostic biomarker for poor prognosis, and is also a potential therapeutic target in breast cancer.}, }
@article {pmid25120811, year = {2014}, author = {Cao, YW and Wan, GX and Zhao, CX and Hu, JM and Li, L and Liang, WH and Li, WQ and Li, YC and Li, YX and Du, XM and Yu, SY and Li, F}, title = {Notch1 single nucleotide polymorphism rs3124591 is associated with the risk of development of invasive ductal breast carcinoma in a Chinese population.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {7}, pages = {4286-4294}, pmid = {25120811}, issn = {1936-2625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asian People/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Female ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Immunohistochemistry ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Receptor, Notch1/*genetics ; Risk Factors ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Accumulated evidence has revealed the presence of Notch receptor polymorphisms in non-tumorous diseases; however, few studies have investigated the association of Notch polymorphisms with breast cancer risk. A total of 100 invasive ductal carcinoma (IDC) and 50 ductal carcinoma in situ (DCIS) patients and 100 usual ductal hyperplasia (UDH) controls were genotyped for the following Notch receptor single nucleotide polymorphisms (SNPs) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Notch1, rs3124591; Notch2, rs11249433; Notch3, rs3815188, and rs1043994; and Notch4, rs367398, and rs520692. Immunohistochemistry was used to determine the effect of Notch polymorphisms on corresponding Notch protein expression in successfully genotyped patients. The frequency of rs3124591 TC genotype was significantly higher in IDC (24.7%, 20/81) and DCIS (30%, 12/40) patients than in UDH controls (8%, 8/97) (P = 0.002 and P = 0.011, respectively). However, the distribution of other SNP genotypes was not significantly different between IDC and DCIS patients and UDH controls. The frequency of TC genotype was significantly higher in poorly differentiated tumors than in well-differentiated and moderately differentiated tumors (P = 0.022). Importantly, a positive correlation between the rs3124591 TC genotype and high Notch1 protein expression was observed in DCIS patients (P = 0.043) but not in IDC patients. This is the first study to suggest an increased risk of IDC and DCIS of the breast for the Notch1 rs3124591 variant. Furthermore, given the inconsistent associations between the rs3124591 variant and Notch1 expression in IDC and DCIS, this variant may affect breast cancer risk through mechanisms in the latter stage other than alterations in Notch1 protein expression.}, }
@article {pmid25119012, year = {2014}, author = {Colović, M and Todorović, M and Colović, N and Terzic, T and Karadzic, K and Jurišić, V}, title = {Appearance of estrogen positive bilateral breast carcinoma with HER2 gene amplification in a patient with aplastic anemia.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {65}, number = {1}, pages = {66-69}, doi = {10.5114/pjp.2014.42672}, pmid = {25119012}, issn = {1233-9687}, mesh = {*Adenocarcinoma/complications/genetics/metabolism ; Anemia, Aplastic/*complications ; *Breast Neoplasms/complications/genetics/metabolism ; *Carcinoma, Ductal, Breast/complications/genetics/metabolism ; Estrogens/*metabolism ; Female ; Gene Amplification ; Humans ; Middle Aged ; Receptor, ErbB-2/*genetics ; }, abstract = {Immunosuppressive therapy is one of the standard therapy protocols for aplastic anemia (AA). However, immunosuppressive therapy and androgenic steroids can promote development of solid tumors such as squamous carcinoma, head and neck tumors, adenocarcinoma of the stomach, hepatocarcinoma and breast carcinoma in long surviving patients with aplastic anemia. We present here a rare case of a 56-year-old woman in whom bilateral adenocarcinoma of the breast developed 11 years after the start of immunosuppressive and androgenic steroid therapy for aplastic anemia. Histological examination showed invasive ductal carcinoma with intense nuclear staining for estrogen receptors. Her2 immunohistochemistry was positive for 80% of stained cells, and chromogenic in situ hybridization showed a high level of HER2 gene amplification. This case indicated that a new therapy option is needed for estimation and evaluation to avoid the consequence of cancer occurrence.}, }
@article {pmid25118162, year = {2014}, author = {Reyna, C and Lee, MC and Frelick, A and Khakpour, N and Laronga, C and Kiluk, JV}, title = {Axillary burden of disease following false-negative preoperative axillary evaluation.}, journal = {American journal of surgery}, volume = {208}, number = {4}, pages = {577-581}, doi = {10.1016/j.amjsurg.2014.05.015}, pmid = {25118162}, issn = {1879-1883}, mesh = {Axilla ; Biopsy, Fine-Needle/*methods ; Breast Neoplasms/diagnosis/*secondary/surgery ; Diagnosis, Differential ; False Negative Reactions ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes/*diagnostic imaging/*pathology ; Lymphatic Metastasis ; Neoplasm Staging/methods ; Predictive Value of Tests ; Preoperative Period ; Retrospective Studies ; Sentinel Lymph Node Biopsy/*methods ; Ultrasonography ; }, abstract = {BACKGROUND: Preoperative axillary ultrasound (AUS) and fine-needle aspiration (FNA) are sensitive and specific for breast cancer nodal metastases. We hypothesize that false-negative result predicts minimal axillary disease (≤2 +nodes).<br><br>METHODS: A retrospective review of breast cancer patients receiving AUS identified T1/T2 tumors and positive sentinel node with axillary dissection. Chi-square analysis was performed using Fisher's exact test.<br><br>RESULTS: Of 903 AUS cases, 384 had T1/T2 tumors. False-negative rate of AUS &#xb1; FNA was 48% and 45%, respectively. Of 384 cases, 73 were sentinel node positive and had axillary dissection; 55 (75.3%) were invasive ductal carcinoma (IDC). Negative predictive value for greater than or equal to 2 nodes was 71% in IDC versus 44% for in non-IDC patients. Sixteen (29.0%) IDC patients had greater than or equal to 3 positive nodes versus 10 (55.5%) non-IDC (P = .05) patients.<br><br>CONCLUSION: The high negative predictive value for AUS with FNA for IDC suggests that the AUS plus FNA interpretation may be better limited to the ipsilateral nodes of IDC.}, }
@article {pmid25112791, year = {2015}, author = {Klomek, AB and Lev-Wiesel, R and Shellac, E and Hadas, A and Berger, U and Horwitz, M and Fennig, S}, title = {The relationship between self-injurious behavior and self-disclosure in adolescents with eating disorders.}, journal = {Eating and weight disorders : EWD}, volume = {20}, number = {1}, pages = {43-48}, pmid = {25112791}, issn = {1590-1262}, mesh = {Adolescent ; Child ; Feeding and Eating Disorders/complications/*psychology ; Female ; Humans ; *Self Disclosure ; Self-Injurious Behavior/complications/*psychology ; Young Adult ; }, abstract = {PURPOSE: The aim of the current study is to examine the association between self disclosure and self-injurious behaviors among adolescent patients diagnosed with an eating disorder.<br><br>METHODS: Sixty three female patients who fulfilled the DSM-IV diagnostic criteria of eating disorders were included (i.e. anorexia, bulimia, binge eating disorder and eating disorders not otherwise specified). Participants' age ranged from 11.5 to 20 years (M = 15.42, SD = 1.82). Participants completed self- report questionnaires about eating disorders, self-disclosure, self-injurious behaviors (FASM) and depression (BDI-II) RESULTS: 82.5% of the sample endorsed severe self-injurious behaviors. A moderate negative relationship was found between general disclosure to parents and self-injurious behaviors indicating that patients who generally self-disclose to their parents (on different topics, apart from suicidal ideation) engage less frequently in self-injurious behaviors. In addition, the more patients self-disclose their suicidal ideation to others, the more they tend to self-injure.<br><br>CONCLUSION: Self-disclosure to parents on any topic may buffer against self-injurious behaviors and therefore it is important to work with adolescents suffering from eating disorders on effective self disclosure. In addition, self-disclosure about suicidal ideation to others by adolescents suffering from eating disorders should always be taken seriously, since it may be related to self-injurious behaviors.}, }
@article {pmid25109497, year = {2014}, author = {Tanaka, N and Yoshida, H and Suzuki, Y and Harigaya, K}, title = {Relative expression of hMena11a and hMenaINV splice isoforms is a useful biomarker in development and progression of human breast carcinoma.}, journal = {International journal of oncology}, volume = {45}, number = {5}, pages = {1921-1928}, doi = {10.3892/ijo.2014.2591}, pmid = {25109497}, issn = {1791-2423}, mesh = {Alternative Splicing/genetics ; Biomarkers ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Microfilament Proteins/*biosynthesis/genetics ; Neoplasm Staging ; Protein Isoforms/*biosynthesis ; RNA, Messenger/*biosynthesis ; }, abstract = {Alternative splicing provides additional genomic complexity by producing multiple mRNAs and protein variants from any given gene. Splice variants have been identified in a large variety of cancer genes, suggesting that widespread aberrant and alternative splicing may be a consequence or even a cause of cancer. Human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoproteins (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility. hMena has been shown to have several splice variants, including the hMena(INV) isoform, expressed in invasive cancer cells, and the epithelial-specific isoform, hMena(11a). We assessed the relative mRNA expression of hMena splice variants in 50 cases of invasive ductal breast carcinoma of no special type (IDC-NST) and 45 cases of ductal breast carcinoma in situ (DCIS) with special reference to non-neoplastic breast epithelial tissues. The samples were dissected from their respective regions by laser microdissection. Our results confirmed previous reports that hMena(INV) expression is augmented during tumor progression, while hMena(11a) is downregulated. Furthermore, simultaneous expression of hMena(11a) and hMena(INV) was found only in malignant lesions, while their expression was hardly detected in normal breast tissue and benign proliferative breast lesions. These results indicate that the higher relative expression of hMena(11a) compared with hMena(INV) may predict malignant transformation in breast epithelial cells, and, furthermore, a reversal of expression of hMena(11a) and hMena(INV) may dictate the state of cancer progression. Here, we demonstrate that determination of hMena(11a) and hMena(INV) expression could be a useful biomarker for predicting malignant behavior in breast epithelial lesions, and show that their relative expression is linked to adverse prognostic factors. Although the biological activity of the majority of alternatively spliced isoforms and their contribution to cancer biology has yet to be determined, their elucidation will have a large impact on therapeutic strategies for cancer.}, }
@article {pmid25100562, year = {2014}, author = {Arthur, LM and Turnbull, AK and Webber, VL and Larionov, AA and Renshaw, L and Kay, C and Thomas, JS and Dixon, JM and Sims, AH}, title = {Molecular changes in lobular breast cancers in response to endocrine therapy.}, journal = {Cancer research}, volume = {74}, number = {19}, pages = {5371-5376}, doi = {10.1158/0008-5472.CAN-14-0620}, pmid = {25100562}, issn = {1538-7445}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/genetics ; Carcinoma, Lobular/*drug therapy/genetics ; Cohort Studies ; Female ; Humans ; Letrozole ; Nitriles/*therapeutic use ; Postmenopause ; Triazoles/*therapeutic use ; }, abstract = {Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor-positive (ER(+)) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray. Dynamic clinical response was assessed using periodic three-dimensional ultrasound measurements performed during treatment and defined as a reduction of >70% in tumor volume by 3 months. Pretreatment profiles of ILC and IDC tumors showed distinctive expression of genes associated with E-cadherin signaling, epithelial adhesion, and stromal rearrangement. The changes in gene expression in response to letrozole were highly similar between responding ILC and IDC tumors; genes involved in proliferation were downregulated and those involved with immune function and extracellular matrix remodeling were upregulated. However, molecular differences between the histologic subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes that change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis are maintained at each time point on treatment.}, }
@article {pmid25097518, year = {2014}, author = {Hong, L and Tang, S}, title = {Does HPV 16/18 infection affect p53 expression in invasive ductal carcinoma? An experimental study.}, journal = {Pakistan journal of medical sciences}, volume = {30}, number = {4}, pages = {789-792}, pmid = {25097518}, issn = {1682-024X}, abstract = {Objective : To determine the relations between human papilloma viruses type 16 and type 18 infection and the expression of p53 protein in invasive ductal carcinoma. Methods : We detected the expression of HPV 16/18 DNA and p53 protein in invasive ductal carcinoma in 45 cases, breast fibroadenoma in 20 cases and normal breast tissues in 20 cases. HPV detection was performed on paraffin sections using biotin-labeled probes by in situ hybridization and p53 protein expression was evaluated by immunohistochemistry. Results : The expression rate of HPV 16/18 DNA and p53 protein in invasive ductal carcinoma is significantly higher than those in breast fibroadenoma and normal breast tissues (p<0.05); the expression in cases with axillary lymph node metastasis is dramatically higher than those without (p<0.05); the expression of p53 protein increases with TMN staging advance. The expression of HPV16/18 DNA was significantly correlated with the expression of p53 protein (p<0.05). Conclusion : Both HPV16/18 infection and p53 mutation participate the occurrence and progress of invasive ductal carcinoma, and HPV 16/18 infection may be the major factor to cause p53 mutation.}, }
@article {pmid25081092, year = {2014}, author = {Picillo, M and Barone, P and Amboni, M and Moccia, M and Pellecchia, MT}, title = {Comment on Szewczyk-Krolikowski et al.: the influence of age and gender on motor and non-motor features of early Parkinson's disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort.}, journal = {Parkinsonism &amp; related disorders}, volume = {20}, number = {11}, pages = {1319-1320}, doi = {10.1016/j.parkreldis.2014.03.014}, pmid = {25081092}, issn = {1873-5126}, mesh = {Female ; Humans ; Male ; Parkinson Disease/*complications/*epidemiology ; }, }
@article {pmid25076063, year = {2015}, author = {Türker, K and Albayrak, M and Öksüzoğlu, B and Balc, E and Oğan, MC and Iskender, G and Altuntaş, F}, title = {Entecavir as a first-line treatment for hepatitis B virus reactivation following polychemotherapy for chronic lymphocytic leukemia and invasive ductal carcinoma: a report of two cases and review of the literature.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {27}, number = {1}, pages = {39-45}, doi = {10.1097/MEG.0000000000000115}, pmid = {25076063}, issn = {1473-5687}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/*therapeutic use ; Breast Neoplasms/complications/*drug therapy ; Carcinoma, Ductal, Breast/complications/*drug therapy ; Female ; Guanine/*analogs &amp; derivatives/therapeutic use ; Hepatitis B Antibodies/blood ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*physiology ; Hepatitis B, Chronic/blood/complications/*drug therapy ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/complications/*drug therapy ; Male ; Middle Aged ; Recurrence ; Virus Activation ; }, abstract = {OBJECTIVE: Hepatitis B reactivation has been reported in chronic carriers of hepatitis B [hepatitis B surface antigen (HBsAg)] or in patients with prior hepatitis B virus (HBV) infection who are HBsAg-negative and have antibodies against hepatitis B core antigen (anti-HBc) with or without antibodies to HBsAg (anti-HBs). Lamivudine has been the first and commonly used nucleoside analog to inhibit HBV replication; however, prolonged therapy has been associated with an increased risk for drug-resistant mutations and mortality rates. Entecavir, a deoxyguanosine analog, offers several advantages over lamivudine for the treatment of HBV reactivation following chemotherapy while exhibiting more potent antiviral activity and a lower resistance rate.<br><br>METHODS: Herein, we report rapid and sustained suppression of polychemotherapy-related HBV reactivation by entecavir administered as a prompt antiviral therapy in the cases of two patients with chronic lymphocytic leukemia and invasive ductal carcinoma. A review of the literature is discussed.<br><br>RESULTS: Entecavir produced a rapid and sustained suppression of polychemotherapy-related HBV reactivation as a prompt antiviral therapy in the cases of two patients with chronic lymphocytic leukemia and invasive ductal carcinoma.<br><br>CONCLUSION: Allowing a rapid and sustained control of HBV replication, entecavir seems to be a promising drug for first-line prompt treatment of HBV reactivation in patients undergoing chemotherapy for hematological as well as solid organ malignancies, with safe long-term use enabling maintenance of resolved hepatitis.}, }
@article {pmid25074542, year = {2014}, author = {Xiang, DB and Wei, B and Abraham, SC and Huo, L and Albarracin, CT and Zhang, H and Babiera, G and Caudle, AS and Akay, CL and Rao, P and Zhao, YJ and Lu, X and Wu, Y}, title = {Molecular cytogenetic characterization of mammary neuroendocrine carcinoma.}, journal = {Human pathology}, volume = {45}, number = {9}, pages = {1951-1956}, doi = {10.1016/j.humpath.2014.06.002}, pmid = {25074542}, issn = {1532-8392}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Neuroendocrine/*genetics/pathology ; *Chromosome Aberrations ; Chromosome Banding/methods ; Chromosomes, Human, Pair 12/*genetics ; Chromosomes, Human, Pair 7/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping/methods ; Middle Aged ; Trisomy ; }, abstract = {Primary mammary neuroendocrine carcinoma (NEC) is an uncommon entity that accounts for 2% to 5% of breast carcinomas. Recent reports have shown that NEC of the breast is an aggressive subtype of mammary carcinoma that is distinct from invasive ductal carcinoma, not otherwise specified, and have suggested that these tumors have a poorer prognosis than invasive ductal carcinoma, not otherwise specified. In this study, we provide the first cytogenetic characterization of mammary NEC using both conventional G-banding and spectral karyotype on a group of 7 tumors. We identified clonal chromosomal aberrations in 5 (71.4%) cases, with 4 of them showing complex karyotypes. Of these, recurrent numerical aberrations included gain of chromosome 7 (n = 2) and loss of chromosome 15 (n = 2). Recurrent clonal structural chromosomal aberrations involved chromosomes 1 (n = 3), 3 (n = 2), 6q (n = 3), and 17q (n = 3). Of the 4 (57.1%) cases with complex karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. One of these had evidence of chromothripsis involving chromosomes 1, 6, 8, and 15. The other also had evidence of chromosome 8 chromothripsis, making this a recurrent finding shared by both cases. We also found that mammary NEC shared some cytogenetic abnormalities--such as trisomy 7 and 12--with other neuroendocrine tumors in the lung and gastrointestinal tract, suggesting trisomy 7 and 12 as potential common molecular aberrations in neuroendocrine tumors. To our knowledge, this is the first report on molecular cytogenetic characterization of mammary NEC.}, }
@article {pmid25064063, year = {2014}, author = {Tong, LC and Silar, P and Lalucque, H}, title = {Genetic control of anastomosis in Podospora anserina.}, journal = {Fungal genetics and biology : FG &amp; B}, volume = {70}, number = {}, pages = {94-103}, doi = {10.1016/j.fgb.2014.07.006}, pmid = {25064063}, issn = {1096-0937}, mesh = {Fungal Proteins/genetics/*metabolism ; *Gene Expression Regulation, Fungal ; Hyphae/genetics/*physiology ; Microscopy/methods ; Mutation ; Podospora/genetics/*physiology ; Signal Transduction ; }, abstract = {We developed a new microscopy procedure to study anastomoses in the model ascomycete Podospora anserina and compared it with the previous method involving the formation of balanced heterokaryons. Both methods showed a good correlation. Heterokaryon formation was less quantifiable, but enabled to observe very rare events. Microscopic analysis evidenced that anastomoses were greatly influence by growth conditions and were severely impaired in the IDC mutants of the PaMpk1, PaMpk2, IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons, albeit with a delay when compared to the wild type. We also identified IDC(821), a new mutant presenting a phenotype similar to the other IDC mutants, including lack of anastomosis. Complete genome sequencing revealed that IDC(821) was affected in the orthologue of the Neurospora crassa So gene known to control anastomosis in several other ascomycetes.}, }
@article {pmid25063898, year = {2013}, author = {Villalón-López, JS and Souto-del Bosque, R and Alonso-Briones, MV and Trujillo-de Anda, AP}, title = {[Carcinosarcoma of the breast a rare entity with fatal prognosis. One case report].}, journal = {Cirugia y cirujanos}, volume = {81}, number = {4}, pages = {328-332}, pmid = {25063898}, issn = {2444-054X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology/therapy ; Capecitabine ; Carcinosarcoma/*pathology/secondary/therapy ; Combined Modality Therapy ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Docetaxel ; Fatal Outcome ; Female ; Fluorouracil/administration &amp; dosage/analogs &amp; derivatives ; Humans ; Lung Neoplasms/secondary/therapy ; Lymphatic Metastasis ; Mastectomy ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local ; Paclitaxel/administration &amp; dosage ; Palliative Care ; Taxoids/administration &amp; dosage ; Gemcitabine ; }, abstract = {BACKGROUND: breast metaplastic carcinomas are a heterogeneous group of neoplasms that exhibit a poor prognosis compared with invasive ductal carcinoma. Correspond less than 1% of all malignant neoplasms of the mammary gland. They usually present as high-grade tumors with a lower rate of lymph node metastases and decreased expression of estrogen and progesterone receptors and Her2 and increased expression of Her1 and Ki-67.<br><br>CLINICAL CASE: we report a 52 year old woman with a breast carcinosarcoma presented with a left breast tumor fungated, ulcerated, polypoid and 18 cm in major diameter with lymph node metastases at diagnosis. She received multimodal management with neoadjuvant chemotherapy, followed by mastectomy and adjuvant chemotherapy; she presented progression of the disease with lung metastases and local massive recurrence, eventually died from complications associated to the disease.<br><br>CONCLUSIONS: metaplastic carcinomas of the breast are extremely rare entities. Due the nature of disease and presentation, the prognosis is poor in these patients. There are several histologic subtypes based on studies of hematoxylin and eosin and immunohistochemical stains. It requires multimodal therapy (surgery, radiotherapy and chemotherapy) for best results.}, }
@article {pmid25059790, year = {2015}, author = {Yajima, R and Fujii, T and Yanagita, Y and Fujisawa, T and Miyamoto, T and Hirakata, T and Tsutsumi, S and Iijima, M and Kuwano, H}, title = {Prognostic value of extracapsular invasion of axillary lymph nodes combined with peritumoral vascular invasion in patients with breast cancer.}, journal = {Annals of surgical oncology}, volume = {22}, number = {1}, pages = {52-58}, doi = {10.1245/s10434-014-3941-x}, pmid = {25059790}, issn = {1534-4681}, mesh = {Adenocarcinoma/mortality/*secondary/therapy ; Adenocarcinoma, Scirrhous/mortality/*secondary/therapy ; Axilla ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Carcinoma, Papillary/mortality/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/mortality/*pathology/therapy ; Neoplasm Staging ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Extracapsular invasion (ECI) of metastatic axillary lymph nodes has been associated with aggressive nodal disease but its prognostic role in breast cancer is unclear. The present study evaluated nodal ECI as a predictor of breast cancer recurrence.<br><br>METHODS: We evaluated 154 women with histologically proven node-positive breast cancer who were diagnosed with invasive ductal carcinoma, and investigated the relationships between ECI and recurrences and other clinicopathological factors, particularly vascular invasion and the number of lymph node metastases.<br><br>RESULTS: The presence of ECI at positive nodes was significantly associated with the number of positive nodes, and with disease recurrence and survival in univariate (but not multivariate) analysis. Interestingly, all ECI(+) patients with distant metastases in our series had peritumoral vascular invasion (PVI), which may have reflected systemic disease; ECI with PVI of the primary tumor strongly predicted recurrent disease and shorter survival.<br><br>CONCLUSION: ECI of axillary metastases combined with PVI indicates high tumor aggressiveness. Patients with ECI and PVI may be considered for stronger adjuvant therapies because of their high risk for distant recurrences.}, }
@article {pmid25049275, year = {2014}, author = {Frittoli, E and Palamidessi, A and Marighetti, P and Confalonieri, S and Bianchi, F and Malinverno, C and Mazzarol, G and Viale, G and Martin-Padura, I and Garré, M and Parazzoli, D and Mattei, V and Cortellino, S and Bertalot, G and Di Fiore, PP and Scita, G}, title = {A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination.}, journal = {The Journal of cell biology}, volume = {206}, number = {2}, pages = {307-328}, pmid = {25049275}, issn = {1540-8140}, mesh = {Animals ; Breast Neoplasms/*genetics/pathology ; Cell Line, Tumor ; Disease Progression ; Extracellular Matrix/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Neoplasm Invasiveness/genetics ; Neoplasm Recurrence, Local/genetics/pathology ; Proteolysis ; Transplantation, Heterologous ; rab5 GTP-Binding Proteins/*genetics/metabolism/*physiology ; }, abstract = {The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5-dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and β3 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program.}, }
@article {pmid25047051, year = {2014}, author = {Hadiji, N and Previnaire, JG and Benbouzid, R and Robain, G and Leblond, C and Mieusset, R and Enjalbert, M and Soler, JM}, title = {Are oxybutynin and trospium efficacious in the treatment of detrusor overactivity in spinal cord injury patients?.}, journal = {Spinal cord}, volume = {52}, number = {9}, pages = {701-705}, doi = {10.1038/sc.2014.113}, pmid = {25047051}, issn = {1476-5624}, mesh = {Adult ; Benzilates/*therapeutic use ; Female ; Humans ; Male ; Mandelic Acids/*therapeutic use ; Nortropanes/*therapeutic use ; Retrospective Studies ; Spinal Cord Injuries/*complications ; Time Factors ; Treatment Outcome ; Urinary Bladder, Overactive/*drug therapy/*etiology ; Urodynamics ; Urological Agents/*therapeutic use ; }, abstract = {OBJECTIVES: To evaluate the efficacy of anticholinergic agents in the treatment of neurogenic overactive bladder (NOAB) and neurogenic detrusor overactivity (NDO) in spinal cord injury (SCI) patients on clean intermittent catheterisation (CIC).<br><br>METHODS: Chronic suprasacral SCI patients on CIC presenting with at least one urinary leakage a day were included. Urodynamics and voiding diaries were performed at baseline and 1 month follow-up. In case of NDO at baseline, an anticholinergic drug was prescribed.<br><br>RESULTS: The 231 SCI patients presented with one to five urinary leakages per day (mean 2.1). Urodynamics showed NDO in all patients. A new anticholinergic treatment was started in all, either in monotherapy (134 patients) or in association with the existing anticholinergic drug (oxybutynin+trospium bitherapy, 97 patients). The mean maximum bladder capacity significantly increased from 225 to 441&#x2009;ml, and the mean involuntary detrusor contractions (IDC) significantly decreased from 67 to 41&#x2009;cm H2O. Only 75 SCI patients (32%) were fully continent. However, 25 out of these 75 patients showed persistent NDO, with amplitudes of IDC above 40&#x2009;cm H2O in 12 patients. Incontinence was still found in 156 SCI patients (67%), with an average of 1,2 leakages a day. In 100 patients, amplitudes of IDC remained above 40&#x2009;cm H2O. There was no statistical difference between patients on anticholinergic monotherapy or bitherapy at follow-up.<br><br>CONCLUSION: Anticholinergic treatment is not always satisfactory in terms of control of NDO and rarely allows full continence. Urodynamic follow-up is mandatory in all patients, even in those showing clinical continence.}, }
@article {pmid25041824, year = {2014}, author = {Piscuoglio, S and Ng, CK and Martelotto, LG and Eberle, CA and Cowell, CF and Natrajan, R and Bidard, FC and De Mattos-Arruda, L and Wilkerson, PM and Mariani, O and Vincent-Salomon, A and Weigelt, B and Reis-Filho, JS}, title = {Integrative genomic and transcriptomic characterization of papillary carcinomas of the breast.}, journal = {Molecular oncology}, volume = {8}, number = {8}, pages = {1588-1602}, pmid = {25041824}, issn = {1878-0261}, mesh = {Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Papillary/*genetics/*metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/genetics/physiology ; Genomics/*methods ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Papillary carcinoma (PC) is a rare type of breast cancer, which comprises three histologic subtypes: encapsulated PC (EPC), solid PC (SPC) and invasive PC (IPC). Microarray-based gene expression and Affymetrix SNP 6.0 gene copy number profiling, and RNA-sequencing revealed that PCs are luminal breast cancers that display transcriptomic profiles distinct from those of grade- and estrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs), and that the papillary histologic pattern is unlikely to be underpinned by a highly recurrent expressed fusion gene or a highly recurrent expressed mutation. Despite displaying similar patterns of gene copy number alterations, significant differences in the transcriptomic profiles of EPCs, SPCs and IPCs were found, and may account for their different histologic features.}, }
@article {pmid25036908, year = {2015}, author = {Kitahashi, T and Takahashi, M and Imai, T}, title = {Biphasic Alterations in Expression and Subcellular Localization of MUC1 in Pancreatic Ductal Carcinogenesis in Syrian Hamsters.}, journal = {Pancreas}, volume = {44}, number = {1}, pages = {76-86}, doi = {10.1097/MPA.0000000000000178}, pmid = {25036908}, issn = {1536-4828}, mesh = {Animals ; Biomarkers, Tumor/genetics/*metabolism ; Carcinoma, Pancreatic Ductal/chemically induced/genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/metabolism/pathology ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Mesocricetus ; Mucin-1/genetics/*metabolism ; Neoplasms, Experimental/chemically induced/genetics/*metabolism/pathology ; Nitrosamines ; Oligonucleotide Array Sequence Analysis ; RNA Interference ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; Transfection ; }, abstract = {OBJECTIVES: The aim of the present study was to characterize molecular targets for the prevention/diagnosis of pancreatic cancer using a chemically induced hamster pancreatic carcinogenesis model, in which background injuries to the parenchyma, for example, chronic pancreatitis or acinar atrophy, are limited.<br><br>METHODS: Gene expression profiles in atypical hyperplasias were first investigated using a microarray technique. Immunohistochemical analyses of early lesions and invasive ductal carcinoma (IDC) were then conducted for MUC1, of which mRNA levels were prominent among the up-regulated genes, in contrast with the coexpression of epithelial-mesenchymal transition (EMT)-related proteins.<br><br>RESULTS: Immunohistochemistry for MUC1 cytoplasmic domain (MUC1-CD), which was not detected in normal-like pancreatic ducts, was positive in the apical surfaces of the epithelia of hyperplasias with and without atypia and IDC areas with distinct tubular patterns. In contrast, cytoplasmic/nuclear positivity for MUC1-CD was observed in the invasive front of IDCs. The coexpression of EMT-related proteins, such as slug and vimentin, with cytoplasmic/nuclear MUC1-CD was also detected.<br><br>CONCLUSIONS: Alterations in the expression and subcellular localization of MUC1 represent a biphasic phenomenon, and the latter may be associated with EMT in pancreatic carcinogenesis in hamsters, which indicates that changes in MUC1 are important targets for pancreatic cancer prevention and chemotherapy.}, }
@article {pmid25034035, year = {2014}, author = {Akabori, H and Shiomi, H and Naka, S and Murakami, K and Murata, S and Ishida, M and Kurumi, Y and Tani, T}, title = {Resectable carcinoma developing in the remnant pancreas 7 years and 10 months after distal pancreatectomy for invasive ductal carcinoma of the pancreas: report of a case.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {224}, pmid = {25034035}, issn = {1477-7819}, mesh = {Carcinoma, Pancreatic Ductal/*etiology/secondary/*surgery ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Second Primary/*etiology ; *Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; Prognosis ; Reoperation ; }, abstract = {BACKGROUND: Pancreatic ductal adenocarcinoma, which represents 90% of pancreatic cancers, is one of the most lethal and aggressive malignancies. Operative resection remains the only treatment providing prolonged survival, however, recurrence of pancreatic ductal adenocarcinoma occurs in up to 80% of patients with pancreatic cancer within 2 years of a potential curative resection. There are few reports of pancreatic carcinoma recurrence (primary second cancer) in the remnant pancreas after pancreatectomy.<br><br>CASE PRESENTATION: A 52-year-old woman underwent a distal pancreatectomy for pancreatic cancer in September 2004. Adjuvant chemotherapy was started after surgery and continued for 4&#xa0;years. In March 2012, marked elevation of DUPAN-II was observed, followed by an irregular stenotic finding in the main duct. We performed an en bloc resection of the remnant pancreas in July 2012. Histologically, the tumor contained a second primary pancreatic carcinoma with lymph node metastasis. At follow-up 20&#xa0;months after the second operation, the patient was alive without recurrence. Fourteen cases of resectable cancer developing in the remnant pancreas after a pancreatectomy for cancer have been reported; a minority of these was identified as second primary tumors. Therefore, our patient's primary second cancer is a rare event.<br><br>CONCLUSION: The patient is considered to have shown a rare, unique pancreatic cancer recurrence. Persistent elevation of a tumor marker and extensive imaging led to proper diagnosis and treatment.}, }
@article {pmid25031282, year = {2014}, author = {Croall, ID and Cowie, CJ and He, J and Peel, A and Wood, J and Aribisala, BS and Mitchell, P and Mendelow, AD and Smith, FE and Millar, D and Kelly, T and Blamire, AM}, title = {White matter correlates of cognitive dysfunction after mild traumatic brain injury.}, journal = {Neurology}, volume = {83}, number = {6}, pages = {494-501}, pmid = {25031282}, issn = {1526-632X}, mesh = {Adolescent ; Adult ; Aged ; Brain Injuries/*complications/*diagnosis ; Cognition Disorders/*diagnosis/*etiology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Nerve Fibers, Myelinated/*pathology ; Young Adult ; }, abstract = {OBJECTIVE: To relate neurophysiologic changes after mild/moderate traumatic brain injury to cognitive deficit in a longitudinal diffusion tensor imaging investigation.<br><br>METHODS: Fifty-three patients were scanned an average of 6 days postinjury (range = 1-14 days). Twenty-three patients were rescanned 1 year later. Thirty-three matched control subjects were recruited. At the time of scanning, participants completed cognitive testing. Tract-Based Spatial Statistics was used to conduct voxel-wise analysis on diffusion changes and to explore regressions between diffusion metrics and cognitive performance.<br><br>RESULTS: Acutely, increased axial diffusivity drove a fractional anisotropy (FA) increase, while decreased radial diffusivity drove a negative regression between FA and Verbal Letter Fluency across widespread white matter regions, but particularly in the ascending fibers of the corpus callosum. Raised FA is hypothesized to be caused by astrogliosis and compaction of axonal neurofilament, which would also affect cognitive functioning. Chronically, FA was decreased, suggesting myelin sheath disintegration, but still regressed negatively with Verbal Letter Fluency in the anterior forceps.<br><br>CONCLUSIONS: Acute mild/moderate traumatic brain injury is characterized by increased tissue FA, which represents a clear neurobiological link between cognitive dysfunction and white matter injury after mild/moderate injury.}, }
@article {pmid25029110, year = {2014}, author = {Rizwani, W and Schaal, C and Kunigal, S and Coppola, D and Chellappan, S}, title = {Mammalian lysine histone demethylase KDM2A regulates E2F1-mediated gene transcription in breast cancer cells.}, journal = {PloS one}, volume = {9}, number = {7}, pages = {e100888}, pmid = {25029110}, issn = {1932-6203}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA077301/CA/NCI NIH HHS/United States ; CA77301/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; E2F1 Transcription Factor/*genetics ; Epithelial Cells/metabolism/pathology ; F-Box Proteins/genetics/*metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism ; Matrix Metalloproteinases/metabolism ; Neoplasm Invasiveness ; Neovascularization, Pathologic/metabolism ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Retinoblastoma Protein/metabolism ; *Transcription, Genetic ; Up-Regulation ; Vascular Endothelial Growth Factor Receptor-1/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; }, abstract = {It is established that histone modifications like acetylation, methylation, phosphorylation and ubiquitination affect chromatin structure and modulate gene expression. Lysine methylation/demethylation on Histone H3 and H4 is known to affect transcription and is mediated by histone methyl transferases and histone demethylases. KDM2A/JHDM1A/FBXL11 is a JmjC-containing histone demethylase that targets mono- and dimethylated Lys36 residues of Histone H3; its function in breast cancer is not fully understood. Here we show that KDM2A is strongly expressed in myoepithelial cells (MEPC) in breast cancer tissues by immunohistochemistry. Ductal cells from ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) show positive staining for KDM2A, the expression decreases with disease progression to metastasis. Since breast MEPCs have tumor-suppressive and anti-angiogenic properties, we hypothesized that KDM2A could be contributing to some of these functions. Silencing KDM2A with small interfering RNAs demonstrated increased invasion and migration of breast cancer cells by suppressing a subset of matrix metalloproteinases (MMP-2, -9, -14 and -15), as seen by real-time PCR. HUVEC cells showed increased angiogenic tubule formation ability in the absence of KDM2A, with a concomitant increase in the expression of VEGF receptors, FLT-1 and KDR. KDM2A physically bound to both Rb and E2F1 in a cell cycle dependent manner and repressed E2F1 transcriptional activity. Chromatin immunoprecipitation (ChIP) assays revealed that KDM2A associates with E2F1-regulated proliferative promoters CDC25A and TS in early G-phase and dissociates in S-phase. Further, KDM2A could also be detected on MMP9, 14 and 15 promoters, as well as promoters of FLT1 and KDR. KDM2A could suppress E2F1-mediated induction of these promoters in transient transfection experiments. These results suggest a regulatory role for KDM2A in breast cancer cell invasion and migration, through the regulation of E2F1 function.}, }
@article {pmid25027758, year = {2014}, author = {Rask, L and Balslev, E and Søkilde, R and Høgdall, E and Flyger, H and Eriksen, J and Litman, T}, title = {Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status.}, journal = {Cellular oncology (Dordrecht)}, volume = {37}, number = {3}, pages = {215-227}, pmid = {25027758}, issn = {2211-3436}, mesh = {Aged ; Blotting, Western ; Breast Neoplasms/classification/diagnosis/*genetics ; Down-Regulation ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; MicroRNAs/*genetics ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; PTEN Phosphohydrolase/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Up-Regulation ; }, abstract = {PURPOSE: Therapeutic decisions in breast cancer are increasingly guided by prognostic and predictive biomarkers. Non-protein-coding microRNAs (miRNAs) have recently been found to be deregulated in breast cancers and, in addition, to be correlated with several clinico-pathological features. One of the most consistently up-regulated miRNAs is miR-21. Here, we specifically searched for differentially expressed miRNAs in high-risk breast cancer patients as compared to low-risk breast cancer patients. In the same patients, we also compared miR-21 expression with the expression of its presumed target PTEN.<br><br>METHODS: Both microarray and RT-qPCR techniques were used to assess miRNA expression levels in lymph node-positive and -negative human invasive ductal carcinoma tissues. Simultaneously, PTEN protein expression levels were assessed using immunohistochemistry.<br><br>RESULTS: miR-486-5p and miR-139-5p were found to be down-regulated in patients with lymph node metastases, whereas miR-21 was found to be up-regulated in patients with a positive lymph node status. miR-21 expression levels were found to significantly correlate with tumour size (r&#x2009;=&#x2009;0.403, p&#x2009;=&#x2009;0.009; Spearman's rank), whereas no relation was found between miR-21 and PTEN expression levels (Kruskal-Wallis test).<br><br>CONCLUSION: Down-regulation of miR-486-5p and miR-139-5p, in conjunction with up-regulation of miR-21, may represent a useful signature for the identification of high-risk breast cancer patients.}, }
@article {pmid25027116, year = {2014}, author = {Ramalho, EA and Silva-Filho, JL and Cartaxo, MF and Cavalcanti, CB and Rêgo, MJ and Oliveira, MB and Beltrão, EI}, title = {Assessment of changes in the BRCA2 and P53 genes in breast invasive ductal carcinoma in northeast Brazil.}, journal = {Biological research}, volume = {47}, number = {1}, pages = {3}, pmid = {25027116}, issn = {0717-6287}, mesh = {Alleles ; Brazil ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; CpG Islands/genetics ; DNA Methylation/*genetics ; Female ; *Genes, BRCA2 ; *Genes, p53 ; Genotype ; Humans ; Mutation ; Polymerase Chain Reaction/methods ; Polymorphism, Genetic ; Promoter Regions, Genetic/genetics ; Risk Factors ; Statistics as Topic ; }, abstract = {BACKGROUND: BRCA protein interacts with at least 13 different proteins that have been implicated with cancer susceptibility and loss of BRCA function is correlated to sensitivity to DNA crosslinking agents in preclinical models.<br><br>RESULTS: BRCA2 methylation frequency was 44%, p53 Pro22 allele frequency was 32% and heterozygous frequency of Arg/Pro72 genotype was 60% which could be associated as risk factor for metastasis (p = 0.046 OR = 4.190). Regarding to polymorphism of codon 249 the frequency of Arg249 allele presented 82% which was considered not statistically significant.<br><br>CONCLUSIONS: There was not statistical significance to BRCA2 promoter methylation with any parameters chosen. However, our findings suggest that patients who present heterozygous genotype at codon 72 of p53 gene may have a major susceptibility to any type of metastasis and this could serve as potential auxiliary biomarker for poor prognosis.}, }
@article {pmid25009006, year = {2014}, author = {Fujihira, A and Suzuki, T and Chang, MO and Moriyama, T and Kitajima, M and Takaku, H}, title = {Antitumor effects of baculovirus-infected dendritic cells against human pancreatic carcinoma.}, journal = {Gene therapy}, volume = {21}, number = {9}, pages = {849-854}, doi = {10.1038/gt.2014.59}, pmid = {25009006}, issn = {1476-5462}, mesh = {Animals ; Baculoviridae/physiology ; CD8-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Dendritic Cells/immunology/*virology ; Female ; Humans ; Immunotherapy ; Killer Cells, Natural/*immunology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Pancreatic Neoplasms/*immunology/pathology/*therapy ; Survival Analysis ; }, abstract = {Recently, we showed that baculovirus (BV)-infected dendritic cells (DCs) (BV-DCs) induced antitumor immunity against established tumors in mice. These antitumor effects were CD8(+) T-cell and natural killer (NK) cell dependent but CD4(+) T-cell independent. In the current study, we examined the antitumor effect of BV-DCs on human pancreatic cancer cells (AsPC-1). After treatment with BV-infected bone marrow-derived dendritic cells (BMDCs), human pancreatic tumors caused by AsPC-1 cells in a nude mouse model were significantly reduced in size, and the survival of the mice was improved compared with that of non-immature BMDC (iDC)- and BV-DC-immunized mice. We also found that wild-type BV could activate human DCs (HDCs) and that NK cells were activated by BV-infected HDCs (BHDCs). Our findings show that BV-DCs can induce antitumor immunity, which paves the way for the use of this technique as an effective tool for DC immunotherapy against malignancies.}, }
@article {pmid25007177, year = {2014}, author = {Rêgo, MJ and da Silva Filho, AF and Cordeiro, MF and Santos, PB and Beltrão, EI}, title = {The glycomic profile of invasive ductal carcinoma of the breast is altered in patients with hypoxic regions: implications for tumor behavior.}, journal = {Folia histochemica et cytobiologica}, volume = {52}, number = {2}, pages = {96-103}, doi = {10.5603/FHC.2014.0017}, pmid = {25007177}, issn = {1897-5631}, mesh = {Adult ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Carbonic Anhydrases/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Case-Control Studies ; Cell Hypoxia ; Female ; Galectin 1/*genetics/metabolism ; Galectin 3/*genetics/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Oxygen/*metabolism ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; }, abstract = {Hypoxic areas in solid tumors are often associated with poor prognosis and resistance to chemotherapy. The aim of the study was to analyze the expression of galectin-1 (Gal-1), galectin-3 (Gal-3), sialic acid and b1-6 branched glycan structures in hypoxic environment of invasive ductal carcinoma (IDC) of the breast. We performed lectin histochemistry with phytohemag glutinin-L (L-PHA) and Sambucus nigra lectin (SNA); and immunohistochemistry for Gal-1, Gal-3, carbonic anhydrase IX, hypoxia-inducible factor, estrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor type-2 for 86 IDC samples. Patients with markers positive for hypoxia were mostly ER-negative (p = 0.003) and presented with more nodal invasion than the non-hypoxic group (p = 0.0439). Concerning the glycobiological aspects, the hypoxic group expressed more of Gal-3 (p = 0.0021) and SNA ligands (p = 0.0498), however, there was no association between lectin- and galectin-staining and clinical and histopathological data. Our results suggest a change in the glycomic profile of patients within hypoxic regions of IDC. However, further studies are needed to evaluate the role of lectin- and galectin-ligands in tumor's hypoxic environment, as well as their potential to be used as therapeutic targets.}, }
@article {pmid25001103, year = {2014}, author = {Fang, X and Reifman, J and Wallqvist, A}, title = {Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle.}, journal = {Molecular bioSystems}, volume = {10}, number = {10}, pages = {2526-2537}, doi = {10.1039/c4mb00115j}, pmid = {25001103}, issn = {1742-2051}, mesh = {Animals ; Biomass ; Energy Metabolism ; Erythrocytes/*parasitology ; Host-Parasite Interactions ; Humans ; *Life Cycle Stages ; Malaria, Falciparum/*metabolism/*parasitology ; *Metabolic Networks and Pathways ; *Models, Biological ; Plasmodium falciparum/*growth &amp; development/*metabolism ; Time Factors ; }, abstract = {The human malaria parasite Plasmodium falciparum goes through a complex life cycle, including a roughly 48-hour-long intraerythrocytic developmental cycle (IDC) in human red blood cells. A better understanding of the metabolic processes required during the asexual blood-stage reproduction will enhance our basic knowledge of P. falciparum and help identify critical metabolic reactions and pathways associated with blood-stage malaria. We developed a metabolic network model that mechanistically links time-dependent gene expression, metabolism, and stage-specific growth, allowing us to predict the metabolic fluxes, the biomass production rates, and the timing of production of the different biomass components during the IDC. We predicted time- and stage-specific production of precursors and macromolecules for P. falciparum (strain HB3), allowing us to link specific metabolites to specific physiological functions. For example, we hypothesized that coenzyme A might be involved in late-IDC DNA replication and cell division. Moreover, the predicted ATP metabolism indicated that energy was mainly produced from glycolysis and utilized for non-metabolic processes. Finally, we used the model to classify the entire tricarboxylic acid cycle into segments, each with a distinct function, such as superoxide detoxification, glutamate/glutamine processing, and metabolism of fumarate as a byproduct of purine biosynthesis. By capturing the normal metabolic and growth progression in P. falciparum during the IDC, our model provides a starting point for further elucidation of strain-specific metabolic activity, host-parasite interactions, stress-induced metabolic responses, and metabolic responses to antimalarial drugs and drug candidates.}, }
@article {pmid24997789, year = {2014}, author = {Kim, JY and Kim, YJ and Kim, SH and Kang, BJ and Song, BJ}, title = {Invasive ductal carcinoma of the breast in a 14-year-old girl.}, journal = {Pediatric radiology}, volume = {44}, number = {11}, pages = {1446-1449}, pmid = {24997789}, issn = {1432-1998}, mesh = {Adolescent ; Breast Neoplasms/genetics/*pathology/*therapy ; Carcinoma, Ductal, Breast/genetics/*pathology/*therapy ; *Chemoradiotherapy, Adjuvant ; Female ; Genetic Predisposition to Disease/genetics ; Humans ; Magnetic Resonance Imaging ; *Mastectomy, Segmental ; Neoplasm Staging ; Rare Diseases/diagnosis/genetics/therapy ; Ultrasonography, Mammary ; }, abstract = {Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer.}, }
@article {pmid24996432, year = {2014}, author = {Asch-Kendrick, RJ and Samols, MA and Lilo, MT and Subhawong, AP and Sharma, R and Illei, PB and Argani, P and Cimino-Mathews, A}, title = {NKX3.1 is expressed in ER-positive and AR-positive primary breast carcinomas.}, journal = {Journal of clinical pathology}, volume = {67}, number = {9}, pages = {768-771}, pmid = {24996432}, issn = {1472-4146}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Carcinoma, Lobular/*chemistry/secondary ; Female ; Homeodomain Proteins/*analysis ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Receptors, Androgen/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/analysis ; Tissue Array Analysis ; Transcription Factors/*analysis ; Tumor Burden ; }, abstract = {AIMS: NKX3.1 is an androgen-regulated tumour suppressor gene that is downregulated in prostate carcinoma. Immunohistochemistry for NKX3.1 is primarily specific for prostatic-derived tumours and tissue but is reported in a small number of breast carcinomas. NKX3.1 is also shown to inhibit estrogen receptor (ER) signalling in breast carcinoma models. Here, we investigate labelling of NKX3.1 in invasive ductal (IDC) and lobular (ILC) carcinomas of the breast with full characterisation of ER, progesterone receptor (PR), androgen receptor (AR) and Her2 status.<br><br>METHODS: Tissue microarrays of 86 primary IDC and 37 ILC were labelled for NKX3.1. The IDC consisted of 20 luminal A, 7 luminal B, 14 Her2, and 45 triple negative carcinomas. The ILC consisted of 34 luminal A and 3 luminal B cases. NKX3.1 expression was scored as percentage nuclear labelling and labelling intensity.<br><br>RESULTS: Nuclear NKX3.1 labelling was seen in 2 IDC (2%) and 10 ILCs (27%). labelling intensity was weak in all cases (1&#x2013;100% nuclear positivity). Positive NKX3.1 labelling was significantly associated with ILC (p<0.0001). NKX3.1 labelling was seen only in ER and AR-positive carcinomas, which showed a significant correlation (p=0.0003 and p=0.0079, respectively). Expression was not correlated with tumour stage, size, Her2 expression, presence of lymph node metastases or age.<br><br>CONCLUSIONS: This is the first study to evaluate NKX3.1 expression in breast carcinomas with known ER, PR, AR and Her2 status. Further studies are needed to evaluate what potential role NKX3.1 plays in ER and AR signalling and hormonal treatment response in breast carcinomas.}, }
@article {pmid24989617, year = {2014}, author = {Saunderson, RB and Gouliouris, T and Cartwright, EJ and Nickerson, EJ and Aliyu, SH and O'Donnell, DR and Kelsall, W and Limmathurotsakul, D and Peacock, SJ and Török, ME}, title = {Impact of infectious diseases consultation on the management of Staphylococcus aureus bacteraemia in children.}, journal = {BMJ open}, volume = {4}, number = {7}, pages = {e004659}, pmid = {24989617}, issn = {2044-6055}, support = {G1000803/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/microbiology/*therapy ; Child ; Child, Preschool ; Dimethoate ; *Disease Management ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Prognosis ; *Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/microbiology/*therapy ; Staphylococcus aureus/*isolation &amp; purification ; }, abstract = {OBJECTIVES: Infectious diseases consultation (IDC) in adults with Staphylococcus aureus bacteraemia (SAB) has been shown to improve management and outcome. The aim of this study was to evaluate the impact of IDC on the management of SAB in children.<br><br>STUDY DESIGN: Observational cohort study of children with SAB.<br><br>SETTING: Cambridge University Hospitals National Health Service (NHS) Foundation Trust, a large acute NHS Trust in the UK.<br><br>PARTICIPANTS: All children with SAB admitted to the Cambridge University Hospitals NHS Foundation Trust between 16 July 2006 and 31 December 2012.<br><br>METHODS: Children with SAB between 2006 and 31 October 2009 were managed by routine clinical care (pre-IDC group) and data were collected retrospectively by case notes review. An IDC service for SAB was introduced in November 2009. All children with SAB were reviewed regularly and data were collected prospectively (IDC group) until 31 December 2012. Baseline characteristics, quality metrics and outcome were compared between the pre-IDC group and IDC group.<br><br>RESULTS: There were 66 episodes of SAB in 63 children-28 patients (30 episodes) in the pre-IDC group, and 35 patients (36 episodes) in the IDC group. The median age was 3.4&#x2005;years (IQR 0.2-10.7&#x2005;years). Patients in the IDC group were more likely to have echocardiography performed, a removable focus of infection identified and to receive a longer course of intravenous antimicrobial therapy. There were no differences in total duration of antibiotic therapy, duration of hospital admission or outcome at 30 or 90&#x2005;days following onset of SAB.<br><br>CONCLUSIONS: IDC resulted in improvements in the investigation and management of SAB in children.}, }
@article {pmid24989112, year = {2016}, author = {Kotani, H and Yoshimura, A and Adachi, Y and Ishiguro, J and Hisada, T and Ichikawa, M and Gondou, N and Hattori, M and Kondou, N and Sawaki, M and Fujita, T and Iwata, H}, title = {Sentinel lymph node biopsy is not necessary in patients diagnosed with ductal carcinoma in situ of the breast by stereotactic vacuum-assisted biopsy.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {23}, number = {2}, pages = {190-194}, doi = {10.1007/s12282-014-0546-y}, pmid = {24989112}, issn = {1880-4233}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Image-Guided Biopsy/*methods ; Lymph Nodes/diagnostic imaging/*pathology/surgery ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node Biopsy/*statistics &amp; numerical data ; Vacuum ; }, abstract = {BACKGROUND: This study evaluated the role and need of a sentinel lymph node biopsy (SLNB) in patients with an initial diagnosis of ductal carcinoma in situ (DCIS) made by stereotactic vacuum-assisted biopsy (VAB).<br><br>MATERIALS AND METHODS: A retrospective analysis was performed of 1,458 patients who underwent stereotactic VAB between January 1999 and December 2012 at Aichi Cancer Center Hospital. The rates of axillary node metastasis and the underestimation of invasive ductal carcinoma (IDC) were examined.<br><br>RESULTS: Of the 1,458 patients who underwent stereotactic VAB, 199 had a preoperative diagnosis of DCIS and underwent surgery. In these patients, 20 % (39/199) were upstaged to IDC or at least microinvasion in final pathology. Axillary lymph node status was investigated in 81 % (161/199) of initially diagnosed DCIS patients, and resulted in finding lymph node metastasis in 0.62 % (1/161) patients. To assess the potential preoperative predictors of invasiveness, the value of DCIS histological grade on biopsy samples, the distribution of calcifications on mammograms, and the combination of these factors were studied. The underestimation rate was higher (30 %) in the combination of high DCIS histological grade and extensive calcification although there was no significant association (p = 0.23).<br><br>CONCLUSION: The rate of lymph node metastasis was extremely low (0.62 %), even when invasive carcinoma was identified on excision in patients initially diagnosed with DCIS by stereotactic VAB. Because of the low prevalence of metastatic involvement, the cessation of SLNB is a reasonable consideration in patients initially diagnosed with DCIS by stereotactic VAB.}, }
@article {pmid24978026, year = {2014}, author = {Pape-Zambito, D and Jiang, Z and Wu, H and Devarajan, K and Slater, CM and Cai, KQ and Patchefsky, A and Daly, MB and Chen, X}, title = {Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients.}, journal = {PloS one}, volume = {9}, number = {6}, pages = {e100488}, pmid = {24978026}, issn = {1932-6203}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; R01 CA138819/CA/NCI NIH HHS/United States ; R21 CA186853/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/complications/*diagnosis/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*diagnosis/genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Female ; Formaldehyde ; Gene Expression ; *Genetic Heterogeneity ; Humans ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tissue Embedding ; Tissue Fixation ; Tumor Suppressor Protein p53/genetics ; }, abstract = {The heterogeneity among multiple ductal carcinoma in situ (DCIS) lesions within the same patient also diagnosed with invasive ductal carcinoma (IDC) has not been well evaluated, leaving research implications of intra-individual DCIS heterogeneity yet to be explored. In this study formalin-fixed paraffin embedded sections from 36 patients concurrently diagnosed with DCIS and IDC were evaluated by immunohistochemistry. Ten DCIS lesions from each patient were then randomly selected and scored. Our results showed that expression of PR, HER2, Ki-67, and p16 varied significantly within DCIS lesions from a single patient (P<0.05 for PR; P<1×10(-8) for HER2, Ki-67 and p16). In addition, seventy-two percent of the individuals had heterogeneous expression of at least 2/6 markers. Importantly, by evaluating the expression of promising DCIS risk biomarkers (Ki-67, p53 and p16) among different DCIS subgroups classified by comparing DCIS molecular subtypes with those of adjacent normal terminal duct lobular units (TDLU) and IDC, our results suggest the existence of a highly-aggressive DCIS subgroup, which had the same molecular subtype as the adjacent IDC but not the same subtype as the adjacent normal TDLU. By using a systematic approach, our results clearly demonstrate that intra-individual heterogeneity in DCIS is very common in patients concurrently diagnosed with IDC. Our novel findings of a DCIS subpopulation with aggressive characteristics will provide a new paradigm for mechanistic studies of breast tumor progression and also have broad implications for prevention research as heterogeneous pre-invasive lesions are present in many other cancer types.}, }
@article {pmid24969877, year = {2014}, author = {Sharma, M and Sharma, JD and Sarma, A and Ahmed, S and Kataki, AC and Saxena, R and Sharma, D}, title = {Triple negative breast cancer in people of North East India: critical insights gained at a regional cancer centre.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {11}, pages = {4507-4511}, doi = {10.7314/apjcp.2014.15.11.4507}, pmid = {24969877}, issn = {2476-762X}, mesh = {Adult ; Biomarkers, Tumor/genetics ; Female ; Humans ; India ; Lymph Nodes/pathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Retrospective Studies ; Triple Negative Breast Neoplasms/genetics/*pathology ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with many targeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy for triple negative breast cancer has been discovered to date and hence further research is needed.<br><br>AIM: The aim and objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC) in North-East India and to compare the clinicopathological parameters in two study groups defined by immunohistochemistry (IHC) -"TNBC" and "Others".<br><br>MATERIALS AND METHODS: We carried out a retrospective study in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr. B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3 years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into two groups - "TNBC" and "Others". All relevant clinicopathological parameters were compared in both. TNBC were defined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while those positive for any of these markers were defined as "Others".<br><br>RESULTS: In this study, out of total 972 cases 31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as "Others" based on IHC markers. Compared to the "Others" category, TNBC presented at an early age (mean 40 years), were associated with high grade large tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC.<br><br>CONCLUSIONS: TNBC accounts for a significant portion of breast cancers in this part of India and commonly present at younger age and tend to be large high grade tumours.}, }
@article {pmid24966964, year = {2014}, author = {Miyai, K and Divatia, MK and Shen, SS and Miles, BJ and Ayala, AG and Ro, JY}, title = {Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between "precursor-like" and "regular type" lesions.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {5}, pages = {2518-2526}, pmid = {24966964}, issn = {1936-2625}, mesh = {Aged ; Biopsy ; Carcinoma, Ductal/blood/chemistry/mortality/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/blood/chemistry/mortality/*secondary/surgery ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Kallikreins/blood ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/blood/chemistry/mortality/*secondary/surgery ; Prostatic Neoplasms/blood/chemistry/mortality/*pathology/surgery ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically "regular type" IDC-P and "precursor-like" IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.}, }
@article {pmid24966944, year = {2014}, author = {dos-Santos, PB and Zanetti, JS and Vieira-de-Mello, GS and Rêgo, MB and Ribeiro-Silva A, A and Beltrão, EI}, title = {Lectin histochemistry reveals SNA as a prognostic carbohydrate-dependent probe for invasive ductal carcinoma of the breast: a clinicopathological and immunohistochemical auxiliary tool.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {5}, pages = {2337-2349}, pmid = {24966944}, issn = {1936-2625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*enzymology/genetics/mortality/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/genetics/mortality/pathology ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; *Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; N-Acetylglucosaminyltransferases/*analysis ; Neoplasm Invasiveness ; *Plant Lectins ; Predictive Value of Tests ; Proportional Hazards Models ; *Ribosome Inactivating Proteins ; Risk Factors ; Time Factors ; Tissue Array Analysis ; }, abstract = {Increased sialylation and β1,6-branched oligosaccharides has been associated with a variety of structural changes in cell surface carbohydrates, most notably in tumorigenesis. Lectins are defined as proteins that preferentially recognize and bind carbohydrate complexes protruding from glycolipids and glycoproteins. This interaction with carbohydrates can be as specific as the interaction between antigen and antibody. Due to this type of interaction lectins have been used as experimental auxiliary tools in histopathological diagnosis of cancer. This study was designed to evaluate the differential expression of sialic acids and β1,6-N-acetylglucosaminyltransferase V (MGAT5) in invasive (IDC) and in situ (DCIS) ductal carcinoma of the breast and its possible application as prognostic biomarkers. A possible transition between pre-malign and malign lesions was evaluated using DCIS samples. Biopsies were analyzed regarding the expression of MUC1, p53, Ki-67, estrogen receptor, progesterone receptor, HER-2 and MGAT5. α2,6-linked sialic acids residues recognized by SNA lectin was overexpressed in 33.3% of IDC samples and it was related with Ki-67 (p=0.042), PR (p=0.029), lymphnodes status (p=0.017) and death (p=0.011). Regarding survival analysis SNA was the only lectin able to correlate with specific-disease survival and disease-free survival (p=0.024 and p=0.041, respectively), besides, it presents itself as an independent variable by Cox Regression analysis (p= 0.004). Comparing IDC and DCIS cases, only SNA showed different staining pattern (p=0.034). The presence of sialic acids on tumor cell surface can be an indicative of poor prognosis and our study provides further evidence that SNA lectin can be used as a prognostic probe in IDC and DCIS patients.}, }
@article {pmid24950714, year = {2014}, author = {Aggarwal, A and Al-Rohil, RN and Batra, A and Feustel, PJ and Jones, DM and DiPersio, CM}, title = {Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {459}, pmid = {24950714}, issn = {1471-2407}, support = {R01CA129637/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cyclooxygenase 2/genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Integrin alpha3beta1/genetics/*metabolism ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; }, abstract = {BACKGROUND: Expression of integrin α3β1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin α3β1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin α3β1 and COX2 by testing for their correlated expression among various forms of human breast cancer.<br><br>METHODS: Immunohistochemistry was performed to assess co-expression of &#x3b1;3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n = 59 samples) or obtained from Albany Medical Center archives (n = 68 samples). Immunostaining intensity for the integrin &#x3b1;3 subunit or COX2 was scored, and Spearman's rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria.<br><br>RESULTS: Although expression of integrin &#x3b1;3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between &#x3b1;3 and COX2 in both tissue microarrays (r(s) = 0.49, p < 0.001, n = 59) and archived samples (r(s) = 0.59, p < 0.0001, n = 68). In both sample sets, this correlation was independent of hormone receptor status, histological grade, or disease stage.<br><br>CONCLUSIONS: COX2 and &#x3b1;3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin &#x3b1;3&#x3b2;1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of &#x3b1;3&#x3b2;1-dependent COX2 gene expression that we reported previously in breast cancer cells. The findings also suggest that COX2-positive breast carcinomas of various subtypes might be vulnerable to therapeutic strategies that target &#x3b1;3&#x3b2;1, and that &#x3b1;3 expression might serve as an independent prognostic biomarker.}, }
@article {pmid24937677, year = {2014}, author = {Engels, CC and Fontein, DB and Kuppen, PJ and de Kruijf, EM and Smit, VT and Nortier, JW and Liefers, GJ and van de Velde, CJ and Bastiaannet, E}, title = {Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma.}, journal = {British journal of cancer}, volume = {111}, number = {3}, pages = {532-538}, pmid = {24937677}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Carcinoma, Lobular/*immunology/pathology ; Caspase 3/metabolism ; Disease-Free Survival ; Female ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential.<br><br>METHODS: Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery.<br><br>RESULTS: No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC.<br><br>CONCLUSIONS: Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.}, }
@article {pmid24937604, year = {2014}, author = {Chatfield, KC and Sparagna, GC and Sucharov, CC and Miyamoto, SD and Grudis, JE and Sobus, RD and Hijmans, J and Stauffer, BL}, title = {Dysregulation of cardiolipin biosynthesis in pediatric heart failure.}, journal = {Journal of molecular and cellular cardiology}, volume = {74}, number = {}, pages = {251-259}, pmid = {24937604}, issn = {1095-8584}, support = {R01 HL107715/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01HL107715/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Cardiolipins/*biosynthesis/chemistry ; Cardiomyopathy, Dilated/*metabolism/pathology/surgery ; Child ; Child, Preschool ; Female ; Gene Expression ; Heart Failure/*metabolism/pathology/surgery ; Heart Transplantation ; Heart Ventricles/*metabolism/pathology ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Mitochondria, Heart/*metabolism/pathology ; Mitochondrial Proteins/genetics/metabolism ; Myocardium/*metabolism/pathology ; }, abstract = {Cardiolipin, a unique phospholipid in the inner mitochondrial membrane, is critical for optimal mitochondrial function. CL abnormalities have been demonstrated in the failing rodent and adult human heart. The aim of this study was to determine whether abnormalities in CL content and the CL biosynthesis and remodeling pathways are present in pediatric idiopathic dilated cardiomyopathy (IDC). A cross-sectional analysis of myocardial tissue from 119 IDC and non-failing (NF) control samples was performed. Electrospray ionizing mass spectrometry was used to measure total CL and CL species content in LV tissue. RT-PCR was employed to measure gene expression of the enzymes in the CL biosynthesis and remodeling pathways in both the adult and pediatric heart. Significantly lower total and (18:2)4CL (the beneficial species) content was demonstrated in myocardium from pediatric patients with IDC compared to NF controls. Analysis of mitochondrial gene transcripts was used to demonstrate that there is no decrease in mitochondrial content. Expression of two biosynthesis enzymes and one remodeling enzyme was significantly lower in pediatric IDC compared to NF controls. Expression of two phospholipases involved in CL degradation were also altered, one up- and one down-regulated. Except for one remodeling enzyme, these changes are unique from those in the failing adult heart. Similar to what has been seen in adults and in a rat model of IDC, total and (18:2)4CL are lower in pediatric IDC. Unique CL species profiles are seen in heart tissue from children with IDC compared to adults. Differences in CL biosynthesis and remodeling enzyme expression likely explain the differences in CL profiles observed in IDC and implicate unique age-related mechanisms of disease.}, }
@article {pmid24931343, year = {2014}, author = {Oda, Y and Aishima, S and Morimatsu, K and Shindo, K and Fujino, M and Mizuuchi, Y and Hattori, M and Miyazaki, T and Tanaka, M and Oda, Y}, title = {Pancreatic intraepithelial neoplasia in the background of invasive ductal carcinoma of the pancreas as a prognostic factor.}, journal = {Histopathology}, volume = {65}, number = {3}, pages = {389-397}, doi = {10.1111/his.12397}, pmid = {24931343}, issn = {1365-2559}, mesh = {Aged ; Atrophy ; Carcinoma in Situ/*pathology ; Carcinoma, Pancreatic Ductal/*pathology/secondary ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Pancreatic Neoplasms/*pathology ; Prognosis ; }, abstract = {AIMS: Of the recognized precursor lesions of pancreatic adenocarcinoma, pancreatic intraepithelial neoplasia (PanIN) is the most common form. However, little is known about the relationship between the grade of PanIN and prognosis for patients with invasive ductal carcinoma.<br><br>METHODS AND RESULTS: In 124 patients with invasive ductal carcinoma, we examined the grade and number of PanIN lesions in all slides of resected pancreas. The prevalence rates of PanIN-1A, PanIN-1B, PanIN-2 and PanIN-3 were 86%, 84%, 57% and 30%, respectively. We allocated PanIN-2 and PanIN-3 cases into a PanIN-high group, and cases showing PanIN-1A, PanIN-1B or absence of PanIN into a PanIN-low group. In clinicopathological analysis, PanIN-high status was significantly correlated with the number of PanIN lesions (P < 0.0001). Disease-free and overall survival were statistically better in the PanIN-high group than in the PanIN-low group (P = 0.0005 and P = 0.0003). Univariate and multivariate analyses revealed that tumour size and PanIN-low status were statistically significant factors for a poorer prognosis (P = 0.042 and P = 0.007).<br><br>CONCLUSIONS: In a pathological examination, it is important to evaluate the grade and number of PanINs in assessing the prognosis of pancreatic cancer.}, }
@article {pmid24919244, year = {2014}, author = {So, K and Habashy, D and Doyle, B and Chan, L}, title = {Indwelling urinary catheters: pattern of use in a public tertiary-level Australian hospital.}, journal = {Urologic nursing}, volume = {34}, number = {2}, pages = {69-73}, pmid = {24919244}, issn = {1053-816X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Australia ; Catheter-Related Infections/*etiology/nursing ; Female ; Hospitals, Public ; Humans ; Male ; Middle Aged ; Nursing Audit ; Tertiary Care Centers ; Urinary Catheterization/*adverse effects/nursing/*statistics &amp; numerical data ; Urinary Catheters/*adverse effects ; }, abstract = {An audit of charts from patients identified as having an indwelling urinary catheter (IDC) was conducted in a 450-bed, tertiary level hospital (Concord Repatriation General Hospital) in Australia. Documentation of relevant information regarding IDC in the medical record included indication for catheterization, insertion and removal dates, use of antibiotics, place of insertion, designation of inserter, catheter type, availability of IDC kits, and use of catheter fixation devices.}, }
@article {pmid24909183, year = {2014}, author = {Min, KW and Kim, DH and Do, SI and Kim, K and Lee, HJ and Chae, SW and Sohn, JH and Pyo, JS and Oh, YH and Kim, WS and Lee, SY and Oh, S and Choi, SH and Park, YL and Park, CH}, title = {Expression patterns of stromal MMP-2 and tumoural MMP-2 and -9 are significant prognostic factors in invasive ductal carcinoma of the breast.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {122}, number = {12}, pages = {1196-1206}, doi = {10.1111/apm.12285}, pmid = {24909183}, issn = {1600-0463}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/*genetics/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2/genetics/*metabolism ; Matrix Metalloproteinase 9/genetics/*metabolism ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {Matrix metalloproteinases (MMPs) are matrix-degrading enzymes that play a pivotal role in aggressive behaviours, such as rapid tumour growth, invasion, and metastasis, of several types of solid tumours. In particular, stromal MMP-2 plays important roles in the progression of malignant tumours, but most clinical studies have focused on tumoural MMP-2 and -9 expression, and not stromal MMP-2 expression. One hundred and seventy-seven cases diagnosed as invasive ductal carcinoma of the breast between 2000 and 2005 were included in this study. Expressions of tumoural MMP-2 and -9 and stromal MMP-2 were analysed by immunostaining on a tissue microarray. Subsequently, the associations between those results and various clinicopathological parameters were evaluated. Stromal MMP-2 expression correlated significantly with clinicopathological parameters such as advanced T category, larger tumour size, high histological grade, tumour necrosis, ER- and PR-negative, and HER-2-positive (all p < 0.05). In univariate and multivariate analyses, overall survival was linked with stromal MMP-2 expression as well as dual expression of stromal MMP-2 and tumoural MMP-2 and -9 (all p < 0.05). Stromal MMP-2 expression may play a crucial role in predicting aggressive clinical behaviour in breast cancer patients.}, }
@article {pmid24894013, year = {2014}, author = {Das, U and Lakshmaiah, KC and Govind Babu, K and Suresh, TM and Lokanatha, D and Jacob, L and Babu, S}, title = {The actual scenario of neoadjuvant chemotherapy of breast cancer in developing country: a report of 80 cases of breast cancer from a tertiary cancer center in India.}, journal = {Journal of cancer research and clinical oncology}, volume = {140}, number = {10}, pages = {1777-1782}, pmid = {24894013}, issn = {1432-1335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/economics/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/*drug therapy/secondary/surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration &amp; dosage ; Epirubicin/administration &amp; dosage ; Female ; Fluorouracil/administration &amp; dosage ; Humans ; India/epidemiology ; Induction Chemotherapy ; Lymphatic Metastasis ; Medical Records ; Middle Aged ; Molecular Targeted Therapy/*economics ; Neoadjuvant Therapy/*methods ; Neoplasm Staging ; Postmenopause ; Premenopause ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Rural Population/statistics &amp; numerical data ; Tertiary Care Centers ; Treatment Outcome ; }, abstract = {BACKGROUND: Preoperative or neoadjuvant chemotherapy is an option in patients with large operable breast cancer to facilitate the breast conservation and to downstage the disease to make inoperable breast cancer to operable one. It is also called the window of opportunity; it provides a unique opportunity to derive biological information related to tumor response. Neoadjuvant chemotherapy has been compared with standard, postoperative adjuvant chemotherapy with goals of improving survival and facilitating local therapies. Unfortunately, neoadjuvant chemotherapy does not seem to improve overall survival. There is a lack of data from India regarding the neoadjuvant chemotherapy. The present study was carried out to assess the response to neoadjuvant chemotherapy in breast cancer.<br><br>MATERIALS AND METHODS: We retrospectively analyzed the records of patients who were started on neoadjuvant chemotherapy (NACT) at our center for 1 year (August 2012 to July 2013). Case files were thoroughly reviewed, and patient's characteristics (age, pre-/postmenopausal status, family history of breast/ovarian/other cancer), mode of detection, treatment, and histological features were analyzed.<br><br>RESULTS: Out of 322 patients with breast cancer registered in our institute, 80 patients received neoadjuvant chemotherapy. Median age was 45 years. The most common presentation was left-sided breast lump (Lt > Rt) with a median duration of symptoms was 4 months. Postmenopausal patients (53.75 %) were more than premenopausal (46.25 %). Seventy-two patients were stage III and 8 were stage II disease. Bilateral breast cancer was seen in 8 patients. Most common histological type was invasive ductal carcinoma (95 %). Estrogen receptor (ER) and/or progesterone (PR) positive were seen in 47 (58.75 %) patients. Ten patients were HER2 positive and ER/PR negative, and 5 patients were triple positive. Triple-negative patients were 22 (27.5 %). The most common neoadjuvant chemotherapy protocol used was FEC. Clinical response before surgery was CR 13 %, PR 68.68 %, stable disease 11.62 %, and progressive disease 4.65 %. Pathological CR was seen in 6.9 % of tumors. Nodal status at surgery was ypN0-40 %, ypN1-28. 5 %. ypN2-27 %, and ypN3-4.28 %.<br><br>CONCLUSION: In a population of predominantly locally advanced patients, NACT with anthracyclines yielded pCR rates comparable to published studies. There were a high proportion of HER2-positive patients, most of whom could not receive anti-HER2 therapy due to financial reasons.}, }
@article {pmid24888777, year = {2014}, author = {Tajiri, R and Inokuchi, M and Sawada-Kitamura, S and Kawashima, H and Nakamura, R and Oyama, T and Dobashi, Y and Ooi, A}, title = {Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.}, journal = {Pathology international}, volume = {64}, number = {5}, pages = {231-236}, doi = {10.1111/pin.12158}, pmid = {24888777}, issn = {1440-1827}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; Biopsy, Needle ; Breast/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/therapy ; Carcinoma, Ductal, Breast/*genetics/metabolism/therapy ; Carcinoma, Lobular/*genetics/metabolism/therapy ; Cyclin D1/genetics/metabolism ; DNA Fingerprinting/*methods ; DNA, Neoplasm/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Mastectomy ; Multiplex Polymerase Chain Reaction/*methods ; Receptor, ErbB-2/genetics/metabolism ; Treatment Outcome ; }, abstract = {A needle biopsy of a mass in the right breast of a 36-year-old woman revealed invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed unequivocal membranous staining with the HercepTest. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E-cadherin-negative invasive lobular carcinoma (ILC), and the rest was ERBB2-positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma. Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization (FISH) analyses revealed that ILC and IDC shared high-level amplification of CCND1 in homogeneously staining regions (HSR) and that IDC had an additional HSR-type amplicon of ERBB2. These findings strongly indicate that IDC and ILC had a common precursor cell with CCND1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2 as a minor component, IDC without amplification of CCND1 or ERBB2 as a major component, and a minute portion of ILC with CCND1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC with CCND1 amplification was resistant to chemotherapy and grew.}, }
@article {pmid24887297, year = {2014}, author = {Gruel, N and Benhamo, V and Bhalshankar, J and Popova, T and Fréneaux, P and Arnould, L and Mariani, O and Stern, MH and Raynal, V and Sastre-Garau, X and Rouzier, R and Delattre, O and Vincent-Salomon, A}, title = {Polarity gene alterations in pure invasive micropapillary carcinomas of the breast.}, journal = {Breast cancer research : BCR}, volume = {16}, number = {3}, pages = {R46}, pmid = {24887297}, issn = {1465-542X}, mesh = {Axonemal Dyneins/genetics ; Base Sequence ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Calmodulin-Binding Proteins/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Polarity/*genetics ; Chaperonins ; Class I Phosphatidylinositol 3-Kinases ; Cytoskeletal Proteins/genetics ; DNA Copy Number Variations ; Exome/genetics ; Female ; Forkhead Box Protein O3 ; Forkhead Transcription Factors/biosynthesis/genetics ; Formins ; Gene Amplification/genetics ; Group II Chaperonins/genetics ; Humans ; Membrane Glycoproteins/genetics ; Membrane Proteins/biosynthesis/genetics ; Microfilament Proteins/biosynthesis ; Molecular Chaperones ; Mutation, Missense ; Neoplasm Invasiveness/*genetics ; Neoplasm Proteins/genetics ; Nuclear Proteins/biosynthesis ; Phosphatidylinositol 3-Kinases/genetics ; Protein Tyrosine Phosphatases, Non-Receptor/genetics ; RNA-Binding Proteins ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Retrospective Studies ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Sequence Deletion/genetics ; Serine C-Palmitoyltransferase/genetics ; Tumor Suppressor Protein p53/genetics ; Ubiquitin-Protein Ligases ; }, abstract = {INTRODUCTION: Pure invasive micropapillary carcinoma (IMPC) is a special type of breast carcinoma characterised by clusters of cells presenting polarity abnormalities. The biological alterations underlying this pattern remain unknown.<br><br>METHODS: Pangenomic analysis (n=39), TP53 (n=43) and PIK3CA (n=41) sequencing in a series of IMPCs were performed. A subset of cases was also analysed with whole-exome sequencing (n=4) and RNA sequencing (n=6). Copy number variation profiles were compared with those of oestrogen receptors and grade-matched invasive ductal carcinomas (IDCs) of no special type.<br><br>RESULTS: Unsupervised analysis of genomic data distinguished two IMPC subsets: one (Sawtooth/8/16) exhibited a significant increase in 16p gains (71%), and the other (Firestorm/Amplifier) was characterised by a high frequency of 8q (35%), 17q (20% to 46%) and 20q (23% to 30%) amplifications and 17p loss (74%). TP53 mutations (10%) were more frequently identified in the amplifier subset, and PIK3CA mutations (4%) were detected in both subsets. Compared to IDC, IMPC exhibited specific loss of the 6q16-q22 region (45%), which is associated with downregulation of FOXO3 and SEC63 gene expression. SEC63 and FOXO3 missense mutations were identified in one case each (2%). Whole-exome sequencing combined with RNA sequencing of IMPC allowed us to identify somatic mutations in genes involved in polarity, DNAH9 and FMN2 (8% and 2%, respectively) or ciliogenesis, BBS12 and BBS9 (2% each) or genes coding for endoplasmic reticulum protein, HSP90B1 and SPTLC3 (2% each) and cytoskeleton, UBR4 and PTPN21 (2% each), regardless of the genomic subset. The intracellular biological function of the mutated genes identified by gene ontology analysis suggests a driving role in the clinicopathological characteristics of IMPC.<br><br>CONCLUSION: In our comprehensive molecular analysis of IMPC, we identified numerous genomic alterations without any recurrent fusion genes. Recurrent somatic mutations of genes participating in cellular polarity and shape suggest that they, together with other biological alterations (such as epigenetic modifications and stromal alterations), could contribute to the morphological pattern of IMPC. Though none of the individual abnormalities demonstrated specificity for IMPC, whether their combination in IMPC may have a cumulative effect that drives the abnormal polarity of IMPC needs to be examined further with in vitro experiments.}, }
@article {pmid24886617, year = {2014}, author = {Wani, N and Nasser, MW and Ahirwar, DK and Zhao, H and Miao, Z and Shilo, K and Ganju, RK}, title = {C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates breast cancer growth and metastasis by modulating the tumor microenvironment.}, journal = {Breast cancer research : BCR}, volume = {16}, number = {3}, pages = {R54}, pmid = {24886617}, issn = {1465-542X}, support = {P30 CA016058/CA/NCI NIH HHS/United States ; R01 CA109527/CA/NCI NIH HHS/United States ; R01 CA153490/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Chemokine CXCL12/*metabolism ; Female ; Humans ; Lung Neoplasms/genetics/mortality/*secondary ; Macrophage Activation/genetics ; Macrophage Colony-Stimulating Factor/biosynthesis ; Macrophages/immunology ; Matrix Metalloproteinase 2/biosynthesis ; Matrix Metalloproteinase 9/biosynthesis ; Mice ; Mice, Inbred BALB C ; Neoplasm Invasiveness/genetics ; Neoplasm Transplantation ; Protein Binding ; RNA Interference ; RNA, Small Interfering ; Receptor, Macrophage Colony-Stimulating Factor/biosynthesis ; Receptors, CXCR/antagonists &amp; inhibitors/biosynthesis/genetics/*metabolism ; STAT3 Transcription Factor/antagonists &amp; inhibitors/genetics/*metabolism ; Tumor Microenvironment ; Vascular Cell Adhesion Molecule-1/biosynthesis ; }, abstract = {INTRODUCTION: Although C-X-C motif chemokine 12 (CXCL12) has been shown to bind to C-X-C chemokine receptor type 7 (CXCR7), the exact molecular mechanism regulations by CXCL12/CXCR7 axis in breast tumor growth and metastasis are not well understood. CXCR7 expression has been shown to be upregulated during pathological processes such as inflammation and cancer.<br><br>METHODS: Breast cancer cell lines were genetically silenced or pharmacologically inhibited for CXCR7 and/or its downstream target signal transducer and activator of transcription 3 (STAT3). 4T1 or 4T1 downregulated for CXCR7 and 4T1.2 breast cancer cell lines were injected in mammary gland of BALB/c mice to form tumors, and the molecular pathways regulating tumor growth and metastasis were assessed.<br><br>RESULTS: In this study, we observed that CXCL12 enhances CXCR7-mediated breast cancer migration. Furthermore, genetic silencing or pharmacologic inhibition of CXCR7 reduced breast tumor growth and metastasis. Further elucidation of mechanisms revealed that CXCR7 mediates tumor growth and metastasis by activating proinflammatory STAT3 signaling and angiogenic markers. Furthermore, enhanced breast tumorigenicity and invasiveness were associated with macrophage infiltration. CXCR7 recruits tumor-promoting macrophages (M2) to the tumor site through regulation of the macrophage colony-stimulating factor (M-CSF)/macrophage colony-stimulating factor receptor (MCSF-R) signaling pathway. In addition, CXCR7 regulated breast cancer metastasis by enhancing expression of metalloproteinases (MMP-9, MMP-2) and vascular cell-adhesion molecule-1 (VCAM-1). We also observed that CXCR7 is highly expressed in invasive ductal carcinoma (IDC) and metastatic breast tissue in human patient samples. In addition, high CXCR7 expression in tumors correlates with worse prognosis for both overall survival and lung metastasis-free survival in IDC patients.<br><br>CONCLUSION: These observations reveal that CXCR7 enhances breast cancer growth and metastasis via a novel pathway by modulating the tumor microenvironment. These findings identify CXCR7-mediated STAT3 activation and modulation of the tumor microenvironment as novel regulation of breast cancer growth and metastasis. These studies indicate that new strategies using CXCR7 inhibitors could be developed for antimetastatic therapy.}, }
@article {pmid24885919, year = {2014}, author = {Xie, R and Wang, Y and Nie, W and Huang, W and Song, W and Wang, Z and Guan, X}, title = {Lin28B expression correlates with aggressive clinicopathological characteristics in breast invasive ductal carcinoma.}, journal = {Cancer biotherapy &amp; radiopharmaceuticals}, volume = {29}, number = {5}, pages = {215-220}, pmid = {24885919}, issn = {1557-8852}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Female ; Humans ; Middle Aged ; RNA-Binding Proteins/*biosynthesis/genetics ; }, abstract = {Lin28B is a RNA-binding protein that inhibits the let-7 microRNA family and acts as an oncogene in various human malignant diseases. Conversely, the members of let-7 family function as tumor suppressers and are often inactivated in cancers. The interaction of Lin28B/let-7 plays a crucial part of tumorigenesis. In this study, the authors examined the Lin28B expression using immunohistochemistry in 190 breast cancers and analyzed the correlation of Lin28B immunostaining and clinicopathological characteristics. Breast cancer patients previously diagnosed with invasive ductal carcinomas were enrolled in this study. All cases went through surgical procedures as the initial treatment. The characteristics of every case were collected, including tumor size, pathologic grade, metastatic lymphoid nodes, and estrogen receptor α (ERα), progesterone receptor (PR), and HER2 status. The immunostaining was scored by two independent investigators. Eighty-three (43.7%) of 190 cases showed positive expression of Lin28B. Lin28B immunostaining was increased in tumors compared with the adjacent tissues. Overexpression of Lin28B was linked to poor differentiation, advanced-stage disease, and Ki67-positive status (all p<0.05). Besides, Lin28B expression was significantly different among breast cancer subtypes. This study addresses the role of Lin28B in breast cancers and provides insight of its predictive effects in disease development.}, }
@article {pmid24870789, year = {2014}, author = {Rathore, AS and Goel, MM and Makker, A and Kumar, S and Srivastava, AN}, title = {Is the tumor infiltrating natural killer cell (NK-TILs) count in infiltrating ductal carcinoma of breast prognostically significant?.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {8}, pages = {3757-3761}, doi = {10.7314/apjcp.2014.15.8.3757}, pmid = {24870789}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/pathology ; CD56 Antigen/immunology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Cell Count ; Female ; Humans ; Immunohistochemistry ; Killer Cells, Natural/*immunology ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; }, abstract = {PURPOSE: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast.<br><br>MATERIAL AND METHODS: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively.<br><br>RESULTS: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (&#x3c7;2=4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (&#x3c7;2=1.60, p>0.05).<br><br>CONCLUSION: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.}, }
@article {pmid24868030, year = {2014}, author = {Muss, HB}, title = {Adjuvant chemotherapy in older women with breast cancer: who and what?.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {32}, number = {19}, pages = {1996-2000}, doi = {10.1200/JCO.2013.54.8586}, pmid = {24868030}, issn = {1527-7755}, mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/diagnosis/*drug therapy/*surgery ; Carcinoma, Ductal, Breast/drug therapy/surgery ; Chemotherapy, Adjuvant ; Clinical Trials as Topic ; Comorbidity ; Female ; Filgrastim ; Granulocyte Colony-Stimulating Factor/administration &amp; dosage ; Humans ; *Life Expectancy ; Lymphatic Metastasis ; Polyethylene Glycols ; *Quality of Life ; Receptor, ErbB-2/analysis ; Recombinant Proteins/administration &amp; dosage ; Referral and Consultation ; Risk Assessment ; Risk Factors ; Taxoids/administration &amp; dosage ; }, abstract = {A 73-year-old woman has been diagnosed with a mammographically detected grade 3, 2.2-cm invasive ductal carcinoma that is sentinel lymph node negative, estrogen receptor positive (80%), progesterone receptor negative, and human epidermal growth factor receptor 2 negative (0 by immunohistochemistry). A gene expression assay (Oncotype DX, Genomic Health, Redwood City, CA) showed a recurrence score of 28. Except for well-controlled hypertension and some aches and pains in her hands and knees, she has no other major illnesses. Her medications include an antihypertensive, vitamin D, and calcium. She discontinued cigarette smoking 20 years ago and has an occasional glass of wine. She describes her health as good, is fully functional, drives, has had no falls, and provides the majority of care for her sick husband. Her blood pressure is 146/88, her body mass index is 29.7, and her physical examination is normal. She is aware of the benefits and risks of adjuvant endocrine therapy and has been referred to discuss the role of chemotherapy.}, }
@article {pmid24866608, year = {2014}, author = {Sohn, YM and Hong, IK and Han, K}, title = {Role of [18F]fluorodeoxyglucose positron emission tomography-computed tomography, sonography, and sonographically guided fine-needle aspiration biopsy in the diagnosis of axillary lymph nodes in patients with breast cancer: comparison of diagnostic performance.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {33}, number = {6}, pages = {1013-1021}, doi = {10.7863/ultra.33.6.1013}, pmid = {24866608}, issn = {1550-9613}, mesh = {Adult ; Aged ; Axilla/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology/*secondary ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; False Negative Reactions ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Middle Aged ; Positron-Emission Tomography/methods ; Radiopharmaceuticals ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy/*methods ; Tomography, X-Ray Computed/methods ; Ultrasonography, Mammary/*methods ; }, abstract = {OBJECTIVES: The aim of this study was to compare the diagnostic performance of [(18)F]fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) with that of sonography and sonographically guided fine-needle aspiration (FNA) for determining the preoperative axillary lymph node (ALN) status and to evaluate the factors related to false-negative PET-CT, sonographic, and FNA results in ALN staging of invasive ductal carcinoma.<br><br>METHODS: From March 2009 to July 2012, 226 patients had a diagnosis of primary breast cancer. Among these patients, 107 constituted the study population after exclusion of transferred patients and patients with breast cancer other than invasive ductal carcinoma. The diagnostic performance of the modalities was compared with pathologic reports. Univariate and multivariate analyses were used to evaluate the relationship between clinicopathologic factors (symptoms, T stage, hormone receptors, and histologic grade), false-negative results, and true-negative results on PET-CT, sonography, and FNA.<br><br>RESULTS: Of the 107 patients, 45 (42.1%) had positive results on final pathologic analysis of ALNs. Sonographically guided FNA had a significantly higher specificity, positive predictive value, accuracy, and area under the receiver operating characteristic curve than sonography and PET-CT (P < .01). When sonography and PET-CT were combined, the sensitivity was significantly improved (P = .019) compared with sonography alone. When FNA and PET-CT were combined, the sensitivity and negative predictive value were significantly increased compared with each modality (P < .01).<br><br>CONCLUSIONS: Sonographically guided FNA was found to be an excellent diagnostic tool for preoperative evaluation of the ALN status. To obviate the step of sentinel lymph node biopsy for determining the ALN status, combined evaluation of ALNs by these modalities may be more complementary than the use of a single modality.}, }
@article {pmid24865535, year = {2014}, author = {Hirota, M and Ogawa, M}, title = {No-touch pancreatectomy for invasive ductal carcinoma of the pancreas.}, journal = {JOP : Journal of the pancreas}, volume = {15}, number = {3}, pages = {243-249}, doi = {10.6092/1590-8577/2502}, pmid = {24865535}, issn = {1590-8577}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/mortality/secondary/*surgery ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology/prevention &amp; control ; Neoplasm Recurrence, Local/pathology/prevention &amp; control ; Neoplastic Cells, Circulating/*pathology ; Pancreatectomy/adverse effects/*methods/mortality ; Pancreatic Neoplasms/mortality/pathology/*surgery ; Prognosis ; Retroperitoneal Space/surgery ; Surgical Instruments ; Touch ; }, abstract = {BACKGROUND: Pancreatectomy is the only effective treatment for cancers of the pancreas. Surgeons usually grasp tumors during pancreatectomy; however, this procedure may increase the risk of squeezing and shedding of the cancer cells into the portal vein, retroperitoneum, and/or peritoneal cavity. In an effort to overcome these problems, we have developed surgical techniques for no-touch pancreatectomy.<br><br>METHODS: From April 2008 through September 2013, 52 patients have been operated on no-touch pancreatectomy for invasive ductal carcinoma of the pancreas by a single operator (M.H.). Among them, 40 received pancreatoduodenectomy (PD), and 12 did distal pancreatectomy (DP). Twenty two cases (42%) required SMV-PV resection. This is a study to see if pancreatectomy can be technically done using a no-touch surgical technique without deteriorating the post-operative prognosis. During the procedure, the pancreatic tumor is neither grasped nor squeezed by the surgeon. Furthermore, for improved dissection of the retroperitoneal tissue (leftward and posterior margins for PD and rightward and posterior margins for DP), we use a hanging and clamping maneuver and dissection behind Gerota fascia.<br><br>RESULTS: Overall 2- and 5-year survival rates were 64 and 42% with mean follow-up periods of 34.4 months (range: 6-68 months). Recurrence free 2- and 5-year survival rates were 49 and 31%, respectively. The 5-year survival rates of patients with JPS-stage III and those with JPS-stage IV were 57 and 20%, respectively. The 5-year survival rates of patients with UICC-stage IIA and those with UICC- stage IIB were 49 and 39%, respectively. Patients with UICC-stage III or IV did not survive for more than 2 years.<br><br>CONCLUSIONS: No-touch pancreatectomy has many theoretic advantages that merit further investigation in future randomized controlled trials.}, }
@article {pmid24862985, year = {2014}, author = {Takagi, K and Moriguchi, T and Miki, Y and Nakamura, Y and Watanabe, M and Ishida, T and Yamamoto, M and Sasano, H and Suzuki, T}, title = {GATA4 immunolocalization in breast carcinoma as a potent prognostic predictor.}, journal = {Cancer science}, volume = {105}, number = {5}, pages = {600-607}, pmid = {24862985}, issn = {1349-7006}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Disease-Free Survival ; Female ; GATA4 Transcription Factor/genetics/*metabolism ; Gene Expression ; Humans ; Immunohistochemistry ; Laser Capture Microdissection ; Middle Aged ; Neoplasm Recurrence, Local/genetics/*pathology ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Transcriptional GATA factors are known lineage selector genes and regulate a variety of biological processes including specification and differentiation of tissues. In the present study, we examined expression profiles of six GATA factor genes in invasive ductal carcinomas (IDC) of the breast using microarray analysis (n = 20) and found that GATA4 expression was closely correlated with recurrence in patients. Because the significance of GATA4 has remained largely unknown in breast carcinoma, we further immunolocalized GATA4 in ductal carcinoma in situ (DCIS) of the breast (n = 48) and IDC (n = 163). GATA4 immunoreactivity was detected in the nuclei of carcinoma cells and was positive in 27% of DCIS and 31% of IDC cases. GATA4 status was significantly associated with nuclear grade and van Nuys classification in DCIS and was positively associated with distant metastasis, histological grade and HER2 status, but negatively correlated with progesterone receptor labeling index in IDC. Subsequent multivariate analysis demonstrated that GATA4 status was an independent prognostic factor for both disease-free and breast cancer-specific survival of IDC patients. All of these results indicate that GATA4 plays important roles in the progression of breast carcinoma from an early stage and that immunohistochemical GATA4 status is considered a potent prognostic factor in human breast cancer patients.}, }
@article {pmid24848193, year = {2015}, author = {Santangelo, G and Vitale, C and Trojano, L and Picillo, M and Moccia, M and Pisano, G and Pezzella, D and Cuoco, S and Erro, R and Longo, K and Pellecchia, MT and Amboni, M and De Rosa, A and De Michele, G and Barone, P}, title = {Relationship between apathy and cognitive dysfunctions in de novo untreated Parkinson's disease: a prospective longitudinal study.}, journal = {European journal of neurology}, volume = {22}, number = {2}, pages = {253-260}, doi = {10.1111/ene.12467}, pmid = {24848193}, issn = {1468-1331}, mesh = {Aged ; Apathy/*physiology ; Cognition Disorders/*etiology/physiopathology ; Disease Progression ; Executive Function/*physiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications/physiopathology ; }, abstract = {BACKGROUND AND PURPOSE: Apathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the present study was to determine the progression of cognitive impairment in drug-naïve untreated PD patients with or without clinically significant apathy.<br><br>METHODS: Sixty-two PD patients with a disease duration <2 years and without history of present or past therapy with pro-dopaminergic agents were included and underwent the Apathy Evaluation Scale (S-AES), a clinical interview based on diagnostic criteria for apathy and a comprehensive neuropsychological battery to assess memory, frontal functions and visuospatial functions. Two years after the first assessment, all patients were re-evaluated on the S-AES, a clinical interview and neuropsychological tests.<br><br>RESULTS: According to the cut-off value of the S-AES and diagnostic criteria for apathy, eight patients experienced apathy at both baseline and follow-up (A+A+), nine patients had apathy only at follow-up (A-A+), 37 patients never experienced apathy (A-A-) and eight patients showed apathy at the baseline only (A+A-). Cognitive performance significantly declined in all four groups. At both baseline and follow-up A+A+ performed worse than A-A- on visuospatial and frontal tests; A-A+ had lower scores than A-A- on the interference task of the Stroop test (IT-ST). Regression analysis showed that poor performance on the IT-ST at baseline was the only independent predictor of onset of apathy at follow-up.<br><br>CONCLUSIONS: The results indicated a relationship between apathy and dysexecutive syndrome in early PD. Reduced scores on the IT-ST may predict development of apathy in PD patients.}, }
@article {pmid24842702, year = {2014}, author = {Picillo, M and Erro, R and Amboni, M and Longo, K and Vitale, C and Moccia, M and Pierro, A and Scannapieco, S and Santangelo, G and Spina, E and Orefice, G and Barone, P and Pellecchia, MT}, title = {Gender differences in non-motor symptoms in early Parkinson's disease: a 2-years follow-up study on previously untreated patients.}, journal = {Parkinsonism &amp; related disorders}, volume = {20}, number = {8}, pages = {850-854}, doi = {10.1016/j.parkreldis.2014.04.023}, pmid = {24842702}, issn = {1873-5126}, mesh = {Aged ; Antiparkinson Agents/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications/*drug therapy ; Sex Characteristics ; }, abstract = {BACKGROUND: We recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking.<br><br>METHODS: In the present study, we first report a prospective assessment of gender-related differences in the spectrum of NMS before (baseline) and after starting dopaminergic therapy (2-year follow-up) in a large cohort of newly diagnosed PD patients. Differences in NMS frequency between baseline and follow-up were evaluated by McNemar test. Spearman's rank test was employed to explore interactions between NMS and drug treatment.<br><br>RESULTS: One-hundred and thirty four PD patients (86M and 48W) were included in the present study. At 2-year follow-up, Sadness/blues presented a significant percentage reduction as compared to baseline in both sexes, while Urgency, Daytime sleepiness, Weight change and Sex drive presented a significant percentage increase only in men. At follow up men complained of a greater number of NMS as compared to women. Occurrence of Weight change was related to therapy in both sexes. Male gender was found to be a risk factor for developing Dribbling and Nocturia, irrespective of therapy and clinical features.<br><br>CONCLUSIONS: In conclusion, our study showed that mood symptoms improved after the introduction of therapy in both sexes, while men appeared to be more prone to develop some NMS possibly linked to dopaminergic treatment.}, }
@article {pmid24842355, year = {2014}, author = {Vázquez Vicente, D and Di Fiore, HA and Garcia-Foncillas, J and Plaza Arranz, J}, title = {Endometrial adenocarcinoma in one horn of a didelphic uterus with vaginal duplication.}, journal = {BMJ case reports}, volume = {2014}, number = {}, pages = {}, pmid = {24842355}, issn = {1757-790X}, mesh = {Abnormalities, Multiple/diagnosis ; Adenocarcinoma/complications/*diagnosis/surgery ; Endometrial Neoplasms/complications/*diagnosis/surgery ; Endosonography/methods ; Female ; Follow-Up Studies ; Humans ; Hysterectomy/methods ; Hysteroscopy/methods ; Laparoscopy/methods ; Magnetic Resonance Imaging/methods ; Middle Aged ; Ovariectomy/methods ; Postmenopause ; Risk Assessment ; Treatment Outcome ; Urogenital Abnormalities/*diagnosis/surgery ; Uterine Hemorrhage/diagnosis/etiology ; Uterus/*abnormalities/surgery ; Vagina/*abnormalities/surgery ; }, abstract = {A 59-year-old female patient presented with vaginal bleeding. A didelphic uterus with vaginal duplication was diagnosed on the basis of physical examination and radiology tests. Biopsy revealed an endometrial cancer in the left horn, while the right was atrophic. Laparoscopic hysterectomy, bilateral salphingo-oophorectomy, pelvic and para-aortic lymphadenectomy were performed. According to Federation International of Gynecology and Obstetrics (FIGO) staging the tumour was classified Ib. The adjuvant therapy was vaginal cuff brachytherapy. After 6 months, she has no evidence of the disease.}, }
@article {pmid24841533, year = {2014}, author = {Engstrom, LM and Brinkmeyer, MK and Ha, Y and Raetz, AG and Hedman, B and Hodgson, KO and Solomon, EI and David, SS}, title = {A zinc linchpin motif in the MUTYH glycosylase interdomain connector is required for efficient repair of DNA damage.}, journal = {Journal of the American Chemical Society}, volume = {136}, number = {22}, pages = {7829-7832}, pmid = {24841533}, issn = {1520-5126}, support = {T32 ES007058/ES/NIEHS NIH HHS/United States ; R01 CA067985/CA/NCI NIH HHS/United States ; T32 ES007059/ES/NIEHS NIH HHS/United States ; P41GM103393/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; CA069785/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cysteine/chemistry/genetics ; DNA Damage ; DNA Glycosylases/*chemistry/genetics ; DNA Repair Enzymes/*chemistry ; Humans ; Kinetics ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis ; Protein Conformation ; Serine/chemistry/genetics ; Zinc Compounds/*chemistry ; }, abstract = {Mammalian MutY glycosylases have a unique architecture that features an interdomain connector (IDC) that joins the catalytic N-terminal domain and 8-oxoguanine (OG) recognition C-terminal domain. The IDC has been shown to be a hub for interactions with protein partners involved in coordinating downstream repair events and signaling apoptosis. Herein, a previously unidentified zinc ion and its coordination by three Cys residues of the IDC region of eukaryotic MutY organisms were characterized by mutagenesis, ICP-MS, and EXAFS. In vitro kinetics and cellular assays on WT and Cys to Ser mutants have revealed an important function for zinc coordination on overall protein stability, iron-sulfur cluster insertion, and ability to mediate DNA damage repair. We propose that this "zinc linchpin" motif serves to structurally organize the IDC and coordinate the damage recognition and base excision functions of the C- and N-terminal domains.}, }
@article {pmid24833443, year = {2015}, author = {Matsuda, H and Takahashi, Y and Nakata, K and Kitamura, A and Kakizaki, H}, title = {No Intense 18F-Fluorodeoxyglucose Uptake in Positron Emission Tomography of a Metastatic Orbital Tumor From Breast Carcinoma.}, journal = {Ophthalmic plastic and reconstructive surgery}, volume = {31}, number = {4}, pages = {e95-8}, doi = {10.1097/IOP.0000000000000115}, pmid = {24833443}, issn = {1537-2677}, mesh = {Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/secondary ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Magnetic Resonance Imaging ; Mastectomy, Radical ; Medroxyprogesterone/therapeutic use ; Middle Aged ; Muscle Neoplasms/diagnostic imaging/secondary ; Oculomotor Muscles/diagnostic imaging ; Orbital Neoplasms/*diagnostic imaging/secondary ; Paclitaxel/therapeutic use ; *Positron-Emission Tomography ; Radiopharmaceuticals/*metabolism ; Vision Disorders/diagnosis ; }, abstract = {A 47-year-old woman with a history of invasive ductal carcinoma in the right breast reported decreased vision in the OD for the past 3 months. Her best corrected visual acuity was 0.1 OD and 1.0 OS. T1-weighted MRI revealed enlargement of the right lateral rectus muscle with a faint tumor outline and no contrast enhancement in the lesion. F-fluorodeoxyglucose positron emission tomography did not demonstrate intense uptake at the lesion. Because the patient demonstrated optic neuropathy due to compression by the enlarged muscle, balanced orbital decompression (of the deep lateral and medial orbital walls) was performed simultaneously with a tumor biopsy. Visual acuity of the OD was dramatically improved to 1.0. The histopathological examination demonstrated similar findings to her breast carcinoma. F-fluorodeoxyglucose positron emission tomography does not always show a positive result for an orbital tumor that has metastasized from the breast.}, }
@article {pmid24810926, year = {2014}, author = {Calvano Filho, CM and Calvano-Mendes, DC and Carvalho, KC and Maciel, GA and Ricci, MD and Torres, AP and Filassi, JR and Baracat, EC}, title = {Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {8}, pages = {7733-7741}, pmid = {24810926}, issn = {1423-0380}, mesh = {Breast/metabolism ; Carcinoma, Ductal, Breast/genetics ; Female ; Forkhead Box Protein O1 ; Forkhead Transcription Factors/genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*analysis ; Triple Negative Breast Neoplasms/*genetics ; }, abstract = {New concepts in epigenetics, microRNAs, and gene expression analysis have significantly enhanced knowledge of cancer pathogenesis over the last decade. MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene expression by base pairing with target messenger RNAs (mRNAs), resulting in the repression of translation or the degradation of mRNA. To compare the carcinogenic process in tumors with different prognoses, we used real-time RT-PCR to evaluate the miRNA expression profiles of 24 triple-negative breast invasive ductal carcinoma, 20 luminal A breast invasive ductal carcinoma, and 13 normal breast parenchyma controls. We extracted total RNA from tissues fixed in formol and embedded in paraffin (FFPE). Results revealed the upregulation of miR-96-5p (9.35-fold; p = 0.000115), miR-182-5p (7.75-fold; p = 0.000033), miR-7-5p (6.71-fold; p = 0.015626), and miR-21-5p (6.10-fold; p = 0.000000) in tumors group. In addition, the expression of miR-125b-5p (4.49-fold; p = 0.000000) and miR-205-5p (4.36-fold; p = 0.006098) was downregulated. When the expression profiles of triple-negative and luminal A tumors were compared, there was enhanced expression of miR-17-5p (4.27-fold; p = 0.000664), miR-18a-5p (9.68-fold; p = 0.000545), and miR-20a-5 (4.07-fold; p = 0.001487) in the triple-negative tumors compared with luminal A. These data suggest that there is a similar regulation of certain miRNAs in triple-negative and luminal A tumors. However, it is possible that differences in the expression of miR-17-92 cluster will explain the phenotypic differences between these molecular tumor subtypes.}, }
@article {pmid24799764, year = {2014}, author = {Stumpfova, Z and Hezova, R and Meli, AC and Slaby, O and Michalek, J}, title = {MicroRNA profiling of activated and tolerogenic human dendritic cells.}, journal = {Mediators of inflammation}, volume = {2014}, number = {}, pages = {259689}, pmid = {24799764}, issn = {1466-1861}, mesh = {Cells, Cultured ; Dendritic Cells/drug effects/*metabolism ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-10/pharmacology ; Interleukin-4/pharmacology ; Lipopolysaccharides/pharmacology ; MicroRNAs/*genetics ; Transforming Growth Factor beta/pharmacology ; }, abstract = {Dendritic cells (DCs) belong to the immune system and are particularly studied for their potential to direct either an activated or tolerogenic immune response. The roles of microRNAs (miRNAs) in posttranscriptional gene expression regulation are being increasingly investigated. This study's aim is to evaluate the miRNAs' expression changes in prepared human immature (iDCs), activated (aDCs), and tolerogenic dendritic cells (tDCs). The dendritic cells were prepared using GM-CSF and IL-4 (iDC) and subsequently maturated by adding LPS and IFN-γ (aDC) or IL-10 and TGF-β (tDC). Surface markers, cytokine profiles, and miRNA profiles were evaluated in iDC, tDC, and aDC at 6 h and 24 h of maturation. We identified 4 miRNAs (miR-7, miR-9, miR-155 and miR-182), which were consistently overexpressed in aDC after 6 h and 24 h of maturation and 3 miRNAs (miR-17, miR-133b, and miR-203) and miR-23b cluster solely expressed in tDC. We found 5 miRNAs (miR-10a, miR-203, miR-210, miR-30a, and miR-449b) upregulated and 3 miRNAs downregulated (miR-134, miR-145, and miR-149) in both tDC and aDC. These results indicate that miRNAs are specifically modulated in human DC types. This work may contribute to identifying specific modulating miRNAs for aDC and tDC, which could in the future serve as therapeutic targets in the treatment of cancer and autoimmune diseases.}, }
@article {pmid24795533, year = {2014}, author = {Zahir, MN and Minhas, K and Shabbir-Moosajee, M}, title = {Pleomorphic lobular carcinoma of the male breast with axillary lymph node involvement: a case report and review of literature.}, journal = {BMC clinical pathology}, volume = {14}, number = {}, pages = {16}, pmid = {24795533}, issn = {1472-6890}, abstract = {BACKGROUND: Carcinoma of the male breast is responsible for less than 1% of all malignancies in men but the incidence is rising. Invasive ductal carcinoma is the most common histological subtype while invasive lobular carcinoma is responsible for only 1.5% of the total cases of which pleomorpic lobular carcinoma is an extremely rare variant. We report the case of a gentleman with node positive, pleomorphic lobular carcinoma of the breast.<br><br>CASE PRESENTATION: An elderly gentleman with a past history of type 2 diabetes and long term ethanol use presented to us with a self-discovered palpable lump in the left breast. Physical examination revealed bilateral gynaecomastia along with a well circumscribed subareolar mass and palpable lymphadenopathy in the ipsilateral axilla. The breast nodule revealed atypical cells on fine needle aspiration biopsy and the patient underwent a modified radical mastectomy after systemic surveillance was negative for metastatic disease. The lesion was reported as grade III pleomorphic lobular carcinoma with a lack of E-cadherin expression on immunohistochemistry and the neoplastic cells exhibited strong positivity for estrogen receptor in the absence of Her2 gene amplification. Six out of the eleven dissected regional lymph nodes showed evidence of disease. The patient completed 4&#xa0;cycles of adjuvant chemotherapy without evidence of recurrent disease and was subsequently lost to follow up.<br><br>CONCLUSIONS: Although invasive lobular carcinomas comprise 12% of all female breast cancers, they are very rare in males due to lack of acini and lobules in the normal male breast. Pleomorphic lobular carcinoma, an aggressive variant of ILC is even rarer in males. Chronic consumption of ethanol by our patient may have resulted in some degree of hepatic impairment with resultant hyperestrogenism. This in theory may have been the cause of his gynaecomastia, resultant breast cancer and is a plausible explanation for development of the invasive lobular subtype in a male. The prognosis and clinicopatholocial features of pleomorphic lobular carcinoma in men are less clearly defined due to its rarity. Additional studies are hence necessary to improve our understanding of this disease in males.}, }
@article {pmid24794782, year = {2014}, author = {Li, X and Luo, R and Jiang, R and Kong, H and Tang, Y and Shu, Y and Hua, W}, title = {The prognostic use of serum concentrations of cardiac troponin-I, CK-MB and myoglobin in patients with idiopathic dilated cardiomyopathy.}, journal = {Heart &amp; lung : the journal of critical care}, volume = {43}, number = {3}, pages = {219-224}, doi = {10.1016/j.hrtlng.2014.03.001}, pmid = {24794782}, issn = {1527-3288}, mesh = {Adult ; Aged ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/diagnostic imaging/mortality ; Cohort Studies ; Creatine Kinase, MB Form/*blood ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Myoglobin/*blood ; Prognosis ; Proportional Hazards Models ; Troponin I/*blood ; }, abstract = {OBJECTIVE: To examine the association between survival and serum concentrations of cTnI, CK-MB, and myoglobin in patients with idiopathic dilated cardiomyopathy (IDC).<br><br>BACKGROUND: It has been suggested that elevated circulating biomarkers of myocardial damage such as cardiac troponin-I (cTnI), creatine kinase MB (CK-MB) and myoglobin are independent risk factors for mortality in patients with heart failure, and recent studies, although limited, showed that there was a potential association between cTnI and the prognosis of patients with dilated cardiomyopathy (DCM).<br><br>METHODS: A cohort study was undertaken in 310 patients with IDC. Standard demographic information, transthoracic echocardiography, and routine blood tests were obtained shortly after hospital admission. Outcome was assessed with all-cause mortality.<br><br>RESULTS: Among the 310 patients studied, 61 (19.7%) died during a mean follow-up of 2.2 years. There was a significant difference in the all-cause mortality rate between patients with serum cTnI >0.05 ng/mL and with cTnI &#x2264; 0.05 ng/mL (37.5% vs 15%, log-rank &#x3c7;(2) = 18.423, P < 0.001). After adjustment for other factors associated with prognosis at baseline, serum cTnI >0.05 ng/mL, QRS duration, NYHA functional class and systolic blood pressure predicted all-cause mortality in patients with IDC. There was no association between circulating CK-MB and myoglobin levels and all-cause mortality in the studied IDC patients.<br><br>CONCLUSION: Serum concentrations of cTnI but not CK-MB or myoglobin are an independent predictor of all-cause mortality in patients with IDC.}, }
@article {pmid24790704, year = {2014}, author = {Mohamed, MM and Sabet, S and Peng, DF and Nouh, MA and El-Shinawi, M and El-Rifai, W}, title = {Promoter hypermethylation and suppression of glutathione peroxidase 3 are associated with inflammatory breast carcinogenesis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2014}, number = {}, pages = {787195}, pmid = {24790704}, issn = {1942-0994}, mesh = {Breast/pathology ; Breast Neoplasms/enzymology/*pathology ; *DNA Methylation ; Down-Regulation ; Female ; Glutathione Peroxidase/*genetics/metabolism ; Humans ; Middle Aged ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; }, abstract = {Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients' in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients' clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression.}, }
@article {pmid24789732, year = {2014}, author = {Erro, R and Santangelo, G and Barone, P and Picillo, M and Amboni, M and Longo, K and Giordano, F and Moccia, M and Allocca, R and Pellecchia, MT and Vitale, C}, title = {Do subjective memory complaints herald the onset of mild cognitive impairment in Parkinson disease?.}, journal = {Journal of geriatric psychiatry and neurology}, volume = {27}, number = {4}, pages = {276-281}, doi = {10.1177/0891988714532015}, pmid = {24789732}, issn = {0891-9887}, mesh = {Aged ; Cognitive Dysfunction/complications/diagnosis/*psychology ; Disease Progression ; Educational Status ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Memory ; Memory Disorders/*diagnosis/psychology ; Middle Aged ; Neuropsychological Tests/statistics &amp; numerical data ; Parkinson Disease/complications/diagnosis/*psychology ; Predictive Value of Tests ; Prospective Studies ; Psychiatric Status Rating Scales/statistics &amp; numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Longitudinal studies on healthy participants have shown that subjective memory impairment (defined as subjective cognitive complaints with normal cognitive objective performance) might be a strong predictor of mild cognitive impairment (MCI). Parkinson disease (PD) also manifests cognitive disturbances, but whether subjective memory complaints may predict the development of MCI in PD has not yet been explored.<br><br>METHODS: We prospectively screened newly diagnosed, untreated patients with PD in order to evaluate whether subjective memory complaints may predict development of MCI over a 2-year follow-up evaluation.<br><br>RESULTS: We enrolled 76 de novo untreated patients with PD. Of the 76 patients, 23 (30.3%) complained memory issues. Among the patients cognitively unimpaired at baseline, those with subjective complaints were more likely to develop MCI at follow-up. The regression model confirmed that presence of subjective memory complaints at baseline was an independent predictor of development of MCI at follow-up.<br><br>DISCUSSION: This is the first prospective study to explore the relationship between subjective and objective cognitive deficits in newly diagnosed, untreated patients. Our results provide preliminary evidence that subjective memory complaints might predict future development of MCI.}, }
@article {pmid24786829, year = {2014}, author = {Paul, A and Gunewardena, S and Stecklein, SR and Saha, B and Parelkar, N and Danley, M and Rajendran, G and Home, P and Ray, S and Jokar, I and Vielhauer, GA and Jensen, RA and Tawfik, O and Paul, S}, title = {PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis.}, journal = {Cell death and differentiation}, volume = {21}, number = {9}, pages = {1469-1481}, pmid = {24786829}, issn = {1476-5403}, support = {HL094892/HL/NHLBI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R01 HD062546/HD/NICHD NIH HHS/United States ; R21 HL094892/HL/NHLBI NIH HHS/United States ; HD075233/HD/NICHD NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; R21 HD075233/HD/NICHD NIH HHS/United States ; R21 HL104322/HL/NHLBI NIH HHS/United States ; HD062546/HD/NICHD NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Isoenzymes/genetics/*metabolism ; Lung Neoplasms/metabolism/pathology/*secondary ; Mice ; Mice, Inbred NOD ; Mice, Nude ; Mice, SCID ; Neoplasm Transplantation ; Protein Kinase C/genetics/*metabolism ; *Signal Transduction ; Triple Negative Breast Neoplasms/*metabolism/*pathology ; }, abstract = {Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are often diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKCλ/ι, significantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKCλ/ι signaling as a potential therapeutic target for TNBC. Our observations indicated that PKCλ/ι signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKCλ/ι expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKCλ/ι significantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identified a PKCλ/ι-regulated gene signature consisting of 110 genes, which are significantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGFβ and IL1β could activate PKCλ/ι signaling in TNBC cells and depletion of PKCλ/ι impairs NF-κB p65 (RelA) nuclear localization. We observed that cytokine-PKCλ/ι-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKCλ/ι promote TNBC growth, invasion and metastasis. Thus, targeting PKCλ/ι signaling could be a therapeutic option for breast cancer, including the TNBC subtype.}, }
@article {pmid24781343, year = {2016}, author = {Madden, NA and Macdonald, OK and Call, JA and Schomas, DA and Lee, CM and Patel, S}, title = {Radiotherapy and Male Breast Cancer: A Population-based Registry Analysis.}, journal = {American journal of clinical oncology}, volume = {39}, number = {5}, pages = {458-462}, doi = {10.1097/COC.0000000000000078}, pmid = {24781343}, issn = {1537-453X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*mortality/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*mortality/*radiotherapy/secondary/surgery ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Mastectomy/methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; SEER Program ; Survival Rate ; Tumor Burden ; United States/epidemiology ; }, abstract = {BACKGROUND: The local-regional management of female breast cancer has been extensively investigated worldwide. The optimal approach for males diagnosed with breast cancer is less clear. We have analyzed the treatment of male breast cancer using a population-based national registry to determine the impact of surgery and radiation therapy on survival.<br><br>MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried to identify males with invasive ductal carcinoma of the breast who underwent primary surgical resection (radical mastectomy, modified radical mastectomy, total mastectomy, or segmental) for the years 1983 to 2002. Demographic, clinical, and pathologic data were culled and analyzed to determine the impact of radiation therapy (RT) following resection. Survival rates were estimated using the Kaplan-Meier method and significance was determined using the log-rank test (P<0.05). Multivariate analysis with the Cox proportional hazards model was performed to determine factors significant for overall (OS) and cause-specific survival (CSS).<br><br>RESULTS: A total of 1337 patients met the eligibility criteria and were analyzed. Median follow-up was 7.3 years (range, 1 mo to 25 y). Most men underwent modified radical mastectomy (n=1062) with a minority undergoing segmental (n=113). About 329 men received postoperative external beam RT. The median rates of OS and CSS for all men were 10.5 years and not yet reached, respectively. The surgical procedure did not significantly associate with OS or CSS. By stage, RT was associated with improved OS for stage I (P=0.03). There was a trend for improved survival with stage II (P=0.21) and III (P=0.15). RT was not associated with improved CSS by stage. RT improved rates of OS and CSS in N2 patients without reaching statistical significance (P=0.10 and 0.22). On multivariate analysis, advancing age, stage and grade, and no postoperative RT predicted for worse OS. However, when controlled for those with known hormone receptor status (n=978), only the factors of advancing age, stage, grade, and hormone receptor negativity predicted for worse OS. Advancing age, stage, and grade were the only predictors of CSS irrespective of the cohort analyzed.<br><br>CONCLUSIONS: The primary surgical procedure did not ultimately influence OS or CSS in this population-based registry of males with breast cancer. A statistically nonsignificant improvement with postoperative RT was observed in men with lymph node involvement, larger tumor size, or higher stage. When controlled for age, stage, and grade in multivariate analysis, postoperative RT predicted for improved OS but not CSS. These data suggest a beneficial effect of RT in the postoperative setting. A prospective study is necessary to further elucidate appropriate treatment strategies for men with breast cancer.}, }
@article {pmid24781337, year = {2014}, author = {Petrović, N and Mandušić, V and Dimitrijević, B and Roganović, J and Lukić, S and Todorović, L and Stanojević, B}, title = {Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia.}, journal = {Medical oncology (Northwood, London, England)}, volume = {31}, number = {6}, pages = {977}, pmid = {24781337}, issn = {1559-131X}, mesh = {Aged ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; Female ; Humans ; MicroRNAs/*genetics/metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Reference Values ; Serbia ; }, abstract = {MicroRNAs play essential role in breast carcinoma progression and invasion. Our principal goals were to assess clinicopathological and prognostic correlations of microRNA-21 (miR-21) expression levels in a group of 39 Serbian breast cancer patients with invasive lobular (ILC), ductal (IDC), or mixed (ILC-IDC) breast carcinomas and in order to discover the role of miR-21 in potential novel form of stratification of the patients with different estrogen receptor (ER) and progesterone receptor (PR) status. MiR-21 expression levels were measured by stem-loop real-time RT-PCR using TaqMan technology. ER, PR, human epidermal growth factor 2 receptor (Her-2), and proliferative index (Ki-67) were evaluated by immunohistochemistry. MiR-21 levels do not vary among ILC, IDC, and ILC-IDC subgroups. MiR-21 expression levels varied significantly in the age, tumor size, Ki-67, and different grade (p = 0.030, p = 0.036, p = 0.027 and p = 0.032, respectively) subgroups. ER+ and PR+ showed higher miR-21 levels than their negative receptor status paired groups ER- and PR- with p = 0.012 and p = 0.018, respectively. MiR-21 positively correlated with ER and PR status (p = 0.018, ρ = 0.379 and p = 0.034, ρ = 0.345, respectively). Our findings suggest that miR-21 emulates transitional form of expression and that the levels of expression might be useful for stratification of the patients with different receptor status with the purpose to seek for new therapy approaches especially for the patients with the lack of response to conventional endocrine therapy.}, }
@article {pmid24768572, year = {2014}, author = {Purushotham, A and Shamil, E and Cariati, M and Agbaje, O and Muhidin, A and Gillett, C and Mera, A and Sivanadiyan, K and Harries, M and Sullivan, R and Pinder, SE and Garmo, H and Holmberg, L}, title = {Age at diagnosis and distant metastasis in breast cancer--a surprising inverse relationship.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {50}, number = {10}, pages = {1697-1705}, doi = {10.1016/j.ejca.2014.04.002}, pmid = {24768572}, issn = {1879-0852}, mesh = {Adult ; Age Factors ; Aged ; Biomarkers, Tumor/analysis ; Bone Neoplasms/chemistry/mortality/*secondary/therapy ; Breast Neoplasms/chemistry/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary/therapy ; Carcinoma, Lobular/chemistry/mortality/*secondary/therapy ; Disease-Free Survival ; ErbB Receptors/analysis ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Proportional Hazards Models ; Prospective Studies ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Registries ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; }, abstract = {INTRODUCTION: Predictors for site of distant metastasis and impact on survival in breast cancer are incompletely understood.<br><br>METHODS: Clinico-pathological risk factors for site of distant metastasis and survival were analysed in patients with invasive breast cancer treated between 1986 and 2006.<br><br>RESULTS: Of 3553 patients, with median follow-up 6.32years, 825 (23%) developed distant metastasis. The site of metastasis was bone in 196/825 (24%), viscera in 540/825 (65%) and unknown in 89 (11%). Larger primary invasive tumour size, higher tumour grade and axillary nodal positivity increased risk of metastasis to all sites. Lobular carcinoma was more likely to first metastasise to bone compared to invasive ductal carcinoma (NST). Oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and/or Human epidermal growth factor (HER2) positive tumours were more likely to metastasise to viscera. A striking relationship between increasing age at diagnosis and a reduction in risk of distant metastasis to bone and viscera was observed. Median time to death from onset of metastatic disease was 1.52 (Interquartile range (IQR) 0.7-2.9)years for patients with bone metastasis and 0.7 (IQR 0.2-1.5)years for visceral metastasis. On multivariate analysis, despite the decrease in risk of distant metastasis with increasing age, there was an elevated hazard for death in patients >50years at diagnosis of metastasis if they developed bone metastasis, with a similar trend observed in the >70years age group if they developed visceral metastasis.<br><br>CONCLUSION: These findings indicate that there are biological mechanisms underlying the impact of age on the development of distant metastasis and subsequent death. This may have important implications in the treatment of breast cancer.}, }
@article {pmid24762482, year = {2014}, author = {Singh, R and Gupta, S and Pawar, SB and Pawar, RS and Gandham, SV and Prabhudesai, S}, title = {Evaluation of ER, PR and HER-2 receptor expression in breast cancer patients presenting to a semi urban cancer centre in Western India.}, journal = {Journal of cancer research and therapeutics}, volume = {10}, number = {1}, pages = {26-28}, doi = {10.4103/0973-1482.131348}, pmid = {24762482}, issn = {1998-4138}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/*metabolism ; Cancer Care Facilities ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; India ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Retrospective Studies ; Risk Factors ; Urban Health Services ; Young Adult ; }, abstract = {BACKGROUND: Hormone receptor expression has been reported to be low in breast cancer patients from developing countries. The pattern of receptor expression from urban and rural areas is not well studied.<br><br>MATERIALS AND METHODS: This is a retrospective analysis of 206 consecutive breast cancer patients presenting to a semi urban cancer centre from 2009-2010. The demographic and clinical variables included age, residential area (rural, semi urban, or urban), menopausal status, and clinical stage. The pathological variables included tumor type, the presence of ductal carcinoma in situ, lymphovascular invasion, and expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) receptors by immunohistochemical (IHC) analysis.<br><br>RESULTS: The majority of patients were postmenopausal with the median age of 50 years. Invasive ductal carcinoma was the most common subtype (94%). The ER status was available in 101 (49.3%), PR in 99 (48.0%), and HER2 in 82 (39.8%) cases. In patients in whom this data were available, ER was positive in 44.6%, PR in 40.4%, and HER2 in 34.2%. Out of the 82 patients in whom data on all three receptors were available, 34.1% patients had triple negative tumors. Analysis of our data showed a trend toward increasing ER and PR expression with age but this was not statistically significant. The average age of menopause was between 40-50 years of age.<br><br>CONCLUSION: This report is an important documentation of the pathological characteristics in a predominantly rural/semi urban population of Indian breast cancer patients. Further studies from other centers with a similar background are required to confirm these results.}, }
@article {pmid24759678, year = {2014}, author = {Ramos, CS and Gonçalves, AS and Marinho, LC and Gomes Avelino, MA and Saddi, VA and Lopes, AC and Simões, RT and Wastowski, IJ}, title = {Analysis of HLA-G gene polymorphism and protein expression in invasive breast ductal carcinoma.}, journal = {Human immunology}, volume = {75}, number = {7}, pages = {667-672}, doi = {10.1016/j.humimm.2014.04.005}, pmid = {24759678}, issn = {1879-1166}, mesh = {Alleles ; Breast Neoplasms/*genetics/immunology/mortality/pathology ; Carcinoma, Ductal, Breast/*genetics/immunology/mortality/pathology ; Case-Control Studies ; Female ; Gene Expression ; Gene Frequency ; HLA-G Antigens/*genetics/immunology ; Humans ; *INDEL Mutation ; Lymph Nodes/immunology/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Survival Analysis ; }, abstract = {The human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule predominantly expressed in trophoblastic placental cells to protect the fetus during pregnancy. However, evidence has shown that this molecule may be implicated in the immune escape mechanism of tumor cells. Thus, the aim of this study was to evaluate the frequency of 14-bp insertion/deletion HLA-G polymorphism, as well as the expression of this molecule in patients with invasive breast ductal carcinoma (IDC). A significant association between the expression of HLA-G and the presence of metastasis in lymph nodes (p=0.01) was observed and the expression of HLA-G was significantly higher in patients with shorter survival time (p=0.03). The analysis suggests that the polymorphism observed in patients with IDC may be inducing a higher expression of the HLA-G molecule, which may possibly contribute to shorter survival time and a worse clinical prognosis for such patients.}, }
@article {pmid24756760, year = {2014}, author = {Do, SI and Ko, E and Kang, SY and Lee, JE and Nam, SJ and Cho, EY and Kim, DH}, title = {Aberrant DNA methylation of integrin α4 in human breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {7}, pages = {7079-7084}, pmid = {24756760}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; CpG Islands/*genetics ; DNA Methylation/*genetics ; Female ; Humans ; Integrin alpha4/*genetics ; Lymphatic Metastasis ; MCF-7 Cells ; Middle Aged ; Neoplasm Staging ; Prognosis ; Promoter Regions, Genetic ; Receptor, ErbB-2/metabolism ; Signal Transduction ; }, abstract = {Integrins are cell surface receptors that mediate cell-cell/extracellular interactions and have shown an association with metastasis or transformation in several cancers. However, the correlation between the clinicopathological status of breast cancer and the altered integrin α4 status is not clear. In this study, we investigated DNA methylation of integrin α4 in breast cancer. We retrieved 351 cases of surgically resected breast cancer (290 invasive carcinoma and 61 intraductal carcinoma). Methylation-specific polymerase chain reaction was performed to determine integrin α4 methylation status. Integrin α4 methylation was frequently observed in breast cancer specimens (145/351 cases, 41.3 %). In addition, DNA methylation of integrin α4 showed statistical correlation with HER2 positivity and higher histologic grade (p = 0.001, 0.008 in ductal carcinoma in situ and 0.003 in invasive ductal carcinoma). However, other clinicopathological data such as estrogen receptor, progesterone receptor, metastasis, and TNM status showed no statistical correlation. Moreover, we found that the downregulated expression of integrin α4 in a heavily methylated breast cancer cell line (ZR-75) was restored by treatment with 5-aza-2'deoxycytidine, a DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. We observed that integrin α4 methylation is associated with the histologic grade of tumors and lymph node metastasis. Also, this data supports a previous study that suggested integrin α4 and HER2 are involved in the same signaling pathway. DNA methylation of integrin α4 may be a poor prognostic factor which affects undifferentiated histologic change of breast cancer.}, }
@article {pmid24748104, year = {2014}, author = {Ruan, X and Liu, H and Boardman, L and Kocher, JP}, title = {Genome-wide analysis of loss of heterozygosity in breast infiltrating ductal carcinoma distant normal tissue highlights arm specific enrichment and expansion across tumor stages.}, journal = {PloS one}, volume = {9}, number = {4}, pages = {e95783}, pmid = {24748104}, issn = {1932-6203}, support = {P30 CA015083/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Chromosome Fragile Sites ; Chromosome Mapping ; *Chromosomes, Human ; Female ; *Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; *Loss of Heterozygosity ; Neoplasm Staging ; }, abstract = {Studies have shown concurrent loss of heterozygosity (LOH) in breast infiltrating ductal carcinoma (IDC) and adjacent or distant normal tissue. However, the overall extent of LOH in normal tissue and their significance to tumorigenesis remain unknown, as existing studies are largely based on selected microsatellite markers. Here we present the first autosome-wide study of LOH in IDC and distant normal tissue using informative loci deduced from SNP array-based and sequencing-based techniques. We show a consistently high LOH concurrence rate in IDC (mean = 24%) and distant normal tissue (m = 54%), suggesting for most patients (31/33) histologically normal tissue contains genomic instability that can be a potential marker of increased IDC risk. Concurrent LOH is more frequent in fragile site related genes like WWOX (9/31), NTRK2 (10/31), and FHIT (7/31) than traditional genetic markers like BRCA1 (0/23), BRCA2 (2/29) and TP53 (1/13). Analysis at arm level shows distant normal tissue has low level but non-random enrichment of LOH (topped by 8p and 16q) significantly correlated with matched IDC (Pearson r = 0.66, p = 3.5E-6) (topped by 8p, 11q, 13q, 16q, 17p, and 17q). The arm-specific LOH enrichment was independently observed in tumor samples from 548 IDC patients when stratified by tumor size based T stages. Fine LOH structure from sequencing data indicates LOH in low order tissues non-randomly overlap (∼67%) with LOH that usually has longer tract length (the length of genomic region affected by LOH) in high order tissues. The consistent observations from multiple datasets suggest progressive LOH in the development of IDC potentially through arm-specific pile up effect with discernible signature in normal tissue. Our finding also suggests that LOH detected in IDC by comparing to paired adjacent or distant normal tissue are more likely underestimated.}, }
@article {pmid24744949, year = {2014}, author = {Santivasi, WL and Routt, MM and Terando, AM}, title = {Idiopathic thrombocytopenic purpura after mastectomy and axillary lymph node dissection.}, journal = {Case reports in surgery}, volume = {2014}, number = {}, pages = {316064}, pmid = {24744949}, issn = {2090-6900}, abstract = {First described in 1916, idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease resulting in the destruction of platelets. Here, we present a case of an 85-year-old patient diagnosed with invasive ductal carcinoma of the breast whose surgical treatment was complicated postoperatively by acute-onset thrombocytopenia with a resultant hematoma at the operative site. Diagnostic Workup revealed no clear etiology for the thrombocytopenia; therefore, a presumptive diagnosis of idiopathic thrombocytopenic purpura was made. Previous literature has associated the development of idiopathic thrombocytopenic purpura with breast cancer. However, to the authors' knowledge, there are no reported cases of ITP presenting immediately following surgical intervention for breast cancer in the absence of other etiologic factors.}, }
@article {pmid24743323, year = {2014}, author = {Sawyer, E and Roylance, R and Petridis, C and Brook, MN and Nowinski, S and Papouli, E and Fletcher, O and Pinder, S and Hanby, A and Kohut, K and Gorman, P and Caneppele, M and Peto, J and Dos Santos Silva, I and Johnson, N and Swann, R and Dwek, M and Perkins, KA and Gillett, C and Houlston, R and Ross, G and De Ieso, P and Southey, MC and Hopper, JL and Provenzano, E and Apicella, C and Wesseling, J and Cornelissen, S and Keeman, R and Fasching, PA and Jud, SM and Ekici, AB and Beckmann, MW and Kerin, MJ and Marme, F and Schneeweiss, A and Sohn, C and Burwinkel, B and Guénel, P and Truong, T and Laurent-Puig, P and Kerbrat, P and Bojesen, SE and Nordestgaard, BG and Nielsen, SF and Flyger, H and Milne, RL and Perez, JI and Menéndez, P and Benitez, J and Brenner, H and Dieffenbach, AK and Arndt, V and Stegmaier, C and Meindl, A and Lichtner, P and Schmutzler, RK and Lochmann, M and Brauch, H and Fischer, HP and Ko, YD and ,  and Nevanlinna, H and Muranen, TA and Aittomäki, K and Blomqvist, C and Bogdanova, NV and Dörk, T and Lindblom, A and Margolin, S and Mannermaa, A and Kataja, V and Kosma, VM and Hartikainen, JM and Chenevix-Trench, G and ,  and Lambrechts, D and Weltens, C and Van Limbergen, E and Hatse, S and Chang-Claude, J and Rudolph, A and Seibold, P and Flesch-Janys, D and Radice, P and Peterlongo, P and Bonanni, B and Volorio, S and Giles, GG and Severi, G and Baglietto, L and McLean, CA and Haiman, CA and Henderson, BE and Schumacher, F and Le Marchand, L and Simard, J and Goldberg, MS and Labrèche, F and Dumont, M and Kristensen, V and Winqvist, R and Pylkäs, K and Jukkola-Vuorinen, A and Kauppila, S and Andrulis, IL and Knight, JA and Glendon, G and Mulligan, AM and Devillee, P and Tollenaar, RA and Seynaeve, CM and Kriege, M and Figueroa, J and Chanock, SJ and Sherman, ME and Hooning, MJ and Hollestelle, A and van den Ouweland, AM and van Deurzen, CH and Li, J and Czene, K and Humphreys, K and Cox, A and Cross, SS and Reed, MW and Shah, M and Jakubowska, A and Lubinski, J and Jaworska-Bieniek, K and Durda, K and Swerdlow, A and Ashworth, A and Orr, N and Schoemaker, M and Couch, FJ and Hallberg, E and González-Neira, A and Pita, G and Alonso, MR and Tessier, DC and Vincent, D and Bacot, F and Bolla, MK and Wang, Q and Dennis, J and Michailidou, K and Dunning, AM and Hall, P and Easton, D and Pharoah, P and Schmidt, MK and Tomlinson, I and Garcia-Closas, M}, title = {Genetic predisposition to in situ and invasive lobular carcinoma of the breast.}, journal = {PLoS genetics}, volume = {10}, number = {4}, pages = {e1004285}, pmid = {24743323}, issn = {1553-7404}, support = {U01 CA69417/CA/NCI NIH HHS/United States ; UM1 CA164920/CA/NCI NIH HHS/United States ; U01 CA069467/CA/NCI NIH HHS/United States ; 2010NOVPR61/BCN_/Breast Cancer Now/United Kingdom ; R01 CA128978/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; 090532/WT_/Wellcome Trust/United Kingdom ; R01 CA132839/CA/NCI NIH HHS/United States ; 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; CA098758/CA/NCI NIH HHS/United States ; U01 CA069417/CA/NCI NIH HHS/United States ; CA54281/CA/NCI NIH HHS/United States ; U01 CA069638/CA/NCI NIH HHS/United States ; 10124/CRUK_/Cancer Research UK/United Kingdom ; CA63464/CA/NCI NIH HHS/United States ; C490/A10124/CRUK_/Cancer Research UK/United Kingdom ; C1287/A12014/CRUK_/Cancer Research UK/United Kingdom ; R01 CA063464/CA/NCI NIH HHS/United States ; R01 CA054281/CA/NCI NIH HHS/United States ; U01 CA69638/CA/NCI NIH HHS/United States ; U01 CA063464/CA/NCI NIH HHS/United States ; U01 CA098758/CA/NCI NIH HHS/United States ; CA132839/CA/NCI NIH HHS/United States ; C1287/A10118/CRUK_/Cancer Research UK/United Kingdom ; U01 CA69467/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Carcinoma in Situ/*genetics ; Carcinoma, Lobular/*genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.}, }
@article {pmid24743129, year = {2014}, author = {Gudadze, M and Kankava, Q and Mariamidze, A and Burkadze, G}, title = {Features of CD44+/CD24-low phenotypic cell distribution in relation to predictive markers and molecular subtypes of invasive ductal carcinoma of the breast.}, journal = {Georgian medical news}, volume = {}, number = {228}, pages = {81-87}, pmid = {24743129}, issn = {1512-0112}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/*pathology ; CD24 Antigen/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*pathology ; Female ; Humans ; Hyaluronan Receptors/*metabolism ; Middle Aged ; Neoplastic Stem Cells/metabolism/pathology ; Phenotype ; Prognosis ; Young Adult ; }, abstract = {Breast cancer is the most widespread pathology among women. Despite the current progresses in research and treatment of metastatic breast cancer, mortality caused by this disease is still high, because above mentioned therapy is limited due to existence of cells resistant to therapy . Cancer stem cells are the only cells with ability of unlimited proliferative activity and cancerous potential, thus, they participate in the growth, progression and dissemination of cancer. Cancer stem cells are resistant to various forms of therapy, including chemotherapy and radiotherapy . Results of examination showed that 50% of all cases are positive on so called markers of stem cells, thus 45% of cases are negative. CD44+/CD24-low cases (cases that reveal stem cell-phenotype) in the group of invasive ductal carcinoma of Luminal A molecular subtype are almost as many as CD44+/CD24+ and CD44-/CD24+ phenotype cancers. In this group non-stem phenotype cases are 65%, so 5 times more than stem cell phenotype cancers. 1324 postoperative breast materials studied through 2008-2012 at the laboratory of "Pathgeo-Union of Pathologists" LTD and Academician N. Kipshidze Central University Clinic were used as test materials and specimens from 393 patients with invasive ductal carcinoma were selected. CD44/CD24 markers' expression in phenotypically different cancers and clinic-pathologic parameters as well as various biological features was conducted by the Pearson's correlation analysis and using X2 test. Statistical analysis of obtained numeral data was held using SPSS V.19.0 program. Confidence interval of 95% was considered statistically significant. Stem cell phenotype positive cases are with the highest percentage represented in Luminal B and basal-like molecular subgroup that to our minds is associated with their aggressive behavior and resistance to chemotherapy. Relatively good prognosis and response to chemotherapy of Luminal A molecular subtype cancers are to be stipulated by lower percentage of cases with stem cells phenotype. With regard to the dimension of cancer the analysis of stem cell phenotype cancers showed that frequency of stem cell phenotype (CD44+/CD24-low) dramatically increases from T1 to T4 cancers. High density of stem cell phenotype cancers in cancers with metastatic lymphatic nodes proves that presence of mentioned phenotype plays a role in progression and dissemination. On the one hand, little amount of stem cells phenotype cancers (CD44+/CD24-low), on the other hand absence of negative cases for markers of stem cell in Her2 subtype makes us consider that come phenotype, close to stem-cell phenotype, plays the leading role in Her2 positive cases.}, }
@article {pmid24725754, year = {2014}, author = {Moccia, M and Picillo, M and Erro, R and Vitale, C and Longo, K and Amboni, M and Santangelo, G and Spina, E and De Rosa, A and De Michele, G and Santoro, L and Barone, P and Pellecchia, MT}, title = {Is serum uric acid related to non-motor symptoms in de-novo Parkinson's disease patients?.}, journal = {Parkinsonism &amp; related disorders}, volume = {20}, number = {7}, pages = {772-775}, doi = {10.1016/j.parkreldis.2014.03.016}, pmid = {24725754}, issn = {1873-5126}, mesh = {Adult ; Aged ; Biomarkers/blood ; Cardiovascular Diseases/blood/complications/diagnosis ; Cross-Sectional Studies ; Female ; Humans ; Male ; Mental Disorders/blood/complications/diagnosis ; Middle Aged ; Parkinson Disease/*blood/complications/*diagnosis ; Pilot Projects ; Uric Acid/*blood ; }, abstract = {BACKGROUND: Low serum uric acid (UA) has been consistently shown to be associated with increased risk of Parkinson's disease (PD), and to predict faster motor and cognitive decline in established PD. The aim of the present study is to evaluate the relationship between serum UA and non-motor symptoms (NMS) in de novo PD.<br><br>METHODS: Serum UA was measured in consecutively recruited, early drug-na&#xef;ve PD patients. Exclusion criteria were: treatment with UA modifying drugs; current smoking status; metabolic or cardiac morbidity. All patients completed the NMS Questionnaire (NMSQuest). The relationship between UA levels and NMSQuest domains was explored by logistic regression, subsequently adjusted for age, gender, disease duration (months since reported motor onset) UPDRS part III, H&amp;Y scale, and MMSE. Regression analysis studied the overall relationship between UA levels and total NMS score, and was subsequently adjusted for age, gender, disease duration UPDRS part III, H&amp;Y scale and MMSE.<br><br>RESULTS: Eighty PD patients were recruited. At logistic regression, higher UA levels were related to lower involvement of Attention/Memory (p = 0.004), Cardiovascular (0.009) and Sleep (p = 0.028) domains of NMSQuest. UA levels showed a significant negative correlation with total NMSQuest score at regression analysis (p = 0.001; Adjusted R-squared = 0.319).<br><br>DISCUSSION: The present study investigated, for the first time, the relationship between NMSQuest and UA in de novo PD. Lower UA was related to higher NMSQuest total score and in particular to Attention/Memory, Cardiovascular and Sleep domains. Thus, UA seems to be a major candidate to be a valuable biomarker of such early features of PD as NMS.}, }
@article {pmid24715382, year = {2014}, author = {McNamara, KM and Yoda, T and Nurani, AM and Shibahara, Y and Miki, Y and Wang, L and Nakamura, Y and Suzuki, K and Yang, Y and Abe, E and Hirakawa, H and Suzuki, T and Nemoto, N and Miyashita, M and Tamaki, K and Ishida, T and Brown, KA and Ohuchi, N and Sasano, H}, title = {Androgenic pathways in the progression of triple-negative breast carcinoma: a comparison between aggressive and non-aggressive subtypes.}, journal = {Breast cancer research and treatment}, volume = {145}, number = {2}, pages = {281-293}, doi = {10.1007/s10549-014-2942-6}, pmid = {24715382}, issn = {1573-7217}, mesh = {3-Hydroxysteroid Dehydrogenases/genetics/metabolism ; Aldo-Keto Reductase Family 1 Member C3 ; Androgens/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cholestenone 5 alpha-Reductase/genetics/metabolism ; Dihydrotestosterone/pharmacology ; ErbB Receptors/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hydroxyprostaglandin Dehydrogenases/genetics/metabolism ; Keratin-5/metabolism ; Keratin-6/metabolism ; Receptors, Androgen/metabolism ; Triple Negative Breast Neoplasms/drug therapy/*metabolism/*pathology ; }, abstract = {One of the active intracellular pathways/networks in triple-negative breast carcinoma (TNBC) is that of the androgen receptor (AR). In this study, we examined AR and androgen-metabolising enzyme immunoreactivity in subcategories of TNBC to further elucidate the roles of androgenic pathways in TNBC. We utilised formalin-fixed paraffin-embedded breast cancer samples from ductal carcinoma in situ (DCIS) and invasive ductal carcinoma patient cohorts. We then used immunohistochemistry to classify these samples into basal-like and non-basal samples and to assess interactions between AR, androgen-metabolising enzymes and proliferation. To further substantiate our hypothesis and provide mechanistic insights, we also looked at the expression and regulation of these factors in publically available microarray data and in a panel of TNBC AR-positive cell lines. DCIS was associated with higher levels of AR and enzymes (p < 0.02), although a similar difference was not noticed in basal and non-basal samples. AR and enzymes were correlated in all states. In TNBC cell lines (MDA-MD-453, MFM-223 and SUM185-PE), we found that DHT treatment up-regulated 5αR1 and 17βHSD5 suggesting a mechanistic explanation for the correlations observed in the histological samples. Publicly available microarray data in TNBC cases suggested similar patterns to those observed in histological samples. In the majority of settings, including publically available microarray data, an inverse association between AR and proliferation was detected. These findings suggest that decreases in AR and androgen-metabolising enzymes may be involved in the increased biological aggressiveness in TNBC development.}, }
@article {pmid24713490, year = {2014}, author = {Ruiz Santiago, F and Pozuelo Calvo, R and Almansa López, J and Guzmán Álvarez, L and Castellano García, MDM}, title = {T2 mapping in patellar chondromalacia.}, journal = {European journal of radiology}, volume = {83}, number = {6}, pages = {984-988}, doi = {10.1016/j.ejrad.2014.03.007}, pmid = {24713490}, issn = {1872-7727}, mesh = {Adolescent ; Adult ; *Algorithms ; Arthralgia/*diagnosis/*etiology ; Chondromalacia Patellae/*complications/*pathology ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Young Adult ; }, abstract = {OBJECTIVE: To study the correlation between the T2 relaxation times of the patellar cartilage and morphological MRI findings of chondromalacia.<br><br>METHODS: This prospective study comprises 50 patients, 27 men and 23 women suffering of anterior knee pain (mean age: 29.7, SD 8.3 years; range: 16-45 years). MRI of 97 knees were performed in these patients at 1.5T magnet including sagittal T1, coronal intermediate, axial intermediate fat sat and T2 mapping. Chondromalacia was assessed using a modified version of Noyes classification. The relaxation time, T2, was studied segmenting the full thickness of the patellar cartilage in 12 areas: 4 proximal (external facet-proximal-lateral (EPL), external facet-proximal-central (EPC), internal facet-proximal-central (IPC), internal facet-proximal-medial (IPM), 4 in the middle section (external facet-middle-lateral (EML), external facet-middle-central (EMC), internal facet-middle-central (IMC), internal facet-middle-medial (IMM) and 4 distal (external facet-distal-lateral (EDL), external facet-distal-central (EDC), internal facet-distal-central (IDC), internal facet-distal-medial (IDM).<br><br>RESULTS: T2 values showed a significant increase in mild chondromalacia regarding normal cartilage in most of the cartilage areas (p<0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM. Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistical significant differences in comparison with normal cartilage, except in EMC and IMC, where similar values as mild chondromalacia were maintained (p<0.05).<br><br>CONCLUSIONS: Steepest increase in T2 values of patellar cartilage occurs in early stages of patellar cartilage degeneration. Progression of morphologic changes of chondromalacia to more severe degrees is associated to a new drop of T2 relaxation times approaching basal values in most of the areas of the patellar cartilage, except in the central area of the middle section, where T2 values remain increased.}, }
@article {pmid24708527, year = {2014}, author = {Schoellhammer, HF and Hsu, F and Vito, C and Chu, P and Park, J and Waisman, J and Kim, J}, title = {Complete pathologic response of HER2-positive breast cancer liver metastasis with dual anti-HER2 antagonism.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {242}, pmid = {24708527}, issn = {1471-2407}, mesh = {Antibodies, Monoclonal, Humanized/*administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage ; Breast Neoplasms/*drug therapy/genetics/pathology ; Clinical Trials as Topic ; Female ; Humans ; Liver Neoplasms/*drug therapy/pathology/secondary ; Middle Aged ; Molecular Targeted Therapy ; Receptor, ErbB-2/antagonists &amp; inhibitors/*genetics ; Trastuzumab ; }, abstract = {BACKGROUND: Although breast cancer frequently metastasizes to the bones and brain, rarely breast cancer patients may develop isolated liver metastasis. There is increasing data that anti-HER2 targeted therapy in conjunction with systemic chemotherapy may lead to increased rates of pathologic complete response in the primary breast cancer. However, little is known about its effects on metastatic liver disease.<br><br>CASE PRESENTATION: We report the treatment of a 54-year-old female who was diagnosed with HER2-positive invasive ductal carcinoma and synchronous breast cancer liver metastasis (BCLM). The patient underwent eight cycles of standard docetaxel with two anti-HER2 targeted agents, trastuzumab and pertuzumab. Subsequent radiographic imaging demonstrated complete radiographic response in the primary lesion with an approximate 75% decrease in the liver metastasis. After informed consent the patient underwent modified radical mastectomy that revealed pathologic complete response. Re-staging demonstrated no new disease outside the liver and a left hepatectomy was performed for resection of BCLM. Final pathologic examination revealed no residual malignant cells in the liver specimen, indicating pathologic complete response. Herein, we discuss the anti-HER2 targeted agents trastuzumab and pertuzumab and review the data on dual HER2 antagonism for HER2-positive breast cancer and the role of surgical resection of BCLM.<br><br>CONCLUSIONS: The role of targeted agents for metastatic HER2-positive breast cancer is under active clinical trial investigation and we await the maturation of trial results and long-term survival data. Our results suggest that these agents may also be effective for producing considerable pathologic response in patients with BCLM.}, }
@article {pmid24687377, year = {2014}, author = {Yang, F and Zhou, X and Miao, X and Zhang, T and Hang, X and Tie, R and Liu, N and Tian, F and Wang, F and Yuan, J}, title = {MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis.}, journal = {Breast cancer research and treatment}, volume = {145}, number = {1}, pages = {23-32}, pmid = {24687377}, issn = {1573-7217}, mesh = {Adult ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/analysis ; Blotting, Western ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Epithelial-Mesenchymal Transition/physiology ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Metastasis ; Neoplasm Proteins/*metabolism ; Prognosis ; Risk Factors ; Tissue Array Analysis ; }, abstract = {MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.}, }
@article {pmid24655736, year = {2014}, author = {Moccia, M and Picillo, M and Erro, R and Vitale, C and Amboni, M and Palladino, R and Cioffi, DL and Barone, P and Pellecchia, MT}, title = {How does smoking affect olfaction in Parkinson's disease?.}, journal = {Journal of the neurological sciences}, volume = {340}, number = {1-2}, pages = {215-217}, doi = {10.1016/j.jns.2014.02.018}, pmid = {24655736}, issn = {1878-5883}, mesh = {Aged ; Analysis of Variance ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Olfaction Disorders/*etiology ; Parkinson Disease/*complications ; Severity of Illness Index ; *Smoking ; }, abstract = {Smoke-induced upper airway damage and Parkinson's disease (PD) can be considered independent risk factors for smell impairment. Interestingly, cigarette smoking has been strongly associated with reduced risk of PD and, therefore, has been suggested to have neuroprotective effects. Our pilot study aimed to evaluate the relationship between smoking and olfaction in PD patients and matched controls. Sixty-eight PD patients and 61 healthy controls were categorized in relation to PD diagnosis and current smoking status, and evaluated by means of the Italian version of the University of Pennsylvania 40-item Smell Identification Test (UPSIT-40). ANOVA analysis with post-hoc Bonferroni correction showed that non-smoker controls presented a higher UPSIT-40 total score than smoker controls (p<0.001), non-smoker PD patients (p<0.001) and smoker PD patients (p<0.001). In this view, smoking seems to affect olfaction in controls but not in PD patients, and no significant differences were found when comparing smoker controls, smoker PD patients and non-smoker PD patients. Several epidemiological studies showed a negative effect of smoking on olfaction in the general population. Otherwise the sense of smell is similar in smoker and non-smoker PD patients. These results suggest that PD and smoking are not independent risk factors for impairment of sense of smell, but they might variably interact.}, }
@article {pmid24654594, year = {2014}, author = {Son, CH and Bae, JH and Shin, DY and Lee, HR and Yang, K and Park, YS}, title = {Antitumor effect of dendritic cell loaded ex vivo and in vivo with tumor-associated antigens in lung cancer model.}, journal = {Immunological investigations}, volume = {43}, number = {5}, pages = {447-462}, doi = {10.3109/08820139.2014.884576}, pmid = {24654594}, issn = {1532-4311}, mesh = {Animals ; Antigens, Neoplasm/*immunology ; Cancer Vaccines/administration &amp; dosage/*immunology ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; Injections, Intralesional ; Injections, Subcutaneous ; Interferon-gamma/biosynthesis ; Lung Neoplasms/*immunology/mortality/therapy ; Male ; Mice ; T-Cell Antigen Receptor Specificity/immunology ; T-Lymphocyte Subsets/immunology/metabolism ; }, abstract = {Various ex vivo or in vivo loading protocols have been developed or evaluated for the delivery of tumor antigens to dendritic cells (DCs). We compared the antitumor effect of mature DCs electroporation-pulsed (EP/mDC) ex vivo with tumor cell lysate and immature DCs (iDCs) injected into the tumor apoptosed by ionizing radiation (IR/iDC) in lung cancer model. DCs were generated from bone marrow of C57BL/6 mice. Ionizing radiation (IR) was applied at a dose of 10 Gy to the tumor on the right thigh. iDCs were intratumorally injected into the irradiated tumor and EP/mDC was injected subcutaneously in the right flank. DC injection induced strong tumor-specific immunity against Lewis lung carcinoma, as compared with the tumor-bearing control and IR only treated mice. The growth of a distant tumor on the right and left flank was inhibited by IR/iDC and EP/mDC. Particularly, IR/iDC resulted in a more significant inhibition of tumor growth and prolonged survival time. It was related to increase of tumor-specific interferon-gamma, cytotoxicity, and decrease of regulatory T-cells. The results indicate that DCs electroporation-pulsed with tumor cell lysate induce a potent antitumor effect, but that iDCs intratumoral injected into the irradiated tumor induce a more potent antitumor effect.}, }
@article {pmid24652232, year = {2014}, author = {Yoon, HJ and Kang, KW and Chun, IK and Cho, N and Im, SA and Jeong, S and Lee, S and Jung, KC and Lee, YS and Jeong, JM and Lee, DS and Chung, JK and Moon, WK}, title = {Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from [68]Ga-RGD PET/CT and [18]F-FDG PET/CT.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {41}, number = {8}, pages = {1534-1543}, pmid = {24652232}, issn = {1619-7089}, mesh = {Adult ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*diagnosis/diagnostic imaging/genetics ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/genetics ; Coordination Complexes ; Female ; Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; Multimodal Imaging ; Oligopeptides ; *Positron-Emission Tomography ; Radiopharmaceuticals ; Receptor, ErbB-2/*genetics/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Receptors, Progesterone/*genetics/metabolism ; Tomography, X-Ray Computed ; }, abstract = {PURPOSE: Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes.<br><br>METHODS: In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6&#x2009;&#xb1;&#x2009;7.5&#xa0;years old). (68)Ga-Labeled arginine-glycine-aspartic acid (RGD) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUVmax and SUVavg) from RGD PET/CT and SUVmax and SUVavg from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2-, ER/PR+,Her2+, ER/PR-,Her2+, and ER/PR-,Her2-), were considered.<br><br>RESULTS: Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88&#x2009;&#xb1;&#x2009;8.73 vs 10.48&#x2009;&#xb1;&#x2009;6.01, p&#x2009;=&#x2009;0.02 for SUVmax; 9.40&#x2009;&#xb1;&#x2009;5.19 vs 5.92&#x2009;&#xb1;&#x2009;4.09, p&#x2009;=&#x2009;0.02 for SUVavg) and the PR-negative group (8.37&#x2009;&#xb1;&#x2009;4.94 vs 4.79&#x2009;&#xb1;&#x2009;3.93, p&#x2009;=&#x2009;0.03 for SUVavg). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42&#x2009;&#xb1;&#x2009;0.59 vs 2.90&#x2009;&#xb1;&#x2009;0.75, p&#x2009;=&#x2009;0.04 for SUVmax; 1.60&#x2009;&#xb1;&#x2009;0.38 vs 1.95&#x2009;&#xb1;&#x2009;0.53, p&#x2009;=&#x2009;0.04 for SUVavg) and showed a significant positive correlation with the HER2/CEP17 ratio (r&#x2009;=&#x2009;0.38, p&#x2009;=&#x2009;0.03 for SUVmax and r&#x2009;=&#x2009;0.46, p&#x2009;<&#x2009;0.01 for SUVavg). FDG PET parameters showed significantly higher values in the ER/PR-,Her2- subgroup versus the ER/PR+,Her2- or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER/PR-,Her2- subgroup versus the other subgroups. There was no correlation between FDG and RGD PET parameters in the overall group. Only the ER/PR-,Her2- subgroup showed a significant positive correlation between FDG and RGD PET parameters (r&#x2009;=&#x2009;0.59, p&#x2009;=&#x2009;0.03 for SUVmax).<br><br>CONCLUSION: (68)Ga-RGD and (18)F-FDG PET/CT are promising functional imaging modalities for predicting biomarkers and molecular phenotypes in breast cancer patients.}, }
@article {pmid24648320, year = {2015}, author = {Nakiwogga-Muwanga, A and Musaazi, J and Katabira, E and Worodria, W and Talisuna, SA and Colebunders, R}, title = {Patients who return to care after tracking remain at high risk of attrition: experience from a large HIV clinic, Uganda.}, journal = {International journal of STD &amp; AIDS}, volume = {26}, number = {1}, pages = {42-47}, doi = {10.1177/0956462414529098}, pmid = {24648320}, issn = {1758-1052}, mesh = {Adult ; Ambulatory Care Facilities ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Appointments and Schedules ; CD4 Lymphocyte Count ; Continuity of Patient Care/*organization &amp; administration ; Female ; Follow-Up Studies ; HIV Infections/*drug therapy/psychology ; Humans ; *Lost to Follow-Up ; Male ; Middle Aged ; Patient Compliance/psychology/*statistics &amp; numerical data ; Patient Dropouts/psychology/*statistics &amp; numerical data ; Socioeconomic Factors ; Time Factors ; Treatment Outcome ; Treatment Refusal ; }, abstract = {We determined the retention rate of patients infected with HIV who resumed care after being tracked at the Infectious Diseases Clinic (IDC) in Kampala, Uganda. Between April 2011 and September 2013, patients who missed their clinic appointment for 8-90 days were tracked, and those who returned to the clinic within 120 days were followed up. The proportion of patients retained among tracked patients, and those who resumed care before tracking started was compared. At 18 months of follow up, 33 (39%) of the tracked patients and 72 (61%) of those who had resumed care before tracking started were retained in care. The most important cause of attrition among the traceable was self-transfer to another clinic (38 [73%] patients), whereas among those who resumed care before tracking was loss to follow up (LTFU) (32 [71%] patients). Tracked patients who resume care following a missed appointment are at high risk of attrition. To increase retention, antiretroviral therapy clinics need to adopt a chronic care model which takes into consideration patients' changing needs and their preference for self-management.}, }
@article {pmid24628533, year = {2014}, author = {Aiad, HA and Wahed, MM and Asaad, NY and El-Tahmody, M and Elhosary, E}, title = {Immunohistochemical expression of GPR30 in breast carcinoma of Egyptian patients: an association with immunohistochemical subtypes.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {122}, number = {10}, pages = {976-984}, doi = {10.1111/apm.12241}, pmid = {24628533}, issn = {1600-0463}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/*pathology ; Egypt ; Female ; Humans ; Immunohistochemistry/methods ; Lymph Nodes/pathology ; Middle Aged ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/*genetics ; Receptors, G-Protein-Coupled/*genetics ; Retrospective Studies ; }, abstract = {Breast carcinoma in Egyptian women is a biologically more aggressive disease than those diagnosed in Western women, although a substantial number of cases are hormone responsive. G protein-coupled receptor-30 (GPR30), a seven transmembrane domain protein, is currently recognized as an estrogen receptor. This study aimed at evaluating the expression of GPR30 in breast carcinomas of Egyptian patients and its association with clinicopathologic parameters and immunohistochemical subtypes of breast carcinoma. Immunohistochemical staining for GPR30 was applied on 51 archival formalin-fixed paraffin-embedded cases of invasive ductal carcinoma. Staining was assessed using a semiquantitative scoring system taking staining intensity and extent into consideration. GPR30 was observed in 33/51 (65%) of invasive ductal carcinoma cases. GPR30 was significantly associated with larger tumor size (p = 0.009), increased number of positive lymph nodes (p = 0.04), definite lymph-vascular invasion (LVI) (p = 0.002), peri-nodal invasion (p = 0.02), and the presence of coagulative tumor cell necrosis (p = 0.02). Moreover, a significant association between positive GPR30 expression and ER positivity (p = 0.02), as well as HER2/neu positivity (p = 0.03), were also observed. Most of the luminal A and B subtypes were GPR30 positive; however, all the triple negative cases were GPR30 negative (p = 0.010). GPR30 might contribute to the aggressive behavior of Egyptian breast carcinoma. Therefore, it could be useful in the therapeutic decision making in breast cancer patients.}, }
@article {pmid24623017, year = {2014}, author = {Feldman, AM and Begay, RL and Knezevic, T and Myers, VD and Slavov, DB and Zhu, W and Gowan, K and Graw, SL and Jones, KL and Tilley, DG and Coleman, RC and Walinsky, P and Cheung, JY and Mestroni, L and Khalili, K and Taylor, MR}, title = {Decreased levels of BAG3 in a family with a rare variant and in idiopathic dilated cardiomyopathy.}, journal = {Journal of cellular physiology}, volume = {229}, number = {11}, pages = {1697-1702}, pmid = {24623017}, issn = {1097-4652}, support = {R01 HL147064/HL/NHLBI NIH HHS/United States ; R01 HL109209/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; 1R01HL109209-01A1/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01 HL116906/HL/NHLBI NIH HHS/United States ; P01 HL091799/HL/NHLBI NIH HHS/United States ; R01 HL123093/HL/NHLBI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Apoptosis Regulatory Proteins/*genetics/metabolism ; Base Sequence ; Cardiomyopathy, Dilated/*genetics ; Family ; Female ; Heart Failure/genetics ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation/*genetics ; Pedigree ; Phenotype ; RNA, Messenger/genetics/metabolism ; Sequence Deletion ; }, abstract = {The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole-exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10-nucleotide deletion in the BCL2-associated athanogene 3 (BAG3) gene (Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C-terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end-stage HF undergoing cardiac transplantation when compared with non-failing controls. Diminished levels of BAG3 protein may be associated with both familial and non-familial forms of dilated cardiomyopathy.}, }
@article {pmid24621503, year = {2014}, author = {Mercier, I and Gonzales, DM and Quann, K and Pestell, TG and Molchansky, A and Sotgia, F and Hulit, J and Gandara, R and Wang, C and Pestell, RG and Lisanti, MP and Jasmin, JF}, title = {CAPER, a novel regulator of human breast cancer progression.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {13}, number = {8}, pages = {1256-1264}, pmid = {24621503}, issn = {1551-4005}, mesh = {Animals ; Breast Neoplasms/*metabolism/pathology ; Cell Cycle Checkpoints ; Cell Proliferation ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; MCF-7 Cells ; Mice, Nude ; Neoplasm Transplantation ; Nuclear Proteins/genetics/*metabolism ; Phosphorylation ; Proliferating Cell Nuclear Antigen/metabolism ; Protein Biosynthesis ; Proto-Oncogene Proteins c-jun/metabolism ; RNA, Small Interfering/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; }, abstract = {CAPER is an estrogen receptor (ER) co-activator that was recently shown to be involved in human breast cancer pathogenesis. Indeed, we reported increased expression of CAPER in human breast cancer specimens. We demonstrated that CAPER was undetectable or expressed at relatively low levels in normal breast tissue and assumed a cytoplasmic distribution. In contrast, CAPER was expressed at higher levels in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specimens, where it assumed a predominantly nuclear distribution. However, the functional role of CAPER in human breast cancer initiation and progression remained unknown. Here, we used a lentiviral-mediated gene silencing approach to reduce the expression of CAPER in the ER-positive human breast cancer cell line MCF-7. The proliferation and tumorigenicity of MCF-7 cells stably expressing control or human CAPER shRNAs was then determined via both in vitro and in vivo experiments. Knockdown of CAPER expression significantly reduced the proliferation of MCF-7 cells in vitro. Importantly, nude mice injected with MCF-7 cells harboring CAPER shRNAs developed smaller tumors than mice injected with MCF-7 cells harboring control shRNAs. Mechanistically, tumors derived from mice injected with MCF-7 cells harboring CAPER shRNAs displayed reduced expression of the cell cycle regulators PCNA, MCM7, and cyclin D1, and the protein synthesis marker 4EBP1. In conclusion, knockdown of CAPER expression markedly reduced human breast cancer cell proliferation in both in vitro and in vivo settings. Mechanistically, knockdown of CAPER abrogated the activity of proliferative and protein synthesis pathways.}, }
@article {pmid24621330, year = {2014}, author = {Lim, ST and Yu, JH and Park, HK and Moon, BI and Ko, BK and Suh, YJ}, title = {A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {56}, pmid = {24621330}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/mortality/*secondary/therapy ; Carcinoma, Lobular/epidemiology/mortality/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Republic of Korea/epidemiology ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: To investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma (ILC) patients compared to invasive ductal carcinoma (IDC) patients according to their molecular subtype.<br><br>METHODS: We compared the clinicopathological characteristics, breast cancer-specific survival (BCSS) and overall survival (OS) between patients with IDC (n&#x2009;=&#x2009;14,547) and ILC (n&#x2009;=&#x2009;528).<br><br>RESULTS: The ILC presented with a larger tumor size, more advanced cancer stage, increased rate of hormonal receptor positivity, human epidermal growth factor 2 (HER2) negativity and mastectomy than the IDC. The ILC patients more frequently presented with the luminal A subtype, whereas the IDC patients more frequently presented with the luminal B, HER2-overexpression, or triple negative subtype. The BCSS and OS were not significantly different between the IDC and ILC for each molecular subtype.<br><br>CONCLUSIONS: Similar to IDC patients, molecular subtype should be considered when determining the prognosis and treatment regimen for ILC patients.}, }
@article {pmid24609797, year = {2015}, author = {Caliskan, M and Gullu, H and Erdogan, D and Ozulku, M and Kulaksızoglu, S and Ciftci, O and Muderrisoglu, H}, title = {Association between serum total antioxidant status and coronary microvascular function in idiopathic dilated cardiomyopathy.}, journal = {Herz}, volume = {40}, number = {3}, pages = {487-494}, pmid = {24609797}, issn = {1615-6692}, mesh = {Adolescent ; Adult ; Aged ; Antioxidants/*analysis ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/*complications/diagnosis ; Coronary Artery Disease/*blood/*complications/diagnosis ; Cytokines/*blood ; Female ; Humans ; Male ; Microvessels/diagnostic imaging ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Ultrasonography ; Young Adult ; }, abstract = {BACKGROUND: Coronary microvascular impairment may cause myocardial ischemia and systolic dysfunction in patients with idiopathic dilated cardiomyopathy (IDC).<br><br>PATIENTS AND METHODS: The study included 41 patients with IDC and 33 healthy control subjects. Serum total antioxidant status (TAS), serum interleukin (IL)-6 levels, and tumor necrosis factor (TNF)-&#x3b1; levels were assayed and coronary flow reserve (CFR) was measured in all subjects via echocardiography.<br><br>RESULTS: High-sensitivity C-reactive protein (hsCRP) levels were significantly higher in patients with IDC than in the control group (3.42&#x2009;&#xb1;&#x2009;2.14 vs. 1.91&#xb1;&#x2009;1.40, p&#x2009;=&#x2009;0.001). Serum TAS was statistically lower in patients with IDC than in controls (1.23&#x2009;&#xb1;&#x2009;0.16 vs. 1.77&#x2009;&#xb1;&#x2009;0.12, p&#x2009;<&#x2009;0.001). CFR was statistically and significantly lower in the IDC group (2.10&#x2009;&#xb1;&#x2009;0.39 vs. 3.09&#x2009;&#xb1;&#x2009;0.49, p&#x2009;<&#x2009;0.001). The IDC group was subsequently subdivided into two groups according to CFR values, as CFR &#x2265;&#x2009;2 and CFR <&#x2009;2. HsCRP (4.30&#x2009;&#xb1;&#x2009;2.42 vs. 2.58&#x2009;&#xb1;&#x2009;1.42, p&#x2009;=&#x2009;0.01), TNF-&#x3b1; (16.67&#x2009;&#xb1;&#x2009;8.08 vs. 10.97&#x2009;&#xb1;&#x2009;1.63, p&#x2009;=&#x2009;0.01), and IL-6 (7.54&#x2009;&#xb1;&#x2009;6.16 vs. 3.14&#x2009;&#xb1;&#x2009;1.10, p&#x2009;=&#x2009;0.05) values were significantly higher in the CFR <&#x2009;2 group compared with the higher CFR group. TAS (1.3&#x2009;&#xb1;&#x2009;0.16 vs. 1.14&#x2009;&#xb1;&#x2009;0.10, p&#x2009;<&#x2009;0.001) was significantly lower in the CFR <&#x2009;2 group. CFR correlated significantly with hsCRP, TAS, red cell distribution width (RDW), IL-6, and TNF-&#x3b1;.<br><br>CONCLUSION: Plasma proinflammatory cytokine levels are increased in patients with IDC. CFR was impaired as a reflection of impaired coronary microvascular dysfunction in association with increasing plasma proinflammatory cytokine levels and hsCRP levels.}, }
@article {pmid24605219, year = {2014}, author = {Demirhan, O and Ordu, C and Toker, A}, title = {Prolonged pleural catheters in the management of pleural effusions due to breast cancer.}, journal = {Journal of thoracic disease}, volume = {6}, number = {2}, pages = {74-78}, pmid = {24605219}, issn = {2072-1439}, abstract = {BACKGROUND: Breast cancer is the second most common etiologic cause in malignant pleural effusions (MPE). The aim of this study was to investigate the efficacy of long term pleural catheters in inducing self sclerosis in pleural effusions of breast cancer patients.<br><br>METHODS: In this study, 26 patients with breast cancer relapleural effusions that occurred between January 2011 and July 2013, who were considered not to undergo any other treatments and managed with prolonged pleural catheters (Jackson-Pratt silicone flat drain), were retrospectively analyzed. Thirty pleural catheters were inserted in 26 patients. All patients were female, mean age was 52 (range, 37-66) years old. Drainage over 1,500 mL per day was not allowed in order to avoid a lung edema. The catheters were removed in patients who had restoration of lung expansion and drainage under 50 mL/day.<br><br>RESULTS: The histologic subtypes in pleural effusions were invasive ductal carcinoma in 18 patients, ductal carcinoma in situ in 4, invasive lobular carcinoma in 2, tubular carcinoma in 1, and medullary carcinoma in 1. Three of the 26 patients underwent bilateral catheter insertion, and one patient underwent a reinsertion of the catheter into the same hemithorax due to a recurrence. The catheters were retained for a mean period of 18 days (range, 11-38 days). In one patient with invasive ductal carcinoma and paramalignant pleural effusion (PMPE) (3.8%), a recurrent pleural effusion was seen 34 days after removal of the catheter. There were no complications. One patient died while the catheter was in place.<br><br>CONCLUSIONS: Prolonged catheters for the management of pleural effusions in selected patients have become more popular than other treatment alternatives due to a shorter length of stay and lower costs. We recommend the use of Jackson Pratt (JP) silicone flat drains which in our opinion provide effective pleurodesis in addition to easy application in recurrent effusions caused by breast cancer.}, }
@article {pmid24603690, year = {2014}, author = {Yin, J and Liu, Z and Li, H and Sun, J and Chang, X and Liu, J and He, S and Li, B}, title = {Association of PKCζ expression with clinicopathological characteristics of breast cancer.}, journal = {PloS one}, volume = {9}, number = {6}, pages = {e90811}, pmid = {24603690}, issn = {1932-6203}, mesh = {Adult ; Breast Neoplasms/*enzymology/mortality/pathology ; Carcinoma, Ductal, Breast/*enzymology/mortality/secondary ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Isoenzymes/*metabolism ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Protein Kinase C/*metabolism ; Receptor, ErbB-2/metabolism ; }, abstract = {The protein kinase C (PKC) family has been functionally linked to cancer. It has been suggested that atypical PKCs contribute to cell proliferation and cancer progression. With respect to breast cancer, PKCζ has been found to play a key role in intracellular transduction of mitogenic and apoptotic signals using mammary cell lines. However, little is known about its function in vivo. Here we examined the correlation between PKCζ protein levels and important clinicopathologic factors in breast cancer using patient samples. To conduct the study, 30 invasive ductal carcinoma cases and their paired normal tissues were used for tissue microarray analysis (TMA) and 16 were used for western blot analysis. In addition, the correlation between PKCζ expression levels and clinicopathologic characteristics was determined in 176 cases with relevant clinical data. Finally, the correlation between PKCζ and epithelial growth factor receptor 2 (HER2) expressions was determined using three breast cancer cell lines by western blot analysis. Both TMA and western blot results showed that PKCζ protein was highly expressed in primary tumors but not in paired normal tissue. The correlation study indicated that high PKCζ levels were associated with premenopausal patients (p = 0.019) and worse prognostic factors, such as advanced clinical stage, more lymph node involvement and larger tumor size. Both disease-free survival and overall survival rates were lower in the high PKCζ group than those in the low PKCζ group. No correlation was observed between PKCζ levels and age, histological grade, or estrogen or progesterone receptor expression status. A positive correlation between PKCζ and HER2 levels was observed in both tumor samples and cell lines. Our observations link PKCζ expression with factors pointing to worse prognosis, higher HER2 levels and a lower survival rate. This suggests that PKCζ protein levels may serve as a prognostic marker of breast cancer.}, }
@article {pmid24596383, year = {2014}, author = {Merdad, A and Karim, S and Schulten, HJ and Dallol, A and Buhmeida, A and Al-Thubaity, F and Gari, MA and Chaudhary, AG and Abuzenadah, AM and Al-Qahtani, MH}, title = {Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis.}, journal = {Anticancer research}, volume = {34}, number = {3}, pages = {1355-1366}, pmid = {24596383}, issn = {1791-7530}, mesh = {Animals ; Apoptosis/*drug effects ; Biomarkers, Tumor/*genetics/metabolism ; Blotting, Western ; Breast Neoplasms/drug therapy/*enzymology/pathology ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Immunoenzyme Techniques ; Matrix Metalloproteinases/*metabolism ; Mitochondria/drug effects/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; Quinuclidines/pharmacology ; RNA, Messenger/genetics ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; beta Catenin/genetics/metabolism ; }, abstract = {BACKGROUND/AIM: Breast cancer (BC) is the most common type of cancer in Saudi women. Matrix metalloproteinases (MMPs) are endopeptidases with the ability to degrade extracellular matrix proteins. In healthy individual tissue disruption is prevented by precised regulation of MMPs; however, in cancer a number of MMPs are overexpressed causing tissue disruption and making tumor cells capable of invasion and metastasis. Invasive ductal carcinoma (IDC) of BCs are classified into grade 1 (G1), grade 2 (G2) and grade 3 (G3) tumors.<br><br>MATERIALS AND METHODS: We performed a transcriptomic profiling of 38 surgically-resected breast tumors (4 G1, 17 G2 and 17 G3) using Affymetrix Gene 1.0 ST microarrays. Differentially expressed genes for each grade were identified by the Partek Genomic Suite 6.4 and expression analysis results were validated by immunohistochemistry at the protein level. Pathway analyses and establishment of clinical significance of findings were performed using the appropriate software.<br><br>RESULTS: We identified 1,593 differentially expressed genes in BC grades in comparison to normal samples using a cut-off of p<0.05 and fold change >2. Out of these genes 429 were expressed throughout in all grades along with tumor progression while many others associated with specific grades (440 genes in G1, 203 in G2 and 394 in G3 only) were exclusively. Microarray results indicate that mRNA expression of MMP-1, -9,-11,-12, and -13 were up-regulated in higher BC grades when compared to normal breast tissues. MMP-9 was expressed in most IDC (97.5%) samples and was highly expressed in 55% of the tumors. Differential expression of MMP-9 significantly correlated with histological BC grades of (p=0.03) and strongly correlated with overall survival (p=0.08).<br><br>CONCLUSION: Gene expression signatures are unique for specific grades. Overexpression of MMPs in higher grades might be associated with BC tumor invasion and metastasis. Therefore, MMPs, and MMP-9 in particular, are reliable candidates for diagnostic biomarker and drug target and further functional analyses have to be performed in order to confirm their role in BC. Our results also suggest the incidence of MMP-9 expression is high in IDC, but it is of limited prognostic value.}, }
@article {pmid24586742, year = {2014}, author = {Hung, MH and Liu, CY and Shiau, CY and Hsu, CY and Tsai, YF and Wang, YL and Tai, LC and King, KL and Chao, TC and Chiu, JH and Su, CH and Lo, SS and Tzeng, CH and Shyr, YM and Tseng, LM}, title = {Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.}, journal = {PloS one}, volume = {9}, number = {2}, pages = {e89389}, pmid = {24586742}, issn = {1932-6203}, mesh = {Adult ; Age Factors ; Brain/pathology ; Brain Neoplasms/metabolism/*pathology/*secondary ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk ; Triple Negative Breast Neoplasms/metabolism/*pathology ; }, abstract = {BACKGROUND: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.<br><br>PATIENTS AND METHODS: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis.<br><br>RESULTS: Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P&#x200a;=&#x200a;0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years.<br><br>CONCLUSIONS: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.}, }
@article {pmid24585434, year = {2014}, author = {Endo, M and Yamamoto, Y and Nakano, M and Masuda, T and Odagiri, H and Horiguchi, H and Miyata, K and Kadomatsu, T and Motokawa, I and Okada, S and Iwase, H and Oike, Y}, title = {Serum ANGPTL2 levels reflect clinical features of breast cancer patients: implications for the pathogenesis of breast cancer metastasis.}, journal = {The International journal of biological markers}, volume = {29}, number = {3}, pages = {e239-45}, doi = {10.5301/jbm.5000080}, pmid = {24585434}, issn = {1724-6008}, mesh = {Adult ; Aged ; Aged, 80 and over ; Angiopoietin-Like Protein 2 ; Angiopoietin-like Proteins ; Angiopoietins/*blood ; Animals ; Breast Neoplasms/*blood/*pathology ; Carcinoma, Ductal, Breast/*blood/*pathology ; Case-Control Studies ; Cell Line, Tumor ; Cell Proliferation/physiology ; Disease Progression ; Female ; Heterografts ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasm Metastasis ; Triple Negative Breast Neoplasms/*blood/*pathology ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression.<br><br>METHODS: We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients.<br><br>RESULTS: Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades.<br><br>CONCLUSIONS: These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.}, }
@article {pmid24581736, year = {2014}, author = {Wei, S and Bleiweiss, IJ and Nagi, C and Jaffer, S}, title = {Characteristics of breast carcinoma cases with false-negative sentinel lymph nodes.}, journal = {Clinical breast cancer}, volume = {14}, number = {4}, pages = {280-284}, doi = {10.1016/j.clbc.2013.12.009}, pmid = {24581736}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Carcinoma, Lobular/*secondary/surgery ; False Negative Reactions ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: In the past decade, sentinel lymph node biopsy (SLNB) has become standard for patients with early-stage clinically node-negative breast carcinoma (BC). Despite high overall surgical identification success rates with introduction of the dual-tracer techniques (dye and radiolabeled probe), false-negative rates remained unchanged in most recent meta-analyses.<br><br>PATIENTS AND METHODS: We analyzed cases with false-negative SLN biopsy results over a 12-year period in a single institution to evaluate their clinicopathologic characteristics. Sixty-three false-negative cases (3.1%) were found in 2043 successful SLN mapping procedures, all of which were followed by varying amounts of additional axillary sampling.<br><br>RESULTS: There was a higher proportion of invasive lobular carcinomas (ILCs; 23 cases [37%]) when compared with this lesion's overall reported frequency (5%-15%). The majority of invasive ductal carcinoma (IDC) cases (31 of 40) were poorly differentiated. In 80% of the ductal-type cases, 1 or more nonsentinel nodes (NSLNs) were completely or partially replaced by tumor, as opposed to less than half of such cases of the lobular type. Twenty-two cases had multiple positive NSLN metastases, which were significantly associated with larger tumor size (&#x2265; 1.0 cm) and tumor replacement of NSLNs. Eighty-two percent of the cases with known hormone receptor status were positive for estrogen or progesterone receptors, or both.<br><br>CONCLUSION: False-negative SLN biopsy results were more often associated with a primary BC characterized by a lobular or poorly differentiated ductal histologic type or partial to complete replacement of NSLNs with tumor, or both.}, }
@article {pmid24574467, year = {2014}, author = {Starmer, HM and Liu, Z and Akst, LM and Gourin, C}, title = {Attendance in voice therapy: can an interdisciplinary care model have an impact?.}, journal = {The Annals of otology, rhinology, and laryngology}, volume = {123}, number = {2}, pages = {117-123}, doi = {10.1177/0003489414523708}, pmid = {24574467}, issn = {0003-4894}, mesh = {Adult ; Aged ; Dysphonia/etiology/*rehabilitation ; Female ; Humans ; Male ; Middle Aged ; Otolaryngology/*statistics &amp; numerical data ; Patient Compliance/*statistics &amp; numerical data ; Referral and Consultation/*statistics &amp; numerical data ; Retrospective Studies ; Speech-Language Pathology/*statistics &amp; numerical data ; Treatment Outcome ; *Voice Training ; Young Adult ; }, abstract = {OBJECTIVES: We sought to determine the effect of referral patterns on attendance in voice therapy.<br><br>METHODS: Patients who were seen by a laryngologist for vocal concerns and referred for voice therapy comprised the study population. Outcomes were compared between those who were initially evaluated through the interdisciplinary voice clinic (IDC), which combined speech-language pathology and laryngology care, and those who were evaluated by a laryngologist alone. Adherence was measured by completion of the plan of care.<br><br>RESULTS: There were 79 patients evaluated through the IDC and 100 patients evaluated initially by a laryngologist. Patients evaluated through the IDC had more visits with the speech-language pathologist (mean, 3.1 versus 1.24; p < 0.0001). Those initially evaluated through the IDC were more likely to complete their plan of care (p = 0.02). Completion of voice therapy was significantly more likely for individuals coded as being of "other" race (odds ratio, 7.98; p = 0.002) and for patients who participated in the IDC (odds ratio, 2.56; p = 0.018). The cause of dysphonia, sex, marital status, insurance status, days from laryngology referral to the initial speech-language pathologist consultation, the initial Voice-Related Quality of Life score, and distance to the clinic were not associated with patient attendance.<br><br>CONCLUSIONS: Patients evaluated in a coordinated IDC should be more likely to attend voice therapy and complete their plan of care, regardless of other factors.}, }
@article {pmid24574065, year = {2014}, author = {Kwon, SY and Lee, JH and Kim, B and Park, JW and Kwon, TK and Kang, SH and Kim, S}, title = {Complexity in regulation of microRNA machinery components in invasive breast carcinoma.}, journal = {Pathology oncology research : POR}, volume = {20}, number = {3}, pages = {697-705}, pmid = {24574065}, issn = {1532-2807}, mesh = {Argonaute Proteins/*genetics/metabolism ; Breast/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; DEAD-box RNA Helicases/*genetics/metabolism ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proteins/*genetics/metabolism ; RNA, Messenger/genetics ; RNA-Binding Proteins ; Real-Time Polymerase Chain Reaction ; Ribonuclease III/*genetics/metabolism ; }, abstract = {Altered expression of microRNA (miRNA) machinery components may play an important role in breast cancer progression. The objective of the current study was to evaluate Drosha, the DiGeorge syndrome critical region gene 8 (DGCR8), Dicer, and Argonaute 2 (AGO2) mRNA expression in invasive breast carcinoma (IBC) and to assess the value of clinical parameters on their expression. By using quantitative real-time PCR, we examined the expression of the four miRNA machinery components in 52 breast tumor tissues which are diagnosed as invasive ductal carcinoma and adjacent non-neoplastic tissues. In the present study, decreased mRNA expression levels of major miRNA machinery components were observed in IBC. The altered mRNA expression levels of DGCR8 and AGO2 are positively correlated with to each other. This study revealed for the first time that expression alterations of DGCR8 are significantly associated with estrogen receptor and Ki-67 status in IBC. Moreover, AGO2 mRNA expression level was significantly correlated with N stage. These results provided evidences that down-regulated the four miRNA machinery components may play an important role in breast pathobiology and that DGCR8 and AGO2 might be associated with important clinical factors.}, }
@article {pmid24571647, year = {2014}, author = {Rodrigues Dos Santos, C and Fonseca, I and Dias, S and Mendes de Almeida, JC}, title = {Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {132}, pmid = {24571647}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood/mortality/*pathology ; Cholesterol, LDL/*blood ; Disease Progression ; Female ; Humans ; Lipids/blood ; Lipoproteins/blood ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Among women, breast cancer (BC) is the leading cancer and the most common cause of cancer-related death between 30 and 69 years. Although lifestyle and diet are considered to have a role in global BC incidence pattern, the specific influence of dyslipidemia in BC onset and progression is not yet completely understood.<br><br>METHODS: Fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who were enrolled according to pre-set inclusion criteria: diagnosis of non-hereditary invasive ductal carcinoma; selection for surgery as first treatment, and no history of treatment with lipid-lowering or anti-diabetic drugs in the previous year. Pathological and clinical follow-up data were recorded for further inclusion in the statistical analysis.<br><br>RESULTS: Univariate associations show that BC patients with higher levels of LDL-C at diagnosis have tumors that are larger, with higher differentiation grade, higher proliferative rate (assessed by Ki67 immunostaining), are more frequently Her2-neu positive and are diagnosed in more advanced stages. Cox regression model for disease-free survival (DFS), adjusted to tumor T and N stages of TNM classification, and immunohistochemical subtypes, revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile compared to those in the first tertile.<br><br>CONCLUSIONS: This is a prospective study where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this parameter can be useful in the identification and follow-up of high-risk groups. Our results further support a possible role for systemic cholesterol in BC progression and show that cholesterol metabolism may be an important therapeutic target in BC patients.}, }
@article {pmid24559473, year = {2014}, author = {Siegel, TN and Hon, CC and Zhang, Q and Lopez-Rubio, JJ and Scheidig-Benatar, C and Martins, RM and Sismeiro, O and Coppée, JY and Scherf, A}, title = {Strand-specific RNA-Seq reveals widespread and developmentally regulated transcription of natural antisense transcripts in Plasmodium falciparum.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {150}, pmid = {24559473}, issn = {1471-2164}, support = {250320/ERC_/European Research Council/International ; }, mesh = {3' Untranslated Regions ; Cell Nucleus/metabolism ; Cluster Analysis ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Library ; High-Throughput Nucleotide Sequencing ; Plasmodium falciparum/*genetics ; Polyadenylation ; RNA Splicing ; *RNA, Antisense ; RNA, Messenger/genetics/metabolism ; *RNA, Protozoan ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Advances in high-throughput sequencing have led to the discovery of widespread transcription of natural antisense transcripts (NATs) in a large number of organisms, where these transcripts have been shown to play important roles in the regulation of gene expression. Likewise, the existence of NATs has been observed in Plasmodium but our understanding towards their genome-wide distribution remains incomplete due to the limited depth and uncertainties in the level of strand specificity of previous datasets.<br><br>RESULTS: To gain insights into the genome-wide distribution of NATs in P. falciparum, we performed RNA-ligation based strand-specific RNA sequencing at unprecedented depth. Our data indicate that 78.3% of the genome is transcribed during blood-stage development. Moreover, our analysis reveals significant levels of antisense transcription from at least 24% of protein-coding genes and that while expression levels of NATs change during the intraerythrocytic developmental cycle (IDC), they do not correlate with the corresponding mRNA levels. Interestingly, antisense transcription is not evenly distributed across coding regions (CDSs) but strongly clustered towards the 3'-end of CDSs. Furthermore, for a significant subset of NATs, transcript levels correlate with mRNA levels of neighboring genes.Finally, we were able to identify the polyadenylation sites (PASs) for a subset of NATs, demonstrating that at least some NATs are polyadenylated. We also mapped the PASs of 3443 coding genes, yielding an average 3' untranslated region length of 523 bp.<br><br>CONCLUSIONS: Our strand-specific analysis of the P. falciparum transcriptome expands and strengthens the existing body of evidence that antisense transcription is a substantial phenomenon in P. falciparum. For a subset of neighboring genes we find that sense and antisense transcript levels are intricately linked while other NATs appear to be regulated independently of mRNA transcription. Our deep strand-specific dataset will provide a valuable resource for the precise determination of expression levels as it separates sense from antisense transcript levels, which we find to often significantly differ. In addition, the extensive novel data on 3' UTR length will allow others to perform searches for regulatory motifs in the UTRs and help understand post-translational regulation in P. falciparum.}, }
@article {pmid24551675, year = {2013}, author = {M, Y and Ahmadi M R, H and J, K and H, P and K H, A and M R, Y and K, H}, title = {An 8 years retrospective study of breast cancer incidence in ilam province, Western iran.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {7}, number = {12}, pages = {2923-2925}, pmid = {24551675}, issn = {2249-782X}, abstract = {INTRODUCTION: Breast cancer is the most common cancer (27% of all cancers) and common cause of death (16%) which occurs due to cancers among women, either in developed or developing countries. The current study aimed to assess incidence of breast cancer in west of Iran (Ilam province).<br><br>METHODS: During a cross-sectional study, all documented records of patients who were referred to the health centre of Ilam province in a period of 8 years (2002-2009) were investigated and 82 files which were related to breast cancer were identified. Patients' data were entered into SPSS, version 16 and using X2, t-test and descriptive statistics, they were analyzed.<br><br>RESULTS: Totally, 82 confirmed breast cancer cases were diagnosed between 2002-2009 and this figure accounted for 21.4% of all cancers in Ilam province. The mean age with standard deviation (SD) of patients was 47.4 &#xb1; 14.5 years and the disease was most frequent in the age group of 30-40 years (38.3%). The highest incidence rate was seen in 2006- 2007 and the lowest rate was seen in 2002-2003. The most prevalent morphologic pattern of breast caner (86.2%) was invasive ductal carcinoma (IDC). There was a 23% incidence rate for breast cancer, with a significant increase in its incidence rate during 2002-2009.<br><br>CONCLUSION: Due to diagnosis of the disease in its advanced stages, and also involvement of low age groups and young population in the country, screening programs such as self examination, examination by doctors and mammography should be started in the lower age groups, in ages which are lower than 30 years.}, }
@article {pmid24551288, year = {2014}, author = {Zhao, H and Chen, D and Wang, J and Yin, Y and Gao, Q and Zhang, Y}, title = {Downregulation of the transcription factor, FoxD3, is associated with lymph node metastases in invasive ductal carcinomas of the breast.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {2}, pages = {670-676}, pmid = {24551288}, issn = {1936-2625}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/secondary ; Case-Control Studies ; Down-Regulation ; Female ; Forkhead Transcription Factors/*metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/metabolism ; Lymphatic Metastasis ; MCF-7 Cells ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Triple Negative Breast Neoplasms/genetics/*metabolism/pathology ; }, abstract = {FoxD3 is a transcription factor of the forkhead gene family. We investigated its expression in invasive ductal carcinomas (IDC) of the breast and its association with metastasis. The expression of FoxD3, human epidermal growth factor receptor-2 (HER-2), estrogen receptor (ER), progesterone receptor (PR) and Ki67 was examined by immunohistochemistry in samples from 121 patients with IDC. Non-tumorous breast adenosis tissues served as controls. HER2 expression was confirmed by fluorescence in situ hybridization (FISH). The expression levels of FoxD3 in IDC tissues and the breast cancer cell lines MCF-7 and MDA-MB-231 were additionally measured by western blotting. A greater percentage of total IDC patients and patients with lymph node metastases showed reduced FoxD3 expression compared to adenosis controls (p<0.05). Overall, FoxD3 was associated with metastatic status of IDC but not with age, pathological or clinical staging, or status of HER-2, ER, or PR. In particular, FoxD3 protein expression was down-regulated in the tumor epithelia of IDC samples from patients with metastases. Furthermore, FoxD3 protein expression was decreased in the metastatic MDA-MB-231 breast cancer cell line relative to the non-metastatic cell line, MCF-7. A greater number of patients with invasive, triple-negative breast cancer were also negative for FoxD3 expression than in other, non-triple-negative tumor types. These results suggest an inverse relationship between FoxD3 expression and tumor metastasis and warrants further investigation.}, }
@article {pmid24535908, year = {2014}, author = {Oliveira, AL and Oliveira Rodrigues, FF and Dos Santos, RE and Rozenowicz, RL and Barbosa de Melo, M}, title = {GSTT1, GSTM1, and GSTP1 polymorphisms as a prognostic factor in women with breast cancer.}, journal = {Genetics and molecular research : GMR}, volume = {13}, number = {2}, pages = {2521-2530}, doi = {10.4238/2014.January.22.9}, pmid = {24535908}, issn = {1676-5680}, mesh = {Adult ; Aged ; Antineoplastic Agents/administration &amp; dosage ; Breast Neoplasms/drug therapy/*genetics/pathology ; Disease-Free Survival ; Female ; Genetic Predisposition to Disease ; Genotype ; Glutathione S-Transferase pi/*genetics ; Glutathione Transferase/*genetics ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Polymorphism, Single Nucleotide ; Prognosis ; }, abstract = {The glutathione S-transferase (GST) family comprises phase-II cellular detoxification enzymes that catalyze the conjugation of chemotherapy drugs to glutathione and act on the apoptotic pathway. The aim of this study was to determine whether polymorphisms of the GSTT1, GSTM1, and GSTP1 genes are associated with different rates of overall survival (OS) and disease-free survival (DFS) after neoadjuvant chemotherapy in the management of locally advanced breast cancer, using either simple or combined analyses, and in relation to the post-therapy axillary lymph node status. Forty women with invasive ductal carcinoma of the breast submitted to neoadjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide were genotyped for GSTT1, GSTM1, and GSTP1. Comparisons were performed for the three genes, either isolated or in pairs, in polymorphic or wild-type combinations. Finally, the OS and DFS of patients were analyzed with respect to axillary lymph node status and with respect to wild-type or polymorphic presentations of each gene. No statistically significant difference in OS and DFS was evident between women with wild-type or polymorphic forms of the genes, either isolated or in pairs, after neoadjuvant chemotherapy. By contrast, after treatment, lymph node-negative women had better OS and DFS only in the presence of polymorphisms of GSTP1, and improved DFS only in the presence of the polymorphic types of GSTT1 and GSTM1 compared to women with positive lymph nodes. The presence of polymorphic forms of GSTP1, GSTM1, and GSTT1 was crucial to conferring better OS and DFS among women with negative axillary lymph nodes.}, }
@article {pmid24530247, year = {2014}, author = {Chen, TD and Lee, LY}, title = {A case of renal cell carcinoma metastasizing to invasive ductal breast carcinoma.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {113}, number = {2}, pages = {133-136}, doi = {10.1016/j.jfma.2012.07.022}, pmid = {24530247}, issn = {0929-6646}, mesh = {Aged ; Breast Neoplasms/*pathology/*secondary ; Carcinoma, Ductal/*pathology/*secondary ; Carcinoma, Renal Cell/*pathology ; Female ; Humans ; Kidney Neoplasms/*pathology ; }, abstract = {Tumor-to-tumor metastasis is an uncommon but well-documented phenomenon. We present a case of a clear cell renal cell carcinoma (RCC) metastasizing to an invasive ductal carcinoma (IDC) of the breast. A 74-year-old woman with a past history of clear cell RCC status after radical nephrectomy underwent right modified radical mastectomy for an enlarging breast mass 3 years after nephrectomy. Histological examination revealed a small focus with distinct morphological features similar to clear cell RCC encased in the otherwise typical IDC. Immunohistochemical studies showed that this focus was positive for CD10 and vimentin, in contrast to the surrounding IDC, which was negative for both markers and positive for Her2/neu. Based on the histological and immunohistochemical features, the patient was diagnosed with metastasis of clear cell RCC to the breast IDC. To the best of our knowledge, this is the first reported case of a breast neoplasm as the recipient tumor in tumor-to-tumor metastasis.}, }
@article {pmid24525508, year = {2014}, author = {Boulos, FI and Granja, NM and Simpson, JF and O'Malley, FP and Saadeldine, MM and Page, DL and Sanders, ME}, title = {Intranodal papillary epithelial proliferations: a local process with a spectrum of morphologies and frequent association with papillomas in the breast.}, journal = {The American journal of surgical pathology}, volume = {38}, number = {3}, pages = {383-388}, doi = {10.1097/PAS.0000000000000115}, pmid = {24525508}, issn = {1532-0979}, mesh = {Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology ; Breast Neoplasms, Male/pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; *Cell Proliferation ; Diagnostic Errors/prevention &amp; control ; Epithelial Cells/*pathology ; Female ; Humans ; Hyperplasia ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Papilloma/*pathology ; Predictive Value of Tests ; }, abstract = {Lymph nodes, particularly those draining in major anatomic sites like axilla, pelvis, and neck are potential sites for the occasional presence of ectopic tissue, usually representative of the organ being drained. Owing to the uncertainty surrounding the processes causing such findings, and particularly in the setting of lymph node dissection and sampling for cancer staging, intranodal epithelial inclusions, rare as they may be, might be fertile soil for overdiagnosis of metastatic disease. Intranodal papillary inclusions are particularly problematic and challenging because of their complex architecture that may easily mimic a metastasis. From the files of the Breast Consultation Service, Department of Pathology at the Vanderbilt University Medical Center in Nashville, we identified 6 cases in which histopathologic examination of axillary lymph nodes revealed intranodal papillary inclusions (papillary epithelial proliferations). One case showed atypical ductal hyperplasia, 1 showed low-grade ductal carcinoma in situ, and 1 showed usual ductal hyperplasia. The corresponding breast lesions were papillomas in 5 of 6 cases, 2 of which displayed atypical ductal hyperplasia, whereas 3 showed low-grade ductal carcinoma in situ. One case showed intermediate-grade invasive ductal carcinoma, and the associated intranodal papilloma lacked atypia. Our findings suggest that intranodal papillary proliferations are often, although not exclusively, associated with papillary and noninvasive breast neoplasms, hence highlighting the origin of these intranodal lesions as independent de novo nodal processes rather than metastatic deposits.}, }
@article {pmid24523870, year = {2014}, author = {Blancato, J and Graves, A and Rashidi, B and Moroni, M and Tchobe, L and Ozdemirli, M and Kallakury, B and Makambi, KH and Marian, C and Mueller, SC}, title = {SYK allelic loss and the role of Syk-regulated genes in breast cancer survival.}, journal = {PloS one}, volume = {9}, number = {2}, pages = {e87610}, pmid = {24523870}, issn = {1932-6203}, support = {9R01 CA112673/CA/NCI NIH HHS/United States ; 1 S10 RR019291-01A2/RR/NCRR NIH HHS/United States ; 2P30-CA-51008/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA112673/CA/NCI NIH HHS/United States ; U56 CA101563/CA/NCI NIH HHS/United States ; 1S10RR15768-01/RR/NCRR NIH HHS/United States ; S10 RR019291/RR/NCRR NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*metabolism/mortality ; Carcinoma, Ductal, Breast/*genetics/*metabolism/mortality ; Chromosome Mapping ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Genomic Instability ; Humans ; In Situ Hybridization, Fluorescence ; Intracellular Signaling Peptides and Proteins/*genetics ; Kaplan-Meier Estimate ; *Loss of Heterozygosity ; Neoplasm Invasiveness ; Prognosis ; Promoter Regions, Genetic ; Protein-Tyrosine Kinases/*genetics ; Syk Kinase ; Treatment Outcome ; }, abstract = {Heterozygotic loss of SYK, a non-receptor tyrosine kinase, gives rise to mouse mammary tumor formation where Syk protein levels are reduced by about half; loss of SYK mRNA is correlated with invasive cell behavior in in vitro models; and SYK loss has been correlated with distant metastases in patients. Here, allelic loss of the SYK gene was explored in breast ductal carcinoma in situ (DCIS) using fluorescence in situ hybridization and pyrosequencing, respectively, and in infiltrating ductal carcinoma (IDC) using genomic data from The Cancer Genome Atlas (TCGA). Allelic loss was present in a subset of DCIS cases where adjacent IDC was present. SYK copy number loss was found in about 26% of 1002 total breast cancer cases and 30% of IDC cases. Quantitative immunofluorescence revealed Syk protein to be six-fold higher in infiltrating immune cells compared with epithelial cells. This difference distorted tumor cell mRNA and protein levels in extracts. 20% of 1002 IDC cases contained elevated immune cell infiltration as estimated by elevated immune-specific mRNAs. In cases without immune cell infiltration, loss of SYK copy number was associated with a significant reduction of SYK mRNA. Here we define a 55 Gene Set consisting of Syk interacting, motility- and invasion-related genes. We found that overall survival was significantly reduced in IDC and Luminal A+B cases where copy number and mutations of these 55 genes were affected (Kaplan-Meier, Logrank test p-value 0.007141 and Logrank test p-value 0.001198, respectively). We conclude that reduction in Syk expression and contributions of genomic instability to copy number and mutations in the 55 Syk interacting genes significantly contribute to poorer overall patient survival. A closer examination of the role of Syk interacting motility and invasion genes and their prognostic and/or causative association with metastatic disease and patient outcome is warranted.}, }
@article {pmid24512624, year = {2014}, author = {Babina, IS and McSherry, EA and Donatello, S and Hill, AD and Hopkins, AM}, title = {A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44.}, journal = {Breast cancer research : BCR}, volume = {16}, number = {1}, pages = {R19}, pmid = {24512624}, issn = {1465-542X}, mesh = {Breast/cytology/physiology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Cytoskeletal Proteins/metabolism ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Hyaluronan Receptors/genetics/*metabolism ; *Lipoylation ; Membrane Microdomains/*metabolism ; Mutagenesis, Site-Directed ; Neoplasm Invasiveness/*pathology ; Protein Binding ; Protein Processing, Post-Translational ; }, abstract = {INTRODUCTION: Most breast cancer-related deaths result from metastasis, a process involving dynamic regulation of tumour cell adhesion and migration. The adhesion protein CD44, a key regulator of cell migration, is enriched in cholesterol-enriched membrane microdomains termed lipid rafts. We recently reported that raft affiliation of CD44 negatively regulates interactions with its migratory binding partner ezrin. Since raft affiliation is regulated by post-translational modifications including palmitoylation, we sought to establish the contribution of CD44 palmitoylation and lipid raft affiliation to cell migration.<br><br>METHODS: Recovery of CD44 and its binding partners from raft versus non-raft membrane microdomains was profiled in non-migrating and migrating breast cancer cell lines. Site-directed mutagenesis was used to introduce single or double point mutations into both CD44 palmitoylation sites (Cys286 and Cys295), whereupon the implications for lipid raft recovery, phenotype, ezrin co-precipitation and migratory behaviour was assessed. Finally CD44 palmitoylation status and lipid raft affiliation was assessed in primary cultures from a small panel of breast cancer patients.<br><br>RESULTS: CD44 raft affiliation was increased during migration of non-invasive breast cell lines, but decreased during migration of highly-invasive breast cells. The latter was paralleled by increased CD44 recovery in non-raft fractions, and exclusive non-raft recovery of its binding partners. Point mutation of CD44 palmitoylation sites reduced CD44 raft affiliation in invasive MDA-MB-231 cells, increased CD44-ezrin co-precipitation and accordingly enhanced cell migration. Expression of palmitoylation-impaired (raft-excluded) CD44 mutants in non-invasive MCF-10a cells was sufficient to reversibly induce the phenotypic appearance of epithelial-to-mesenchymal transition and to increase cell motility. Interestingly, cell migration was associated with temporal reductions in CD44 palmitoylation in wild-type breast cells. Finally, the relevance of these findings is underscored by the fact that levels of palmitoylated CD44 were lower in primary cultures from invasive ductal carcinomas relative to non-tumour tissue, while CD44 co-localisation with a lipid raft marker was less in invasive ductal carcinoma relative to ductal carcinoma in situ cultures.<br><br>CONCLUSION: Our results support a novel mechanism whereby CD44 palmitoylation and consequent lipid raft affiliation inversely regulate breast cancer cell migration, and may act as a new therapeutic target in breast cancer metastasis.}, }
@article {pmid24512329, year = {2014}, author = {Kulzer, L and Rubner, Y and Deloch, L and Allgäuer, A and Frey, B and Fietkau, R and Dörrie, J and Schaft, N and Gaipl, US}, title = {Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells.}, journal = {Journal of immunotoxicology}, volume = {11}, number = {4}, pages = {328-336}, doi = {10.3109/1547691X.2014.880533}, pmid = {24512329}, issn = {1547-6901}, mesh = {Antigens, CD/metabolism ; Antineoplastic Protocols ; CD4-Positive T-Lymphocytes/*immunology ; Cell Death ; Cell Differentiation ; Cell Line, Tumor ; Colorectal Neoplasms/immunology/*radiotherapy ; Cytokines/metabolism ; Dendritic Cells/*immunology/*radiation effects ; *Dose Fractionation, Radiation ; Humans ; Lymphocyte Activation ; Paracrine Communication ; }, abstract = {Despite the transient immunosuppressive properties of local radiotherapy (RT), this classical treatment modality of solid tumors is capable of inducing immunostimulatory forms of tumor-cell death. The resulting 'immunotoxicity' in the tumor, but not in healthy tissues, may finally lead to immune-mediated destruction of the tumor. However, little is known about the best irradiation scheme in this setting. This study examines the immunological effects of differently irradiated human colorectal tumor cells on human monocyte-derived dendritic cells (DC). Human SW480 tumor cells were irradiated with a norm-fractionation scheme (5 × 2 Gy), a hypo-fractionated protocol (3 × 5 Gy), and with a high single irradiation dose (radiosurgery; 1 × 15 Gy). Subsequently, human immature DC (iDC) were co-incubated with supernatants (SN) of these differently treated tumor cells. Afterwards, DC were analyzed regarding the expression of maturation markers, the release of cytokines, and the potential to stimulate CD4(+) T-cells. The co-incubation of iDC with SN of tumor cells exposed to norm- or hypo-fractionated RT resulted in a significantly increased secretion of the immune activating cytokines IL-12p70, IL-8, IL-6, and TNFα, compared to iDC co-incubated with SN of tumor cells that received a high single irradiation dose or were not irradiated. In addition, DC-maturation markers CD80, CD83, and CD25 were also exclusively elevated after co-incubation with the SN of fractionated irradiated tumor cells. Furthermore, the SN of tumor cells that were irradiated with norm- or hypo-fractionated RT triggered iDC to stimulate CD4(+) T-cells not only in an allogenic, but also in an antigen-specific manner like mature DC. Collectively, these results demonstrate that norm- and hypo-fractionated RT induces a fast human colorectal tumor-cell death with immunogenic potential that can trigger DC maturation and activation in vitro. Such findings may contribute to the improvement of irradiation protocols for the most beneficial induction of anti-tumor immunity.}, }
@article {pmid24511745, year = {2013}, author = {Talghini, S}, title = {Is macromastia a risk factor for breast cancer? A study on 198 patients.}, journal = {Pakistan journal of biological sciences : PJBS}, volume = {16}, number = {21}, pages = {1348-1352}, doi = {10.3923/pjbs.2013.1348.1352}, pmid = {24511745}, issn = {1028-8880}, mesh = {Adult ; Breast/*abnormalities/pathology ; Breast Neoplasms/*pathology/surgery ; Cross-Sectional Studies/methods ; Female ; Humans ; Hypertrophy/*pathology ; Mammaplasty/methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {Macromastia, or breast hypertrophy, is a very common finding and a frequent cause of reduction mammaplasty all over the world. This study aims to examine the breast tissue specimens obtained by reduction mammaplasty in patients with macromastia in terms of the frequency of histopathological abnormalities (malignant and non-malignant lesions). In this cross-sectional, retrospective study, paraffin-embedded specimens of breast tissue after reduction mammaplasty were histopathologically reviewed in Tabriz Imam Reza Teaching Hospital in three years (2010-2013). All the specimens were sectioned, stained and examined by an adroit pathologist. One hundred ninety eight out of 271 primary specimens were eligible for this study. The mean age of the patients was 37.09 +/- 8.98 (range: 20-59) years, with mean body mass index of 27.44 +/- 3.85 (range: 21-35) kg m(-2). Based on the findings of microscopic examination, normal tissue was present in 98 cases (49.5%), all with increased content of fat. Fibrocystic change was the prominent benign entity, which was reported in 47.5% of the cases. Intraductal papilloma was detected 2 cases (1%). There were 4 cases with malignant lesions (2%), including 2 cases (1%) with invasive ductal carcinoma (age: 22 and 31 years old) and 2 cases (1%) with lobular carcinoma in situ (age: 21 and 35 years old). Considering the intraductal papilloma as a premalignant condition, the total rate of non-benign lesions reached to 3%. Based on the results of the present study, macromastia may be considered as a risk factor of breast malignancy. Thorough histopathological examination of the breast specimens after reduction mammaplasty, as well as strict screening of the women with nonsurgical macromastia is highly recommended.}, }
@article {pmid24508527, year = {2014}, author = {Goodyear, AW and Kumar, A and Dow, S and Ryan, EP}, title = {Optimization of murine small intestine leukocyte isolation for global immune phenotype analysis.}, journal = {Journal of immunological methods}, volume = {405}, number = {}, pages = {97-108}, doi = {10.1016/j.jim.2014.01.014}, pmid = {24508527}, issn = {1872-7905}, mesh = {Animals ; Antigens, CD/immunology/metabolism ; CD4-Positive T-Lymphocytes/cytology/immunology/metabolism ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Separation/methods ; Cell Survival/immunology ; Dendritic Cells/cytology/immunology/metabolism ; Epithelial Cells/cytology/immunology/metabolism ; Female ; Immunophenotyping/methods ; Intestinal Mucosa/cytology/*immunology/metabolism ; Intestine, Small/cytology/*immunology/metabolism ; Killer Cells, Natural/cytology/immunology/metabolism ; Leukocytes/cytology/*immunology/metabolism ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Monocytes/cytology/immunology/metabolism ; Reproducibility of Results ; }, abstract = {New efforts to understand complex interactions between diet, gut microbiota, and intestinal immunity emphasize the need for a standardized murine protocol that has been optimized for the isolation of lamina propria immune cells. In this study multiple mouse strains including BALB/c, 129S6/Sv/EvTac and ICR mice were utilized to develop an optimal protocol for global analysis of lamina propria leukocytes. Incubation temperature was found to significantly improve epithelial cell removal, while changes in media formulation had minor effects. Tissue weight was an effective method for normalization of solution volumes and incubation times. Collagenase digestion in combination with thermolysin was identified as the optimal method for release of leukocytes from tissues and global immunophenotyping, based on the criteria of minimizing marker cleavage, improving cell viability, and reagent cost. The effects of collagenase in combination with dispase or thermolysin on individual cell surface markers revealed diverse marker specific effects. Aggressive formulations cleaved CD8α, CD138, and B220 from the cell surface, and resulted in relatively higher expression levels of CD3, γδ TCR, CD5, DX5, Ly6C, CD11b, CD11c, MHC-II and CD45. Improved collagenase digestion significantly improved viability and reduced debris formation, eliminating the need for density gradient purification. Finally, we demonstrate that two different digestion protocols yield significant differences in detection of CD4(+) and CD8(+) T cells, NK cells, monocytes and interdigitating DC (iDC) populations, highlighting the importance and impact of cell collection protocols on assay outputs. The optimized protocol described herein will help assure the reproducibility and robustness of global assessment of lamina propria immune responses. Moreover, this technique may be applied to isolation of leukocytes from the entire gastrointestinal tract.}, }
@article {pmid24506966, year = {2013}, author = {Nie, D and You, QS and Luan, JW and Li, Y and Li, XL and Guo, RT and Zhang, LP and Wu, J}, title = {[Long-term results of personalized treatment in 72 breast cancer patients who failed chemotherapy].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {35}, number = {12}, pages = {941-945}, pmid = {24506966}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aromatase Inhibitors/therapeutic use ; Bone Density Conservation Agents/therapeutic use ; Bone Neoplasms/drug therapy/secondary ; Brain Neoplasms/drug therapy/secondary ; Breast Neoplasms/*drug therapy/pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/radiotherapy/secondary/surgery ; Chemotherapy, Adjuvant ; Diphosphonates/therapeutic use ; Drugs, Chinese Herbal/*therapeutic use ; Female ; Follow-Up Studies ; Humans ; Imidazoles/therapeutic use ; Letrozole ; Lung Neoplasms/drug therapy/secondary ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasm Staging ; Nitriles/therapeutic use ; Radiotherapy, Adjuvant ; Radiotherapy, Conformal/*methods ; Remission Induction ; Retrospective Studies ; Survival Rate ; Treatment Failure ; Triazoles/therapeutic use ; Zoledronic Acid ; }, abstract = {OBJECTIVE: To evaluate the efficacy and prognostic factors of personalized treatment for breast cancer patients who failed chemotherapy.<br><br>METHODS: Seventy-two patients with breast cancer who failed chemotherapy were treated at the Tumor Hospital of Harbin Medical University from January 2001 to January 2012. Among them, 42 cases received 5.6 cycles (range, 4-8 cycles) of postoperative adjuvant chemotherapy, and 30 cases received 12.2 cycles (range, 6-22 cycles), both postoperative adjuvant and salvage chemotherapy. All of the 72 patients of stage IV were given personalized treatment. Under guidance of the principle that multidisciplinary treatment improves control rate but does not or less damage the normal tissues and host immune function, precise radiotherapy combined with Chinese herbal medicine (CHM), biological agent and others were chosen for the patients.<br><br>RESULTS: The median survival time was 20 months. Univariate analysis showed that non-invasive ductal carcinoma, less metastasized organs, without brain, liver and lung metastasis, Karnofsky performance scores &#x2265; 80, not combined with chemotherapy, and multiple courses of Chinese herbal medicine and biolojical agent treatment had significant impact on survival (P < 0.05). Multivariate analysis showed that no brain metastasis, non-invasive ductal carcinoma, and Chinese herbal medicine and biological agent treatment &#x2265; 7 courses and not combined with chemotherapy had obvious significance (P < 0.05). The rate of grade 3 and 4 treatment-related hematological toxicity was 8.3% (6/72) and 5.6% (4/72), respectively. All the patients with grade 4 hematological toxicity were the cases of grade 3 at hospital admission. No grade 3 and 4 acute radiation damages of the lung and liver were noticed.<br><br>CONCLUSION: Chinese herbal medicine combined with biological agents and others prolongs survival time in breast cancer patients who failed chemotherapy, and provides an alternative treatment modality for them.}, }
@article {pmid24502182, year = {2013}, author = {Fernández, A and Reigosa, A}, title = {[Molecular classification of breast cancer patients obtained through the technique of chromogenic in situ hybridization (CISH)].}, journal = {Investigacion clinica}, volume = {54}, number = {4}, pages = {406-416}, pmid = {24502182}, issn = {0535-5133}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*classification/*genetics ; Cross-Sectional Studies ; Female ; Humans ; In Situ Hybridization/*methods ; Middle Aged ; Retrospective Studies ; Young Adult ; }, abstract = {Breast cancer is a heterogeneous disease composed of a growing number of biological subtypes, with substantial variability of the disease progression within each category. The aim of this research was to classify the samples object of study according to the molecular classes of breast cancer: luminal A, luminal B, HER2 and triple negative, as a result of the state of HER2 amplification obtained by the technique of chromogenic in situ hybridization (CISH). The sample consisted of 200 biopsies fixed in 10% formalin, processed by standard techniques up to paraffin embedding, corresponding to patients diagnosed with invasive ductal carcinoma of the breast. These biopsies were obtained from patients from private practice and the Institute of Oncology "Dr. Miguel Pérez Carreño", for immunohistochemistry (IHC) of hormone receptors and HER2 made in the Hospital Metropolitano del Norte, Valencia, Venezuela. The molecular classification of the patient's tumors considering the expression of estrogen and progesterone receptors by IHC and HER2 amplification by CISH, allowed those cases originally classified as unknown, since they had an indeterminate (2+) outcome for HER2 expression by IHC, to be grouped into the different molecular classes. Also, this classification permitted that some cases, initially considered as belonging to a molecular class, were assigned to another class, after the revaluation of the HER2 status by CISH.}, }
@article {pmid24497139, year = {2013}, author = {Kobierzycki, C and Wojnar, A and Dziegiel, P}, title = {Expression of SATB1 protein in the ductal breast carcinoma tissue microarrays - preliminary study.}, journal = {Folia histochemica et cytobiologica}, volume = {51}, number = {4}, pages = {333-338}, doi = {10.5603/FHC.2013.0045}, pmid = {24497139}, issn = {1897-5631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Female ; Humans ; Ki-67 Antigen/genetics/metabolism ; Matrix Attachment Region Binding Proteins/genetics/*metabolism ; Middle Aged ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Tissue Array Analysis ; }, abstract = {Special AT-rich sequence-binding protein 1 (SATB1) is a nuclear matrix protein which interacts with specific regions of DNA, ensuring its proper organization and function in the cell. The expression of SATB1 was primarily found in thymocytes, but its increased levels were observed in various types of cancers. However, the knowledge of the function and application possibilities of this protein is still limited. The aim of this study was to investigate the expression of SATB1 protein using immunohistochemistry and tissue microarray (TMA) technique and determine its possible relationship with the proliferative marker Ki-67, estrogen a (ER) and progesterone (PR) receptors as well as grade of histological malignancy (G). The study was performed on material of 48 archival invasive ductal breast cancers (IDC). The TMAs were prepared with the use of 0.6 mm diameter punches. Immunohistochemical reactions were carried out using antibodies against Ki-67, ER, PR and SATB1 proteins. The intensity of the nuclear reaction was evaluated using a light microscope and computer-assisted image analysis. Expression of Ki-67 and SATB1 protein was observed in 89.58% and 31.25% of cancer cases, respectively. 62.5% of tumors were classified as ER-positive, and 47.92% as PR-positive. Statistical analysis showed a moderate positive correlation between Ki-67 and SATB1 expression (r = 0.291, p = 0.045 independently on the receptor status, and r = 0.392, p = 0.032 in ER-negative tumors). The expression of the Ki-67 antigen increased with higher grade of histological malignancy (G). The results suggest that SATB1 protein may play an indirect role in the cell proliferation and should be evaluated in relation to the other markers. Further studies concerning determination of its role in cancer progression and metastasis, in terms of application as therapeutic target and prognostic marker, are recommended.}, }
@article {pmid24489812, year = {2014}, author = {Liu, T and Zhang, XY and He, XH and Geng, JS and Liu, Y and Kong, DJ and Shi, QY and Liu, F and Wei, W and Pang, D}, title = {High levels of BCOX1 expression are associated with poor prognosis in patients with invasive ductal carcinomas of the breast.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e86952}, pmid = {24489812}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Demography ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*genetics/metabolism ; Prognosis ; Proportional Hazards Models ; RNA, Messenger/genetics/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; }, abstract = {This study was to examine the breast cancer-overexpressed gene 1 (BCOX1) expression in invasive ductal carcinomas (IDC) of the breast and its value in the prognosis of the disease. The levels of BCOX1 expression in 491 paired IDC and surrounding non-tumor breast tissues as well as 40 paired fresh specimens were evaluated by tissue microarray, immunohistochemistry and quantitative RT-PCR. The potential associations of high BCOX1 expression with clinicopathological variables and the overall survival of these patients were analyzed. The relative levels of BCOX1 mRNA transcripts in the IDC breast tissues were significantly higher than that in the corresponding non-tumor tissues (P = 0.005). The anti-BCOX1 was predominantly stained in the cytoplasm of breast tissue cells and the levels of BCOX1 expression in the majority of breast cancer tissues were obviously higher than that in the corresponding non-tumor breast tissues. High levels of BCOX1 expression were found in 59.5% (292/491) of breast cancer tissues. The high BCOX1 expression was significantly associated with high histological grade (P = 0.037), positive expression of human epidermal growth factor receptor 2 (HER2, P = 0.031) and triple negative breast cancer (P = 0.027). The high BCOX1 expression in breast cancers was significantly associated with a shorter overall survival of these patients (P = 0.023), particularly in patients with triple negative breast cancer (P = 0.005). Therefore, the high BCOX1 expression may serve as a novel marker of poor prognosis and a potential therapeutic target for patients with IDC of the breast.}, }
@article {pmid24489766, year = {2014}, author = {Jiang, YZ and Xia, C and Peng, WT and Yu, KD and Zhuang, ZG and Shao, ZM}, title = {Preoperative measurement of breast cancer overestimates tumor size compared to pathological measurement.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e86676}, pmid = {24489766}, issn = {1932-6203}, mesh = {Adult ; Breast/*pathology ; Carcinoma, Ductal, Breast/diagnosis/diagnostic imaging/mortality/*pathology ; Female ; Humans ; Mammography ; Middle Aged ; Neoplasm Grading ; Preoperative Period ; Retrospective Studies ; Survival Analysis ; Tumor Burden ; }, abstract = {BACKGROUND: Tumor size is one of the most important factors in making clinical and pathological assessment of breast cancer. In the present study, we aimed to determine whether the preoperative measurement of tumor size, by imaging modalities, deviate from the postoperative pathological measurement in breast cancer.<br><br>PATIENTS AND METHODS: 1296 patients diagnosed with invasive ductal breast carcinoma (IDC) during 2007 and 2009 were involved. Pre- and postoperative measurements of tumor size were compared using paired t-test and Chi-square test.<br><br>RESULTS: The mean maximum diameters of tumors by imaging modalities and pathology were 27.9 mm and 22.4 mm, respectively. There was a statistically significant difference of 5.5 mm (95% CI: 4.7-6.2, p<0.001) between them. The discordance between pre- and post-surgical measurements of tumor size had significant effect on choosing surgery type, causing less application of breast conserving therapy (p<0.0001).<br><br>CONCLUSION: Compared to pathological size, preoperative measurement by imaging modalities tends to overestimate tumor size. These differences could have implications in the treatment of patients with breast cancer.}, }
@article {pmid24481994, year = {2014}, author = {Lee, SK and Kim, SW and Han, SA and Kil, WH and Lee, JE and Nam, SJ}, title = {The protective effect of parity in hormone receptor-positive, Ki-67 expressing breast cancer.}, journal = {World journal of surgery}, volume = {38}, number = {5}, pages = {1065-1069}, pmid = {24481994}, issn = {1432-2323}, mesh = {Adult ; Breast Neoplasms/*epidemiology/*metabolism/pathology ; Female ; Humans ; Ki-67 Antigen/*biosynthesis ; Middle Aged ; Neoplasm Invasiveness ; *Parity ; Protective Factors ; Receptor, ErbB-2/*biosynthesis ; Retrospective Studies ; }, abstract = {BACKGROUND: Epidemiologic studies showed that the experience of pregnancy is associated with a reduced risk of breast cancer. We hypothesized that parity may differentially be associated with the development of invasive breast cancer by each subtype.<br><br>METHODS: We reviewed the clinical, radiological, and pathological records of women diagnosed with invasive ductal carcinoma of the breast at Samsung Medical Center between 2005 and 2009. Clinicopathologic results were assessed by &#x3c7;(2) and Fisher's exact tests with a Bonferroni correction for categorical variables, and by the Kruskal-Wallis test for nonparametric continuous variables. A multinomial logistic regression model was used for multivariate analysis.<br><br>RESULTS: Among a total of 3,095 patients, 283 (9.14 %) patients were nulliparous. Older age, higher pN, and expression of HER2 were associated with parity. In the analysis between parity and molecular subtypes, parity also had a variable influence on breast cancer subtypes (p = 0.032). Intergroup analysis with multiple comparison showed that luminal B subtype was related to nulliparity compared with HER2-positive subtypes (p = 0.03).<br><br>CONCLUSIONS: The effect of parity on the development of breast cancer differed by hormone receptor and HER2 expression. It seems that parity might have a protective effect against hormone receptor-positive breast cancer, especially cancers expressing HR+ and Ki-67. Further basic research to define and understand this result is ongoing.}, }
@article {pmid24479854, year = {2014}, author = {Kővári, B and Rusz, O and Schally, AV and Kahán, Z and Cserni, G}, title = {Differential immunostaining of various types of breast carcinomas for growth hormone-releasing hormone receptor - Apocrine epithelium and carcinomas emerging as uniformly positive.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {122}, number = {9}, pages = {824-831}, doi = {10.1111/apm.12224}, pmid = {24479854}, issn = {1600-0463}, mesh = {Breast Neoplasms/classification/diagnosis/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Mammary Glands, Human/*metabolism ; Mammography ; RNA, Messenger/biosynthesis ; Receptor, ErbB-2/metabolism ; Receptors, Neuropeptide/biosynthesis/genetics/*metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/biosynthesis/genetics/*metabolism ; Retrospective Studies ; }, abstract = {Different classes of breast cancers were explored for their positivity for growth hormone-releasing hormone receptors (GHRH-R) in this pilot study, as no systematic evaluation of such tumors has been performed to date. Seventy-two small primary breast carcinomas were evaluated for GHRH-R expression by immunohistochemistry using a polyclonal antibody and a cutoff value of 10% staining. GHRH-R positivity was detected in 58% of all cases, 20/23 (87%) of invasive lobular carcinomas (ILC) and 22/46 (48%) of invasive ductal carcinomas (IDC). GHRH-R positivity was more frequent in grade 2 tumors (86%), as compared to grade 1 (18%) or grade 3 (47%) cancers. GHRH-R expression was not associated with mitotic scores, the Ki-67 labeling indices or nodal status. IDCs with casting-type calcifications on the mammogram showed positivity for GHRH-R in 9/12 (75%) cases. Most importantly, apocrine epithelium, and all 10 apocrine carcinomas added later to the study were GHRH-R-positive. These preliminary results suggest a greater than average GHRH-R expression in ILCs and IDCs associated with casting-type calcifications on the mammogram. Apocrine carcinomas seem uniformly positive for GHRH-R. Whether these findings could indicate a potential role of GHRH-antagonists in targeted treatment of these types of breast cancer requires further studies.}, }
@article {pmid24477715, year = {2014}, author = {O'Donnell, E and Havyer, R}, title = {Breast malignancy masquerading under the cloak of acute urticaria.}, journal = {BMJ case reports}, volume = {2014}, number = {}, pages = {}, pmid = {24477715}, issn = {1757-790X}, mesh = {Breast Neoplasms/*complications/diagnosis/surgery ; Carcinoma, Ductal, Breast/*complications/diagnosis/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Urticaria/*etiology ; }, abstract = {Urticaria is a common disorder characterised by well-demarcated and intensely pruritic erythematous skin swellings. Common triggers include infection, allergic reactions or medications. While often idiopathic, the presence of urticaria can be associated with underlying systemic disease. We report a case of a patient who presented with diffuse and refractory urticaria. A thorough workup was conducted to determine the aetiology including routine age-appropriate cancer screening. Mammography revealed four lesions in the patient's left breast with biopsy consistent with invasive ductal carcinoma. Disappearance of the urticarial lesions with mastectomy suggests an association between breast malignancy and urticaria. Thus, refractory urticaria with unknown cause should prompt a thorough history, physical examination and review of age-appropriate cancer screening.}, }
@article {pmid24475103, year = {2014}, author = {Yang, AX and Chong, N and Jiang, Y and Catalano, J and Puri, RK and Khleif, SN}, title = {Molecular characterization of antigen-peptide pulsed dendritic cells: immature dendritic cells develop a distinct molecular profile when pulsed with antigen peptide.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e86306}, pmid = {24475103}, issn = {1932-6203}, mesh = {Antigen Presentation/*genetics ; Dendritic Cells/*cytology/*metabolism ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation/*immunology ; HLA-A2 Antigen/metabolism ; Humans ; Image Processing, Computer-Assisted ; Immunotherapy/*methods ; Microarray Analysis ; Papillomavirus E7 Proteins/*metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {As dendritic cells (DCs) are the most potent professional antigen-presenting cells, they are being tested as cancer vaccines for immunotherapy of established cancers. Although numerous studies have characterized DCs by their phenotype and function, few have identified potential molecular markers of antigen presentation prior to vaccination of host. In this study we generated pre-immature DC (piDC), immature DC (iDC), and mature DC (mDC) from human peripheral blood monocytes (PBMC) obtained from HLA-A2 healthy donors, and pulsed them with human papillomavirus E7 peptide (p11-20), a class I HLA-A2 binding antigen. We then characterized DCs for cell surface phenotype and gene expression profile by microarray technology. We identified a set of 59 genes that distinguished three differentiation stages of DCs (piDC, iDC and mDC). When piDC, iDC and mDC were pulsed with E7 peptide for 2 hrs, the surface phenotype did not change, however, iDCs rather than mDCs showed transcriptional response by up-regulation of a set of genes. A total of 52 genes were modulated in iDC upon antigen pulsing. Elongation of pulse time for iDCs to 10 and 24 hrs did not significantly bring further changes in gene expression. The E7 peptide up-modulated immune response (KPNA7, IGSF6, NCR3, TREM2, TUBAL3, IL8, NFKBIA), pro-apoptosis (BTG1, SEMA6A, IGFBP3 and SRGN), anti-apoptosis (NFKBIA), DNA repair (MRPS11, RAD21, TXNRD1), and cell adhesion and cell migration genes (EPHA1, PGF, IL8 and CYR61) in iDCs. We confirmed our results by Q-PCR analysis. The E7 peptide but not control peptide (PADRE) induced up-regulation of NFKB1A gene only in HLA-A2 positive iDCs and not in HLA-A2 negative iDCs. These results suggest that E7 up-regulation of genes is specific and HLA restricted and that these genes may represent markers of antigen presentation and help rapidly assess the quality of dendritic cells prior to administration to the host.}, }
@article {pmid24465383, year = {2014}, author = {Di Caro, V and Phillips, B and Engman, C and Harnaha, J and Trucco, M and Giannoukakis, N}, title = {Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e83575}, pmid = {24465383}, issn = {1932-6203}, support = {R21 DK063499/DK/NIDDK NIH HHS/United States ; R33 DK063499/DK/NIDDK NIH HHS/United States ; DK063499/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD19/metabolism ; B-Lymphocytes/cytology/drug effects/*immunology ; Cell Proliferation/drug effects ; Dendritic Cells/drug effects/*immunology ; Diabetes Mellitus, Type 1/*immunology/pathology ; Female ; Flow Cytometry ; Humans ; Hyperglycemia/immunology ; *Immune Tolerance/drug effects ; Immunomodulation/drug effects ; Interleukin-10/metabolism ; Lymphocyte Activation/drug effects ; Lymphocyte Culture Test, Mixed ; Mice ; Mice, Inbred NOD ; Mice, Transgenic ; Oligonucleotides, Antisense/pharmacology ; Receptors, Retinoic Acid/metabolism ; Spleen/cytology ; }, abstract = {The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD) mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.}, }
@article {pmid24458308, year = {2014}, author = {Fu, J and Zhang, L and Song, S and Sheng, K and Li, Y and Li, P and Song, S and Wang, Q and Chu, J and Wei, W}, title = {Effect of bone marrow-derived CD11b(+)F4/80 (+) immature dendritic cells on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {63}, number = {5}, pages = {357-367}, pmid = {24458308}, issn = {1420-908X}, mesh = {Animals ; Antigens, Differentiation/*analysis ; Arthritis, Experimental/*immunology/therapy ; Bone Marrow Cells/*physiology ; CD11b Antigen/*analysis ; Cell Proliferation ; Cells, Cultured ; Cytokines/*physiology ; Dendritic Cells/*physiology ; Interleukin-10/physiology ; Interleukin-17/physiology ; Male ; Mice ; Mice, Inbred DBA ; Thymocytes/physiology ; }, abstract = {OBJECTIVE: To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis (CIA).<br><br>METHODS: BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine 2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)-&#x3b2;1 and mixed leukocyte reaction (MLR). CIA was established in DBA/1 mice by immunization with type II collagen. CIA mice were injected intravenously with BM CD11b(+)F4/80(+)iDC three times after immunization. The effect of BM CD11b(+)F4/80(+)iDC on CIA was evaluated by the arthritis index, joint histopathology, body weight, thymus index, thymocytes proliferation, IL-1&#x3b2;, tumor necrosis factor (TNF)-&#x3b1;, IL-17, IL-10 and TGF-&#x3b2;1 levels.<br><br>RESULTS: BM CD11b(+)F4/80(+)iDC induced with rmGM-CSF and rmIL-4 expressed high levels of TLR-2, IDO, IL-10 and TGF-&#x3b2;1. Infusion of BM CD11b(+)F4/80(+)iDC in CIA mice significantly reduced the arthritis index and pathological scores of joints, recovered the weight, decreased the thymus index and inhibited thymocyte proliferation. Levels of IL-1&#x3b2;, TNF-&#x3b1; and IL-17 were decreased in BM CD11b(+)F4/80(+)iDC-treated mice.<br><br>CONCLUSIONS: BM CD11b(+)F4/80(+)iDC can be induced successfully with rmGM-CSF and rmIL-4. BM CD11b(+)F4/80(+)iDC treatment can ameliorate the development and severity of CIA by regulating the balance between pro-inflammatory cytokines and anti-inflammatory cytokines.}, }
@article {pmid24451159, year = {2014}, author = {Peressin, M and Proust, A and Schmidt, S and Su, B and Lambotin, M and Biedma, ME and Laumond, G and Decoville, T and Holl, V and Moog, C}, title = {Efficient transfer of HIV-1 in trans and in cis from Langerhans dendritic cells and macrophages to autologous T lymphocytes.}, journal = {AIDS (London, England)}, volume = {28}, number = {5}, pages = {667-677}, doi = {10.1097/QAD.0000000000000193}, pmid = {24451159}, issn = {1473-5571}, mesh = {CD4-Positive T-Lymphocytes/*virology ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/*virology ; Flow Cytometry ; HIV Core Protein p24/analysis ; HIV Infections/*virology ; HIV-1/*isolation &amp; purification ; Humans ; Infant, Newborn ; Macrophages/*virology ; Time Factors ; }, abstract = {OBJECTIVE: The chronology of HIV infection in mucosal tissue after sexual transmission is unknown. Several potential HIV target cells are present at these sites, including dendritic cells, macrophages, and CD4(+) T lymphocytes. Dendritic cells and macrophages are antigen-presenting cells (APCs) and are thus involved in cross-talk with T cells. This close contact may favor efficient HIV-1 transfer to T lymphocytes, resulting in rapid HIV-1 dissemination.<br><br>DESIGN: We investigated the role of APCs in HIV transfer to T cells by incubating Langerhans cells and interstitial dendritic cells (IDCs) or monocyte-derived macrophages (MDMs) with HIV for 2&#x200a;h before addition of uninfected autologous CD4(+) T lymphocytes.<br><br>METHODS: HIV infection was recorded after different time points. Following staining, the measurement of intracellular p24 in the different cell populations was analyzed by flow cytometry.<br><br>RESULTS: We showed that Langerhans cells/IDCs and macrophages efficiently transferred HIV to CD4(+) T cells. Interestingly, a rapid HIV transfer in trans predominated in MDMs, whereas cis transfer mainly occurred in Langerhans cells/IDC cocultures. Neutralizing antibody 2G12, added to HIV-loaded APCs, efficiently blocked both the trans and the cis infection of T cells.<br><br>CONCLUSION: These findings highlight the major contributions of various mucosal cells in HIV dissemination and suggest that HIV hijacks the different properties of APCs to favor its dissemination through the body. They emphasize the role of macrophages in the rapid transmission of HIV to T lymphocytes at mucosal sites, dendritic cells being prone to migration to lymphoid organ for subsequent dissemination by cis transfer.}, }
@article {pmid24425047, year = {2014}, author = {Sikora, MJ and Cooper, KL and Bahreini, A and Luthra, S and Wang, G and Chandran, UR and Davidson, NE and Dabbs, DJ and Welm, AL and Oesterreich, S}, title = {Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response.}, journal = {Cancer research}, volume = {74}, number = {5}, pages = {1463-1474}, pmid = {24425047}, issn = {1538-7445}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; P30CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents, Hormonal/*pharmacology ; Breast Neoplasms/drug therapy/genetics/metabolism ; Carcinoma, Lobular/*drug therapy/*genetics/metabolism ; Cell Line, Tumor ; Estrogens/*genetics/metabolism ; Female ; Gene Expression/drug effects/*genetics ; Humans ; MCF-7 Cells ; Middle Aged ; Receptor, Fibroblast Growth Factor, Type 1/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Signal Transduction/drug effects/genetics ; Tamoxifen/*pharmacology ; }, abstract = {Invasive lobular carcinoma (ILC) is a histologic subtype of breast cancer that is frequently associated with favorable outcomes, as approximately 90% of ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest that patients with ILC receiving adjuvant endocrine therapy may not benefit as much as patients with invasive ductal carcinoma. On the basis of these observations, we characterized ER function and endocrine response in ILC models. The ER-positive ILC cell lines MDA MB 134VI (MM134) and SUM44PE were used to examine the ER-regulated transcriptome via gene expression microarray analyses and ER ChIP-Seq, and to examine response to endocrine therapy. In parallel, estrogen response was assessed in vivo in the patient-derived ILC xenograft HCI-013. We identified 915 genes that were uniquely E2 regulated in ILC cell lines versus other breast cancer cell lines, and a subset of these genes were also E2 regulated in vivo in HCI-013. MM134 cells were de novo tamoxifen resistant and were induced to grow by 4-hydroxytamoxifen, as well as other antiestrogens, as partial agonists. Growth was accompanied by agonist activity of tamoxifen on ER-mediated gene expression. Though tamoxifen induced cell growth, MM134 cells required fibroblast growth factor receptor (FGFR)-1 signaling to maintain viability and were sensitive to combined endocrine therapy and FGFR1 inhibition. Our observation that ER drives a unique program of gene expression in ILC cells correlates with the ability of tamoxifen to induce growth in these cells. Targeting growth factors using FGFR1 inhibitors may block survival pathways required by ILC and reverse tamoxifen resistance.}, }
@article {pmid24419371, year = {2013}, author = {Vucicevic, D and Carey, EJ and Karlin, NJ}, title = {Trastuzumab-induced hepatotoxicity: a case report.}, journal = {Breast care (Basel, Switzerland)}, volume = {8}, number = {2}, pages = {146-148}, pmid = {24419371}, issn = {1661-3791}, abstract = {BACKGROUND: Trastuzumab is a humanized monoclonal antibody approved for the treatment of breast cancer with HER2 amplification and/or overexpression. There are only 2 prior cases of trastuzumab-related hepatotoxicity reported in the literature.<br><br>CASE REPORT: We report the case of a 60-year-old woman who was treated with trastuzumab for stage I invasive ductal carcinoma of the right breast. She successfully completed 6 months of therapy when an increase in liver transaminases was noted on routine examination. A full work-up for causes of acute and chronic liver disease was negative. After review of the patient's medication list, trastuzumab was thought to be the most likely culprit for the liver injury, based on timing of administration and rise in liver enzymes.}, }
@article {pmid24411296, year = {2014}, author = {Benkerroum, Z and Babahabib, A and Kouach, J and Chahdi, H and Al Bouzidi, A and Moussaoui Rehali, D and Dehayni, M}, title = {[Metrorrhagia disclosing a synchronous bilateral breast cancer: report of a case].}, journal = {Gynecologie, obstetrique &amp; fertilite}, volume = {42}, number = {5}, pages = {360-364}, doi = {10.1016/j.gyobfe.2013.11.009}, pmid = {24411296}, issn = {1769-6682}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology/secondary ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Metrorrhagia/*etiology ; Middle Aged ; Neoplasms, Multiple Primary/pathology ; Uterine Cervical Neoplasms/diagnosis/*secondary ; }, abstract = {Genital metastases are very rarely indicative of breast cancer; they are exceptionally located at the cervix. These atypical locations are more common when it comes to a metastatic breast cancer or a histological infiltrating lobular type. The simultaneous association of a lobular and a ductal infiltrating cancer under a synchronous bilateral breast cancer still remains a rare entity. In this work, we report the observation of a woman aged 48 who has a synchronous bilateral breast cancer, of different histological types, and who reported at first a genital bleeding which is caused by a metastasis in the cervix of the uterus.}, }
@article {pmid24394137, year = {2013}, author = {Kameyama, A and Noda, T and Hatano, H and Dono, K and Oshima, K and Miyake, M and Komori, T and Kawanishi, K and Imamura, H and Morita, S and Iwazawa, T and Akagi, K and Kitada, M}, title = {[A case of a patient with giant mucinous cystadenocarcinoma who presented with abdominal pain].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {40}, number = {12}, pages = {2437-2440}, pmid = {24394137}, issn = {0385-0684}, mesh = {Abdominal Pain/*etiology ; Adult ; Cystadenocarcinoma, Mucinous/complications/*surgery ; Female ; Humans ; Neoplasm Invasiveness ; Pancreatic Neoplasms/complications/*pathology/surgery ; Treatment Outcome ; }, abstract = {We report a case of a patient in whom a giant mucinous cystadenocarcinoma was treated with distal pancreatectomy. A 37-year-old woman was admitted to the hospital complaining of intermittent epigastric pain. The laboratory data revealed a marked increase in serum levels of carcinoembryonic antigen(CEA 22 ng/mL), cancer antigen(CA) 19-9(258,129 U/ mL), and CA125 (53 U/mL). A computed tomography (CT) scan revealed a cystic tumor, 15 cm in diameter, in the body of the pancreas. The tumor presented as a multilocular cyst with enhanced nodules. On positron emission tomography (PET)-CT,[ 18F] fluorodeoxyglucose uptake by the nodules of the cyst was noted. Under the diagnosis of malignant mucinous cystic neoplasm, we performed distal pancreatectomy, splenectomy, partial gastrectomy, and left adrenalectomy because the tumor was suspected to be invading the stomach and left adrenal gland. The tumor was histologically diagnosed as invasive mucinous cystadenocarcinoma with ovarian-like stroma. The patient survived for 14 months after surgery without tumor recurrence. Invasive mucinous cystadenocarcinoma of the pancreas has high rates of lymph node metastasis and early recurrence after surgery. We believe that we would have had to perform complete tumor resection equivalent to that of invasive ductal carcinoma of the pancreas if the mucinous cystic neoplasm was found to be malignant preoperatively.}, }
@article {pmid24394131, year = {2013}, author = {Oshida, S and Hayashi, K and Habiro, T and Hatate, K and Sengoku, N}, title = {[A case of acute appendicitis which occurred during chemotherapy for breast cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {40}, number = {12}, pages = {2417-2419}, pmid = {24394131}, issn = {0385-0684}, mesh = {Acute Disease ; Adenocarcinoma, Scirrhous/*drug therapy/surgery ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Appendicitis/complications/*surgery ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration &amp; dosage ; Docetaxel ; Female ; Humans ; Mastectomy, Segmental ; Sentinel Lymph Node Biopsy ; Taxoids/administration &amp; dosage ; }, abstract = {The patient was a 66-year-old woman with left breast cancer who underwent left segmental mastectomy with sentinel lymph node biopsy. The histopathological diagnosis was estrogen receptor-positive (ER+), progesterone receptor-positive(PgR+), human epidermal growth factor receptor-2-equivocal(HER2()2+)(with no HER2 gene amplification by fluorescence in-situ hybridization analysis) invasive ductal carcinoma (scirrhous carcinoma) with Ki-67 expression of less than 10% (pathological T1c, N0, M0, stage I). The patient requested chemotherapy, and 4 cycles of docetaxel plus cyclophosphamide (TC) were scheduled. Fever and epigastric pain developed on day 13 of cycle 2. On day 22, the patient was examined before the third cycle of TC, and right lower abdominal pain was reported. Computed tomography revealed appendicitis and an intraperitoneal abscess. She was admitted to the hospital and underwent partial ileocecal resection. The patient was discharged on the 12th postoperative day with no further complications. Acute abdomen during chemotherapy for malignant tumors has been reported sporadically in patients with leukemia. A diagnosis of acute abdomen in patients undergoing cancer treatment requires careful assessment of gastrointestinal symptoms such as nausea and vomiting during chemotherapy, fever associated with granulocytopenia, and findings indicative of local inflammation. The patient in this case recovered uneventfully because imaging studies and surgery were performed promptly after presentation.}, }
@article {pmid24394124, year = {2013}, author = {Yabe, N and Murai, S and Shimizu, H and Kitasato, K and Yoshikawa, T and Oto, I and Nakadai, J and Jinno, H and Kitagawa, Y}, title = {[A case of effective trastuzumab plus gemcitabine therapy for human epidermal growth factor receptor 2-positive breast cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {40}, number = {12}, pages = {2396-2398}, pmid = {24394124}, issn = {0385-0684}, mesh = {Aged ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/drug therapy/secondary ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/surgery ; Combined Modality Therapy ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Female ; Humans ; Receptor, ErbB-2/analysis ; Trastuzumab ; Gemcitabine ; }, abstract = {A 71-year-old postmenopausal woman was undergoing treatment for depression. She visited the hospital with a chief complaint of fibrosclerosis of the entire left breast 8 years previously. She was diagnosed as having stage IV(T3N1M1b) left breast cancer (papillotubular>scirrhous carcinoma, g+, f+, estrogen receptor [ER]-negative, progesterone receptor [PgR]-negative, and human epidermal growth factor receptor 2[ HER2/neu]-positive[ 3+]). Synchronous bone metastases were detected in the left tenth rib, the eleventh dorsal vertebra, and in the area spanning the lower lumbar to sacral vertebrae. First-line treatment was systemic therapy with 4 cycles of Adriamycin and cyclophosphamide (AC) followed by 4 cycles of trastuzumab and paclitaxel. The breast mass initially observed on clinical imaging disappeared and only calcifications were observed. Bone metastases were detected only in the left tenth rib. As an additional therapy, 3-dimensional radiotherapy(50 Gy/25 fractions), which irradiated the left mammary gland, axilla, and supraclavicular fossa, was administered. The tumor was well controlled for approximately 3 years. However, a gradual increase in the level of carcinoembryonic antigen(CEA) was accompanied by an increase in the left breast mass and enlargement of left axillary lymph nodes. Modified radical mastectomy (Bt+Ax [level I]) was performed for this condition 3 years ago. Papillotubular-type invasive ductal carcinoma (INF β, ly3, v0, g+, f+, s+, nuclear grade 3 [atypia 3+mitosis 3]) was diagnosed histopathologically. Lymph node metastases were also detected. As histopathological examination of the bone metastatic lesion showed no progression, administration of lapatinib and capecitabine was initiated. After 15 cycles of treatment, enlarged right axillary lymph nodes were observed and local excision was performed. Histopathological examination revealed recurrence of the breast cancer. The patient was diagnosed as having grade 3(atypia 3, mitosis 2) breast cancer(ER-negative, PgR-negative, HER2/neu positive[ 3+], and MIB-1 index 50%). The response to treatment with lapatinib and capecitabine was progressive disease(PD), and therefore, trastuzumab and gemcitabine therapy was selected. Currently, the patient has undergone 30 cycles of this regimen and the tumor is well controlled. This regimen was considered effective for the treatment of patients with HER2-positive metastatic breast cancer.}, }
@article {pmid24391224, year = {2013}, author = {Brakohiapa, EK and Armah, GE and Clegg-Lamptey, JN and Brakohiapa, WO}, title = {Pattern of breast diseases in Accra: review of mammography reports.}, journal = {Ghana medical journal}, volume = {47}, number = {3}, pages = {101-106}, pmid = {24391224}, issn = {2616-163X}, mesh = {Adult ; Age Distribution ; Aged ; Breast Neoplasms/complications/*diagnostic imaging ; Carcinoma, Ductal, Breast/complications/*diagnostic imaging ; *Early Detection of Cancer ; Female ; Ghana ; Humans ; *Mammography ; Middle Aged ; Pain/etiology ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVES: To document the mammographic patterns in females seeking medical attention in Accra.<br><br>DESIGN: An analytic retrospective study was conducted using data extracted from mammography request forms and corresponding radiological reports of 180 females.<br><br>SETTING: The radiology departments of Korle-Bu Teaching Hospital the Trust Hospital and Medical Imaging Ghana all located in Accra.<br><br>RESULTS: One hundred and eighty radiologic request forms for mammographic evaluations and their corresponding reports from the study period were reviewed. The mean age of the study population was 48.7 years (SD=10.0), and the median age group was the 41-50 group. There were more screening mammography evaluations (115 examinations) than diagnostic mammography evaluations (65 examinations). Most of the cases diagnosed as breast cancer were in the age group 41-50 years. Benign lesions were commoner than cancer (55 and 16 cases respectively). The commonest presenting complaint was of pain.<br><br>CONCLUSION: The larger number of screening mammographic evaluations conducted for asymptomatic females during the study period, as compared to diagnostic mammographic evaluations for symptomatic females, suggests that educational programs on early breast cancer detection are having a positive impact on the target population. The observation that 22.8% of lesions had features suggestive of breast cancer in the study is significantly high to also warrant intensification of the existing awareness programs. As non-specific masses were the most common radiographically observed lesions, hospitals equipped with sonography and biopsy facilities that compliment their mammography are better suited for thorough breast disease evaluation.}, }
@article {pmid24388733, year = {2014}, author = {Guillot, E and Vaysse, C and Goetgeluck, J and Falcou, MC and Couturaud, B and Fitoussi, A and Fourchotte, V and Laki, F and Malhaire, C and Sigal-Zafrani, B and Sastre-Garau, X and Bollet, MA and Mosseri, V and Reyal, F}, title = {Extensive pure ductal carcinoma in situ of the breast: identification of predictors of associated infiltrating carcinoma and lymph node metastasis before immediate reconstructive surgery.}, journal = {Breast (Edinburgh, Scotland)}, volume = {23}, number = {2}, pages = {97-103}, doi = {10.1016/j.breast.2013.12.002}, pmid = {24388733}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*secondary/surgery ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mammaplasty/methods ; Middle Aged ; Risk Factors ; }, abstract = {AIM: To identify predictors for infiltrating carcinoma and lymph node involvement, before immediate breast reconstructive surgery, in patients with an initial diagnosis of extensive pure ductal carcinoma in situ of the breast (DCIS).<br><br>PATIENTS AND METHODS: Between January 2000 and December 2009, 241 patients with pure extensive DCIS in preoperative biopsy had underwent mastectomy. Axillary staging (sentinel node and/or axillary dissection) was performed in 92% (n = 221) of patients. Patients with micro-invasive lesions at initial diagnosis, recurrence or contralateral breast cancer were excluded.<br><br>RESULTS: Respectively 14% and 21% of patients had a final diagnosis of micro-invasive carcinoma (MIC) and invasive ductal carcinoma (IDC). Univariate analysis showed that the following variables at diagnosis were significantly correlated with the presence of either MIC or IDC in the mastectomy specimen: palpable tumor (p = 0.002), high grade DCIS (p = 0.002) and detection of an opacity by mammography (p = 0.019). Axillary lymph node (ALN) involvement was reported in 9% of patients. Univariate analysis suggested that a body mass index higher than 25 (p = 0.007), a palpable tumor (p = 0.012) and the detection of an opacity by mammography (p = 0.044) were associated with an increased rate of ALN involvement.<br><br>CONCLUSION: Skin-sparing mastectomy and immediate breast reconstruction (IBRS) has become increasingly popular, especially for patients with extended DCIS of the breast. This study confirmed that extended DCIS is associated with a substantial risk of finding MIC or IDC on the surgical specimen but also ALN involvement. Adjuvant systemic treatment and/or radiotherapy could be indicated for some of these patients after the surgery. Patients should be informed of the rate of 1) complications associated to IBRS that will potentially delay the introduction of systemic or local therapy 2) complications associated to radiotherapy after IBRS.}, }
@article {pmid24384092, year = {2014}, author = {Tan, D and Chen, KE and Deng, C and Tang, P and Huang, J and Mansour, T and Luben, RA and Walker, AM}, title = {An N-terminal splice variant of human Stat5a that interacts with different transcription factors is the dominant form expressed in invasive ductal carcinoma.}, journal = {Cancer letters}, volume = {346}, number = {1}, pages = {148-157}, pmid = {24384092}, issn = {1872-7980}, support = {R01 DK061005/DK/NIDDK NIH HHS/United States ; Z01 DK061005//Intramural NIH HHS/United States ; }, mesh = {Base Sequence ; Blotting, Western ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Humans ; Molecular Sequence Data ; Protein Isoforms ; Reverse Transcriptase Polymerase Chain Reaction ; STAT5 Transcription Factor/*genetics/metabolism ; Signal Transduction ; Transcription Factors/genetics/metabolism ; Transfection ; Tumor Suppressor Proteins/*genetics/metabolism ; Up-Regulation ; }, abstract = {We have identified a new variant of human Stat5a, found at higher ratios to full-length Stat5a in invasive ductal carcinoma versus contiguous normal tissue. The variant, missing exon 5, inhibits p21 and Bax production and increases cell number. After prolactin stimulation, only full-length Stat5a interacts with the vitamin D and retinoid X receptors, whereas only Δ5 Stat5a interacts with activating protein 1-2 and specificity protein 1. Prolactin also oppositely regulates interaction of the two Stat5a forms with β-catenin. We propose that a change in splicing leading to upregulation of this new isoform is a pathogenic aspect of invasive ductal carcinoma.}, }
@article {pmid24377578, year = {2014}, author = {Seifi-Alan, M and Shamsi, R and Ghafouri-Fard, S and Mirfakhraie, R and Zare-Abdollahi, D and Movafagh, A and Modarressi, MH and Kazemi, G and Geranpayeh, L and Najafi-Ashtiani, M}, title = {Expression analysis of two cancer-testis genes, FBXO39 and TDRD4, in breast cancer tissues and cell lines.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {11}, pages = {6625-6629}, doi = {10.7314/apjcp.2013.14.11.6625}, pmid = {24377578}, issn = {2476-762X}, mesh = {Antigens, Neoplasm/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; F-Box Proteins/*genetics/metabolism ; Female ; Fibroadenoma/*genetics/metabolism/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleoproteins/*genetics/metabolism ; Tumor Cells, Cultured ; }, abstract = {Breast cancer accounts for one third of new cancer cases among women. The need for biomarkers for early detection is the stimulus to researchers to evaluate altered expression of genes in tumours. Cancer-testis (CT) genes are a group with limited expression in normal tissues except testis but up-regulation in a wide variety of cancers. We here evaluated expression of two CT genes named FBXO39 and TDRD4 in 32 invasive ductal carcinoma samples, 10 fibroadenomas and 6 normal breast tissue samples, in addition to two breast cancer cell lines, MCF-7 and MDA-MB-231, by the means of quantitative real time RT-PCR. FBXO39 showed significant up-regulation in invasive ductal carcinoma samples in comparison with normal samples. It also was expressed in both cell lines and after RHOXF1 gene knock down it was down-regulated in MCF-7 but up-regulated in the MDA-MB-231 cell line. TDRD4 was not expressed in the MCF-7 cell line and any of the tissue samples except testis. However, it was expressed in MDA-MB-231 and was up-regulated after RHOXF1 gene knock down. Our results show that FBXO39 but not TDRD4 can be used for cancer detection and if proved to be immunogenic, might be a putative candidate for breast cancer immunotherapy.}, }
@article {pmid24375061, year = {2013}, author = {Faghih, Z and Rezaeifard, S and Safaei, A and Ghaderi, A and Erfani, N}, title = {IL-17 and IL-4 producing CD8+ T cells in tumor draining lymph nodes of breast cancer patients: positive association with tumor progression.}, journal = {Iranian journal of immunology : IJI}, volume = {10}, number = {4}, pages = {193-204}, pmid = {24375061}, issn = {1735-367X}, mesh = {Adult ; Breast Neoplasms/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Carcinogenesis ; Carcinoma/*immunology ; Cell Separation ; Cells, Cultured ; Disease Progression ; Down-Regulation ; Female ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Interferon-gamma/genetics/metabolism ; Interleukin-17/metabolism ; Interleukin-4/metabolism ; Lymph Nodes/*pathology ; Lymphatic Metastasis/immunology ; Middle Aged ; T-Lymphocyte Subsets/*immunology ; }, abstract = {BACKGROUND: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile.<br><br>OBJECTIVE: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer.<br><br>METHODS: Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes (Tc1, Tc2 and Tc17) were quantified in CD8+ T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status.<br><br>RESULTS: The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma (IDC), the mean expression of IFN-&#x3b3; by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages (p=0.018 and p=0.009, respectively).<br><br>CONCLUSION: As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-&#x3b3; by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.}, }
@article {pmid24373403, year = {2013}, author = {Zhou, SJ and Guo, H}, title = {[Ki-67 expression and significance of different molecular subtypes of breast invasive ductal carcinoma].}, journal = {Zhonghua yi xue za zhi}, volume = {93}, number = {36}, pages = {2895-2897}, pmid = {24373403}, issn = {0376-2491}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Ki-67 Antigen/genetics/*metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {OBJECTIVE: To analyze Ki-67 expression and explore its significance in different molecular subtypes of breast invasive ductal carcinoma (IDC).<br><br>METHODS: The expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and Ki-67 were detected in 126 cases of IDC by immunohistochemical staining. Then the molecular subtype of each case of IDC was determined.Statistical analysis was performed to determine the relationship between Ki-67 expression and the molecular subtypes with clinicopathological features of IDC.<br><br>RESULTS: There was no statistically significant difference of Ki-67 expression in age and tumor size (P > 0.05).However, significant difference existed in histological grading and lymph node metastasis (P < 0.05). The expression level of Ki-67 was negatively correlated with ER expression (r = -0.273, P = 0.002) and PR expression (r = -0.242, P = 0.007) and positively with HER-2 expression (r = 0.245, P = 0.006) . A low expression of Ki-67 was in LumianlA subtype (17/17) and high expression in other molecular subtypes. Moreover, the rate of high expression (Ki-67 LI>50%) in each subtype progressively increased with the degree of molecular typing and Ki-67 expression in different molecular subtypes showed significant difference (P < 0.05).<br><br>CONCLUSIONS: The expression level of Ki-67 is correlated with histological grading and molecular type of IDC. High expression of Ki-67 carries poor prognosis. Thus it is necessary to perform a variety of routine clinicopathological examinations, such as Ki-67, ER, PR and HER-2.}, }
@article {pmid24368622, year = {2014}, author = {Moore, T and Rodriguez, A and Bakken, JS}, title = {Fecal microbiota transplantation: a practical update for the infectious disease specialist.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {58}, number = {4}, pages = {541-545}, doi = {10.1093/cid/cit950}, pmid = {24368622}, issn = {1537-6591}, mesh = {Biological Therapy/*methods ; Drugs, Investigational/*therapeutic use ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; *Investigational New Drug Application ; United States ; }, abstract = {Fecal microbiota transplantation (FMT) has been shown to be a superior therapeutic modality for the treatment of recurrent Clostridium difficile infection (RCDI). Recently the US Food and Drug Administration (FDA) determined that human stool should be classified as a biological agent and its use should be regulated to ensure patient safety. Consequently, the FDA determined that prescribers of FMT must possess an approved investigational new drug (IND) permit to administer FMT for the purpose of conducting research or treating any gastrointestinal condition other than RCDI. Although an IND is not required for use of FMT to treat RCDI, an IND is strongly encouraged and may ultimately be required. This article provides step-by-step guidance to infectious disease specialists on how to navigate the regulatory requirements and successfully obtain an IND before they can begin to use FMT as part of their clinical practice.}, }
@article {pmid24366300, year = {2014}, author = {Airley, RE and McHugh, P and Evans, AR and Harris, B and Winchester, L and Buffa, FM and Al-Tameemi, W and Leek, R and Harris, AL}, title = {Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression.}, journal = {British journal of cancer}, volume = {110}, number = {3}, pages = {715-723}, pmid = {24366300}, issn = {1532-1827}, mesh = {Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*biosynthesis/genetics ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*genetics/pathology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Glucose Transporter Type 1/biosynthesis/genetics ; Humans ; Hypoxia/*genetics/pathology ; Immunohistochemistry ; MCF-7 Cells ; Prognosis ; }, abstract = {BACKGROUND: The lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) may play a key role in malignant progression of breast cancer by allowing metabolic adaptations to take place in response to changes in oxygenation.<br><br>METHODS: Immunohistochemical analysis of ChREBP was carried out in human breast tumour tissue microarrays representative of malignant progression from normal breast through to metastatic cancer. The ChREBP protein and mRNA expressions were then analysed in a series of breast cancers for correlative analysis with common and breast-specific hypoxia signatures, and survival.<br><br>RESULTS: In invasive ductal carcinoma, ChREBP correlated significantly with mean 'downregulated' hypoxia scores (r=0.3, P<0.015, n=67) and in two distinct breast progression arrays, ChREBP protein also increased with malignant progression (P<0.001). However, bioinformatic analysis of a large data set (2136 cases) revealed an apparent reversal in the relationship between ChREBP mRNA level and clinical outcome - not only being significantly correlated with increased survival (log rank P<0.001), but also downregulated in malignant tissue compared with adjacent normal tissue.<br><br>CONCLUSION: The ChREBP expression may be reflective of an aerobic metabolic phenotype that may conflict with hypoxia-induced signalling but provide a mechanism for growth at the oxygenated edge of the tumours.}, }
@article {pmid24356765, year = {2013}, author = {Alipour, S and Seifollahi, A and Anbiaee, R}, title = {Lactating breast abscess: a rare presentation of adenosquamous breast carcinoma.}, journal = {Singapore medical journal}, volume = {54}, number = {12}, pages = {e247-9}, doi = {10.11622/smedj.2013251}, pmid = {24356765}, issn = {2737-5935}, mesh = {Adult ; Breast Neoplasms/*diagnosis/drug therapy/radiotherapy/surgery ; Carcinoma, Adenosquamous/*diagnosis/drug therapy/radiotherapy/surgery ; Carcinoma, Ductal, Breast/diagnosis/drug therapy/radiotherapy/surgery ; Female ; Humans ; Inflammation ; *Lactation ; Risk Factors ; Treatment Outcome ; }, abstract = {We report the case of a 33-year-old lactating woman who presented with a 10-cm breast abscess. Biopsy of the abscess wall revealed a poorly differentiated invasive ductal carcinoma. The patient had no family history of breast cancer or other risk factors for breast cancer. The disease was considered to be a large noninflammatory invasive breast cancer, for which the patient received neoadjuvant chemotherapy, breast-conserving surgery using axillary dissection (the patient did not consent to a mastectomy), and postoperative radiotherapy. Final histologic examination revealed a 4-cm, triple negative, high-grade adenosquamous carcinoma. At follow-up four years after surgery, the patient was doing well with no signs of recurrence. Adenosquamous carcinoma is an extremely rare disease that mainly presents in low-grade forms. High-grade forms are aggressive and frequently present with axillary involvement. To the best of our knowledge, there has been no report of adenosquamous carcinoma presenting as a breast abscess in the literature. The case we report highlights that, although rare, cancer should be considered in lactating breast abscesses.}, }
@article {pmid24354864, year = {2013}, author = {Shindo, K and Aishima, S and Ohuchida, K and Fujiwara, K and Fujino, M and Mizuuchi, Y and Hattori, M and Mizumoto, K and Tanaka, M and Oda, Y}, title = {Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas.}, journal = {Molecular cancer}, volume = {12}, number = {1}, pages = {168}, pmid = {24354864}, issn = {1476-4598}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*metabolism/mortality/pathology ; Coculture Techniques ; Disease Progression ; Female ; Fibroblasts/*metabolism ; Gene Expression ; Humans ; Kaplan-Meier Estimate ; Male ; Membrane Glycoproteins/genetics/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*metabolism/mortality/pathology ; Proportional Hazards Models ; RNA, Messenger/genetics/metabolism ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer.<br><br>METHODS: Expression of PDPN in pancreatic IDCs was assessed by immunohistochemical examination in 105 patients who underwent pancreatic resection. Primary CAFs were established from pancreatic cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis were performed to investigate PDPN expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the functional differences between PDPN+&#x2009;CAFs and PDPN- CAFs using indirect co-culture with pancreatic cancer cell lines. We also investigated the culture conditions to regulate PDPN expression in CAFs.<br><br>RESULTS: PDPN expression in stromal fibroblasts was associated with lymphatic vessel invasion (P&#x2009;=&#x2009;0.0461), vascular invasion (P&#x2009;=&#x2009;0.0101), tumor size &#x2265; 3 cm (P&#x2009;=&#x2009;0.0038), histological grade (P&#x2009;=&#x2009;0.0344), Union for International Cancer Control classification T stage (P&#x2009;=&#x2009;0.029), and shorter survival time (P&#x2009;<&#x2009;0.0001). Primary CAFs showed heterogeneous PDPN expression in vitro. Moreover, migration and invasion of pancreatic cancer cell lines (PANC-1 and SUIT-2) were associated with PDPN expression in CAFs (P&#x2009;<&#x2009;0.01) and expression of CD10, matrix metalloproteinase (MMP) 2, and MMP3. In cultured CAFs, PDPN positivity changed over time under several conditions including co-culture with cancer cells, different culture media, and addition of growth factor.<br><br>CONCLUSIONS: PDPN-expressing CAFs enhance the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an independent predictor of poor outcome. Understanding the regulation of the tumor microenvironment is an important step towards developing new therapeutic strategies.}, }
@article {pmid24333009, year = {2014}, author = {Cuzick, J and Sestak, I and Forbes, JF and Dowsett, M and Knox, J and Cawthorn, S and Saunders, C and Roche, N and Mansel, RE and von Minckwitz, G and Bonanni, B and Palva, T and Howell, A and , }, title = {Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.}, journal = {Lancet (London, England)}, volume = {383}, number = {9922}, pages = {1041-1048}, doi = {10.1016/S0140-6736(13)62292-8}, pmid = {24333009}, issn = {1474-547X}, support = {5032/CRUK_/Cancer Research UK/United Kingdom ; BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; C569/A5032/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Aromatase Inhibitors/*therapeutic use ; Breast Neoplasms/*prevention &amp; control ; Carcinoma, Ductal, Breast/*prevention &amp; control ; Carcinoma, Intraductal, Noninfiltrating/*prevention &amp; control ; Carcinoma, Lobular/*prevention &amp; control ; Double-Blind Method ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Nitriles/*therapeutic use ; Postmenopause ; Proportional Hazards Models ; Risk Factors ; Treatment Outcome ; Triazoles/*therapeutic use ; }, abstract = {BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.<br><br>METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319.<br><br>FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5&#xb7;0 years (IQR 3&#xb7;0-7&#xb7;1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0&#xb7;47, 95% CI 0&#xb7;32-0&#xb7;68, p<0&#xb7;0001). The predicted cumulative incidence of all breast cancers after 7 years was 5&#xb7;6% in the placebo group and 2&#xb7;8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0&#xb7;836).<br><br>INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer.<br><br>FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.}, }
@article {pmid24331309, year = {2014}, author = {Babar, M and Madani, R and Thwaites, L and Jackson, PA and Devalia, HL and Chakravorty, A and Irvine, TE and Layer, GT and Kissin, MW}, title = {A differential intra-operative molecular biological test for the detection of sentinel lymph node metastases in breast carcinoma. An extended experience from the first U.K. centre routinely offering the service in clinical practice.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {40}, number = {3}, pages = {282-288}, doi = {10.1016/j.ejso.2013.10.030}, pmid = {24331309}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/surgery ; Carcinoma, Ductal, Breast/mortality/*secondary/surgery ; Chi-Square Distribution ; Cohort Studies ; Female ; Humans ; Lymph Node Excision/methods ; Lymph Nodes/pathology/surgery ; Middle Aged ; Monitoring, Intraoperative/*methods ; Neoplasm Invasiveness/pathology ; Neoplasm Micrometastasis/pathology ; Neoplasm Staging ; Nucleic Acid Amplification Techniques/*methods ; Oncology Service, Hospital ; Prognosis ; RNA, Messenger/analysis ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Sentinel Lymph Node Biopsy/*methods ; Survival Rate ; United Kingdom ; }, abstract = {INTRODUCTION: One-Step Nucleic acid Amplification (OSNA) is a molecular biological assay of cytokeratin-19 (a breast epithelial marker) mRNA. It can be employed intra-operatively for detection of lymph node metastases in breast carcinoma. Patients with positive sentinel nodes may proceed to axillary lymph node dissection (ALND) level I or higher dependent upon the OSNA quantitative result, during the same surgical procedure, avoiding a second operation and eliminating the technical difficulties possibly associated with delayed ALND.<br><br>AIMS: Our Breast Unit was the first in the UK to implement this novel technique in routine practice. This study reviews our first 44-month data following introduction of OSNA "live" on whole sentinel nodes following an extensive validation study (Snook et&#xa0;al.).(9) METHODS: Data was collected prospectively from the period of introduction 01/12/2008 to 30/08/2012. All patients eligible for sentinel node biopsy were offered OSNA and operations were performed by five consultant breast surgeons. On detection of macro-metastasis a level II/III and for a micro-metastasis a level I ALND was performed.<br><br>RESULTS: A total of 859 patients (1709 sentinel lymph nodes) were analysed. All except one were females. The majority underwent wide local excision (73.4%, n&#xa0;=&#xa0;631) or mastectomy 25% (n&#xa0;=&#xa0;215) and 1.6% (13) underwent SLN biopsy alone. IDC was seen in 79% (n&#xa0;=&#xa0;680) of the patients and 53.5% (n&#xa0;=&#xa0;460) had grade II tumours. One-third (30.8%, n&#xa0;=&#xa0;265) had positive sentinel nodes and had further axillary surgery at the time of SLN biopsy. Of these, 47% (n&#xa0;=&#xa0;125/265) had macro-metastases, 38% (n&#xa0;=&#xa0;101/265) had micro-metastases and 14.7% (n&#xa0;=&#xa0;39/265) had "positive but inhibited" results. Positive non-sentinel lymph nodes (NSLN) were seen in 35% (44/125) of those with macro-metastases; 17.8% (18/101) of the patients with micro-metastases and 10.2% (4/39) of the "positive but inhibited" group.<br><br>CONCLUSION: In our series over a third of our patients had positive lymph nodes detected with OSNA allowing them to proceed directly to axillary surgery at the same operation. This technique eliminates the need for a second operation in sentinel lymph node positive patients and avoids the anxiety waiting for histological results.}, }
@article {pmid24321462, year = {2014}, author = {O'Malley, DP and Zuckerberg, L and Smith, LB and Barry, TS and Gunn, S and Tam, W and Orazi, A and Kim, YS and Weiss, LM}, title = {The genetics of interdigitating dendritic cell sarcoma share some changes with Langerhans cell histiocytosis in select cases.}, journal = {Annals of diagnostic pathology}, volume = {18}, number = {1}, pages = {18-20}, doi = {10.1016/j.anndiagpath.2013.10.003}, pmid = {24321462}, issn = {1532-8198}, mesh = {Comparative Genomic Hybridization ; Dendritic Cell Sarcoma, Interdigitating/*genetics/*pathology ; Histiocytosis, Langerhans-Cell/*genetics/*pathology ; Humans ; }, abstract = {Histiocytic disorders have been noted to have evidence of transdifferentiation; examples of cases with combinations of different lineages have been shown. In our index case, we identified interdigitating dendritic cell (IDC) differentiation in a case of Langerhans cell histiocytosis (LCH). Little is currently known about the genetics of IDC sarcoma (IDCS) because they are exceedingly rare. Using array comparative genomic hybridization (aCGH), we evaluated 4 cases of IDCS and compared them with our index case, as well as genetic abnormalities previously found in LCH. Four cases of paraffin-embedded samples of IDCS and 1 case of LCH with IDC differentiation were evaluated using aCGH. Array CGH results showed no abnormalities in a case of LCH with interdigitating cell differentiation. In 3 of 4 cases of IDCS, genetic abnormalities were identified; 1 case had no identifiable abnormalities. Interdigitating dendritic cell sarcoma case 1 had gains of 3q and 13q; IDCS case 2 had trisomy 12; IDCS case 3 had deletions of 7p, 12p, 16p, 18q, 19q, and 22q; and IDCS case 4 had no detectable abnormalities. Our index case, LCH with IDC differentiation, showed no abnormalities by aCGH. A number of LCH cases do not have detectable genetic abnormalities. In contrast, 3 of 4 cases of IDCS evaluated had identifiable abnormalities by aCGH. Furthermore, 2 of these shared abnormalities, albeit of large genetic regions, with published abnormalities seen in LCH. No recurrent abnormalities were identified in the IDCS cases. However, the possibility of a relationship between IDCS and LCH cannot be entirely excluded by these results.}, }
@article {pmid24316550, year = {2014}, author = {Son, CH and Bae, JH and Shin, DY and Lee, HR and Choi, YJ and Jo, WS and Ho Jung, M and Kang, CD and Yang, K and Park, YS}, title = {CTLA-4 blockade enhances antitumor immunity of intratumoral injection of immature dendritic cells into irradiated tumor in a mouse colon cancer model.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {37}, number = {1}, pages = {1-7}, doi = {10.1097/CJI.0000000000000007}, pmid = {24316550}, issn = {1537-4513}, mesh = {Animals ; Antibodies, Monoclonal/immunology/*pharmacology ; CTLA-4 Antigen/*antagonists &amp; inhibitors/immunology ; Cell Line, Tumor ; Colonic Neoplasms/*immunology/mortality/radiotherapy/therapy ; Dendritic Cells/*immunology/*transplantation ; Disease Models, Animal ; Immunotherapy, Adoptive ; Interferon-gamma/biosynthesis ; Lymphocyte Activation/drug effects/immunology ; Male ; Mice ; T-Lymphocytes, Cytotoxic/immunology ; Th1 Cells/drug effects/immunology ; }, abstract = {Dendritic cells (DCs)-based cancer immunotherapy has been used various strategies to inhibit immune suppressive mechanisms. CD25 antibodies and cyclophosphamide are well-studied immunomodulators through inhibition of regulatory T cells (Treg) and a blockade the immune-checkpoint molecule, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) was recently targeted for immunomodulation. We used anti-CTLA-4 antibody, which is known to induce effective antitumor immunity by facilitating tumor-specific T-cell activation and suppressing Treg cells, as useful immunomodulator to provide a potentiating effect in the intratumoral injection of immature DCs (iDCs) into the irradiated tumor (IR/iDC). Ionizing radiation (IR) was applied at a dose of 10 Gy to the tumor on the right thigh of mice. Then, iDCs were intratumorally injected into the irradiated tumor. Anti-CTLA-4 antibody (100 µg/mouse) was administered intraperitoneally to mice on the same day with every iDCs injection. The growth of distant tumors was inhibited by IR/iDC and this effect was significantly augmented by combination treatment of anti-CTLA-4 antibody. Furthermore, the survival rate of tumor-bearing mice improved more by the combination treatment of anti-CTLA-4 antibody and IR/iDC compared with other groups. It was related to the increased tumor-specific interferon-γ-secreting T cells and CTL activity. Therefore, our results demonstrated that immunomodulator such as anti-CTLA-4 antibody enhances antitumor immunity of intratumoral injection of iDCs into irradiated tumor and suggested a new strategy to get more clinical benefits for cancer treatment.}, }
@article {pmid24309373, year = {2014}, author = {Thakur, C and Lu, Y and Sun, J and Yu, M and Chen, B and Chen, F}, title = {Increased expression of mdig predicts poorer survival of the breast cancer patients.}, journal = {Gene}, volume = {535}, number = {2}, pages = {218-224}, pmid = {24309373}, issn = {1879-0038}, support = {R01 ES017217/ES/NIEHS NIH HHS/United States ; R01 ES020137/ES/NIEHS NIH HHS/United States ; }, mesh = {Breast Neoplasms/*metabolism/*mortality/pathology ; Dioxygenases ; Female ; Gene Expression Regulation, Neoplastic ; Gene Order ; Histone Demethylases ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Nuclear Proteins/genetics/*metabolism ; Prognosis ; }, abstract = {Breast cancer is the most common cancer and the second leading cause of cancer death among women of all races and Hispanic origin populations in the United States. In the present study, we reported that the survival time of the breast cancer patients is influenced by the expression level of mdig, a previously identified lung cancer-associated oncogene encoding a JmjC-domain protein. By checking the expression levels of mRNA and protein of mdig through both RT-PCR and immunohistochemistry in samples from 204 patients, we noticed that about 30% of breast cancer samples showed increased expression of mdig. Correlation of the mdig expression levels with the survival time of the breast cancer patients indicated a clear inverse relationship between mdig expression and patient survival, including poorer overall survival, distant metastasis free survival, relapse free survival, and post-progression survival. Taken together, these data suggest that an increased expression of mdig is an important prognostic factor for poorer survival time of the breast cancer patients.}, }
@article {pmid24305978, year = {2014}, author = {Fortune-Greeley, AK and Wheeler, SB and Meyer, AM and Reeder-Hayes, KE and Biddle, AK and Muss, HB and Carpenter, WR}, title = {Preoperative breast MRI and surgical outcomes in elderly women with invasive ductal and lobular carcinoma: a population-based study.}, journal = {Breast cancer research and treatment}, volume = {143}, number = {1}, pages = {203-212}, pmid = {24305978}, issn = {1573-7217}, support = {P50 CA058223/CA/NCI NIH HHS/United States ; R25 CA116339/CA/NCI NIH HHS/United States ; 5R25CA116339/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/epidemiology/*surgery ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular ; Female ; Humans ; *Magnetic Resonance Imaging ; Mastectomy ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Preoperative Care ; Retreatment ; Retrospective Studies ; Risk Factors ; SEER Program ; Treatment Outcome ; }, abstract = {Existing evidence suggests that preoperative breast magnetic resonance imaging (MRI) might not improve surgical outcomes in the general breast cancer population. To determine if patients differentially benefit from breast MRI, we examined surgical outcomes-initial mastectomy, reoperation, and final mastectomy rates-among patients grouped by histologic type. We identified women diagnosed with early-stage breast cancer from 2004 to 2007 in the SEER-Medicare dataset. We classified patients as having invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), mixed ductal/lobular carcinoma (IDLC) or other histologic type. Medicare claims were used to identify breast MRI and definitive surgeries during the initial surgical treatment episode. We used propensity score methods to account for the differential likelihood of exposure to MRI. Of the 20,332 patients who met our inclusion criteria for this study, 12.2 % had a preoperative breast MRI. Patients with ILC as compared to other histologic groups were most likely to receive MRI [OR 2.32; 95 % CI (2.02-2.67)]. In the propensity score-adjusted analyses, breast MRI was associated with an increased likelihood of an initial mastectomy for all patients and among all histologic subgroups. Among patients with ILC, having a breast MRI was associated with lower odds of a reoperation [OR 0.59; 95 % CI (0.40-0.86)], and an equal likelihood of a final mastectomy compared to similar patients without a breast MRI. Overall and among patients with IDC and IDLC, breast MRI was not significantly associated with a likelihood of a reoperation but was associated with greater odds of a final mastectomy. Our study provides evidence in support of the targeted use of preoperative breast MRI among patients with ILC to improve surgical planning; it does not provide evidence for the routine use of breast MRI among all newly diagnosed breast cancer patients or among patients with IDC.}, }
@article {pmid24304285, year = {2014}, author = {Vacas-Córdoba, E and Bastida, H and Pion, M and Hameau, A and Ionov, M and Bryszewska, M and Caminade, AM and Majoral, JP and Muñoz-Fernández, M&#xc1;}, title = {HIV-antigens charged on phosphorus dendrimers as tools for tolerogenic dendritic cells-based immunotherapy.}, journal = {Current medicinal chemistry}, volume = {21}, number = {16}, pages = {1898-1909}, doi = {10.2174/0929867321666131129114022}, pmid = {24304285}, issn = {1875-533X}, mesh = {Cell Movement ; Cytokines/metabolism ; Dendrimers/chemistry/*therapeutic use ; Dendritic Cells/*immunology/metabolism ; HIV Antigens/*immunology ; Humans ; *Immunotherapy ; Phosphorus/*chemistry ; }, abstract = {AIMS: The objective was to study if cationic phosphorus dendrimers can be used as DC-based vaccine or adjuvant in anti-HIV-1 vaccine development when associated with HIV-1 derived peptides.<br><br>MATERIALS &amp; METHODS: The HIV derived peptides uptake in DC and the phenotype of iDC and mDC were studied using Flow Cytometry analysis. Migration of mDC was evaluated by an in vitro chemotaxis assay. Allogenic T-cells proliferative response induced by DC was studied using Flow Cytometry assays. Cytokines production was analysed by Diaclon DIAplex Th1/Th2/Inflammation kit.<br><br>RESULTS: All phosphorus dendrimers showed the ability to deliver HIV-derived peptides in DC. The phosphorus dendrimers from second and third generations induced important changes in phenotype. Moreover, the treatment of mDC with the second generation dendrimer and derivated dendriplexes modified cellular migratory properties, altered their capacity to stimulate allogenic na&#xef;ve T cells in vitro and impeded the production of pro-inflammatory cytokines.<br><br>CONCLUSIONS: The phosphorus dendrimers cannot be used as vaccines because they would not have the ability to induce an immune response. The cationic phosphorus dendrimers associated with HIV-derived peptides have the ability to deliver peptides as non-viral vectors. However, there are other potential therapeutic applications of these compounds, for instance as topical antiinflammatory agents, as compounds for allograft rejection or autoimmune diseases and as agents inducing specific tolerance with antigen-loaded DC against allergy reaction. Nevertheless, these applications need to be evaluated.}, }
@article {pmid24301790, year = {2013}, author = {Zhang, Y and Meng, FY and Li, WL and Zhou, CX and Guan, Z and Fan, HY}, title = {Association of chemotactic factor receptor 5 gene with breast cancer.}, journal = {Genetics and molecular research : GMR}, volume = {12}, number = {4}, pages = {5289-5300}, doi = {10.4238/2013.November.7.4}, pmid = {24301790}, issn = {1676-5680}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology/therapy ; Female ; Gene Expression Regulation, Neoplastic ; *Genetic Association Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics/metabolism ; Receptor, ErbB-2 ; Receptors, CCR5/*genetics/metabolism ; Risk Factors ; }, abstract = {We designed a 2-stage study to investigate chemotactic factor receptor 5 (CCR5) gene expression in breast cancer tissues and axillary lymph nodes and analyze the association between the CCR5-Î"32 gene polymorphism and the clinical features and prognosis of breast cancer patients. The first stage examined 72 cases of invasive ductal carcinoma and axillary lymph node tissue, 50 cases of breast fibroadenoma tissue, and 40 cases of normal breast tissue. The tissues specimens were embedded in paraffin, and CCR5 expression was detected using immunohistochemical methods. C-erbB-2, p53, Ki-67, estrogen receptor, and progesterone receptor expression were also detected in the breast cancer tissues. The second stage examined 35 cases of surgically removed tissue. Relative expression levels of CCR5 messenger RNA (mRNA) in primary foci, axillary lymph node, and cancer-adjacent tissues of the breast cancer and breast fibroadenoma samples were detected using real-time quantitative reverse transcription-polymerase chain reaction assay. We found that 1) CCR5 mRNA relative expression levels in breast cancer tissue were significantly higher than those in adjacent normal tissue (P < 0.01) and benign tumors (P < 0.05). The relative CCR5 mRNA relative expression level between phase II and phase III breast cancer tissues was statistically significant (P < 0.05). The CCR5 mRNA relative expression level between adjacent normal tissues and fibroadenoma tissues was not significantly different (P > 0.05). 2) Relative CCR5 mRNA expression level was significantly higher in metastatic lymph node tissues than that in non-metastatic lymph nodes (P < 0.05), and 3) CCR5 expression in breast cancer tissue was positively correlated with axillary lymph node metastasis (chi-square = 4.982, P = 0.026, r = 0.305). CCR5 expression was mildly and positively correlated with the oncogene C-erbB-2 (P < 0.05, r = 0.291). 4) CCR5 expression in breast cancer tissue was not correlated with age, menopause, maximum tumor size, tumor phase, p53, Ki-67, estrogen receptor, progesterone receptor, or other clinical features (P > 0.05). We concluded that CCR5 expression significantly increases in breast cancer tissues and metastatic lymph nodes. CCR5 plays a role in breast cancer development and axillary lymph node metastasis. It can be used indirectly as an indicator of axillary lymph node metastasis and prognosis.}, }
@article {pmid24275943, year = {2014}, author = {Erro, R and Lees, AJ and Moccia, M and Picillo, M and Penco, S and Mosca, L and Vitale, C and Barone, P}, title = {Progressive parkinsonism, balance difficulties, and supranuclear gaze palsy.}, journal = {JAMA neurology}, volume = {71}, number = {1}, pages = {104-107}, doi = {10.1001/jamaneurol.2013.5149}, pmid = {24275943}, issn = {2168-6157}, mesh = {Aged ; CADASIL/diagnosis/genetics/physiopathology ; Diagnosis, Differential ; Humans ; Magnetic Resonance Imaging ; Male ; Ocular Motility Disorders/diagnosis/physiopathology ; Parkinsonian Disorders/*diagnosis/*physiopathology ; Supranuclear Palsy, Progressive/*diagnosis/*physiopathology ; Syndrome ; Vestibule, Labyrinth/*physiopathology ; }, abstract = {A 76-year-old man presented with a 4-year history of a progressive parkinsonian syndrome. It started with slowness of gait and mood dysfunction. Symptoms slowly progressed and further included occasional unexplained falls. On examination, he showed a severe parkinsonian syndrome featuring bradykinesia, rigidity (axial > appendicular), and positive pull-test finding. Moreover, there was an upgaze supranuclear palsy and slow saccades on vertical plane. Magnetic resonance imaging was performed that revealed significant basal ganglia lesions and white matter hyperintensities, including periventricular regions and both frontal and temporal subcortical areas, along with moderate widespread atrophy and ventricular enlargement. Here, we reveal the pathological diagnosis and discuss the approach to the clinical data.}, }
@article {pmid24262078, year = {2014}, author = {Giordani, L and Del Pinto, T and Vincentini, O and Felli, C and Silano, M and Viora, M}, title = {Two wheat decapeptides prevent gliadin-dependent maturation of human dendritic cells.}, journal = {Experimental cell research}, volume = {321}, number = {2}, pages = {248-254}, doi = {10.1016/j.yexcr.2013.11.008}, pmid = {24262078}, issn = {1090-2422}, mesh = {Celiac Disease/*therapy ; Cell Differentiation/*drug effects/immunology ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/*drug effects/physiology ; Gliadin/*adverse effects ; Humans ; Oligopeptides/*pharmacology ; Plant Proteins, Dietary/*pharmacology ; Receptors, CCR7/metabolism ; Triticum/*chemistry ; }, abstract = {Celiac disease (CD) is a small intestinal enteropathy, triggered in susceptible individuals by the ingestion of dietary gluten. Dendritic cells (DC) are instrumental in the generation and regulation of immune responses and oversee intestinal immune homeostasis promoting and maintaining oral tolerance to food antigens. The aim of this study was to monitor the effect of peptic-tryptic digest of gliadin (PT-gliadin) on the maturation of human monocyte-derived DC and the impact of pDAV and pRPQ decapeptides in the modulation of PT-gliadin-induced phenotypic and functional DC maturation. Immature DC (iDC) were challenged in vitro with PT-gliadin. In some experiments iDC were pre-treated with pDAV or pRPQ and after 2h PT-gliadin was added to the cultures. We found that PT-gliadin up-regulates the expression of the maturation markers HLA-DR, CD83, CD80 and CD86. The functional consequence of PT-gliadin treatment of iDC is a significant increase in IL-12, TNF-alpha production as well as in their T cell stimulatory capacity. On the contrary, the digest of zein had no effect on DC maturation. Interestingly, we found that pre-treatment of iDC with pDAV or pRPQ decapeptides significantly prevents the functional maturation of DC induced by PT-gliadin. On the other hand, pDAV and pRPQ did not revert the PT-gliadin-induced phenotypic maturation of DC. Here we report, for the first time, that naturally occurring peptides are able to prevent the gliadin-dependent DC maturation. This finding could have implication for CD, raising the perspective of a potential therapeutic strategy alternative to a gluten free diet.}, }
@article {pmid24260046, year = {2013}, author = {Thorat, D and Sahu, A and Behera, R and Lohite, K and Deshmukh, S and Mane, A and Karnik, S and Doke, S and Kundu, GC}, title = {Association of osteopontin and cyclooxygenase-2 expression with breast cancer subtypes and their use as potential biomarkers.}, journal = {Oncology letters}, volume = {6}, number = {6}, pages = {1559-1564}, pmid = {24260046}, issn = {1792-1074}, abstract = {Breast cancer is one of the most common malignant tumors among females worldwide and remains a leading cause of cancer-related mortality. Due to the heterogeneous clinical nature of breast cancer, it is necessary to identify new biomarkers that are associated with tumor growth, angiogenesis and metastasis. Osteopontin (OPN) and cyclooxygenase-2 (COX-2) are known to be overexpressed in invasive breast cancer and their overexpression is associated with aggressive histological and clinical features. The present study assessed OPN and COX-2 expression in various subtypes of breast cancer. The expression of OPN and COX-2 was analyzed using immunohistochemistry (IHC) in a cohort of 67 invasive ductal breast carcinoma patients. The statistical analysis was performed using standard statistical software SPSS version 18.0. The associations between OPN and COX-2 and the human epidermal growth factor receptor type 2 (HER2)-overexpressing and non-HER2-overexpressing subtypes were evaluated using the Mann-Whitney U test. The mean OPN level was significantly higher in the HER2-overexpressing subtype compared with the non-HER2-overexpressing subtype. Furthermore, the mean COX-2 expression levels were higher in the HER2-overexpressing subtype compared with the luminal A, luminal B or triple-negative groups. It is well known that carcinomas overexpressing HER2/neu have a worse prognosis than luminal tumors. Hence, it may be hypothesized that an elevated expression of OPN and COX-2 in a HER2-overexpressing subtype may contribute to a more aggressive behavior and be used as diagnostic and prognostic markers in breast cancer.}, }
@article {pmid24254879, year = {2014}, author = {Rehman, S and Husnain, SM}, title = {A probable risk factor of female breast cancer: study on benign and malignant breast tissue samples.}, journal = {Biological trace element research}, volume = {157}, number = {1}, pages = {24-29}, doi = {10.1007/s12011-013-9865-7}, pmid = {24254879}, issn = {1559-0720}, mesh = {Breast/*chemistry ; Breast Neoplasms/*chemistry/epidemiology ; Copper/analysis ; Female ; Humans ; Iron/analysis ; Limit of Detection ; Probability ; Risk Factors ; Spectrophotometry, Atomic ; Zinc/analysis ; }, abstract = {The study reports enhanced Fe, Cu, and Zn contents in breast tissues, a probable risk factor of breast cancer in females. Forty-one formalin-fixed breast tissues were analyzed using atomic absorption spectrophotometry. Twenty malignant, six adjacent to malignant and 15 benign tissues samples were investigated. The malignant tissues samples were of grade 11 and type invasive ductal carcinoma. The quantitative comparison between the elemental levels measured in the two types of specimen (benign and malignant) tissues (removed after surgery) suggests significant elevation of these metals (Fe, Cu, and Zn) in the malignant tissue. The specimens were collected just after mastectomy of women aged 19 to 59 years from the hospitals of Islamabad and Rawalpindi, Pakistan. Most of the patients belong to urban areas of Pakistan. Findings of study depict that these elements have a promising role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu, and Zn was observed. The results showed the excessive accumulation of Fe (229 ± 121 mg/L) in malignant breast tissue samples of patients (p < 0.05) to that in benign tissues samples (49.1 ± 11.4 mg/L). Findings indicated that excess accumulation of iron in malignant tissues can be a risk factor of breast cancer. In order to validate our method of analysis, certified reference material muscle tissue lyophilized (IAEA) MA-M-2/TM was analyzed for metal studied. Determined concentrations were quite in good agreement with certified levels. Asymmetric concentration distribution for Fe, Cu, and Zn was observed in both malignant and benign tissue samples.}, }
@article {pmid24252817, year = {2015}, author = {Nam, SY and Ko, ES and Han, BK and Shin, S and Ko, EY and Shin, JH and Hahn, SY}, title = {Ultrasonographic hyperechoic lesions of the breast: are they always benign?.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {56}, number = {1}, pages = {18-24}, doi = {10.1177/0284185113512482}, pmid = {24252817}, issn = {1600-0455}, mesh = {Adipose Tissue/*diagnostic imaging ; Adult ; Aged ; *Artifacts ; Breast Neoplasms/*diagnostic imaging ; Diagnostic Errors/prevention &amp; control/*statistics &amp; numerical data ; False Negative Reactions ; Female ; Humans ; Middle Aged ; Prevalence ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; Ultrasonography, Mammary/methods/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: Most of the breast lesions show hypoechogenicity relative to fat on ultrasonography. The frequency and malignancy rate of hyperechoic lesions are not investigated in a large series.<br><br>PURPOSE: To evaluate the frequency and malignancy rate of hyperechoic lesions on breast sonography and to investigate sonographic characteristics that may predict malignancy in hyperechoic breast lesions.<br><br>MATERIAL AND METHODS: Radiologic reports of 16,416 patients who underwent breast sonography between 2007 and 2008 were searched using "hyperechoic", "echogenic" or "heterogeneous echoic" to describe lesions. Sonographic findings were evaluated according to the Breast Imaging Reporting and Data System lexicon. Clinical records including follow-up and pathologic findings were also reviewed. We calculated the frequency of hyperechoic lesions and their malignancy rate. Differences in sonographic appearances between benign and malignant lesions were also investigated.<br><br>RESULTS: Among the 16,416 patients, 103 (0.6%) hyperechoic lesions were identified (mean size, 1.79&#x2009;cm). Of these 103 lesions, 27 (26.2%) were pathologically evaluated and five (4.9%, 4 invasive ductal carcinoma and 1 mucinous carcinoma) were confirmed as malignant. Among the 819 malignant lesions diagnosed using sonography-guided core needle biopsy, five (0.6%) were hyperechoic. In benign lesions, fat necrosis and fibroadenoma were common pathologic diagnoses. Malignant lesions were more likely to have irregular shape (P&#x2009;=&#x2009;0.003), non-parallel orientation (P&#x2009;=&#x2009;0.002), non-circumscribed margin (P&#x2009;=&#x2009;0.007), and a hypoechoic area (P&#x2009;=&#x2009;0.027) than benign lesions. All hyperechoic carcinomas were seen as suspicious masses on mammograms.<br><br>CONCLUSION: Hyperechoic masses are very rare and mostly benign. As an adjunct to mammography, the imaging findings reported here could help to avoid misdiagnosis for malignant hyperechoic lesion.}, }
@article {pmid24236052, year = {2013}, author = {Chen, X and Qiu, J and Yang, D and Lu, J and Yan, C and Zha, X and Yin, Y}, title = {MDM2 promotes invasion and metastasis in invasive ductal breast carcinoma by inducing matrix metalloproteinase-9.}, journal = {PloS one}, volume = {8}, number = {11}, pages = {e78794}, pmid = {24236052}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*enzymology/pathology/surgery ; Carcinoma, Ductal, Breast/*enzymology/secondary/surgery ; Disease-Free Survival ; Enzyme Induction ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; MCF-7 Cells ; Matrix Metalloproteinase 9/*genetics/metabolism ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Promoter Regions, Genetic ; Proportional Hazards Models ; Proto-Oncogene Proteins c-mdm2/*physiology ; Tumor Burden ; Up-Regulation ; Young Adult ; }, abstract = {The molecular mechanisms that underpin invasive ductal breast cancer (IDC) invasion and metastasis are incompletely understood. The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers, where it stimulates the expression of matrix metalloproteinase 9 (MMP9), an important enzyme in the breakdown of the extracellular matrix. However, its role in breast cancer remains poorly understood. This study assessed the clinical significance of MDM2 expression in IDC and used in vitro expression assays to determine the molecular roles of MDM2. Immunohistochemical staining for MMP9 and MDM2 was performed using archived tumor blocks from 321 women who underwent surgical resection for IDC at the First Affiliated Hospital of Nanjing Medical University, China between January 2002 and December 2003. MCF-7 and MDA-MD-231 cell lines were transfected with siRNA targeted against MDM2, or MDM2 was overexpressed using transiently expressed vectors. The invasion, cell migration and proteolytic capabilities of cells that over- or underexpressed MDM2 was then assessed and compared against control cells, in addition to the consequent effects on MMP9 expression using RT-PCR. In vivo, 54.9% and 49.6% of samples were positive for MMP9 and MDM2 expression, respectively, and their expression was significantly correlated (r[2] = 0.171, P = 0.012). Moreover, MDM2 expression was markedly correlated with disease-free survival (HR 2.56, 95% CI 1.02-6.40, P = 0.038). In vitro, MDM2 overexpression significantly enhanced cell invasion, migration and proteolysis compared with control cells, and the converse effects were observed after MDM2-siRNA treatment. MDM2 overexpression induced MMP9 expression in a dose-dependent manner. Taken together, these results suggest that high levels of MDM2 are associated with a poorer prognosis in IDC. This might result from increased tumor invasiveness due to enhanced MMP9 expression causing increased extracellular matrix breakdown.}, }
@article {pmid24224997, year = {2014}, author = {Vaidya, JS and Wenz, F and Bulsara, M and Tobias, JS and Joseph, DJ and Keshtgar, M and Flyger, HL and Massarut, S and Alvarado, M and Saunders, C and Eiermann, W and Metaxas, M and Sperk, E and Sütterlin, M and Brown, D and Esserman, L and Roncadin, M and Thompson, A and Dewar, JA and Holtveg, HM and Pigorsch, S and Falzon, M and Harris, E and Matthews, A and Brew-Graves, C and Potyka, I and Corica, T and Williams, NR and Baum, M and , }, title = {Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial.}, journal = {Lancet (London, England)}, volume = {383}, number = {9917}, pages = {603-613}, doi = {10.1016/S0140-6736(13)61950-9}, pmid = {24224997}, issn = {1474-547X}, support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; HTA/07/60/49/DH_/Department of Health/United Kingdom ; }, mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/surgery ; Female ; Humans ; Intraoperative Care/methods/mortality ; Kaplan-Meier Estimate ; Mastectomy, Segmental/methods/mortality ; Middle Aged ; Neoplasm Recurrence, Local/mortality/prevention &amp; control ; Radiotherapy/methods/mortality ; Treatment Outcome ; }, abstract = {BACKGROUND: The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival.<br><br>METHODS: TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2&#xb7;5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684.<br><br>FINDINGS: Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15&#xb7;2% [239 of 1571] of patients who received TARGIT (21&#xb7;6% prepathology, 3&#xb7;6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3&#xb7;3% (95% CI 2&#xb7;1-5&#xb7;1) for TARGIT versus 1&#xb7;3% (0&#xb7;7-2&#xb7;5) for EBRT (p=0&#xb7;042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2&#xb7;1% (1&#xb7;1-4&#xb7;2) versus 1&#xb7;1% (0&#xb7;5-2&#xb7;5; p=0&#xb7;31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2&#xb7;5% (TARGIT 5&#xb7;4% [3&#xb7;0-9&#xb7;7] vs EBRT 1&#xb7;7% [0&#xb7;6-4&#xb7;9]; p=0&#xb7;069). Overall, breast cancer mortality was much the same between groups (2&#xb7;6% [1&#xb7;5-4&#xb7;3] for TARGIT vs 1&#xb7;9% [1&#xb7;1-3&#xb7;2] for EBRT; p=0&#xb7;56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1&#xb7;4% [0&#xb7;8-2&#xb7;5] vs 3&#xb7;5% [2&#xb7;3-5&#xb7;2]; p=0&#xb7;0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3&#xb7;9% (2&#xb7;7-5&#xb7;8) for TARGIT versus 5&#xb7;3% (3&#xb7;9-7&#xb7;3) for EBRT (p=0&#xb7;099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0&#xb7;029).<br><br>INTERPRETATION: TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT.<br><br>FUNDING: University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research.}, }
@article {pmid24209961, year = {2013}, author = {Luncsford, PJ and Manvilla, BA and Patterson, DN and Malik, SS and Jin, J and Hwang, BJ and Gunther, R and Kalvakolanu, S and Lipinski, LJ and Yuan, W and Lu, W and Drohat, AC and Lu, AL and Toth, EA}, title = {Coordination of MYH DNA glycosylase and APE1 endonuclease activities via physical interactions.}, journal = {DNA repair}, volume = {12}, number = {12}, pages = {1043-1052}, pmid = {24209961}, issn = {1568-7856}, support = {R56 CA078391/CA/NCI NIH HHS/United States ; GM 72711/GM/NIGMS NIH HHS/United States ; CA 78391/CA/NCI NIH HHS/United States ; R01 GM072711/GM/NIGMS NIH HHS/United States ; R01 CA078391/CA/NCI NIH HHS/United States ; }, mesh = {Binding Sites ; Biocatalysis ; Cell Cycle Proteins/genetics/metabolism ; DNA/metabolism ; DNA Damage ; DNA Glycosylases/chemistry/*metabolism ; DNA Repair ; DNA-(Apurinic or Apyrimidinic Site) Lyase/chemistry/*metabolism ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Mutation ; Protein Binding ; Protein Stability ; }, abstract = {MutY homologue (MYH) is a DNA glycosylase which excises adenine paired with the oxidative lesion 7,8-dihydro-8-oxoguanine (8-oxoG, or G(o)) during base excision repair (BER). Base excision by MYH results in an apurinic/apyrimidinic (AP) site in the DNA where the DNA sugar-phosphate backbone remains intact. A key feature of MYH activity is its physical interaction and coordination with AP endonuclease I (APE1), which subsequently nicks DNA 5' to the AP site. Because AP sites are mutagenic and cytotoxic, they must be processed by APE1 immediately after the action of MYH glycosylase. Our recent reports show that the interdomain connector (IDC) of human MYH (hMYH) maintains interactions with hAPE1 and the human checkpoint clamp Rad9-Rad1-Hus1 (9-1-1) complex. In this study, we used NMR chemical shift perturbation experiments to determine hMYH-binding site on hAPE1. Chemical shift perturbations indicate that the hMYH IDC peptide binds to the DNA-binding site of hAPE1 and an additional site which is distal to the APE1 DNA-binding interface. In these two binding sites, N212 and Q137 of hAPE1 are key mediators of the MYH/APE1 interaction. Intriguingly, despite the fact that hHus1 and hAPE1 both interact with the MYH IDC, hHus1 does not compete with hAPE1 for binding to hMYH. Rather, hHus1 stabilizes the hMYH/hAPE1 complex both in vitro and in cells. This is consistent with a common theme in BER, namely that the assembly of protein-DNA complexes enhances repair by efficiently coordinating multiple enzymatic steps while simultaneously minimizing the release of harmful repair intermediates.}, }
@article {pmid24203627, year = {2013}, author = {Gojis, O and Kubecova, M and Rosina, J and Vranova, J and Celko, M and Frajerova, D and Zmrhal, J and Zahumensky, J and Bacova, T and Baca, V and Mandys, V and Kucera, E}, title = {Expression of selected proteins in breast cancer brain metastases.}, journal = {Folia histochemica et cytobiologica}, volume = {51}, number = {3}, pages = {213-218}, doi = {10.5603/FHC.2013.0030}, pmid = {24203627}, issn = {1897-5631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms/diagnosis/*metabolism/secondary ; Breast Neoplasms/diagnosis/*metabolism ; Carcinoma/diagnosis/*metabolism ; ErbB Receptors/genetics/metabolism ; Estrogen Receptor alpha/genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/genetics/metabolism ; Middle Aged ; Nuclear Receptor Coactivator 3/genetics/metabolism ; PAX2 Transcription Factor/genetics/metabolism ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; }, abstract = {The aim of the study was to assess the immunohistochemical (IHC) profiles of SRC3, Pax2, ER, PgR, Her2, EGFR, CK5/6, and Ki67 proteins in breast-cancer brain metastasis. The study utilized tumor samples from 30 metastatic patients and calculated correlations between all IHC variables. In fourteen cases, primary breast cancers paired with secondary deposits were analyzed. We evaluated the association between IHC status in the primary and secondary deposits, grade, and histotype of the tumors. The examination of the metastatic deposits in all 30 patients resulted in positive detection in the following cases: SRC3 in 20 cases (66.6%), Pax2 in 22 (73.3%), ER in 22 (73.3%), PgR in 25 (83.3%), Her2 in 10 (33.3%), EGFR in 12 (40%), CK5/6 in 7 (23.3%), and Ki67 in 23 (76.6%). Grade 2 was found in 13.3% of all patients, and grade 3 in 86.7%. SRC3 and Pax2 were positive in both G2 and G3. Invasive lobular carcinoma and invasive ductal carcinoma were diagnosed in 23.3% and 76.7% of cases, respectively. There were no differences between the IHC expression of the studied proteins in either grading or histotype of the tumors. In the IHC profiles, which included SRC3, Pax2, ER, PgR, Her2, CK5/6, Ki67, and EGFR, we found no statistically significant differences between the primary cancer and the brain metastasis. In our study of metastatic breast carcinoma deposits, there was no correlation between SRC3, Pax2 status and histotype, and tumor grade. The IHC status of the paired primary and metastatic deposits did not differ in a statistically significant manner.}, }
@article {pmid24146864, year = {2013}, author = {Shan, M and Zhang, X and Liu, X and Qin, Y and Liu, T and Liu, Y and Wang, J and Zhong, Z and Zhang, Y and Geng, J and Pang, D}, title = {P16 and p53 play distinct roles in different subtypes of breast cancer.}, journal = {PloS one}, volume = {8}, number = {10}, pages = {e76408}, pmid = {24146864}, issn = {1932-6203}, mesh = {Adolescent ; Breast Neoplasms/*classification/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Down-Regulation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Mutation/genetics ; Risk Factors ; Signal Transduction/genetics ; Triple Negative Breast Neoplasms/genetics/pathology ; Tumor Suppressor Protein p53/genetics/*metabolism ; Up-Regulation/genetics ; }, abstract = {Breast cancers are heterogeneous and complex diseases, and subtypes of breast cancers may involve unique molecular mechanisms. The p16(INK4a) and p53 pathways are two of the major pathways involved in control of the cell cycle. They also play key roles in tumorigenesis. However, whether the roles of these pathways differ in the subtypes of breast cancer is unclear. Therefore, p16 and p53 expression were investigated in different breast cancer subtypes to ascertain their contributions to these cancers. A total of 400 cases of non-invasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), including the major molecular subtypes luminal-A, luminal-B, Her-2, and triple-negative subtypes, and 50 cases of normal controls were compared. Luminal-A cancers expressed the lowest level of p16 among the subtypes in DCIS, and the level of p16 expression was up-regulated in the luminal-A of IDC (P<0.008). Triple-negative breast cancers were characterized by a correlation of p53 overexpression with a high level of p16 expression. Luminal lesion types with high p16 expression in DCIS were found to be more likely to develop into aggressive breast cancers, possibly promoted by p53 dysfunction. Taken together, the present study suggest that p16 expression in luminal-A breast cancers is associated with their progression from DCIS to IDC, and both p53 and p16 expressions are important for the development of triple-negative breast cancers in DCIS and IDC.}, }
@article {pmid24129963, year = {2014}, author = {Oh, Y and Oh, I and Morimoto, J and Uede, T and Morimoto, A}, title = {Osteopontin has a crucial role in osteoclast-like multinucleated giant cell formation.}, journal = {Journal of cellular biochemistry}, volume = {115}, number = {3}, pages = {585-595}, doi = {10.1002/jcb.24695}, pmid = {24129963}, issn = {1097-4644}, mesh = {Arthritis, Rheumatoid/*genetics/pathology ; Cell Differentiation/genetics ; Dendritic Cells/cytology/metabolism ; Giant Cells/drug effects ; Histiocytosis, Langerhans-Cell/*genetics/metabolism ; Humans ; Oligopeptides ; Osteoclasts/cytology/*metabolism ; Osteopontin/genetics/*metabolism ; RNA, Small Interfering ; }, abstract = {The osteoclast (OC) is a major player in the pathogenic bone destruction of inflammatory bone diseases such as rheumatoid arthritis and Langerhans cell histiocytosis. Recently, it was shown that immature dendritic cells (iDC) fuse faster and more efficiently than monocytes in forming OC-like multinucleated giant cells (MGCs), and that osteopontin (OPN) is involved in the pathogenesis of inflammatory bone diseases. In this study, we hypothesized that OPN is a key factor for generation of OC-like MGCs from iDCs. We used an in vitro culture system to differentiate iDCs, derived from monocytes obtained from the blood of healthy donors, into OC-like MGCs. We evaluated OPN levels and expression of OPN receptors during the course of differentiation. OPN has an arginine-glycine-aspartic acid (RGD) motif, and protease cleavage reveals a SVVYGLR motif. The concentrations of both full-length and cleaved forms of OPN increased during the course of OC-like MGC formation. Expression of OPN RGD- and SVVYGLR-recognizing receptors also increased at later stages. We analyzed whether blocking OPN binding to its receptors affected OC-like MGC formation. Monocytes treated with OPN siRNA were able to differentiate into iDCs effectively; however, differentiation of these iDCs into OC-like MGCs was significantly reduced. The formation of OC-like MGCs was not significantly reduced by RGD synthetic peptide. By contrast, SVVYGLR synthetic peptide caused a significant reduction. These data suggest that the cleaved form of OPN plays a critical role in driving iDC differentiation into OC-like MGCs in the early phase of differentiation, in an autocrine and/or paracrine fashion.}, }
@article {pmid24128082, year = {2014}, author = {Verma, S and Dey, P}, title = {Correlation of morphological markers of chromosomal instability in fine needle aspiration cytology with grade of breast cancer.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {25}, number = {4}, pages = {259-263}, doi = {10.1111/cyt.12096}, pmid = {24128082}, issn = {1365-2303}, mesh = {*Biopsy, Fine-Needle ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma/*diagnosis/genetics/pathology ; Chromosomal Instability/genetics ; *Cytodiagnosis ; Female ; Humans ; Neoplasm Grading ; }, abstract = {OBJECTIVE: The aim of the present study was to investigate morphological markers of chromosomal instability (CI) in relation to cytological grade of breast cancer in fine needle aspiration cytology (FNAC) specimens.<br><br>METHODS: Herein we selected 55 cases of invasive ductal carcinoma diagnosed on FNAC. Representative haematoxylin and eosin (H&amp;E)-stained smears were chosen to count chromatin bridges, multipolar mitoses per smear, and micronuclei and nuclear budding per 1000 carcinoma cells. The cases were also graded by two independent observers as grade I, II and III. The CI markers were correlated with the grade of breast carcinomas.<br><br>RESULTS: Out of 55 carcinomas, nine were grade I, nine grade II and 37 grade III. While none of the grade I carcinomas showed chromosomal bridges, the number per smear was 0.4 (&#xb1;&#xa0;0.7) and 3.1 (&#xb1;&#xa0;2.5) for grade II and III carcinomas, respectively. No multipolar mitoses were observed in grade I or II carcinomas; the number per smear was 3.7 (&#xb1;3.0) in grade III carcinomas. The mean number per 1000 malignant cells of micronuclei was 1.2 (&#xb1;1.7), 3.7 (&#xb1;2.1) and 12.2 (&#xb1;5.1) and of nuclear buds was 2.3 (&#xb1;3.2), 4.7 (&#xb1;2.1) and 12.4 (&#xb1;4.7) in grade I, II and III carcinomas, respectively. There was a significant increase in the mean numbers of chromatin bridges, micronuclei and nuclear buds in grade I, II and III carcinomas (anova test; P&#xa0;<&#xa0;0.001).<br><br>CONCLUSION: This is the first study of four morphological markers of CI in FNAC smears of breast cancer. This study establishes strong correlation of these markers with other criteria for cytological grading.}, }
@article {pmid24125077, year = {2013}, author = {Kranz, AL and Jiao, CY and Winterkorn, LH and Albritton, SE and Kramer, M and Ercan, S}, title = {Genome-wide analysis of condensin binding in Caenorhabditis elegans.}, journal = {Genome biology}, volume = {14}, number = {10}, pages = {R112}, pmid = {24125077}, issn = {1474-760X}, support = {P40 OD010440/OD/NIH HHS/United States ; U01 HG0044270/HG/NHGRI NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/*genetics/*metabolism ; Animals ; Base Sequence ; Binding Sites ; Caenorhabditis elegans/*genetics/*metabolism ; Chromatin Immunoprecipitation ; Chromosomes/genetics/metabolism ; DNA-Binding Proteins/*genetics/*metabolism ; *Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Male ; Multiprotein Complexes/*genetics/*metabolism ; Mutation ; Nucleotide Motifs ; Position-Specific Scoring Matrices ; Promoter Regions, Genetic ; Protein Binding ; Reproducibility of Results ; Transcription Factors/metabolism ; Transcription, Genetic ; }, abstract = {BACKGROUND: Condensins are multi-subunit protein complexes that are essential for chromosome condensation during mitosis and meiosis, and play key roles in transcription regulation during interphase. Metazoans contain two condensins, I and II, which perform different functions and localize to different chromosomal regions. Caenorhabditis elegans contains a third condensin, I(DC), that is targeted to and represses transcription of the X chromosome for dosage compensation.<br><br>RESULTS: To understand condensin binding and function, we performed ChIP-seq analysis of C. elegans condensins in mixed developmental stage embryos, which contain predominantly interphase nuclei. Condensins bind to a subset of active promoters, tRNA genes and putative enhancers. Expression analysis in kle-2-mutant larvae suggests that the primary effect of condensin II on transcription is repression. A DNA sequence motif, GCGC, is enriched at condensin II binding sites. A sequence extension of this core motif, AGGG, creates the condensin IDC motif. In addition to differences in recruitment that result in X-enrichment of condensin I(DC) and condensin II binding to all chromosomes, we provide evidence for a shared recruitment mechanism, as condensin I(DC) recruiter SDC-2 also recruits condensin II to the condensin I(DC) recruitment sites on the X. In addition, we found that condensin sites overlap extensively with the cohesin loader SCC-2, and that SDC-2 also recruits SCC-2 to the condensin I(DC) recruitment sites.<br><br>CONCLUSIONS: Our results provide the first genome-wide view of metazoan condensin II binding in interphase, define putative recruitment motifs, and illustrate shared loading mechanisms for condensin I(DC) and condensin II.}, }
@article {pmid24111705, year = {2014}, author = {Buchanan, J and Beckmann, M}, title = {Postpartum voiding dysfunction: identifying the risk factors.}, journal = {The Australian &amp; New Zealand journal of obstetrics &amp; gynaecology}, volume = {54}, number = {1}, pages = {41-45}, doi = {10.1111/ajo.12130}, pmid = {24111705}, issn = {1479-828X}, mesh = {Adult ; Cesarean Section/adverse effects ; Female ; Humans ; Incidence ; Labor, Obstetric ; Organ Size ; Postpartum Period ; Pregnancy ; Puerperal Disorders/*etiology ; Retrospective Studies ; Risk Factors ; Urinary Bladder/anatomy &amp; histology ; Urinary Retention/epidemiology/*etiology ; Urine ; }, abstract = {BACKGROUND: Postpartum urinary retention (PPUR) (also known as voiding dysfunction) is a common problem, defined as the inability to completely void after giving birth. If voiding dysfunction is not recognised, bladder overdistension can lead to denervation, detrusor atony and prolonged voiding dysfunction.<br><br>AIM: To describe the incidence of PPUR amongst postpartum women undergoing routine bladder scanning and to identify the factors that lead to postpartum voiding dysfunction.<br><br>METHODS: A retrospective analysis of all postpartum women at Mater Health Services, Brisbane between February and December 2012 was undertaken. Routinely collected postvoid residual bladder volumes (PVRBV) were reported using a bladder scanner at four and six hours and two to three days postbirth or following removal of an indwelling catheter (IDC). The characteristics of women with or without increased PVRBV were analysed.<br><br>RESULTS: Postvoid residual bladder volumes at four-hours postbirth/removal of IDC were available for 5558 women of whom 281 (5.1%) had a residual volume measured >150 mL. Obstetric factors explored included mode of birth, method of analgesia or anaesthesia, duration of labour, degree of perineal trauma, birth weight, gestation, parity, maternal age and body mass index. After controlling for confounders, nulliparity (aOR 1.53; 95% CI 1.05-2.26), birth by caesarean section (aOR 2.21; 95% CI 1.10-4.41) and 3rd/4th degree perineal trauma (aOR 2.01; 95% CI 1.09-3.72) were significant independent predictors of PPUR.<br><br>CONCLUSION: Following the introduction of a protocol of timed voiding and routine measurement of PVRBV after birth/removal of IDC, PPUR is uncommon. Adopting a risk-factor-based approach to PVRBV screening is not supported by these data.}, }
@article {pmid24106833, year = {2013}, author = {Shaheed, SU and Rustogi, N and Scally, A and Wilson, J and Thygesen, H and Loizidou, MA and Hadjisavvas, A and Hanby, A and Speirs, V and Loadman, P and Linforth, R and Kyriacou, K and Sutton, CW}, title = {Identification of stage-specific breast markers using quantitative proteomics.}, journal = {Journal of proteome research}, volume = {12}, number = {12}, pages = {5696-5708}, doi = {10.1021/pr400662k}, pmid = {24106833}, issn = {1535-3907}, mesh = {Adult ; Aged ; Amine Oxidase (Copper-Containing)/genetics/isolation &amp; purification/metabolism ; Biological Transport ; Biomarkers, Tumor/*genetics/isolation &amp; purification/metabolism ; Breast Neoplasms/diagnosis/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/metabolism/pathology ; Case-Control Studies ; Cofilin 1/*genetics/isolation &amp; purification/metabolism ; Female ; Fibroadenoma/diagnosis/*genetics/metabolism/pathology ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Lipid Metabolism ; Middle Aged ; Neoplasm Staging ; Oxidation-Reduction ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; Proteolysis ; Proteomics ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; Tissue Array Analysis ; Tumor Protein, Translationally-Controlled 1 ; }, abstract = {Matched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.}, }
@article {pmid24103354, year = {2013}, author = {Kim, TY and Kim, SH and Kang, BJ and Kim, HS and Cha, ES and Kim, JY and Song, BJ}, title = {Characterization of the enhancing lesions on dynamic contrast enhanced magnetic resonance imaging in patients with interstitial mammoplasty.}, journal = {European journal of radiology}, volume = {82}, number = {12}, pages = {2205-2211}, doi = {10.1016/j.ejrad.2013.09.008}, pmid = {24103354}, issn = {1872-7727}, mesh = {Adult ; Aged ; Breast Neoplasms/*etiology/*pathology ; Contrast Media ; Female ; Foreign-Body Reaction/*etiology/*pathology ; *Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging/*methods ; Mammaplasty/*adverse effects ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Treatment Outcome ; }, abstract = {PURPOSE: The purpose of this study was to categorize the morphologic and kinetic features of enhancing lesions in breasts with interstitial mammoplasty using dynamic contrast-enhanced magnetic resonance imaging and to assess factors predictive of breast cancer.<br><br>MATERIALS AND METHODS: We retrospectively reviewed the clinical and radiological data of 21 enhancing lesions in 19 patients with interstitial mammoplasty, who underwent breast magnetic resonance imaging and biopsy or an operation in our hospital from September 2008 to July 2012. These lesions were sorted by morphological and kinetic features and final assessment category according to the BI-RADS lexicon.<br><br>RESULTS: Nine cases were confirmed to be ductal carcinoma in situ (n = 2) and invasive ductal carcinoma (n = 7), and the remaining 12 cases were fibrocystic disease (n = 2), fibroadenoma (n = 2), fat necrosis (n = 1), foreign body granuloma (n = 3) and silicone mastitis (n = 1). Common features of malignancy included irregular shape (50.0%), spiculated margins (75.0%), heterogeneous enhancement (50.0%) and type III kinetic pattern (87.5%). The correlations of margins and kinetic curve pattern with benignity and malignancy approached statistical significance (p = 0.02, respectively). We found no correlation for shape (p = 0.33) or internal enhancement (p = 0.42) between lesion types. The malignancy rate of enhancing lesions was 42.8% (9/21). The sensitivity and specificity of dynamic contrast-enhanced magnetic resonance imaging were 100% and 16.67%, respectively. The positive predictive value, negative predictive value and accuracy of magnetic resonance imaging were 47.38%, 100% and 52.38%. Overall inter-observer agreement for the kinetic curve pattern was good (&#x3ba; = 0.67). Moderate agreement was seen in describing the shape, margin, enhancement and assessing the final category (&#x3ba; = 0.59, 0.46, 0.58 and 0.49, respectively).<br><br>CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging had a high sensitivity, negative predictive value for the prediction of breast cancer but a low specificity due to features of foreign body-related lesions that mimicked malignant lesions. The significant predictive factors for malignancy were margins, kinetic curve pattern and final assessment category. Overall inter-observer agreement for the kinetic curve pattern was good.}, }
@article {pmid24099815, year = {2013}, author = {Gudadze, M and Kankava, K and Mariamidze, A and Mosidze, T and Burkadze, G}, title = {Distribution of CD44/CD24 positive cells in ductal invasive carcinoma of breast of different grade and molecular subtype.}, journal = {Georgian medical news}, volume = {}, number = {222}, pages = {50-57}, pmid = {24099815}, issn = {1512-0112}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/metabolism/pathology ; CD24 Antigen/immunology/*metabolism ; Carcinoma, Ductal, Breast/metabolism/pathology ; Female ; Humans ; Hyaluronan Receptors/immunology/*metabolism ; *Immunity, Cellular ; Immunohistochemistry ; Middle Aged ; *Neoplasm Staging ; Neoplastic Stem Cells/*immunology/metabolism/pathology ; Retrospective Studies ; Young Adult ; }, abstract = {The purpose of our study was to learn the distribution characteristics of cancer stem cell markers (CD24, CD44) in invasive carcinomas with different grade and molecular subtype. For research was used 1324 postoperative breast cancer samples, from which were selected 393 patient with invasive ductal carcinoma samples examined 2008-2012 in Laboratory of "Pathgeo Union of Pathologist" is and N.Kipshidze Central University Hospital. The age range is between 23-73 year. For all cases were performed immunohistochemical study using ER, PR, Her2, Ki67, CK5- molecular markers (Leica Microsystems). For identify cancer stem cells mononuclear antibodies CD24 (BIOCARE MEDICAL, CD44 - Clone 156-3C11; CD24 - Clone SN3b) were used. Association of CD44/CD24 expression in different subtypes of cells, between clinicopathological parameters and different biological characteristics were performed by Pearson correlation and usind X2 tests. Obtained quantitative statistical analyses were performed by using SPSS V.19.0 program. Statistically significant were considered 95% of confidence interval. The data shows, that towards G1-G3, amount of CD44 positive cases increased twice. CD44 positive cases are evenly distributed between Luminal A, Luminal B, HER2+, triple negative basal like cell subtypes and in significantly less (4,8 times) in Her2+ cases. Maximum amount of CD44 negative cases is shown in Luminal A subtype, which could be possible cause of better prognosis and high sensitivity for chemotherapy. For one's part such aggressive subtypes of breast cancer as Luminal B and basal like cell type, are characterized by CD44 positive and antigen high expression, which can be reason of aggressive nature of this types and also reason of chemotherapy resistance. As well as amount of CD24 positive cases according to malignancy degree, also antigen expression features does not show any type of correlation between malignancy degree and CD24 positivity or with CD24 expression features, or presence of stem cells. That can be the reason of tumor aggressivity and chemoresistance. exceptions are Her2 positive tumors because they have different base of carcinogenesis.}, }
@article {pmid24096546, year = {2014}, author = {Xiao, Y and Zhang, S and Hou, G and Zhang, X and Hao, X and Zhang, J}, title = {Clinical pathological characteristics and prognostic analysis of diabetic women with luminal subtype breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {3}, pages = {2035-2045}, pmid = {24096546}, issn = {1423-0380}, mesh = {Adult ; Aged ; Breast Neoplasms/*complications/*mortality/*pathology ; Diabetes Mellitus, Type 2/*complications/*mortality/*pathology ; Female ; Humans ; Hypoglycemic Agents/therapeutic use ; Kaplan-Meier Estimate ; Metformin/therapeutic use ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, abstract = {This study selected luminal-type breast cancer patients as the study subjects. The patients were divided into groups according to the presence of diabetes and the types of medication used, and the patients' clinicopathological characteristics and prognostic indicators were explored. A total of 5,785 patients with luminal-type breast cancer admitted to Tianjin Medical University Cancer Institute and Hospital between January 2002 and December 2006 were selected as the study subjects. The subjects included 680 breast cancer patients with diabetes and 5,105 breast cancer patients without diabetes. The patients were divided into Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes. Each subtype was further divided into a metformin group, a non-metformin group, and a nondiabetic group. The research indicators included breast cancer mortality, age, body mass index (BMI), amenorrhea, the presence of cardiovascular and cerebrovascular disease, pathological stage, pathological type, lymph node involvement, vessel carcinoma embolus, and the chemotherapy and endocrine regimen. A Kaplan-Meier analysis was conducted to analyze the differences in breast cancer mortality rates among the groups. The Cox proportional hazard model was adopted to detect independent factors related to prognosis. Kaplan-Meier univariate analysis showed that for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes, the cancer-specific mortality rates differed significantly among the metformin, non-metformin, and nondiabetic groups. The 5-year survival rates were 94%, 82%, and 91% (P = 0.002); 93.5%, 81%, and 89% (P < 0.001); and 84%, 77%, and 83% (P = 0.035) for the subtypes within each group, respectively. Cox regression multivariate analysis showed that compared with the metformin group, all three subtypes of the, the non-metformin group showed poorer prognosis (hazard ratio [HR], 3.579; 95% confidence interval [CI], 1.506-8.506 [P = 0.004]; HR, 3.232; 95% CI, 1.839-5.678 [P < 0.001]; HR, 2.034; 95% CI,1.019-4.059 [P = 0.044] for Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+, respectively). Compared with the metformin group, the diabetic group showed poorer prognosis only for the Luminal B (high ki67) subtype (HR, 1.762; 95% CI, 1.033-3.005 [P = 0.038]). In addition, for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subgroups, there was a higher proportion of elderly patients (P < 0.001) and postmenopausal patients (P < 0.001) in the metformin and non-metformin groups than in the nondiabetic group. Moreover, the probability of having cardiovascular and cerebrovascular disease was also higher (P < 0.001) in the metformin and non-metformin groups. For the Luminal B (high ki67) and Luminal B (her-2/neu +) subgroups, there was a higher proportion of obese patients in the metformin and non-metformin groups (P < 0.001). In terms of clinical characteristics, for the Luminal B (high ki67) subtype, the proportion of patients with invasive ductal carcinoma was lower in the non-metformin group than in the other two groups (P = 0.001). In both the metformin and non-metformin groups, the proportion of T3/4 patients was higher (P < 0.001), the proportion of patients with lymph node metastasis was higher (P = 0.001), and the proportion of patients with vessel carcinoma embolus was higher (P = 0.001) compared with the nondiabetic group. In conclusion, compared with the metformin group, the non-metformin group had a poorer prognosis for all subtypes of luminal breast cancer. In the diabetic group, only patients with the Luminal B (high ki67) subtype exhibited a poorer prognosis. Therefore, different diabetes medication may have a different impact on the prognosis of different subtypes of luminal breast cancer.}, }
@article {pmid24090706, year = {2013}, author = {Cleary, M and Trefz, F and Muntau, AC and Feillet, F and van Spronsen, FJ and Burlina, A and Bélanger-Quintana, A and Giżewska, M and Gasteyger, C and Bettiol, E and Blau, N and MacDonald, A}, title = {Fluctuations in phenylalanine concentrations in phenylketonuria: a review of possible relationships with outcomes.}, journal = {Molecular genetics and metabolism}, volume = {110}, number = {4}, pages = {418-423}, doi = {10.1016/j.ymgme.2013.09.001}, pmid = {24090706}, issn = {1096-7206}, mesh = {Adult ; Age Factors ; Biopterin/*analogs &amp; derivatives/therapeutic use ; Diet ; Humans ; Phenylalanine/*blood/*genetics/metabolism ; Phenylalanine Hydroxylase/genetics/metabolism ; Phenylketonurias/*blood/drug therapy/genetics/physiopathology ; PubMed ; }, abstract = {Fluctuations in blood phenylalanine concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). This review evaluates the studies on phenylalanine fluctuations, factors affecting fluctuations, and if stabilizing phenylalanine concentrations affects outcomes, particularly neurocognitive outcome. Electronic literature searches of Embase and PubMed were performed for English-language publications, and the bibliographies of identified publications were also searched. In patients with PKU, phenylalanine concentrations are highest in the morning. Factors that can affect phenylalanine fluctuations include age, diet, timing and dosing of protein substitute and energy intake, dietary adherence, phenylalanine hydroxylase genotype, changes in dietary phenylalanine intake and protein metabolism, illness, and growth rate. Even distribution of phenylalanine-free protein substitute intake throughout 24h may reduce blood phenylalanine fluctuations. Patients responsive to and treated with 6R-tetrahydrobiopterin seem to have less fluctuation in their blood phenylalanine concentrations than controls. An increase in blood phenylalanine concentration may result in increased brain and cerebrospinal fluid phenylalanine concentrations within hours. Although some evidence suggests that stabilization of blood phenylalanine concentrations may have benefits in patients with PKU, more studies are needed to distinguish the effects of blood phenylalanine fluctuations from those of poor metabolic control.}, }
@article {pmid24086515, year = {2013}, author = {He, W and Tong, Y and Wang, Y and Liu, J and Luo, G and Wu, J and Zhang, J}, title = {Serum soluble CD14 is a potential prognostic indicator of recurrence of human breast invasive ductal carcinoma with Her2-enriched subtype.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e75366}, pmid = {24086515}, issn = {1932-6203}, mesh = {Area Under Curve ; Biomarkers, Tumor/*blood ; Breast Neoplasms/blood/*epidemiology ; Carcinoma, Ductal, Breast/blood/*epidemiology ; Female ; Humans ; Lipopolysaccharide Receptors/*blood ; Neoplasm Recurrence, Local/blood/*epidemiology ; Proteomics/methods ; ROC Curve ; Receptor, ErbB-2/genetics/*metabolism ; Risk Factors ; }, abstract = {In clinical practice, breast cancers with lymph node positive, ER/PR-negative and overexpressed human epidermal growth factor receptor 2 (LN+ER/PR-Her2+) have high risk of recurrence, but the effective biomarkers of prognostic for this type tumor are still lacking. Since breast cancers with LN+ER/PR-Her2+ is at higher risk of recurrence than those with LN-ER/PR+Her2-. The differential proteins between those two groups could be related to the risk of recurrence. Herein, we report that serum soluble CD14 (sCD14) was revealed as the stable differential protein between LN+ER/PR-Her2+ (n=50) and LN-ER/PR+Her2- (n=50) breast cancer patients by proteomics analysis. To validate sCD14 as a biomarker for predicting recurrence of breast cancer, 90 breast cancer patients with LN+ER/PR-Her2+ and 93 patients with LN-ER/PR+Her2- were recruited. The patients with higher level of serum sCD14 at primary surgery showed to be at significantly lower risk of relapse in 3 years follow-up than those with lower level of serum sCD14 at primary surgery. The levels of serum sCD14 at primary surgery were significantly correlated to the risk of 3-year recurrence of LN+ER/PR-Her2+ breast cancer and the corresponding AUC of the ROC curve was 0.833 (95% CI, and 0.742 to 0.920). Therefore, we surmise that serum sCD14 could be a potential biomarker for predicting the prognosis of breast invasive ductal carcinoma with LN+ER/PR-Her2+.}, }
@article {pmid24080478, year = {2014}, author = {Nakiwogga-Muwanga, A and Alamo-Talisuna, S and Musaazi, J and Kambugu, A and Ssekawungu, P and Katabira, E and Colebunders, R}, title = {Inadequate monitoring in advanced stages of disease with lack of supportive counseling increases attrition among patients on antiretroviral treatment at a large urban clinic in Uganda.}, journal = {Journal of the International Association of Providers of AIDS Care}, volume = {13}, number = {6}, pages = {547-554}, doi = {10.1177/2325957413501719}, pmid = {24080478}, issn = {2325-9574}, mesh = {Adult ; Ambulatory Care Facilities ; Anti-Retroviral Agents/*therapeutic use ; Case-Control Studies ; *Directive Counseling ; Female ; HIV Infections/*diagnosis/psychology/*therapy ; Humans ; Lost to Follow-Up ; Male ; Patient Compliance ; Risk Factors ; *Social Support ; Uganda ; *Urban Health Services ; }, abstract = {BACKGROUND: The purpose of this case-control study was to identify risk factors for loss to follow-up (LTFU).<br><br>METHODS: Cases and controls were selected from HIV-positive patients, aged 18 years and older, on antiretroviral therapy (ART) at the Infectious Diseases Clinic (IDC) in January 2008. As cases, we selected 209 patients who in 2008 did not return to the clinic within 90 days of their scheduled appointment date. As controls, we randomly selected 626 patients from the 5872 patients who were following up at the end of December 2008.<br><br>RESULTS: In multivariable logistic regression analysis, urban or semiurban residence, World Health Organization disease stage III or IV at ART initiation, a median CD4 count at last visit <200 cells/mm(3), tuberculosis (TB) in the 6 months before the last visit, absence of counseling before ART initiation, and no disclosure of HIV status were associated with LTFU.<br><br>CONCLUSION: This study demonstrates the importance of close patient monitoring in advanced stages of disease, supportive counseling for patients initiating ART, extra psychosocial support for patients with TB and HIV coinfection, assisting patients with disclosure, and setting up a good referral system to retain patients on ART.}, }
@article {pmid24065215, year = {2013}, author = {Pula, B and Olbromski, M and Wojnar, A and Gomulkiewicz, A and Witkiewicz, W and Ugorski, M and Dziegiel, P and Podhorska-Okolow, M}, title = {Impact of SOX18 expression in cancer cells and vessels on the outcome of invasive ductal breast carcinoma.}, journal = {Cellular oncology (Dordrecht)}, volume = {36}, number = {6}, pages = {469-483}, pmid = {24065215}, issn = {2211-3436}, mesh = {Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Vessels/metabolism ; MCF-7 Cells ; Microvessels/metabolism ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; SOXF Transcription Factors/*biosynthesis/blood/genetics/metabolism ; Vascular Endothelial Growth Factor D/genetics/metabolism ; }, abstract = {PURPOSE: SOX18 is a transcription factor known to be involved in hair follicle, blood and lymphatic vessel development, as well as wound healing processes (together with SOX7 and SOX17). In addition, it has been reported that SOX18 may affect the growth of cancer cells in vitro. Until now, the exact role of SOX18 expression in invasive ductal breast carcinoma (IDC) has remained unknown.<br><br>METHODS: In this study, we have investigated SOX18 expression in cancer cells and endothelial cells in 122 IDC samples using immunohistochemistry (IHC). SOX18 expression was also determined using real-time PCR and Western blotting in a series of breast cancer-derived cell lines (i.e., MCF-7, BT-474, SK-BR-3, MDA-MB-231, BO2).<br><br>RESULTS: Using IHC, we observed SOX18 nuclear expression in cancer cells, as well as in blood and lymphatic vessels of the IDC samples tested. SOX18 expression in the IDC samples correlated with a higher malignancy grade (Grade 2 and Grade 3 versus Grade 1; p&#x2009;=&#x2009;0.02 and p&#x2009;=&#x2009;0.009, respectively) and VEGF-D expression (r&#x2009;=&#x2009;0.27, p&#x2009;=&#x2009;0.007). SOX18 expression was also associated with HER2 positivity (p&#x2009;=&#x2009;0.02). A significantly higher SOX18 expression was found in the HER2-positive cell line BT-474, and a significantly lower expression in the triple negative cell lines MDA-MB-231 and BO2. Laser capture microdissection of IDC samples revealed significantly higher mRNA SOX7, SOX17 and SOX18 expression levels in the vessels as compared to the cancer cells (p&#x2009;=&#x2009;0.02 and p&#x2009;=&#x2009;0.0002, p&#x2009;<&#x2009;0.0001, respectively). SOX18 positive intratumoral and peritumoral microvessel counts (MVC) were associated with higher malignancy grades (p&#x2009;=&#x2009;0.04 and p&#x2009;=&#x2009;0.02, respectively). Moreover, peritumoral SOX18 positive MVC were found to act as an independent marker for a poor prognosis (p&#x2009;=&#x2009;0.04).<br><br>CONCLUSION: SOX18 expression may serve as a marker for a poor prognosis in IDC.}, }
@article {pmid24061465, year = {2013}, author = {Rathore, AS and Kumar, S and Konwar, R and Srivastava, AN and Makker, A and Goel, MM}, title = {Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast.}, journal = {Indian journal of cancer}, volume = {50}, number = {3}, pages = {239-244}, doi = {10.4103/0019-509X.118744}, pmid = {24061465}, issn = {1998-4774}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/*mortality/pathology ; CD3 Complex/immunology ; Carcinoma, Ductal, Breast/*immunology/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, abstract = {BACKGROUND: Aim of this study was to investigate the prognostic significance of CD3+ TILs in infiltrating ductal carcinoma (IDC) of the breast.<br><br>MATERIALS AND METHODS: Immuno-histochemistry was done with CD3 antibodies in tissue sections of 127 breast cancer patients, and CD3+ intra-tumoral and stromal TILs were counted in relation to clinico-pathological variables.<br><br>RESULTS: Intra-tumoral and stromal CD3+ TILs were significantly associated with positive lymph node status (P = 0.006, P = 0.043, respectively) without significant association with age, menopausal status, family history, and hormonal status. The higher CD3 intra-tumoral and stromal counts both showed significant association with good prognosis (P = 0.039, P = 0.044, respectively). The intra-tumoral count was higher than stromal count and was independently associated with disease-free survival in stage I and II cancer (P = 0.021).<br><br>CONCLUSIONS: CD3+ TILs may serve as independent marker of good prognosis in IDC breast. The findings of this study need further validation on a larger sample size.}, }
@article {pmid24059386, year = {2013}, author = {Seo, M and Chang, JM and Kim, WH and Park, IA and Lee, SH and Cho, N and Moon, WK}, title = {Columnar cell lesions without atypia initially diagnosed on breast needle biopsies: is imaging follow-up enough?.}, journal = {AJR. American journal of roentgenology}, volume = {201}, number = {4}, pages = {928-934}, doi = {10.2214/AJR.12.9906}, pmid = {24059386}, issn = {1546-3141}, mesh = {Adult ; Aged ; Biopsy, Needle/*statistics &amp; numerical data ; Breast Neoplasms/*diagnosis/*epidemiology ; Female ; Humans ; Incidence ; Mammography/*statistics &amp; numerical data ; Middle Aged ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: The purpose of this study was to evaluate the underestimation rate and predictive factor of underestimation of columnar cell lesions (CCLs) without atypia diagnosed through breast core needle biopsies (CNBs).<br><br>MATERIALS AND METHODS: From January 2007 through December 2011, 141 CCLs without atypia, including columnar cell change and columnar cell hyperplasia, were diagnosed in 138 women by CNB. Excisional (n = 16) or imaging follow-up (n = 125) findings were available in all cases. On a per-lesion basis, the underestimation rate and predictive factor of underestimation were evaluated.<br><br>RESULTS: Among the 16 surgically excised lesions, there were two malignancies (one ductal carcinoma in situ and one invasive ductal carcinoma) and one lobular carcinoma in situ. Overall, the pooled underestimation rate of malignancy was 1.4% (2/141). With regard to lesion variables, the mean lesion size was significantly larger in the underestimation group of CCLs (p = 0.007). Fine pleomorphic morphology of microcalcifications (p < 0.001), the distribution of the microcalcifications (p = 0.007), BI-RADS final assessment (p = 0.001), and imaging-pathologic correlation (p < 0.001) were significantly associated with underestimation. Multivariate analysis showed that fine pleomorphic morphology of microcalcifications (p < 0.0001) was an independent predictor of underestimation in 58 lesions with microcalcifications on mammography.<br><br>CONCLUSION: The overall underestimation rate of malignancy was 1.4%. Imaging follow-up is reasonable for CCLs without atypia at CNB, especially in small lesions with less suspicious imaging findings. Fine pleomorphic microcalcifications and higher BI-RADS category might be helpful in the prediction of underestimation of a high-risk lesion or malignancy.}, }
@article {pmid24058567, year = {2013}, author = {Assi, J and Srivastava, G and Matta, A and Chang, MC and Walfish, PG and Ralhan, R}, title = {Transglutaminase 2 overexpression in tumor stroma identifies invasive ductal carcinomas of breast at high risk of recurrence.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e74437}, pmid = {24058567}, issn = {1932-6203}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*enzymology/*pathology ; Carcinoma, Ductal, Breast/*enzymology/*pathology ; Cytoplasm/enzymology/pathology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Focal Adhesion Protein-Tyrosine Kinases ; GTP-Binding Proteins ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/*enzymology/*pathology ; Phosphorylation ; Protein Glutamine gamma Glutamyltransferase 2 ; Risk Factors ; Stromal Cells/enzymology/pathology ; Transglutaminases/*metabolism ; }, abstract = {INTRODUCTION: Molecular markers for predicting breast cancer patients at high risk of recurrence are urgently needed for more effective disease management. The impact of alterations in extracellular matrix components on tumor aggressiveness is under intense investigation. Overexpression of Transglutaminase 2 (TG2), a multifunctional enzyme, in cancer cells impacts epithelial mesenchymal transition, growth, invasion and interactions with tumor microenvironment. The objective of our study is to determine the clinical relevance of stromal TG2 overexpression and explore its potential to identify breast cancers at high risk of recurrence.<br><br>METHODS: This retrospective study is based on immunohistochemical analysis of TG2 expression in normal breast tissues (n&#x200a;=&#x200a;40) and breast cancers (n&#x200a;=&#x200a;253) with clinical, pathological and follow-up data available for up to 12 years. TG2 expression was correlated with clinical and pathological parameters as well as disease free survival (DFS) of breast cancer patients.<br><br>RESULTS: Stromal TG2 overexpression was observed in 114/253 (45.0%) breast cancer tissues as compared to breast normal tissues. Among invasive ductal carcinomas (IDC) of the breast, 97/168 (57.7%) showed strong TG2 expression in tumor stroma. Importantly, IDC patients showing stromal TG2 accumulation had significantly reduced DFS (mean DFS&#x200a;=&#x200a;110 months) in comparison with patients showing low expression (mean DFS&#x200a;=&#x200a;130 months) in Kaplan-Meier survival analysis (p<0.001). In Cox multivariate regression analysis, stromal TG2 accumulation was an independent risk factor for recurrence (p&#x200a;=&#x200a;0.006, Hazard's ratio, H.R.&#x200a;=&#x200a;3.79). Notably, these breast cancer patients also showed immunostaining of N-epsilon gamma-glutamyl lysine amino residues in tumor stroma demonstrating the transamidating activity of TG2.<br><br>CONCLUSIONS: Accumulation of TG2 in tumor stroma is an independent risk factor for identifying breast cancer patients at high risk of recurrence. TG2 overexpression in tumor stroma may serve as a predictor of poor prognosis for IDC of the breast.}, }
@article {pmid24054033, year = {2013}, author = {Moon, A and Lim, SJ and Jo, YH and Lee, S and Kim, JY and Lee, J and Park, JH}, title = {Downregulation of GLTSCR2 expression is correlated with breast cancer progression.}, journal = {Pathology, research and practice}, volume = {209}, number = {11}, pages = {700-704}, doi = {10.1016/j.prp.2013.07.010}, pmid = {24054033}, issn = {1618-0631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/mortality/pathology ; Cell Line, Tumor ; Disease Progression ; Disease-Free Survival ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Time Factors ; Tissue Array Analysis ; Transfection ; Tumor Suppressor Proteins/genetics/*metabolism ; Young Adult ; }, abstract = {Glioma tumor-suppressor candidate region gene2 (GLTSCR2) is a recently identified nucleolus-localized protein participating in the regulation of cell cycle progression and apoptosis. Down-regulation of GLTSCR2 in several types of cancers and increased transforming activity in GLTSCR2-downregulated cancer cells indicated its tumor suppressive potential. The aim of this study was to evaluate GLTSCR2 expression in breast cancer and to investigate the question of whether reduced expression of GLTSCR2 may have any pathological significance in breast cancer development or progression. In this study, we performed quantitative RT-PCR and immunohistochemistry to evaluate the expression of GLTSCR2 and relevance with clinicopathological factors in the invasive ductal carcinoma (IDC). GLTSCR2 expression was reduced in 48% of IDC (n=426) by a semi-quantitative scoring system using tissue microarray. GLTSCR2 mRNA was significantly reduced by 0.16 fold in 15 out of 17 (88%) cases of IDC. Reduction of GLTSCR2 was significantly correlated with increased histological grade (p<0.005), increased tumor size (p<0.001), axillary lymph node involvement (p<0.001) and decreased disease free survival (p<0.025). In addition, we show that upregulation of GLTSCR2 decreases the invasive potential of breast cancer cells. Taken together, our data suggest that GLTCR2 may play a role in the tumorigenesis, progression and biological behavior in breast cancer.}, }
@article {pmid24028863, year = {2013}, author = {Walcourt, A and Kurantsin-Mills, J and Kwagyan, J and Adenuga, BB and Kalinowski, DS and Lovejoy, DB and Lane, DJ and Richardson, DR}, title = {Anti-plasmodial activity of aroylhydrazone and thiosemicarbazone iron chelators: effect on erythrocyte membrane integrity, parasite development and the intracellular labile iron pool.}, journal = {Journal of inorganic biochemistry}, volume = {129}, number = {}, pages = {43-51}, pmid = {24028863}, issn = {1873-3344}, support = {UH1HL03679/HL/NHLBI NIH HHS/United States ; UL1 RR031975/RR/NCRR NIH HHS/United States ; UL1 TR000101/TR/NCATS NIH HHS/United States ; 5 SO6 GM008016-39/GM/NIGMS NIH HHS/United States ; UL1RR031975/RR/NCRR NIH HHS/United States ; 2MO1RR10284/RR/NCRR NIH HHS/United States ; M01 RR010284/RR/NCRR NIH HHS/United States ; S06 GM008016/GM/NIGMS NIH HHS/United States ; UH1 HL003679/HL/NHLBI NIH HHS/United States ; G12 MD007597/MD/NIMHD NIH HHS/United States ; G12MD007597/MD/NIMHD NIH HHS/United States ; }, mesh = {*Antimalarials/chemistry/pharmacology ; Erythrocyte Membrane/chemistry/*metabolism ; Hemolysis/drug effects ; Humans ; *Hydrazones/chemistry/pharmacology ; *Iron Chelating Agents/chemistry/pharmacology ; Plasmodium falciparum/*metabolism ; *Semicarbazides/chemistry/pharmacology ; }, abstract = {Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum, in culture and in animal and human studies. We previously reported the anti-plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In fact, these ligands showed greater growth inhibition of chloroquine-sensitive (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture compared to desferrioxamine (DFO). The present study examined the effects of 311, N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development. While the characteristic biconcave disk shape of the erythrocytes was unaffected, the chelators caused very slight hemolysis at IC50 values that inhibited parasite growth. The chelators 311, N4mT and N4pT affected all stages of the intra-erythrocytic development cycle (IDC) of P. falciparum in culture. However, while these ligands primarily affected the ring-stage, DFO inhibited primarily trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC were inhibited by significantly lower concentrations of 311, N4mT, and N4pT (IC50=4.45±1.70, 10.30±4.40, and 3.64±2.00μM, respectively) than DFO (IC50=23.43±3.40μM). Complexation of 311, N4mT and N4pT with iron reduced their anti-plasmodial activity. Estimation of the intracellular labile iron pool (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT corresponded to their anti-plasmodial activities, suggesting that the LIP may be a potential source of non-heme iron for parasite metabolism within the erythrocyte. This study has implications for malaria chemotherapy that specifically disrupts parasite iron utilization.}, }
@article {pmid24022309, year = {2013}, author = {El Deeb, NM and Mehanna, RA}, title = {Assessment of maturation status of tumor-infiltrating dendritic cells in invasive ductal carcinoma of the breast: relation with vascular endothelial growth factor expression.}, journal = {Turk patoloji dergisi}, volume = {29}, number = {3}, pages = {193-200}, doi = {10.5146/tjpath.2013.01186}, pmid = {24022309}, issn = {1309-5730}, mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/metabolism/pathology ; Carcinoma, Ductal, Breast/*immunology/metabolism/pathology ; Dendritic Cells/*immunology/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Vascular Endothelial Growth Factor A/*biosynthesis ; }, abstract = {OBJECTIVE: Poor immunogenicity has been described in breast carcinoma although dendritic cells, the major antigen presenters, are known to infiltrate the tumor. Vascular endothelial growth factor has been proposed to reduce local immune response in tumors. We investigated the maturation status of dendritic cells in invasive ductal carcinoma of the breast in relation to vascular endothelial growth factor expression and clinicopathological parameters.<br><br>MATERIAL AND METHOD: Fifty invasive ductal carcinomas of the breast were immunostained with CD1a (marker of immature dendritic cells); CD83 (marker of mature dendritic cells), vascular endothelial growth factor, estrogen receptor and progesterone receptor.<br><br>RESULTS: Mature dendritic cells were detected in 36 cases (72%), and correlated with smaller tumor size, negative lymph nodes, positive steroid receptor status, and lower grade (P < 0.001). Immature dendritic cells were found in 100% of cases and correlated only with negative steroid receptor expression (estrogen receptor and progesterone receptor) (P=0.006 and 0.020 respectively). Vascular endothelial growth factor expression was detected in 44 cases (88%), and correlated directly with positive nodal metastases (P=0.014), correlated inversely with mature dendritic cell count (P=0.005); and did not correlate with immature dendritic cell count (P=0.104).<br><br>CONCLUSION: Mature dendritic cell count correlates with good prognostic features in invasive ductal carcinoma of the breast, suggesting their role in initiating primary anti-tumor immune response. Vascular endothelial growth factor expression may play a role in inhibition of dendritic cell maturation sequence in the tumor microenvironment.}, }
@article {pmid24018805, year = {2013}, author = {Zhou, M}, title = {Intraductal carcinoma of the prostate: the whole story.}, journal = {Pathology}, volume = {45}, number = {6}, pages = {533-539}, doi = {10.1097/PAT.0b013e3283653322}, pmid = {24018805}, issn = {1465-3931}, mesh = {Carcinoma, Ductal/genetics/*pathology ; Humans ; Male ; Prostatic Neoplasms/genetics/*pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is characterised by proliferation of malignant secretory cells that markedly expand prostatic ducts and acini. Its morphological features and diagnostic criteria have been refined in recent studies. Its molecular characteristics have also been increasingly elucidated. IDC-P is strongly associated with high grade and high volume invasive prostate cancer and unfavourable clinical outcomes. Therefore, it is critical to recognise and report IDC-P, especially in prostate biopsies where the clinical implications of the diagnosis are greatest. IDC-P has to be distinguished from several other prostate lesions with similar histological appearance. The distinction between IDC-P and high grade prostatic intraepithelial neoplasia is most important as they have drastically different implications for patient management. IDC-P is an uncommon finding in prostate biopsies, and is even rarer as an isolated finding without concomitant prostate cancer in biopsies. However, patients with isolated IDC-P in biopsies are recommended for either definitive treatment or immediate repeat biopsy. This article will review the historical aspect, diagnostic criteria, molecular genetics, and clinical significance of IDC-P.}, }
@article {pmid24004816, year = {2013}, author = {Okubo, M and Tada, K and Niwa, T and Nishioka, K and Tsuji, E and Ogawa, T and Seto, Y}, title = {A case of breast cancer in the axillary tail of Spence - enhanced magnetic resonance imaging and positron emission tomography for diagnostic differentiation and preoperative treatment decision.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {217}, pmid = {24004816}, issn = {1477-7819}, mesh = {Adenocarcinoma/*diagnosis/surgery ; Adult ; Axilla ; Breast Neoplasms/*diagnosis/surgery ; Decision Making ; Diagnosis, Differential ; Female ; Humans ; *Magnetic Resonance Imaging ; *Multimodal Imaging ; *Positron-Emission Tomography ; Preoperative Care ; Prognosis ; }, abstract = {BACKGROUND: The management of cancer in the axillary area depends on the etiology of the tumor.<br><br>CASE REPORT: A 37-year-old woman presented with a 2 cm mass in the axillary fossa. Core needle biopsy revealed adenocarcinoma. There were no abnormal breast findings on physical examination, mammography, or ultrasonography. However, enhanced magnetic resonance imaging (MRI) and positron emission tomography (PET) showed a segmentally-distributed, abnormal area in the upper-outer quadrant, continuous with the axillary mass. Samples of this area obtained by vacuum-assisted biopsy showed intraductal carcinoma. These findings indicated that the axillary lesion was a part of primary breast cancer originating from the axillary tail. Based on these results, the patient underwent total mastectomy with sentinel lymph node biopsy. Pathological examination of the specimen showed invasive ductal carcinoma accompanied by intraductal carcinoma extending up to 8.5 cm. Our case suggests that enhanced MRI and PET can provide useful preoperative information for the management of axillary breast lesions.}, }
@article {pmid24001613, year = {2013}, author = {Zhang, B and Yin, C and Li, H and Shi, L and Liu, N and Sun, Y and Lu, S and Liu, Y and Sun, L and Li, X and Chen, W and Qi, Y}, title = {Nir1 promotes invasion of breast cancer cells by binding to chemokine (C-C motif) ligand 18 through the PI3K/Akt/GSK3β/Snail signalling pathway.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {49}, number = {18}, pages = {3900-3913}, doi = {10.1016/j.ejca.2013.07.146}, pmid = {24001613}, issn = {1879-0852}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Breast Neoplasms/genetics/*metabolism/pathology ; Calcium-Binding Proteins/genetics/*metabolism ; Cell Line, Tumor ; Chemokines, CC/genetics/*metabolism ; Chromones/pharmacology ; Epithelial-Mesenchymal Transition/drug effects/genetics ; Female ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; MCF-7 Cells ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Morpholines/pharmacology ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Protein Binding ; Proto-Oncogene Proteins c-akt/metabolism ; *Signal Transduction ; Snail Family Transcription Factors ; Transcription Factors/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Chemokine (C-C motif) ligand 18 (CCL18), which is derived from tumour-associated macrophages (TAMs), plays a critical role in promoting breast cancer metastasis via its receptor, PYK2 N-terminal domain interacting receptor 1 (Nir1). However, the molecular mechanism by which Nir1 promotes breast cancer metastasis by binding to CCL18 remains elusive. In this study, Nir1 expression was associated with lymph node and distant metastasis in patients with invasive ductal carcinoma. For the first time, we report that Nir1 binding to CCL18 promotes the phosphorylation of Akt, LIN-11, Isl1 and MEC-3 protein domain kinase (LIMK), and cofilin, which is a critical step in cofilin recycling and actin polymerisation. Interestingly, Nir1 binding to CCL18 can enhance cell mesenchymal properties and induce epithelial-mesenchymal transition (EMT). Mechanistically, Nir1 binding to CCL18 stabilises Snail via the Akt/GSK3β signalling pathway. In support of these observations, Nir1 binding to CCL18 promoted lung metastasis and LY294002 could inhibit it in vivo. In summary, our in vitro and in vivo results indicate that Nir1 binding to CCL18 plays an important role in breast cancer invasion/metastasis. This study identified both Nir1 and CCL18 as potential anti-invasion targets for therapeutic intervention in breast cancer.}, }
@article {pmid23996076, year = {2013}, author = {Kariagina, A and Xie, J and Langohr, IM and Opreanu, RC and Basson, MD and Haslam, SZ}, title = {Progesterone decreases levels of the adhesion protein E-cadherin and promotes invasiveness of steroid receptor positive breast cancers.}, journal = {Hormones &amp; cancer}, volume = {4}, number = {6}, pages = {371-380}, pmid = {23996076}, issn = {1868-8500}, support = {U01 ES012800/ES/NIEHS NIH HHS/United States ; U01 ES/CA 012800/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*metabolism/pathology ; Cadherins/genetics/*metabolism ; Carcinoma, Ductal/*metabolism/pathology ; Cell Line, Tumor ; Estrogens/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Neoplasms, Experimental/*metabolism/pathology ; Neoplasm Invasiveness ; Progesterone/*metabolism ; Promegestone/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Progesterone/metabolism ; Wnt Signaling Pathway ; }, abstract = {Progestins are reported to increase the risk of invasive breast cancers in postmenopausal women receiving hormone therapy with estrogen plus progestin. We report here that estrogen and progesterone receptor positive (ER+PR+) rat mammary tumors arising in the presence of estrogen and progesterone exhibit increased invasiveness and decreased expression of E-cadherin protein compared with tumors growing in the presence of estrogen alone. A similar decrease of E-cadherin expression was observed in human ER+PR+ invasive ductal carcinoma compared with ductal carcinoma in situ. In agreement with findings in the rat, estrogen plus progestin R5020 treatment decreased E-cadherin expression in vitro in T47D human breast cancer cells. Decrease of E-cadherin protein was mediated by progesterone receptor B (PRB) and dependent on the activation of the Wnt pathway. These results suggest that progesterone signaling via PRB contributes to tumor invasiveness and can provide an important therapeutic target for treatment of invasive ER+PR+ breast cancers.}, }
@article {pmid23988541, year = {2013}, author = {Serra, R and Buffone, G and Perri, P and Renne, M and Amato, B and de Franciscis, S}, title = {Male breast cancer manifesting as cephalic vein thrombosis.}, journal = {Annals of vascular surgery}, volume = {27}, number = {8}, pages = {1188.e9-11}, doi = {10.1016/j.avsg.2013.01.016}, pmid = {23988541}, issn = {1615-5947}, mesh = {Aged ; Anticoagulants/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast Neoplasms, Male/*complications/diagnosis/therapy ; Carcinoma, Ductal, Breast/*complications/diagnosis/therapy ; Chemotherapy, Adjuvant ; Humans ; Male ; Mastectomy, Simple ; Treatment Outcome ; Ultrasonography, Doppler, Duplex ; Upper Extremity/*blood supply ; Venous Thromboembolism/diagnosis/drug therapy/*etiology ; Venous Thrombosis/diagnosis/drug therapy/*etiology ; }, abstract = {Male breast cancer is an uncommon disease with a low annual prevalence in Western countries. Venous thromboembolism may be associated during malignancy of the breast. We report a 70-year-old man who presented with superficial vein thrombosis of right upper limb that predicted the diagnosis of breast invasive ductal carcinoma. Key issues surrounding the diagnosis, treatment, and relationship between breast cancer and venous disorders are discussed. Breast cancer and venous thromboembolism are 2 conditions that are often correlated more than expected, and attention to the combination of these clinical presentations is required.}, }
@article {pmid23983079, year = {2014}, author = {Nakash, O and Levav, I and Aguilar-Gaxiola, S and Alonso, J and Andrade, LH and Angermeyer, MC and Bruffaerts, R and Caldas-de-Almeida, JM and Florescu, S and de Girolamo, G and Gureje, O and He, Y and Hu, C and de Jonge, P and Karam, EG and Kovess-Masfety, V and Medina-Mora, ME and Moskalewicz, J and Murphy, S and Nakamura, Y and Piazza, M and Posada-Villa, J and Stein, DJ and Taib, NI and Zarkov, Z and Kessler, RC and Scott, KM}, title = {Comorbidity of common mental disorders with cancer and their treatment gap: findings from the World Mental Health Surveys.}, journal = {Psycho-oncology}, volume = {23}, number = {1}, pages = {40-51}, pmid = {23983079}, issn = {1099-1611}, support = {R01 DA016558/DA/NIDA NIH HHS/United States ; R03 TW006481/TW/FIC NIH HHS/United States ; R01 MH069864/MH/NIMH NIH HHS/United States ; R01-MH069864/MH/NIMH NIH HHS/United States ; U01 MH060220/MH/NIMH NIH HHS/United States ; R13-MH066849/MH/NIMH NIH HHS/United States ; R01 MH070884/MH/NIMH NIH HHS/United States ; R01 MH059575/MH/NIMH NIH HHS/United States ; K05 DA015799/DA/NIDA NIH HHS/United States ; R03-TW006481/TW/FIC NIH HHS/United States ; R03 TW006481-01/TW/FIC NIH HHS/United States ; R13 MH066849/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Comorbidity ; Developed Countries/statistics &amp; numerical data ; Developing Countries/statistics &amp; numerical data ; Female ; Global Health/statistics &amp; numerical data ; Health Surveys ; Humans ; Male ; Mental Disorders/complications/*epidemiology/therapy ; Mental Health Services/statistics &amp; numerical data ; Neoplasms/complications/epidemiology/*psychology ; Socioeconomic Factors ; Survivors/psychology/statistics &amp; numerical data ; }, abstract = {OBJECTIVE: This study aimed to study the comorbidity of common mental disorders (CMDs) and cancer, and the mental health treatment gap among community residents with active cancer, cancer survivors and cancer-free respondents in 13 high-income and 11 low-middle-income countries.<br><br>METHODS: Data were derived from the World Mental Health Surveys (N&#x2009;=&#x2009;66,387; n&#x2009;=&#x2009;357 active cancer, n&#x2009;=&#x2009;1373 cancer survivors, n&#x2009;=&#x2009;64,657 cancer-free respondents). The World Health Organization/Composite International Diagnostic Interview was used in all surveys to estimate CMDs prevalence rates. Respondents were also asked about mental health service utilization in the preceding 12&#x2009;months. Cancer status was ascertained by self-report of physician's diagnosis.<br><br>RESULTS: Twelve-month prevalence rates of CMDs were higher among active cancer (18.4%, SE&#x2009;=&#x2009;2.1) than cancer-free respondents (13.3%, SE&#x2009;=&#x2009;0.2) adjusted for sociodemographic confounders and other lifetime chronic conditions (adjusted odds ratio (AOR)&#x2009;=&#x2009;1.44, 95% CI 1.05-1.97). CMD rates among cancer survivors (14.6%, SE&#x2009;=&#x2009;0.9) compared with cancer-free respondents did not differ significantly (AOR&#x2009;=&#x2009;0.95, 95% CI 0.82-1.11). Similar patterns characterized high-income and low-middle-income countries. Of respondents with active cancer who had CMD in the preceding 12&#x2009;months, 59% sought services for mental health problems (SE&#x2009;=&#x2009;5.3). The pattern of service utilization among people with CMDs by cancer status (highest among persons with active cancer, lower among survivors and lowest among cancer-free respondents) was similar in high-income (64.0%, SE&#x2009;=&#x2009;6.0; 41.2%, SE&#x2009;=&#x2009;3.0; 35.6%, SE&#x2009;=&#x2009;0.6) and low-middle-income countries (46.4%, SE&#x2009;=&#x2009;11.0; 22.5%, SE&#x2009;=&#x2009;9.1; 17.4%, SE&#x2009;=&#x2009;0.7).<br><br>CONCLUSIONS: Community respondents with active cancer have higher CMD rates and high treatment gap. Comprehensive cancer care should consider both factors.}, }
@article {pmid23982804, year = {2014}, author = {Jennings, VA and Ilett, EJ and Scott, KJ and West, EJ and Vile, R and Pandha, H and Harrington, K and Young, A and Hall, GD and Coffey, M and Selby, P and Errington-Mais, F and Melcher, AA}, title = {Lymphokine-activated killer and dendritic cell carriage enhances oncolytic reovirus therapy for ovarian cancer by overcoming antibody neutralization in ascites.}, journal = {International journal of cancer}, volume = {134}, number = {5}, pages = {1091-1101}, pmid = {23982804}, issn = {1097-0215}, support = {13244/CRUK_/Cancer Research UK/United Kingdom ; R01 CA107082/CA/NCI NIH HHS/United States ; R01 CA175386/CA/NCI NIH HHS/United States ; /MRC_/Medical Research Council/United Kingdom ; }, mesh = {Antibodies, Neutralizing/*immunology ; Apoptosis ; Ascites/*immunology ; Cytokines/biosynthesis ; Dendritic Cells/*immunology ; Female ; Humans ; Killer Cells, Lymphokine-Activated/*immunology ; *Oncolytic Virotherapy ; Ovarian Neoplasms/immunology/*therapy ; Reoviridae/*immunology ; Tumor Cells, Cultured ; }, abstract = {Reovirus is an oncolytic virus (OV), which acts by both direct tumor cell killing and priming of antitumor immunity. A major obstacle for effective oncolytic virotherapy is effective delivery of OV to tumor cells. Ovarian cancer is often confined to the peritoneal cavity and therefore i.p. delivery of reovirus may provide the ideal locoregional delivery, avoiding systemic dissemination. However, ovarian cancer is associated with an accumulation of ascitic fluid, which may interfere with oncolytic viral therapy. Here, we investigated the effect of ascites on reovirus-induced oncolysis against primary ovarian cancer cells and ovarian cancer cell lines. In the absence of ascites, reovirus was cytotoxic against ovarian cancer cells; however, cytotoxicity was abrogated in the presence of ascitic fluid. Neutralizing antibodies (NAb) were identified as the cause of this inhibition. Loading OV onto cell carriers may facilitate virus delivery in the presence of NAb and immune cells which have their own antitumor effector activity are particularly appealing. Immature dendritic cells (iDC), Lymphokine-activated killer (LAK) cells and LAKDC cocultures were tested as potential carriers for reovirus for tumor cell killing and immune cell priming. Reovirus-loaded LAKDC, and to a lesser degree iDC, were able to: (i) protect from NAb and hand-off reovirus for tumor cell killing; (ii) induce a proinflammatory cytokine milieu (IFNɣ, IL-12, IFNα and TNFα) and (iii) generate an innate and specific antitumor adaptive immune response. Hence, LAKDC pulsed with reovirus represent a novel, clinically practical treatment for ovarian cancer to maximise both direct and innate/adaptive immune-mediated tumor cell killing.}, }
@article {pmid23972507, year = {2015}, author = {Ogawa, T}, title = {Goldilocks mastectomy for obese Japanese females with breast ptosis.}, journal = {Asian journal of surgery}, volume = {38}, number = {4}, pages = {232-235}, doi = {10.1016/j.asjsur.2013.07.003}, pmid = {23972507}, issn = {0219-3108}, mesh = {Aged ; Breast Neoplasms/complications/*surgery ; Carcinoma, Ductal, Breast/complications/*surgery ; Carcinoma, Intraductal, Noninfiltrating/complications/*surgery ; Female ; Humans ; Japan ; Mastectomy, Subcutaneous/*methods ; Obesity/*complications ; }, abstract = {The Goldilocks mastectomy is a method that uses redundant mastectomy flap tissue alone to create a breast mound in female American patients with macromastia. Goldilocks mastectomy was performed for obese Japanese females with breast ptosis, and its indications were considered for Japanese female patients. This report presents the results of five patients who underwent Goldilocks mastectomy, including one with bilateral breast cancer. The average age of the patients was 72 years (range: 67-76 years). The body mass index (BMI) was more than 25 in all the cases. Four patients had invasive ductal carcinoma, and one patient had noninvasive ductal carcinoma of bilateral breasts. The cosmetic results were found to be good in two cases [a patient with bilateral breast cancer and a severely obese patient (BMI = 39)]. The cosmetic results in the other three cases were poor. Although the reconstructed breast size was small, this procedure resulted in better cosmetic results than what would be achieved with the usual method of mastectomy for Japanese patients with bilateral breast cancer and severely obese Japanese patients.}, }
@article {pmid23971832, year = {2013}, author = {Borges, S and Döppler, H and Perez, EA and Andorfer, CA and Sun, Z and Anastasiadis, PZ and Thompson, E and Geiger, XJ and Storz, P}, title = {Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks breast tumor cell invasion and metastasis.}, journal = {Breast cancer research : BCR}, volume = {15}, number = {2}, pages = {R66}, pmid = {23971832}, issn = {1465-542X}, support = {CA116201-03DR4/CA/NCI NIH HHS/United States ; GM086435/GM/NIGMS NIH HHS/United States ; R01 CA140182/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; R21 NS070117/NS/NINDS NIH HHS/United States ; CA140182/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antimetabolites, Antineoplastic/pharmacology ; Apoptosis ; Azacitidine/*analogs &amp; derivatives/pharmacology ; Breast Neoplasms/*drug therapy/*genetics/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/secondary ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/genetics/secondary ; Carcinoma, Lobular/drug therapy/genetics/secondary ; Cell Movement ; Cell Proliferation ; DNA Methylation/drug effects ; Decitabine ; Epigenesis, Genetic/*drug effects ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; *Gene Silencing ; Humans ; Immunoenzyme Techniques ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Invasiveness ; Promoter Regions, Genetic/*genetics ; Protein Kinase C/*antagonists &amp; inhibitors/genetics ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {INTRODUCTION: DNA methylation-induced silencing of genes encoding tumor suppressors is common in many types of cancer, but little is known about how such epigenetic silencing can contribute to tumor metastasis. The PRKD1 gene encodes protein kinase D1 (PKD1), a serine/threonine kinase that is expressed in cells of the normal mammary gland, where it maintains the epithelial phenotype by preventing epithelial-to-mesenchymal transition.<br><br>METHODS: The status of PRKD1 promoter methylation was analyzed by reduced representation bisulfite deep sequencing, methylation-specific PCR (MSP-PCR) and in situ MSP-PCR in invasive and noninvasive breast cancer lines, as well as in humans in 34 cases of "normal" tissue, 22 cases of ductal carcinoma in situ, 22 cases of estrogen receptor positive, HER2-negative (ER+/HER2-) invasive lobular carcinoma, 43 cases of ER+/HER2- invasive ductal carcinoma (IDC), 93 cases of HER2+ IDC and 96 cases of triple-negative IDC. A reexpression strategy using the DNA methyltransferase inhibitor decitabine was used in vitro in MDA-MB-231 cells as well as in vivo in a tumor xenograft model and measured by RT-PCR, immunoblotting and immunohistochemistry. The effect of PKD1 reexpression on cell invasion was analyzed in vitro by transwell invasion assay. Tumor growth and metastasis were monitored in vivo using the IVIS Spectrum Pre-clinical In Vivo Imaging System.<br><br>RESULTS: Herein we show that the gene promoter of PRKD1 is aberrantly methylated and silenced in its expression in invasive breast cancer cells and during breast tumor progression, increasing with the aggressiveness of tumors. Using an animal model, we show that reversion of PRKD1 promoter methylation with the DNA methyltransferase inhibitor decitabine restores PKD1 expression and blocks tumor spread and metastasis to the lung in a PKD1-dependent fashion.<br><br>CONCLUSIONS: Our data suggest that the status of epigenetic regulation of the PRKD1 promoter can provide valid information on the invasiveness of breast tumors and therefore could serve as an early diagnostic marker. Moreover, targeted upregulation of PKD1 expression may be used as a therapeutic approach to reverse the invasive phenotype of breast cancer cells.}, }
@article {pmid23970633, year = {2014}, author = {Nakiwogga-Muwanga, A and Katabira, E and Kiragga, A and Kambugu, A and Nakibuuka-Lubwama, E and Manabe, YC and Alamo, ST and Colebunders, R}, title = {Factors before enrolment are associated with being removed from a Pharmacy-only Refill Programme at a large urban HIV/AIDS clinic, Uganda.}, journal = {International journal of STD &amp; AIDS}, volume = {25}, number = {2}, pages = {105-112}, doi = {10.1177/0956462413492715}, pmid = {23970633}, issn = {1758-1052}, mesh = {Adult ; Ambulatory Care Facilities ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Appointments and Schedules ; CD4 Lymphocyte Count ; Case-Control Studies ; Female ; Follow-Up Studies ; HIV Infections/*drug therapy/virology ; Health Resources/organization &amp; administration ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Patient Care Team/*organization &amp; administration ; Patient Compliance/*statistics &amp; numerical data ; Pharmacy ; Referral and Consultation/*organization &amp; administration ; Risk Factors ; Uganda ; Urban Population ; Viral Load ; }, abstract = {A Pharmacy-only Refill Programme (PRP) a type of task shifting in which stable HIV-positive patients are managed through pharmacy-only visits instead of physician visits. We performed a study to identify factors for being removed from the PRP in order to establish better referral criteria. The study was performed at the Infectious Disease Clinic (IDC) in Kampala, Uganda. We selected a random sample of 588 patients from 2431 patients on antiretroviral therapy referred to the PRP at least 12 months before commencement of the PRP evaluation. We compared the characteristics of patients who during 12 months of follow-up were removed from the PRP with those who continued to be followed up. Data were abstracted from the IDC data base, the pharmacy register and the patient clinical notes. Of 588 patients, 106 (18%) were removed from the PRP. In multivariate analysis, less than 100% self-reported adherence to antiretroviral therapy, missing at least one scheduled appointment in the six months before referral to the PRP and being on a lopinavir/ritonavir-containing regimen were independently associated with being removed from the PRP. Criteria for referring patients to a PRP should focus on antiretroviral therapy adherence and appointment keeping. Patients on a lopinavir/ritonavir-containing regimen should not be targeted for a PRP. On the other hand a PRP is an efficient strategy that targets stable adherent patients in clinics with high patient load.}, }
@article {pmid23944930, year = {2013}, author = {Osako, T and Takeuchi, K and Horii, R and Iwase, T and Akiyama, F}, title = {Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis.}, journal = {Histopathology}, volume = {63}, number = {4}, pages = {509-519}, doi = {10.1111/his.12172}, pmid = {23944930}, issn = {1365-2559}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma/*diagnosis ; Carcinoma, Acinar Cell/diagnosis ; Carcinoma, Ductal, Breast/diagnosis ; *Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Young Adult ; }, abstract = {AIMS: Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers.<br><br>METHODS AND RESULTS: We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for &#x3b1;-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC.<br><br>CONCLUSIONS: In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, &#x3b1;-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis.}, }
@article {pmid23940990, year = {2013}, author = {Milanović, R and Roje, Z and Korusić, A and Deno, IT and Barić, A and Stanec, Z}, title = {Clinical and patohistological factors affecting the 5 year survival rate in a population of Croatian women with invasive ductal breast carcinoma.}, journal = {Collegium antropologicum}, volume = {37}, number = {2}, pages = {459-464}, pmid = {23940990}, issn = {0350-6134}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/*pathology ; Carcinoma, Ductal, Breast/*mortality/*secondary ; Croatia/epidemiology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Grading/mortality ; Neoplasm Recurrence, Local/mortality ; Risk Factors ; Survival Rate ; }, abstract = {Breast carcinoma falls into a heterogeneous group of diseases which can be determined by various prognostic factors. The identification of clinical and histopathologic factors is of great value in predicting the progression of tumor growth and survival outcome. Due to a high degree of cell proliferation in breast tumors and high genetic instability of these tumors, as a consequence of defective DNA repair mechanisms, chemotherapy as a treatment option often renders very successful results. During our scientific study of the expression of genes responsible for mismatch repair of DNA in cells of invasive ductal carcinoma we also compared the patient survival rate with the major prognostic factors. This study included 108 patients who were surgically treated for invasive breast cancer at the Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital "Dubrava". The overall survival rate was compared to factors such as initial tumor stage, regional lymph node involvement and distant metastasis. The overall five year survival rate of our patients was 78.7%. Patients without the presence of distant metastasis, a lower rate of local lymph node involvement and a lower. tumor stage statistically had a longer overall survival period. It is important that physicians recognize the various clinico-pathohistological factors in patients with breast carcinoma. This study confirms that this prognostic factors determine the type of treatment required and most important, the patient overall survival period.}, }
@article {pmid23932764, year = {2014}, author = {Larribe, M and Thomassin-Piana, J and Jalaguier-Coudray, A}, title = {Breast cancers with round lumps: correlations between imaging and anatomopathology.}, journal = {Diagnostic and interventional imaging}, volume = {95}, number = {1}, pages = {37-46}, doi = {10.1016/j.diii.2013.04.003}, pmid = {23932764}, issn = {2211-5684}, mesh = {Adenocarcinoma, Mucinous/diagnosis/pathology ; Breast/*pathology ; Breast Neoplasms/*diagnosis/*pathology/secondary ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Carcinoma, Medullary/diagnosis/pathology ; Carcinoma, Papillary/diagnosis/pathology ; Female ; Humans ; Lymphatic Metastasis/pathology ; Lymphoma/diagnosis/pathology ; *Mammography ; Neoplasm Grading ; Neoplasm Staging ; Phyllodes Tumor/diagnosis/pathology ; Prognosis ; Statistics as Topic ; *Ultrasonography, Mammary ; }, abstract = {A round lump with a well-defined outline is, in most cases, benign. However, in 10 to 20% of all cases, a round and well-defined lump may correspond to a cancer. Most often, it consists of grade III infiltrating ductal carcinoma (IDC). Other histological sub-types may provide round masses with smooth contours: colloid carcinoma (still called mucinous carcinoma), medullary carcinoma, intramammary metastases, intra-cystic papillary carcinoma, lymphoma and high-grade phyllode tumours.}, }
@article {pmid23928534, year = {2013}, author = {Yang, M and Xu, SP and Ao, QL}, title = {[Expression of fatty acid synthase and its association with HER2 in invasive ductal carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {42}, number = {4}, pages = {257-261}, doi = {10.3760/cma.j.issn.0529-5807.2013.04.010}, pmid = {23928534}, issn = {0529-5807}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Fatty Acid Synthases/*metabolism ; Female ; Fibrocystic Breast Disease/metabolism ; Gene Amplification ; Genes, erbB-2 ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2/*metabolism ; }, abstract = {OBJECTIVE: To investigate the expression of fatty acid synthase (FAS) in adenosis, atypical ductal epithelial hyperplasia, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of breast, and the correlation of FAS expression with HER2 gene amplification in IDC.<br><br>METHODS: Immunohistochemical EnVision method staining for FAS was performed in 100 cases of breast lesions and 10 normal breast tissues. HER2 gene amplification was detected with FISH in 60 cases of IDC.<br><br>RESULTS: The cohort included 10 cases of adenosis, 10 atypical ductal epithelial hyperplasia, 20 DCIS (8 high-grade, 9 intermediated-grade and 3 low-grade), and 60 cases of IDC (5 grade 1, 40 grade 2 and 15 grade 3). FAS expression was negative in all 10 normal breast tissues; in the 10 cases of adenosis, strongly positive FAS expression was detected in one case, positive in 2, weakly positive in 4, and negative in 3; in the 10 cases of atypical ductal epithelial hyperplasia, FAS immunohistochemistry showed that 1 was strongly positive, 4 positive, 4 weakly positive, and 1 negative; in the 20 cases of DCIS, FAS immunostaining showed that 12 were strongly positive, 5 positive, 1 weakly positive, and 2 negative; FAS expression showed a clear increasing trend from normal breast tissue, atypical ductal epithelial hyperplasia to DCIS (&#x3c7;(2) = 42.02, P < 0.01). Likewise, the increasing trend was also demonstrated from adenosis to DCIS (&#x3c7;(2) = 34.69, P < 0.01). There was also a positive correlation between FAS expression and extent of lesion among normal breast tissue, adenosis, atypical ductal epithelial hyperplasia and DCIS (&#x3c7;(2) = 86.02, P < 0.01; r = 0.568, P < 0.01). FAS expression was not correlated with the grade of DCIS (&#x3c7;(2) = 9.12, P = 0.16). In the five cases of grade 1 IDC, FAS immunostaining showed that 4 cases were strongly positive and 1 positive; in the 40 cases of grade 2 IDC, FAS immunostaining showed that 27 strongly positive, 12 positive, and 1 negative; in the 15 cases of grade 3 IDC, FAS immunostaining showed that 6 were strongly positive, 5 positive, 3 weakly positive, and 1 negative; FAS expression was stronger and more extensive in DCIS, IDC grades 1 and 2 than that in other groups. However, FAS expression was weaker in the IDC grade 3 (&#x3c7;(2) = 11.26, P = 0.01). The positive expression rate of FAS in IDC was generally higher than that in benign breast lesions (&#x3c7;(2) = 47.19, P < 0.01). In the 60 cases of IDC, FISH showed HER2 gene amplification in 22 cases, but not in the remaining 38 cases. FAS expression in IDC was highly correlated with HER2 gene amplification (r = 0.44, P < 0.01). The expression of FAS had significant correlation with status of ER and PR and tumor size (P < 0.05). There was no significant correlation with age, immunohistochemical HER2 expression, lymph node metastasis and clinical stage (P > 0.05).<br><br>CONCLUSIONS: FAS may be closely related to the carcinogenesis of breast IDC. FAS expression is closely associated with HER2 gene amplification in IDC.}, }
@article {pmid23917522, year = {2014}, author = {Patange, A and Thomas, R and Ross, RD}, title = {Severity of mitral regurgitation predicts risk of death or cardiac transplantation in children with idiopathic dilated cardiomyopathy.}, journal = {Pediatric cardiology}, volume = {35}, number = {2}, pages = {232-238}, pmid = {23917522}, issn = {1432-1971}, mesh = {Adolescent ; Cardiomyopathy, Dilated/*complications/mortality/surgery ; Child ; Child, Preschool ; Death, Sudden, Cardiac/*epidemiology/etiology ; Echocardiography ; Female ; Follow-Up Studies ; Forecasting ; *Heart Transplantation ; Humans ; Incidence ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging, Cine ; Male ; Mitral Valve Insufficiency/complications/*diagnosis/surgery ; Prognosis ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate/trends ; United States/epidemiology ; }, abstract = {Clinical outcomes among children with idiopathic dilated cardiomyopathy (IDC) are diverse, which makes the decision as to when a patient should be listed for a cardiac transplantation challenging. This study aimed to determine echocardiographic and clinical variables that can help clinicians identify those at highest risk for death or cardiac transplantation. The study was a single-center, retrospective chart review of children with IDC. Patients younger than 18 years with a diagnosis of IDC, as defined by a left ventricular end-diastolic dimension (LVEDD) z-score higher than 2, and fractional shortening of less than 28 % on the initial echocardiogram, were included in the study. Echocardiographic parameters including mitral regurgitation (MR) grade and certain clinical parameters at the time of presentation were assessed. A follow-up echocardiogram was similarly studied. The study included 49 children with IDC. Those who died or underwent cardiac transplantation were grouped as "nonsurvivors" (n = 26). The remaining children who either completely recovered or experienced chronic dilated cardiomyopathy were grouped as "survivors" (n = 23). The median age overall was 1.25 years (range 0.1-17 years). The follow-up echocardiograms of the survivors showed significant improvement in left ventricle size, systolic function, left atrial volume, and MR grade, whereas these parameters did not change in the nonsurvivor group. The use of inotropic medications at initial presentation was an independent predictor of death or cardiac transplantation (p < 0.05). The presence of moderate to severe MR at diagnosis also was predictive of a worse outcome.}, }
@article {pmid23910495, year = {2013}, author = {Guilbert, A and Gautier, M and Dhennin-Duthille, I and Rybarczyk, P and Sahni, J and Sevestre, H and Scharenberg, AM and Ouadid-Ahidouch, H}, title = {Transient receptor potential melastatin 7 is involved in oestrogen receptor-negative metastatic breast cancer cells migration through its kinase domain.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {49}, number = {17}, pages = {3694-3707}, doi = {10.1016/j.ejca.2013.07.008}, pmid = {23910495}, issn = {1879-0852}, mesh = {Breast Neoplasms/*genetics/*pathology ; Calcium/metabolism ; Cell Movement/drug effects/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Neoplasm Metastasis ; Phosphotransferases/chemistry/physiology ; Protein Structure, Tertiary/physiology ; RNA, Small Interfering/pharmacology ; Receptors, Estrogen/metabolism ; TRPM Cation Channels/antagonists &amp; inhibitors/chemistry/*physiology ; Tumor Cells, Cultured ; }, abstract = {Oestrogen receptor negative (ER(-)) invasive ductal carcinoma (IDC) represents a significant clinical challenge and therefore prompts the discovery of novel biomarkers. Transient receptor potential melastatin 7 (TRPM7), a channel protein that also contains a regulatory kinase domain, is overexpressed in IDC and regulates migration. However, the molecular mechanism remains poorly defined. Here, we examined whether TRPM7 regulates migration by its channel function or by its kinase domain. A Magnesium Inhibited Cation current was recorded in two ER(-) highly metastatic breast cancer cell lines. Down-regulation of TRPM7 neither affected Ca(2+)-, nor Mg(2+)-homoeostasis but significantly reduced cell migration via a Ca(2+)-independent pathway. Notably, the overexpression of the truncated kinase domain form of TRPM7 decreased cell migration, while the overexpression of the wild-type form strongly increased it. Concomitantly, TRPM7 silencing reduced the myosin IIA heavy chain phosphorylation. Furthermore, we found higher TRPM7 expression in ER(-) IDC tissues and lymph nodes than in the non-invasive tumoural samples. In conclusion, TRPM7 plays a critical role in breast cancer cell migration through its kinase domain, and our data support the consideration of using TRPM7 as a novel biomarker and a potential therapeutic target in the treatment of human ER(-) IDC.}, }
@article {pmid23907150, year = {2014}, author = {Khoury, T and Hu, Q and Liu, S and Wang, J}, title = {Intracystic papillary carcinoma of breast: interrelationship with in situ and invasive carcinoma and a proposal of pathogenesis: array comparative genomic hybridization study of 14 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {27}, number = {2}, pages = {194-203}, pmid = {23907150}, issn = {1530-0285}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/classification/*genetics/pathology ; Carcinoma, Ductal, Breast/classification/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/classification/*genetics/pathology ; Carcinoma, Papillary/classification/*genetics/pathology ; Cluster Analysis ; Comparative Genomic Hybridization ; Female ; Gene Dosage ; Humans ; Laser Capture Microdissection ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {Classifying intracystic papillary carcinoma under invasive or in situ ductal carcinoma is still a matter of debate. The purpose of this study was to explore the genomic relationship of this tumor to its concurrent invasive ductal carcinoma and ductal carcinoma in situ using array comparative genomic hybridization. Intracystic papillary carcinoma cases were classified into three categories: pure, with concurrent ductal carcinoma in situ or with concurrent invasive ductal carcinoma. Each component was dissected using laser capture microdissection. DNA was extracted and array comparative genomic hybridization was performed. The test of difference in copy number changes among the three tumors was carried out using CGHMultiArray. Intracystic papillary carcinoma clustered with four of five concurrent ductal carcinoma in situ cases and with two of two invasive ductal carcinoma cases. Intracystic papillary carcinoma showed the highest proportions of genome copy number aberration, followed by ductal carcinoma in situ, and then by invasive ductal carcinoma (P=0.06). Comparing intracystic papillary carcinoma with invasive ductal carcinoma vs without invasive ductal carcinoma, the former had 11q22.1-23.3 loss (P=0.031) and chr5 gain (P=0.085), and was enriched with matrix metalloproteinase genes. Comparing intracystic papillary carcinoma with ductal carcinoma in situ vs without ductal carcinoma in situ, the former had gain in 5q35.3 (P=0.041), 8q24.3 (P=0.041) and 21q13.2 to 21q13.31 (P=0.011). Comparing intracystic papillary carcinoma with ductal carcinoma in situ, the latter acquired a group of genes involved in cell adhesion and motility, whereas intracystic papillary carcinoma differentially expressed genes that are involved in papillary carcinomas of other organs (thyroid and kidney). We conclude that the overall molecular change in intracystic papillary carcinoma is closer to ductal carcinoma in situ than to invasive ductal carcinoma, which may explain the indolent behavior of this tumor. We offer herein a proposal of intracystic papillary carcinoma pathogenesis through its relation to invasive ductal carcinoma and ductal carcinoma in situ.}, }
@article {pmid23899963, year = {2014}, author = {Maschio, LB and Madallozo, BB and Capellasso, BA and Jardim, BV and Moschetta, MG and Jampietro, J and Soares, FA and Zuccari, DA}, title = {Immunohistochemical investigation of the angiogenic proteins VEGF, HIF-1α and CD34 in invasive ductal carcinoma of the breast.}, journal = {Acta histochemica}, volume = {116}, number = {1}, pages = {148-157}, doi = {10.1016/j.acthis.2013.06.005}, pmid = {23899963}, issn = {1618-0372}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, CD34/*metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/secondary ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; ROC Curve ; Tissue Array Analysis ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {The expression of prognostic markers in cancer has become important in diagnostic routine and research. A high mitotic rate compromises the individual cell access to oxygen and nutrients, due to reduced blood supply. Cells undertake adaptive measures such as vascular endothelial growth factor (VEGF), expressed under the control of hypoxia-inducible factor-1α (HIF-1α). CD34 is an endothelial marker which can show the presence and distribution of blood vessels. This study evaluated the presence and relative expression of VEGF, HIF-1α and CD34 using immunohistochemistry of 60 breast tumors and double staining, correlating the findings with clinical and pathological variables. High VEGF expression was correlated with low cell proliferation, lymph node-negative, smaller tumor size and patients not receiving hormone therapy. High HIF-1α expression predominated in younger (<50-year) patients, subjected to neo-adjuvant therapy and in p53-negative tumors. Absence of metastasis, radiotherapy or hormone treatment, and estrogen receptor (ER)-positive tumors showed high CD34 immunoreactivity. We suggest that the angiogenic factors VEGF, HIF-1α and CD34 are important in breast cancer progression and their abundance in breast tumors has prognostic and predictive value.}, }
@article {pmid23891136, year = {2013}, author = {Amin, M and Radkay, L and Pantanowitz, L and Fine, J and Parwani, A}, title = {Tumor-to-tumor metastasis (TTM) of breast carcinoma within a solitary renal angiomyolipoma: a case report.}, journal = {Pathology, research and practice}, volume = {209}, number = {9}, pages = {605-608}, doi = {10.1016/j.prp.2013.06.011}, pmid = {23891136}, issn = {1618-0631}, mesh = {Aged ; Angiomyolipoma/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Female ; Humans ; Kidney Neoplasms/*pathology/secondary ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {Angiomyolipomas of the kidney have been known to harbor malignant neoplasms including renal cell carcinoma. We report a case of a tumor-to-tumor metastasis (TTM) involving metastatic breast carcinoma and angiomyolipoma. The patient was a 67-year-old female with a history of invasive ductal carcinoma of the breast. Follow-up positron emission tomography 9 years later revealed a left renal mass, suspicious for a primary renal neoplasm, as well as a suspicious subpectoral lymph node. An ultrasound-guided needle biopsy of the lymph node demonstrated metastatic breast carcinoma. The patient underwent a left radical nephrectomy. Pathologic examination demonstrated an ill-defined 2cm estrogen receptor (ER)-positive metastatic breast carcinoma within a 6cm angiomyolipoma. To our knowledge, this is the first reported case of metastatic breast carcinoma to a solitary renal angiomyolipoma. This case highlights the importance of a patient's prior history of malignancy, as well as appropriate sampling of renal neoplasms.}, }
@article {pmid23883300, year = {2013}, author = {Wang, S and Zhang, Y and Yang, X and Fan, L and Qi, X and Chen, Q and Jiang, J}, title = {Shrink pattern of breast cancer after neoadjuvant chemotherapy and its correlation with clinical pathological factors.}, journal = {World journal of surgical oncology}, volume = {11}, number = {1}, pages = {166}, pmid = {23883300}, issn = {1477-7819}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Chemotherapy, Adjuvant ; Epirubicin/administration &amp; dosage ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Recurrence, Local/*drug therapy/metabolism/pathology ; Neoplasm Staging ; Neoplasm, Residual/*drug therapy/metabolism/pathology ; Paclitaxel/administration &amp; dosage ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Breast conservation therapy (BCS) after neoadjuvant chemotherapy (NCT) can improve patients' quality of life. Currently used intraoperative examination for negative margins may not be sufficient to detect microresidual foci, which are a risk factor for local recurrence. This study was conducted to investigate the shrinking pattern of breast cancer and residual tumors as a risk factor for BCS after NCT.<br><br>METHODS: Ninety women with stage II or III invasive ductal carcinoma who achieved partial response after NCT with paclitaxel and epirubicin were enrolled. All patients had undergone modified radical mastectomy. One-half of the surgical specimens were subjected to subserial sectioning. Pathological changes of tumor bed and pericancerous tissues were examined with an optical microscope. The levels of estrogen receptors, progesterone receptors and HER2 were analyzed by immnohistochemical staining.<br><br>RESULTS: The residual tumors were classified into three types according to their microscopic morphology: solitary lesion, multifocal and patchlike lesions, and main residual tumor with satellite lesions. Type I residual tumors were found in 55 patients (61%), type II in 30 patients (33%) and type III in 5 patients (6%). Types II and III were often associated with larger primary tumors. The types of residual tumors were not correlated with the status of hormone receptors or HER2.<br><br>CONCLUSION: Three types of residual tumors were observed after NCT. The solitary residual tumor is most common, but main residual tumors with satellite lesions are most likely to cause local recurrence after BCS. Subserial sectioning would improve the identification of microfoci and patient survival after BCS.}, }
@article {pmid23879372, year = {2014}, author = {Tuomainen, PO and Magga, J and Fedacko, J and Kärkkäinen, S and Miettinen, K and Vanninen, E and Kuusisto, J and Peuhkurinen, KJ}, title = {Idiopathic dilated cardiomyopathy and chronic atrial fibrillation.}, journal = {Clinical physiology and functional imaging}, volume = {34}, number = {2}, pages = {133-137}, doi = {10.1111/cpf.12075}, pmid = {23879372}, issn = {1475-097X}, mesh = {Adolescent ; Adult ; Aged ; Arterial Pressure ; Atrial Fibrillation/blood/diagnosis/*etiology/physiopathology ; Biomarkers/blood ; Cardiomyopathy, Dilated/blood/*complications/diagnosis/*physiopathology ; Chronic Disease ; Female ; Heart Atria/diagnostic imaging ; Heart Ventricles/diagnostic imaging/physiopathology ; Humans ; Interleukin-6/blood ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Pulmonary Artery/physiopathology ; Pulmonary Wedge Pressure ; Stroke Volume ; Tomography, Emission-Computed, Single-Photon ; Ultrasonography ; Ventricular Function, Left ; Young Adult ; }, abstract = {BACKGROUND: Atrial fibrillation (AF) is common in idiopathic dilated cardiomyopathy (IDC). We explored the clinical characteristics of IDC patients with chronic AF compared with those with sinus rhythm (SR).<br><br>METHODS: A group of patients with IDC underwent extensive non-invasive and invasive evaluation during a hospitalization period. The patients were further divided into two groups with AF (n&#xa0;=&#xa0;19) and SR (n&#xa0;=&#xa0;68).<br><br>RESULTS: Left atrial diameter was greater (P<0&#xb7;001), left ventricular end-diastolic diameter smaller (P<0&#xb7;05), left ventricular end-diastolic and end-systolic volumes smaller (P<0&#xb7;01 for all), mean pulmonary artery pressure and pulmonary capillary wedge pressure higher (P<0&#xb7;05 for both), cardiac output and maximal oxygen consumption lower (P<0&#xb7;01 and P<0&#xb7;05, respectively), and the levels of N-terminal pro-brain natriuretic peptide and interleukin-6 higher (P<0&#xb7;05 for both) in AF group compared with SR group. Left ventricular ejection fraction and left ventricular end-diastolic pressure were similar in both groups.<br><br>CONCLUSIONS: In spite of otherwise more unfavourable prognostic factor profile, left ventricular size was observed to be smaller in chronic AF compared with SR in well-characterized patients with IDC. The confirmation and possible explainers of this paradoxical phenomenon need further studies in larger patient cohorts.}, }
@article {pmid23870824, year = {2013}, author = {Kis-Toth, K and Bacskai, I and Gogolak, P and Mazlo, A and Szatmari, I and Rajnavolgyi, E}, title = {Monocyte-derived dendritic cell subpopulations use different types of matrix metalloproteinases inhibited by GM6001.}, journal = {Immunobiology}, volume = {218}, number = {11}, pages = {1361-1369}, doi = {10.1016/j.imbio.2013.06.012}, pmid = {23870824}, issn = {1878-3279}, mesh = {Antigens, CD1/metabolism ; Cell Differentiation/immunology ; Cell Movement/*drug effects/immunology ; Cells, Cultured ; Dendritic Cells/*immunology ; Dipeptides/*pharmacology ; Humans ; Inflammation/*immunology ; Matrix Metalloproteinase 12/biosynthesis/metabolism ; Matrix Metalloproteinase 9/biosynthesis/metabolism ; Matrix Metalloproteinase Inhibitors/*pharmacology ; Monocytes ; Tissue Inhibitor of Metalloproteinase-1/biosynthesis/metabolism ; Tissue Inhibitor of Metalloproteinase-2/biosynthesis/metabolism ; }, abstract = {Matrix metalloproteinases (MMPs) are endopeptidases with the potential to cleave extracellular matrix, support tissue renewal and regulate cell migration. Functional activities of MMPs are regulated by tissue inhibitors of MMPs (TIMPs) and disruption of the MMP-TIMP balance has pathological consequences. Here we studied the expression and secretion of MMPs and TIMPs in CD1a(-) and CD1a(+) monocyte-derived dendritic cell (DC) subpopulations. Our results showed that monocytes express TIMPs but lack MMPs, whereas upon differentiation to moDCs and in response to activation signals the expression of MMPs is increased and that of TIMPs is decreased. MMP-9 is expressed dominantly in the CD1a(-) subpopulation, while MMP-12 is preferentially expressed in CD1a(+) cells. Experiments performed with the synthetic MMP inhibitor GM6001 revealed that this drug efficiently inhibits the migration of moDCs through inactivation of MMPs. We conclude that modulation of MMP activity by GM6001 emerges as a novel approach to manipulate DC migration under inflammatory conditions.}, }
@article {pmid23863867, year = {2013}, author = {Korhonen, T and Kuukasjärvi, T and Huhtala, H and Alarmo, EL and Holli, K and Kallioniemi, A and Pylkkänen, L}, title = {The impact of lobular and ductal breast cancer histology on the metastatic behavior and long term survival of breast cancer patients.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {6}, pages = {1119-1124}, doi = {10.1016/j.breast.2013.06.001}, pmid = {23863867}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Carcinoma, Lobular/*pathology/*secondary ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms/secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/secondary ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*pathology ; Proportional Hazards Models ; Skin Neoplasms/secondary ; Survival Rate ; }, abstract = {The aim of the study was to evaluate the long-term survival of patients with invasive lobular carcinomas (ILC) and invasive ductal carcinomas (IDC) and the metastatic behavior of these two disease entities. Originally, all consecutive patients with pure lobular invasive breast cancers diagnosed between 1990 and 1999 in the area served by the Tampere University Hospital and their matched IDC controls were identified and re-evaluated histopathologically in this follow-up study, resulting in a total of 243 ILCs and 243 IDCs. Data on recurrences and survival were collected until the end of year 2009. Statistical analyses including Kaplan-Meier method, log-rank test, Fisher's exact test and Cox regression analysis were performed with the PASW Statistics 18.0 computer program. P-values of <0.05 were considered statistically significant. Within the mean follow-up time of 10.04 years, locoregional recurrences were significantly more common among the ILCs than IDCs (35 vs. 20, p = 0.04), but no differences in the total number of distant recurrences or bilaterality were observed. However, when the first distant recurrence sites were studied, ILC patients had significantly less lung metastases (p = 0.04), but more skin metastases (p = 0.04). During the whole follow-up period IDCs metastasized significantly more frequently to the lungs (p = 0.002), whereas gastrointestinal metastases were more common among ILCs (p = 0.02). Although the known favorable prognostic factors (hormone receptor positivity, low grade, low s-phase) were more common for the ILCs, the disease-free survival, the overall survival and the survival after recurrence did not differ between the groups. However, the Cox-regression model showed significantly worse survival for ILCs after adjusting for age, TNM-status, grade and ER-positivity (p = 0.004). In conclusion, ILC and IDC differ in respect for visceral metastases. Despite the known favorable prognostic factors and originally favorable survival, patients with lobular histology appear to have a worse survival in the multivariate analysis after a prolonged follow-up.}, }
@article {pmid23863656, year = {2013}, author = {Matsuda, T and Fujita, H and Kunimoto, Y and Hosono, M and Kimura, T and Hayashi, T and Maeda, T and Yamakawa, J and Maeda, N and Mizumoto, T and Maruyama, S and Uenaka, Y and Ogino, K}, title = {[Successful ventilator weaning by trastuzumab in a HER2-positive breast cancer patient with multiple lung metastases].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {40}, number = {6}, pages = {773-776}, pmid = {23863656}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Female ; Humans ; Lung Neoplasms/*drug therapy/secondary ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/analysis ; Trastuzumab ; Ventilator Weaning ; }, abstract = {We report a case of breast cancer with severe respiratory dysfunction due to multiple lung metastases, which was recovered by treatment with weekly trastuzumab administration. A 47-year-old woman with breast cancer had received a folk remedy from a general practitioner for 4 years. However, she was delivered to a hospital because of severe dyspnea, and intubation was found to be needed and performed. She was diagnosed with left breast cancer with skin and pleural wall invasion, and multiple lung metastases. Pathological examination showed invasive ductal carcinoma which was ER-postive, PgR-negative, and HER2-postive. After transfer to our hospital, treatment with trastuzumab(4mg/kg/weekly for the first course, and 2 mg/kg/weekly thereafter)was administered. Respiratory function improved gradually, and ventilator weaning was successful at 53 days after trastuzumab administration. CT examination also showed a remarkable reduction of lung and lymph node metastases and pleural effusion. She was discharged from our hospital 80 days after treatment, and her treatment with trastuzumab and capecitabine has been ongoing at an outpatient clinic.}, }
@article {pmid23863654, year = {2013}, author = {Kobayashi, T and Matsuda, Y and Azama, T}, title = {[A case of a patient with breast cancer, diagnosed from sternal metastasis].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {40}, number = {6}, pages = {765-767}, pmid = {23863654}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/*drug therapy/secondary ; Breast Neoplasms/pathology/*therapy ; Bridged-Ring Compounds/administration &amp; dosage ; Carcinoma, Ductal, Breast/pathology/*therapy ; Chemoradiotherapy ; Cyclophosphamide/administration &amp; dosage ; Epirubicin/administration &amp; dosage ; Female ; Humans ; Mastectomy, Segmental ; Neoplasm Staging ; Sternum/*pathology ; Taxoids/administration &amp; dosage ; }, abstract = {A 32-year-old woman was seen in our hospital for complaints of bulge and pain in the sternum, and upon examination showed a lump in the left breast and enlarged left axillary lymph nodes. The patient was diagnosed with invasive ductal carcinoma with metastasis to the sternum that was T2N1M1(OSS), Stage IV, hormone-receptor-positive, and HER2-negative. Four courses each of EC and taxane therapy were performed as primary systemic chemotherapy in combination with zoledronic acid, which resulted in calcification of the osteolytic lesion in the sternum and reduced tumor mass in the breast. The patient was judged to have a partial response(PR)to the treatment. Eight months later, breast-conserving surgery and axillary lymph node dissection were performed, followed by radiation therapy to the left breast and sternum. Treatment with zoledronicac id is ongoing and postoperative hormonal therapy has been started. Four years and 4 months after the initial diagnosis, the lesion in the sternum has calcified and hardened and the patient has not had a recurrence in the same breast or elsewhere in the body.}, }
@article {pmid23863653, year = {2013}, author = {Morishita, A and Mitsuhashi, S and Fujisawa, F and Hirano, M and Kojima, H}, title = {[Usefulness of bevacizumab with paclitaxel for advanced breast cancer - a case report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {40}, number = {6}, pages = {761-764}, pmid = {23863653}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab ; Biopsy, Needle ; Breast Neoplasms/*drug therapy/pathology ; Female ; Humans ; Lung Neoplasms/drug therapy/secondary ; Middle Aged ; Paclitaxel/administration &amp; dosage ; Tomography, X-Ray Computed ; }, abstract = {A 55-year-old woman with an exudative, necrotizing left breast tumor consulted Ibaraki Prefectural Central Hospital and Cancer Center. We diagnosed her as advanced ER+, PgR-, HER2- invasive ductal carcinoma of the left breast by tumor needle biopsy. FDG-PET/CT revealed multiple lymph node, pulmonary, bone, and hepatic metastases. Systemic chemotherapy with biweekly bevacizumab and weekly paclitaxel(PTX)was administered. The chemotherapy induced a widespread tumor lysis in her left chest wall. We continued chemotherapy, and the ulcer has been healing gradually. We recognized that bevacizumab with PTX successfully brought about a rapid, good local response, and improved the patient's quality of life.}, }
@article {pmid23850271, year = {2013}, author = {Lu, Z and Yong, T and Wen, Y and Yifei, G and Xinwei, W and Lili, Y and Ye, T}, title = {Vesicle consisted of calcified core and intervening turbid fluid, a possible composition of calcification in intervertebral disc calcification in children.}, journal = {Medical hypotheses}, volume = {81}, number = {3}, pages = {503-505}, doi = {10.1016/j.mehy.2013.06.021}, pmid = {23850271}, issn = {1532-2777}, mesh = {Calcinosis/diagnostic imaging/*physiopathology/surgery ; Child ; Humans ; Intervertebral Disc/diagnostic imaging/*physiopathology/surgery ; Secretory Vesicles/*diagnostic imaging ; Tomography, X-Ray Computed ; }, abstract = {Intervertebral disc calcification (IDC) is one of the uncommon diseases in children. Normally, it is a benign lesion which is self-limited and has an excellent prognosis under conservative treatments and symptomatic support. Surgical treatment is usually carried out only for patients with progressive neurological deterioration in order to prevent the spinal cord from being irreversible injured. After conservative treatments for months or years, the calcification reduces gradually or even disappears through imaging. Until now, the etiology remains unclear and the mechanism for resorption of IDC is still unknown. Surgery was performed on an IDC patient with progressive neurological deterioration, it was found that the high density calcification region on CT is actually not "hard" but more like an enlarged cell. In such a cell, a calcified nuclear was surrounded by limewater-like liquid inside a large membrane. This study aims to unveil the mechanism for the resorption of IDC. We hypothesize that the high density calcification on imaging is a vesicle consisted of calcified core and intervening turbid fluid. Furthermore, the increase or diminution of calcification is caused by the production or resorption of inflammatory fluid around the calcified core in lesion disc. This could explain the mechanism of IDC resorption in children.}, }
@article {pmid23835924, year = {2013}, author = {Liu, M and Guo, X and Wang, S and Jin, M and Wang, Y and Li, J and Liu, J}, title = {BOLD-MRI of breast invasive ductal carcinoma: correlation of R2* value and the expression of HIF-1α.}, journal = {European radiology}, volume = {23}, number = {12}, pages = {3221-3227}, pmid = {23835924}, issn = {1432-1084}, mesh = {Adult ; Aged ; Breast Neoplasms/blood/*chemistry/*pathology ; Carcinoma, Ductal/blood/*chemistry/*pathology/secondary ; Cell Hypoxia ; Feasibility Studies ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*analysis ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Grading ; Oxygen/blood ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Reproducibility of Results ; Tumor Suppressor Protein p53/analysis ; }, abstract = {OBJECTIVE: To explore the reliability and feasibility of blood oxygenation level-dependent-based functional magnetic resonance imaging (BOLD-fMRI) to depict hypoxia in breast invasive ductal carcinoma.<br><br>METHODS: A total of 103 women with 104 invasive ductal carcinomas (IDCs) underwent breast BOLD-fMRI at 3.0 T. Histological specimens were analysed for tumour size, grade, axillary lymph nodes and expression of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, p53, Ki-67 and hypoxia inducible factor 1&#x3b1; (HIF-1&#x3b1;). The distribution and reliability of R2* were analysed. Correlations of the R2* value with the prognostic factors and HIF-1&#x3b1; were respectively analysed.<br><br>RESULTS: The R2* map of IDC demonstrated a relatively heterogeneous signal. The mean R2* value was (53.4&#x2009;&#xb1;&#x2009;18.2) Hz. The Shapiro-Wilk test (W&#x2009;=&#x2009;0.971, P&#x2009;=&#x2009;0.020) suggested that the sample did not follow a normal distribution. The inter-rater and intrarater correlation coefficient was 0.967 and 0.959, respectively. The R2* values of IDCs were significantly lower in patients without axillary lymph nodes metastasis. The R2* value had a weak correlation with Ki67 expression (r&#x2009;=&#x2009;0.208, P&#x2009;=&#x2009;0.038). The mean R2* value correlated moderately with the level of HIF-1&#x3b1; (r&#x2009;=&#x2009;0.516, P&#x2009;=&#x2009;0.000).<br><br>CONCLUSION: BOLD-fMRI is a simple and non-invasive technique that yields hypoxia information on breast invasive ductal carcinomas.}, }
@article {pmid23833125, year = {2013}, author = {McDougall, JA and Malone, KE and Daling, JR and Cushing-Haugen, KL and Porter, PL and Li, CI}, title = {Long-term statin use and risk of ductal and lobular breast cancer among women 55 to 74 years of age.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {22}, number = {9}, pages = {1529-1537}, pmid = {23833125}, issn = {1538-7755}, support = {R01 CA085913/CA/NCI NIH HHS/United States ; T32 CA009168/CA/NCI NIH HHS/United States ; R01 CA 85913/CA/NCI NIH HHS/United States ; T32CA09168/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/chemically induced/*epidemiology/pathology ; Carcinoma, Ductal, Breast/chemically induced/*epidemiology/pathology ; Carcinoma, Lobular/chemically induced/*epidemiology/pathology ; Case-Control Studies ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration &amp; dosage/adverse effects ; Middle Aged ; Risk Factors ; Washington/epidemiology ; }, abstract = {BACKGROUND: Mechanistic studies largely support the chemopreventive potential of statins. However, results of epidemiologic studies investigating statin use and breast cancer risk have been inconsistent and lacked the ability to evaluate long-term statin use.<br><br>METHODS: We used data from a population-based case-control study of breast cancer conducted in the Seattle-Puget Sound region to investigate the relationship between long-term statin use and breast cancer risk. Nine hundred sixteen invasive ductal carcinoma (IDC) and 1,068 invasive lobular carcinoma (ILC) cases in patients 55 to 74 years of age diagnosed between 2000 and 2008 were compared with 902 control women. All participants were interviewed in-person and data on hypercholesterolemia and all episodes of lipid-lowering medication use were collected through a structured questionnaire. We assessed the relationship between statin use and IDC and ILC risk using polytomous logistic regression.<br><br>RESULTS: Current users of statins for 10 years or longer had a 1.83-fold increased risk of IDC [95% confidence interval (CI): 1.14-2.93] and a 1.97-fold increased risk of ILC (95% CI: 1.25-3.12) compared with never users of statins. Among women diagnosed with hypercholesterolemia, current users of statins for 10 years or longer had more than double the risk of both IDC (OR: 2.04, 95% CI: 1.17-3.57) and ILC (OR: 2.43, 95% CI: 1.40-4.21) compared with never users.<br><br>CONCLUSION: In this contemporary population-based case-control study, long-term use of statins was associated with increased risks of both IDC and ILC.<br><br>IMPACT: Additional studies with similarly high frequencies of statin use for various durations are needed to confirm this novel finding.}, }
@article {pmid23831470, year = {2013}, author = {Erez, N and Glanz, S and Raz, Y and Avivi, C and Barshack, I}, title = {Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.}, journal = {Biochemical and biophysical research communications}, volume = {437}, number = {3}, pages = {397-402}, doi = {10.1016/j.bbrc.2013.06.089}, pmid = {23831470}, issn = {1090-2104}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Chemokine CXCL1/biosynthesis ; Cyclooxygenase 2/biosynthesis ; Disease Progression ; Female ; Fibroblasts/metabolism/*pathology ; *Gene Expression Regulation, Neoplastic ; Humans ; Inflammation Mediators/*metabolism/physiology ; Interleukin-6/biosynthesis ; NF-kappa B/biosynthesis ; Ovarian Neoplasms/genetics/metabolism/*pathology ; Retrospective Studies ; Signal Transduction/genetics ; Stromal Cells/metabolism/pathology ; }, abstract = {Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.}, }
@article {pmid23826974, year = {2013}, author = {Pang, JM and Dobrovic, A and Fox, SB}, title = {DNA methylation in ductal carcinoma in situ of the breast.}, journal = {Breast cancer research : BCR}, volume = {15}, number = {3}, pages = {206}, pmid = {23826974}, issn = {1465-542X}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinogenesis ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; DNA Methylation/*genetics ; *Epigenesis, Genetic ; Female ; Humans ; Promoter Regions, Genetic ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of invasive carcinoma of the breast. Current prognostic markers based on histopathological examination are unable to accurately predict which DCIS cases will progress to invasive carcinoma or recur after surgical excision. Epigenetic changes have been shown to be a significant driver of tumorigenesis, and DNA methylation of specific gene promoters provides predictive and prognostic markers in many types of cancer, including invasive breast cancer. In general, the spectrum of genes that are methylated in DCIS strongly resembles that seen in invasive ductal carcinoma. The identification of specific prognostic markers in DCIS remains elusive and awaits additional work investigating a large panel of methylatable genes by using sensitive and reproducible technologies. This review critically appraises the role of methylation in DCIS and its use as a biomarker.}, }
@article {pmid23826420, year = {2013}, author = {Zhang, J and Wang, Y and Yin, Q and Zhang, W and Zhang, T and Niu, Y}, title = {An associated classification of triple negative breast cancer: the risk of relapse and the response to chemotherapy.}, journal = {International journal of clinical and experimental pathology}, volume = {6}, number = {7}, pages = {1380-1391}, pmid = {23826420}, issn = {1936-2625}, mesh = {Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/analysis ; Carcinoma, Ductal, Breast/chemistry/*classification/*drug therapy/secondary ; Carcinoma, Medullary/chemistry/*classification/*drug therapy/secondary ; Chi-Square Distribution ; China ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/chemistry/*classification/*drug therapy/pathology ; }, abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is heterogeneous and considered as an aggressive tumor. This study was to evaluate the associated classification and its correlations with prognosis and the response to chemotherapy in Chinese women.<br><br>METHODS: Four hundred and twenty-eight cases of invasive TNBC were involved in this study. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 (CK5/6), Ki67 and p53 were analyzed by immunohistochemistry and compared with patient outcome, and its implications and chemotherapy response were evaluated in four subgroups: typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), non-specific invasive ductal carcinoma (IDC) and other types.<br><br>RESULTS: The factors of tumor grade, tumor stage, lymph node status, EGFR/CK5/6 status and p53 labeling index were different among the groups. TMC tumors had the lowest rate of relapse (5.8%), while AMC, IDC and other types were associated with an increased risk of relapse (19.1%, 26.7% and 38.2% respectively). Many factors were risk predictors of relapse for TNBC and IDC, while only positive lymph node was for AMC. For MC tumors, adjunctive chemotherapy decreased the risk of relapse in lymph node positive subgroup (36.8% and 66.7%), while not significant in lymph node negative one (8.1% and 10.0%).<br><br>CONCLUSION: The classification based on histologic and IHC findings may be a significant improvement in predicting outcome in TNBC. The different chemotherapy response in subgroups may contribute to guiding the treatment of TNBC.}, }
@article {pmid23809739, year = {2013}, author = {Padilha, M and Gonçalves, S and Fardilha, C and Melo, G and Miranda, C and Alves, P}, title = {[Hypofractionation in locally advanced breast cancer: "flash" scheme].}, journal = {Acta medica portuguesa}, volume = {26}, number = {2}, pages = {98-101}, pmid = {23809739}, issn = {1646-0758}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*radiotherapy ; *Dose Fractionation, Radiation ; Female ; Humans ; Middle Aged ; Retrospective Studies ; }, abstract = {INTRODUCTION: Breast cancer is a major cause of death in our country. The Department of Radiation Oncology of Portuguese Institute of Oncology in Coimbra are using a scheme of hypofraccionation called "Flash" as a treatment option for elderly patients or low performance status, with locally advanced breast cancer, or with stage IIb or IV, as a neoadjuvante or palliative aim.<br><br>OBJECTIVES: Evaluation of the therapeutic response, for the group of patients selected, who did the hypofractionated schemed, in a retrospective study.<br><br>METHODS: Between January 2006 and December 2008, a total of 83 patients diagnosed with locally advanced breast cancer or with stage IIb or IV, were subjected to breast "Flash". The radiation dose prescribed was 13Gy in 2 fractions in 3 days (in 23 patients - 27.7%) and 26 Gy in 4 fractions in 5 weeks (60 patients - 72.3%), with 4MV photons, in the sick breast. Global survival was evaluated using the Kaplan-Meier method. Statistical analysis was performed by applying the version 17.0 of SPSS and statistical tests were evaluated at a significance level of 5%.<br><br>RESULTS: 80 patients (96.4%) who have made breast "Flash" were female, aged between 59 and 93 years and performance status (Karnosfky scale) between 90 and 50%. In 72 patients (86.7%) the histology was invasive ductal carcinoma. Surgery was held in 53% of patients (44) after breast "Flash", the radical modified mastectomy was the most common surgical technique. The diagnosis of bone metastasis was made in 10 patients (12%), while the global survival rate was 68.7% (57 patients). 10 patients (12%) died because disease progression or persistence. In 50.6% (42 patients) there was no evidence of disease progression and 3.6% (3 patients) showed clinical improvement.<br><br>CONCLUSIONS: The "Breast Flash" is a safe treatment modality, in terms of secondary effects, and a valid therapeutic option for elderly patients or low performance status, with the diagnosis of locally advanced cancer or stage IIb or IV, as neoadjuvante, adjuvant or palliative aim. There is a little risk of relapse or progression in patients with good conditions, so the global survival rate is greater in these cases. There is a little iatrogenesis associated with this type of treatment; just one patient had grade III radiodermatitis.}, }
@article {pmid23807171, year = {2013}, author = {Bamias, A and Tzannis, K and Beuselinck, B and Oudard, S and Escudier, B and Diosynopoulos, D and Papazisis, K and Lang, H and Wolter, P and de Guillebon, E and Stravodimos, K and Chrisofos, M and Fountzilas, G and Elaidi, RT and Dimopoulos, MA and Bamia, C}, title = {Development and validation of a prognostic model in patients with metastatic renal cell carcinoma treated with sunitinib: a European collaboration.}, journal = {British journal of cancer}, volume = {109}, number = {2}, pages = {332-341}, pmid = {23807171}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Carcinoma, Renal Cell/*drug therapy/*mortality/secondary ; Cohort Studies ; European Union ; Female ; Humans ; Indoles/*therapeutic use ; Kidney Neoplasms/*drug therapy/mortality/pathology ; Male ; Middle Aged ; *Models, Statistical ; Neoplasm Metastasis ; Predictive Value of Tests ; Prognosis ; Pyrroles/*therapeutic use ; Sunitinib ; Survival Analysis ; }, abstract = {BACKGROUND: Accurate prediction of outcome for metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy is essential. Most of the available models have been developed in patients treated with cytokines, while most of them are fairly complex, including at least five factors. We developed and externally validated a simple model for overall survival (OS) in mRCC. We also studied the recently validated International Database Consortium (IDC) model in our data sets.<br><br>METHODS: The development cohort included 170 mRCC patients treated with sunitinib. The final prognostic model was selected by uni- and multivariate Cox regression analyses. Risk groups were defined by the number of risk factors and by the 25th and 75th percentiles of the model's prognostic index distribution. The model was validated using an independent data set of 266 mRCC patients (validation cohort) treated with the same agent.<br><br>RESULTS: Eastern Co-operative Oncology Group (ECOG) performance status (PS), time from diagnosis of RCC and number of metastatic sites were included in the final model. Median OS of patients with 1, 2 and 3 risk factors were: 24.7, 12.8 and 5.9 months, respectively, whereas median OS was not reached for patients with 0 risk factors. Concordance (C) index for internal validation was 0.712, whereas C-index for external validation was 0.634, due to differences in survival especially in poor-risk populations between the two cohorts. Predictive performance of the model was improved after recalibration. Application of the mRCC International Database Consortium (IDC) model resulted in a C-index of 0.574 in the development and 0.576 in the validation cohorts (lower than those recently reported for this model). Predictive ability was also improved after recalibration in this analysis. Risk stratification according to IDC model showed more similar outcomes across the development and validation cohorts compared with our model.<br><br>CONCLUSION: Our model provides a simple prognostic tool in mRCC patients treated with a targeted agent. It had similar performance with the IDC model, which, however, produced more consistent survival results across the development and validation cohorts. The predictive ability of both models was lower than that suggested by internal validation (our model) or recent published data (IDC model), due to differences between observed and predicted survival among intermediate and poor-risk patients. Our results highlight the importance of external validation and the need for further refinement of existing prognostic models.}, }
@article {pmid23790130, year = {2014}, author = {Santangelo, G and Vitale, C and Trojano, L and Angrisano, MG and Picillo, M and Errico, D and Agosti, V and Grossi, D and Barone, P}, title = {Subthreshold depression and subjective cognitive complaints in Parkinson's disease.}, journal = {European journal of neurology}, volume = {21}, number = {3}, pages = {541-544}, doi = {10.1111/ene.12219}, pmid = {23790130}, issn = {1468-1331}, mesh = {Aged ; Cognition Disorders/*etiology ; Depression/*etiology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*complications ; Psychiatric Status Rating Scales ; }, abstract = {BACKGROUND AND PURPOSE: Subthreshold depression (SubD) is characterized by clinically relevant depressive symptoms not meeting criteria for major depression. The possible association of SubD with subjective cognitive complaints and/or objective cognitive impairments was investigated in a sample of consecutive, non-demented Parkinson's disease (PD) outpatients.<br><br>METHODS: Amongst 115 patients, SubD was identified in 30 patients, major depression in 33; 36 patients were classified as non-depressed. Enrolled patients were administered tests and questionnaires validated in PD for assessing objective and subjective cognitive dysfunctions.<br><br>RESULTS: On objective cognitive measures SubD patients did not differ from non-depressed patients, whereas depressed patients achieved significantly lower scores than the other two groups. SubD and depressed patients reported more cognitive complaints than non-depressed patients.<br><br>CONCLUSIONS: SubD is a non-motor aspect of PD that is not related to objective cognitive deficits but is associated with subjective cognitive complaints, thus impacting on patients' well-being.}, }
@article {pmid23782331, year = {2013}, author = {Tazaki, E and Shishido-Hara, Y and Mizutani, N and Nomura, S and Isaka, H and Ito, H and Imi, K and Imoto, S and Kamma, H}, title = {Histopathologcial and clonal study of combined lobular and ductal carcinoma of the breast.}, journal = {Pathology international}, volume = {63}, number = {6}, pages = {297-304}, pmid = {23782331}, issn = {1440-1827}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/genetics/*pathology ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; DNA Methylation ; Female ; Humans ; Immunohistochemistry ; Japan ; Middle Aged ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Receptors, Androgen/genetics ; Retrospective Studies ; Risk Factors ; beta Catenin/metabolism ; }, abstract = {Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty-two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re-examination using immunostain of E-cadherin and β-catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation-specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways.}, }
@article {pmid23765060, year = {2013}, author = {Jardim, BV and Moschetta, MG and Leonel, C and Gelaleti, GB and Regiani, VR and Ferreira, LC and Lopes, JR and Zuccari, DA}, title = {Glutathione and glutathione peroxidase expression in breast cancer: an immunohistochemical and molecular study.}, journal = {Oncology reports}, volume = {30}, number = {3}, pages = {1119-1128}, doi = {10.3892/or.2013.2540}, pmid = {23765060}, issn = {1791-2431}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibiotics, Antineoplastic/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Apoptosis/drug effects ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/pathology ; Cell Proliferation/drug effects ; Chemotherapy, Adjuvant ; Doxorubicin/pharmacology ; Female ; Follow-Up Studies ; Glutathione/*metabolism ; Glutathione Peroxidase/genetics/*metabolism ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Tumor Cells, Cultured ; Glutathione Peroxidase GPX1 ; }, abstract = {The use of prognostic markers for breast cancer allows therapeutic strategies to be defined more efficiently. The expression of glutathione (GSH) and glutathione peroxidase (GPX) in tumor cells has been evaluated as a predictor of prognosis and response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results showed that high GSH expression was associated with tumors negative for the estrogen receptor (ER) (P<0.05), and GPX expression was associated with tumors negative for the progesterone receptor (PR) and patient mortality. Focusing on the 37 patients who received adjuvant chemotherapy/radiotherapy (Group I), high expression of GPX was associated with a high rate of patient mortality (P<0.05). The 19 patients who received only adjuvant chemotherapy (Group II) showed high expression of GSH in relation to metastasis (P<0.05). In addition, high levels of GPX expression were significantly associated with a shorter overall survival (P<0.05). To confirm this, the expression of precursor genes of GSH [glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS)] and the GPX gene was analyzed using quantitative PCR in cultured neoplastic mammary cells treated with doxorubicin. Doxorubicin treatment was able to eliminate tumor cells without alterations in the gene expression of GSS, but led to underexpression of the GCLC and GPX genes. Our results suggest that high levels of GPX may be related to the development of resistance to chemotherapy in these tumors, response to treatment and the clinical course of the breast cancer patients.}, }
@article {pmid23763700, year = {2013}, author = {Vingiani, A and Maisonneuve, P and Dell'orto, P and Farante, G and Rotmensz, N and Lissidini, G and Del Castillo, A and Renne, G and Luini, A and Colleoni, M and Viale, G and Pruneri, G}, title = {The clinical relevance of micropapillary carcinoma of the breast: a case-control study.}, journal = {Histopathology}, volume = {63}, number = {2}, pages = {217-224}, doi = {10.1111/his.12147}, pmid = {23763700}, issn = {1365-2559}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology/secondary ; Carcinoma, Papillary/metabolism/*pathology/secondary ; Case-Control Studies ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {AIMS: To ascertain the prognostic relevance of micropapillary carcinoma, a specific type of breast tumour.<br><br>METHODS AND RESULTS: We interrogated the clinical records of a series of 49 pure micropapillary carcinoma patients and 13 487 invasive ductal carcinoma patients, diagnosed and treated consecutively in our institution over a 9-year time-frame. Compared with invasive ductal carcinoma, patients with micropapillary carcinoma more frequently had moderately differentiated tumours (P = 0.02) with extensive peritumoral vascular invasion (P < 0.0001), associated with a significantly higher rate of axillary lymph node involvement (P < 0.0001). Survival data obtained by comparing 49 micropapillary carcinoma patients with a set of 98 invasive ductal carcinoma patients matched for age, tumour size and grade, peritumoral vascular invasion, immunohistochemically defined molecular subtype, number of positive lymph nodes and year of surgery showed that the micropapillary histotype did not add any independent information to the risk of locoregional (P = 0.48) or distant (P = 0.79) relapse, or overall survival (P = 0.60).<br><br>CONCLUSIONS: Our data reinforce the notion that micropapillary carcinoma usually arises as a locally advanced disease, and provide evidence that micropapillary histology does not add any additional information on clinical outcome independent of clinicopathological characteristics such as lymph node status and immunohistochemically defined molecular subtype.}, }
@article {pmid23761327, year = {2013}, author = {Wong, JL and Berk, E and Edwards, RP and Kalinski, P}, title = {IL-18-primed helper NK cells collaborate with dendritic cells to promote recruitment of effector CD8+ T cells to the tumor microenvironment.}, journal = {Cancer research}, volume = {73}, number = {15}, pages = {4653-4662}, pmid = {23761327}, issn = {1538-7445}, support = {P01 CA101944/CA/NCI NIH HHS/United States ; P50 CA121973/CA/NCI NIH HHS/United States ; P01CA101944/CA/NCI NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; TL1 RR024155/RR/NCRR NIH HHS/United States ; T32 CA082084/CA/NCI NIH HHS/United States ; F30 CA165410/CA/NCI NIH HHS/United States ; P01 CA132714/CA/NCI NIH HHS/United States ; }, mesh = {CD8-Positive T-Lymphocytes/*immunology/metabolism ; Cell Communication/immunology ; Cell Separation ; Chemotaxis, Leukocyte/*immunology ; Coculture Techniques ; Cytokines/biosynthesis/immunology ; Dendritic Cells/*immunology/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Humans ; Interleukin-18/immunology/metabolism ; Killer Cells, Natural/*immunology/metabolism ; Lymphocyte Activation/immunology ; Lymphocytes, Tumor-Infiltrating/cytology/immunology/metabolism ; Ovarian Neoplasms ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes, Helper-Inducer/*immunology/metabolism ; *Tumor Microenvironment/immunology ; }, abstract = {Chemokine-driven interactions of immune cells are essential for effective antitumor immunity. Human natural killer (NK) cells can be primed by the interleukin (IL)-1-related proinflammatory cytokine IL-18 for unique helper activity, which promotes dendritic cell (DC) activation and DC-mediated induction of type-1 immune responses against cancer. Here, we show that such IL-18-primed "helper" NK cells produce high levels of the immature DC (iDC)-attracting chemokines CCL3 and CCL4 upon exposure to tumor cells or the additional inflammatory signals IFN-α, IL-15, IL-12, or IL-2. These "helper" NK cells potently attract iDCs in a CCR5-dependent mechanism and induce high DC production of CXCR3 and CCR5 ligands (CXCL9, CXCL10, and CCL5), facilitating the subsequent recruitment of type-1 effector CD8(+) T (Teff) cells. Using cells isolated from the malignant ascites of patients with advanced ovarian cancer, we show that "helper" NK cell-inducing factors can be used to enhance local production of Teff cell-recruiting chemokines. Our findings reveal the unique chemokine expression profile of "helper" NK cells and highlight the potential for using two-signal-activated NK cells to promote homing of type-1 immune effectors to the human tumor environment.}, }
@article {pmid23756727, year = {2013}, author = {Yust-Katz, S and Garciarena, P and Liu, D and Yuan, Y and Ibrahim, N and Yerushalmi, R and Penas-Prado, M and Groves, MD}, title = {Breast cancer and leptomeningeal disease (LMD): hormone receptor status influences time to development of LMD and survival from LMD diagnosis.}, journal = {Journal of neuro-oncology}, volume = {114}, number = {2}, pages = {229-235}, pmid = {23756727}, issn = {1573-7373}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Meningeal Carcinomatosis/diagnosis/metabolism/*secondary/therapy ; Middle Aged ; Multivariate Analysis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Time Factors ; }, abstract = {Leptomeningeal disease (LMD) occurs in 5 % of breast cancer patients. The aim of this study was to identify risk factors related to survival and time to development of LMD in breast cancer patients. A retrospective analysis of breast cancer patients with LMD, evaluated in MDACC between 1995 and 2011. 103 patients with diagnosis of breast cancer and LMD were identified (one male). The median age at LMD diagnosis was 49.2 years. 78.2 % had invasive ductal carcinoma. Hormone receptors (HRs) were positive in 55.3 % of patients, 47.4 % were human epidermal growth factor receptor 2-positive and 22.8 % were triple negative. 52 % of the patients were treated with WBRT, 19 % with spinal radiation, 36 % with systemic chemotherapy and 55 % with intrathecal chemotherapy. Estimated median overall survival from time of breast cancer diagnosis was 3.66 years. Median survival from time of LMD diagnosis was 4.2 months. Time from breast cancer diagnosis to LMD was 2.48 years. In multivariate analysis, HR status and stage at diagnosis were significantly associated with time to LMD diagnosis (p < 0.05). In triple negative patients, time to LMD was shorter. In patients who were HR positive, time to LMD was longer. Survival from LMD diagnosis was significantly associated with both treatment, as well as positive HR status (multivariate analysis p < 0.05). In conclusion LMD has dismal prognosis in breast cancer patients. HR status contributes to time to LMD diagnosis and survival from LMD diagnosis. The impact of treatment aimed at LMD cannot be ascertained in our retrospective study due to the inherent bias associated with the decision to treat.}, }
@article {pmid23754601, year = {2013}, author = {Pécuchet, N and Popova, T and Manié, E and Lucchesi, C and Battistella, A and Vincent-Salomon, A and Caux-Moncoutier, V and Bollet, M and Sigal-Zafrani, B and Sastre-Garau, X and Stoppa-Lyonnet, D and Stern, MH}, title = {Loss of heterozygosity at 13q13 and 14q32 predicts BRCA2 inactivation in luminal breast carcinomas.}, journal = {International journal of cancer}, volume = {133}, number = {12}, pages = {2834-2842}, doi = {10.1002/ijc.28315}, pmid = {23754601}, issn = {1097-0215}, mesh = {Breast Neoplasms/*genetics/pathology ; Chromosome Aberrations ; *Chromosomes, Human, Pair 13 ; *Chromosomes, Human, Pair 14 ; Female ; *Genes, BRCA2 ; Humans ; *Loss of Heterozygosity ; Middle Aged ; Mutation ; Ploidies ; Polymorphism, Single Nucleotide ; }, abstract = {BRCA2 is the major high-penetrance predisposition gene for luminal (estrogen receptor [ER] positive) breast cancers. However, many BRCA2 mutant carriers lack family history of breast/ovarian cancers and do not benefit from genetic testing. Specific genomic features associated with BRCA2 inactivation in tumors could help identify patients for whom a genetic test for BRCA2 may be proposed. A series of ER-positive invasive ductal carcinomas (IDCs) including 30 carriers of BRCA2 mutations and 215 control cases was studied by single-nucleotide polymorphism (SNP) arrays. Cases and controls were stratified by grade and HER2 status. Independently, 7 BRCA2 and 51 control cases were used for validation. Absolute copy number and Loss of heterozygosity (LOH) profiles were obtained from SNP arrays by the genome alteration print (GAP) method. BRCA2 tumors were observed to display a discriminatively greater number of chromosomal breaks calculated after filtering out and smoothing <3 Mb variations. This argues for a BRCA2-associated genomic instability responsible for long-segment aberrations. Co-occurrence of two genomic features-LOH of 13q13 and 14q32-was found to predict BRCA2 status with 90% of sensitivity and 87% of specificity in discovery series of high-grade HER2-negative IDCs and 100% of sensitivity and 88% of specificity in an independent series of 58 IDCs. Estimated positive predictive value was 17.2% (confidence interval: 6.7-33.5) in the whole series. In conclusion, the simplified BRCA2 classifier based on the co-occurrence of LOH at 13q13 and 14q32 could provide an indication to test for BRCA2 mutation in patients with ER-positive IDC.}, }
@article {pmid23752191, year = {2014}, author = {Li, Q and Yao, Y and Eades, G and Liu, Z and Zhang, Y and Zhou, Q}, title = {Downregulation of miR-140 promotes cancer stem cell formation in basal-like early stage breast cancer.}, journal = {Oncogene}, volume = {33}, number = {20}, pages = {2589-2600}, pmid = {23752191}, issn = {1476-5594}, support = {R01 CA157779/CA/NCI NIH HHS/United States ; P30 CA134274/CA/NCI NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, mesh = {Aldehyde Dehydrogenase 1 Family ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Line, Tumor ; *Down-Regulation ; Epigenesis, Genetic ; Female ; Humans ; Isoenzymes/metabolism ; MicroRNAs/*metabolism ; Neoplastic Stem Cells/*pathology ; Retinal Dehydrogenase/metabolism ; SOX9 Transcription Factor/metabolism ; }, abstract = {The major goal of breast cancer prevention is to reduce the incidence of ductal carcinoma in situ (DCIS), an early stage of breast cancer. However, the biology behind DCIS formation is not well understood. It is suspected that cancer stem cells (CSCs) are already programmed in pre-malignant DCIS lesions and that these tumor-initiating cells may determine the phenotype of DCIS. MicroRNA (miRNA) profiling of paired DCIS tumors revealed that loss of miR-140 is a hallmark of DCIS lesions. Previously, we have found that miR-140 regulates CSCs in luminal subtype invasive ductal carcinoma. Here, we find that miR-140 has a critical role in regulating stem cell signaling in normal breast epithelium and in DCIS. miRNA profiling of normal mammary stem cells and cancer stem-like cells from DCIS tumors revealed that miR-140 is significantly downregulated in cancer stem-like cells compared with normal stem cells, linking miR-140 and dysregulated stem cell circuitry. Furthermore, we found that SOX9 and ALDH1, the most significantly activated stem-cell factors in DCIS stem-like cells, are direct targets of miR-140. Currently, targeted therapies (tamoxifen) are only able to reduce DCIS risk in patients with estrogen receptor α (ERα)-positive disease. We examined a model of ERα-negative/basal-like DCIS and found that restoration of miR-140 via a genetic approach or with the dietary compound sulforaphane decreased SOX9 and ALDH1, and reduced tumor growth in vivo. These results support that a miR-140/ALDH1/SOX9 axis is critical to basal CSC self-renewal and tumor formation in vivo, suggesting that the miR-140 pathway may be a promising target for preventative strategies in patients with basal-like DCIS.}, }
@article {pmid23742135, year = {2014}, author = {Atwood, SE and O'Rourke, JA and Peiffer, GA and Yin, T and Majumder, M and Zhang, C and Cianzio, SR and Hill, JH and Cook, D and Whitham, SA and Shoemaker, RC and Graham, MA}, title = {Replication protein A subunit 3 and the iron efficiency response in soybean.}, journal = {Plant, cell &amp; environment}, volume = {37}, number = {1}, pages = {213-234}, doi = {10.1111/pce.12147}, pmid = {23742135}, issn = {1365-3040}, mesh = {Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Gene Silencing ; Genome, Plant/*genetics ; *Iron Deficiencies ; Models, Biological ; Oligonucleotide Array Sequence Analysis ; Phylogeny ; Plant Proteins/metabolism ; Protein Binding ; Replication Protein A/genetics/*metabolism ; Soybeans/genetics/*physiology ; Stress, Physiological ; Symbiosis ; }, abstract = {In soybean [Glycine max (L.) Merr.], iron deficiency results in interveinal chlorosis and decreased photosynthetic capacity, leading to stunting and yield loss. In this study, gene expression analyses investigated the role of soybean replication protein A (RPA) subunits during iron stress. Nine RPA homologs were significantly differentially expressed in response to iron stress in the near isogenic lines (NILs) Clark (iron efficient) and Isoclark (iron inefficient). RPA homologs exhibited opposing expression patterns in the two NILs, with RPA expression significantly repressed during iron deficiency in Clark but induced in Isoclark. We used virus induced gene silencing (VIGS) to repress GmRPA3 expression in the iron inefficient line Isoclark and mirror expression in Clark. GmRPA3-silenced plants had improved IDC symptoms and chlorophyll content under iron deficient conditions and also displayed stunted growth regardless of iron availability. RNA-Seq comparing gene expression between GmRPA3-silenced and empty vector plants revealed massive transcriptional reprogramming with differential expression of genes associated with defense, immunity, aging, death, protein modification, protein synthesis, photosynthesis and iron uptake and transport genes. Our findings suggest the iron efficient genotype Clark is able to induce energy controlling pathways, possibly regulated by SnRK1/TOR, to promote nutrient recycling and stress responses in iron deficient conditions.}, }
@article {pmid23739738, year = {2013}, author = {Oki, Y and Onoyama, H and Nikaido, M and Iinuma, S and Endo, K and Tomita, Y and Mizuno, K and Yasui, H}, title = {[Pancreatic cancer in a patient with congenital agenesis of the dorsal pancreas].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {110}, number = {6}, pages = {1044-1053}, pmid = {23739738}, issn = {0446-6586}, mesh = {Aged ; Carcinoma, Ductal/*complications ; Humans ; Male ; Pancreas/*abnormalities ; Pancreatic Neoplasms/*complications ; }, abstract = {A 65-year-old man with back pain showed a hypovascular lesion of the head of the pancreas on dynamic computed tomography and abdominal ultrasonography. The distal portion of the pancreas was not visible. Endoscopic retrograde cholangiopancreatography revealed pancreatic duct obstruction, and the duodenal minor papilla was not visible. Therefore, we diagnosed the patient's condition as stage IVa pancreatic cancer with congenital agenesis of the dorsal pancreas. The patient underwent successful chemotherapy with 3 courses of gemcitabine and S-1, which was followed by pancreaticoduodenectomy. Pathological staging revealed invasive ductal carcinoma, pT3, pN0, pM0, stage III. We report a rare case of pancreatic cancer with congenital agenesis of the dorsal pancreas.}, }
@article {pmid23734899, year = {2013}, author = {Angarita, FA and Rodríguez, JL and Meek, E and Sánchez, JO and Tawil, M and Torregrosa, L}, title = {Locally-advanced primary neuroendocrine carcinoma of the breast: case report and review of the literature.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {128}, pmid = {23734899}, issn = {1477-7819}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/secondary/therapy ; Breast Neoplasms/*diagnosis/therapy ; Carboplatin/administration &amp; dosage ; Carcinoma, Ductal, Breast/*diagnosis/therapy ; Carcinoma, Neuroendocrine/*diagnosis/therapy ; Cisplatin/administration &amp; dosage ; Combined Modality Therapy ; Diagnosis, Differential ; Etoposide/administration &amp; dosage ; Female ; Humans ; Liver Neoplasms/secondary/therapy ; Lung Neoplasms/secondary/therapy ; Magnetic Resonance Imaging ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Paclitaxel/administration &amp; dosage ; Prognosis ; Review Literature as Topic ; }, abstract = {BACKGROUND: Primary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor.<br><br>CASE PRESENTATION: We describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neoadjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis.<br><br>CONCLUSION: The breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.}, }
@article {pmid23712790, year = {2013}, author = {Lal, A and Chan, L and Devries, S and Chin, K and Scott, GK and Benz, CC and Chen, YY and Waldman, FM and Hwang, ES}, title = {FOXP3-positive regulatory T lymphocytes and epithelial FOXP3 expression in synchronous normal, ductal carcinoma in situ, and invasive cancer of the breast.}, journal = {Breast cancer research and treatment}, volume = {139}, number = {2}, pages = {381-390}, doi = {10.1007/s10549-013-2556-4}, pmid = {23712790}, issn = {1573-7217}, support = {R21 CA155679/CA/NCI NIH HHS/United States ; P50 CA58207/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/immunology/*metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/immunology/*metabolism/*pathology ; Disease Progression ; Epithelium/metabolism ; Female ; Forkhead Transcription Factors/*metabolism ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Stromal Cells/metabolism ; T-Lymphocytes, Regulatory/immunology/*metabolism ; p21-Activated Kinases/metabolism ; }, abstract = {FOXP3-expressing T regulatory lymphocytes (Tregs) have been described as putative mediators of immune tolerance, and thus facilitators of tumor growth. When found in association with various malignancies, Tregs are generally markers of poor clinical outcome. However, it is unknown whether they are also associated with cancer progression. We evaluated quantitative FOXP3 expression in lymphocytes as well as in epithelial cells in a set of thirty-two breast tumors with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Tumors were stained for FOXP3 and CD3 expression and Tregs quantified by determining the ratio of colocalized FOXP3 and CD3 relative to 1) total CD3-expressing lymphocytes and 2) to FOXP3-expressing epithelial cells. The median proportion of FOXP3-expressing CD3 cells significantly increased with malignant progression from normal to DCIS to IDC components (0.005, 0.019 and 0.030, respectively; p ≤ 0.0001 for normal vs. IDC and p = 0.004 for DCIS vs. IDC). The median intensity of epithelial FOXP3 expression was also increased with invasive progression and most markedly augmented between normal and DCIS components (0.130 vs. 0.175, p ≤ 0.0001). Both Treg infiltration and epithelial FOXP3 expression were higher in grade 3 vs. grade 1 tumors (p = 0.014 for Tregs, p = 0.038 for epithelial FOXP3), but did not vary significantly with hormone receptor status, size of invasive tumor, lymph node status, or disease stage. Notably, Treg infiltration significantly correlated with epithelial up-regulation of FOXP3 expression (p = 0.013 for normal, p = 0.001 for IDC). These findings implicate both Treg infiltration and up-regulated epithelial FOXP3 expression in breast cancer progression.}, }
@article {pmid23704896, year = {2013}, author = {Colak, D and Nofal, A and Albakheet, A and Nirmal, M and Jeprel, H and Eldali, A and Al-Tweigeri, T and Tulbah, A and Ajarim, D and Malik, OA and Inan, MS and Kaya, N and Park, BH and Bin Amer, SM}, title = {Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e63204}, pmid = {23704896}, issn = {1932-6203}, mesh = {Adult ; Aging/*genetics/pathology ; Animals ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/*pathology ; Carcinogenesis/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cohort Studies ; Computational Biology ; *Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks/genetics ; Genes, Neoplasm/genetics ; Genome, Human/genetics ; Humans ; Immunohistochemistry ; Mice ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; Species Specificity ; *Transcriptome ; Young Adult ; }, abstract = {Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.}, }
@article {pmid23703345, year = {2013}, author = {Bhatia, A and Dey, P and Goel, S and Singh, G}, title = {Expression of γH2AX may help in defining a genetically more stable subtype of infiltrating ductal carcinoma of breast.}, journal = {The Indian journal of medical research}, volume = {137}, number = {4}, pages = {759-766}, pmid = {23703345}, issn = {0975-9174}, mesh = {Adult ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics ; Carcinoma, Ductal/*genetics/pathology ; Female ; Fibroadenoma/*genetics/pathology ; Gene Expression Regulation, Neoplastic ; Histones/*biosynthesis/genetics ; Humans ; Prognosis ; }, abstract = {BACKGROUND &amp; OBJECTIVES: Gamma H2AX, a marker of DNA double stranded breaks (DSB) has been found to be over expressed in various tumours. The objective of the present work was to study the expression of γH2AX in infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) cases and to associate the expression in IDC with cytomorphological features and DNA ploidy.<br><br>METHODS: The expression of &#x3b3;H2AX was studied in fine needle aspirates of 16 cases of IDC and 15 FA cases. The expression in IDC was correlated with the cytological grade, apoptotic (AI) and mitotic indices (MI) and ploidy status.<br><br>RESULTS: A high &#x3b3;H2AX expression was noted in IDC as compared to FA. Amongst the IDC cases the &#x3b3;H2AX was found to be significantly over expressed in DNA diploid IDC cases as compared to the aneuploid ones.<br><br>The study suggests a role of &#x3b3;H2AX in breast carcinogenesis which needs to be explored further. Moreover, the &#x3b3;H2AX expression together with ploidy status may serve as a means of assigning the patients of IDC to a better prognostic category irrespective of the cytomorphogical parameters.}, }
@article {pmid23696929, year = {2013}, author = {Arnutti, P and Kotepui, M and Asanprakit, W and Punyarit, P and Chavalitshewinkoon-Petmitr, P and Harnroongroj, T and Petmitr, S}, title = {Determination of whole transcription profiles and specific pathways in invasive ductal breast carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {6}, number = {6}, pages = {1112-1120}, pmid = {23696929}, issn = {1936-2625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Case-Control Studies ; Female ; *Gene Expression Profiling/methods ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; Genetic Testing/*methods ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Predictive Value of Tests ; Prognosis ; Reproducibility of Results ; }, abstract = {Breast cancer is the most common cancer affecting women worldwide including Thailand. Whole transcription profiles of invasive ductal breast carcinoma (IDC) obtained by oligonucleotide microarray should lead to a better understanding of the molecular basis of IDCs, allow for examination of specific markers for diagnosis, and provide novel targets for therapy. This study aimed to detect the whole transcript expression of approximately 35,000 target genes in Thai breast cancer patients, using Affymetrix GeneChip(®) Exon 1.0 Sense Target Arrays. Analysis revealed that the differential expression profiles of 928 genes (423 up-regulated and 505 down-regulated genes) were 2-fold or greater (unpaired t-test, p < 0.05) in invasive ductal breast cancer, compared with normal tissues. The Gene Ontology (GO) databases support important associations in 17 gene sets with p-value < 1E-10 and ≥ 4-fold changes, involving the tumorigenic pathways of cell cycles, extracellular regions, as well as cellular component organization. Likewise, the TGFBR and IL-6 pathways contain gene expression with statistically significant changes in IDC.}, }
@article {pmid23692343, year = {2013}, author = {Bjelogrlic, SK and Lukic, ST and Djuricic, SM}, title = {Activity of dexrazoxane and amifostine against late cardiotoxicity induced by the combination of doxorubicin and cyclophosphamide in vivo.}, journal = {Basic &amp; clinical pharmacology &amp; toxicology}, volume = {113}, number = {4}, pages = {228-238}, doi = {10.1111/bcpt.12086}, pmid = {23692343}, issn = {1742-7843}, mesh = {Amifostine/*pharmacology ; Animals ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Cardiomyopathies/chemically induced/*drug therapy/*prevention &amp; control ; Cardiotonic Agents/pharmacology ; Cyclophosphamide/adverse effects ; Dexrazoxane/*pharmacology ; Doxorubicin/adverse effects ; Drug Combinations ; Female ; Mice ; Mice, Inbred BALB C ; Myocardium/pathology ; }, abstract = {Cardiotoxicity is one of the main limiting side effects of doxorubicin and cyclophosphamide (DC) treatment, and this study was organized to identify cardioprotective activity of amifostine and dexrazoxane against DC combination. BalbC/NIH mice underwent DC treatment (DC group), were pre-treated with amifostine (ADC group) or dexrazoxane (IDC group) and were killed at 1.5 and 3 months after treatments when the grade of myocardial damage was analysed by light microscopy using the Billingham scoring method. DC treatment induced severe myocardial damage with one lethal event before evaluation at 3 months. Main characteristics of DC cardiotoxicity were polymorphic myocyte degeneration and alterations in blood vessels followed by ecchymoses, haemorrhage and thromboses. Polymorphism was also found in the IDC and ADC groups, but its morphological patterns were different. In animals subject to IDC treatment, the blood vessels were better preserved than in the ADC group, whereas thrombosis was not seen in either of these two groups. Quantitatively, grade of myocardial injury in the ADC and IDC groups was significantly higher compared with the non-treated group at both times of estimation and significantly lower compared with the DC group at 1.5 months. At 3 months, significance against DC treatment was lost in the ADC group, while preserved in the IDC-treated animals. Also, there was significant progression in the ADC group comparing scores between 1.5 and 3 months. These results revealed that the cardiotoxicity of DC combination displays specific morphological hallmark and evolution in time, different to those described after doxorubicin single treatment. Neither amifostine nor dexrazoxane prevented development of cardiomyopathy induced by DC treatment.}, }
@article {pmid23686806, year = {2013}, author = {Zhao, T and Miao, Z and Wang, Z and Xu, Y and Wu, J and Liu, X and You, Y and Li, J}, title = {Overexpression of CRKL correlates with malignant cell proliferation in breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {34}, number = {5}, pages = {2891-2897}, pmid = {23686806}, issn = {1423-0380}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1/genetics/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; *Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Nuclear Proteins/genetics/*metabolism ; Phosphorylation ; Protein Processing, Post-Translational ; }, abstract = {Crk-like (CRKL) is an adapter protein that has crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration. However, the expression pattern of CRKL protein and its clinical significance in human breast cancers have not been well characterized. In this study, expression of CRKL was evaluated in 108 human invasive ductal carcinoma (IDC) tissues by immunohistochemistry. CRKL protein was upregulated in the cancer tissues compared with adjacent normal mammary glands. Overexpression of CRKL was found in 40 of 108 (37.03 %) breast cancer samples and correlated with advanced p-tumor-node-metastasis stage (p = 0.002), nodal metastasis (p = 0.0323), and tumor size (p = 0.0075). In addition, overexpression of CRKL in the MDA-MB-435 cell line promoted cell proliferation, and small interfering RNA knockdown of CRKL in the MDA-MB-453 cell line inhibited proliferation. Further analysis of cell cycle-related molecules showed that CRKL induced cyclin D1 and phosphorylated extracellular signal-regulated kinase expression. In conclusion, this study demonstrated that overexpression of CRKL correlated with progression and malignant proliferation of human breast cancers.}, }
@article {pmid23667202, year = {2013}, author = {de Bruin, MA and Ford, JM and Kurian, AW}, title = {A young woman with bilateral breast cancer: identifying a genetic cause and implications for management.}, journal = {Journal of the National Comprehensive Cancer Network : JNCCN}, volume = {11}, number = {5}, pages = {512-517}, doi = {10.6004/jnccn.2013.0068}, pmid = {23667202}, issn = {1540-1413}, mesh = {Adult ; Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis/*etiology/therapy ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genes, p53 ; Humans ; Li-Fraumeni Syndrome/*complications/diagnosis/*genetics ; Mammography ; Mastectomy, Modified Radical ; Neoplasm Staging ; Risk Factors ; }, abstract = {Breast cancer is a common manifestation of an underlying genetic susceptibility to cancer, and 5% to 10% of all breast cancers are associated with a germline mutation in a known risk allele. Detection of mutations has implications for targeted screening and prevention strategies for probands, and for genetic counseling and testing of their family members. This report presents a case involving a 35-year-old woman with no family history of breast or ovarian cancer who presented with a palpable right breast lump. Imaging revealed multiple bilateral breast masses and right axillary adenopathy, and core needle biopsies showed invasive ductal carcinoma in both the right and left breast. This report discusses the appropriate genetics evaluation for a patient with bilateral breast cancer at a young age, including testing for mutations in BRCA1 and BRCA2, followed, if negative, by consideration of testing for mutations in TP53 (Li-Fraumeni syndrome). Given the specialized counseling and testing needs of patients with Li-Fraumeni syndrome, and the implications for targeted screening strategies if a mutation is found, referral to a cancer genetics expert is strongly recommended.}, }
@article {pmid23658717, year = {2013}, author = {Guest, JL and Weintrob, AC and Rimland, D and Rentsch, C and Bradley, WP and Agan, BK and Marconi, VC and , }, title = {A comparison of HAART outcomes between the US military HIV Natural History Study (NHS) and HIV Atlanta Veterans Affairs Cohort Study (HAVACS).}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e62273}, pmid = {23658717}, issn = {1932-6203}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; Y01 AI005072/AI/NIAID NIH HHS/United States ; Y1-AI-5072/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Cohort Studies ; Disease-Free Survival ; Female ; HIV Infections/*drug therapy/immunology/mortality ; HIV-1/*immunology ; Humans ; Male ; Observational Studies as Topic ; Proportional Hazards Models ; Treatment Outcome ; Veterans ; Veterans Health ; Viral Load ; }, abstract = {INTRODUCTION: The Department of Defense (DoD) and the Department of Veterans Affairs (VA) provide comprehensive HIV treatment and care to their beneficiaries with open access and few costs to the patient. Individuals who receive HIV care in the VA have higher rates of substance abuse, homelessness and unemployment than individuals who receive HIV care in the DoD. A comparison between individuals receiving HIV treatment and care from the DoD and the VA provides an opportunity to explore the impact of individual-level characteristics on clinical outcomes within two healthcare systems that are optimized for clinic retention and medication adherence.<br><br>METHODS: Data were collected on 1065 patients from the HIV Atlanta VA Cohort Study (HAVACS) and 1199 patients from the US Military HIV Natural History Study (NHS). Patients were eligible if they had an HIV diagnosis and began HAART between January 1, 1996 and June 30, 2010. The analysis examined the survival from HAART initiation to all-cause mortality or an AIDS event.<br><br>RESULTS: Although there was substantial between-cohort heterogeneity and the 12-year survival of participants in NHS was significantly higher than in HAVACS in crude analyses, this survival disparity was reduced from 21.5% to 1.6% (mortality only) and 26.8% to 4.1% (combined mortality or AIDS) when controlling for clinical and demographic variables.<br><br>CONCLUSION: We assessed the clinical outcomes for individuals with HIV from two very similar government-sponsored healthcare systems that reduced or eliminated many barriers associated with accessing treatment and care. After controlling for clinical and demographic variables, both 12-year survival and AIDS-free survival rates were similar for the two study cohorts who have open access to care and medication despite dramatic differences in socioeconomic and behavioral characteristics.}, }
@article {pmid23658133, year = {2013}, author = {Kim, JH and Baek, TH and Yim, HS and Kim, KH and Jeong, SH and Kang, HB and Oh, SS and Lee, HG and Kim, JW and Kim, KD}, title = {Collagen triple helix repeat containing-1 (CTHRC1) expression in invasive ductal carcinoma of the breast: the impact on prognosis and correlation to clinicopathologic features.}, journal = {Pathology oncology research : POR}, volume = {19}, number = {4}, pages = {731-737}, pmid = {23658133}, issn = {1532-2807}, mesh = {Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Extracellular Matrix Proteins/*biosynthesis/genetics/metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; }, abstract = {CTHRC1 has been known as a regulator of collagen expression and cell migration. The aim of this research was to clarify the clinicopathologic significance of CTHRC1 expression in human breast cancer. 22 cases of breast cancer tissues, randomly selected from clinically diagnosed patients, showed a significant increase of CTHRC1 mRNA expression compared to the normal tissue from the same patients using RT-PCR and real-time PCR. Additionally we investigated breast cancers from 189 patients by immunohistochemistry (IHC). A high level of CTHRC1 expression was observed in 111 (58.7 %) out of 189 breast cancer patients and the expression was significantly correlated with histologic grade (P = 0.026), nodal status (P < 0.001), and TNM pathologic stage (P = 0.002). High CTHRC1 expression was associated with a shorter recurrence free survival (P = 0.008). Taken together, the results showed that CTHRC1 over-expression was significantly associated with clinicopathological factors of poor prognosis in invasive ductal carcinoma. CTHRC1 could be used as a supplementary prognostic biomarker and a potential therapeutic target in breast cancer.}, }
@article {pmid23652305, year = {2013}, author = {van Hoesel, AQ and Sato, Y and Elashoff, DA and Turner, RR and Giuliano, AE and Shamonki, JM and Kuppen, PJ and van de Velde, CJ and Hoon, DS}, title = {Assessment of DNA methylation status in early stages of breast cancer development.}, journal = {British journal of cancer}, volume = {108}, number = {10}, pages = {2033-2038}, pmid = {23652305}, issn = {1532-1827}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Transformation, Neoplastic/genetics/pathology ; *DNA Methylation ; Disease Progression ; Female ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Humans ; Laser Capture Microdissection ; Neoplasm Invasiveness ; Neoplasm Staging ; Precancerous Conditions/*genetics/pathology ; Time Factors ; }, abstract = {BACKGROUND: Molecular pathways determining the malignant potential of premalignant breast lesions remain unknown. In this study, alterations in DNA methylation levels were monitored during benign, premalignant and malignant stages of ductal breast cancer development.<br><br>METHODS: To study epigenetic events during breast cancer development, four genomic biomarkers (Methylated-IN-Tumour (MINT)17, MINT31, RAR&#x3b2;2 and RASSF1A) shown to represent DNA hypermethylation in tumours were selected. Laser capture microdissection was employed to isolate DNA from breast lesions, including normal breast epithelia (n=52), ductal hyperplasia (n=23), atypical ductal hyperplasia (n=31), ductal carcinoma in situ (DCIS, n=95) and AJCC stage I invasive ductal carcinoma (IDC, n=34). Methylation Index (MI) for each biomarker was calculated based on methylated and unmethylated copy numbers measured by Absolute Quantitative Assessment Of Methylated Alleles (AQAMA). Trends in MI by developmental stage were analysed.<br><br>RESULTS: Methylation levels increased significantly during the progressive stages of breast cancer development; P-values are 0.0012, 0.0003, 0.012, <0.0001 and <0.0001 for MINT17, MINT31, RAR&#x3b2;2, RASSF1A and combined biomarkers, respectively. In both DCIS and IDC, hypermethylation was associated with unfavourable characteristics.<br><br>CONCLUSION: DNA hypermethylation of selected biomarkers occurs early in breast cancer development, and may present a predictor of malignant potential.}, }
@article {pmid23648645, year = {2013}, author = {Alvarez, B and Poderoso, T and Alonso, F and Ezquerra, A and Domínguez, J and Revilla, C}, title = {Antigen targeting to APC: from mice to veterinary species.}, journal = {Developmental and comparative immunology}, volume = {41}, number = {2}, pages = {153-163}, doi = {10.1016/j.dci.2013.04.021}, pmid = {23648645}, issn = {1879-0089}, mesh = {Adaptive Immunity/*immunology ; Animals ; Antigen-Presenting Cells/*immunology/metabolism ; Antigens/*immunology ; Cattle ; Mice ; Receptors, Cell Surface/*immunology/metabolism ; Sheep ; Species Specificity ; Swine ; }, abstract = {Antigen delivery to receptors expressed on antigen presenting cells (APC) has shown to improve immunogenicity of vaccines in mice. An enhancement of cytotoxic T lymphocyte (CTL), helper T cell or humoral responses was obtained depending on the type of APC and the surface molecule targeted. Although this strategy is being also evaluated in livestock animals with promising results, some discrepancies have been found between species and pathogens. The genetic diversity of livestock animals, the different pattern of expression of some receptors among species, the use of different markers to characterize APC in large animals and sometimes the lack of reagents make difficult to compare results obtained in different species. In this review, we summarize the data available regarding antigen targeting to APC receptors in cattle, sheep and pig and discuss the results found in these animals in the context of what has been obtained in mice.}, }
@article {pmid23640233, year = {2013}, author = {Dobbs, NB and Latifi, HR}, title = {Diffuse FDG uptake due to fat necrosis following transverse rectus abdominus myocutaneous (TRAM) flap reconstruction.}, journal = {Clinical nuclear medicine}, volume = {38}, number = {8}, pages = {652-654}, doi = {10.1097/RLU.0b013e31828e9948}, pmid = {23640233}, issn = {1536-0229}, mesh = {Biological Transport ; Breast Neoplasms/surgery ; Carcinoma, Ductal, Breast/surgery ; Fat Necrosis/diagnostic imaging/*etiology/*metabolism ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Mammaplasty/*adverse effects ; Middle Aged ; Postoperative Complications/diagnostic imaging/*etiology/*metabolism ; Radiography ; Radionuclide Imaging ; Rectus Abdominis/*surgery ; }, abstract = {We report a case of a 57-year-old female patient with right breast invasive ductal carcinoma. Bilateral mastectomy and TRAM flap reconstructions were performed. Postoperatively, a palpable focus was identified within the left breast. PET/CT showed hypermetabolism throughout the reconstructed left breast, correlating with mixed fat attenuation and inflammatory soft tissue. MRI showed extensive fat necrosis/oil cyst formation in the left breast. As a TRAM flap reconstruction with fat-rich tissue can be damaged intraoperatively due to surgical manipulation, abnormal FDG uptake in this setting is more likely related to fat necrosis than recurrent tumor.}, }
@article {pmid23609359, year = {2013}, author = {Zhang, BH and Liu, J and Zhou, QX and Zuo, D and Wang, Y}, title = {Analysis of differentially expressed genes in ductal carcinoma with DNA microarray.}, journal = {European review for medical and pharmacological sciences}, volume = {17}, number = {6}, pages = {758-766}, pmid = {23609359}, issn = {1128-3602}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis/methods ; Transcriptome ; }, abstract = {AIM: The aim of this study is to investigate the dysregulated biological functions that play important role in the occurrence and development of breast invasive ductal carcinoma (IDC).<br><br>MATERIALS AND METHODS: We downloaded the gene expression profile data from gene expression omnibus (GEO) database, including 42 disease samples and 143 adjacent histological normal samples. Significance analysis of microarrays (SAM) was employed to identify differentially expressed genes (DEGs) between the normal and disease samples. Gene ontology (GO) function enrichment analysis was based on Software DAVID, followed by KEGG pathway enrichment analysis. TRANSFAC database and HPRD database were employed to construct the transcriptional regulatory network (Tnet) and protein-protein interaction (PPI) network, respectively.<br><br>RESULTS: We got a total of 1769 genes significantly differentially expressed, including 907 up-regulated genes and 862 down-regulated genes. Functional analysis revealed that hormone-responsive genes are related with the occurrence of cancer. Then, we successfully constructed IDC-specific Tnet and PPI network with DEGs response to hormone and obtained some hub genes, such as FOS and PIK3R1, in these networks. Besides, ten modules were found in these networks.<br><br>CONCLUSIONS: Hormone-responsive genes and modules may play an important role in the occurrence and development of IDC. Based on the findings above, we got a preliminary understand of the occurrence, development and metastasis of the IDC and possibly provided effective information on the biogenesis of IDC.}, }
@article {pmid23607710, year = {2013}, author = {Cao, AY and He, M and Huang, L and Shao, ZM and Di, GH}, title = {Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {91}, pmid = {23607710}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/*mortality/secondary/therapy ; Carcinoma, Medullary/epidemiology/*mortality/secondary/therapy ; China/epidemiology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*mortality/pathology/therapy ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Few studies have addressed the biological features of medullary breast carcinoma (MBC) in the context of clinical outcomes. We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between MBC and infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) using a large database.<br><br>METHODS: A total of 2,202 cases with pure IDC-NOS and 188 cases with typical MBC meeting the inclusion criteria were identified. The clinical and biological features, the overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups.<br><br>RESULTS: There were a higher proportion of patients diagnosed prior to 40 years of age in the MBC group compared to the IDC-NOS group. MBC cases demonstrated less aggressive tumor features such as lower tumor stage, smaller tumor size and a lower proportion of nodal involvement than IDC-NOS; however, immunohistochemical staining revealed that MBC displayed the triple-negative phenotype more often than IDC-NOS cases (40.4% versus 26.2%; P <0.001). Although the clinical behavior of MBC was not commensurate with its pathologic features, women diagnosed with MBC had a lower frequency of recurrence/metastasis (P = 0.032) and death (P = 0.042) than those with IDC-NOS, and the 10-year OS and RFS were significantly higher for MBC (91% and 74%) compared to IDC-NOS (81% and 64%). Moreover, multivariate analysis revealed that TNM stage was a statistically significant factor for survival.<br><br>CONCLUSIONS: MBC in Chinese women demonstrated less aggressive behavior and better prognosis than IDC-NOS. This favorable outcome was maintained after 10 years.}, }
@article {pmid23600833, year = {2013}, author = {Lloberas, N and Rama, I and Llaudó, I and Torras, J and Cerezo, G and Cassis, L and Franquesa, M and Merino, A and Benitez-Ribas, D and Cruzado, JM and Herrero-Fresneda, I and Bestard, O and Grinyó, JM}, title = {Dendritic cells phenotype fitting under hypoxia or lipopolysaccharide; adenosine 5'-triphosphate-binding cassette transporters far beyond an efflux pump.}, journal = {Clinical and experimental immunology}, volume = {172}, number = {3}, pages = {444-454}, pmid = {23600833}, issn = {1365-2249}, mesh = {ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists &amp; inhibitors/metabolism ; ATP-Binding Cassette Transporters/antagonists &amp; inhibitors/*metabolism ; Cell Differentiation ; Cell Hypoxia ; Cell Proliferation ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/cytology/drug effects/immunology/*metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Lipopolysaccharides/pharmacology ; Lymphocyte Culture Test, Mixed ; Lymphocyte Subsets/cytology/drug effects/immunology/metabolism ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/antagonists &amp; inhibitors/metabolism ; Phenotype ; }, abstract = {This study examines adenosine 5'-triphosphate-binding cassette (ABC) transporters as a potential therapeutic target in dendritic cell (DC) modulation under hypoxia and lipopolysaccharide (LPS). Functional capacity of dendritic cells (DCs) (mixed lymphocyte reaction: MLR) and maturation of iDCs were evaluated in the presence or absence of specific ABC-transporter inhibitors. Monocyte-derived DCs were cultured in the presence of interleukin (IL)-4/granulocyte-macrophage colony-stimulating factor (GM-CSF). Their maturation under hypoxia or LPS conditions was evaluated by assessing the expression of maturation phenotypes using flow cytometry. The effect of ABC transporters on DC maturation was determined using specific inhibitors for multi-drug resistance (MDR1) and multi-drug resistance proteins (MRPs). Depending on their maturation status to elicit T cell alloresponses, the functional capacity of DCs was studied by MLR. Mature DCs showed higher P-glycoprotein (Pgp) expression with confocal microscopy. Up-regulation of maturation markers was observed in hypoxia and LPS-DC, defining two different DC subpopulation profiles, plasmacytoid versus conventional-like, respectively, and different cytokine release T helper type 2 (Th2) versus Th1, depending on the stimuli. Furthermore, hypoxia-DCs induced more B lymphocyte proliferation than control-iDC (56% versus 9%), while LPS-DCs induced more CD8-lymphocyte proliferation (67% versus 16%). ABC transporter-inhibitors strongly abrogated DC maturation [half maximal inhibitory concentration (IC50): P-glycoprotein inhibition using valspodar (PSC833) 5 μM, CAS 115104-28-4 (MK571) 50 μM and probenecid 2·5 μM], induced significantly less lymphocyte proliferation and reduced cytokine release compared with stimulated-DCs without inhibitors. We conclude that diverse stimuli, hypoxia or LPS induce different profiles in the maturation and functionality of DC. Pgp appears to play a role in these DC events. Thus, ABC-transporters emerge as potential targets in immunosuppressive therapies interfering with DCs maturation, thereby abrogating innate immune response when it is activated after ischaemia.}, }
@article {pmid23593567, year = {2013}, author = {Zavyalova, MV and Denisov, EV and Tashireva, LA and Gerashchenko, TS and Litviakov, NV and Skryabin, NA and Vtorushin, SV and Telegina, NS and Slonimskaya, EM and Cherdyntseva, NV and Perelmuter, VM}, title = {Phenotypic drift as a cause for intratumoral morphological heterogeneity of invasive ductal breast carcinoma not otherwise specified.}, journal = {BioResearch open access}, volume = {2}, number = {2}, pages = {148-154}, pmid = {23593567}, issn = {2164-7844}, abstract = {Invasive ductal carcinoma (IDC) not otherwise specified (NOS), the most common type of breast cancer, demonstrates great intratumoral morphological heterogeneity, which encompasses the presence of different types of morphological structures-tubular, trabecular, solid, and alveolar structures and discrete groups of tumor cells, the origins of which remain unclear at present. In this study of 162 IDC NOS patients, we investigated whether the distribution of different types of morphological structures is related to the basic clinicopathological parameters of IDC NOS. Our results showed that in patients with only one type of tumor structure, the presence of any one of the five types was equally probable; however, cases with two types of structures were more likely to contain trabecular structures than the other four types. The development of intratumoral morphological heterogeneity was not associated with menopausal status, tumor size, histological grade, hematogenic metastasis, or recurrence. However, the number of different types of morphological structures was significantly higher in luminal tumors than in triple-negative tumors. An increase in the frequency of lymph node metastasis correlated with the increased number of different types of structures in breast tumors; however, in contrast to premenopausal patients, this association was explained by the presence of alveolar structures in postmenopausal women. In addition, we showed a significant decrease in the numbers of positive lymph nodes in tumors with high numbers of morphological variants. The frequency of lymph node metastases and the number of positive nodes were generally independent features and formed by different mechanisms. Based on the evidence, the term "phenotypic drift" has been designated as the basis for the development of intratumoral morphological heterogeneity of IDC NOS.}, }
@article {pmid23589849, year = {2013}, author = {Volinia, S and Croce, CM}, title = {Prognostic microRNA/mRNA signature from the integrated analysis of patients with invasive breast cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {18}, pages = {7413-7417}, pmid = {23589849}, issn = {1091-6490}, support = {U01 CA152758/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/classification/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Cohort Studies ; DNA Methylation/genetics ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genes, Neoplasm/genetics ; Genome, Human/genetics ; Humans ; Kaplan-Meier Estimate ; MicroRNAs/*genetics/metabolism ; Neoplasm Invasiveness ; Prognosis ; RNA, Messenger/genetics/metabolism ; ROC Curve ; Reproducibility of Results ; Risk Factors ; }, abstract = {The optimal management of breast cancer (BC) presents challenges due to the heterogeneous molecular classification of the disease. We performed survival analysis on a cohort of 466 patients with primary invasive ductal carcinoma (IDC), the most frequent type of BC, by integrating mRNA, microRNA (miRNA), and DNA methylation next-generation sequencing data from The Cancer Genome Atlas (TCGA). Expression data from eight other BC cohorts were used for validation. The prognostic value of the resulting miRNA/mRNA signature was compared with that of other prognostic BC signatures. Thirty mRNAs and seven miRNAs were associated with overall survival across different clinical and molecular subclasses of a 466-patient IDC cohort from TCGA. The prognostic RNAs included PIK3CA, one of the two most frequently mutated genes in IDC, and miRNAs such as hsa-miR-328, hsa-miR-484, and hsa-miR-874. The area under the curve of the receiver-operator characteristic for the IDC risk predictor in the TCGA cohort was 0.74 at 60 mo of overall survival (P < 0.001). Most relevant for clinical application, the integrated signature had the highest prognostic value in early stage I and II tumors (receiver-operator characteristic area under the curve = 0.77, P value < 0.001). The genes in the RNA risk predictor had an independent prognostic value compared with the clinical covariates, as shown by multivariate analysis. The integrated RNA signature was successfully validated on eight BC cohorts, comprising a total of 2,399 patients, and it had superior performance for risk stratification with respect to other RNA predictors, including the mRNAs used in MammaPrint and Oncotype DX assays.}, }
@article {pmid23584595, year = {2015}, author = {Ono, M and Tsuda, H and Yunokawa, M and Yonemori, K and Shimizu, C and Tamura, K and Kinoshita, T and Fujiwara, Y}, title = {Prognostic impact of Ki-67 labeling indices with 3 different cutoff values, histological grade, and nuclear grade in hormone-receptor-positive, HER2-negative, node-negative invasive breast cancers.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {22}, number = {2}, pages = {141-152}, doi = {10.1007/s12282-013-0464-4}, pmid = {23584595}, issn = {1880-4233}, mesh = {Asian People ; Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/genetics/metabolism/*mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence/methods ; Ki-67 Antigen/*analysis/metabolism ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; }, abstract = {BACKGROUND: The criteria for classifying hormone receptor (HR)-positive/HER2-negative breast cancers into low-risk and high-risk subgroups remain undetermined. Supportive data for optimal criteria to identify tumors in the high-risk subgroup are necessary for Japanese patients with HR-positive/HER2-negative breast cancers.<br><br>METHODS: Using immunohistochemistry and fluorescence in situ hybridization, we identified 369 consecutive patients with HR-positive/HER2-negative, node-negative invasive breast cancers. We examined the prognostic impact of the Ki-67 labeling index (LI) based on 3 cutoff values, 10, 14, and 20&#xa0;%, along with that of histological grade (HG) and nuclear grade (NG) by Cox's univariate and multivariate analyses.<br><br>RESULTS: The univariate analyses clearly showed that Ki-67 LI with any cutoff value divided the patients into distinct high-risk and low-risk groups, and that HG and NG were also powerful prognostic indicators. High Ki-67 LI with any cutoff value was strongly correlated with HG and NG, and when these parameters were included in the multivariate analyses, the impact of HG/NG was stronger than Ki-67 LIs. When the 10&#xa0;% cutoff value was adopted, discordance between Ki-67 LI and grades was frequent in papillotubular-type invasive ductal carcinoma, predominantly intraductal carcinoma, and mucinous carcinoma.<br><br>CONCLUSIONS: Any of the Ki-67 LI values, regardless of cutoff value, could be applicable for the classification of high-risk and low-risk HR-positive/HER2-negative, node-negative invasive breast cancers. Luminal A/B subtyping according to Ki-67 LI, or HG/NG, in combination with histological type, appeared to be able to create an optimum risk estimation system for patients with HR-positive/HER2-negative, node-negative invasive breast cancers in Japan.}, }
@article {pmid23575073, year = {2013}, author = {Rao, C and Shetty, J and Kishan Prasad, HL}, title = {Morphological profile and receptor status in breast carcinoma: an institutional study.}, journal = {Journal of cancer research and therapeutics}, volume = {9}, number = {1}, pages = {44-49}, doi = {10.4103/0973-1482.110358}, pmid = {23575073}, issn = {1998-4138}, mesh = {Adult ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Burden ; }, abstract = {CONTEXT: The data on histological and receptor status in breast cancer in an Indian population is limited as receptor status is not routinely carried out for these patients. In the present study, receptor status was analyzed and it was correlated with morphological prognostic parameters.<br><br>OBJECTIVE: To analyze the morphological prognostic parameters and its correlation with receptor status in Indian women.<br><br>DESIGN: The sample consisted of 126 specimens of invasive breast cancer received in department of pathology of our institution with teaching hospital attached to it, situated in South Canara district of, Karnataka, South India between year 2009 and 2011.<br><br>RESULT: Sixty-seven percent of patients were 50 years or younger. Histological types were invasive ductal carcinoma, not otherwise specified (58.7%), and overall (15.9%) were grade 3. Estrogen receptor was positive in 36.5%, HER/neu was overexpressed in only three cases; 50.0% were "triple" negative (estrogen receptor, progesterone receptor, HER/neu negative). Estrogen receptor (ER) and progesterone receptor (PR) positivity decreased with increase in tumor grade. There was significant association between tumor size and ER positivity.<br><br>CONCLUSIONS: Breast carcinoma in our population presents at younger age than Western population. Our results showed very high proportion of triple-negative breast cancers. The tumor size and grade is related to expression of only ER. The findings suggest that women in our population more often have histologically aggressive breast carcinoma at young age, likely to be less susceptible to conventional hormonal and targeted antibody treatment. Detecting and treating this increasing important cause of mortality will be an enormous challenge.}, }
@article {pmid23573438, year = {2013}, author = {Arslan, D and Tural, D and Tatlı, AM and Akar, E and Uysal, M and Erdoğan, G}, title = {Isolated uterine metastasis of invasive ductal carcinoma.}, journal = {Case reports in oncological medicine}, volume = {2013}, number = {}, pages = {793418}, pmid = {23573438}, issn = {2090-6706}, abstract = {Introduction. Most common metastasis sites of breast cancer are the lungs, bones, liver, and brain, whereas uterine involvement by metastatic breast disease is rare. Metastatic carcinoma of the uterus usually originates from other genital sites, most commonly being from the ovaries. Invasive lobular carcinoma spreads to gynecologic organs more frequently than invasive ductal carcinoma. Case Report. A 57-year-old postmenopausal woman was diagnosed with breast carcinoma 2 years ago and modified radical mastectomy was performed. Pathological examination of tumor revealed invasive ductal carcinoma, stage IIIc. She presented with abdominal pain and distension. Diagnostic workup and gynecologic examination revealed lesions that caused diffuse thickening of the uterus wall. Endometrial sampling was performed for confirmation of the diagnosis. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically. Conclusion. We herein report the first case of isolated uterine patient who had invasive ductal carcinoma of breast.}, }
@article {pmid23561623, year = {2013}, author = {Liang, F and Cao, W and Wang, Y and Li, L and Zhang, G and Wang, Z}, title = {The prognostic value of tumor budding in invasive breast cancer.}, journal = {Pathology, research and practice}, volume = {209}, number = {5}, pages = {269-275}, doi = {10.1016/j.prp.2013.01.009}, pmid = {23561623}, issn = {1618-0631}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*secondary ; Cell Proliferation ; China/epidemiology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Observer Variation ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Reproducibility of Results ; Retrospective Studies ; Survival Rate ; }, abstract = {We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&amp;E slides with a maximal invasive margin in a 0.950mm(2) field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (P<0.001). By immunohistochemical staining, budded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, P<0.001) together with tumor size (HR 2.468, P=0.002), node status (HR 2.362, P<0.001), and LVI status (HR 1.910, P=0.035) was the independent prognostic factor in IDC-NOS. In conclusion, tumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS.}, }
@article {pmid23549810, year = {2013}, author = {Eom, M and Lkhagvadorj, S and Oh, SS and Han, A and Park, KH}, title = {ROS1 expression in invasive ductal carcinoma of the breast related to proliferation activity.}, journal = {Yonsei medical journal}, volume = {54}, number = {3}, pages = {650-657}, pmid = {23549810}, issn = {1976-2437}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Proliferation ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Prognosis ; Protein-Tyrosine Kinases/genetics/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Survival Analysis ; }, abstract = {PURPOSE: ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast.<br><br>MATERIALS AND METHODS: Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR).<br><br>RESULTS: ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant.<br><br>CONCLUSION: Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.}, }
@article {pmid23534591, year = {2012}, author = {Pinto, AE and Pereira, T and Silva, GL and Ferreira, MC and André, S}, title = {[DNA ploidy is an independent prognostic biomarker in breast invasive ductal carcinoma].}, journal = {Acta medica portuguesa}, volume = {25}, number = {6}, pages = {399-407}, pmid = {23534591}, issn = {1646-0758}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/mortality ; Carcinoma, Ductal, Breast/*genetics/mortality ; Female ; Genetic Markers ; Humans ; Middle Aged ; *Ploidies ; Prognosis ; Prospective Studies ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate 'classic' prognostic parameters, as well as DNA ploidy and S-phase fraction, in relation to disease-free and overall survival in breast invasive ductal carcinoma with long-term follow-up.<br><br>MATERIAL AND METHODS: The study involved 400 patients with breast invasive ductal carcinoma and median follow-up of 134 months (50-240). Histological grading, tumour size, axillary nodal involvement, pathological staging and hormone-receptor status were assessed as established prognostic markers. Ploidy and S-phase fraction were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables.<br><br>RESULTS: There were 106 deaths (26.5%) and 141 disease recurrences (35.2%) during follow-up. Two hundred thirty-five (58.7%) tumours were aneuploid. High S-phase fraction and aneuploidy were associated with tumours with higher grade of differentiation, greater size and negative hormonal receptors. In univariate analysis, all the clinicopathological and cytometric features (including patients < 40 years and a subgroup presenting hipertetraploid/multiploid tumours), but S-phase fraction and estrogen receptors for disease free survival, significantly correlated with clinical outcome. In multivariate analysis, advanced disease stage, DNA aneuploidy and lack of progesterone receptors retained statistically significant association with shorter survival. In the subgroup of patients with intermediate differentiation tumours (G2), aneuploidy associated with worse prognosis. In the subset of node-negative patients, only estrogen receptors showed significant correlation with disease evolution. In node-positive patients, greater size tumours and aneuploidy (in relation to overall survival) were indicators of worse prognosis.<br><br>CONCLUSION: Along with disease staging and hormone-receptor expression, DNA ploidy is an independent prognostic biomarker of long-term survival in breast invasive ductal carcinoma.}, }
@article {pmid23529839, year = {2013}, author = {Benevides, L and Cardoso, CR and Tiezzi, DG and Marana, HR and Andrade, JM and Silva, JS}, title = {Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor.}, journal = {European journal of immunology}, volume = {43}, number = {6}, pages = {1518-1528}, doi = {10.1002/eji.201242951}, pmid = {23529839}, issn = {1521-4141}, mesh = {Antigens, CD/metabolism ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal/*immunology/pathology ; Cell Proliferation ; Cell Transformation, Neoplastic/immunology ; Chemokine CCL22/metabolism ; Female ; Forkhead Transcription Factors/metabolism ; Glucocorticoid-Induced TNFR-Related Protein/metabolism ; Humans ; Interleukin-17/genetics/*metabolism ; Neoplasm Invasiveness ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; Receptors, CCR6/metabolism ; T-Lymphocytes, Regulatory/*immunology ; Th17 Cells/*immunology ; Tumor Cells, Cultured ; Up-Regulation ; }, abstract = {Breast cancer is a leading cause of neoplasia-associated death in women worldwide. Regulatory T (Treg) and Th17 cells are enriched within some tumors, but the role these cells play in invasive ductal carcinoma (IDC) of the breast is unknown. We show that CD25(+) CD4(+) T cells from PBMCs and tumor express high levels of Foxp3, GITR, CTLA-4, and CD103, indicating that tumor-infiltrating Treg cells are functional and possibly recruited by CCL22. Additionally, we observed upregulation of Th17-related molecules (IL-17A, RORC, and CCR6) and IL-17A produced by tumor-infiltrating CD4(+) and CD8(+) T lymphocytes. The angiogenic factors CXCL8, MMP-2, MMP-9, and vascular endothelial growth factor detected within the tumor are possibly induced by IL-17 and indicative of poor disease prognosis. Treg and Th17 cells were synchronically increased in IDC patients, with positive correlation between Foxp3, IL-17A, and RORC expression, and associated with tumor aggressiveness. Therefore, Treg and Th17 cells can affect disease progression by Treg-cell-mediated suppression of the effector T-cell response, as indicated by a decrease in the proliferation of T cells isolated from PBMCs of IDC patients and induction of angiogenic factors by IL-17-producing Th17. The understanding of regulation of the Treg/Th17 axis may result in novel perspectives for the control of invasive tumors.}, }
@article {pmid23528301, year = {2013}, author = {Fernández-Caggiano, M and Barallobre-Barreiro, J and Rego-Pérez, I and Crespo-Leiro, MG and Paniagua, MJ and Grillé, Z and Blanco, FJ and Doménech, N}, title = {Mitochondrial DNA haplogroup H as a risk factor for idiopathic dilated cardiomyopathy in Spanish population.}, journal = {Mitochondrion}, volume = {13}, number = {4}, pages = {263-268}, doi = {10.1016/j.mito.2013.03.005}, pmid = {23528301}, issn = {1872-8278}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/*epidemiology/*genetics ; DNA, Mitochondrial/*genetics ; Female ; Gene Frequency ; *Haplotypes ; Humans ; Male ; Middle Aged ; Risk Factors ; Spain/epidemiology ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is a structural heart disease with strong genetic background. The different single nucleotide polymorphisms (SNPs) that constitute mitochondrial haplogroups could play an important role in IDC progression. The aim of this study was to test frequencies of mitochondrial haplogroups in healthy controls (n=422) and IDC patients (n=304) of a Caucasian Spanish population. To achieve this, ten major European haplogroups were identified. Frequencies and Odds Ratios for the association between IDC and haplogroups were calculated in both groups. We found that compared to healthy controls, the prevalence of haplogroup H was significantly higher in IDC patients (40.0% vs 50.7%, p-value=0.040).}, }
@article {pmid23526630, year = {2013}, author = {Tjomsland, V and Ellegård, R and Burgener, A and Mogk, K and Che, KF and Westmacott, G and Hinkula, J and Lifson, JD and Larsson, M}, title = {Complement opsonization of HIV-1 results in a different intracellular processing pattern and enhanced MHC class I presentation by dendritic cells.}, journal = {European journal of immunology}, volume = {43}, number = {6}, pages = {1470-1483}, pmid = {23526630}, issn = {1521-4141}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; R01 AI052731/AI/NIAID NIH HHS/United States ; R37 AI052731/AI/NIAID NIH HHS/United States ; }, mesh = {Antibodies, Blocking/metabolism ; Antigen Presentation ; Antigens, Viral/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cell Differentiation ; Cells, Cultured ; Complement System Proteins/*immunology ; Dendritic Cells/*immunology ; Endocytosis ; HIV Infections/*immunology ; HIV-1/*immunology ; Histocompatibility Antigens Class I/*immunology ; Humans ; Integrin beta Chains/immunology ; Lectins, C-Type/immunology ; Lymphocyte Activation ; Mannose Receptor ; Mannose-Binding Lectins/immunology ; Protein Binding ; Receptors, Cell Surface/immunology ; Receptors, Complement/immunology ; }, abstract = {Induction of optimal HIV-1-specific T-cell responses, which can contribute to controlling viral infection in vivo, depends on antigen processing and presentation processes occurring in DCs. Opsonization can influence the routing of antigen processing and pathways used for presentation. We studied antigen proteolysis and the role of endocytic receptors in MHC class I (MHCI) and II (MHCII) presentation of antigens derived from HIV-1 in human monocyte-derived immature DCs (IDCs) and mature DCs, comparing free and complement opsonized HIV-1 particles. Opsonization of virions promoted MHCI presentation by DCs, indicating that complement opsonization routes more virions toward the MHCI presentation pathway. Blockade of macrophage mannose receptor (MMR) and β7-integrin enhanced MHCI and MHCII presentation by IDCs and mature DCs, whereas the block of complement receptor 3 decreased MHCI and MHCII presentation. In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure; complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and β7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery.}, }
@article {pmid23523041, year = {2013}, author = {Niu, Y and Wang, S and Liu, T and Zhang, T and Wei, X and Wang, Y and Jiang, L}, title = {Expression of centrosomal tubulins associated with DNA ploidy in breast premalignant lesions and carcinoma.}, journal = {Pathology, research and practice}, volume = {209}, number = {4}, pages = {221-227}, doi = {10.1016/j.prp.2012.12.006}, pmid = {23523041}, issn = {1618-0631}, mesh = {Aneuploidy ; Breast Neoplasms/*chemistry/genetics/pathology ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/genetics/pathology ; Centrosome/*chemistry ; Chi-Square Distribution ; Disease Progression ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Hyperplasia ; Neoplasm Grading ; Neoplasm Invasiveness ; *Ploidies ; Precancerous Conditions/*chemistry/genetics/pathology ; Tubulin/*analysis ; }, abstract = {The centrosome plays an essential role in chromosomal segregation during cell division. Centrosome dysfunction might lead to aneuploidy and chromosomal instability. Invasive breast tumors with centrosome amplification often show aneuploidy. Flow cytometry (FCM) was used to examine the aneuploidy rate in 30 cases of each of the following seven tissue types: normal breast tissue, usual ductal hyperplasia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ, high-grade ductal carcinoma in situ, low-grade invasive ductal carcinoma, and high-grade invasive ductal carcinoma. Centrosomal α, γ-tubulin expression was examined by FCM immunofluorescence and compared between diploid and aneuploid cells. The aneuploidy rate was 0, 6.7%, 26.7%, 30.0%, 46.7%, 56.7%, and 86.7%, respectively, in the seven tissue types. The percentage of cells expressing α- and γ-tubulins was significantly different between the seven groups, and the positive rate of α- and γ-tubulin expression in ADH, DCIS and IDC was higher than that in NBT and UDH. The percentage of cells expressing α- and γ-tubulins in the diploid state was significantly lower than that in the aneuploid state. Expression of centrosomal α- and γ-tubulins seems to be associated with DNA ploidy in breast premalignant lesions and carcinoma during the progression of breast cancer.}, }
@article {pmid23520664, year = {2012}, author = {Jana, D and Sarkar, DK and Maji, A and Chikkala, BR and Hassanujjaman, S and Mukhopadhyay, M and Ganguly, S}, title = {Can cyclo-oxygenase-2 be a useful prognostic and risk stratification marker in breast cancer?.}, journal = {Journal of the Indian Medical Association}, volume = {110}, number = {7}, pages = {429-433}, pmid = {23520664}, issn = {0019-5847}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal/*genetics/pathology ; Cyclooxygenase 2/*genetics ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Genetic Markers/*genetics ; Humans ; Lymphatic Metastasis/pathology ; Neoplasm Staging ; Neoplasms, Hormone-Dependent/genetics/pathology ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Tumor Burden/physiology ; }, abstract = {Cyclo-oxygenase-2 (COX-2) is a prostaglandin synthease that catalyses the synthesis of prostaglandin G2 (PGG2) and PGH2 from arachidonic acid. COX-2 plays an important role in tumourigenesis of different carcinoma types and it is thought to take part in breast carcinoma. In this study, the aim was to investigate the relationship of COX-2 with clinical parameters such as menopausal status, tumour size, grade, nodal status, Nottingham prognostic index (NPI), oestrogen receptor(ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER-2/ neu). The patients were divided into two groups, first group (group A) comprised 57 primary breast cancer patients and the second group (group B) comprised control group 27 patients consisting of fibro-adenoma and benign breast disease. In control groups COX-2 (0%) is not over expressed and we observed that high frequency of COX-2 (73.68%) over expressed in breast carcinoma. In high grade, large tumour size and positive lymph node metastasis, COX-2 expression rate was 78.6%, 59.5% and 90.5% respectively. COX-2 expression is directly correlated with ER negative (88.1%, p = 0.001) and also associated with higher NPI value (78.6%, p = 0.006). In invasive ductal carcinoma (IDC) COX-2 over expression had a significant relationship with HER-2/neu over expression (p < 0.001). The results indicated that COX-2 over expression correlates with aggressive phenotypic features, such as high histological grade, large tumour size, higher NPI value, ER negativity and HER-2/neu positivity.}, }
@article {pmid23515911, year = {2013}, author = {Parker, A and Schroen, AT and Brenin, DR}, title = {MRI utilization in newly diagnosed breast cancer: a survey of practicing surgeons.}, journal = {Annals of surgical oncology}, volume = {20}, number = {8}, pages = {2600-2606}, doi = {10.1245/s10434-013-2934-5}, pmid = {23515911}, issn = {1534-4681}, support = {P30 CA044579/CA/NCI NIH HHS/United States ; }, mesh = {Breast Density ; Breast Neoplasms/*diagnosis/diagnostic imaging/genetics ; Carcinoma/*diagnosis/diagnostic imaging/genetics ; Chi-Square Distribution ; Data Collection ; Female ; Humans ; Institutional Practice/statistics &amp; numerical data ; Logistic Models ; Magnetic Resonance Imaging/*statistics &amp; numerical data ; Mammary Glands, Human/abnormalities ; *Practice Patterns, Physicians' ; Private Practice/statistics &amp; numerical data ; Radiography ; Specialization/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: Whereas guidelines supporting breast MRI in high-risk screening exist, guidelines for MRI use in newly diagnosed breast cancer are lacking. We, therefore, conducted a study of breast surgeons to determine practice beliefs surrounding MRI use in newly diagnosed breast cancer.<br><br>METHODS: A survey sent to 2,274 American Society of Breast Surgeons members in December 2010 queried routine MRI use (defined as >75&#xa0;% of time) in specific clinical scenarios. Analyses were performed by respondent practice setting, practice volume, and practice specialization. Descriptive statistics and subgroup analysis using a &#x3c7;(2) and logistic regression were used.<br><br>RESULTS: Responses from 1,012 surgeons (45.5&#xa0;% response rate) were eligible for analysis. Respondents represented diverse practice settings (20&#xa0;% academic, 72&#xa0;% private practice) and volume (&#x2264;50 new breast cancer patients, 36&#xa0;%; 51-100, 26&#xa0;%; 101-200, 25&#xa0;%; >200, 13&#xa0;%). Also, 41&#xa0;% of surgeons indicated routine MRI use for newly diagnosed patients, with higher rates of use among surgeons from high-volume practices, high specialization, and private practice. Greater consensus in routine MRI use was seen in the setting of extreme mammographic density (87.9&#xa0;%), strong family history of breast cancer (73.4&#xa0;%), and invasive lobular carcinoma (69.4&#xa0;%). Responses were increasingly discordant in setting of pursuing breast conservation (47.4&#xa0;%), invasive ductal carcinoma (41.8&#xa0;%), and ductal carcinoma in situ (37.2&#xa0;%). Personal experience was the most commonly cited influence on MRI use.<br><br>CONCLUSIONS: Divergent responses in MRI use in newly diagnosed breast cancer reflect clinical uncertainty and variable practice beliefs among breast surgeons. Such diverging practice patterns highlight areas where clinical research and guidelines may be most helpful.}, }
@article {pmid23506949, year = {2013}, author = {Córdoba, EV and Pion, M and Rasines, B and Filippini, D and Komber, H and Ionov, M and Bryszewska, M and Appelhans, D and Muñoz-Fernández, MA}, title = {Glycodendrimers as new tools in the search for effective anti-HIV DC-based immunotherapies.}, journal = {Nanomedicine : nanotechnology, biology, and medicine}, volume = {9}, number = {7}, pages = {972-984}, doi = {10.1016/j.nano.2013.03.004}, pmid = {23506949}, issn = {1549-9642}, mesh = {Biomarkers/metabolism ; Cell Death/drug effects ; Cell Differentiation/drug effects ; Cell Movement/drug effects ; Cytokines/metabolism ; Dendrimers/*chemistry/pharmacology ; Dendritic Cells/drug effects/*immunology/metabolism ; HIV/drug effects/*immunology ; HIV Infections/*immunology/*therapy ; Humans ; *Immunotherapy ; Maltose/chemistry ; Peptides/immunology ; Phenotype ; T-Lymphocytes/cytology/drug effects ; }, abstract = {UNLABELLED: Dendritic cells (DC), which play a major role in development of cell-mediated immunity, represent opportunities to develop novel anti-HIV vaccines. Dendrimers have been proposed as new carriers to ameliorate DC antigen loading and in this way, we have determined the potential use of maltose decorated neutrally and positively charged G4 glycodendrimers. Thus, immunostimulatory properties of these glycodendrimers on human DC were evaluated in the context of HIV infection. We have demonstrated that DC treated with glycodendrimers were fully functional with respect to viability, maturation and HIV-derived antigens uptake. Nevertheless, iDC and mDC phenotypes as well as mDC functions such as migration ability and cytokines profile production were changed. Our results showed the potential carrier properties of glycodendrimers to activate the immune system by the way of DC stimulation. This is the first study for exploring the use of maltose-functionalized dendrimers-peptides complexes as a potential DC-based vaccine candidate.<br><br>FROM THE CLINICAL EDITOR: In this paper, maltose-functionalized dendrimer-peptide complexes are demonstrated to activate the immune system by way of dendritic cell (DC) stimulation. DC vaccination using this methodology may be applicable to a variety of conditions, including infections and potentially cancer.}, }
@article {pmid23490334, year = {2013}, author = {Biglia, N and Maggiorotto, F and Liberale, V and Bounous, VE and Sgro, LG and Pecchio, S and D'Alonzo, M and Ponzone, R}, title = {Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC).}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {39}, number = {5}, pages = {455-460}, doi = {10.1016/j.ejso.2013.02.007}, pmid = {23490334}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Breast Neoplasms/*pathology/radiotherapy/*surgery ; Carcinoma, Ductal, Breast/*pathology/radiotherapy/*surgery ; Carcinoma, Lobular/*pathology/radiotherapy/*surgery ; Chi-Square Distribution ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Logistic Models ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Reoperation ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node Biopsy ; Survival Rate ; Treatment Outcome ; }, abstract = {PURPOSE OF THE STUDY: A retrospective analysis on 1407 patients with invasive ductal carcinoma (IDC) and 243 invasive lobular carcinoma (ILC) was performed in order to compare the histological features, the immunohistochemical characteristics, the surgical treatment and the clinical outcome in the two groups.<br><br>RESULTS: ILC seems to be more likely multifocal, estrogen receptor positive, HER-2 negative and to have a lower proliferative index compared to IDC. ILC, when treated with conservative surgery, required more frequently re-excision and/or mastectomy because of positive resection margins. No difference was observed in terms of 5-year disease free survival and local relapse free survival between the two groups, in the whole series and in the subgroup of patients treated with breast-conserving treatment.<br><br>CONCLUSION: ILC can be safely treated with conservative surgery but a more accurate preoperative evaluation of tumor size and multifocality could be advocated, in order to reduce the re-excision rate.}, }
@article {pmid23479571, year = {2013}, author = {McKimmie, CS and Singh, MD and Hewit, K and Lopez-Franco, O and Le Brocq, M and Rose-John, S and Lee, KM and Baker, AH and Wheat, R and Blackbourn, DJ and Nibbs, RJ and Graham, GJ}, title = {An analysis of the function and expression of D6 on lymphatic endothelial cells.}, journal = {Blood}, volume = {121}, number = {18}, pages = {3768-3777}, doi = {10.1182/blood-2012-04-425314}, pmid = {23479571}, issn = {1528-0020}, support = {ETM/276/CSO_/Chief Scientist Office/United Kingdom ; 19656/ARC_/Arthritis Research UK/United Kingdom ; G0901113/MRC_/Medical Research Council/United Kingdom ; 19656/VAC_/Versus Arthritis/United Kingdom ; G1001724/MRC_/Medical Research Council/United Kingdom ; ETM/115/CSO_/Chief Scientist Office/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; RG/09/005/27915/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Animals ; CHO Cells ; Cell Communication/genetics/immunology ; Cell Differentiation/genetics/immunology ; Cells, Cultured ; Cricetinae ; Cricetulus ; Dendritic Cells/immunology/metabolism/physiology ; Endothelial Cells/immunology/*metabolism ; HEK293 Cells ; Humans ; Inflammation/genetics/immunology/metabolism ; Neoplasms/genetics/immunology/metabolism ; Receptors, CCR10/analysis/*genetics/metabolism/*physiology ; Transfection ; }, abstract = {The mechanisms by which CC chemokine receptor (CCR)7 ligands are selectively presented on lymphatic endothelium in the presence of inflammatory chemokines are poorly understood. The chemokine-scavenging receptor D6 is expressed on lymphatic endothelial cells (LEC) and contributes to selective presentation of CCR7 ligands by suppressing inflammatory chemokine binding to LEC surfaces. As well as preventing inappropriate inflammatory cell attachment to LECs, D6 is specifically involved in regulating the ability of LEC to discriminate between mature and immature dendritic cells (DCs). D6 overexpression reduces immature DC (iDC) adhesion to LECs, whereas D6 knockdown increases adhesion of iDCs that displace mature DCs. LEC D6 expression is regulated by growth factors, cytokines, and tumor microenvironments. In particular, interleukin-6 and interferon-γ are potent inducers, indicating a preferential role for D6 in inflamed contexts. Expression of the viral interleukin-6 homolog from Kaposi sarcoma-associated herpesvirus is also sufficient to induce significant D6 upregulation both in vitro and in vivo, and Kaposi sarcoma and primary effusion lymphoma cells demonstrate high levels of D6 expression. We therefore propose that D6, which is upregulated in both inflammatory and tumor contexts, is an essential regulator of inflammatory leukocyte interactions with LECs and is required for immature/mature DC discrimination by LECs.}, }
@article {pmid23469238, year = {2013}, author = {Catteau, X and Simon, P and Vanhaeverbeek, M and Noël, JC}, title = {Variable stromal periductular expression of CD34 and smooth muscle actin (SMA) in intraductal carcinoma of the breast.}, journal = {PloS one}, volume = {8}, number = {3}, pages = {e57773}, pmid = {23469238}, issn = {1932-6203}, mesh = {Actins/genetics/metabolism ; Antigens, CD34/genetics/metabolism ; Breast Neoplasms/genetics/*pathology ; Carcinoma in Situ/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Case-Control Studies ; Female ; Gene Expression ; Humans ; Myofibroblasts/metabolism/*pathology ; Necrosis/*genetics/pathology ; Neoplasm Grading ; Neoplasm Invasiveness ; Stromal Cells/metabolism/*pathology ; }, abstract = {In breast carcinoma, the stromal loss of CD34 expression and acquisition of SMA myofibroblastic features may constitute a prerequisite for tumor invasiveness. However, this hypothesis remains controversial, with some authors describing the loss of CD34 fibrocytes in the absence of SMA myofibroblastic-like cells in the stroma of invasive carcinoma. Others have also described the disappearance of CD34 fibrocytes from in situ carcinoma. To clarify this issue, we compared the distribution of CD34 fibrocytes and SMA reactive myofibroblasts between stromal areas of tumor-free mammary tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). In addition to 28 IDC, 300 normal duct-lobular units and 600 ducts with DCIS (158 low-grade, 266 intermediate, and 176 high-grade) were scored. The relationships between staining patterns and different histological features (grade of DCIS and presence or absence of necrosis) were compared. Loss of CD34 expression and acquisition of SMA expression were more frequent in high-grade in situ lesions than in intermediate and low-grade lesions (p<0.001). When necrosis was found in association with grade 2 or 3 DCIS, the decrease in CD34 expression was higher than in lesions without necrosis and that independently of the grade of DCIS (p<0.05). Necrosis did not appear to play a significant role in the expression of SMA (p = 0.35). In all cases, the stroma of invasive carcinomas showed a complete loss of CD34 fibrocytes. Future research on both CD34 fibrocytes and mechanisms stromal changes are essential in the future and may potentially lead to new treatment approaches.}, }
@article {pmid23468622, year = {2013}, author = {Gupta, AP and Chin, WH and Zhu, L and Mok, S and Luah, YH and Lim, EH and Bozdech, Z}, title = {Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum.}, journal = {PLoS pathogens}, volume = {9}, number = {2}, pages = {e1003170}, pmid = {23468622}, issn = {1553-7374}, mesh = {Animals ; *Epigenesis, Genetic ; *Gene Expression Regulation, Developmental ; Genome, Protozoan ; Histones/genetics ; Life Cycle Stages/*physiology ; Plasmodium falciparum/*genetics ; Real-Time Polymerase Chain Reaction ; Time Factors ; Transcription, Genetic ; }, abstract = {Epigenetic mechanisms are emerging as one of the major factors of the dynamics of gene expression in the human malaria parasite, Plasmodium falciparum. To elucidate the role of chromatin remodeling in transcriptional regulation associated with the progression of the P. falciparum intraerythrocytic development cycle (IDC), we mapped the temporal pattern of chromosomal association with histone H3 and H4 modifications using ChIP-on-chip. Here, we have generated a broad integrative epigenomic map of twelve histone modifications during the P. falciparum IDC including H4K5ac, H4K8ac, H4K12ac, H4K16ac, H3K9ac, H3K14ac, H3K56ac, H4K20me1, H4K20me3, H3K4me3, H3K79me3 and H4R3me2. While some modifications were found to be associated with the vast majority of the genome and their occupancy was constant, others showed more specific and highly dynamic distribution. Importantly, eight modifications displaying tight correlations with transcript levels showed differential affinity to distinct genomic regions with H4K8ac occupying predominantly promoter regions while others occurred at the 5' ends of coding sequences. The promoter occupancy of H4K8ac remained unchanged when ectopically inserted at a different locus, indicating the presence of specific DNA elements that recruit histone modifying enzymes regardless of their broad chromatin environment. In addition, we showed the presence of multivalent domains on the genome carrying more than one histone mark, highlighting the importance of combinatorial effects on transcription. Overall, our work portrays a substantial association between chromosomal locations of various epigenetic markers, transcriptional activity and global stage-specific transitions in the epigenome.}, }
@article {pmid23466672, year = {2013}, author = {Kawada, N and Uehara, H and Takada, R and Yamai, T and Fukutake, N and Katayama, K and Takenaka, A and Nagata, S and Tomita, Y}, title = {Microinvasion of high-grade pancreatic intraepithelial neoplasia.}, journal = {Case reports in gastroenterology}, volume = {7}, number = {1}, pages = {30-36}, pmid = {23466672}, issn = {1662-0631}, abstract = {High-grade pancreatic intraepithelial neoplasia (PanIN-3) is recognized as a precursor lesion of invasive ductal carcinoma (IDC). However, histological evidence that PanIN-3 invades beyond the basement membrane of pancreatic ductal epithelium, that is, the moment PanIN-3 becomes IDC, has not been captured yet. This may be because PanINs which are microscopic papillary or flat lesion rarely develop clinical symptoms and are not detectable on imaging examination. On the other hand, most IDCs were found in the advanced stage with massive invasion. In this report, PanIN-3 obstructed several branch pancreatic ducts and subsequently caused pancreatitis which developed clinical symptom and was detectable as a pancreatic mass in imaging studies. A 65-year-old woman was referred to our institution for further examination of her repeated pancreatitis. Abdominal ultrasound revealed a low echoic mass of 13 mm in diameter in the pancreatic body without upstream dilatation of the main pancreatic duct (MPD). Endoscopic retrograde pancreatography showed a strictured segment of 2 mm in length in the MPD at the pancreatic body. Cytological examination of pancreatic juice revealed adenocarcinoma and distal pancreatectomy was performed. A resected specimen revealed a whitish mass of 15 mm in diameter in the pancreatic body, which was identified as pancreatitis by histological examination. Papillary growth of PanIN-3 was seen mainly in the branch ducts. Each PanIN-3 was located separately in the branch ducts with normal epithelia in the MPD between them. In three adjacent branch ducts, PanIN-3 was observed to be invading microscopically beyond the basement membrane.}, }
@article {pmid23466329, year = {2013}, author = {Yu, XF and Feng, WL and Miao, LL and Chen, B and Yang, HJ}, title = {The prognostic significance of molecular subtype for male breast cancer: a 10-year retrospective study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {5}, pages = {824-827}, doi = {10.1016/j.breast.2013.02.005}, pmid = {23466329}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*chemistry ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Male breast cancer (MBC) is rare. Molecular subtype has been utilized widely in female breast cancer. But the relationship between subtype and prognosis in MBC patients is still unknown. We aim to study the impact of molecular subtype on the prognosis of MBC.<br><br>METHODS: We identified MBC cases from 1990 to 2011 retrospectively; molecular subtype was assigned by immunohistochemistry. We compared overall survival in different subtypes by Kaplan-Meier method and COX proportional hazard regression model.<br><br>RESULTS: 68 patients with MBC were included in analysis with 115 months of a median follow-up time. Comparing to non-luminal A (subtypes of Luminal B, HER2 over-express and Basal-like) group, patients with luminal A had a lower recurrent rate and better overall survival (10-year survival rate was 78.0% vs 67.0%, mean survival time 197.46 &#xb1; 12.22 months vs 146.51 &#xb1; 16.88 months, p < 0.05).<br><br>CONCLUSION: Molecular subtype may have prognosis-predicting value for MBC.}, }
@article {pmid23456318, year = {2013}, author = {Kulkarni, N and Pezzi, CM and Greif, JM and Suzanne Klimberg, V and Bailey, L and Korourian, S and Zuraek, M}, title = {Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base.}, journal = {Annals of surgical oncology}, volume = {20}, number = {7}, pages = {2236-2241}, doi = {10.1245/s10434-013-2911-z}, pmid = {23456318}, issn = {1534-4681}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms/metabolism/*pathology/*therapy ; Carcinoma, Adenoid Cystic/metabolism/*secondary/*therapy ; Carcinoma, Ductal, Breast/metabolism/*secondary/*therapy ; Chemotherapy, Adjuvant ; Female ; Hormones/therapeutic use ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Receptors, Estrogen/metabolism ; Receptors, Progesterone ; }, abstract = {BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare subtype of breast malignancy.<br><br>METHODS: Patients with ACC and infiltrating ductal carcinoma (IDC) reported to the National Cancer Data Base from 1998 to 2008 were reviewed for patient age, ethnicity, tumor size, nodal status, American Joint Committee on Cancer TNM Stage, tumor grade, initial treatment, hormone receptor status (for patients from 2004 to 2008), and survival (for patients from 1998 to 2003).<br><br>RESULTS: A total of 933 patients with ACC and 729,938 with IDC were identified. No differences were found for incidence by race/ethnicity (p = 0.97). The group with ACC was older (median 60 vs. 58 years), had larger tumors (median 18 vs. 16 mm), had more grade 1 tumors (46 vs. 18 %), was less likely to undergo axillary lymph node evaluation (75.9 vs. 96.3 %), had fewer node-positive patients (5.1 vs. 35.5 %), had fewer estrogen receptor-positive tumors (15.4 vs. 75.6 %), had fewer progesterone receptor-positive tumors (13.3 vs. 65.2 %), and underwent breast-conserving surgery more often (69.8 vs. 59.8 %). Chemotherapy was provided less often for ACC (11.3 vs. 46.4 %), as was hormone therapy (9.1 vs. 42.3 %). All of these differences were statistically significant (p < 0.0001). With a median follow-up of 65.7 months (ACC) and 64.9 months (IDC), 5-year overall survival (OS) was 88 % for ACC vs. 84 % for IDC (p = 0.02). Grade 1 OS (ACC, 91 % vs. IDC, 92 %; p = 0.50) and stage I OS (ACC, 90 % vs. IDC, 91 %; p = 0.93) were equal.<br><br>CONCLUSIONS: Compared with IDC, ACC has different characteristics (lower grade, hormone receptor negative, node negative), is treated differently (less axillary surgery, fewer mastectomies, less chemotherapy, less hormone therapy), and has an improved prognosis, with 88 % 5-year survival.}, }
@article {pmid25031990, year = {2013}, author = {Radcliff, L}, title = {Breast cancer and autism.}, journal = {Journal of the advanced practitioner in oncology}, volume = {4}, number = {2}, pages = {113-117}, pmid = {25031990}, issn = {2150-0878}, abstract = {Case Study Amy is a 44-year-old woman with severe autism. She lives with her sister Susan, who is her caregiver and guardian. Amy is ambulatory and able to dress and feed herself. She is a healthy individual with no other significant comorbidities. She walks daily and enjoys her sister's company. Amy's life expectancy is greater than 10 years. However, she is difficult to care for medically, as she will not allow a physical examination and strikes out when strangers try to touch her. She is nonverbal and unable to participate in decision-making. INITIAL DIAGNOSIS Amy has a history of breast cancer diagnosed 2 years ago, originally presenting as a stage I lesion (T2N0) that was palpated by her caregiver while bathing. She underwent right simple mastectomy with sentinel lymph node resection. Susan recalls that the mastectomy was a very challenging ordeal, as Amy kept pulling out IV lines, drains, and dressings. Susan felt that Amy withdrew from her after the procedure as she most likely associated Susan with the cause of the pain, making her role as caregiver more difficult. Pathology confirmed an invasive ductal carcinoma, moderately differentiated, 2.4 cm, estrogen/progesterone receptor negative, HER2/neu negative, with negative surgical margins. Two right axillary sentinel lymph nodes were negative for disease. The standard of care for a patient with these tumor features is surgery plus adjuvant chemotherapy (National Comprehensive Cancer Network [NCCN], 2012). According to the Adjuvant Online! database (2012), Amy's risk for relapse was approximately 40% without adjuvant treatment; her risk for mortality was approximately 29%. After meeting with a medical oncologist, Amy did not receive adjuvant chemotherapy. According to Susan, she was not offered the choice, and the decision was not explained to them. She was simply told that it was not necessary. Aside from pathology, previous records were unavailable for review. Medical assessment of Amy's level of autism reveals marked impairments in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body posture, and gestures to regulate social interaction. She exhibits a total lack of development of spoken language, with no attempt to compensate through alternative modes of communication such as gesture. During the visit, she occupies herself with repetitive motor mannerisms. Susan believes that Amy struggles with overstimulation from tactile input. Therefore, she is combative with health-care providers and intolerant of invasive devices. Susan has an intimate understanding of Amy's ability to communicate her needs and wants through nonverbal changes. RECURRENCE Approximately 2 months ago, Amy began favoring her right arm and appeared to be in pain when participating in various activities. Susan became aware of Amy's pain issues by noticing that her posture was slightly altered and she was carrying herself differently. Further investigation with a CT scan showed concern for local disease recurrence involving the axillary lymph nodes. No distant metastases were seen. The standard of care for this diagnosis is surgical resection and consideration of radiation therapy, followed by adjuvant chemotherapy (NCCN, 2012). Susan does not want Amy to undergo further surgery and believes radiation would be too difficult to maneuver. The next best option would be a medical approach with chemotherapy as the main modality. DIFFICULT DECISIONS If treatment is pursued, the advanced practitioner will need to perform regular examinations and prescribe and monitor chemotherapy. The delivery of therapy, requiring frequent blood draws and IV access, will be a challenge for the health-care staff. The APN is apprehensive about the ability to accomplish these tasks safely given Amy's limited capacity to participate. The APN is also concerned with how treatment will affect Amy's life. The APN may have her own individual conflict of morals to contend with, given the limited understanding of the patient vs. nontreatment of a potentially curative malignancy. Chemotherapy is not an easy task for any patient to undertake, especially for a patient with challenges such as Amy has. Although Susan can give legal consent for her sister, Amy is unable to participate in this decision-making. Susan strongly believes that Amy's quality of life is much more important than the quantity. Withholding treatment may shorten the natural course of Amy's life, yet administering chemotherapy will alter the quality of life that she now enjoys without her understanding or consent. Should Amy receive chemotherapy or should Susan refuse treatment on her behalf?}, }
@article {pmid23445447, year = {2013}, author = {Duan, R and Zuo, X and Wang, S and Quan, X and Chen, D and Chen, Z and Jiang, L and Fan, C and Xia, F}, title = {Lab in a tube: ultrasensitive detection of microRNAs at the single-cell level and in breast cancer patients using quadratic isothermal amplification.}, journal = {Journal of the American Chemical Society}, volume = {135}, number = {12}, pages = {4604-4607}, doi = {10.1021/ja311313b}, pmid = {23445447}, issn = {1520-5126}, mesh = {Breast/*metabolism/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Line, Tumor ; Female ; Humans ; Limit of Detection ; MicroRNAs/*analysis/genetics ; Nucleic Acid Amplification Techniques/*methods ; }, abstract = {Through rational design of a functional molecular probe with high sequence specificity that takes advantage of sensitive isothermal amplification with simple operation, we developed a one-pot hairpin-mediated quadratic enzymatic amplification strategy for microRNA (miRNA) detection. Our method exhibits ultrahigh sensitivity toward miR-21 with detection limits of 10 fM at 37 °C and 1 aM at 4 °C, which corresponds to nine strands of miR-21 in a 15 μL sample, and it is capable of distinguishing among miRNA family members. More importantly, the proposed approach is also sensitive and selective when applied to crude extractions from MCF-7 and PC3 cell lines and even patient tissues from intraductal carcinoma and invasive ductal carcinoma of the breast.}, }
@article {pmid23440416, year = {2013}, author = {Mochizuki, K and Xie, F and He, S and Tong, Q and Liu, Y and Mochizuki, I and Guo, Y and Kato, K and Yagita, H and Mineishi, S and Zhang, Y}, title = {Delta-like ligand 4 identifies a previously uncharacterized population of inflammatory dendritic cells that plays important roles in eliciting allogeneic T cell responses in mice.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {190}, number = {7}, pages = {3772-3782}, pmid = {23440416}, issn = {1550-6606}, support = {P30 CA046592/CA/NCI NIH HHS/United States ; R01 CA172106/CA/NCI NIH HHS/United States ; R01-CA-172106-01/CA/NCI NIH HHS/United States ; 5P30CA46592/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology/metabolism ; Dendritic Cells/*immunology/*metabolism ; Disease Models, Animal ; Gastrointestinal Tract/immunology/metabolism ; Gene Expression ; Gene Expression Profiling ; Graft vs Host Disease/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Interferon-gamma/biosynthesis ; Interleukin-17/biosynthesis ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Isoantigens/*immunology ; Ligands ; Lymphocyte Activation/immunology ; Membrane Proteins/genetics/*metabolism ; Mice ; Receptors, Notch/metabolism ; Spleen/immunology/metabolism ; T-Lymphocytes/*immunology ; Transplantation, Homologous/immunology ; Tumor Necrosis Factor-alpha/biosynthesis ; }, abstract = {Graft-versus-host disease (GVHD) reflects an exaggerated inflammatory allogeneic T cell response in hosts receiving allogeneic hematopoietic stem cell transplantation (HSCT). Inhibition of pan-Notch receptor signaling in donor T cells causes reduction of GVHD. However, which Notch ligand(s) in what APCs is important for priming graft-versus-host reaction remains unknown. We demonstrate that δ-like ligand-4 (Dll4) and Dll4-positive (Dll4(high)) inflammatory dendritic cells (i-DCs) play important roles in eliciting allogeneic T cell responses. Host-type Dll4(high) i-DCs occurred in the spleen and intestine of HSCT mice during GVHD induction phase. These Dll4(high) i-DCs were CD11c(+)B220(+)PDCA-1(+), resembling plasmacytoid dentritic cells (pDCs) of naive mice. However, as compared with unstimulated pDCs, Dll4(high) i-DCs expressed higher levels of costimulatory molecules, Notch ligands Jagged1 and Jagged2, and CD11b, and produced more Ifnb and Il23 but less Il12. In contrast, Dll4-negative (Dll4(low)) i-DCs were CD11c(+)B220(-)PDCA-1(-), and had low levels of Jagged1. In vitro assays showed that Dll4(high) i-DCs induced significantly more IFN-γ- and IL-17-producing effector T cells (3- and 10-fold, respectively) than Dll4(low) i-DCs. This effect could be blocked by anti-Dll4 Ab. In vivo administration of Dll4 Ab reduced donor-alloreactive effector T cells producing IFN-γ and IL-17 in GVHD target organs, leading to reduction of GVHD and improved survival of mice after allogeneic HSCT. Our findings indicate that Dll4(high) i-DCs represent a previously uncharacterized i-DC population distinctive from steady state DCs and Dll4(low) i-DCs. Furthermore, Dll4 and Dll4(high) i-DCs may be beneficial targets for modulating allogeneic T cell responses, and could facilitate the discovery of human counterparts of mouse Dll4(high) i-DCs.}, }
@article {pmid23436478, year = {2013}, author = {Pierobon, D and Bosco, MC and Blengio, F and Raggi, F and Eva, A and Filippi, M and Musso, T and Novelli, F and Cappello, P and Varesio, L and Giovarelli, M}, title = {Chronic hypoxia reprograms human immature dendritic cells by inducing a proinflammatory phenotype and TREM-1 expression.}, journal = {European journal of immunology}, volume = {43}, number = {4}, pages = {949-966}, doi = {10.1002/eji.201242709}, pmid = {23436478}, issn = {1521-4141}, mesh = {Cell Hypoxia ; Cells, Cultured ; Cytokines/*metabolism ; Dendritic Cells/*immunology/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammation Mediators/*metabolism ; Membrane Glycoproteins/genetics/*metabolism ; *Phenotype ; Receptors, Immunologic/genetics/immunology/*metabolism ; Th1 Cells/immunology/metabolism ; Th17 Cells/immunology/metabolism ; Triggering Receptor Expressed on Myeloid Cells-1 ; }, abstract = {DCs are powerful antigen-presenting cells central in the orchestration of innate and acquired immunity. DC development, migration, and activities are intrinsically linked to the microenvironment. DCs migrate through pathologic tissues before reaching their final destination in the lymph nodes. Hypoxia, a condition of low partial oxygen pressure, is a common feature of many pathologic situations, capable of modifying DC phenotype and functional behavior. We studied human monocyte-derived immature DCs generated under chronic hypoxic conditions (H-iDCs). We demonstrate by gene expression profiling the upregulation of a cluster of genes coding for antigen-presentation, immunoregulatory, and pattern recognition receptors, suggesting a stimulatory role for hypoxia on iDC immunoregulatory functions. In particular, we show that H-iDCs express triggering receptor expressed on myeloid cells(TREM-1), a member of the Ig superfamily of immunoreceptors and an amplifier of inflammation. This effect is reversible because H-iDC reoxygenation results in TREM-1 down-modulation. TREM-1 engagement promotes upregulation of T-cell costimulatory molecules and homing chemokine receptors, typical of mature DCs, and increases the production of proinflammatory, Th1/Th17-priming cytokines/chemokines, resulting in increased T-cell responses. These results suggest that TREM-1 induction by the hypoxic microenvironment represents a mechanism of regulation of Th1-cell trafficking and activation by iDCs differentiated at pathologic sites.}, }
@article {pmid23432978, year = {2013}, author = {Baslaim, MM and Al-Amoudi, SA and Al-Ghamdi, MA and Ashour, AS and Al-Numani, TS}, title = {Case report: Breast cancer associated with contralateral tuberculosis of axillary lymph nodes.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {43}, pmid = {23432978}, issn = {1477-7819}, mesh = {Aged ; Axilla ; Breast Neoplasms/complications/*microbiology/pathology ; Carcinoma, Ductal, Breast/complications/*microbiology/secondary ; Female ; Humans ; Lymph Nodes/*microbiology/pathology ; Lymphatic Metastasis ; Neoplasm Grading ; Prognosis ; Tuberculosis, Lymph Node/*complications/microbiology ; }, abstract = {BACKGROUND: Breast cancer coexisting with tuberculous axillary lymph nodes is rare.<br><br>CASE REPORT: We report a 69 years old Yemeni patient with a left breast invasive ductal carcinoma associated with contralateral tuberculous axillary lymph nodes containing microcalcifications mimicking malignancy. The patient had to be investigated for the possibility of bilateral breast cancer since she had no history of previous exposure to tuberculosis.<br><br>CONCLUSION: Tuberculosis involving lymph nodes can create a diagnostic dilemma in the presence of a malignant process. The presence of calcifications in lymph nodes should raise the possibility of tuberculosis even in the absence of contact history with tuberculosis.}, }
@article {pmid23421821, year = {2013}, author = {Contino, F and Mazzarella, C and Ferro, A and Lo Presti, M and Roz, E and Lupo, C and Perconti, G and Giallongo, A and Feo, S}, title = {Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {81}, pmid = {23421821}, issn = {1471-2407}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; *Genes, erbB-2 ; Histone Deacetylase 1/genetics/*metabolism ; Humans ; Immunohistochemistry ; Neoplasm Proteins/genetics/*metabolism ; Promoter Regions, Genetic ; Receptor, ErbB-2/metabolism ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: The human ERBB2 gene is frequently amplified in breast tumors, and its high expression is associated with poor prognosis. We previously reported a significant inverse correlation between Myc promoter-binding protein-1 (MBP-1) and ERBB2 expression in primary breast invasive ductal carcinoma (IDC). MBP-1 is a transcriptional repressor of the c-MYC gene that acts by binding to the P2 promoter; only one other direct target of MBP-1, the COX2 gene, has been identified so far.<br><br>METHODS: To gain new insights into the functional relationship linking MBP-1 and ERBB2 in breast cancer, we have investigated the effects of MBP-1 expression on endogenous ERBB2 transcript and protein levels, as well as on transcription promoter activity, by transient-transfection of SKBr3 cells. Reporter gene and chromatin immunoprecipitation assays were used to dissect the ERBB2 promoter and identify functional MBP-1 target sequences. We also investigated the relative expression of MBP-1 and HDAC1 in IDC and normal breast tissues by immunoblot analysis and immunohistochemistry.<br><br>RESULTS: Transfection experiments and chromatin immunoprecipitation assays in SKBr3 cells indicated that MBP-1 negatively regulates the ERBB2 gene by binding to a genomic region between nucleotide -514 and -262 of the proximal promoter; consistent with this, a concomitant recruitment of HDAC1 and loss of acetylated histone H4 was observed. In addition, we found high expression of MBP-1 and HDAC1 in normal tissues and a statistically significant inverse correlation with ErbB2 expression in the paired tumor samples.<br><br>CONCLUSIONS: Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC.}, }
@article {pmid23418456, year = {2013}, author = {El-Shinawi, M and Mohamed, HT and El-Ghonaimy, EA and Tantawy, M and Younis, A and Schneider, RJ and Mohamed, MM}, title = {Human cytomegalovirus infection enhances NF-κB/p65 signaling in inflammatory breast cancer patients.}, journal = {PloS one}, volume = {8}, number = {2}, pages = {e55755}, pmid = {23418456}, issn = {1932-6203}, mesh = {Adult ; Aged ; Cytomegalovirus Infections/complications/*metabolism/virology ; Female ; Gene Expression Profiling ; Humans ; Inflammatory Breast Neoplasms/complications/*metabolism/virology ; Middle Aged ; NF-kappa B/genetics/*metabolism ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics/metabolism ; Signal Transduction/*physiology ; Up-Regulation ; }, abstract = {Human Cytomegalovirus (HCMV) is an endemic herpes virus that re-emerges in cancer patients enhancing oncogenic potential. Recent studies have shown that HCMV infection is associated with certain types of cancer morbidity such as glioblastoma. Although HCMV has been detected in breast cancer tissues, its role, if any, in the etiology of specific forms of breast cancer has not been investigated. In the present study we investigated the presence of HCMV infection in inflammatory breast cancer (IBC), a rapidly progressing form of breast cancer characterized by specific molecular signature. We screened for anti-CMV IgG antibodies in peripheral blood of 49 non-IBC invasive ductal carcinoma (IDC) and 28 IBC patients. In addition, we screened for HCMV-DNA in postsurgical cancer and non-cancer breast tissues of non-IBC and IBC patients. We also tested whether HCMV infection can modulate the expression and activation of transcriptional factor NF-κB/p65, a hallmark of IBC. Our results reveal that IBC patients are characterized by a statistically significant increase in HCMV IgG antibody titers compared to non-IBC patients. HCMV-DNA was significantly detected in cancer tissues than in the adjacent non-carcinoma tissues of IBC and IDC, and IBC cancer tissues were significantly more infected with HCMV-DNA compared to IDC. Further, HCMV sequence analysis detected different HCMV strains in IBC patients tissues, but not in the IDC specimens. Moreover, HCMV-infected IBC cancer tissues were found to be enhanced in NF-κB/p65 signaling compared to non-IBC patients. The present results demonstrated a correlation between HCMV infection and IBC. Etiology and causality of HCMV infection with IBC now needs to be rigorously examined.}, }
@article {pmid23416046, year = {2013}, author = {Dreyer, G and Vandorpe, T and Smeets, A and Forceville, K and Brouwers, B and Neven, P and Janssens, H and Deraedt, K and Moerman, P and Van Calster, B and Christiaens, MR and Paridaens, R and Wildiers, H}, title = {Triple negative breast cancer: clinical characteristics in the different histological subtypes.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {5}, pages = {761-766}, doi = {10.1016/j.breast.2013.01.009}, pmid = {23416046}, issn = {1532-3080}, mesh = {Age Factors ; Aged ; Carcinoma/*pathology/secondary/therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy ; Radiotherapy, Adjuvant ; Treatment Outcome ; Triple Negative Breast Neoplasms/*pathology/therapy ; }, abstract = {PURPOSE: To investigate the clinical behavior of triple negative breast cancer (TNC), including age distribution, occurrence of LN (lymph node) invasion and prognosis in different histological subtypes.<br><br>METHODS: For this cohort study we used data on 476 patients with newly diagnosed TNC at the University Hospitals Leuven (Belgium) between 1999 and 2009. Of these, 395 received upfront surgery, 68 neoadjuvant chemotherapy and 21 had metastases at diagnosis.<br><br>RESULTS: Apocrine and invasive lobular TNC occur more often in older patients compared to IDC-NOS. Of the primarily operated patients with TNC, 35.1% has pathological LN involvement. There were no significant differences in nodal invasion between different histological subtypes, but most subtypes contained few patients. In contrast to previous reports, 6/14 of apocrine TNC had LN involvement. Disease free survival (DFS) was different in different histological subtypes, but group sizes were insufficient to be able to draw firm conclusions. Within the histologically 'homogeneous' IDC-NOS group with primary surgery and outcome data (n = 300), DFS with 3.5 year median follow-up decreased with increasing age, but chemotherapy and radiotherapy were much less frequently given with increasing age. In multivariable analysis, lower age, presence of LN involvement, lack of administration of chemotherapy and radiotherapy were significant predictors of relapse.<br><br>CONCLUSION: TNC is not a uniform disease. Different histological subtypes have different age distribution and behavior. The prognosis of the most common histological subgroup, IDC-NOS, is better in older patients, but this is counterbalanced by significantly decreased use of chemotherapy and radiotherapy.}, }
@article {pmid23412907, year = {2013}, author = {Khurana, A and Jung-Beom, D and He, X and Kim, SH and Busby, RC and Lorenzon, L and Villa, M and Baldi, A and Molina, J and Goetz, MP and Shridhar, V}, title = {Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts.}, journal = {Clinical &amp; experimental metastasis}, volume = {30}, number = {4}, pages = {407-415}, pmid = {23412907}, issn = {1573-7276}, support = {P50 CA136393/CA/NCI NIH HHS/United States ; R01 CA106954/CA/NCI NIH HHS/United States ; R01 CA123249/CA/NCI NIH HHS/United States ; CA106954-04/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Carcinoma, Lobular/drug therapy/*metabolism/secondary ; Cell Proliferation ; Extracellular Matrix/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Mice ; Neoplasm Grading ; Proteasome Inhibitors/*pharmacology ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfatases ; Sulfotransferases/antagonists &amp; inhibitors/genetics/*metabolism ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death.}, }
@article {pmid23412348, year = {2013}, author = {Zhang, W and Zhang, T and Lin, Z and Zhang, X and Liu, F and Wang, Y and Liu, H and Yang, Y and Niu, Y}, title = {Invasive cribriform carcinoma in a Chinese population: comparison with low-grade invasive ductal carcinoma-not otherwise specified.}, journal = {International journal of clinical and experimental pathology}, volume = {6}, number = {3}, pages = {445-457}, pmid = {23412348}, issn = {1936-2625}, mesh = {Adult ; Aged ; Axilla ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Cell Proliferation ; China ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {Invasive cribriform carcinoma (ICC) and low-grade invasive ductal carcinoma (IDC) were recently considered to belong to a low-grade breast neoplasia family. However, none of publications has compared ICC and low-grade IDC at present. Meanwhile, in order to evaluate prognostic significance of clinicopathological characteristics of different cribriform contents in ICC and invasive breast cancer with less cribriform structures, a retrospective review of fifty-one cases of ICC and forty cases of invasive breast cancer with less cribriform pattern (less than fifty percent) was conducted in a Chinese population. Forty-nine cases of low-grade IDC without cribriform elements were selected as a control. ICC presented more favorable prognostic factors than those of invasive breast carcinoma with less cribriform pattern and low-grade IDC, such as smaller tumor size, less frequent axillary lymph node involvement, higher positive rate of estrogen receptor and/or progestogen receptor expression, and lower proliferation index. The expression of human epidermal growth factor receptor two in ICC and invasive breast cancer with less cribriform pattern was mostly negative. Pure ICC showed less frequency of axillary lymph node involvement, but not its number. The proliferation index in the pure type was lower, although the tumor size in these two types was not obviously different. Tumors contained cribriform structures had a more favorable prognosis than those with low-grade IDC. Considering the tumor biology, and the benign course of pure ICC studied, chemotherapy may not be indicated in the typical case.}, }
@article {pmid23406456, year = {2013}, author = {Erro, R and Barone, P and Moccia, M and Amboni, M and Vitale, C}, title = {Abnormal eating behaviors in progressive supranuclear palsy.}, journal = {European journal of neurology}, volume = {20}, number = {3}, pages = {e47-e48}, doi = {10.1111/ene.12077}, pmid = {23406456}, issn = {1468-1331}, mesh = {Aged ; *Feeding Behavior ; Feeding and Eating Disorders/*etiology ; Humans ; Middle Aged ; Supranuclear Palsy, Progressive/*complications ; }, }
@article {pmid23404186, year = {2013}, author = {Philippin-Lauridant, G and Baranzelli, MC and Samson, C and Fournier, C and Pinte, S and Mattot, V and Bonneterre, J and Soncin, F}, title = {Expression of Egfl7 correlates with low-grade invasive lesions in human breast cancer.}, journal = {International journal of oncology}, volume = {42}, number = {4}, pages = {1367-1375}, doi = {10.3892/ijo.2013.1820}, pmid = {23404186}, issn = {1791-2423}, mesh = {3T3 Cells ; Adult ; Aged ; Aged, 80 and over ; Animals ; Axilla/pathology ; Breast Neoplasms/metabolism/mortality/pathology ; Breast Neoplasms, Male/*metabolism/mortality/pathology ; Calcium-Binding Proteins ; Carcinoma, Ductal, Breast/*metabolism/mortality/secondary ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/secondary ; Carcinoma, Lobular/*metabolism/mortality/secondary ; Cells, Cultured ; Disease-Free Survival ; EGF Family of Proteins ; Endothelial Growth Factors/genetics/*metabolism ; Female ; Gene Expression ; Human Umbilical Vein Endothelial Cells ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis ; Male ; Mice ; Middle Aged ; Neoplasm Invasiveness ; Organ Specificity ; }, abstract = {Egfl7 (VE-statin) is specifically expressed by endothelial cells of normal tissues but its expression is deregulated in human cancers. Analysis of expression of Egfl7 protein and transcripts in 211 human breast cancer samples shows that Egfl7 is strongly expressed by breast tumor cells. Egfl7 expression is significantly higher in invasive ductal than in invasive lobular carcinoma. Expression of Egfl7 transcripts is also higher in lower SBR grade lesions and in lesions which are not associated with lymph node invasion. Within the invasive ductal carcinoma sub-population, expression of Egfl7 transcripts is correlated with the SBR score and with the ER+ status. High transcript and Egfl7 protein levels significantly correlate with the absence of axillary lymph node invasion. In lymph nodes, the levels of Egfl7 are correlated with the histological type of the primary lesions; they are higher in ductal than in lobular carcinoma. Egfl7 expression is thus associated with better prognosis factors and with the absence of lymph node invasion in human breast cancer lesions.}, }
@article {pmid23399321, year = {2013}, author = {Li, S and Meng, H and Zhou, F and Zhai, L and Zhang, L and Gu, F and Fan, Y and Lang, R and Fu, L and Gu, L and Qi, L}, title = {MicroRNA-132 is frequently down-regulated in ductal carcinoma in situ (DCIS) of breast and acts as a tumor suppressor by inhibiting cell proliferation.}, journal = {Pathology, research and practice}, volume = {209}, number = {3}, pages = {179-183}, doi = {10.1016/j.prp.2012.12.002}, pmid = {23399321}, issn = {1618-0631}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Cell Proliferation ; Down-Regulation ; Female ; *Genes, Tumor Suppressor ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Real-Time Polymerase Chain Reaction ; }, abstract = {Ductal carcinoma in situ (DCIS) is the most common type of non-invasive breast cancer. The currently accepted step-wise model suggests that breast cancer progressed in the following manner: normal breast cell→usually ductal hyperplasia (UDH)→atypical ductal hyperplasia (ADH)→DCIS→invasive ductal carcinoma (IDC). Therefore, DCIS can serve as a good model to analyze the mechanism underlying invasive breast cancer occurrence. MicroRNAs (miRNAs) are a novel class of small non-coding RNAs (~22nt) involved in the regulation of various biological processes. Altered miRNA expression could also contribute to the origination of cancer, including breast cancer. Here, by using miRNA microarray and real time PCR, we analyzed the miRNA expression profile in 21 DCIS and the corresponding normal tissues. miR-10b, miR-125b, miR-132, miR-145, miR-154-3p, miR-382-5p and miR-409-3p were found to be significantly deregulated in DCIS. Results from CCK-8 assay showed that the overexpression of miR-132 could inhibit the proliferation of breast cancer cell line. High expression of miR-132 could also inhibit the colony formation. Our findings will lead to further understanding of the development of breast cancer.}, }
@article {pmid23389824, year = {2013}, author = {Rovner, E and Dmochowski, R and Chapple, C and Thompson, C and Lam, W and Haag-Molkenteller, C}, title = {OnabotulinumtoxinA improves urodynamic outcomes in patients with neurogenic detrusor overactivity.}, journal = {Neurourology and urodynamics}, volume = {32}, number = {8}, pages = {1109-1115}, doi = {10.1002/nau.22376}, pmid = {23389824}, issn = {1520-6777}, mesh = {Adult ; Aged ; Botulinum Toxins, Type A/pharmacology/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/complications/*physiopathology ; Neuromuscular Agents/pharmacology/*therapeutic use ; Quality of Life ; Spinal Cord Injuries/complications/*physiopathology ; Treatment Outcome ; Urinary Bladder, Neurogenic/*drug therapy/etiology/physiopathology ; Urinary Bladder, Overactive/*drug therapy/etiology/physiopathology ; Urodynamics/*drug effects/physiology ; }, abstract = {AIMS: To evaluate the effect of onabotulinumtoxinA on urodynamic outcomes in patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).<br><br>METHODS: Results from two pivotal Phase III trials (n&#x2009;=&#x2009;691) were pooled. MS or SCI patients with NDO, received intradetrusor onabotulinumtoxinA 200&#x2009;U (n&#x2009;=&#x2009;227), 300&#x2009;U (n&#x2009;=&#x2009;223), or placebo (n&#x2009;=&#x2009;241). Change from baseline in UI episodes/week (Week 6), maximum cystometric capacity (MCC), maximum detrusor pressure at first involuntary detrusor contraction (IDC) (PdetmaxIDC), volume at first IDC (VpmaxIDC), and detrusor compliance (DC) were measured.<br><br>RESULTS: OnabotulinumtoxinA significantly increased MCC overall (+153.6&#x2009;ml with 200&#x2009;U vs. +11.9&#x2009;ml with placebo). Over 60% of onabotulinumtoxinA-treated patients had no IDC at Week 6; in patients with an IDC at Week 6, VpmaxIDC improved (+183.4&#x2009;ml with 200&#x2009;U vs. +17.5&#x2009;ml with placebo), and PdetmaxIDC decreased (-32.4&#x2009;cmH2O with 200&#x2009;U vs. +1.1&#x2009;cmH2O with placebo). OnabotulinumtoxinA-treated patients had a significant increase in DC (+59.8&#x2009;ml/cmH2O with 200&#x2009;U vs. -5.2 with placebo). Urodynamic improvements were comparable in patients regardless of baseline DC and corresponded with significant reductions in UI episodes/week for both onabotulinumtoxinA doses versus placebo, with no clinically relevant differences between 200 and 300&#x2009;U groups. Most common adverse event was urinary tract infection (UTI); complicated UTIs were low across all treatment groups. In patients not catheterizing at baseline, a dose-dependent increase in post-void residual urine was observed at Week 2 following onabotulinumtoxinA treatment.<br><br>CONCLUSIONS: OnabotulinumtoxinA significantly improved urodynamic outcomes in NDO patients, even in those with low baseline DC, and corresponded with improvements in UI episodes. Both doses of onabotulinumtoxinA were well tolerated.}, }
@article {pmid23374397, year = {2013}, author = {Ripamonti, CB and Colombo, M and Mondini, P and Siranoush, M and Peissel, B and Bernard, L and Radice, P and Carcangiu, ML}, title = {First description of an acinic cell carcinoma of the breast in a BRCA1 mutation carrier: a case report.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {46}, pmid = {23374397}, issn = {1471-2407}, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism/surgery ; Carcinoma, Acinar Cell/*genetics/metabolism/surgery ; Carcinoma, Ductal, Breast/*genetics/surgery ; Female ; *Genes, BRCA1 ; Heterozygote ; Humans ; Mutation ; Neoplasms, Second Primary/*genetics/surgery ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/genetics ; }, abstract = {BACKGROUND: Acinic cell carcinoma (ACC) is a rare malignant epithelial neoplasm characterized by the presence of malignant tubular acinar exocrine gland structures. Diagnosis is generally made in salivary glands and in the pancreas. ACC of the breast has been reported in few cases only. Carriers of inherited mutations in the BRCA1 gene are prone to the development of breast cancer, mainly invasive ductal or medullary type carcinomas. We describe for the first time a BRCA1 mutation carrier with a diagnosis of ACC of the breast.<br><br>CASE PRESENTATION: The patient developed an invasive ductal carcinoma (IDC) at the age of 40 years and an ACC in the contralateral breast at 44 years. Immunohistochemical examination of the ACC revealed a triple negative status (i.e., negativity for estrogen receptor, progesterone receptor and HER2 protein) and positivity for p53. Using a combination of loss of heterozygosity (LOH) and sequencing analyses, the loss of the wild-type BRCA1 allele was detected in both the ACC and the IDC. In addition, two different somatic TP53 mutations, one in the ACC only and another one in the IDC only, were observed.<br><br>CONCLUSION: Both the immunohistochemical and molecular features observed in the ACC are typical of BRCA1-associated breast cancers and suggest an involvement of the patient's germline mutation in the disease. The occurrence of rare histological types of breast cancers, including malignant phyllodes tumor, atypical medullary carcinoma and metaplastic carcinoma, in BRCA1 mutation carriers has been already reported. Our findings further broaden the spectrum of BRCA1-associated breast malignancies.}, }
@article {pmid23372687, year = {2013}, author = {Chen, L and Li, Y and Fu, Y and Peng, J and Mo, MH and Stamatakos, M and Teal, CB and Brem, RF and Stojadinovic, A and Grinkemeyer, M and McCaffrey, TA and Man, YG and Fu, SW}, title = {Role of deregulated microRNAs in breast cancer progression using FFPE tissue.}, journal = {PloS one}, volume = {8}, number = {1}, pages = {e54213}, pmid = {23372687}, issn = {1932-6203}, support = {R21 CA159103/CA/NCI NIH HHS/United States ; R21CA159103/CA/NCI NIH HHS/United States ; }, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/diagnosis/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Disease Progression ; Female ; Formaldehyde ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia/diagnosis/*genetics/metabolism/pathology ; MicroRNAs/*genetics/metabolism ; Neoplasm Proteins/*genetics/metabolism ; Neoplasm Staging ; Paraffin Embedding ; Tissue Fixation ; }, abstract = {MicroRNAs (miRNAs) contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-β pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.}, }
@article {pmid23372178, year = {2013}, author = {Cooper, CL and Karim, RZ and Selinger, C and Carmalt, H and Lee, CS and O'Toole, SA}, title = {Molecular alterations in metaplastic breast carcinoma.}, journal = {Journal of clinical pathology}, volume = {66}, number = {6}, pages = {522-528}, doi = {10.1136/jclinpath-2012-201086}, pmid = {23372178}, issn = {1472-4146}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology/therapy ; Carcinoma/genetics/*metabolism/pathology/therapy ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Metaplasia ; Neoplastic Stem Cells/metabolism/pathology ; Signal Transduction ; }, abstract = {Metaplastic carcinoma of the breast is a rare and heterogeneous subtype of breast carcinoma with a generally poor outcome, and few therapeutic options once disease recurs or progresses. Metaplastic carcinomas of the breast are usually of a larger size at diagnosis, with less frequent nodal metastasis compared with invasive ductal carcinoma no special type, and lack hormone and HER2 receptor expression. Recent research has revealed some potentially actionable genetic changes in a subset of these rare tumours. However, ongoing efforts to further characterise the genetic basis and the molecular alterations underlying the distinctive morphological and clinical characteristics of these tumours are needed in order to identify new targets for treatment. This review will describe the theories of pathogenesis of metaplastic breast carcinoma, and highlight genetic changes and potential therapeutic targets in this generally poor prognosis malignancy.}, }
@article {pmid23363467, year = {2013}, author = {Holtick, U and Wang, XN and Marshall, SR and Scheid, C and von Bergwelt-Baildon, M and Dickinson, AM}, title = {Immature DC isolated after co-culture with PUVA-treated peripheral blood mononuclear cells downregulate graft-versus-host reactions in the human skin explant model.}, journal = {Current stem cell research &amp; therapy}, volume = {8}, number = {4}, pages = {324-332}, doi = {10.2174/1574888x11308040008}, pmid = {23363467}, issn = {2212-3946}, mesh = {Cells, Cultured ; Coculture Techniques ; Dendritic Cells/*physiology ; Ficusin/*pharmacology ; Graft vs Host Disease/immunology/*prevention &amp; control ; *Graft vs Host Reaction ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppression Therapy ; Interferon-gamma/metabolism ; Interleukin-6/metabolism ; Lymphocytes/physiology ; Photopheresis ; Photosensitizing Agents/*pharmacology ; Skin/immunology/metabolism ; Transplantation, Homologous ; }, abstract = {Graft-versus-host disease (GvHD) remains the major barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) is a potent immunomodulatory treatment option for GvHD. In contrast to conventional immunosuppressants, ECP is considered not to increase relapse and infection rates resulting from generalised immunosuppression. ECP involves the mechanical separation of 5-10% of patient peripheral blood mononuclear cells, which are then exposed to psoralen and UVA light (PUVA) before they are returned to the patient. ECP has been shown to induce apoptosis in various cell types, in particular lymphocytes. Several studies describe downregulation of pro-inflammatory cytokines as well as promotion of peripheral tolerance through enhanced production of T regulatory cells in the course of ECP-treatment. Modulation of antigen-presenting cells such as dendritic cells (DC) by PUVA-treated lymphocytes might be implicated in these regulatory processes. We evaluated the impact of PUVA-treated lymphocytes on immature DC and further demonstrated the functional capacity of such modified DC to modulate GVH reactions using a well-established human skin-explant model of GvHD. Addition of immature DC isolated after co-culture with PUVA-treated but not untreated MLR cells significantly downregulated skin-GvH reactions (p=0.023, Mann-Whitney-Test). IFN-gamma levels were non-significantly decreased in MLR and skin supernatants. We observed a non-significant increase in PD-L1 expression in iDC after co-culture with PUVA-treated MLR cells whereas expression levels of IDO and ILT-3 were not affected. We conclude that iDC modulated by PUVA-induced apoptotic cells potently downregulate allogeneic immune responses possibly through PD-L1- dependent signaling.}, }
@article {pmid23354842, year = {2013}, author = {Yamashita, N and Tokunaga, E and Kitao, H and Hisamatsu, Y and Taketani, K and Akiyoshi, S and Okada, S and Aishima, S and Morita, M and Maehara, Y}, title = {Vimentin as a poor prognostic factor for triple-negative breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {139}, number = {5}, pages = {739-746}, pmid = {23354842}, issn = {1432-1335}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/mortality/pathology ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Vimentin/*genetics/metabolism ; }, abstract = {PURPOSE: Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, is a highly heterogeneous disease. Recent studies suggest that there are links between TNBC and the epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, vimentin, one of the most major factors associated with EMT was investigated in TNBC.<br><br>MATERIALS AND METHODS: Sporadic invasive ductal carcinoma specimens were obtained from 659 Japanese patients, and 90 (14 %) cases were diagnosed as TNBC. The vimentin mRNA and protein expression levels were evaluated by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry.<br><br>RESULTS: The mRNA expression of vimentin was significantly upregulated in the basal-type breast cancer cell line. Immunohistochemically, the vimentin expression was significantly higher (p = 0.0042) in TNBC compared with the other subtypes. Vimentin expression was associated with a younger age (p = 0.016), high nuclear grade (p = 0.023) and high Ki67 expression (p < 0.0001), and a poorer prognosis in terms of both the recurrence-free survival (RFS) (p = 0.0058) and overall survival (OS) (p = 0.013) in TNBC patients. A multivariate analysis showed that vimentin expression was an independent prognostic factor for the RFS (p = 0.043). Vimentin expression was also associated with a significantly shorter RFS (p = 0.021) and OS (p = 0.017) in patients with basal-like breast cancer (BLBC).<br><br>CONCLUSIONS: The elevated expression of vimentin contributes to the aggressive phenotype and poor prognosis in TNBC. Vimentin expression might be useful as a biomarker for the prognosis of TNBC.}, }
@article {pmid23353551, year = {2013}, author = {Chaturbhuj, DN and Deshmukh, PS and Hingankar, NK and Siddhaarth, K and Deshpande, SN and Sen, S and Kabra, S and Paranjape, RS and Tripathy, SP}, title = {Evaluations of an in-house drug resistance method for HIV-1 drug resistance using ViroSeq™ 2.0 genotyping system as a gold standard.}, journal = {Journal of virological methods}, volume = {189}, number = {1}, pages = {87-92}, doi = {10.1016/j.jviromet.2013.01.001}, pmid = {23353551}, issn = {1879-0984}, mesh = {Anti-HIV Agents/pharmacology ; Base Sequence ; Drug Resistance, Viral/*genetics ; Genotype ; HIV Infections/*drug therapy/virology ; HIV Reverse Transcriptase/genetics ; HIV-1/*drug effects/*genetics ; Humans ; Mutation ; Peptide Hydrolases/genetics ; Sequence Analysis, DNA ; }, abstract = {An in-house method was evaluated for its efficiency to detect the HIV-1 drug resistance mutations. This method was compared with the ViroSeq™ Genotyping System 2.0 (Celera Diagnostics, US) a gold standard. Sixty-five stored plasma samples, previously tested for HIV-1 drug resistance using the ViroSeq™ method were used to evaluate the in-house method. Out of the sixty five plasma samples, sixty were HIV-1 positive clinical samples; four samples from the Virology Quality Assessment (VQA) program and one positive control from the ViroSeq™ kit were used in this study. The sequences generated by the ViroSeq™ and an in-house method showed 99.5±0.5% and 99.7±0.4% (mean±SD) nucleotide and amino acid identity, respectively. Out of 214 Stanford HIVdb listed HIV-1 drug resistance mutations in the protease and reverse transcriptase regions, concordance was observed in 203 (94.9%), partial discordance in 11 (5.1%) and complete discordance was absent. The in-house primers are broadly sensitive in genotyping multiple HIV-1 group M subtypes. The amplification sensitivity of the in-house method was 1000 copies/ml. The evaluation of the in-house method provides results comparable with that of ViroSeq™ method thus, making the in-house method suitable for HIV-1 drug resistance testing in the developing countries.}, }
@article {pmid23352319, year = {2013}, author = {Trovo, M and Roncadin, M and Polesel, J and Piccoli, E and Mileto, M and Micheli, E and Perin, T and Carbone, A and Massarut, S and Trovo, MG}, title = {Toxicity and cosmesis following partial breast irradiation consisting of 40 Gy in 10 daily fractions.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {5}, pages = {744-747}, doi = {10.1016/j.breast.2012.12.012}, pmid = {23352319}, issn = {1532-3080}, mesh = {Aged ; Aged, 80 and over ; Breast/*pathology/*radiation effects/surgery ; Breast Neoplasms/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/surgery ; *Dose Fractionation, Radiation ; Erythema/etiology ; Female ; Fibrosis/etiology ; Humans ; Mastectomy, Segmental ; Middle Aged ; Pain/etiology ; Radiotherapy, Adjuvant/adverse effects/methods ; }, abstract = {PURPOSE: To assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction).<br><br>METHODS AND MATERIALS: Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1-T2 pN0-N1a) invasive ductal carcinoma.<br><br>RESULTS: 77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged "good/excellent" and "poor" in 75 (97%) and in 2 (3%) patients, respectively.<br><br>CONCLUSIONS: 40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI.}, }
@article {pmid23347178, year = {2013}, author = {Rakha, EA and Teoh, TK and Lee, AH and Nolan, CC and Ellis, IO and Green, AR}, title = {Further evidence that E-cadherin is not a tumour suppressor gene in invasive ductal carcinoma of the breast: an immunohistochemical study.}, journal = {Histopathology}, volume = {62}, number = {5}, pages = {695-701}, doi = {10.1111/his.12066}, pmid = {23347178}, issn = {1365-2559}, mesh = {Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/*genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; Cell Membrane/metabolism/pathology ; Female ; *Genes, Tumor Suppressor ; Humans ; Multiprotein Complexes/genetics/metabolism ; Neoplasm Staging ; beta Catenin/genetics/metabolism ; }, abstract = {AIMS: E-cadherin is a cell adhesion molecule expressed in normal breast tissue; it is used generally as a phenotypical marker in breast cancer, with the absence of its expression observed frequently in lobular tumours. We have reported E-cadherin expression previously in 1516 ductal breast carcinoma using tissue microarray (TMA), where 7% of cases showed a complete absence of membrane staining. In this study, we investigated further the existence of E-cadherin-negative ductal carcinoma and evaluated the status of the E-cadherin-catenin complex in this subgroup.<br><br>MATERIAL AND METHODS: Full-face sections from excision specimens of 72 ductal breast carcinomas reported previously as E-cadherin-negative were assessed morphologically using haematoxylin and eosin staining, and immunohistochemically using two E-cadherin antibodies (HECD-1 and CDH1/4A2C7) and antibodies recognizing &#x3b2;-catenin and p120 proteins. Only membrane expression was considered.<br><br>RESULTS: Forty-seven ductal carcinomas were assessed after the exclusion of inappropriate cases; 34 of these showed positive E-cadherin (HECD-1) membrane expression which was focal and weak and seen mainly in invasion fronts. Ten cases showed E-cadherin (4A2C7) staining. Staining for p120 and &#x3b2;-catenin showed membrane staining in all cases for both antibodies, which was variable in both intensity and the proportion of positive cells.<br><br>CONCLUSION: These results demonstrate that E-cadherin-negative ductal carcinoma is rare, and in these cases p120 and &#x3b2;-catenin maintained their membranous localization, suggesting a functional E-cadherin-membrane complex.}, }
@article {pmid23341385, year = {2013}, author = {Zhou, J and Zhan, W and Chang, C and Zhang, J and Yang, Z and Dong, Y and Zhou, C and Song, Y}, title = {Role of acoustic shear wave velocity measurement in characterization of breast lesions.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {32}, number = {2}, pages = {285-294}, doi = {10.7863/jum.2013.32.2.285}, pmid = {23341385}, issn = {1550-9613}, mesh = {Adipose Tissue/*diagnostic imaging/pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Diseases/*diagnostic imaging/pathology ; Breast Neoplasms/diagnostic imaging/pathology ; Carcinoma/diagnostic imaging/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology ; Diagnosis, Differential ; Elasticity ; *Elasticity Imaging Techniques ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Young Adult ; }, abstract = {OBJECTIVES: To analyze the value of acoustic radiation force impulse imaging quantification in characterization of breast lesions and to analyze the stiffness of glandular and subcutaneous fatty tissue in benign and malignant lesions.<br><br>METHODS: A total of 175 breast lesions (67 malignant and 108 benign) in 173 women were studied. With acoustic radiation force impulse imaging, shear wave velocity (SWV), which can reflect the stiffness of tissue, was measured within the lesion (internal SWV [SWVi]), in the boundary zone (boundary SWV [SWVb]), in normal-appearing glandular tissue (glandular SWV [SWVg]), and in subcutaneous fatty tissue (fatty SWV [SWVf]). All lesions underwent core needle biopsy or surgical excision. Differences among the SWV types in malignant and benign lesions were evaluated. We also assessed how different lesion types affected the SWV types. Receiver operating characteristic analysis was performed to assess the sensitivity and specificity of the SWV types in differentiating malignant from benign lesions.<br><br>RESULTS: Internal SWV was significantly higher than SWVb, SWVg, and SWVf; SWVb was significantly higher than SWVg and SWVf; and SWVg was significantly higher than SWVf in both malignant and benign groups (P < .05). All 4 SWV types were significantly higher in the malignant group than the benign group (P < .05). In the malignant group, grade 3 invasive ductal carcinoma had the highest SWVi. The sensitivity and specificity for differentiating malignant lesions were 55.2% and 95.8% for SWVi, 85.1% and 53.3% for SWVb, 68.2% and 69.6% for SWVg, and 67.2% and 66.0% for SWVf.<br><br>CONCLUSIONS: Acoustic radiation force impulse imaging has potential to characterize breast lesions, both internally and within the boundary zone, and to reflect changes in stiffness within surrounding glandular and subcutaneous fatty tissues caused by malignant tumors.}, }
@article {pmid23340254, year = {2013}, author = {Holloway, KR and Barbieri, A and Malyarchuk, S and Saxena, M and Nedeljkovic-Kurepa, A and Cameron Mehl, M and Wang, A and Gu, X and Pruitt, K}, title = {SIRT1 positively regulates breast cancer associated human aromatase (CYP19A1) expression.}, journal = {Molecular endocrinology (Baltimore, Md.)}, volume = {27}, number = {3}, pages = {480-490}, pmid = {23340254}, issn = {1944-9917}, support = {R01 CA155223/CA/NCI NIH HHS/United States ; CA155223/CA/NCI NIH HHS/United States ; }, mesh = {Aromatase/*genetics/metabolism ; Breast Neoplasms/*enzymology/*genetics ; Carcinoma, Ductal, Breast/enzymology/genetics/pathology ; Cell Line, Tumor ; Female ; *Gene Expression Regulation, Enzymologic ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Promoter Regions, Genetic ; Sirtuin 1/antagonists &amp; inhibitors/*metabolism ; Sirtuin 2/antagonists &amp; inhibitors/metabolism ; }, abstract = {Breast cancer remains one of the leading causes of death in women diagnosed with cancer. In breast cancer, aberrant expression of the CYP19A1 gene, which encodes the aromatase enzyme, contributes to increased intratumoral levels of estradiol. Regardless of whether this estrogen is produced by peripheral tissues or within specific subpopulations of cells within the breast tumor, it is clear that the aromatase enzymatic activity is critical for the growth of estrogen-dependent tumors. Currently, aromatase inhibitors have proven to be highly effective in blocking the growth of estrogen-dependent forms of breast cancer. CYP19A1 transcription is tightly controlled by 10 tissue-specific promoters. In breast cancer, however, aromatase transcription is driven by multiple promoters that somehow override the tissue-specific regulation of normal tissue. Here, we explore the role that the deacetylase, sirtuin-1 (SIRT1), plays in positively regulating aromatase in breast cancer. We demonstrate that the use of cambinol and the SIRT1/2 inhibitor VII, 2 small molecule inhibitors of SIRT1 and SIRT2, as well as small molecule inhibitors and small interfering RNA specific to SIRT1, all reduce the levels of aromatase mRNA. We further demonstrate that pharmacologic inhibition causes a marked reduction in aromatase protein levels. Additionally, by chromatin immunoprecipitation, we demonstrate that SIRT1 occupies the promoter regions PI.3/PII and PI.4, and its inhibition leads to increased acetylation of estrogen-related receptorα, a transcription factor that positively regulates CYP19A1 transcription in epithelial cells. Finally, we demonstrate by immunohistochemistry that SIRT1 is significantly up-regulated in invasive ductal carcinoma relative to normal tissue adjacent to tumor, further suggesting a role of SIRT1 in breast cancer. This work uncovers a new mechanism for the regulation of aromatase and provides rationale for further investigation of how the inhibition of specific sirtuins may provide a unique strategy for inhibiting aromatase that may complement or synergize with existing therapies.}, }
@article {pmid23337025, year = {2013}, author = {Foschini, MP and Morandi, L and Leonardi, E and Flamminio, F and Ishikawa, Y and Masetti, R and Eusebi, V}, title = {Genetic clonal mapping of in situ and invasive ductal carcinoma indicates the field cancerization phenomenon in the breast.}, journal = {Human pathology}, volume = {44}, number = {7}, pages = {1310-1319}, doi = {10.1016/j.humpath.2012.09.022}, pmid = {23337025}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Transformation, Neoplastic/*genetics ; Clone Cells ; Disease Progression ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease/genetics ; Humans ; Middle Aged ; Precancerous Conditions/genetics/pathology ; }, abstract = {Nearly 80% of well-differentiated in situ duct carcinomas (g1 DCIS) have been shown to be multicentric (multilobar) lesions, while most in situ poorly differentiated duct carcinomas (g3 DCIS) were unifocal (unilobar) lesions. Here we present a clonality study of 15 cases of DCIS, all showing multiple foci. Twelve of these cases were associated with an invasive duct carcinoma. Fifteen cases of female breast cancer patients all showing multiple DCIS foci (5 g1 DCIS, 5 g2 DCIS, 5 g3 DCIS) were randomly selected and histologically studied using large histological sections. Care was taken to laser-microdissect DCIS foci that were most distantly located from one another in the same large section, and pertinent cells were genetically studied. Invasive duct carcinoma and ipsilateral lymph node metastases and/or contralateral lesions, whenever present, were additionally microdissected. DNA of neoplastic cells was purified, and the mtDNA D-loop region was sequenced. Genetic distance of different foci from the same case was visualized by phylogenetic analyses using the neighbor-joining method. Patients ranged in age from 36 to 87 years (mean 65.1). All 9 cases of widely spread DCIS were not clonal. Four of 6 cases that showed multiple adjacent foci were clonally related on mtDNA analysis. In the present series, 11/15 DCIS appeared as multiple synchronous primary breast tumors, genetically not related to one another. The present data enhance the view that breast can also show the field cancerization phenomenon, paralleling what has already been proposed in other organs.}, }
@article {pmid23330703, year = {2014}, author = {Morrone, A and Bordignon, V and Barnabas, GA and Dassoni, F and Latini, O and Padovese, V and Ensoli, F and Cristaudo, A}, title = {Clinical-epidemiological features of contact dermatitis in rural and urban communities in northern Ethiopia: correlation with environmental or occupational exposure.}, journal = {International journal of dermatology}, volume = {53}, number = {8}, pages = {975-980}, doi = {10.1111/j.1365-4632.2012.05777.x}, pmid = {23330703}, issn = {1365-4632}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Cobalt/toxicity ; Dermatitis, Allergic Contact/*epidemiology/etiology ; Eczema/chemically induced/epidemiology ; Ethiopia/epidemiology ; Female ; Foot Dermatoses/chemically induced/epidemiology ; Hand Dermatoses/chemically induced/epidemiology ; Head ; Humans ; Male ; Middle Aged ; Neck ; Nickel/toxicity ; Occupational Exposure/*adverse effects ; Patch Tests ; Perfume/toxicity ; Phenylenediamines/toxicity ; Potassium Dichromate/toxicity ; Prevalence ; Resins, Synthetic/toxicity ; Rural Population/*statistics &amp; numerical data ; Torso ; Urban Population/*statistics &amp; numerical data ; Young Adult ; }, abstract = {BACKGROUND: The widespread diffusion of low-quality products as well as the local cultural habits could be a relevant cause of allergic diseases in developing countries. In the present observational study, we explored the prevalence of allergic contact dermatitis in both rural and urban settings in northern Ethiopia, where skin diseases represent a frequent cause of morbidity. Clinical features and specific reactivities in association with environmental or occupational exposure were investigated.<br><br>PATIENTS AND METHODS: We patch tested 480 consecutive patients, visited at the Mekele IDC, exhibiting symptoms of contact dermatitis. A detailed medical history of each patient was collected.<br><br>RESULTS: A positive patch-test response was observed in 50% of subjects; nickel was the most frequent sensitizer (26.2%), followed by p-tert-butylphenol formaldehyde resin (10%), fragrance mix (7.1%), potassium dichromate (5.4%), cobalt chloride (4.6%), disperse blue (2.3%), and p-phenylenediamine (1.7%). Gender-related differences were analyzed for single allergen. Eczema represented the most common manifestation, affecting the head and neck as primary skin areas. While reactivity to nickel interested almost all the occupational categories, sensitization to other allergens could be ascribed to working habits or environmental exposure.<br><br>CONCLUSIONS: The results gathered from this study, the first one conducted within the Tigray region in Ethiopia, confirm the need to take appropriate measures to limit the nickel rate in metal objects and may be useful to design allergenic series suitable for patch testing in those geographical settings.}, }
@article {pmid23330677, year = {2013}, author = {Jablonska, K and Pula, B and Zemla, A and Owczarek, T and Wojnar, A and Rys, J and Ambicka, A and Podhorska-Okolow, M and Ugorski, M and Dziegiel, P}, title = {Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.}, journal = {Journal of pineal research}, volume = {54}, number = {3}, pages = {334-345}, doi = {10.1111/jpi.12032}, pmid = {23330677}, issn = {1600-079X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/chemistry ; Breast Neoplasms/chemistry/genetics/*metabolism ; Carcinoma, Ductal, Breast/chemistry/genetics/*metabolism ; Female ; Fibrocystic Breast Disease/chemistry/genetics/metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Real-Time Polymerase Chain Reaction ; Receptor, Melatonin, MT1/*biosynthesis/genetics ; Statistics, Nonparametric ; }, abstract = {In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC.}, }
@article {pmid23292359, year = {2013}, author = {Kim, Y and Othmer, HG}, title = {A hybrid model of tumor-stromal interactions in breast cancer.}, journal = {Bulletin of mathematical biology}, volume = {75}, number = {8}, pages = {1304-1350}, pmid = {23292359}, issn = {1522-9602}, support = {R01 GM029123/GM/NIGMS NIH HHS/United States ; GM-29123/GM/NIGMS NIH HHS/United States ; }, mesh = {Breast Neoplasms/*etiology/pathology/physiopathology ; Carcinoma, Ductal, Breast/etiology ; Carcinoma, Intraductal, Noninfiltrating/etiology ; Epidermal Growth Factor/physiology ; Female ; Humans ; Mathematical Concepts ; *Models, Biological ; Neoplasm Invasiveness ; Signal Transduction ; Stromal Cells/pathology/physiology ; Transforming Growth Factor beta/physiology ; Tumor Microenvironment ; }, abstract = {Ductal carcinoma in situ (DCIS) is an early stage noninvasive breast cancer that originates in the epithelial lining of the milk ducts, but it can evolve into comedo DCIS and ultimately, into the most common type of breast cancer, invasive ductal carcinoma. Understanding the progression and how to effectively intervene in it presents a major scientific challenge. The extracellular matrix (ECM) surrounding a duct contains several types of cells and several types of growth factors that are known to individually affect tumor growth, but at present the complex biochemical and mechanical interactions of these stromal cells and growth factors with tumor cells is poorly understood. Here we develop a mathematical model that incorporates the cross-talk between stromal and tumor cells, which can predict how perturbations of the local biochemical and mechanical state influence tumor evolution. We focus on the EGF and TGF-β signaling pathways and show how up- or down-regulation of components in these pathways affects cell growth and proliferation. We then study a hybrid model for the interaction of cells with the tumor microenvironment (TME), in which epithelial cells (ECs) are modeled individually while the ECM is treated as a continuum, and show how these interactions affect the early development of tumors. Finally, we incorporate breakdown of the epithelium into the model and predict the early stages of tumor invasion into the stroma. Our results shed light on the interactions between growth factors, mechanical properties of the ECM, and feedback signaling loops between stromal and tumor cells, and suggest how epigenetic changes in transformed cells affect tumor progression.}, }
@article {pmid23286959, year = {2013}, author = {Sakr, RA}, title = {[Does molecular biology play any role in ductal carcinoma in situ?].}, journal = {Gynecologie, obstetrique &amp; fertilite}, volume = {41}, number = {1}, pages = {45-53}, doi = {10.1016/j.gyobfe.2012.11.004}, pmid = {23286959}, issn = {1769-6682}, mesh = {Apoptosis/genetics ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology/therapy ; Cell Cycle Proteins/analysis/genetics ; Female ; Humans ; Ki-67 Antigen/analysis/genetics ; Mastectomy ; Neoplasm Invasiveness/*genetics/pathology ; Prognosis ; Receptor, ErbB-2/analysis/genetics ; Receptors, Steroid/analysis/genetics ; Risk Factors ; }, abstract = {The natural history of ductal carcinoma in situ (DCIS) is not fully elucidated, but it is recognized that DCIS is the true precursor of invasive carcinoma. Studies could show that DCIS is as heterogeneous as invasive ductal carcinoma, yet, they were unable to predict which DCIS will progress to invasion. Several biomarkers were also demonstrated to have a certain prognostic value. However, except for estrogen receptors and HER2, biomarkers are not yet widely used in clinical practice since their predictive value has not proven to be better than the grade and the classical classifying systems of DCIS. Identifying biomarkers for risk of invasiveness in DCIS could be of great value to help high risk patients through the management of their disease and to avoid overtreatment in low risk patients.}, }
@article {pmid23276718, year = {2013}, author = {Kim, YH and Kim, JH and Choi, YW and Lim, SK and Yim, H and Kang, SY and Chung, YS and Lee, GY and Park, TJ}, title = {Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression.}, journal = {Experimental and molecular pathology}, volume = {94}, number = {2}, pages = {360-365}, doi = {10.1016/j.yexmp.2012.12.002}, pmid = {23276718}, issn = {1096-0945}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Proteasome Endopeptidase Complex/genetics/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Up-Regulation ; Young Adult ; }, abstract = {Gankyrin is a subunit of the 26S proteasome, and has been known to degrade p53 and retinoblastoma protein and promote the tumorigenicity and metastasis in some malignancies. However, the role of gankyrin in breast cancer has not been explored. In this study, we investigated the expression of gankyrin in breast cancer and evaluated its effect on breast cancer. Representative cancer tissues including normal breasts from 60 patients with breast cancer were stained immunohistochemically for gankyrin, estrogen receptor, progesterone receptor, and ErbB2. We evaluated the relationship between gankyrin expression and clinicopathologic parameters or prognostic markers. We also attempted to clarify the mechanism of gankyrin involved in breast carcinogenesis by using MCF7 breast cancer cells. Gankyrin was weakly expressed in normal breast epithelial cells, however, tumor regions of 37/60 (61.7%) cases showed an overexpression of gankyrin. Gankyrin overexpression was associated with extensive intraductal carcinoma (p=0.014) and ErbB2 positivity (p=0.031) in invasive ductal carcinoma. In MCF7 breast cancer cells, downregulation of gankyrin was associated with a reduction of cell proliferation and tumorigenicity. In conclusion, gankyrin was identified in normal breasts and overexpressed in invasive breast cancers. The overexpression of gankyrin was associated with extensive intraductal carcinoma and ErbB2 expression in breast cancer.}, }
@article {pmid23274650, year = {2013}, author = {Yu, FD and Yang, SY and Li, YY and Hu, W}, title = {Co-expression network with protein-protein interaction and transcription regulation in malaria parasite Plasmodium falciparum.}, journal = {Gene}, volume = {518}, number = {1}, pages = {7-16}, doi = {10.1016/j.gene.2012.11.092}, pmid = {23274650}, issn = {1879-0038}, mesh = {Algorithms ; *Gene Expression Regulation ; Humans ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/*genetics/growth &amp; development/metabolism/*pathogenicity ; Protozoan Proteins/genetics/*metabolism ; }, abstract = {BACKGROUND: Malaria continues to be one of the most severe global infectious diseases, as a major threat to human health and economic development. Network-based biological analysis is a promising approach to uncover key genes and biological processes from a network viewpoint, which could not be recognized from individual gene-based signatures.<br><br>RESULTS: We integrated gene co-expression profile with protein-protein interaction and transcriptional regulation information to construct a comprehensive gene co-expression network of Plasmodium falciparum. Based on this network, we identified 10 core modules by using ICE (Iterative Clique Enumeration) algorithm, which were essential for malaria parasite development in intraerythrocytic developmental cycle (IDC) stages. In each module, all genes were highly correlated probably due to co-regulation or formation of a protein complex. Some of these genes were recognized to be differentially coexpressed among three close-by IDC stages. The gene of prpf8 (PFD0265w) encoding pre-mRNA processing splicing factor 8 product was identified as DCGs (differentially co-expressed genes) among IDC stages, although this gene function was seldom reported in previous researches. Integrating the species-specific gene prediction and differential co-expression gene detection, we found some modules could perform species-specific functions according to some of genes in these modules were species-specific genes, like the module 10. Furthermore, in order to reveal the underlying mechanisms of the erythrocyte invasion by P. falciparum, Steiner Tree algorithm was employed to identify the invasion subnetwork from our gene co-expression network. The subnetwork-based analysis indicated that some important Plasmodium parasite specific genes could corporate with each other and be co-regulated during the parasite invasion process, which including a head-to-head gene pair of PfRH2a (PF13_0198) and PfRH2b (MAL13P1.176).<br><br>CONCLUSIONS: This study based on gene co-expression network could shed new insights on the mechanisms of pathogenesis, even virulence and P. falciparum development.}, }
@article {pmid23267983, year = {2012}, author = {Hara, Y and Sakurai, K and Enomoto, K and Matsumoto, K and Ueda, Y and Hagiwara, M and Waga, E and Nagashima, S and Tani, M and Amano, S}, title = {[Complete response of advanced breast cancer with lymph node metastases to nab-paclitaxel therapy-report of a case].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {12}, pages = {2080-2082}, pmid = {23267983}, issn = {0385-0684}, mesh = {Albumins/*therapeutic use ; Antineoplastic Agents, Phytogenic/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/secondary ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Paclitaxel/*therapeutic use ; }, abstract = {We report a case of breast cancer with lymph node metastases. A complete response was recognized in response to nab-paclitaxel as a first-line therapy after recurrence. The patient was a 50-year-old woman who had a tumor in her right breast. We palpated a mass with clear boundaries in her right breast. The tumor was 2 cm in diameter. Core-needle biopsy of the breast tumor led to a diagnosis of invasive ductal carcinoma (estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2-negative). She received 4 cycles of EC (E: 90 mg/m2/tri-weekly; C: 600 mg/m2 /tri-weekly) plus 4 cycles of TC(T: 75 mg/m2/tri-weekly; C: 600 mg/m2/tri-weekly)as preoperative adjuvant chemotherapy. After chemotherapy, she underwent quadrantectomy plus axillary lymph node dissection. Six months after the operation, lymph node metastases were observed in her right supraclavicular lymph nodes. She received 8 cycles of nab-paclitaxel(260 mg/m2/tri-weekly) therapy. After 8 cycles of treatment, ultrasonography and computed tomography revealed the disappearance of the metastatic lymph nodes. Therefore, a clinical complete response was observed.}, }
@article {pmid23267982, year = {2012}, author = {Yamauchi, S and Nakagawa, T and Kasahara, M and Sugimoto, H and Ishiba, T and Tamura, N and Nagahara, M and Sato, T and Sugihara, K}, title = {[A case of metastatic breast cancer with bilateral hydronephrosis effectively treated with capecitabine].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {12}, pages = {2077-2079}, pmid = {23267982}, issn = {0385-0684}, mesh = {Adenocarcinoma, Scirrhous/*drug therapy/secondary ; Antimetabolites, Antineoplastic/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Capecitabine ; Deoxycytidine/*analogs &amp; derivatives/therapeutic use ; Female ; Fluorouracil/*analogs &amp; derivatives/therapeutic use ; Humans ; Hydronephrosis/*etiology ; Middle Aged ; Peritoneal Neoplasms/*drug therapy/secondary ; }, abstract = {A 54-year-old female was diagnosed with invasive ductal carcinoma (pT3N1M0, Stage IIIA, estrogen receptor positive [ER (+)], progesterone receptor positive [PgR (+)], human epidermal growth factor receptor type 2 [HER2] score 0) and was treated by preoperative chemotherapy with weekly paclitaxel followed by 5-fluorouracil(5-FU) plus epirubicin plus cyclophosphamide regimen(FEC). Partial mastectomy with axillary dissection was performed. The pathological examination disclosed that the tumor was scirrhous carcinoma, and a pathological partial response was achieved by chemotherapy. Multiple bone metastases were detected 18 months after the surgery during treatment with letrozole as adjuvant therapy. Retroperitoneal metastases with hydronephrosis and a lung metastasis were detected 28 months after the surgery, even though exemestane and zoledronate were administrated after detection of the bone metastases. Chemotherapy with capecitabine was started and she recovered from hydronephrosis 4 months after the start of treatment. After 32 months from the first treatment with capecitabine, the patient is presently alive without hydronephrosis due to continued chemotherapy.}, }
@article {pmid23267981, year = {2012}, author = {Yoshitomi, S and Tsuji, H}, title = {[A case of recurrent breast cancer with solitary adrenal metastasis treated with surgery and endocrine therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {12}, pages = {2074-2076}, pmid = {23267981}, issn = {0385-0684}, mesh = {Adrenal Gland Neoplasms/*drug therapy/secondary/surgery ; Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/surgery ; Female ; Humans ; Middle Aged ; Recurrence ; Toremifene/*therapeutic use ; }, abstract = {We present a case in which a 46-year-old woman underwent mastectomy (Bt+AX) for right breast cancer (T4bN0M0, Stage IIIB) at the age of 42. A histopathological examination confirmed her cancer to be an invasive ductal carcinoma n (-),ER (+), PgR (+),HER 2 (1+). For postoperative medication therapy, she was taking goserelin plus tamoxifen for 2 years and tamoxifen thereafter. A right adrenal tumor was discovered during a follow-up CT scan and MRI after the operation. There was no indication of metastasis in any other location. A laparoscopic right adrenalectomy was performed to establish a definitive diagnosis and to cure the cancer. According to the histopathological examination, the tumor was ER (+), PgR (+), and HER2 (0) and metastasized from the breast. After this operation, the regimen was changed to high- dose toremifene as endocrine therapy. No recurrence of the cancer has been reported 2 years and 4 months after the operation. In most cases, metastasis to the adrenal gland is due to systemic metastasis as seen in the last stage of breast cancer, and a solitary adrenal gland metastasis from breast cancer is extremely rare. The combination of surgical removal and medication for solitary distant metastasis from breast cancer may be effective in improving the long-term survival rate.}, }
@article {pmid23267979, year = {2012}, author = {Ueda, H and Nakagawa, T and Sato, T and Nagahara, M and Sugihara, K}, title = {[A case of breast cancer liver metastases with jaundice responding to trastuzumab monotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {12}, pages = {2068-2070}, pmid = {23267979}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Female ; Humans ; Jaundice/*etiology ; Liver Neoplasms/complications/*drug therapy ; Middle Aged ; Neoplasm Staging ; Trastuzumab ; }, abstract = {We report the case of a 60-year-old female with liver dysfunction resulting from diffuse liver metastases, which, atypically, had originated from breast cancer. She responded remarkably well to trastuzumab monotherapy. She was referred to our hospital because of left breast cancer with multiple general lymphadenopathies. She presented with jaundice and liver dysfunction without a space-occupying lesion or a dilatation of the intrahepatic bile duct on computed tomography images. A liver biopsy was done to rule out autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis, and histopathological examination showed adenocarcinoma in the lymph duct of the liver. Both the primary breast cancer and the liver metastases were negative for hormone receptor expression(ER-, PR-), but overexpressed HER2(HercepTest 3+). She was diagnosed as invasive ductal carcinoma(T1N3cM1, Stage IV). We started trastuzumab monotherapy, which improved her jaundice and liver dysfunction, and resulted in a decrease in lymph node size.}, }
@article {pmid23267972, year = {2012}, author = {Sakurai, K and Fujisaki, S and Maeda, T and Nagashima, S and Hara, Y and Tomita, R and Suzuki, S and Waga, E and Enomoto, K and Amano, S}, title = {[The problems of breast-conserving surgery for calcification undetected by ultrasonography].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {12}, pages = {2048-2050}, pmid = {23267972}, issn = {0385-0684}, mesh = {Breast Neoplasms/complications/diagnostic imaging/*pathology/surgery ; Calcinosis/etiology/*surgery ; Carcinoma, Ductal, Breast/complications/diagnostic imaging/*pathology/surgery ; Female ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Sentinel Lymph Node Biopsy ; Ultrasonography ; }, abstract = {The patient was a 58-year-old woman. Mammography showed grouped heterogeneous calcifications in the M area of the right breast. The area of the grouped heterogeneous calcifications was 1 cm in diameter. A vacuum-assisted biopsy (VAB) of the area led to a diagnosis of invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and negative for human epidermal growth factor receptor type 2/neu protein expression. A micro mark was made by VAB enforcement in the lesion. At operation, we performed ultrasonography to detect the cancer lesion, but we could not detect the micro mark. It was difficult to determine the resection area. We detected architectural distortion after VAB and determined the resection area. Breast-conserving surgery and a sentinel lymph node biopsy was performed. Histopathologically, the surgical margins were negative and the sentinel lymph node was negative for cancer. This case suggested that it was necessary to make a new micro mark.}, }
@article {pmid23267971, year = {2012}, author = {Hirano, T and Sakurai, K and Fujisaki, S and Maeda, T and Nagashima, S and Hara, Y and Tomita, R and Suzuki, S and Enomoto, K and Amano, S}, title = {[Lapatinib is useful for metastatic breast cancer patients who cannot be treated with trastuzumab-report of a case].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {12}, pages = {2045-2047}, pmid = {23267971}, issn = {0385-0684}, mesh = {Aged ; Antibodies, Monoclonal, Humanized/adverse effects ; Antineoplastic Agents/*therapeutic use ; Biopsy, Needle ; Breast Neoplasms/*drug therapy/pathology/surgery ; Combined Modality Therapy ; Female ; Humans ; Lapatinib ; Liver Neoplasms/*drug therapy/secondary ; Mastectomy ; Neoplasm Staging ; Quinazolines/*therapeutic use ; Trastuzumab ; }, abstract = {The patient was a 71-year-old woman. Mammography revealed an irregularly shaped mass in the U area of her left breast. Ultrasonography revealed an irregularly shaped mass in the C area of her breast. The mass was 22 mm in diameter. Core-needle biopsy of the area led to a diagnosis of invasive ductal carcinoma. The lesion was negative for estrogen receptor and progesterone receptor expression and positive for human epidermal growth factor receptor 2 protein expression. Distant metastasis was not detected. Muscle-preserving mastectomy and lymph node dissection were performed. Eight months after the operation, multiple liver metastases were found. We attempted to treat these metastases with trastuzumab. However, an infusion reaction was recognized. Therefore, we attempted treatment with lapatinib and capecitabine. This treatment was administered for 2 months without incident. After 2 months, hand-foot syndrome was recognized. Then, we attempted treatment with lapatinib alone. Lapatinib alone was effective against the multiple liver metastases. The patient's condition has remained stable for 1 year after treatment.}, }
@article {pmid23250736, year = {2013}, author = {Pinto, AE and Pereira, T and Santos, M and Branco, M and Dias, A and Silva, GL and Ferreira, MC and André, S}, title = {DNA ploidy is an independent predictor of survival in breast invasive ductal carcinoma: a long-term multivariate analysis of 393 patients.}, journal = {Annals of surgical oncology}, volume = {20}, number = {5}, pages = {1530-1537}, doi = {10.1245/s10434-012-2804-6}, pmid = {23250736}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Aneuploidy ; Breast Neoplasms/*genetics/secondary/surgery ; Carcinoma, Ductal, Breast/*genetics/*pathology/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Proportional Hazards Models ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *S Phase ; Time Factors ; Young Adult ; }, abstract = {PURPOSE: To evaluate "classic" prognostic parameters, as well as DNA ploidy and S-phase fraction (SPF), in relation to disease-free (DFS) and disease-specific (DSS) survival in breast invasive ductal carcinoma (IDC) with long-term follow-up study.<br><br>METHODS: The study involved 393 patients with IDC and median follow-up of 134 months (50-240). Histological grading, tumor size, axillary nodal involvement, pathological staging and hormone receptor status were considered as established prognostic markers. Ploidy and SPF were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables.<br><br>RESULTS: There were 105 (26.7 %) deaths and 140 (35.6 %) disease recurrences during follow-up. Two hundred thirty-one (58.8 %) tumors were aneuploid. High SPF and aneuploidy were associated with tumors with higher grade of differentiation, greater size and negative hormone receptors. Higher SPF and advanced disease stage are correlated. In univariate analysis, all the clinicopathological and cytometric features, including patients <40 years and a subgroup presenting hypertetraploid/multiploid tumors, are significantly correlated with clinical outcome, apart from SPF and estrogen receptors for DFS. In multivariate analysis, nodal involvement, DNA aneuploidy and lack of progesterone receptors (for DSS) retained statistically significant association with shorter survival. In node-negative patients, ploidy (for DFS) and estrogen receptors (for DSS) significantly predicted survival. In both subgroups of node-positive patients and those (n = 195) with intermediate differentiation tumors (G2), aneuploidy was an indicator of worse prognosis.<br><br>CONCLUSIONS: Along with nodal status and hormone receptor expression, DNA ploidy is an independent predictor of long-term survival in IDC.}, }
@article {pmid23240012, year = {2012}, author = {Casanova, V and Naval-Macabuhay, I and Massanella, M and Rodríguez-García, M and Blanco, J and Gatell, JM and García, F and Gallart, T and Lluis, C and Mallol, J and Franco, R and Climent, N and McCormick, PJ}, title = {Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals.}, journal = {PloS one}, volume = {7}, number = {12}, pages = {e51287}, pmid = {23240012}, issn = {1932-6203}, mesh = {*Adenosine Deaminase/immunology/metabolism ; Adult ; Aged ; CD4-Positive T-Lymphocytes/cytology/immunology/metabolism ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Differentiation/immunology ; Cell Proliferation ; Cells, Cultured ; Cytokines/immunology/metabolism ; *Dendritic Cells/cytology/immunology/metabolism ; Female ; *HIV Infections/immunology/metabolism/virology ; HIV-1/immunology/metabolism ; Humans ; *Immunity ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; Receptors, Purinergic P1/immunology/metabolism ; }, abstract = {ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of ADA are implicated in the enhancement of CD80, CD83, CD86, CD40 and CCR7 expression on immature dendritic cells from healthy and HIV-infected individuals. These ADA-mediated increases in CD83 and costimulatory molecule expression is concomitant to an enhanced IL-12, IL-6, TNF-α, CXCL8(IL-8), CCL3(MIP1-α), CCL4(MIP-1β) and CCL5(RANTES) cytokine/chemokine secretion both in healthy and HIV-infected individuals and to an altered apoptotic death in cells from HIV-infected individuals. Consistently, ADA-mediated actions on iDCs are able to enhance allogeneic CD4 and CD8-T-cell proliferation, globally yielding increased iDC immunogenicity. Taken together, these findings suggest that ADA would promote enhanced and correctly polarized T-cell responses in strategies targeting asymptomatic HIV-infected individuals.}, }
@article {pmid23232912, year = {2013}, author = {Chakraborty, A and Mukhopadhyay, A and Bhattacharyya, D and Bose, CK and Choudhuri, K and Mukhopadhyay, S and Basak, J}, title = {Frequency of 5382insC mutation of BRCA1 gene among breast cancer patients: an experience from Eastern India.}, journal = {Familial cancer}, volume = {12}, number = {3}, pages = {489-495}, pmid = {23232912}, issn = {1573-7292}, mesh = {Adult ; BRCA1 Protein/*genetics ; Breast Neoplasms/*congenital/epidemiology/genetics/pathology ; Carcinoma, Ductal, Breast/epidemiology/genetics/pathology ; Carcinoma, Lobular/epidemiology/genetics/pathology ; Case-Control Studies ; DNA Mutational Analysis ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; India/epidemiology ; Middle Aged ; Mutation/*genetics ; Neoplasm Grading ; Neoplasm Invasiveness ; Ovarian Neoplasms/genetics/pathology ; Polymerase Chain Reaction ; Prognosis ; Young Adult ; }, abstract = {The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in females pushing the cervical cancer to the second position. The mutations in two breast cancer susceptibility genes, BRCA1 and BRCA2, are frequently associated with familial breast cancer. The main objective of the study was to determine the frequency of the mutation 5382insC in BRCA1 of eastern Indian breast cancer patients and also study the hormonal receptor status and histopathology of the patients. Altogether 92 patients affected with breast cancer were included in this study. ARMS-PCR based amplification was used to detect the presence of mutation. The mutations were considered only after pedigree analysis. Out of 92 patients (age range: 20-77 years) with family history (57 individuals) and without family history (35 individuals) were screened. Fifty controls have been systematically investigated. Seven patients and two family members were found to be carriers of 5382insC mutation in BRCA1 gene. We have found 42.64 % ER(-)/PR(-) cancer and 20.58 % triple negative cancer. Invasive ductal carcinoma is the most common histology among the investigated individuals. The presented data confirm a noticeable contribution of BRCA1 5382insC mutation in BC development in Eastern India, which may justify an extended BRCA1 5382insC testing within this patient population. We found HER-2/neu negativity and BRCA1 positivity associated with familial breast cancer. From the hospital's patient history, it was revealed that the age of menarche plays an important role in development of breast cancer.}, }
@article {pmid23222490, year = {2013}, author = {Lu, S and Singh, K and Mangray, S and Tavares, R and Noble, L and Resnick, MB and Yakirevich, E}, title = {Claudin expression in high-grade invasive ductal carcinoma of the breast: correlation with the molecular subtype.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {26}, number = {4}, pages = {485-495}, pmid = {23222490}, issn = {1530-0285}, support = {P20 GM103421/GM/NIGMS NIH HHS/United States ; P20GM103421/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Claudins/analysis/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Prognosis ; Proportional Hazards Models ; Tissue Array Analysis ; }, abstract = {Claudin proteins are a major component of the tight junctions. Dysregulation of claudin protein expression has been described in a number of malignancies. Gene expression profiling has stratified breast cancers into distinct molecular subtypes: luminal, HER2 positive (HER2+), and basal-like. Recently, a novel claudin-low molecular subtype has been described. In this study, we correlated the expression patterns of claudins with the molecular subtypes of breast cancer. On the basis of immunohistochemical expression, 226 grade 3 invasive ductal carcinomas were stratified into 65 luminal (estrogen receptor positive (ER+)), 65 HER2+, 86 basal-like, including 14 metaplastic carcinomas (ER-, HER2-, CK5/6, and/or epidermal growth factor receptor positive), and 10 unclassified. Tissue microarrays were analyzed for the expression of claudins 1, 3, 4, 7, and 8 by immunohistochemistry and scored semiquantitatively. High levels of expression were detected in 17% of all cases for claudin 1, 32% claudin 3, 41% claudin 4, 44% claudin 7, and 40% claudin 8. Luminal cancers exhibited increased claudins 7 and 8; basal-like tumors demonstrated increased expression of claudins 1 and 4. Low expression of all five claudins was detected in 30 of 226 cases (13%) and this group was designated 'claudin-low'. The majority of the claudin-low subgroup were basal-like cancers (23 of 30, 77%). In contrast, only 1 of 30 (3%) claudin-low tumors was of the luminal phenotype and 6 of 30 cases (20%) were HER2+ (P<0.001). Within the basal-like subgroup, 64% of the metaplastic and 19% of the non-metaplastic tumors were claudin-low. The claudin-low group was strongly associated with disease recurrence (P=0.0093). In conclusion, this study is the first to examine comprehensively the differential expression of claudins 1, 3, 4, 7, and 8 in the molecular subtypes of high-grade breast cancer. Claudin-low subtype is a frequent phenomenon in metaplastic and basal-like breast cancer and appears to be a strong predictor of disease recurrence.}, }
@article {pmid23188440, year = {2012}, author = {Pătrană, N and Georgescu, CV and Fota, GL and Enache, DE and Pirici, E}, title = {Invasive mammary carcinoma: assessment of HER-2/neu status by immunohistochemistry.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {53}, number = {3 Suppl}, pages = {781-787}, pmid = {23188440}, issn = {2066-8279}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*enzymology/*immunology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; }, abstract = {HER-2/neu oncoprotein overexpression in breast cancer patients has an impact on prognosis and treatment methods so assessment of its status is therefore much needed. The study group consisted of 90 cases of mammary invasive carcinoma. The distribution of HER-2/neu immunoexpression for scores 0, 1+, 2+ and 3+ were 54.44%, 11.11%, 18.8% and 15.56% respectively. HER-2/neu -positive cases comprised 21.42% of patients less than 50-year-old compared to 14.47% of patients of 50-year-old or older. Tumor size was negative correlated with HER-2/neu immunoexpression: positive tumors comprised 37.5% of tumor larger than 5 cm and this percentage decreases with tumor dimension to 2.94% in tumors of 2 cm or less. Regarding the histopathological subtype of invasive mammary carcinoma, only some types were positive, like 17.57% of IDC NOS and one case of mixed ductal-lobular invasive carcinoma. The highest proportion (21.31%) of positive HER-2/neu cases presented high-grade carcinomas (GIII), comparing with well-differentiated (GI) that were all negative. Regarding the axillary lymph node status the lowest proportion of positive HER-2/neu cases was 4.54% in the absence of metastasis, and rises to 34.78% in cases with more than three axillary lymph nodes involved. HER-2/neu-positive tumors showed a low incidence of ER+ or PR+ cases unlike HER-2/neu -negative cases (35.71% vs. 83.05% for ER, respective 21.42% vs. 76.27% for PR). Therefore, in conclusion, HER-2/neu-positive tumors are significantly fewer than the negative ones, but these are found in younger women and are associated with: large tumor size, high grade of malignancy (GIII) and increased number of axillary lymph node involvement. HER-2/neu immunoexpression is related to histological subtype of invasive breast carcinomas. Hormonal status is negative related to HER-2/neu expression.}, }
@article {pmid23197249, year = {2013}, author = {Petrelli, F and Borgonovo, K and Lonati, V and Elia, S and Barni, S}, title = {Regression of liver metastases after treatment with intraperitoneal catumaxomab for malignant ascites due to breast cancer.}, journal = {Targeted oncology}, volume = {8}, number = {4}, pages = {291-294}, pmid = {23197249}, issn = {1776-260X}, mesh = {Aged ; Antibodies, Bispecific/*administration &amp; dosage ; Ascites/*drug therapy/pathology ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology/secondary ; Female ; Humans ; Injections, Intraperitoneal ; Liver Neoplasms/*drug therapy/*secondary ; Treatment Outcome ; }, abstract = {Malignant ascites is quite rare in breast cancer and is mainly associated with a lobular histology. To date, no studies have evaluated locoregional therapy for malignant ascites in breast cancer. The anti-epithelial cell adhesion molecule (EpCAM), trifunctional antibody catumaxomab was approved in the European Union for the intraperitoneal (i.p.) treatment of malignant ascites in patients with EpCAM-positive carcinomas where standard therapy is not available or no longer feasible. We report the case of a 69-year-old female with pretreated breast cancer who received i.p. catumaxomab for the treatment of malignant ascites and showed a regression of liver metastases. The patient originally underwent a left mastectomy and ipsilateral axillary lymph node dissection for an invasive ductal carcinoma in 1995. Following several lines of treatment, she was enrolled in February 2010 in a phase IIIb study (CASIMAS) investigating the safety of a 3-h i.p. catumaxomab infusion. In addition to a local benefit, as shown by an improvement in malignant ascites and a prolongation of the paracentesis-free interval with i.p. catumaxomab, a computed tomography scan, performed some weeks after catumaxomab administration, showed a regression of liver metastases. In addition to a locoregional effect on EpCAM-positive disease, i.p. catumaxomab may also show systemic effects. The use of i.p. catumaxomab for the treatment of malignant ascites due to breast cancer should be explored further in appropriate clinical studies and its possible systemic effects should also be further investigated.}, }
@article {pmid23183846, year = {2012}, author = {Glenn, WK and Heng, B and Delprado, W and Iacopetta, B and Whitaker, NJ and Lawson, JS}, title = {Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e48788}, pmid = {23183846}, issn = {1932-6203}, mesh = {Aged ; Animals ; Base Sequence ; Breast Neoplasms/pathology/*virology ; Carcinoma, Intraductal, Noninfiltrating/pathology/virology ; Case-Control Studies ; Cell Nucleus/virology ; DNA, Neoplasm/genetics ; Epstein-Barr Virus Nuclear Antigens/metabolism ; Female ; Genome, Viral/genetics ; Herpesvirus 4, Human/*genetics ; Humans ; Lipopolysaccharide Receptors/metabolism ; Mammary Tumor Virus, Mouse/*genetics ; Mice ; Middle Aged ; Molecular Sequence Data ; Neoplasm Grading ; Neoplasm Invasiveness ; Papillomaviridae/*genetics ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; Viral Matrix Proteins/metabolism ; }, abstract = {BACKGROUND: The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers.<br><br>MATERIALS AND METHODS: All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc).<br><br>RESULTS: EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples.<br><br>CONCLUSIONS: We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.}, }
@article {pmid23181716, year = {2012}, author = {Kostianets, O and Antoniuk, S and Filonenko, V and Kiyamova, R}, title = {Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {161}, pmid = {23181716}, issn = {1746-1596}, mesh = {Acid Anhydride Hydrolases ; Adult ; Aged ; Antigens, Neoplasm/analysis ; Autoantigens/*analysis ; Biomarkers, Tumor/*analysis ; Blood Proteins/analysis ; Breast Neoplasms/classification/*immunology/pathology ; Carcinoma, Ductal, Breast/classification/*immunology/pathology ; Carcinoma, Lobular/classification/*immunology/pathology ; Carcinoma, Medullary/classification/*immunology/pathology ; Carrier Proteins/analysis ; DNA Repair Enzymes/analysis ; DNA-Binding Proteins/analysis ; Female ; Fibrocystic Breast Disease/immunology/pathology ; Glycoproteins/analysis ; Humans ; *Immunohistochemistry ; Middle Aged ; Nuclear Proteins/analysis ; Pilot Projects ; Poly(A)-Binding Proteins/analysis ; RNA-Binding Proteins ; }, abstract = {BACKGROUND: On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer.<br><br>METHODS: Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five) was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples.<br><br>RESULTS: All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors.<br><br>CONCLUSIONS: This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy.<br><br>VIRTUAL SLIDES: The virtual slides' for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892.}, }
@article {pmid23175652, year = {2013}, author = {Remus, DM and Bongers, RS and Meijerink, M and Fusetti, F and Poolman, B and de Vos, P and Wells, JM and Kleerebezem, M and Bron, PA}, title = {Impact of Lactobacillus plantarum sortase on target protein sorting, gastrointestinal persistence, and host immune response modulation.}, journal = {Journal of bacteriology}, volume = {195}, number = {3}, pages = {502-509}, pmid = {23175652}, issn = {1098-5530}, mesh = {Aminoacyltransferases/genetics/*metabolism ; Animals ; Bacterial Proteins/genetics/*metabolism ; Cysteine Endopeptidases/genetics/*metabolism ; Dendritic Cells/immunology ; Gastrointestinal Tract/immunology/*microbiology ; Gene Deletion ; Gene Expression Regulation, Bacterial/*physiology ; Gene Expression Regulation, Enzymologic/physiology ; Humans ; Lactobacillus plantarum/*enzymology/genetics/immunology ; Membrane Proteins ; Mice ; Protein Transport/*physiology ; Transcriptome ; }, abstract = {Sortases are transpeptidases that couple surface proteins to the peptidoglycan of Gram-positive bacteria, and several sortase-dependent proteins (SDPs) have been demonstrated to be crucial for the interactions of pathogenic and nonpathogenic bacteria with their hosts. Here, we studied the role of sortase A (SrtA) in Lactobacillus plantarum WCFS1, a model Lactobacillus for probiotic organisms. An isogenic srtA deletion derivative was constructed which did not show residual SrtA activity. DNA microarray-based transcriptome analysis revealed that the srtA deletion had only minor impact on the full-genome transcriptome of L. plantarum, while the expression of SDP-encoding genes remained completely unaffected. Mass spectrometry analysis of the bacterial cell surface proteome, which was assessed by trypsinization of intact bacterial cells and by LiCl protein extraction, revealed that SrtA is required for the appropriate subcellular location of specific SDPs and for their covalent coupling to the cell envelope, respectively. We further found that SrtA deficiency did not affect the persistence and/or survival of L. plantarum in the gastrointestinal tract of mice. In addition, an in vitro immature dendritic cell (iDC) assay revealed that the removal of surface proteins by LiCl strongly affected the proinflammatory signaling properties of the SrtA-deficient strain but not of the wild type, which suggests a role of SDPs in host immune response modulation.}, }
@article {pmid23167359, year = {2012}, author = {Ch'ng, ES and Tuan Sharif, SE and Jaafar, H}, title = {Characteristics of invasive breast ductal carcinoma, NOS, diagnosed in a tertiary institution in the East Coast of Malaysia with a focus on tumor angiogenesis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {9}, pages = {4445-4452}, doi = {10.7314/apjcp.2012.13.9.4445}, pmid = {23167359}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Antigens, CD34/metabolism ; Breast Neoplasms/*blood supply/metabolism/*pathology ; Carcinoma, Ductal, Breast/*blood supply/metabolism/*secondary ; Chi-Square Distribution ; Cross-Sectional Studies ; Female ; Humans ; Lymphatic Metastasis ; Malaysia ; Microvessels/metabolism/*pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors.<br><br>METHODS: Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density.<br><br>RESULTS: At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05).<br><br>CONCLUSIONS: Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.}, }
@article {pmid23167341, year = {2012}, author = {Harhra, NA and Basaleem, HO}, title = {Trends of breast cancer and its management in the last twenty years in Aden and adjacent governorates, Yemen.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {9}, pages = {4347-4351}, doi = {10.7314/apjcp.2012.13.8.4247}, pmid = {23167341}, issn = {2476-762X}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/pathology/surgery ; Breast Neoplasms, Male/*epidemiology/pathology/surgery ; Carcinoma in Situ/*epidemiology/pathology/surgery ; Carcinoma, Ductal, Breast/*epidemiology/pathology/surgery ; Carcinoma, Lobular/*epidemiology/pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; Male ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Yemen/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the most common cancer of women and the principal cause of death in middle aged women. The objective of this study was to describe the trend of breast cancer and its management in Aden and adjacent south-eastern governorates of Yemen during the last 20 years.<br><br>PATIENTS AND METHODS: This is a retrospective analysis of previous studies on patients with breast cancer in Aden and adjacent south-eastern governorates, Yemen (January 1989 through December 2007). The studied variables were: sex, age, time and type of presentation, disease stage, pathological types and the performed surgical treatment. The sources of information were the treatment registry of Aden health office, archives of Al-Gamhouria teaching hospital; major referral and other public and private hospitals in Aden and Aden Cancer Registry.<br><br>RESULTS: The total number of patients was 476, 99% being females. The age range was 19-88 years. The most affected age was 30-50 years (60.5%), 95% presenting after one month of having breast symptoms. Forty-five percent presented with signs of advanced local disease, while 59.2% had palpable axillary lymph nodes on presentation. Early breast cancer (stages I-II) occurred in 47%, and late breast cancer (stages III-IV) in 51.5%. Invasive ductal carcinoma was the commonest pathology (89.3%). The main surgical treatment was mastectomy (modified radical mastectomy (50%).<br><br>CONCLUSION: Breast cancer is predominantly a disease of young with late presentation and advanced disease. Improving health awareness and earlier diagnosis of the disease by health education, encouraging breast self-examination, and providing the mammography equipment and mammary clinics in hospitals are recommended. Establishment of oncology and radiotherapy centers in Aden is a necessity.}, }
@article {pmid23160758, year = {2013}, author = {Apostolidis, A and Thompson, C and Yan, X and Mourad, S}, title = {An exploratory, placebo-controlled, dose-response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity.}, journal = {World journal of urology}, volume = {31}, number = {6}, pages = {1469-1474}, pmid = {23160758}, issn = {1433-8726}, mesh = {Adult ; Aged ; Aged, 80 and over ; Botulinum Toxins, Type A/adverse effects/pharmacology/*therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Spinal Cord Injuries/*complications ; Treatment Outcome ; Urinary Bladder, Neurogenic/*complications ; Urinary Bladder, Overactive/*complications ; Urinary Incontinence/*drug therapy/*etiology/physiopathology ; Urodynamics/drug effects/physiology ; }, abstract = {PURPOSE: To explore the dose response to onabotulinumtoxinA 50, 100, and 200 U in patients with spinal cord injury (SCI) with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).<br><br>METHODS: Patients (N&#xa0;=&#xa0;73) with SCI (level T1 or lower) with NDO and UI (&#x2265;14&#xa0;UI episodes/week) received 30 intradetrusor injections of onabotulinumtoxinA (50&#xa0;U [n&#xa0;=&#xa0;19], 100&#xa0;U [n&#xa0;=&#xa0;21], or 200&#xa0;U [n&#xa0;=&#xa0;17]) or placebo (n&#xa0;=&#xa0;16) via cystoscopy, avoiding the trigone. Changes from baseline in UI episodes/week, volume voided/micturition, maximum cystometric capacity, and maximum detrusor pressure (MDP) during first involuntary detrusor contraction (IDC) were evaluated. Adverse events (AEs) were assessed.<br><br>RESULTS: A significant linear dose response for UI episodes/week was identified at weeks 18, 30, 36, 42, and 54 (P&#xa0;<&#xa0;0.05) with a similar trend (P&#xa0;=&#xa0;0.092) at week 6 (primary time point). A significant linear dose response was observed in volume/void at all post-treatment time points up to week 54 (P&#xa0;<&#xa0;0.05) and in MDP during first IDC at week 6 (P&#xa0;=&#xa0;0.034). The proportion of patients who achieved continence at week 6 was highest in the 200&#xa0;U group. Duration of effect was longest with the 200&#xa0;U dose, compared with other treatment groups. The AEs were comparable across groups; urinary tract infection was the most common AE across all treatment groups.<br><br>CONCLUSIONS: In this exploratory dose-response study of SCI patients with UI due to NDO, onabotulinumtoxinA 200&#xa0;U was the most effective dose. The AE profile was comparable across all groups.}, }
@article {pmid23158999, year = {2012}, author = {Yang, YF and Liu, J and Fang, ZY and Gu, L}, title = {[Clinical features and prognosis of 25 cases of breast carcinosarcoma].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {34}, number = {8}, pages = {620-623}, doi = {10.3760/cma.j.issn.0253-3766.2012.08.014}, pmid = {23158999}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/*therapy ; Carcinosarcoma/metabolism/*pathology/*therapy ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/secondary ; Mastectomy/methods ; Middle Aged ; Neoplasm Recurrence, Local ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Tumor Burden ; }, abstract = {OBJECTIVE: To improve the recognition, appropriate diagnosis and treatment of breast carcinosarcoma through analysis of their clinical features, diagnosis, management and prognosis.<br><br>METHODS: The clinicopathological data from 25 patients with breast carcinosarcoma treated in our hospital between January 1976 and January 2008 were retrospectively reviewed. The correlation between prognosis and age, tumor size, axillary node status, and treatment modality was analyzed using the statistical software SPSS 13.0. The survival rate was calculated by Kaplan-Meier analysis and compared using log-rank test. Univariate and multivariate factors for survival were analyzed using Cox proportional hazards regression model.<br><br>RESULTS: All patients were female and their median age was 56-years. The median tumor diameter was 5.1 cm. The misdiagnosis rate was high by mammography, B-ultrasound and pathological examination of needle aspiration biopsy before operation. So that the diagnosis primarily depended on postoperative histopathologic examination. The ER/PR and HER-2 positive rate of the breast carcinosarcomas was 8.3% and 7.7%, respectively. Invasive ductal carcinoma was the main malignant component accounting for 92.3%, while the sarcoma element was constitutive of fibrosarcoma with a proportion of 46.2%. The overall 5-year survival rate was 57.9% with a median survival time of 86 months after a median follow-up of 52 months. Univariate factor analysis showed that the tumor size (P = 0.012) and treatment methods (P = 0.028) were impact factors, while age and axillary lymph node status were not significantly related with prognosis. Cox multivariate analysis validated that the therapy modality was an independent prognostic factor for breast carcinosarcoma (P = 0.047).<br><br>CONCLUSIONS: Breast carcinosarcoma is rare and its clinical features are not specific, so that its final diagnosis is mainly based on the postoperative pathology. Tumor size and treatment modality are independent prognostic factors, so the comprehensive therapy mainly based on radical resection is the best treatment modality. The positive expression of ER/PR and HER-2 in breast carcinosarcoma is low, while exploring new target is one of future research directions.}, }
@article {pmid23157907, year = {2012}, author = {Sheng, WW and Zhou, JP and Kong, FM and Li, YJ and Dong, M}, title = {[Clinicopathological significance of the expression of carbonic anhydrase II in human pancreatic invasive ductal cancer].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {50}, number = {8}, pages = {728-731}, pmid = {23157907}, issn = {0529-5815}, mesh = {Carbonic Anhydrase II/genetics/*metabolism ; Carcinoma, Pancreatic Ductal/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Pancreas/metabolism ; Pancreatic Neoplasms/metabolism/pathology ; RNA, Messenger/genetics ; }, abstract = {OBJECTIVE: To study the clinicopathological significance of the expression of carbonic anhydrase (CA)II protein and mRNA in primary invasive ductal cancer (IDC) of human pancreas.<br><br>METHODS: The expression of CAII protein in 33 paired paraffin embedded IDC specimens of the pancreas and paired adjacent non-cancerous pancreatic tissues was detected by immunohistochemistry. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to examine the expression of CAII protein and mRNA level in 12 paired fresh IDC specimens of the pancreas and adjuvant non-cancerous pancreatic tissues. The relationship between the protein expression and clinicopathological features was analyzed.<br><br>RESULTS: Overexpression of CAII protein was shown in 11 cases of pancreatic IDC tissues (33.3%, 11/33), which was much lower than that in paired non-cancerous pancreatic tissues (72.7%, t = 6.275, P = 0.000). The expression of CAII protein had no correlation with tumor position (&#x3c7;&#xb2; = 0.992, P = 0.319), differentiation (&#x3c7;&#xb2; = 0.866, P = 0.352), TNM stage (&#x3c7;&#xb2; = 1.210, P = 0.271) and Lymph node metastasis (&#x3c7;&#xb2; = 0.798, P = 0.372), but had bordering statistic sig with the prognosis of the patients (&#x3c7;&#xb2; = 3.233, P = 0.072). The median survival time in the patients with high expression of CAII protein was 540 days, while that in the patients with low expression was 320 days. The expression of CAII protein and mRNA was lower in IDC than that in paired non-cancerous pancreatic tissues detected by Western blot and RT-PCR respectively (t = 3.399, P = 0.006; t = 2.281, P = 0.043).<br><br>CONCLUSION: CAII is down regulated in pancreatic IDC and might be relative with the prognosis.}, }
@article {pmid23155282, year = {2012}, author = {Watrowski, R and Striepecke, E and Jäger, C and Bauknecht, T and Horst, C}, title = {Papillary-serous adenocarcinoma of the uterine cervix during tamoxifen therapy after bilateral breast cancer.}, journal = {Anticancer research}, volume = {32}, number = {11}, pages = {5075-5078}, pmid = {23155282}, issn = {1791-7530}, mesh = {Adenocarcinoma, Papillary/*complications/*drug therapy/metabolism/surgery ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*complications/*drug therapy ; Carcinoma, Ductal, Breast/drug therapy ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Second Primary/metabolism/*pathology/surgery ; Selective Estrogen Receptor Modulators/*therapeutic use ; Tamoxifen/*therapeutic use ; Uterine Cervical Neoplasms/*complications/metabolism/surgery ; }, abstract = {BACKGROUND: Papillary-serous adenocarcinoma (PSCC) is a very rare subtype of cervical cancer. To our knowledge, this is the first report on PSCC of the uterine cervix following bilateral breast cancer.<br><br>CASE REPORT: A 61-year-old Caucasian woman underwent conserving surgery of both breasts at the age of 57 years, because of bilateral invasive ductal carcinoma. Radiation and tamoxifen treatment followed. Routine surveillance examinations, including pelvic examination, Papanicolaou (Pap) smear, and transvaginal ultrasound, were uneventful. Recently, a small contact-bleeding mass of the cervix was found. The Pap smear was II (reactive); HPV-DNA test was negative. The biopsy of the mass revealed PSCC with a high expression of p53, carcinoembryonic antigen (CEA), and Ki67 (50%). Staining for estrogen receptor (ER), progesterone receptor (PR), and vimentin was negative. The serum carbohydrate antigen 125 (CA-125) reached 159 U/ml. The patient was treated with radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy. A poorly-differentiated papillary-serous, non-secretory adenocarcinoma, pT1b1, pN0 (0/44), pM0, G3, R0, V0, L0, was confirmed. According to the German recommendations for early-stage cervical cancer, the patient received no adjuvant treatment. Currently, the patient is free of relapse 38 months after the diagnosis of cervical cancer and 87 months after that of breast cancer.<br><br>CONCLUSION: Immunohistochemistry is helpful in diagnosing rare entities. This case adds further evidence that the prognosis for early-stage PSCC is probably not poorer than that for other cervical adenocarcinomas.}, }
@article {pmid23146383, year = {2012}, author = {Deb, S and Jene, N and ,  and Fox, SB}, title = {Genotypic and phenotypic analysis of familial male breast cancer shows under representation of the HER2 and basal subtypes in BRCA-associated carcinomas.}, journal = {BMC cancer}, volume = {12}, number = {}, pages = {510}, pmid = {23146383}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; BRCA1 Protein/metabolism ; BRCA2 Protein/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms, Male/*genetics/metabolism/pathology ; Cohort Studies ; *Genes, BRCA1 ; *Genes, BRCA2 ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Immunohistochemistry ; Male ; Microarray Analysis ; Middle Aged ; Mutation ; Phenotype ; Receptor, ErbB-2/genetics ; Survival Rate ; }, abstract = {BACKGROUND: Male breast cancer (MBC) is an uncommon and relatively uncharacterised disease accounting for <1% of all breast cancers. A significant proportion occurs in families with a history of breast cancer and in particular those carrying BRCA2 mutations. Here we describe clinicopathological features and genomic BRCA1 and BRCA2 mutation status in a large cohort of familial MBCs.<br><br>METHODS: Cases (n=60) included 3 BRCA1 and 25 BRCA2 mutation carries, and 32 non-BRCA1/2 (BRCAX) carriers with strong family histories of breast cancer. The cohort was examined with respect to mutation status, clinicopathological parameters including TNM staging, grade, histological subtype and intrinsic phenotype.<br><br>RESULTS: Compared to the general population, MBC incidence was higher in all subgroups. In contrast to female breast cancer (FBC) there was greater representation of BRCA2 tumours (41.7% vs 8.3%, p=0.0008) and underrepresentation of BRCA1 tumours (5.0% vs 14.4%, p=0.0001). There was no correlation between mutation status and age of onset, disease specific survival (DSS) or other clincopathological factors. Comparison with sporadic MBC studies showed similar clinicopathological features. Prognostic variables affecting DSS included primary tumour size (p=0.003, HR:4.26 95%CI 1.63-11.11), age (p=0.002, HR:4.09 95%CI 1.65-10.12), lymphovascular (p=0.019, HR:3.25 95%CI 1.21-8.74) and perineural invasion (p=0.027, HR:2.82 95%CI 1.13-7.06). Unlike familial FBC, the histological subtypes seen in familial MBC were more similar to those seen in sporadic MBC with 46 (76.7%) pure invasive ductal carcinoma of no special type (IDC-NST), 2 (3.3%) invasive lobular carcinomas and 4 (6.7%) invasive papillary carcinoma. A further 8 (13.3%) IDC-NST had foci of micropapillary differentiation, with a strong trend for co-occurrence in BRCA2 carriers (p=0.058). Most tumours were of the luminal phenotype (89.7%), with infrequent HER2 (8.6%) and basal (1.7%) phenotype tumours seen.<br><br>CONCLUSION: MBC in BRCA1/2 carriers and BRCAX families is different to females. Unlike FBC, a clear BRCA1 phenotype is not seen but a possible BRCA2 phenotype of micropapillary histological subtype is suggested. Comparison with sporadic MBCs shows this to be a high-risk population making further recruitment and investigation of this cohort of value in further understanding these uncommon tumours.}, }
@article {pmid23144339, year = {2012}, author = {Mohamad, B and Iqbal, MN and Gopal, KV and Arshad, S and Daw, HA}, title = {Mai infection simulating metastatic breast cancer.}, journal = {BMJ case reports}, volume = {2012}, number = {}, pages = {}, pmid = {23144339}, issn = {1757-790X}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Breast Neoplasms/*diagnosis/therapy ; Carcinoma, Ductal/*diagnosis/therapy ; Female ; Granuloma/microbiology ; Humans ; Inflammation/microbiology ; Lung/*microbiology/pathology/surgery ; Lung Neoplasms/*diagnosis/secondary ; *Mycobacterium avium Complex ; Mycobacterium avium-intracellulare Infection/*diagnosis/drug therapy/microbiology ; }, abstract = {We represent a case of an asymptomatic female who was found to have a mass in the right breast which confirmed an invasive ductal carcinoma by core biopsy. After 3&amp;emsp14;months of completion of chemo-radiotherapy, the patient remained totally asymptomatic. However, positron emission tomography scan showed four hypermetabolic lesions in the left lung thought to be consistent with metastatic disease. Standard uptake value ranged between 3.86 and 6; the results were consistent with metastatic breast cancer, so wedge resection was performed. Caseating granulomatous inflammation with necrosis was reported. Ultimately culture revealed Mycobacterium avium intracellulare infection. The lesions resolved completely after a course of antibiotics.}, }
@article {pmid23103133, year = {2013}, author = {Courtier, N and Gambling, T and Enright, S and Barrett-Lee, P and Abraham, J and Mason, MD}, title = {A prognostic tool to predict fatigue in women with early-stage breast cancer undergoing radiotherapy.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {4}, pages = {504-509}, doi = {10.1016/j.breast.2012.10.002}, pmid = {23103133}, issn = {1532-3080}, mesh = {Aged ; Breast Neoplasms/*complications/pathology/radiotherapy ; Carcinoma/*complications/pathology/radiotherapy ; Carcinoma, Ductal, Breast/complications/pathology/radiotherapy ; Carcinoma, Lobular/complications/pathology/radiotherapy ; Fatigue/*complications/diagnosis ; Female ; Humans ; Logistic Models ; Middle Aged ; Prognosis ; Risk Assessment/methods ; }, abstract = {BACKGROUND: Fatigue during and after radiotherapy impacts negatively on normal functioning and quality of life. A pre-treatment estimate of the risk of fatigue would facilitate the targeting of timely interventions to limit consequential behavioural symptoms arising. We have developed a prognostic tool to predict the risk of fatigue in women with early-stage breast cancer undergoing radiotherapy.<br><br>METHODS: Socio-demographic, clinical and self-reported characteristics were recorded for 100 women prescribed adjuvant radiotherapy for stages Tis-T2N1 breast cancer. Multiple logistic regression was used to develop a parsimonious prognostic model. The performance of the model when predicting fatigue for individuals not in the study was estimated by a leave-one-out cross-validation. A statistical weighting was assigned to the model variables to render a Fatigue Propensity Score of between 0 and 15. The ability of the Propensity Score to discriminate fatigued participants was estimated via receiver operating characteristic curve analysis.<br><br>RESULTS: 38% of participants reported significant fatigue during radiotherapy. Fatigue risk was predicted by elevated pre-treatment fatigue and anxiety, and diagnoses other than invasive ductal carcinoma (ductal carcinoma in-situ, invasive lobular and rarer carcinoma subtypes). The positive predictive value of the prognostic model was 80%. A Propensity Score threshold of &#x2265;6 corresponded to a specificity of 90.3% and a sensitivity of 76.3%. The area under the receiver operating characteristic curve was 0.83 for the cross-validation sample.<br><br>CONCLUSIONS: Application of the Fatigue Propensity Score in the patient pathway can help direct fatigue management resources at those patients most likely to benefit.}, }
@article {pmid23100210, year = {2012}, author = {Ulus, T and Yurtseven, E and Cavdar, S and Erginoz, E and Erdogan, MS}, title = {The suitability of using death certificates as a data source for cancer mortality assessment in Turkey.}, journal = {Croatian medical journal}, volume = {53}, number = {5}, pages = {480-485}, pmid = {23100210}, issn = {1332-8166}, mesh = {Cause of Death/trends ; Data Collection ; *Death Certificates ; Humans ; Neoplasms/*mortality ; Population ; Turkey/epidemiology ; }, abstract = {AIM: To compare the quality of the 2008 cancer mortality data of the Istanbul Directorate of Cemeteries (IDC) with the 2008 data of International Agency for Research on Cancer (IARC) and Turkish Statistical Institute (TUIK), and discuss the suitability of using this databank for estimations of cancer mortality in the future.<br><br>METHODS: We used 2008 and 2010 death records of the IDC and compared it to TUIK and IARC data.<br><br>RESULTS: According to the WHO statistics, in Turkey in 2008 there were 67255 estimated cancer deaths. As the population of Turkey was 71517100, the cancer mortality rate was 9.4 per 10000. According to the IDC statistics, the cancer mortality rate in Istanbul in 2008 was 5.97 per 10000.<br><br>CONCLUSION: IDC estimates were higher than WHO probably because WHO bases its estimates on a sample group and because of the restrictions of IDC data collection method. Death certificates could be a reliable and accurate data source for mortality statistics if the problems of data collection are solved.}, }
@article {pmid23098509, year = {2012}, author = {Baloch, AH and Shuja, J and Daud, S and Ahmed, M and Ahmad, A and Tareen, M and Khan, F and Kakar, MA and Baloch, DM and Kakar, N and Naseeb, HK and Ahmad, J}, title = {Various aspects, patterns and risk factors in breast cancer patients of Balochistan.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {8}, pages = {4013-4016}, doi = {10.7314/apjcp.2012.13.8.4013}, pmid = {23098509}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*etiology/pathology ; Carcinoma, Ductal, Breast/epidemiology/*etiology/pathology ; Carcinoma, Lobular/epidemiology/*etiology/pathology ; Ethnicity ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Pakistan/epidemiology ; Prognosis ; Risk Factors ; Young Adult ; }, abstract = {PURPOSE: Breast cancer is the commonest malignancy of females throughout the world with one million new cases each year. In Pakistan, the burden of breast cancer disease is high with late stage presentation being a common feature, more than half being stage III or stage IV. The objective of this study was to study various aspects, patterns and risk factors in breast cancer patients of Balochistan.<br><br>METHOD: Present study was performed on 134 patients of breast cancer who were registered in CENAR. The patients were interviewed by providing a questionnaire. Informed consent was taken from all the patients who took part in this study after explanation of the study aims. Body mass index (BMI) was calculated andbiopsy reports were obtained from patients files. All the cases were classified with respect to age, gender, ethnic group (Baloch, Pashtoon, Punjabi, Afghani, Hazara) BMI, cancer type, cancer grade, hormonal status, side of the cancer, fertility and marital status.<br><br>RESULTS: Out of 134 patients, the most common ethnic group was Pashtoon with a total of 42 and the common age group was 41-50 years with a total of 51. Invasive ductal carcinoma (IDC) was the most common type, accounting for in 128 patients (95.5%) followed by invasive lobular carcinoma (ILC).<br><br>CONCLUSION: Pashtoon was the most common ethnic group, IDC was common type and most of the patients had an ER/PR positive hormonal status.}, }
@article {pmid23046680, year = {2012}, author = {Loo, WY and Yue, Y and Fan, CB and Bai, LJ and Dou, YD and Wang, M and Liang, H and Cheung, MN and Chow, LW and Li, JL and Tian, Y and Qing, L}, title = {Comparing serum levels of cardiac biomarkers in cancer patients receiving chemotherapy and subjects with chronic periodontitis.}, journal = {Journal of translational medicine}, volume = {10 Suppl 1}, number = {Suppl 1}, pages = {S5}, pmid = {23046680}, issn = {1479-5876}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers/*blood ; Breast Neoplasms/*blood/*drug therapy ; Case-Control Studies ; Chronic Periodontitis/*blood ; Female ; Humans ; Inflammation Mediators/blood ; Male ; Middle Aged ; Myocardium/*metabolism ; Young Adult ; }, abstract = {BACKGROUND: Chronic periodontitis (CP) is a chronic inflammation associated with elevations of several inflammatory and cardiac markers. Studies implicated CP as one of the etiologies in coronary heart disease (CHD). Cardiotoxicity is a major complication of anticancer drugs, including anthracyclines and 5-fluorouracil (5FU). The most severe cardiac complications are heart failure, arrhythmia and coronary heart disease (CHD). In this study, we compared the level of inflammatory factors and cardiac markers between chronic periodontitis patients and cancer patients receiving chemotherapy.<br><br>METHODS: 108 blood samples of periodontally healthy subjects were obtained on random from Hong Kong Red Cross, and these represented the controlled population. Forty-four patients diagnosed with chronic periodontitis were recruited from the West China Hospital of Stomatology, Sichuan University. They have received scaling and root planning with mean pocket depths of 6.05 mm. Thirty breast cancer patients diagnosed with invasive ductal carcinoma from UNIMED Medical Institute, Hong Kong gave consent to participate in this study. They received 4 cycles of 500mg/m2 5-fluorouracil, 75 mg/m2 epirubicin and 500mg/m2 cyclophosphamide at a 3-week interval between each cycle. Peripheral venous blood from each group was taken for measurement of blood cells, inflammatory marker (P-selectin, high sensitvity C-reactive protein) and cardiac markers (troponin T; troponin I; N-terminal pro brain natriuretic peptide (Nt-proBNP) and Lactate dehydrogenase (LDH).<br><br>RESULTS: The lymphocyte count was higher (p < 0.05) in periodontitis patients than the other two groups, and more neutrophils (p < 0.05) were seen in cancer patients receiving chemotherapy. The two test groups demonstrated higher levels (p < 0.01) of inflammatory and cardiac markers than the control group.<br><br>CONCLUSIONS: The elevated cardiac markers found in periodontitis patients suggested that they may carry potential risks in developing cardiac lesions. Troponin T, troponin I, pro-BNP, LDH and high sensitvity C-reactive protein may be used as markers to monitor cardiac lesions in chronic inflammatory patients.}, }
@article {pmid23077390, year = {2012}, author = {Barry, S and Ha, KY and Laurie, L}, title = {Carcinoma of the breast in men.}, journal = {Proceedings (Baylor University. Medical Center)}, volume = {25}, number = {4}, pages = {367-368}, pmid = {23077390}, issn = {1525-3252}, abstract = {Male breast cancer is an uncommon disease of uncertain etiology. We describe a 66-year-old man who presented with a palpable mass in the left breast with associated nipple inversion. Mammographic images demonstrated a spiculated mass within the subareolar left breast at the palpable area of concern. Sonographic evaluation demonstrated a hypoechoic mass within the subareolar left breast at the location of the mammographic abnormality. The patient underwent an excisional biopsy and was subsequently diagnosed with high-grade invasive ductal carcinoma, the most common histologic type of carcinoma identified in men.}, }
@article {pmid23070345, year = {2012}, author = {Santos, GC and Góes, AC and Vitto, Hd and Moreira, CC and Avvad, E and Rumjanek, FD and Moura Gallo, CV}, title = {Genomic instability at the 13q31 locus and somatic mtDNA mutation in the D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {67}, number = {10}, pages = {1181-1190}, pmid = {23070345}, issn = {1980-5322}, mesh = {Adult ; Age Distribution ; Aged ; Biomarkers, Tumor ; Brazil ; Breast Neoplasms/*genetics/pathology ; Carcinoma/*genetics/pathology ; Chromosomes, Human, Pair 13/*genetics ; Cohort Studies ; DNA, Mitochondrial/*genetics ; Female ; Genes, p53/genetics ; Genetic Loci/genetics ; Genomic Instability/*genetics ; Humans ; Loss of Heterozygosity/genetics ; Microsatellite Repeats/genetics ; Middle Aged ; Neoplasm Grading ; }, abstract = {OBJECTIVE: Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data.<br><br>METHODS: We analyzed 64 matched pairs of breast cancer and adjacent non-cancerous breast samples by genotyping 13 nuclear short tandem repeat loci (namely, D2S123, TPOX, D3S1358, D3S1611, FGA, D7S820, TH01, D13S317, D13S790, D16S539, D17S796, intron 12 BRCA1 and intron 1 TP53) that were amplified with the fluorescent AmpFlSTR Identifiler Genotyping system (Applied Biosystems, USA) and by silver nitrate staining following 6% denaturing polyacrylamide gel electrophoresis. Somatic mtDNA mutations in the D-loop site were assessed with direct sequencing of the hypervariable HVI and HVII mitochondrial regions.<br><br>RESULTS: Half of the cancer tissues presented some nuclear instability. Interestingly, the D13S790 locus was the most frequently affected (36%), while the D2S123 locus presented no alterations. Forty-two percent of the cases showed somatic mitochondrial mutations, the majority at region 303-315 poly-C. We identified associations between Elston grade III, instabilities at 13q31 region (p = 0.0264) and mtDNA mutations (p = 0.0041). Furthermore, instabilities at 13q31 region were also associated with TP53 mutations in the invasive ductal carcinoma cases (p= 0.0207).<br><br>CONCLUSION: Instabilities at 13q31 region and the presence of somatic mtDNA mutations in a D-loop site correlated with tumor aggressiveness.}, }
@article {pmid23062488, year = {2012}, author = {Heselmeyer-Haddad, K and Berroa Garcia, LY and Bradley, A and Ortiz-Melendez, C and Lee, WJ and Christensen, R and Prindiville, SA and Calzone, KA and Soballe, PW and Hu, Y and Chowdhury, SA and Schwartz, R and Schäffer, AA and Ried, T}, title = {Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression.}, journal = {The American journal of pathology}, volume = {181}, number = {5}, pages = {1807-1822}, pmid = {23062488}, issn = {1525-2191}, support = {R01 AI076318/AI/NIAID NIH HHS/United States ; 1R01AI076318/AI/NIAID NIH HHS/United States ; R01 CA140214/CA/NCI NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; 1R01CA140214/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Chromosomal Instability/*genetics ; Clone Cells ; Disease Progression ; Female ; Genes, Neoplasm/genetics ; *Genetic Heterogeneity ; Genome, Human/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Invasiveness ; Ploidies ; Proto-Oncogene Proteins c-myc/*genetics ; Single-Cell Analysis/*methods ; }, abstract = {Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the IDC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum.}, }
@article {pmid23056525, year = {2012}, author = {Honda, K and Okusaka, T and Felix, K and Nakamori, S and Sata, N and Nagai, H and Ioka, T and Tsuchida, A and Shimahara, T and Shimahara, M and Yasunami, Y and Kuwabara, H and Sakuma, T and Otsuka, Y and Ota, N and Shitashige, M and Kosuge, T and Büchler, MW and Yamada, T}, title = {Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e46908}, pmid = {23056525}, issn = {1932-6203}, mesh = {Adult ; Amino Acid Sequence ; Antibody Specificity ; Apolipoproteins/*blood/chemistry/immunology ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pancreatic Neoplasms/*blood ; Protein Multimerization ; Protein Structure, Quaternary ; Reproducibility of Results ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection.<br><br>METHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1) using a newly developed matrix-assisted laser desorption/ionization (oMALDI) QqTOF (quadrupole time-of-flight) mass spectrometry (MS) system.<br><br>RESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z), unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z), and their summed value were significantly decreased in the pancreatic cancer patients [P&#x200a;=&#x200a;1.36&#xd7;10(-21), P&#x200a;=&#x200a;4.35&#xd7;10(-14), and P&#x200a;=&#x200a;1.83&#xd7;10(-24) (Mann-Whitney U-test); area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n&#x200a;=&#x200a;103) and Cohort 3 (n&#x200a;=&#x200a;163)] and a prospective cohort [Cohort 4 (n&#x200a;=&#x200a;833)] collected from 8 medical institutions in Japan and Germany.<br><br>CONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.}, }
@article {pmid23056178, year = {2012}, author = {Jones, DT and Lechertier, T and Mitter, R and Herbert, JM and Bicknell, R and Jones, JL and Li, JL and Buffa, F and Harris, AL and Hodivala-Dilke, K}, title = {Gene expression analysis in human breast cancer associated blood vessels.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e44294}, pmid = {23056178}, issn = {1932-6203}, support = {11359/CRUK_/Cancer Research UK/United Kingdom ; 12-1068/AICR_/Worldwide Cancer Research/United Kingdom ; 12007/CRUK_/Cancer Research UK/United Kingdom ; G0901609/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Angiogenesis Inhibitors/therapeutic use ; Animals ; Antibodies/immunology/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Aorta, Thoracic/drug effects/metabolism ; Bevacizumab ; Breast Neoplasms/blood supply/*genetics/metabolism ; Carcinoma, Ductal, Breast/blood supply/*genetics/metabolism ; Cell Line, Tumor ; Female ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; Microscopy, Confocal ; Neoplasms, Experimental/blood supply/drug therapy/genetics ; Neovascularization, Pathologic/drug therapy/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Platelet Endothelial Cell Adhesion Molecule-1/genetics/metabolism ; RNA Interference ; Transplantation, Heterologous ; Tumor Burden/drug effects/genetics ; Vascular Endothelial Growth Factor A/genetics/immunology/pharmacology ; }, abstract = {Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold) in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC) of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of potentially novel anti-angiogenic targets that are likley to be, but not exclusivley, relevant to breast cancer.}, }
@article {pmid23042770, year = {2012}, author = {Frick, SU and Bacher, N and Baier, G and Mailänder, V and Landfester, K and Steinbrink, K}, title = {Functionalized polystyrene nanoparticles trigger human dendritic cell maturation resulting in enhanced CD4+ T cell activation.}, journal = {Macromolecular bioscience}, volume = {12}, number = {12}, pages = {1637-1647}, doi = {10.1002/mabi.201200223}, pmid = {23042770}, issn = {1616-5195}, mesh = {CD4-Positive T-Lymphocytes/*immunology ; Cytokines/immunology ; Dendritic Cells/drug effects/*immunology ; Humans ; Immunologic Factors/*chemistry/pharmacology ; Interferon-gamma/immunology ; Lymphocyte Activation/*drug effects ; Microscopy, Confocal ; Nanoparticles/*chemistry ; Organophosphonates ; Polystyrenes/*chemistry/pharmacology ; Sulfonic Acids ; }, abstract = {Nanoparticles (NP) represent a promising tool for biomedical applications. Here, sulfonate- and phosphonate-functionalized polystyrene NP are analyzed for their interaction with human monocyte-derived dendritic cells (DC). Immature dendritic cells (iDC) display a higher time- and dose-dependent uptake of functionalized polystyrene NP compared to mature dendritic cells (mDC). Notably, NP induce an enhanced maturation of iDC but not of mDC (upregulation of stimulatory molecules and cytokines). NP-triggered maturation results in a significantly enhanced T cell stimulatory capacity (increased CD4(+) T cell proliferation and IFN-γ production), indicating a shift to a pronounced Th1 response. Immunomodulatory properties of NP may be a useful strategy for strengthening the efficacy of NP-based approaches in immunotherapy.}, }
@article {pmid23038687, year = {2013}, author = {Lee, S and de Boer, WB and Subramaniam, K and Kumarasinghe, MP}, title = {Pointers and pitfalls of mycophenolate-associated colitis.}, journal = {Journal of clinical pathology}, volume = {66}, number = {1}, pages = {8-11}, doi = {10.1136/jclinpath-2012-200888}, pmid = {23038687}, issn = {1472-4146}, mesh = {Acute Disease ; Adult ; Apoptosis/drug effects ; Biopsy ; Colitis/*chemically induced/diagnosis ; Colonoscopy ; Diagnosis, Differential ; Female ; Humans ; Immunosuppressive Agents/*adverse effects ; Intestinal Mucosa/*drug effects/pathology ; Male ; Middle Aged ; Mycophenolic Acid/adverse effects/*analogs &amp; derivatives ; Organ Transplantation ; Postoperative Complications ; Retrospective Studies ; Young Adult ; }, abstract = {AIMS: Mycophenolate-associated colitis has been previously reported to show patterns of colonic mucosal injury mimicking a host of conditions, including graft-versus-host disease, ischaemia and inflammatory bowel disease (IBD). The aim of this study is to characterise, semiquantitatively, pathological changes of mycophenolate mofetil (MMF) mucosal injury.<br><br>METHODS: Seven transplant patients receiving MMF who underwent colonoscopic examination and biopsy were identified retrospectively over a 2-year period. Multiple histologic parameters, including architectural distortion, cryptitis, stromal active inflammation, individual damaged crypts (IDC) and crypt apoptotic figures were evaluated in the biopsies semiquantitatively. Where biopsy site was identified, the parameters were assessed separately in biopsies from right and left colon.<br><br>RESULTS: All cases showed mixed patterns of mucosal injury. All seven cases showed focal architectural distortion (in 58% of fragments per case), focal cryptitis (mean 3.0 foci per case), increased crypt apoptosis (mean 26.5/100 crypts) and IDC (mean 3.0 foci). Focal changes resembling acute self-limited colitis were noted in three cases. Possible proximal accentuation of some changes was noted with right side biopsies tending to show greater crypt apoptotic activity and more foci of architectural distortion. Three cases showed dual pathology (two with cytomegalovirus (CMV) infection and one with IBD).<br><br>CONCLUSIONS: Although a wide spectrum of changes may be seen in MMF-associated colitis, important microscopic clues include a mixed pattern of injury (typically a combination of crypt apoptosis, isolated crypt damage and architectural distortion), and possible proximal accentuation of pathologic changes. The need for clinical correlation and follow-up is emphasised by the occurrence of dual pathology in patients treated with MMF.}, }
@article {pmid23035035, year = {2013}, author = {Raymond, AR and Norton, GR and Sareli, P and Woodiwiss, AJ and Brooksbank, RL}, title = {Relationship between average leucocyte telomere length and the presence or severity of idiopathic dilated cardiomyopathy in black Africans.}, journal = {European journal of heart failure}, volume = {15}, number = {1}, pages = {54-60}, doi = {10.1093/eurjhf/hfs147}, pmid = {23035035}, issn = {1879-0844}, mesh = {Adult ; Black People/*genetics ; Cardiomyopathy, Dilated/ethnology/*genetics/physiopathology ; Female ; Humans ; *Leukocytes ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Stroke Volume ; Telomere/*genetics ; *Ventricular Function, Left ; }, abstract = {AIMS: A reduced average leucocyte telomere length is associated with ischaemic heart failure. Whether this relationship represents a cause or consequence of heart failure or is attributed to associated risk factors and coronary artery disease is uncertain. We evaluated if average leucocyte telomere length is associated with idiopathic dilated cardiomyopathy (IDC) or its severity.<br><br>METHODS AND RESULTS: We compared average leucocyte telomere length in 223 patients with heart failure due to IDC and 227 healthy controls of black African ancestry. We also evaluated the relationship between average leucocyte telomere length and left ventricular ejection fraction (LVEF). LVEF was determined using echocardiography and radionuclide multiple-gated acquisition (MUGA) scan in patients with IDC. Relative leucocyte telomere length (T/S) was measured using a quantitative real-time polymerase chain reaction assay. Log T/S was negatively correlated with age in patients with IDC (P = 0.0007) and in controls (P = 0.030), and with alcohol consumption (P = 0.032) and regular smoking (P = 0.021) in patients with IDC. Log T/S did not differ between IDC and control groups either before (P = 0.11) or after (IDC = 0.071 &#xb1; 0.187, control = 0.071 &#xb1; 0.187, P = 0.99) adjustments for confounders. Log T/S was not associated with echocardiographic (P = 0.47) or MUGA (P = 0.99) LVEF or LV end-diastolic diameter (LVEDD) (P = 0.34) in patients with IDC. With adjustments for age, sex, alcohol consumption, and smoking, log T/S was similarly not associated with echocardiographic (P = 0.60) or MUGA (P = 0.91) LVEF or LVEDD (P = 0.53) in patients with IDC.<br><br>CONCLUSIONS: Average relative leucocyte telomere length is not associated with IDC or its severity in groups of black African ancestry.}, }
@article {pmid23032353, year = {2013}, author = {Nakash, O and Gerber, Y and Goldbourt, U and Benyamini, Y and Drory, Y and , }, title = {Ethnicity and long-term prognosis after myocardial infarction: a population-based cohort study.}, journal = {Medical care}, volume = {51}, number = {2}, pages = {137-143}, doi = {10.1097/MLR.0b013e318270bab5}, pmid = {23032353}, issn = {1537-1948}, mesh = {Aged ; Chi-Square Distribution ; Cohort Studies ; Comorbidity ; Educational Status ; Employment/statistics &amp; numerical data ; Female ; Humans ; Incidence ; Income/statistics &amp; numerical data ; Interviews as Topic ; Israel/epidemiology ; *Jews ; Male ; Middle Aged ; Myocardial Infarction/*ethnology/mortality/therapy ; Prognosis ; Proportional Hazards Models ; Residence Characteristics ; Risk Factors ; Social Class ; Treatment Outcome ; }, abstract = {BACKGROUND: Health disparities are systematic differences in health, favoring members of advantaged over disadvantaged groups in the society. This study examines the contribution of multiple socioeconomic status (SES) measures to ethnic differences in after myocardial infarction (MI) prognosis.<br><br>METHODS: Patients aged 65 years and younger (n=1040) belonging to Ashkenazi and Mizrahi advantaged and disadvantaged ethnic groups discharged from 8 hospitals in central Israel after incident MI in 1992-1993, were followed up through 2005 for all-cause mortality, recurrent MI, heart failure, and ischemic stroke.<br><br>RESULTS: Advantaged Ashkenazi had higher education, income, employment, and neighborhood SES compared with disadvantaged Mizrahi. Cardiovascular risk factors varied among the different ethnic groups. Results showed that the association between ethnic group and all outcomes differed substantially between models that included a single SES measure and those that included multiple measures. For example, the hazard ratio for mortality in disadvantaged Mizrahi compared with advantaged Ashkenazi was 1.87 [95% confidence interval (CI), 1.40-2.48] in a model adjusting only for demographic variables; 1.58 (95% CI, 1.18-2.12) in a model adjusting also for income; and 1.03 (95% CI, 0.74-2.04) in a model adjusting for all measured SES indicators. Further adjustment for clinical variables did not appreciably change the results.<br><br>CONCLUSIONS: Findings show that a wide array of modifiable social factors shaped by income, education, and neighborhood socioeconomic conditions can explain ethnic health differences and highlight the importance of using multivariable models of SES.}, }
@article {pmid23031786, year = {2013}, author = {Lin, H and Huang, JF and Qiu, JR and Zhang, HL and Tang, XJ and Li, H and Wang, CJ and Wang, ZC and Feng, ZQ and Zhu, J}, title = {Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer.}, journal = {Experimental and molecular pathology}, volume = {94}, number = {1}, pages = {73-78}, doi = {10.1016/j.yexmp.2012.08.004}, pmid = {23031786}, issn = {1096-0945}, mesh = {Antigens, Neoplasm/*biosynthesis/genetics ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*metabolism/pathology/therapy ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/therapy ; Cell Adhesion Molecules/*biosynthesis/genetics ; Cyclin D1/*biosynthesis/genetics ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics/metabolism ; Up-Regulation ; }, abstract = {The tumor-associated calcium signal transducer 2 (TACSTD2) gene has been reported to be highly expressed in many types of human epithelial cancers, and is associated with tumor metastasis and poor prognosis. The aims of the present investigation were to analyze the TACSTD2 and Cyclin D1 expression at the mRNA and protein levels and to assess its prognostic significance in invasive ductal breast cancer (IDC). The expressions of TACSTD2 and Cyclin D1 in IDC tissues were consistently higher than those in the tumor-adjacent non-malignant tissues by a one-step real-time polymerase chain reaction and immunohistochemistry (P<0.001 and P=0.023, respectively). The statistical analysis of clinicopathologic characteristics and immunohistochemistry by the χ(2) test showed that the high expression of TACSTD2 in IDC was correlated to histological grade (P=0.023), P53 status (P=0.042), Cyclin D1 status (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.004) and TNM staging (P<0.001). Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. These analyses also showed that a high TACSTD2 expression (P=0.003), a high Cyclin D1 expression (P=0.041), and lymph node metastasis (P=0.006) were independent prognosis factors. Collectively, our studies demonstrated that the high expression of TACSTD2 correlates with a poor prognosis in IDC.}, }
@article {pmid23017667, year = {2012}, author = {Madeira, KP and Daltoé, RD and Sirtoli, GM and Rezende, LC and Carvalho, AA and Guimarães, Idos S and Silva, IV and Rangel, LB}, title = {Comparison of immunohistochemical analysis with estrogen receptor SP1 and 1D5 monoclonal antibodies in breast cancer.}, journal = {Pathology, research and practice}, volume = {208}, number = {11}, pages = {657-661}, doi = {10.1016/j.prp.2012.07.010}, pmid = {23017667}, issn = {1618-0631}, mesh = {Adenocarcinoma/*diagnosis ; *Antibodies, Monoclonal ; Biomarkers, Tumor/*immunology ; Breast Neoplasms/*diagnosis ; Estrogen Receptor alpha/*immunology ; Female ; Humans ; Immunohistochemistry/methods ; Reproducibility of Results ; Tissue Array Analysis ; }, abstract = {In the present study, we aimed to evaluate estrogen receptor ER-alpha status in 61 breast cancer cases using Sp1 and 1D5 monoclonal antibodies. Tissue array platforms were generated containing samples of breast cancer and positive controls that were assayed by immunohistochemistry applying monoclonal primary antibodies anti-ER alpha, SP1 and 1D5. We noted a high concordance rate (96.7%) between the referred antibodies. Moreover, we calculated the Kappa factor (0.921), indicating that 1D5 and SP1 provided overlapping ERα expression results. Indeed, we observed controversial results only in 2 samples studied, which were ER-negative when stained with 1D5 and ER-positive when assessed with SP1. Total concordance of PS was obtained (Pearson and intraclass CF, 0.7351 and 0.6193, respectively). However, concordance between the antibodies seems to be more accurate in higher PS values. An excellent IS correlation between antibodies was observed throughout the population (Spearman's CF, ρ=0.9150). Following the Allred score, 17 out of 42 positive BC samples diverged, with 1D5 always pointing to weaker staining than SP1. When calculating Spearman's CF of Total Score (TS) within the population, an excellent correlation between both the antibodies (ρ=0.9238) was noted. Nonetheless, the results were less concordant among the BC-positive cases (ρ=0.7743). Indeed, 20 samples were differentially classified using the antibodies (only 3 had higher TS with 1D5). Considering the mean TS of all samples or of invasive ductal carcinoma, SP1 provided higher scores than 1D5 (p<0.05). We recommend the use of the anti-ER RMAb SP1 due to the high probability that the BC ERα status can be determined accurately as the reagent provides higher IS. Therefore, the A-score was higher than the MMAb 1D5. Ultimately, higher IS and A-score decrease the possibility of ERα status misinterpretation and, consequently, inappropriate BC treatment that would compromise the patient's quality of life and overall survival. We recommend the use of anti-ER RMAb SP1 due to the high probability that the BC ER status can be determined accurately as the reagent provides higher IS, therefore higher A-score, than the MMAb 1D5.}, }
@article {pmid23011826, year = {2012}, author = {Pala, EE and Bayol, &#xdc; and Cumurcu, S and Keskın, E}, title = {[Immunohistochemical characteristics of triple negative/basal-like breast cancer].}, journal = {Turk patoloji dergisi}, volume = {28}, number = {3}, pages = {238-244}, doi = {10.5146/tjpath.2012.01130}, pmid = {23011826}, issn = {1309-5730}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carrier Proteins/analysis/biosynthesis ; ErbB Receptors/analysis/biosynthesis ; Female ; Glycoproteins/analysis/biosynthesis ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Keratin-5/analysis/biosynthesis ; Keratin-6/analysis/biosynthesis ; Membrane Transport Proteins ; }, abstract = {OBJECTIVE: Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers.<br><br>MATERIAL AND METHOD: We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytokeratine 5/6, p53, Ki67, GCDFP-15 expression profiles, HER2 and Chromosome 17 centromere gene status by fluorescence-in-situ-hybridization method.<br><br>RESULTS: Histological type was invasive ductal carcinoma in 90.2% of the tumors. p53, Ki67, GCDFP-15 mean positivity rates were 55.6%, 51.7%, and 3.2%, respectively. GCDFP-15 positivity was noted in 8 cases of which 6 were Cytokeratine 5/6 negative. The cut-off value for Cytokeratine 5/6 positivity was 5%. EGFR immunoreactivity was grouped into 0, 1+ as negative; 2+, 3+ as positive categories. Cytokeratine 5/6 was positive in 56,1%, EGFR was positive in 51.2% of the patients. The relation between Cytokeratine 5/6 and EGFR expression was statistically significant (p < 0.01). None of the cases showed HER2 amplification by fluorescence-in-situ-hybridization method.<br><br>CONCLUSION: GCDFP-15 alone is not a useful marker to detect the metastasis of basaloid type breast cancers. Cytokeratine 5/6 and EGFR expressions showed correlation so these markers are reliable to diagnose basaloid type tumors with a 5% cut-off value.}, }
@article {pmid22996366, year = {2012}, author = {Son, CH and Shin, DY and Kim, SD and Park, HS and Jung, MH and Bae, JH and Kang, CD and Yang, K and Park, YS}, title = {Improvement of antitumor effect of intratumoral injection of immature dendritic cells into irradiated tumor by cyclophosphamide in mouse colon cancer model.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {35}, number = {8}, pages = {607-614}, doi = {10.1097/CJI.0b013e31826f79a6}, pmid = {22996366}, issn = {1537-4513}, mesh = {Animals ; Antineoplastic Agents, Alkylating/*administration &amp; dosage ; CD4 Antigens/metabolism ; Carcinoma/pathology/*therapy ; Cell Growth Processes/drug effects ; Cell Line, Tumor ; Colonic Neoplasms/pathology/*therapy ; Combined Modality Therapy ; Cyclophosphamide/*administration &amp; dosage ; Dendritic Cells/transplantation ; Disease Models, Animal ; Humans ; Interferon-gamma/metabolism ; Interleukin-2 Receptor alpha Subunit/metabolism ; Lymphocyte Activation/drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Radioimmunotherapy/*methods ; T-Lymphocyte Subsets/*drug effects/immunology ; T-Lymphocytes, Regulatory/*drug effects/immunology ; }, abstract = {Recently, chemotherapy and radiotherapy are known to directly affect some immunosuppressive barriers within a tumor microenviroment. We used cyclophosphamide (CTX), which is known to enhance the immune response by suppressing CD4+CD25+ regulatory T cells (Treg cells) when used at a low dose, as a chemotherapeutic agent to provide a synergic effect in the irradiation and dendritic cells (DC) combination therapy. Some previous studies observed that a single-dose CTX treatment significantly reduced the number of Treg cells in 3-5 days, however, the reduced Treg cells increased rapidly after 5 days. To overcome the disadvantages of a single-dose CTX, we used 30 mg/kg dose of CTX, which was treated intraperitoneally to mice 3 days before every immature DC (iDC) injection (known as "metronomic schedule CTX"). Irradiation was applied at a dose of 10 Gy to the tumor on the right thigh by a linear accelerator. Then, iDC was intratumorally injected into the irradiated tumor site. Growth of a distant tumor on the right and left flank was suppressed by an injection of iDC into the irradiated tumor, and this effect was increased by the metronomic schedule CTX. Also, combinations treated with the metronomic schedule CTX and ionizing radiation (IR)/iDC, showed the longest survival time compared with other groups. This antitumor immune response of IR/iDC was improved by metronomic schedule CTX and this result was associated with decreasing the proportion of CD4+CD25+ Treg cells and increasing the number of tumor-specific interferon-γ-secreting T cells. Our results demonstrated that metronomic schedule CTX improves the antitumor effect of immunization with an injection of DC s into the irradiated tumor.}, }
@article {pmid22989547, year = {2012}, author = {Kung, YH and Wu, TT and Lin, CS}, title = {Tumor seeding after diagnostic vitrectomy for choroidal metastasis in breast cancer.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {75}, number = {9}, pages = {483-486}, doi = {10.1016/j.jcma.2012.06.023}, pmid = {22989547}, issn = {1728-7731}, mesh = {Breast Neoplasms/*pathology ; Choroid Neoplasms/diagnosis/pathology/*secondary ; Female ; Humans ; Middle Aged ; *Neoplasm Seeding ; *Vitrectomy ; }, abstract = {Choroidal metastasis is the most common type of intraocular tumor in adults, and in females the most common primary site is the breast. We report a case of unilateral choroidal metastasis with exudative retinal detachment as the initial presentation of recurrent breast cancer, and subsequent ophthalmic metastasis following diagnostic vitrectomy. A 49-year-old woman with a 7-year-history of well-treated bilateral breast cancer had been suffering from blurred vision in the left eye for 1 week. Ocular examination was normal except for superotemporal retinal detachment in the left eye. Neither retinal break nor choroidal mass was seen. The patient received scleral buckling and pneumatic retinopexy without significant improvement. Fluorescein angiography revealed a suspected choroidal metastasis in the left eye, but ocular ultrasonography did not show a visible choroidal mass. Two consecutive diagnostic vitrectomies with cytology could not confirm malignancy. A systemic workup was also negative. Six months later, two tumor masses were noted over two of the sclerotomy wounds of the left eye. Pathology showed adenocarcinoma compatible with invasive ductal carcinoma of the breast. Ocular metastasis may present as infiltrative choroidal lesions with exudative retinal detachment without a visible mass. Invasive procedures, such as fine-needle aspiration biopsy and diagnostic vitrectomy, may risk tumor seeding.}, }
@article {pmid22984615, year = {2012}, author = {van Balkom, ID and Bresnahan, M and Vuijk, PJ and Hubert, J and Susser, E and Hoek, HW}, title = {Paternal age and risk of autism in an ethnically diverse, non-industrialized setting: Aruba.}, journal = {PloS one}, volume = {7}, number = {9}, pages = {e45090}, pmid = {22984615}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Age Factors ; Autistic Disorder/*epidemiology/ethnology ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Indians, South American ; Logistic Models ; Male ; Maternal Age ; Middle Aged ; Netherlands/ethnology ; *Paternal Age ; Risk Assessment/methods/*statistics &amp; numerical data ; Risk Factors ; Spain/ethnology ; West Indies/epidemiology ; }, abstract = {OBJECTIVE: The aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.<br><br>DESIGN: A case-control study of Aruban-born children (1990-2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (&#x2264; 29, 30-39, 40-49, &#x2265; 50 y). The analysis was made, using conditional logistic regression.<br><br>RESULTS: Advanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (&#x2264; 29 y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.<br><br>CONCLUSION: This study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.}, }
@article {pmid22976804, year = {2012}, author = {Li, S and Yang, C and Zhai, L and Zhang, W and Yu, J and Gu, F and Lang, R and Fan, Y and Gong, M and Zhang, X and Fu, L}, title = {Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast.}, journal = {Breast cancer research and treatment}, volume = {136}, number = {1}, pages = {77-87}, doi = {10.1007/s10549-012-2166-6}, pmid = {22976804}, issn = {1573-7217}, mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Carcinoma, Papillary/genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphatic Metastasis ; *MicroRNAs/genetics/isolation &amp; purification ; Neoplasm Invasiveness/genetics ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of breast cancer. IMPC has a special growth pattern and a more aggressive behavior than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a large class of non-coding RNAs involved in the regulation of various biological processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by means of next-generation sequencing, generating a total of >170,000,000 clean reads. In an unsupervised cluster analysis, differently expressed miRNAs generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By means of RT-qPCR, we further investigated miRNA expression in more IMPC (n = 22) and IDC-NSTs (n = 24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a, miR-181a*, and miR-181b were significantly differently expressed between the two groups. We also elucidated several features of miRNA in these breast cancer tissues including 5' variability, miRNA editing, and 3' untemplated addition. Our findings will lead to further understanding of the invasive potency of IMPC and gain an insight into the diversity and complexity of small RNA molecules in breast cancer tissues.}, }
@article {pmid22961104, year = {2012}, author = {Uzoaru, I and Morgan, BR and Liu, ZG and Bellafiore, FJ and Gaudier, FS and Lo, JV and Pakzad, K}, title = {Flat epithelial atypia with and without atypical ductal hyperplasia: to re-excise or not. Results of a 5-year prospective study.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {461}, number = {4}, pages = {419-423}, pmid = {22961104}, issn = {1432-2307}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Breast/*pathology/*surgery ; Breast Neoplasms/diagnosis/*epidemiology/*surgery ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/surgery ; Carcinoma, Lobular/diagnosis/epidemiology/surgery ; Epithelial Cells/*pathology ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/pathology ; Incidence ; Longitudinal Studies ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Retrospective Studies ; Risk Factors ; }, abstract = {Flat epithelial atypia (FEA) of the breast have a tendency to calcify and, as such, are becoming increasingly detected by mammography. There is no consensus yet on whether to excise these lesions or not after diagnosis on core needle biopsies (CNB). We reviewed 3,948 cases of breast CNB between June 2004 and June 2009 correlating histomorphologic, radiological, and clinical features. There were 3.7 % (145/3,948) pure FEA and 1.5 % (58/3,948) concomitant FEA and atypical ductal hyperplasia (ADH). In the pure FEA population, 46.2 % (67/145) had microcalcifications on mammography with 65.5 % (95/145) of patients undergoing subsequent excisional biopsies with the following findings: benign 20 % (19/95), ADH 37.9 % (36/95), ductal carcinoma in situ (DCIS) 1.1 % (1/95), and DCIS and invasive ductal carcinoma (IDC) 2.1 % (2/95). In the concomitant FEA and ADH group, 86.2 % (50/58) patients had microcalcifications on radiograph with 74.1 % (43/58) of patients undergoing subsequent excisions with: benign 23.3 % (10/43), DCIS 9.3 % (4/43), DCIS and IDC 4.7 % (2/43), DCIS + lobular carcinoma in situ + invasive lobular carcinoma 2.3 % (1/43), and tubular carcinoma 2.3 % (1/43). The incidence of carcinoma in the FEA + ADH group is 18.6 % (8/43) and 3.2 % (3/95) for the pure FEA group. This difference is statistically significant (p = 0.0016). The relative risk of carcinoma in the ADH + FEA group versus the pure FEA group is 6.4773, with 95 % CI of 1.8432 and 22.76 24. Five-year mean follow-up in the unexcised pure FEA did not show any malignancies. These findings suggest that pure FEA has a very low association with carcinoma, and these patients may benefit from close clinical and mammographic follow-up while the combined pure FEA and ADH cases may be re-excised.}, }
@article {pmid22961065, year = {2012}, author = {Lips, EH and Mukhtar, RA and Yau, C and de Ronde, JJ and Livasy, C and Carey, LA and Loo, CE and Vrancken-Peeters, MJ and Sonke, GS and Berry, DA and Van't Veer, LJ and Esserman, LJ and Wesseling, J and Rodenhuis, S and Shelley Hwang, E and , }, title = {Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {136}, number = {1}, pages = {35-43}, pmid = {22961065}, issn = {1573-7217}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Breast Neoplasms/drug therapy/metabolism/pathology/surgery ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology/surgery ; *Carcinoma, Lobular/drug therapy/metabolism/pathology/surgery ; Clinical Trials as Topic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mastectomy, Segmental ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/genetics/metabolism ; Treatment Outcome ; }, abstract = {Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.}, }
@article {pmid22957844, year = {2012}, author = {Zhu, J and Li, X and Kong, X and Moran, MS and Su, P and Haffty, BG and Yang, Q}, title = {Testin is a tumor suppressor and prognostic marker in breast cancer.}, journal = {Cancer science}, volume = {103}, number = {12}, pages = {2092-2101}, pmid = {22957844}, issn = {1349-7006}, mesh = {Animals ; Biomarkers, Tumor/genetics/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Cell Proliferation ; Cytoskeletal Proteins/genetics/*metabolism ; Disease-Free Survival ; Female ; Humans ; LIM Domain Proteins/genetics/*metabolism ; Mice ; Mice, Nude ; NIH 3T3 Cells ; Prognosis ; RNA-Binding Proteins ; Xenograft Model Antitumor Assays ; }, abstract = {The testin (TES) gene was previously identified in the fragile chromosomal region FRA7G at 7q31.2. In the present study, we aimed to investigate the candidate tumor suppressor function of TES and explore its correlations to clinicopathologic features and prognosis in breast cancer. In clinical samples, we showed that the expression of TES decreased gradually from normal through ductal hyperplasia without atypia, atypical ductal hyperplasia, and ductal carcinoma in situ, to invasive ductal carcinoma. To explore the possible tumor suppressing function of TES, the expression of TES in breast cancer cells was manipulated by ectopic expression or by RNAi. We revealed that ectopic TES expression significantly inhibited cell proliferation, invasive ability, and angiogenesis, whereas knockdown of TES by RNAi enhanced cell proliferation, invasive ability, and angiogenesis. In an animal model, TES markedly inhibited breast cancer cell xenograft formation in athymic nude mice and reduced breast cancer cell metastasis to lung. Moreover, we revealed that TES inhibited the invasion and angiogenesis of breast cancer partially through miR-29b-mediated MMP-2 inhibition. Using the tissue microarray of breast cancer from Yale University, we found that lower TES expression was an independent prognostic factor for shorter overall survival and disease-free survival with univariate and multivariate analyses. Taken together, these data suggest that TES, as a valuable marker of breast cancer prognosis, plays an important role in the development and progression of breast cancer. TES may be an effective novel target in breast cancer prevention and treatment.}, }
@article {pmid22949099, year = {2013}, author = {Bonkhoff, H and Wheeler, TM and van der Kwast, TH and Magi-Galluzzi, C and Montironi, R and Cohen, RJ}, title = {Intraductal carcinoma of the prostate: precursor or aggressive phenotype of prostate cancer?.}, journal = {The Prostate}, volume = {73}, number = {4}, pages = {442-448}, doi = {10.1002/pros.22579}, pmid = {22949099}, issn = {1097-0045}, mesh = {Animals ; Carcinoma, Ductal/*genetics/*pathology ; Humans ; Male ; Neoplasm Invasiveness/*genetics/*pathology ; *Phenotype ; Prostatic Neoplasms/*genetics/*pathology ; }, abstract = {BACKGROUND: Although the term "intraductal carcinoma of the prostate" (IDC-P) was introduced almost 40 years ago, there is still the lack of appreciation that this entity represents a clinically aggressive disease that continues to be misreported under the diagnostic category of high grade prostatic intraepithelial neoplasia (HGPIN).<br><br>METHODS: Recent data obtained from histological, molecular, and clinical studies were reviewed to demonstrate that IDC-P significantly differs from HGPIN, and has a major impact in terms of diagnosis, prognosis and therapy of prostate cancer (PCa).<br><br>RESULTS: HGPIN is the only accepted precursor of PCa. Its diagnosis in prostate biopsies has no prognostic implications, and does not dictate therapeutic decisions. By contrast, IDC-P correlates with a worse pathological and clinical outcome. IDC-P differs from HGPIN by distinct histological and molecular features. Recent clinical studies report that IDC-P is associated with neoadjuvant androgen deprivation therapy (ADT) and, chemotherapy (CT) failure as well as early disease recurrence after external beam radiation. Finally, IDC-P is associated with TMPRSS2-ERG gene fusion, which was reported to be regulated by estrogens and their receptors.<br><br>CONCLUSIONS: IDC-P is an aggressive phenotype of prostate cancer and predicts poor response to ADT, CT, and external beam radiation. IDC-P should be separated from HGPIN and should be reported in prostate biopsies and prostatectomy specimens.}, }
@article {pmid22932921, year = {2013}, author = {Liu, ZY and Liu, N and Wang, YH and Yang, CC and Zhang, J and Lv, SH and Niu, Y}, title = {Clinicopathologic characteristics and molecular subtypes of invasive papillary carcinoma of the breast: a large case study.}, journal = {Journal of cancer research and clinical oncology}, volume = {139}, number = {1}, pages = {77-84}, pmid = {22932921}, issn = {1432-1335}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/mortality/*pathology/*therapy ; Carcinoma, Ductal, Breast/pathology/therapy ; Carcinoma, Lobular/pathology/therapy ; Carcinoma, Papillary/metabolism/mortality/*pathology/*therapy ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; Immunophenotyping ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Proportional Hazards Models ; Retrospective Studies ; }, abstract = {PURPOSE: Although patients with invasive papillary carcinoma (IPC) often have favorable prognoses, it remains unclear whether this special type of breast cancer represents a distinct morphological entity with its own biological features and clinical behavior distinct from those of invasive ductal carcinoma (IDC) and whether its four molecular subtypes are associated with different prognoses.<br><br>METHODS: The study is a retrospective analysis of a large patient cohort from a single institution. 284 IPC samples were collected from January 2000 to May 2011. 300 IDC cases were selected randomly from 13,428 cases of IDC during the same periods. We assessed the clinicopathologic characteristics, molecular features, and prognostic value of IPC (n = 284) and compared them to those of IDC (n = 300). Clinicopathologic features and survival status of the four subtypes of IPC were also evaluated.<br><br>RESULTS: IPC differed from IDC with respect to age upon diagnosis, tumor grade, lymph node status, and menopausal status (P < 0.05). IPC was associated with a better 5-year overall survival rate (OS) (92.77 vs. 87.95 %) and disease-free survival rate (DFS) (87.95 vs. 80.72 %) than IDC. Tumors of the luminal A subtype had a better 5-year OS (97.78 %) and DFS (95.56 %) than other subtypes.<br><br>CONCLUSIONS: The biologic behavior of IPC is more favorable to patient outcome than that of IDC. The chance of pure IPC causing death without an intervening event of a different histologic type is exceptionally low. Luminal A subtypes have better outcomes when compared to the other subtypes.}, }
@article {pmid22929011, year = {2012}, author = {To, SQ and Takagi, K and Miki, Y and Suzuki, K and Abe, E and Yang, Y and Sasano, H and Simpson, ER and Knower, KC and Clyne, CD}, title = {Epigenetic mechanisms regulate the prostaglandin E receptor 2 in breast cancer.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {132}, number = {3-5}, pages = {331-338}, doi = {10.1016/j.jsbmb.2012.07.007}, pmid = {22929011}, issn = {1879-1220}, mesh = {Adipose Tissue/cytology ; Azacitidine/analogs &amp; derivatives/pharmacology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Line, Tumor ; CpG Islands ; DNA Methylation ; Decitabine ; *Epigenesis, Genetic ; Female ; Fibroblasts/metabolism ; Gene Expression Regulation, Neoplastic ; Histone Deacetylase Inhibitors/pharmacology ; Histones/metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Promoter Regions, Genetic ; Receptors, Prostaglandin E, EP2 Subtype/*genetics/metabolism ; Reference Values ; Stromal Cells/metabolism ; }, abstract = {The increase in local oestrogen production seen in oestrogen receptor positive (ER+) breast cancers is driven by increased activity of the aromatase enzyme. CYP19A1, the encoding gene for aromatase, is often overexpressed in the oestrogen-producing cells of the breast adipose fibroblasts (BAFs) surrounding an ER+ tumour, and the molecular processes underlying this upregulation is important in the development of breast-specific aromatase inhibitors for breast cancer therapy. Prostaglandin E2 (PGE2), a factor secreted by tumours, is known to stimulate CYP19A1 expression in human BAFs. The hormonal regulation of this process has been examined; however, what is less well understood is the emerging role of epigenetic mechanisms and how they modulate PGE2 signalling. This present study characterises the epigenetic processes underlying expression of the prostanoid receptor EP2 in the context of ER+ breast cancer. Sodium bisulphite sequencing of CpG methylation within the promoter region of EP2 revealed that an inverse correlation existed between methylation levels and relative EP2 expression in breast cancer cell lines MDA-MB-231, MCF7 and MCF10A but not in HS578t and T47D. Inhibition of DNA methylation with 5-aza-2'-deoxycytidine (5aza) and histone deacetylation with Trichostatin A (TSA) resulted in upregulation of EP2 mRNA in all cell lines with varying influences of each epigenetic process observed. Expression of EP2 was detected in human BAFs despite a natively methylated promoter, and this expression was further increased upon 5aza treatment. An examination of 3 triple negative, 3 ductal carcinoma in situ and 3 invasive ductal carcinoma samples revealed that there was no change in EP2 promoter methylation status between normal and cancer associated stroma, despite observed differences in relative mRNA levels. Although EP2 methylation status is inversely correlated to expression levels in established breast cancer cell lines, we could not identify that such a correlation existed in tumour-associated stroma cells.}, }
@article {pmid22925754, year = {2012}, author = {Armağan, H and Tüzün, E and Içöz, S and Birişik, O and Ulusoy, C and Demir, G and Altıntaş, A and Akman-Demir, G}, title = {Long extensive transverse myelitis associated with aquaporin-4 antibody and breast cancer: favorable response to cancer treatment.}, journal = {The journal of spinal cord medicine}, volume = {35}, number = {4}, pages = {267-269}, pmid = {22925754}, issn = {1079-0268}, mesh = {Antineoplastic Agents/therapeutic use ; Aquaporin 4/*immunology ; Autoantibodies/blood/immunology ; Autoantigens/immunology ; Breast Neoplasms/*complications/immunology/therapy ; Carcinoma, Ductal, Breast/*complications/immunology/therapy ; Combined Modality Therapy ; Female ; Humans ; Mastectomy ; Middle Aged ; Myelitis, Transverse/*complications/immunology ; Paraneoplastic Syndromes/*etiology/immunology ; }, abstract = {CONTEXT: Long extensive transverse myelitis (LETM) seldom develops in patients with breast cancer who are aquaporin-4 antibody (Aqp-4 Ab)-positive. Whether this association is coincidental is not well understood.<br><br>FINDINGS: A 62-year-old woman presented with treatment-resistant LETM and Aqp-4 Ab. Two months later, a stage 3 invasive ductal carcinoma was detected in her right breast. Following tumor resection and chemotherapy, her neurologic symptoms and magnetic resonance imaging findings significantly improved and serum Aqp-4 Ab disappeared. The breast tumor samples of this patient and neurologically normal patients showed inflammatory infiltrates and Aqp-4 expressing cells.<br><br>CONCLUSION/CLINICAL RELEVANCE: The temporal association between tumor treatment, amelioration of clinical findings, and seroreversion suggest that coexistence of cancer and LETM is not coincidental. Cancer screening should be considered at least in treatment-resistant LETM cases.}, }
@article {pmid22925694, year = {2012}, author = {Marzese, DM and Hoon, DS and Chong, KK and Gago, FE and Orozco, JI and Tello, OM and Vargas-Roig, LM and Roqué, M}, title = {DNA methylation index and methylation profile of invasive ductal breast tumors.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {14}, number = {6}, pages = {613-622}, doi = {10.1016/j.jmoldx.2012.07.001}, pmid = {22925694}, issn = {1943-7811}, mesh = {Adult ; Breast/metabolism/pathology ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Cluster Analysis ; *CpG Islands ; *DNA Methylation ; DNA-Binding Proteins/genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Nuclear Proteins/genetics ; Prognosis ; Receptors, Retinoic Acid/genetics ; Tumor Protein p73 ; Tumor Suppressor Proteins/genetics ; WT1 Proteins/genetics ; }, abstract = {Breast carcinogenesis is a multistep process that involves both genetic and epigenetic alterations. Identification of aberrantly methylated genes in breast tumors and their relation to clinical parameters can contribute to improved diagnostic, prognostic, and therapeutic decision making. Our objective in the present study was to identify the methylation status of 34 cancer-involved genes in invasive ductal carcinomas (IDC). Each of the 70 IDC cases analyzed had a unique methylation profile. The highest methylation frequency was detected in the WT1 (95.7%) and RASSF1 (71.4%) genes. Hierarchical cluster analysis revealed three clusters with different distribution of the prognostic factors tumor grade, lymph node metastasis, and proliferation rate. Methylation of TP73 was associated with high histological grade and high proliferation rate; methylation of RARB was associated with lymph node metastasis. Concurrent methylation of TP73 and RARB was associated with high histological grade, high proliferation rate, increased tumor size, and lymph node metastasis. Patients with more than six methylated genes had higher rates of relapse events and cancer deaths. In multivariate analysis, TP73 methylation and the methylation index were associated with disease outcome. Our results indicate that methylation index and methylation of TP73 and/or RARB are related to unfavorable prognostic factors in patients with IDC. These epigenetic markers should be validated in further studies to improve breast cancer management.}, }
@article {pmid22925655, year = {2012}, author = {Guo, Y and Xu, X and Liu, Z and Zhang, T and Zhang, X and Wang, L and Wang, M and Liu, Y and Lu, Y and Liu, Y and Quan, C}, title = {Apoptosis signal-regulating kinase 1 is associated with the effect of claudin-6 in breast cancer.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {111}, pmid = {22925655}, issn = {1746-1596}, mesh = {Adult ; Aged ; Apoptosis ; Blotting, Western ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; Cell Line, Tumor ; Claudins/genetics/*metabolism ; Enzyme Activation ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; MAP Kinase Kinase Kinase 5/genetics/*metabolism ; MCF-7 Cells ; Middle Aged ; RNA, Messenger/metabolism ; Receptor, ErbB-2/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Transfection ; }, abstract = {BACKGROUND: Previous studies have demonstrated that claudin-6 functions as a cancer suppressor in human MCF-7 breast cancer cells. The growth inhibitory effect could be attributed to inhibition of cell proliferation and induction of apoptosis. The purpose of the current study was to examine the involvement of apoptosis signal-regulating kinase 1 (ASK1) in the anticancer effect of claudin-6.<br><br>METHODS: Immunohistochemical analysis was performed to evaluate the ASK1 protein expression and the correlation between ASK1, claudin-6 and clinicopathological features in 85 samples of breast invasive ductal carcinomas (IDC). Western blotting and RT-PCR was carried out to examine the expression of ASK1 and claudin-6 in MCF-7 cell clones transfected with claudin-6.<br><br>RESULTS: Immunohistochemical analysis showed that ASK1 expression was significantly related with that of claudin-6 in breast invasive ductal carcinomas (P < 0.05). In addition, a positive correlation between ASK1 and C-erb B 2 protein expression was identified (P < 0.05). Western blotting and RT-PCR consistently revealed that the level of ASK1 protein and mRNA was upregulated in MCF-7 cell clones transfected with claudin-6.<br><br>CONCLUSIONS: Our data suggests, for the first time, that the ASK1 signal may play a positive role in the inhibitory effect of claudin-6 in breast cancer.<br><br>VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1200314318763661.}, }
@article {pmid22914783, year = {2012}, author = {Yuan, SS and Hou, MF and Hsieh, YC and Huang, CY and Lee, YC and Chen, YJ and Lo, S}, title = {Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer.}, journal = {Journal of the National Cancer Institute}, volume = {104}, number = {19}, pages = {1485-1502}, doi = {10.1093/jnci/djs355}, pmid = {22914783}, issn = {1460-2105}, mesh = {Animals ; Apoptosis ; Breast Neoplasms/genetics/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/mortality/*pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; *Cell Proliferation ; Cell Survival ; Colorimetry ; *DNA Repair ; DNA-Binding Proteins/genetics/*metabolism ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immunoblotting ; Immunohistochemistry ; Kaplan-Meier Estimate ; MRE11 Homologue Protein ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Proportional Hazards Models ; Tissue Array Analysis ; Transplantation, Heterologous ; Tumor Stem Cell Assay ; Up-Regulation ; }, abstract = {BACKGROUND: Previous studies have shown that altered forms of MRE11, a protein known to play a vital role in DNA double-strand break repair, DNA replication, and telomere maintenance are associated with cancer outcomes. We investigated the role of MRE11 in breast cancer in both clinical and in vitro settings.<br><br>METHODS: We examined MRE11 expression in tumor tissues from invasive ductal carcinoma breast cancer patients (n = 254) by immunohistochemistry, and associations with clinicopathological characteristics and overall survival were assessed using Cox proportional hazards regression models and Kaplan-Meier survival curves. Effect of MRE11 overexpression and knockdown on cell proliferation, invasion, and radioresistance was assessed in vitro using breast cancer cell lines (MCF-7 and MDA-MB-231). We also investigated the mechanisms involved. Effect of MRE11 overexpression on tumor growth was assessed in an orthotopic xenograft model (n = 8 mice per group). All statistical tests were two-sided.<br><br>RESULTS: Of the 254 tissue samples, 69.3% and 30.7% showed high and low MRE11 expression, respectively. High MRE11 expression was statistically significantly associated with malignant cancer behavior compared with low MRE11 expression (eg, stages III and IV vs stage I, P = .004; poor overall survival, P = .005). MRE11 overexpression in breast cancer cell lines promoted cell proliferation through STAT3, cell cycle entry, invasion and migration, and radioresistance via enhanced DNA repair activity and also inhibited apoptosis; knockdown of MRE11 had the opposite effect. In xenograft tumor-bearing mice (n = 8 per group), increased tumor growth was observed in the MRE11-overexpressing group compared with the control group (tumor volume at week 8, control vs MRE11-overexpressing tumor originating from MCF-7 cells, mean = 280.4 mm(3), 95% confidence interval [CI] = 62.4 to 498.4 mm(3) vs mean = 631.0 mm(3), 95% CI = 296.9 to 965.0 mm(3), P = .043).<br><br>CONCLUSION: High MRE11 expression was associated with a more malignant behavior in breast cancer. MRE11 may be a novel oncoprotein and may therefore serve as a new therapeutic intervention against breast cancer.}, }
@article {pmid22907853, year = {2012}, author = {Zafar, A and Neary, P and O'Donoghue, G and Fiuza-Castinieria, C}, title = {A breast surgeon's paranoia pays off: the importance of keen clinical acumen in a case of postradiotherapy breast angiosarcoma.}, journal = {BMJ case reports}, volume = {2012}, number = {}, pages = {}, pmid = {22907853}, issn = {1757-790X}, mesh = {Aged ; Breast Neoplasms/*diagnosis/etiology/surgery ; Carcinoma, Ductal, Breast/*therapy ; Female ; Hemangiosarcoma/*diagnosis/etiology/surgery ; Humans ; Magnetic Resonance Imaging ; Neoplasms, Radiation-Induced/*diagnosis/etiology/surgery ; Radiotherapy, Adjuvant/adverse effects ; }, abstract = {A 72-year-old woman underwent left wide local excision and an axillary node sampling in 2005 for a T2, N0, M0 invasive ductal carcinoma followed by adjuvant chemotherapy, radiotherapy and hormonal therapy. In 2011, she developed spontaneous blue breast discolouration. Initial examination revealed global breast firmness, skin thickening and ecchymosis. Despite no evidence of recurrent disease, the patient was scheduled for fortnightly review. This review demonstrated marked worsening discolouration and new nipple areolar complex blood-filled blisters. Despite concurrent antiplatelet therapy as a possible cause, the breast clinician's clinical concern of angiosarcoma led to a skin punch biopsy, revealing only non-specific lymphocytic infiltrate. Interval mammographic assessment demonstrated non-specific architectural distortion. Regardless of these benign findings, a breast MRI was performed demonstrating possible breast angiosarcoma. Ultrasound-guided biopsy demonstrated low-grade breast angiosarcoma. The patient underwent completion mastectomy, for a 150 mm high-grade postradiotherapy angiosarcoma. Annual clinical review and contralateral mammography is planned.}, }
@article {pmid22907775, year = {2013}, author = {Matsukawa, Y and Hattori, R and Sassa, N and Yamamoto, T and Gotoh, M}, title = {What are the factors contributing to failure in improvement of subjective symptoms following silodosin administration in patients with benign prostatic hyperplasia? Investigation using a pressure-flow study.}, journal = {Neurourology and urodynamics}, volume = {32}, number = {3}, pages = {266-270}, doi = {10.1002/nau.22286}, pmid = {22907775}, issn = {1520-6777}, mesh = {Adrenergic alpha-1 Receptor Antagonists/*therapeutic use ; Aged ; Aged, 80 and over ; Humans ; Indoles/*therapeutic use ; Lower Urinary Tract Symptoms/diagnosis/*drug therapy/physiopathology ; Male ; Middle Aged ; Predictive Value of Tests ; Pressure ; Prospective Studies ; Prostatic Hyperplasia/diagnosis/*drug therapy/physiopathology ; Risk Factors ; Surveys and Questionnaires ; Time Factors ; Treatment Failure ; Urinary Bladder/*drug effects/physiopathology ; Urinary Bladder, Overactive/diagnosis/*drug therapy/physiopathology ; Urodynamics/*drug effects ; }, abstract = {AIMS: To investigate the factors responsible for failure in improvement of subjective symptoms following silodosin treatment on the basis of findings of a pressure-flow study (PFS).<br><br>METHODS: A post hoc analysis of a prospective study to investigate the efficacy of silodosin in patients with BPH was conducted, and 104 patients were analyzed. The patients were administered silodosin 8&#x2009;mg/day for 4 weeks. At the baseline and after treatment, subjective symptoms were evaluated using the IPSS and OABSS. A PFS was conducted to measure storage and voiding function. The patients were divided into two groups: good responders (GR), patients with 25% or more improvement in IPSS, and poor responders (PR), <25% improvement. The clinical and objective findings for the two groups were compared.<br><br>RESULTS: The mean IPSS and OABSS significantly improved in GR, but no significant improvement was observed in PR. PFS analysis revealed that all voiding and storage function parameters improved significantly in GR. Although PR showed a significant improvement in the voiding function parameters, it did not show significant changes in the storage function. Involuntary detrusor contraction (IDC) resolved in 68.6% of the patients in GR and in only 30% of the patients in PR, thereby showing a significant difference in the remedial effect between the two groups.<br><br>CONCLUSIONS: The findings suggest that insufficient improvement in storage function is a contributing factor to the failure in improvement of subjective symptoms after silodosin treatment in patients with BPH.}, }
@article {pmid22903146, year = {2012}, author = {Szajnik, M and Szczepanski, MJ and Elishaev, E and Visus, C and Lenzner, D and Zabel, M and Glura, M and DeLeo, AB and Whiteside, TL}, title = {17β Hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma.}, journal = {Gynecologic oncology}, volume = {127}, number = {3}, pages = {587-594}, pmid = {22903146}, issn = {1095-6859}, support = {N01HB37165/HL/NHLBI NIH HHS/United States ; P01 CA109688/CA/NCI NIH HHS/United States ; N01-HB37165/HB/NHLBI NIH HHS/United States ; P0-1-CA109688/CA/NCI NIH HHS/United States ; }, mesh = {17-Hydroxysteroid Dehydrogenases/antagonists &amp; inhibitors/*metabolism ; Apoptosis ; Biomarkers, Tumor/antagonists &amp; inhibitors/*metabolism ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Ovarian Neoplasms/*enzymology/mortality/pathology ; Prognosis ; RNA, Small Interfering/genetics ; }, abstract = {OBJECTIVE: 17β-hydroxysteroid dehydrogenase isoform 12 (HSD17B12) overexpression is associated with poor clinical outcome in invasive ductal carcinoma of the breast. Here, we evaluated HSD17B12 overexpression and its activity in ovarian carcinoma (OvCa) to determine its role in the growth and progression of this tumor.<br><br>METHODS: Immunohistochemical analysis of HSD17B12 expression was performed in 100 tissue samples of untreated OvCa and was correlated with clinicopathologic characteristics and patient outcome. In A2780 OvCa cell line expressing HSD17B12, siRNA knockdown of the enzyme was performed, and its effects on tumor cell growth and Annexin V binding were determined.<br><br>RESULTS: HSD17B12 expression was detected in all tumor samples, but the staining intensity was variable. Normal ovarian epithelium was negative. Patients with tumor showing weak/moderate expression of HSD17B12 had a better overall survival than those with strongly positive tumors (p<0.001). The time to first recurrence was longer for patients with tumors with heterogeneous staining relative to patients with tumors that were uniformly positive (p<0.001). Upon silencing of HSD17B12 in tumor cells, their growth was inhibited (p<0.005) and apoptosis was increased (p<0.05). Arachidonic acid but not estradiol reversed the growth inhibition mediated by HSD17B12 knockdown.<br><br>CONCLUSION: HSD17B12 overexpression is shown to be a marker of poor survival in patients with OvCa. Expression in the tumor and function of this enzyme facilitates OvCa progression.}, }
@article {pmid22897789, year = {2013}, author = {Ling, H and Liu, ZB and Xu, LH and Xu, XL and Liu, GY and Shao, ZM}, title = {Malignant calcification is an important unfavorable prognostic factor in primary invasive breast cancer.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {9}, number = {2}, pages = {139-145}, doi = {10.1111/j.1743-7563.2012.01572.x}, pmid = {22897789}, issn = {1743-7563}, mesh = {Adult ; Aged ; Breast Neoplasms/complications/mortality/*pathology/therapy ; Calcinosis/*diagnosis/etiology ; Carcinoma, Ductal, Breast/complications/mortality/*secondary/therapy ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms/complications/mortality/*secondary/therapy ; Lung Neoplasms/complications/mortality/*secondary/therapy ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {AIMS: To explore the clinical characteristics and prognostic value of malignant calcification in operable breast cancer.<br><br>METHODS: A total of 721 patients with invasive ductal carcinoma were divided into two groups based on whether malignant calcifications were observed on mammograms. The association of calcification with pathological features and survival were evaluated. The relative importance of each of the potential prognostic variables was tested using a Cox regression analysis.<br><br>RESULTS: Compared with tumors without calcification, those with calcification had a larger tumor size, more lymph node involvement, lower estrogen and progesterone receptor expression and higher human epithelial growth factor receptor 2 expression. The 8-year relapse-free survival was lower for patients with calcifications than for those without (77.5 vs 89.2%, P < 0.01). The 8-year overall survival for patients with calcifications was 82.2% compared with 91.9% for those without (P < 0.01). In multivariate analysis, node status, existence of calcification and tumor size were demonstrated to have a prognostic value for relapse-free survival. The node status, existence of calcifications and estrogen receptor status were also prognostic factors for overall survival.<br><br>CONCLUSION: Mammographic calcification is a poor prognostic factor for patients with invasive ductal carcinoma. Its prognostic value is second only to axillary node status and greater than the other factors evaluated. Thus, breast cancers with calcifications should be regarded as high risk when determining adjuvant treatment.}, }
@article {pmid22895267, year = {2012}, author = {Duan, X and Sneige, N and Gullett, AE and Prieto, VG and Resetkova, E and Andino, LM and Wu, Y and Gilcrease, MZ and Bedrosian, I and Dawood, S and Arun, B and Albarracin, CT}, title = {Invasive paget disease of the breast: clinicopathologic study of an underrecognized entity in the breast.}, journal = {The American journal of surgical pathology}, volume = {36}, number = {9}, pages = {1353-1358}, doi = {10.1097/PAS.0b013e318259ef7f}, pmid = {22895267}, issn = {1532-0979}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/therapy ; Carcinoma, Ductal, Breast/*diagnosis/secondary/therapy ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/secondary ; Combined Modality Therapy ; Dermis/pathology ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Paget's Disease, Mammary/*diagnosis/therapy ; Treatment Outcome ; }, abstract = {Mammary Paget disease (MPD) is considered an intraepidermal manifestation of an underlying mammary carcinoma. In contrast to extramammary Paget disease, invasion of mammary Paget cells into the dermis (invMPD) has not been reported, except for 2 cases described in Rosen's textbook. Our study was designed to identify the presence of dermal invasion of mammary Paget cells and characterize the associated clinicopathologic features. Slides from 146 MPD patients were retrieved. Six cases of invMPD were identified. One case of invMPD was not associated with an underlying breast cancer, 1 was associated with invasive ductal carcinoma (IDC), 1 with ductal carcinoma in situ (DCIS) with microinvasion, and 3 with DCIS only. The underlying breast carcinomas was separate from the area of invMPD. The depth of invasion, measured from the dermal-epidermal junction to the focus of deepest invasion, ranged from 0.02 to 0.9 mm. The horizontal extent ranged from 0.01 to 4.0 mm. Lymph node with isolated tumor clusters was present in case 1, which had no underlying carcinoma but had the greatest extent of invasion, and in case 3, which had DCIS with microinvasion. One patient (case 1) died of unrelated causes 2 years later, and the remaining patients were alive without disease at last follow-up. In summary, we describe 6 cases of MPD with invasion of Paget cells into the dermis and provide histopathologic criteria for the diagnosis of this rare and underrecognized entity. Further studies are required to determine whether invasion in MPD has clinical significance.}, }
@article {pmid22894137, year = {2012}, author = {dos Santos, PB and Zanetti, JS and Ribeiro-Silva, A and Beltrão, EI}, title = {Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {104}, pmid = {22894137}, issn = {1746-1596}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*chemistry/mortality/secondary/therapy ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/mortality/secondary/therapy ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Integrin beta1/*analysis ; Kaplan-Meier Estimate ; Middle Aged ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Time Factors ; Tissue Array Analysis ; Up-Regulation ; Vascular Endothelial Growth Factor A/analysis ; }, abstract = {BACKGROUND: The main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, β1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of β1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC). In addition, we compared the expression of β1 integrin in patients with ductal carcinoma in situ (DCIS).<br><br>METHODS: Through tissue microarray (TMA) slides containing 225 samples of IDC and 67 samples of DCIS, &#x3b2;1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance.<br><br>RESULTS: &#x3b2;1 integrin was overexpressed in 32.8% of IDC. In IDC, &#x3b2;1 integrin was related with HER-2 (p&#x2009;=&#x2009;0.019) and VEGF (p&#x2009;=&#x2009;0.011) expression and it had a significant relationship with metastasis and death (p&#x2009;=&#x2009;0.001 and p&#x2009;=&#x2009;0.05, respectively). Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p&#x2009;=&#x2009;0.002) in specific survival (number of months between diagnosis and death caused by the disease). There were no correlation between IDC and DCIS (p&#x2009;=&#x2009;0.559) regarding &#x3b2;1 integrin expression.<br><br>CONCLUSIONS: Considering that the expression of &#x3b2;1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that &#x3b2;1 integrin can be a marker of poor prognosis in breast cancer.<br><br>VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6652215267393871.}, }
@article {pmid22891313, year = {2012}, author = {Tanaka, H and Abe, S and Huda, N and Tu, L and Beam, MJ and Grimes, B and Gilley, D}, title = {Telomere fusions in early human breast carcinoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {35}, pages = {14098-14103}, pmid = {22891313}, issn = {1091-6490}, mesh = {Breast/cytology ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Female ; Fibroblasts/cytology ; Foreskin/cytology ; Gene Expression Regulation, Neoplastic/*genetics ; Genomic Instability/genetics ; Humans ; Male ; Neoplasm Staging ; Retroelements/*genetics ; Telomerase/genetics ; Telomere/*genetics ; Tissue Banks ; }, abstract = {Several lines of evidence suggest that defects in telomere maintenance play a significant role in the initiation of genomic instability during carcinogenesis. Although the general concept of defective telomere maintenance initiating genomic instability has been acknowledged, there remains a critical gap in the direct evidence of telomere dysfunction in human solid tumors. To address this topic, we devised a multiplex PCR-based assay, termed TAR (telomere-associated repeat) fusion PCR, to detect and analyze chromosome end-to-end associations (telomere fusions) within human breast tumor tissue. Using TAR fusion PCR, we found that human breast lesions, but not normal breast tissues from healthy volunteers, contained telomere fusions. Telomere fusions were detected at similar frequencies during early ductal carcinoma in situ and in the later invasive ductal carcinoma stage. Our results provide direct evidence that telomere fusions are present in human breast tumor tissue and suggest that telomere dysfunction may be an important component of the genomic instability observed in this cancer. Development of this robust method that allows identification of these genetic aberrations (telomere fusions) is anticipated to be a valuable tool for dissecting mechanisms of telomere dysfunction.}, }
@article {pmid22888636, year = {2012}, author = {Davalieva, K and Kiprijanovska, S and Broussard, C and Petrusevska, G and Efremov, GD}, title = {Proteomic analysis of infiltrating ductal carcinoma tissues by coupled 2-D DIGE/MS/MS analysis.}, journal = {Molekuliarnaia biologiia}, volume = {46}, number = {3}, pages = {469-480}, pmid = {22888636}, issn = {0026-8984}, mesh = {Aged ; Biomarkers, Tumor/*genetics ; *Breast Neoplasms/diagnosis/genetics/pathology ; *Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Electrophoresis, Gel, Two-Dimensional ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Hydrogen-Ion Concentration ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*genetics ; Protein Interaction Mapping ; Proteome/*analysis/genetics ; Proteomics ; Tandem Mass Spectrometry ; }, abstract = {There is a growing interest in protein expression profiling aiming to identify novel diagnostic markers in breast cancer. Proteomic approaches such as two-dimensional differential gel electrophoresis coupled with tandem mass spectrometry analysis (2-D DIGE/MS/MS) have been used successfully for the identification of candidate biomarkers for screening, diagnosis, prognosis and monitoring of treatment response in various types of cancer. Identifying previously unknown proteins of potential clinical relevance will ultimately help in reaching effective ways to manage the disease. We analyzed breast cancer tissues from five tumor and five normal tissue samples from ten breast cancer subjects with infiltrating ductal carcinoma (IDC) by 2-D DIGE using two types of immobilized pH gradient (IPG) strips: pH 3-10 and pH 4-7. From all the spots detected, differentially expressed (p < 0.05 and ratio > 2) were 50 spots. Of these, 39 proteins were successfully identified by MS, representing 29 different proteins. Ten proteins were overexpressed in the tumor samples. The 2-D DIGE/MS/MS analysis revealed an increase in the expression levels in tumor samples of several proteins not previously associated with breast cancer, such as: macrophage-capping protein (CAPG), phosphomannomutase 2 (PMM2), ATPase ASN1, methylthioribose-1-phosphate isomerase (MRI1), peptidyl-prolyl cis-trans isomerase FKBP4, cellular retinoic acid-binding protein 2 (CRABP2), lamin B1 and keratin, type II cytoskeletal 8 (KRT8). Ingenuity Pathway Analysis (IPA) revealed highly significant (p = 10(-26)) interactions between the identified proteins and their association with cancer. These proteins are involved in many diverse pathways and have established roles in cellular metabolism. It remains the goal of future work to test the suitability of the identified proteins in samples of larger and independent patient groups.}, }
@article {pmid22887771, year = {2012}, author = {Liao, S and Desouki, MM and Gaile, DP and Shepherd, L and Nowak, NJ and Conroy, J and Barry, WT and Geradts, J}, title = {Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast.}, journal = {Genes, chromosomes &amp; cancer}, volume = {51}, number = {12}, pages = {1067-1078}, pmid = {22887771}, issn = {1098-2264}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; R21 CA106676/CA/NCI NIH HHS/United States ; 5P30CA016056-34/CA/NCI NIH HHS/United States ; R21CA106676/CA/NCI NIH HHS/United States ; }, mesh = {Breast/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Comparative Genomic Hybridization ; *DNA Copy Number Variations ; Disease Progression ; Female ; Humans ; }, abstract = {Only a minority of intraductal carcinomas of the breast give rise to stromally invasive disease. We microdissected 206 paraffin blocks representing 116 different cases of low-grade ductal carcinoma in situ (DCIS). Fifty-five were pure DCIS (PD) cases without progression to invasive carcinoma. Sixty-one cases had a small invasive component. DNA was extracted from microdissected sections and hybridized to high-density bacterial artificial chromosome arrays. Array comparative genomic hybridization analysis of 118 hybridized DNA samples yielded data on 69 samples that were suitable for further statistical analysis. This cohort included 20 pure DCIS cases, 25 mixed DCIS (MD), and 24 mixed invasive carcinoma samples. PD cases had a higher frequency of DNA copy number changes than MD cases, and the latter had similar DNA profiles compared to paired invasive carcinomas. Copy number changes on 13 chromosomal arms occurred at different rates in PD versus MD lesions. Eight of 19 candidate genes residing at those loci were confirmed to have differential copy number changes by quantitative PCR. NCOR2/SMRT and NR4A1 (both on 12q), DYNLRB2 (16q), CELSR1, UPK3A, and ST13 (all on 22q) were more frequently amplified in PD. Moreover, NCOR2, NR4A1, and DYNLRB2 showed more frequent copy number losses in MD. GRAP2 (22q) was more often amplified in MD, whereas TAF1C (16q) was more commonly deleted in PD. A multigene model comprising these candidate genes discriminated between PD and MD lesions with high accuracy. These findings suggest that the propensity to invade the stroma may be encoded in the genome of intraductal carcinomas.}, }
@article {pmid22886719, year = {2013}, author = {Siegfried, JD and Morales, A and Kushner, JD and Burkett, E and Cowan, J and Mauro, AC and Huggins, GS and Li, D and Norton, N and Hershberger, RE}, title = {Return of genetic results in the familial dilated cardiomyopathy research project.}, journal = {Journal of genetic counseling}, volume = {22}, number = {2}, pages = {164-174}, pmid = {22886719}, issn = {1573-3599}, support = {R01 HL058626/HL/NHLBI NIH HHS/United States ; R01-HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Cardiomyopathy, Dilated/*genetics ; Genetic Counseling ; *Genetic Predisposition to Disease ; Genetic Testing ; Humans ; United States ; }, abstract = {The goal of the Familial Dilated Cardiomyopathy (FDC) Research Project, initiated in 1993, has been to identify and characterize FDC genetic cause. All participating individuals have been consented for the return of genetic results, an important but challenging undertaking. Since the inception of the Project we have enrolled 606 probands, and 269 of these had 1670 family members also enrolled. Each subject was evaluated for idiopathic dilated cardiomyopathy (IDC) and pedigrees were categorized as familial or sporadic. The coding regions of 14 genes were resequenced in 311 to 324 probands in five studies. Ninety-two probands were found to carry nonsynonymous rare variants absent in controls, and with Clinical Laboratory Improvement Amendment of 1988 (CLIA) compliant protocols, relevant genetic results were returned to these probands and their consented relatives by study genetic counselors and physicians in 353 letters. In 10 of the 51 families that received results >1 year ago, at least 23 individuals underwent CLIA confirmation testing for their family's rare variant. Return of genetic results has been successfully undertaken in the FDC Research Project. This report describes the methods utilized in the process of returning research results. We use this information as a springboard for providing guidance to other genetic research groups and proposing future directions in this arena.}, }
@article {pmid22883666, year = {2012}, author = {Ying, JM and Liu, XY and Guo, L and Xie, YQ and Lü, N}, title = {[Analysis of HER2 status in breast carcinoma using fully automated HER2 staining and fluorescence in-situ hybridization technology].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {41}, number = {5}, pages = {296-300}, doi = {10.3760/cma.j.issn.0529-5807.2012.05.003}, pmid = {22883666}, issn = {0529-5807}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Breast Neoplasms/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Female ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Prospective Studies ; Quality Control ; Receptor, ErbB-2/*genetics ; Young Adult ; }, abstract = {OBJECTIVE: To determine human epidermal growth factor receptor 2 (HER2) status in breast carcinoma by the techniques of a fully automated immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), to compare the concordance of protein expression with gene amplification and to explore the optimization in process quality control.<br><br>METHODS: A prospective study of invasive breast cancer specimens excised between May 2009 and April 2011 at the Cancer Hospital, Chinese Academy of Medical Sciences was conducted by automated IHC staining with the new 4B5 rabbit monoclonal antibody and FISH. An evaluation was performed according to the ASCO/CAP guidelines (2007) and Chinese guidelines (2009). The gene amplification status of 740 cases were detected by FISH.<br><br>RESULTS: A total of 2420 cases of breast invasive ductal carcinoma without pre-operation therapy were tested by automated IHC. 551 cases (22.8%) were scored as positive (3+), 664 cases (27.4%) as equivocal (2+), and 1205 cases (49.8%) as negative (1+/0). Gene amplification was detected in 98.0% (242/247) HER2 protein expression positive (3+) cases and in 13.6% (53/389) equivocal (2+) cases. One of 247 (0.4%) HER2 expression 3+ cases and 5 of 389 (1.3%) HER2 expression 2+ cases were equivocal for gene amplification. No gene amplification was detected in expression negative (1+/0) cases by FISH (0/104). The overall concordance between IHC and FISH was 98.6% [(242 + 104)/(247 + 104)].<br><br>CONCLUSIONS: There is a high concordance rate between automated IHC with 4B5 rabbit monoclonal antibody and FISH results for assessing the HER2 gene amplification status in surgically-excised breast cancer specimens, suggesting that automated IHC with 4B5 antibody can provide a reliable method to detect HER2 overexpression for eligibility of HER2 targeted therapy.}, }
@article {pmid22877570, year = {2013}, author = {Ergül, N and Kadıoğlu, H and S Yıldız,  and Başkaya Yücel, S and Aydın, M}, title = {Autoamputation of breast caused by invasive ductal carcinoma.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {32}, number = {3}, pages = {199-200}, doi = {10.1016/j.remn.2012.06.005}, pmid = {22877570}, issn = {2253-8070}, mesh = {Breast Neoplasms/complications/*pathology ; Carcinoma, Ductal, Breast/complications/*pathology ; Female ; Humans ; Middle Aged ; }, }
@article {pmid22864797, year = {2012}, author = {Cheng, CW and Liu, YF and Yu, JC and Wang, HW and Ding, SL and Hsiung, CN and Hsu, HM and Shieh, JC and Wu, PE and Shen, CY}, title = {Prognostic significance of cyclin D1, β-catenin, and MTA1 in patients with invasive ductal carcinoma of the breast.}, journal = {Annals of surgical oncology}, volume = {19}, number = {13}, pages = {4129-4139}, doi = {10.1245/s10434-012-2541-x}, pmid = {22864797}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Cyclin D1/genetics/*metabolism ; Female ; Follow-Up Studies ; Histone Deacetylases/genetics/*metabolism ; Humans ; Immunoenzyme Techniques ; Laser Capture Microdissection ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Repressor Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Trans-Activators ; beta Catenin/genetics/*metabolism ; }, abstract = {BACKGROUND: To investigate markers for predicting breast cancer progression, we performed a candidate gene-based study that assessed expression change of three genes, cyclin D1, β-catenin, and metastasis-associated protein-1 (MTA1), involving in aggressive phenotypes of cancerous cells, namely hyperproliferation, epithelial-mesenchymal transition, and global transcriptional regulation.<br><br>METHODS: Specimens were from 150 enrolled female patients, with invasive ductal carcinoma, followed up for more than 10 years. mRNA expression of cyclin D1, &#x3b2;-catenin, and MTA1 in cancerous and noncancerous cells microdissected from the primary tumor site was determined by quantitative real-time PCR. The relationship between mRNA expression levels of the genes and clinicopathologic features was assessed by statistical analysis. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan-Meier analysis with log-rank test and a multivariate Cox regression model.<br><br>RESULTS: Cyclin D1 was shown to be overexpressed in late-stage breast cancer (stage III/IV). Breast cancer with lymph node metastasis (LNM) showed significantly higher frequency of overexpressed cyclin D1, &#x3b2;-catenin, and MTA1 (P < 0.05). Patients carrying greater numbers of overexpressed genes had joint effects on increased risk in tumors of advanced stages (P (trend) = 0.03) and LNM (P (trend) < 0.01). In the LNM-negative group, patients whose tumors with greater number of cyclin D1, &#x3b2;-catenin, and MTA1 overexpressions were associated with poorer clinical outcomes, with hazard ratio of 14.79 for OS (P = 0.015) and 7.54 for DFS (P = 0.015) using multivariate Cox regression analysis during the 10-year follow-up.<br><br>CONCLUSIONS: Higher expression of cyclin D1, &#x3b2;-catenin, and MTA1 mRNAs in breast cancers may prove effective in predicting unfavorable outcomes of breast cancer.}, }
@article {pmid22862431, year = {2012}, author = {Matsumoto, K and Tanaka, H and Tatsumi, K and Kaneko, A and Tsuji, T and Ryo, K and Kawai, H and Hirata, K}, title = {Regional heterogeneity of systolic dysfunction is associated with ventricular dyssynchrony in patients with idiopathic dilated cardiomyopathy and narrow QRS complex.}, journal = {Echocardiography (Mount Kisco, N.Y.)}, volume = {29}, number = {10}, pages = {1201-1210}, doi = {10.1111/j.1540-8175.2012.01791.x}, pmid = {22862431}, issn = {1540-8175}, mesh = {Cardiomyopathy, Dilated/complications/diagnostic imaging/*physiopathology ; Echocardiography, Three-Dimensional/*methods ; *Electrocardiography ; Female ; Follow-Up Studies ; Heart Ventricles/diagnostic imaging/*physiopathology ; Humans ; Male ; Middle Aged ; Stroke Volume ; Systole ; Ventricular Dysfunction, Left/diagnostic imaging/etiology/*physiopathology ; Ventricular Function, Left/*physiology ; }, abstract = {BACKGROUND: Regional heterogeneity of left ventricular (LV) contraction, known as dyssynergy, in idiopathic dilated cardiomyopathy (IDC) patients has been previously reported, but no comprehensive analysis of this abnormality has been made. The purpose of this study was to test the hypothesis that regional heterogeneity of systolic dysfunction is associated with LV dyssynchrony in IDC patients with a narrow QRS complex using novel three-dimensional (3D) speckle-tracking strain.<br><br>METHODS: We studied 54 consecutive IDC patients with ejection fraction (EF) of 34 &#xb1; 12% and QRS duration of 102 &#xb1; 13 msec (all <120 msec), and 30 age-matched normal controls. The 3D speckle-tracking LV dyssynchrony (LV dyssynchrony index) was quantified from all 16 LV sites to determine the standard deviation (SD) of time-to-peak strain. Similarly, regional heterogeneity of LV systolic function (LV dyssynergy index) was quantified from all 16 LV sites to establish the SD of peak 3D speckle-tracking strain.<br><br>RESULTS: The LV dyssynergy and dyssynchrony indices of IDC patients were significantly larger than those of normal controls. Furthermore, IDC patients showed significantly higher Z-scores for septum and inferior regions than for the free wall (3.34 &#xb1; 1.21 vs. 1.69 &#xb1; 1.06 and 2.79 &#xb1; 1.30 vs. 1.69 &#xb1; 1.06, respectively, P < 0.001). An important findings of multivariable analysis was that the LV dyssynergy index (&#x3b2; = 0.69, P < 0.001) and LVEF (&#x3b2; = -0.34, P = 0.001) were independent determinants of the LV dyssynchrony index.<br><br>CONCLUSION: 3D speckle-tracking strain revealed that the myocardial systolic dysfunction of IDC patients with a narrow QRS complex has a marked heterogeneous regional distribution. This regional heterogeneity as well as systolic dysfunction is thought to lead to LV dyssynchrony.}, }
@article {pmid25083433, year = {2012}, author = {Niu, L and Zhou, L and Xu, K}, title = {Cryosurgery of breast cancer.}, journal = {Gland surgery}, volume = {1}, number = {2}, pages = {111-118}, pmid = {25083433}, issn = {2227-684X}, abstract = {With recent improvements in breast imaging, the ability to identify small breast tumors is markedly improved, prompting significant interest in the use of cryoablation without surgical excision to treat early-stage breast cancer. The cryoablation is often performed using ultrasound-guided tabletop argon-gas-based cryoablation system with a double freeze/thaw cycle. Recent studies have demonstrated that, as a primary therapy for small breast cancer, cryoablation is safe and effective with durable results, and can successfully destroy all cancers <1.0 cm and tumors between 1.0 and 1.5 cm without a significant ductal carcinoma-in-situ (DCIS) component. Presence of noncalcified DCIS is the cause of most cryoablation failures. At this time, cryoablation should be limited to patients with invasive ductal carcinoma <1.5 cm and with <25% DCIS in the core biopsy. For unresectable advanced breast cancer, cryoablation is a palliation modality and may be used as complementary for subsequent resection or other therapies.}, }
@article {pmid22842170, year = {2012}, author = {Ranade, KJ and Nerurkar, AV and Phulpagar, MD and Shirsat, NV}, title = {Myoepithelial expression of Fas and strong nuclear expression of FasL in epithelial cells: a marker for risk stratification of breast cancer.}, journal = {Indian journal of cancer}, volume = {49}, number = {1}, pages = {60-65}, doi = {10.4103/0019-509X.98921}, pmid = {22842170}, issn = {1998-4774}, mesh = {Adolescent ; Adult ; Apoptosis ; *Breast Neoplasms/genetics/metabolism/pathology ; Epithelium/metabolism ; *Fas Ligand Protein/genetics/metabolism ; Female ; *Fibroadenoma/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Muscle Cells/metabolism ; Retrospective Studies ; Risk Factors ; *fas Receptor/genetics/metabolism ; }, abstract = {AIM: The clinical significance of Fas and FasL in hormone-sensitive carcinomas has been reported. Our objective was to evaluate the expression of apoptosis-regulating genes Fas and FasL in Indian breast cancer and fibroadenoma patients in relation to hormone receptor status.<br><br>STUDY DESIGN: Retrospective.<br><br>MATERIALS AND METHODS: Paraffin-embedded tissue samples from 63 untreated female patients with invasive ductal carcinoma (IDC) and 32 female patients with fibroadenoma were studied. Expression of Fas and FasL was evaluated using immunohistochemical staining method.<br><br>STATISTICAL ANALYSIS: Fisher's exact test and nonparametric correlation test (Spearman rank correlation test) were performed.<br><br>RESULT: Fas was detected in 97% of the fibroadenomas and there was a slight decrease in levels of expression with histological grades of IDC. The expression of FasL was detected in 75% fibroadenomas and its expression increased in IDC. There was no correlation between Fas, FasL expression and hormone receptor status. Strong expression of Fas in myoepithelial cells was noted in 12 out of 32 fibroadenoma cases.<br><br>CONCLUSION: Expression of Fas and FasL alone is unlikely to be important as a predictive factor as they express in both normal and malignant breast epithelium. But strong expression of Fas in myoepithelial cells along with strong nuclear expression of FasL in epithelial cells of fibroadenoma could be useful as an early predictive factor for onset of malignancy.}, }
@article {pmid22824957, year = {2012}, author = {Liu, Z and Wang, Y and Wang, S and Zhang, J and Zhang, F and Niu, Y}, title = {Nek2C functions as a tumor promoter in human breast tumorigenesis.}, journal = {International journal of molecular medicine}, volume = {30}, number = {4}, pages = {775-782}, doi = {10.3892/ijmm.2012.1069}, pmid = {22824957}, issn = {1791-244X}, mesh = {Breast/metabolism/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics ; Cell Line, Tumor ; Cell Movement ; Cell Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia/*genetics ; NIMA-Related Kinases ; Protein Serine-Threonine Kinases/*genetics ; RNA Interference ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Up-Regulation ; }, abstract = {The serine⁄threonine kinase Nek2 has been proposed as a requirement for the progression of breast cancer. The aim of this study was to investigate the expression of Nek2C, which is a splice variant of Nek2, and the role it plays in the different stages of breast cancer. We investigated the role of Nek2C in the MCF10 breast cancer cell lines, MCF10A, MCF10AT, MCF10DCIS.com and MCF10CA1a, using RNA interference and plasmid transfection, as well as breast tissue samples of normal breast tissue (NBT), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). We detected the mRNA Nek2C expression levels in the MCF10 cell lines and in human breast samples. Our results revealed that the mRNA expression of Nek2C was significantly upregulated in the MCF10DCIS.com and MCF10CA1a cell lines as well as in human primary breast cancer tissue (DCIS and IDC). As expected, the Nek2C downregulation, using RNA interference, decreased the survival, invasion and migration of MCF10DCIS.com and MCF10CA1a cells. Consistent with these results, the Nek2C upregulation in MCF10A and MCF10AT cells using plasmid transfection increased the survival ability of these cells. Our results also revealed a correlation between Nek2C mRNA expression levels and tumor grade. Taken together, our findings suggest that Nek2C plays a signicficant role in breast cancer development and that Nek2C inhibition may be a useful therapeutic approach to targeting human breast tumors.}, }
@article {pmid22819916, year = {2012}, author = {Nanashima, A and Shibata, K and Nakayama, T and Abo, T and Nonaka, T and Fukuda, D and Fukuoka, H and Hidaka, S and Takeshita, H and Sawai, T and Yasutake, T and Nagayasu, T}, title = {Relationship between microvessel count and clinicopathological characteristics and postoperative survival in patients with pancreatic carcinoma.}, journal = {Hepato-gastroenterology}, volume = {59}, number = {118}, pages = {1964-1969}, doi = {10.5754/hge10618}, pmid = {22819916}, issn = {0172-6390}, mesh = {Antigens, CD34/analysis ; Disease-Free Survival ; Female ; Gastrostomy ; Humans ; Immunohistochemistry ; Japan ; Kaplan-Meier Estimate ; Male ; Microvessels/immunology/*pathology ; Middle Aged ; Multivariate Analysis ; *Pancreatectomy/adverse effects/methods/mortality ; Pancreatic Neoplasms/*blood supply/mortality/pathology/*surgery ; Pancreaticoduodenectomy ; Pancreaticojejunostomy ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: The present study aimed to elucidate the relationship between microvessel count (MVC) according to CD34 expression and clinicopathological characteristics or prognosis in pancreatic carcinoma (PC) patients who underwent hepatectomy.<br><br>METHODOLOGY: CD34 expression was analyzed using immunohistochemical methods. Mean MVC in 5 areas per specimen and clinicopathological factors were consecutively examined in 42 PC patients.<br><br>RESULTS: Median MVC for PC patients was 123/mm2, which was applied as a cut-off value. Higher MVC was significantly associated with the advanced Japanese tumor-node-metastasis stage IVa and IVb (p=0.034). Univariate survival analysis identified higher carcinoembryonic antigen (CEA) and CA19-9 level, infiltrative type on macroscopic examination, invasive ductal carcinoma, node metastasis and higher tumor-node-metastasis classification were significantly associated with poor survival. The 5-year overall survival rate in the higher MVC group tended to be lower than that in the higher MVC group (37 vs. 55%), but not statistically significant (p=0.15).<br><br>CONCLUSIONS: Tumor MVC might be a candidate prognostic marker of PC patient survival after pancreatectomy and further investigation in a larger series is warranted to clarify the significance of this marker.}, }
@article {pmid22811748, year = {2012}, author = {Santos Araújo, Mdo C and Farias, IL and Gutierres, J and Dalmora, SL and Flores, N and Farias, J and de Cruz, I and Chiesa, J and Morsch, VM and Chitolina Schetinger, MR}, title = {Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2012}, number = {}, pages = {676984}, pmid = {22811748}, issn = {1741-4288}, abstract = {Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.}, }
@article {pmid22810087, year = {2012}, author = {Kwast, AB and Groothuis-Oudshoorn, KC and Grandjean, I and Ho, VK and Voogd, AC and Menke-Pluymers, MB and van der Sangen, MJ and Tjan-Heijnen, VC and Kiemeney, LA and Siesling, S}, title = {Histological type is not an independent prognostic factor for the risk pattern of breast cancer recurrences.}, journal = {Breast cancer research and treatment}, volume = {135}, number = {1}, pages = {271-280}, doi = {10.1007/s10549-012-2160-z}, pmid = {22810087}, issn = {1573-7217}, mesh = {Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Disease-Free Survival ; Female ; Humans ; *Neoplasm Metastasis ; *Neoplasm Recurrence, Local ; Netherlands ; Receptors, Estrogen/metabolism ; Receptors, Progesterone ; Risk Factors ; }, abstract = {Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC) and appears to have a distinct biology. Inconsistent findings regarding disease-free survival (DFS) are probably due to the fact that histologic type is related to hormone receptor status. This study aims to determine whether the type of the primary breast cancer histology is an independent prognostic factor for DFS, the risk pattern of loco-regional recurrences and distant metastases (DM), and whether it is a prognostic factor for the site of DM. All Dutch women diagnosed between 2003 and 2005 with ILC (n = 2,949) or IDC (n = 22,378) were selected from the Netherlands Cancer Registry. DFS was assessed using proportional hazard regression analysis. Compared to patients with IDC, those with ILC were significantly older and more likely to have more than three positive lymph nodes and have larger, better differentiated, more multifocal, and hormone receptor positive tumors (all P < 0.001). ILC was more likely to metastasize to the gastrointestinal organs and bones and less likely to the lung, central nervous system, and lymph nodes. Within the ER+PR+ and ER+PR- subgroups ILC was still more likely to metastasize to gastrointestinal organs and less likely to the lung. The timing of recurrence was correlated to hormone receptor status, independent of histological type. Highest risks were observed among ER-PR- patients within 2 years of surgery. Multivariable analysis showed that histological type is not an independent significant prognostic factor of DFS for the first 3 years post-surgery and thereafter (<3 years HR 0.91, 95 % CI 0.78-1.06, >3 years HR 1.07, 95 % CI 0.88-1.30). Histological type should not be considered an important prognostic factor for the risk and risk pattern of recurrences.}, }
@article {pmid22808818, year = {2011}, author = {Pudasaini, S and Talwar, OP}, title = {Study of fine needle aspiration cytology of breast lumps and its histopathological correlation in Pokhara Valley.}, journal = {Nepal Medical College journal : NMCJ}, volume = {13}, number = {3}, pages = {208-212}, pmid = {22808818}, issn = {2676-1319}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Cohort Studies ; Female ; Humans ; Middle Aged ; Nepal ; Sensitivity and Specificity ; Young Adult ; }, abstract = {Breast carcinoma is the leading cause of cancer death in women. Most of the time breast carcinoma presents as breast lump. Fine Needle Aspiration Cytology (FNAC) is a convenient and rapid preoperative diagnostic procedure. This is a prospective and correlative study done in department of Pathology of Manipal Teaching Hospital, Pokhara from December 2003 to December 2005. FNAC was performed in patients presenting with breast lump and its findings were correlated with histopathological findings. Out of total 343 cases of breast FNAC, 73 cases had histopathology correlation. Age group of the patient ranged from 17 to 84 years. Breast lumps were most commonly seen in age group 21 to 30 years which comprises of benign lesions. Maximum number of malignancy (26%) was seen in age group 41 to 50 years. Out of 73 cases, malignancy was seen in 15 cases (20.5%). The most common carcinoma was Invasive Ductal Carcinoma (IDC) with 46.7% cases. With correlation of FNAC and histopathology, the sensitivity and specificity of both benign and malignant lesions were high. In malignant lesions, the sensitivity and specificity were 93.3% and 100% respectively. FNAC is a safe diagnostic procedure in the preoperative diagnosis of breast lumps in our setting. It gives the accurate result with proper technique and interpretation.}, }
@article {pmid22797464, year = {2013}, author = {Yoo, EH and Kim, D}, title = {Predictors of postoperative antimuscarinics in women with mixed urinary incontinence after transobturator surgery.}, journal = {International urogynecology journal}, volume = {24}, number = {3}, pages = {401-406}, pmid = {22797464}, issn = {1433-3023}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Follow-Up Studies ; *Gynecologic Surgical Procedures ; Humans ; Incidence ; Middle Aged ; Muscarinic Antagonists/pharmacology/*therapeutic use ; Postoperative Period ; Retrospective Studies ; Risk Factors ; *Suburethral Slings ; Urinary Bladder, Overactive/physiopathology/*surgery ; Urinary Incontinence/physiopathology/*surgery ; Urodynamics/drug effects/physiology ; }, abstract = {INTRODUCTION AND HYPOTHESIS: The study sought to identify the risk factors of postoperative use of antimuscarinics after transobturator surgery in women with mixed urinary incontinence (MUI) displaying both urodynamic stress urinary incontinence (SUI) and involuntary detrusor contraction (IDC) with leakage in urodynamic study.<br><br>METHODS: The clinical data of 103 patients with MUI who underwent transobturator tape (TOT) sling surgery were retrospectively reviewed. The patients were followed at least a year. To determine risk factors for postoperative use of antimuscarinics, variables of only those with P values < 0.05 on univariate analysis were included in the multivariate logistic regression analysis with forward stepwise building.<br><br>RESULTS: Eight-four (81.6 %) of 103 patients were included in this study. The cure rate of urge urinary incontinence (UUI) was 69.0 % (58/84). Antimuscarinics were prescribed postoperatively in 22 (26.2 %) of 84 patients. Variables affecting postoperative use of antimuscarinics were age, parity, episode of any UUI, preoperative use of antimuscarinics, predominant urgency incontinence type, detrusor pressure at maximum flow, and Urogenital Distress Inventory 6. Increasing age and preoperative use of antimuscarinics increased the odds of postoperative use of antimuscarinics following TOT surgery.<br><br>CONCLUSION: Patients who were older and had taken antimuscarinics preoperatively were significantly associated with postoperative use of antimuscarinics.}, }
@article {pmid22789011, year = {2012}, author = {Ruan, JW and Liao, YC and Lua, I and Li, MH and Hsu, CY and Chen, JH}, title = {Human pituitary tumor-transforming gene 1 overexpression reinforces oncogene-induced senescence through CXCR2/p21 signaling in breast cancer cells.}, journal = {Breast cancer research : BCR}, volume = {14}, number = {4}, pages = {R106}, pmid = {22789011}, issn = {1465-542X}, mesh = {Breast Neoplasms/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Cellular Senescence/genetics ; Epithelial Cells/metabolism ; Female ; *Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Ligands ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Phenotype ; Proto-Oncogene Proteins p21(ras)/genetics/*metabolism ; Receptors, Interleukin-8B/*metabolism ; Securin/*genetics ; *Signal Transduction ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {INTRODUCTION: hPTTG1 (human pituitary tumor-transforming gene 1) is an oncogene overexpressed in breast cancer and several other types of cancer. Increased hPTTG1 expression has been shown to be associated with poor patient outcomes in breast cancer. Although hPTTG1 overexpression plays important roles in promoting the proliferation, invasion, and metastasis of cancer cells, it also has been suggested to induce cellular senescence. Deciphering the mechanism by which hPTTG1 overexpression induces these contradictory actions in breast cancer cells is critical to our understanding of the role of hPTTG1 in breast cancer development.<br><br>METHODS: MCF-10A and MCF-7 cells were used to identify the mechanism of hPTTG1-induced senescence. The interplay between hPTTG1 overexpression and chemokine C-X-C motif receptor 2 (CXCR2)/p21-dependent senescence in tumor growth and metastasis of MCF-7 cells was investigated by orthotopic transplantation of severe combined immunodeficiency (SCID) mice. Additionally, human invasive ductal carcinoma (IDC) tissue arrays were used to confirm the hPTTG1/CXCR2/p21 axis established in vitro.<br><br>RESULTS: In this study, we investigated the mechanism of hPTTG1-induced senescence as well as its role in breast cancer progression and metastasis. Herein, we showed that hPTTG1 overexpression reinforced senescence through the CXCR2/p21 signaling. Furthermore, hPTTG1 overexpression activated NF-&#x3ba;B signaling to transactivate the expression of interleukin (IL)-8 and growth-regulated oncogene alpha (GRO&#x3b1;) to execute CXCR2 signaling in MCF-7 cells. When CXCR2 expression was knocked down in hPTTG1-overexpressing MCF-7 cells, hPTTG1-induced senescence was abrogated by alleviating CXCR2-induced p21 expression. In a mouse model, CXCR2-mediated senescence limited hPTTG1-induced tumor growth and metastasis. Moreover, CXCR2 knockdown in hPTTG1-overexpressing MCF-7 tumors dramatically accelerated tumor growth and metastasis. Our in vitro and in vivo results demonstrated that hPTTG1 overexpression reinforces senescence through CXCR2 signaling, and the evasion of CXCR2/p21-dependent senescence was critical to hPTTG1 exerting its oncogenic potential. Interestingly, although CXCR2-dependent senescence restrained hPTTG1-induced tumor progression, when MCF-7 cells and hPTTG1-overexpressing MCF-7 cells were co-transplanted into the mammary fat pads of SCID mice, hPTTG1-overexpressing senescent cells created a metastasis-promoting microenvironment that promoted lung metastasis of the MCF-7 cells. Immunohistochemical analysis of human breast tumor samples also confirmed the importance of the hPTTG1/CXCR2 axis in promoting breast cancer metastasis.<br><br>CONCLUSIONS: Our findings provide novel molecular insights into hPTTG1-induced senescence and identify a novel mechanism by which hPTTG1 promotes metastasis by regulating the senescence-associated microenvironment.}, }
@article {pmid22782361, year = {2014}, author = {Tamaki, K and Ishida, T and Tamaki, N and Kamada, Y and Uehara, K and Miyashita, M and Amari, M and Tadano-Sato, A and Takahashi, Y and Watanabe, M and McNamara, K and Ohuchi, N and Sasano, H}, title = {Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {21}, number = {3}, pages = {325-333}, doi = {10.1007/s12282-012-0387-5}, pmid = {22782361}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asian People ; Breast Neoplasms/metabolism/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry/methods/standards ; Ki-67 Antigen/*analysis/*immunology/metabolism ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; }, abstract = {BACKGROUND: It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion.<br><br>METHODS: We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index.<br><br>RESULTS: There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P&#xa0;<&#xa0;0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P&#xa0;<&#xa0;0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P&#xa0;=&#xa0;0.031) and DFS (HR 10.85, P&#xa0;=&#xa0;0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and "20&#xa0;% luminal A" in DFS (P&#xa0;=&#xa0;0.039) but not between classical luminal A group and "25&#xa0;% luminal A" (P&#xa0;=&#xa0;0.105).<br><br>CONCLUSIONS: A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25&#xa0;% in ER positive and HER2 negative breast cancer patients.}, }
@article {pmid22777354, year = {2013}, author = {Scribner, KC and Behbod, F and Porter, WW}, title = {Regulation of DCIS to invasive breast cancer progression by Singleminded-2s (SIM2s).}, journal = {Oncogene}, volume = {32}, number = {21}, pages = {2631-2639}, pmid = {22777354}, issn = {1476-5594}, support = {R00 CA127462/CA/NCI NIH HHS/United States ; R01 CA111551/CA/NCI NIH HHS/United States ; R01CA111551/CA/NCI NIH HHS/United States ; 5R00CA127462-06/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/biosynthesis/genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Caseins/biosynthesis/genetics ; *Cell Differentiation ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Keratin-14/biosynthesis/genetics ; Keratin-18/biosynthesis/genetics ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Receptors, G-Protein-Coupled/biosynthesis/genetics ; Smoothened Receptor ; Transcription Factors/biosynthesis/genetics ; Transplantation, Heterologous ; Tumor Suppressor Proteins/biosynthesis/genetics ; Vimentin/biosynthesis/genetics ; }, abstract = {Singleminded-2s (SIM2s) is a member of the bHLH/PAS family of transcription factors and a key regulator of mammary epithelial cell differentiation. SIM2s is highly expressed in mammary epithelial cells and downregulated in human breast cancer. Loss of Sim2s causes aberrant mouse mammary ductal development, with features suggestive of malignant transformation, whereas overexpression of SIM2s promotes precocious alveolar differentiation in nulliparous mouse mammary glands, suggesting that SIM2s is required for establishing and enhancing mammary gland differentiation. To test the hypothesis that SIM2s regulates tumor cell differentiation, we analyzed SIM2s expression in human primary breast ductal carcinoma in situ (DCIS) samples and found that SIM2s is lost with progression from DCIS to invasive ductal cancer (IDC). Using a MCF10DCIS.COM progression model, we have shown that SIM2s expression is decreased in MCF10DCIS.COM cells compared with MCF10A cells, and reestablishment of SIM2s in MCF10DCIS.COM cells significantly inhibits growth and invasion both in vitro and in vivo. Analysis of SIM2s-MCF10DCIS.com tumors showed that SIM2s promoted a more differentiated tumor phenotype including the expression of a broad range of luminal markers (CSN2 (β-casein), CDH1 (E-cadherin), and KER18 (keratin-18)) and suppressed genes associated with stem cell maintenance and a basal phenotype (SMO (smoothened), p63, SLUG (snail-2), KER14 (keratin-14) and VIM (vimentin)). Furthermore, loss of SIM2s expression in MCF10DCIS.COM xenografts resulted in a more invasive phenotype and increased lung metastasis likely due to an increase in Hedgehog signaling and matrix metalloproteinase expression. Together, these exciting new data support a role for SIM2s in promoting human breast tumor differentiation and maintaining epithelial integrity.}, }
@article {pmid22766516, year = {2012}, author = {Spano, JP and Lanoy, E and Mounier, N and Katlama, C and Costagliola, D and Heard, I}, title = {Breast cancer among HIV infected individuals from the ONCOVIH study, in France: therapeutic implications.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {48}, number = {18}, pages = {3335-3341}, doi = {10.1016/j.ejca.2012.05.019}, pmid = {22766516}, issn = {1879-0852}, mesh = {Adult ; Aged ; Alcohol Drinking/epidemiology ; Anti-HIV Agents/pharmacokinetics/therapeutic use ; Antineoplastic Agents/pharmacokinetics/therapeutic use ; Antiretroviral Therapy, Highly Active ; Breast Neoplasms/drug therapy/*epidemiology/radiotherapy/surgery ; Breast Neoplasms, Male/epidemiology/therapy ; CD4 Lymphocyte Count ; Carcinoma, Ductal, Breast/drug therapy/epidemiology/radiotherapy/surgery ; Combined Modality Therapy ; Cross-Sectional Studies ; Drug Interactions ; Estrogens ; Female ; France/epidemiology ; HIV Infections/drug therapy/*epidemiology ; Humans ; Immunocompromised Host ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multicenter Studies as Topic/statistics &amp; numerical data ; Neoplasms, Hormone-Dependent/drug therapy/epidemiology/radiotherapy/surgery ; Progesterone ; Prospective Studies ; Risk Factors ; Smoking/epidemiology ; Surveys and Questionnaires ; Survival Rate ; Tumor Burden ; Viral Load ; }, abstract = {BACKGROUND: The cross-sectional ONCOVIH study prospectively enrolled HIV-infected adults and children with newly diagnosed malignancies in France in 2006.<br><br>METHOD: We report the characteristics HIV-infected patients with breast cancer from the ONCOVIH study. Standardised questionnaires included characteristics of HIV infection and malignancy. Survival was estimated using Kaplan-Meier estimates.<br><br>RESULTS: Overall, 21 patients with breast cancer (two men and 19 women) were included with a median age of 43.8 years, (range: 30.1-65.5). At time of tumour diagnosis, the median CD4 count was 384/mm(3) (range: 180-1039) the median duration of known seropositivity 7.7 years (range: 0-20.3); 14 patients were under combined antiretroviral therapy for a median duration of 5.7 years (range: 1.1-10.6), of whom 11 had a controlled viral load (<500 copies/mL). The median tumour size was 1.8 cm (range: 1.0-7.0). In women, 17 (89.5%) had invasive ductal carcinoma, 17 (89.5%) with HER2 negative receptors, 8 (42.1%) with ER+ expression, and 7 (36.8%) with PR+ expression. A majority of women received chemotherapy (73.7%), surgery (68.4%) and radiotherapy (57.9%). Their one-year survival rate was estimated as 77.8% (95%confidence interval (CI): 58.6-97.0%).<br><br>CONCLUSIONS: We discuss the risk of breast cancer in infected patients, and the importance of taking into account the different contributing factors for breast cancer in HIV-infected individuals.}, }
@article {pmid22761192, year = {2012}, author = {Soltan Dallal, MM and Yazdi, MH and Holakuyee, M and Hassan, ZM and Abolhassani, M and Mahdavi, M}, title = {Lactobacillus casei ssp.casei induced Th1 cytokine profile and natural killer cells activity in invasive ductal carcinoma bearing mice.}, journal = {Iranian journal of allergy, asthma, and immunology}, volume = {11}, number = {2}, pages = {183-189}, pmid = {22761192}, issn = {1735-1502}, mesh = {Animals ; Breast Neoplasms/immunology/pathology/*therapy ; Carcinoma, Ductal, Breast/immunology/pathology/*therapy ; Coculture Techniques ; Cytokines/*metabolism ; Cytotoxicity, Immunologic ; Female ; Humans ; Immunotherapy/*methods ; Interferon-gamma/metabolism ; Interleukin-12/metabolism ; K562 Cells ; Killer Cells, Natural/*immunology ; Lacticaseibacillus casei/*immunology ; Mice ; Mice, Inbred BALB C ; Neoplasm Invasiveness ; *Probiotics ; Th1 Cells/*immunology ; Time Factors ; Tumor Burden ; }, abstract = {Lactic acid bacteria which are used as probiotics have ability to modulate immune responses and modify immune mechanisms. It has also been indicated that some strains of this family can affect the immune responses against solid tumors. In the present work, we proposed to study the effects of oral administration of L.cacesi ssp casei on the NK cells cytotoxicity and also production of cytokines in spleen cells culture of BALB/c mice bearing invasive ductal carcinoma. 30 female In-bred BALB/c mice, were used and divided in two groups of test and control each containing 15 mice. Every day from 2 weeks before tumor transplantation 0.5 ml of PBS containing 2.7×108 CFU/ml of L.casei spp casei was orally administered to the test mice and it was followed 3 weeks after transplantation as well with 3 days interval between each week. Control mice received an equal volume of PBS in a same manner. Results showed that oral administration of L. casei significantly increased the production of IL-12 and IFN-γ (P<0.05) and increased the natural killer cells (NK) cytotoxicity in spleen cells culture of test mice (P<0.05). It has also been demonstrated that the growth rate of tumor in the test mice was decreased and their survival was significantly prolonged in comparison to the controls. Our findings suggest that daily intake of L.casei can improve immune responses in mice bearing invasive ductal carcinoma, but further studies are needed to investigate the other involving mechanisms in this case.}, }
@article {pmid22736333, year = {2012}, author = {Marras, F and Bozzano, F and Bentivoglio, G and Ugolotti, E and Biassoni, R and Moretta, L and De Maria, A}, title = {Receptor modulation and functional activation of human CD34+ Lin- -derived immature NK cells in vitro by Mycobacterium bovis Bacillus Calmette-Guerin (BCG).}, journal = {European journal of immunology}, volume = {42}, number = {9}, pages = {2459-2470}, doi = {10.1002/eji.201242375}, pmid = {22736333}, issn = {1521-4141}, mesh = {Antigens, CD34/genetics/*immunology/metabolism ; Antigens, Differentiation, T-Lymphocyte/genetics/metabolism ; BCG Vaccine/*immunology ; Cytotoxicity, Immunologic/genetics/*immunology ; Dendritic Cells/immunology/metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics/immunology/metabolism ; Humans ; Interferon-gamma/genetics/immunology/metabolism ; Interleukin-10/genetics/immunology/metabolism ; Interleukin-18/genetics/immunology/metabolism ; K562 Cells ; Killer Cells, Natural/*immunology/metabolism ; Lymphocyte Activation ; Monocytes/immunology/metabolism ; Mycobacterium bovis/genetics/*immunology/metabolism ; Receptors, Immunologic/genetics/*immunology/metabolism ; Transforming Growth Factor beta/genetics/immunology/metabolism ; }, abstract = {It is not yet clear whether immature NK (iNK) cells are bystanders to or rather participate in immune responses to pathogens that may colocalize in areas of NK-cell maturation such as bone marrow or lymph nodes. Mycobacteria, including Bacillus Calmette-Guerin (BCG), have been shown to interact with peripheral NK cells and in vivo may colocalize in areas of iNK-cell development. We studied infection with BCG of human cord blood CD34(+) Lin(-)-derived cultures containing myelomonocytes and iNK cells in vitro. Increased iNK-cell DNAM-1 expression, transient natural cytotoxicity receptor modulation, and production of IFN-γ were observed. Transcriptional receptor modulation was associated to BCG challenge, which determined increased iNK-cell cytotoxic activity against tumor cell lines and also increased killing of immature dendritic cells (iDCs). No requirement for cell contact was recorded for BCG-induced iNK-cell activation, while cytokine production including IL-18, IL-10, GM-CSF, and TGF-β contributed to the observed effects. Thus, iNK cells are affected by mycobacteria in vitro and may contribute to shaping of adaptive mature innate responses through iDC-iNK cross-talk. In addition, iNK-cell activation by BCG may represent a novel additional mechanism contributing to the effects observed upon BCG administration in vivo.}, }
@article {pmid22730654, year = {2012}, author = {Wang, SH and Li, DP and Zhang, YJ and Zhang, P and Zeng, LY and Pan, XY and Xu, KL and Huang, YH}, title = {[Effects of immature dendritic cells genetically modified to express sTNFR I on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) in allogeneic bone marrow transplantation mice].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {33}, number = {2}, pages = {88-93}, pmid = {22730654}, issn = {0253-2727}, mesh = {Animals ; Bone Marrow Transplantation/adverse effects/*methods ; Dendritic Cells/*immunology ; Female ; Graft vs Host Disease/*prevention &amp; control ; *Graft vs Leukemia Effect ; Immune Tolerance ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Receptors, Tumor Necrosis Factor, Type I/*genetics ; Transplantation, Homologous ; }, abstract = {OBJECTIVE: To investigate the effect of immature dendritic cells (inDC) genetically modified to express sTNFR I on acute graft-versus-host disease (aGVHD) and the graft-versus-leukemia (GVL) effect ofter allogeneic bone marrow transplantation (allo-BMT) in leukemic mice and its mechanism.<br><br>METHODS: An EL4 leukemia allo-BMT model was established with the BALB/c (H-2d) donor mice (DM)and C57BL/6 (H-2b) recipient mice (RM). The RM received DM bone marrow (BM) cells at a 1:1 ratio with spleen cells intravenously via tail vein at 4 h after TBI. Fifty DM were separated randomly into five groups: (1) Group A: total body irradiation (TBI) group, (2) Group B: lymphoma cell leukemia group, (3) Group C: allo-BMT group, (4) Group D: pXZ9-DC group, (5) Group E: sTNFR I-DC group. Acute GVHD scores, incidence of leukemic cell infiltration, histopathological analysis, survival rate, and survival rate of the recipients were estimated after allo-BMT. Enzyme-linked immunosorbent assay (ELISA) method was used to detect cytokines (INF-gamma and IL-4) production. Flow cytometry (FCM) analysis was used to detect allogeneic chimerism.<br><br>RESULTS: (1) The mice in group A and group B all died of the BM failure and lymphoma cell leukemia, respectively. The mice in group C developed typical clinical signs of a GVHD after BMT with an average survival time(AST) of (11.50 +/- 3.50) d. The signs of aGVHD were less evident in the group D and E, and their AST (21.70 +/- 5.80 and 25.80 +/- 5.20 days, respectively) were all longer than that in group C (P < 0.05). AST of group E was the longest (P < 0.05). The mice in group B all died of leukemia within 18 days after engraftment of EL4 cells. There was was no significant difference in groups C, D and E in the incidence of leukemia (P > 0.05). (2) Serum IFN-gamma level reached peak value. At + 12 d, then decreased gradually in group C, D, and E, and then reached the nadir at +18 d post-BMT, with the lowest in group E (P < 0.05), and the level was significantly lower in group D than in group C (P < 0.05). After BMT, serum IL-4 level slightly decreased in group C, but gradually elevated in group D and E and reached their peak at +12 d, and even more significantly increased in group E (P < 0.05). There was no statistical significance in the pair wise comparison among three group (P < 0.05). (3) The average proportion of H-2d positive cells in RM was 95%-100% on day 30 post-BMT, with complete donor-type implantation.<br><br>CONCLUSION: Immature DC can induce immuno tolerance. Immature DC genetically modified to express sTNFR I has been shown to prevent acute GVHD in lethally irradiated mice reconstituted with allogeneic bone marrow grafts while maintaining the GVL response.}, }
@article {pmid22729910, year = {2012}, author = {Hussain, SR and Babu, SG and Raza, ST and Singh, P and Ahmed, F and Naqvi, H and Mahdi, F}, title = {Screening of the c-kit gene missense mutation in invasive ductal carcinoma of breast among north Indian population.}, journal = {Molecular biology reports}, volume = {39}, number = {9}, pages = {9139-9144}, pmid = {22729910}, issn = {1573-4978}, mesh = {Adult ; Aged ; Amino Acid Sequence ; Base Sequence ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Exons ; Female ; Humans ; India ; Middle Aged ; Molecular Sequence Data ; *Mutation, Missense ; Neoplasm Grading ; Neoplasm Invasiveness ; Proto-Oncogene Proteins c-kit/*genetics ; }, abstract = {Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer deaths among females across the world, accounting for 23 % (1.38 million) of total new cancer cases and 14 % (0.45 million) of the total cancer deaths in 2008. c-kit is expressed in mast cell growth factor, cellular migration, proliferation, melanoblasts, haematopoietic progenitors and germ cells. We have designed our study with aim to explore the c-kit gene mutations in invasive ductal carcinoma (IDC) breast. To ascertain the range of mutations in exon 11, 13 and 17 of c-kit gene in 53 cases of IDC breast, we carried out PCR-SSCP followed by DNA sequencing. The mutation frequency of c-kit gene in exon 11, 13 and 17 were 9.43 % (5/53), 1.88 % (1/53) and 3.77 % (2/53), respectively. During our mutational analysis, we have detected five missense mutations in exon 11 (Pro551Leu, Glu562Val, Leu576Phe, His580Tyr and Phe584Leu), one missense mutation in exon 13 (Ser639Pro) and two missense mutations in exon 17 (Arg796Gly and Asn822Ser). It seems that c-kit mutations might participate in breast cancer pathogenesis and may be utilized as predictive marker, since the loss of c-kit positivity is generally linked with different types of breast cancer. Further molecular studies are necessary to validate the association of c-kit gene mutation in IDC breast pathogenesis.}, }
@article {pmid22718308, year = {2012}, author = {Vargas, AC and McCart Reed, AE and Waddell, N and Lane, A and Reid, LE and Smart, CE and Cocciardi, S and da Silva, L and Song, S and Chenevix-Trench, G and Simpson, PT and Lakhani, SR}, title = {Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression.}, journal = {Breast cancer research and treatment}, volume = {135}, number = {1}, pages = {153-165}, doi = {10.1007/s10549-012-2123-4}, pmid = {22718308}, issn = {1573-7217}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Collagen Type V/biosynthesis/genetics ; Collagen Type XI/biosynthesis/genetics ; Disease Progression ; Epithelial Cells/*metabolism ; Extracellular Matrix/genetics ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins/biosynthesis/genetics ; Matrix Metalloproteinase 13/biosynthesis/genetics ; Membrane Proteins/biosynthesis/genetics ; Stromal Cells/*metabolism ; Tumor Microenvironment ; }, abstract = {The progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) marks a critical step in the evolution of breast cancer. There is some evidence to suggest that dynamic interactions between the neoplastic cells and the tumour microenvironment play an important role. Using the whole-genome cDNA-mediated annealing, selection, extension and ligation assay (WG-DASL, Illumina), we performed gene expression profiling on 87 formalin-fixed paraffin-embedded (FFPE) samples from 17 patients consisting of matched IDC, DCIS and three types of stroma: IDC-S (<3 mm from IDC), DCIS-S (<3 mm from DCIS) and breast cancer associated-normal stroma (BC-NS; >10 mm from IDC or DCIS). Differential gene expression analysis was validated by quantitative real time-PCR, immunohistochemistry and immunofluorescence. The expression of several genes was down-regulated in stroma from cancer patients relative to normal stroma from reduction mammoplasties. In contrast, neoplastic epithelium underwent more gene expression changes during progression, including down regulation of SFRP1. In particular, we observed that molecules related to extracellular matrix (ECM) remodelling (e.g. COL11A1, COL5A2 and MMP13) were differentially expressed between DCIS and IDC. COL11A1 was overexpressed in IDC relative to DCIS and was expressed by both the epithelial and stromal compartments but was enriched in invading neoplastic epithelial cells. The contributions of both the epithelial and stromal compartments to the clinically important scenario of progression from DCIS to IDC. Gene expression profiles, we identified differential expression of genes related to ECM remodelling, and specifically the elevated expression of genes such as COL11A1, COL5A2 and MMP13 in epithelial cells of IDC. We propose that these expression changes could be involved in facilitating the transition from in situ disease to invasive cancer and may thus mark a critical point in disease development.}, }
@article {pmid22712893, year = {2012}, author = {Van Balkom, ID and Vuijk, PJ and Franssens, M and Hoek, HW and Hennekam, RC}, title = {Development, cognition, and behaviour in Pitt-Hopkins syndrome.}, journal = {Developmental medicine and child neurology}, volume = {54}, number = {10}, pages = {925-931}, doi = {10.1111/j.1469-8749.2012.04339.x}, pmid = {22712893}, issn = {1469-8749}, mesh = {Adolescent ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics ; Belgium ; Child ; Child Behavior Disorders/*diagnosis/genetics/*psychology ; Child Development Disorders, Pervasive/*diagnosis/genetics/*psychology ; Child, Preschool ; Cognition Disorders/*diagnosis/genetics/*psychology ; DNA Mutational Analysis ; Developmental Disabilities/diagnosis/genetics/psychology ; Diagnosis, Differential ; Facies ; Female ; Humans ; Hyperventilation/*diagnosis/genetics/*psychology ; Intellectual Disability/*diagnosis/genetics/*psychology ; Language Development Disorders/diagnosis/genetics/psychology ; Male ; Netherlands ; Neuropsychological Tests ; Stereotypic Movement Disorder/diagnosis/genetics/psychology ; Transcription Factor 4 ; Transcription Factors/*genetics ; Young Adult ; }, abstract = {AIM: The aim of the study was to collect detailed data on behavioural, adaptive, and psychological functioning in 10 individuals with Pitt-Hopkins syndrome (PTHS), with specific attention to manifestations of autism spectrum disorder (ASD).<br><br>METHOD: The participants (four females, six males), residing in the Netherlands and Belgium, were ascertained through the Dutch national PTHS support group. Median age of participants was 10 years, the age range was between 32 and 289 months. They underwent psychiatric examinations and neuropsychological measurements using a comprehensive assessment battery. Additionally, parental information was gathered through standardized interviews and questionnaires. Findings were compared with those from the literature.<br><br>RESULTS: All participants showed profound intellectual disability, amiable demeanour with minimal maladaptive behaviours, severe impairments of communication and language, and intense, frequent motor stereotypies. Impairments in all participants were beyond what would be expected for cognitive abilities, fitting a classification of ASD.<br><br>INTERPRETATION: Patients with PTHS are characterized not only by specific physical and genetic manifestations but also by specific behavioural and cognitive characteristics. Studying behaviour and cognition may improve diagnosis and prognosis, allows recognition of comorbidities, and contributes to adequate counselling of families.}, }
@article {pmid22705704, year = {2012}, author = {Fujikawa, T and Mukai, K and Tanaka, A and Abe, T and Yoshimoto, Y and Tada, S and Maekawa, H and Shimoike, N and Tanaka, H and Kawashima, T and Yokota, T}, title = {[A long survival of a patient with poor performance status who suffered from advanced right breast cancer with multiple lung metastases controlled by trastuzumab as a key drug].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {6}, pages = {1009-1012}, pmid = {22705704}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Autopsy ; Bone Neoplasms/drug therapy/secondary ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*drug therapy/secondary ; Middle Aged ; Trastuzumab ; }, abstract = {We report a case of a 60-year-old woman with poor performance status (PS). She suffered from advanced right breast cancer with multiple lung metastases, which was controlled by chemotherapy with trastuzumab as the key drug. The patient presented with a 4 cm-sized large right breast mass. Her PS was poor due to progressive spinocerebellar degeneration. The biopsy specimen of the breast mass showed scirrhous type of the invasive ductal carcinoma (ER+, HER2 2+). Multiple lung metastases were also detected by computed tomography. Considering her poor PS, the patient was treated with mild systemic therapy using trastuzumab as the key drug. A different drug response was achieved between the breast mass and lung metastatic lesions, and the tumors were maintained as stable disease (SD) during first 18 months. However, she finally passed away due to respiratory failure resulting from lung metastasis, 33 months after starting treatment. The autopsy findings showed a difference of HER2 expression between the breast tumor and lung metastatic lesions. It must be recognized that differences of HER2 expression between the primary tumor and metastatic lesions are sometimes demonstrated in patients with breast cancer, and that trastuzumab can be used as a key drug in some patients as in the current case.}, }
@article {pmid22705703, year = {2012}, author = {Sasaki, Y and Okuyama, M and Hibino, M and Tenma, K and Nakamura, M}, title = {[A case of elderly locally-advanced breast cancer with skin ulcer responding to letrozole].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {6}, pages = {1005-1008}, pmid = {22705703}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Biopsy ; Breast Neoplasms/complications/*drug therapy/pathology ; Carcinoma, Ductal, Breast/complications/*drug therapy/pathology ; Female ; Humans ; Letrozole ; Neoplasm Grading ; Neoplasm Staging ; Nitriles/*therapeutic use ; Skin Ulcer/*etiology ; Triazoles/*therapeutic use ; }, abstract = {We report an 84-year-old woman with an ulcerated tumor of her right breast. The histological examination showed invasive ductal carcinoma, ER (allred-score 8), PgR (allred-score 0), and HER2 (0). Computed tomography and bone scintigraphy showed no distant metastases. She was diagnosed with right locally advanced breast cancer (cT4bN2aM0, stageIIIB) and received hormone therapy with letrozole. One year after, the carcinoma was reduced in size and the skin ulcer had disappeared. Two years later, the carcinoma had grown back slightly, but the skin ulcer was still undetectable. Hormone therapy alone was considered useful for treatment of elderly locally advanced breast cancer patients.}, }
@article {pmid22692290, year = {2012}, author = {Shah, RB and Zhou, M}, title = {Atypical cribriform lesions of the prostate: clinical significance, differential diagnosis and current concept of intraductal carcinoma of the prostate.}, journal = {Advances in anatomic pathology}, volume = {19}, number = {4}, pages = {270-278}, doi = {10.1097/PAP.0b013e31825c6c0e}, pmid = {22692290}, issn = {1533-4031}, mesh = {Biopsy, Needle ; Carcinoma, Ductal/pathology ; Colorectal Neoplasms/pathology ; Humans ; Male ; Prostate/*pathology ; Prostatic Intraepithelial Neoplasia/genetics/*pathology ; Prostatic Neoplasms/genetics/*pathology ; Serine Endopeptidases/genetics ; Urothelium/pathology ; }, abstract = {Atypical cribriform lesions of the prostate gland consist of cribriform and rarely solid proliferation of prostate glands populated with cytologically atypical cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P). IDC-P is almost always associated with clinically aggressive and high-volume prostate carcinoma. In contrast, cribriform HGPIN is a putative neoplastic precursor lesion, and recent data have questioned whether HGPIN on needle biopsy is associated with a significantly increased cancer risk in subsequent biopsies, and whether the diagnosis mandates rebiopsy within the first year after its diagnosis. As the result, the distinction between these 2 lesions has profound clinical implications, especially on needle biopsies. Since its original description, several studies have attempted to further refine histologic definition of IDC-P in the past decade. Even though presence of certain morphologic features (eg, pleomorphic nuclei or nuclei 6× the size of adjacent nuclei, intraluminal necrosis, and dense cribriform and solid architecture) are seen only in IDC-P, IDC-P may also exhibit "low-grade" morphologic features that overlap with cribriform HGPIN. Emerging molecular data on TMPRSS:ERG gene fusions further support the fact that these 2 lesions are biologically distinct. IDC-P is an uncommon finding in prostate biopsies; however, patients with IDC-P as sole findings without concomitant prostate carcinoma in biopsy are recommended for either definitive treatment or immediate repeat biopsy. This article summarizes the morphologic and molecular characteristics of IDC-P and cribriform HGPIN and an approach to work-up of atypical cribriform lesions in prostate needle biopsies.}, }
@article {pmid22691433, year = {2012}, author = {Daenthanasanmak, A and Salguero, G and Borchers, S and Figueiredo, C and Jacobs, R and Sundarasetty, BS and Schneider, A and Schambach, A and Eiz-Vesper, B and Blasczyk, R and Weissinger, EM and Ganser, A and Stripecke, R}, title = {Integrase-defective lentiviral vectors encoding cytokines induce differentiation of human dendritic cells and stimulate multivalent immune responses in vitro and in vivo.}, journal = {Vaccine}, volume = {30}, number = {34}, pages = {5118-5131}, doi = {10.1016/j.vaccine.2012.05.063}, pmid = {22691433}, issn = {1873-2518}, mesh = {Animals ; Antigens, Viral/genetics/immunology/metabolism ; CD8-Positive T-Lymphocytes/immunology ; *Cell Differentiation ; Cell Survival ; Culture Media/metabolism ; Cytokines/genetics/*immunology/metabolism ; Cytomegalovirus/genetics/immunology ; Dendritic Cells/cytology/*immunology ; Epitopes/immunology ; Genetic Vectors/genetics/immunology/metabolism ; Humans ; Immunity, Cellular ; Immunization ; Immunophenotyping ; Integrases/genetics ; Killer Cells, Natural/immunology ; Lentivirus/genetics/*metabolism ; Lymphocyte Activation ; Mice ; Mice, Inbred NOD ; Monocytes/immunology ; Phosphoproteins/genetics/immunology/metabolism ; Transgenes ; Viral Matrix Proteins/genetics/immunology/metabolism ; Viral Proteins/genetics/immunology/metabolism ; }, abstract = {Integrase-defective lentiviral vectors (ID-LVs) show several hallmarks of conventional lentiviral vectors such as absence of cytotoxic effects and long-term expression in non-replicating target cells. The integration rate of ID-LVs into the genome of target cells is dramatically reduced, which enhances safety and opens perspectives for their use in vaccine development. ID-LVs have been shown to be effective vaccines in mouse models, but functional studies with human cells in vitro and in vivo are lacking. Here, we evaluated whether ID-LVs expressing combinations of cytokines (GM-CSF/IL-4 or GM-CSF/IFN-α) used to transduce human monocytes would result in functional "induced dendritic cells" (iDCs). Overnight transduction of monocytes with high titer ID-LVs generated highly viable (14 days) and immunophenotypically stable iDCs expressing GM-CSF/IL-4 ("SmartDCs") or GM-CSF/IFN-α ("SmyleDCs"). SmartDCs and SmyleDCs maintained in vitro continuously secreted the transgenic cytokines and showed up-regulation of several endogenously produced inflammatory cytokines (IFN-γ, IL-2, -5, -6, and -8). Both iDC types potently stimulated T cells in mixed lymphocyte reactions at levels comparable to conventional DCs (maintained with exogenous cytokines). A single in vitro stimulation of CD8(+) T cells with autologous SmartDCs or SmyleDCs pulsed with peptide pools of pp65 (a human cytomegalovirus antigen) resulted in high expansion of central memory and effector memory CTLs reactive against different pp65 epitopes. We further evaluated the effects of SmartDCs and SmyleDCs to expand anti-pp65 CTLs in vivo using immune deficient NOD/Rag1((-/-))/IL-2rγ((-/-)) (NRG) mice. NRG mice immunized subcutaneously with SmartDCs or SmyleDCs co-expressing the full-length pp65 were subsequently infused with autologous CD8(+) T cells. Both types of iDCs effectively stimulated human CTLs reactive against different pp65 antigenic determinants in vivo. Due to the simplicity of generation, robust viability and combined capacity to stimulate homeostatic, antigenic and multivalent responses, iDCs are promising vaccines to be explored in immunization of lymphopenic patients in the post-transplantation setting.}, }
@article {pmid22673183, year = {2012}, author = {Kim, BG and Gao, MQ and Choi, YP and Kang, S and Park, HR and Kang, KS and Cho, NH}, title = {Invasive breast cancer induces laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype during tissue remodeling.}, journal = {Breast cancer research : BCR}, volume = {14}, number = {3}, pages = {R88}, pmid = {22673183}, issn = {1465-542X}, mesh = {*Anoikis ; Antibodies, Blocking ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Caspase 3/metabolism ; Cell Adhesion Molecules/immunology/*metabolism ; Cell Communication ; Cell Line, Tumor ; Cell Survival ; Female ; Fibrosis ; Humans ; Integrin alpha3beta1/metabolism ; Integrin beta1/immunology ; Integrin beta4/immunology/*metabolism ; MCF-7 Cells ; Myofibroblasts/*metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Up-Regulation ; rac1 GTP-Binding Protein/metabolism ; }, abstract = {INTRODUCTION: Although development of anoikis-resistant myofibroblasts during tissue remodeling is known to be associated with tumor invasion, the mechanism by which myofibroblasts become resistant to anoikis is unknown. We previously demonstrated laminin-332 upregulation in the fibrosis around invasive ductal carcinoma (IDC). Because laminin-332 promotes cell survival through binding to integrins, we hypothesized that invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts by upregulating laminin-332 expression during tissue remodeling. Here, we demonstrate that invasive breast cancer cells induce laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype.<br><br>METHODS: Three types of fibroblasts were isolated from the tumor burden, the fibrosis, and normal tissue of patients with early stage IDC (less than 10 mm diameter), designated cancer-associated fibroblasts (CAFs), interface fibroblasts (InFs), and normal breast fibroblasts (NBFs), respectively. To investigate direct and indirect crosstalk with tumor cells, fibroblasts were co-cultured with invasive MDA-MB-231 or noninvasive MCF7 cells or in conditioned medium. Anoikis resistance of fibroblasts was measured by cell viability and caspase-3 activity after incubation on poly-HEMA coated plates for 72 hours. Involvement of laminin-332/integrin &#x3b1;3&#x3b2;1 or &#x3b1;6&#x3b2;4 signaling in anoikis resistance was confirmed by treatment with purified laminin-332 or blocking antibodies against laminin-332, integrin &#x3b2;1, or integrin &#x3b2;4.<br><br>RESULTS: MDA-MB-231 cells induced laminin-332 upregulation and integrin &#x3b2;4 neoexpression in fibroblasts, leading to anoikis resistance. InFs showed a higher endogenous level of laminin-332 than did CAFs and NBFs. After stimulation with MDA-MB-231-conditioned medium, laminin-332 expression of InFs was dramatically increased and maintained under anoikis conditions. Laminin-332 upregulation was also observed in CAFs and NBFs, but at a lower level than in InFs. Laminin-332 induced Akt (Ser473) phosphorylation by binding to integrin &#x3b1;3&#x3b2;1. Integrin &#x3b2;4 neoexpression induced laminin-332-independent Rac1 activation and promoted anoikis resistance in fibroblasts approximately twofold more effectively than did laminin-332, regardless of the type of fibroblast. In addition, integrin &#x3b2;4 expression suppressed fibroblast aggregation in conditions of anoikis.<br><br>CONCLUSION: Invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts during tissue remodeling by inducing laminin-332 upregulation and integrin &#x3b2;4 neoexpression. Interface fibroblasts appear to be the primary myofibroblasts that interact with invasive tumor cells during tissue remodeling.}, }
@article {pmid22662240, year = {2012}, author = {Vermeulen, JF and van de Ven, RA and Ercan, C and van der Groep, P and van der Wall, E and Bult, P and Christgen, M and Lehmann, U and Daniel, J and van Diest, PJ and Derksen, PW}, title = {Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e37864}, pmid = {22662240}, issn = {1932-6203}, mesh = {Adherens Junctions/metabolism ; Adult ; Aged ; Aged, 80 and over ; Animals ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cadherins/metabolism ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Cell Line ; Cell Nucleus/*metabolism ; ErbB Receptors/metabolism ; Female ; Gene Expression ; Humans ; Mice ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Protein Transport ; Receptor, ErbB-2/deficiency ; Receptors, Estrogen/deficiency ; Receptors, Progesterone/deficiency ; Transcription Factors/genetics/*metabolism ; p120 GTPase Activating Protein/metabolism ; }, abstract = {Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC) (p = 0.007), while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC) (p = 0.006). Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023), ERα negativity (p = 0.001), and the HER2-driven and basal/triple-negative breast cancers (p = 0.018). Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001) and invasive breast cancer overexpressing EGFR (p = 0.019). We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120) (p<0.01). In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005). We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.}, }
@article {pmid22616572, year = {2012}, author = {Atalay, C and Irkkan, C}, title = {Predictive factors for residual disease in re-excision specimens after breast-conserving surgery.}, journal = {The breast journal}, volume = {18}, number = {4}, pages = {339-344}, doi = {10.1111/j.1524-4741.2012.01249.x}, pmid = {22616572}, issn = {1524-4741}, mesh = {Adult ; Axilla/pathology/surgery ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm, Residual/*pathology ; Pathology, Surgical/*methods ; Predictive Value of Tests ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Factors ; }, abstract = {Local recurrence is an issue of concern after breast-conserving therapy and removing the primary tumor with negative surgical margins is the most important determinant of local recurrence. However, some patients with positive margins after initial surgery will have no residual tumor in the re-excision specimen. To avoid unnecessary re-excisions, factors predicting residual disease in re-excision material should be determined. This study aimed to determine the predictive factors for residual disease in the re-excision material in a homogeneous group of patients with positive margins and only invasive ductal carcinoma. Breast cancer patients treated between 2005 and 2008 with breast-conserving surgery and subsequent re-excisions due to positive surgical margins after initial surgery were included in the study. Patients were divided into two groups as those with and without residual disease in the re-excision material. One hundred and four breast cancer patients were included in the study. Forty-seven patients (45.2%) had residual tumor in re-excision specimen. Patient characteristics such as age (p = 0.42) and physical findings (p = 1.0) and specimen volume (p = 0.24), tumor grade (p = 0.33), estrogen (p = 1.0), and progesterone (p = 0.37) receptor status, axillary lymph node metastases (p = 0.16), extensive intraductal component (p = 0.8), and lymphovascular invasion (p = 0.064) were found as insignificant factors for predicting residual tumor. Large tumor size (>3 cm) (p = 0.026), human epidermal growth factor receptor2 (HER2) positivity (p = 0.013), and tumor to specimen volume ratio of >70% (p = 0.002) significantly increased the probability of finding residual disease after re-excision. In multivariate analysis, HER2 positivity (p = 0.046) and tumor to specimen volume ratio of >70% (p = 0.006) independently predicted the presence of residual disease. As a result, in patients with HER2 positive tumors larger than 3 cm, larger volume of breast tissue around the tumor should be removed to decrease the number of re-excisions due to positive surgical margins.}, }
@article {pmid22612513, year = {2012}, author = {Deng, Y and Xue, D and Wang, X and Xu, S and Ao, Q and Hu, Z and Wang, G}, title = {Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype.}, journal = {Pathology international}, volume = {62}, number = {6}, pages = {429-432}, doi = {10.1111/j.1440-1827.2012.02810.x}, pmid = {22612513}, issn = {1440-1827}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Basal Cell/metabolism/*secondary ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Cystadenocarcinoma, Mucinous/metabolism/*secondary ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis ; Mastectomy ; Neoplasm Staging ; Neoplasms, Multiple Primary ; }, abstract = {Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype.}, }
@article {pmid22611364, year = {2012}, author = {Okamoto, H and Kawaoi, A and Ogawara, T and Fujii, H}, title = {Invasive ductal carcinoma arising from an ectopic pancreas in the gastric wall: a long-term survival case.}, journal = {Case reports in oncology}, volume = {5}, number = {1}, pages = {69-73}, pmid = {22611364}, issn = {1662-6575}, abstract = {A case of invasive ductal carcinoma of an ectopic pancreas in the stomach in a 74-year-old woman is presented. A 4.0 cm gastric submucosal tumor (SMT) was resected surgically. Histologically, the tumor showed cystic tissue consisting of an ectopic pancreas with foci of a moderately differentiated tubular adenocarcinoma. In this tumor, small pancreatic tissues, acini, Langerhans islets, and ductular cells were detected in the gastric SMT. The patient has experienced long-term survival. The incidence of pancreatic cancer of an ectopic pancreas is rare, and the etiology of this disease is discussed in the literature.}, }
@article {pmid22586447, year = {2012}, author = {Huang, AJ and Yu, KD and Li, J and Fan, L and Shao, ZM}, title = {Polymorphism rs4919510:C&gt;G in mature sequence of human microRNA-608 contributes to the risk of HER2-positive breast cancer but not other subtypes.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e35252}, pmid = {22586447}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Case-Control Studies ; DNA-Binding Proteins/genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Heat Shock Transcription Factors ; Humans ; Logistic Models ; MicroRNAs/*genetics ; Middle Aged ; Neoplasms, Hormone-Dependent/*genetics/pathology ; Polymorphism, Genetic ; Receptor, ErbB-2/*genetics ; Risk Factors ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: A few polymorphisms are located in the mature microRNA sequences. Such polymorphisms could directly affect the binding of microRNA to hundreds of target mRNAs. It remains unknown whether rs4919510:C>G located in the mature miR-608 alters breast cancer susceptibility.<br><br>METHODS: The association of rs4919510:C>G with risk and pathologic features of breast cancer were investigated in two independent case-control studies, the first set including 1,138 sporadic breast cancer patients (including 927 invasive ductal carcinoma patients, 777 of them with known subtypes: 496 luminal-like, 133 HER2-positive, and 148 triple-negative) and 1,434 community-based controls, and the second set including 294 familial/early-onset breast cancer patients and 500 hospital-based cancer-free controls. Odds ratios (ORs) were estimated by logistic regression. Predicted targets of miR-608 and complementary sequences containing rs4919510:C>G were surveyed to reveal potential pathological mechanism.<br><br>RESULTS: In the first set, although rs4919510:C>G was unrelated to breast cancer in general patients, variant genotypes (CG/GG) were specifically associated with increased risk of HER2-positive subtype (Adjusted OR = 1.97, 95% CI, 1.34-2.90 in the recessive model). Variant G-allele was the risk allele with OR of 1.62 (95% CI, 1.23-2.15). Patients carrying GG-genotype also had larger HER2-positive tumors (P for Kruskal-Wallis test = 0.006). The relationship between rs4919510:C>G and risk of HER2-positive subgroup was validated in the second set (Bonferroni corrected P = 0.06). The adjusted combined OR (total 164 HER2-positive cases) in the recessive model was 1.97 (95% CI, 1.43-2.72) for GG genotype (corrected P = 1.1 &#xd7; 10(-4)). Bioinformatic analysis indicated that, HSF1, which is required for HER2-induced tumorigenesis, might be a target of miR-608. The minimum free-energy of ancestral-miR-608 (C-allele) binding to HSF1 is -35.9 kcal/mol, while that of variant-form (G-allele) is -31.5 kcal/mol, indicating a lower affinity of variant-miR-608 to HSF1 mRNA.<br><br>CONCLUSION: rs4919510:C>G in mature miR-608 may influence HER2-positive breast cancer risk and tumor proliferation.}, }
@article {pmid22569827, year = {2012}, author = {Ebata, A and Suzuki, T and Takagi, K and Miki, Y and Onodera, Y and Nakamura, Y and Fujishima, F and Ishida, K and Watanabe, M and Tamaki, K and Ishida, T and Ohuchi, N and Sasano, H}, title = {Oestrogen-induced genes in ductal carcinoma in situ: their comparison with invasive ductal carcinoma.}, journal = {Endocrine-related cancer}, volume = {19}, number = {4}, pages = {485-496}, doi = {10.1530/ERC-11-0345}, pmid = {22569827}, issn = {1479-6821}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism ; Estrogens/*pharmacology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, Neoplasm/drug effects ; Humans ; Microarray Analysis ; Middle Aged ; Up-Regulation/drug effects/genetics ; }, abstract = {It is well known that oestrogens play important roles in both the pathogenesis and development of invasive ductal carcinoma (IDC) of human breast. However, molecular features of oestrogen actions have remained largely unclear in pure ductal carcinoma in situ (pDCIS), regarded as a precursor lesion of many IDCs. This is partly due to the fact that gene expression profiles of oestrogen-responsive genes have not been examined in pDCIS. Therefore, we first examined the profiles of oestrogen-induced genes in oestrogen receptor (ER)-positive pDCIS and DCIS (DCIS component (DCIS-c)) and IDC (IDC component (IDC-c)) components of IDC cases (n=4 respectively) by microarray analysis. Oestrogen-induced genes identified in this study were tentatively classified into three different groups in the hierarchical clustering analysis, and 33% of the genes were predominantly expressed in pDCIS rather than DCIS-c or IDC-c cases. Among these genes, the status of MYB (C-MYB), RBBP7 (RBAP46) and BIRC5 (survivin) expressions in carcinoma cells was significantly higher in ER-positive pDCIS (n=53) than that in ER-positive DCIS-c (n=27) or IDC-c (n=27) by subsequent immunohistochemical analysis of the corresponding genes (P<0.0001, P=0.03 and P=0.0003 respectively). In particular, the status of C-MYB immunoreactivity was inversely (P=0.006) correlated with Ki67 in the pDCIS cases. These results suggest that expression profiles of oestrogen-induced genes in pDCIS may be different from those in IDC; and C-MYB, RBAP46 and survivin may play important roles particularly among oestrogen-induced genes in ER-positive pDCIS.}, }
@article {pmid22562451, year = {2012}, author = {Yamamoto, Y and Shimada, K and Takeuchi, Y and Sofue, K and Shibamoto, K and Nara, S and Esaki, M and Sakamoto, Y and Kosuge, T and Hiraoka, N}, title = {Assessment of the interface between retroperitoneal fat infiltration of pancreatic ductal carcinoma and the major artery by multidetector-row computed tomography: surgical outcomes and correlation with histopathological extension.}, journal = {World journal of surgery}, volume = {36}, number = {9}, pages = {2192-2201}, pmid = {22562451}, issn = {1432-2323}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/*diagnostic imaging/pathology/surgery ; Female ; Hepatic Artery/*diagnostic imaging ; Humans ; Intra-Abdominal Fat/*diagnostic imaging/pathology ; Male ; Mesenteric Arteries/*diagnostic imaging ; Mesenteric Veins/diagnostic imaging ; Middle Aged ; *Multidetector Computed Tomography ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*diagnostic imaging/pathology/surgery ; Pancreaticoduodenectomy ; Portal Vein/diagnostic imaging ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; Vascular Neoplasms/*diagnostic imaging/secondary/surgery ; }, abstract = {BACKGROUND: Precise assessment of retroperitoneal invasion is clinically important to allow the achievement of negative margin resections.<br><br>METHODS: The clinical records of 132 patients who underwent macroscopic curative pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas between 2004 and 2008 were retrospectively examined. The clinicopathological factors, including retroperitoneal fat infiltration classified into four groups by multidetector-row computed tomography (MDCT), were analyzed. The relationship between the grade of retroperitoneal fat infiltration and surgical outcomes, as well as various histopathological factors, was also investigated.<br><br>RESULTS: The 5 year survival rate was 55.6 % for grade 0 infiltration (n = 8), 38.7 % for grade 1 (n = 54), 16.4 % for grade 2 (n = 49), and 0 % for grade 3 (n = 21). There were significant differences in survival in each group. Extrapancreatic nerve invasion and the surgical margin status were significantly associated with retroperitoneal fat infiltration demonstrated on MDCT. According to the grading classification among the 43 patients with pathological portal vein invasion, the 5 year survival rate was 45.9 % for patients with grade 1, which was significantly better survival that those with grade 2 (P = 0.007).<br><br>CONCLUSION: The grading criteria for retroperitoneal fat infiltration may be useful as a predictor of survival after pancreaticoduodenectomy for pancreatic head carcinoma. Pancreaticoduodenectomy with portal vein resection could provide favorable survival in patients with grade 1 retroperitoneal fat infiltration, even if histopathological portal vein invasion is present.}, }
@article {pmid22558599, year = {2011}, author = {Singhai, R and Patil, VW and Jaiswal, SR and Patil, SD and Tayade, MB and Patil, AV}, title = {E-Cadherin as a diagnostic biomarker in breast cancer.}, journal = {North American journal of medical sciences}, volume = {3}, number = {5}, pages = {227-233}, pmid = {22558599}, issn = {1947-2714}, abstract = {BACKGROUND: E-cadherin is expressed in most normal epithelial tissues. Selective loss of E-cadherin can cause dedifferentiation and invasiveness in human carcinomas, leading E-cadherin to be classified as a tumor suppressor. Loss of E-cadherin has been demonstrated in invasive lobular carcinoma of the breast, but the relationship between E-cadherin expression and breast cancer histopathology and prognosis is less clear.<br><br>AIM: Our objective was to assess loss of E-cadherin as a diagnostic breast cancer biomarker and as an aid to the sub-classification of invasive breast cancer. We also correlated the loss of expression of E-cadherin with various clinical and pathologic prognostic factors.<br><br>MATERIAL AND METHODS: Breast cancer specimens after modified radical mastectomy were obtained from women who underwent surgery at Grant Medical College and Sir J.J Group of Hospitals, Mumbai, India between May 2007 and October 2010. We stained 276 breast cancers specimens with monoclonal antibodies to E-cadherin. The breast cancers were classified by histopathological type.<br><br>RESULTS: A statistical correlation of E-cadherin loss with a positive diagnosis of invasive lobular carcinoma was found, but there was no correlation with any prognostic tumor variables. A negative E-cadherin stain was a sensitive and specific biomarker to confirm the diagnosis of invasive lobular carcinoma (specificity 97.7%; negative predictive value 96.8%; sensitivity 88.1%; and positive predictive value 91.2%). Positive E-cadherin expression was also associated with tubulolobular carcinomas.<br><br>CONCLUSIONS: E-cadherin immunohistochemistry is helpful in classifying breast cancer cases with indeterminate histopathologic features. E-cadherin loss is uncommon in non-lobular carcinomas but shows no correlation to currently established prognostic variables.}, }
@article {pmid22553811, year = {2012}, author = {Lin, X and Zhu, B and Finkelstein, SD and Saad, RS and Snitchler, A and Silverman, JF}, title = {Significance of loss of heterozygosity in predicting axillary lymph node metastasis of invasive ductal carcinoma of the breast.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {20}, number = {2}, pages = {116-123}, doi = {10.1097/pai.0b013e31822afce2}, pmid = {22553811}, issn = {1533-4058}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal/*genetics/*pathology ; Chromosomes, Human/*genetics ; DNA, Neoplasm/*genetics ; Female ; Humans ; *Loss of Heterozygosity ; Lymphatic Metastasis ; Middle Aged ; }, abstract = {Invasive ductal carcinoma (IDC) of breast metastatic to axillary lymph node (ALN) is a critical factor in determining stage and is a strong predictor of disease prognosis and survival. We studied ALN metastasis using a combined histopathologic/molecular approach to gain insights into the pathobiology implications. Fourteen patients with IDC with positive ALN and 19 with negative ALN were retrieved. Analysis of 17 polymorphic microsatellite repeat markers targeting 1p34-36, 3p24-26, 5q23, 9p21, 10q23, 17p13, 17q12, 17q21, 21q22, and 22q13 was carried out in DNA isolated from primary tumors and metastatic tumors. ALN metastasis correlated with fractional mutation rate of primary and ALN metastatic tumors, primary tumor size, and nuclear grade, and did not correlate with expression of estrogen receptor, progesterone receptor, and Her2/neu. Loss of heterozygosity (LOH) detected at 1p34-36, 3p24-26, 9p21, 10q23, 17p13, 17q12, 21q22, and 22q13 may play an important role in the development and aggressiveness of IDC, and LOHs at 1p34-36, 17p13, and 22q13 may play an important role in metastasis. None of the LOHs were shared by all the tumors, suggesting that IDC develops through various pathways that have unique and personalized patterns of mutational changes, although they share similar morphology. Detection of LOH in IDC is not only useful in studying oncogenesis, but also predicting aggressiveness and ALN metastasis.}, }
@article {pmid22553225, year = {2012}, author = {Stivalet, A and Luciani, A and Pigneur, F and Dao, TH and Beaussart, P and Merabet, Z and Perlbarg, J and Meyblum, E and Baranes, L and Calitchi, E and Lepage, C and Belkacemi, Y and Lagrange, JL and Lantieri, L and Rahmouni, A}, title = {Invasive lobular carcinoma of the breast: MRI pathological correlation following bilateral total mastectomy.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {53}, number = {4}, pages = {367-375}, doi = {10.1258/ar.2012.110477}, pmid = {22553225}, issn = {1600-0455}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Lobular/drug therapy/*pathology/surgery ; Combined Modality Therapy ; Contrast Media ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Mammaplasty ; Mammography ; Mastectomy, Simple ; Meglumine ; Middle Aged ; Neoplasm Invasiveness ; Organometallic Compounds ; Predictive Value of Tests ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is more often multifocal and bilateral than invasive ductal carcinoma. MRI is usually recommended for detection of all ILC sites. The performance of known diagnostic breast MRI criteria for ILC characterization has not been evaluated to date using bilateral mastectomy specimens as gold standard.<br><br>PURPOSE: To determine the value of BI-RADS 2006 MRI criteria for ILC detection and characterization, using pathological examination of bilateral mastectomy specimens as the reference standard.<br><br>MATERIAL AND METHODS: Between 2004 and 2007, we retrospectively included all patients with pathologically documented ILC referred to our institution for bilateral mastectomy and preoperative bilateral breast MRI. The location, diameter, and characteristics (BI-RADS) of all lesions were compared with pathological findings. The sensitivity and positive predictive value of bilateral breast MRI for the diagnosis of ILC were calculated. Association of MRI BI-RADS categorical variables and characterization of ILC were assessed (Fisher exact test).<br><br>RESULTS: Among 360 patients treated for ILC in 2004-2007, 15 patients qualified for this study. Thirty-one ILC foci were found on pathological examination (30 ipsilateral and 1 contralateral tumor; mean diameter 23 mm; range 2-60 mm) and all were identified on MRI, with 90% of masses and 10% non-mass-like enhancements; MRI features significantly associated with ILC included absence of smooth margins (P = 0.02) and rim-shaped enhancement (P = 0.039). Enhancement kinetics of the 31 foci were evenly distributed among wash-out, plateau, and persistent profiles. Eleven additional lesions were seen on MRI, mainly corresponding to fibrocystic disease; 91% presented as masses and 9% had a wash-out profile.<br><br>CONCLUSION: Based on the 2006 BI-RADS criteria, breast MRI shows a high sensitivity for ILC detection, at the expense of a 26% false-positive rate, suggesting that a pathological proof by US- or MR-guided biopsy is required in case of suspicious MRI images in this context.}, }
@article {pmid22539628, year = {2013}, author = {Nakash, O and Barchana, M and Liphshitz, I and Keinan-Boker, L and Levav, I}, title = {The effect of cancer on suicide in ethnic groups with a differential suicide risk.}, journal = {European journal of public health}, volume = {23}, number = {1}, pages = {114-115}, doi = {10.1093/eurpub/cks045}, pmid = {22539628}, issn = {1464-360X}, mesh = {Adult ; Age Distribution ; Aged ; Asian People/psychology/statistics &amp; numerical data ; Black People/psychology/statistics &amp; numerical data ; Confidence Intervals ; Ethnicity/psychology/*statistics &amp; numerical data ; Female ; Humans ; Incidence ; Israel/ethnology ; Male ; Middle Aged ; Neoplasms/ethnology/*psychology ; Population Surveillance ; Registries ; Risk Factors ; Self-Injurious Behavior/ethnology/*psychology ; Sex Distribution ; Socioeconomic Factors ; Suicide/*ethnology/*psychology ; White People/psychology/statistics &amp; numerical data ; }, abstract = {This study examined the suicide risk among persons with cancer in ethnic groups with differential suicide mortality in the general population. We calculated the suicide standardized incidence ratios (SIRs) among Europe-America and Asia-North Africa-born Israelis with cancer, relative to the respective rates in the general population. The SIRs were higher in the European-American group [men: 1.96, 95% confidence interval (CI) 1.62-2.30; women: 2.03, 95% CI 1.51-2.56], but not significantly different in the Asian-North African group (men: 0.86, 95% CI 0.52-1.20; women: 0.80, 95% CI 0.10-1.50). Assessment of suicide risk must consider the 'suicide culture' of the person with cancer.}, }
@article {pmid22534285, year = {2012}, author = {Neto, GB and Rossetti, C and Souza, NA and LA Fonseca, F and Azzalis, LA and Junqueira, VB and Valenti, VE and de Abreu, LC}, title = {Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report.}, journal = {European journal of medical research}, volume = {17}, number = {1}, pages = {8}, pmid = {22534285}, issn = {2047-783X}, mesh = {*Breast Neoplasms/complications/pathology/surgery ; *Carcinoma, Ductal/complications/pathology/surgery ; Female ; Humans ; Neoplasm Invasiveness/*pathology ; *Phyllodes Tumor/complications/pathology/surgery ; }, abstract = {This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.}, }
@article {pmid22531532, year = {2012}, author = {,  and Permi, HS and Kishan Prasad, HL and Mohan, R and Shetty, KJ and Patil, C}, title = {Synchronous bilateral medullary carcinoma of breast: is it metastasis or second primary?.}, journal = {Journal of cancer research and therapeutics}, volume = {8}, number = {1}, pages = {129-131}, doi = {10.4103/0973-1482.95193}, pmid = {22531532}, issn = {1998-4138}, mesh = {Adult ; Breast Neoplasms/*diagnosis/pathology/therapy ; Carcinoma, Medullary/*diagnosis/pathology/therapy ; Chemoradiotherapy ; Female ; Humans ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplasms, Second Primary/*diagnosis/pathology/therapy ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; }, abstract = {Bilateral breast cancer is a rare event accounting for 2-5% of all breast malignancies. A second tumor in contralateral breast may be either synchronous or metachronous lesion. Synchronous bilateral invasive ductal carcinoma is known but medullary carcinoma is rare. The etiology of bilateral breast cancer is uncertain and prognosis in these cases once thought to be poor but recent data suggest a similar survival compared to unilateral disease. We report a case of triple negative synchronous bilateral medullary carcinoma in a 38-year-old female who presented with lump in both the breasts for three months. Multidetector computed tomography breast scan revealed bilateral heterogeneously enhancing well-defined lesion in both the breasts. Fine needle aspiration cytology from both the breast lump was suggestive of malignancy. Patient underwent bilateral modified radical mastectomy with axillary clearance in a single sitting. Histopathology showed synchronous bilateral medullary carcinoma of breast with ER, PR and HER- 2/ neu negativity. Patient was treated with chemoradiation and she is on regular follow up for one year without any recurrence or metastasis.}, }
@article {pmid22527124, year = {2012}, author = {Zheng, J and Liu, Q and Yang, J and Ren, Q and Cao, W and Yang, J and Yu, Z and Yu, F and Wu, Y and Shi, H and Liu, W}, title = {Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {45}, number = {6}, pages = {510-515}, pmid = {22527124}, issn = {1414-431X}, mesh = {Analysis of Variance ; Antibiotics, Antineoplastic/*pharmacology ; Apoptosis/*drug effects ; Breast Neoplasms/*immunology ; Cancer Vaccines/*immunology ; Coculture Techniques ; Dendritic Cells/cytology/*immunology ; Doxorubicin/*pharmacology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interferon-gamma/metabolism ; Lymphocyte Activation ; MCF-7 Cells ; }, abstract = {A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.}, }
@article {pmid22524805, year = {2012}, author = {Ramezani, F and Salami, S and Omrani, MD and Maleki, D}, title = {CpG island methylation profile of estrogen receptor alpha in Iranian females with triple negative or non-triple negative breast cancer: new marker of poor prognosis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {2}, pages = {451-457}, doi = {10.7314/apjcp.2012.13.2.451}, pmid = {22524805}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; CpG Islands/*genetics ; *DNA Methylation ; DNA, Neoplasm/genetics ; Estrogen Receptor alpha/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Immunoenzyme Techniques ; Iran ; Menopause ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Prognosis ; Promoter Regions, Genetic/genetics ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {One decade early onset of the breast cancer in Iranian females was reported but the basis of the observed difference has remained unclear and difference in gene silencing by epigenetic processes is suggested. Hence, this study was sought to map the methylation status of ER gene CpG islands and its impact on clinicopathological factors of triple negative and non-triple negative ductal cell carcinoma of the breast in Iranian females. Surgically resected formalin-fixed paraffin-embedded breast tissues from sixty Iranian women with confirmed invasive ductal carcinoma were assessed by methylation-specific PCR using primer sets encompassing some of the 29 CpGs across the ER gene CpG island. The estrogen and progesterone receptors, Her-2 overexpression, and nuclear accumulation of P53 were examined using immunohistochemistry (IHC). Methylated ER3, ER4, and ER5 were found in 41.7, 11.3, and 43.3% of the samples, respectively. Significantly higher methylation of ER4 was found in the tumors with nuclear accumulation of P53, and significantly higher methylation of ER5 was found in patients with lymph node involvement and tumor with bigger size or higher grades. Furthermore, significantly higher rate of ER5 methylation was found in patients with Her-2+ tumors and in postmenopausal patients with ER-, PgR-, or ER-/PgR- tumors. However, no significant difference in ERs methylation status was found between triple negative and non-triple negative tumors in pre- and postmenopausal patients. Findings revealed that aberrant hypermethylation of ER-a gene frequently occur in Iranian women with invasive ductal cell carcinoma of the breast. However, methylation of different CpG islands produced a diverse impact on the prognosis of breast cancer, and ER5 was found to be the most frequently methylated region in the Iranian women, and could serve as a marker of poor prognosis.}, }
@article {pmid22523546, year = {2012}, author = {Wang, H and Tan, G and Dong, L and Cheng, L and Li, K and Wang, Z and Luo, H}, title = {Circulating MiR-125b as a marker predicting chemoresistance in breast cancer.}, journal = {PloS one}, volume = {7}, number = {4}, pages = {e34210}, pmid = {22523546}, issn = {1932-6203}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Breast Neoplasms/*drug therapy/genetics ; Carcinoma, Ductal, Breast/*drug therapy/genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; E2F3 Transcription Factor/drug effects/genetics ; Female ; Humans ; MicroRNAs/*blood ; Middle Aged ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Chemotherapy is an important component in the treatment paradigm for breast cancers. However, the resistance of cancer cells to chemotherapeutic agents frequently results in the subsequent recurrence and metastasis. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of circulating microRNAs (miRNAs) can predict clinical outcome in breast cancer patients treated with adjuvant chemotherapy.<br><br>Circulating miRNAs in blood serum prior to treatment were determined by quantitative Real-Time PCR in 56 breast cancer patients with invasive ductal carcinoma and pre-operative neoadjuvant chemotherapy. Proliferating cell nuclear antigen (PCNA) immunostaining and TUNEL were performed in surgical samples to determine the effects of chemotherapy on cancer cell proliferation and apoptosis, respectively. Among the miRNAs tested, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression level in non-responsive patients (n&#x200a;=&#x200a;26, 46%; p&#x200a;=&#x200a;0.008). In addition, breast cancers with high miR-125b expression had higher percentage of proliferating cells and lower percentage of apoptotic cells in the corresponding surgical specimens obtained after neoadjuvant chemotherapy. Increased resistance to anticancer drug was observed in vitro in breast cancer cells with ectopic miR-125b expression; conversely, reducing miR-125b level sensitized breast cancer cells to chemotherapy. Moreover, we demonstrated that the E2F3 was a direct target of miR-125b in breast cancer cells.<br><br>CONCLUSIONS/SIGNIFICANCE: These data suggest that circulating miR-125b expression is associated with chemotherapeutic resistance of breast cancer. This finding has important implications in the development of targeted therapeutics for overcoming chemotherapeutic resistance in novel anti-cancer strategies.}, }
@article {pmid22515290, year = {2012}, author = {Ren, X and Daa, T and Yada, N and Kashima, K and Fujitomi, Y and Yokoyama, S}, title = {Expression and mutational status of RON in neoplastic lesions of the breast: analysis of MSP/RON signaling in ductal carcinoma in situ and invasive ductal carcinoma.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {120}, number = {5}, pages = {358-367}, doi = {10.1111/j.1600-0463.2011.02841.x}, pmid = {22515290}, issn = {1600-0463}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; DNA, Neoplasm/chemistry/genetics ; Female ; Hepatocyte Growth Factor/biosynthesis/genetics/*metabolism ; Humans ; Immunohistochemistry ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Proto-Oncogene Proteins/biosynthesis/genetics/*metabolism ; Receptor Protein-Tyrosine Kinases/biosynthesis/genetics/*metabolism ; Retrospective Studies ; Statistics, Nonparametric ; }, abstract = {Recepteur d'origine nantais (RON) is a receptor tyrosine kinase closely related to MET and involved in tumorigenesis. We investigated the roles of aberrations in RON and its ligand, macrophage-stimulating protein (MSP), in invasive ductal carcinoma (IDC, n = 81), ductal carcinoma in situ (DCIS, n = 26), and in benign lesions (n = 20) of mammary gland. Expression of RON and MSP was evaluated by immunohistochemistry and the mutational status of a region containing the proteolytic cleavage site in exon 1 and each exon of the kinase domain (exon 14-20) of RON was screened by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. The proportion of cases positive for RON expression was significantly different between malignant [86% (92/107)] and benign [40% (8/20)] lesions. RON expression was positive in both IDC and DCIS [90% (73/81) and 73% (19/26), respectively], whereas MSP expression was present in 54% (44/81) of IDC and absent in DCIS. RON expression correlated significantly with the histological grade of DCIS. No mutations were detected in the examined regions of RON in breast cancer samples as confirmed by PCR-SSCP. The findings suggest the involvement of RON expression in the development of breast cancer, and that an autocrine/paracrine loop of RON seems to affect tumor invasiveness.}, }
@article {pmid22503535, year = {2012}, author = {de Oliveira, MM and de Oliveira, SF and Lima, RS and de Andrade Urban, C and Cavalli, LR and de Souza Fonseca Ribeiro, EM and Cavalli, IJ}, title = {Differential loss of heterozygosity profile on chromosome 3p in ductal and lobular breast carcinomas.}, journal = {Human pathology}, volume = {43}, number = {10}, pages = {1661-1667}, doi = {10.1016/j.humpath.2011.12.008}, pmid = {22503535}, issn = {1532-8392}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Chromosomes, Human, Pair 3/*genetics ; Female ; Humans ; Loss of Heterozygosity/*genetics ; Polymerase Chain Reaction ; }, abstract = {The 2 main histologic types of infiltrating breast cancer, invasive lobular and invasive ductal carcinoma, are morphologically and clinically distinct. Studies revealed that different patterns of gene expression and loss of heterozygosity can also distinguish these 2 subtypes. A whole-genome study using single nucleotide polymorphism array found a significantly higher frequency of loss of heterozygosity on 3p in invasive ductal carcinoma when compared with invasive lobular carcinoma. In this study, we performed a loss of heterozygosity analysis of the 3p chromosome region in ductal and lobular breast tumors. Seven microsatellite markers were evaluated in a series of 136 sporadic breast cancer cases (118 invasive ductal carcinoma and 18 invasive lobular carcinoma) and correlated with clinical-histopathologic parameters from the patients. A significantly higher frequency of loss of heterozygosity was observed in invasive ductal carcinoma (65.3%) when compared with invasive lobular carcinoma (38.9%). When the markers were analyzed separately, loss of heterozygosity at 3 of them, D3S1307 in 3p26.3, D3S1286 in 3p24.3, and D3S1300 in 3p14.2, were significantly more frequent in ductal than in lobular tumors. D3S1307 marker showed the highest frequency of loss of heterozygosity in invasive ductal carcinoma (46.2%), and associations between loss of this marker and loss of estrogen and progesterone receptors were found in these samples. Our results confirm the observations that invasive ductal carcinoma has a higher frequency of loss of heterozygosity events across the 3p region than invasive lobular carcinoma and show that specific losses on 3p26.3, 3p24.3, and 3p14.2 regions are more frequent in ductal than in lobular tumors. We discuss our data in relation to the known tumor suppressor genes that are mapped at the 3p loci investigated and their present relevant roles in breast cancer.}, }
@article {pmid22498883, year = {2012}, author = {Hodgkinson, VC and Agarwal, V and ELFadl, D and Fox, JN and McManus, PL and Mahapatra, TK and Kneeshaw, PJ and Drew, PJ and Lind, MJ and Cawkwell, L}, title = {Pilot and feasibility study: comparative proteomic analysis by 2-DE MALDI TOF/TOF MS reveals 14-3-3 proteins as putative biomarkers of response to neoadjuvant chemotherapy in ER-positive breast cancer.}, journal = {Journal of proteomics}, volume = {75}, number = {9}, pages = {2745-2752}, doi = {10.1016/j.jprot.2012.03.049}, pmid = {22498883}, issn = {1876-7737}, mesh = {14-3-3 Proteins/*genetics ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy/genetics ; Drug Resistance, Neoplasm/*genetics ; Electrophoresis, Gel, Two-Dimensional ; Feasibility Studies ; Female ; Humans ; Neoadjuvant Therapy ; Pilot Projects ; Receptors, Estrogen/genetics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Neoadjuvant chemotherapy is used to treat oestrogen receptor-positive breast cancer however chemo-resistance is a major obstacle in this molecular subtype. The ability to predict tumour response would allow chemotherapy administration to be directed towards patients who would most benefit, thus maximising treatment efficacy. We aimed to identify protein biomarkers associated with response to neoadjuvant chemotherapy, in a pilot study using comparative 2-DE MALDI TOF/TOF MS proteomic analysis of breast tumour samples. A total of 3 comparative proteomic experiments were performed, comparing protein expression between chemotherapy-sensitive and chemotherapy-resistant oestrogen receptor-positive invasive ductal carcinoma tissue samples. This identified a list of 132 unique proteins that were significantly differentially expressed (≥ 2 fold) in chemotherapy resistant samples, 57 of which were identified in at least two experiments. Ingenuity® Pathway Analysis was used to map the 57 DEPs onto canonical signalling pathways. We implicate several isoforms of 14-3-3 family proteins (theta/tau, gamma, epsilon, beta/alpha and zeta/delta), which have previously been associated with chemotherapy resistance in breast cancer. Extensive clinical validation is now required to fully assess the role of these proteins as putative markers of chemotherapy response in luminal breast cancer subtypes.}, }
@article {pmid22495877, year = {2012}, author = {Hammadi, M and Chopin, V and Matifat, F and Dhennin-Duthille, I and Chasseraud, M and Sevestre, H and Ouadid-Ahidouch, H}, title = {Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.}, journal = {Journal of cellular physiology}, volume = {227}, number = {12}, pages = {3837-3846}, doi = {10.1002/jcp.24095}, pmid = {22495877}, issn = {1097-4652}, mesh = {Breast Neoplasms/metabolism/pathology ; Calcium/*metabolism ; Calcium Channels/genetics/*metabolism ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/*physiology ; Cell Survival ; Ether-A-Go-Go Potassium Channels/genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Manganese ; Neoplasm Invasiveness ; ORAI1 Protein ; Patch-Clamp Techniques ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development.}, }
@article {pmid22489664, year = {2012}, author = {Krell, J and Frampton, AE and Jacob, J and Pellegrino, L and Roca-Alonso, L and Zeloof, D and Alifrangis, C and Lewis, JS and Jiao, LR and Stebbing, J and Castellano, L}, title = {The clinico-pathologic role of microRNAs miR-9 and miR-151-5p in breast cancer metastasis.}, journal = {Molecular diagnosis &amp; therapy}, volume = {16}, number = {3}, pages = {167-172}, pmid = {22489664}, issn = {1179-2000}, support = {10-0510/AICR_/Worldwide Cancer Research/United Kingdom ; G1100425/MRC_/Medical Research Council/United Kingdom ; NIHR-RP-011-053/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis/*genetics ; MicroRNAs/*genetics ; Middle Aged ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) may function as suppressors or promoters of tumor metastasis according to their messenger RNA targets. Previous studies have suggested that miR-9 and miR-151-5p are associated with metastasis in breast cancer and hepatocellular carcinoma, respectively. We aimed to further establish the potential roles of miR-9 and miR-151-5p in tumor invasion and metastasis and investigate their use as biomarkers.<br><br>METHODS: We used quantitative real-time PCR (qRT-PCR) to measure differences in miR-9 and miR-151-5p expression between primary breast tumors and their lymph-node metastases in 194 paired tumor samples from 97 patients. We also correlated expression levels with histologic data to investigate their utility as biomarkers.<br><br>RESULTS: There were no significant differences in miR-9 expression between the primary tumors and lymph nodes; however, miR-151-5p expression was significantly lower in the lymph-node metastases than in their corresponding tumors (p < 0.05). miR-9 levels were elevated in primary breast tumors from patients diagnosed with higher-grade tumors (p < 0.05); however, no differences were observed in miR-151-5p levels between different grades of tumor. Interestingly, miR-9 levels were elevated in invasive lobular carcinomas (ILC) compared with invasive ductal carcinomas (IDC; p < 0.01).<br><br>CONCLUSIONS: In aggregate, these data suggest that miR-151-5p upregulation may suppress metastasis in primary breast tumors. Both miRNAs may serve as useful biomarkers in future clinical trials in breast cancer.}, }
@article {pmid22484590, year = {2012}, author = {Wang, GY and Zhang, Q and Yang, Y and Chen, WJ and Liu, W and Jiang, N and Chen, GH}, title = {Rapamycin combined with allogenic immature dendritic cells selectively expands CD4+CD25+Foxp3+ regulatory T cells in rats.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {11}, number = {2}, pages = {203-208}, doi = {10.1016/s1499-3872(12)60149-0}, pmid = {22484590}, issn = {1499-3872}, mesh = {Animals ; CD4 Antigens/*metabolism ; Dendritic Cells/*transplantation ; Forkhead Transcription Factors/*metabolism ; Immune Tolerance/immunology ; Immunosuppressive Agents/pharmacology ; In Vitro Techniques ; Interferon-gamma/blood ; Interleukin-2/blood ; Interleukin-2 Receptor alpha Subunit/*metabolism ; Interleukin-4/blood ; Models, Animal ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Sirolimus/*pharmacology ; T-Lymphocytes, Regulatory/*drug effects/*immunology/pathology ; Transforming Growth Factor beta1/blood ; Transplantation Tolerance/immunology ; }, abstract = {BACKGROUND: Dendritic cells (DCs) can initiate the expansion of regulatory T cells (Tregs), which play an indispensable role in inducing transplantation tolerance. Some studies have investigated the effect of the immunosuppressant rapamycin (Rapa) on Tregs in vitro. However, the in vivo effect of Rapa combined with immature DCs (iDCs) on Tregs is unknown. This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectively expand the CD4+CD25+Foxp3+ Tregs in a rat model.<br><br>METHODS: Brown Norway rats were injected intravenously with 2X10(6) Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days. On day 8, the levels of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry. IL-2, IL-4, TGF-beta1, and IFN-gamma levels in serum were assessed by ELISA. The experimental animals were divided into four groups: control, Rapa-treated, iDC-treated, and combination-treated.<br><br>RESULTS: CD4+CD25+Foxp3+ Tregs comprised 7%-8% of CD4+ T cells in control rats. Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen. However, the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone. The levels of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3- T cells in CD4+ T cells did not significantly change in the combined group. The TGF-beta1 level in serum from the combined group increased significantly compared with the other groups.<br><br>CONCLUSIONS: A significantly higher percentage of CD4+ CD25+ Foxp3+ Tregs was found in rats treated with allogenic iDCs and a short course of Rapa, along with an increase in the TGF-beta1 level in serum. This improved protocol may be a promising therapeutic strategy to increase Tregs, which are beneficial to the induction of peritransplant tolerance.}, }
@article {pmid22475781, year = {2012}, author = {Lee, Y and Ryu, Y and Jeong, H and Chang, H and Kim, Y and Kim, A}, title = {Effectiveness of silver-enhanced in situ hybridization for evaluating HER2 gene status in invasive breast carcinoma: a comparative study.}, journal = {Archives of medical research}, volume = {43}, number = {2}, pages = {139-144}, doi = {10.1016/j.arcmed.2012.03.010}, pmid = {22475781}, issn = {1873-5487}, mesh = {Breast Neoplasms/*genetics/pathology ; *Genes, erbB-2 ; Humans ; In Situ Hybridization/*methods ; Neoplasm Invasiveness ; Silver/*chemistry ; }, abstract = {BACKGROUND AND AIMS: HER2 gene amplification occurs in breast cancers and has implications for treatment and prognosis. Recently, a new direct evaluation technique, silver enhanced in situ hybridization (SISH) was developed for evaluating HER2 gene status. This study was performed to evaluate the SISH technique for clinical use by comparing it to that of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).<br><br>METHODS: We studied 543 cases of excised breast specimens diagnosed as invasive ductal carcinoma by IHC, FISH, and SISH using a tissue microarray. IHC, FISH, and SISH results were interpreted according to the American Society of Clinical Oncology/College of American Pathologists guidelines. A total of seven English studies that reported the concordance rates of SISH and BDISH compared to FISH published before July 2011 were retrieved.<br><br>RESULTS: The consensus concordance rate between SISH and FISH was 96.69% (kappa value = 0.9175). The pooled sensitivity was 0.94 [95% confidence interval (CI) = 0.91-0.97], and the pooled specificity was 0.98 (95% CI = 0.96-099) in a meta-analysis of the retrieved studies and this study. Area under the receiver operating characteristics curve was 0.9906.<br><br>CONCLUSIONS: SISH technique is an effective modality and is comparable with FISH for evaluating HER2 gene amplification in patients with breast carcinoma.}, }
@article {pmid22472881, year = {2012}, author = {Xu, C and Tran-Thanh, D and Ma, C and May, K and Jung, J and Vecchiarelli, J and Done, SJ}, title = {Mitochondrial D310 mutations in the early development of breast cancer.}, journal = {British journal of cancer}, volume = {106}, number = {9}, pages = {1506-1511}, pmid = {22472881}, issn = {1532-1827}, mesh = {Breast/metabolism/*pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; DNA, Mitochondrial/*genetics ; Disease Progression ; Female ; Humans ; Mutation/*genetics ; Repetitive Sequences, Nucleic Acid/genetics ; }, abstract = {BACKGROUND: The role of mitochondrial DNA (mtDNA) mutations in the development of breast cancer is largely unknown. In this study, we investigated the frequency and pattern of mutations in the D310 region, the most commonly mutated region in mtDNA, in a series of breast lesions.<br><br>METHODS: Using capillary electrophoresis, we genotyped the D310 sequence of neoplastic epithelial cells from 23 patients with synchronous ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), 26 patients with IDC only and 29 patients with DCIS only.<br><br>RESULTS: A majority of DCIS (68.4%) and IDC (71.4%) lesions harbour different D310 sequences compared with their matched normal control. Specific D310 sequences were more frequently identified in tumour samples (77.1% of DCIS and 75.5% of IDC) compared with normal tissues (35.3% of normal; P<0.0001). No difference was identified between DCIS lesions with synchronous IDC and those from pure DCIS cases. In five cases, histologically normal tissue adjacent to tumour was found to share D310 sequences with the tumour, while normal tissue taken further away did not.<br><br>CONCLUSION: Although D310 alterations do not seem to be related to DCIS progression, they were found in histologically normal cells adjacent to tumour. This suggests a field of genetically altered cells, thus D310 mutations could represent a potential marker for the clonal expansion of premalignant breast cancer cells.}, }
@article {pmid22458904, year = {2012}, author = {Robinson, B and Magi-Galluzzi, C and Zhou, M}, title = {Intraductal carcinoma of the prostate.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {136}, number = {4}, pages = {418-425}, doi = {10.5858/arpa.2011-0519-RA}, pmid = {22458904}, issn = {1543-2165}, mesh = {Biopsy ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Diagnosis, Differential ; Humans ; Male ; Molecular Biology ; Prognosis ; Prostate/*pathology ; Prostatectomy ; Prostatic Neoplasms/genetics/*pathology ; }, abstract = {CONTEXT: Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathologic entity, characterized by an expansile proliferation of secretory cells within prostatic ducts and acini that demonstrate marked architectural and cytologic atypia. Intraductal carcinoma of the prostate is strongly associated with high-grade and high-volume, invasive prostate cancer and a poorer prognosis than cases without IDC-P.<br><br>OBJECTIVE: To review the historic perspectives, pathologic and genetic features, diagnostic criteria and differential diagnoses, and the clinical significance of IDC-P.<br><br>DATA SOURCES: Relevant studies indexed in PubMed.<br><br>CONCLUSIONS: It is critical to recognize IDC-P, especially in prostate biopsies in which the clinical implications of IDC-P are greatest. Morphologic criteria have been proposed to distinguish IDC-P from several other lesions with similar histologic appearance such as high-grade prostatic intraepithelial neoplasia, invasive cribriform prostate cancer, and urothelial carcinoma involving the prostate. Intraductal carcinoma of the prostate is an uncommon finding in prostate biopsies, and it is even rarer as an isolated finding without concomitant prostate cancer in biopsies. However, patients with isolated IDC-P in biopsies are recommended for either definitive treatment or immediate repeat biopsy.}, }
@article {pmid22452996, year = {2012}, author = {Xiang, L and Liu, ZH and Huan, Q and Su, P and Du, GJ and Wang, Y and Gao, P and Zhou, GY}, title = {Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {32}, pmid = {22452996}, issn = {1746-1596}, mesh = {ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters/*biosynthesis ; Basic Helix-Loop-Helix Transcription Factors/*biosynthesis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*biosynthesis ; Neoplasm Grading ; Neoplasm Proteins/*biosynthesis ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer mortality in women worldwide. Hypoxia is an important factor involved in the progression of solid tumors and has been associated with various indicators of tumor metabolism, angiogenesis and metastasis. But little is known about the contribution of Hypoxia-Inducible Factor-2a (HIF-2a) to the drug resistance and the clinicopathological characteristics in breast cancer.<br><br>METHODS: Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 invasive breast cancer patients with clinicopathological data. The correlations between the expression of HIF-2a and ABCG2 as well as other patients' clinicopathological data were investigated.<br><br>RESULTS: The results showed that HIF-2a was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive staining for HIF-2a was defined as a brown staining observed mainly in the nucleus. A statistically significant correlation was demonstrated between HIF-2a expression and ABCG2 expression (p = 0.001), histology-grade (p = 0.029), and Ki67 (p = 0. 043) respectively.<br><br>CONCLUSION: HIF-2a was correlated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma. HIF-2a could regulate ABCG2 in breast cancer cells, and could be a novel potential bio-marker to predict chemotherapy effectiveness. The hypoxia/HIF-2a/ABCG2 pathway could be a new mechanism of breast cancer multidrug-resistance.<br><br>VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/2965948166714795.}, }
@article {pmid22451233, year = {2012}, author = {Cao, AY and He, M and Liu, ZB and Di, GH and Wu, J and Lu, JS and Liu, GY and Shen, ZZ and Shao, ZM}, title = {Outcome of pure mucinous breast carcinoma compared to infiltrating ductal carcinoma: a population-based study from China.}, journal = {Annals of surgical oncology}, volume = {19}, number = {9}, pages = {3019-3027}, doi = {10.1245/s10434-012-2322-6}, pmid = {22451233}, issn = {1534-4681}, mesh = {Adenocarcinoma, Mucinous/metabolism/*pathology/secondary/therapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/secondary/therapy ; Chemotherapy, Adjuvant ; China ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Young Adult ; }, abstract = {PURPOSE: Pure mucinous breast carcinoma (PMBC) is a rare pathologic finding. Few studies have addressed the biologic features of PMBC and prognostic factors among patients with this disease. We performed a study to compare PMBC and invasive ductal carcinoma (IDC) by means of a large database to reliably assess the biologic phenotype and clinical behavior of PMBC.<br><br>METHODS: A total of 2,511 patients who met the inclusion criteria were identified from 1999 to 2010; 2,202 patients had pure IDC and 309 had PMBC. Clinical and biologic features, overall survival, and recurrence/metastasis-free survival (RFS) were compared for both groups.<br><br>RESULTS: PMBC had favorable characteristics including smaller size, lower rates of lymph node positivity, lower stage, higher expression of hormone receptors, and less HER2 overexpression. Patients with PMBC had better 10-year RFS (71 %) than patients with IDC (64 %). Multivariate analysis revealed that node status and tumor, node, metastasis system (TNM) stage were statistically significant prognostic factors for survival. RFS curves stratified for node status revealed a highly significant difference between node negative and node positive patients. Additionally, patients with PMBC underwent breast-conserving surgery (BCS) more frequently than patients with IDC, and the 5-year overall survival rate of the BCS group was not significantly different from the total mastectomy group.<br><br>CONCLUSIONS: PMBC in Chinese women showed less aggressive behavior and had a better prognosis than IDC, and this favorable outcome was maintained after 10 years. Node status and TNM stage appeared to be the most significant predictors of worse prognosis. BCS should be preferred over mastectomy in the treatment of early-stage PMBC.}, }
@article {pmid22439598, year = {2012}, author = {Wang, CC and Liau, JY and Lu, YS and Chen, JW and Yao, YT and Lien, HC}, title = {Differential expression of moesin in breast cancers and its implication in epithelial-mesenchymal transition.}, journal = {Histopathology}, volume = {61}, number = {1}, pages = {78-87}, doi = {10.1111/j.1365-2559.2012.04204.x}, pmid = {22439598}, issn = {1365-2559}, mesh = {Adenocarcinoma/*metabolism/mortality/secondary ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Combined Modality Therapy ; Disease Progression ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; Immunohistochemistry/methods ; Microfilament Proteins/*metabolism ; Prognosis ; Survival Rate ; Taiwan/epidemiology ; Tissue Array Analysis ; }, abstract = {AIMS: Moesin belongs to the ERM (ezrin, radixin and moesin) family. Recent in-vitro studies have shown the possible involvement of moesin in epithelial-mesenchymal transition (EMT), but correlating in-vivo evidence is lacking.<br><br>METHODS AND RESULTS: To study the biological significance of moesin, we used immunohistochemistry to investigate the in-situ expression profiles of moesin in 322 breast carcinomas of different subtypes, including 23 cases of metaplastic carcinoma (MCB) which is pathogenetically considered to involve EMT. Moesin was highly expressed in 95.7% of cases of MCB, and in 16% of cases of invasive ductal carcinoma (IDC), but was negative in all other subtypes of breast carcinomas. In IDCs, moesin expression correlated positively with a high histological grade (P < 0.001), basal-like phenotype (P < 0.001) and poor overall survival (P = 0.0263). Transfection of MCF7 cells with Snail, one of the key regulators of EMT, showed up-regulation of moesin at the transcriptional level. Finally, mRNA level of moesin correlated positively with Snail and EMT-related genes in a microarray data set using primary breast cancer samples.<br><br>CONCLUSION: These results offer biological evidence of moesin as an EMT marker, support the association between moesin, Snail and EMT and suggest a role for moesin in breast cancer prognostication.}, }
@article {pmid22424944, year = {2012}, author = {Chen, YH and Huang, CH}, title = {Reversible posterior leukoencephalopathy syndrome induced by vinorelbine.}, journal = {Clinical breast cancer}, volume = {12}, number = {3}, pages = {222-225}, doi = {10.1016/j.clbc.2012.01.006}, pmid = {22424944}, issn = {1938-0666}, mesh = {Adult ; Antineoplastic Agents/adverse effects/therapeutic use ; Breast Neoplasms/drug therapy ; Carcinoma, Ductal, Breast/drug therapy ; Female ; Humans ; Posterior Leukoencephalopathy Syndrome/*chemically induced/diagnosis ; Vinblastine/adverse effects/*analogs &amp; derivatives/therapeutic use ; Vinorelbine ; }, abstract = {Reversible posterior leukoencephalopathy syndrome (RPLS) was first described in 1996; clinical symptoms include the presence of headache, visual disturbance,seizure, hypertension, and encephalopathy. The syndrome is most commonly encountered in association with chemotherapeutic agents or targeted therapy. Many chemotherapeutic agents, such as cisplatin,gemcitabine, methotrexate, were reported to be associated with RPLS. Vinorelbine is commonly used for the treatment of metastatic breast cancer, but vinorelbine-induced RPLS has not been reported. We reported a 34-year-old woman, diagnosed with invasive ductal carcinoma of the left breast, who experienced acute hypertension after vinorelbine intravenous infusion. Accompanied symptoms included headache,seizure, and conscious disturbance. Magnetic resonance imaging of the brain showed symmetric signal hyperintensity with the cortical and subcortical white matter of bilateral frontal, parietal, and occipital (predominant) lobes. Vinorelbine is a semisynthetic vinca alkaloid and prevents cell division by inhibiting tubulin polymerization.Brain metastasis or leptomeningeal carcinomatosis is an important issue for patients with breast cancer who present with headache, seizure, or altered consciousness.However, now RPLS may be a new consideration,especially with the presentation of acute hypertension. Unlike brain or meningeal metastasis, RPLS is usually benign, and most patients recover within 2 weeks. Our case highlights an association between vinorelbine and RPLS, and the drug has not been described as a predisposing factor of RPLS in past reports. In the era of cancer treatment with chemotherapy or targeted therapy,clinicians should be aware of this syndrome.}, }
@article {pmid22415745, year = {2012}, author = {Görkem, SB and O'Connell, AM}, title = {Abnormal axillary lymph nodes on negative mammograms: causes other than breast cancer.}, journal = {Diagnostic and interventional radiology (Ankara, Turkey)}, volume = {18}, number = {5}, pages = {473-479}, doi = {10.4261/1305-3825.DIR.5491-11.2}, pmid = {22415745}, issn = {1305-3612}, mesh = {Adult ; Axilla ; Biopsy, Needle ; Breast Implants/adverse effects ; Breast Neoplasms/diagnostic imaging/*pathology/secondary ; Calcinosis/complications/diagnostic imaging/pathology ; Connective Tissue Diseases/complications/diagnostic imaging/pathology ; Female ; Hodgkin Disease/complications/pathology ; Humans ; Immunohistochemistry ; Lymph Nodes/diagnostic imaging/*pathology ; Lymphatic Diseases/*etiology/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/pathology ; Prognosis ; Radiography ; Risk Assessment ; Tattooing/adverse effects ; }, abstract = {Enlargement of lymph nodes can be due to a variety of benign and malignant causes. The most common malignant cause is invasive ductal carcinoma, which is usually visualized with mammography. Excluding breast cancer, other causes of abnormal lymph nodes that produce a negative mammogram include lymphoma, metastases from other malignancies, and benign etiologies such as inflammatory processes, infectious diseases, collagen vascular diseases, and miscellaneous causes. In this essay, we described common causes of abnormal axillary lymph nodes on negative mammograms excluding breast cancer.}, }
@article {pmid22412048, year = {2012}, author = {Lee, H and Jung, SY and Ro, JY and Kwon, Y and Sohn, JH and Park, IH and Lee, KS and Lee, S and Kim, SW and Kang, HS and Ko, KL and Ro, J}, title = {Metaplastic breast cancer: clinicopathological features and its prognosis.}, journal = {Journal of clinical pathology}, volume = {65}, number = {5}, pages = {441-446}, doi = {10.1136/jclinpath-2011-200586}, pmid = {22412048}, issn = {1472-4146}, mesh = {Biomarkers, Tumor/analysis ; Breast/*pathology ; Breast Neoplasms/chemistry/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/drug therapy/mortality/*secondary ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy, Segmental/methods ; Metaplasia ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Republic of Korea/epidemiology ; Survival Rate ; }, abstract = {AIMS: The prognosis of metaplastic breast cancer (MBC) is reportedly worse than that of triple-negative invasive ductal carcinoma (TN-IDC), but the determinants of poor prognosis are not yet known.<br><br>METHODS: Patients from two Korean cancer centres were included in this study (67 MBC and 520 TN-IDC). Characteristics of the two disease groups, including clinical parameters, histological features, chemoresponsiveness, disease recurrence and survival estimates, were evaluated.<br><br>RESULTS: MBC presented with larger tumours, more frequent distant metastasis and higher histological grade compared with TN-IDC (p<0.001). All but nine patients with MBC had triple-negative disease. Disease-free survival and overall survival (OS) of MBC were worse than TN-IDC (p<0.001). Multivariable analysis of disease-free survival revealed MBC type as an independent prognostic factor (HR 2.53; 95% CI 1.32 to 4.84) along with lymph node metastasis and implementation of breast conserving surgery. For OS, MBC type remained a significant prognostic factor (HR 2.56; 95% CI 1.18 to 5.54). Chemoresponsiveness of MBC and TN-IDC were similar in both neoadjuvant (p=1.000) and advanced disease settings (p=0.508). For a given MBC type, risk factors for disease recurrence included the presence of a squamous component (HR 4.0; 95% CI 1.46 to 10.99) and lymph node metastasis (HR 4.76; 95% CI 1.67 to 13.60); the risk factor for OS was initial distant metastasis (HR 10.77; 95% CI 2.59 to 44.76).<br><br>CONCLUSIONS: MBC had worse survival outcomes compared with TN-IDC. Poor prognosis for MBC was likely caused by frequent recurrence with high initial stage and the unique biology of MBC itself.}, }
@article {pmid22410125, year = {2012}, author = {Khurana, A and McKean, H and Kim, H and Kim, SH and mcguire, J and Roberts, LR and Goetz, MP and Shridhar, V}, title = {Silencing of HSulf-2 expression in MCF10DCIS.com cells attenuate ductal carcinoma in situ progression to invasive ductal carcinoma in vivo.}, journal = {Breast cancer research : BCR}, volume = {14}, number = {2}, pages = {R43}, pmid = {22410125}, issn = {1465-542X}, support = {CA106954-04/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Cell Line, Tumor ; Disease Progression ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mammary Neoplasms, Experimental/genetics/pathology ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Nude ; Sulfatases ; Sulfotransferases/*genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of proliferative cellular lesions that have the potential to become invasive. Very little is known about the molecular alterations involved in the progression from DCIS to invasive ductal carcinoma (IDC). Heparan endosulfatase (HSulf-2) edits sulfate moieties on heparan sulfate proteoglycans (HSPGs) and has been implicated in modulating heparin binding growth factor signaling, angiogenesis and tumorigenesis. However, the role of HSulf-2 in breast cancer progression is poorly understood. MCF10DCIS.com cells (referred as MCF10DCIS) express HSulf-2 and form comedo type DCIS and progress to IDC when transplanted in immune-deficient mice and, therefore, is an ideal model to study breast cancer progression. We evaluated the role of HSulf-2 in progression from DCIS to IDC using mouse fat pad mammary xenografts.<br><br>METHODS: Non-target control (NTC) and HSulf-2 knockdown in MCF10DCIS breast cancer cells were achieved by NTC shRNA and two different lentiviral shRNA against HSulf-2 respectively. Xenografts were established by injecting NTC and HSulf-2 deficient MCF10DCIS cells in mouse mammary fat pads. Xenografts were subjected to H&amp;E staining for morphological analysis, TUNEL and Propidium iodide staining (to determine the extent of apoptosis), Western blot analysis and zymography.<br><br>RESULTS: Using a mouse mammary fat pad derived xenograft model, we observed that compared to control treated xenografts, down-regulation of HSulf-2 was associated with significant delays in growth at Week 7 (P-value < 0.05). Histological examination of the tumors demonstrated substantial differences in comedo necrosis, with marked luminal apoptosis and up-regulation of apoptotic markers Bim, cleaved PARP and cleaved caspase 3 in HSulf-2 depleted xenografts. Furthermore, HSulf-2 depleted xenografts retained the basement membrane integrity with decreased activity and expression of matrix metalloproteinase 9 (MMP-9), an enzyme critical for degradation of extracellular matrix compared to nontargeted control.<br><br>CONCLUSION: Our data suggest that HSulf-2 expression may be critical for human breast cancer progression. Down-regulation of HSulf-2 leads to retention of comedo type DCIS and delays the progression of DCIS to IDC. Further studies are necessary to determine if therapeutic targeting of HSulf-2 expression might delay the progression of DCIS to IDC.}, }
@article {pmid22405699, year = {2012}, author = {Van der Kwast, T and Al Daoud, N and Collette, L and Sykes, J and Thoms, J and Milosevic, M and Bristow, RG and Van Tienhoven, G and Warde, P and Mirimanoff, RO and Bolla, M}, title = {Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high risk prostate cancer patients treated by radiotherapy.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {48}, number = {9}, pages = {1318-1325}, doi = {10.1016/j.ejca.2012.02.003}, pmid = {22405699}, issn = {1879-0852}, mesh = {Aged ; Aged, 80 and over ; Biopsy/methods ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*pathology/radiotherapy/surgery ; Cohort Studies ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/*diagnosis/*pathology/radiotherapy/surgery ; Risk Factors ; Treatment Outcome ; }, abstract = {AIM: We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in biopsies and transurethral resections prior to external beam radiotherapy with or without androgen deprivation.<br><br>METHODS: Cohort 1 consisted of 118 intermediate risk prostate cancer patients treated by radiotherapy, with biochemical relapse as primary end-point (median follow-up 6.5 years). Cohort 2 consisted of 132 high risk patients, enrolled in a phase III randomised trial (EORTC 22863) comparing radiotherapy alone to radiotherapy with long-term androgen deprivation (LTAD) with clinical progression free survival as primary end-point (median follow-up 9.1 years). Presence of IDC-P was identified after central review. Multivariable regression modelling and Kaplan-Meier analysis were performed with IDC-P as dichotomous variable.<br><br>RESULTS: IDC-P was a strong prognosticator for early (<36 months) biochemical relapse (HR 7.3; p = 0.007) in cohort 1 and for clinical disease-free survival in both arms of cohort 2 (radiotherapy arm: HR 3.5; p < 0.0001; radiotherapy plus LTAD arm: HR 2.8, p = 0.018). IDC-P retained significance after stratification for reviewed Gleason score in the radiotherapy arm (HR 2.3; p = 0.03). IDC-P was a strong prognosticator for metastatic failure rate (radiotherapy arm: HR 5.3; p < 0.0001; radiotherapy plus LTAD arm: HR 3.6; p = 0.05).<br><br>CONCLUSIONS: IDC-P in diagnostic samples of patients with intermediate or high risk prostate cancer is an independent prognosticator of early biochemical relapse and metastatic failure rate after radiotherapy. We suggest that the presence of IDC-P in prostate biopsies should routinely be reported.}, }
@article {pmid22393683, year = {2011}, author = {Pusiol, T and Morichetti, D and Zorzi, MG}, title = {Oncocytic carcinoma of the parotid gland: case report and review of the literature.}, journal = {Pathologica}, volume = {103}, number = {5}, pages = {279-289}, pmid = {22393683}, issn = {0031-2983}, mesh = {Adenocarcinoma/*pathology/surgery ; Axilla ; Breast Neoplasms, Male/*pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Combined Modality Therapy ; Disease-Free Survival ; Humans ; Lymph Nodes/pathology/surgery ; Lymphatic Metastasis ; Male ; Mastectomy ; Middle Aged ; *Neoplasms, Multiple Primary ; Oxyphil Cells/*pathology ; Parotid Neoplasms/*pathology/surgery ; }, abstract = {OBJECTIVES: To date 70 cases of oncocytic carcinomas (OCs) have been described in 55 reports. We describe an OC of the parotid gland in a 56-year-old man with simultaneous breast cancer.<br><br>METHODS: In June 2006, a 56-year-old man was referred to the Otorhinolaryngology Division for a painless right preauricolar mass. The facial nerve was functionally normal. Total parotidectomy with facial nerve preservation was performed. In January 2007, the patient was referred to the Surgical Division for a left mammary nodule. Total mastectomy with axillary lymphoadenectomy was performed.<br><br>RESULTS: The mass of the parotid gland measured 3.5 x 3 cm. Histology showed sheets, islands and nests composed of large, round to polyhedral cells with fine, granular, eosinophilic cytoplasm and round vesicular nuclei, with prominent nucleoli. The tumour cells were positive for immunohistochemical staining with antimitochondria antibodies. Histological examination of the mammary tumour showed invasive ductal carcinoma Grade III (Nottingham Histologic Score) with metastasis in 12 axillary lymph nodes. Chemotherapy was performed. At present, the patient is free of recurrences or metastases.<br><br>CONCLUSIONS: Histologically, there is a spectrum of malignant parotid gland neoplasms that have prominent eosinophilic granular cytoplasm due to increased number of mitochondria. OCs have cytoplasm packed with mitochondria, while the term "oncocytoid" should be employed for tumours that have abundant eosinophilic granular cytoplasm, but ultrastructurally do not possess marked mitochondrial hyperplasia. All reported cases of OC should be defined "oncocytic-like carcinoma" when only haematoxylin and eosin staining is performed.}, }
@article {pmid22385318, year = {2012}, author = {Tsuchiya, B and Iwaya, K and Kohno, N and Kawate, T and Akahoshi, T and Matsubara, O and Mukai, K}, title = {Clinical significance of DJ-1 as a secretory molecule: retrospective study of DJ-1 expression at mRNA and protein levels in ductal carcinoma of the breast.}, journal = {Histopathology}, volume = {61}, number = {1}, pages = {69-77}, doi = {10.1111/j.1365-2559.2012.04202.x}, pmid = {22385318}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/secondary ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/pathology/surgery ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; *Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Japan/epidemiology ; Kaplan-Meier Estimate ; Ki-67 Antigen/metabolism ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Staging ; *Oncogene Proteins/genetics/metabolism ; Prognosis ; Protein Deglycase DJ-1 ; RNA, Messenger/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Tissue Array Analysis ; Young Adult ; }, abstract = {AIMS: DJ-1 is a molecule secreted into serum by some breast cancer cells. However, little is known about the clinical significance of the DJ-1 expression.<br><br>METHODS AND RESULTS: Expression of DJ-1 protein was examined by immunohistochemistry, and expression of DJ-1 mRNA was detected using in-situ hybridization in 273 invasive ductal carcinomas (IDCs) and 41 ductal carcinomas in situ (DCISs) of the breast, and also in breast cancer cell lines. Breast cancer cells were examined for their secretion of DJ-1 using immunoblot analysis. By immunohistochemistry DJ-1 protein expression was lower than adjacent non-cancerous epithelium in 6 (14.6%) of the 41 DCISs and 146 (53%) of the 273 IDCs, even although all 314 carcinomas retained expression of DJ-1 mRNA, which was higher than that in adjacent non-cancerous epithelium in 220 cases (70%). Patients with IDC whose cancer cells showed low expression of DJ-1 protein had significantly shorter disease-free survival (P = 0.0152) and overall survival (P = 0.0196) than those whose cancer cells retained DJ-1 expression. MDA-MB-231 cells, which secreted DJ-1, showed low expression of DJ-1 protein.<br><br>CONCLUSIONS: Low expression of DJ-1 protein with high expression of its mRNA, which may reflect a secretory expression pattern, is predictive of poor outcome in patients with IDC.}, }
@article {pmid22382854, year = {2012}, author = {Zaha, H and Onomura, M and Nishikuramori, Y}, title = {Pyogenic vertebral osteomyelitis in a breast cancer patient: report of a case.}, journal = {Surgery today}, volume = {42}, number = {10}, pages = {1022-1025}, pmid = {22382854}, issn = {1436-2813}, mesh = {Aged ; Breast Neoplasms/complications/*diagnosis ; Carcinoma, Ductal, Breast/complications/*diagnosis/secondary ; *Cervical Vertebrae ; Diagnosis, Differential ; Escherichia coli Infections/complications/*diagnosis ; Female ; Humans ; Osteomyelitis/complications/*diagnosis ; Spinal Neoplasms/*diagnosis/secondary ; *Thoracic Vertebrae ; }, abstract = {We herein report a rare case of pyogenic vertebral osteomyelitis (PVO) coexisting with breast carcinoma. A 71-year-old female presented with neck pain without fever. Magnetic resonance imaging (MRI) showed suspected metastatic lesions in her neck (C7 and Th1). Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased FDG uptake in the neck spines and in the left breast. A core needle biopsy of the left breast revealed the presence of invasive ductal carcinoma. Our first tentative diagnosis of the patient was left breast carcinoma with bone metastases, and first-line endocrine therapy was started. However, surgical intervention for the spines had to be considered, because her neurological symptoms progressed. A repeated MRI scan showed a narrowing of the disc space and fluid accumulation around the vertebrae. This suggested the presence of PVO rather than metastases. Surgery confirmed the presence of PVO in C7 and Th1, and a culture of the abscess yielded Escherichia coli. The patient's neurological symptoms dramatically improved after surgery. Breast conserving surgery was performed 3 months after the surgery for PVO. The patient is well and has no clinical evidence of disease 18 months after the breast conserving surgery. PVO is rare, but should be included in the differential diagnosis in patients presenting with early breast carcinoma.}, }
@article {pmid22382823, year = {2012}, author = {Robinson, JO and Pozzi-Langhi, S and Phillips, M and Pearson, JC and Christiansen, KJ and Coombs, GW and Murray, RJ}, title = {Formal infectious diseases consultation is associated with decreased mortality in Staphylococcus aureus bacteraemia.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {31}, number = {9}, pages = {2421-2428}, pmid = {22382823}, issn = {1435-4373}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration &amp; dosage ; Bacteremia/*diagnosis/drug therapy/*mortality ; Child ; Critical Care/statistics &amp; numerical data ; Endocarditis, Bacterial/epidemiology ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Referral and Consultation/*statistics &amp; numerical data ; Retrospective Studies ; Staphylococcal Infections/*diagnosis/drug therapy/*mortality ; Staphylococcus aureus/*isolation &amp; purification ; Survival Analysis ; Treatment Outcome ; Young Adult ; }, abstract = {To determine the impact of infectious diseases consultation (IDC) in Staphylococcus aureus bacteraemia. All MRSA bacteraemia and a random subset of MSSA bacteraemia were retrospectively analysed. Out of 599 SAB episodes, 162 (27%) were followed by an IDC. Patients with IDC were younger and more frequently intravenous drug users, but fewer resided in a long-term care facility or were indigenous. Hospital length of stay was longer (29.5 vs 17 days, p < 0.001), and endocarditis (19.1% vs 7.3%, p < 0.001) and metastatic seeding (22.2% vs 10.1%, p < 0.001) were more frequent in the IDC group; however, SAPS II scores were lower in the IDC group (27 vs 37, p < 0.001). ICU admission rates in the two groups were similar. The isolate tested susceptible to empirical therapy more frequently in the IDC group (88.9% vs 78.0%, p = 0.003). Seven-day (3.1 vs 16.5%), 30-day (8.0% vs 27.0%) and 1-year mortality (22.2% vs 44.9%) were all lower in the IDC group (all p < 0.001). Multivariate analysis showed that effective initial therapy was the only variable associated with the protective effect of IDC. In patients with SAB, all-cause mortality was significantly lower in patients who had an IDC, because of the higher proportion of patients receiving effective initial antibiotics.}, }
@article {pmid22377956, year = {2012}, author = {Zheng, S and Bai, JQ and Li, J and Fan, JH and Pang, Y and Song, QK and Huang, R and Yang, HJ and Xu, F and Lu, N and Qiao, YL}, title = {The pathologic characteristics of breast cancer in China and its shift during 1999-2008: a national-wide multicenter cross-sectional image over 10 years.}, journal = {International journal of cancer}, volume = {131}, number = {11}, pages = {2622-2631}, doi = {10.1002/ijc.27513}, pmid = {22377956}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/metabolism/*pathology ; China/epidemiology ; Cross-Sectional Studies ; Diagnostic Imaging/methods ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Young Adult ; }, abstract = {In China, breast cancer is currently the most common malignancy and the sixth leading cause of cancer death in women. But, the characteristics of breast cancer in the whole population are not determined. The aim of this study was to perform a detailed study on pathologic characteristics of breast cancer representing the whole population in China during 1999-2008 and to compare the difference in invasive breast cancer between the Western and Chinese. We randomly collected 4,211 inpatient at seven hospitals in representative geographical regions of China during 1999-2008. All the hospitals had the ability of comprehensive cancer treatment. The pathologic characters including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status were surveyed. The shift of pathologic characters was evaluated and the data from China were also compared with those of the Western, both using Chi-square test. We found as follow. (i) The median age of the patients was 48 years and showed the similar characters of Asia. (ii) Breast cancer in China showed more invasive ductal carcinoma with larger tumor size, later stage, lower ER and PR expression and higher HER2 overexpression than those in the Western (p < 0.001). (iii) Both tumor size and stage at diagnosis decreased year by year (p < 0.001). Breast cancer in China showed more aggressive behavior than those in western countries, although tumor size and stage at diagnosis decreased by year during 1999-2008. We addressed the urgent needs for employ race-specific breast cancer screen, diagnosis methods, and therapeutic models in China.}, }
@article {pmid22333638, year = {2012}, author = {Hata, K and Hirai, I and Tanaka, T and Tanino, H}, title = {[A case of liver metastasis of breast cancer responding to letrozole].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {39}, number = {2}, pages = {257-260}, pmid = {22333638}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Female ; Humans ; Letrozole ; Liver Neoplasms/*drug therapy/secondary ; Nitriles/*therapeutic use ; Tomography, X-Ray Computed ; Triazoles/*therapeutic use ; }, abstract = {The patient was a 68-year-old woman who had a right mastectomy performed in another hospital in 1987. Her right breast tumor was histologically diagnosed IDC and ER(-), with an uncertain PgR and HER2. Tamoxifen was administered as adjuvant therapy for five years after surgery. Because she had abdominal pain in January, 2007, she consulted her family doctor. At that doctor's hospital, metastatic tumors of the liver were found, and she was therefore referred to our hospital. A liver biopsy of the tumor was conducted in our hospital, and hormone therapy was also conducted because her cancer status was ER(+), PgR(+), HER2(0), and was not life-threatening. Hormone therapy had a good effect on the tumor. ER, PgR and HER2 expression might make the difference between a primary tumor and a metastatic one, as in this case. Therefore, we should perform biopsies on metastatic tumors to determine the best treatment method. There is a possibility that hormone therapy will become an effective therapeutic procedure for breast cancer patients who are hormone receptor positive, are not in a life threatening situation, and have had a long, disease-free survival. We reported one case in which the aromatase third generation inhibitor letrozole was effective for treating liver metastases of breast cancer.}, }
@article {pmid22322949, year = {2012}, author = {Lohsiriwat, V and Martella, S and Rietjens, M and Botteri, E and Rotmensz, N and Mastropasqua, MG and Garusi, C and De Lorenzi, F and Manconi, A and Sommario, M and Barbieri, B and Cassilha, M and Minotti, I and Petit, JY}, title = {Paget's disease as a local recurrence after nipple-sparing mastectomy: clinical presentation, treatment, outcome, and risk factor analysis.}, journal = {Annals of surgical oncology}, volume = {19}, number = {6}, pages = {1850-1855}, doi = {10.1245/s10434-012-2226-5}, pmid = {22322949}, issn = {1534-4681}, mesh = {Adult ; Breast Neoplasms/*complications/pathology/surgery ; Carcinoma, Ductal, Breast/complications/pathology/surgery ; Carcinoma, Lobular/complications/pathology/surgery ; Female ; Humans ; Incidence ; Italy/epidemiology ; Mastectomy/*adverse effects ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/surgery ; Neoplasm Staging ; Nipples/*pathology/surgery ; Paget's Disease, Mammary/epidemiology/*etiology ; *Postoperative Complications ; Prognosis ; Risk Assessment ; Risk Factors ; }, abstract = {BACKGROUND: Paget's disease is a rare clinical and histological type of local recurrence (LR) after breast cancer treatment both in case of conservative surgery or nipple-sparing mastectomy (NSM) with or without intraoperative radiation.<br><br>METHODS: We performed an analysis of 861 NSM with electron beam intraoperative radiotherapy (ELIOT) patients treated at the European Institute of Oncology from 2002 to 2008, focused on Paget's disease local recurrence.<br><br>RESULTS: In 861 patients (713 invasive carcinoma and 148 intraepithelial neoplasia), there were 36 local recurrences (4.18%), and among these were 7 Paget's disease local recurrences (0.8%). Median follow-up was 50 months. Four cases presented with nipple areola complex (NAC) erosions, two crusted lesions, and one ulcerated NAC. The average latency period from the NSM to Paget's disease local recurrence is 32 months (range, 12-49). Complete NAC removal was performed in all seven recurrences. The average follow-up after NAC removal was 47.4 months (range, 20-78). We found neither locoregional relapse nor metastatic event in this group. All patients were alive without disease.<br><br>CONCLUSIONS: Paget's disease local recurrence can be found in a significant proportion after NSM. Any suspicious lesion on NAC requires prompt pathological confirmation. Primary carcinoma with ductal intraepithelial neoplasia or invasive ductal carcinoma with extensive in situ component, negative hormonal receptor, high pathological grade, overexpression of HER2/neu, and "HER2 positive (nonluminal)" subtype tend to be significantly associated with more Paget's disease local recurrence and should be followed carefully.}, }
@article {pmid22315424, year = {2012}, author = {Volinia, S and Galasso, M and Sana, ME and Wise, TF and Palatini, J and Huebner, K and Croce, CM}, title = {Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {8}, pages = {3024-3029}, pmid = {22315424}, issn = {1091-6490}, support = {U01 CA152758/CA/NCI NIH HHS/United States ; U01 CA154200/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm/genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Kaplan-Meier Estimate ; MicroRNAs/*genetics/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; }, abstract = {The transition from ductal carcinoma in situ to invasive ductal carcinoma is a key event in breast cancer progression that is still not well understood. To discover the microRNAs regulating this critical transition, we used 80 biopsies from invasive ductal carcinoma, 8 from ductal carcinoma in situ, and 6 from normal breast. We selected them from a recently published deep-sequencing dataset [Farazi TA, et al. (2011) Cancer Res 71:4443-4453]. The microRNA profile established for the normal breast to ductal carcinoma in situ transition was largely maintained in the in situ to invasive ductal carcinoma transition. Nevertheless, a nine-microRNA signature was identified that differentiated invasive from in situ carcinoma. Specifically, let-7d, miR-210, and -221 were down-regulated in the in situ and up-regulated in the invasive transition, thus featuring an expression reversal along the cancer progression path. Additionally, we identified microRNAs for overall survival and time to metastasis. Five noncoding genes were associated with both prognostic signatures--miR-210, -21, -106b*, -197, and let-7i, with miR-210 the only one also involved in the invasive transition. To pinpoint critical cellular functions affected in the invasive transition, we identified the protein coding genes with inversely related profiles to miR-210: BRCA1, FANCD, FANCF, PARP1, E-cadherin, and Rb1 were all activated in the in situ and down-regulated in the invasive carcinoma. Additionally, we detected differential splicing isoforms with special features, including a truncated EGFR lacking the kinase domain and overexpressed only in ductal carcinoma in situ.}, }
@article {pmid22315090, year = {2013}, author = {Alvarez, C and Tapia, T and Cornejo, V and Fernandez, W and Muñoz, A and Camus, M and Alvarez, M and Devoto, L and Carvallo, P}, title = {Silencing of tumor suppressor genes RASSF1A, SLIT2, and WIF1 by promoter hypermethylation in hereditary breast cancer.}, journal = {Molecular carcinogenesis}, volume = {52}, number = {6}, pages = {475-487}, doi = {10.1002/mc.21881}, pmid = {22315090}, issn = {1098-2744}, mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Base Sequence ; Breast/metabolism/*pathology ; Breast Neoplasms/*genetics/pathology ; DNA/genetics/isolation &amp; purification ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; *Gene Silencing ; Humans ; Intercellular Signaling Peptides and Proteins/*genetics ; Nerve Tissue Proteins/*genetics ; Promoter Regions, Genetic ; Repressor Proteins/*genetics ; Tumor Suppressor Proteins/*genetics ; }, abstract = {Promoter hypermethylation is gaining strength as one of the main mechanisms through which tumor suppressor genes are silenced during tumor progression. Three tumor suppressor genes are frequently found methylated in their promoter, in concordance with absence of expression, RASSF1A, SLIT2, and WIF1. In addition, a previous array-CGH analysis from our group showed that these genes are found in deleted genomic regions observed in hereditary breast cancer tumors. In the present work we analyzed the methylation status of these three tumor suppressor gene promoters in 47 hereditary breast cancer tumors. Promoter methylation status analysis of hereditary breast tumors revealed high methylation frequencies for the three genes (67% RASSF1A, 80% SLIT2, and 72% WIF1). Additionally, the presence of methylated PCR products was associated with absence of protein expression for the three genes and statistically significant for RASSF1A and WIF1. Interestingly, methylation of all the three genes was found in 4 out of 6 grade I invasive ductal carcinoma tumors. Association between RASSF1A methylation and DCIS tumors was found. These results suggest that silencing of these tumor suppressor genes is an early event in hereditary breast cancer, and could be a marker for pre-malignant phenotypes.}, }
@article {pmid22311972, year = {2012}, author = {Yeang, HXA and Hamdam, JM and Al-Huseini, LMA and Sethu, S and Djouhri, L and Walsh, J and Kitteringham, N and Park, BK and Goldring, CE and Sathish, JG}, title = {Loss of transcription factor nuclear factor-erythroid 2 (NF-E2) p45-related factor-2 (Nrf2) leads to dysregulation of immune functions, redox homeostasis, and intracellular signaling in dendritic cells.}, journal = {The Journal of biological chemistry}, volume = {287}, number = {13}, pages = {10556-10564}, pmid = {22311972}, issn = {1083-351X}, support = {G0700420/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; G0700654/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; CD8-Positive T-Lymphocytes/metabolism ; Dendritic Cells/cytology/*metabolism ; Glutathione/genetics/metabolism ; Histone Deacetylases/genetics/metabolism ; Homeostasis/*physiology ; MAP Kinase Signaling System/*physiology ; Mice ; Mice, Knockout ; NF-E2-Related Factor 2/genetics/*metabolism ; NF-kappa B/genetics/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/*metabolism ; p38 Mitogen-Activated Protein Kinases/genetics/metabolism ; }, abstract = {Dendritic cells (DCs) are critical mediators of immunity and immune tolerance by orchestrating multiple aspects of T cell activation and function. Immature DCs (iDCs) expressing low levels of co-stimulatory receptors are highly efficient at antigen capture but are poor activators of T cells. Maturation of DCs is associated with increased expression of co-stimulatory molecules. Co-stimulatory receptor gene expression is regulated by intracellular redox, NF-κB, and MAPK pathways and by histone deacetylase (HDAC) activity. The transcription factor, Nrf2, is important for maintaining intracellular glutathione (GSH) levels and redox homeostasis and has been implicated in modulating DC co-stimulatory receptor expression. It is unclear whether Nrf2 mediates this effect by GSH-dependent mechanisms and whether it influences DC signaling pathways. Using bone marrow-derived iDCs from Nrf2(+/+) and Nrf2(-/-) mice, we demonstrate that Nrf2(-/-) iDCs have lower basal GSH levels, enhanced co-stimulatory receptor expression, impaired phagocytic functions, and increased antigen-specific CD8 T cell stimulation capacity. Interestingly, lowering GSH levels in Nrf2(+/+) iDCs did not recapitulate the Nrf2(-/-) iDC phenotype. Loss of Nrf2 resulted in elevated basal levels of reactive oxygen species but did not affect basal NF-κB activity or p38 MAPK phosphorylation. Using pharmacological inhibitors, we demonstrate that enhanced co-stimulatory receptor phenotype of Nrf2(-/-) iDC does not require ERK activity but is dependent on HDAC activity, indicating a potential interaction between Nrf2 function and HDAC. These results suggest that Nrf2 activity is required to counter rises in intracellular reactive oxygen species and to regulate pathways that control DC co-stimulatory receptor expression.}, }
@article {pmid22308937, year = {2011}, author = {Castello Botia, I and Wanden-Berghe, C}, title = {[New classification of causes of mortality of nutritional origin by means of the Delphi method].}, journal = {Archivos latinoamericanos de nutricion}, volume = {61}, number = {2}, pages = {120-126}, pmid = {22308937}, issn = {0004-0622}, mesh = {*Cause of Death ; *Consensus ; *Delphi Technique ; Humans ; *International Classification of Diseases ; Nutrition Disorders/*classification/*mortality ; Nutritional Status ; }, abstract = {The causes of mortality of nutritional origin (MNO) are not classified in the consecutive reviews of the international disease classification (IDC) and there is no agreement for their most proper classification. The objective of this study is to elaborate, using the last ICD as a guide, a list of causes of mortality of nutritional origin which will be used as a reference in future studies. A two round Delphi method was organized with an expert's consenssus in clinical nutrition. The experts were asked to classify a list of causes of MNO in 4 groups; 1) group A: congenital errors related to nutrition, 2) group B: Causes associated with other pathologies, 3) group 3: Excess and defect nutrition disorders, and 4) excluded. In total, 86 causes of MNO were taken under the consensus of experts, and 79 (91.9%) came to an agreement. 14 (17.7%) causes were classified in group A, 5 (6.3%) causes in group B, 37 (46.8%) causes in group C and 23 (29.1%) were excluded. This is a first approach to the classification of mortality causes of nutritional origin, probably due to the ambiguity and disparity of opinions between experts with respect to these causes. This new classification will be very useful due to the fact that it will enable homogenization of the studies and that way we will have comparable studies, using it as a clarifier annex for the ICD of the moment.}, }
@article {pmid22292636, year = {2011}, author = {Wang, ZH and Gong, JL and Yu, M and Yang, H and Lai, JH and Ma, MX and Wu, H and Li, L and Tan, DY}, title = {Up-regulation of human arrest-defective 1 protein is correlated with metastatic phenotype and poor prognosis in breast cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {12}, number = {8}, pages = {1973-1977}, pmid = {22292636}, issn = {2476-762X}, mesh = {Acetyltransferases/biosynthesis/*genetics/metabolism ; Adult ; Breast Cyst/genetics/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/*pathology/secondary ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Female ; Fibroadenoma/genetics/metabolism/pathology ; Humans ; Hyperplasia/genetics/metabolism/pathology ; Immunohistochemistry ; Inflammation/genetics/metabolism/pathology ; Lymphatic Metastasis ; Middle Aged ; N-Terminal Acetyltransferase A ; N-Terminal Acetyltransferase E ; Phenotype ; Postoperative Period ; Prognosis ; Up-Regulation ; }, abstract = {BACKGROUND: Human arrest defective 1 protein (ARD1), as a N-terminal acetyltransferase, has been reported to play a crucial role in tumorigenesis, but the results are somewhat controversial. To explore the clinical and pathological significance of ARD1 in breast tumorigenesis, we analyzed ARD1 status in multiple types of breast disease.<br><br>METHODS: The expression of ARD1 protein was assessed by immunohistochemistry in 356 cases including 82 invasive ductal carcinomas (IDC), 159 fibroadenomas, 66 hyperplasia of mammary glands, 19 inflammatory breast disease, 30 breast cysts, and in 29 postoperative treatment patients. We assessed the relationship of ARD1 protein with clinical and pathological characteristics using &#x3c7;2 test.<br><br>RESULTS: ARD1 protein was observed at 61.0% (50/82), 54.7% (87/159), 37.9% (25/66), 36.8% (7/19) in IDC, fibroadenoma, hyperplasia, and inflammation, respectively, and less than 30.0% for breast cyst. Thus, high ARD1 expression correlated with breast cancer (relative risk = 1.32, P < 0.005). Moreover, the level of ARD1 protein in carcinoma patients was distinctly related to lymph node metastasis and ER status, with 94.0% (47/50) as copmpared to 6.0% (3/50) in metastatic and non-metastatic (P < 0.001), and 84.0% (42/50) and 16.0% (8/50) for ER + and ER - (P < 0.01), respectively. In addition, the level of ARD1 appeared to have potential for evaluation of prognosis in breast cancer patients after postoperative therapy.<br><br>CONCLUSIONS: These results suggest that ARD1 expression may be as a potential target for exploring the mechanism of breast cancer metastasic to lymph nodes and hormone-responsive regulation.}, }
@article {pmid22271313, year = {2012}, author = {Raviraj, V and Zhang, H and Chien, HY and Cole, L and Thompson, EW and Soon, L}, title = {Dormant but migratory tumour cells in desmoplastic stroma of invasive ductal carcinomas.}, journal = {Clinical &amp; experimental metastasis}, volume = {29}, number = {3}, pages = {273-292}, pmid = {22271313}, issn = {1573-7276}, mesh = {Breast Neoplasms/chemistry/*pathology ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Cell Movement ; Collagen Type II/analysis ; Cyclin-Dependent Kinase Inhibitor p27/physiology ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Immunohistochemistry ; Keratin-19/analysis ; Neoplasm Invasiveness ; Tumor Microenvironment ; Vimentin/analysis ; rho-Associated Kinases/physiology ; }, abstract = {Mortality in breast cancer is linked to metastasis and recurrence yet there is no acceptable biological model for cancer relapse. We hypothesise that there might exist primary tumour cells capable of escaping surgery by migration and resisting radiotherapy and chemotherapy to cause cancer recurrence. We investigated this possibility in invasive ductal carcinoma (IDC) tissue and observed the presence of solitary primary tumour cells (SPCs) in the dense collagen stroma that encapsulates intratumoural cells (ICs). In IDC tissue sections, collagen was detected with either Masson's Trichrome or by second harmonics imaging. Cytokeratin-19 (CK-19) and vimentin (VIM) antibodies were, respectively, used to identify epithelial-derived tumour cells and to indicate epithelial to mesenchymal transition (EMT). Confocal/multiphoton microscopy showed that ICs from acini were mainly CK-19(+ve) and were encapsulated by dense stromal collagen. Within the stroma, SPCs were detected by their staining for both CK-19 and VIM (confirming EMT). ICs and SPCs were subsequently isolated by laser capture microdissection followed by multiplex tandem-PCR studies. SPCs were found to be enriched for pro-migratory and anti-proliferative genes relative to ICs. In vitro experiments using collagen matrices at 20 mg/cm(3), similar in density to tumour matrices, demonstrated that SPC-like cells were highly migratory but dormant, phenotypes that recapitulated the genotypes of SPCs in clinical tissue. These data suggest that SPCs located at the breast cancer perimeter are invasive and dormant such that they may exceed surgical margins and resist local and adjuvant therapies. This study has important connotations for a role of SPCs in local recurrence.}, }
@article {pmid22270930, year = {2012}, author = {Zhao, X and Mirza, S and Alshareeda, A and Zhang, Y and Gurumurthy, CB and Bele, A and Kim, JH and Mohibi, S and Goswami, M and Lele, SM and West, W and Qiu, F and Ellis, IO and Rakha, EA and Green, AR and Band, H and Band, V}, title = {Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.}, journal = {Breast cancer research and treatment}, volume = {134}, number = {1}, pages = {171-180}, pmid = {22270930}, issn = {1573-7217}, support = {R01 CA087986/CA/NCI NIH HHS/United States ; CA105489/CA/NCI NIH HHS/United States ; U01 CA151806/CA/NCI NIH HHS/United States ; CA116552/CA/NCI NIH HHS/United States ; R01 CA116552/CA/NCI NIH HHS/United States ; CA99163/CA/NCI NIH HHS/United States ; R01 CA099163/CA/NCI NIH HHS/United States ; CA144027/CA/NCI NIH HHS/United States ; 5U01CA151806-02/CA/NCI NIH HHS/United States ; CA87986/CA/NCI NIH HHS/United States ; R01 CA096844/CA/NCI NIH HHS/United States ; CA96844/CA/NCI NIH HHS/United States ; R01 CA144027/CA/NCI NIH HHS/United States ; R01 CA105489/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Antibody Specificity ; Biomarkers, Tumor/genetics/*metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/pathology ; Carrier Proteins/genetics/immunology/*metabolism ; Cohort Studies ; Disease-Free Survival ; Female ; Gene Expression ; Humans ; Hyperplasia/metabolism ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Young Adult ; }, abstract = {Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.}, }
@article {pmid22252965, year = {2012}, author = {Hernandez, L and Wilkerson, PM and Lambros, MB and Campion-Flora, A and Rodrigues, DN and Gauthier, A and Cabral, C and Pawar, V and Mackay, A and A'Hern, R and Marchiò, C and Palacios, J and Natrajan, R and Weigelt, B and Reis-Filho, JS}, title = {Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection.}, journal = {The Journal of pathology}, volume = {227}, number = {1}, pages = {42-52}, pmid = {22252965}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; CTR-Q3REIS-FILHO/BCN_/Breast Cancer Now/United Kingdom ; IM-CTR-HER2REIS-FILHO/BCN_/Breast Cancer Now/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Class I Phosphatidylinositol 3-Kinases ; Clonal Evolution ; Clone Cells ; Comparative Genomic Hybridization ; *DNA Mutational Analysis ; DNA, Neoplasm/analysis ; Disease Progression ; Female ; *Gene Expression Profiling ; *Genetic Heterogeneity ; Genomics/methods ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mutation ; Neoplasms, Multiple Primary ; Phosphatidylinositol 3-Kinases/genetics ; }, abstract = {The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, and the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCI and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDC were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridization (aCGH) and Sequenom MassARRAY (Oncocarta v 1.0 panel). Fluorescence in situ hybridization and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCI and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (ie 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations.}, }
@article {pmid22238453, year = {2012}, author = {Hsu, YH and Hsing, CH and Li, CF and Chan, CH and Chang, MC and Yan, JJ and Chang, MS}, title = {Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {188}, number = {4}, pages = {1981-1991}, doi = {10.4049/jimmunol.1102843}, pmid = {22238453}, issn = {1550-6606}, mesh = {Animals ; *Antibodies, Monoclonal/administration &amp; dosage/immunology/pharmacology/therapeutic use ; Bone Neoplasms/metabolism/pathology/secondary ; Bone and Bones/pathology ; Breast/pathology ; Breast Neoplasms/drug therapy/*immunology/metabolism ; Carcinoma, Ductal, Breast/drug therapy/*immunology/metabolism ; Cathepsin G/biosynthesis ; Cathepsin K/biosynthesis ; Cell Line, Tumor ; Cell Movement/drug effects/immunology ; Cell Proliferation/drug effects ; Disease Progression ; Female ; Humans ; Interleukins/*biosynthesis/*immunology/pharmacology ; Matrix Metalloproteinase 12/biosynthesis ; Matrix Metalloproteinase 9/biosynthesis ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis ; *Osteolysis/drug therapy/immunology/pathology ; }, abstract = {IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about its role in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, as well as in clinical outcome. Tumor expression of IL-20 was assessed by immunohistochemical staining among 198 patients with invasive ductal carcinoma of the breast, using available clinical and survival data. IL-20 expression was associated with advanced tumor stage, greater tumor metastasis, and worse survival. Reverse transcription quantitative polymerase chain reaction showed that clinical breast tumor tissue expressed higher levels of IL-20 and its receptors than did nontumorous breast tissue. IL-20 was also highly expressed in breast cancer bone-metastasis tissue. In vitro, IL-20 upregulated matrix metalloproteinase-9, matrix metalloproteinase-12, cathepsin K, and cathepsin G, and enhanced proliferation and migration of breast cancer cells, which were inhibited by anti-IL-20 mAb 7E. In vivo, we generated murine models to evaluate the therapeutic potential of 7E, using luminescence intensity, radiological scans, and micro-computed tomography. 7E reduced tumor growth, suppressed bone colonization, diminished tumor-mediated osteolysis, and lessened bone density decrement in mice injected with breast cancer cells. In conclusion, our results suggest that IL-20 plays pivotal roles in the tumor progression of breast cancer. IL-20 expression in breast cancer tissue is associated with a poor clinical outcome. Anti-IL-20 mAb 7E suppressed bone colonization and decreased osteolytic bone lesions. Therefore, IL-20 may be a novel target in treating breast tumor-induced osteolysis.}, }
@article {pmid22234886, year = {2012}, author = {Wang, S and Li, W and Liu, N and Zhang, F and Liu, H and Liu, F and Liu, J and Zhang, T and Niu, Y}, title = {Nek2A contributes to tumorigenic growth and possibly functions as potential therapeutic target for human breast cancer.}, journal = {Journal of cellular biochemistry}, volume = {113}, number = {6}, pages = {1904-1914}, doi = {10.1002/jcb.24059}, pmid = {22234886}, issn = {1097-4644}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Cell Cycle Checkpoints/genetics ; Cell Differentiation/genetics ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; Ki-67 Antigen/genetics ; NIMA-Related Kinases ; Protein Serine-Threonine Kinases/biosynthesis/*genetics/*physiology ; RNA Interference ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {Nek2A (NIMA-related kinases 2A) has been known as an important centrosome regulatory factor. The aim of this study was to investigate the expression of Nek2A and the role it played in different stages of breast cancer. We detected the expression of Nek2A in both mRNA and protein levels in MCF10 cell lines including MCF-10A, MCF-10DCIS.com, MCF-10CA1a and in human breast samples which contained normal breast tissue (NBT), breast ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). Our study revealed that the mRNA and protein expression of Nek2A were significantly up-regulated in MCF-10DCIS.com and MCF-10CA1a cell lines as well as in human primary breast cancer tissue (DCIS and IDC). Our study also presented a correlation between Nek2A mRNA expression and some clinic pathological factors. We found that Nek2A mRNA expression was associated with molecular subtypes, ER, PR and Ki-67 immunoreactivity (P<0.05) in DCIS and associated with histological grade, lymph node metastasis, molecular subtypes, c-erbB-2, and Ki-67 expression (P<0.05) in IDC. In addition, we observed that ectopic expression of Nek2A in "normal" immortalized MCF-10A breast epithelial cell resulted in increased Nek2A which lead to abnormal centrosomes. Furthermore, knockdown of Nek2A in MCF-10DCIS.com could remarkably inhibit cell proliferation and induce cell cycle arrest in MCF-10DCIS.com cell line. These data suggested that Nek2A might bear a close relationship with development and progression of breast carcinoma, and highlighted its role as a novel potential biomarker for diagnosis and a possible therapeutic target for human breast cancer especially for DCIS.}, }
@article {pmid22233382, year = {2012}, author = {Marsden, CG and Wright, MJ and Carrier, L and Moroz, K and Pochampally, R and Rowan, BG}, title = {"A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies".}, journal = {BMC cancer}, volume = {12}, number = {}, pages = {10}, pmid = {22233382}, issn = {1471-2407}, mesh = {Animals ; Biomarkers, Tumor/metabolism ; Biopsy ; Breast/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Disease Models, Animal ; Female ; Humans ; Mammary Neoplasms, Experimental/metabolism/*pathology ; Mice ; Mice, Nude ; }, abstract = {BACKGROUND: The study of breast cancer metastasis depends on the use of established breast cancer cell lines that do not accurately represent the heterogeneity and complexity of human breast tumors. A tumor model was developed using primary breast tumor-initiating cells isolated from patient core biopsies that would more accurately reflect human breast cancer metastasis.<br><br>METHODS: Tumorspheres were isolated under serum-free culture conditions from core biopsies collected from five patients with clinical diagnosis of invasive ductal carcinoma (IDC). Isolated tumorspheres were transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. Tumors and metastatic lesions were analyzed by hematoxylin and eosin (H+E) staining and immunohistochemistry (IHC).<br><br>RESULTS: Tumorspheres were successfully isolated from all patient core biopsies, independent of the estrogen receptor &#x3b1; (ER&#x3b1;)/progesterone receptor (PR)/Her2/neu status or tumor grade. Each tumorsphere was estimated to contain 50-100 cells. Transplantation of 50 tumorspheres (1-5 &#xd7; 103 cells) in combination with Matrigel into the mammary fat pad of NUDE mice resulted in small, palpable tumors that were sustained up to 12 months post-injection. Tumors were serially transplanted three times by re-isolation of tumorspheres from the tumors and injection into the mammary fat pad of NUDE mice. At 3 months post-injection, micrometastases to the lung, liver, kidneys, brain and femur were detected by measuring content of human chromosome 17. Visible macrometastases were detected in the lung, liver and kidneys by 6 months post-injection. Primary tumors variably expressed cytokeratins, Her2/neu, cytoplasmic E-cadherin, nuclear &#x3b2; catenin and fibronectin but were negative for ER&#x3b1; and vimentin. In lung and liver metastases, variable redistribution of E-cadherin and &#x3b2; catenin to the membrane of tumor cells was observed. ER&#x3b1; was re-expressed in lung metastatic cells in two of five samples.<br><br>CONCLUSIONS: Tumorspheres isolated under defined culture conditions from patient core biopsies were tumorigenic when transplanted into the mammary fat pad of NUDE mice, and metastasized to multiple mouse organs. Micrometastases in mouse organs demonstrated a dormancy period prior to outgrowth of macrometastases. The development of macrometastases with organ-specific phenotypic distinctions provides a superior model for the investigation of organ-specific effects on metastatic cancer cell survival and growth.}, }
@article {pmid22207430, year = {2012}, author = {Arafah, M}, title = {Correlation of hormone receptors with Her-2 Neu protein expression and the histological grade in invasive breast cancers in a cohort of Saudi Arabia.}, journal = {Turk patoloji dergisi}, volume = {28}, number = {1}, pages = {38-43}, doi = {10.5146/tjpath.2012.01095}, pmid = {22207430}, issn = {1309-5730}, mesh = {Biomarkers, Tumor/analysis/genetics ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cohort Studies ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/analysis/*biosynthesis/genetics ; Receptors, Estrogen/analysis/biosynthesis/genetics ; Receptors, Progesterone/analysis/biosynthesis/genetics ; Receptors, Steroid/*biosynthesis/genetics ; Retrospective Studies ; Saudi Arabia ; }, abstract = {OBJECTIVE: Data on Hormone Receptor and Her-2/neu expression in breast cancers from Saudi Arabia and Gulf Region is sparse. We undertook this study to describe the patterns of hormone receptor and Her-2/neu protein expression in breast carcinoma and compared them with the histological grade at a University Hospital in Riyadh.<br><br>MATERIAL AND METHOD: We conducted a retrospective study on 164 invasive ductal carcinoma of breast between the year 2002 and 2008. Immunohistochemical analysis for Estrogen and Progesterone Receptor and Her-2/neu was done in all the cases. Fluorescent in situ hybridization for Her-2/neu gene amplification was performed in all 2+ cases and few equivocal 1+ and 3+cases by immunohistochemistry. Correlation between Estrogen and Progesterone Receptor and Her-2/ neu amplification and grade of tumor was calculated.<br><br>RESULTS: The expression of Estrogen Receptor, Progesterone Receptor were significantly correlated (p < 0.001). Also, there was a significant negative correlation between expression of hormone receptor and Her-2/neu amplification. The histologic grade of the tumor was significantly correlated to the expression of both Estrogen and Progesterone Receptor. However, the relationship between Her-2/ neu amplification and grade was not significant and many of the grade III tumor were Her-2/neu negative. In addition, Her-2/neu gene amplification by fluorescent in situ hybridization was observed in 84.6% of breast cancer that were 3+ and in 18.75 % cases that were 2+ by immunohistochemistry.<br><br>CONCLUSION: Prevalence of Estrogen and Progesterone Receptor expression and Her-2/neu amplification in breast cancer in the Saudi Arabian population is similar to that reported internationally. There is a negative correlation between hormone receptors expression and Her-2/neu amplification. However not all of the high-grade breast cancers showed Her-2/neu positive status.}, }
@article {pmid22202322, year = {2011}, author = {Sato, T and Nakagawa, T and Kuwayama, T and Oda, G and Sugimoto, H and Ishiba, T and Sugihara, K}, title = {[A case of breast cancer liver metastases responding to lapatinib and capecitabine therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {38}, number = {12}, pages = {2180-2182}, pmid = {22202322}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Capecitabine ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Deoxycytidine/administration &amp; dosage/*analogs &amp; derivatives/therapeutic use ; Fatal Outcome ; Female ; Fluorouracil/administration &amp; dosage/*analogs &amp; derivatives/therapeutic use ; Humans ; Lapatinib ; Liver Neoplasms/*drug therapy/secondary ; Middle Aged ; Quinazolines/administration &amp; dosage/*therapeutic use ; }, abstract = {We report a 55-year-old female with liver metastases from breast cancer who responded to lapatinib and capecitabine combination therapy as third-line. She was diagnosed as invasive ductal carcinoma (T1cN1M0, stage IIA). Biomarker of breast cancer was negative hormone receptor (ER-, PgR-) and overexpression of HER2(HercepTest 3+). We started preoperative chemotherapy with weekly paclitaxel followed by FEC100. Then mastectomy with axillary dissection was performed. Histopathology of the breast and lymph nodes showed complete disappear of invasive cancer cells(pCR, grade 3). We performed her adjuvant therapy with trastuzumab after surgery. The liver metastases developed 5 months after surgery. We treated her in trasutumab combined with vinorelbine, and followed by docetaxel during one year and four months. Because liver metastases re-grew during the combination therapy with trastuzumab, we switched to lapatinib and capecitabine combination therapy. After four months of administration, abdominal CT revealed liver metastases were remarkably reduced in size. The efficacy of chemotherapy lasted for eight months.}, }
@article {pmid22202268, year = {2011}, author = {Suzuki, S and Sakurai, K and Nagashima, S and Fujisaki, S and Shibata, M and Tomita, R and Hara, Y and Matsumoto, K and Enomoto, K and Amano, S}, title = {[Surgical resection for elderly patient with skin invasion of breast cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {38}, number = {12}, pages = {2011-2013}, pmid = {22202268}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Biopsy ; Breast Neoplasms/pathology/*surgery ; Female ; Humans ; Neoplasm Invasiveness ; Skin Neoplasms/secondary/*surgery ; Tomography, X-Ray Computed ; }, abstract = {We report a locally advanced elderly breast carcinoma with skin invasion. The patient was a 96-year-old woman who had a breast lump. The palpable tumor was 3 .5 cm in diameter. Ultrasonography revealed a low echoic mass. A core needle biopsy for the breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesteron receptor, and negative for HER2/neu protein expression. She underwent a tumorectomy including the cancer invasive skin by local anesthesia. Because her respiratory function was unbearable to perform a muscle-preserving mastectomy with general anesthesia. The surgical margins of the resected specimen were negative. The clinicopathological stage, according to the UICC-pTNM classification, was Stage III C (T4b, N0, M0). After the operation, she was administered aromatase inhibitor. The patient has been well and remained disease-free during a follow-up period of 3 years. The surgical excision with local anesthesia was useful for locally advanced super senior breast cancer patients who were impossible to perform general anesthesia by various kinds of factors.}, }
@article {pmid22172957, year = {2012}, author = {Fernandez-Flores, A and Valerdiz, S and Crespo, LG and Rodriguez-Cernuda, P}, title = {Areolar sebaceous hyperplasia with underlying primary duct carcinoma of the breast in a woman with Donohue syndrome (leprechaunism).}, journal = {The American Journal of dermatopathology}, volume = {34}, number = {2}, pages = {e15-8}, doi = {10.1097/DAD.0b013e318231311a}, pmid = {22172957}, issn = {1533-0311}, mesh = {Adult ; Breast Neoplasms/*complications/pathology ; Carcinoma, Ductal, Breast/*complications/pathology ; Donohue Syndrome/*complications/pathology ; Female ; Humans ; Hyperplasia/pathology ; Immunohistochemistry ; Nipples/*pathology ; Sebaceous Glands/*pathology ; }, abstract = {Areolar hyperplasia is only reported when exaggerated, and even so, exaggerated areolar sebaceous hyperplasia is rare. We have recently seen a case of areolar sebaceous hyperplasia in a 32-year-old woman with Donohue syndrome (leprechaunism), who also had an invasive ductal carcinoma in the same breast. The patient showed typical "elfin-like" face with wide nostrils and thick lips, large and low-set ears, and dysplastic nails. The areola showed a yellowish thickened plaque of 5-cm diameter that corresponded to a hyperplasia of the sebaceous glands. Immunohistochemistry for the mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) was performed on the sebaceous hyperplasia and on the breast carcinoma, and no lack of expression of the markers was evidenced. We have found no other reported case of areolar sebaceous hyperplasia either in cases of breast carcinoma or in cases of leprechaunism.}, }
@article {pmid22151989, year = {2011}, author = {Ma, D and Dong, X and Zang, S and Ma, R and Zhao, P and Guo, D and Dai, J and Chen, F and Ye, J and Ji, C}, title = {Aberrant expression and clinical correlation of Notch signaling molecules in breast cancer of Chinese population.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {7}, number = {4}, pages = {385-391}, doi = {10.1111/j.1743-7563.2011.01433.x}, pmid = {22151989}, issn = {1743-7563}, mesh = {Biomarkers, Tumor/biosynthesis/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; China ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Receptors, Notch/*biosynthesis/genetics/metabolism ; Signal Transduction ; }, abstract = {AIMS: Notch signaling molecules play crucial roles in cell proliferation and apoptosis, yet their function in breast cancer remains unclear.<br><br>METHODS: Samples and clinical data from 62 breast cancer patients were collected. After total RNA isolation, reverse transcription polymerase chain reaction was applied to analyze the expression of Notch receptors (Notch1, Notch3 and Notch4) and ligands (DLL4 and JAG1), and their clinical association. Immunohistochemical analysis was used to detect the intracellular domain of Notch1 (Notch1-IC) expression.<br><br>RESULTS: Notch1 was the dominant receptor while DLL4 was the dominant ligand. The Notch molecules expression pattern for infiltrating ductal carcinoma (IDC) was similar to that for infiltrating lobular carcinoma (ILC) except for JAG1, while Notch1 standard coefficients in ILC were statistically higher than that in IDC. Immunohistochemical results showed that Notch1-IC protein expression paralleled the mRNA level. Breast cancer patients' clinical parameters suggested that Notch1 expression was higher in stage II disease and lower in more advanced stages. The Notch3 positive rate was higher in patients with lower levels of Notch1, and the Notch3 positive rate was lower in patients with higher levels of Notch1. No apparent correlation of Notch molecules with estrogen receptor (ER), progesterone receptor (PR) was found. Though high Notch1 and Notch3 RNA levels tended to correlate with c-erbB2 expression, no statistical significance was found.<br><br>CONCLUSION: Notch molecules are useful biomarkers in breast cancer especially for Notch1 and DLL4, and Notch1 is expressed differently in different stages of human breast cancer.}, }
@article {pmid22145049, year = {2011}, author = {Jung, HJ and Park, JY and Jeon, HS and Kwon, TH}, title = {Aquaporin-5: a marker protein for proliferation and migration of human breast cancer cells.}, journal = {PloS one}, volume = {6}, number = {12}, pages = {e28492}, pmid = {22145049}, issn = {1932-6203}, mesh = {Aquaporin 5/antagonists &amp; inhibitors/genetics/*metabolism ; Blotting, Western ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*secondary ; *Cell Movement ; *Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Indicators and Reagents/pharmacology ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Osmosis/drug effects ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Sorbitol/pharmacology ; Stress, Physiological/drug effects ; Tumor Cells, Cultured ; }, abstract = {Aquaporin (AQP) is a family of transmembrane proteins for water transport. Recent studies revealed that AQPs are likely to play a role in tumor progression and invasion. We aimed to examine the potential role of AQP5 in the progression of human breast cancer cells. Expression of AQP5 mRNA and protein was seen in human breast cancer cell line (both MCF7 and MDA-MB-231) by RT-PCR and immunoblotting analysis. Immunoperoxidase labeling of AQP5 was observed at ductal epithelial cells of human breast tissues. In benign tumor, AQP5 labeling was mainly seen at the apical domains of ductal epithelial cells. In contrast, in invasive ductal carcinoma, prominent AQP5 labeling was associated with cancer cells, whereas some ducts were unlabeled and apical polarity of AQP5 in ducts was lost. Cell proliferation (BrdU incorporation assay) and migration of MCF7 cells were significantly attenuated by lentivirus-mediated AQP5-shRNA transduction. Hyperosmotic stress induced by sorbitol treatment (100 mM, 24 h) reduced AQP5 expression in MCF7 cells, which was also associated with a significant reduction in cell proliferation and migration. Taken together, prominent AQP5 expression in breast cancer cells with the loss of polarity of ductal epithelial cells was seen during the progression of breast carcinoma. shRNA- or hyperosmotic stress-induced reduction in AQP5 expression of MCF7 cells was associated with significantly reduced cell proliferation and migration. In conclusion, AQP5 overexpression is likely to play a role in cell growth and metastasis of human breast cancer and could be a novel target for anti-breast cancer treatment.}, }
@article {pmid22141605, year = {2011}, author = {Seow, JH and Metcalf, C and Wylie, E}, title = {Nipple discharge in a screening programme: imaging findings with pathological correlation.}, journal = {Journal of medical imaging and radiation oncology}, volume = {55}, number = {6}, pages = {577-586}, doi = {10.1111/j.1754-9485.2011.02294.x}, pmid = {22141605}, issn = {1754-9485}, mesh = {Adult ; Aged ; Aged, 80 and over ; Australia/epidemiology ; Breast Neoplasms/*diagnostic imaging/*epidemiology/pathology ; Comorbidity ; Female ; Humans ; Mammography/*statistics &amp; numerical data ; Mass Screening/*statistics &amp; numerical data ; Middle Aged ; Nipples/*diagnostic imaging/*metabolism ; Prevalence ; Risk Assessment ; Risk Factors ; }, abstract = {BreastScreen Australia provides free mammographic screening for asymptomatic women over the age of 40, targeting women aged 50-69. Occasionally women will present to screening programmes with a history of nipple discharge, which is uncommonly associated with significant underlying breast disease. Seventy-six women with a history of nipple discharge were recalled to BreastScreen Western Australia assessment centres from 2004 to 2008, of whom 72 were recalled primarily for their symptoms. Thirty-six of these patients had pathology investigations, including 18 nipple discharge smears, 17 fine needle aspirations, 11 core biopsies and eight surgical biopsies or therapeutic resections. The biopsies found 11 intraduct papillomas and one invasive ductal carcinoma with ductal carcinoma in situ. Fourteen patients had imaging findings consistent with benign mammary duct ectasia. Our findings confirm that the presentation of nipple discharge in a screening programme is uncommonly associated with significant breast disease, and present representative cases of the radiological findings with pathological correlation of benign and malignant causes including mammary duct ectasia, intraduct papillomas, multiple papillomas, invasive ductal carcinoma and ductal carcinoma in situ.}, }
@article {pmid22116537, year = {2012}, author = {Lin, RS and Plevritis, SK}, title = {Comparing the benefits of screening for breast cancer and lung cancer using a novel natural history model.}, journal = {Cancer causes &amp; control : CCC}, volume = {23}, number = {1}, pages = {175-185}, pmid = {22116537}, issn = {1573-7225}, support = {R01 CA105366/CA/NCI NIH HHS/United States ; U01 CA088248/CA/NCI NIH HHS/United States ; 1R01CA105366/CA/NCI NIH HHS/United States ; 1U01CA088248/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/diagnosis/epidemiology/*pathology/prevention &amp; control ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology/prevention &amp; control ; Carcinoma, Non-Small-Cell Lung/diagnosis/epidemiology/pathology/prevention &amp; control ; Cell Growth Processes/physiology ; Early Detection of Cancer/methods ; Female ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*pathology/prevention &amp; control ; Male ; Middle Aged ; *Models, Biological ; Neoplasm Metastasis ; SEER Program ; United States/epidemiology ; }, abstract = {To estimate the impact of early detection of cancer, knowledge of how quickly primary tumors grow and at what size they shed lethal metastases is critical. We developed a natural history model of cancer to estimate the probability of disease-specific cure as a function of tumor size, the tumor volume doubling time (TVDT), and disease-specific mortality reduction achievable by screening. The model was applied to non-small-cell lung carcinoma (NSCLC) and invasive ductal carcinoma (IDC), separately. Model parameter estimates were based on Surveillance Epidemiology and End Results (SEER) cancer registry datasets and validated on screening trials. Compared to IDC, NSCLC is estimated to have a lower probability of disease-specific cure at the same detected tumor size, shed lethal metastases at smaller sizes (median: 19 mm for IDC versus 8 mm for NSCLC), have a TVDT that is almost half as long (median: 252 days for IDC versus 134 days for NSCLC). Consequently, NSCLC is associated with a lower mortality reduction from screening at the same screen detection threshold and screening interval. In summary, using a similar natural history model of cancer, we quantify the disease-specific curability attributable to screening for breast cancer, and separately lung cancer, in terms of the TVDT and onset of lethal metastases.}, }
@article {pmid22097094, year = {2011}, author = {Halimi, M and Aghbali, AA and Tabrizi, AD and Sahebmadarek, EO}, title = {Expression of epidermal growth factor receptor tyrosine kinase family in fine needle aspiration and permanent specimens of invasive lobular and ductal breast cancers.}, journal = {Pakistan journal of biological sciences : PJBS}, volume = {14}, number = {10}, pages = {584-589}, doi = {10.3923/pjbs.2011.584.589}, pmid = {22097094}, issn = {1028-8880}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/*methods/standards ; Carcinoma, Ductal, Breast/*enzymology/*pathology ; Carcinoma, Lobular/*enzymology/*pathology ; False Negative Reactions ; False Positive Reactions ; Female ; Histocytochemistry/methods/standards ; Humans ; Iran ; Middle Aged ; Receptor, ErbB-2/genetics/*metabolism ; }, abstract = {Recently, the role of HER-2/Neu gene amplification has been enthusiastically investigated in breast cancer. Determining the HER-2/Neu status could be achieved by evaluating either histologic samples or cytologic specimens obtained by Fine Needle Aspiration (FNA). This study aimed at determining the concordance of HER-2/Neu expression in FNA and histologic sections. FNA samples, as well as their corresponding histologic sections of 90 cases with breast cancer were evaluated in Tabriz Sina Teaching Center in a 13-month period of time. The immunohistochemistry was employed for determining the HER-2/Neu amplification for both methods. The concordance rate and agreement were determined between the two methods. Ninety specimens of women with a mean age of 50.93 +/- 10.64 (29-84) years were assessed. There were 84 cases with invasive ductal carcinoma and 6 cases with invasive lobular carcinoma. Lymph nodes were involved in 50 cases and there were vascular and neural involvement in 40 and 35 cases, respectively. Her-2/Neu was not detected in 27 cases (30%) with weak and strong amplifications in 47 (52.2%) and 16 (17.8%) cases of FNA specimens, respectively. Her-2/Neu was not detected in 29 cases (32.2%) with weak and strong amplifications in 42 (46.7%) and 19 (21.1%) cases of histologic specimens, respectively. The concordance rate was 70% between the two methods. The agree ment was statistically significant between the two methods, as well (kappa = 0.51, p < 0.001). HER-2/neu gene amplification can be reliably estimated by immunohistochemistry on breast cancer FNAs and a good correlation has been found between this and results on histological sections.}, }
@article {pmid22096760, year = {2011}, author = {Arrangoiz, R and Papavasiliou, P and Dushkin, H and Farma, JM}, title = {Case report and literature review: Metastatic lobular carcinoma of the breast an unusual presentation.}, journal = {International journal of surgery case reports}, volume = {2}, number = {8}, pages = {301-305}, pmid = {22096760}, issn = {2210-2612}, abstract = {INTRODUCTION: Invasive lobular carcinoma is the second most common type of invasive breast carcinoma (between 5% and 15%). The incidence of invasive lobular carcinoma has been increasing while the incidence of invasive duct carcinoma has not changed in the last two decades. This increase is postulated to be secondary to an increased use of combined replacement hormonal therapy. Patients with invasive lobular carcinoma tend to be slightly older than those with non-lobular invasive carcinoma with a reported mean age of 57 years compared to 64 years. On mammography, architectural distortion is more common and microcalcifications less common with invasive lobular carcinoma than invasive ductal carcinoma. The incidence of extrahepatic gastrointestinal (GI) tract metastases observed in autopsy studies varies in the literature from 6% to 18% with the most commonly affected organ being the stomach, followed by colon and rectum. Gastric lesions seem to be slightly more frequent, compared to colorectal lesions (6-18% compared to 8-12%, respectively).<br><br>PRESENTATION OF CASE: We present the case of a 70-year-old woman who was referred to our institution with a concurrent gastric and rectal cancer that on further evaluation was diagnosed as metastatic invasive lobular carcinoma of the breast. She has a stage IV clinical T3N1M1 left breast invasive lobular carcinoma (ER positive at 250, PR negative, HER-2/neu 1+ negative) with biopsy proven metastases to left axillary lymph nodes, gastric mucosa, peritoneum, rectal mass, and bone who presented with a partial large bowel obstruction. She is currently being treated with weekly intravenous paclitaxel, bevacizumab that was added after her third cycle, and she is also receiving monthly zoledronic acid. She is currently undergoing her 12-month of treatment and is tolerating it well. Discussion Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women aged 20-59 years. It accounts for 26% of all newly diagnosed cancers in females and is responsible for 15% of the cancer-related deaths in women.(9) Breast cancer is one of the most common malignancies that metastasize to the GI tract, along with melanoma, ovarian and bladder cancer.<br><br>CONCLUSION: We present one of the first reports of metastatic lobular breast cancer presenting as a synchronous rectal and gastric tumors. Metastatic lobular carcinoma of the breast is a rare entity with a wide range of clinical presentations. A high level of suspicion, repetition of endoscopic procedures, and a detailed pathological analysis is necessary for early diagnosis, which might help to avoid surgical treatment due to incorrect diagnosis. Patients with a history of breast cancer who present with new gastrointestinal lesions should have these lesions evaluated for evidence of metastasis through histopathologic evaluation and immunohistochemical analysis. Differentiating between a primary GI lesion and metastatic breast cancer will allow initiation of appropriate treatment and help prevent unnecessary operations.}, }
@article {pmid22090465, year = {2012}, author = {Choi, BB and Shu, KS}, title = {Metaplastic carcinoma of the breast: multimodality imaging and histopathologic assessment.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {53}, number = {1}, pages = {5-11}, doi = {10.1258/ar.2011.110341}, pmid = {22090465}, issn = {1600-0455}, mesh = {Adult ; Aged ; Breast/pathology/ultrastructure ; Breast Neoplasms/*diagnosis/ultrastructure ; Carcinoma, Ductal, Breast/*diagnosis/*secondary/ultrastructure ; Diagnosis, Differential ; Female ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Metaplasia ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Ultrasonography, Mammary/*methods ; }, abstract = {BACKGROUND: Metaplastic carcinomas are ductal carcinomas that display metaplastic transformation of the glandular epithelium to non-glandular mesenchymal tissue. Metaplastic carcinoma has a poorer prognosis than most other breast cancers, so the differential diagnosis is important. Although many clinical and pathologic findings have been reported, to our knowledge, few imaging findings related to metaplastic carcinoma have been reported.<br><br>PURPOSE: To investigate whole-breast imaging findings, including mammography, sonography, MRI, and pathologic findings, including immunohistochemical studies of metaplastic carcinomas of the breast.<br><br>MATERIAL AND METHODS: We analyzed 33 cases of metaplastic carcinoma between January 2001 and January 2011. Mammography, ultrasonography, and MRI were recorded retrospectively using the American College of Radiology (ACR) breast imaging reporting and data system (BI-RADS) lexicon. Immunohistochemical studies of estrogen receptor (ER), progesterone receptor (PR), p53, and C-erbB-2 were performed.<br><br>RESULTS: The most common mammographic findings were oval shape (37%), circumscribed margin (59%), and high density (74%). The most common sonographic findings were irregular shape (59.4%), microlobulated margin (41%), complex echogenicity (81%), parallel orientation (97%), and posterior acoustic enhancement (50%). Axillary lymph node metastases were noted for 25% of the sonographic examinations. On MRI, the most common findings of margin and shape were irregularity (57% and 52.4%, respectively). High signal intensity was the most common finding on T2-weighted images (57%). Immunohistochemical profile was negative for ER (91%, 29/32) and PR (81%, 26/32).<br><br>CONCLUSION: Metaplastic carcinomas might display more benign features and less axillary lymph node metastasis than IDC. High signal intensity on T2 MRI images and hormone receptor negativity would be helpful in differentiating this tumor from other breast cancers.}, }
@article {pmid22086737, year = {2012}, author = {Zeng, F and Xu, G and Zhou, T and Yang, C and Wang, X and Peng, C and Zhou, H}, title = {Reduced expression of activin receptor-like kinase 7 in breast cancer is associated with tumor progression.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {4}, pages = {2519-2526}, pmid = {22086737}, issn = {1559-131X}, mesh = {Activin Receptors, Type I/analysis/*physiology ; Activins/pharmacology ; Adult ; Aged ; Breast Neoplasms/enzymology/*pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Protein Serine-Threonine Kinases/genetics ; Receptor, Transforming Growth Factor-beta Type II ; Receptors, Transforming Growth Factor beta/genetics ; }, abstract = {To explore the clinical implication of activin receptor-like kinase 7 (ALK7) expression in breast cancer, we evaluated its protein level in six kinds of human breast tissue samples, including adjacent normal tissues, adenosis, breast fibroadenoma, ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and lymph node metastases (LNM). Immunohistochemical analyses showed that ALK7 was more frequently and much more intensely expressed in adjacent normal tissues, adenosis, and fibroadenoma tissues than in malignant tissues (DCIS, IDC, and LNM). Furthermore, the ALK7 expression in primary tumors and the corresponding LNM was evaluated in parallel samples from 60 patients with IDC. Results showed that the ALK7 expression status in primary tumors and LNM was concordant in 53 patients (88%), suggesting that ALK7 expression was retained in LNM. Moreover, our results suggested that ALK7 expression inversely correlated with the tumor grade (P=0.009) and clinical stage (P=0.004) in IDC significantly. Finally, the effect of activin-ALK7 pathway on the breast cancer cell growth was elucidated, and results revealed that overexpression of ALK7 could restore the inhibitory effect of activin B on the growth of ALK7-negative breast cancer cell line, ZR-75-30. These findings provide the evidence that the reduction or lack of ALK7 expression may account for the loss of its ligand sensitivity of breast cancer cells, thereby leading to breast tumor progression.}, }
@article {pmid22083198, year = {2011}, author = {Muraoka, T and Taira, N and Shien, T and Doihara, H and Takaki, A and Miyoshi, S}, title = {[A case of the usage of entecavir to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patient].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {38}, number = {11}, pages = {1861-1864}, pmid = {22083198}, issn = {0385-0684}, mesh = {Antiviral Agents/*therapeutic use ; Breast Neoplasms/complications/*drug therapy/pathology/surgery ; Combined Modality Therapy ; Female ; Guanine/*analogs &amp; derivatives/therapeutic use ; Hepatitis B/complications/*drug therapy ; Hepatitis B virus/*drug effects/physiology ; Humans ; Mammaplasty ; Middle Aged ; Neoplasm Staging ; Virus Activation/*drug effects ; }, abstract = {Hepatitis B virus(HBV)reactivation is a serious clinical problem for HBV infected patients, and one of its possible causes is chemotherapy for malignant disease. At the onset of active hepatitis, planned chemotherapy should be discontinued and acute or fetal fulminant hepatitis must be induced in some cases. Therefore, it is desirable to prevent virus reactivation during chemotherapy in HBV-positive patients. We report a case in which adjuvant chemotherapy for a breast cancer patient was accomplished safely by using entecavir. The patient was a 48-year-old woman with breast cancer whose HBV infection had been pointed out when she was 20 years old. Breast reconstruction was performed, followed by mastectomy. Pathological findings were invasive ductal carcinoma, three positive nodes, estrogen and progesterone receptor-positive, and HER2-negative. An adjuvant chemotherapy with anthracycline followed by taxane was planned. Blood chemistry revealed the seroconversion of HBV and the quantity of HBV-DNA was 2. 8 log copies/mL. Administration of the anti-virus agent, entecavir, was started three weeks before chemotherapy. The HBV-DNA was decreased under the titer of detection and no re-increase in HBV-DNA was found during chemotherapy. Planned chemotherapy was accomplished safely without HBV reactivation.}, }
@article {pmid23776766, year = {2011}, author = {Singhai, R and Patil, V and Patil, A}, title = {Status of HER-2/neu receptors and Ki-67 in breast cancer of Indian women.}, journal = {International journal of applied &amp; basic medical research}, volume = {1}, number = {1}, pages = {15-19}, pmid = {23776766}, issn = {2229-516X}, abstract = {BACKGROUND: Breast cancer is a leading cause of death in women. Receptor status is the most important prognostic and predictive marker for breast cancer.<br><br>AIMS: The present study was conducted with an aim to analyze breast cancer of Indian women with discordant receptor status, probably hormone dependent estrogen receptor (ER) positive, progesterone receptor (PgR) negative or ER- negative and PgR+ positive subgroup profile, infiltrating ductal breast cancer (IDC) not otherwise specified.<br><br>MATERIALS AND METHODS: Specimens from 100 IDC were grouped into three categories according to hormonal status (group 1: ER+ positive and PgR+ positive, group 2: ER+ positive and PgR- negative or ER- negative and PgR+ positive, group 3: ER- negative and PgR- negative) evaluated prognostic parameters.<br><br>STATISTICAL ANALYSIS: Statistically significant difference was found between tumor receptor status distribution and menopausal status (P = 0.0235), age of patients (P < 0.001), histopathologic grade (P < 0.001), vascular invasion (P = 0.006), HER-2/neu status (P = 0.004) and Ki-67 proliferation rate (P < 0.001).<br><br>RESULTS: Group 1 tumors were found exclusively in post-menopausal patients with average age 68.9 years, most of which had intermediate grade II, without vascular invasion, with HER-2/neu status score predominantly 0 or 1+ and lower Ki-67 proliferation rate. Group 2 tumors were found predominantly in younger post-menopausal patients with average age 57.5 years, with vascular invasion found in 23% of cases. Group 3 tumors mostly had higher histopathologic grade, showed the highest percentage of the Ki-67 positive tumor cells and vascular invasion in 30% of the cases.<br><br>CONCLUSION: It is concluded that patients with group 2 breast cancer were younger post-menopausal women, with tumors moderately differentiated, HER-2/neu score 0 or 1+ and with lower Ki-67 proliferation rate.}, }
@article {pmid22393991, year = {2011}, author = {Moatter, T and Aban, M and Iqbal, W and Azam, I and Pervaiz, A and Siddiqui, F and Murad, F and Pervez, S}, title = {Status of HER2 amplification, polysomy 17 and histopathological features of 425 Pakistani breast cancer patients.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {12}, number = {11}, pages = {3069-3073}, pmid = {22393991}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/pharmacology/therapeutic use ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy/*genetics/*pathology ; *Chromosome Duplication ; Chromosomes, Human, Pair 17/*genetics ; Female ; Gene Amplification/genetics ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Pakistan ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Trastuzumab ; }, abstract = {HER2 gene amplification in invasive breast cancer is a robust predictive marker for response to transtuzumab therapy. This study was undertaken to measure concordance between immunohistochemistry (IHC) and FISH for HER2 gene amplification in invasive breast tumors, as well as the presence of polysomy 17 and possible correlation with demographics and histopathological variables, including ER and PR positivity. A total of 425 cases of infiltrating carcinoma of breast (99% IDC-NOS) were studied. HER2 over expression was tested by IHC and FISH methods. Association between IHC and FISH in both subsets was calculated by amplification ratio including polysomy 17. Out of 425 specimens, 128 (30%) were positive for HER2 amplification by FISH test, whereas only 78 (24%) tumors with 2+ expression showed amplification. In contrast, 39 (74%) demonstrated 3+ IHC score and HER2 gene amplification. The histological variables including tumor size, tumor type, and lymph node involvement did not influence the outcome of FISH analysis. The ER and PR status showed significantly greater positivity in patients negative for HER2 amplification. Polysomy 17 was detected in 23.7% patients and was positively associated with ER and PR expression (P= <0.05). Our study showed a concordance of 24% between 2+ IHC and FISH amplification, while in 3+ IHC cases the concordance was 74%. Significant links of HER2 amplification was seen with ER andPR negativity and higher tumor grade. In addition, non-significant correlations were noted with other variables like tumor type, size and lymph node status.}, }
@article {pmid22767367, year = {2010}, author = {Fernandes, R}, title = {Metastatic disease causing unilateral isolated hypoglossal nerve palsy.}, journal = {BMJ case reports}, volume = {2010}, number = {}, pages = {}, pmid = {22767367}, issn = {1757-790X}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Lobular/*secondary/surgery ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Hypoglossal Nerve Diseases/*etiology/pathology/therapy ; Liver Neoplasms/pathology/therapy ; Lung Neoplasms/pathology/therapy ; Magnetic Resonance Imaging/methods ; Mammaplasty ; Mastectomy/methods ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*surgery ; Neoplasms, Multiple Primary/*pathology/surgery ; Risk Assessment ; }, abstract = {The authors present the case of a middle-aged woman diagnosed with lobar carcinoma in situ in her right breast. She eventually underwent a mastectomy and reconstruction. Histology revealed grade II invasive ductal carcinoma and she was commenced on adjuvant letrozole. The following year a MRI scan revealed she had developed spinal metastases and CT confirmed the presence of liver and lung metastases. She presented with a 5-month history of tongue weakness and difficulty manipulating food to the back of her mouth. On examination, there was marked right-sided hemiatrophy of the tongue with deviation of the tongue to the right side upon protrusion. MRI demonstrated ill-defined enhancing material close to the intracranial opening of the right hypoglossal canal. The patient was referred for consideration of radiotherapy. Due to the comorbidities of the patient, she was not a candidate for neurosurgical intervention.}, }
@article {pmid22242072, year = {2010}, author = {Joyce, D and O'Donoghue, G and Kerin, M}, title = {Metastatic breast disease: an all too common cause of back pain.}, journal = {BMJ case reports}, volume = {2010}, number = {}, pages = {}, pmid = {22242072}, issn = {1757-790X}, abstract = {A 50-year-old multiparous woman presented with a 3 month history of back pain. She was initially treated for non-mechanical back pain by her primary care physician, but was subsequently discovered to have a right sided clinical breast cancer and palpable axillary lymphadenopathy. An oestrogen/progesterone receptor positive invasive ductal carcinoma with axillary metastatic disease was confirmed on breast clinic triple assessment. Magnetic resonance imaging of the spine revealed an L1 vertebral body metastatic fracture with cord compression and other axial and non-axial stable skeletal metastases. The patient underwent immediate orthopaedic spinal stabilisation with full resolution of her back pain, and began primary endocrine breast cancer therapy with outpatient spinal radiotherapy planned.}, }
@article {pmid26141267, year = {2001}, author = {Hanson, EL and Hershberger, RE}, title = {Genetic Counseling and Screening Issues in Familial Dilated Cardiomyopathy.}, journal = {Journal of genetic counseling}, volume = {10}, number = {5}, pages = {397-415}, pmid = {26141267}, issn = {1573-3599}, abstract = {Idiopathic dilated cardiomyopathy (IDC), a treatable condition characterized by left ventricular dilatation and systolic dysfunction of unknown cause, has only recently been recognized to have genetic etiologies. Although familial dilated cardiomyopathy (FDC) was thought to be infrequent, it is now believed that 30-50% of cases of IDC may be familial. Echocardiographic and electrocardiographic (ECG) screening of first-degree relatives of individuals with IDC and FDC is indicated because detection and treatment are possible prior to the onset of advanced, symptomatic disease. However, such screening often creates uncertainty and anxiety surrounding the significance of the results. Furthermore, FDC demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making genetic counseling complex. The provision of genetic counseling for IDC and FDC will require collaboration between cardiologists and genetics professionals, and may also improve the recognition of FDC, the availability of support services, and overall outcomes for patients and families.}, }
@article {pmid22080244, year = {2012}, author = {Morrogh, M and Andrade, VP and Giri, D and Sakr, RA and Paik, W and Qin, LX and Arroyo, CD and Brogi, E and Morrow, M and King, TA}, title = {Cadherin-catenin complex dissociation in lobular neoplasia of the breast.}, journal = {Breast cancer research and treatment}, volume = {132}, number = {2}, pages = {641-652}, pmid = {22080244}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD ; Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/genetics/pathology ; Cadherins/*analysis/genetics ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/genetics/pathology ; Carcinoma, Lobular/*chemistry/genetics/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Microdissection ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Complex and Mixed/*chemistry/genetics/pathology ; New York City ; Nuclear Proteins/analysis ; Phosphorylation ; Prognosis ; Prospective Studies ; Protein Binding ; Snail Family Transcription Factors ; Transcription Factors/analysis ; Twist-Related Protein 1/analysis ; alpha Catenin/*analysis/genetics ; beta Catenin/*analysis/genetics ; }, abstract = {E-cadherin (E-CD) inactivation with loss of E-CD-mediated cell adhesion is the hallmark of lesions of the lobular phenotype. E-CD is typically absent by immunohistochemistry in both lobular carcinoma in situ (LCIS) and invasive lobular lesions, suggesting it occurs early in the neoplastic process. In laboratory models, downstream post-transcriptional modifiers such as TWIST and SNAIL contribute to the dissociation of the intracellular component of the cadherin-catenin complex (CCC), resulting in tumor progression and invasion. We hypothesized that complete CCC dissociation may play a role in lobular neoplasia progression. Here we explore the relationship between loss of E-CD and dissociation of the CCC in pure LCIS and LCIS associated with invasive cancer. Fresh-frozen tissues were obtained from 36 patients undergoing mastectomy for pure LCIS (n = 11), LCIS with ILC (n = 18) or LCIS with IDC (n = 7). Individual lesions were subject to laser-capture microdissection and gene-expression analysis (Affymetrix HG-U133A 2.0). Immunohistochemistry for ER,PR,HER2, E-CD,N-CD,α-,β-, and phosphoβ-catenin, TWIST, and SNAIL were evaluated in normal, in situ, and invasive components from matched formalin-fixed paraffin-embedded samples (n = 36). CCC-dissociation was defined as negative membranous E-CD, α- and β-catenin expression. E-CD was negative in all LCIS and ILC lesions, and positive in all normal and IDC lesions. Membranous α and β-catenin expressions decreased with the transition from LCIS to ILC (pure LCIS 82%; LCIS w/ILC 28%; ILC 0%), while TWIST expression increased (pure LCIS low; LCIS w/ILC moderate; ILC high). Gene expression paralleled IHC-staining patterns with a stepwise downregulation of E-CD, α and β-catenins from normal to LCIS to invasive lesions, and increasing expression of TWIST from normal to LCIS to ILC. Loss of E-CD expression is an early event in lobular neoplasia. Decreasing membranous catenin expression in tandem with increasing levels of TWIST across the spectrum of lobular lesions suggests that CCC dissociation is a progressive process.}, }
@article {pmid22070025, year = {2011}, author = {Li, CX and Hussain, A and Kamali, A}, title = {A hip simulator study of metal-on-metal hip joint device using acetabular cups with different fixation surface conditions.}, journal = {Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine}, volume = {225}, number = {9}, pages = {877-887}, doi = {10.1177/0954411911411604}, pmid = {22070025}, issn = {0954-4119}, mesh = {Acetabulum ; Durapatite ; Hip Joint ; *Hip Prosthesis ; Humans ; Materials Testing/*methods ; Metals ; Microscopy, Electron, Scanning ; Prosthesis Design ; Reproducibility of Results ; Surface Properties ; }, abstract = {In vitro wear data for hip joint devices reported in the literature vary in a wide range from one simulator study to another sometimes for the same type of device tested under identical physiological testing conditions. We hypothesized that non-bearing surface condition of the testing components could be an important factor affecting the simulator wear results. To confirm this hypothesis, fifteen 50 mm metal-on-metal hip resurfacing devices with identical bearing specifications were tested in a ProSim hip wear simulator for 5 million cycles. The heads were standard Birmingham Hip Resurfacing (BHR) heads; whilst the pairing acetabular cups were identical to the standard BHR cup except their different back surface conditions, including: (a) off-the-shelf products after removing the hydroxyapatite (HA) coating; (b) semi-finished products without HA coating; and (c) purposely-made cups without cast-in beads and HA coating. Results showed that the different back surfaces of the cups used indeed caused significantly large variations in the gravimetrically measured wear loss. We postulated that materials loss from the non-bearing surface of the testing components could contribute to the gravimetrically measured wear loss during a wear simulator test both directly and indirectly. The results presented in this paper pertain to In vitro wear simulator study and have little clinical relevance to the performance of any implant in vivo.}, }
@article {pmid22057904, year = {2011}, author = {Shankayi, Z and Firoozabadi, SM}, title = {Tumor growth inhibited by low-voltage amplitude and 5-kHz frequency electrochemotherapy.}, journal = {The Journal of membrane biology}, volume = {244}, number = {3}, pages = {121-128}, pmid = {22057904}, issn = {1432-1424}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Bleomycin/therapeutic use ; Carcinoma, Ductal/drug therapy ; Electrochemotherapy/*methods ; Female ; Mice ; Mice, Inbred BALB C ; Neoplasms/*drug therapy ; }, abstract = {The most important unpleasant sensation of electrochemotherapy is muscle contraction. One of the causes of this discomfort is electrochemotherapy in the low-frequency range (1 Hz). To resolve this problem, there are two solutions: first, increasing the repetition frequency of electric pulses above the tetanic frequency and, second, reducing the voltage amplitude. This study examines the antitumor effectiveness of treatment using low electric fields and high frequency in the presence and absence of chemotherapeutic agents. High-voltage amplitude electrochemotherapy was performed by eight pulses, at 1,000 V/cm, of 100-μs duration at 1-Hz and 5-kHz repetition frequency. In the low-voltage amplitude protocol, 4,000 pulses, of 100-μs duration at 5-kHz repetition frequency with 70, 100 and 150 V/cm were delivered to invasive ductal carcinoma tumors after intratumoral injection of bleomycin. Our data demonstrate significant differences in tumor volumes and the curability rate between mice treated by 70 V/cm compared to other groups. Electrochemotherapy, which is specified by a higher repetition frequency of electric pulses (5 kHz) and low voltage, inhibits tumor growth. This protocol has a comparable effect to 1-Hz pulse repetition electric pulses with high voltage. Based on these results, the 4,000 pulses of 70 V/cm with 5-kHz frequency are most effective. This protocol demonstrates inhibition of tumor growth without any need for drug administration.}, }
@article {pmid22055399, year = {2012}, author = {Yakirevich, E and Samkari, A and Holloway, MP and Lu, S and Singh, K and Yu, J and Fenton, MA and Altura, RA}, title = {Total Survivin and acetylated Survivin correlate with distinct molecular subtypes of breast cancer.}, journal = {Human pathology}, volume = {43}, number = {6}, pages = {865-873}, doi = {10.1016/j.humpath.2011.07.014}, pmid = {22055399}, issn = {1532-8392}, mesh = {Acetylation ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins/*biosynthesis/genetics ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Survivin ; Tissue Array Analysis ; }, abstract = {Global gene expression profiling studies led to the recent classification of breast cancer into 4 distinct molecular subtypes including luminal, human epidermal growth factor receptor 2 enriched, basal like, and unclassified. Here, we used immunohistochemistry to evaluate expression of the antiapoptotic protein Survivin and its recently described acetylated form, Survivin acetyl129, in normal breast tissue and in 226 primary breast tumors of different molecular subtypes. Correlation of Survivin expression with molecular markers and its impact on patient outcomes were analyzed. Eighty-four percent of basal-like tumors expressed high levels of total Survivin, whereas 52% of luminal tumors expressed high levels of acetylated Survivin (P < .001). Overall survival (91%) for tumors expressing low levels of total Survivin was better than that for tumors expressing high levels of total Survivin (72%, P = .02), whereas the reverse was true for tumors expressing acetylated Survivin. In hierarchical cluster analysis, total Survivin clustered with basal marker expression, whereas acetylated Survivin clustered with luminal marker expression. In multivariate analysis, high total Survivin expression was an independent predictor of worse overall survival in patients with breast cancer (relative risk, 11; P < .01). These data indicate that high levels of total Survivin predict poor outcome in patients with grade 3 invasive ductal carcinoma and correlate directly with a basal-like phenotype. In contrast, high expression of the acetylated form of the protein associates with a favorable outcome and preferentially correlates with luminal-type tumors. Survivin likely has different functions in distinct breast cancer subtypes, and diagnostic strategies that incorporate immunohistochemical markers that detect both Survivin forms may help better strategize patient risk and direct therapy.}, }
@article {pmid22053985, year = {2011}, author = {Bi, X and Hameed, M and Mirani, N and Pimenta, EM and Anari, J and Barnes, BJ}, title = {Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis.}, journal = {Breast cancer research : BCR}, volume = {13}, number = {6}, pages = {R111}, pmid = {22053985}, issn = {1465-542X}, mesh = {Animals ; Apoptosis/genetics/radiation effects ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Chemokine CXCL12/metabolism ; Chemotaxis/genetics ; DNA Damage ; Down-Regulation/genetics ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Interferon Regulatory Factor-1/genetics/metabolism ; Interferon Regulatory Factors/*genetics/metabolism ; Lymph Nodes/metabolism/pathology ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Staging ; Radiation Tolerance/genetics ; Receptors, CXCR4/genetics/metabolism ; Transcription, Genetic ; }, abstract = {INTRODUCTION: New signaling pathways of the interleukin (IL) family, interferons (IFN) and interferon regulatory factors (IRF) have recently been found within tumor microenvironments and in metastatic sites. Some of these cytokines stimulate while others inhibit breast cancer proliferation and/or invasion. IRFs, a family of nine mammalian transcription factors, have multiple biologic functions that when dysregulated may contribute to tumorigenesis; most well-known are their roles in regulating/initiating host immunity. Some IRF family members have been implicated in tumorigenesis yet little is still known of their expression in primary human tumors or their role(s) in disease development/progression. IRF5 is one of the newer family members to be studied and has been shown to be a critical mediator of host immunity and the cellular response to DNA damage. Here, we examined the expression of IRF5 in primary breast tissue and determined how loss of expression may contribute to breast cancer development and/or progression.<br><br>METHODS: Formalin-fixed paraffin-embedded archival breast tissue specimens from patients with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were examined for their expression of IRF1 and IRF5. Knockdown or overexpression of IRF5 in MCF-10A, MCF-7 and MDA-MB-231 mammary epithelial cell lines was used to examine the role of IRF5 in growth inhibition, invasion and tumorigenesis.<br><br>RESULTS: Analysis of IRF expression in human breast tissues revealed the unique down-regulation of IRF5 in patients with different grades of DCIS and IDC as compared to IRF1; loss of IRF5 preceded that of IRF1 and correlated with increased invasiveness. Overexpression of IRF5 in breast cancer cells inhibited in vitro and in vivo cell growth and sensitized them to DNA damage. Complementary experiments with IRF5 siRNAs made normal mammary epithelial cells resistant to DNA damage. By 3-D culture, IRF5 overexpression reverted MDA-MB-231 to normal acini-like structures; cells overexpressing IRF5 had decreased CXCR4 expression and were insensitive to SDF-1/CXCL12-induced migration. These findings were confirmed by CXCR4 promoter reporter assays.<br><br>CONCLUSIONS: IRF5 is an important tumor suppressor that regulates multiple cellular processes involved in the conversion of normal mammary epithelial cells to tumor epithelial cells with metastatic potential.}, }
@article {pmid22052326, year = {2012}, author = {Johnson, CE and Gorringe, KL and Thompson, ER and Opeskin, K and Boyle, SE and Wang, Y and Hill, P and Mann, GB and Campbell, IG}, title = {Identification of copy number alterations associated with the progression of DCIS to invasive ductal carcinoma.}, journal = {Breast cancer research and treatment}, volume = {133}, number = {3}, pages = {889-898}, doi = {10.1007/s10549-011-1835-1}, pmid = {22052326}, issn = {1573-7217}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Chromosome Aberrations ; *DNA Copy Number Variations ; Disease Progression ; Female ; Humans ; Neoplasm Invasiveness/genetics ; Recurrence ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma (IDC). Annotation of the genetic differences between the two lesions may assist in the identification of genes that promote the invasive phenotype. Synchronous DCIS and IDC cells were microdissected from FFPE tissue and analysed by molecular inversion probe (MIP) copy number arrays. Matched IDC and DCIS showed highly similar copy number profiles (average of 83% of the genome shared) indicating a common clonal origin although there is evidence that the DCIS continues to evolve in parallel with the co-existing IDC. Four chromosomal regions of loss (3q, 6q, 8p and 11q) and four regions of gain (5q, 16p, 19q and 20) were recurrently affected in IDC but not in DCIS. CCND1 and MYC showed increased amplitude of gain in IDC. One region of loss (17p11.2) was specific to DCIS. IDC-specific regions include genes with previous links to breast cancer progression and potential therapeutic targets such as AXL, SPHK1 and PLAUR.}, }
@article {pmid22051146, year = {2011}, author = {Li, W and Yang, D and Wang, S and Guo, X and Lang, R and Fan, Y and Gu, F and Zhang, X and Niu, Y and Yan, X and Fu, L}, title = {Increased expression of CD146 and microvessel density (MVD) in invasive micropapillary carcinoma of the breast: Comparative study with invasive ductal carcinoma-not otherwise specified.}, journal = {Pathology, research and practice}, volume = {207}, number = {12}, pages = {739-746}, doi = {10.1016/j.prp.2011.09.009}, pmid = {22051146}, issn = {1618-0631}, mesh = {Adult ; Aged ; Breast/metabolism/pathology ; Breast Neoplasms/*blood supply/*metabolism/pathology ; CD146 Antigen/analysis/genetics/metabolism ; Carcinoma, Ductal, Breast/*blood supply/*metabolism/pathology ; Carcinoma, Papillary/*blood supply/*metabolism/pathology ; Endothelial Cells/metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/pathology ; Microvessels/pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a rare variant of ductal carcinoma of the breast, and is characterized by a high metastatic potential and an aggressive clinical course. Studies of CD146 expression and function in breast cancer remain scarce. The aim of this study was to evaluate the role of CD146 and microvessel density (MVD) in breast IMPC. CD146 mRNA expression and immunohistochemistry for CD146 and MVD measured by CD31 were assessed in 82 cases of IMPC and 137 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The mRNA level of CD146 in cancer specimens was higher in IMPC than in IDC-NOS. CD146 expression in tumor cells was up-regulated in IMPC as compared with that in IDC-NOS, and was positively correlated with histological grade, ER, PR status, and P53 expression in IMPC and IDC-NOS. CD146 expression in vascular endothelial cells was significantly higher than that in IDC, and was positively correlated with tumor progression in IMPC and IDC-NOS. MVD in IMPC was significantly higher than that in IDC. CD146 expression in tumor cells was positively correlated with that in vascular endothelial cells of IMPC and IDC-NOS. The association of CD146 expression with MVD and its correlation with progression in breast carcinoma indicated that CD146 is a potentially useful prognostic marker for breast cancer. CD146 could be a new drug target in the treatment of breast cancer.}, }
@article {pmid22042364, year = {2012}, author = {Kim, J and Lee, S and Bae, S and Choi, MY and Lee, J and Jung, SP and Kim, S and Choe, JH and Kim, JH and Kim, JS and Lee, JE and Nam, SJ and Yang, JH}, title = {Comparison between screen-detected and symptomatic breast cancers according to molecular subtypes.}, journal = {Breast cancer research and treatment}, volume = {131}, number = {2}, pages = {527-540}, doi = {10.1007/s10549-011-1836-0}, pmid = {22042364}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*classification/*diagnosis/mortality ; Carcinoma, Ductal, Breast/*classification/*diagnosis/mortality ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; }, abstract = {Breast cancer screening programs make it possible to detect early cancer, thus reducing breast cancer mortality. We studied the clinicopathologic characteristics and prognosis of screen-detected invasive breast cancer compared with symptomatic breast cancer. And we compared the result according to molecular subtypes (luminal A, luminal B, Her2, and triple negative), with the goal of identifying the role of screening in each subtypes. From January 2002 to June 2008, 3,141 patients who underwent surgery for the treatment of invasive ductal carcinoma at Samsung Medical Center were included. Among them, 1,025 patients were screen-detected, and 2,116 patients who were screened over 2 years or never were symptomatic. We retrospectively reviewed the clinical and pathologic data. Screen-detected breast cancer was associated with older age, smaller tumor size, more hormone-receptor positive, less lymph node involvement, earlier stage, and reduced mortality compared with symptomatic breast cancer (P < 0.001). According to the molecular subtype, luminal A was most common (63.6%) and showed the most obvious survival benefit in screen-detected tumors in comparison with symptomatic tumors (5-year OS: 99.7 vs. 96.5%, 5-year DFS: 96.4 vs. 90.7%). Screen detection was independently associated with improved overall and disease-free survival outcomes after adjustment for covariates (HR 0.32, P = 0.035; HR 0.58, P = 0.020, respectively) only in the luminal A subtype. Differences in pathological features such as tumor size, nodal status, grade, and age at diagnosis with different molecular subtype distributions may explain the survival advantage of patients with screen-detected breast cancer. Screening programs seem to have a different efficacy depending on the molecular subtype of the breast cancer, especially in the luminal A subtype, for which screen detection acts as an independent prognostic factor itself.}, }
@article {pmid22030565, year = {2011}, author = {Barbosa, AP and Cardinalli Neto, A and Otaviano, AP and Rocha, BF and Bestetti, RB}, title = {Comparison of outcome between Chagas cardiomyopathy and idiopathic dilated cardiomyopathy.}, journal = {Arquivos brasileiros de cardiologia}, volume = {97}, number = {6}, pages = {517-525}, doi = {10.1590/s0066-782x2011005000112}, pmid = {22030565}, issn = {1678-4170}, mesh = {Adrenergic beta-Antagonists/adverse effects/therapeutic use ; Cardiomyopathy, Dilated/diagnostic imaging/drug therapy/*mortality ; Chagas Cardiomyopathy/diagnostic imaging/drug therapy/*mortality ; Digoxin/adverse effects/therapeutic use ; Epidemiologic Methods ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Treatment Outcome ; Ultrasonography ; }, abstract = {BACKGROUND: Little is known about the outcome of patients with Chagas cardiomyopathy in comparison to that of patients with idiopathic dilated cardiomyopathy in the contemporary era.<br><br>OBJECTIVE: To compare the outcome of chagasic patients with chronic systolic heart failure secondary to Chagas cardiomyopathy with that observed in patients with IDC in the contemporary era.<br><br>METHODS: A total of 352 patients (246 with Chagas cardiomyopathy, 106 with idiopathic dilated cardiomyopathy) prospectively followed at our Institution from January, 2000 to January, 2008 were included. All patients received standard contemporary medical therapy.<br><br>RESULTS: In Cox proportional hazards model multivariate analysis, digoxin use (Hazard Ratio=3.17; 95% Confidence Interval 1.62 to 6.18; p=0.001), need of inotropic support (Hazard Ratio=2.08; 95% Confidence Interval 1.43 to 3.02; p<0.005), left ventricular ejection fraction (Hazard Ratio=0.97; 95% Confidence Interval 0.95 to 0.99; p<0.005), and Chagas cardiomyopathy etiology (Hazard Ratio=3.29; 95% Confidence Interval 1.89 to 5.73; p<0.005) were positively associated with mortality, whereas beta-blocker therapy (Hazard Ratio=0.39; 95% Confidence Interval 0.26 to 0.56; p<0.005) was negatively associated with mortality. Survival probability for patients with Chagas cardiomyopathy at 8, 24, and 49 months was 83%, 61%, and 41%, respectively, and for patients with idiopathic dilated cardiomyopathy 97%, 92%, and 82%, respectively (p<0.005).<br><br>CONCLUSION: In the current era of heart failure therapy, patients with Chagas cardiomyopathy have a poorer outcome in comparison to patients with idiopathic dilated cardiomyopathy.}, }
@article {pmid22025283, year = {2012}, author = {Duprez, R and Wilkerson, PM and Lacroix-Triki, M and Lambros, MB and MacKay, A and A'Hern, R and Gauthier, A and Pawar, V and Colombo, PE and Daley, F and Natrajan, R and Ward, E and MacGrogan, G and Arbion, F and Michenet, P and Weigelt, B and Vincent-Salomon, A and Reis-Filho, JS}, title = {Immunophenotypic and genomic characterization of papillary carcinomas of the breast.}, journal = {The Journal of pathology}, volume = {226}, number = {3}, pages = {427-441}, pmid = {22025283}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; CTR-Q3REIS-FILHO/BCN_/Breast Cancer Now/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Papillary/*genetics/pathology ; Case-Control Studies ; Class I Phosphatidylinositol 3-Kinases ; Female ; Humans ; Immunophenotyping/methods ; Lymphatic Metastasis ; Mutation/genetics ; Phenotype ; Phosphatidylinositol 3-Kinases/genetics ; Receptors, Estrogen/genetics ; }, abstract = {Papillary carcinomas are a special histological type of breast cancer and have a relatively good outcome. We characterized the genomic and phenotypic characteristics of papillary carcinomas to determine whether they would constitute an entity distinct from grade- and oestrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs). The phenotype of 63 papillary carcinomas of the breast and grade- and ER-matched IDC-NSTs was determined by immunohistochemistry. DNA of sufficient quality was extracted from 49 microdissected papillary carcinomas and 49 microdissected grade- and ER-matched IDC-NSTs. These samples were subjected to high-resolution microarray-based comparative genomic hybridization (aCGH) and Sequenom MassARRAY sequencing analysis of 19 known oncogenes. Papillary carcinomas were predominantly of low histological grade, expressed immunohistochemical markers consistent with a luminal phenotype, and a lower rate of lymph node metastasis and p53 expression than grade- and ER-matched IDC-NSTs. Papillary carcinomas displayed less genomic aberrations than grade- and ER-matched IDC-NSTs; however, the patterns of gene copy number aberrations found in papillary carcinomas were similar to those of ER- and grade-matched IDC-NSTs, including 16q losses. Furthermore, PIK3CA mutations were found in 43% and 29% of papillary carcinomas and grade- and ER-matched IDC-NSTs, respectively. The genomic profiles of encapsulated, solid and invasive papillary carcinomas, the three morphological subtypes, were remarkably similar. Our results demonstrate that papillary carcinomas are a homogeneous special histological type of breast cancer. The similarities in the genomic profiles of papillary carcinomas and grade- and ER-matched IDC-NSTs suggest that papillary carcinomas may be best positioned as part of the spectrum of ER-positive breast cancers, rather than as a distinct entity. Furthermore, the good prognosis of papillary carcinomas may stem from the low rates of lymph node metastasis and p53 expression, low number of gene copy number aberrations and high prevalence of PIK3CA mutations.}, }
@article {pmid22015727, year = {2012}, author = {Wetterskog, D and Lopez-Garcia, MA and Lambros, MB and A'Hern, R and Geyer, FC and Milanezi, F and Cabral, MC and Natrajan, R and Gauthier, A and Shiu, KK and Orr, N and Shousha, S and Gatalica, Z and Mackay, A and Palacios, J and Reis-Filho, JS and Weigelt, B}, title = {Adenoid cystic carcinomas constitute a genomically distinct subgroup of triple-negative and basal-like breast cancers.}, journal = {The Journal of pathology}, volume = {226}, number = {1}, pages = {84-96}, doi = {10.1002/path.2974}, pmid = {22015727}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Adenoid Cystic/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Female ; Gene Dosage ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Microdissection ; Oncogene Proteins, Fusion/*genetics ; Receptor, ErbB-3/biosynthesis/genetics ; Receptors, Estrogen/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; }, abstract = {Adenoid cystic carcinoma (AdCC) is a rare form of triple-negative and basal-like breast cancer that has an indolent clinical behaviour. Four breast AdCCs were recently shown to harbour the recurrent chromosomal translocation t(6;9)(q22-23;p23-24), which leads to the formation of the MYB-NFIB fusion gene. Our aims were (i) to determine the prevalence of the MYB-NFIB fusion gene in AdCCs of the breast; (ii) to characterize the gene copy number aberrations found in AdCCs; and (iii) to determine whether AdCCs are genomically distinct from histological grade-matched or triple-negative and basal-like invasive ductal carcinomas of no special type (IDC-NSTs). The presence of the MYB-NFIB fusion gene was investigated in 13 AdCCs of the breast by fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR), and MYB and BRCA1 RNA expression was determined by quantitative RT-PCR. Fourteen AdCCs, 14 histological grade-matched IDC-NSTs, and 14 IDC-NSTs of triple-negative and basal-like phenotype were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). The MYB-NFIB fusion gene was detected in all but one AdCC. aCGH analysis demonstrated a relatively low number of copy number aberrations and a lack of recurrent amplifications in breast AdCCs. Contrary to grade-matched IDC-NSTs, AdCCs lacked 1q gains and 16q losses, and in contrast with basal-like IDC-NSTs, AdCCs displayed fewer gene copy number aberrations and expressed MYB and BRCA1 at significantly higher levels. Breast AdCCs constitute an entity distinct from grade-matched and triple-negative and basal-like IDC-NSTs, emphasizing the importance of histological subtyping of triple-negative and basal-like breast carcinomas.}, }
@article {pmid22011761, year = {2012}, author = {Wu, T and Li, Y and Gong, L and Lu, JG and Du, XL and Zhang, WD and He, XL and Wang, JQ}, title = {Multi-step process of human breast carcinogenesis: a role for BRCA1, BECN1, CCND1, PTEN and UVRAG.}, journal = {Molecular medicine reports}, volume = {5}, number = {2}, pages = {305-312}, doi = {10.3892/mmr.2011.634}, pmid = {22011761}, issn = {1791-3004}, mesh = {Adult ; Aged ; Apoptosis Regulatory Proteins/genetics/*metabolism ; BRCA1 Protein/genetics/*metabolism ; Beclin-1 ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cyclin D1/genetics/*metabolism ; Female ; G1 Phase ; Humans ; Membrane Proteins/genetics/*metabolism ; Middle Aged ; PTEN Phosphohydrolase/genetics/*metabolism ; RNA, Messenger/metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; }, abstract = {In the female population in Asia, systematic investigation concerning alterations in cancer-related genes in breast carcinoma is rare, and the correlation among oncogene or suppressor gene expression with tumor cell apoptosis, cell cycle regulation and tumor cell autophagy remains to be clarified. In this study, a tissue microarray consisting of 360 individual samples from three different breast tissues was generated. By comparing the expression of the tumor-suppressor genes (BRCA1, BECN1, CCND1, PTEN and UVRAG) in ductal breast cancer and normal breast tissues, respectively, we were able to assign changes in the expression of these mRNAs to specific stages and allocate them to define the roles in the multi‑step process of breast carcinogenesis. Tumor-suppressor genes, such as BRCA1 and BECN1, usually had lower signals in the carcinomatous tissues (10.2 and 6.6%) compared to the normal tissues (31 and 32.6%), while stronger positive dots (positive cells >30%) usually existed in the normal tissues. The patients in the oldest age group had the lowest expression rate. Only BECN1 and CCND1 expression showed a significant association with patient age (p=0.030 and p=0.003). A significant association was observed between BRCA1 and BECN1 expression and tumor size (p=0.028 and p=0.021). BECN1 gene expression was positively correlated with UVRAG and PTEN expression (p=0.006 and p=0.000). CCND1 was negatively correlated with PTEN, BECN1 and BRCA1 expression (p=0.011, p=0.000 and p=0.000). Abnormal expression of BRCA1, BECN1, CCND1, PTEN and UVRAG may play a role in human breast carcinogenesis through dysregulated mRNA expression. Overexpressed CCND1 may shorten the G1 phase of the cell cycle, suppress cell apoptosis and contribute to the formation of invasive ductal carcinoma (IDC).}, }
@article {pmid22000861, year = {2012}, author = {Jardim, BV and Moschetta, MG and Gelaleti, GB and Leonel, C and Regiani, VR and de Santi Neto, D and Bordin-Junior, NA and Perea, SA and Zuccari, DA}, title = {Glutathione transferase pi (GSTpi) expression in breast cancer: an immunohistochemical and molecular study.}, journal = {Acta histochemica}, volume = {114}, number = {5}, pages = {510-517}, doi = {10.1016/j.acthis.2011.09.005}, pmid = {22000861}, issn = {1618-0372}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Glutathione S-Transferase pi/*genetics ; Humans ; Immunohistochemistry ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; }, abstract = {Breast cancer is the most frequent cancer in women worldwide. Prognostic markers are important for diagnosis, allowing therapeutic strategies to be defined more efficiently. The expression of the glutathione S-transferase pi isoenzyme (GSTpi) in tumor cells has been evaluated as a predictor of prognosis and in response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results were statistically correlated with clinicopathological parameters of patients. The results showed that high GSTpi expression was related to p53-positive tumors, grade III histology, large tumor size and death (p<0.05). The 37 patients who received adjuvant treatment, checked separately, showed high expression of GSTpi in relation to local recurrence, metastasis and death (p<0.05). In addition, high levels of GSTpi expression were significantly associated with a shorter overall survival (p<0.05). To confirm this suspicion, GSTpi gene expression was checked by Real-time PCR in neoplastic mammary cells cultured and subjected to treatment with doxorubicin. Our results suggest that high levels of GSTpi may be related to the development of resistance to chemotherapy in these tumors, the response of these tumors to treatment and the clinical course of the patients involved.}, }
@article {pmid21987494, year = {2013}, author = {Akashi, S and Kuwabara, H and Kurisu, Y and Takahashi, Y and Yasuda, E and Takeshita, A and Ishizaki, S and Tsuji, M and Shibayama, Y}, title = {Fine-needle aspiration cytology of triple-negative basal-like breast cancer.}, journal = {Diagnostic cytopathology}, volume = {41}, number = {4}, pages = {283-287}, doi = {10.1002/dc.21807}, pmid = {21987494}, issn = {1097-0339}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Biopsy, Fine-Needle/*methods ; Carcinoma, Medullary/diagnosis ; Cell Nucleus/pathology ; Cell Nucleus Shape ; Chromatin/pathology ; Female ; Humans ; Middle Aged ; Mitotic Index ; Neoplasm Grading ; Neoplasm Metastasis/diagnosis ; Receptor, ErbB-2/genetics/metabolism ; Sensitivity and Specificity ; Triple Negative Breast Neoplasms/*diagnosis ; }, abstract = {Invasive breast cancer is divided into luminal A, luminal B, HER2 overexpression, basal-like (BL) and normal-like subtypes, among which the BL subtype has the worst prognosis. The purpose of this study was to determine the clinicopathological and cytological characteristics of BL breast cancer (BLBC). Fine-needle aspiration cytology samples from 17 patients with consecutive BLBC were investigated, and the findings were compared with those of other subtypes (10 cases each) for the following cytomorphological features: necrosis; lymphocyte infiltration; mitotic index; apoptosis; naked nuclei; nuclear/cytoplasmic ratio; nuclear margin, size and pleomorphism; chromatin granularity and density; and nucleolar appearance. Histologically, the BLBCs were heterogeneous, and included medullary carcinoma and metaplastic carcinoma, in addition to invasive ductal carcinoma. Cytologically, high mitotic index, naked nuclei, and irregular nuclear margin were significantly observed when compared with both the luminal A and B subtypes. Large nuclei with nucleoli and lymphocyte infiltration were frequently seen compared with the luminal A and B subtypes, respectively. Squamous nodules were seen in all metaplastic cases, but not in the HER2 overexpression subtype. Lymphocyte infiltration, squamous metaplasia, and nuclear findings such as a high mitotic index, naked or large nuclei, an irregular nuclear margin and the presence of nucleoli, may be clues indicating BLBC.}, }
@article {pmid21987236, year = {2012}, author = {Naushad, SM and Prayaga, A and Digumarti, RR and Gottumukkala, SR and Kutala, VK}, title = {Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast.}, journal = {Molecular and cellular biochemistry}, volume = {361}, number = {1-2}, pages = {189-195}, pmid = {21987236}, issn = {1573-4919}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Amplified Fragment Length Polymorphism Analysis ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; DNA Methylation ; Deoxyguanosine/analogs &amp; derivatives/metabolism ; *Epigenesis, Genetic ; Female ; Ferredoxin-NADP Reductase/*genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Glycine Hydroxymethyltransferase/*genetics/metabolism ; Humans ; Membrane Proteins/*genetics/metabolism ; Oxidative Stress ; Phenotype ; Polymorphism, Genetic ; Prognosis ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/*genetics/metabolism ; Sequence Analysis, DNA ; }, abstract = {In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influence CIMP phenotype of BNIP3. In order to substantiate the prognostic relevance of BNIP3, we explored its association with 8-oxo-2'deoxyguanosine (8-oxodG), a marker of oxidative stress with prognostic relevance. BNIP3 expression and CIMP phenotype were studied using semi-quantitative RT-PCR and combined bisulfite restriction analysis (COBRA), respectively, in 56 IDC tumors. Eight polymorphisms in one-carbon metabolism were studied using PCR-RFLP and PCR-AFLP approaches. 8-oxodG was measured using competitive ELISA kit. BNIP3 was found to be upregulated in IDC (cases vs. controls: 0.94 ± 0.05 vs. 0.18 ± 0.08, P < 0.0001). COBRA analysis confirmed hypomethylation of BNIP3 promoter CpG island in these cases. CIMP phenotype of BNIP3 showed positive association with tubule formation (P = 0.034) and methionine synthase reductase (MTRR) A66G (P = 0.002); inverse association with cytosolic serine hydroxyl methyltransferase (cSHMT) C1420T (P < 0.005) and 8-oxodG (<10% vs. >10% methylation: 7.24 ± 2.77 ng/ml vs. 4.42 ± 2.93 ng/ml, P < 0.0005); and no association with nuclear pleomorphism or mitotic index or ER, PR, and HER statuses. Synergistic effect of MTR A2756G and MTRR A66G variants on BNIP3 hypermethylator phenotype was clearly evident (P < 0.0007). MTRR A66G and cSHMT C1420T polymorphisms influence CIMP phenotype of BNIP3, thus epigenetically regulating BNIP3 in breast cancer. The linear association between BNIP3 and 8-oxodG substantiates the role of BNIP3 as redox sensor as well as prognostic marker in breast cancer.}, }
@article {pmid21983893, year = {2012}, author = {Endo, H and Saito, T and Kenjo, A and Hoshino, M and Terashima, M and Sato, T and Anazawa, T and Kimura, T and Tsuchiya, T and Irisawa, A and Ohira, H and Hikichi, T and Takagi, T and Gotoh, M}, title = {Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {19}, number = {4}, pages = {465-475}, doi = {10.1007/s00534-011-0457-7}, pmid = {21983893}, issn = {1868-6982}, mesh = {Adenocarcinoma/*immunology/pathology/surgery/*therapy ; Aged ; Antineoplastic Agents/*administration &amp; dosage ; Combined Modality Therapy ; Dendritic Cells/*immunology ; *Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Feasibility Studies ; Female ; Humans ; Immunohistochemistry ; Injections, Intralesional ; Lymph Nodes/pathology ; Lymphocytes, Tumor-Infiltrating ; Male ; Middle Aged ; Pancreatic Neoplasms/*immunology/pathology/surgery/*therapy ; Picibanil/*administration &amp; dosage ; Preoperative Period ; }, abstract = {PURPOSE: To determine the feasibility, safety and histological change of preoperative endoscopic ultrasound-guided fine-needle injection (PEU-FNI) of immature DCs (iDCs) with OK-432 in pancreatic cancer patients.<br><br>METHODS: Nine patients enrolled in the trial (DC group) and were compared with 15 patients operated on without iDC injection (non-DC group). Adverse events of PEU-FNI and postoperative complications were evaluated according to CTC-AE ver.3.0 and the Clavien-Dindo classification/ISGPF definition, respectively. Histological changes within the tumor and lymph nodes were evaluated by immunohistochemical examination of infiltrating inflammatory cells (CD4+, CD8+, Foxp3+ and CD83+).<br><br>RESULTS: There were no severe toxicities following PEU-FNI, except for one transient grade 3 fever, and there were no significant differences in the incidence of postoperative complications between the two groups. Colliquative necrosis and diffusely scattered TUNEL-positive cells were observed at the injection sites. CD83+ cells significantly accumulated in the regional lymph nodes of the DC group as well as Foxp3+ cells in the regional and distant lymph nodes. The two DC group patients, one of which was stage IV with distant lymph node metastasis, survived more than 5 years without requiring adjuvant theraphy.<br><br>CONCLUSION: PEU-FNI was feasible and safe, and further study needs to confirm and enhance antitumor responses.}, }
@article {pmid21980445, year = {2011}, author = {van Damme, P and Kafeja, F and Anemona, A and Basile, V and Hilbert, AK and De Coster, I and Rondini, S and Micoli, F and Qasim Khan, RM and Marchetti, E and Di Cioccio, V and Saul, A and Martin, LB and Podda, A}, title = {Safety, immunogenicity and dose ranging of a new Vi-CRM197 conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.}, journal = {PloS one}, volume = {6}, number = {9}, pages = {e25398}, pmid = {21980445}, issn = {1932-6203}, mesh = {Adult ; Bacterial Proteins/*adverse effects/*immunology ; Dose-Response Relationship, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Female ; Health ; Humans ; Male ; Polysaccharides, Bacterial/*adverse effects/*immunology ; Typhoid Fever/immunology/*prevention &amp; control ; Typhoid-Paratyphoid Vaccines/*adverse effects/*immunology ; Vaccines, Conjugate/adverse effects/immunology ; Young Adult ; }, abstract = {BACKGROUND: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM197 in European adults.<br><br>METHODOLOGY: Following randomized blinded comparison of single vaccination with either Vi-CRM&#x2081;&#x2089;&#x2087; or licensed polysaccharide vaccines (both containing 25&#xb7;0 &#xb5;g of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM&#x2081;&#x2089;&#x2087; (1&#xb7;25 &#xb5;g, 5&#xb7;0 &#xb5;g and 12&#xb7;5 &#xb5;g of Vi antigen) with the polysaccharide vaccine.<br><br>PRINCIPAL FINDINGS: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM&#x2081;&#x2089;&#x2087; induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM&#x2081;&#x2089;&#x2087; formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.<br><br>CONCLUSIONS: Vi-CRM&#x2081;&#x2089;&#x2087; did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT01123941 NCT01193907.}, }
@article {pmid21966777, year = {2011}, author = {Carabias-Meseguer, P and Cusidó-Gimferrer, M and Zapardiel-Gutiérrez, I and Tresserra-Casas, F and Fábregas-Xauradó, R and Xercavins-Montoya, J}, title = {[Node status in 454 ductal breast cancers cases according to the association with in situ component].}, journal = {Ginecologia y obstetricia de Mexico}, volume = {79}, number = {1}, pages = {5-10}, pmid = {21966777}, issn = {0300-9041}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology/*secondary ; Carcinoma, Intraductal, Noninfiltrating/classification/epidemiology/*pathology ; Disease Progression ; Female ; Humans ; Hyperplasia/pathology ; *Lymphatic Metastasis ; Mexico/epidemiology ; Middle Aged ; Necrosis ; Neoplasm Invasiveness/pathology ; Precancerous Conditions/epidemiology/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Studies have shown that breast infiltrating ductal carcinoma develops from precursor lesions or pre-invasive. It is accepted that the risk of invasive ductal carcinoma increased slightly in hyperplasia, but especially in cases of atypical hyperplasia and intraductal carcinoma.<br><br>OBJECTIVES: To evaluate and compare the nodal status between ductal breast cancer with in situ component (group 1) or without it (group 2).<br><br>MATERIAL AND METHOD: Descriptive and retrospective study that included 454 ductal breast cancers. Data concerning clinical and pathological variables was collected. All data was compared between both groups.<br><br>RESULTS: Among all cases, 176 (38.8%) showed positive lymph nodes, 136 patients (39.5%) from group 1 and 40 cases (36.4%) from group 2. Among group 1 cases, high-grade subgroup showed higher positive lymph node rate (82 cases, 55.4%) than the extensive in situ carcinomas subgroup (84 cases, 49.7%). Both of them had a significant higher rate than group 2 cases (p = 0.003 y p = 0.028, respectively). Moreover, the low-grade in situ carcinomas without cellular necrosi had positive lymph nodes just in 30 cases (24%), significantly lower (p = 0.034) than group 2.<br><br>CONCLUSIONS: We did not find overall statistical differences between groups depending on in situ associated component. But when we analyzed in situ subgroups, we found differences with higher positive lymph node rate in high grade carcinomas and extensive in situ carcinomas subgroups, while lower affectation rates were observed in low grade carcinomas (without cellular necrosis), compared to the group of breast cancers without in situ component associated.}, }
@article {pmid21943448, year = {2011}, author = {Critchley, AC and Harvey, J and Carr, M and Iwuchukwu, O}, title = {Synchronous gastric and colonic metastases of invasive lobular breast carcinoma: case report and review of the literature.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {93}, number = {5}, pages = {e49-50}, pmid = {21943448}, issn = {1478-7083}, mesh = {*Breast Neoplasms ; Carcinoma, Lobular/*secondary ; Colonic Neoplasms/*secondary ; Female ; Humans ; Middle Aged ; Stomach Neoplasms/*secondary ; }, abstract = {Breast cancer is the most common malignancy in women and the main cause of cancer death in the UK. Gastrointestinal (GI) tract metastasis and carcinomatosis from primary breast cancer are rare but breast cancer is the second most common primary malignancy to metastasise to the GI tract after malignant melanoma. The metastatic patterns of invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) have been shown to differ considerably. Liver, lung and brain metastases are more common in IDC. Most series report a greater prediliction for lobular carcinoma to metastasise to the GI tract, gynaecological organs or peritoneum. The presentation of GI metastasis due to breast cancer is typically vague and the clinical, radiological, endoscopic and histopathologic findings are often difficult to distinguish from primary gastric carcinoma. Such a patient is more likely to present to a luminal surgeon or gastroenterologist than a breast surgeon. Therefore a high index of clinical suspicion with early endoscopy in those with non-specific symptoms and a past history of breast cancer, particularly ILC, are recommended. It is imperative to differentiate between metastatic breast cancer and primary gastric carcinoma as treatment strategies differ hugely. Therefore, correlation of endoscopic biopsy histology with the primary breast cancer histology is essential. Treatment modalities are limited to appropriate systemic therapy, which may have a palliative effect in up to 50%. Surgical intervention is nearly always limited to palliative bypass only. Prognosis is consistent with the median survival of all women with metastatic disease secondary to breast cancer.}, }
@article {pmid21935605, year = {2011}, author = {Akbulut, S and Sogutcu, N and Yagmur, Y}, title = {Coexistence of breast cancer and tuberculosis in axillary lymph nodes: a case report and literature review.}, journal = {Breast cancer research and treatment}, volume = {130}, number = {3}, pages = {1037-1042}, doi = {10.1007/s10549-011-1634-8}, pmid = {21935605}, issn = {1573-7217}, mesh = {Aged ; Axilla ; Carcinoma, Ductal, Breast/*complications/*pathology ; Female ; Granuloma/pathology ; Humans ; Lymph Nodes/*pathology ; Tuberculosis, Lymph Node/*complications/*pathology ; }, abstract = {Coexistence of breast cancer and tuberculosis (TB) of the breast and/or axillary lymph nodes is uncommon. In this article, we present a case of tuberculous axillary lymphadenitis existing simultaneously with invasive ductal carcinoma of the left breast. We also conducted an extensive literature review of English language studies published on the coexistence of breast cancer and TB of the breast and/or axillary lymph nodes from 1899 to 2011 using the PubMed and Google Scholar databases. Twenty-nine cases of coexisting breast cancer and TB of the breast and/or axillary lymph nodes have been published to date, including a 74-year-old female diagnosed with left breast cancer and TB of the axillary lymph nodes. A tumor in the right breast was detected in 14 patients and in the left breast in 12 patients between the ages of 28 and 81 years, but no data were available regarding the side on which the tumor occurred in three patients. Eighteen patients underwent a modified radical mastectomy, five patients underwent a radical mastectomy, two a lumpectomy and an axillary lymph node dissection (ANLD), two a quadrantectomy (Q) and an ALND, and two an applied excision. TB was detected at the axilla in all 21 patients in patients with no TB of the breast, and TB was also detected in the axilla in five of eight patients with breast TB. Both a tumor and TB lymphadenitis were detected following an axillary dissection in 14 patients, and both cancer metastasis and TB lymphadenitis were detected at the same lymph nodes in six of these patients. The simultaneous occurrence of these two major illnesses in the breast and/or axillary lymph nodes can produce many problems with respect to diagnosis and treatment. Accurate diagnoses are necessary for down-staging carcinoma of the breast and for identifying curable disease.}, }
@article {pmid21934215, year = {2011}, author = {Murthy, SS and Sandhya, DG and Ahmed, F and Goud, KI and Dayal, M and Suseela, K and Rajappa, SJ}, title = {Assessment of HER2/Neu status by fluorescence in situ hybridization in immunohistochemistry-equivocal cases of invasive ductal carcinoma and aberrant signal patterns: a study at a tertiary cancer center.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {54}, number = {3}, pages = {532-538}, doi = {10.4103/0377-4929.85087}, pmid = {21934215}, issn = {0974-5130}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal/*diagnosis/pathology ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence/*methods ; India ; Mastectomy ; Microscopy ; Middle Aged ; Pathology, Molecular/*methods ; Receptor, ErbB-2/*genetics ; }, abstract = {INTRODUCTION: HER-2/neu status determines the eligibility for targeted therapy with trastuzumab in breast carcinoma. Evaluation for HER-2/neu protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in situ hybridization (FISH) has become the gold standard.<br><br>AIMS: Since data on HER-2/neu assessment by IHC and FISH and studies regarding concordance between the results of the two techniques are limited, especially from India, we sought to study HER-2 gene amplification status by FISH in equivocal (2+) cases by IHC and also study aberrant signal patterns.<br><br>SETTINGS AND DESIGN: Mastectomies and breast core biopsies, equivocal for HER-2/neu protein expression, were analyzed for HER-2 amplification by FISH.<br><br>MATERIALS AND METHODS: IHC (DAKO) and FISH (PathVysion dual-probe system) tests were performed on 68 of 112 (after exclusion) 10% neutral buffered formalin (NBF)-fixed paraffin-embedded tissues and evaluated according to American Society of Clinical Oncology ASCO guidelines.<br><br>STATISTICAL ANALYSIS USED: Chi-square (&#x3c7;2) test and the two-tailed P value were applied using Graphpad Quickcels software, version 2006.<br><br>RESULTS: It was found that 73.5% of the IHC 2+ patients were negative for HER-2/neu amplification, 25% were positive (ratios ranging from 2.3 to 5.6) and 1 patient was equivocal (2.2). Retesting FISH HER-2 equivocal case on another tumor block by IHC demonstrated HER-2 overexpression of protein 3+, thus resolving the equivocal status. Polysomy and HER-2 genetic heterogeneity were seen frequently.<br><br>CONCLUSIONS: The findings reiterate that IHC HER-2 equivocal cases are a heterogeneous group and need FISH for further categorization. Low concurrence (25%) rate between both IHC and FISH results in the equivocal scenario can be attributed to tumors with polysomy 17 and HER-2/neu genetic heterogeneity.}, }
@article {pmid21933790, year = {2011}, author = {Xia, Y and Jiang, S and Weng, S and Lv, X and Cheng, H and Fang, C}, title = {Antigen-specific immature dendritic cell vaccine ameliorates anti-dsDNA antibody-induced renal damage in a mouse model.}, journal = {Rheumatology (Oxford, England)}, volume = {50}, number = {12}, pages = {2187-2196}, doi = {10.1093/rheumatology/ker231}, pmid = {21933790}, issn = {1462-0332}, mesh = {Analysis of Variance ; Animals ; Antibodies, Antinuclear/*immunology ; Cytokines/biosynthesis ; DNA, Protozoan/*administration &amp; dosage/immunology ; Dendritic Cells/*immunology ; Female ; Immunophenotyping ; Kidney Diseases/immunology/pathology/*prevention &amp; control ; Lupus Erythematosus, Systemic/immunology/pathology/*prevention &amp; control ; Mice ; Mice, Inbred BALB C ; Proteinuria/etiology ; Rats ; Rats, Wistar ; T-Lymphocytes/metabolism ; Trypanosoma/immunology ; Vaccines, DNA/*administration &amp; dosage ; }, abstract = {OBJECTIVES: Dendritic cells (DCs) can inhibit immune response by clonal anergy when immature. Recent studies have shown that immature DCs (iDCs) may serve as a live cell vaccine after specific antigen pulse based on its potential of blocking antibody production. In this study, we aimed to investigate the effects of nuclear antigen-pulsed iDCs in the treatment of lupus-like renal damages induced by anti-dsDNA antibodies.<br><br>METHODS: iDCs were generated from haemopoietic stem cells in bone marrow and then pulsed in vitro with nuclear antigen. The iDC vaccine and corresponding controls were injected into mice with lupus-like renal damages. The evaluation of disease was monitored by biochemical parameters and histological scores. Anti-dsDNA antibody isotypes and T-lymphocyte-produced cytokines were analysed for elucidating therapeutic mechanisms. RESULTS; The mice treated with antigen-pulsed iDCs had a sustained remission of renal damage compared with those injected with non-pulsed iDCs or other controls, including decreased anti-dsDNA antibody level, less proteinuria, lower blood urea nitrogen and serum creatinine values, and improved histological evaluation. Analysis on isotypes of anti-dsDNA antibody showed that iDC vaccine preferentially inhibited the production of IgG3, IgG2b and IgG2a. Furthermore, administration of antigen-treated iDCs to mice resulted in significantly reduced IL-2, IL-4 and IL-12 and IFN-&#x3b3; produced by T-memory cells. Conversely, the vaccination of antigen-pulsed mature DCs led to increased anti-dsDNA antibody production and an aggravation of lupus-like disease in the model. CONCLUSIONS; These results suggested the high potency of iDC vaccine in preventing lupus-like renal injuries induced by pathogenic autoantibodies.}, }
@article {pmid21925246, year = {2011}, author = {Gabrovska, PN and Smith, RA and Tiang, T and Weinstein, SR and Haupt, LM and Griffiths, LR}, title = {Semaphorin-plexin signalling genes associated with human breast tumourigenesis.}, journal = {Gene}, volume = {489}, number = {2}, pages = {63-69}, doi = {10.1016/j.gene.2011.08.024}, pmid = {21925246}, issn = {1879-0038}, mesh = {Antigens, CD/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Adhesion Molecules/genetics/metabolism ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Membrane Proteins/*genetics/metabolism ; Neovascularization, Pathologic/genetics/metabolism ; Nerve Tissue Proteins/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Real-Time Polymerase Chain Reaction ; Receptors, Cell Surface/*genetics/metabolism ; Semaphorins/*genetics/metabolism ; Signal Transduction ; }, abstract = {INTRODUCTION: Gene expression profiling has enabled us to demonstrate the heterogeneity of breast cancers. The potential of a tumour to grow and metastasise is partly dependant on its ability to initiate angiogenesis or growth and remodelling of new blood vessels, usually from a pre-existing vascular network, to ensure delivery of oxygen, nutrients, and growth factors to rapidly dividing transformed cells along with access to the systemic circulation. Cell-cell signalling of semaphorin ligands through interaction with their plexin receptors is important for the homeostasis and morphogenesis of many tissues and has been widely studied for a role in neural connectivity, cancer, cell migration and immune responses. This study investigated the role of four semaphorin/plexin signalling genes in human breast cancers in vivo and in vitro.<br><br>MATERIALS AND METHODS: mRNA was extracted from formalin fixed paraffin embedded archival breast invasive ductal carcinoma tissue samples of progressive grades (grades I-III) and compared to tissue from benign tumours. Gene expression profiles were determined by microarray using the Affymetrix GeneChip&#xae; Human Genome U133 Plus 2.0 Arrays and validated by Q-PCR using a Corbett RotorGene 6000. Following validation, the gene expression profile of the identified targets was correlated with those of the human breast cancer cell lines MCF-7 and MDA-MD-231.<br><br>RESULTS: The array data revealed that 888 genes were found to be significantly (p&#x2264;0.05) differentially expressed between grades I and II tumours and 563 genes between grade III and benign tumours. From these genes, we identified four genes involved in semaphorin-plexin signalling including SEMA4D which has previously been identified as being involved in increased angiogenesis in breast cancers, and three other genes, SEMA4F, PLXNA2 and PLXNA3, which in the literature were associated with tumourigenesis, but not directly in breast tumourigenesis. The microarray analysis revealed that SEMA4D was significantly (P=0.0347) down-regulated in the grade III tumours compared to benign tumours; SEMA4F, was significantly (P=0.0159) down-regulated between grades I and II tumours; PLXNA2 was significantly (P=0.036) down-regulated between grade III and benign tumours and PLXNA3 significantly (P=0.042) up-regulated between grades I and II tumours. Gene expression of SEMA4D was validated using Q-PCR, demonstrating the same expression profile in both data sets. When the sample set was increased to incorporate more cases, SEMA4D continued to follow the same expression profile, including statistical significance for the differences observed and small standard deviations. In vitro the same pattern was present where expression for SEMA4D was significantly higher in MDA-MB-231 cells when compared to MCF-7 cells. The expression of SEMA4F, PLXNA2 and PLXNA3 could not be validated using Q-PCR, however in vitro analysis of these three genes revealed that both SEMA4F and PLXNA3 followed the microarray trend in expression, although they did not reach significance. In contrast, PLXNA2 demonstrated statistical significance and was in concordance with the literature.<br><br>DISCUSSION: We, and others, have proposed SEMA4D to be a gene with a potentially protective effect in benign tumours that contributes to tumour growth and metastatic suppression. Previous data supports a role for SEMA4F as a tumour suppressor in the peripheral nervous system but our data seems to indicate that the gene is involved in tumour progression in breast cancer. Our in vitro analysis of PLXNA2 revealed that the gene has higher expression in more aggressive breast cancer cell types. Finally, our in vitro analysis on PLXNA3 also suggest that this gene may have some form of growth suppressive role in breast cancer, in addition to a similar role for the gene previously reported in ovarian cancer. From the data obtained in this study, SEMA4D may have a role in more aggressive and potentially metastatic breast tumours.<br><br>CONCLUSIONS: Semaphorins and their receptors, the plexins, have been implicated in numerous aspects of neural development, however their expression in many other epithelial tissues suggests that the semaphorin-plexin signalling system also contributes to blood vessel growth and development. These findings warrant further investigation of the role of semaphorins and plexins and their role in normal and tumour-induced angiogenesis in vivo and in vitro. This may represent a new front of attack in anti-angiogenic therapies of breast and other cancers.}, }
@article {pmid21922383, year = {2011}, author = {Yuri, T and Lai, YC and Kanematsu, S and Kuwata, M and Yoshizawa, K and Tsubura, A}, title = {Effects of short-term estrogen treatment on the progression of N-methyl-N-nitrosourea-induced premalignant mammary lesions in female Lewis rats.}, journal = {Medical molecular morphology}, volume = {44}, number = {3}, pages = {125-130}, pmid = {21922383}, issn = {1860-1499}, mesh = {Animals ; Antineoplastic Agents/pharmacology/*therapeutic use ; Cell Transformation, Neoplastic/*drug effects ; Cyclin D1/metabolism ; Estrogens/pharmacology/*therapeutic use ; Female ; Mammary Glands, Animal/drug effects/metabolism/pathology ; Mammary Neoplasms, Experimental/*chemically induced/*drug therapy/pathology ; Methylnitrosourea ; Precancerous Conditions/*chemically induced/*drug therapy/pathology ; Proliferating Cell Nuclear Antigen/metabolism ; Rats ; Rats, Inbred Lew ; }, abstract = {We studied the effects of short-term estrogen treatment (STET) on the progression of mammary lesions from ductal hyperplasia (DH) through ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) in the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis model. Three-week-old female Lewis rats (n = 40) received an intraperitoneal injection of MNU (50 mg/kg). Three weeks later, a 3-week-release, 0.25-mg, 17β-estradiol pellet was subcutaneously implanted for 2 weeks in 20 rats (STET); the remaining 20 rats did not receive the estradiol pellets (age-matched control). All rats were killed at 12 weeks of age, and their abdominal-inguinal mammary glands were histologically examined. The incidence and multiplicity of DHs were similar between groups (STET, 90% and 3.9 ± 0.6 vs. age-matched controls, 80% and 3.0 ± 0.5). However, DCIS and IDC did not develop in STET rats, whereas DCIS (25% and 1.4 ± 0.2) and IDC (35% and 1.4 ± 0.3) developed in the age-matched controls. Immunoscores of estrogen and progesterone receptors and positive rate of proliferative cell nuclear antigen (PCNA) in DH were similar in both groups, while the positive rate of cyclin D1 was significantly reduced in the STET group (P < 0.05). Thus, STET blocked the progression from DH to DCIS in MNU-induced mammary carcinogenesis, and decreased expression of cyclin D1 may play an important role in the blockade of cell transition from DH to DCIS.}, }
@article {pmid21921327, year = {2011}, author = {Faghani, M and Ghasemi, FM and Nikhbakht, M and Salehi, M}, title = {TP53 PIN3 polymorphism associated with breast cancer risk in Iranian women.}, journal = {Indian journal of cancer}, volume = {48}, number = {3}, pages = {298-302}, doi = {10.4103/0019-509X.84925}, pmid = {21921327}, issn = {1998-4774}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal/epidemiology/*genetics ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Association Studies ; Genotype ; Humans ; Introns/genetics ; Iran ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Segmental Duplications, Genomic/genetics ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {BACKGROUND: Breast cancer is one of the most common cancers in Iranian women. The p53 gene plays a principal role in genomic stability, and its function varies according to polymorphisms. The aim of our study was to determine the relationship between the intron3 16bp duplication polymorphism of the p53 gene and breast cancer in Iranian women.<br><br>MATERIALS AND METHODS: We performed a case-control study among 145 patients with invasive ductal carcinoma of the breast and 145 controls in Isfahan, Iran. The distribution of the intron3 16bp duplication polymorphism was determined by polymerase chain reaction (PCR). The relationship between clinicopathological data and the PIN3 polymorphism was examined using chi-squared analysis.<br><br>RESULTS: A significant difference was observed in the polymorphism variants in breast cancer specimens compared with controls (P < .001). Among the cancer patients, 59.9% were below the age of 50 years; and 67.5% of the patients in this group had the intron3 16bp duplication polymorphism.<br><br>CONCLUSIONS: PIN3 Ins 16bp duplication polymorphism is a genetically predisposing factor for breast cancer development in Iranian women and may be causal in patients under the age of 50 years.}, }
@article {pmid21914346, year = {2011}, author = {Hao, JY and Yang, YL and Li, S and Qian, XL and Liu, FF and Fu, L}, title = {[PSCA expression in invasive micropapillary carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {40}, number = {6}, pages = {382-386}, pmid = {21914346}, issn = {0529-5807}, mesh = {Antigens, Neoplasm/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Papillary/genetics/*metabolism/pathology ; Female ; GPI-Linked Proteins/genetics/metabolism ; Humans ; *Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins/genetics/*metabolism ; Neoplasm Staging ; RNA, Messenger/metabolism ; }, abstract = {OBJECTIVE: To study the expression of prostate stem cell antigen (PSCA) at protein and mRNA levels in invasive micropapillary carcinoma of the breast (IMPC) and to analyze the relationship between PSCA expression and clinicopathologic features.<br><br>METHODS: The expression of PSCA protein was analyzed by immunohistochemistry (LSAB) in 66 cases of IMPC and 67 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The association between PSCA expression and clinicopathologic features was also analyzed in IMPC. Furthermore, RT-PCR was used to detect PSCA mRNA in 10 cases of primary IMPC and 10 cases of primary IDC-NOS with paired normal breast tissues, each from the same subject.<br><br>RESULTS: Immunohistochemical analysis revealed the overexpression of PSCA in 47 of 66 (71.2%) cases of IMPC and 35 of 67 (52.2%) IDC-NOS. Statistical analysis showed a significant difference of PSCA expression between IMPC and IDC-NOS (P = 0.024). In IMPC, the expression of PSCA was correlated with lymph nodes metastasis (P = 0.039). RT-PCR showed the mRNA level of PSCA was significantly higher in primary IMPC and IDC-NOS tissue than that in paired normal breast tissue (7/10 and 5/10, respectively), and it was also significantly higher in primary IMPC tissue than that in IDC-NOS tissue.<br><br>CONCLUSION: PSCA might play an important role in lymph node metastasis in IMPC.}, }
@article {pmid21913743, year = {2011}, author = {Dong, SW and Wang, L and Sui, J and Deng, XY and Chen, XD and Zhang, ZW and Liu, X and Liu, ZM and Zhang, JH and Yang, QS and Jia, YF and Song, X}, title = {Expression patterns of ER, HER2, and NM23-H1 in breast cancer patients with different menopausal status: correlations with metastasis.}, journal = {Molecular diagnosis &amp; therapy}, volume = {15}, number = {4}, pages = {211-219}, pmid = {21913743}, issn = {1179-2000}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/secondary ; Female ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; *Menopause ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases/*metabolism ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/genetics/*metabolism ; }, abstract = {OBJECTIVE: This study was designed to analyze expression patterns of estrogen receptor (ER), human epidermal growth factor receptor-2 (HER2/ERBB2), and nonmetastatic protein 23 (NM23-H1/NME1) proteins in patients with invasive ductal carcinoma and different menopausal status to identify their relationships with axillary lymph node metastasis.<br><br>MATERIALS AND METHODS: 213 pre-menopausal and 177 post-menopausal women diagnosed with invasive ductal carcinoma were evaluated for ER, HER2, and NM23-H1 protein expression by immunohistochemistry. When HER2 immunoreactivity was equivocal (category 2+), specimens were confirmed by fluorescence in situ hybridization.<br><br>RESULTS: ER expression showed no correlation with menopausal status or lymph node metastasis (each p&#x2009;>&#x2009;0.05). However, expression of ER was associated with negative expression of HER2 (r&#x2009;=&#x2009;-0.214, p&#x2009;<&#x2009;0.05) and positive expression of NM23-H1 (r&#x2009;=&#x2009;0.137, p&#x2009;<&#x2009;0.05) in the pre-menopausal group. Over-expression of HER2 was correlated with menopausal status (r&#x2009;=&#x2009;-0.107, p&#x2009;<&#x2009;0.05) and lymph node metastasis in the ER-negative post-menopausal group (r&#x2009;=&#x2009;0.222, p&#x2009;<&#x2009;0.05). NM23-H1 was associated with less lymph node metastasis in the ER-positive pre-menopausal group (r&#x2009;=&#x2009;-0.237, p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: Our results indicated that expression patterns of ER, NM23-H1, and HER2 in primary breast cancer lesions warn that cells might have metastatic potential, which could assist clinicians to provide a more accurate prognosis and tailor therapeutic management for individual patients.}, }
@article {pmid21881484, year = {2011}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Kinoshita, T and Tsuda, H}, title = {Important histologic outcome predictors for patients with invasive ductal carcinoma of the breast.}, journal = {The American journal of surgical pathology}, volume = {35}, number = {10}, pages = {1484-1497}, doi = {10.1097/PAS.0b013e318224ca28}, pmid = {21881484}, issn = {1532-0979}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/mortality/therapy ; Carcinoma, Ductal, Breast/*diagnosis/mortality/secondary/therapy ; Combined Modality Therapy ; Female ; Fibrosis/pathology ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating ; Predictive Value of Tests ; Survival Rate ; Young Adult ; }, abstract = {The pathologic diagnosis is regarded as the final diagnosis of a disease, and pathologic examination based on tumor histology is very important for the accurate assessment of the biological characteristics of tumors. The purpose of this study was to investigate the histologic factors that accurately predict patient outcome among 1042 patients with invasive ductal carcinoma of the breast. Both well-known histologic factors and our proposed histologic factors were examined according to several tumor statuses using multivariate analysis. This study clearly demonstrated that type 4 invasive ductal carcinomas having fibrotic foci and atypical tumor-stromal fibroblasts within the fibrotic foci are significant outcome predictors for lymph node-negative and lymph node-positive, the pathologic UICC-TNM stage II and III, luminal A-subtype, luminal B-subtype, and equivocal HER2 subtype invasive ductal carcinoma patients. Lymph vessel tumor embolus grades 2 and 3 were significant outcome predictors for lymph node-positive, UICC pTNM stages II and III, luminal A-subtype, and triple-negative invasive ductal carcinoma patients (except lymph vessel tumor embolus grade 2 in luminal A-subtype patients). More than 5 mitotic figures in metastatic carcinoma to the lymph nodes was a significant outcome predictor for lymph node-positive, UICC pTNM stage II, and luminal A-subtype invasive ductal carcinoma patients. A fibrotic focus diameter >8 mm was a significant outcome predictor for UICC pTNM stages I and III invasive ductal carcinoma patients. These findings strongly suggest that these histologic factors are very useful for accurately predicting the outcomes of patients with invasive ductal carcinoma of the breast.}, }
@article {pmid21875486, year = {2011}, author = {Wang, J and Wang, L and Liu, FF and Ma, YJ and Fu, L and Li, WL and Gu, F}, title = {[Robo1 expression in breast cancer and its relationship to brain metastasis].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {33}, number = {6}, pages = {447-451}, pmid = {21875486}, issn = {0253-3766}, mesh = {Adult ; Age Factors ; Aged ; Brain Neoplasms/*secondary ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/metabolism/secondary/surgery ; Female ; Fibroadenoma/metabolism ; Follow-Up Studies ; Humans ; Middle Aged ; Nerve Tissue Proteins/*metabolism ; Receptors, Immunologic/*metabolism ; Survival Rate ; }, abstract = {OBJECTIVE: To detect the expression of Robo1 in different breast tumors and its association with the breast cancer brain metastasis.<br><br>METHODS: Labelled streptavidin-biotin (LSAB) staining was used to examine the Robo1 expression in specimens from 24 cases of invasive ductal carcinoma (IDC) with brain metastasis, 71 cases of IDC without brain metastasis, 22 cases of ductal carcinoma in situ (DCIS) and 23 cases of fibroadenoma.<br><br>RESULTS: The expression pattern of Robo1 in DCIS (59.1%) and IDC (45.3%) was significantly lower than that in adenofibroma (87.0%, P < 0.05). The expression of Robo1 in IDC with brain metastasis (12.5%) was significantly lower than that in IDC without brain metastasis (56.3%, P < 0.05). The expression of Robo1 was much higher in more than 50 year-old-group (57.8%) than that in less than 50 year-old-group (34.0%) of IDC patients. The overall survival time in patients with the Robo1 negative expression was significantly shorter than those with positive expression (P < 0.05). No correlation was found between the Robo1 expression and the tumor size, lymph node metastasis, pathologic stage, histological grade and clinical stage (P > 0.05).<br><br>CONCLUSIONS: The Robo1 expression correlates negatively with IDC brain metastasis, and correlates positively with the age and prognosis of IDC patients. Robo1 may be applied as a marker in evaluation of the IDC prognosis and brain metastasis.}, }
@article {pmid21874750, year = {2011}, author = {Teoh, KH and Looi, LM and Sabaratnam, S and Cheah, PL and Nazarina, AR and Mun, KS}, title = {An analysis of predictive biomarkers in routine histopathological reporting of infiltrating ductal breast carcinoma in a tertiary hospital in Malaysia with a focus on limitations and directions for future development.}, journal = {The Malaysian journal of pathology}, volume = {33}, number = {1}, pages = {35-42}, pmid = {21874750}, issn = {0126-8635}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Female ; Histology/standards ; Hospitals ; Humans ; Malaysia ; Medical Oncology/standards ; Middle Aged ; Receptor, ErbB-2/biosynthesis/genetics ; Receptors, Estrogen/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; Research Design ; Retrospective Studies ; }, abstract = {Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.}, }
@article {pmid21867691, year = {2011}, author = {Suhane, S and Berel, D and Ramanujan, VK}, title = {Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.}, journal = {Biochemical and biophysical research communications}, volume = {412}, number = {4}, pages = {590-595}, pmid = {21867691}, issn = {1090-2104}, support = {R21 CA124843/CA/NCI NIH HHS/United States ; R21 CA124843-01A2/CA/NCI NIH HHS/United States ; R21-CA124843/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/enzymology/mortality/*pathology ; Carcinoma/enzymology/*pathology ; Female ; Humans ; Mitochondria/*enzymology ; NADH Dehydrogenase/genetics/*metabolism ; Neoplasm Invasiveness ; RNA, Small Interfering/genetics ; }, abstract = {We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma.}, }
@article {pmid21862942, year = {2011}, author = {Usmani, S and Khan, HA and Al Saleh, N and abu Huda, F and Marafi, F and Amanguno, HG and Al Nafisi, N and Al Kandari, F}, title = {Selective approach to radionuclide-guided sentinel lymph node biopsy in high-risk ductal carcinoma in situ of the breast.}, journal = {Nuclear medicine communications}, volume = {32}, number = {11}, pages = {1084-1087}, doi = {10.1097/MNM.0b013e328349eafc}, pmid = {21862942}, issn = {1473-5628}, mesh = {Adult ; Aged ; Axilla/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/*secondary/surgery ; Female ; Humans ; Lymph Nodes/diagnostic imaging ; Lymphatic Metastasis ; Lymphoscintigraphy/*methods ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging ; Radiopharmaceuticals ; Sentinel Lymph Node Biopsy/*methods ; Technetium Tc 99m Aggregated Albumin ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) currently represents approximately 15-25% of all breast cancers detected. Although inherently a noninvasive disease, occult invasive disease can be found at definitive histology. The role of sentinel lymph node (SLN) biopsy in DCIS is still unclear. The aim of this study was to evaluate the clinical usefulness of SLN biopsy and the incidence of SLN metastases in selected patients with high-risk DCIS, who are at highest risk for being upstaged to invasive carcinoma.<br><br>MATERIALS AND METHODS: Twenty-three high-risk patients with DCIS proven on core biopsy (mean age, 50 years; median age, 48 years; age range, 37-78 years) were included in the study. SLN scintigraphy was performed 2-4 h before surgery by injecting Tc-99m-labeled nanocolloid intradermally in the periareolar region. The first lymph node to appear on the scan was labeled as SLN and was marked on the skin by using a &#x3b3; probe. The lymph node was explored in the axilla using a &#x3b3; probe.<br><br>RESULTS: The SLN was identified in all patients (100% success rate). Of 23 cases of DCIS on core biopsy, seven patients (30%) were shown to have invasive ductal carcinoma on final histological specimen. Among these seven patients, three had minimal invasive carcinoma (<1 cm) and none of these patients had positive SLN for metastases. Among 23 cases, only one patient with (4%) SLN was positive for metastasis despite histopathological diagnosis of pure DCIS.<br><br>CONCLUSION: Although the study population is small, our findings suggest that patients with high-risk DCIS have an increased risk of invasive disease, as approximately one-third of these patients had invasive component at the time of definitive operative procedure. Furthermore, the study also suggests that SLNB appears to be reliable in identifying axillary lymph nodes status of these patients.}, }
@article {pmid21854742, year = {2011}, author = {Mazzanti, CM and Al Hamad, M and Fanelli, G and Scatena, C and Zammarchi, F and Zavaglia, K and Lessi, F and Pistello, M and Naccarato, AG and Bevilacqua, G}, title = {A mouse mammary tumor virus env-like exogenous sequence is strictly related to progression of human sporadic breast carcinoma.}, journal = {The American journal of pathology}, volume = {179}, number = {4}, pages = {2083-2090}, pmid = {21854742}, issn = {1525-2191}, mesh = {Base Sequence ; Breast Neoplasms/*pathology/*virology ; Carcinoma, Intraductal, Noninfiltrating/pathology/virology ; *Disease Progression ; Epithelial Cells/pathology ; Female ; Genes, env/*genetics ; Humans ; In Situ Hybridization ; Lasers ; Mammary Tumor Virus, Mouse/*genetics ; Microdissection ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Viral Load ; }, abstract = {A viral etiology of human breast cancer (HBC) has been postulated for decades since the identification of mouse mammary tumor virus (MMTV). The detection of MMTV env-like exogenous sequences (MMTVels) in 30% to 40% of invasive HBCs increased attention to this hypothesis. Looking for MMTVels during cancer progression may contribute to a better understanding of their role in HBC. Herein, we analyzed HBC preinvasive lesions for the presence of MMTVels. Samples were obtained by laser microdissection of FFPE tissues: 20 usual-type ductal hyperplasias, 22 atypical ductal hyperplasias (ADHs), 49 ductal carcinomas in situ (DCISs), 20 infiltrating ductal carcinomas (IDCs), and 26 normal epithelial cells collateral to a DCIS or an IDC. Controls included reductive mammoplastic tissue, thyroid and colon carcinoma, and blood samples from healthy donors. MMTVels were detected by fluorescence-nested PCR. DNA samples from the tissues of nine patients were analyzed by real-time quantitative PCR, revealing a different viral load correlated with stage of progression. Furthermore, as never previously described, the presence of MMTVels was investigated by chromogenic in situ hybridization. MMTVels were found in 19% of normal epithelial cells collateral to a DCIS or an IDC, 27% of ADHs, 82% of DCISs, and 35% of IDCs. No MMTVels were found in the control samples. Quantitative PCR and chromogenic in situ hybridization confirmed these results. These data could contribute to our understanding of the role of MMTVels in HBC.}, }
@article {pmid21853149, year = {2011}, author = {Tjomsland, V and Ellegård, R and Che, K and Hinkula, J and Lifson, JD and Larsson, M}, title = {Complement opsonization of HIV-1 enhances the uptake by dendritic cells and involves the endocytic lectin and integrin receptor families.}, journal = {PloS one}, volume = {6}, number = {8}, pages = {e23542}, pmid = {21853149}, issn = {1932-6203}, support = {AI52731/AI/NIAID NIH HHS/United States ; R01 AI052731/AI/NIAID NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; R37 AI052731/AI/NIAID NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {CD4 Antigens/metabolism ; Cell Differentiation/immunology ; Complement System Proteins/*immunology ; Dendritic Cells/*cytology/immunology/virology ; Endocytosis/immunology ; HIV-1/*immunology ; Humans ; Integrins/*metabolism ; Kinetics ; Lectins, C-Type/*metabolism ; Opsonin Proteins/*immunology ; Receptors, Cell Surface/*metabolism ; Virion/immunology ; Virus Internalization ; }, abstract = {Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and the type of receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV) and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the internalization rate was dependent on both opsonization of the virus and DC maturation state. Increased DC uptake of C-HIV was not due to opsonization related increased binding of virus to the surface of DC but rather increased internalization of C-HIV despite utilizing a similar repertoire of receptors as F-HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and blocking these receptor families prevented HIV-1 from binding to DC at 4°C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C-HIV implicating the involvement of several integrins such as β1-integrin, CR3, LFA-1, and α4β7. Distinctive for C-HIV was usage of β1-integrin and for F-HIV, usage of β7-integrin, whereas both F-HIV and C-HIV utilized both integrin chains of CR3. We have in this study identified the receptor types used by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which may entail different intracellular processing of the virus leading to both elevated infection and altered activation of HIV specific immune responses.}, }
@article {pmid21850995, year = {2011}, author = {Sułko, J}, title = {[Intervertebral disc calcification in children].}, journal = {Chirurgia narzadow ruchu i ortopedia polska}, volume = {76}, number = {1}, pages = {31-35}, pmid = {21850995}, mesh = {Adolescent ; Anti-Inflammatory Agents, Non-Steroidal/administration &amp; dosage ; Calcinosis/complications/*diagnosis/*therapy ; Child ; Child, Preschool ; Female ; Humans ; Intervertebral Disc/*physiopathology ; Male ; Rest ; Retrospective Studies ; Spinal Diseases/complications/*diagnosis/*therapy ; Spine/*physiopathology ; Treatment Outcome ; }, abstract = {THE AIM: Evaluation of children with intervertebral disc calcification (IDC) and own experience.<br><br>MATERIALS AND METHODS: A retrospective analysis of 7 patients (2 girls and 5 boys) with detected, in the years 1990-2009, IDC. Age at the onset of symptoms (neck pain in 6 patients, torticollis in 4, hip pain in one) was on average 8.7 years (5-13 years). The diagnosis was based on review of radiographs of the spine, which revealed the presence of calcifications within the intervertebral discs in the cervical (4 patients), cervical and thoracic (2 patients) and thoracic spine (1 patient). The mean level of IDC on average was 3.3 spaces (1-6).<br><br>RESULTS: After conservative treatment, including use of nonsteroidal anti-inflammatory drugs and rest, the symptoms subsided within 1-2 weeks. 4 patients had a return of pain in the neck, in one year, but the symptoms were milder and resolved within a few days. The mean observation period was 9 years (3.5-16 years). In 4 patients, changes disappeared completely, while in the remaining three there was a very discrete calcifications. One patient, after 6 years, had a pain in the neck, and CT showed minor lytic changes on the surface of the vertebral bodies between which calcification occurred.<br><br>DISCUSSION: &#x15b; IDC is a rare disease of the spine in children, but should be taken into account in cases of vertebral pain. Usually the disease affects children before the age of 10 and locates in the cervical spine. But it can be located in every segment of the spine. Most patients have multilevel location. Acute phase of the disease requires conservative treatment. Rarely used surgical treatment should be considered only in patients with persistant neurological symptoms. The natural course of the disease is mild, and over the years calcification gradually disappear spontaneously.}, }
@article {pmid21847697, year = {2011}, author = {de Alcantara Filho, P and Capko, D and Barry, JM and Morrow, M and Pusic, A and Sacchini, VS}, title = {Nipple-sparing mastectomy for breast cancer and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience.}, journal = {Annals of surgical oncology}, volume = {18}, number = {11}, pages = {3117-3122}, doi = {10.1245/s10434-011-1974-y}, pmid = {21847697}, issn = {1534-4681}, mesh = {Adult ; Aged ; Breast Neoplasms/pathology/psychology/*surgery ; Carcinoma, Ductal, Breast/pathology/psychology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; Cohort Studies ; Female ; Humans ; *Mastectomy ; Middle Aged ; Nipples/*pathology/surgery ; Prognosis ; Prospective Studies ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Nipple-sparing mastectomy (NSM) has been gathering increased recognition as an alternative to more traditional mastectomy approaches. Initially, questions concerning its oncologic safety limited the use of NSM. Nevertheless, mounting evidence supporting the practice of NSM for both prophylactic and oncologic purposes is leading to its more widespread use and broadened indications.<br><br>METHODS: Using a prospectively maintained database, we reviewed our experience of 353 NSM procedures performed in 200 patients over the past 10 years.<br><br>RESULTS: The indications for surgery were: 196 prophylactic risk-reduction (55.5%), 74 ductal carcinoma in situ (DCIS) (20.8%), 82 invasive cancer (23.2%), and 1 phyllodes tumor (0.5%). The nipple areolar complex (NAC) was entirely preserved in 341 mastectomies (96.7%). There were 11 patients (3.1%) who were found to have cancer at the nipple margin, warranting further excision. A total of 69 breasts (19.5%) had some degree of skin desquamation or necrosis, but only 12 (3.3%) required operative debridement, of which 3 breasts (1%) necessitated removal of a breast implant. Also, 6 patients (2%) were treated for infection. Of the 196 prophylactic NSMs, 11 specimens (5.6%) were found to harbor occult cancer (8 DCIS and 3 invasive cancers). One patient who underwent NSM for invasive ductal carcinoma in 2006 developed metastatic disease to her brain. No other recurrences are attributable to the 353 NSMs.<br><br>CONCLUSIONS: The trends demonstrate the increasing acceptance of NSM as a prophylactic procedure as well as for therapeutic purposes. Although NSM is not standard, our experience supports the selective use of NSM in both prophylactic and malignant settings.}, }
@article {pmid21811891, year = {2011}, author = {Dragu, A and Hohenberger, W and Lang, W and Schmidt, J and Horch, RE}, title = {[Forequarter amputation of the right upper chest: limitations of ultra radical interdisciplinary oncological surgery].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {82}, number = {9}, pages = {834-838}, pmid = {21811891}, issn = {1433-0385}, mesh = {Amputation, Surgical/*methods ; Blood Loss, Surgical/physiopathology ; Brachial Plexus/pathology/surgery ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal/pathology/*surgery ; Chemoradiotherapy, Adjuvant ; Combined Modality Therapy ; *Cooperative Behavior ; Fatal Outcome ; Female ; Fibrosarcoma/pathology/*surgery ; Free Tissue Flaps/*blood supply ; Humans ; *Interdisciplinary Communication ; Lymphatic Metastasis/pathology ; Microsurgery/methods ; Middle Aged ; Multiple Organ Failure/etiology/therapy ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasms, Second Primary/pathology/*surgery ; *Patient Care Team ; Postoperative Complications/*etiology/therapy ; Sternum/*surgery ; Surgical Flaps ; Surgical Mesh ; Thoracic Neoplasms/pathology/*surgery ; Thoracic Wall/*surgery ; }, abstract = {Total forearm free flap procedures after forequarter amputations have been sparsely described in the literature. Using the amputated arm as a "free filet flap" remains a viable surgical option after radical forequarter amputations performed for the resection of large, invasive tumors of the shoulder or thoracic wall region. Using the forequarter specimen as a donor site seems favorable in that it eliminates the usual donor site morbidity. Nevertheless, in our patient with invasive ductal carcinoma of the breast and a fibrosarcoma suffering from severe pain and septic conditions - which failed to respond properly to conservative therapy - as well as rapidly progressive tumor ulceration despite repeated radiation therapy, we decided to attempt complete tumor removal by hemithoracectomy as a last resort. This decision was taken following multiple interdisciplinary consultations and thorough patient information. Although technically feasible with complete tumor removal and safe soft tissue free flap coverage, the postoperative course raises questions about the advisability of such ultra radical surgical procedures, as well as about the limitations of respiratory recovery after hemithoracectomy with removal of the sternum. Hence, based on our experience with such radical tumor surgery, we discuss the issues of diminished postoperative pulmonary function, intensive care possibilities and ethical issues. The English full-text version of this article is available at SpringerLink (under "Supplemental").}, }
@article {pmid21811256, year = {2011}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Sasajima, Y and Kinoshita, T and Tsuda, H}, title = {Modified primary tumour/vessel tumour/nodal tumour classification for patients with invasive ductal carcinoma of the breast.}, journal = {British journal of cancer}, volume = {105}, number = {5}, pages = {698-708}, pmid = {21811256}, issn = {1532-1827}, mesh = {Adult ; Aged ; Breast Neoplasms/*classification/diagnosis/mortality/pathology ; Carcinoma, Ductal, Breast/*classification/diagnosis/mortality/pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging/*methods ; Neoplasms, Vascular Tissue/*classification/diagnosis/mortality/secondary ; Prognosis ; Recurrence ; Survival Analysis ; Young Adult ; }, abstract = {BACKGROUND: We previously reported that the primary tumour/vessel tumour/nodal tumour (PVN) classification is significantly superior to the UICC pTNM classification and the Nottingham Prognostic Index for accurately predicting the outcome of patients with invasive ductal carcinoma of the breast in a manner that is independent of the nodal status and the hormone receptor status.<br><br>METHODS: The purpose of the present study was to compare the outcome predictive power of a modified PVN classification to that of the newly devised pathological UICC pTNM classification and the reclassified Nottingham Prognostic Index in a different group of patients with invasive ductal carcinoma (n=1042) using multivariate analyses by the Cox proportional hazard regression model.<br><br>RESULTS: The modified PVN classification clearly exhibited a superior significant power, compared with the other classifications, for the accurate prediction of tumour recurrence and tumour-related death among patients with invasive ductal carcinoma in a manner that was independent of the nodal status, the hormone receptor status, and adjuvant therapy status.<br><br>CONCLUSION: The modified PVN classification is a useful classification system for predicting the outcome of invasive ductal carcinoma of the breast.}, }
@article {pmid21810278, year = {2011}, author = {Mok, S and Imwong, M and Mackinnon, MJ and Sim, J and Ramadoss, R and Yi, P and Mayxay, M and Chotivanich, K and Liong, KY and Russell, B and Socheat, D and Newton, PN and Day, NP and White, NJ and Preiser, PR and Nosten, F and Dondorp, AM and Bozdech, Z}, title = {Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription.}, journal = {BMC genomics}, volume = {12}, number = {}, pages = {391}, pmid = {21810278}, issn = {1471-2164}, support = {093956//Wellcome Trust/United Kingdom ; }, mesh = {Antimalarials/*pharmacology ; Artemisinins/*pharmacology ; DNA Copy Number Variations/drug effects/genetics ; Drug Resistance/*genetics ; *Gene Expression Profiling ; Genomics ; Genotype ; Humans ; Plasmodium falciparum/cytology/*drug effects/*genetics/metabolism ; Protozoan Proteins/biosynthesis/genetics/metabolism ; Time Factors ; Transcription, Genetic/*drug effects ; Trophozoites/cytology/drug effects/metabolism ; }, abstract = {BACKGROUND: Artemisinin resistance in Plasmodium falciparum malaria has emerged in Western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. To identify key features associated with the delayed parasite clearance phenotype, we employed DNA microarrays to profile the physiological gene expression pattern of the resistant isolates.<br><br>RESULTS: In the ring and trophozoite stages, we observed reduced expression of many basic metabolic and cellular pathways which suggests a slower growth and maturation of these parasites during the first half of the asexual intraerythrocytic developmental cycle (IDC). In the schizont stage, there is an increased expression of essentially all functionalities associated with protein metabolism which indicates the prolonged and thus increased capacity of protein synthesis during the second half of the resistant parasite IDC. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of regulatory proteins such as transcription factors or chromatin remodeling associated proteins. In addition, there is a unique and uniform copy number variation pattern in the Cambodian parasites which may represent an underlying genetic background that contributes to the resistance phenotype.<br><br>CONCLUSIONS: The decreased metabolic activities in the ring stages are consistent with previous suggestions of higher resilience of the early developmental stages to artemisinin. Moreover, the increased capacity of protein synthesis and protein turnover in the schizont stage may contribute to artemisinin resistance by counteracting the protein damage caused by the oxidative stress and/or protein alkylation effect of this drug. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides insight to the complexities of the molecular basis of pathogens with drug resistance phenotypes in vivo.}, }
@article {pmid21793875, year = {2011}, author = {Klomek, AB and Kleinman, M and Altschuler, E and Marrocco, F and Amakawa, L and Gould, MS}, title = {High school bullying as a risk for later depression and suicidality.}, journal = {Suicide &amp; life-threatening behavior}, volume = {41}, number = {5}, pages = {501-516}, pmid = {21793875}, issn = {1943-278X}, support = {R01 MH064632/MH/NIMH NIH HHS/United States ; R01 MH064632-01/MH/NIMH NIH HHS/United States ; R49 CE000258/CE/NCIPC CDC HHS/United States ; R01-MH64632/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Bullying/*psychology ; Cross-Sectional Studies ; Depression/diagnosis/*psychology ; Depressive Disorder/diagnosis/*psychology ; Female ; Humans ; Longitudinal Studies ; Male ; Risk Factors ; Schools ; Students/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; Surveys and Questionnaires ; }, abstract = {This is the first study to examine whether high school students experiencing frequent bullying behaviors are at risk for later depression and suicidality. A total of 236 students who reported frequent bullying behavior without depression or suicidality during a suicide screening were interviewed 4 years later to reassess depression, suicidal ideation, attempts, substance problems, and functional impairment and were compared to at-risk youth identified during the screen, including 96 youth who also experienced bullying behavior. Youth who only reported frequent bullying behaviors (as bullies, victims, or both) did not develop later depression or suicidality and continued to have fewer psychiatric problems than students identified as at-risk for suicide. Students who experienced bullying behaviors and depression or suicidality were more impaired 4 years later than those who had only reported depression or suicidality. Thus, assessment of bullying behaviors in screening protocols is recommended.}, }
@article {pmid21790824, year = {2011}, author = {van Balkom, ID and Shaw, A and Vuijk, PJ and Franssens, M and Hoek, HW and Hennekam, RC}, title = {Development and behaviour in Marshall-Smith syndrome: an exploratory study of cognition, phenotype and autism.}, journal = {Journal of intellectual disability research : JIDR}, volume = {55}, number = {10}, pages = {973-987}, doi = {10.1111/j.1365-2788.2011.01451.x}, pmid = {21790824}, issn = {1365-2788}, mesh = {Abnormalities, Multiple/*diagnosis/*genetics/psychology ; Adaptation, Psychological ; Adolescent ; Autistic Disorder/*diagnosis/*genetics/psychology ; Bone Diseases, Developmental/*diagnosis/*genetics/psychology ; Child ; Child Behavior Disorders/*diagnosis/*genetics/psychology ; Child, Preschool ; Communication ; Craniofacial Abnormalities/*diagnosis/*genetics/psychology ; DNA Mutational Analysis ; Developmental Disabilities/diagnosis/genetics/psychology ; Female ; Humans ; Intellectual Disability/*diagnosis/*genetics/psychology ; Male ; NFI Transcription Factors/genetics ; Neurologic Examination ; Neuropsychological Tests ; Personality Assessment ; *Phenotype ; Prognosis ; Septo-Optic Dysplasia/*diagnosis/*genetics/psychology ; }, abstract = {BACKGROUND: Marshall-Smith syndrome (MSS) is an infrequently described entity characterised by failure to thrive, developmental delay, abnormal bone maturation and a characteristic face. In studying the physical features of a group of patients, we noticed unusual behavioural traits. This urged us to study cognition, behavioural phenotype and autism in six patients.<br><br>METHODS: Information on development, behavioural characteristics, autism symptoms, and adaptive and psychological functioning of six MSS children was collected through in-person examinations, questionnaires, semi-structured interviews of parents and neuropsychological assessments.<br><br>RESULTS: Participants showed moderate to severe delays in mental age, motor development and adaptive functioning, with several similarities in communication, social interactions and behaviour. There was severe delay of speech and motor milestones, a friendly or happy demeanour and enjoyment of social interactions with familiar others. They exhibited minimal maladaptive behaviours. Deficits in communication and social interactions, lack of reciprocal social communication skills, limited imaginary play and the occurrence of stereotyped, repetitive behaviours were noted during assessments.<br><br>CONCLUSIONS: Systematic collection of developmental and behavioural data in very rare entities such as MSS allows recognition of specific patterns in these qualities. Clinical recognition of physical,developmental and behavioural features is important not only for diagnosis, prognosis and counselling of families, but also increases our understanding of the biological basis of the human physical and behavioural phenotype.}, }
@article {pmid21785902, year = {2012}, author = {Kandemir, NO and Barut, F and Bektas, S and Ozdamar, SO}, title = {Can lymphatic vascular density be used in determining metastatic spreading potential of tumor in invasive ductal carcinomas?.}, journal = {Pathology oncology research : POR}, volume = {18}, number = {2}, pages = {253-262}, pmid = {21785902}, issn = {1532-2807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived/metabolism ; Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Cell Proliferation ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Node Excision ; *Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels/*pathology ; Mastectomy ; Middle Aged ; *Neovascularization, Pathologic ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Prognosis ; Retrospective Studies ; }, abstract = {Regional lymph node status is the primary parameter determining treatment strategies and prognoses in breast cancer. Lymphatic vessels in primary tumor tissue play a significant role in lymphatic metastasis. The aim of this study was to investigate the correlation of intra- and peritumoral lymphatic microvessel densities (LVD) with prognostic parameters in breast cancer, including lymphatic invasion (LI). Lymphangiogenesis was investigated using D2-40 monoclonal antibody in 69 invasive ductal carcinoma cases who underwent mastectomy and axillary lymph node dissection. Positively stained microvessels were counted at 400× in dense lymphatic vascular foci (hotspots). Tumor LI was established when at least one neoplastic cell cluster was clearly visible inside a D2-40-positive lymph vessel. Relationships were sought between clinicopathological parameters and mean LVD and LI in primary tumor tissue. Peritumoral LVD was markedly higher than intratumoral LVD (p < 0.001). No significant relationship was found between intratumoral LVD and clinicopathological parameters (p > 0.05). However, significant relationships were detected between peritumoral LVD and LVI [H&amp;E] (p = 0.04), number of lymphatic invasion [n/mm2, D2-40] (p = 0.001), tumor size (p = 0.01), lymph node status (p = 0.03), and tumor stage (p = 0.04). The immunohistochemical determination of LI and LVD can contribute to the prediction of a tumor's biological behavior in invasive ductal carcinomas. Peritumoral LVD in primary tumor tissue is closely related to parameters influencing the prognosis of a tumor.}, }
@article {pmid21782124, year = {2011}, author = {Le-Petross, H and Lane, D}, title = {Challenges and potential pitfalls in magnetic resonance imaging of more elusive breast carcinomas.}, journal = {Seminars in ultrasound, CT, and MR}, volume = {32}, number = {4}, pages = {342-350}, doi = {10.1053/j.sult.2011.03.004}, pmid = {21782124}, issn = {0887-2171}, mesh = {Adenocarcinoma, Mucinous/*pathology ; Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Inflammatory Breast Neoplasms/pathology ; Magnetic Resonance Imaging/*methods ; Middle Aged ; }, abstract = {Breast cancer is a heterogeneous group of diseases caused by differences in the biological, clinical, radiologic, and pathologic features of the different types of invasive carcinoma in the breast. The majority of invasive breast carcinomas are the invasive ductal or no special-type (NST) carcinomas. The rest of the invasive carcinomas are either nonductal carcinoma subtypes or special-type carcinomas, making up 20%-30% of all invasive carcinomas. The latter group comprises very different and distinctive types of cancer with imaging characteristics and challenges that are unique to each subtype. The invasive lobular carcinoma is the most common type of the nonductal carcinomas and can be difficult to detect on imaging because of the distinct pattern of tumor growth in sheets of single file cells with minimal desmoplastic reaction. The mucinous carcinoma of the breast contains extracellular mucin, secreted by the tumor cells. The mucin within these tumors result in imaging features that overlap with benign breast lesions, and may lead to misdiagnosis. Other rare and aggressive breast cancers include metaplastic breast carcinoma and inflammatory breast carcinoma. Both diseases have a poorer prognosis than invasive ductal carcinoma. This article will focus on the rarer non-NST carcinoma of the breast that can be a challenge to assess with imaging, partially related to the unique biology of these cancers.}, }
@article {pmid21779814, year = {2014}, author = {Koike, K and Kitahara, K and Higaki, M and Urata, M and Yamazaki, F and Noshiro, H}, title = {Clinicopathological features of gastric metastasis from breast cancer in three cases.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {21}, number = {5}, pages = {629-634}, doi = {10.1007/s12282-011-0284-3}, pmid = {21779814}, issn = {1880-4233}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla/pathology/surgery ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Lymph Node Excision ; Middle Aged ; Stomach Neoplasms/drug therapy/*pathology/*secondary ; Treatment Outcome ; }, abstract = {The common sites for metastases from breast cancer are lymph nodes, bone, lung, liver, and brain. Gastrointestinal (GI) metastasis is rarely found or diagnosed in patients with breast cancer. This report presents three cases of gastric metastasis from breast cancer. Case 1 was a 42-year-old female diagnosed with gastric metastasis after mastectomy with axillary lymph node dissection for invasive lobular carcinoma of the left breast. Case 2 was a 54-year-old female who was diagnosed to have invasive lobular carcinoma of the left breast with systemic bone and gastric metastasis. Case 3 was a 54-year-old female who was diagnosed to have bilateral invasive ductal carcinoma of the breast with simultaneous bone and gastric metastasis. The immunohistochemical statuses for estrogen receptor, progesterone receptor, mammaglobin, and gross cystic disease fluid protein-15 (GCDFP-15) between the primary and gastric metastatic lesions were all well matched. All three cases were treated with systemic chemotherapy, hormone therapy or both, without surgical intervention for gastric lesions. Two patients with disseminated disease died 27 and 58 months after diagnosis of gastric metastasis, while one patient without organ metastasis is still alive at 56 months after diagnosis. It is important to make a correct diagnosis by distinguishing gastric metastasis from breast cancer in order to select the optimal initial treatment for systemic disease of breast cancer.}, }
@article {pmid21779299, year = {2011}, author = {Sunwoo, MK and Kim, SM and Lee, S and Lee, PH}, title = {Parkinsonism associated with glucocerebrosidase mutation.}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {7}, number = {2}, pages = {99-101}, pmid = {21779299}, issn = {2005-5013}, abstract = {BACKGROUND: Gaucher's disease is an autosomal recessive, lysosomal storage disease caused by mutations of the β-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinson's disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations.<br><br>CASE REPORT: A 44-year-old woman suffering from slowness and paresthesia of the left arm for the previous 1.5years, visited our hospital to manage known invasive ductal carcinoma. During a preoperative evaluation, she was diagnosed with Gaucher's disease and double mutations of S271G and R359X in GBA. Parkinsonian features including low amplitude postural tremors, rigidity, bradykinesia and shuffling gait were observed. Genetic analysis also revealed that her older sister, who had also been diagnosed with PD and had been taking dopaminergic drugs for 8-years, also possessed a heterozygote R359X mutation in GBA. (18)F-fluoropropylcarbomethoxyiodophenylnortropane positron-emission tomography in these patients revealed decreased uptake of dopamine transporter in the posterior portion of the bilateral putamen.<br><br>CONCLUSIONS: This case study demonstrates Korean familial cases of PD with heterozygote mutation of GBA, further supporting the association between PD and GBA mutation.}, }
@article {pmid21766182, year = {2012}, author = {Gabrovska, PN and Smith, RA and Tiang, T and Weinstein, SR and Haupt, LM and Griffiths, LR}, title = {Development of an eight gene expression profile implicating human breast tumours of all grade.}, journal = {Molecular biology reports}, volume = {39}, number = {4}, pages = {3879-3892}, pmid = {21766182}, issn = {1573-4978}, mesh = {Axin Protein/genetics/metabolism ; Breast Neoplasms/*genetics/*pathology ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genes, Neoplasm/*genetics ; Humans ; Immunohistochemistry ; Microarray Analysis ; Middle Aged ; Neoplasm Grading ; Polymerase Chain Reaction ; }, abstract = {The goal of improving systemic treatment of breast cancers is to evolve from treating every patient with non-specific cytotoxic chemotherapy/hormonal therapy, to a more individually-tailored direct treatment. Although anatomic staging and histological grade are important prognostic factors, they often fail to predict the clinical course of this disease. This study aimed to develop a gene expression profile associated with breast cancers of differing grades. We extracted mRNA from FFPE archival breast IDC tissue samples (Grades I-III), including benign tumours. Affymetrix GeneChip(®) Human Genome U133 Plus 2.0 Arrays were used to determine gene expression profiles and validated by Q-PCR. IHC was used to detect the AXIN2 protein in all tissues. From the array data, an independent group t-test revealed that 178 genes were significantly (P ≤ 0.01) differentially expressed between three grades of malignant breast tumours when compared to benign tissues. From these results, eight genes were significantly differentially expressed in more than one comparison group and are involved in processes implicated in breast cancer development and/or progression. The two most implicated candidates genes were CLD10 and ESPTI1 as their gene expression profile from the microarray analysis was replicated in Q-PCR analyses of the original tumour samples as well as in an extended population. The IHC revealed a significant association between AXIN2 protein expression and ER status. It is readily acknowledged and established that significant differences exist in gene expression between different cancer grades. Expansion of this approach may lead to an improved ability to discriminate between cancer grade and other pathological factors.}, }
@article {pmid21756827, year = {2011}, author = {Zhang, N and Sun, ZZ and Li, F and Cao, YW and Zhao, CX and Liang, WH and Sun, HP and Li, HA and Fu, XG}, title = {[Detection and clinical significance of Notch1 methylation in breast cancer and intraductal proliferative breast lesions].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {40}, number = {5}, pages = {324-329}, pmid = {21756827}, issn = {0529-5807}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; CpG Islands/genetics ; *DNA Methylation ; DNA, Neoplasm/genetics ; Disease Progression ; Female ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Precancerous Conditions/genetics/metabolism/pathology ; Promoter Regions, Genetic ; Receptor, Notch1/*genetics/metabolism ; Young Adult ; }, abstract = {OBJECTIVE: To explore the relevance between the promoter methylation status of Notch1 gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast.<br><br>METHODS: Methylation status of Notch1 gene in human breast invasive ductal carcinoma (IDC, n = 89), ductal carcinoma in situ (DCIS, n = 20), atypical ductal hyperplasia (ADH, n = 11) and usual ductal hyperplasia (UDH, n = 20) were quantitatively evaluated by MALDI-TOF MS. The expression of Notch1 protein was detected by immunohistochemical stain (SP method).<br><br>RESULTS: Positive expression rates of Notch1 protein in IDC and DCIS were 91.0% (81/89) and 75.0% (15/20), respectively, which were significantly higher than those of ADH (4/11) and UDH (30.0%, 6/20;P < 0.05). Notch1 protein expression was correlated significantly with lymph node metastasis, pathological grades and TNM stages of IDC. The mean methylation levels of Notch1 gene at CpG_3, CpG_4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS, ADH and UDH groups (P < 0.0083). In breast carcinomas, the mean methylation rates of Notch1 gene at CpG_4.5, CpG_10.11, and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis (P < 0.05); and the methylation rates at CpG_14.15.16 and CpG_18 loci in stage Iwere lower than that in stage II, further lower than that in stage III (P < 0.05); and that in CpG_1.2, CpG_12.13 loci in grade I (highly-differentiated group) were higher than that in grade II (moderate-differentiated group) and grade III (poorly-differentiated group) (P < 0.05); and the methylation rates at CpG_3, CpG_8 and CpG_14.15.16 loci in ER(+) PR(+) HER2(-) group were lower than that in ER(-) PR(-) HER2(+) group (P < 0.05).<br><br>CONCLUSIONS: There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notch1 protein. This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1, and this change may have important significance in breast tumorigenesis and the development. Specific hypomethylation at CpG_3, CpG_ 4.5 and CpG_8 loci of Notch1 gene may play a role in the pathogenesis of breast carcinoma, suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.}, }
@article {pmid21744349, year = {2011}, author = {Ruidiaz, ME and Cortes-Mateos, MJ and Sandoval, S and Martin, DT and Wang-Rodriguez, J and Hasteh, F and Wallace, A and Vose, JG and Kummel, AC and Blair, SL}, title = {Quantitative comparison of surgical margin histology following excision with traditional electrosurgery and a low-thermal-injury dissection device.}, journal = {Journal of surgical oncology}, volume = {104}, number = {7}, pages = {746-754}, doi = {10.1002/jso.22012}, pmid = {21744349}, issn = {1096-9098}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*pathology/*surgery ; Burns/etiology/pathology/*prevention &amp; control ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Collagen ; Diagnostic Errors/*prevention &amp; control ; Electrosurgery/adverse effects/*instrumentation ; Female ; Humans ; Mastectomy, Segmental/adverse effects/*instrumentation ; Middle Aged ; Neoplasm, Residual/pathology ; Pilot Projects ; Prospective Studies ; Protein Denaturation ; Sensitivity and Specificity ; Soft Tissue Injuries/etiology/pathology/*prevention &amp; control ; }, abstract = {BACKGROUND: This study is the first to examine in vivo the effect of thermal injury in breast conservation pathology in a direct comparison of traditional electrosurgery and an alternative low-thermal-injury device.<br><br>METHODS: A prospective study of 20 consecutive subjects with biopsy-proven invasive ductal carcinoma (IDC) tumors 1 cm was conducted. Following excision, incisions were made into the tumor with the two devices. Thermal injury depth, margin distance, tissue type, and histological effect were compared on the same breast tissue cut with each excision instrument. A probability evaluation of close and positive margin cases for the true tumor margins was conducted.<br><br>RESULTS: Compared to traditional electrosurgery, the low-thermal-injury instrument reduced collagen denaturation depth from 435 to 102 &#xb5;m (77%), fused tissue depth from 262 to 87 &#xb5;m (67%), and distortion depth from 1,132 to 774 &#xb5;m (30%).<br><br>CONCLUSIONS: Based on analysis of the close subset of the true margins, using the traditional electrosurgical device in place of the low-thermal-injury device would have resulted in 48% of the close margin samples being negatively converted to false-positive, and in 11% converting from close to false-negative. The methodology of this work may be readily applied to larger, more definitive studies.}, }
@article {pmid21738806, year = {2011}, author = {Teixeira, PC and Santos, RH and Fiorelli, AI and Bilate, AM and Benvenuti, LA and Stolf, NA and Kalil, J and Cunha-Neto, E}, title = {Selective decrease of components of the creatine kinase system and ATP synthase complex in chronic Chagas disease cardiomyopathy.}, journal = {PLoS neglected tropical diseases}, volume = {5}, number = {6}, pages = {e1205}, pmid = {21738806}, issn = {1935-2735}, mesh = {ATP Synthetase Complexes/genetics/*metabolism ; Adolescent ; Adult ; Chagas Cardiomyopathy/*physiopathology ; Creatine Kinase, Mitochondrial Form/genetics/*metabolism ; Gene Expression Profiling ; Humans ; Immunoblotting ; Male ; Middle Aged ; Myocardium/*enzymology ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult ; }, abstract = {BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies.<br><br>Myocardium homogenates from CCC (N=5), IC (N=5) and IDC (N=5) patients, as well as from heart donors (N=5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels.<br><br>CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.}, }
@article {pmid21733550, year = {2012}, author = {Choi, Y and Kim, EJ and Seol, H and Lee, HE and Jang, MJ and Kim, SM and Kim, JH and Kim, SW and Choe, G and Park, SY}, title = {The hormone receptor, human epidermal growth factor receptor 2, and molecular subtype status of individual tumor foci in multifocal/multicentric invasive ductal carcinoma of breast.}, journal = {Human pathology}, volume = {43}, number = {1}, pages = {48-55}, doi = {10.1016/j.humpath.2010.08.026}, pmid = {21733550}, issn = {1532-8392}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cell Nucleus/genetics/metabolism/pathology ; DNA, Neoplasm/analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Mastectomy ; Middle Aged ; Neoplasms, Multiple Primary/genetics/*metabolism/pathology ; Phenotype ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Steroid/genetics/*metabolism ; Tissue Array Analysis ; Young Adult ; }, abstract = {Multifocal/multicentric breast cancers are common. However, investigations of biomarkers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 in individual tumor foci of such cancers are rare. This study was designed to evaluate the status of the hormone receptors, human epidermal growth factor receptor 2, and its molecular subtypes in individual foci of multifocal/multicentric invasive ductal carcinoma of the breast and to identify the factors associated with the different phenotypes of individual foci. We performed immunohistochemical analyses of the estrogen receptor, progesterone receptor, cytokeratin 5/6, epidermal growth factor receptor, and p53 and fluorescence in situ hybridization of human epidermal growth factor receptor 2 in individual foci of 65 cases of multifocal/multicentric invasive ductal carcinoma and the associated ductal carcinoma in situ components using tissue microarrays. The estrogen receptor status differed in 2 (3%) of the 65 invasive ductal carcinomas, progesterone receptor status in 7 (11%), human epidermal growth factor receptor 2 status in 4 (6%), and molecular subtypes in 5 (8%). The presence of different molecular subtypes in the invasive tumor foci was associated with differences in histologic features (P = .005), high histologic and nuclear grade (P = .012 and P = .021, respectively), p53 overexpression (P = .006), and mixed molecular subtypes in the ductal carcinoma in situ components (P = .011). Multifocal/multicentric invasive ductal carcinomas usually have a single phenotype in terms of hormone receptors, human epidermal growth factor receptor 2, and molecular subtypes; and thus, immunohistochemical analyses of the index tumor may be sufficient in routine practice. However, if multifocal/multicentric invasive ductal carcinomas are of high grade, of different histologic features, or of heterogeneous ductal carcinoma in situ component, biomarkers of the various foci need to be evaluated separately.}, }
@article {pmid21715690, year = {2011}, author = {Kis-Toth, K and Hajdu, P and Bacskai, I and Szilagyi, O and Papp, F and Szanto, A and Posta, E and Gogolak, P and Panyi, G and Rajnavolgyi, E}, title = {Voltage-gated sodium channel Nav1.7 maintains the membrane potential and regulates the activation and chemokine-induced migration of a monocyte-derived dendritic cell subset.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {187}, number = {3}, pages = {1273-1280}, doi = {10.4049/jimmunol.1003345}, pmid = {21715690}, issn = {1550-6606}, mesh = {Cell Differentiation/immunology ; Cell Movement/*immunology ; Cells, Cultured ; Chemokines/*physiology ; Cytokines/metabolism ; Dendritic Cells/cytology/*immunology/*metabolism ; Humans ; Membrane Potentials/*immunology ; Monocytes/cytology/*immunology/*metabolism ; NAV1.7 Voltage-Gated Sodium Channel ; Resting Phase, Cell Cycle/immunology ; Sodium Channels/*physiology ; }, abstract = {Expression of CD1a protein defines a human dendritic cell (DC) subset with unique functional activities. We aimed to study the expression of the Nav1.7 sodium channel and the functional consequences of its activity in CD1a(-) and CD1a(+) DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments performed on sorted CD1a(-) and CD1a(+) immature DC (IDC) showed that the frequency of cells expressing Na(+) current, current density, and the relative expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a(+) cells than in their CD1a(-) counterparts. The activity of Nav1.7 results in a depolarized resting membrane potential (-8.7 ± 1.5 mV) in CD1a(+) IDC as compared with CD1a(-) cells lacking Nav1.7 (-47 ± 6.2 mV). Stimulation of DC by inflammatory signals or by increased intracellular Ca(2+) levels resulted in reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a(+) IDC, resulting in decreased cell migration, whereas pharmacological inhibition of Nav1.7 by tetrodotoxin sensitized the cells for activation signals. Fine-tuning of IDC functions by a voltage-gated sodium channel emerges as a new regulatory mechanism modulating the migration and cytokine responses of these DC subsets.}, }
@article {pmid21713550, year = {2012}, author = {Tiezzi, DG and Valejo, FA and Marana, HR and Carrara, HH and Benevides, L and Antonio, HM and Sicchieri, RD and Milanezi, CM and Silva, JS and de Andrade, JM}, title = {CD44+/CD24- cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {3}, pages = {1479-1485}, pmid = {21713550}, issn = {1559-131X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; CD24 Antigen/analysis ; Carcinoma, Ductal, Breast/*pathology ; Female ; Flow Cytometry ; Humans ; Hyaluronan Receptors/analysis ; Immunohistochemistry ; Lymphatic Metastasis/*pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neoplastic Stem Cells/*pathology ; }, abstract = {The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), anti-human CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumor-initiating cells in stage I and II breast cancer.}, }
@article {pmid21712309, year = {2011}, author = {Fernández, B and Paish, EC and Green, AR and Lee, AH and Macmillan, RD and Ellis, IO and Rakha, EA}, title = {Lymph-node metastases in invasive lobular carcinoma are different from those in ductal carcinoma of the breast.}, journal = {Journal of clinical pathology}, volume = {64}, number = {11}, pages = {995-1000}, doi = {10.1136/jclinpath-2011-200151}, pmid = {21712309}, issn = {1472-4146}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology/*secondary ; Carcinoma, Lobular/pathology/*secondary ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Survival Analysis ; }, abstract = {AIM: Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast are distinct morphological entities with different biological features and clinical behaviour. In the present study, the authors compare the axillary-lymph-node (ALN) status of patients with grade-matched ILC (no=426) and IDC (no=820). The pattern of nodal metastatic deposits (nodular, sinusoidal and diffuse) and the proportion of involved nodes were also analysed in a selected group of 246 tumours, which were associated with a single positive ALN.<br><br>RESULTS: Compared with grade-matched IDC, ILC was associated with a higher nodal stage (13.1% vs 4.5% of ILC and IDC were stage 3), higher absolute number of positive nodes and higher ratio of positive nodes (0.46&#xb1;0.30 and 0.33&#xb1;0.23 in ILC and IDC respectively). These differences were maintained in the different size subgroups. The most common metastatic morphological pattern was nodular in both types of carcinomas. A sinusoidal pattern was more frequent in IDC, and the diffuse pattern was more frequent in ILC. Despite these differences, ILC and grade-matched IDC exhibited similar rates of regional recurrences (RR) and breast-cancer survival.<br><br>CONCLUSION: This study provides clinical evidence which further demonstrates that ILC and IDC are biologically distinct entities with different lymph-node involvement patterns and ILC having a tendency to metastasise to more nodes than IDC. However, this difference was not associated with a significant impact on patient outcome.}, }
@article {pmid21710692, year = {2011}, author = {Moelans, CB and Verschuur-Maes, AH and van Diest, PJ}, title = {Frequent promoter hypermethylation of BRCA2, CDH13, MSH6, PAX5, PAX6 and WT1 in ductal carcinoma in situ and invasive breast cancer.}, journal = {The Journal of pathology}, volume = {225}, number = {2}, pages = {222-231}, doi = {10.1002/path.2930}, pmid = {21710692}, issn = {1096-9896}, mesh = {Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Methylation/*genetics ; DNA-Binding Proteins/genetics ; Eye Proteins/genetics ; Female ; Genes, BRCA2 ; Genes, Wilms Tumor ; Homeodomain Proteins/genetics ; Humans ; Microdissection ; PAX5 Transcription Factor/genetics ; PAX6 Transcription Factor ; Paired Box Transcription Factors/genetics ; Promoter Regions, Genetic/*genetics ; Repressor Proteins/genetics ; }, abstract = {Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism to inactivate tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. In search of epigenetic events related to progression, we used MS-MLPA (ME-0002-B1, MRC-Holland, Amsterdam, The Netherlands) to compare the methylation status of 25 breast cancer-related genes between laser-microdissected ductal carcinoma in situ (DCIS) and adjacent invasive ductal cancer (IDC) lesions in 33 breast cancer patients. Using absolute methylation percentages or, alternatively, a 15% cut-off for methylation, promoter methylation in DCIS and IDC was not significantly different for any of the genes studied. Aberrant methylation in at least 50% of both the DCIS and adjacent IDC lesions was observed for PAX6, BRCA2, PAX5, WT1, CDH13 and MSH6. Methylation of MSH6, however, was also frequent in normal breast tissue. In contrast, CDKN2A, CHFR, PYCARD and one of the two analysed RB1 CpG loci were rarely (<5%) methylated in both lesions. CDKN2A and GSTP1 showed significantly (p < 0.002) higher mean methylation levels in increasing grades (I, II, III) of DCIS (1% versus 4% versus 7% for CDKN2A and 6% versus 26% versus 28% for GSTP1). The mean number of methylated genes per sample increased with increasing grades of DCIS (p = 0.014) and IDC (p = 0.109). In contrast to the observations in DCIS, none of the analysed genes showed significantly higher methylation levels with increasing grades of IDC. In conclusion, there were no differences in promoter methylation between DCIS and IDC in the 25 analysed genes, suggesting that DCIS, at the epigenetic level, is as advanced as IDC. Promoter hypermethylation of PAX6, BRCA2, PAX5, WT1, CDH13 and MSH6 seems to be a frequent early event in breast cancer and methylation levels of GSTP1 (and CDKN2A, although still low) seem to increase with increasing DCIS grade.}, }
@article {pmid21707845, year = {2011}, author = {Shui, R and Bi, R and Cheng, Y and Lu, H and Wang, J and Yang, W}, title = {Matrix-producing carcinoma of the breast in the Chinese population: a clinicopathological study of 13 cases.}, journal = {Pathology international}, volume = {61}, number = {7}, pages = {415-422}, doi = {10.1111/j.1440-1827.2011.02676.x}, pmid = {21707845}, issn = {1440-1827}, mesh = {Adenocarcinoma/metabolism/*secondary/therapy ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*secondary/therapy ; Cell Nucleus/metabolism/pathology ; Combined Modality Therapy ; Extracellular Matrix/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Second Primary ; Retrospective Studies ; }, abstract = {Matrix-producing carcinoma (MPC) of the breast is an extremely rare variant of metaplastic carcinoma. The aim of this study was to evaluate the clinicopathological features and immunohistochemical expression profile of this rare tumor in Chinese population. Thirteen cases of MPC were evaluated using morphology observation and immunohistochemistry. All tumors had invasive carcinoma with an abrupt transition to chondromyxoid matrix without an intervening spindle cell sarcomatoid component. The distribution of tumor cells was diffuse in eight cases and peripheral in five cases. Matrix distribution was diffuse or multifocal. Necrosis was present in 11 cases. An overt invasive ductal carcinoma was observed in 11 cases and the other two tumors were consistent with MPC arising in microglandular adenosis. Ten of 13 cases were triple negative (ER-, PR-, Her2/neu-). Eight of 10 triple negative cases were cytokeratin 5/6, cytokeratin 14 or epidermal growth factor receptor positive, consistent with the basal-like phenotype. S-100 protein was positive in all cases. At the time of initial diagnosis, one of 13 patients had lung metastasis and axillary lymph nodes metastasis. Follow-up time ranged from 6 to 30 months. All patients remained alive. One patient developed a soft tissue metastasis 24 months after surgery.}, }
@article {pmid21702220, year = {2011}, author = {Damle, AA and Narkar, AA and Badwe, RA}, title = {Radioiodide uptake and sodium iodide symporter expression in breast carcinoma.}, journal = {Indian journal of experimental biology}, volume = {49}, number = {6}, pages = {416-422}, pmid = {21702220}, issn = {0019-5189}, mesh = {Adult ; Aged ; Base Sequence ; Breast Neoplasms/*genetics/metabolism/*radiotherapy ; Female ; Gene Expression ; Humans ; Iodine Radioisotopes/pharmacokinetics/*therapeutic use ; Middle Aged ; RNA, Neoplasm/genetics/metabolism ; Symporters/*genetics ; }, abstract = {Breast cancer is a common malignancy in women all over the world and novel therapeutic approaches are required for the treatment of patients who become refractory to conventional therapies. Thyroid cancer is being treated successfully with radioiodine since many years. The iodide is transported inside the thyroid epithelial cell via sodium iodide symporter (NIS) which is a trans-membrane protein. The present study was aimed to explore the uptake of radioiodide (RAI) and the expression of NIS in breast tissues of invasive ductal carcinoma patients. Breast tissues from tumor region (Tu-Br) as well as corresponding normal region (N-Br) were collected from patients of invasive ductal carcinoma. In vitro RAI uptake, its efflux and NIS expression were studied. The uptake of RAI (1.98+/-1.75 x 10(5) cpm/g) in Tu-Br was significantly higher as compared to that observed in N-Br (0.31+/-0.27 x 10(5) cpm/g) and fast efflux was observed in the tissue samples. NIS gene expression was positive in 41.66% (10/24) samples of Tu-Br. None of the N-Br samples expressed NIS gene. In 14 samples of Tu-Br, RAI uptake as well as NIS expression was studied. In 50% of these Tu-Br samples RAI uptake as well as of NIS gene expression was positive. The results indicate that RAI uptake is significantly higher in breast tumor tissues as compared to their normal counterpart and in future radioiodine may be an important agent for treatment of breast cancer.}, }
@article {pmid21699039, year = {2011}, author = {Rappaport, A and Van Steen, A and Van Ongeval, C}, title = {A rare presentation of breast cancer.}, journal = {JBR-BTR : organe de la Societe royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)}, volume = {94}, number = {2}, pages = {75-77}, doi = {10.5334/jbr-btr.499}, pmid = {21699039}, issn = {1780-2393}, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; Axilla ; Biopsy ; Breast/microbiology/pathology/surgery ; Breast Neoplasms/complications/*diagnosis/*therapy ; Carcinoma, Ductal, Breast/complications/*diagnosis/*therapy ; Diagnosis, Differential ; Docetaxel ; Female ; Follow-Up Studies ; Granulomatous Mastitis/complications/*diagnosis/*therapy ; Humans ; Lymph Node Excision ; Lymph Nodes/surgery ; Mammography/methods ; Mastectomy ; Positron-Emission Tomography/methods ; Radiotherapy, Adjuvant/methods ; Staphylococcal Infections/complications/diagnosis/drug therapy ; Staphylococcus aureus/drug effects ; Taxoids/therapeutic use ; Tomography, X-Ray Computed/methods ; Ultrasonography, Mammary/methods ; }, abstract = {The case of a 67-year-old woman with a large lump in the left axillary region and the left breast is presented. Pathologic investigation of these masses in 2 hospitals was inconclusive. Further work-up in our radiologic department showed beside the presence of the two tumoral masses, abnormalities with the radiologic characteristics of granulomatous mastitis. Final pathologic analysis showed the presence of an invasive ductal carcinoma in the two masses in combination with a granulomatous stromal reaction.}, }
@article {pmid21691700, year = {2011}, author = {Martins Junior, DF and Costa, TM and Lordelo, MS and Felzemburg, RD}, title = {Trends of mortality from ill-defined causes in the Northeast region of Brazil, 1979-2009.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {57}, number = {3}, pages = {332-340}, pmid = {21691700}, issn = {1806-9282}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Brazil/epidemiology ; Cause of Death/*trends ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Middle Aged ; Sex Distribution ; Young Adult ; }, abstract = {OBJECTIVE: This study aimed to analyze the trends of mortality from symptoms, signs and ill-defined causes (SSIDC) in the Northeast region of Brazil, during the period of 1979- 2009.<br><br>METHODS: The study used secondary data provided by the Mortality Information System SIM/Datasus/Ministry of Health.<br><br>RESULTS: There was a reduction in the proportion of this type of death (y = -1.3751x + 55.953 R&#xb2; = 0.9035), from 45.7% in 1979 to 8.1% in 2009, as well as according to sex: males (y = -1.3716x + 54.559 R&#xb2; = 0.9197) and females (y = -1.3828x + 57.932 R&#xb2; = 0.8771). The proportion of deaths due to ill-defined causes showed a decreasing tendency in all age groups. The highest reduction was observed in the upper and lower age ranges, < 1 and 1 to 4 year and elderly group, namely 60 years old and older. Capitals and countryside also showed a decreasing tendency in proportional mortality due to IDC, (y = -0.1118x + 9.4275 R&#xb2; = 0.3087) and (y = -1.7908x + 71.178 R&#xb2; = 0.9151) respectively, but with different temporal patterns. The capital cities had the lower rates since the beginning of the series regardless of the age groups, but the great reduction in rates was observed in the countryside, being 7.1 times higher among adults (20 to 59 years old).<br><br>CONCLUSION: Decreased trends were observed, but it is necessary to reinforce the actions to improve the capacity of health service assistance and coverage and data registration in order to maintain this trend.}, }
@article {pmid21685944, year = {2012}, author = {Shenoy, SK and Han, S and Zhao, YL and Hara, MR and Oliver, T and Cao, Y and Dewhirst, MW}, title = {β-arrestin1 mediates metastatic growth of breast cancer cells by facilitating HIF-1-dependent VEGF expression.}, journal = {Oncogene}, volume = {31}, number = {3}, pages = {282-292}, pmid = {21685944}, issn = {1476-5594}, support = {R01 HL080525/HL/NHLBI NIH HHS/United States ; CA40355/CA/NCI NIH HHS/United States ; R01 HL080525-04S1/HL/NHLBI NIH HHS/United States ; HL080525/HL/NHLBI NIH HHS/United States ; R01 CA040355/CA/NCI NIH HHS/United States ; }, mesh = {Active Transport, Cell Nucleus/drug effects ; Angiogenesis Inhibitors/pharmacology ; Animals ; Antineoplastic Agents/pharmacology ; Benzamides ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Imatinib Mesylate ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Piperazines/pharmacology ; Protein Stability/drug effects ; Pyrimidines/pharmacology ; Thalidomide/pharmacology ; Transcription, Genetic/drug effects ; Vascular Endothelial Growth Factor A/*biosynthesis ; }, abstract = {β-Arrestins 1 and 2 are multifunctional adaptor proteins originally discovered for their role in desensitizing seven-transmembrane receptor signaling via the heterotrimeric guanine nucleotide-binding proteins. Recently identified roles of β-arrestins include regulation of cancer cell chemotaxis and proliferation. Herein, we report that β-arrestin1 expression regulates breast tumor colonization in nude mice and cancer cell viability during hypoxia. β-Arrestin1 robustly interacts with nuclear hypoxia-induced factor-1α (HIF-1α) that is stabilized during hypoxia and potentiates HIF-1-dependent transcription of the angiogenic factor vascular endothelial growth factor-A (VEGF-A). Increased expression of β-arrestin1 in human breast cancer (infiltrating ductal carcinoma or IDC and metastatic IDC) correlates with increased levels of VEGF-A. While the anti-angiogenic drug thalidomide inhibits HIF-1-dependent VEGF transcription in breast carcinoma cells, it does not prevent HIF-1α stabilization, but leads to aberrant localization of HIF-1α to the perinuclear compartments and surprisingly stimulates nuclear export of β-arrestin1. Additionally, imatinib mesylate that inhibits release of VEGF induces nuclear export of β-arrestin1-HIF-1α complexes. Our findings suggest that β-arrestin1 regulates nuclear signaling during hypoxia to promote survival of breast cancer cells via VEGF signaling and that drugs that induce its translocation from the nucleus to the cytoplasm could be useful in anti-angiogenic and breast cancer therapies.}, }
@article {pmid21683981, year = {2011}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Sasajima, Y and Kinoshita, T and Tsuda, H}, title = {Prognostic significance of mitotic figures in metastatic mammary ductal carcinoma to the lymph nodes.}, journal = {Human pathology}, volume = {42}, number = {12}, pages = {1823-1832}, doi = {10.1016/j.humpath.2011.02.015}, pmid = {21683981}, issn = {1532-8392}, mesh = {Adult ; Aged ; Antineoplastic Agents/*administration &amp; dosage ; Breast Neoplasms/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology/secondary ; Chemotherapy, Adjuvant ; Disease Progression ; Female ; Fibrosis/pathology ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mitotic Index/*statistics &amp; numerical data ; Neoplasm Grading ; Neoplasm Recurrence, Local/pathology ; Predictive Value of Tests ; Prognosis ; Survival Analysis ; Tumor Suppressor Protein p53/*analysis ; Young Adult ; }, abstract = {We previously reported that the number of mitotic figures in metastatic mammary carcinoma to the lymph nodes accurately predicted the outcome of patients with invasive ductal carcinoma with nodal metastasis. To confirm these previous findings, the present study investigated the number of mitotic figures and other histologic characteristics in metastatic mammary carcinoma to the lymph nodes and their associations with patient outcome according to nodal status and the histologic grade of primary invasive ductal carcinomas in a different series of 1039 patients with invasive ductal carcinoma. Multivariate analyses examining well-known clinicopathologic factors, the number of mitotic figures in the primary invasive ductal carcinomas, the grading system for lymph vessel tumor emboli, the p53 Allred score risk classes of tumor-stromal fibroblasts forming and not forming a fibrotic focus, and 9 histologic features of metastatic mammary carcinoma to the lymph nodes were performed. The presence of 6 or more mitotic figures in metastatic mammary carcinoma to the lymph nodes significantly increased the hazard ratios for tumor recurrence and tumor-related death among patients with invasive ductal carcinoma as a whole, those with nodal metastasis, and those with a histologic grade of 2 or 3. The presence of 6 or more mitotic figures in metastatic mammary carcinoma to the lymph nodes also significantly increased the hazard ratio for tumor recurrence among patients with histologic grade 1 invasive ductal carcinoma. In conclusion, this study clearly confirmed the excellent outcome predictive power of the number of mitotic figures in metastatic mammary carcinoma to the lymph nodes.}, }
@article {pmid21683430, year = {2012}, author = {Serra, KP and Sarian, LO and Rodrigues-Peres, RM and Vassallo, J and Soares, FA and Pinto, GA and da Cunha, IW and Shinzato, JY and Derchain, SF}, title = {Expression of cyclooxygenase-2 (COX-2) and p53 in neighboring invasive and in situ components of breast tumors.}, journal = {Acta histochemica}, volume = {114}, number = {3}, pages = {226-231}, doi = {10.1016/j.acthis.2011.05.001}, pmid = {21683430}, issn = {1618-0372}, mesh = {Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast/metabolism/*pathology ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal/genetics/metabolism/*pathology ; Cyclooxygenase 2/genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Tumor Microenvironment ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {The aim of the study was to assess the relationship between the expression of COX-2 and p53, hormone receptors and HER-2 in the in situ (DCIS) and invasive components of ductal carcinomas (IDC) of the same breast. The expression of COX-2, p53, and hormone receptors was assessed in 87 cases of IDC with contiguous areas of DCIS. Results showed that there was no difference in COX-2 expression comparing the in situ and invasive components of the tumors. In the in situ component, there was a statistically borderline increase in p53 expression in tumors that also expressed COX-2. ER-positive specimens were more common in the group of tumors that expressed COX-2 in the invasive component. From this study we conclude that the expression of COX-2 was similar in the in situ and invasive components of the breast carcinomas. COX-2 positivity was marginally related with the expression of p53 in the in situ components, and with the ER expression in the invasive components.}, }
@article {pmid21679619, year = {2011}, author = {Kumano, H and Hozumi, Y and Shiozawa, M and Takehara, M and Koizumi, M and Sata, N and Lefor, AT and Yasuda, Y}, title = {Recurrent invasive ductal carcinoma of the breast presenting as a metastasis to the duodenum with long-term survival.}, journal = {The American surgeon}, volume = {77}, number = {6}, pages = {e107-8}, pmid = {21679619}, issn = {1555-9823}, mesh = {Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/*secondary ; Duodenal Neoplasms/complications/*secondary/surgery ; Endoscopy, Gastrointestinal ; Female ; Humans ; Melena/etiology ; Middle Aged ; Neoplasm Recurrence, Local/*surgery ; Pancreaticoduodenectomy ; }, }
@article {pmid21678409, year = {2012}, author = {Balestrieri, ML and Dicitore, A and Benevento, R and Di Maio, M and Santoriello, A and Canonico, S and Giordano, A and Stiuso, P}, title = {Interplay between membrane lipid peroxidation, transglutaminase activity, and cyclooxygenase 2 expression in the tissue adjoining to breast cancer.}, journal = {Journal of cellular physiology}, volume = {227}, number = {4}, pages = {1577-1582}, doi = {10.1002/jcp.22874}, pmid = {21678409}, issn = {1097-4652}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cyclooxygenase 2/*metabolism ; Disease Progression ; Female ; Fibroadenoma/metabolism/pathology ; GTP-Binding Proteins/*metabolism ; Humans ; Hyperplasia/metabolism/pathology ; Lipid Peroxidation ; Membrane Lipids/*metabolism ; Middle Aged ; Models, Biological ; Oxidative Stress ; Protein Glutamine gamma Glutamyltransferase 2 ; Reactive Oxygen Species/metabolism ; Transglutaminases/*metabolism ; Ubiquitin/metabolism ; }, abstract = {Breast cancer, a leading cause of cancer related deaths worldwide, is one of the most common neoplasms in women. The increased generation of reactive oxygen species (ROS) in breast lesion is critically involved in the mutagenic processes that drive to breast carcinoma initiation and progression. To date, the molecular events occurring in the tissue adjoin the cancer lesion have not been elucidated. Here, we investigated the role of excess ROS generation during human breast carcinogenesis by evaluating oxidative stress biomarkers, tissue transglutaminase (t-TGase) activity, and expression levels of ubiquitin and cyclooxygenase-2 (COX-2) in the normal tissue adjoin to fibroadenoma (nFA), atypical ductal hyperplasia (nADH), and invasive ductal carcinoma (nIDC) from 45 breast cancer patients. We found that lipid peroxidation and nitric oxide production significantly increased in nIDC respect to nFA and nADH (P < 0.005) whereas the 4-hydroxy-2-nonenal (HNE) protein-adducts increased only in nADH (P < 0.005). The increased lipid damage observed in nIDC correlates with estrogen receptor exposure in IDC (R(2) = 0.89). Moreover, nIDC and invasive ductal carcinoma (IDC) showed a 10-fold higher t-TGase activity compared to nFA and nADH. Contrary, COX-2 expression levels significantly decreased nIDC and IDC respect to the nFA and nADH (P < 0.001). The analysis of the free ubiquitin expression revealed equal levels in nADH and nIDC samples whereas high molecular weight-ubiquitin conjugate increased about fivefold only in nIDC (P < 0.01 vs. nADH). These novel findings reveal an interplay between membrane lipid peroxidation, t-TGase activity, and COX-2 expression levels in the tissue adjoining to neoplastic lesion during breast cancer progression.}, }
@article {pmid21676924, year = {2011}, author = {Patani, N and Barbashina, V and Lambros, MB and Gauthier, A and Mansour, M and Mackay, A and Reis-Filho, JS}, title = {Direct evidence for concurrent morphological and genetic heterogeneity in an invasive ductal carcinoma of triple-negative phenotype.}, journal = {Journal of clinical pathology}, volume = {64}, number = {9}, pages = {822-828}, doi = {10.1136/jclinpath-2011-200135}, pmid = {21676924}, issn = {1472-4146}, support = {G1100450/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Chromosome Aberrations ; Comparative Genomic Hybridization ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Oligonucleotide Array Sequence Analysis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; }, abstract = {Triple-negative breast cancers account for 12-17% of all invasive breast carcinomas and comprise a heterogeneous group of tumours, with varying histological features and clinical behaviours. Focal apocrine differentiation can be associated with a subset of these lesions. To establish whether morphological diversity is associated with divergent genetic aberrations the genomic profiles of microdissected, morphologically distinct components from an invasive ductal carcinoma of no special type with triple-negative phenotype and a region of apocrine differentiation were determined by high-resolution microarray-based comparative genomic hybridisation and validated by fluorescence in-situ hybridisation. Morphologically distinct components were found to harbour differing genetic aberrations, with the region of apocrine differentiation demonstrating genomic gains and losses on chromosome arms 9p and 9q, respectively, not present in non-apocrine areas. The results provide additional direct evidence of intra-tumour genetic heterogeneity in breast cancer and demonstrate that morphologically distinct regions can be associated with distinct genetic aberrations.}, }
@article {pmid21658239, year = {2011}, author = {Abrhale, T and Brodie, A and Sabnis, G and Macedo, L and Tian, C and Yue, B and Serrero, G}, title = {GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells.}, journal = {BMC cancer}, volume = {11}, number = {}, pages = {231}, pmid = {21658239}, issn = {1471-2407}, support = {1R43CA124179-01/CA/NCI NIH HHS/United States ; 2R44CA124179-02/CA/NCI NIH HHS/United States ; }, mesh = {Aromatase/genetics/*metabolism ; Aromatase Inhibitors/*pharmacology ; Breast Neoplasms/*enzymology/genetics/physiopathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Down-Regulation/drug effects ; Drug Resistance, Neoplasm/*drug effects ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; Gene Silencing ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism/pharmacology ; Letrozole ; Nitriles/*pharmacology ; Progranulins ; Proto-Oncogene Proteins c-bcl-2/antagonists &amp; inhibitors ; RNA, Small Interfering/metabolism ; Triazoles/*pharmacology ; }, abstract = {BACKGROUND: Aromatase inhibitors (AI) that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+) breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88), also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells<br><br>METHODS: We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined.<br><br>RESULTS: GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole.<br><br>CONCLUSION: Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.}, }
@article {pmid21649468, year = {2011}, author = {Gupta, R and Babb, JS and Singh, B and Chiriboga, L and Liebes, L and Adams, S and Demaria, S}, title = {The numbers of FoxP3+ lymphocytes in sentinel lymph nodes of breast cancer patients correlate with primary tumor size but not nodal status.}, journal = {Cancer investigation}, volume = {29}, number = {6}, pages = {419-425}, pmid = {21649468}, issn = {1532-4192}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; 5P30CA016087-31/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/immunology/*pathology ; Female ; Forkhead Transcription Factors/*analysis ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Sentinel Lymph Node Biopsy ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Regulatory T cells, lymphocytes marked by expression of the transcription factor Forkhead Box Protein P3 (FoxP3), inhibit the activation of tumor-specific T cells in tumor-draining lymph nodes. Immunohistochemical analyses of sentinel lymph nodes (SLNs) from 104 breast cancer patients showed a significant association (p = .0028, Pearson correlation) between the number of FoxP3+ cells and the size of primary breast invasive ductal carcinoma. In contrast, there was no correlation between the number of FoxP3+ cells and the presence of SLN metastases, or other clinicopathological parameters. These results suggest the presence of an immune suppressive environment in SLNs of larger tumors.}, }
@article {pmid21641801, year = {2011}, author = {Pantanowitz, L and Sen, S and Crisi, GM and Makari-Judson, G and Garb, J and Skiest, D}, title = {Spectrum of breast disease encountered in HIV-positive patients at a community teaching hospital.}, journal = {Breast (Edinburgh, Scotland)}, volume = {20}, number = {4}, pages = {303-308}, doi = {10.1016/j.breast.2010.08.003}, pmid = {21641801}, issn = {1532-3080}, mesh = {AIDS-Related Opportunistic Infections/diagnosis/*epidemiology ; Adult ; Breast Diseases/diagnosis/*epidemiology ; Breast Neoplasms/diagnosis/epidemiology ; Comorbidity ; Female ; Gynecomastia/epidemiology ; HIV Seropositivity/*epidemiology ; Hospitals, Teaching ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; *Severity of Illness Index ; }, abstract = {INTRODUCTION: HIV infection directly and indirectly affects breast tissue. This study describes the spectrum of HIV-related breast disease encountered at a community teaching hospital.<br><br>METHODS: A 9 year retrospective review was performed of HIV-positive patients with a breast-related diagnosis seen at our institution. Patient demographics, HIV status, comorbid disease, medications, clinical findings, diagnostic procedure, pathology, treatment and outcome were recorded.<br><br>RESULTS: A total of 46 individuals were included with a median age of 47 years (range 24-64 years) and male:female ratio of 1:3 (12 men and 34 women). Mean duration of HIV infection was 7 years during which time 46% of patients had an AIDS defining illness. Median CD4 cell count was 437 cells/mm(3) (range 2 to &#x2265;500 cells/mm(3)) at the time of the breast diagnosis. Breast disease identified included benign conditions (59% total: 92% for men, 47% for women), infection (17% total: 8% for men, 21% for women), cancer (22% total: 0% for men, 29% for women), and atypia (2% total: 0% for men, 3% for women). Patients with a breast infection had a lower median CD4 cell count than those with breast cancer or benign conditions. Gynecomastia was detected in seven out of 12 (58%) men. In these men, antiretroviral therapy (ART) of all drug classes was associated with gynecomastia. Breast cancer occurred only in women and included patients with invasive ductal carcinoma (n = 7), ductal carcinoma in situ (n = 2), and liposarcoma diagnosed in one individual. Specific risk factors for breast cancer in this setting were not identified. Five (11%) patients died, only one from breast disease during the study period.<br><br>CONCLUSION: These data indicate that increased longevity in patients with chronic HIV infection may be associated with the occurrence of breast conditions in both men and women. A broad spectrum of breast disease should be anticipated in HIV-infected persons living longer with effective ART.}, }
@article {pmid21640491, year = {2011}, author = {Shah, C and Wilkinson, JB and Shaitelman, S and Grills, I and Wallace, M and Mitchell, C and Vicini, F}, title = {Clinical outcomes using accelerated partial breast irradiation in patients with invasive lobular carcinoma.}, journal = {International journal of radiation oncology, biology, physics}, volume = {81}, number = {4}, pages = {e547-51}, doi = {10.1016/j.ijrobp.2011.04.050}, pmid = {21640491}, issn = {1879-355X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/drug therapy/mortality/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/chemistry/drug therapy/mortality/pathology/radiotherapy ; Carcinoma, Lobular/chemistry/drug therapy/mortality/pathology/*radiotherapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Radiotherapy/methods ; Treatment Outcome ; Tumor Burden ; }, abstract = {PURPOSE: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI).<br><br>METHODS AND MATERIALS: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed.<br><br>RESULTS: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients.<br><br>CONCLUSION: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.}, }
@article {pmid21632715, year = {2011}, author = {Harden, JL and Gu, T and Kilinc, MO and Rowswell-Turner, RB and Virtuoso, LP and Egilmez, NK}, title = {Dichotomous effects of IFN-γ on dendritic cell function determine the extent of IL-12-driven antitumor T cell immunity.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {187}, number = {1}, pages = {126-132}, pmid = {21632715}, issn = {1550-6606}, support = {R01 CA100656/CA/NCI NIH HHS/United States ; R01 CA100656-06/CA/NCI NIH HHS/United States ; R01-CA100656/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Movement/genetics/immunology ; Coculture Techniques ; Dendritic Cells/*immunology/metabolism/*pathology ; Granulocyte-Macrophage Colony-Stimulating Factor/administration &amp; dosage/physiology ; Immune Tolerance/genetics ; Interferon-gamma/deficiency/genetics/*physiology ; Interleukin-12/*administration &amp; dosage/physiology ; Lung Neoplasms/immunology/pathology/prevention &amp; control ; Lymph Nodes/immunology/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Mice, Transgenic ; Pulmonary Alveoli/immunology/metabolism/pathology ; T-Lymphocyte Subsets/*immunology/metabolism/*pathology ; Tumor Escape/genetics/*immunology ; }, abstract = {Sustained intratumoral delivery of IL-12 and GM-CSF can overcome tumor immune suppression and promote T cell-dependent eradication of established disease in murine tumor models. However, the antitumor effector response is transient and rapidly followed by a T suppressor cell rebound. The mechanisms that control the switch from an effector to a regulatory response in this model have not been defined. Because dendritic cells (DC) can mediate both effector and suppressor T cell priming, DC activity was monitored in the tumors and the tumor-draining lymph nodes (TDLN) of IL-12/GM-CSF-treated mice. The studies demonstrated that therapy promoted the recruitment of immunogenic DC (iDC) to tumors with subsequent migration to the TDLN within 24-48 h of treatment. Longer-term monitoring revealed that iDC converted to an IDO-positive tolerogenic phenotype in the TDLN between days 2 and 7. Specifically, day 7 DC lost the ability to prime CD8(+) T cells but preferentially induced CD4(+)Foxp3(+) T cells. The functional switch was reversible, as inhibition of IDO with 1-methyl tryptophan restored immunogenic function to tolerogenic DC. All posttherapy immunological activity was strictly associated with conventional myeloid DC, and no functional changes were observed in the plasmacytoid DC subset throughout treatment. Importantly, the initial recruitment and activation of iDC as well as the subsequent switch to tolerogenic activity were both driven by IFN-γ, revealing the dichotomous role of this cytokine in regulating IL-12-mediated antitumor T cell immunity.}, }
@article {pmid21569821, year = {2011}, author = {Tucci, M and Ciavarella, S and Strippoli, S and Brunetti, O and Dammacco, F and Silvestris, F}, title = {Immature dendritic cells from patients with multiple myeloma are prone to osteoclast differentiation in vitro.}, journal = {Experimental hematology}, volume = {39}, number = {7}, pages = {773-83.e1}, doi = {10.1016/j.exphem.2011.04.006}, pmid = {21569821}, issn = {1873-2399}, mesh = {Bone Marrow Cells/immunology/metabolism/pathology ; Cell Differentiation/*immunology ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12/immunology/metabolism ; Coculture Techniques ; Dendritic Cells/*immunology/metabolism/pathology ; Flow Cytometry ; Humans ; Immunohistochemistry ; Multiple Myeloma/*immunology/metabolism/pathology ; Osteoclasts/*immunology/metabolism ; RANK Ligand/immunology/metabolism ; Receptors, CXCR4/immunology/metabolism ; Receptors, Chemokine/genetics/immunology/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transmembrane Activator and CAML Interactor Protein/immunology/metabolism ; Tumor Cells, Cultured ; Tumor Necrosis Factor Ligand Superfamily Member 13/immunology/metabolism ; }, abstract = {OBJECTIVE: Recent studies demonstrated that the interactions of immature dendritic cells (iDCs) with myeloma cells enhance the clonogenic capacity of tumor cells while iDCs undergo osteoclast (OC) transformation. Here, we investigated these interactions as well as iDC behavior in terms of both migration and OC differentiation.<br><br>MATERIALS AND METHODS: We studied 12 patients with multiple myeloma (MM) and 5 with monoclonal gammopathy of undetermined significance. Chemokine receptors, tumor-mediated chemotaxis, and a proliferation-inducing ligand (APRIL) expression were investigated in iDCs, whereas receptor activator of nuclear factor &#x3ba;B ligand (RANKL) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) levels were measured in primary plasma cells. Furthermore, cocultures of myeloma cells with autologous iDCs were installed to verify OC differentiation of these cells. Finally, the role of RANK/RANKL in such OC differentiation was investigated by inhibiting this molecular pathway.<br><br>RESULTS: Peripheral and marrow iDCs from MM showed high CXCR4 expression and were augmented in bone marrow of MM patients with respect to monoclonal gammopathy of undetermined significance. Also, iDCs expressed APRIL, whereas RANKL and TACI were upregulated by malignant cells. The cellular contact of myeloma cells with iDCs enhanced the clonogenic effect on tumor growth, whereas iDCs were directly primed to undergo OC transformation. These iDCs, indeed, exerted typical bone resorption that was abrogated by disabling the RANK/RANKL pathway signals. By contrast, plasma cells from monoclonal gammopathy of undetermined significance patients were ineffective in transforming autologous iDCs.<br><br>CONCLUSIONS: Our results emphasize the marrow cross-talk of iDCs with myeloma cells as an additional mechanism that upregulates osteoclastogenesis in MM, and suggest that such a RANKL-mediated OC differentiation of iDCs observed in vitro may also occur in vivo.}, }
@article {pmid21558492, year = {2011}, author = {Foth, BJ and Zhang, N and Chaal, BK and Sze, SK and Preiser, PR and Bozdech, Z}, title = {Quantitative time-course profiling of parasite and host cell proteins in the human malaria parasite Plasmodium falciparum.}, journal = {Molecular &amp; cellular proteomics : MCP}, volume = {10}, number = {8}, pages = {M110.006411}, pmid = {21558492}, issn = {1535-9484}, mesh = {Aryldialkylphosphatase/genetics/metabolism ; Catalase/genetics/metabolism ; Cell Culture Techniques ; Erythrocytes/enzymology/metabolism/*parasitology ; *Host-Parasite Interactions ; Humans ; Lactoferrin/genetics/metabolism ; Malaria, Falciparum/*metabolism/parasitology ; Models, Biological ; Oxidoreductases Acting on CH-CH Group Donors/genetics/metabolism ; Plasmodium falciparum/growth &amp; development/metabolism/*physiology ; Protein Isoforms/genetics/metabolism ; Proteome/genetics/metabolism ; Protozoan Proteins/genetics/*metabolism ; Spores, Protozoan/metabolism ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase-1 ; Transcription, Genetic ; }, abstract = {Studies of the Plasmodium falciparum transcriptome have shown that the tightly controlled progression of the parasite through the intra-erythrocytic developmental cycle (IDC) is accompanied by a continuous gene expression cascade in which most expressed genes exhibit a single transcriptional peak. Because the biochemical and cellular functions of most genes are mediated by the encoded proteins, understanding the relationship between mRNA and protein levels is crucial for inferring biological activity from transcriptional gene expression data. Although studies on other organisms show that <50% of protein abundance variation may be attributable to corresponding mRNA levels, the situation in Plasmodium is further complicated by the dynamic nature of the cyclic gene expression cascade. In this study, we simultaneously determined mRNA and protein abundance profiles for P. falciparum parasites during the IDC at 2-hour resolution based on oligonucleotide microarrays and two-dimensional differential gel electrophoresis protein gels. We find that most proteins are represented by more than one isoform, presumably because of post-translational modifications. Like transcripts, most proteins exhibit cyclic abundance profiles with one peak during the IDC, whereas the presence of functionally related proteins is highly correlated. In contrast, the abundance of most parasite proteins peaks significantly later (median 11 h) than the corresponding transcripts and often decreases slowly in the second half of the IDC. Computational modeling indicates that the considerable and varied incongruence between transcript and protein abundance may largely be caused by the dynamics of translation and protein degradation. Furthermore, we present cyclic abundance profiles also for parasite-associated human proteins and confirm the presence of five human proteins with a potential role in antioxidant defense within the parasites. Together, our data provide fundamental insights into transcript-protein relationships in P. falciparum that are important for the correct interpretation of transcriptional data and that may facilitate the improvement and development of malaria diagnostics and drug therapy.}, }
@article {pmid21557333, year = {2011}, author = {Ismail, HM and Medhat, AM and Karim, AM and Zakhary, NI}, title = {FHIT gene and flanking region on chromosome 3p are subjected to extensive allelic loss in Egyptian breast cancer patients.}, journal = {Molecular carcinogenesis}, volume = {50}, number = {8}, pages = {625-634}, doi = {10.1002/mc.20797}, pmid = {21557333}, issn = {1098-2744}, mesh = {Acid Anhydride Hydrolases/*genetics ; Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosomes, Human, Pair 3 ; Egypt ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *Loss of Heterozygosity ; Microsatellite Repeats ; Middle Aged ; Neoplasm Proteins/*genetics ; }, abstract = {The fragile histidine triad gene (FHIT) is a candidate tumor suppressor gene at chromosome 3p14.2. Deletions in FHIT gene were reported in different types of cancer including breast cancer. In this study, we investigated the loss of heterozygosity (LOH) incidence that target FHIT genomic structure and chromosome 3p in cancerous and pre-neoplastic lesions of Egyptian breast patients. Genomic DNA was isolated from tumor tissues and their normal counterparts of 55 Egyptian patients diagnosed with breast cancer and 11 patients diagnosed with preneoplastic breast lesions. LOH was detected in 51% of breast cancer cases in at least one microsatellite marker of the four investigated markers. While, none of the markers showed LOH among the pre-neoplastic breast lesions. We also observed a significant association between LOH and invasive ductal carcinoma (IDC) histopathological type while no association observed between LOH and patients' age, tumor grade, or lymph node involvement. We also investigated FHIT gene expression profiles in breast cancer using Oncomine database. We found that FHIT is significantly reduced in all investigated studies. We conclude that, FHIT is underexpressed in breast cancer tissues compared to their normal counterparts due to the extensive allelic loss that is observed in its gene structure.}, }
@article {pmid21556773, year = {2012}, author = {Jin, B and Luo, XP and Ni, HC and Shen, W and Shi, HM and Li, Y}, title = {A meta-analysis of HLA-DR polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy.}, journal = {Molecular biology reports}, volume = {39}, number = {1}, pages = {221-226}, pmid = {21556773}, issn = {1573-4978}, mesh = {Cardiomyopathy, Dilated/*genetics ; Case-Control Studies ; Genetic Association Studies ; Genetic Predisposition to Disease/*genetics ; HLA-DR Antigens/*genetics ; Humans ; Polymorphism, Genetic/*genetics ; Sensitivity and Specificity ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR polymorphism and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 19 case-control studies including 1,378 cases and 10,383 controls provided data on the association between HLA-DR polymorphism and genetic susceptibility to IDC. Overall, statistically elevated frequencies of HLA-DR4 (OR 1.58; 95% CI 1.21-2.07; P=0.0009) and HLA-DR5 (OR 1.35; 95% CI 1.05-1.73; P=0.02) alleles were found in patients with IDC compared with controls. Individuals with HLA-DR3 antigen have a protective effect against IDC (OR 0.72; 95% CI 0.58-0.90; P=0.004). In summary, this meta-analysis indicated that certain HLA-DR alleles may be genetic markers for susceptibility and resistance to IDC.}, }
@article {pmid21555521, year = {2011}, author = {Li, X and Wen, W and Liu, K and Zhu, F and Malakhova, M and Peng, C and Li, T and Kim, HG and Ma, W and Cho, YY and Bode, AM and Dong, Z and Dong, Z}, title = {Phosphorylation of caspase-7 by p21-activated protein kinase (PAK) 2 inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell lines.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {25}, pages = {22291-22299}, pmid = {21555521}, issn = {1083-351X}, support = {CA120388/CA/NCI NIH HHS/United States ; R01 CA077646/CA/NCI NIH HHS/United States ; R37 CA081064/CA/NCI NIH HHS/United States ; CA077646/CA/NCI NIH HHS/United States ; R01 CA120388/CA/NCI NIH HHS/United States ; ES016548/ES/NIEHS NIH HHS/United States ; R01 ES016548/ES/NIEHS NIH HHS/United States ; CAR37CA081064//PHS HHS/United States ; }, mesh = {Amino Acid Sequence ; Antineoplastic Agents/*pharmacology/therapeutic use ; Apoptosis/*drug effects/genetics ; Base Sequence ; Breast Neoplasms/drug therapy/enzymology/metabolism/*pathology ; Carcinoma, Ductal/drug therapy/enzymology/metabolism/pathology ; Caspase 7/chemistry/*metabolism ; Cell Line, Tumor ; *Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockdown Techniques ; Humans ; Phosphorylation/drug effects ; Protein Transport ; p21-Activated Kinases/deficiency/genetics/*metabolism ; }, abstract = {p21-activated kinase (PAK) 2, a member of the PAK family of serine/threonine protein kinases, plays an important role in physiological processes such as motility, survival, mitosis, and apoptosis. However, the role of PAK2 in resistance to chemotherapy is unclear. Here we report that PAK2 is highly expressed in human breast cancer cell lines and human breast invasive carcinoma tissue compared with a human non-tumorigenic mammary epithelial cell line and adjacent normal breast tissue, respectively. Interestingly, we found that PAK2 can bind with caspase-7 and phosphorylate caspase-7 at the Ser-30, Thr-173, and Ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis. Our data indicate that highly expressed PAK2 mediates chemotherapeutic resistance in human breast invasive ductal carcinoma by negatively regulating caspase-7 activity.}, }
@article {pmid21527182, year = {2011}, author = {Tsai, SM and Hou, MF and Wu, SH and Hu, BW and Yang, SF and Chen, WT and Chai, CY and Ma, H and Tsai, LY}, title = {Expression of manganese superoxide dismutase in patients with breast cancer.}, journal = {The Kaohsiung journal of medical sciences}, volume = {27}, number = {5}, pages = {167-172}, doi = {10.1016/j.kjms.2010.11.003}, pmid = {21527182}, issn = {2410-8650}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Superoxide Dismutase/*metabolism ; Tumor Burden ; }, abstract = {Breast cancer has become the second leading cancer among females in Taiwan. Even though the etiology of breast cancer is multifactorial, oxidative stress plays an important role in the carcinogenesis. The purpose of this study was to investigate the expression of manganese superoxide dismutase (MnSOD), one of the major antioxidant enzymes that is involved against oxidative stress, in adjacent cancer-free breast tissues and neoplasm tissues within the same patient. Sixty-five breast cancer patients' formalin-fixed tissue blocks, including ductal carcinoma in situ (DCIS) tissues, invasive ductal carcinoma (IDC) tissues, and adjacent cancer-free tissues, were evaluated by immunohistochemical stain. Meanwhile, their demographic and clinical information was also collected. The combined scores of MnSOD-positive cell proportion and MnSOD staining intensity were compared for different tissues within the same patient. The results showed that the mean combined scores of MnSOD expression in adjacent cancer-free tissues (6.33), IDC (5.30), and DCIS (3.78) were significantly different when assessed by repeated-measurement analysis of variance (F=14.17, p<0.001). Additionally, the results revealed that the distribution of strong MnSOD protein expression was 80.0%, 72.3%, and 52.3% in adjacent cancer-free tissues, IDC, and DCIS, respectively. However, there was no statistically significant relationship between the expression of MnSOD and grades of breast cancer or other clinicopathologic variables. We suggest that the expression of MnSOD in neoplasm tissues, independent of the clinicopathologic characters, plays a critical role in breast cancer biology.}, }
@article {pmid21517259, year = {2011}, author = {Asif, M and Khadim, MT and Mushtaq, S and Mamoon, N and Akhtar, F and Ali, Z}, title = {Determination of her-2/neu by chromogenic in situ hybridization on borderline (2+) immunohistochemistry cases in carcinoma breast.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {12}, number = {1}, pages = {211-214}, pmid = {21517259}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/therapeutic use ; Breast Neoplasms/*enzymology/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/*metabolism/pathology ; Chromogenic Compounds/chemistry ; Cross-Sectional Studies ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Middle Aged ; Receptor, ErbB-2/genetics/*metabolism ; Trastuzumab ; Young Adult ; }, abstract = {OBJECTIVE: To determine the HER-2/neu status by chromogenic in situ hybridization (CISH) on tissue specimens with a borderline (2+) immunohistochemistry (IHC) score in carcinoma breast by a descriptive, cross-sectional study in the Histopathology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jun 2008 to Dec 2009.<br><br>METHODS: Tissue block specimens from 50 consecutive patients having HER-2/neu score of borderline (2+) on IHC assay were tested for HER-2/neu gene amplification by CISH. Mean and standard deviation were calculated for quantitative variables like age and HER-2/neu gene copy signal/clusters by using SPSS version 14. Frequencies and percentages were also calculated for qualitative variables like type of carcinoma and results of HER-2/neu by CISH (amplified/nonamplified).<br><br>RESULTS: HER-2/neu gene amplification by CISH was found in 10 (20%) out of 50 patients with borderline (2+) IHC score. All CISH amplified cases belonged to invasive ductal carcinoma type. No significant correlation was noted between type of carcinoma and HER-2/neu gene amplification.<br><br>CONCLUSION: Chromogenic in situ hybridization (CISH) is a practical, cost-effective and reliable method for analysis of HER-2/neu borderline (2+) cases which may be candidates for Herceptin therapy.}, }
@article {pmid21515791, year = {2011}, author = {Hawkins, O and Verma, B and Lightfoot, S and Jain, R and Rawat, A and McNair, S and Caseltine, S and Mojsilovic, A and Gupta, P and Neethling, F and Almanza, O and Dooley, W and Hildebrand, W and Weidanz, J}, title = {An HLA-presented fragment of macrophage migration inhibitory factor is a therapeutic target for invasive breast cancer.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {186}, number = {11}, pages = {6607-6616}, doi = {10.4049/jimmunol.1003995}, pmid = {21515791}, issn = {1550-6606}, mesh = {Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/*immunology/therapeutic use ; Antibody Affinity/immunology ; Antibody Specificity/immunology ; Apoptosis/drug effects/immunology ; Breast Neoplasms/drug therapy/*immunology/pathology ; Carcinoma, Ductal, Breast/drug therapy/immunology/pathology ; Cell Line ; Cell Line, Tumor ; Cell Survival/drug effects/immunology ; Dose-Response Relationship, Drug ; Female ; HLA-A Antigens/*immunology/metabolism ; HLA-A2 Antigen ; Humans ; Kinetics ; Macrophage Migration-Inhibitory Factors/chemistry/*immunology/metabolism ; Mice ; Mice, Nude ; Peptides/immunology/metabolism ; Prognosis ; Protein Binding/immunology ; Xenograft Model Antitumor Assays ; }, abstract = {This report describes a novel HLA/peptide complex with potential prognostic and therapeutic roles for invasive breast cancer. Macrophage migration inhibitory factor (MIF) mediates inflammation and immunity, and MIF overexpression is observed in breast cancer. We hypothesized that the HLA class I of cancerous breast epithelial cells would present MIF-derived peptides. Consistent with this hypothesis, the peptide FLSELTQQL (MIF(19-27)) was eluted from the HLA-A*0201 (HLA-A2) of breast cancer cell lines. We posited that if this MIF(19-27)/HLA-A2 complex was exclusively found in invasive breast cancer, it could be a useful prognostic indicator. To assess the presentation of MIF peptides by the HLA of various cells and tissues, mice were immunized with the MIF(19-27)/HLA-A2 complex. The resulting mAb (RL21A) stained invasive ductal carcinoma (IDC) but not ductal carcinoma in situ, fibroadenoma, or normal breast tissues. RL21A did not stain WBCs (total WBCs) or normal tissues from deceased HLA-A2 donors, substantiating the tumor-specific nature of this MIF/HLA complex. As this MIF/HLA complex appeared specific to the surface of IDC, RL21A was tested as an immunotherapeutic for breast cancer in vitro and in vivo. In vitro, RL21A killed the MDA-MB-231 cell line via complement and induction of apoptosis. In an in vivo orthotopic mouse model, administration of RL21A reduced MDA-MB-231 and BT-20 tumor burden by 5-fold and by >2-fold, respectively. In summary, HLA-presented MIF peptides show promise as prognostic cell surface indicators for IDC and as targets for immunotherapeutic intervention.}, }
@article {pmid21492377, year = {2011}, author = {Boccola, MA and Sharma, A and Taylor, C and Wong, LM and Travis, D and Chan, S}, title = {The infusion method trial of void vs standard catheter removal in the outpatient setting: a prospective randomized trial.}, journal = {BJU international}, volume = {107 Suppl 3}, number = {}, pages = {43-46}, doi = {10.1111/j.1464-410X.2011.10044.x}, pmid = {21492377}, issn = {1464-410X}, mesh = {Acute Disease ; Age Factors ; Aged ; Ambulatory Care/methods ; Confidence Intervals ; Device Removal/*methods ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pilot Projects ; Prospective Studies ; Reference Values ; Risk Assessment ; Statistics, Nonparametric ; Therapeutic Irrigation/methods ; Time Factors ; Treatment Outcome ; Urinary Catheterization/instrumentation/*methods ; Urinary Retention/etiology/physiopathology/*therapy ; Urination/physiology ; }, abstract = {OBJECTIVE: • To ascertain if filling the bladder with warm normal saline before trial of void (TOV) reduces time to decision of outcome of TOV and time to discharge compared with standard in-dwelling catheter (IDC) removal in the outpatient setting.<br><br>PATIENTS AND METHODS: &#x2022;&#x2007;A prospective randomized controlled trial (not blinded) was carried out in the day procedure unit. Randomization was done using computer-generated random numbers. The sample size was calculated based on initial pilot data using &#x3b1;= 0.05 and &#x3b2;= 0.2 and a clinically important reduction of &#x2265;60 min for time to decision of outcome of TOV (primary outcome measure). &#x2022;&#x2007;In all, 60 consecutive patients were recruited from two referral sources: presentations of acute urinary retention to the emergency department and patients discharged home after failing TOV postoperatively. &#x2022;&#x2007;The infusion method group (32 patients) had 300-500 mL warm normal saline infused into the bladder before removing their IDC and the control group (28) had standard IDC removal. &#x2022;&#x2007;Data were collected and analysed using the two-tailed Mann-Whitney U-test. Statistical significance was set at P < 0.05.<br><br>RESULTS: &#x2022;&#x2007;The median time to decision was 135.0 (95% confidence interval CI 95.0-190.0) min in the infusion group and 247.5 (95% CI 189.6-294.1) min in the control group. &#x2022;&#x2007;Patients undergoing a bladder infusion had a shorter discharge time [180.0 (95% CI 126.0-226.9) min] than patients in the standard-IDC-removal group [262.5 (95% CI 233.8-315.0) min]. &#x2022;&#x2007;The infusion arm shortened time to decision by 112.5 min (P < 0.001) and time to discharge by 82.5 min (P < 0.001). &#x2022;&#x2007;Furthermore, patients in the infusion group were 1.56 times more likely to achieve catheter-free state after TOV (risk ratio 1.56, 95% CI 1.03-2.36; P= 0.03).<br><br>CONCLUSION: &#x2022;&#x2007;The infusion method for TOV is safe and expeditious, making it ideal for the outpatient setting. This randomized study shows that the infusion method enables a rapid determination of outcome of TOV with a greater chance of success and shortened discharge times.}, }
@article {pmid21501039, year = {2011}, author = {Carvalho, R and Macias, V and Marques-Pinto, G and Afonso, A and Cardoso, J}, title = {Intertriginous pattern of toxic erythema of chemotherapy.}, journal = {Cutaneous and ocular toxicology}, volume = {30}, number = {4}, pages = {309-311}, doi = {10.3109/15569527.2011.572572}, pmid = {21501039}, issn = {1556-9535}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*adverse effects/therapeutic use ; Erythema/*chemically induced/diagnosis/drug therapy ; Female ; Glucocorticoids/administration &amp; dosage/therapeutic use ; Humans ; Intertrigo/*chemically induced/diagnosis/drug therapy ; Prednisolone/administration &amp; dosage/therapeutic use ; Treatment Outcome ; }, abstract = {Chemotherapeutic agents may induce both local and systemic cutaneous toxicity, and evaluation of these reactions in oncologic patients constitutes a real challenge. The authors describe a 78-year-old Caucasian woman, with a past medical history relevant for right radical mastectomy with axillary dissection because of stage 2 breast invasive ductal carcinoma (T2N3M0), referred to our department because of an intertriginous eruption in her groin. Two weeks before the eruption, a chemotherapy regime with cyclophosphamide, methotrexate, and 5-fluorouracil was performed. Examination revealed erythematous and dusky violaceous papules coalescing into edematous patches in the inguinal intertriginous area, including the internal surface of her thighs, groin, genital area, and intergluteal cleft. Skin cultures for bacteria and fungus were negative. Clinical and histological data were consistent with an intertriginous pattern of toxic erythema of chemotherapy (TEC). Oral prednisolone therapy (0.5 mg/kg) was started, tapered over a 1-week period, and along with general measures that included topical zinc oxide suspension, cutaneous lesions cleared completely within the first days. Although patient reassurance, she refused any kind of new chemotherapy infusions. Due to their high metabolic rate, the skin, mucous membranes, and annexes are one of the most important target organs of the toxicity associated with systemic chemotherapy. Several patterns of cutaneous eruptions to chemotherapy have been reported in the literature. Trying to resolve this issue, recently recommended was a new clinically descriptive term, TEC, in order to emphasize the overlapping features of these entities. Early recognition of this entity is critical, not just from a prognostic standpoint, but also to avoid unnecessary, potentially harmful therapeutic interventions.}, }
@article {pmid21498851, year = {2011}, author = {Isohashi, F and Konishi, K and Umegaki, N and Tanei, T and Koizumi, M and Yoshioka, Y}, title = {A case of bullous pemphigoid exacerbated by irradiation after breast conservative radiotherapy.}, journal = {Japanese journal of clinical oncology}, volume = {41}, number = {6}, pages = {811-813}, doi = {10.1093/jjco/hyr049}, pmid = {21498851}, issn = {1465-3621}, mesh = {Acute Disease ; Breast Neoplasms/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/radiotherapy/surgery ; Dose Fractionation, Radiation ; Drug Administration Schedule ; Female ; Glucocorticoids/administration &amp; dosage ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Pemphigoid, Bullous/diagnosis/*drug therapy/etiology/*prevention &amp; control ; Postmenopause ; Prednisone/*administration &amp; dosage ; Radiotherapy, Adjuvant/adverse effects ; }, abstract = {We present a case, considered to be a form of the Koebner phenomenon, of bullous pemphigoid that was exacerbated mainly within the irradiated field after breast conservative radiotherapy. In May 2009, a 60-year-old woman was diagnosed with bullous pemphigoid, which was treated with steroid therapy. The following month, she was diagnosed with breast cancer (invasive ductal carcinoma, pT1cN0M0). After breast conservative surgery in December 2009, conservative radiotherapy to the right breast was performed (50 Gy in 25 fractions). Portal skin showed no serious change (up to grade 1 skin erythema) and no bullous neogenesis during conservative radiotherapy. However, 2 months after conservative radiotherapy, new blisters became exacerbated mainly within the irradiated field but also in the area outside the irradiated field. Increasing the dosage of oral steroid and minocycline resulted in relief of bullous pemphigoid, although patchy skin pigmentation remained especially in the irradiated skin.}, }
@article {pmid21492761, year = {2011}, author = {Hershberger, RE and Siegfried, JD}, title = {Update 2011: clinical and genetic issues in familial dilated cardiomyopathy.}, journal = {Journal of the American College of Cardiology}, volume = {57}, number = {16}, pages = {1641-1649}, pmid = {21492761}, issn = {1558-3597}, support = {R01 HL058626/HL/NHLBI NIH HHS/United States ; R01 HL058626-11/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Cardiomyopathy, Dilated/diagnosis/genetics ; Genetic Testing/methods/trends ; Genotype ; High-Throughput Nucleotide Sequencing/methods/trends ; Humans ; Mutation/genetics ; Phenotype ; }, abstract = {A great deal of progress has recently been made in the discovery and understanding of the genetics of familial dilated cardiomyopathy (FDC). A consensus has emerged that with a new diagnosis of idiopathic dilated cardiomyopathy (IDC), the clinical screening of first-degree family members will reveal FDC in at least 20% to 35% of those family members. Point mutations in 31 autosomal and 2 X-linked genes representing diverse gene ontogeny have been implicated in causing FDC but account for only 30% to 35% of genetic causes. Next-generation sequencing methods have dramatically decreased sequencing costs, making clinical genetic testing feasible for extensive panels of dilated cardiomyopathy genes. Next-generation sequencing also provides opportunities to discover additional genetic causes of FDC and IDC. Guidelines for evaluation and testing of FDC and IDC are now available, and when combined with FDC genetic testing and counseling, will bring FDC/IDC genetics to the forefront of cardiovascular genetic medicine.}, }
@article {pmid21479713, year = {2011}, author = {Vaiyapuri, GR and Han, HC and Lee, LC and Tseng, LA and Wong, HF}, title = {Use of the Gynecare Prolift system in surgery for pelvic organ prolapse: 1-year outcome.}, journal = {International urogynecology journal}, volume = {22}, number = {7}, pages = {869-877}, pmid = {21479713}, issn = {1433-3023}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Loss, Surgical ; Buttocks ; Clinical Competence ; Female ; Gynecologic Surgical Procedures/adverse effects/instrumentation/*methods ; Hematoma/etiology ; Humans ; Learning Curve ; Length of Stay ; Middle Aged ; Pain, Postoperative/etiology ; Pelvic Organ Prolapse/complications/*surgery ; Recurrence ; Reoperation ; Retrospective Studies ; Suburethral Slings ; *Surgical Mesh ; Surgical Wound Dehiscence/etiology ; Thigh ; Treatment Outcome ; Urinary Incontinence, Stress/etiology/surgery ; Vagina/*surgery ; }, abstract = {INTRODUCTION AND HYPOTHESIS: This retrospective study reports the 1-year outcome in women who underwent mesh-augmented Prolift surgery performed from 2006 to 2008. There were a total of 254 patients, with 128, 106 and 20 patients receiving total, anterior and posterior Prolift, respectively.<br><br>METHODS: Incidence of thigh pain was lower in 2008 compared to 2006 and 2007 (p < 0.0001). The percentage of patients requiring blood transfusions (p = 0.09), duration of IDC &#x2265; 7 days (p = 0.27), wound dehiscence and re-operation rate were lower in 2008 in contrast to 2006 and 2007 (p = 0.43). Only 209 patients (82.3%) were available for review at 1 year. There were two (1.0%) cases of recurrent vault prolapse.<br><br>RESULTS: The subjective and objective cure rates at 1 year after this mesh implant surgery in 2006, 2007 and 2008 were 92.1% and 92.1%; 97.0% and 92.4% and 100% and 97%, respectively. The mesh erosion rate was remarkably lower in 2008 as compared to 2007 and 2006 (p < 0.001).<br><br>CONCLUSIONS: This synthetic mesh-augmented implant surgery is effective and safe, and surgical outcome appears related to the learning curve of the surgeon.}, }
@article {pmid21477174, year = {2011}, author = {Stolnicu, S and Preda, O and Kinga, S and Marian, C and Nicolau, R and Andrei, S and Nicolae, A and Nogales, FF}, title = {Florid, papillary endosalpingiosis of the axillary lymph nodes.}, journal = {The breast journal}, volume = {17}, number = {3}, pages = {268-272}, doi = {10.1111/j.1524-4741.2011.01081.x}, pmid = {21477174}, issn = {1524-4741}, mesh = {Axilla ; Breast Neoplasms/complications/metabolism/*pathology ; Carcinoma, Ductal, Breast/complications/metabolism/*pathology ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Diseases/complications/metabolism/*pathology ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {A 55-year-old woman underwent radical mastectomy and axillary node dissection because of an invasive ductal carcinoma with neuroendocrine features. Histologically, all 22 sampled lymph nodes had widespread cystic inclusions lined by a regular, serous-type epithelium positive for cytokeratin-7, WT-1, CA125, and estrogen receptors. Papillary projections were found in the lumen of some cysts. The lesions were consistent with florid, papillary endosalpingiosis (FPE), a hitherto unreported condition in a supradiaphragmatic location. Metastases from papillary carcinomas of ovary, breast, or thyroid were excluded considering the lesion's immunophenotype (negative for mammaglobin and TTF-1) and the absence of both atypical features and a concurrent abdominal serous tumor. In only one node, lesions co-existed with a metastasis of breast carcinoma. Supradiaphragmatic FPE represents a pitfall in the differential diagnosis of metastases, especially in sentinel nodes, since it may increase their size and reveal an unusual ultrasonographic image. Clinicopathologic findings and a focused immunohistochemical study led to the correct diagnosis of this benign lesion.}, }
@article {pmid21476934, year = {2011}, author = {Singh, AK and Parshad, R and Pasi, S and Madhavan, T and Das, SN and Mishra, B and Gill, K and Dalal, K and Dey, S}, title = {Prognostic significance of cyclooxygenase-2 and response to chemotherapy in invasive ductal breast carcinoma patients by real time surface plasmon resonance analysis.}, journal = {DNA and cell biology}, volume = {30}, number = {10}, pages = {801-807}, doi = {10.1089/dna.2011.1215}, pmid = {21476934}, issn = {1557-7430}, mesh = {Adult ; Aged ; Antineoplastic Agents/*administration &amp; dosage/therapeutic use ; *Biomarkers, Tumor/blood/genetics ; Blotting, Western ; Breast Neoplasms/blood/*diagnosis/mortality/pathology/therapy ; Breast Neoplasms, Male/blood/*diagnosis/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/blood/*diagnosis/mortality/pathology/therapy ; Chemotherapy, Adjuvant ; *Cyclooxygenase 2/blood/genetics ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Prognosis ; Surface Plasmon Resonance/instrumentation/*methods ; }, abstract = {Cyclooxygenase-2 (COX-2), an inducible enzyme, has been implicated in the progression and angiogenesis of breast cancer. The aim of the study is to quantify the concentration of COX-2 and its association with clinico-pathological parameters and response to treatment in patients with invasive ductal carcinoma receiving both neo-adjuvant and adjuvant chemotherapy. The level of COX-2 was estimated using a novel biosensor-based surface plasmon resonance technique in serum of 84 patients with breast cancer (48 patients of neo-adjuvant chemotherapy and 36 patients of adjuvant chemotherapy) and 40 age- and gender-matched normal individuals. A significant increase in COX-2 level was observed in patients compared with normal individuals (p>0.0001). The COX-2 level in serum was found to be significantly higher in patients with lymph node involvement (p<0.0061). 68% (33/48) of the patients receiving neo-adjuvant chemotherapy showed significantly (p<0.0025) reduced COX-2 levels. This study shows significant decrease of COX-2 level in patients with breast cancer treated with both neo-adjuvant and adjuvant chemotherapy. Estimation of COX-2 level in serum may serve as a tumor biomarker in patients with breast cancer.}, }
@article {pmid21464011, year = {2011}, author = {Sakr, R and Fleury, J and Prengel, C and Roynard, P and Daraï, E and Uzan, S and Rouzier, R and Bernaudin, JF}, title = {[Are centrosomal abnormalities correlated to DNA ploidy in breast cancer?].}, journal = {Annales de biologie clinique}, volume = {69}, number = {2}, pages = {181-189}, doi = {10.1684/abc.2011.0525}, pmid = {21464011}, issn = {0003-3898}, mesh = {Breast Neoplasms/*genetics ; *Centrosome ; DNA, Neoplasm/*genetics ; Humans ; *Ploidies ; Tumor Cells, Cultured ; }, abstract = {ADN ploidy was shown to play a role in genomic instability of cancer cells and prognosis. The implication of the centrosome in the cell cycle was also described. Therefore, new prognostic factors could be suggested for a better-tailored therapy. The purpose of this study is to search for correlation between centrosomal abnormality and ADN ploidy in breast cancer. Cell prints were prepared from cell culture of mesothelial ascitis, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Fresh cell prints were also obtained from cases with invasive carcinoma. The centrosome was labelled by an indirect immunofluorescence assay using anti-γ-tubulin antibody and F(ab')(2) FITC before quantification with fluorescence microscopy. ADN ploidy was scored with DNA index obtained by means of flux cytometry. The normal mesothelial cells (94% of cells with only one centrosome) and the diploid cell line MRC5 (68% of cells with two centrosomes) were used as controls. DNA ploidy was found to be correlated with centrosomal abnormality in MCF7 cell line (64% of cells had more than three centrosomes) but not in the 10 cases of invasive ductal carcinoma analysed in this study. The absence of correlation between DNA ploidy and centrosomal abnormality in breast cancer samples may be due to the small numbers of cases, the cell prints or tumorigenesis. Correlation analysis of a larger number of cases and types of breast lesions to numerical and morphological abnormalities of the centrosome are ongoing.}, }
@article {pmid21445088, year = {2012}, author = {van de Ven, R and Lindenberg, JJ and Reurs, AW and Scheper, RJ and Scheffer, GL and de Gruijl, TD}, title = {Preferential Langerhans cell differentiation from CD34(+) precursors upon introduction of ABCG2 (BCRP).}, journal = {Immunology and cell biology}, volume = {90}, number = {2}, pages = {206-215}, doi = {10.1038/icb.2011.25}, pmid = {21445088}, issn = {1440-1711}, mesh = {ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters/*metabolism ; Antigens, CD1/metabolism ; Antigens, CD34/metabolism ; Breast Neoplasms ; Cell Differentiation ; Cell Line, Tumor ; Dendritic Cells/cytology/immunology/*metabolism ; Female ; Hematopoietic Stem Cells/cytology/immunology/metabolism ; Humans ; Langerhans Cells/cytology/immunology/*metabolism ; Lectins, C-Type/immunology/metabolism ; Leukemia, Myeloid, Acute ; Neoplasm Proteins/*metabolism ; Skin/metabolism ; Transcription Factor RelB/metabolism ; Transforming Growth Factor beta/immunology/metabolism ; }, abstract = {Epidermal Langerhans cells (LC) and dermal interstitial dendritic cells (IDC) were found to express the ATP-binding cassette (ABC) transporter breast cancer resistance protein (BCRP; ABCG2). Also, low BCRP expression was present on CD34(+) blood DC precursors and expression was increased upon their differentiation to LC. The CD34(+) acute myeloid leukemia-derived DC cell line MUTZ3 can be cultured into LC or IDC, depending on the cytokine cocktail used. Introduction of functional BCRP in MUTZ3 progenitor cells through retroviral transduction resulted in the emergence of typical LC-characteristics in IDC cultures; the majority of cells remained negative for the IDC-specific C-type lectin DC-SIGN, but rather displayed enhanced expression of the LC-specific C-type lectin Langerin and characteristic high expression levels of CD1a. BCRP-induced skewing toward LC-like differentiation coincided with early RelB expression in 'IDC', derived from MUTZ3-BCRP, and depended on endogenous transforming growth factor beta (TGF-β) production. Intriguingly, cellular BCRP localization differed between skin LC and IDC, and a more cytoplasmic BCRP localization, as observed in primary skin LC, seemed to relate to LC-like differentiation in IDC cultures upon BCRP introduction in MUTZ3 progenitors. Together these data support a role for BCRP in preferential LC differentiation from CD34(+) myeloid DC progenitors.}, }
@article {pmid21443541, year = {2011}, author = {Kayashima, T and Nakata, K and Ohuchida, K and Ueda, J and Shirahane, K and Fujita, H and Cui, L and Mizumoto, K and Tanaka, M}, title = {Insig2 is overexpressed in pancreatic cancer and its expression is induced by hypoxia.}, journal = {Cancer science}, volume = {102}, number = {6}, pages = {1137-1143}, doi = {10.1111/j.1349-7006.2011.01936.x}, pmid = {21443541}, issn = {1349-7006}, mesh = {Carcinoma in Situ/genetics/metabolism/pathology ; Carcinoma, Pancreatic Ductal/*genetics/metabolism/pathology/secondary ; *Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; *Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics ; Lymphatic Metastasis ; Membrane Proteins/biosynthesis/*genetics ; Microarray Analysis ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*genetics/metabolism/pathology ; Polymerase Chain Reaction ; RNA, Messenger/biosynthesis/genetics ; RNA, Small Interfering ; *Tumor Microenvironment ; }, abstract = {A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin-induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. In this study, we evaluated Insig2 mRNA expression and the biological function of Insig2 in pancreatic cancer. We measured Insig2 mRNA expression in cultured pancreatic cancer cell lines and invasive ductal carcinoma (IDC) cells, normal pancreatic epithelial cells, and pancreatic intraepithelial neoplasia cells obtained by laser-capture microdissection. We also investigated the effects of Insig2-targeting siRNAs on the cell proliferation and cell invasion of pancreatic cancer cell lines. All pancreatic cancer cell lines expressed Insig2 mRNA. The PANC-1 and MIA PaCa-2 pancreatic cancer cell lines showed >2-fold higher Insig2 mRNA expression levels under hypoxic conditions (1% O2) than under normoxic conditions (21% O2). Cell proliferation was significantly decreased in SUIT-2 cells and cell invasion was significantly decreased in SUIT-2, Capan-2, and CFPAC-1 cells after transfection of the Insig2-targeting siRNAs. In analyses of microdissected cells, cells from IDC tissues expressed significantly higher levels of Insig2 mRNA than normal pancreatic cells (P < 0.001) and pancreatic intraepithelial neoplasia cells (P = 0.082). In analyses of IDC cells, the levels of Insig2 mRNA expression were significantly higher in late-stage patients than in early-stage patients. The present data suggest that Insig2 is associated with the malignant potential of pancreatic cancer under hypoxic conditions.}, }
@article {pmid21427206, year = {2011}, author = {Goldwich, A and Prechtel, AT and Mühl-Zürbes, P and Pangratz, NM and Stössel, H and Romani, N and Steinkasserer, A and Kummer, M}, title = {Herpes simplex virus type I (HSV-1) replicates in mature dendritic cells but can only be transferred in a cell-cell contact-dependent manner.}, journal = {Journal of leukocyte biology}, volume = {89}, number = {6}, pages = {973-979}, doi = {10.1189/jlb.0310180}, pmid = {21427206}, issn = {1938-3673}, mesh = {Animals ; Blotting, Western ; Cell Adhesion ; Cell Communication ; Cell Movement ; Chlorocebus aethiops ; Dendritic Cells/*immunology/metabolism/*virology ; Herpes Simplex/immunology/metabolism/*transmission ; Herpesvirus 1, Human/*physiology ; RNA, Messenger/genetics ; RNA, Viral/genetics ; Vero Cells ; Viral Proteins/genetics/metabolism ; Virion/*physiology ; *Virus Replication ; }, abstract = {HSV-1 is a very successful representative of the α-herpesvirus family, and ∼ 90% of the population is seropositive for this particular virus. Although the pathogen usually causes the well-known mild lesions on the lips, also, severe infections of the eye or the brain can be observed in rare cases. It is well known, that this virus can efficiently infect the most potent APCs, i.e., the DCs, in their immature and mature state. Although the infection of the iDC has been shown to be productive, infection of mMDDCs is believed to be abortive in the early phase of the viral replication cycle. In line with these findings, no virus particles can be detected in the supernatant of HSV-1-infected mMDDC. In this study, however, we show for the first time that this pathogen completes its replication cycle in mMDDCs. We detected the presence of viral gene transcripts of all three phases of the replication cycle, as well as of late viral proteins, and even the generation of small amounts of progeny virus. Although we could confirm the findings that these particles are not released into the supernatant, surprisingly, the newly generated viral particles can be passed on to Vero cells, as well as to primary keratinocytes in a cell-cell contact-dependent manner. Finally, we provide evidence that the viral gE is involved in the transfer of infectious virus from mMDDCs to other permissive cells.}, }
@article {pmid21423094, year = {2011}, author = {Sosonkina, N and Nakashima, M and Ohta, T and Niikawa, N and Starenki, D}, title = {Down-regulation of ABCC11 protein (MRP8) in human breast cancer.}, journal = {Experimental oncology}, volume = {33}, number = {1}, pages = {42-46}, pmid = {21423094}, issn = {2312-8852}, mesh = {ATP-Binding Cassette Transporters/*genetics/*metabolism ; Breast Neoplasms/*genetics/*metabolism/pathology ; Down-Regulation/*genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; RNA, Messenger/metabolism ; }, abstract = {AIM: To investigate the expression of ABCC11 (MRP8) protein in normal breast tissue, and examine the difference in ABCC11 mRNA and protein expression between normal breast and breast cancer tissues taking into account ABCC11 genotype (a functional SNP, rs17822931) and estrogen receptor (ER) status.<br><br>METHODS: Sections of paraffin-embedded normal and malignant tissues from 10 patients with invasive ductal carcinoma were used for immunohistochemical analysis. DNA and RNA were extracted from the same sections and used for genotyping and ABCC11 transcript expression measurement by quantitative RT-PCR.<br><br>RESULTS: A strong expression of ABCC11 was found in epithelial and myoepithelial cells of normal breast lobules and ducts in individuals with different ABCC11 genotypes. A predominant decrease of ABCC11 expression was observed in malignant tissue compared to normal beast specimen (8 of 10 cases), despite four out of ten tumors showed the elevated ABCC11 mRNA level as compared to the normal counterpart. Neither ABCC11 mRNA nor protein expression in normal or cancerous tissue correlated with ER status.<br><br>CONCLUSION: The expression of ABCC11 protein appears to be decreased in most BC. The effect of ABCC11 protein on breast cancer chemosensitivity is likely to be more complex than that which can be directly inferred from ABCC11 genotype and mRNA expression level in the tumor.}, }
@article {pmid21421525, year = {2011}, author = {Wernicke, AG and Goltser, Y and Trichter, S and Sabbas, A and Gaan, J and Swistel, AJ and Magro, CM}, title = {Morphea as a consequence of accelerated partial breast irradiation.}, journal = {Clinical breast cancer}, volume = {11}, number = {1}, pages = {67-70}, doi = {10.3816/CBC.2011.n.012}, pmid = {21421525}, issn = {1938-0666}, mesh = {Aged ; Brachytherapy/*adverse effects ; Breast Neoplasms/complications/*radiotherapy ; Carcinoma, Ductal, Breast/complications/*radiotherapy ; Female ; Humans ; Radiation Injuries/drug therapy/*etiology ; Scleroderma, Localized/drug therapy/*etiology ; Treatment Outcome ; }, abstract = {Morphea is a localized form of scleroderma usually unaccompanied by the typical systemic stigmata that characterize progressive systemic scleroderma. It rarely manifests at the site of whole breast external-beam radiation therapy. We present an unusual case of radiation-induced morphea (RIM) that occurred after accelerated partial breast irradiation (APBI) using intracavitary Contura brachytherapy. A 65-year-old white woman was treated for stage IIA invasive ductal carcinoma of the left breast with APBI to a dose of 34 Gy in 3.4-Gy fractions twice daily over the course 5 days with intracavitary brachytherapy. At 1.5 years after completion of APBI, the patient developed an area of tenderness, erythema, and induration at the site of irradiation. A skin biopsy was consistent with morphea. To our knowledge, this is the first case of RIM confined to the area of APBI.}, }
@article {pmid21410586, year = {2011}, author = {Zhang, F and Qi, X and Xu, Y and Zhou, Y and Zhang, Y and Fan, L and Zhong, L and Yang, X and Jiang, J}, title = {Breast cancer and Poland's syndrome: a case report and literature review.}, journal = {The breast journal}, volume = {17}, number = {2}, pages = {196-200}, doi = {10.1111/j.1524-4741.2010.01042.x}, pmid = {21410586}, issn = {1524-4741}, mesh = {Adult ; Breast Neoplasms/*complications/*diagnosis/surgery ; Carcinoma, Ductal/*complications/*diagnosis/surgery ; Female ; Humans ; Lymphatic Metastasis/diagnosis ; Mammography ; Mastectomy, Modified Radical ; Neoplasm Invasiveness ; Poland Syndrome/*complications/diagnostic imaging/pathology ; Ultrasonography ; }, abstract = {Poland's syndrome is a rare congenital development malformation characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. It is also known to be associated with some malignant diseases. We herein report a case of Poland's syndrome associated with invasive ductal carcinoma of breast, and review the literatures to investigate the clinical characteristics of breast cancer with Poland's syndrome.}, }
@article {pmid21403445, year = {2011}, author = {Kusama, M}, title = {[A case of secondary inflammatory breast cancer with multiple metastases in which operation was possible through letrozole monotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {38}, number = {3}, pages = {419-422}, pmid = {21403445}, issn = {0385-0684}, mesh = {Antineoplastic Agents/*therapeutic use ; Biopsy, Needle ; Carcinoma, Ductal, Breast/diagnostic imaging/*drug therapy/pathology/surgery ; Catheter Ablation ; Combined Modality Therapy ; Female ; Humans ; Inflammatory Breast Neoplasms/diagnostic imaging/*drug therapy/secondary ; Letrozole ; Middle Aged ; Neoplasm Metastasis/drug therapy ; Nitriles/*therapeutic use ; Positron-Emission Tomography ; Triazoles/*therapeutic use ; }, abstract = {A 55-year-old woman visited our clinic for rapid swelling of her left breast. The left breast was palpated, and a mass of about 10 cm with thick skin, and multiple lymph nodes in the supraclavicle and axilla were found. PET-CT images showed an increased uptake in her left breast, lymph nodes, spine of TH5, sternum, left lobe of liver, and both lungs. The serum tumor markers were also found to be elevated. A core needle biopsy was performed, and the tumor was diagnosed as secondary inflammatory carcinoma (invasive ductal carcinoma). Immunohistochemical staining showed negative for HER2 protein, but strongly positive for ER and PgR. Letrozole monotherapy administered her starting June, 2008. After 3 months, the metastases showed a notable response, which was subsequently maintained for 19 months. The tumor markers decreased to the normal range after 6 months, and the multiple metastases were not found by PET-CT after 1 year. A radiofrequency ablation operation was conducted on the remaining 3 cm breast cancer. Neoadjuvant endocrine therapy with letrozole was shown to be useful for post-menopausal breast cancer patients with strong hormone receptor expression.}, }
@article {pmid21377646, year = {2011}, author = {Fernandes, FP and Manlhiot, C and McCrindle, BW and Mertens, L and Kantor, PF and Friedberg, MK}, title = {Usefulness of mitral regurgitation as a marker of increased risk for death or cardiac transplantation in idiopathic dilated cardiomyopathy in children.}, journal = {The American journal of cardiology}, volume = {107}, number = {10}, pages = {1517-1521}, doi = {10.1016/j.amjcard.2011.01.030}, pmid = {21377646}, issn = {1879-1913}, mesh = {Cardiomyopathy, Dilated/drug therapy/*mortality/*surgery ; Child ; Echocardiography ; Female ; *Heart Transplantation ; Humans ; Male ; Mitral Valve Insufficiency/*complications/physiopathology ; Prognosis ; Retrospective Studies ; Risk Factors ; }, abstract = {In adults with idiopathic dilated cardiomyopathy (IDC), mitral regurgitation (MR) is associated with adverse prognosis and is often addressed by surgery or intervention. MR is commonly found in children with IDC, but its prognostic relevance has not been defined, and interventions to reduce MR are not routinely performed in this population. In this study, it was hypothesized that MR is an independent risk factor for death or transplantation. This was a single-center, retrospective study of sequential patients with IDC or familial IDC (left ventricular end-diastolic dimension z score >2 and ejection fraction <50%). Patients with acute myocarditis or previous mitral surgery were excluded. MR severity was graded according to American Society of Echocardiography guidelines as mild, moderate, or severe on the basis of MR jet vena contracta width. Left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were measured by biplane Simpson's method. Forty-two children with IDC were studied. The mean follow-up period was 25 months. At initial assessment, 34 children (82%) were taking angiotensin-converting enzyme inhibitors, 25 (60%) furosemide, 27 (65%) β blockers, and 7 (17%) intravenous inotropes. The mean indexed end-systolic volume was 91 ± 51 ml/m(2). The mean ejection fraction was 27 ± 16%. MR was mild in 42%, moderate in 19%, severe in 2%, and absent in 35% of patients. MR severity progressed from initial to last evaluation. MR severity was an independent risk factor for lower freedom from death or transplantation. Progression in MR severity increased the annual hazard of death or transplantation by a factor of 2.4 (p = 0.003). In conclusion, MR severity is independently associated with worse clinical status and decreased freedom from death or transplantation in children with IDC.}, }
@article {pmid21368500, year = {2011}, author = {Takamizawa, J and Kuze, S and Kyokane, T and Shibahara, H and Nakamura, H and Baba, S}, title = {[A case of pancreatic metastasis from breast cancer during multimodality therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {38}, number = {2}, pages = {301-303}, pmid = {21368500}, issn = {0385-0684}, mesh = {Biopsy ; Breast Neoplasms/*drug therapy/pathology ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Pancreatic Neoplasms/*drug therapy/secondary ; Tomography Scanners, X-Ray Computed ; }, abstract = {We report a case of pancreatic metastasis from breast cancer during multimodality therapy. A 53-year-old woman received right breast-conserving surgery for invasive ductal carcinoma and then chemo-radiotherapy for liver, brain, bone, neck and axillary lymphnodes, mediastinum, pleural, and spinal cord metastasis. Although she then survived in a tumor-free condition, a blood examination performed 4 years after the surgery showed an elevated serum amylase level. Abdominal CT and US revealed swelling of the pancreas head and body with main pancreatic duct dilatation of the pancreatic tail. ERCP showed diffuse stenosis of the extrahepatic bile duct and the main pancreatic duct of the pancreatic head and body. Immunohistochemical staining of the biopsy specimen from the pancreatic head confirmed pancreatic metastasis from breast cancer. Despite the intensive chemotherapy including trastuzumab, she died 2 years after the onset of pancreatic metastasis. Metastatic breast cancer to the pancreas is very rare. However, considering the recent advances of multimodality therapy for breast cancer, this clinical state may become more common.}, }
@article {pmid21358084, year = {2010}, author = {Piroozmand, A and Hassan, ZM}, title = {Evaluation of natural killer cell activity in pre and post treated breast cancer patients.}, journal = {Journal of cancer research and therapeutics}, volume = {6}, number = {4}, pages = {478-481}, doi = {10.4103/0973-1482.77110}, pmid = {21358084}, issn = {1998-4138}, mesh = {Adult ; Breast Neoplasms/*immunology/surgery ; Carcinoma, Ductal, Breast/*immunology/surgery ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural/*immunology ; Mastectomy ; Middle Aged ; }, abstract = {AIM: To evaluate natural killer (NK) cells activity in breast cancer patients and its comparison with normal individuals.<br><br>SETTINGS AND DESIGN: Breast cancer is the most prevalent type of spontaneous tumor in humans, and NK cells are the first line defense against such tumors. There is a reverse correlation between NK activity and metastasis and reducing the tumor mass by surgery may be monitoring the NK activity. In this study, we evaluate NK activity in pre and post mastectomy patients.<br><br>MATERIALS AND METHODS: Eighteen patients with invasive ductal carcinoma attended to cancer research institute were included in this study. NK cells were evaluated in pre and post mastectomy patients. PBMCs were isolated by ficoll hypaque. NK cell activity (% lysis of K562) was evaluated by flow cytometer.<br><br>STATISTICAL ANALYSIS USED: One way analysis of variation (ANOVA) and Kruskal Wallis nonparametric test were employed using SPSS software.<br><br>RESULTS: While NK cell activity was greatly impaired in breast cancer patients (average lysis of K562 target cells: 24.4% vs. 62.5% in healthy controls, n = 18), it was found to be significantly increased after mastectomy (37.7%).<br><br>CONCLUSIONS: Mastectomy may lead to increased activity of NK cells among patients suffering from breast cancer and their increased activity may produce positive therapeutic effect.}, }
@article {pmid21351127, year = {2011}, author = {Rovner, E and Kennelly, M and Schulte-Baukloh, H and Zhou, J and Haag-Molkenteller, C and Dasgupta, P}, title = {Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder.}, journal = {Neurourology and urodynamics}, volume = {30}, number = {4}, pages = {556-562}, doi = {10.1002/nau.21021}, pmid = {21351127}, issn = {1520-6777}, support = {//Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Botulinum Toxins, Type A/administration &amp; dosage/*therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Humans ; Injections, Intramuscular ; Intention to Treat Analysis ; Male ; Middle Aged ; Patient Selection ; Treatment Outcome ; Urinary Bladder, Overactive/complications/*drug therapy ; Urinary Incontinence/complications/*drug therapy ; Urodynamics/drug effects ; }, abstract = {AIMS: We assessed the effects of onabotulinumtoxinA (BOTOX®) on clinical and urodynamic variables in patients with idiopathic overactive bladder (OAB) and urinary urgency incontinence (UUI) with or without detrusor overactivity (DO), inadequately managed with anticholinergics.<br><br>METHODS: Three hundred thirteen patients with OAB were randomized to double-blind intradetrusor injection with placebo (n&#x2009;=&#x2009;44) or 1 of 5 onabotulinumtoxinA doses (50-300&#x2009;U; n&#x2009;=&#x2009;269). Primary efficacy variable was change from baseline in UUI episodes/week at week 12. Urodynamic assessments at baseline and weeks 12 and 36 included maximum cystometric capacity (MCC) and volume at first involuntary detrusor contraction (IDC).<br><br>RESULTS: 76.0% of patients had baseline DO. Changes from baseline in MCC and volume at first IDC with onabotulinumtoxinA &#x2265;100&#x2009;U were superior to placebo at week 12, generally decreasing by week 36. Significant dose-dependent increases in MCC were observed for all onabotulinumtoxinA doses at week 12, and for 150, 200, and 300&#x2009;U at week 36. Data suggested a dose-response relationship. At week 12 on diary, 15.9% of placebo and 29.8-57.1% of onabotulinumtoxinA 50-300&#x2009;U recipients, respectively, did not demonstrate UUI. OnabotulinumtoxinA doses >150&#x2009;U were more commonly associated with post-void residual urine volumes >200&#x2009;ml.<br><br>CONCLUSIONS: Improvements in urodynamic parameters and clinical outcomes generally trended together following onabotulinumtoxinA treatment. This therapy improved key urodynamic parameters in patients with idiopathic OAB and UUI, with no differences in outcomes between those with and those without baseline DO. Therefore, successful idiopathic OAB treatment with onabotulinumtoxinA does not appear to be related to pretreatment finding of DO.}, }
@article {pmid21336547, year = {2011}, author = {Molyneux, G and Smalley, MJ}, title = {The cell of origin of BRCA1 mutation-associated breast cancer: a cautionary tale of gene expression profiling.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {16}, number = {1}, pages = {51-55}, pmid = {21336547}, issn = {1573-7039}, mesh = {Animals ; BRCA1 Protein/*genetics ; Breast Neoplasms/*genetics ; Female ; Gene Expression Profiling ; Genes, BRCA1 ; Humans ; Mice ; Microarray Analysis ; }, abstract = {Breast tumours are highly heterogeneous with several distinct sub-types recognised according to their histological and molecular features. The biological basis for this heterogeneity is largely unknown, although there are some distinct phenotype-genotype correlations. These include BRCA1 mutation-associated breast cancers, which are typically high grade invasive ductal carcinomas of no special type (IDC-NSTs) with pushing margins that do not express estrogen receptor (ER), progesterone receptor (PR) or the HER2 receptor tyrosine kinase ('triple negative'). Gene expression analysis of these tumours has grouped them with so called 'basal-like' breast cancers and this, together with evidence that knock-down of BRCA1 in vitro blocked luminal differentiation, led to speculation that these tumours arose from the normal basal stem cells within the mammary gland. Recently, however, human breast tissue from BRCA1 mutation carriers was shown to contain an expanded population of luminal progenitor cells which have increased in vitro clonogenic ability. In the mouse, targeted deletion of Brca1 in luminal ER negative progenitors resulted in the formation of mammary tumours which phenocopied human BRCA1 breast tumour pathology, while the deletion of Brca1 in basal stem cells resulted in the formation of tumours which neither resembled human BRCA1 tumours or sporadic basal-like breast tumours. Importantly, however, both sets of mouse tumours were classified as 'basal-like' by methods used for human tumour classification based on gene expression profiles. This demonstrates that, as it stands, expression profiling is poor at distinguishing tumour histological subtypes and is also a poor guide to the cell of tumour origin. These human and rodent studies support an origin of BRCA1-mutation associated breast cancer (and indeed of the majority of sporadic basal-like breast cancers) in a luminal ER negative mammary epithelial progenitor. This is a key finding, as identification of the cells of origin in breast cancer subtypes makes possible the identification of key processes associated with initiation, progression and maintenance of each tumour subtype, the development of novel targeted therapies and, potentially, of new preventative approaches in high risk groups.}, }
@article {pmid21334720, year = {2011}, author = {Tian, Z and Wei, B and Tang, F and Wei, W and Gilcrease, MZ and Huo, L and Albarracin, CT and Resetkova, E and Middleton, L and Sahin, A and Xing, Y and Hunt, KK and Chen, J and Bu, H and Rashid, A and Abraham, SC and Wu, Y}, title = {Prognostic significance of tumor grading and staging in mammary carcinomas with neuroendocrine differentiation.}, journal = {Human pathology}, volume = {42}, number = {8}, pages = {1169-1177}, doi = {10.1016/j.humpath.2010.11.014}, pmid = {21334720}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/mortality/*pathology/surgery ; Carcinoma, Ductal, Breast/mortality/*secondary/surgery ; Carcinoma, Neuroendocrine/mortality/*secondary/surgery ; Cell Nucleus/pathology ; Cell Proliferation ; Cell Transformation, Neoplastic/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Mastectomy/methods ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Survival Rate ; }, abstract = {Invasive mammary carcinoma with neuroendocrine differentiation has been controversial in terms of its definition and clinical outcome. In 2003, the World Health Organization histologic classification of tumors designated this entity as neuroendocrine carcinoma of the breast and defined mammary neuroendocrine carcinoma as expression of neuroendocrine markers in more than 50% of tumor cells. It is an uncommon neoplasm. Our recent study showed that it is a unique clinicopathologic entity and has a poor clinical outcome compared with invasive mammary carcinoma with similar pathologic stage. Other investigators have also demonstrated a different molecular profile in this type of tumor from that of invasive ductal carcinoma. It is unknown whether the current prognostic markers for invasive mammary carcinoma are also applicable for neuroendocrine carcinoma of the breast. In the current study, we reviewed the clinicopathologic features and outcome data in 74 cases of mammary neuroendocrine carcinoma from the surgical pathology files at The University of Texas, MD Anderson Cancer Center, to identify relevant prognostic markers for this tumor type. As shown previously by univariate analysis, large tumor size, high nuclear grade, and presence of regional lymph node metastasis are adverse prognostic factors for overall survival and distant recurrence-free survival. In the current study, multivariate analysis revealed that overall survival was predicted by tumor size, lymph node status, and proliferation rate as judged by Ki-67 immunohistochemistry. Only nodal status proved to be a significant independent prognostic factor for distant recurrence-free survival. Neither mitosis score nor histologic grade predicted survival in mammary neuroendocrine carcinoma. Our data suggest that routine evaluation of Ki-67 proliferation index in these unusual tumors may provide more valuable information than mitotic count alone.}, }
@article {pmid21333994, year = {2011}, author = {Buttari, B and Profumo, E and Di Cristofano, C and Pietraforte, D and Lionetti, V and Capoano, R and Salvati, B and Businaro, R and Di Giammarco, G and Riganò, R}, title = {Haemoglobin triggers chemotaxis of human monocyte-derived dendritic cells: possible role in atherosclerotic lesion instability.}, journal = {Atherosclerosis}, volume = {215}, number = {2}, pages = {316-322}, doi = {10.1016/j.atherosclerosis.2010.12.032}, pmid = {21333994}, issn = {1879-1484}, mesh = {Actins/metabolism ; Antigens, CD/immunology ; Antigens, Differentiation, Myelomonocytic/immunology ; Cell Adhesion ; Chemotaxis, Leukocyte/*drug effects ; Dendritic Cells/*immunology ; Endothelial Cells ; Extracellular Signal-Regulated MAP Kinases/physiology ; Hemoglobins/metabolism/*pharmacology ; Humans ; Monocytes/cytology ; Plaque, Atherosclerotic/blood/physiopathology ; Receptors, Cell Surface/immunology ; Signal Transduction ; Transendothelial and Transepithelial Migration/*drug effects ; p38 Mitogen-Activated Protein Kinases/physiology ; }, abstract = {OBJECTIVE: Mechanisms that drive innate immune cell recruitment into atherosclerotic lesions are still not well defined. We tested the role of haemoglobin (Hb) to promote chemotaxis, adhesion to endothelial cells and transendothelial migration of human monocytes and monocyte-derived immature dendritic cells (iDCs) and its possible role in atherogenic cell recruitment.<br><br>METHODS AND RESULTS: We demonstrated that Hb triggers chemotaxis, adhesion to endothelial cells and transendothelial migration of monocytes and monocyte-derived iDCs. Innate immune cell chemotaxis significantly increased in the presence of Hb in a dose-dependent manner involving extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) activation and actin remodeling. The pre-treatment of cells with pre-titrated concentration of the anti-CD163 blocking antibody reduced the Hb-induced cell migration, thus suggesting the involvement of CD163 receptor. Conversely, N-acetyl cysteine and soluble Hb-scavenger protein haptoglobin (Hp) inhibited the Hb-induced iDC migration. Finally, spontaneous iDC migration significantly increased in the presence of serum of patients with haemorrhagic complicated plaques and partially decreased in the presence of Hp.<br><br>CONCLUSION: Hb by interacting with CD163 on monocytes and iDCs might induce cell recruitment and activation within vascular wall, thus contributing to the complex cross talk of chemotactic signals that mediate atherosclerotic lesions instability.}, }
@article {pmid21321311, year = {2011}, author = {Chakravarty, G and Moroz, K and Makridakis, NM and Lloyd, SA and Galvez, SE and Canavello, PR and Lacey, MR and Agrawal, K and Mondal, D}, title = {Prognostic significance of cytoplasmic SOX9 in invasive ductal carcinoma and metastatic breast cancer.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {236}, number = {2}, pages = {145-155}, doi = {10.1258/ebm.2010.010086}, pmid = {21321311}, issn = {1535-3699}, mesh = {Biomarkers ; Breast Neoplasms/*diagnosis/*pathology/secondary ; Carcinoma, Ductal, Breast/*diagnosis/*pathology/secondary ; Cytoplasm/*enzymology ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Lymph Nodes/pathology ; Microarray Analysis ; Neoplasm Metastasis/diagnosis/pathology ; Prognosis ; SOX9 Transcription Factor/*metabolism ; Severity of Illness Index ; Survival Analysis ; }, abstract = {SOX9, a high mobility group (HMG) box transcription factor, is required for development, differentiation and lineage commitment. It is known to exert its effects through nuclear translocation, such as cell cycle changes in response to retinoic acid treatment in breast cancer cells. However, it is not known whether SOX9 has prognostic significance in human breast cancer. Over-expression and cytoplasmic sequestration of nuclear proteins are implicated in tumor progression. To determine whether SOX9 has any prognostic significance in human breast cancer, its expression and subcellular localization were analyzed in more than 200 human breast carcinomas (BCs). SOX9 mRNA expression data for human BCs were computed from microarray studies available in public databases and correlated with known poor prognostic parameters of BCs. SOX9 protein expression and its correlation with Ki-67 staining in human BCs were assessed using immunohistochemistry. Higher SOX9 mRNA levels were significantly associated with estrogen receptor negative (P ≤ 0.001) and higher grade (P ≤ 0.01) human breast tumors. Patients with higher SOX9 mRNA level had significantly shorter overall survival (P ≤ 0.0001). SOX9 protein, which is normally nuclear, was instead localized in the cytoplasm of 25-30% invasive ductal carcinomas (IDCs) and lymph node metastases. Its cytoplasmic accumulation significantly correlated with enhanced proliferation in breast tumors (Kendall's tau = 0.337 with a P value < 0.0001). Cytoplasmic SOX9 can serve as a valuable prognostic marker for IDCs and metastatic breast cancer. Its significant correlation with breast tumor cell proliferation implies that SOX9 directly contributes to the poor clinical outcomes associated with invasive breast cancer.}, }
@article {pmid21314937, year = {2011}, author = {Kretschmer, C and Sterner-Kock, A and Siedentopf, F and Schoenegg, W and Schlag, PM and Kemmner, W}, title = {Identification of early molecular markers for breast cancer.}, journal = {Molecular cancer}, volume = {10}, number = {1}, pages = {15}, pmid = {21314937}, issn = {1476-4598}, mesh = {Animals ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Mammary Neoplasms, Experimental/*diagnosis/metabolism/pathology ; Mice ; Microarray Analysis ; Neoplasm Invasiveness/diagnosis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: The ductal carcinoma in situ (DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma. Since DCIS is a curable disease, it would be highly desirable to identify molecular markers that allow early detection. Mice transgenic for the WAP-SV40 early genome region were used as a model for DCIS development. Gene expression profiling was carried out on DCIS-bearing mice and control animals. Additionally, a set of human DCIS and invasive mammary tumors were analyzed in a similar fashion. Enhanced expression of these marker genes in human and murine samples was validated by quantitative RT-PCR. Besides, marker gene expression was also validated by immunohistochemistry of human samples. Furthermore in silico analyses using an online microarray database were performed.<br><br>RESULTS: In DCIS-mice seven genes were identified that were significantly up-regulated in DCIS: DEPDC1, NUSAP1, EXO1, RRM2, FOXM1, MUC1 and SPP1. A similar up-regulation of homologues of the murine genes was observed in human DCIS samples. Enhanced expression of these genes in DCIS and IDC (invasive ductal carcinoma) was validated by quantitative RT-PCR and immunohistochemistry.<br><br>CONCLUSIONS: By comparing murine markers for the ductal carcinoma in situ (DCIS) of the mammary gland with genes up-regulated in human DCIS-samples we were able to identify a set of genes which might allow early detection of DCIS and invasive carcinomas in the future. The similarities between gene expression in DCIS and invasive carcinomas in our data suggest that the early detection and treatment of DCIS is of utmost relevance for the survival of patients who are at high risk of developing breast carcinomas.}, }
@article {pmid21312071, year = {2012}, author = {Liang, H and Zhong, Y and Huang, Y and Chen, G}, title = {Type 1 receptor parathyroid hormone (PTH1R) influences breast cancer cell proliferation and apoptosis induced by high levels of glucose.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {2}, pages = {439-445}, pmid = {21312071}, issn = {1559-131X}, mesh = {Animals ; Apoptosis ; Blotting, Western ; Breast Neoplasms/complications/drug therapy/metabolism/*pathology ; Carcinoma, Ductal, Breast/complications/drug therapy/metabolism/*pathology ; Cell Proliferation ; Cohort Studies ; Diabetes Mellitus, Type 2/drug therapy/etiology/metabolism/*pathology ; Female ; Follow-Up Studies ; Glucose/*pharmacology ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Rats ; Real-Time Polymerase Chain Reaction ; Receptor, Parathyroid Hormone, Type 1/antagonists &amp; inhibitors/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; Up-Regulation ; }, abstract = {Increased breast cancer incidence parallels the increase in cases of type 2 diabetes. We investigated the effect of type 1 receptor parathyroid hormone (PTH1R) expression on viability and apoptosis of breast cancer cells exposed to high levels of glucose. Upregulation of PTH1R was detected in patients with invasive ductal carcinoma of the breast and diabetes. In vitro, PTH1R silencing suppressed cell proliferation and apoptosis induced by high levels of glucose by regulating Bax/Bcl-2 expression. These results suggest PTH1R silencing may represent a novel treatment approach for patients diagnosed with invasive ductal carcinoma of the breast who are also managing diabetes.}, }
@article {pmid21299347, year = {2011}, author = {Lü, X and Xu, K and Lü, H and Yin, Y and Ma, C and Liu, Y and Li, H and Suo, Z}, title = {CD44(+)/CD24(-) cells are transit progenitors and do not determine the molecular subtypes and clinical parameters in breast carcinomas.}, journal = {Ultrastructural pathology}, volume = {35}, number = {2}, pages = {72-78}, doi = {10.3109/01913123.2010.544843}, pmid = {21299347}, issn = {1521-0758}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*immunology/pathology ; CD24 Antigen/*metabolism ; Carcinoma, Ductal, Breast/*immunology/pathology ; Cell Line, Tumor ; Female ; Fibroadenoma/*immunology/pathology ; Humans ; Hyaluronan Receptors/*metabolism ; Immunohistochemistry ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplastic Stem Cells/*immunology/pathology ; Phenotype ; }, abstract = {CD44(+)/CD24(-) cells have been associated with breast cancer stem/progenitor cell features. However, the status of this phenotype cells in normal, benign and malignant breast tissues has not been studied, and the clinical correlation of this subpopulation in breast cancer is not fully understood. The present study sought to identify these cells in a series of normal, benign, and malignant breast tissues and explore their correlation to the molecular subtypes of breast carcinoma and conventional pathological features. Double-staining immunohistochemistry (DIHC) of CD44 and CD24 was performed on 30 normal breast tissues, 30 breast fibroadenomas (FA), 60 breast invasive ductal carcinomas (IDC), and 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231). In the normal breast tissues and FAs, three phenotypes were observed including CD44(+)/CD24(+), CD44(+)/CD24(-), and CD44(-)/CD24(-) cells. In the IDCs, CD44(-)/CD24(+) cells were detected, in addition to the three aforementioned phenotypes. The strong positive rate (+++, incidence >60%) of CD44(+)/CD24(-) was significantly increased from normal breast tissue, FAs to IDCs (0.0%-->6.7%-->21.7%). However, the CD44(+)/CD24(-) cells didn't correlate with ages of patients, lymph node metastasis, tumor size, molecular subtypes, and the expression of ER, PR, HER-2, PS2, Bcl-2, nm23. The proportion of CD44(+)/CD24(-) cells in MCF-7, MDA-MB-468, and MDA-MB-231 was about 1, 5, and 80%, respectively. The results indicate that the CD44(+)/CD24(-) cells are transit progenitors and have no association with the molecular subtypes and clinicopathological parameters in the IDCs.}, }
@article {pmid21291532, year = {2011}, author = {Madeira, M and Mattar, A and Passos, RJ and Mora, CD and Mamede, LH and Kishino, VH and Torres, TZ and de Sá, AF and dos Santos, RE and Gebrim, LH}, title = {A case report of male breast cancer in a very young patient: what is changing?.}, journal = {World journal of surgical oncology}, volume = {9}, number = {}, pages = {16}, pmid = {21291532}, issn = {1477-7819}, mesh = {Adult ; Breast Neoplasms, Male/*diagnosis/therapy ; Carcinoma, Ductal, Breast/*diagnosis/therapy ; Combined Modality Therapy ; Fatal Outcome ; Fertility ; Humans ; Male ; Mammography ; Risk Factors ; }, abstract = {Male breast cancer accounts for 1% of all breast cancer cases, and men tend to be diagnosed at an older age than women (mean age is about 67 years). Several risk factors have been identified, such as genetic and hormonal abnormalities. The present study reported the case of a 25-year-old man who was diagnosed with an advanced invasive ductal carcinoma; however, he did not have any important risk factors. Even though more data is emerging about this disease, more efforts to understand risk factors, treatment options and survival benefits are needed. In this case, we discussed the risk factors as well as the impaired fertility associated with breast cancer therapies.}, }
@article {pmid21289332, year = {2011}, author = {Zakharchenko, O and Greenwood, C and Lewandowska, A and Hellman, U and Alldridge, L and Souchelnytskyi, S}, title = {Meta-data analysis as a strategy to evaluate individual and common features of proteomic changes in breast cancer.}, journal = {Cancer genomics &amp; proteomics}, volume = {8}, number = {1}, pages = {1-14}, pmid = {21289332}, issn = {1790-6245}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Down-Regulation ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Metabolic Networks and Pathways/genetics ; Neoplasm Invasiveness ; *Proteomics ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Tumor Suppressor Protein p53/genetics ; Up-Regulation ; }, abstract = {BACKGROUND: Individual differences among breast tumours in patients is a significant challenge for the treatment of breast cancer. This study reports a strategy to assess these individual differences and the common regulatory mechanisms that may underlie breast tumourigenesis.<br><br>MATERIALS AND METHODS: The two-step strategy was based firstly on a full-scale proteomics analysis of individual cases, and secondly on the analysis of common features of the individual proteome-centred networks (meta-data).<br><br>RESULTS: Proteomic profiling of human invasive ductal carcinoma tumours was performed and each case was analysed individually. Analysis of primary datasets for common cancer-related proteins identified keratins. Analysis of individual networks built with identified proteins predicted features and regulatory mechanisms involved in each individual case. Validation of these findings by immunohistochemistry confirmed the predicted deregulation of expression of CK2&#x3b1;, PDGFR&#x3b1;, PYK and p53 proteins.<br><br>CONCLUSION: Meta-data analysis allowed efficient evaluation of both individual and common features of the breast cancer proteome.}, }
@article {pmid21287281, year = {2011}, author = {Bagaria, SP and Shamonki, J and Kinnaird, M and Ray, PS and Giuliano, AE}, title = {The florid subtype of lobular carcinoma in situ: marker or precursor for invasive lobular carcinoma?.}, journal = {Annals of surgical oncology}, volume = {18}, number = {7}, pages = {1845-1851}, doi = {10.1245/s10434-011-1563-0}, pmid = {21287281}, issn = {1534-4681}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/classification/*diagnosis/metabolism ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/classification/*diagnosis/metabolism ; Carcinoma, Intraductal, Noninfiltrating/classification/*diagnosis/metabolism ; Carcinoma, Lobular/classification/*diagnosis/metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Risk Factors ; Survival Rate ; }, abstract = {BACKGROUND: Lobular carcinoma in situ (LCIS) is considered a risk factor-not a precursor-for both invasive lobular and ductal carcinoma. Florid LCIS (F-LCIS) is an architectural subtype of LCIS that does not express E-cadherin, yet has the histologic and often radiographic appearance of solid-type ductal carcinoma in situ (DCIS). Since DCIS is considered a precursor to invasive ductal carcinoma, should F-LCIS be considered a precursor to invasive lobular carcinoma (ILC)?<br><br>METHODS: Review of an institutional database identified cases of LCIS and solid-type DCIS diagnosed by excisional biopsy, segmentectomy, or mastectomy between 1991 and 2000 to determine the prevalence of associated invasive breast cancer. Archival specimens were evaluated for florid and nonflorid LCIS, nuclear grade of LCIS, and the presence and subtype of invasive breast cancer. Solid-type DCIS that lacked E-cadherin expression was classified as F-LCIS.<br><br>RESULTS: Of 210 consecutive specimens of LCIS examined, 171 had nonflorid LCIS (81%) and 39 had F-LCIS (19%). Nonflorid LCIS had a diffuse pattern, whereas F-LCIS appeared as discrete foci adjacent to ILC. An invasive component was identified with 87% of F-LCIS lesions versus 73% of nonflorid LCIS lesions (P = 0.064); this component was lobular in 100% of F-LCIS lesions versus 82% of nonflorid LCIS lesions, a significant difference (P = 0.0044) that persisted when the analysis was adjusted for nuclear grade (P = 0.0082).<br><br>CONCLUSION: Its close spatial relationship to an invasive component and increased association with ILC suggest that F-LCIS may be a precursor for ILC.}, }
@article {pmid21284437, year = {2011}, author = {Roy, I and Othieno, E}, title = {Breast carcinoma in Uganda: microscopic study and receptor profile of 45 cases.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {135}, number = {2}, pages = {194-199}, doi = {10.5858/2008-0421-SOR1.1}, pmid = {21284437}, issn = {1543-2165}, mesh = {Adult ; Age Factors ; Age of Onset ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Receptor, ErbB-2/biosynthesis/genetics ; Receptors, Estrogen/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; Uganda ; }, abstract = {CONTEXT: Histologic and receptor data on breast carcinoma in Uganda are scarce. Estrogen receptor status is not routinely available. Breast cancer blocks from Uganda were studied in Montreal, Canada, and clinical correlations subsequently discussed in Kampala, Uganda.<br><br>OBJECTIVE: To correlate histologic features (tumor type, histologic grade), receptor profile (estrogen receptor, progesterone receptor, and HER2/neu), and age in Ugandan women.<br><br>DESIGN: Pathology reports for 2000-2004 from Nsambya Hospital, reporting invasive breast carcinoma, provided 45 microscopically confirmed cases.<br><br>RESULTS: Seventy-three percent of patients were 50 years or younger. Histologic types were invasive ductal carcinoma (78%) and "good" prognosis types (11%). Overall 40% were grade 3, but 48% of invasive ductal carcinomas were grade 3. Estrogen receptor was positive in 60% overall and in 51% of invasive ductal carcinomas. HER2/neu was overexpressed in 11%; 36% were "triple" negative (estrogen receptor, progesterone receptor, HER2/neu negative).<br><br>CONCLUSIONS: Breast carcinoma in Ugandan women presents at a younger age and is histologically and by receptor profile more aggressive than carcinoma in Caucasian women.}, }
@article {pmid21255198, year = {2011}, author = {Barone, P}, title = {Treatment of depressive symptoms in Parkinson's disease.}, journal = {European journal of neurology}, volume = {18 Suppl 1}, number = {}, pages = {11-15}, doi = {10.1111/j.1468-1331.2010.03325.x}, pmid = {21255198}, issn = {1468-1331}, mesh = {Antidepressive Agents, Tricyclic/*therapeutic use ; Antiparkinson Agents/*therapeutic use ; Benzothiazoles/therapeutic use ; Depression/complications/*drug therapy ; Desipramine/therapeutic use ; Dopamine Agonists/*therapeutic use ; Humans ; Levodopa/therapeutic use ; Nortriptyline/therapeutic use ; Parkinson Disease/complications/*drug therapy ; Pramipexole ; Randomized Controlled Trials as Topic ; Selective Serotonin Reuptake Inhibitors/*therapeutic use ; Sertraline/therapeutic use ; }, abstract = {Significant depressive disorders are present in approximately 30-40% of patients with Parkinson's disease (PD). Depressive symptoms are correlated with poor health-related quality-of-life (HRQoL) scores, and are the major determinant of HRQoL. Studies that have evaluated pharmacotherapy for depressive symptoms in PD have shown that there is substantial variability in outcomes. Recently, two double-blind, placebo-controlled studies showed the superiority of nortriptyline and desipramine versus placebo and selective serotonin reuptake inhibitors. The antidepressant effects of dopamine agonists have been explored mainly in open and non-controlled studies. In a 14-week randomized trial comparing pramipexole with sertraline in depressed patients without motor complications, the Hamilton Depression Rating Scale score decreased in both groups; however, in the pramipexole group, the proportion of patients who recovered was significantly higher. Recently, in the first 12-week double-blind placebo-controlled clinical trial in PD patients without motor fluctuations on stable levodopa treatment, pramipexole reduced depressive symptoms as measured by Beck Depression Inventory score, with a significant difference in efficacy in favour of pramipexole. These data suggest that pramipexole might represent an alternative to antidepressant drugs to treat depressive symptoms in PD without adding the risk of antidepressant adverse events, and avoid polypharmacy.}, }
@article {pmid21266630, year = {2011}, author = {Kramer, F and Schippert, C and Rinnau, F and Hillemanns, P and Park-Simon, TW}, title = {The First Description of Docetaxel-Induced Recall Inflammatory Skin Reaction After Previous Drug Extravasation.}, journal = {The Annals of pharmacotherapy}, volume = {45}, number = {2}, pages = {e11}, doi = {10.1345/aph.1P440}, pmid = {21266630}, issn = {1542-6270}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Breast Neoplasms/drug therapy ; Carboplatin/administration &amp; dosage ; Carcinoma, Ductal, Breast/drug therapy ; Docetaxel ; Drug Eruptions/*etiology ; Erythema/*chemically induced ; Extravasation of Diagnostic and Therapeutic Materials ; Female ; Humans ; Neoplasm Metastasis ; Recurrence ; Taxoids/administration &amp; dosage/*adverse effects ; }, abstract = {OBJECTIVE: To describe a cutaneous recall soft tissue injury at the site of previous extravasation of docetaxel.<br><br>CASE SUMMARY: A 65-year-old white female with an invasive ductal carcinoma of the right breast was treated with carboplatin AUC 2 and docetaxel 30 mg/m(2) weekly via a peripheral vein access. During the 14th cycle, drug extravasation of docetaxel occurred in the left antecubital fossa characterized by a mild erythema without edema. A severe erythema developed in the former area of extravasation after the 15th cycle of carboplatin/docetaxel. The recall dermatitis continued to exacerbate after each course of systemic docetaxel chemotherapy and finally led to termination of this therapy.<br><br>DISCUSSION: In general, extravasation of docetaxel causes only mild local skin reactions without further necessity of intervention. For pegylated liposomal doxorubicin and paclitaxel, inflammatory recall phenomena at sites of previous drug extravasation are rare and often occur as single events following administration of the same cytotoxic drug. According to the Naranjo probability scale, the administration of docetaxel in this case probably led to the cutaneous soft tissue injury as a result of extravasation.<br><br>CONCLUSIONS: Caution is needed after an episode of docetaxel extravasation. Even after a therapy interruption of several weeks, resumption of chemotherapy with docetaxel might lead to recrudescence of the inflammatory skin reaction.}, }
@article {pmid21266359, year = {2011}, author = {Zhang, L and Sullivan, PS and Goodman, JC and Gunaratne, PH and Marchetti, D}, title = {MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase.}, journal = {Cancer research}, volume = {71}, number = {3}, pages = {645-654}, pmid = {21266359}, issn = {1538-7445}, support = {2R01 CA086832-07/CA/NCI NIH HHS/United States ; P50CA58183/CA/NCI NIH HHS/United States ; R01 CA086832/CA/NCI NIH HHS/United States ; R01 CA086832-07/CA/NCI NIH HHS/United States ; R01 CA160335/CA/NCI NIH HHS/United States ; R01 CA216991/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Brain Neoplasms/enzymology/genetics/*secondary/*therapy ; Breast Neoplasms/enzymology/genetics/pathology/*therapy ; Cell Line, Tumor ; Down-Regulation ; Female ; Genetic Therapy ; Glucuronidase/biosynthesis/*genetics ; Humans ; Mice ; Mice, Nude ; MicroRNAs/*administration &amp; dosage/genetics ; Molecular Targeted Therapy ; Neoplasm Invasiveness ; Transfection ; Xenograft Model Antitumor Assays ; }, abstract = {Heparanase (HPSE) is a potent protumorigenic, proangiogenic, and prometastatic enzyme that is overexpressed in brain metastatic breast cancer (BMBC). However, little is known about the regulation of this potential therapeutic target in BMBC, which remains very poorly managed in the clinic. We hypothesized that HPSE gene expression might be regulated by micro RNA that might be exploited therapeutically. Using miRanda and RNAhybrid, we identified miR-1258 as a candidate micro RNA that may directly target HPSE and suppress BMBC. In support of our hypothesis, we found that miR-1258 levels inversely correlated with heparanase expression, enzymatic activity, and cancer cell metastatic propensities, being lowest in highly aggressive BMBC cell variants compared with either nontumorigenic or nonmetastatic human mammary epithelial cells. These findings were validated by analyses of miR-1258 and heparanase content in paired clinical specimens of normal mammary gland versus invasive ductal carcinoma, and primary breast cancer versus BMBC. In regulatory experiments, miR-1258 inhibited the expression and activity of heparanase in BMBC cells, whereas modulating heparanase blocked the phenotypic effects of miR-1258. In functional experiments, stable expression of miR-1258 in BMBC cells inhibited heparanase in vitro cell invasion and experimental brain metastasis. Together, our findings illustrate how micro RNA mechanisms are linked to brain metastatic breast cancer through heparanase control, and they offer a strong rationale to develop heparanase-based therapeutics for treatment of cancer patients with brain metastases, BMBC in particular.}, }
@article {pmid21264256, year = {2011}, author = {Morton, CO and Varga, JJ and Hornbach, A and Mezger, M and Sennefelder, H and Kneitz, S and Kurzai, O and Krappmann, S and Einsele, H and Nierman, WC and Rogers, TR and Loeffler, J}, title = {The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro.}, journal = {PloS one}, volume = {6}, number = {1}, pages = {e16016}, pmid = {21264256}, issn = {1932-6203}, support = {1R21AI052236/AI/NIAID NIH HHS/United States ; }, mesh = {Aspergillus fumigatus/*genetics ; Cells, Cultured ; Dendritic Cells/*microbiology ; Gene Expression Regulation/*immunology ; Host-Pathogen Interactions/*genetics ; Humans ; Immune Evasion/genetics ; Inflammation/genetics ; Phagocytosis ; }, abstract = {Dendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Monocyte-derived immature DCs (iDC) were infected with viable resting conidia of Aspergillus fumigatus (Af293) for 12 hours at an MOI of 5; cells were sampled every three hours. RNA was extracted from both organisms at each time point and hybridised to microarrays. iDC cell death increased at 6 h in the presence of A. fumigatus which coincided with fungal germ tube emergence; >80% of conidia were associated with iDC. Over the time course A. fumigatus differentially regulated 210 genes, FunCat analysis indicated significant up-regulation of genes involved in fermentation, drug transport, pathogenesis and response to oxidative stress. Genes related to cytotoxicity were differentially regulated but the gliotoxin biosynthesis genes were down regulated over the time course, while Aspf1 was up-regulated at 9 h and 12 h. There was an up-regulation of genes in the subtelomeric regions of the genome as the interaction progressed. The genes up-regulated by iDC in the presence of A. fumigatus indicated that they were producing a pro-inflammatory response which was consistent with previous transcriptome studies of iDC interacting with A. fumigatus germ tubes. This study shows that A. fumigatus adapts to phagocytosis by iDCs by utilising genes that allow it to survive the interaction rather than just up-regulation of specific virulence genes.}, }
@article {pmid21250864, year = {2011}, author = {Flechsig, C and Suezer, Y and Kapp, M and Tan, SM and Löffler, J and Sutter, G and Einsele, H and Grigoleit, GU}, title = {Uptake of antigens from modified vaccinia Ankara virus-infected leukocytes enhances the immunostimulatory capacity of dendritic cells.}, journal = {Cytotherapy}, volume = {13}, number = {6}, pages = {739-752}, doi = {10.3109/14653249.2010.549123}, pmid = {21250864}, issn = {1477-2566}, mesh = {Antigen-Presenting Cells/immunology/metabolism ; Apoptosis ; Cell Survival ; Cells, Cultured ; Chemokine CXCL10/metabolism ; Cytokines/metabolism ; Dendritic Cells/*cytology/*immunology ; Humans ; Interleukin-10/metabolism ; Interleukin-12/metabolism ; Interleukin-6/metabolism ; Leukocytes, Mononuclear/cytology/*immunology/*virology ; Phagocytosis/immunology ; Receptors, CCR7/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cell Transplantation ; Transplantation, Homologous ; Tumor Necrosis Factor-alpha/metabolism ; Vaccinia virus/*physiology ; }, abstract = {BACKGROUND AIMS: Modified vaccinia Ankara (MVA) is a promising vaccine vector for infectious diseases and malignancies. It is fundamental to ascertain its tropism in human leukocyte populations and immunostimulatory mechanisms for application in immunotherapy.<br><br>METHODS: Human peripheral blood mononuclear cells (PBMC) and leukocyte subpopulations [monocyte-derived dendritic cells (DC), monocytes and B cells] were infected with MVA in order to evaluate their infection rate, changes in surface markers, cytokine expression and apoptosis.<br><br>RESULTS: Monocytes, DC and B cells were most susceptible to MVA infection, followed by natural killer (NK) cells. Monocytes were activated strongly, with upregulation of co-stimulatory molecules, major histocompatibility complex (MHC) molecules and chemokine (C-C motif) receptor (CCR7), while immature DC showed partial activation and B cells were inhibited. Furthermore, expression of chemokine (C-X-C motif) ligand (CXCL10), tumor necrosis factor (TNF)-&#x3b1;, interleukin (IL)-6 and IL-12p70 was enhanced but IL-1&#x3b2; and IL-10 were stable or even downregulated. MVA induced a high apoptosis rate of antigen-presenting cells (APC). Nevertheless, incubation of MVA-infected leukocytes with uninfected immature DC (iDC) led to complete maturation of the DC. Subsequently, the matured DC were able to stimulate cytomegalovirus (CMV)-immediate early protein (IE1)-specific T cells.<br><br>CONCLUSIONS: MVA induces a T-helper (Th)-1-polarizing cytokine expression in APC. Furthermore, incubation of MVA-infected leukocytes with uninfected iDC leads to complete maturation of the DC and may be the basis for cross-presentation of MVA-encoded antigens. Thus this approach seems to be an ideal model for further studies with MVA-encoded viral antigens regarding immunotherapy and vaccination strategies.}, }
@article {pmid21234642, year = {2011}, author = {de Azevedo, CR and Cruz, MR and Chinen, LT and Peres, SV and Peterlevitz, MA and de Azevedo Pereira, AE and Fanelli, MF and Gimenes, DL}, title = {Meningeal carcinomatosis in breast cancer: prognostic factors and outcome.}, journal = {Journal of neuro-oncology}, volume = {104}, number = {2}, pages = {565-572}, pmid = {21234642}, issn = {1573-7373}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*pathology/therapy ; Combined Modality Therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Meningeal Carcinomatosis/mortality/*secondary/therapy ; Middle Aged ; Neoplasm Staging ; Prognosis ; Radiotherapy ; Treatment Outcome ; }, abstract = {Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.}, }
@article {pmid21228925, year = {2010}, author = {Lacroix-Triki, M and Lambros, MB and Geyer, FC and Suarez, PH and Reis-Filho, JS and Weigelt, B}, title = {Absence of microsatellite instability in mucinous carcinomas of the breast.}, journal = {International journal of clinical and experimental pathology}, volume = {4}, number = {1}, pages = {22-31}, pmid = {21228925}, issn = {1936-2625}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Adenocarcinoma, Mucinous/*genetics/pathology ; Adenosine Triphosphatases/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; DNA Repair Enzymes/metabolism ; DNA, Neoplasm ; DNA-Binding Proteins/metabolism ; Female ; Humans ; Immunohistochemistry ; Microdissection ; *Microsatellite Instability ; Mismatch Repair Endonuclease PMS2 ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein/metabolism ; Neoplasm Staging ; Nuclear Proteins/metabolism ; Tissue Array Analysis ; }, abstract = {Microsatellite instability (MSI) is a form of genetic instability that results from defects in DNA mismatch repair. MSI is reported to be rare in unselected breast cancers, however it is a common feature in subsets of colorectal, ovarian and endometrial cancers. In these anatomical sites, MSI-high carcinomas often display a mucinous histology. The aim of this study was to determine whether mucinous carcinomas of the breast would more frequently display MSI-high than invasive ductal carcinomas of no special type (IDC-NSTs). The expression of four MSI markers (i.e. MSH2, MSH6, MLH1 and PMS2) was immunohistochemically assessed in 35 mucinous breast carcinomas and 35 histological grade- and oestrogen receptor (ER) status-matched IDC-NSTs, and in a series of 245 invasive breast cancers. Cases were considered as potentially MSI-high if tumour cells lacked expression of at least two MSI markers and internal controls displayed nuclear staining. Nine mucinous carcinomas were microdissected and subjected to MSI analysis by PCR using the MSI markers BAT26 and BAT40. No immunohistochemical evidence of MSI-high was found in the 35 mucinous carcinomas and 35 grade- and ER-matched IDC-NSTs, and in the cohort of 245 invasive breast cancers. In addition, no evidence of MSI-high was observed by PCR analysis using the BAT26 and BAT40 markers in the nine mucinous carcinomas tested. Our results demonstrate that MSI-high phenotype is remarkably rare in invasive breast cancer, and that, in contrast to mucinous carcinomas of other anatomical sites, MSI is not a common event in mucinous carcinomas of the breast.}, }
@article {pmid21224702, year = {2010}, author = {Oda, G and Nakagawa, T and Sato, T and Kuwayama, T and Yamamoto, K and Kawachi, H and Kubota, K and Sugihara, K}, title = {[A case of stage IV breast cancer with bone metastases that responded well for long-term to hormonal therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {37}, number = {12}, pages = {2753-2755}, pmid = {21224702}, issn = {0385-0684}, mesh = {Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Bone Neoplasms/drug therapy/*secondary ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*pathology ; Diphosphonates/therapeutic use ; Female ; Gonadotropin-Releasing Hormone/*therapeutic use ; Humans ; Middle Aged ; Nitriles/*therapeutic use ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tamoxifen/*therapeutic use ; Triazoles/*therapeutic use ; }, abstract = {A case was a 48 years old woman. She was aware of a lump in her left breast and visited our hospital. We diagnosed it as an invasive ductal carcinoma. Immunostaining for both ER and PgR was strongly positive. CT of the initial consultation showed multiple bone metastases (thoracic vertebrae, lumbar vertebrae, and iliac bone). After AC followed by docetaxel and tamoxifen, LH-RH analogue was started. We used anastrozole after menopause. The bisphosphonate has been used from the beginning of the treatment. After the chemotherapy, the clinical response of primary tumor was judged as partial response. For six years, the size of primary tumor has not been changed, and PET-CT has not showed another metastasis. Anastrozole was superior to tamoxifen with respect to TTP (median values of 10.7 and 6.4 months for anastrozole and tamoxifen, respectively) in postmenopausal women with ER and/or PgR receptor positive tumors. Our study indicated that many patients responding to hormonal therapy appear to have been increasing from now on.}, }
@article {pmid21224074, year = {2011}, author = {Kim, BG and An, HJ and Kang, S and Choi, YP and Gao, MQ and Park, H and Cho, NH}, title = {Laminin-332-rich tumor microenvironment for tumor invasion in the interface zone of breast cancer.}, journal = {The American journal of pathology}, volume = {178}, number = {1}, pages = {373-381}, pmid = {21224074}, issn = {1525-2191}, mesh = {Breast Neoplasms/*genetics/*pathology ; Cadherins/genetics ; Cell Adhesion Molecules/*genetics ; Epithelial Cells/metabolism/pathology ; Epithelial-Mesenchymal Transition/genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics ; Humans ; Integrin alpha6beta4/genetics ; Matrix Metalloproteinase 14/genetics ; MicroRNAs/genetics ; Myofibroblasts/metabolism/pathology ; Neoplasm Invasiveness ; Snail Family Transcription Factors ; Transcription Factors/genetics ; *Tumor Microenvironment ; Zinc Finger E-box-Binding Homeobox 1 ; }, abstract = {Dense fibrosis, which is caused by desmoplastic reaction, is usually found in invasive ductal carcinoma and may represent the alteration of the tumor microenvironment preceding tumor invasion. Thus, the dense fibrotic zone around invasive ductal carcinoma can be considered to be the actual tissue site of tumor microenvironment, where the precedent alterations for tumor invasion occur. To characterize the dense fibrotic zone, we classified invasive ductal carcinoma tissue into a tumor zone, a normal zone, and the novel interface zone (IZ), which shows dense fibrosis. The postulated IZ is a 5-mm-wide belt that circles the tumor margin and overlaps with normal tissue. Of the extracellular matrix components, laminin-332 was specifically overexpressed in the IZ. Events that appear to be similar to the epithelial-mesenchymal transition, a novel source of myofibroblast formation from epithelial cells, were observed in the IZ, according to the following characteristics: overexpression of matrix metalloproteinase 3, membrane type 1-matrix metalloproteinase, snail, and zinc finger E-box-binding homeobox 1, and the gain of N-cadherin expression, as well as the down-regulation of miR200c. The myofibroblasts isolated from the IZ, which were designated interface zone-fibroblast, displayed laminin-332 and membrane type 1-matrix metalloproteinase overexpression, in contrast with both cancer-associated fibroblasts and normal breast fibroblasts. Taken together, our results suggest that the IZ, which shows dense fibrosis, may provide a specialized microenvironment for guiding tumor invasion: the fibrosis caused by laminin-332 overexpressing myofibroblast formation (interface zone-fibroblast) via epithelial-mesenchymal transition.}, }
@article {pmid21221635, year = {2011}, author = {Kuba, S and Ohtani, H and Yamaguchi, J and Hayashi, H and Uga, T and Kanematsu, T and Shimokawa, I}, title = {Incomplete inside-out growth pattern in invasive breast carcinoma: association with lymph vessel invasion and recurrence-free survival.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {458}, number = {2}, pages = {159-169}, pmid = {21221635}, issn = {1432-2307}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Carcinoma, Papillary/metabolism/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Mucin-1/biosynthesis ; Prognosis ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast.}, }
@article {pmid21218740, year = {2010}, author = {Alwan, NA}, title = {Breast cancer: demographic characteristics and clinico-pathological presentation of patients in Iraq.}, journal = {Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit}, volume = {16}, number = {11}, pages = {1159-1164}, pmid = {21218740}, issn = {1020-3397}, mesh = {Adult ; Age Distribution ; Aged ; Aneuploidy ; *Breast Neoplasms/epidemiology/etiology/pathology ; DNA Mutational Analysis ; DNA, Neoplasm/analysis/genetics ; Female ; Genes, erbB-2/genetics ; Humans ; Immunohistochemistry ; Iraq/epidemiology ; Middle Aged ; Neoplasm Staging ; Population Surveillance ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Residence Characteristics ; Risk Factors ; }, abstract = {Breast cancer is the commonest type of malignancy in Iraq. The study was carried out on 721 out of a total of 5044 patients (14.3%) presenting with palpable breast lumps that were diagnosed as cancer. Approximately one third of the breast cancer patients were diagnosed at age 40-49 years; 71.9% came from urban areas; and 75% were married. History of lactation was reported in 63.1% and hormonal therapy in 29%. Positive family history was recorded in 16.2%. Although the lump was detected by the patient herself in 90.6% of cases, only 32% sought medical advice within the first month. Accordingly, 47% of these patients presented in advanced stages (III and IV). The main histological type was invasive ductal carcinoma, in which pathological changes of grade II and III were observed in 56.6% and 39.9% respectively. DNA analysis showed that 80.3% of the carcinomas were aneuploid. The findings of this study justify increasing efforts for establishing comprehensive breast cancer control programmes in Iraq.}, }
@article {pmid21214522, year = {2011}, author = {Jin, B and Ni, H and Geshang, Q and Li, Y and Shen, W and Shi, H}, title = {HLA-DR4 antigen and idiopathic dilated cardiomyopathy susceptibility: a meta-analysis involving 11,761 subjects.}, journal = {Tissue antigens}, volume = {77}, number = {2}, pages = {107-111}, doi = {10.1111/j.1399-0039.2010.01589.x}, pmid = {21214522}, issn = {1399-0039}, mesh = {Cardiomyopathy, Dilated/*genetics/immunology ; Case-Control Studies ; *Genetic Predisposition to Disease ; HLA-DR4 Antigen/*genetics/immunology ; Histocompatibility Testing ; Humans ; Risk Factors ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR4 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies in English-language articles were identified by a search of PubMed and Embase database (inception to June 2010). A total of 19 case-control studies including 1378 cases and 10,383 controls provided data on the association between HLA-DR4 antigen and genetic susceptibility to IDC. Overall, statistically elevated frequency of HLA-DR4 allele [OR (odds ratio), 1.58; 95% CI (confidence interval), 1.21-2.07; P = 0.0009] was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically increased risks were found for IDC in both subgroups. In the subgroup analysis by ethnicity, significantly increased risk was found among Europeans from 12 case-control studies (OR, 1.54; 95% CI, 1.11-2.12; P = 0.009). In conclusion, our results suggest that HLA-DR4 antigen is a low-penetrant risk factor for developing IDC in Europeans.}, }
@article {pmid21212063, year = {2011}, author = {Huang, Y and Malone, KE and Cushing-Haugen, KL and Daling, JR and Li, CI}, title = {Relationship between menopausal symptoms and risk of postmenopausal breast cancer.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {20}, number = {2}, pages = {379-388}, pmid = {21212063}, issn = {1538-7755}, support = {R01 CA085913-05/CA/NCI NIH HHS/United States ; R01-CA8591/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Body Composition ; Body Mass Index ; Breast Neoplasms/drug therapy/*epidemiology ; Carcinoma, Ductal, Breast/drug therapy/*epidemiology ; Carcinoma, Lobular/drug therapy/*epidemiology ; Case-Control Studies ; Cohort Studies ; Female ; Follow-Up Studies ; Hot Flashes ; Humans ; *Menopause ; Middle Aged ; *Postmenopause ; Prognosis ; Risk Factors ; Survival Rate ; United States/epidemiology ; }, abstract = {BACKGROUND: Prior studies indicate that women with menopausal symptoms have lower estrogen levels because they go through menopause as compared with women who do not experience them. Given the central role of hormones in the etiology of breast cancer, a link between menopausal symptoms and breast cancer is plausible. However, no prior studies have evaluated the association between menopausal symptoms and breast cancer risk.<br><br>METHODS: Utilizing data from a population-based case-control study we examined associations between menopausal symptoms and risks of different histologic types of breast cancer among postmenopausal women. We calculated multivariate adjusted odds ratios (OR) using polytomous logistic regression and evaluated several potential effect modifiers.<br><br>RESULTS: Women who ever experienced menopausal symptoms had lower risks of invasive ductal carcinoma [(IDC) OR = 0.5; 95% CI: 0.3-0.7], invasive lobular carcinoma (ILC, OR = 0.5; 95% CI: 0.3-0.8), and invasive ductal-lobular carcinoma (IDLC, OR = 0.7; 95% CI: 0.4-1.2), and these reductions in risk were independent of recency and timing of hormone therapy use, age at menopause, and body mass index. Increasing intensity of hot flushes among women who ever experienced hot flushes was also associated with decreasing risks of all three breast cancer subtypes (P values for trend all &#x2264; 0.017).<br><br>CONCLUSION: This is the first study to report that women who ever experienced menopausal symptoms have a substantially reduced risk of breast cancer, and that severity of hot flushes is also inversely associated with risk.<br><br>IMPACT: If confirmed, these findings could enhance our understanding of breast cancer etiology and factors potentially relevant to prevention.}, }
@article {pmid21207256, year = {2011}, author = {Kadivar, M and Monabati, A and Joulaee, A and Hosseini, N}, title = {Epstein-Barr virus and breast cancer: lack of evidence for an association in Iranian women.}, journal = {Pathology oncology research : POR}, volume = {17}, number = {3}, pages = {489-492}, pmid = {21207256}, issn = {1532-2807}, mesh = {Adolescent ; Adult ; Breast/metabolism/pathology ; Breast Neoplasms/*diagnosis/genetics/virology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/virology ; Carcinoma, Lobular/*diagnosis/genetics/virology ; DNA, Viral/genetics ; Epstein-Barr Virus Infections/*diagnosis/genetics/virology ; Epstein-Barr Virus Nuclear Antigens/*genetics/metabolism ; Female ; Herpesvirus 4, Human/genetics ; Humans ; Immunoenzyme Techniques ; Iran ; Middle Aged ; Polymerase Chain Reaction ; Viral Matrix Proteins/*genetics/metabolism ; Viral Proteins/*genetics/metabolism ; Young Adult ; }, abstract = {Controversies regarding the role of Epstein-Barr virus (EBV) in breast cancer and lack of published literature in this regard in Iran, prompted us to assess EBV presence in 100 breast carcinoma and 42 control biopsies obtained from Iranian women. Breast carcinoma cases were comprised of 81 invasive ductal carcinoma NOS, 9 invasive lobular carcinoma, 1 apocrine carcinoma, 2 cribriform carcinoma, 2 papillary carcinoma and 5 mucinous carcinoma. Control biopsies consisted of 13 fibroadenoma, 9 benign epithelial proliferation (adenosis and sclerosing adenosis), 9 usual ductal hyperplasia, 4 atypical ductal hyperplasia, 4 non-proliferative fibrocystic changes and 3 normal breast tissue. To identify EBV-infected cells we applied immunohistochemical analysis, using monoclonal antibody against Epstein-Barr virus-encoded nuclear antigen 2 (EBNA-2) and latent membrane protein 1 (LMP-1). Further, polymerase chain reaction (PCR) was used to amplify EBV DNA, with primers that cover the EBV encoded RNA (EBER) and BamHIW regions. EBNA-2 and LMP-1 immunohistochemistry were negative in all breast cancer and control specimens. Using PCR, none of the 100 breast cancer samples or the 42 control specimens showed detectable EBV DNA. These results indicate that EBV may not play a significant role in the etiology of breast cancer in Iranian women.}, }
@article {pmid21206008, year = {2010}, author = {Liang, S and Singh, M and Dharmaraj, S and Gam, LH}, title = {The PCA and LDA analysis on the differential expression of proteins in breast cancer.}, journal = {Disease markers}, volume = {29}, number = {5}, pages = {231-242}, doi = {10.3233/DMA-2010-0753}, pmid = {21206008}, issn = {1875-8630}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*biosynthesis ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Female ; Humans ; Linear Models ; Malaysia ; Middle Aged ; Principal Component Analysis ; Protein Biosynthesis ; Proteome/metabolism ; }, abstract = {Breast cancer is a leading cause of mortality in women. In Malaysia, it is the most common cancer to affect women. The most common form of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was undertaken to identify protein profile changes between cancerous and normal breast tissues from 18 patients. Two protein extracts; aqueous soluble and membrane associated protein extracts were studied. Thirty four differentially expressed proteins were identified. The intensities of the proteins were used as variables in PCA and reduced data of six principal components (PC) were subjected to LDA in order to evaluate the potential of these proteins as collective biomarkers for breast cancer. The protein intensities of SEC13-like 1 (isoform b) and calreticulin contributed the most to the first PC while the protein intensities of fibrinogen beta chain precursor and ATP synthase D chain contributed the most to the second PC. Transthyretin precursor and apolipoprotein A-1 precursor contributed the most to the third PC. The results of LDA indicated good classification of samples into normal and cancerous types when the first 6 PCs were used as the variables. The percentage of correct classification was 91.7% for the originally grouped tissue samples and 88.9% for cross-validated samples.}, }
@article {pmid21199632, year = {2010}, author = {Breton, AL and Poulalhon, N and Balme, B and Thomas, L and Dalle, S}, title = {Primary cutaneous marginal zone lymphoma as a complication of radiation therapy: Case report and review.}, journal = {Dermatology online journal}, volume = {16}, number = {12}, pages = {6}, pmid = {21199632}, issn = {1087-2108}, mesh = {Aged ; Antibodies, Monoclonal, Murine-Derived/administration &amp; dosage ; Antineoplastic Agents, Hormonal/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy/radiotherapy/surgery ; Carcinoma, Ductal, Breast/drug therapy/radiotherapy/surgery ; Chlorambucil/administration &amp; dosage ; Combined Modality Therapy ; Female ; Humans ; Lymphoma, B-Cell, Marginal Zone/drug therapy/*etiology ; Neoplasms, Radiation-Induced/drug therapy/*etiology ; Neoplasms, Second Primary/drug therapy/*etiology ; Radiotherapy, Adjuvant/*adverse effects ; Rituximab ; Skin Neoplasms/drug therapy/*etiology ; }, abstract = {BACKGROUND: The occurrence of primary cutaneous B-cell lymphoma at the site of radiation therapy is exceptional. We report herein the case of a primary cutaneous marginal zone lymphoma arising at the site of radiotherapy for breast cancer.<br><br>METHODS/RESULTS: A seventy-year-old woman was diagnosed in 2005 with an invasive ductal carcinoma of the left breast, which was treated with surgery, adjuvant chemotherapy, and radiation therapy. Three years later she developed several cutaneous nodules on her left breast, followed by similar lesions on her back. Histologic, immunohistochemistry, and molecular findings were consistent with the diagnosis of cutaneous marginal zone lymphoma. Physical examination was otherwise negative, as well as mammography, total body CT, bone marrow biopsy, and Borrelia serology.<br><br>CONCLUSIONS: To our knowledge, this is the first published case of primary cutaneous marginal zone lymphoma occurring at the site of radiotherapy. Cutaneous surveillance is proposed from the first year after irradiation in order to detect new primary malignancies, including this rare cutaneous neoplasm.}, }
@article {pmid21197096, year = {2010}, author = {Liang, S and Singh, M and Gam, LH}, title = {The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to stage and grade of patients.}, journal = {Journal of biomedicine &amp; biotechnology}, volume = {2010}, number = {}, pages = {516469}, pmid = {21197096}, issn = {1110-7251}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*biosynthesis ; Breast/metabolism ; Breast Neoplasms/*metabolism ; Cohort Studies ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Immunoblotting ; Malaysia ; Mass Spectrometry ; Middle Aged ; Neoplasm Proteins/*biosynthesis ; Protein Biosynthesis ; Proteomics/*methods ; }, abstract = {Breast cancer is a leading cause of female deaths worldwide. In Malaysia, it is the most common form of female cancer while Infiltrating ductal carcinoma (IDC) is the most common form of breast cancer. A proteomic approach was used to identify changes in the protein profile of breast cancerous and normal tissues. The patients were divided into different cohorts according to tumour stage and grade. We identified twenty-four differentially expressed hydrophilic proteins. A few proteins were found significantly related to various stages and grades of IDC, amongst which were SEC13-like 1 (isoform b), calreticulin, 14-3-3 protein zeta, and 14-3-3 protein eta. In this study, we found that by defining the expression of the proteins according to stages and grades of IDC, a significant relationship between the expression of the proteins with the stage or grade of IDC can be established, which increases the usefulness of these proteins as biomarkers for IDC.}, }
@article {pmid21176537, year = {2010}, author = {Shen, PH and Zhang, W and Zhang, YH and Zhang, HX and Fan, QX}, title = {[Expression of BCSG1-siRNA in tumor transplants of human breast cancer cell line in nude mice].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {39}, number = {10}, pages = {691-694}, pmid = {21176537}, issn = {0529-5807}, mesh = {Animals ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism ; Cell Line, Tumor ; Female ; Fibroadenoma/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Mice, Nude ; Neoplasm Proteins/*biosynthesis/genetics ; Neoplasm Transplantation ; *RNA Interference ; RNA, Messenger/metabolism ; RNA, Small Interfering/*genetics ; Random Allocation ; Transfection ; Tumor Burden ; gamma-Synuclein/*biosynthesis/genetics ; }, abstract = {OBJECTIVE: To investigate the inhibitory effects of siRNA targeting BCSG1 gene expression in tumor transplants of human breast cancer cell line in nude mice.<br><br>METHODS: Four-pairs of small interfering RNA sequences of BCSG1 were chemically synthesized and inserted into the plasmid expression vectors, and were then transfected into human breast carcinoma cell line MCF7 by liposome method. Plasmid vector with unrelated sequence was used as the vector control. Cells transfected with 4 siRNA sequences, control vector and naive FCF7 cells were transplanted into the nude mice. The tumor inhibition was analysised. Immunohistochemical SP method and semi-quantitative RT-PCR were adopted to detect the BCSG1 mRNA and protein expression, respectively. Breast tissue samples of human infiltrating ductal carcinoma, ductal hyperplasia and fibroadenoma were also used as the controls.<br><br>RESULTS: The inhibition rates of tumor growth in four BCSG1-siRNA transfected groups were remarkably higher than those of the vector control group and naive MCF7 cells (P<0.01). Compared with that of the vector control and na&#xef;ve MCF7 cell group, there was a significant decrease of BCSG-1 protein expression in the four experimental groups by immuno-histochemistry staining (P<0.01). In addition, BCSG1 mRNA expression in the four groups transfected with BCSG1-siRNA were significantly less than that of the control vector group, naive MCF7 cell control group and human breast IDC (P<0.01).<br><br>CONCLUSION: BCSG1-siRNA down-regulates the expression of BCSG1 and inhibits effectively growth of the transplaned human breast cancer cell line in nude mice.}, }
@article {pmid21160270, year = {2010}, author = {Ikeda, M and Sonoo, H and Oota, Y and Fujii, S and Shimo, T and Miyake, A and Seki, M and Nomura, T and Yamamoto, Y and Shiiki, S and Nakashima, K and Tanaka, K and Kurebayashi, J}, title = {[A case of HER2 overexpressing advanced breast cancer with CTF therapy [cyclophosphamide, pirarubicin (THPADM), fluorouracil] showed long-term effectiveness after paclitaxel shock].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {37}, number = {13}, pages = {2917-2920}, pmid = {21160270}, issn = {0385-0684}, mesh = {Antimetabolites, Antineoplastic/administration &amp; dosage ; Antineoplastic Agents/administration &amp; dosage ; Antineoplastic Agents, Alkylating/administration &amp; dosage ; Antineoplastic Agents, Phytogenic/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Cyclophosphamide/administration &amp; dosage ; Doxorubicin/administration &amp; dosage/analogs &amp; derivatives ; Female ; Fluorouracil/administration &amp; dosage ; Humans ; Middle Aged ; Paclitaxel/*adverse effects ; Receptor, ErbB-2/*analysis ; Shock/chemically induced ; }, abstract = {A 53-year-old woman with left breast tumor was diagnosed as bilateral breast cancer(left; T3N3M0, Stage III C/right; T2N0M0, Stage II)in our hospital, both of which were revealed as invasive ductal carcinoma shown to be ER-negative, PgR negative and HER2-positive by core needle biopsy. In December 2004, paclitaxel and trastuzumab combination therapy was tried, but she went into shock just during administration of paclitaxel, and this therapy was discontinued. After that the triweekly CTF therapy was tried as an anthracycline containing regimen, and the lymph node metastases obtained a complete response after a month and a 38. 5% reduction of left primary breast tumor, which was the best response observed after three months. Time to progression was prolonged to 7 months(9 cycles). Although febrile neutropenia occurred in the first cycle, the therapy could be continued safely thereafter as an outpatient. Anthracycline-containing regimens are likely to be avoided because of the difficulty of combining with trastuzumab in the treatment of HER2 overexpressing advanced/metastatic breast cancer. But the CTF therapy of less cardiotoxicity and less alopecia, can expect longer use and better QOL as an alternative for HER2 overexpressing advanced/metastatic breast cancer patients.}, }
@article {pmid21160269, year = {2010}, author = {Ichinose, Y and Kobayashi, T and Fujimoto, A and Uchida, S and Sasaoki, T and Goto, K}, title = {[Advanced breast cancer in a patient achieving long-term SD after letrozole administration for liver metastasis developing during anastrozole therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {37}, number = {13}, pages = {2913-2916}, pmid = {21160269}, issn = {0385-0684}, mesh = {Aged ; Anastrozole ; Antineoplastic Agents/*therapeutic use ; Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Female ; Humans ; Letrozole ; Liver Neoplasms/*drug therapy/*secondary ; Nitriles/*therapeutic use ; Triazoles/*therapeutic use ; }, abstract = {We report a 69-year-old woman with breast cancer who was effectively treated with letrozole as a second-line therapy after becoming resistant to anastrozole. Her chief complaint at presentation was back pain. Physical examination and imaging studies showed a left breast tumor with skin invasion, multiple intramammary lesions, enlarged left axillary lymph node, and multiple bone metastases. Needle biopsy revealed invasive ductal carcinoma(scirrhous carcinoma)that was ER+/PgR+/ HER2-. The administration of anastrozole and bisphosphonate for 13 months resulted in a 33% reduction of the longest diameters of the breast tumors, but a liver metastasis developed. The treatment was changed to letrozole administration from January 2007.T he optimal effect of letrozole as determined by measurement on CT images was long-term SD maintained for about 13 months. No significant side effects were observed, and the QOL was favorable.}, }
@article {pmid21160267, year = {2010}, author = {Hanada, N and Tomiyama, N and Hori, K and Kusano, S and Yoshida, Y and Kawata, K and Uchino, R and Sakashita, N}, title = {[A case of recurrent breast cancer with lung metastasis resection showing four disease-free years under trastuzumab treatment].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {37}, number = {13}, pages = {2905-2907}, pmid = {21160267}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/surgery ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms/*secondary/surgery ; Mastectomy ; Middle Aged ; Pneumonectomy ; Trastuzumab ; }, abstract = {We report a case of recurrent breast cancer with solitary lung metastasis that has shown no recurrence with treatment by trastuzumab alone after partial resection of the right lung upper lobe. A 56-year-old woman, who presented with left breast cancer, underwent quadrantectomy and axillar lymph node dissection in March 2004. Pathological findings were as follows: invasive ductal carcinoma, 3. 7 cm in size, histological grade 3, positive invasion of lymphatic and blood vessels, negative nodal status, negative ER/PgR status, and overexpression of HER2/ neu. She had received adjuvant radiotherapy followed by cyclophosphamide, methotrexate and fluorouracil combination chemotherapy; however, a lung nodule developed 14 months after first operation, which had grown gradually. Partial resection of the lung with thoracoscope assistance revealed metastatic lung cancer from breast cancer. Trastuzumab treatment for 6 months after second operation has maintained no recurrence for 4 years.}, }
@article {pmid21160266, year = {2010}, author = {Yoshida, H and Yamamoto, D and Kanematsu, S and Tanaka, K and Ah, K}, title = {[A case of multi-drug resistant breast cancer with liver metastasis treated effectively by S-1 monotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {37}, number = {13}, pages = {2901-2903}, pmid = {21160266}, issn = {0385-0684}, mesh = {Antimetabolites, Antineoplastic/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Drug Combinations ; Drug Resistance, Multiple ; *Drug Resistance, Neoplasm ; Female ; Humans ; Liver Neoplasms/secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Metastasis ; Oxonic Acid/*therapeutic use ; Tegafur/*therapeutic use ; }, abstract = {We report a case of multi-drug-resistant breast cancer with liver metastases which completely responded and improved the quality of life (QOL)by S-1 monotherapy. The patient was a 53-year-old woman, who was diagnosed as breast cancer with invasive chest wall, cervical lymph node metastases, multiple bone metastases and bilateral pleural effusion[invasive ductal carcinoma, scirrhous type, ER(-), PgR(+), HER2(1+)]. After six courses of cyclophosphamide+epirubicin(CE)and weekly paclitaxel for 3 months, cervical lymph node metastasis was judged as a partial response(PR)and the bilateral pleural effusion disappeared. After chemotherapy, aromatase inhibitor (AI) was used. However, primary lesion and multiple bone metastases no change(NC). Following pass through AI+ oral anticancer drug combination chemotherapy and oral anticancer drug monotherapy, the therapy was changed to palliative, and she was referred to our hospital in January 2007. On arrival at the hospital, respiratory distress and bilateral pleural effusion had appeared, so it was an emergency admission. After removing the pleural effusion, pleurodesis was done and the symptoms disappeared. Although AI plus bisphosphonate therapy were started at hospital discharge, disease progression and fatigue appeared. In December 2007, we started S-1 monotherapy. S-1 was given orally at 80 mg/m2 for day 1-28 followed by a 2-week rest period, within a 6-week courses. Six months after treatment was started, multiple liver metastases disappeared and peritoneal effusion decreased. During the period of S-1 treatment, there were no serious adverse events, and treatment was possible without compromising QOL. This result suggested that S-1 treatment was a reasonable option for multi-drug-resistant breast cancer.}, }
@article {pmid21140366, year = {2011}, author = {Cho, HK and Park, SH and Shin, SY}, title = {Isolated optic nerve metastasis of breast cancer initially mimicking retrobulbar optic neuritis.}, journal = {European journal of ophthalmology}, volume = {21}, number = {4}, pages = {513-515}, doi = {10.5301/EJO.2010.6099}, pmid = {21140366}, issn = {1724-6016}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*secondary/therapy ; Combined Modality Therapy ; Diagnosis, Differential ; Female ; Humans ; Immunoenzyme Techniques ; Magnetic Resonance Imaging ; Mastectomy, Modified Radical ; Middle Aged ; Optic Nerve Neoplasms/diagnosis/*secondary/therapy ; Optic Neuritis/*diagnosis ; Radiosurgery ; Visual Acuity ; }, abstract = {PURPOSE: To report a pathologically confirmed case of optic nerve metastasis of breast carcinoma, which was initially misdiagnosed as a retrobulbar optic neuritis. There have been no case reports of isolated optic nerve metastasis of breast carcinoma with nonspecific initial fundus and neuroimaging findings.<br><br>METHODS: A 51-year-old woman presented with decreased visual acuity in her left eye for 15 days. She had undergone a left modified radical mastectomy 10 years earlier. The funduscopic findings were nonspecific, except for a slightly enlarged cup-to-disc ratio of 0.6 in both eyes. The brain magnetic resonance imaging (MRI) findings were nonspecific and cerebrospinal fluid (CSF) findings were also nonspecific and negative for malignant cells. Therefore, she was diagnosed with idiopathic retrobulbar optic neuritis rather than metastasis of breast carcinoma. Intravenous steroid pulse therapy was given for 3 days.<br><br>RESULTS: The left visual acuity decreased gradually, and after 2 months was light perception-negative in the left eye. Fundus findings and CSF study results were also nonspecific as the initial presentation. On the subsequent orbit MRI, diffuse enlargement and an enhancing segment of the left optic nerve was observed, which suggested metastasis to the left optic nerve. A craniotomy and biopsy of the left optic nerve was performed. The pathologic results revealed metastatic invasive ductal carcinoma of the breast. She underwent Cyberknife surgery followed by systemic chemotherapy.<br><br>CONCLUSIONS: Patients with known cancer at another site of the body who develop optic neuropathy, with or without evidence of metastasis, should be suspected to have cancer as a cause.}, }
@article {pmid21126378, year = {2010}, author = {Jung, SY and Jeong, J and Shin, SH and Kwon, Y and Kim, EA and Ko, KL and Shin, KH and Lee, KS and Park, IH and Lee, S and Kim, SW and Kang, HS and Ro, J}, title = {The invasive lobular carcinoma as a prototype luminal A breast cancer: a retrospective cohort study.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {664}, pmid = {21126378}, issn = {1471-2407}, mesh = {Adult ; Asian People ; Biomarkers, Tumor/analysis ; Breast Neoplasms/classification/ethnology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/classification/ethnology/mortality/*pathology/therapy ; Carcinoma, Lobular/classification/ethnology/mortality/*pathology/therapy ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Korea/epidemiology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/*analysis ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Survival Rate ; Terminology as Topic ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known.<br><br>METHODS: We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC).<br><br>RESULTS: The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (&#x2265; T2, 59.8% vs. 38.8%, P = 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P < 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, P < 0.001), progesterone receptor positive (71.1% vs. 50.1%, P < 0.001) and HER2 negative (97.5% vs. 74.6%, P < 0.001) status, and lower Ki-67 expression (10.3% &#xb1; 10.6% vs. 20.6% &#xb1; 19.8%, P < 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, P < 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07).<br><br>CONCLUSIONS: ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC.}, }
@article {pmid21125683, year = {2011}, author = {Bombonati, A and Sgroi, DC}, title = {The molecular pathology of breast cancer progression.}, journal = {The Journal of pathology}, volume = {223}, number = {2}, pages = {307-317}, pmid = {21125683}, issn = {1096-9896}, support = {R01 CA112021/CA/NCI NIH HHS/United States ; R01 CA112021-02/CA/NCI NIH HHS/United States ; R01-1CA112021-02/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Disease Progression ; Female ; Gene Expression Profiling/methods ; Humans ; Models, Genetic ; Neoplastic Stem Cells/pathology ; }, abstract = {The current model of human breast cancer progression proposes a linear multi-step process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into DCIS and culminates in the potentially lethal stage of invasive ductal carcinoma. For several decades a major challenge to human breast cancer research has been the identification of the molecular alterations associated with the different stages of breast cancer progression. Until recently, progress in attaining this goal has been hampered by technical limitations associated with applying advanced molecular technologies to the microscopic preinvasive stages of breast tumorigenesis. Recent advances in comprehensive, high-throughput genetic, transcriptomic and epigenetic technologies in combination with advanced microdissection and ex vivo isolation techniques have provided for a more complete understanding of the complex molecular genetic and molecular biological inter-relationships of the different stages of human breast cancer evolution. Here we review the molecular biological data suggesting that breast cancer develops and evolves along two distinct molecular genetic pathways. We also briefly review gene expression and epigenetic data that support the view of the tumour microenvironment as an important co-conspirator rather than a passive bystander during human breast tumorigenesis.}, }
@article {pmid21120523, year = {2011}, author = {Park, SY and Kwon, HJ and Lee, HE and Ryu, HS and Kim, SW and Kim, JH and Kim, IA and Jung, N and Cho, NY and Kang, GH}, title = {Promoter CpG island hypermethylation during breast cancer progression.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {458}, number = {1}, pages = {73-84}, pmid = {21120523}, issn = {1432-2307}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; CpG Islands/*genetics ; DNA Methylation/genetics/*physiology ; DNA, Neoplasm/genetics/*metabolism ; *Disease Progression ; Female ; Homeodomain Proteins/metabolism ; Humans ; Hyperplasia/genetics/metabolism/pathology ; Membrane Proteins/metabolism ; Metallothionein/metabolism ; Middle Aged ; Neoplasm Proteins/metabolism ; Promoter Regions, Genetic/*genetics ; Proto-Oncogene Proteins/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Retrospective Studies ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/metabolism ; }, abstract = {This study was designed to evaluate the changes in promoter CpG islands hypermethylation during breast cancer progression from pre-invasive lesions [flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS)] to invasive ductal carcinoma (IDC). We performed MethyLight analysis for the methylation status of 57 promoter CpG island loci in 20 IDCs and their paired normal breast tissues. After selecting 15 CpG island loci showing breast cancer-specific DNA methylation, another set of normal breast tissue (n = 10), ADH/FEA (n = 30), DCIS (n = 35), and IDC (n = 30) of the breast were analyzed for these loci. We found six new methylation markers of breast cancer, namely DLEC1, GRIN2B, HOXA1, MT1G, SFRP4, and TMEFF2, in addition to APC, GSTP1, HOXA10, IGF2, RARB, RASSF1A, RUNX3, SCGB3A1 (HIN-1), and SFRP1. The number of methylated genes increased stepwise from normal breast to ADH/FEA and DCIS, while IDC did not differ from DCIS. Methylation levels and frequencies of APC, DLEC1, HOXA1, and RASSF1A promoter CpG islands were significantly higher in ADH/FEA than in normal breast tissue. GRIN2B, GSTP1, HOXA1, RARB, RUNX3, SFRP1, and TMEFF2 showed higher methylation levels and frequencies in DCIS than in ADH/FEA. DICS and IDC did not differ in the methylation levels or frequencies for most CpG island loci except SFRP1 and HOXA10. Our findings showed that promoter CpG island methylation changed significantly in pre-invasive lesions, and was similar in IDC and DCIS, suggesting that CpG island methylation of tumor-related genes is an early event in breast cancer progression.}, }
@article {pmid21119286, year = {2010}, author = {Rao, S and Latha, PS and Ravi, A and Thanka, J}, title = {Ductal carcinoma in a multiple fibroadenoma: diagnostic inaccuracies.}, journal = {Journal of cancer research and therapeutics}, volume = {6}, number = {3}, pages = {385-387}, doi = {10.4103/0973-1482.73350}, pmid = {21119286}, issn = {1998-4138}, mesh = {Adult ; Biopsy, Needle ; Breast Neoplasms/complications/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/complications/*diagnosis/diagnostic imaging ; Diagnostic Errors ; Female ; Fibroadenoma/complications/*diagnosis/diagnostic imaging ; Humans ; Mammography ; }, abstract = {We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.}, }
@article {pmid21114180, year = {2010}, author = {Munjal, K and Jain, VK and Agrawal, A and Bandi, PK}, title = {Co-existing tubercular axillary lymphadenitis with carcinoma breast can falsely over-stage the disease--case series.}, journal = {The Indian journal of tuberculosis}, volume = {57}, number = {2}, pages = {104-107}, pmid = {21114180}, issn = {0019-5707}, mesh = {Adult ; Aged ; Axilla/*microbiology ; Breast Neoplasms/*complications/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Tuberculosis, Lymph Node/*complications ; }, abstract = {The synchronous occurrence of tuberculosis and carcinoma in breast is unusual. The simultaneous occurrence of both the diseases can complicate the neoplastic disease. The diagnosis and treatment of tuberculosis in a patient with cancer assumes importance as it can prevent high mortality in patients with co-existent disease and thereby create problems in treatment decision. Axillary lymph node enlargement in breast cancer patient is not always caused by metastatic tumour of the breast even in the ipsilateral axillary nodes. We present here six case reports as an example of tuberculous axillary lymphadenitis co-existing with invasive ductal carcinoma of the breast. Accurate diagnosis has helped in down-staging carcinoma of the breast and also in identifying curable disease.}, }
@article {pmid21109569, year = {2011}, author = {Yu, Q and Niu, Y and Liu, N and Zhang, JZ and Liu, TJ and Zhang, RJ and Wang, SL and Ding, XM and Xiao, XQ}, title = {Expression of androgen receptor in breast cancer and its significance as a prognostic factor.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {22}, number = {6}, pages = {1288-1294}, doi = {10.1093/annonc/mdq586}, pmid = {21109569}, issn = {1569-8041}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/genetics/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/genetics/metabolism ; China ; Disease Progression ; Female ; Fluorescent Antibody Technique ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptors, Androgen/genetics/*metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; }, abstract = {BACKGROUND: Breast cancer is an extraordinarily hormone-dependent tumor. This study was to evaluate androgen receptor (AR) status and its significance in breast cancer in Chinese women.<br><br>METHODS: Three hundred and thirty-five consecutive cases of invasive ductal breast carcinoma, 34 ductal carcinoma in situ (DCIS), and 82 DCIS adjacent to invasive tissues were involved in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient outcome, and its implications were evaluated in five molecular subgroups of invasive ductal carcinoma (IDC) and in DCIS lesions.<br><br>RESULTS: AR expression was related to that of estrogen receptor (P < 0.001) and progesterone receptor (P = 0.035) but not correlated with the other conventional parameters. AR retained independent prognostic significance (hazard ratio 0.309, 95% confidence interval, 0.192-0.496; P < 0.001). The majority (61.0%) of basal-like breast cancers showed loss of AR expression (P < 0.001), which had poor prognosis. The percentage of AR-positive cases was significantly higher in DCIS adjacent to IDC group than in pure DCIS and IDC groups (93.9%, 79.4%, and 72.5%; P = 0.046 and P < 0.001, respectively).<br><br>CONCLUSIONS: Our data suggest that AR may provide another specific definition of breast cancer subtypes and reveal a potential role in DCIS progression. These findings may help develop new therapies.}, }
@article {pmid21084819, year = {2010}, author = {Nakamura, Y and Aono, T and Nomura, M and Iwase, K and Tanaka, Y}, title = {[Two cases of HER2-positive advanced or metastatic breast cancer, responding to lapatinib and capecitabine].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {37}, number = {11}, pages = {2165-2168}, pmid = {21084819}, issn = {0385-0684}, mesh = {Adenocarcinoma, Scirrhous/*drug therapy/pathology ; Aged ; Antimetabolites, Antineoplastic/administration &amp; dosage ; Antineoplastic Agents/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy/pathology ; Capecitabine ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Female ; Fluorouracil/administration &amp; dosage/analogs &amp; derivatives ; Humans ; Lapatinib ; Lung Neoplasms/secondary ; Lymph Node Excision ; Mastectomy ; Middle Aged ; Quinazolines/administration &amp; dosage ; Receptor, ErbB-2/*analysis ; }, abstract = {The first patient was a 59-year-old woman who was diagnosed with invasive scirrhous carcinoma. The tumor was estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, and human epidermal growth factor receptor 2 (HER2)-positive. The patient was treated with adjuvant chemotherapy and endocrine therapy after surgery. Liver metastases developed 5 years after surgery. She was treated with trastuzumab combined with vinorelbine, paclitaxel, or docetaxel. The liver metastases increased in size, 9 years after surgery, and she was treated with lapatinib and capecitabine. The efficacy of chemotherapy was judged as a partial response. The second patient was a 74-year-old woman who was diagnosed with invasive ductal carcinoma in 2005. The tumor was ER-negative, PgR-positive, and HER2-positive; she was treated with trastuzumab and paclitaxel. She developed dyspnea in January 2010. Chest radiograph showed increased lung metastases and left pleural effusion; she was treated with lapatinib and capecitabine. Lung metastases decreased and left pleural effusion disappeared after the first cycle of chemotherapy. The efficacy of chemotherapy was judged as a partial response.}, }
@article {pmid21073252, year = {2010}, author = {Morrone, A and Dassoni, F and Pajno, MC and Marrone, R and Calcaterra, R and Franco, G and Maiani, E}, title = {Ulcers of the face and neck in a woman with pulmonary tuberculosis: presentation of a clinical case.}, journal = {Rural and remote health}, volume = {10}, number = {4}, pages = {1485}, pmid = {21073252}, issn = {1445-6354}, mesh = {Aged ; Antitubercular Agents/therapeutic use ; Ethiopia ; Female ; Humans ; Neck/*microbiology ; Rural Health Services ; Skin Ulcer/*microbiology ; Tuberculosis, Cutaneous/*diagnosis/drug therapy ; Tuberculosis, Pulmonary ; }, abstract = {INTRODUCTION: Tuberculosis (TB), which is endemic in developing countries, is an important public health problem. Cutaneous TB (CT) represents 1.5% of all TB cases and is considered to be a re-emerging pathology in developing countries due to co-infections with HIV, multidrug-resistant TB, a shortage of health facilities with appropriate diagnostic equipment, reduced access to treatment, and poor treatment compliance among patients who often resort to traditional medicine.<br><br>CASE REPORT: This report describes the case of a 70 year-old woman who attended the outpatients department of the Italian Dermatological Centre (IDC) in Mekelle, the capital city of Tigray (Northern Ethiopia), complaining of the appearance of two ulcers on her face and neck. The patient had a history of pulmonary TB, with her initial systemic treatment ceased after 1 month. Cytological examination of a needle aspiration from the neck lesion showed a non-specific bacterial superinfection. No acid-fast bacilli were found on Ziehl-Nielsen staining. On the basis of clinical suspicion of CT, it was decided to avoid biopsy for histology and culture and to immediately start anti-tubercular treatment. A significant improvement of the cutaneous lesions was noted after approximately 40 days.<br><br>CONCLUSION: Currently, the diagnosis of CT is based on careful clinical and histopathological correlation. The standard diagnostic approach is to biopsy for Ziehl-Nielsen stain, culture and histology. However, in rural areas of DC where diagnostic methods may not be available and advanced stages of disease such as CT are likely to be encountered, after the use of the most effective diagnostic tests available, empirical treatment on the basis of medical history and physical examination is suggested. Appropriate training of healthcare workers and public health education programs encouraging early presentation and improved patient treatment compliance are additional important preventative strategies.}, }
@article {pmid21060149, year = {2010}, author = {Ben-Batalla, I and Seoane, S and Garcia-Caballero, T and Gallego, R and Macia, M and Gonzalez, LO and Vizoso, F and Perez-Fernandez, R}, title = {Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis.}, journal = {The Journal of clinical investigation}, volume = {120}, number = {12}, pages = {4289-4302}, pmid = {21060149}, issn = {1558-8238}, mesh = {Adenocarcinoma/genetics/metabolism/pathology/secondary ; Animals ; Apoptosis ; Base Sequence ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology/secondary ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, SCID ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; RNA, Small Interfering/genetics ; Transcription Factor Pit-1/antagonists &amp; inhibitors/*genetics/*metabolism ; Transplantation, Heterologous ; Tumor Stem Cell Assay ; }, abstract = {The Pit-1 transcription factor (also know as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. Some of these protumorigenic effects of Pit-1 were mediated by upregulation of Snai1, an inductor of the epithelial-mesenchymal transition. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumor, high expression of Pit-1 was significantly correlated with Snai1 positivity. Notably, in these patients elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node-positive breast cancer and may represent a new therapeutic target.}, }
@article {pmid21059199, year = {2010}, author = {Heymann, S and Delaloge, S and Rahal, A and Caron, O and Frebourg, T and Barreau, L and Pachet, C and Mathieu, MC and Marsiglia, H and Bourgier, C}, title = {Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome.}, journal = {Radiation oncology (London, England)}, volume = {5}, number = {}, pages = {104}, pmid = {21059199}, issn = {1748-717X}, mesh = {Adult ; Breast Neoplasms/genetics/radiotherapy/surgery ; Cohort Studies ; Female ; Genes, p53 ; Humans ; Incidence ; Li-Fraumeni Syndrome/*complications/genetics ; Middle Aged ; Neoplasms, Radiation-Induced/*epidemiology ; Radiotherapy, Adjuvant/adverse effects ; Young Adult ; }, abstract = {BACKGROUND: There are no specific recommendations for the management of breast cancer patients with germ-line p53 mutations, an exceptional genetic condition, particularly regarding postoperative radiotherapy. Preclinical data suggested that p53 mutations conferred enhanced radiosensitivity in vitro and in vivo and the few clinical observations showed that Li-Fraumeni families were at a higher risk of secondary radio-induced malignancies.<br><br>METHODS: We reviewed a cohort of patients with germ-line p53 mutations who had been treated for breast cancer as the first tumor event. We assessed their outcome and the incidence of secondary radio-induced malignancies.<br><br>RESULTS: Among 47 documented Li-Fraumeni families treated from 1997 to 2007 at the Institut Gustave Roussy, 8 patients had been diagnosed with breast cancer as the first tumor event. Three patients had undergone conservative breast surgery followed by postoperative radiotherapy and five patients had undergone a mastectomy (3 with postoperative radiotherapy). Thus, 6/8 patients had received postoperative radiotherapy. Median follow-up was 6 years. Median age at the diagnosis of the primary breast cancer was 30 years. The histological characteristics were as follows: intraductal carcinoma in situ (n = 3), invasive ductal carcinoma (n = 4) and a phyllodes tumor (n = 1). Among the 6 patients who had received adjuvant radiotherapy, the following events had occurred: 3 ipsilateral breast recurrences, 3 contralateral breast cancers, 2 radio-induced cancers, and 3 new primaries (1 of which was an in-field thyroid cancer with atypical histology). In contrast, only one event had occurred (a contralateral breast cancer) among patients who had not received radiation therapy.<br><br>CONCLUSIONS: These observations could argue in favor of bilateral mastectomy and the avoidance of radiotherapy.}, }
@article {pmid21056685, year = {2011}, author = {Levy, CB and Stumbo, AC and Ano Bom, AP and Portari, EA and Cordeiro, Y and Silva, JL and De Moura-Gallo, CV}, title = {Co-localization of mutant p53 and amyloid-like protein aggregates in breast tumors.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {43}, number = {1}, pages = {60-64}, doi = {10.1016/j.biocel.2010.10.017}, pmid = {21056685}, issn = {1878-5875}, mesh = {Adult ; *Amyloid/chemistry/metabolism/ultrastructure ; *Breast Neoplasms/genetics/pathology/ultrastructure ; DNA, Neoplasm/metabolism ; Female ; Fluorescent Antibody Technique ; Gene Expression Regulation, Neoplastic ; *Genes, p53 ; Genetic Association Studies ; Humans ; Molecular Sequence Data ; Mutation ; *Tumor Suppressor Protein p53/chemistry/genetics/metabolism/ultrastructure ; }, abstract = {P53 is one of the most important tumor suppressor proteins in human cancers. Mutations in the TP53 gene are common features of malignant tumors and normally correlate to a more aggressive disease. In breast cancer, these gene alterations are present in approximately 20% of cases and are characteristically of missense type. In the present work we describe TP53 mutations in breast cancer biopsies and investigate whether wild and mutant p53 participate in protein aggregates formation in these breast cancer cases. We analyzed 88 biopsies from patients residing in the metropolitan area of Rio de Janeiro, and performed TP53 mutation screening using direct sequencing of exons 5-10. Seventeen mutations were detected, 12 of them were of missense type, 2 nonsenses, 2 deletions and 1 insertion. The presence of TP53 mutation was highly statistically associated to tumor aggressiveness of IDC cases, indicated here by Elston Grade III (p<0.0001). Paraffin embedded breast cancer tissues were analyzed for the presence of p53 aggregates through immunofluorescence co-localization assay, using anti-aggregate primary antibody A11, and anti-p53. Our results show that mutant p53 co-localizes with amyloid-like protein aggregates, depending on mutation type, suggesting that mutant p53 may form aggregates in breast cancer cells, in vivo.}, }
@article {pmid21039041, year = {2010}, author = {Looi, LM and Cheah, PL and Ng, MH and Yip, CH and Mun, KS and Rahman, NA}, title = {Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {11}, number = {3}, pages = {713-716}, pmid = {21039041}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood ; Breast/metabolism/*pathology ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibroadenoma/genetics/metabolism/*pathology ; Humans ; Middle Aged ; Polymerase Chain Reaction ; Prognosis ; Telomerase/*metabolism ; Telomere/*genetics ; }, abstract = {A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.}, }
@article {pmid21036723, year = {2010}, author = {Al-Khattabi, H and Kelany, A and Buhmeida, A and Al-Maghrabi, J and Lari, S and Chaudhary, A and Gari, M and Abuzenadah, A and Al-Qahtani, M}, title = {Evaluation of HER-2/neu gene amplification by fluorescence in situ hybridization and immunohistochemistry in saudi female breast cancer.}, journal = {Anticancer research}, volume = {30}, number = {10}, pages = {4081-4088}, pmid = {21036723}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*enzymology/*genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Receptor, ErbB-2/biosynthesis/*genetics ; Saudi Arabia ; Young Adult ; }, abstract = {BACKGROUND: Amplification of the HER-2/neu oncogene and concomitant over-expression of its protein are detected in approximately 18% of invasive ductal carcinoma of the breast and is associated with poor prognosis. This study tested the use of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to evaluate the HER-2/neu gene status and to ascertain the concordance rate between the two methods.<br><br>PATIENTS AND METHODS: Eighty two tumour samples containing representative tumour were divided for testing using each assay. HER-2/neu gene amplification is scored as a ratio of HER-2/neu gene amplification to chromosome 17. The ratio should be >2.2 to be considered as positive. 20 cells should be counted and an average score taken. An extra 20 cells should be counted if the ratio is between 1.8-2.2.<br><br>RESULTS: Seventy five effective samples were used. HER-2/neu gene was amplified in 19 out of 75 cases (25%) whereas, HER-2 protein, by IHC was over-expressed in 18 out of 75 cases (24%). In the 44 negative cases by IHC analysis only 7 cases (16%) of them showed amplification by FISH. Three out of 13 cases (23 %) scored as +2 showed gene amplification by FISH while 9 cases out of 18 cases (50%) were scored as +3. High concordance with FISH results 37:44 (84 %) was noted in negative cases (0/+1 cases), while lower concordance 3:13 (23 %) was seen in +2 cases.<br><br>CONCLUSION: This study revealed a significant concordance between FISH results and IHC results. The study also showed that HER2/neu amplification is higher in Saudi patients than other western populations. However, due to the inherent failures of the IHC assay, FISH should always be used when the IHC results are inconclusive. The rational algorithm for HER-2/neu testing would be to perform IHC first, followed by FISH to validate equivocal IHC results.}, }
@article {pmid20979875, year = {2010}, author = {Ying, JM and Guo, L and Liu, XY and Qiu, T and Lü, N}, title = {[Automated silver-enhanced in situ hybridization detection assay for human epidermal growth factor receptor 2 gene status determination in breast cancer].}, journal = {Zhonghua yi xue za zhi}, volume = {90}, number = {24}, pages = {1674-1677}, pmid = {20979875}, issn = {0376-2491}, mesh = {Adult ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; Humans ; In Situ Hybridization/*methods ; Middle Aged ; Prospective Studies ; Receptor, ErbB-2/*genetics ; Silver Compounds ; }, abstract = {OBJECTIVE: To evaluate the concordance of human epidermal growth factor receptor 2 (HER2) gene amplification in invasive breast cancer by the techniques of fluorescence in situ hybridization (FISH) and silver-enhanced in situ hybridization (SISH).<br><br>METHODS: A prospective study of 63 invasive breast cancer specimens excised between May 2009 and November 2009 was conducted by automated immunohistochemistry (IHC) staining and bright field automated SISH. HER2 gene status was also examined by FISH in 43 cases. An evaluation was performed according to the ASCO/CAP guidelines (2007).<br><br>RESULTS: Among 63 breast invasive ductal carcinoma tested by automated SISH, 61 cases were successfully evaluated. Gene amplification was detected in 97% (29/30) HER2 protein expression positive (3+) cases and in 18% (2/11) equivocal (2+) cases. Two of 11 (18%) HER2 expression 2+ cases were equivocal for gene amplification. In 43 cases examined by FISH, HER2 gene amplification was detected in 95% (20/21) HER2 expression positive (3+) cases and in one equivocal (2+) cases. Three of 10 (30%) expression 2+ cases were equivocal for gene amplification. No gene amplification was detected in expression negative (1 +/0) cases by either SISH or FISH (0/20 and 0/12 respectively). The results of SISH and FISH were identical in 42 cases examined by the above two techniques, including 21 HER2 gene amplification positive, 2 equivocal and 19 negative cases. One case was FISH equivocal and SISH negative. And the overall concordance between FISH and SISH was 98%.<br><br>CONCLUSIONS: There is high concordance rate between SISH and FISH results for assessing the HER2 gene amplification status of excised breast cancer specimens. However, SISH has more advantages and it is particularly suited for routine application in surgical pathology.}, }
@article {pmid20977948, year = {2011}, author = {Kou, PM and Schwartz, Z and Boyan, BD and Babensee, JE}, title = {Dendritic cell responses to surface properties of clinical titanium surfaces.}, journal = {Acta biomaterialia}, volume = {7}, number = {3}, pages = {1354-1363}, pmid = {20977948}, issn = {1878-7568}, support = {AR052102/AR/NIAMS NIH HHS/United States ; R01 EB004633/EB/NIBIB NIH HHS/United States ; R01 AR052102/AR/NIAMS NIH HHS/United States ; R01 AR052102-04/AR/NIAMS NIH HHS/United States ; R01 EB004633-04/EB/NIBIB NIH HHS/United States ; EB004633/EB/NIBIB NIH HHS/United States ; }, mesh = {Cell Differentiation ; Cytokines/metabolism ; Dendritic Cells/*immunology ; Humans ; Microscopy, Electron, Scanning ; Osteoblasts/cytology/metabolism/ultrastructure ; Principal Component Analysis ; Surface Properties ; Titanium/*chemistry ; }, abstract = {Dendritic cells (DCs) play pivotal roles in responding to foreign entities during the innate immune response and in initiating effective adaptive immunity as well as maintaining immune tolerance. The sensitivity of DCs to foreign stimuli also makes them useful cells to assess the inflammatory response to biomaterials. Elucidating material property-DC phenotype relationships using a well-defined biomaterial system is expected to provide criteria for immunomodulatory biomaterial design. Clinical titanium (Ti) substrates, including pretreatment (PT), sand blasted and acid etched (SLA), and modified SLA (modSLA), with different roughnesses and surface energies were used to treat DCs and resulted in differential DC responses. PT and SLA induced a mature DC (mDC) phenotype, while modSLA promoted a non-inflammatory environment by supporting an immature DC (iDC) phenotype, based on surface marker expression, cytokine production profiles and cell morphology. Principal component analysis (PCA) confirmed these experimental results, and also indicated that the non-stimulating property of modSLA covaried with certain surface properties, such as high surface hydrophilicity, percent oxygen and percent Ti of the substrates. In addition to previous research that demonstrated superior osteogenic properties of modSLA compared with PT and SLA, the results reported herein indicates that modSLA may further benefit implant osteointegration by reducing local inflammation and its associated osteoclastogenesis.}, }
@article {pmid20963473, year = {2011}, author = {Szasz, AM and Tokes, AM and Micsinai, M and Krenacs, T and Jakab, C and Lukacs, L and Nemeth, Z and Baranyai, Z and Dede, K and Madaras, L and Kulka, J}, title = {Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis.}, journal = {Clinical &amp; experimental metastasis}, volume = {28}, number = {1}, pages = {55-63}, pmid = {20963473}, issn = {1573-7276}, mesh = {Breast Neoplasms/*diagnosis/*metabolism/pathology ; Claudins/*biosynthesis/metabolism ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/*diagnosis/genetics ; Middle Aged ; Prognosis ; Tissue Array Analysis ; }, abstract = {Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated semiquantitatively. When compared to LNMs, in the IDC group beta-catenin and claudin-2, -3, -4 and -7 protein expression showed different pattern while claudin-1, -2, -3, -4 and -7 were differently expressed in the ILC group. Lymph node metastases developed a notable increase of claudin-5 expression in both groups. Decrease or loss of claudin-1 and expression of claudin-4 in lymph node metastases correlated with reduced disease-free survival in our patients. According to our observations, the expression of epithelial junctional molecules, especially claudins, is different in primary breast carcinomas compared to their lymph node metastases as demonstrated by immunohistochemistry. Loss of claudin junctional molecules might contribute to tumor progression, and certain claudin expression pattern might be of prognostic relevance.}, }
@article {pmid20956025, year = {2011}, author = {Odumosu, O and Payne, K and Baez, I and Jutzy, J and Wall, N and Langridge, W}, title = {Suppression of dendritic cell activation by diabetes autoantigens linked to the cholera toxin B subunit.}, journal = {Immunobiology}, volume = {216}, number = {4}, pages = {447-456}, pmid = {20956025}, issn = {1878-3279}, support = {R21 DK057206-02/DK/NIDDK NIH HHS/United States ; R21 DK063576/DK/NIDDK NIH HHS/United States ; R21 DK-99-013/DK/NIDDK NIH HHS/United States ; }, mesh = {Autoantigens/genetics/immunology/*pharmacology ; Cells, Cultured ; Cholera Toxin/genetics/immunology/*pharmacology ; Dendritic Cells/*drug effects/immunology ; Gene Order ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/*pharmacology ; Interleukin-10/metabolism ; Proinsulin/genetics/immunology/*pharmacology ; Recombinant Fusion Proteins/genetics/immunology/metabolism/*pharmacology ; Toll-Like Receptor 2/metabolism ; Up-Regulation/*drug effects ; }, abstract = {Antigen presenting cells, specifically dendritic cells (DCs) are a focal point in the delicate balance between T cell tolerance and immune responses contributing to the onset of type I diabetes (T1D). Weak adjuvant proteins like the cholera toxin B subunit when linked to autoantigens may sufficiently alter the balance of this initial immune response to suppress the development of autoimmunity. To assess adjuvant enhancement of autoantigen mediated immune suppression of Type 1 diabetes, we examined the cholera toxin B subunit (CTB)-proinsulin fusion protein (CTB-INS) activation of immature dendritic cells (iDC) at the earliest detectable stage of the human immune response. In this study, Incubation of human umbilical cord blood monocyte-derived immature DCs with CTB-INS autoantigen fusion protein increased the surface membrane expression of DC Toll-like receptor (TLR-2) while no significant upregulation in TLR-4 expression was detected. Inoculation of iDCs with CTB stimulated the biosynthesis of both CD86 and CD83 co-stimulatory factors demonstrating an immunostimulatory role for CTB in both DC activation and maturation. In contrast, incubation of iDCs with proinsulin partially suppressed CD86 co-stimulatory factor mediated DC activation, while incubation of iDCs with CTB-INS fusion protein completely suppressed iDC biosynthesis of both CD86 and CD83 costimulatory factors. The incubation of iDCs with increasing amounts of insulin did not increase the level of immune suppression but rather activated DC maturation by stimulating increased biosynthesis of both CD86 and CD83 costimulatory factors. Inoculation of iDCs with CTB-INS fusion protein dramatically increased secretion of the immunosuppressive cytokine IL-10 and suppressed synthesis of the pro-inflammatory cytokine IL12/23 p40 subunit protein suggesting that linkage of CTB to insulin (INS) may play an important role in mediating DC guidance of cognate naïve Th0 cell development into immunosuppressive T lymphocytes. Taken together, the experimental data suggests Toll like receptor 2 (TLR-2) plays a dominant role in CTB mediated INS inhibition of DC induced type 1 diabetes onset in human Type 1 diabetes autoimmunity. Further, fusion of CTB to the autoantigen was found to be essential for enhancement of immune suppression as co-delivery of CTB and insulin did not significantly inhibit DC costimulatory factor biosynthesis. The experimental data presented supports the hypotheses that adjuvant enhancement of autoantigen mediated suppression of islet beta cell inflammation is dependent on CTB stimulation of dendritic cell TLR2 receptor activation and co-processing of both CTB and the autoantigen in the same dendritic cell.}, }
@article {pmid20955380, year = {2010}, author = {Subramaniam, MM and Chan, JY and Omar, MF and Ito, K and Ito, Y and Yeoh, KG and Salto-Tellez, M and Putti, TC}, title = {Lack of RUNX3 inactivation in columnar cell lesions of breast.}, journal = {Histopathology}, volume = {57}, number = {4}, pages = {555-563}, doi = {10.1111/j.1365-2559.2010.03675.x}, pmid = {20955380}, issn = {1365-2559}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Core Binding Factor Alpha 3 Subunit/genetics/*metabolism ; DNA Methylation ; Female ; Humans ; Immunohistochemistry ; Promoter Regions, Genetic ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {AIMS: Ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) exhibit frequent RUNX3 inactivation by promoter hypermethylation and protein mislocalization. The aim of this study was to analyse columnar cell lesions (CCLs) to further characterize RUNX3 involvement in breast carcinogenesis.<br><br>METHODS AND RESULTS: &#x2002; RUNX3 expression and methylation was analysed by immunohistochemistry and methylation-specific polymerase chain reaction (PCR), respectively, in 75 CCLs. Our previously reported DCIS and IDC data were also included. Consistent with terminal duct lobular units (TDLUs) (73 of 75, 97%), active nuclear RUNX3 protein was observed in 73 of 75 (97%) CCLs [columnar cell change, 46 of 48 (96%); columnar cell hyperplasia, 12 of 12 (100%) and flat epithelial atypia, 15 of 15 (100%). In contrast to matched TDLUs from cancer specimens [four of 40 (10%)] and CCLs, significantly inactivated RUNX3 expression was detected in DCIS [17 of 20 (85%)] and IDC [18 of 20 (90%)] (all P < 0.001). RUNX3 methylation was more frequent in DCIS [15 of 20 (75%)] and IDC [16 of 20 (80%)] than CCLs [(none of 20 (0%)] and matched TDLUs [one of 10 (10%)] from cancer patients (all P < 0.001).<br><br>CONCLUSIONS: &#x2002; RUNX3 inactivation occurs specifically in DCIS and IDC cells. In addition, RUNX3 inactivation may not be a common association between CCLs and breast carcinomas.}, }
@article {pmid20953905, year = {2011}, author = {Fu, Z and Jiao, M and Zhang, M and Xu, F and Yuan, W and Pang, D and Li, D}, title = {LFA-1 gene polymorphisms are associated with the sporadic infiltrative duct breast carcinoma in Chinese Han women of Heilongjiang Province.}, journal = {Breast cancer research and treatment}, volume = {127}, number = {1}, pages = {265-271}, doi = {10.1007/s10549-010-1203-6}, pmid = {20953905}, issn = {1573-7217}, mesh = {Adult ; Aged ; Alleles ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; China ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Lymphocyte Function-Associated Antigen-1/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tumor Suppressor Protein p53/genetics ; Young Adult ; }, abstract = {The infiltrative duct carcinoma (IDC) is the most common malignant breast cancer in females and genetic factors appear to play a significant role in the susceptibility of IDC. The LFA-1 is a crucial co-stimulatory molecule in immune system and may affect the development of breast IDC. In order to clarify the association of LFA-1 polymorphisms with IDC, a case-control study was conducted in women from Heilongjiang Province, Northeast of China. We scrutinized four genetic polymorphisms in LFA-1 gene, which may influence the activity and function of LFA-1. Our research subjects consist of 537 cases with IDC and 577 age-matched healthy controls. Genotypes were determined by PCR-RFLP. Data were analyzed using the χ(2) test by SPSS 13.0 and Haploview 4.1 softwares. The association between LFA-1 polymorphisms and the clinical features of IDC was analyzed. In rs2230433, the frequency of GG genotype and G allele was lower in cases than in controls (P = 0.0316 and 0.0480). And rs2230433, CG genotype was higher in cases (P = 0.0397). In rs8058823, the frequency of AA genotype and A allele was lower in cases than in controls (P = 0.00000418 and 0.00000267). And rs8058823, AG genotype was higher in cases (P = 0.00000747). The frequency of haplotype CCGA was lower in patients. Significant association was shown between the four SNPs of LFA-1 gene and estrogen receptor (ER), progesterone receptor (PR), C-erbB-2, and P53 statuses. In addition, no association was found between LFA-1 gene polymorphisms and tumor size, and neither was it between LFA-1 gene polymorphisms and lymph node metastasis. Our results primarily suggested that LFA-1 gene polymorphisms may predict the sporadic breast IDC risk and prognosis factors in Chinese Han women in Heilongjiang Province.}, }
@article {pmid20951508, year = {2012}, author = {Zauls, AJ and Watkins, JM and Wahlquist, AE and Brackett, NC and Aguero, EG and Baker, MK and Jenrette, JM and Garrett-Mayer, E and Harper, JL}, title = {Outcomes in women treated with MammoSite brachytherapy or whole breast irradiation stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups.}, journal = {International journal of radiation oncology, biology, physics}, volume = {82}, number = {1}, pages = {21-29}, doi = {10.1016/j.ijrobp.2010.08.034}, pmid = {20951508}, issn = {1879-355X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Analysis of Variance ; Axilla ; Brachytherapy/methods ; Breast Neoplasms/classification/mortality/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/classification/mortality/pathology/*radiotherapy/secondary ; Carcinoma, Intraductal, Noninfiltrating/classification/mortality/pathology/*radiotherapy/secondary ; Chemotherapy, Adjuvant ; *Consensus ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Radiation Oncology ; Risk Assessment/methods ; Survival Analysis ; Time Factors ; Treatment Failure ; }, abstract = {PURPOSE: The American Society for Radiation Oncology published a Consensus Statement for accelerated partial breast irradiation identifying three groups: Suitable, Cautionary, and Unsuitable. The objective of this study was to compare oncologic outcomes in women treated with MammoSite brachytherapy (MB) vs. whole breast irradiation (WBI) after stratification into Statement groups.<br><br>METHODS: Eligible women had invasive carcinoma or ductal carcinoma in situ (DCIS) &#x2264; 3 cm, and &#x2264; 3 lymph nodes positive. Women were stratified by radiation modality and Statement groups. Survival analysis methods including Kaplan-Meier estimation, Cox regression, and competing risks analysis were used to assess overall survival (OS), disease-free survival (DFS), time to local failure (TTLF), and tumor bed failure (TBF).<br><br>RESULTS: A total of 459 (183 MB and 276 WBI) patients were treated from 2002 to 2009. After a median follow-up of 45 months, we found no statistical differences by stratification group or radiation modality with regard to OS and DFS. At 4 years TTLF or TBF were not statistically different between the cohorts. Univariate analysis in the MB cohort revealed that nodal positivity (pN1 vs. pN0) was related to TTLF (hazard ratio 6.39, p = 0.02). There was a suggestion that DCIS histology had an increased risk of failure when compared with invasive ductal carcinoma (hazard ratio 3.57, p = 0.06).<br><br>CONCLUSIONS: MB and WBI patients stratified by Statement groups seem to combine women who will have similar outcomes regardless of radiation modality. Although outcomes were similar, we remain guarded in overinterpretation of these preliminary results until further analysis and long-term follow-up data become available. Caution should be used in treating women with DCIS or pN1 disease with MB.}, }
@article {pmid20947169, year = {2010}, author = {Simone, R and Barbarat, B and Rabellino, A and Icardi, G and Bagnasco, M and Pesce, G and Olive, D and Saverino, D}, title = {Ligation of the BT3 molecules, members of the B7 family, enhance the proinflammatory responses of human monocytes and monocyte-derived dendritic cells.}, journal = {Molecular immunology}, volume = {48}, number = {1-3}, pages = {109-118}, doi = {10.1016/j.molimm.2010.09.005}, pmid = {20947169}, issn = {1872-9142}, mesh = {Apoptosis ; B7-1 Antigen/*immunology ; Blotting, Western ; Cell Line ; Cell Separation ; Dendritic Cells/*immunology/metabolism ; Flow Cytometry ; Humans ; Immunoprecipitation ; Inflammation/*immunology ; Lymphocyte Activation/immunology ; Monocytes/*immunology/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/*immunology ; }, abstract = {BT3 is a new family of immunoreceptors belonging to the extended B7 family. BT3 molecules are expressed on the surface of resting and activated monocytes and monocyte-derived dendritic cells (iDC). We show that BT3 cross-linking, in the absence of other survival factors, provides a survival signal for monocytes and iDC and induces up-regulation of costimulatory molecules, such as CD80 and CD86, and HLA-DR. We further analyzed the effects of BT3 cross-linking on various proinflammatory responses on monocytes and iDC. The results obtained showed that BT3 engagement is able to modulate the production of IL8/CXCL8, IL-1β and IL-12/p70. Moreover, we demonstrated a synergistic effect between BT3 and Toll-like receptors ligands on both monocytes and iDC in up-regulating the production of proinflammatory cytokines. Thus, BT3 could be involved in the regulation of the balance between immune activation and suppression. A better understanding of its physiological role of these families of receptors awaits the precise identification of the nature, origin, expression, and distribution of their ligands.}, }
@article {pmid20946688, year = {2010}, author = {Kwon, JH and Kim, YJ and Lee, KW and Oh, DY and Park, SY and Kim, JH and Chie, EK and Kim, SW and Im, SA and Kim, IA and Kim, TY and Park, IA and Noh, DY and Bang, YJ and Ha, SW}, title = {Triple negativity and young age as prognostic factors in lymph node-negative invasive ductal carcinoma of 1 cm or less.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {557}, pmid = {20946688}, issn = {1471-2407}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Disease-Free Survival ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/biosynthesis ; *Lymphatic Metastasis ; Middle Aged ; Prospective Studies ; Recurrence ; Registries ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Whether a systemic adjuvant treatment is needed is an area of controversy in patients with node-negative early breast cancer with tumor size of ≤1 cm, including T1mic.<br><br>METHODS: We performed a retrospective analysis of clinical and pathology data of all consecutive patients with node-negative T1mic, T1a, and T1b invasive ductal carcinoma who received surgery between Jan 2000 and Dec 2006. The recurrence free survival (RFS) and risk factors for recurrence were identified.<br><br>RESULTS: Out of 3889 patients diagnosed with breast cancer, 375 patients were enrolled (T1mic:120, T1a:93, T1b:162). Median age at diagnosis was 49. After a median follow up of 60.8 months, 12 patients developed recurrences (T1mic:4 (3.3%), T1a:2 (2.2%), T1b:6 (3.7%)), with a five-year cumulative RFS rate of 97.2%. Distant recurrence was identified in three patients. Age younger than 35 years (HR 4.91; 95% CI 1.014-23.763, p = 0.048) and triple negative disease (HR 4.93; 95% CI 1.312-18.519, p = 0.018) were significantly associated with a higher rate of recurrence. HER2 overexpression, Ki-67, and p53 status did not affect RFS.<br><br>CONCLUSIONS: Prognosis of node-negative breast cancer with T1mic, T1a and T1b is excellent, but patients under 35 years of age or with triple negative disease have a relatively high risk of recurrence.}, }
@article {pmid20942802, year = {2011}, author = {Boucher, D and Blais, V and Drag, M and Denault, JB}, title = {Molecular determinants involved in activation of caspase 7.}, journal = {Bioscience reports}, volume = {31}, number = {4}, pages = {283-294}, pmid = {20942802}, issn = {1573-4935}, support = {86563-1//Canadian Institutes of Health Research/Canada ; MOP-86563/CAPMC/CIHR/Canada ; }, mesh = {Amino Acid Sequence ; Binding Sites ; Caspase 3/chemistry/genetics ; Caspase 7/*chemistry/genetics ; Caspase 8/chemistry/genetics ; Caspases/chemistry/genetics ; Caspases, Initiator/chemistry/genetics ; Cells, Cultured ; Dimerization ; Humans ; Kinetics ; Protein Structure, Tertiary ; }, abstract = {During apoptosis, initiator caspases (8, 9 and 10) activate downstream executioner caspases (3, 6 and 7) by cleaving the IDC (interdomain connector) at two sites. Here, we demonstrate that both activation sites, site 1 and site 2, of caspase 7 are suboptimal for activation by initiator caspases 8 and 9 in cellulo, and in vitro using recombinant proteins and activation kinetics. Indeed, when both sites are replaced with the preferred motifs recognized by either caspase 8 or 9, we found an up to 36-fold improvement in activation. Moreover, cleavage at site 1 is preferred to site 2 because of its location within the IDC, since swapping sites does not lead to a more efficient activation. We also demonstrate the important role of Ile195 of site 1 involved in maintaining a network of contacts that preserves the proper conformation of the active enzyme. Finally, we show that the length of the IDC plays a crucial role in maintaining the necessity of proteolysis for activation. In fact, although we were unable to generate a caspase 7 that does not require proteolysis for activity, shortening the IDC of the initiator caspase 8 by four residues was sufficient to confer a requirement for proteolysis, a key feature of executioner caspases. Altogether, the results demonstrate the critical role of the primary structure of caspase 7's IDC for its activation and proteolytic activity.}, }
@article {pmid20921957, year = {2011}, author = {Martens, FM and Heesakkers, JP and Rijkhoff, NJ}, title = {Minimal invasive electrode implantation for conditional stimulation of the dorsal genital nerve in neurogenic detrusor overactivity.}, journal = {Spinal cord}, volume = {49}, number = {4}, pages = {566-572}, doi = {10.1038/sc.2010.134}, pmid = {20921957}, issn = {1476-5624}, mesh = {Adult ; Electric Stimulation Therapy/*methods ; Electrodes, Implanted/standards ; Female ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures/methods ; Muscle Contraction/physiology ; Spinal Cord Injuries/etiology/*physiopathology ; Urinary Bladder/innervation/physiopathology ; Urinary Bladder, Neurogenic/etiology/*physiopathology/*therapy ; Young Adult ; }, abstract = {STUDY DESIGN: Experimental.<br><br>OBJECTIVES: Electrical stimulation of the dorsal genital nerves (DGN) suppresses involuntary detrusor contractions (IDCs) in patients with neurogenic detrusor overactivity (DO). The feasibility of minimal invasive electrode implantation near the DGN and the effectiveness of conditional stimulation to suppress IDCs at different amplitudes in spinal cord injury (SCI) patients with DO were studied.<br><br>SETTING: Radboud University Nijmegen MC, The Netherlands.<br><br>METHODS: In eight healthy volunteers, a needle electrode was inserted from both a medial and lateral-to-midline site at the level of the pubic bone. Electrode insertion was guided by the genito-anal reflex (GAR) evoked by electrical stimulation and by sensation to this stimulation. In eight SCI patients with DO, the bladder was repeatedly filled and emptied partially in between. Conditional stimulation using a needle electrode was applied when an IDC was observed at urodynamics. Different amplitudes were used during each filling. Control cystometry was carried out before electrode insertion and after stimulation.<br><br>RESULTS: The lateral implant approach was preferred, as it was easier to manoeuvre the needle along the pubic bone and fixate the needle. In SCI patients, the electrode was positioned successfully, and IDCs were suppressed (range 1-6 IDC suppressions) with conditional stimulation at maximum tolerable amplitude, except for one patient. Stimulation was less effective at lower amplitudes. Stimulation lowered the intensity of bladder sensations concomitant with IDC.<br><br>CONCLUSION: The lateral-to-midline implant approach, in combination with GAR and sensation to stimulation, is feasible for electrode implantation near the DGN in SCI patients. Conditional stimulation effectively suppresses IDCs.}, }
@article {pmid20920981, year = {2010}, author = {Xiang, G and Zhenkun, F and Shuang, C and Jie, Z and Hua, Z and Wei, J and Da, P and Dianjun, L}, title = {Association of DNMT1 gene polymorphisms in exons with sporadic infiltrating ductal breast carcinoma among Chinese Han women in the Heilongjiang Province.}, journal = {Clinical breast cancer}, volume = {10}, number = {5}, pages = {373-377}, doi = {10.3816/CBC.2010.n.049}, pmid = {20920981}, issn = {1938-0666}, mesh = {Adult ; Aged ; Alleles ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Case-Control Studies ; Chi-Square Distribution ; China ; Exons ; Female ; Haplotypes ; Humans ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Repressor Proteins/*genetics ; Tumor Suppressor Protein p53/metabolism ; Young Adult ; }, abstract = {BACKGROUND: Infiltrating ductal carcinoma (IDC) is the most common malignant breast cancer in women, and genetic factors appear to play a significant role in the susceptibility to IDC. Alteration of DNA methylation is an epigenetic change in human cancers, including breast cancer. DNA-methyltransferase 1 (DNMT1) is a major enzyme that determines genomic methylation patterns. In order to clarify the association of DNMT1 polymorphisms with IDC, a case-control study was conducted in women from the Heilongjiang Province, in the northeast of China.<br><br>PATIENTS AND METHODS: We scrutinized the 2 genetic polymorphisms in exons of DNMT1 that may influence the activity of DNMT1. Our research subjects consisted of 305 patients with IDC and 314 age-matched healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Data were analyzed using the &#x3c7;2 test by SPSS, version 13.0, and Haploview, version 4.1. The association between DNMT1 polymorphisms and the clinical features of IDC was analyzed.<br><br>RESULTS: In rs16999593, the frequency of CT genotype and C allele were lower in patients than in controls (P = .028 and P = .017, respectively). Also, rs2228611 AG genotype was higher in patients than in controls (P = .015). The frequency of haplotype CA was lower in patients than in controls (P = .034). Significant association was shown between the 2 single nucleotide polymorphisms of the DNMT1 gene and progesterone receptor (PgR) and p53 status. No association was found between DNMT1 gene polymorphisms and tumor size or estrogen receptor status.<br><br>CONCLUSION: Our results was a previous study, which suggested that DNMT1 gene polymorphisms in exons may provide valuable information for predicting the sporadic IDC risk and may be associated with prognosis factors such as PgR and p53 status in Chinese Han women in the Heilongjiang Province.}, }
@article {pmid20886042, year = {2010}, author = {Lo Presti, M and Ferro, A and Contino, F and Mazzarella, C and Sbacchi, S and Roz, E and Lupo, C and Perconti, G and Giallongo, A and Migliorini, P and Marrazzo, A and Feo, S}, title = {Myc promoter-binding protein-1 (MBP-1) is a novel potential prognostic marker in invasive ductal breast carcinoma.}, journal = {PloS one}, volume = {5}, number = {9}, pages = {e12961}, pmid = {20886042}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/*genetics/metabolism/pathology ; Carcinoma, Ductal/*diagnosis/*genetics/metabolism/pathology ; Cell Nucleus/genetics/metabolism ; Cytoplasm/enzymology/genetics ; DNA-Binding Proteins/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Phosphopyruvate Hydratase/genetics/metabolism ; Prognosis ; Protein Transport ; }, abstract = {BACKGROUND: Alpha-enolase is a glycolytic enzyme that catalyses the formation of phosphoenolpyruvate in the cell cytoplasm. α-Enolase and the predominantly nuclear Myc promoter-binding protein-1 (MBP-1) originate from a single gene through the alternative use of translational starting sites. MBP-1 binds to the P2 c-myc promoter and competes with TATA-box binding protein (TBP) to suppress gene transcription. Although several studies have shown an antiproliferative effect of MBP-1 overexpression on several human cancer cells, to date detailed observations of α-enolase and MBP-1 relative expression in primary tumors versus normal tissues and their correlation with clinicopathological features have not been undertaken.<br><br>METHODOLOGY AND FINDINGS: We analyzed &#x3b1;-enolase and MBP-1 expression in normal breast epithelium and primary invasive ductal breast carcinoma (IDC) from 177 patients by Western blot and immunohistochemical analyses, using highly specific anti-&#x3b1;-enolase monoclonal antibodies. A significant increase in the expression of cytoplasmic &#x3b1;-enolase was observed in 98% of the tumors analysed, compared to normal tissues. Nuclear MBP-1 was found in almost all the normal tissues while its expression was retained in only 35% of the tumors. Statistically significant associations were observed among the nuclear expression of MBP-1 and ErbB2 status, Ki-67 expression, node status and tumor grade. Furthermore MBP-1 expression was associated with good survival of patients with IDC.<br><br>CONCLUSIONS: MBP-1 functions in repressing c-myc gene expression and the results presented indicate that the loss of nuclear MBP-1 expression in a large number of IDC may be a critical step in the development and progression of breast cancer and a predictor of adverse outcome. Nuclear MBP-1 appears to be a novel and valuable histochemical marker with potential prognostic value in breast cancer.}, }
@article {pmid20878073, year = {2010}, author = {Nie, F and Yu, XL and Wang, XG and Tang, YF and Wang, LL and Ma, L}, title = {Down-regulation of CacyBP is associated with poor prognosis and the effects on COX-2 expression in breast cancer.}, journal = {International journal of oncology}, volume = {37}, number = {5}, pages = {1261-1269}, doi = {10.3892/ijo_00000777}, pmid = {20878073}, issn = {1791-2423}, mesh = {Blotting, Western ; Breast Neoplasms/*genetics/metabolism/pathology ; Calcium-Binding Proteins/biosynthesis/*genetics ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Cyclooxygenase 2/*genetics/metabolism ; Down-Regulation ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Prognosis ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Calcyclin-binding protein (CacyBP) is a tumor suppressor in gastric and renal cell carcinoma, but an oncogene in pancreatic cancer. However, the function of CacyBP in breast cancer has not been well elucidated. In this study, we explored the clinical relevance of CacyBP and investigated the relationship between CacyBP and COX-2 in breast cancer. Immunohistochemical analysis in 172 cases of breast tissues showed that the positive rate of CacyBP protein expression in normal breast tissues (NBT) (89.3%) was higher than that in invasive ductal carcinoma (IDC) (56.1%) (P<0.05). RT-PCR and Western blot analysis showed that CacyBP mRNA and protein expression were significantly lower in tumor tissues as compared to those in the corresponding non-tumorous tissues (P<0.05). The expression trend of COX-2 was opposite with CacyBP in breast carcinogenesis. Moreover, the CacyBP expression was significantly negatively associated with the COX expression in the 132 breast cancer samples (correlation coefficient = 0.505, P<0.001). The clinicopathological data analysis in 132 breast cancer samples showed that CacyBP expression was positively correlated with well differentiated samples (P=0.021), low pathologic TNM stage (P=0.009), and no lymphatic metastasis (P=0.027) of patients with breast cancer. Furthermore, reduced CacyBP expression was associated with poor prognosis. Knockdown of CacyBP gene using siRNA enhanced the proliferation and invasion ability of breast cancer cells, which was dependent on COX-2 expression. In conclusion, CacyBP regulation of COX-2 expression may play an important role in human breast carcinogenesis. Restoration of CacyBP gene is a potential therapeutic target of breast cancer.}, }
@article {pmid20864896, year = {2010}, author = {Hershberger, RE and Morales, A and Siegfried, JD}, title = {Clinical and genetic issues in dilated cardiomyopathy: a review for genetics professionals.}, journal = {Genetics in medicine : official journal of the American College of Medical Genetics}, volume = {12}, number = {11}, pages = {655-667}, pmid = {20864896}, issn = {1530-0366}, support = {R01 HL058626/HL/NHLBI NIH HHS/United States ; R01-HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Age of Onset ; Cardiomyopathy, Dilated/classification/*diagnosis/epidemiology/*genetics ; Genes ; *Genetic Counseling ; Genetic Testing ; Humans ; Pedigree ; }, abstract = {Dilated cardiomyopathy (DCM), usually diagnosed as idiopathic dilated cardiomyopathy (IDC), has been shown to have a familial basis in 20-35% of cases. Genetic studies in familial dilated cardiomyopathy (FDC) have shown dramatic locus heterogeneity with mutations identified in >30 mostly autosomal genes showing primarily dominant transmission. Most mutations are private missense, nonsense or short insertion/deletions. Marked allelic heterogeneity is the rule. Although to date most DCM genetics fits into a Mendelian rare variant disease paradigm, this paradigm may be incomplete with only 30-35% of FDC genetic cause identified. Despite this incomplete knowledge, we predict that DCM genetics will become increasingly relevant for genetics and cardiovascular professionals. This is because DCM causes heart failure, a national epidemic, with considerable morbidity and mortality. The fact that early, even pre-symptomatic intervention can prevent or ameliorate DCM, coupled with more cost-effective genetic testing, will drive further progress in the field. Ongoing questions include: whether sporadic (IDC) disease has a genetic basis, and if so, how it differs from familial disease; which gene-specific or genetic pathways are most relevant; and whether other genetic mechanisms (e.g., DNA structural variants, epigenetics, mitochondrial mutations and others) are operative in DCM. We suggest that such new knowledge will lead to novel approaches to the prevention and treatment of DCM.}, }
@article {pmid20860963, year = {2010}, author = {Szabó, J and Falkus, B and Simon, E and Brünner, S and Baranyay, F}, title = {[Late gastrointestinal metastases of invasive lobular breast carcinoma mimicking Crohn's disease].}, journal = {Orvosi hetilap}, volume = {151}, number = {40}, pages = {1666-1671}, doi = {10.1556/OH.2010.28927}, pmid = {20860963}, issn = {0030-6002}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/chemistry/*secondary ; Carcinoma, Lobular/chemistry/*secondary ; Crohn Disease/*diagnosis ; Diagnosis, Differential ; Female ; Gastrointestinal Neoplasms/chemistry/*diagnosis/*secondary ; Humans ; Middle Aged ; }, abstract = {Invasive lobular carcinoma--comprising approximately 10 percent of breast cancers--is considered to be a histologically, molecular genetically, clinically distinct entity metastasizing mainly the gastrointestinal tract. Gastrointestinal system is much more likely involved in advanced invasive lobular carcinoma, than it is in invasive ductal carcinoma. They manifest after 3-20 years from the recognition of the primary tumor and they appear to be inflammatory disease or a secondary tumor. Here we show the case of a female patient with breast cancer, who died at the age of 53 years. 8 years after tumor-free state upper abdominal spastic pain emerged irradiating into the back with belt-like pattern. Radiologically, Crohn's disease was diagnosed. Ileum biopsy was negative. Patient was treated ex juvantibus with methylprednisolon. In the background of mechanic ileus the resection of the terminal ileum and partly the ascended colon was surgically removed. The patient died in 3 weeks after the operation. Microscopically the thickened wall of the terminal ileum showed diffuse small cell carcinomatous infiltration. Immuno-histochemically the metastatic carcinoma cells were reacting with Breast Carcinoma Antigen (BRCA 1) and CA 15-3. The patient had AB blood group according to her red blood cell phenotype. Lectins and monoclonal antibodies with ABH blood group specificity reacted strongly with the metastatic carcinoma cells.}, }
@article {pmid20854466, year = {2010}, author = {Pal, R and Marwaha, S and Pepponi, I and Mann, JF and Paul, MJ and Reljic, R}, title = {Generation of self-renewing immature dendritic cells from mouse spleen that can take up mycobacteria and present antigens to T cells.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {118}, number = {10}, pages = {729-738}, doi = {10.1111/j.1600-0463.2010.02650.x}, pmid = {20854466}, issn = {1600-0463}, mesh = {Animals ; Antigen Presentation ; Antigens, Bacterial/immunology ; Cell Culture Techniques ; Dendritic Cells/cytology/*immunology ; Female ; Flow Cytometry ; Lymphocyte Activation ; Lymphoid Progenitor Cells/cytology/*immunology ; Mice ; Mice, Inbred BALB C ; Mycobacterium/*immunology ; Spleen/cytology/*immunology ; T-Lymphocytes/cytology/immunology ; Tuberculosis/*immunology ; }, abstract = {Dendritic cells (DC) play a key role in driving the adaptive immune response to Mycobacterium tuberculosis (MTB), the causative pathogen of tuberculosis (TB). However, studying these important yet very sparse immune cells in the context of MTB pathogenesis is severely restricted by the lack of suitable cell lines and the complexity of culturing of DC progenitors, usually obtained from the bone marrow. However, significant advances have been made towards generating long-term DC cultures from various lymphoid tissues. Here, we report the evidence for generating a long-term, self-renewing DC culture from the Balb/c mouse spleen. We demonstrate that these cells, termed IDC-3, have a myeloid DC origin, i.e. they are CD11c(+) CD11b(++) CD8-α(-) F4/80(+/-) and that they also display a phenotype MHC-II(+) CD16/32(++) CD80(+/-) CD86(+) , indicating that they are immature DC. Following incubation with Mycobacterium bovis BCG (Bacillus Calmette Guerin), the IDC-3 efficiently took up bacteria and acquired the morphology of mature DC. Importantly though, when IDC-3 were pre-stimulated with a mycobacterial antigen in vitro, they were able to induce proliferation of T lymphocytes from mice immunized with the same antigen. The T-cell stimulatory potential of IDC-3 was further enhanced when the cells were co-stimulated with an anti-CD40 mAb. We therefore suggest that the IDC-3 culture system could be a useful tool for studying the interaction of DC with mycobacteria.}, }
@article {pmid20846267, year = {2010}, author = {Lee, YH and Dai, YC and Lin, IL and Tu, CW}, title = {Young-aged woman with invasive ductal carcinoma arising in atypical microglandular adenosis: a case report.}, journal = {Pathology international}, volume = {60}, number = {10}, pages = {685-689}, doi = {10.1111/j.1440-1827.2010.02577.x}, pmid = {20846267}, issn = {1440-1827}, mesh = {Adult ; Breast Neoplasms/complications/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/complications/metabolism/*pathology/therapy ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease/complications/metabolism/*pathology/therapy ; Humans ; Immunohistochemistry ; Mastectomy, Segmental ; }, abstract = {Microglandular adenosis (MGA) and atypical microglandular adenosis (AMGA) are extremely rare and unique forms of adenosis of the breast. Both forms of adenosis are strongly associated with carcinoma arising in microglandular adenosis (MGACA) and are recognised as precursor lesions of invasive breast carcinoma. Here we provide a clinical report of a young Taiwanese woman who was diagnosed with MGACA and AMGA by means of echo-guided core biopsy. The subsequent lumpectomy revealed a spectrum of lesions ranging from MGA and AMGA to ductal carcinoma in situ (DCIS) and invasive carcinoma. All of the above lesions have similar immunohistochemical results (expression of S-100 protein, the absence of oestrogen receptors, progesterone receptors and Her2/neu, and the lack of p63 and the smooth muscle myosin-heavy chain) with a rather different Ki-67 labelling proliferation index. This report is of practical interest because the diagnosis of AMGA and MGACA had already been made via needle biopsy.}, }
@article {pmid20830525, year = {2010}, author = {Lage, S and Bueno, M and Andrade, F and Prieto, JA and Delgado, C and Legarda, M and Sanjurjo, P and Aldámiz-Echevarría, LJ}, title = {Fatty acid profile in patients with phenylketonuria and its relationship with bone mineral density.}, journal = {Journal of inherited metabolic disease}, volume = {33 Suppl 3}, number = {}, pages = {S363-71}, doi = {10.1007/s10545-010-9189-0}, pmid = {20830525}, issn = {1573-2665}, mesh = {Absorptiometry, Photon ; Adolescent ; Adult ; Biomarkers/blood ; *Bone Density ; Bone Diseases, Metabolic/blood/diagnosis/*etiology/physiopathology ; Calcium/blood ; Case-Control Studies ; Child ; Cross-Sectional Studies ; Diet, Protein-Restricted/*adverse effects ; Docosahexaenoic Acids/blood ; Eicosapentaenoic Acid/blood ; Fatty Acids/*blood ; Female ; Femur Neck/diagnostic imaging/*physiopathology ; Humans ; Lumbar Vertebrae/diagnostic imaging/*physiopathology ; Male ; Nutritional Status ; Osteoporosis/blood/diagnosis/*etiology/physiopathology ; Phenylalanine/blood ; Phenylketonurias/blood/diagnosis/*diet therapy/physiopathology ; Risk Factors ; Vitamin D/analogs &amp; derivatives/blood ; Young Adult ; }, abstract = {BACKGROUND: Patients with phenylketonuria (PKU) undergo a restrictive vegan-like diet, with almost total absence of n-3 fatty acids, which have been proposed as potential contributors to bone formation in the healthy population. The PKU diet might lead these patients to bone mass loss and, consequently, to the development of osteopenia/osteoporosis. Therefore, we proposed to analyze their plasma fatty acid profile status and its relationship with bone health.<br><br>METHODS: We recruited 47 PKU patients for this cross-sectional study and divided the cohort into three age groups (6-10 years, 11-18 years, 19-42 years). We measured their plasma fatty acid profile and bone mineral density (BMD) (both at the femoral neck and the lumbar spine). Seventy-seven healthy controls also participated as reference values of plasma fatty acids.<br><br>RESULTS: Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and total n-3 fatty acids were significantly diminished in PKU patients compared with healthy controls. DHA, EPA, and total n-3 fatty acids were also positively associated with bone mineral density (r = 0.83, p = 0.010; r = 0.57, p = 0.006; r = 0.73, p = 0.040, respectively). There was no association between phenylalanine (Phe), Index of Dietary Control (IDC), calcium, 25-hydroxivitamin D concentrations, daily calcium intake, and BMD.<br><br>CONCLUSION: Our results suggest a possible influence of essential fatty acids over BMD in PKU patients. The lack of essential n-3 fatty acids intake in the PKU diet might affect bone mineralization. Further clinical trials are needed to confirm the effect of the n-3 essential fatty acids on bone accrual in a cohort of PKU patients.}, }
@article {pmid20816984, year = {2010}, author = {Luncsford, PJ and Chang, DY and Shi, G and Bernstein, J and Madabushi, A and Patterson, DN and Lu, AL and Toth, EA}, title = {A structural hinge in eukaryotic MutY homologues mediates catalytic activity and Rad9-Rad1-Hus1 checkpoint complex interactions.}, journal = {Journal of molecular biology}, volume = {403}, number = {3}, pages = {351-370}, pmid = {20816984}, issn = {1089-8638}, support = {R56 CA078391/CA/NCI NIH HHS/United States ; R01 GM035132/GM/NIGMS NIH HHS/United States ; CA78391/CA/NCI NIH HHS/United States ; GM35132/GM/NIGMS NIH HHS/United States ; R01 CA078391/CA/NCI NIH HHS/United States ; }, mesh = {Cell Cycle Proteins/genetics/*metabolism ; DNA/genetics/metabolism ; DNA Damage ; DNA Glycosylases/*chemistry/genetics/*metabolism ; DNA Repair ; Exonucleases/genetics/*metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Mutation/genetics ; Protein Binding ; Schizosaccharomyces/genetics/growth &amp; development/metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism ; }, abstract = {The DNA glycosylase MutY homologue (MYH or MUTYH) removes adenines misincorporated opposite 8-oxoguanine as part of the base excision repair pathway. Importantly, defects in human MYH (hMYH) activity cause the inherited colorectal cancer syndrome MYH-associated polyposis. A key feature of MYH activity is its coordination with cell cycle checkpoint via interaction with the Rad9-Rad1-Hus1 (9-1-1) complex. The 9-1-1 complex facilitates cell cycle checkpoint activity and coordinates this activity with ongoing DNA repair. The interdomain connector (IDC, residues 295-350) between the catalytic domain and the 8-oxoguanine recognition domain of hMYH is a critical element that maintains interactions with the 9-1-1 complex. We report the first crystal structure of a eukaryotic MutY protein, a fragment of hMYH (residues 65-350) that consists of the catalytic domain and the IDC. Our structure reveals that the IDC adopts a stabilized conformation projecting away from the catalytic domain to form a docking scaffold for 9-1-1. We further examined the role of the IDC using Schizosaccharomyces pombe MYH as model system. In vitro studies of S. pombe MYH identified residues I261 and E262 of the IDC (equivalent to V315 and E316 of the hMYH IDC) as critical for maintaining the MYH/9-1-1 interaction. We determined that the eukaryotic IDC is also required for DNA damage selection and robust enzymatic activity. Our studies also provide the first evidence that disruption of the MYH/9-1-1 interaction diminishes the repair of oxidative DNA damage in vivo. Thus, preserving the MYH/9-1-1 interaction contributes significantly to minimizing the mutagenic potential of oxidative DNA damage.}, }
@article {pmid20815046, year = {2010}, author = {Lacroix-Triki, M and Suarez, PH and MacKay, A and Lambros, MB and Natrajan, R and Savage, K and Geyer, FC and Weigelt, B and Ashworth, A and Reis-Filho, JS}, title = {Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.}, journal = {The Journal of pathology}, volume = {222}, number = {3}, pages = {282-298}, doi = {10.1002/path.2763}, pmid = {20815046}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adenocarcinoma, Mucinous/*genetics/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Chromosome Aberrations ; Cluster Analysis ; Comparative Genomic Hybridization/methods ; Female ; Gene Amplification ; Gene Expression Profiling/methods ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Oncogenes ; }, abstract = {Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the molecular level to pure mucinous cancers, suggesting that mixed mucinous carcinomas may be best classified as variants of mucinous cancers rather than of IDC-NSTs.}, }
@article {pmid20808831, year = {2010}, author = {Chen, J and Gomes, AR and Monteiro, LJ and Wong, SY and Wu, LH and Ng, TT and Karadedou, CT and Millour, J and Ip, YC and Cheung, YN and Sunters, A and Chan, KY and Lam, EW and Khoo, US}, title = {Constitutively nuclear FOXO3a localization predicts poor survival and promotes Akt phosphorylation in breast cancer.}, journal = {PloS one}, volume = {5}, number = {8}, pages = {e12293}, pmid = {20808831}, issn = {1932-6203}, support = {12011/CRUK_/Cancer Research UK/United Kingdom ; 2007NOVPHD16/BCN_/Breast Cancer Now/United Kingdom ; C37/A5606/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Active Transport, Cell Nucleus/drug effects ; Breast Neoplasms/*diagnosis/genetics/*metabolism/pathology ; Carcinoma, Ductal/diagnosis/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/drug effects/*metabolism ; Cell Proliferation/drug effects ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm ; Forkhead Box Protein O3 ; Forkhead Transcription Factors/genetics/*metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Phosphorylation/drug effects ; Prognosis ; Proto-Oncogene Proteins c-akt/*metabolism ; Survival Analysis ; Tamoxifen/pharmacology ; }, abstract = {BACKGROUND: The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis.<br><br>Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway.<br><br>CONCLUSIONS/SIGNIFICANCE: Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell death or cell cycle arrest. As such, sustained nuclear FOXO3a expression in breast cancer may culminate in cancer progression and the development of an aggressive phenotype similar to that observed in cytotoxic chemotherapy resistant breast cancer cell models.}, }
@article {pmid20799942, year = {2010}, author = {Hawthorn, L and Luce, J and Stein, L and Rothschild, J}, title = {Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {460}, pmid = {20799942}, issn = {1471-2407}, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast/metabolism/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Case-Control Studies ; *Chromosome Aberrations ; Comparative Genomic Hybridization ; DNA, Neoplasm ; Female ; *Gene Dosage ; *Gene Expression Profiling ; Humans ; *Loss of Heterozygosity ; Lymphatic Metastasis ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine parallel analyses that assess changes in the copy number alterations (CNAs). This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions which demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes'.<br><br>METHODS: We have performed whole genome analysis of CNAs using the Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs). Analysis of transcript expression alterations was performed using the Affymetrix U133 Plus2.0 array on 16 IDC samples. Fourteen IDC samples were analyzed using both platforms and the data integrated. We also incorporated data from loss of heterozygosity (LOH) analysis to identify genes showing altered expression in LOH regions.<br><br>RESULTS: Common chromosome gains and amplifications were identified at 1q21.3, 6p21.3, 7p11.2-p12.1, 8q21.11 and 8q24.3. A novel amplicon was identified at 5p15.33. Frequent losses were found at 1p36.22, 8q23.3, 11p13, 11q23, and 22q13. Over 130 genes were identified with concurrent increases or decreases in expression that mapped to these regions of copy number alterations. LOH analysis revealed three tumors with whole chromosome or p arm allelic loss of chromosome 17. Genes were identified that mapped to copy neutral LOH regions. LOH with accompanying copy loss was detected on Xp24 and Xp25 and genes mapping to these regions with decreased expression were identified. Gene expression data highlighted the PPAR&#x3b1;/RXR&#x3b1; Activation Pathway as down-regulated in the tumor samples.<br><br>CONCLUSION: We have demonstrated the utility of the application of integrated analysis using high resolution CGH and whole genome transcript analysis for detecting driver genes in IDC. The high resolution platform allowed a refined demarcation of CNAs and gene expression profiling provided a mechanism to detect genes directly impacted by the CNA. This is the first report of LOH integrated with gene expression in IDC using a high resolution platform.}, }
@article {pmid20733117, year = {2010}, author = {Li, CI and Chlebowski, RT and Freiberg, M and Johnson, KC and Kuller, L and Lane, D and Lessin, L and O'Sullivan, MJ and Wactawski-Wende, J and Yasmeen, S and Prentice, R}, title = {Alcohol consumption and risk of postmenopausal breast cancer by subtype: the women's health initiative observational study.}, journal = {Journal of the National Cancer Institute}, volume = {102}, number = {18}, pages = {1422-1431}, pmid = {20733117}, issn = {1460-2105}, support = {N01WH22110/WH/WHI NIH HHS/United States ; N01WH42129-32/WH/WHI NIH HHS/United States ; N01WH32100-2/WH/WHI NIH HHS/United States ; N01WH32108-9/WH/WHI NIH HHS/United States ; N01WH42107-26/WH/WHI NIH HHS/United States ; N01WH32122/WH/WHI NIH HHS/United States ; N01WH32105-6/WH/WHI NIH HHS/United States ; N01WH32111-13/WH/WHI NIH HHS/United States ; N01WH32118-32119/WH/WHI NIH HHS/United States ; N01WH32115/WH/WHI NIH HHS/United States ; N01WH44221/WH/WHI NIH HHS/United States ; N01WH24152/WH/WHI NIH HHS/United States ; }, mesh = {Aged ; Alcohol Drinking/*adverse effects ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/*epidemiology/etiology ; Carcinoma, Ductal, Breast/chemistry/*epidemiology/etiology ; Carcinoma, Lobular/chemistry/*epidemiology/etiology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasms, Hormone-Dependent/chemistry/*epidemiology/etiology ; Observation ; Odds Ratio ; *Postmenopause ; Proportional Hazards Models ; Prospective Studies ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Risk Factors ; United States/epidemiology ; *Women's Health ; }, abstract = {BACKGROUND: Alcohol consumption is a well-established risk factor for breast cancer. This association is thought to be largely hormonally driven, so alcohol use may be more strongly associated with hormonally sensitive breast cancers. Few studies have evaluated how alcohol-related risk varies by breast cancer subtype.<br><br>METHODS: We assessed the relationship between self-reported alcohol consumption and postmenopausal breast cancer risk among 87&#x2009;724 women in the Women's Health Initiative Observational Study prospective cohort from 1993 through 1998. Multivariable adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.<br><br>RESULTS: A total of 2944 invasive breast cancer patients were diagnosed during follow-up through September 15, 2005. In multivariable adjusted analyses, alcohol consumption was positively related to risk of invasive breast cancer overall, invasive lobular carcinoma, and hormone receptor-positive tumors (all P(trend) &#x2264; .022). However, alcohol consumption was more strongly related to risk of certain types of invasive breast cancer compared with others. Compared with never drinkers, women who consumed seven or more alcoholic beverages per week had an almost twofold increased risk of hormone receptor-positive invasive lobular carcinoma (HR = 1.82; 95% CI = 1.18 to 2.81) but not a statistically significant increased risk of hormone receptor-positive invasive ductal carcinoma (HR = 1.14; 95% CI = 0.87 to 1.50; difference in HRs per drink per day among current drinkers = 1.15; 95% CI = 1.01 to 1.32, P = .042). The absolute rates of hormone receptor-positive lobular cancer among never drinkers and current drinkers were, 5.2 and 8.5 per 10&#x2009;000 person-years, respectively, whereas for hormne receptor-positive ductal cancer they were 15.2 and 17.9 per 10&#x2009;000 person-years, respectively.<br><br>CONCLUSIONS: Alcohol use may be more strongly associated with risk of hormone-sensitive breast cancers than hormone-insensitive subtypes, suggesting distinct etiologic pathways for these two breast cancer subtypes.}, }
@article {pmid20731838, year = {2010}, author = {Shishido-Hara, Y and Kurata, A and Fujiwara, M and Itoh, H and Imoto, S and Kamma, H}, title = {Two cases of breast carcinoma with osteoclastic giant cells: are the osteoclastic giant cells pro-tumoural differentiation of macrophages?.}, journal = {Diagnostic pathology}, volume = {5}, number = {}, pages = {55}, pmid = {20731838}, issn = {1746-1596}, mesh = {Adult ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/blood supply/chemistry/immunology/*pathology/surgery ; Carcinoma, Ductal, Breast/blood supply/chemistry/immunology/*pathology/surgery ; Carcinoma, Giant Cell/blood supply/chemistry/immunology/*pathology/surgery ; Carcinosarcoma/blood supply/chemistry/immunology/*pathology/surgery ; *Cell Transdifferentiation ; Female ; Humans ; Immunohistochemistry ; Macrophages/chemistry/immunology/*pathology ; Mastectomy ; Microvessels/pathology ; Neoplasm Staging ; Osteoclasts/chemistry/immunology/*pathology ; Tumor Microenvironment ; }, abstract = {Breast carcinoma with osteoclastic giant cells (OGCs) is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1) had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2) with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K) and a histiocyte marker (CD68), but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.}, }
@article {pmid20704578, year = {2010}, author = {Tamaki, K and Sasano, H and Maruo, Y and Takahashi, Y and Miyashita, M and Moriya, T and Sato, Y and Hirakawa, H and Tamaki, N and Watanabe, M and Ishida, T and Ohuchi, N}, title = {Vasohibin-1 as a potential predictor of aggressive behavior of ductal carcinoma in situ of the breast.}, journal = {Cancer science}, volume = {101}, number = {4}, pages = {1051-1058}, doi = {10.1111/j.1349-7006.2009.01483.x}, pmid = {20704578}, issn = {1349-7006}, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cell Cycle Proteins/*metabolism ; Cell Nucleus/chemistry/genetics/metabolism ; Female ; Humans ; Neovascularization, Pathologic/genetics ; Platelet Endothelial Cell Adhesion Molecule-1/genetics/metabolism ; Risk ; Vascular Endothelial Growth Factor A/genetics/metabolism ; }, abstract = {Vasohibin-1 is a recently identified negative feedback regulator of angiogenesis induced by VEGF-A and bFGF. In this study, we first evaluated mRNA expression of vasohibin-1 and CD31 in 39 Japanese female breast carcinoma specimens including 22 invasive ductal carcinoma (IDC) and 17 ductal carcinoma in situ (DCIS) using a real-time quantitative RT-PCR (QRT-PCR) with LightCycler system. In addition, we also immunolocalized vasohibin-1 and CD31 and compared their immunoreactivity to nuclear grades and histological grades of 100 carcinoma cases (50 IDC and 50 DCIS). There were no statistically significant differences of CD31 mRNA expression and the number of CD31 positive vessels between DCIS and IDC (P = 0.250 and P = 0.191, respectively), whereas there was a statistically significant difference in vasohibin-1 mRNA expression and the number of vasohibin-1 positive vessels in DCIS and IDC (P = 0.022 and P < or = 0.001, respectively). There was a significant positive correlation between vasohibin-1 mRNA level and Ki-67 labeling index in DCIS (r(2) = 0.293, P < or = 0.001). In addition, vasohibin-1 mRNA expression was correlated with high nuclear and histological grades in DCIS cases and a significant positive correlation was detected between the number of vasohibin-1 positive vessels and Ki-67 labeling index or nuclear grade or Van Nuys classification of carcinoma cells (P < or = 0.001, respectively). These results all indicate the possible correlation between aggressive biological features in DCIS including increased tumor cell proliferation and the status of neovascularization determined by vasohibin-1 immunoreactivity.}, }
@article {pmid20703102, year = {2010}, author = {Yu, J and Ohuchida, K and Mizumoto, K and Fujita, H and Nakata, K and Tanaka, M}, title = {MicroRNA miR-17-5p is overexpressed in pancreatic cancer, associated with a poor prognosis, and involved in cancer cell proliferation and invasion.}, journal = {Cancer biology &amp; therapy}, volume = {10}, number = {8}, pages = {748-757}, doi = {10.4161/cbt.10.8.13083}, pmid = {20703102}, issn = {1555-8576}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Line, Tumor ; *Cell Proliferation ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/*genetics ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*genetics/pathology ; Paraffin Embedding ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Analysis ; Tissue Fixation ; }, abstract = {The microRNA-17-92 cluster is an oncogene in human B cell lymphomas and lung cancers. Previous microRNA microarray data revealed that miR-17-5p, a member of the miR-17-92 cluster, is upregulated in pancreatic cancer. However, the involvement of miR-17-5p expression in pancreatic carcinogenesis has not well been studied. In the present study, we measured the miR-17-5p expression levels in pancreatic cancer cell lines, primary cultures of normal human pancreatic ductal cells, formalin-fixed paraffin-embedded (FFPE) tissue samples derived from 80 patients who underwent pancreatectomy for pancreatic cancer and microdissected cells (including normal ductal epithelial, pancreatic intraepithelial neoplasia-1B and invasive ductal carcinoma cells) by qRT-PCR. Furthermore, we investigated the effects of upregulation of miR-17-5p expression on the proliferation and invasion of pancreatic cancer cells. We found that pancreatic cancer cells expressed higher levels of miR-17-5p than primary cultured normal ductal cells. miR-17-5p was also overexpressed in pancreatic cancer in FFPE and microdissected samples. Furthermore, analysis of macrodissected FFPE samples revealed that high miR-17-5p expression was associated with a poor prognosis (p = 0.03). In addition, in vitro experiments revealed that SUIT-2 and KP-2 pancreatic cancer cells transfected with the miR-17-5p precursor showed significantly higher cell growth ratios than the corresponding control cells (p < 0.001 and p = 0.012, respectively), as well as significantly higher numbers of invading cells (p < 0.0001 for both). The present findings suggest that miR-17-5p plays important roles in pancreatic carcinogenesis and cancer progression, and is associated with a poor prognosis in pancreatic cancer.}, }
@article {pmid20701077, year = {2010}, author = {Nese, N and Kandiloglu, AR and Simsek, G and Lekili, M and Ozdamar, A and Catalkaya, A and Coskun, T}, title = {Comparison of the desmoplastic reaction and invading ability in invasive ductal carcinoma of the breast and prostatic adenocarcinoma based on the expression of heat shock protein 47 and fascin.}, journal = {Analytical and quantitative cytology and histology}, volume = {32}, number = {2}, pages = {90-101}, pmid = {20701077}, mesh = {Adenocarcinoma/metabolism/mortality/*secondary ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*secondary ; Carrier Proteins/*metabolism ; Female ; HSP47 Heat-Shock Proteins/*metabolism ; Humans ; Immunoenzyme Techniques ; Male ; Mastectomy ; Microfilament Proteins/*metabolism ; Middle Aged ; Neoplasm Staging ; Prostatectomy ; Prostatic Neoplasms/metabolism/mortality/*pathology ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the diversity within invasive ductal carcinoma (IDC) and prostatic adenocarcinoma (PCa) by evaluating immunohistochemical expression of heat shock protein 47 (HSP47) and fascin, the molecules that are related to desmoplasia and invasion, and analyze its correlation with clinicopathologic parameters.<br><br>STUDY DESIGN: HSP47 and fascin immunoreactivity (IR) was evaluated in 49 mastectomies diagnosed as IDC and 57 radical prostatectomies diagnosed as PCa. IR was evaluated as: 0: < 5%, 1+: 5-25%, 2+: 25-50%, 3+: > 50%.<br><br>RESULTS: HSP47 and fascin were localized to cytoplasm, and HSP47 and fascin IR were higher in IDC and PCa than benign groups (p < 0.05). HSP47 IR in neoplastic cells was 42.1% and 28.6%, in stroma was 81.6% and 15.8% in IDC and PCa, respectively; fascin IR in neoplastic cells was 65.3% in IDC and 15.8% in PCa. Fascin expression correlated with estrogen receptor and progesterone receptor negativity, tumor size and stage in IDC and surgical margin status in PCa. HSP47 expression correlated bilaterality in PCa. HSP47 positively correlated with survival in IDC.<br><br>CONCLUSION: HSP47 and fascin expression may play role in the pathogenesis of IDC and PCa because their expression is significantly higher in IDC and PCa than their normal counterpart. Although there is no relationship with recurrence or metastatic status, fascin overexpression correlated with tumor size, which may prompt its use as a prognostic factor in IDC.}, }
@article {pmid20698136, year = {2010}, author = {Besser-Silconi, Z and Lozić, AA and Misljenović, N}, title = {Fine needle aspiration cytology of minimal breast cancer in Istria County.}, journal = {Collegium antropologicum}, volume = {34}, number = {2}, pages = {605-607}, pmid = {20698136}, issn = {0350-6134}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/methods ; Biopsy, Needle/*methods ; Breast Neoplasms/*pathology ; Croatia ; Female ; Humans ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {Breast cancer is the most frequent malignant tumour and leading cause of death in women aged 35 to 64 years in Istria County. The minimal invasive carcinoma and in situ carcinoma have a better prognosis so we try to find them during preventive exams. The aim of this study was to identify minimal breast cancers in fine needle aspiration biopsies of breast lesions made in Pula General Hospital between the years 2006 and 2008. There were 39 tumours with a maximal diameter of less than 10 mm in 1316 biopsies and 251 cytologically diagnosed breast cancers. In most cases, they were solitary, well differentiated neoplasms (48.7%). They were diagnosed in women aged 39 to 89 years and most frequently found in women aged 60 to 69 years. The most frequent histological type of operated minimal breast carcinomas was invasive ductal carcinoma. In that period, the minimal breast cancer percentage of all cytologically diagnosed breast cancers was 15.5% but in the first 6 months of 2009, the result was 48.7%.}, }
@article {pmid20682973, year = {2010}, author = {Cho, YH and Yazici, H and Wu, HC and Terry, MB and Gonzalez, K and Qu, M and Dalay, N and Santella, RM}, title = {Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients.}, journal = {Anticancer research}, volume = {30}, number = {7}, pages = {2489-2496}, pmid = {20682973}, issn = {1791-7530}, support = {P30 CA013696/CA/NCI NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; ES009089/ES/NIEHS NIH HHS/United States ; CA013696/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood/*genetics ; Breast Neoplasms/*blood/*genetics ; Case-Control Studies ; *DNA Methylation ; DNA, Neoplasm/*blood/genetics ; Female ; Humans ; Leukocytes/chemistry/physiology ; Middle Aged ; Promoter Regions, Genetic ; }, abstract = {BACKGROUND: Promoter hypermethylation and global hypomethylation in the human genome are hallmarks of most cancers. Detection of aberrant methylation in white blood cells (WBC) has been suggested as a marker for cancer development, but has not been extensively investigated. This study was carried out to determine whether aberrant methylation in WBC DNA can be used as a surrogate biomarker for breast cancer risk.<br><br>PATIENTS AND METHODS: Promoter hypermethylation of 8 tumor suppressor genes (RASSF1A, APC, HIN1, BRCA1, CYCLIND2, RARbeta, CDH1 and TWIST1) and DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients by the MethyLight assay. Methylation in WBC from 40 controls was also analyzed.<br><br>RESULTS: Tumor and adjacent tissues showed frequent hypermethylation for all genes tested, while WBC DNA was rarely hypermethylated. For HIN1, RASSF1A, APC and TWIST1, there was agreement between hypermethylation in tumor and adjacent tissues (p=0.04, p=0.02, p=0.005 and p<0.0001, respectively). DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA. Significant correlations in the methylation of Sat2M1 between tumor and adjacent tissues and WBC DNA were found (p<0.0001 and p=0.046, respectively). There was also a significant difference in methylation of Sat2M1 between cases and controls (p=0.01).<br><br>CONCLUSION: These results suggest that further studies of WBC methylation, including prospective studies, may provide biomarkers of breast cancer risk.}, }
@article {pmid20676743, year = {2011}, author = {Lecarpentier, E and Ouaffi, L and Mir, O and Berveiller, P and Maurel, M and Pujade-Lauraine, E and Bouillot, JL and Veyrie, N}, title = {Bevacizumab-induced small bowel perforation in a patient with breast cancer without intraabdominal metastases.}, journal = {Investigational new drugs}, volume = {29}, number = {6}, pages = {1500-1503}, pmid = {20676743}, issn = {1573-0646}, mesh = {Angiogenesis Inhibitors/*adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/*adverse effects/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/pathology/therapy ; Carcinoma, Ductal, Breast/drug therapy/pathology/therapy ; Female ; Humans ; Intestinal Perforation/*chemically induced ; Intestine, Small/injuries ; Middle Aged ; Peritonitis/diagnosis/etiology ; }, abstract = {A 53-years-old woman presented with sudden abdominal pain. One year before, she was diagnosed an inflammatory ductal carcinoma of the left breast (T3N0M0) and received 6 cycles of epirubicin and cyclophosphamide followed by 9 cycles of paclitaxel. A radical left mastectomy with lymphadenectomy was performed. On histopathology, the invasive ductal carcinoma was poorly differentiated, histological grade III without lymphovascular emboli, expressing E-cadherin, with negative hormone receptors status and no HER-2 overexpression. The final staging after chemotherapy was pT3N1M0, necessitating an adjuvant radiotherapy. Four months postoperatively, a CT-scan revealed liver and lung metastases and chemotherapy combining gemcitabine, oxaliplatin and bevacizumab was started for 13 days when she suddenly developed severe abdominal pain. A CT-scan showed a pneumoperitoneum. She had a median laparotomy confirming the diagnosis of peritonitis by digestive perforation without ovarian, uterine, lymphatic, or peritoneal carcinomatosis. Assessment of the totality of the gastrointestinal tract showed two distinct punched out perforations of the small bowel, without macroscopic signs of tumor or metastases: one on the jejunum at 50 cm from the Treitz and the second at 10 cm of the end of the ileum. Small bowel resection with jejunojejunostomy and a lateral ileostomy were performed. Regarding the macroscopical pathological findings, the mucosa showed an ulceration measuring of 1 cm without tumor. On microscopy we found a tranparietal neoplastic infiltration. Vessels were morphologically normal with tumoral cells' morphology and architecture identical to the primary breast carcinoma. Chemotherapy was not reintroduced after surgery and the patient died on the 57th postoperative day.}, }
@article {pmid20672290, year = {2011}, author = {Liu, KJ and Lee, YL and Yang, YY and Shih, NY and Ho, CC and Wu, YC and Huang, TS and Huang, MC and Liu, HC and Shen, WW and Leu, SJ}, title = {Modulation of the development of human monocyte-derived dendritic cells by lithium chloride.}, journal = {Journal of cellular physiology}, volume = {226}, number = {2}, pages = {424-433}, doi = {10.1002/jcp.22348}, pmid = {20672290}, issn = {1097-4652}, mesh = {Adjuvants, Immunologic/pharmacology ; Animals ; Antigens, CD/immunology ; B7-2 Antigen/immunology ; Cell Differentiation/drug effects/immunology ; Cells, Cultured ; Dendritic Cells/cytology/*drug effects/*physiology ; Enzyme Inhibitors/metabolism ; Glycogen Synthase Kinase 3/immunology ; Glycogen Synthase Kinase 3 beta ; Humans ; Immunoglobulins/immunology ; Interleukins/immunology ; Lithium Chloride/*pharmacology ; Membrane Glycoproteins/immunology ; Mitogen-Activated Protein Kinase Kinases/immunology ; Monocytes/cytology/*drug effects/*physiology ; PPAR gamma/immunology ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha/immunology ; }, abstract = {Lithium has been used or explored to treat psychiatric and neurodegenerative diseases that are frequently associated with an abnormal immune status. It is likely that lithium may work through modulation of immune responses in these patients. Because dendritic cells (DC) play a central role in regulating immune responses, this study investigated the influence of lithium chloride (LiCl) on the development and function of DC. Exposure to LiCl during the differentiation of human monocyte-derived immature DCs (iDC) enhances CD86 and CD83 expression and increases the production of IL-1β, IL-6, IL-8, IL-10, and TNF-α. However, the presence of LiCl during LPS-induced maturation of iDC has the opposite effect. During iDC differentiation, LiCl suppresses the activity of glycogen synthase kinase (GSK)-3β, and activates PI3K and MEK. In addition, LiCl activates peroxisome proliferator-activated receptor γ (PPARγ) during iDC differentiation, a pathway not described before. Each of these signaling pathways appears to have distinct impact on the differentiating iDC. The enhanced CD86 expression by LiCl involves the PI3K/AKT and GSK-3β pathway. LiCl modulates the expression of CD83 in iDC mainly through MEK/ERK, PI3K/AKT, and PPARγ pathways, while the increased production of IL-1β and TNF-α mainly involves the MEK/ERK pathway. The effect of LiCl on IL-6/IL-8/IL-10 secretion in iDC is mediated through inhibition of GSK-3β. We have also demonstrated that PPARγ is downstream of GSK-3β and is responsible for the LiCl-mediated modulation of CD86/83 and CD1 expression, but not IL-6/8/10 secretion. The combined influence of these molecular signaling pathways may account for certain clinical effect of lithium.}, }
@article {pmid20667129, year = {2010}, author = {Gunn, S and Yeh, IT and Lytvak, I and Tirtorahardjo, B and Dzidic, N and Zadeh, S and Kim, J and McCaskill, C and Lim, L and Gorre, M and Mohammed, M}, title = {Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {396}, pmid = {20667129}, issn = {1471-2407}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosome Aberrations ; Chromosomes, Human, Pair 17/*genetics ; Comparative Genomic Hybridization ; Female ; *Gene Dosage ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; *Oligonucleotide Array Sequence Analysis ; Receptor, ErbB-2/*genetics ; }, abstract = {BACKGROUND: HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin), remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods.<br><br>METHODS: In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE) tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms.<br><br>RESULTS: Array-based comparative genomic hybridization (array CGH) analysis of chromosome 17 resolved HER2 gene status in [20/20] (100%) of cases and revealed additional chromosome 17 copy number changes in [18/20] (90%) of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to "ratio skewing" caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability.<br><br>CONCLUSIONS: These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17 abnormalities in these cases suggests that the two probe FISH interphase analysis is inadequate and results interpreted using the HER2/CEP17 ratio should be reported "with caution" when the presence of centromeric amplification or monosomy is suspected by FISH signal gains or losses. The presence of these pericentromeric copy number changes may result in artificial skewing of the HER2/CEP17 ratio towards false negative or false positive results in breast cancer with chromosome 17 complexity. Full genomic analysis should be considered in all cases with complex chromosome 17 aneusomy as these cases are likely to have genome-wide instability, amplifications, and a poor prognosis.}, }
@article {pmid20663721, year = {2010}, author = {Muggerud, AA and Hallett, M and Johnsen, H and Kleivi, K and Zhou, W and Tahmasebpoor, S and Amini, RM and Botling, J and Børresen-Dale, AL and Sørlie, T and Wärnberg, F}, title = {Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer.}, journal = {Molecular oncology}, volume = {4}, number = {4}, pages = {357-368}, pmid = {20663721}, issn = {1878-0261}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Cluster Analysis ; Comparative Genomic Hybridization ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; Microarray Analysis ; Middle Aged ; Multigene Family ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the "intrinsic" molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER-status and HER2-status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT-PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re-organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over- and under-treatment of patients.}, }
@article {pmid20661826, year = {2010}, author = {Dave, B and Wynne, R and Su, Y and Korourian, S and Chang, JC and Simmen, RC}, title = {Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats.}, journal = {Nutrition and cancer}, volume = {62}, number = {6}, pages = {774-782}, doi = {10.1080/01635581.2010.494334}, pmid = {20661826}, issn = {1532-7914}, mesh = {Animals ; Carcinoma, Ductal, Breast/etiology ; Carcinoma, Intraductal, Noninfiltrating/etiology ; Cell Line, Tumor ; Disease Progression ; Female ; Genistein/*administration &amp; dosage ; Humans ; Hyaluronan Receptors/genetics ; Isoflavones/*administration &amp; dosage ; Mammary Glands, Animal/chemistry ; Mammary Neoplasms, Experimental/chemistry/*etiology ; Rats ; Receptors, Progesterone/analysis/*physiology ; Transforming Growth Factor beta1/genetics ; }, abstract = {Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-methyl-N-nitrosourea, dietary intake of soy protein isolate (SPI) reduced mammary tumor occurrence but increased incidence of more invasive tumors in tumored rats, relative to the control diet casein. Here we evaluated whether mammary tumor progression in tumor-bearing rats lifetime exposed to SPI is associated with deregulated progesterone receptor (PR) isoform expression. In histologically normal mammary glands of rats with invasive ductal carcinoma lesions, PR-A protein levels were higher for SPI- than casein-fed rats, whereas PR-B was undetectable for both groups. Increased mammary PR-A expression was associated with higher transforming growth factor-beta1, stanniocalcin-1, and CD44 transcript levels; lower E-cadherin and estrogen receptor-alpha expression; and reduced apoptotic status in ductal epithelium. Serum progesterone (ng/ml) (CAS: 25.94 +/- 3.81; SPI: 13.19 +/- 2.32) and estradiol (pg/ml) (CAS: 27.9 +/- 4.49; SPI: 68.48 +/- 23.87) levels differed with diet. However, sera from rats of both diet groups displayed comparable mammosphere-forming efficiency in human MCF-7 cells. Thus, soy-rich diets may influence the development of more aggressive tumors by enhancing PR-A-dependent signaling in premalignant breast tissues.}, }
@article {pmid20631061, year = {2010}, author = {Dietz, L and Esser, PR and Schmucker, SS and Goette, I and Richter, A and Schnölzer, M and Martin, SF and Thierse, HJ}, title = {Tracking human contact allergens: from mass spectrometric identification of peptide-bound reactive small chemicals to chemical-specific naive human T-cell priming.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {117}, number = {2}, pages = {336-347}, doi = {10.1093/toxsci/kfq209}, pmid = {20631061}, issn = {1096-0929}, mesh = {Allergens/chemistry/*metabolism ; Benzenesulfonates/chemistry/*metabolism/toxicity ; Cells, Cultured ; Dendritic Cells/drug effects/immunology/metabolism ; *Dermatitis, Contact ; Dinitrochlorobenzene/chemistry/*metabolism/toxicity ; Humans ; Lymphocyte Activation/drug effects/immunology ; Peptide Fragments/chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; T-Lymphocytes/drug effects/immunology/*metabolism ; }, abstract = {Modification of proteins by reactive small chemicals is a key step in the activation of chemical-specific T cells in allergic contact dermatitis (ACD). However, an integrated approach to characterize both the precise nature of chemically modified proteins and the chemical-specific T cells is currently lacking. Here, we analyze the molecular conditions for adduct formation of the strong human contact sensitizer 2,4-dinitrochlorobenzene (DNCB) and its water-soluble form, 2,4-dinitrobenzenesulfonic acid (DNBS), with both an all amino acid-containing model peptide (± Cys) and the protein human serum albumin (HSA). Mass spectrometric detection and quantification revealed thiol-dependent peptide adduct formation at all pH values found in human skin layers. Highest modification rates were obtained with DNBS. Accordingly, DNBS- but not DNCB-modified human immature dendritic cells (iDC) induced in vitro primary human T-cell responses as did 2,4,6-trinitrobenzenesulfonic acid-modified iDC as measured by dinitrophenyl (DNP)- and trinitrophenyl (TNP)-specific T-cell proliferation and interferon gamma (IFN-γ) production in CD4(+) and CD8(+) T-cell subsets. Moreover, DNP-modified HSA protein effectively induced primary T-cell responses when processed by iDC. Thus, an integrated approach that combines efficient skin-related in chemico coupling analyses with an in vitro T-cell priming assay can be used to predict in vivo reactions of chemical contact allergens with extracellular and cellular proteins. This strategy supports the development of chemical-specific in vitro assays that are urgently required in predictive hazard identification and risk assessment of allergenic and nonallergenic chemicals.}, }
@article {pmid20623525, year = {2010}, author = {Martens, FM and van Kuppevelt, HJ and Beekman, JA and Heijnen, IC and D'Hauwers, KW and Heesakkers, JP}, title = {No primary role of ambulatory urodynamics for the management of spinal cord injury patients compared to conventional urodynamics.}, journal = {Neurourology and urodynamics}, volume = {29}, number = {8}, pages = {1380-1386}, doi = {10.1002/nau.20895}, pmid = {20623525}, issn = {1520-6777}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Netherlands ; Predictive Value of Tests ; Pressure ; Sensitivity and Specificity ; Spinal Cord Injuries/*complications/physiopathology ; Urinary Bladder/*innervation ; Urinary Bladder, Neurogenic/*diagnosis/etiology/physiopathology ; *Urodynamics ; Young Adult ; }, abstract = {AIMS: Adequate urodynamic assessment of bladder behavior is essential in spinal cord injury (SCI) patients. Ambulatory urodynamics are more sensitive to detect detrusor overactivity (DO) than conventional urodynamics. The primary objective of this study was to determine the value of ambulatory urodynamics for the diagnosis of DO in SCI patients compared to conventional urodynamics.<br><br>METHODS: Twenty-seven SCI patients who were suspected of DO underwent both conventional and ambulatory urodynamics at one day. A single involuntary detrusor contraction (IDC) was defined as a detrusor pressure rise of at least 10&#x2009;cmH(2)O. DO according to the ICS definition was used in addition to minimize the influence of catheter artifacts. Outcome of urodynamics was used for decisions on treatment.<br><br>RESULTS: Ambulatory urodynamics were more sensitive to diagnose IDC and DO. Conventional urodynamics had a sensitivity of 82% and specificity of 75% for DO diagnosis compared to ambulatory urodynamics. Mean maximum detrusor pressures did not differ significantly between both urodynamics. When the maximum detrusor pressure at conventional urodynamics did not exceed 40&#x2009;cmH(2)O, 83% (10/12) of patients had a mean maximum detrusor pressure under 40&#x2009;cmH(2)O at ambulatory urodynamics. Although the inter-individual DO diagnostic agreement was lower for ambulatory than conventional urodynamics (58%, K&#x2009;=&#x2009;0.201 vs. 77%, K&#x2009;=&#x2009;0552), the treatment agreement was higher for ambulatory urodynamics (58% vs. 42%).<br><br>CONCLUSIONS: Ambulatory urodynamics do not seem necessary for diagnosis and risk assessment in SCI patients suspected for DO when conventional urodynamics are done properly. The exact role of urodynamics in treatment decision remains to be determined.}, }
@article {pmid20613924, year = {2010}, author = {Ertas, U and Yalcin, E and Erdogan, F}, title = {Invasive ductal carcinoma with multiple metastases to facial and cranial bones: a case report.}, journal = {European journal of dentistry}, volume = {4}, number = {3}, pages = {334-337}, pmid = {20613924}, issn = {1305-7464}, abstract = {Female breast cancer is one of the major causes of death among women. Metastatic tumors to the maxillo-facial bones are rare. We present diagnosis and treatment of multiple metastatic invasive ductal carcinoma involving massive and early stage the left half of the mandibular body, the floor of the orbit, maxilla, left parietal bone, the iliac bone and cervical and thoracal vertebras in a 36 years old female one and half years after operated.}, }
@article {pmid20593406, year = {2010}, author = {Lopez-Garcia, MA and Geyer, FC and Natrajan, R and Kreike, B and Mackay, A and Grigoriadis, A and Reis-Filho, JS and Weigelt, B}, title = {Transcriptomic analysis of tubular carcinomas of the breast reveals similarities and differences with molecular subtype-matched ductal and lobular carcinomas.}, journal = {The Journal of pathology}, volume = {222}, number = {1}, pages = {64-75}, doi = {10.1002/path.2743}, pmid = {20593406}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; Cluster Analysis ; Female ; Gene Expression Profiling/methods ; Humans ; Oligonucleotide Array Sequence Analysis/methods ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Signal Transduction ; }, abstract = {Tubular carcinoma (TC) is an uncommon special type of breast cancer characterized by an indolent clinical course. Although described as part of a spectrum of related lesions named 'low-grade breast neoplasia family' due to immunophenotypical and genetic similarities, TCs, low-grade invasive ductal carcinomas of no special type (IDC-NSTs), and classic invasive lobular carcinomas (ILCs) significantly differ in terms of histological features and clinical outcome. The aim of this study was to investigate whether pure TCs constitute an entity distinct from low-grade IDC-NSTs and from classic ILCs. To define the transcriptomic differences between TCs and IDC-NSTs and ILCs whilst minimizing the impact of histological grade and molecular subtype on their profiles, we subjected a series of grade- and molecular subtype-matched TCs and IDC-NSTs and molecular subtype-matched TCs and classic ILCs to genome-wide gene expression profiling using oligonucleotide microarrays. Unsupervised and supervised analysis revealed that TCs are similar at the transcriptomic level to grade- and molecular subtype-matched IDC-NSTs. However, subtle yet significant differences were detected and validated by quantitative reverse transcriptase-PCR, which may in part explain the reported more favourable outcome of TCs. Transcriptomic differences between TCs and molecular subtype-matched classic ILCs were more overt, predominantly due to lower expression of proliferation and cell cycle genes in TCs and down-regulation of cell adhesion/extracellular matrix-related genes in classic ILCs. Our results support the existence of a 'low-grade breast neoplasia family'; however, the transcriptomes of these lesions display small, yet important differences, which, together with their distinct biological behaviour, warrant their separation as discrete entities.}, }
@article {pmid20593130, year = {2010}, author = {Amaral, P and Miguel, R and Mehdad, A and Cruz, C and Monteiro Grillo, I and Camilo, M and Ravasco, P}, title = {Body fat and poor diet in breast cancer women.}, journal = {Nutricion hospitalaria}, volume = {25}, number = {3}, pages = {456-461}, pmid = {20593130}, issn = {1699-5198}, mesh = {*Adipose Tissue ; Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; *Breast Neoplasms/metabolism ; Cross-Sectional Studies ; *Diet ; Female ; Humans ; Middle Aged ; Nutritional Status ; Pilot Projects ; }, abstract = {BACKGROUND: Breast cancer is the most common cancer in women worldwide. Differences in breast cancer incidence suggest a significant role of environmental factors in the aetiology: obesity, central adiposity, excess body fat and some dietary factors have been suggested as risk factors. This pilot study aimed to analyse the pattern of nutritional status, body fat, and the usual dietary intake among women diagnosed with breast cancer, consecutively referred to the Radiotherapy Department of the University Hospital Santa Maria.<br><br>PATIENTS AND METHODS: Throughout 2006, 71 consecutive women with breast cancer were included.<br><br>EVALUATIONS: weight (kg) &amp; height (m), determined with a SECA(R) floor scale+stadiometer to calculate body mass index (BMI), waist circumference, percentage body fat with bipolar hand-held bio-impedance analysis (BF-306), Food Frequency Questionnaire validated for the Portuguese population to assess the usual dietary intake. Frequency analysis and Mann-Whitney U test were used to evaluate prevalence and associations.<br><br>RESULTS: Mean age was 60+/-12 (36-90) years. Invasive ductal carcinoma was the most frequent histology (68%), p<0.05. Most patients were in stage I (30%) or stage IIA (25%) of disease vs IIB (10%), IIIB (4%), IV (4%) or others (21%), p<0.05. Regarding nutritional status, 82% were overweight/obese; 89% of patients had a %body fat mass above the maximum limit of 30% vs only 8 (11%) with %body fat within normal range (p<0.002); 62% pts had a waist circumference>88 cm (prevalence analysis: p<0.04), and 61% of pts had gained weight after diagnosis. Univariate analysis did not show any association between histology, BMI, %body fat and waist circumference; by multivariate analysis there was an association between higher BMI, %body fat &amp; aggressive histologies (p<0.005). Food frequency analysis showed a low intake of vegetables and whole grain cereals rich in complex carbohydrates (sources of fibre and phytochemicals), of fatty fish &amp; nuts, primary sources of n-3 PUFA's and a high intake of saturated fat; more aggressive histologies were correlated with low intake of green leafy vegetables (p=0.05) and n-3 fatty acids food sources (p=0.01).<br><br>CONCLUSIONS: Our findings show a vast prevalence &amp; homogeneous pattern of overweight/obesity, excessive body and abdominal fat, as well as weight gain after diagnosis, combined with diets deficient in protective nutrients. Further investigation is warranted as cancer rates in Portugal continue to increase.}, }
@article {pmid20587515, year = {2010}, author = {Lo, PK and Lee, JS and Liang, X and Han, L and Mori, T and Fackler, MJ and Sadik, H and Argani, P and Pandita, TK and Sukumar, S}, title = {Epigenetic inactivation of the potential tumor suppressor gene FOXF1 in breast cancer.}, journal = {Cancer research}, volume = {70}, number = {14}, pages = {6047-6058}, pmid = {20587515}, issn = {1538-7445}, support = {P50 CA088843/CA/NCI NIH HHS/United States ; P50 CA088843-080008/CA/NCI NIH HHS/United States ; P50 CA088843-090008/CA/NCI NIH HHS/United States ; 1 P50 CA088843-08/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Cell Line, Tumor ; Cyclin-Dependent Kinase 2/metabolism ; DNA Replication ; E2F Transcription Factors/metabolism ; Epigenesis, Genetic ; Forkhead Transcription Factors/*genetics ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Gene Silencing ; *Genes, Tumor Suppressor ; Humans ; Retinoblastoma Protein/metabolism ; }, abstract = {The expression of several members of the FOX gene family is known to be altered in a variety of cancers. We show that in breast cancer, FOXF1 gene is a target of epigenetic inactivation and that its gene product exhibits tumor-suppressive properties. Loss or downregulation of FOXF1 expression is associated with FOXF1 promoter hypermethylation in breast cancer cell lines and in invasive ductal carcinomas. Methylation of FOXF1 in invasive ductal carcinoma (37.6% of 117 cases) correlated with high tumor grade. Pharmacologic unmasking of epigenetic silencing in breast cancer cells restored FOXF1 expression. Re-expression of FOXF1 in breast cancer cells with epigenetically silenced FOXF1 genes led to G(1) arrest concurrent with or without apoptosis to suppress both in vitro cell growth and in vivo tumor formation. FOXF1-induced G(1) arrest resulted from a blockage at G(1)-S transition of the cell cycle through inhibition of the CDK2-RB-E2F cascade. Small interfering RNA-mediated depletion of FOXF1 in breast cancer cells led to increased DNA re-replication, suggesting that FOXF1 is required for maintaining the stringency of DNA replication and genomic stability. Furthermore, expression profiling of cell cycle regulatory genes showed that abrogation of FOXF1 function resulted in increased expression of E2F-induced genes involved in promoting the progression of S and G(2) phases. Therefore, our studies have identified FOXF1 as a potential tumor suppressor gene that is epigenetically silenced in breast cancer, which plays an essential role in regulating cell cycle progression to maintain genomic stability.}, }
@article {pmid20584319, year = {2010}, author = {Yoon, NK and Maresh, EL and Elshimali, Y and Li, A and Horvath, S and Seligson, DB and Chia, D and Goodglick, L}, title = {Elevated MED28 expression predicts poor outcome in women with breast cancer.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {335}, pmid = {20584319}, issn = {1471-2407}, support = {U24 CA086366/CA/NCI NIH HHS/United States ; 2 P30 CA16042-29/CA/NCI NIH HHS/United States ; CA-86366/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*metabolism/pathology ; Carcinoma, Ductal, Breast/epidemiology/*metabolism/secondary ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/*metabolism/secondary ; Disease Progression ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Mediator Complex/*metabolism ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Rate ; Tissue Array Analysis ; }, abstract = {BACKGROUND: MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression.<br><br>METHODS: Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed.<br><br>RESULTS: MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death.<br><br>CONCLUSIONS: We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information) MED28 is a novel and strong independent prognostic indicator of survival for breast cancer.}, }
@article {pmid20572082, year = {2010}, author = {Lotze, U and Egerer, R and Glück, B and Zell, R and Sigusch, H and Erhardt, C and Heim, A and Kandolf, R and Bock, T and Wutzler, P and Figulla, HR}, title = {Low level myocardial parvovirus B19 persistence is a frequent finding in patients with heart disease but unrelated to ongoing myocardial injury.}, journal = {Journal of medical virology}, volume = {82}, number = {8}, pages = {1449-1457}, doi = {10.1002/jmv.21821}, pmid = {20572082}, issn = {1096-9071}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/*virology ; Enterovirus/isolation &amp; purification ; Enterovirus Infections/pathology/virology ; Female ; Heart/virology ; Humans ; Male ; Middle Aged ; Parvoviridae Infections/pathology/*virology ; Parvovirus B19, Human/*isolation &amp; purification/pathogenicity ; Viral Load ; }, abstract = {While myocardial parvovirus B19 (B19V), aside from enteroviruses (EV) and adenoviruses (ADV), has recently been found often in patients with myocarditis and idiopathic dilated cardiomyopathy (IDC), the pathogenetic significance of B19V genomes in those patients has not yet been sufficiently elucidated. In the present study, left ventricular endomyocardial biopsies from 24 patients with left ventricular ejection fraction (LVEF) below 55% due to IDC, and tissue from the right atrial appendage of 10 control patients undergoing bypass surgery with normal LVEF (>55%) were investigated for B19V, ADV, and EV genomes by specific nested polymerase chain reaction (PCR), by real time PCR or by reverse-transcription PCR, respectively. The myocardial tissue samples from the 10 controls were analyzed each in three different virological laboratories for B19V. In the IDC group, the frequency of the myocardial virus genomes found in 54% (13/24) of the patients was as follows: B19V: 50% (12/24), EV: 8% (2/24), including one patient with B19V and EV, and ADV: 0% (0/24). For comparison, the prevalence of B19V genomes was between 30% and 60% in the control group as detected in three different laboratories, but all these control subjects were EV- and ADV-negative. The number of B19V gene copies, however, was very low and similar both in the IDC and control group. In the majority of patients myocardial B19V persistence was associated with a low virus load irrespective of the underlying heart disease so that it may be of no importance in the pathogenesis of IDC.}, }
@article {pmid20570624, year = {2010}, author = {Gruel, N and Lucchesi, C and Raynal, V and Rodrigues, MJ and Pierron, G and Goudefroye, R and Cottu, P and Reyal, F and Sastre-Garau, X and Fourquet, A and Delattre, O and Vincent-Salomon, A}, title = {Lobular invasive carcinoma of the breast is a molecular entity distinct from luminal invasive ductal carcinoma.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {46}, number = {13}, pages = {2399-2407}, doi = {10.1016/j.ejca.2010.05.013}, pmid = {20570624}, issn = {1879-0852}, mesh = {Breast Neoplasms/*genetics/mortality ; Carcinoma, Ductal, Breast/*genetics/mortality ; Carcinoma, Lobular/*genetics/mortality ; Female ; Genome, Human ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; }, abstract = {In order to get insight into the molecular alterations of invasive lobular carcinoma (ILC), comparative genomic hybridisation array and transcriptomic analyses of a series of 62 oestrogens-positive (ER) invasive tumours [21 ILC and 41 invasive ductal carcinomas (IDC)] were performed. ILC and IDC shared highly recurrent regions of gains (1q12-q44(+) in more than 60% of the cases, 16pter-p11.2(+) in 45% and 63% of ILC and IDC, respectively) and losses (16q11.2-q24.2(-) in 84% of ILC and 67.5% of IDC and 17pter-p12(-) in 50% of ILC and IDC). However, ILC genomic signature was characterised by significantly more frequent losses of 13q21.33-q31.3 region (46.5%) and 22q11.23-q12.1 region (50%) whereas IDC showed significantly more frequent losses of 11q23.1-q23.2 region (in 44% of IDC). Nine different regions of high level amplifications were found in 38% of ILC (8/21 cases). Localised on chromosome 11 (11q13.2 region), the most frequent region of amplification encompassing the CCND1 and FGF3 genes was observed in five different ILC. Unsupervised hierarchical clustering of transcriptomic data showed that ILC and IDC clustered apart. Genes involved in cell adhesion, cell communication and trafficking, extra cellular matrix-interaction pathways or cell mobility contributed to this clustering. Despite these differences, the overall clinical outcome of ILC was identical to that of IDC. This molecular study highlights that lobular and oestrogens-positive ductal invasive carcinomas share common genomic alterations but that ILC present some specific molecular alterations. These molecular specificities should help with the identification of new therapeutic targets for ILC patients.}, }
@article {pmid20546222, year = {2010}, author = {Tan, E and Kuper-Hommel, M and Rademaker, M}, title = {Annular erythema as a sign of recurrent breast cancer.}, journal = {The Australasian journal of dermatology}, volume = {51}, number = {2}, pages = {135-138}, doi = {10.1111/j.1440-0960.2009.00621.x}, pmid = {20546222}, issn = {1440-0960}, mesh = {Aged ; Biopsy ; Breast Neoplasms/*complications/diagnosis ; Carcinoma, Ductal, Breast/*complications/diagnosis ; Dermatitis/diagnosis ; Diagnosis, Differential ; Erythema/diagnosis/*etiology ; Female ; Humans ; Lupus Erythematosus, Cutaneous/diagnosis ; Middle Aged ; Neoplasm Recurrence, Local/*complications/diagnosis ; Skin/pathology ; Tinea/diagnosis ; }, abstract = {Three women with known breast cancer presented with very similar annular erythemas of their chest walls. All women were in remission from their breast cancer for at least 6 months. Their breast cancers had initially responded well to multi-modality treatment with no clinical or radiologic evidence of recurrence, until the development of the annular erythema. In the first case, the annular erythema was treated unsuccessfully as a dermatitis and then as tinea corporis. In the second case, subacute cutaneous lupus was considered but lupus antibodies were negative. In the third case, the annular erythema was promptly recognized and biopsied. Histology in all three cases revealed identical findings of invasive ductal carcinoma involving the lymphatics of the skin. Immunohistochemical staining of the carcinoma was positive for human epidermal growth factor receptor 2 but negative for oestrogen and progesterone receptors. Annular erythema can pose a wide differential but rarely has it been described as a sign of locally recurrent cancer. These cases highlight the importance of recognizing this entity in the oncologic patient, where prompt skin biopsies can confirm the diagnosis and allow early initiation of therapy.}, }
@article {pmid20542612, year = {2010}, author = {Igreja, V and Dias-Lambranca, B and Hershey, DA and Racin, L and Richters, A and Reis, R}, title = {The epidemiology of spirit possession in the aftermath of mass political violence in Mozambique.}, journal = {Social science &amp; medicine (1982)}, volume = {71}, number = {3}, pages = {592-599}, doi = {10.1016/j.socscimed.2010.04.024}, pmid = {20542612}, issn = {1873-5347}, mesh = {Adult ; Female ; Health Status ; Humans ; Male ; Mental Disorders/*epidemiology ; Mozambique/epidemiology ; Patient Acceptance of Health Care ; Qualitative Research ; Severity of Illness Index ; Superstitions/psychology ; Survivors/*psychology ; Violence/*psychology ; *Warfare ; }, abstract = {In this article we assess the prevalence rates of harmful spirit possession, different features of the spirits and of their hosts, the correlates of the spirit possession experience, health patterns and the sources of health care consulted by possessed individuals in a population sample of 941 adults (255 men, 686 women) in post-civil war Mozambique in 2003-2004. A combined quantitative-qualitative research design was used for data collection. A major study outcome is that the prevalence rates vary according to the severity of the possession as measured by the number of harmful spirits involved in the affliction. The prevalence rate of participants suffering from at least one spirit was 18.6 percent; among those individuals, 5.6 percent were suffering from possession by two or more spirits. A comparison between possessed and non-possessed individuals shows that certain types of spirit possession are a major cause of health impairment. We propose that knowledge of both local understandings of harmful spirit possession and the community prevalence of this kind of possession is a precondition for designing public health interventions that sensitively respond to the health needs of people afflicted by spirits.}, }
@article {pmid20541790, year = {2010}, author = {Bidgoli, SA and Ahmadi, R and Zavarhei, MD}, title = {Role of hormonal and environmental factors on early incidence of breast cancer in Iran.}, journal = {The Science of the total environment}, volume = {408}, number = {19}, pages = {4056-4061}, doi = {10.1016/j.scitotenv.2010.05.018}, pmid = {20541790}, issn = {1879-1026}, mesh = {Adolescent ; Adult ; Breast Neoplasms/*epidemiology/etiology/metabolism ; Environmental Exposure/statistics &amp; numerical data ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Fibroadenoma/epidemiology/etiology/metabolism ; Humans ; Incidence ; Iran/epidemiology ; Middle Aged ; Oncogene Protein p21(ras)/metabolism ; Receptors, Aryl Hydrocarbon/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/metabolism ; Young Adult ; }, abstract = {Although the probability of having breast cancer increases with the age in general, this malignancy affects Iranian women at least one decade younger than their counterparts in other countries. However the underlying risk factors for the discrepancy have not been identified. The aryl hydrocarbon receptor (AhR) mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This study was aimed to compare the interactions between AhR and other fundamental genes (p53, K-Ras, ER, PgR) in a clinical setting. To conduct the immunohistochemical studies using appropriate monoclonal antibodies, 25 premenopausal invasive ductal carcinoma, 29 postmenopausal invasive ductal carcinoma and 30 breast fibroadenoma were selected retrospectively from 2004 to 2007 in the pathology department of Imam Khomeini hospital complex of Tehran University of Medical Sciences . Higher levels of AhR in epithelial cells of premenopausal patients and breast fibroadenoma emphasized the susceptibility of these cells to environmental-induced tumors. AhR overexpression contributed to ER-/PgR-immunophenotype in young/premenopausal patients but the same pattern was not observed in benign and postmenopausal malignant tumors. It seems that early incidence of breast cancer in Iran is the result of interactions between hormonal and environmental factors.}, }
@article {pmid20535543, year = {2011}, author = {Zhao, Y and Deng, C and Wang, J and Xiao, J and Gatalica, Z and Recker, RR and Xiao, GG}, title = {Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {127}, number = {1}, pages = {69-80}, doi = {10.1007/s10549-010-0972-2}, pmid = {20535543}, issn = {1573-7217}, mesh = {Apoptosis/genetics ; Base Sequence ; Breast Neoplasms/*genetics/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Estrogen Receptor alpha/*metabolism ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics/*metabolism ; *Signal Transduction ; }, abstract = {In order to understand how microRNAs (miRNAs) regulate breast cancer tumorigenesis, a miRNA expression microarray screening was performed using RNA from formalin-fixed paraffin-embedded (FFPE) breast tissues, which included benign (n = 13), ductal carcinoma in situ (DCIS) (n = 16), and invasive ductal carcinoma (IDC) (n = 15). Twenty-five differentially expressed miRNAs (P < 0.01) were identified, of which let-7 family miRNAs were down-regulated in human breast cancer tissues at stages of DCIS and IDC compared to benign stage. We further found that there was an inverse correlation between ER-α expression and several members of let-7 family in the FFPE tissues. Next, we performed bioinformatics analysis and found that let-7 miRNA sequences match sequence in the 3'-UTR of estrogen receptor alpha (ER-α), suggesting ER-α may be a target of let-7, which was further confirmed by a number of experimental assays, including luciferase assay, protein expression, and mRNA expression. Overexpression of let-7 miRNAs in ER-positive breast cancer MCF7 cell line negatively affected ER-α activity. As expected, dampening of the ER-α signaling by let-7 miRNAs inhibited cell proliferation, and subsequently triggered the cell apoptotic process in MCF7 cells. In conclusion, our findings indicate a new regulatory mechanism of let-7 miRNAs in ER-α mediated cellular malignant growth of breast cancer.}, }
@article {pmid20534901, year = {2010}, author = {Liang, S and Singh, M and Gam, LH}, title = {The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to ethnicity of the patients; Chinese, Malay and Indian.}, journal = {Disease markers}, volume = {28}, number = {3}, pages = {149-165}, doi = {10.3233/DMA-2010-0694}, pmid = {20534901}, issn = {1875-8630}, mesh = {Aged ; Aged, 80 and over ; Breast/*metabolism ; China ; Chromatography, Liquid ; Cohort Studies ; Electrophoresis, Gel, Two-Dimensional ; *Ethnicity ; Female ; Humans ; India ; Malaysia ; Middle Aged ; Neoplasm Proteins/*metabolism ; Proteins/*metabolism ; Solubility ; Tandem Mass Spectrometry ; Water ; }, abstract = {Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.}, }
@article {pmid20533549, year = {2011}, author = {Oka, K and Suzuki, T and Onodera, Y and Miki, Y and Takagi, K and Nagasaki, S and Akahira, J and Ishida, T and Watanabe, M and Hirakawa, H and Ohuchi, N and Sasano, H}, title = {Nudix-type motif 2 in human breast carcinoma: a potent prognostic factor associated with cell proliferation.}, journal = {International journal of cancer}, volume = {128}, number = {8}, pages = {1770-1782}, doi = {10.1002/ijc.25505}, pmid = {20533549}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blotting, Western ; Breast Neoplasms/*metabolism/pathology/therapy ; Carcinoma, Ductal, Breast/*metabolism/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology/therapy ; Cell Adhesion ; Cell Cycle ; Cell Movement ; *Cell Proliferation ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Phosphoric Monoester Hydrolases/antagonists &amp; inhibitors/genetics/*metabolism ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult ; }, abstract = {Nudix-type motif 2 (NUDT2) hydrolyzes diadenosine 5',5'''-p1,p4-tetraphosphate (Ap4A) associated with various cellular functions. Previous studies demonstrated its regulation through estrogens, suggesting possible importance of NUDT2 in breast carcinoma. NUDT2, however, has not been examined in malignant tissues. Therefore, we examined its expression and functions in breast carcinoma. Immunohistochemistry for NUDT2 was examined by invasive ductal carcinoma (IDC: n = 145) and pure ductal carcinoma in situ (DCIS: n = 82), and NUDT2 mRNA was examined by real-time PCR in 9 DCIS, 19 IDC and 6 non-neoplastic breast tissues. We also used T47D breast carcinoma cells in in vitro studies. NUDT2 immunoreactivity was detected in 78% of DCIS and 63% of IDC, and NUDT2 mRNA level was significantly higher in DCIS or IDC than non-neoplastic breast. NUDT2 status was significantly correlated with Van Nuys classification, HER2 or Ki-67 in DCIS, and with stage, lymph node metastasis, histological grade or HER2 in IDC. NUDT2 status was significantly associated with adverse clinical outcome of IDC patients and proved an independent prognostic factor. Results of transfection experiments demonstrated that proliferation activity of T47D cells was significantly associated with NUDT2 expression level according to the treatment of estradiol and/or tamoxifen. NUDT2 expression was significantly decreased by estradiol, and it was also significantly decreased in T47D cells transfected with HER2 siRNA. These findings suggest that NUDT2 is an estrogen-repressed gene and is also induced by HER2 pathways in breast carcinoma cells. NUDT2 promotes proliferation of breast carcinoma cells and is a potent prognostic factor in human breast carcinomas.}, }
@article {pmid20526721, year = {2010}, author = {Chen, CL and Chu, JS and Su, WC and Huang, SC and Lee, WY}, title = {Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1alpha, GLUT1, and CAIX.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {457}, number = {1}, pages = {53-61}, pmid = {20526721}, issn = {1432-2307}, mesh = {Antigens, Neoplasm/*biosynthesis/genetics ; Antimutagenic Agents/toxicity ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Carbonic Anhydrase IX ; Carbonic Anhydrases/*biosynthesis/genetics ; Carcinoma in Situ/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cell Hypoxia/drug effects/genetics ; Cell Line, Tumor ; Cobalt/toxicity ; Female ; Gene Expression/drug effects ; Glucose Transporter Type 1/*biosynthesis/genetics ; Humans ; Hyperplasia ; Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis/genetics ; Immunohistochemistry ; Phenotype ; Precancerous Conditions/genetics/metabolism ; RNA, Messenger/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Hypoxia and acidosis are microenvironmental selection forces during somatic evolution in breast carcinogenesis. The effect of cobalt chloride (CoCl(2))-induced hypoxia on the expression of hypoxia-inducible factor (HIF)-1alpha, glucose transporter 1 (GLUT1), and carbonic anhydrase IX (CAIX) was assessed in breast cancer cells derived from primary sites (HCC1395 and HCC1937) and metastatic sites (MCF-7 and MDA-MB-231) by reverse transcriptase-polymerase chain reaction and immunoblotting. We analyzed these proteins' expression in tissue samples from normal breast tissue, usual ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) using immunohistochemistry. CAIX mRNA was expressed constitutively in MDA-MB-231 cells but not in the other three cell lines. CAIX mRNA expression was increased after CoCl(2)-induced hypoxia in all four breast cancer cell lines. The expression of HIF-1alpha and GLUT1 proteins was increased after CoCl(2)-induced hypoxia in all breast cancer cell lines tested. Hypoxia significantly increased CAIX protein expression in primary cancer cells but not in metastatic ones. HIF-1alpha was not expressed in benign breast tissue, whereas it was significantly expressed in DH, ADH, DCIS, and IDC (p < 0.001). GLUT1 and CAIX were expressed only in DCIS (56.8% and 25.0%) and IDC (44.1% and 30.5%), with higher expression in high grade DCIS than low/intermediate grade DCIS (79.2% vs. 30.0%, p = 0.001 and 37.5% vs. 10.0%, p = 0.036, respectively). High CAIX expression was significantly associated with poor histological grade of IDC (p = 0.005). During breast carcinogenesis, the role of HIF-1alpha changes from response to proliferation to tumor progression. GLUT1 expression (glycolytic phenotype) and CAIX expression (acid-resistant phenotype) may result in a powerful adaptive advantage and represent an aggressive phenotype.}, }
@article {pmid20522561, year = {2010}, author = {Mitra, A and Menezes, ME and Shevde, LA and Samant, RS}, title = {DNAJB6 induces degradation of beta-catenin and causes partial reversal of mesenchymal phenotype.}, journal = {The Journal of biological chemistry}, volume = {285}, number = {32}, pages = {24686-24694}, pmid = {20522561}, issn = {1083-351X}, support = {R01 CA140472/CA/NCI NIH HHS/United States ; R01 CA140472-01A1/CA/NCI NIH HHS/United States ; 1R01CA140472-01A1/CA/NCI NIH HHS/United States ; }, mesh = {Cell Movement ; *Gene Expression Regulation, Neoplastic ; HSP40 Heat-Shock Proteins/*metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Mesoderm/*metabolism ; Models, Biological ; Molecular Chaperones/*metabolism ; Neoplasm Metastasis ; Nerve Tissue Proteins/*metabolism ; Phenotype ; Proteasome Endopeptidase Complex/metabolism ; Wnt Proteins/metabolism ; Wound Healing ; beta Catenin/*metabolism ; }, abstract = {We showed that expression of MRJ (DNAJB6) protein is lost in invasive ductal carcinoma, and restoration of MRJ(L) restricts malignant behavior of breast cancer and melanoma cells. However, the signaling pathways influenced by MRJ(L) are largely unknown. Our observations revealed that MRJ(L) expression causes changes in cell morphology concomitant with down-regulation of several mesenchymal markers, viz. vimentin, N-cadherin, Twist, and Slug, and up-regulation of epithelial marker keratin 18. Importantly, MRJ(L) expression led to reduced levels of beta-catenin, an epithelial mesenchymal transition marker, and a critical player in the Wnt pathway. We found that MRJ(L) up-regulates expression of DKK1, a well known Wnt/beta-catenin signaling inhibitor, that causes degradation of beta-catenin. Re-expression of DNAJB6 alters the Wnt/beta-catenin signaling in cancer cells, leading to partial reversal of the mesenchymal phenotype. Thus, MRJ(L) may play a role in maintaining an epithelial phenotype, and inhibition of the Wnt/beta-catenin pathway may be one of the potential mechanisms contributing to the restriction of malignant behavior by MRJ(L).}, }
@article {pmid20514537, year = {2010}, author = {Teresa, DB and Santos, RA and Takahashi, CS and Carrara, HH and Moreira, HW and Mattos, LC and Lia-Neto, N and Cunha, LA and Bassi, CL and Soares, EG and Donadi, EA and Mello, ER and Soares, CP}, title = {Polymorphisms of Lewis and Secretor genes are related to breast cancer and metastasis in axillary lymph nodes.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {31}, number = {5}, pages = {401-409}, pmid = {20514537}, issn = {1423-0380}, mesh = {ABO Blood-Group System/genetics ; Adult ; Aged ; Aged, 80 and over ; Axilla/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; Fucosyltransferases/*genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lymphatic Metastasis/*genetics ; Middle Aged ; Phenotype ; *Polymorphism, Single Nucleotide ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {ABH and Lewis antigen expression has been associated with cancer development and prognosis, tumor differentiation, and metastasis. Considering that invasive ductal breast carcinoma (IDC) presents multiple molecular alterations, the aim of the present study was to determine whether the polymorphism of ABO, Lewis, and Secretor genes, as well as ABO phenotyping, could be associated with tumor differentiation and lymph nodes metastasis. Seventy-six women with IDC and 78 healthy female blood donors were submitted to ABO phenotyping/genotyping and Lewis and Secretor genotyping. Phenotyping was performed by hemagglutination and genotyping by the polymerase chain reaction with sequence-specific primers. ABO, Lewis, and Secretor genes were classified by individual single nucleotide polymorphism at sites 59, 1067, 202, and 314 of the Lewis gene, 428 of the Secretor gene, and 261 (O1 allele), 526 (O2 and B allele), and 703 (B allele). No association was found between breast cancer and ABO antigen expression (P = 0.9323) or genotype (P = 0.9356). Lewis-negative genotype was associated with IDC (P = 0.0126) but not with anatomoclinical parameters. Nonsecretor genotype was associated with axillary lymph node metastasis (P = 0.0149). In conclusion, Lewis and Secretor genotyping could be useful to predict respectively breast cancer susceptibility and axillary lymph nodes metastasis.}, }
@article {pmid20510078, year = {2010}, author = {Li, L and Bi, XF and Xu, X and Liu, XY and Shen, GH and Guo, L and Yuan, YL and Wang, F and Wang, MR and Yang, HY}, title = {[Expression pattern of E-cadherin and p120-catenin in infiltrating lobular carcinoma and ductal carcinoma of the breast and its significance].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {32}, number = {4}, pages = {273-277}, pmid = {20510078}, issn = {0253-3766}, mesh = {Bone Neoplasms/secondary ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/pathology/secondary ; Carcinoma, Lobular/*metabolism/pathology/secondary ; Catenins/*metabolism ; Cytoplasm/metabolism ; Diagnosis, Differential ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/secondary ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Survival Rate ; Delta Catenin ; }, abstract = {OBJECTIVE: To determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC), and observe the different expression patterns of E-cadherin and p120-catenin proteins in both ILCs and IDCs.<br><br>METHODS: The patients with ILC admitted to our hospital from Jan 1999 to Dec 2006 and patients with IDC from Jan 2000 to Dec 2000 were included in this study. All their pathological slides were reviewed, and their clinical data and treatment variables were analyzed retrospectively. Then the expression patterns of E-cadherin and p120-catenin proteins in both ILCs and IDCs were detected by immunohistochemistry on tissue microarray.<br><br>RESULTS: The 5-year overall survival was 81.7% for ILCs and 79.1% for IDCs (P = 0.055). The 5-year disease-free survival was 61.8% for ILCs and 83.7% for IDCs (P < 0.001). Cytoplasmic localization of p120-catenin and loss of E-cadherin expression were more common in ILCs than in IDCs. The complete losses of E-cadherin in ILCs and IDCs were 55.6% (20/36) and 20.4% (45/221, P < 0.001), respectively. The p120-catenin showed a diffuse cytoplasmic localization in 66.7% (24/36) of ILCs and 16.3% (36/221) of IDCs (P < 0.001). Interestingly, the cytoplasmic localization of p120-catenin was clearly associated with the absence of E-cadherin expression in ILCs (P = 0.002), cytoplasmic localization of p120-catenin and absence of E-cadherin expression were observed 55.6% (20/36) in ILCs compared with 4.1% (9/221) in IDCs (P < 0.001).<br><br>CONCLUSION: ILC has several specific biological and prognostic characteristics which are different in IDC. Different expression patterns of E-cadherin and p120-catenin proteins can be helpful to recognize ILC from IDC.}, }
@article {pmid20509867, year = {2010}, author = {Tang, JP and Tan, CP and Li, J and Siddique, MM and Guo, K and Chan, SW and Park, JE and Tay, WN and Huang, ZY and Li, WC and Chen, J and Zeng, Q}, title = {VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers.}, journal = {Molecular cancer}, volume = {9}, number = {}, pages = {128}, pmid = {20509867}, issn = {1476-4598}, mesh = {Animals ; *Antibodies, Monoclonal ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation ; Cell Separation ; Centrosome/*enzymology ; Dual-Specificity Phosphatases/genetics/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Hybridomas ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; Neoplasms/genetics/*metabolism ; Rabbits ; }, abstract = {BACKGROUND: VHZ is a VH1-like (member Z) dual specific protein phosphatase encoded by DUSP23 gene. Some of the dual specific protein phosphatases (DSPs) play an important role in cell cycle control and have shown to be associated with carcinogenesis. Here, the expression of VHZ associated with cell growth and human cancers was investigated.<br><br>RESULTS: We generated a mouse monoclonal antibody (mAb clone#209) and rabbit polyclonal antibodies (rAb) against VHZ. We performed cell proliferation assay to learn how VHZ is associated with cell cycle by retroviral transduction to express VHZ, VHZ(C95S), and control vector in MCF-7 cells. Overexpression of VHZ [but not VHZ(C95S)] in MCF-7 cells promoted cell proliferation compared to control cells. shRNA-mediated knockdown of VHZ in MCF-7 cells showed that reduction of VHZ resulted in increased G1 but decreased S phase cell populations. Using indirect immunofluorescence, we showed that both exogenous and endogenous VHZ protein was localized at the centrosome in addition to its cytoplasmic distribution. Furthermore, using immunohistochemistry, we revealed that VHZ protein was overexpressed either in enlarged centrosomes (VHZ-centrosomal-stain) of some invasive ductal carcinomas (IDC) Stage I (8/65 cases) or in entire cytoplasm (VHZ-cytosol-stain) of invasive epithelia of some IDC Stage II/III (11/47 cases) of breast cancers examined. More importantly, upregulation of VHZ protein is also associated with numerous types of human cancer, in particular breast cancer. VHZ mAb may be useful as a reagent in clinical diagnosis for assessing VHZ positive tumors.<br><br>CONCLUSIONS: We generated a VHZ-specific mAb to reveal that VHZ has a novel subcellular localization, namely the centrosome. VHZ is able to facilitate G1/S cell cycle transition in a PTP activity-dependent manner. The upregulation of its protein levels in primary human cancers supports the clinical relevance of the protein in cancers.}, }
@article {pmid20493777, year = {2010}, author = {Zelini, P and Lilleri, D and Comolli, G and Rognoni, V and Chiesa, A and Fornara, C and Locatelli, F and Meloni, F and Gerna, G}, title = {Human cytomegalovirus-specific CD4(+) and CD8(+) T-cell response determination: comparison of short-term (24h) assays vs long-term (7-day) infected dendritic cell assay in the immunocompetent and the immunocompromised host.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {136}, number = {2}, pages = {269-281}, doi = {10.1016/j.clim.2010.04.008}, pmid = {20493777}, issn = {1521-7035}, mesh = {Adolescent ; Adult ; Aged ; CD4-Positive T-Lymphocytes/*physiology ; CD8-Positive T-Lymphocytes/*physiology ; Child ; Child, Preschool ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/immunology ; Dendritic Cells/immunology ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoassay/*methods ; Immunocompetence/*immunology ; *Immunocompromised Host ; Infant ; Male ; Middle Aged ; Organ Transplantation ; Reproducibility of Results ; Sensitivity and Specificity ; Time Factors ; Young Adult ; }, abstract = {Human cytomegalovirus (HCMV)-specific CD4(+) and CD8(+) T-cells were measured in the immunocompetent host as well as in 13 solid-organ transplant recipients (SOTR), and 12 young hematopoietic stem cell transplant recipients (HSCTR) by using a long-term (7-day) assay based on PBMC stimulation by HCMV-infected dendritic cells (iDC), and two short-term (24h) assays, one for CD4(+) stimulation by infected cell lysate (iCL), and the other for CD8(+) stimulation by a pool of 34 epitopic peptides (pep-pool). In the immunocompetent, the number of T-cells activated by either iCL or the pep-pool was significantly reduced with respect to iDC. In both SOTR and HSCTR, the number of T-cells activated by iDC was comparable to that activated by iCL or the pep-pool. A significant correlation between iDC-activated T-cells and T-cells activated by either iCL or the pep-pool was observed. In conclusion, whenever a rapid result is needed, short-term assays may efficiently replace the iDC assay.}, }
@article {pmid20492722, year = {2010}, author = {Yamazoe, S and Tanaka, H and Sawada, T and Amano, R and Yamada, N and Ohira, M and Hirakawa, K}, title = {RNA interference suppression of mucin 5AC (MUC5AC) reduces the adhesive and invasive capacity of human pancreatic cancer cells.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {29}, number = {1}, pages = {53}, pmid = {20492722}, issn = {1756-9966}, mesh = {Animals ; Blotting, Western ; *Cell Adhesion ; Cell Movement ; Cell Proliferation ; Humans ; Liver Neoplasms/genetics/*prevention &amp; control/secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mucin 5AC/*antagonists &amp; inhibitors/genetics/*metabolism ; Neoplasm Invasiveness ; Pancreatic Neoplasms/genetics/pathology/*prevention &amp; control ; Phosphorylation ; RNA Interference ; RNA, Messenger/genetics ; RNA, Small Interfering/*pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC de novo expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells.<br><br>METHODS: We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si) RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells in vitro and in vivo. We compared parental cells (SW1990 and BxPC3) with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3).<br><br>RESULTS: MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP) -3 and vascular endothelial growth factor (VEGF) were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. In vivo, si-SW1990 did not establish subcutaneous tumor in nude mice.<br><br>CONCLUSIONS: Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.}, }
@article {pmid20466412, year = {2010}, author = {Kim, JH and Shin, MH and Kweon, SS and Park, MH and Yoon, JH and Lee, JS and Choi, C and Fackler, MJ and Sukumar, S}, title = {Evaluation of promoter hypermethylation detection in serum as a diagnostic tool for breast carcinoma in Korean women.}, journal = {Gynecologic oncology}, volume = {118}, number = {2}, pages = {176-181}, doi = {10.1016/j.ygyno.2010.04.016}, pmid = {20466412}, issn = {1095-6859}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood/*genetics ; Carcinoma in Situ/blood/genetics ; Carcinoma, Ductal, Breast/*blood/*genetics ; Cytokines/genetics ; *DNA Methylation ; Female ; Humans ; Middle Aged ; Nuclear Proteins/genetics ; Promoter Regions, Genetic ; Receptors, Retinoic Acid/genetics ; Republic of Korea ; Tumor Suppressor Proteins/genetics ; Twist-Related Protein 1/genetics ; }, abstract = {OBJECTIVE: We have noted that quantitative multiplex-methylation specific PCR (QM-MSP) analysis of a key panel of genes may be useful as an ancillary tool for ductal carcinoma in situ (DCIS) detection in breast tissue. In this study, we investigated aberrant promoter hypermethylation of four genes as a means to detect epigenetic alterations specific to breast carcinoma in the serum of patients with DCIS and invasive ductal carcinoma (IDC).<br><br>METHODS: Two hundred forty-three serum samples from 89 patients with IDC, 30 patients with DCIS, and 125 age-matched healthy controls were examined. After DNA extraction and sodium bisulfite treatment, QM-MSP was performed for HIN-1, RASSF1A, RAR-beta, and Twist.<br><br>RESULTS: Overall significant differences in methylation levels were observed for HIN-1 (p=0.006), RAR-beta (p<0.001), RASSF1A (p=0.004), and Twist (p<0.001). All four genes showed significantly higher methylation frequencies in DCIS or IDC than in control subjects (p<0.001 for all comparisons). However, methylation frequencies were not significantly different between DCIS and IDC. In receiver-operating characteristic analysis, the two-gene combination (RAR-beta/RASSF1A) showed the best performance in distinguishing DCIS/IDC from control samples. The estimated specificity of this two-gene panel for detecting DCIS/IDC was 88.8%, and its sensitivity was 94.1%.<br><br>CONCLUSIONS: The quantitative detection of aberrant DNA methylation in serum samples may be a promising high throughput approach for the diagnosis of breast cancer including DCIS.}, }
@article {pmid20461805, year = {2010}, author = {Moccia, M and Pellecchia, MT and Erro, R and Zingone, F and Marelli, S and Barone, DG and Ciacci, C and Strambi, LF and Barone, P}, title = {Restless legs syndrome is a common feature of adult celiac disease.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {25}, number = {7}, pages = {877-881}, doi = {10.1002/mds.22903}, pmid = {20461805}, issn = {1531-8257}, mesh = {Adult ; Celiac Disease/diet therapy/*epidemiology ; Comorbidity ; Diet, Gluten-Free ; Female ; Humans ; Male ; Prevalence ; Restless Legs Syndrome/*epidemiology ; }, abstract = {Restless legs syndrome (RLS) is a common neurological condition, frequently idiopathic, sometimes associated with specific disorders such as iron deficiency. We investigated RLS prevalence in celiac disease (CD), an autoimmune disease characterized by several features such as malabsorption-related iron deficiency anemia and peripheral neuropathy. We screened a population of 100 adult CD patients for CD features, iron metabolism, clinical and neurological conditions, and enrolled 100 age- and sex-matched controls in the general population. RLS was ascertained in CD patients and controls by both the presence of the four essential International RLS Study Group diagnostic criteria and neurological examination. The International RLS Study Group rating scale was used to measure RLS severity. We found a 31% prevalence of RLS in the CD population that was significantly higher than the prevalence in the control population (4%; P < 0.001). The average severity of RLS in CD population was moderate (17 +/- 6.5). In the CD population, no significant correlation was found between RLS and either gluten-free diet or iron metabolism, despite hemoglobin levels were significantly lower in CD patients with RLS than without RLS (P = 0.003). We found no correlation between RLS and other possible causes of secondary RLS, including signs of peripheral neuropathy, pregnancy, end-stage renal disease, and pharmacological treatments.Our study broadens the spectrum of neurological disorders associated with CD and indicates that RLS should be sought for in all patients with CD.}, }
@article {pmid20459529, year = {2010}, author = {Zardawi, SJ and Zardawi, I and McNeil, CM and Millar, EK and McLeod, D and Morey, AL and Crea, P and Murphy, NC and Pinese, M and Lopez-Knowles, E and Oakes, SR and Ormandy, CJ and Qiu, MR and Hamilton, A and Spillane, A and Soon Lee, C and Sutherland, RL and Musgrove, EA and O'Toole, SA}, title = {High Notch1 protein expression is an early event in breast cancer development and is associated with the HER-2 molecular subtype.}, journal = {Histopathology}, volume = {56}, number = {3}, pages = {286-296}, doi = {10.1111/j.1365-2559.2009.03475.x}, pmid = {20459529}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mice ; Middle Aged ; Phenotype ; Receptor, ErbB-2/*genetics ; Receptor, Notch1/*biosynthesis/genetics ; Signal Transduction/*physiology ; Tissue Array Analysis ; Young Adult ; }, abstract = {AIMS: Activation of Notch signalling results in hyperplasia and tumorigenesis in murine mammary epithelium. However, there is little information regarding the expression of Notch1 in premalignant lesions and early breast cancer. We investigated expression of Notch1 in breast cancer development and its association with molecular subtypes.<br><br>METHODS AND RESULTS: Immunohistochemical expression of Notch1 was determined in a murine model of mammary carcinogenesis and in breast tissue from two cohorts of breast cancer patients, the first (n=222) comprising a histological progression series and the second an outcome series of 228 patients with operable invasive ductal carcinoma. Enhanced expression of Notch1 protein was an early event in both murine and human breast cancer development with progressive increases in expression with the development of hyperplasia and malignancy. High Notch1 was not prognostic in the outcome cohort. There was, however, a highly significant association of high Notch1 protein with the HER-2 molecular subtype of breast cancer (P=0.008).<br><br>CONCLUSIONS: These data demonstrate that aberrant Notch regulation is an early event in mammary carcinogenesis and is associated with the HER-2 molecular subtype of breast cancer, and suggest the Notch signalling pathway may be a potential therapeutic target worthy of further investigation.}, }
@article {pmid20452823, year = {2010}, author = {Barone, P and Poewe, W and Albrecht, S and Debieuvre, C and Massey, D and Rascol, O and Tolosa, E and Weintraub, D}, title = {Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial.}, journal = {The Lancet. Neurology}, volume = {9}, number = {6}, pages = {573-580}, doi = {10.1016/S1474-4422(10)70106-X}, pmid = {20452823}, issn = {1474-4465}, mesh = {Aged ; Antidepressive Agents/adverse effects/*therapeutic use ; Antiparkinson Agents/adverse effects/*therapeutic use ; Benzothiazoles/adverse effects/*therapeutic use ; Depressive Disorder/complications/*drug therapy ; Dopamine Agonists/adverse effects/therapeutic use ; Double-Blind Method ; Dyskinesias/complications/*drug therapy ; Europe ; Female ; Humans ; Male ; Parkinson Disease/complications/*drug therapy ; Pramipexole ; Psychiatric Status Rating Scales ; Severity of Illness Index ; South Africa ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Depression is common in patients with Parkinson's disease, but evidence on the efficacy of antidepressants in this population is lacking. Because depression in patients with Parkinson's disease might be related to dopaminergic dysfunction, we aimed to assess the efficacy of the dopamine agonist pramipexole for treatment of depressive symptoms in patients with Parkinson's disease.<br><br>METHODS: We did a 12-week randomised, double-blind, placebo-controlled (1:1 ratio) trial of pramipexole (0.125-1.0 mg three times per day) compared with placebo in patients with mild-to-moderate Parkinson's disease. Patients from 76 centres in 12 European countries and South Africa were included if they were on stable antiparkinsonian therapy without motor fluctuations and had depressive symptoms (15-item geriatric depression scale score > or =5 and unified Parkinson's disease rating scale [UPDRS] part 1 depression item score > or =2). Patients were randomly assigned by centre in blocks of four by use of a randomisation number generating system. Clinical monitors, the principal investigator, and patients were masked to treatment allocation. The primary endpoint was change in Beck depression inventory (BDI) score and all treated patients who had at least one post-baseline efficacy assessment were included in the primary analysis. We also did a pre-specified path analysis with regression models to assess the relation between BDI and UPDRS part 3 (motor score) changes. This trial is registered with ClinicalTrials.gov, number NCT00297778, and EudraCT, number 2005-003788-22.<br><br>FINDINGS: Between March, 2006, and February, 2008, we enrolled 323 patients. Of 296 patients randomly assigned to pramipexole or placebo, 287 were included in the primary analysis: 139 in the pramipexole group and 148 in the placebo group. BDI scores decreased by an adjusted mean 5.9 (SE 0.5) points in the pramipexole group and 4.0 (0.5) points in the placebo group (difference 1.9, 95% CI 0.5-3.4; p=0.01, ANCOVA). The UPDRS motor score decreased by an adjusted mean 4.4 (0.6) points in the pramipexole group and 2.2 (0.5) points in the placebo group (difference 2.2, 95% CI 0.7-3.7; p=0.003, ANCOVA). Path analysis showed the direct effect of pramipexole on depressive symptoms accounted for 80% of total treatment effect (p=0.04). Adverse events were reported in 105 of 144 patients in the pramipexole group and 101 of 152 in the placebo group. Adverse events in the pramipexole group were consistent with the known safety profile of the drug.<br><br>INTERPRETATION: Pramipexole improved depressive symptoms in patients with Parkinson's disease, mainly through a direct antidepressant effect. This effect should be considered in the clinical management of patients with Parkinson's disease.}, }
@article {pmid20441684, year = {2010}, author = {van den Berg, MG and Rasmussen-Conrad, EL and Wei, KH and Lintz-Luidens, H and Kaanders, JH and Merkx, MA}, title = {Comparison of the effect of individual dietary counselling and of standard nutritional care on weight loss in patients with head and neck cancer undergoing radiotherapy.}, journal = {The British journal of nutrition}, volume = {104}, number = {6}, pages = {872-877}, doi = {10.1017/S0007114510001315}, pmid = {20441684}, issn = {1475-2662}, mesh = {*Counseling ; Dietetics/*methods ; Female ; Head and Neck Neoplasms/complications/*radiotherapy ; Humans ; Male ; Malnutrition/*prevention &amp; control ; Middle Aged ; Nurses ; *Patient-Centered Care ; Prospective Studies ; Radiotherapy/adverse effects ; *Weight Loss ; }, abstract = {Clinical research shows that nutritional intervention is necessary to prevent malnutrition in head and neck cancer patients undergoing radiotherapy. The objective of the present study was to assess the value of individually adjusted counselling by a dietitian compared to standard nutritional care (SC). A prospective study, conducted between 2005 and 2007, compared individual dietary counselling (IDC, optimal energy and protein requirement) to SC by an oncology nurse (standard nutritional counselling). Endpoints were weight loss, BMI and malnutrition (5% weight loss/month) before, during and after the treatment. Thirty-eight patients were included evenly distributed over two groups. A significant decrease in weight loss was found 2 months after the treatment (P = 0.03) for IDC compared with SC. Malnutrition in patients with IDC decreased over time, while malnutrition increased in patients with SC (P = 0.02). Therefore, early and intensive individualised dietary counselling by a dietitian produces clinically relevant effects in terms of decreasing weight loss and malnutrition compared with SC in patients with head and neck cancer undergoing radiotherapy.}, }
@article {pmid20424617, year = {2010}, author = {Wong, H and Lau, S and Yau, T and Cheung, P and Epstein, RJ}, title = {Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer.}, journal = {British journal of cancer}, volume = {102}, number = {9}, pages = {1391-1396}, pmid = {20424617}, issn = {1532-1827}, mesh = {Adult ; Breast Neoplasms/mortality/*pathology/surgery ; Carcinoma in Situ/pathology ; Carcinoma, Ductal/mortality/*pathology/surgery ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis/genetics ; Lymphatic Metastasis ; Middle Aged ; *Neoplasm Invasiveness ; Neoplasm Metastasis ; Postmenopause ; Premenopause ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis/genetics ; Receptors, Progesterone/analysis/genetics ; Survival Rate ; Survivors ; }, abstract = {BACKGROUND: The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC).<br><br>METHODS: We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2.<br><br>RESULTS: Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%).<br><br>CONCLUSION: IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.}, }
@article {pmid20419158, year = {2010}, author = {Melki, MT and Saïdi, H and Dufour, A and Olivo-Marin, JC and Gougeon, ML}, title = {Escape of HIV-1-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk--a pivotal role of HMGB1.}, journal = {PLoS pathogens}, volume = {6}, number = {4}, pages = {e1000862}, pmid = {20419158}, issn = {1553-7374}, mesh = {Apoptosis/immunology ; CASP8 and FADD-Like Apoptosis Regulating Protein/biosynthesis/immunology ; Cell Communication ; Cell Separation ; Coculture Techniques ; Cytotoxicity, Immunologic/*immunology ; Dendritic Cells/*immunology/metabolism/virology ; Flow Cytometry ; HIV Infections/*immunology/metabolism/virology ; HIV-1/immunology ; HMGB1 Protein/*immunology/metabolism ; Humans ; Inhibitor of Apoptosis Proteins/biosynthesis/immunology ; Killer Cells, Natural/*immunology/metabolism/virology ; Microscopy, Confocal ; Oligonucleotide Array Sequence Analysis ; Receptor Cross-Talk ; Receptors, TNF-Related Apoptosis-Inducing Ligand/immunology/metabolism ; Signal Transduction/immunology ; TNF-Related Apoptosis-Inducing Ligand/*immunology/metabolism ; }, abstract = {Early stages of Human Immunodeficiency Virus-1 (HIV-1) infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK) cells and dendritic cells (DCs). Immature DCs (iDCs) capture HIV-1 through specific receptors and can disseminate the infection to lymphoid tissues following their migration, which is associated to a maturation process. This process is dependent on NK cells, whose role is to keep in check the quality and the quantity of DCs undergoing maturation. If DC maturation is inappropriate, NK cells will kill them ("editing process") at sites of tissue inflammation, thus optimizing the adaptive immunity. In the context of a viral infection, NK-dependent killing of infected-DCs is a crucial event required for early elimination of infected target cells. Here, we report that NK-mediated editing of iDCs is impaired if DCs are infected with HIV-1. We first addressed the question of the mechanisms involved in iDC editing, and we show that cognate NK-iDC interaction triggers apoptosis via the TNF-related apoptosis-inducing ligand (TRAIL)-Death Receptor 4 (DR4) pathway and not via the perforin pathway. Nevertheless, once infected with HIV-1, DC(HIV) become resistant to NK-induced TRAIL-mediated apoptosis. This resistance occurs despite normal amounts of TRAIL released by NK cells and comparable DR4 expression on DC(HIV). The escape of DC(HIV) from NK killing is due to the upregulation of two anti-apoptotic molecules, the cellular-Flice like inhibitory protein (c-FLIP) and the cellular inhibitor of apoptosis 2 (c-IAP2), induced by NK-DC(HIV) cognate interaction. High-mobility group box 1 (HMGB1), an alarmin and a key mediator of NK-DC cross-talk, was found to play a pivotal role in NK-dependent upregulation of c-FLIP and c-IAP2 in DC(HIV). Finally, we demonstrate that restoration of DC(HIV) susceptibility to NK-induced TRAIL killing can be obtained either by silencing c-FLIP and c-IAP2 by specific siRNA, or by inhibiting HMGB1 with blocking antibodies or glycyrrhizin, arguing for a key role of HMGB1 in TRAIL resistance and DC(HIV) survival. These findings provide evidence for a new strategy developed by HIV to escape immune attack, they challenge the question of the involvement of HMGB1 in the establishment of viral reservoirs in DCs, and they identify potential therapeutic targets to eliminate infected DCs.}, }
@article {pmid20409316, year = {2010}, author = {Bae, JS and Choi, JS and Baik, SH and Park, WC and Song, BJ and Kim, JS and Lim, Y and Jung, SS}, title = {Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast.}, journal = {World journal of surgical oncology}, volume = {8}, number = {}, pages = {32}, pmid = {20409316}, issn = {1477-7819}, mesh = {Adult ; Aged ; Breast Neoplasms/*blood/*genetics/pathology ; Carcinoma, Ductal, Breast/*blood/*genetics/pathology ; Comparative Genomic Hybridization ; DNA Copy Number Variations/*genetics ; DNA, Neoplasm/*blood ; Female ; *Genome, Human ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Prognosis ; }, abstract = {BACKGROUND: Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer.<br><br>METHODS: DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction.<br><br>RESULTS: Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001).<br><br>CONCLUSION: Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.}, }
@article {pmid20403244, year = {2010}, author = {Zhang, P and Xu, BH and Ma, F and Li, Q}, title = {[Clinicopathological characteristics and prognostic significance of young patients with triple-negative breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {32}, number = {2}, pages = {128-131}, pmid = {20403244}, issn = {0253-3766}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary ; *Breast Neoplasms/drug therapy/metabolism/pathology/surgery ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology/secondary/surgery ; Carcinoma, Medullary/drug therapy/metabolism/pathology/secondary/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Mastectomy/methods ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the clinicopathological characteristics and prognosis in young patients with estrogen receptor (ER)-negative, progesterone receptor(PR)-negative, and Her-2-negative (triple-negative) breast cancer (TNBC).<br><br>METHODS: 94 young patients (< or = 35 years old) with TNBC at the Cancer Hospital of CAMS between January 1999 and December 2007 were included in this study. The clinicopathological features and prognosis of those 94 patients were retrospectively evaluated.<br><br>RESULTS: Among 786 young patients with breast cancer, 94 patients (12.0%) were triple-negative. The median age of the 94 young TNBC patients was 31 years.81 patients (86.2%) were diagnosed with invasive ductal carcinoma. 82.0% of the patients were classified as T1 or T2. The TNM stages included: 17 patients in stage I (18.1%), 48 in stage II (51.1%), 28 in stage III (29.8%) and 1 in stage IV (1.1%). 14 patients (14.9%) were diagnosed with lymphovascular invasion. The 1-, 3-, 5- and 7-year disease-free survival (DFS) was 88.3%, 66.9%, 59.7% and 59.7%, respectively. The corresponding overall survival (OS) rate was 98.9%, 85.6%, 72.9% and 69.6%, respectively. The univariate analysis showed that T stage, lymph node metastasis, clinical stage and lymphovascular invasion were correlated with the overall survival. However, only vascular invasion was showed to be an independent prognostic factor assessed by multivariate analysis. 33 patients developed recurrence or metastatic TNBC during the follow-up period. Among those 33 cases, 29 had recurrent or metastatic diseases within 3 years postoperatively and the other 4 cases after 3 years following surgery.<br><br>CONCLUSION: Young patients with TNBC represent distinctive clinicopathological and prognostic characteristics. Progression on tailored treatment for such population is still crucial. Further studies on rational individualized treatment regimen are warranted.}, }
@article {pmid20400521, year = {2010}, author = {Broustas, CG and Ross, JS and Yang, Q and Sheehan, CE and Riggins, R and Noone, AM and Haddad, BR and Seillier-Moiseiwitsch, F and Kallakury, BV and Haffty, BG and Clarke, R and Kasid, UN}, title = {The proapoptotic molecule BLID interacts with Bcl-XL and its downregulation in breast cancer correlates with poor disease-free and overall survival.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {16}, number = {11}, pages = {2939-2948}, doi = {10.1158/1078-0432.CCR-09-2351}, pmid = {20400521}, issn = {1557-3265}, support = {P01 CA074175/CA/NCI NIH HHS/United States ; CA68322/CA/NCI NIH HHS/United States ; CA74175/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Apoptosis ; Apoptosis Regulatory Proteins ; BRCA2 Protein/*metabolism ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*metabolism/mortality/pathology ; Cell Line, Tumor ; Disease-Free Survival ; Down-Regulation ; Female ; Humans ; Middle Aged ; Prognosis ; RNA, Messenger/metabolism ; Transfection ; bcl-X Protein/metabolism ; }, abstract = {PURPOSE: BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer.<br><br>EXPERIMENTAL DESIGN: The interaction between BLID and Bcl-X(L) was examined using in vitro transcription/translation, coimmunoprecipitation, and immunoflourescence assays. The relationship between BLID mRNA expression and pathologic measures in breast cancer specimens (n = 55) was examined using the publicly available ONCOMINE microarray database. Immunohistochemistry was done using formalin-fixed, paraffin-embedded sections of 148 cases of invasive ductal breast carcinomas (IDC) and 58 cases of invasive lobular breast carcinomas, and breast tissue microarrays representing additional 437 cases (>85% IDC) with associated clinicopathologic database and long-term clinical follow-up (median 7 years).<br><br>RESULTS: BLID was found to interact with Bcl-X(L), and the binding was enhanced in cancer cells exposed to doxorubicin or cisplatin. Exogenous expression of BLID correlated with activation of Bax and an increase in cytosolic cytochrome c. BLID mRNA expression was significantly reduced in grade 3 relative to grade 1 and 2 breast cancer (P = 0.023). Cytoplasmic BLID immunoreactivity was absent in IDC compared with invasive lobular breast carcinoma (P < 0.001). Lack of BLID expression was associated with younger age (median 40 years), African American ethnicity, tumor size, and triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative; all P < 0.005). Significant correlations were observed between BLID negativity and declines in overall, cause-specific, and local relapse-free survival (all P < 0.03). Multivariate analysis indicated that BLID is an independent prognostic factor of distant metastasis-free survival (hazard ratio, 0.302; 95% confidence interval, 0.160-0.570, P = 0.0002).<br><br>CONCLUSION: BLID is a new binding partner of Bcl-X(L) and a significant prognostic factor in breast cancer.}, }
@article {pmid20393391, year = {2010}, author = {Yang, HS and Chen, DY and Yuan, W and Yang, LL and Tsai, N and Lin, QS}, title = {Paresis associated with aconuresis caused by intervertebral disc calcification at c7-t1: a case report and review of the literature.}, journal = {Spine}, volume = {35}, number = {10}, pages = {E434-9}, doi = {10.1097/BRS.0b013e3181c71ebe}, pmid = {20393391}, issn = {1528-1159}, mesh = {Back Pain/etiology ; Calcinosis/*complications/*pathology/physiopathology ; Cervical Vertebrae/diagnostic imaging/pathology/surgery ; Decompression, Surgical ; Humans ; Intervertebral Disc/diagnostic imaging/pathology/surgery ; Intervertebral Disc Displacement/*complications/*pathology/physiopathology ; Magnetic Resonance Imaging ; Male ; Neurosurgical Procedures ; Paresis/etiology ; Spinal Canal/diagnostic imaging/pathology/surgery ; Spinal Cord/pathology/physiopathology ; Spinal Cord Compression/*etiology/*pathology/physiopathology ; Spinal Fusion/methods ; Thoracic Vertebrae/diagnostic imaging/pathology/surgery ; Tomography, X-Ray Computed ; Treatment Outcome ; Urinary Bladder, Neurogenic/etiology ; Young Adult ; }, abstract = {STUDY DESIGN: Case report.<br><br>OBJECTIVE: To report a case of a 19-year-old boy with intervertebral disc calcification (IDC) at C7-T1, who presented with paresis and aconuresis. Surgical outcome was assessed.<br><br>SUMMARY OF BACKGROUND DATA: IDC, commonly seen in the cervical spine region in children, is well-known as a self-limiting disorder with no or little symptoms. Surgical intervention is usually not required.<br><br>METHODS: A 19-year-old boy presented with acute back pain, progressive numbness, and weakness of both lower extremities and aconuresis for 1 week. There was no traumatic history or signs of infection. Radiograph, computed tomography with reconstruction, and magnetic resonance imaging revealed C7-T1 IDC with severe spinal cord compression. Decompression with anterior cervical corpectomy and fusion was performed.<br><br>RESULTS: Follow-up showed complete resolution of the back pain and complete recovery of motor power and sensory function in both lower extremities and return of normal micturition function. The patient had full recovery with no complications.<br><br>CONCLUSION: Serious neurologic deficit, especially a bladder dysfunction, caused by calcified intervertebral disc is rare. However, favorable outcome can be achieved in those cases where rapid diagnosis is made and followed by spinal cord decompression.}, }
@article {pmid20388779, year = {2010}, author = {Lawson, JS and Glenn, WK and Salmons, B and Ye, Y and Heng, B and Moody, P and Johal, H and Rawlinson, WD and Delprado, W and Lutze-Mann, L and Whitaker, NJ}, title = {Mouse mammary tumor virus-like sequences in human breast cancer.}, journal = {Cancer research}, volume = {70}, number = {9}, pages = {3576-3585}, doi = {10.1158/0008-5472.CAN-09-4160}, pmid = {20388779}, issn = {1538-7445}, mesh = {Animals ; Antigens, Viral, Tumor/genetics ; Base Sequence ; Breast Neoplasms/*genetics/metabolism/pathology/*virology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology/virology ; Genes, env ; Humans ; Immunohistochemistry ; Mammary Tumor Virus, Mouse/*genetics ; Mice ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid ; Wnt1 Protein/biosynthesis/genetics ; }, abstract = {Mouse mammary tumor virus (MMTV) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. In mice, MMTV promotes tumor formation indirectly by insertional mutagenesis of Wnt oncogenes that lead to their activation. In this study, we investigated the status of Wnt-1 in human breast cancers harboring MMTV-like sequences encoding viral envelope (env) genes. We confirmed the detection of env sequences in the nucleus of human breast cancer specimens that are similar in appearance to mouse mammary tumors expressing MMTV env sequences. MMTV env sequences in human breast cancers were also nearly indistinguishable from env sequences in mouse MMTV isolates. Further, Wnt-1 expression was higher in specimens of env-positive ductal carcinoma in situ and invasive ductal carcinoma, relative to env-negative specimens. Our findings extend the evidence that MMTV sequences found in naturally occurring mouse mammary tumors can be found in some human breast cancers, prompting further evaluation of causal roles in these settings.}, }
@article {pmid20302026, year = {2009}, author = {Yagmurdur, MC and Atac, FB and Uslu, N and Ekici, Y and Verdi, H and Ozdemir, BH and Moray, G and Haberal, M}, title = {Clinical importance of vitamin D receptor gene polymorphism in invasive ductal carcinoma.}, journal = {International surgery}, volume = {94}, number = {4}, pages = {304-309}, pmid = {20302026}, issn = {0020-8868}, mesh = {Alleles ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics ; Diagnostic Imaging ; Female ; Genotype ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Metastasis/genetics ; Neoplasm Recurrence, Local/genetics ; Neoplasm Staging ; *Polymorphism, Genetic ; Receptors, Calcitriol/*genetics ; Retrospective Studies ; Statistics, Nonparametric ; Survival Rate ; }, abstract = {In this study, we aimed to investigate the clinical importance of the vitamin D receptor gene polymorphism in invasive ductal breast cancer. All patients included in the study had clinical T1-2, N0-M0 invasive ductal carcinoma. Patients' demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. Vitamin D receptor B genotype frequencies in the patient group (P > 0.05) were as follows: B/b, 43 (77%); B/B, 13 (23%). In conclusion, the vitamin D receptor gene B allele does not seem to be related to local recurrence and distant metastasis of invasive ductal cancer of the breast.}, }
@article {pmid20232453, year = {2010}, author = {Razek, AA and Gaballa, G and Denewer, A and Nada, N}, title = {Invasive ductal carcinoma: correlation of apparent diffusion coefficient value with pathological prognostic factors.}, journal = {NMR in biomedicine}, volume = {23}, number = {6}, pages = {619-623}, doi = {10.1002/nbm.1503}, pmid = {20232453}, issn = {1099-1492}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology/secondary ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Lymphatic Metastasis/pathology ; Middle Aged ; Prognosis ; Prospective Studies ; Young Adult ; }, abstract = {The aim of this study was to correlate the apparent diffusion coefficient (ADC) value of invasive ductal carcinoma with pathological prognostic factors. A prospective study was conducted on 59 untreated female patients (mean age 46 years) with invasive ductal carcinoma. All patients were examined at 1.5 Tesla using dedicated bilateral breast coil. They underwent diffusion weighted MR imaging of the breast using a single shot echo planar imaging with a b-factor of 200 and 400 sec/mm2. Apparent diffusion coefficient (ADC) maps were reconstructed. The ADC value of the breast cancer was calculated and correlated with the pathologic prognostic factors (tumor size, grade and lymph nodes). The mean ADC values of invasive ductal carcinoma were significantly lower in patients with high grade, large breast cancer as well as those with axillary lymph nodes metastasis in a statistically significant way (p = 0.001 for the three factors). The mean ADC value of invasive ductal carcinoma was correlated with histologic grade (r = -0.675, p = 0.001), tumor size (r = 0.504, p = 0.001) and showed lower ADC values with positive lymph node metastasis. Apparent diffusion coefficient value is correlated with pathological parameters of invasive ductal carcinoma. The lower ADC values are associated with higher histological grade, larger tumor size and presence of axillary lymph nodes. So, the ADC value can be considered as a promising prognostic parameter that may identify highly aggressive breast cancer.}, }
@article {pmid20231284, year = {2010}, author = {Sun, XE and Sharling, L and Muthalagi, M and Mudeppa, DG and Pankiewicz, KW and Felczak, K and Rathod, PK and Mead, J and Striepen, B and Hedstrom, L}, title = {Prodrug activation by Cryptosporidium thymidine kinase.}, journal = {The Journal of biological chemistry}, volume = {285}, number = {21}, pages = {15916-15922}, pmid = {20231284}, issn = {1083-351X}, support = {AI082617/AI/NIAID NIH HHS/United States ; T32 GM007596/GM/NIGMS NIH HHS/United States ; U01 AI075466/AI/NIAID NIH HHS/United States ; R56 AI082617/AI/NIAID NIH HHS/United States ; 2T32GM007596/GM/NIGMS NIH HHS/United States ; U01AI75466/AI/NIAID NIH HHS/United States ; R01 AI055268/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antiprotozoal Agents/*pharmacology ; Cell Line, Tumor ; Cryptosporidiosis/*drug therapy/enzymology ; Cryptosporidium parvum/*enzymology/genetics ; Disease Models, Animal ; Floxuridine/pharmacology ; Genome, Protozoan ; Humans ; Mice ; Mice, Knockout ; Prodrugs/*pharmacology ; Protozoan Proteins/*antagonists &amp; inhibitors/genetics/metabolism ; Pyrimidines/metabolism/pharmacology ; Recombinant Proteins/antagonists &amp; inhibitors/genetics/metabolism ; Thymidine Kinase/*antagonists &amp; inhibitors/genetics/metabolism ; }, abstract = {Cryptosporidium spp. cause acute gastrointestinal disease that can be fatal for immunocompromised individuals. These protozoan parasites are resistant to conventional antiparasitic chemotherapies and the currently available drugs to treat these infections are largely ineffective. Genomic studies suggest that, unlike other protozoan parasites, Cryptosporidium is incapable of de novo pyrimidine biosynthesis. Curiously, these parasites possess redundant pathways to produce dTMP, one involving thymidine kinase (TK) and the second via thymidylate synthase-dihydrofolate reductase. Here we report the expression and characterization of TK from C. parvum. Unlike other TKs, CpTK is a stable trimer in the presence and absence of substrates and the activator dCTP. Whereas the values of k(cat) = 0.28 s(-1) and K(m)(,ATP) = 140 microm are similar to those of human TK1, the value of K(m)(thymidine) = 48 microm is 100-fold greater, reflecting the abundance of thymidine in the gastrointestinal tract. Surprisingly, the antiparasitic nucleosides AraT, AraC, and IDC are not substrates for CpTK, indicating that Cryptosporidium possesses another deoxynucleoside kinase. Trifluoromethyl thymidine and 5-fluorodeoxyuridine are good substrates for CpTK, and both compounds inhibit parasite growth in an in vitro model of C. parvum infection. Trifluorothymidine is also effective in a mouse model of acute disease. These observations suggest that CpTK-activated pro-drugs may be an effective strategy for treating cryptosporidiosis.}, }
@article {pmid20229034, year = {2010}, author = {Zhou, D and Cheng, SQ and Ji, HF and Wang, JS and Xu, HT and Zhang, GQ and Pang, D}, title = {Evaluation of protein pigment epithelium-derived factor (PEDF) and microvessel density (MVD) as prognostic indicators in breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {136}, number = {11}, pages = {1719-1727}, pmid = {20229034}, issn = {1432-1335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood supply/metabolism/mortality/*pathology ; Cohort Studies ; Disease Progression ; Eye Proteins/*genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; *Microcirculation ; Middle Aged ; Neoplasm Metastasis/pathology ; Neoplasm Staging ; Neovascularization, Pathologic/metabolism/*pathology ; Nerve Growth Factors/*genetics/metabolism ; Prognosis ; Serpins/*genetics/metabolism ; Survival Analysis ; Survival Rate ; }, abstract = {PURPOSE: Angiogenesis, which plays an important role in tumor growth and metastasis, is regulated by a balance between angiogenic stimulators and inhibitors. Pigment epithelium-derived factor (PEDF), a secreted glycoprotein is an important inhibitor of angiogenesis. Although the precise mechanisms by which PEDF exerts its actions remain poorly understood, there is growing evidence supporting the role of PEDF as a candidate antitumor agent. In this study, we investigated the role of PEDF in breast cancer.<br><br>METHODS: We investigated the correlation of PEDF protein levels with cancer progression and prognosis in patients with invasive ductal breast cancer (IDC). We used immunohistochemistry in a cohort of 119 breast cancer patients to examine the expression of PEDF protein with an anti-PEDF antibody and to measure the microvessel density (MVD) with an anti-CD34 antibody.<br><br>RESULTS: PEDF was an endogenous inhibitor of angiogenesis in endothelial cells. Decreased intratumoral expression of PEDF was associated with a higher microvessel density (MVD), a more metastatic phenotype, and poorer clinical outcome. PEDF was positive in 43.7% patients. Patients with low PEDF expression had a significantly higher MVD count when compared with patients with high PEDF expression. In univariate and multivariate analysis, PEDF was an independent prognostic factor.<br><br>CONCLUSION: The inverse correlation between PEDF expression and MVD in human breast cancer suggests that low PEDF expression is associated with angiogenesis in breast cancer. PEDF expression is therefore a potentially useful prognostic marker for breast cancer.}, }
@article {pmid20220513, year = {2010}, author = {Han, B and Suleman, K and Wang, L and Siddiqui, J and Sercia, L and Magi-Galluzzi, C and Palanisamy, N and Chinnaiyan, AM and Zhou, M and Shah, RB}, title = {ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia.}, journal = {The American journal of surgical pathology}, volume = {34}, number = {4}, pages = {478-485}, doi = {10.1097/PAS.0b013e3181d6827b}, pmid = {20220513}, issn = {1532-0979}, support = {P50CA69568/CA/NCI NIH HHS/United States ; R01 CA102872/CA/NCI NIH HHS/United States ; UO1 CA111275-01/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; Biopsy, Needle ; Carcinoma, Ductal/genetics/*pathology/surgery ; *Chromosome Aberrations ; Diagnosis, Differential ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Prostatic Intraepithelial Neoplasia/genetics/*pathology/surgery ; Prostatic Neoplasms/genetics/*pathology/surgery ; Proto-Oncogene Proteins c-ets/*genetics ; }, abstract = {BACKGROUND: Atypical cribriform lesions (ACLs) of the prostate consist of cribriform glands lined with cytologically malignant cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P), which is almost always associated with clinically aggressive prostate carcinoma (PCa). Distinction between these 2 lesions has profound clinical significance, especially on needle biopsies. However, there are lesions that do not fully satisfy the criteria for IDC-P yet are worse than typical HGPIN and are difficult to distinguish based on morphologic criteria alone.<br><br>METHODS: To better understand the biologic and molecular basis of distinction between cribriform HGPIN and IDC, we used break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations, a specific and commonest molecular alteration involving PCa, in a cohort of 16 isolated ACL, presumed to be an isolated cribriform HGPIN, and 45 carcinoma-associated ACL (ACL-PCa) on radical prostatectomy specimens, presumed to be spectrum of IDC-P. The latter was further divided into 2 groups: group A with marked nuclear atypia (nuclear size 6xnormal or larger) and/or comedonecrosis (n=21) and group B that did not fulfill these criteria (n=24).<br><br>RESULTS: Overall, ERG rearrangement was absent (0 of 16) in isolated cribriform HGPIN, whereas present in 75% (36 of 48) of IDC-P, of which 65% (23 of 36) were through deletion and 35% (13 of 36) through insertion. Notably, 17% (6 of 36) of the IDC-P showed duplication of ERG rearrangement in combination with deletion of 5'-ERG. Hundred percent (34 of 34) of the IDC-P showed concordance of ERG rearrangement status with adjacent invasive carcinoma. There was no difference between the 2 groups of IDC-P lesions regarding prevalence of ERG rearrangement (group A 79% vs. group B 74%) and EDel2+ (20% vs. 15%). No case with ETV1, ETV4, or ETV5 rearrangement was identified.<br><br>CONCLUSIONS: Our molecular data suggest that isolated cribriform HGPIN and IDC-P are biologically distinct lesions. Majority of ACL-PCa most likely represent intraductal spread of PCa. There is a significant overlap between IDC-P and HGPIN at the lower grade morphologic spectrum. ERG break-apart fluorescence in-situ hybridization assay provides insight into understanding the molecular basis of cribriform HGPIN and IDC-P and has potential clinical implications in their distinction on needle biopsies.}, }
@article {pmid20209373, year = {2010}, author = {Périssé, G and Medronho, Rde A and Escosteguy, CC}, title = {[Urban space and mortality from ischemic heart disease in the elderly in Rio de Janeiro].}, journal = {Arquivos brasileiros de cardiologia}, volume = {94}, number = {4}, pages = {463-471}, doi = {10.1590/s0066-782x2010005000009}, pmid = {20209373}, issn = {1678-4170}, mesh = {Age Distribution ; Aged ; Brazil/epidemiology ; Cause of Death ; Ecological and Environmental Phenomena ; Female ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*mortality ; Sex Distribution ; Socioeconomic Factors ; Statistics, Nonparametric ; Urban Population/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: Cardiovascular diseases are the leading cause of death in Brazil, especially among the elderly. In the city of Rio de Janeiro (RJC), ischemic heart disease (IHD) is the predominant cause of mortality. Studies show an association between the process of urbanization, socioeconomic conditions and changes in lifestyle with the occurrence of IHD.<br><br>OBJECTIVE: To describe the geographical distribution of the IHD mortality rates in the elderly of RJC in 2000 and its correlation with socioeconomic variables.<br><br>METHODS: This was an ecological study with a spatial analysis of the distribution of the IHD mortality rates in the elderly residing in RJC in 2000, standardized by gender and age, and its correlation with socioeconomic variables from the demographic census.<br><br>RESULTS: There were no strong correlations between the socioeconomic variables and IHD mortality in the elderly in the districts. Some correlations, albeit weak, showed an association between higher socioeconomic status and higher mortality. After correcting the IHD mortality rate by adding ill-defined causes (IDC) of death, an association between low socioeconomic status and higher mortality from IHD was observed. The study showed spatial dependence for socioeconomic variables, but not for mortality from IHD.<br><br>CONCLUSION: The spatial dependence observed in economic variables shows that the urban space in MRJ, although heterogeneous, has a certain amount of discrimination in the districts. Some correlations between IHD and socioeconomic variables were opposite to those found in the literature, and this may be partly related to the proportion of IDC, or to the exclusive profile of this age group.}, }
@article {pmid20193454, year = {2009}, author = {Hua, BL and Fu, XG and Hu, WH and Yin, L and Kang, XL and Li, HA and Jiang, JF and Li, F}, title = {[Notch1 mRNA and protein expression in human breast cancer and normal mammary gland tissues].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {12}, pages = {806-809}, pmid = {20193454}, issn = {0529-5807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Mammary Glands, Human/*metabolism ; Middle Aged ; Neoplasm Staging ; RNA, Messenger/metabolism ; Receptor, Notch1/genetics/*metabolism ; }, abstract = {OBJECTIVE: To explore the Notch1 mRNA and protein expression in human breast cancers and normal mammary tissues, and their relationship with the clinical indicators of breast cancers were analyzed.<br><br>METHODS: Notch1 gene of human breast invasive ductal carcinoma (IDC) and normal mammary gland tissues were amplified by RT-PCR, and the expression of Notch1 protein was detected by immunohistochemical Streptavidin-Biotin Complex (SP) stain in 60 IDC, 30 ductal carcinoma in situ (DCIS) and 60 normal mammary tissues.<br><br>RESULTS: Notch1 gene of human IDC and normal mammary tissues both could express in a transcription level; the positive rates of Notch1 protein expression in normal mammary tissues and DCIS were 55% and 70%. Respectively, which did not differ statistically (P > 0.05), while the positive rate in IDC was 90%, significantly higher than that of the normal mammary tissues and DCIS (P < 0.05). The high expression of Notch1 protein in IDC correlate significantly with lymph node metastasis, pathological grades and TNM stages.<br><br>CONCLUSIONS: Notch1 protein was over expressed in breast IDC. A high Notch1 protein expression is considered associating with the evolution and malignant transformation of the breast tumor. The expression of Notch1 gene maybe impact the effect of on the progression of breast cancers.}, }
@article {pmid20191033, year = {2010}, author = {Park, S and Koo, J and Kim, JH and Yang, WI and Park, BW and Lee, KS}, title = {Clinicopathological characteristics of mucinous carcinoma of the breast in Korea: comparison with invasive ductal carcinoma-not otherwise specified.}, journal = {Journal of Korean medical science}, volume = {25}, number = {3}, pages = {361-368}, pmid = {20191033}, issn = {1598-6357}, mesh = {Adenocarcinoma, Mucinous/diagnosis/genetics/*pathology ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/classification/diagnosis/genetics/*pathology ; Carcinoma, Ductal/diagnosis/genetics/*pathology ; Disease-Free Survival ; Female ; Genes, erbB-2 ; Humans ; Korea ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Survival Rate ; Young Adult ; }, abstract = {Clinicopathological characteristics and prognostic factors of mucinous carcinoma (MC) were compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS). Clinicopathological characteristics and survivals of 104 MC patients were retrospectively reviewed and compared with those of 3,936 IDC-NOS. The median age at diagnosis was 45 yr in MC and 47 yr in IDC-NOS, respectively. The sensitivity of mammography and sonography for pure MC were 76.5% and 94.7%, respectively. MC showed favorable characteristics including less involvement of lymph node, lower stage, more expression of estrogen receptors, less HER-2 overexpression and differentiated grade, and better 10-yr disease-free survival (DFS) and overall survival (OS) (86.1% and 86.3%, respectively) than IDC-NOS (74.7% and 74.9%, respectively). Ten-year DFS of pure and mixed type was 90.2% and 68.8%, respectively. Nodal status and stage were statistically significant factors for survival. MC in Koreans showed similar features to Western populations except for a younger age of onset than in IDC-NOS. Since only pure MC showed better prognosis than IDC-NOS, it is important to differentiate mixed MC from pure MC. Middle-aged Korean women presenting breast symptoms should be examined carefully and evaluated with an appropriate diagnostic work-up because some patients present radiologically benign-like lesions.}, }
@article {pmid20174726, year = {2010}, author = {Atik, E and Akansu, B and Bakaris, S and Aban, N}, title = {Expression of cyclooxygenase-2 and its relation to histological grade, inducible nitric oxide synthase, matrix metalloproteinase-2, CD-34, Caspase-3, and CD8 in invasive ductal carcinoma of the breast.}, journal = {Saudi medical journal}, volume = {31}, number = {2}, pages = {130-134}, pmid = {20174726}, issn = {1658-3175}, mesh = {Adult ; Aged ; Antigens, CD34/*immunology ; Breast Neoplasms/enzymology/immunology/*pathology ; CD8 Antigens/*immunology ; Carcinoma, Ductal/enzymology/immunology/*pathology ; Caspase 3/*metabolism ; Female ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; Nitric Oxide Synthase Type II/*metabolism ; }, abstract = {OBJECTIVE: To assess by immunohistochemistry the cyclooxygenase-2 (COX-2) expression in invasive ductal carcinoma and its possible correlation with the histological grade, inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP2), and other common immunohistochemical parameters (CD-34, Caspase-3, and CD8).<br><br>METHODS: This was a retrospective pathology archive study including 50 female patients and was performed in Mustafa Kemal University, Hatay, and Sutcu Imam University, Kahraman Maras, Turkey. The routine hematoxylin-eosin staining and COX-2, iNOS, MMP-2, CD-34, CASP-3, and CD8 immunoperoxidase techniques were performed on paraffin-embedded tissues.<br><br>RESULTS: The mean value of COX-2 was 274.02+/-54.49 and MMP-2 was 263.42+/-54.30, whereas the mean iNOS values were 258.10+/-56.05. CD-34 staining also yielded positive results as 26.18+/-8.00. The mean value of CASP-3 was 284.06+/-41.2 and CD8 was 164.17+/-69.5. This reveals an inverse correlation between CASP-3 reactivity and CD8 (Spearman correlation [r]= -0.33, p=0.01). There was also an inverse correlation between iNOS reactivity and patients age (r = -0.29, p=0.03). There was a positive correlation with COX-2 and MMP-2 (p=0.00), but there was no relation with COX-2 and other parameters.<br><br>CONCLUSION: COX-2 expression is an important parameter for invasive ductal carcinoma of the breast. We found a positive correlation between COX-2 and MMP-2, whereas, we could not show direct correlation between COX-2 and iNOS, CD-34, CASP-3, and CD8.}, }
@article {pmid20151319, year = {2010}, author = {Chanplakorn, N and Chanplakorn, P and Suzuki, T and Ono, K and Chan, MS and Miki, Y and Saji, S and Ueno, T and Toi, M and Sasano, H}, title = {Increased estrogen sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type 1(17beta-HSD1) following neoadjuvant aromatase inhibitor therapy in breast cancer patients.}, journal = {Breast cancer research and treatment}, volume = {120}, number = {3}, pages = {639-648}, doi = {10.1007/s10549-010-0785-3}, pmid = {20151319}, issn = {1573-7217}, mesh = {Aged ; Androstadienes/*pharmacology/therapeutic use ; Antineoplastic Agents, Hormonal/*pharmacology/therapeutic use ; Aromatase Inhibitors/*pharmacology/therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*drug therapy/enzymology/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/enzymology/surgery ; Clinical Trials, Phase II as Topic/statistics &amp; numerical data ; Combined Modality Therapy ; Estradiol Dehydrogenases/*biosynthesis/genetics ; Estrogens/*metabolism ; Female ; Humans ; Ki-67 Antigen/analysis ; Mastectomy ; Middle Aged ; Multicenter Studies as Topic/statistics &amp; numerical data ; Neoadjuvant Therapy ; Neoplasm Proteins/*biosynthesis/genetics ; Neoplasms, Hormone-Dependent/chemistry/*drug therapy/enzymology/surgery ; Postmenopause ; Receptors, Steroid/analysis ; Sulfatases/*biosynthesis/genetics ; }, abstract = {Aromatase inhibitors (AIs) are considered the gold standard for endocrine therapy of estrogen receptor (ER) positive postmenopausal breast cancer patients. The therapy may enhance therapeutic response and stabilize disease but resistance and disease progression inevitably occur in the patients. These are considered at least partly due to an emergence of alternative intratumoral estrogen production pathways. Therefore, in this study we evaluated effects of exemestane (EXE) upon the enzymes involved in intratumoral estrogen production including estrogen sulfatase (STS), 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), and estrogen sulfotransferase (EST) and correlated the findings with therapeutic responses including Ki67 labeling index (Ki67). 116 postmenopausal patients with invasive ductal carcinoma, stage II/IIIa, were enrolled in JFMC34-0601 clinical trials between March, 2006 and January, 2008. EXE of 25 mg/day was administered according to the protocol. Pre- and posttreatment specimens of 49 cases were available for this study. Status of STS, EST, 17beta-HSD1, ER, progesterone receptor (PgR), human epidermal growth factor receptor type 2 (Her2), and Ki67 in pre- and post-specimens were evaluated. Specimens examined before the therapy demonstrated following features; ER+ (100%), PgR+ (85.7%), and Her2+ (77.6%). After treatment, the number of Ki67, PgR, and ER positive carcinoma cells demonstrated significant decrement in clinical response (CliR) and pathological response (PaR) groups. Significant increment of 17beta-HSD1 and STS immunoreactivity was detected in all groups examined except for STS in PaR. EST showed significant increment in nonresponsive groups. Alterations of Ki67 of carcinoma cells before and after therapy were subclassified into three groups according to its degrees. Significant alterations of intratumoral enzymes, especially 17beta-HSD1 and STS, were correlated with Ki67 reduction after neoadjuvant EXE therapy. This is the first study demonstrating significant increment of STS and 17beta-HSD1 following AI neoadjuvant therapy of postmenopausal ER positive breast carcinoma patients. This increment may represent the compensatory response of breast carcinoma tissues to estrogen depletion.}, }
@article {pmid20143146, year = {2010}, author = {Guttmann-Steinmetz, S and Gadow, KD and DeVincent, CJ and Crowell, J}, title = {Anxiety symptoms in boys with autism spectrum disorder, attention-deficit hyperactivity disorder, or chronic multiple tic disorder and community controls.}, journal = {Journal of autism and developmental disorders}, volume = {40}, number = {8}, pages = {1006-1016}, pmid = {20143146}, issn = {1573-3432}, support = {MH 45358/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Anxiety Disorders/*complications/psychology ; Attention Deficit Disorder with Hyperactivity/*complications/psychology ; Case-Control Studies ; Child ; Child Development Disorders, Pervasive/*complications/psychology ; Humans ; Male ; Psychiatric Status Rating Scales ; Tic Disorders/*complications/psychology ; Wechsler Scales ; }, abstract = {We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention-deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were assessed using parent and teacher versions of a DSM-IV-referenced rating scale. All three groups of boys with co-morbid ADHD evidenced more severe anxiety than Controls. Group differences in anxiety varied as a function of symptom, disorder, informant, and co-morbidity supporting the notion that co-morbid neurobehavioral syndromes differentially impact clinical features of co-occurring anxiety symptoms. Findings also suggest that GAD and SAD are phenomenologically unique, even in children with ASD. Implications for nosology are discussed.}, }
@article {pmid20110783, year = {2010}, author = {Puente, J and Manzano, A and Martin, M and López-Tarruella, S and Díaz-Rubio, E}, title = {Breast cancer: complete response with the combination of sunitinib and trastuzumab in a patient with grade III ductal carcinoma.}, journal = {Anti-cancer drugs}, volume = {21 Suppl 1}, number = {}, pages = {S19-22}, doi = {10.1097/01.cad.0000361532.36428.42}, pmid = {20110783}, issn = {1473-5741}, mesh = {Antibodies, Monoclonal/*administration &amp; dosage/adverse effects ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*administration &amp; dosage/adverse effects ; *Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/*drug therapy/pathology/radiotherapy ; Carcinoma, Ductal, Breast/*drug therapy/pathology/radiotherapy ; Diarrhea/chemically induced ; Female ; Heart Function Tests/drug effects ; Humans ; Hypothyroidism/chemically induced ; Indoles/*administration &amp; dosage/adverse effects ; Lymphatic Metastasis ; Middle Aged ; Paclitaxel/administration &amp; dosage/adverse effects ; Pyrroles/*administration &amp; dosage/adverse effects ; Remission Induction ; Sunitinib ; Trastuzumab ; }, abstract = {In August 2000, a previously healthy postmenopausal 52-year-old woman was diagnosed with grade III invasive ductal carcinoma. The tumor had an ER -, PR -, and HER2 + profile. Adjuvant treatment with FEC was initiated followed by radiotherapy. In October 2004, the patient presented a clinically asymptomatic supraclavicular and mediastinal lymph node recurrence and treatment with paclitaxel and trastuzumab was initiated. A complete response was achieved after 20 weeks of treatment, and in January 2006 treatment was interrupted due to toxicity. After a 34-month free-of-relapse period, a local recurrence was detected in the chest wall. In September 2007, the patient joined a phase II trial with sunitinib (37.5 mg once a day in 28 days cycles) and trastuzumab (6 mg/kg every 3 weeks), after having verified a normal cardiac function. After two courses, a partial cutaneous response and a complete radiological response were obtained. The most relevant toxicities included cutaneous hyperpigmentation, dysgeusia, mucositis, grade II diarrhea and hypertension. The development of grade III diarrhea led to sunitinib dose reduction (25mg/day). In January 2008, the patient developed hypothyroidism and a significant drop in the left ventricular ejection fraction that led to treatment interruption. In March 2008, once cardiac function was recovered, treatment at the same dose was reinitiated. After two months of treatment, a new descent in cardiac function was noted which led to the suspension of sunitinib, and the interruption of the trastuzumab treatment until recovery of normal cardiac function. In July 2008, trastuzumab monotherapy was resumed and since then no cardiac events have been reported, while maintaining a radiological and clinical response.}, }
@article {pmid20107518, year = {2010}, author = {Chaal, BK and Gupta, AP and Wastuwidyaningtyas, BD and Luah, YH and Bozdech, Z}, title = {Histone deacetylases play a major role in the transcriptional regulation of the Plasmodium falciparum life cycle.}, journal = {PLoS pathogens}, volume = {6}, number = {1}, pages = {e1000737}, pmid = {20107518}, issn = {1553-7374}, mesh = {Enzyme Inhibitors/pharmacology ; Gene Expression Regulation, Developmental/*physiology ; Histone Deacetylases/*genetics ; Immunoprecipitation ; Oligonucleotide Array Sequence Analysis ; Peptides, Cyclic/pharmacology ; Plasmodium falciparum/*growth &amp; development/*physiology ; RNA, Messenger/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; *Transcription, Genetic ; }, abstract = {The apparent paucity of molecular factors of transcriptional control in the genomes of Plasmodium parasites raises many questions about the mechanisms of life cycle regulation in these malaria parasites. Epigenetic regulation has been suggested to play a major role in the stage specific gene expression during the Plasmodium life cycle. To address some of these questions, we analyzed global transcriptional responses of Plasmodium falciparum to a potent inhibitor of histone deacetylase activities (HDAC). The inhibitor apicidin induced profound transcriptional changes in multiple stages of the P. falciparum intraerythrocytic developmental cycle (IDC) that were characterized by rapid activation and repression of a large percentage of the genome. A major component of this response was induction of genes that are otherwise suppressed during that particular stage of the IDC or specific for the exo-erythrocytic stages. In the schizont stage, apicidin induced hyperacetylation of histone lysine residues H3K9, H4K8 and the tetra-acetyl H4 (H4Ac4) and demethylation of H3K4me3. Interestingly, we observed overlapping patterns of chromosomal distributions between H4K8Ac and H3K4me3 and between H3K9Ac and H4Ac4. There was a significant but partial association between the apicidin-induced gene expression and histone modifications, which included a number of stage specific transcription factors. Taken together, inhibition of HDAC activities leads to dramatic de-regulation of the IDC transcriptional cascade, which is a result of both disruption of histone modifications and up-regulation of stage specific transcription factors. These findings suggest an important role of histone modification and chromatin remodeling in transcriptional regulation of the Plasmodium life cycle. This also emphasizes the potential of P. falciparum HDACs as drug targets for malaria chemotherapy.}, }
@article {pmid20105336, year = {2010}, author = {Liu, XJ and Shen, P and Wang, XF and Sun, K and Sun, FF}, title = {Solitary adrenal metastasis from invasive ductal breast cancer: an uncommon finding.}, journal = {World journal of surgical oncology}, volume = {8}, number = {}, pages = {7}, pmid = {20105336}, issn = {1477-7819}, mesh = {Adrenal Gland Neoplasms/*secondary/surgery ; *Adrenalectomy ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; *Mastectomy, Modified Radical ; Middle Aged ; Prognosis ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) of the breast usually metastasizes to the lungs, liver, bones and brain. Solitary adrenal metastasis is extremely rare. Due to the rarity of this condition, the optimal treatment is unclear. We report the first case of IDC of the breast metastasizing solely to the adrenal gland after a modified radical mastectomy but having a long-term disease-free survival while treated merely by a left adrenalectomy.<br><br>CASE PRESENTATION: A 64-year-old woman was found a left adrenal mass on a follow-up visit two years after taking a right modified radical mastectomy for the breast cancer. She was subsequently given a left adrenalectomy. Postoperative histopathology findings were compatible with invasive ductal carcinoma (IDC) of the breast. Due to the patient's refusal, no further treatments were offered after the adrenalectomy. The patient now is still alive and has no sign of relapse. Survival time after taking the right modified radical mastectomy and the left adrenalectomy is more than five years and three years, respectively.<br><br>CONCLUSION: This is the first case of a patient with solitary, metachronous adrenal metastasis from IDC of the breast to be reported. For patients in this condition, complete removal of metastasized organ may translate into survival benefit.}, }
@article {pmid20105298, year = {2010}, author = {Tada, K and Ogiya, A and Kimura, K and Morizono, H and Iijima, K and Miyagi, Y and Nishimura, S and Makita, M and Horii, R and Akiyama, F and Iwase, T}, title = {Ductal carcinoma in situ and sentinel lymph node metastasis in breast cancer.}, journal = {World journal of surgical oncology}, volume = {8}, number = {}, pages = {6}, pmid = {20105298}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Carcinoma, Intraductal, Noninfiltrating/*secondary ; Female ; Humans ; Incidence ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: The impact of sentinel lymph node biopsy on breast cancer mimicking ductal carcinoma in situ (DCIS) is a matter of debate.<br><br>METHODS: We studied the rate of occurrence of sentinel lymph node metastasis in 255 breast cancer patients with pure DCIS showing no invasive components on routine pathological examination. We compared this to the rate of occurrence in 177 patients with predominant intraductal-component (IDC) breast cancers containing invasive foci equal to or less than 0.5 cm in size.<br><br>RESULTS: Most of the clinical and pathological baseline characteristics were the same between the two groups. However, peritumoral lymphatic permeation occurred less often in the pure DCIS group than in the IDC-predominant invasive-lesion group (1.2% vs. 6.8%, p = 0.002). One patient (0.39%) with pure DCIS had two sentinel lymph nodes positive for metastasis. This rate was significantly lower than that in patients with IDC-predominant invasive lesions (6.2%; p < 0.001).<br><br>CONCLUSIONS: Because the rate of sentinel lymph node metastasis in pure DCIS is very low, sentinel lymph node biopsy can safely be omitted.}, }
@article {pmid20091034, year = {2012}, author = {Azar, L and Fischer, HD}, title = {Perivascular carotid inflammation: an unusual case of carotidynia.}, journal = {Rheumatology international}, volume = {32}, number = {2}, pages = {457-459}, pmid = {20091034}, issn = {1437-160X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Carotid Artery Diseases/*chemically induced/diagnostic imaging/pathology ; Carotid Artery, Common/diagnostic imaging/*drug effects/pathology ; Diagnosis, Differential ; Female ; Humans ; Inflammation/chemically induced/diagnosis/pathology ; Middle Aged ; Neck Pain/*etiology/pathology ; Radiography ; Vasculitis/chemically induced/diagnostic imaging/pathology ; }, abstract = {A 59-year-old woman was admitted to the hospital with a fever and rigors for 2 days. She was on chemotherapy (docetaxel, carboplatin, and trastuzumab) for her stage II invasive ductal carcinoma of the breast. Her physical exam was unremarkable except for the fever. The white blood cells were 21,200/mm(3) with 92% of neutrophils. ESR was 106 mm/h. An extensive infectious workup was negative. On day 6, while still febrile, the patient complained of a left-sided neck pain. She exhibited tenderness over the left carotid artery. A CT scan of the neck without intravenous contrast showed perivascular inflammation of the left common carotid artery, without evidence of a collection, arterial thrombosis, aneurysm, or dissection. The etiology of this finding was possibly chemotherapy related. It dramatically responded to oral prednisone. A repeat CT scan of the neck with IV contrast 2 weeks later showed a remarkable improvement. Drug reactions can simulate systemic inflammatory diseases and should always be considered in the diagnosing process.}, }
@article {pmid20082408, year = {2010}, author = {Kelten, C and Sen Turk, N and Kesen, Z and Akbulut, M and Duzcan, E}, title = {Fine-needle aspiration biopsy of an invasive ductal carcinoma with medullary features presented with abscess formation.}, journal = {Diagnostic cytopathology}, volume = {38}, number = {8}, pages = {624-625}, doi = {10.1002/dc.21266}, pmid = {20082408}, issn = {1097-0339}, mesh = {Abscess/*complications ; Adult ; Biopsy, Fine-Needle ; Breast/*pathology ; Breast Neoplasms/*complications/*pathology ; Carcinoma, Ductal, Breast/*complications/*pathology ; Carcinoma, Medullary/*pathology ; Female ; Humans ; }, }
@article {pmid20081807, year = {2010}, author = {van der Vegt, B and Wesseling, J and Pijnappel, RM and Dorrius, MD and den Heeten, GJ and de Roos, MA and de Bock, GH}, title = {Aggressiveness of 'true' interval invasive ductal carcinomas of the breast in postmenopausal women.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {23}, number = {4}, pages = {629-636}, doi = {10.1038/modpathol.2009.188}, pmid = {20081807}, issn = {1530-0285}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/metabolism/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Mammography ; Mass Screening/methods ; Middle Aged ; Postmenopause ; Proportional Hazards Models ; Receptor, ErbB-2/biosynthesis/genetics ; Receptors, Estrogen/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; Retrospective Studies ; Tissue Array Analysis ; Tumor Suppressor Protein p53/biosynthesis/genetics ; }, abstract = {There is debate whether interval carcinomas differ from screen-detected tumours biologically. In this study, clinico-pathological parameters and the expression of well-validated biological markers were compared between 'true' interval carcinomas and screen-detected/missed carcinomas hypothesising that 'true' interval carcinomas show a more aggressive biological behaviour. The study group consisted of 92 consecutive postmenopausal women attending the breast screening programme and presenting with an invasive ductal carcinoma. All screening mammograms were re-reviewed. Sixteen patients had a 'true' interval carcinoma. Seven carcinomas were missed at screening, but detected on re-reviewing of the screening mammogram. Radiological characteristics were assessed from diagnostic mammograms. Data on patient- and tumour characteristics and follow-up data were recorded from hospital records. Median follow-up was 61 months. Immunohistochemistry for ER, PR, Her2/neu and p53 was performed on TMA sections. Univariate and multivariate logistic regression analyses were performed. In univariate analysis, 'true' interval carcinomas were significantly larger (odd ratios (OR) 7.2, 95% CI 1.8-28.1) and less frequently ER (OR 0.3, 95% CI 0.1-0.9) and PR (OR 0.3, 95% CI 0.1-1.0) positive. In multivariate analysis, 'true' interval carcinoma was independently associated with larger tumours (OR 7.0, 95% CI 1.4-36.2). A trend toward ER negativity was found (OR 0.3, 95% CI 0.1-1.1). 'True' interval carcinomas showed a trend toward a decreased relapse-free survival (HR 1.7 95% CI 0.9-3.1). Although 'true' interval carcinomas were significantly larger than screen-detected/missed interval carcinomas, it remains challenging to observe parameters that determine this difference between 'true' interval carcinomas and screen-detected lesions.}, }
@article {pmid20078968, year = {2009}, author = {Yu, L and Yang, WT and Cai, X and Lu, HF and Fan, YZ and Shi, DR}, title = {[Clinicopathologic study of centrally necrotizing carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {10}, pages = {657-662}, pmid = {20078968}, issn = {0529-5807}, mesh = {Actins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma in Situ/metabolism/*pathology/surgery ; Carcinoma, Basal Cell/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Immunophenotyping ; Keratin-14/metabolism ; Keratin-5/metabolism ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Mastectomy/methods ; Middle Aged ; Necrosis ; Neoplasm Recurrence, Local ; Survival Rate ; }, abstract = {OBJECTIVE: To study the clinicopathologic features and immunophenotype of centrally necrotizing carcinoma (CNC) of breast; and to study its relationship with basal-like breast cancer.<br><br>METHODS: The clinical and pathologic characteristics of 35 cases of CNC were analyzed. Immunohistochemical study for estrogen receptor, progesterone receptor, HER2, CK8/18, 34betaE12, CK5/6, CK14, CK17, smooth muscle actin, p63, vimentin and epidermal growth factor receptor was performed using EnVision method. The surival information of 10 case were obtained.<br><br>RESULTS: The age of patients with CNC ranged from 30 to 82 years (mean = 54.2 years). Macroscopically, all tumors were relatively circumscribed, with a mean diameter of 2.4 cm. Histologically, there was a prominent central, necrotic or acellular zone surrounded by a narrow rim of viable tumor cells. The central necrotic foci had the following morphologic patterns: (1) coagulative tumor necrosis associated with various degree of fibrosis or hyaline degeneration (24 cases), (2) predominance of fibrous and scar tissue, with small amount of necrotic debris (8 cases), and (3) infarction (3 cases). The peripheral zone of tumor cells showed features of grade 3 invasive ductal carcinoma in 32 cases and grade 2 in 3 cases. Twenty cases of CNC were associated with ductal carcinoma in-situ. A component of invasive micropapillary carcinoma was identified in 5 cases. Peripheral lymphocytic infiltrates were seen in 17 cases. Immunohistochemical study of 31 cases showed that the expression rate of basal-like markers (83.9%, 26 cases) was higher than that of myoepithelial markers (38.7%, 12 cases). The percentage of basal-like subtype (64.5%, 20 cases) was higher than luminal-A (9.7%, 3 cases), luminal-B (9.7%, 3 cases), HER2 over-expression (12.9%, 4 cases) and null (3.2%, 1 case) subtypes. In 20 cases of basal-like carcinoma, the expression ratio of CK5/6 was highest amongst basal-like markers (18 cases), the other markers ratios of CK17, CK14 and epidermal growth factor receptor were 8/10, 14/19 and 8/16, respectively. Follow-up data were available in 10 patients. The follow-up duration ranged from 15 to 42 months (mean = 21.5 months). The median disease-free and overall survivals were 14.0 and 18.0 months, respectively. Disease progression (as defined by the presence of recurrence, metastasis or tumor-related death) occurred in 9 patients. The mean and median time to disease progression was 16.6 and 13.0 months, respectively.<br><br>CONCLUSIONS: CNC is a rare subtype of breast carcinoma and has distinctive, easily discernible morphologic features. The majority of CNC exhibits basal-like immunophenotype and carries a poor prognosis. CNC is the typical representative of basal-like breast cancer.}, }
@article {pmid20075549, year = {2009}, author = {Ranade, KJ and Nerurkar, AV and Phulpagar, MD and Shirsat, NV}, title = {Expression of survivin and p53 proteins and their correlation with hormone receptor status in Indian breast cancer patients.}, journal = {Indian journal of medical sciences}, volume = {63}, number = {11}, pages = {481-490}, pmid = {20075549}, issn = {1998-3654}, mesh = {Adult ; Apoptosis/drug effects ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/immunology/pathology ; Carcinoma, Ductal, Breast/*genetics/immunology/pathology ; Female ; Fibroadenoma/genetics/immunology/pathology ; Humans ; Immunohistochemistry ; India ; Inhibitor of Apoptosis Proteins/*genetics ; Middle Aged ; Prognosis ; Receptors, Estrogen/*physiology ; Receptors, Progesterone/*physiology ; Retrospective Studies ; Statistics as Topic ; Statistics, Nonparametric ; Survivin ; Tumor Suppressor Protein p53/*genetics ; Young Adult ; }, abstract = {BACKGROUND: In invasive ductal carcinoma (IDC), many antiapoptotic and proapoptotic genes regulate disease outcome. Hormone receptor-mediated mechanisms have also been shown to prevent apoptosis. Therefore, relations between hormone receptor status and other molecular markers need further examination.<br><br>AIMS: In the present study, we analyzed the expression of apoptosis-regulating genes, viz., Survivin and mutant p53, in benign breast disease (fibroadenoma) and IDC patients. Results were then correlated with hormone receptor status of the patients.<br><br>MATERIAL AND METHODS: Paraffin-embedded tissue samples from 63 untreated female patients with IDC and 32 female patients with fibroadenoma were used. Expression of Survivin and mutant p53 was evaluated using immunohistochemical staining method.<br><br>STATISTICAL ANALYSIS: Fisher exact test and nonparametric correlation test (Spearman rank correlation test) were performed. Results : In fibroadenoma, 53% of patients expressed Survivin and 13% of patients expressed p53 protein. Statistically significant increase in Survivin and p53 protein expression was observed in carcinoma cases. Survivin expression correlated negatively with progesterone receptor (PR) status, but its expression was independent of estrogen receptor (ER) status. p53 expression showed negative correlation with both ER and PR status.<br><br>CONCLUSIONS: Increased expression of Survivin and p53 in IDC patients and correlation with hormone receptors suggest that Survivin and p53 along with hormone receptors status are likely to contribute significantly to apoptosis resistance and may serve as therapeutic target that could increase the effectiveness of conventional breast cancer therapy.}, }
@article {pmid20069058, year = {2009}, author = {Ziółkowski, P and Gamian, E and Osiecka, B and Zougman, A and Wiśniewski, JR}, title = {Immunohistochemical and proteomic evaluation of nuclear ubiquitous casein and cyclin-dependent kinases substrate in invasive ductal carcinoma of the breast.}, journal = {Journal of biomedicine &amp; biotechnology}, volume = {2009}, number = {}, pages = {919645}, pmid = {20069058}, issn = {1110-7251}, mesh = {Antibodies, Neoplasm/immunology ; Antibody Specificity/immunology ; Breast Neoplasms/immunology/*metabolism/pathology ; Carcinoma, Ductal, Breast/immunology/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Nuclear Proteins/immunology/*metabolism ; Phosphoproteins/immunology/*metabolism ; *Proteomics ; }, abstract = {Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is 27 kDa chromosomal protein of unknown function. Its amino acid composition as well as structure of its DNA binding domain resembles that of high-mobility group A, HMGA proteins. HMGA proteins are associated with various malignancies. Since changes in expression of HMGA are considered as marker of tumor progression, it is possible that similar changes in expression of NUCKS could be useful tool in diagnosis and prognosis of breast cancer. For identification and analysis of NUCKS we used proteomic and histochemical methods. Analysis of patient-matched samples of normal and breast cancer by mass spectrometry revealed elevated levels of NUCKS in protein extracts from ductal breast cancers. We elicited specific antibodies against NUCKS and used them for immunohistochemistry in invasive ductal carcinoma of breast. We found high expression of NUCKS in 84.3% of cancer cells. We suggest that such overexpression of NUCKS can play significant role in breast cancer biology.}, }
@article {pmid20060718, year = {2010}, author = {McAree, B and O'Donnell, ME and Spence, A and Lioe, TF and McManus, DT and Spence, RA}, title = {Breast cancer in women under 40 years of age: a series of 57 cases from Northern Ireland.}, journal = {Breast (Edinburgh, Scotland)}, volume = {19}, number = {2}, pages = {97-104}, doi = {10.1016/j.breast.2009.12.002}, pmid = {20060718}, issn = {1532-3080}, mesh = {Adult ; Breast Neoplasms/genetics/*pathology/*physiopathology/therapy ; Female ; Genetic Predisposition to Disease ; Humans ; Neoplasm Staging ; Northern Ireland/epidemiology ; Retrospective Studies ; }, abstract = {BACKGROUND: There are few studies examining breast cancer in women under the age of 40 years, particularly in western European populations. Such tumours are reported to be more aggressive, possibly due to a different pathophysiology compared to older patients.<br><br>METHODS: We performed a retrospective review of all women less than 40 years of age, diagnosed or treated with breast cancer, from June 2001 to June 2007 to assess pathophysiological factors that may influence clinical outcome and prognosis including patient demographics, clinical presentation, pre-operative investigations, surgical and pathological findings, treatment and outcome.<br><br>RESULTS: Fifty-eight women (mean age 34.9 years, range 27-39 years) were identified. One patient was excluded due to incomplete data; 98.2% (n=56) patients presented directly to our symptomatic clinic; 89.5% (n=51) patients had a palpable lump; 71.9% (n=41) patients had no family history. Mammography was less sensitive than ultrasound (64.3% vs. 82.4%) while fine needle aspiration cytology was 92.5% sensitive for malignancy. Twenty-nine (50.9%) patients underwent breast-conserving surgery (BCS) of which 7 proceeded subsequently to completion mastectomy due to involved margins. Twenty-six (45.6%) patients required total mastectomy primarily while 2 (3.5%) patients were treated palliatively due to metastatic disease. The mean tumour size (nearest resection margin) was 2.13cm (2.58mm) for BCS and 3.95cm (6.38mm) for mastectomy. From a total of 55 primary resections, 85.5% (n=47) of tumours were invasive ductal carcinoma; 57.4% (n=31) and 40.7% (n=22) were grade II and III tumours respectively. Lymphovascular invasion was identified in 50.9% (n=28) while 40.0% (n=22) were lymph node positive for metastatic disease. 76.8% (n=43), 39.3% (n=22) and 30.2% (n=16) were oestrogen, progesterone and human epidermal growth factor receptor-2 positive respectively. The mean Nottingham prognostic index was 4.37 (range 2.2-8.4). Neo-adjuvant and adjuvant chemotherapy was administered to 9.3% (n=5) and 80.0% (n=44) of surgically treated patients respectively while 76.4% (n=42) patients received adjuvant radiotherapy. 76.4% (n=42) of patients were treated with tamoxifen. Four patients received Herceptin therapy. Statistically significant univariate factors adversely associated with overall survival were time from referral to out-patient department attendance (p=0.038), administration of neo-adjuvant treatment (p=0.019), surgical intervention (p<0.001), progesterone receptor positivity (p=0.018) and tumour recurrence (p<0.001). 86.0% (n=49) patients were alive at mean follow-up of 52 months; 82.5% (n=47) remain disease free.<br><br>CONCLUSION: Our study reports a low familial trait rate combined with a high proportion of hormonally active tumours less than grade III which suggests that breast cancer in this series of young women from Northern Ireland may be less aggressive and more hormonally responsive than anticipated.}, }
@article {pmid20050885, year = {2010}, author = {Barone, P}, title = {Neurotransmission in Parkinson's disease: beyond dopamine.}, journal = {European journal of neurology}, volume = {17}, number = {3}, pages = {364-376}, doi = {10.1111/j.1468-1331.2009.02900.x}, pmid = {20050885}, issn = {1468-1331}, mesh = {Animals ; Dopamine/metabolism ; Humans ; Parkinson Disease/*physiopathology ; Synaptic Transmission/*physiology ; }, abstract = {Parkinson's disease (PD) is most frequently associated with characteristic motor symptoms that are known to arise with degeneration of dopaminergic neurons. However, patients with this disease also experience a multitude of non-motor symptoms, such as sleep disturbances, fatigue, apathy, anxiety, depression, cognitive impairment, dementia, olfactory dysfunction, pain, sweating and constipation, some of which can be at least as debilitating as the movement disorders and have a major impact on patients' quality of life. Many of these non-motor symptoms may be evident prior to the onset of motor dysfunction. The neuropathology of PD has shown that complex, interconnected neuronal systems, regulated by a number of different neurotransmitters in addition to dopamine, are involved in the aetiology of motor and non-motor symptoms. This review focuses on the non-dopaminergic neurotransmission systems associated with PD with particular reference to the effect that their modulation and interaction with dopamine has on the non-motor symptoms of the disease. PD treatments that focus on the dopaminergic system alone are unable to alleviate both motor and non-motor symptoms, particularly those that develop at early stages of the disease. The development of agents that interact with several of the affected neurotransmission systems could prove invaluable for the treatment of this disease.}, }
@article {pmid22072120, year = {2010}, author = {Liang, S and Singh, M and Gam, LH}, title = {Potential hydrophobic protein markers of breast cancer in Malaysian Chinese, Malay and Indian patients.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {8}, number = {6}, pages = {319-330}, doi = {10.3233/CBM-2011-0221}, pmid = {22072120}, issn = {1875-8592}, mesh = {Asian People ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/ethnology/genetics/*metabolism ; Carcinoma, Ductal, Breast/ethnology/genetics/*metabolism ; China/ethnology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hydrophobic and Hydrophilic Interactions ; India/ethnology ; Malaysia ; Neoplasm Proteins/genetics/*metabolism ; }, abstract = {Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested.}, }
@article {pmid21972709, year = {2010}, author = {Gabrovski, N and Poptodorov, G and Velinov, N and Gabrovski, S}, title = {[Late metastases from breast cancer--report of two cases].}, journal = {Khirurgiia}, volume = {}, number = {1}, pages = {62-66}, pmid = {21972709}, issn = {0450-2167}, mesh = {Adult ; Brain/*pathology/*surgery ; Brain Neoplasms/pathology/*secondary/*surgery ; Breast/pathology/surgery ; Breast Neoplasms/*pathology/surgery/therapy ; Carcinoma, Ductal, Breast/*pathology/surgery/therapy ; Female ; Follow-Up Studies ; Humans ; Mastectomy ; Middle Aged ; }, abstract = {INTRODUCTION: Breast cancer is amongst the commonest reasons for brain metastases involving 15-20% of the patients. Metastases discovered 10 or more years after the initial diagnosis of breast cancer are defined as late metastases and present a rare event. We present two cases of late brain metastases of breast cancer discovered 15 and 17 years after initial diagnosis.<br><br>MATERIALS AND METHODS: In a 46-year old female patient a 5 x 6 cm lesion in the breast was observed and was histologically diagnosed to be a breast invasive ductal carcinoma. Mastectomy was performed (TNM grade - T2N1bM0) with postoperative radiotherapy (40 Gy for 20 days) combined with chemotherapy. All control investigations were normal for the next 17 years. During the last examination CA-15-3 levels were raised. CT scan revealed a lesion involving the frontal, temporal and parietal bones and the adjacent soft tissues as well as dura mater and the subdural space. Gross total resection was performed. In a 38-year old female patient a 3 cm lesion in the breast was observed and was histologically diagnosed to be a low differentiated invasive ductal breast carcinoma. Radical mastectomy was performed TNM grade (T2N1M0) with radio- and chemotherapy. For 13 years all control markers were negative. Last examination demonstrated increase of CA-15-3 levels. Due to complain of headache and nausea CT scan was performed showing a tumor lesion in the right frontal lobe. Gross total resection was performed.<br><br>CONCLUSION: In the presented cases we describe late brain metastasis from breast cancer 15 and 17 years after initial diagnosis. This observation is important because, regular followup for patients with breast cancer is 6-10 years. Obviously this approach in clinical practice could lead to mistakes and misdiagnosis of these rare lesions. Based on our experience we suggest that the follow-up, in patients treated for breast cancer, even with apparently total regression of the disease, should be extended beyond the routine period of 10 years and tumour markers should be investigated regularly. Metastasis in CNS should be taken into consideration in patients treated for breast cancer no matter the time from the initial diagnosis when clinical symptoms appear.}, }
@article {pmid21429243, year = {2010}, author = {Harkins, LE and Matlaf, LA and Soroceanu, L and Klemm, K and Britt, WJ and Wang, W and Bland, KI and Cobbs, CS}, title = {Detection of human cytomegalovirus in normal and neoplastic breast epithelium.}, journal = {Herpesviridae}, volume = {1}, number = {1}, pages = {8}, pmid = {21429243}, issn = {2042-4280}, abstract = {INTRODUCTION: Human cytomegalovirus (HCMV) establishes a persistent life-long infection, and can cause severe pathology in the fetus and the immunocompromised host1. Breast milk is the primary route of transmission in humans worldwide, and breast epithelium is thus a likely site of persistent infection and/or reactivation, though this phenomenon has not previously been demonstrated. Increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. We hypothesized that persistent HCMV infection occurs in normal adult breast epithelium and that persistent viral expression might be associated with normal and neoplastic ductal epithelium.<br><br>METHODS: Surgical biopsy specimens of normal breast (n = 38) breast carcinoma (n = 39) and paired normal breast from breast cancer patients (n = 21) were obtained. Specimens were evaluated by immunohistochemistry, in situ hybridization, PCR and DNA sequencing for evidence of HCMV antigens and nucleic acids.<br><br>RESULTS: We detected HCMV expression specifically in glandular epithelium in 17/27 (63%) of normal adult breast cases evaluated. In contrast, HCMV expression was evident in the neoplastic epithelium of 31/32 (97%) patients with ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) cases evaluated (p = 0.0009).<br><br>CONCLUSIONS: These findings are the first to demonstrate that persistent HCMV infection occurs in breast epithelium in a significant percentage of normal adult females. HCMV expression was also evident in neoplastic breast epithelium in a high percentage of normal and neoplastic breast tissues obtained from breast cancer patients, raising the possibility that viral infection may be involved in the neoplastic process.}, }
@article {pmid20037463, year = {2009}, author = {Sakurai, K and Fujisaki, S and Matsuo, S and Ogura, M and Enomoto, K and Kitajima, A and Tani, M and Amano, S and Shiono, M}, title = {[A case of advanced breast cancer with skin ulceration successfully treated with paclitaxel and toremifene therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {36}, number = {12}, pages = {2484-2486}, pmid = {20037463}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Agents, Phytogenic/*therapeutic use ; Breast Neoplasms/complications/*drug therapy ; Carcinoma, Ductal, Breast/complications/*drug therapy ; Female ; Hemorrhage/*complications/*etiology ; Humans ; Organic Chemicals/administration &amp; dosage ; Paclitaxel/*administration &amp; dosage ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Skin Ulcer/*etiology ; }, abstract = {We report a case of advanced breast cancer with skin ulceration and bleeding (T4bN3bM0, Stage IIIC) achieving a significant improvement of QOL by paclitaxel (PTX) and toremifene (TOR) therapy. The patient was a 31-year-old woman who had ulcerative breast lump with skin ulcer. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and negative for HER2/neu protein expression. She received 4 courses of tri-weekly CEF (C: 500 mg, E: 60 mg, F: 500 mg/m2/tri-weekly) and 4 courses of weekly PTX (80 mg/m2) with TOR (120 mg/day). The bleeding from the tumor disappeared after CEF chemotherapy. The response for breast tumor after PTX and TOR therapy was evaluated as partial response, and the infraclavicular, subpectoral, and interpectoral lymph nodes metastasis disappeared. Muscle-preserving radical mastectomy (Bt+Ax: Auchincloss) without skin transplantation were performed. She had no recurrence during one year after operation. PTX and TOR therapy were effective for advanced breast tumor, and can improve patient QOL and the clinical outcomes in Stage IIIC advanced breast cancer.}, }
@article {pmid20037447, year = {2009}, author = {Matsumura, T and Ohzato, H and Yamamoto, T and Ota, K and Mabuchi, E and Miwa, H and Ikeda, H and Fukunaga, M and Furukawa, H}, title = {[A case of postoperative brain metastasis originated from pancreatic cancer which was successfully treated by resection and postoperative irradiation].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {36}, number = {12}, pages = {2433-2435}, pmid = {20037447}, issn = {0385-0684}, mesh = {Antimetabolites, Antineoplastic/therapeutic use ; Brain Neoplasms/*secondary/*therapy ; Carcinoma, Ductal/*pathology ; Combined Modality Therapy ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Drug Combinations ; Humans ; Male ; Middle Aged ; Oxonic Acid/administration &amp; dosage ; Pancreatic Neoplasms/*pathology ; Tegafur/administration &amp; dosage ; Gemcitabine ; }, abstract = {We report a case of metastatic brain tumor originated from pancreatic cancer, which might be clinically considered as rare and has been reported as a remarkably poor-prognostic disease. A 64-year-old male underwent pancreas tail resection for pancreatic cancer (R0 resection). Histological study revealed an invasive ductal carcinoma (T4N2M0, fStage IVb). Following a short term of GEM administration, S-1 (80 mg/m2,day 1-28/42 days) was administered as the second-line. After 7 courses of S-1 chemotherapy, a follow-up CT demonstrated lymph node recurrence in cervical and mediastinum region. S-1 administration was stopped and irradiation to these sites (60 Gy) resulted in PR. Two months after irradiation, dizziness and speech disturbance appeared, and MRI examination demonstrated a solitary brain metastasis, which was removed because of rapid worseness of neurological symptoms. Postoperatively, hemicereberal irradiation (30 Gy) was performed. After the brain surgery, no brain metastasis was appeared. The patient was alive with abdominal lymph node recurrence for 22 months after distal pancreatectomy. It was concluded from these findings that irradiation to systemic recurrence originated from pancreatic cancer might be effective as well as chemotherapy.}, }
@article {pmid20036907, year = {2010}, author = {Barok, M and Balazs, M and Lazar, V and Rakosy, Z and Toth, E and Treszl, A and Vereb, G and Colbern, GT and Park, JW and Szollosi, J}, title = {Characterization of a novel, trastuzumab resistant human breast cancer cell line.}, journal = {Frontiers in bioscience (Elite edition)}, volume = {2}, number = {2}, pages = {627-640}, doi = {10.2741/e119}, pmid = {20036907}, issn = {1945-0508}, support = {P50 CA58207/CA/NCI NIH HHS/United States ; R03 TW 00871-01A2/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; *Cell Line, Tumor ; Comparative Genomic Hybridization ; *Disease Models, Animal ; *Drug Resistance, Neoplasm ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mice ; Mice, SCID ; Oncogenes/genetics ; Receptor, ErbB-2/metabolism ; Trastuzumab ; }, abstract = {HER2-positive breast cancers represent a distinct phenotype and are intrinsically more aggressive than HER2-negative tumors. Although HER2-targeted therapies have been rationally developed, resistance to these treatments represents a process understood poorly. There are few experimental models that allow studying the molecular mechanism of resistance. Our aim was to characterize a trastuzumab resistant breast cancer cell line (B585) that was established from an invasive ductal carcinoma. B585 grows only in immunodeficient mice as a xenograft. CGH and FISH were used to define cytogenetic alterations, gene-expression analysis and immunohistochemistry were applied to detect RNA and protein expression. By array-CGH focused amplifications were identified for C-MYC, EGFR, ErbB2, CCND1 and TOP2-A oncogenes. ErbB2 was co-amplified with TOP2-A. mRNA overexpression was detected for the amplified genes. ErbB2 protein was overexpressed and showed heterogeneous distribution. In summary, molecular cytogenetic analysis and expression profiling of B585 revealed several new alterations. Based on the experiments performed in SCID mice and the genotypic/phenotypic characteristics, this new in vivo breast cancer xenograft is a valuable model to investigate molecular mechanism of trastuzumab resistance.}, }
@article {pmid20027472, year = {2009}, author = {Portella, RS and Andrade, SG}, title = {Trypanosoma cruzi: parasite antigens sequestered in heart interstitial dendritic cells are related to persisting myocarditis in benznidazole-treated mice.}, journal = {Memorias do Instituto Oswaldo Cruz}, volume = {104}, number = {7}, pages = {1023-1030}, doi = {10.1590/s0074-02762009000700015}, pmid = {20027472}, issn = {1678-8060}, mesh = {Animals ; Antibodies, Monoclonal/blood ; Antigens, Protozoan/*analysis/drug effects ; Chagas Cardiomyopathy/drug therapy/*immunology/pathology ; Dendritic Cells/*immunology/pathology ; Disease Models, Animal ; Drug Resistance ; Mice ; Myocarditis/drug therapy/*immunology/pathology ; Myocardium/*cytology/immunology ; Nitroimidazoles/therapeutic use ; Time Factors ; Trypanocidal Agents/therapeutic use ; Trypanosoma cruzi/classification/*immunology ; }, abstract = {We investigated whether sequestered Trypanosoma cruzi antigens found in heart interstitial dendritic cells (IDCs) contribute to the residual myocarditis found in mice following treatment with benznidazole, a specific chemotherapeutic drug. IDCs are antigen-presenting cells that are MHC-II-receptor dependent. Swiss mice were divided into two experimental groups: the 1st group was infected with the Colombian strain of T. cruzi, which is resistant to treatment with benznidazole, and the 2nd group was infected with clone 21SF-C 3, which has a medium susceptibility to the drug. Treatment of the Colombian strain group started on the 120th day post-infection and for the 21SF-C3 strain group treatment was started on the 90th day. In both groups, treatment lasted for 90 days. The animals were sacrificed either 150 or 200 days post-treatment. The myocardium was analysed by immunohistochemistry using anti-MAC3, 33D1, CD11b and CD11c monoclonal antibodies for IDCs or anti-T. cruzi purified antibodies. Parasite antigens were expressed on the IDC membranes in both treated and untreated mice. Myocarditis subsided following treatment, evidenced by both histological and morphometrical evaluation. A reduction in the number of IDCs carrying T. cruzi antigens in the treated group indicates that the elimination of parasites influences antigen presentation with concomitant decreases in inflammation. There is a correlation between the presence of T. cruzi antigens in these cells and the chronic focal, residual myocarditis seen in treated mice.}, }
@article {pmid20018726, year = {2009}, author = {Hermes, GL and Delgado, B and Tretiakova, M and Cavigelli, SA and Krausz, T and Conzen, SD and McClintock, MK}, title = {Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {52}, pages = {22393-22398}, pmid = {20018726}, issn = {1091-6490}, support = {T32 MH019961/MH/NIMH NIH HHS/United States ; BC 061754/BC/NCI NIH HHS/United States ; R25 MH071584/MH/NIMH NIH HHS/United States ; T32HD009007/HD/NICHD NIH HHS/United States ; T32MH19961/MH/NIMH NIH HHS/United States ; P50 ES012382/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal ; Breast Neoplasms/etiology ; Carcinoma, Ductal, Breast/etiology ; Carcinoma, Intraductal, Noninfiltrating/etiology ; Corticosterone/metabolism ; Endocrine Glands/physiopathology ; Female ; Humans ; Mammary Neoplasms, Experimental/*etiology/pathology/physiopathology/*psychology ; Ovary/physiopathology ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid/metabolism ; Risk Factors ; Social Environment ; *Social Isolation ; Stress, Physiological ; Stress, Psychological ; }, abstract = {In a life span study, we examined how the social environment regulates naturally occurring tumor development and malignancy in genetically prone Sprague-Dawley rats. We randomly assigned this gregarious species to live either alone or in groups of five female rats. Mammary tumor burden among social isolates increased to 84 times that of age-matched controls, as did malignancy, specifically a 3.3 relative risk for ductal carcinoma in situ and invasive ductal carcinoma, the most common early breast cancers in women. Importantly, isolation did not extend ovarian function in late middle age; in fact, isolated animals were exposed to lower levels of estrogen and progesterone in the middle-age period of mammary tumor growth, with unchanged tumor estrogen and progesterone receptor status. Isolates, however, did develop significant dysregulation of corticosterone responses to everyday stressors manifest in young adulthood, months before tumor development, and persisting into old age. Among isolates, corticosterone response to an acute stressor was enhanced and recovery was markedly delayed, each associated with increased mammary tumor progression. In addition to being stressed and tumor prone, an array of behavioral measures demonstrated that socially isolated females possessed an anxious, fearful, and vigilant phenotype. Our model provides a framework for studying the interaction of social neglect with genetic risk to identify mechanisms whereby psychosocial stressors increase growth and malignancy of breast cancer.}, }
@article {pmid20015931, year = {2011}, author = {El-Ghannam, DM and Arafa, M and Badrawy, T}, title = {Mutations of p53 gene in breast cancer in the Egyptian province of Dakahliya.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {17}, number = {2}, pages = {119-124}, doi = {10.1177/1078155209356130}, pmid = {20015931}, issn = {1477-092X}, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma/genetics/metabolism/pathology ; Codon, Nonsense ; DNA Mutational Analysis ; Egypt ; Exons ; Female ; Frameshift Mutation ; *Genes, p53 ; Genetic Association Studies ; Humans ; Middle Aged ; *Mutation ; Mutation, Missense ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; Polymerase Chain Reaction ; *Polymorphism, Single-Stranded Conformational ; Tumor Burden ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy among females worldwide. Molecular analysis of p53 is likely to have value in diagnosis, prognosis, and treatment of breast cancer.<br><br>OBJECTIVE: To study the frequency and spectrum of p53 gene mutations in breast cancer patients residing Al Dakahliya district in the north of Egypt.<br><br>MATERIALS AND METHODS: Thirty patients with cancer breast as well as 10 controls were evaluated for p53 status by flow-cytometry, PCR-SSCP, and sequencing analysis.<br><br>RESULTS: P53 mutations were evident in five breast cancer patients (17%) including two missense mutations (A218 T and R279 G) in exon 6, 8; nonsense mutations (S297stop and Y159stop) in exon 8, 5, respectively, and frame shift mutation (M133 fs) in exon 5. p53 mutations were associated with invasive ductal carcinoma, large tumor size, and advanced disease stage<br><br>CONCLUSION: p53 gene mutations is potentially responsible for pathogenesis and clinical aggressiveness of breast cancer in our locality.}, }
@article {pmid20015349, year = {2009}, author = {Westenberger, SJ and Cui, L and Dharia, N and Winzeler, E and Cui, L}, title = {Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes.}, journal = {BMC genomics}, volume = {10}, number = {}, pages = {610}, pmid = {20015349}, issn = {1471-2164}, support = {1F32AI074242-01A1/AI/NIAID NIH HHS/United States ; AI064553/AI/NIAID NIH HHS/United States ; R01AI059472/AI/NIAID NIH HHS/United States ; }, mesh = {Binding Sites ; *Chromatin Assembly and Disassembly ; Chromatin Immunoprecipitation ; Chromosome Mapping ; DNA, Intergenic/genetics ; DNA, Protozoan/genetics ; *Genome, Protozoan ; Histones/*genetics ; Methylation ; Nucleosomes/*genetics ; Oligonucleotide Array Sequence Analysis ; Plasmodium falciparum/*genetics ; RNA, Messenger/genetics ; Telomere/genetics ; Transcription Factors/genetics ; Transcription Initiation Site ; }, abstract = {BACKGROUND: Epigenetic modifications of histones and regulation of chromatin structure have been implicated in regulation of virulence gene families in P. falciparum. To better understand chromatin-mediated gene regulation, we used a high-density oligonucleotide microarray to map the position and enrichment of nucleosomes across the entire genome of P. falciparum at three time points of the intra-erythrocytic developmental cycle (IDC) in vitro. We used an unmodified histone H4 antibody for chromatin immunoprecipitation of nucleosome-bound DNA.<br><br>RESULTS: We observed generally low nucleosomal occupancy of intergenic regions and higher occupancy of protein coding regions. In contract to the overall small fluctuation of nucleosomal occupancy in most coding regions throughout the IDC, subtelomeric genes encoding surface proteins such as var and rif, as well as some core chromosomal genes such as transcription factors, showed large changes in chromatin structure. Telomeres harbored a region with the highest nucleosomal occupancy of the genome and also exhibited large changes with higher nucleosomal occupancy at schizont stages. While many of these subtelomeric genes were previously shown to be modified by H3K9 trimethylation, we also identified some housekeeping genes in core chromosome regions that showed extensive changes in chromatin structure but do not contain this modification. tRNA and basal transcription factor genes showed low nucleosomal occupancy at all times, suggesting of an open chromatin structure that might be permissive for constitutively high levels of expression. Generally, nucleosomal occupancy was not correlated with the steady-state mRNA levels. Several var genes were exceptions: the var gene with the highest expression level showed the lowest nucleosomal occupancy, and selection of parasites for var2CSA expression resulted in lower nucleosomal occupancy at the var2CSA locus. We identified nucleosome-free regions in intergenic regions that may serve as transcription start sites or transcription factor binding sites. Using the nucleosomal occupancy data as the baseline, we further mapped the genome-wide enrichment of H3K9 acetylation and detected general enrichment of this mark in intergenic regions.<br><br>CONCLUSIONS: These data on nucleosome enrichment changes add to our understanding of the influence of chromatin structure on the regulation of gene expression. Histones are generally enriched in coding regions, and relatively poor in intergenic regions. Histone enrichment patterns allow for identification of new putative gene-coding regions. Most genes do not show correlation between chromatin structure and steady-state mRNA levels, indicating the dominant roles of other regulatory mechanisms. We present a genome-wide nucleosomal occupancy map, which can be used as a reference for future experiments of histone modification mapping.}, }
@article {pmid20005901, year = {2010}, author = {Hodrea, J and Demény, MA and Majai, G and Sarang, Z and Korponay-Szabó, IR and Fésüs, L}, title = {Transglutaminase 2 is expressed and active on the surface of human monocyte-derived dendritic cells and macrophages.}, journal = {Immunology letters}, volume = {130}, number = {1-2}, pages = {74-81}, doi = {10.1016/j.imlet.2009.12.010}, pmid = {20005901}, issn = {1879-0542}, mesh = {Animals ; Dendritic Cells/chemistry/*enzymology/*immunology ; Flow Cytometry ; GTP-Binding Proteins/chemistry/*metabolism ; Humans ; Immunoblotting ; Leukocytes, Mononuclear/*immunology ; Macrophages/chemistry/*enzymology/*immunology ; Membrane Proteins/*metabolism ; Mice ; Protein Glutamine gamma Glutamyltransferase 2 ; Transglutaminases/chemistry/*metabolism ; }, abstract = {The multifunctional enzyme, transglutaminase 2 (TG2), can be found intracellularly, in the extracellular matrix and on the cell surface. Cell surface TG2 (csTG2) could not be detected by TG2-specific antibodies or autoantibodies on immunocompetent cells. A supposedly csTG2-specific antibody, 6B9, was recently shown to actually react with CD44. Though the importance of TG2-mediated deamidation of gluten in the pathogenesis of celiac disease has been well recognized, it is not known in which intestinal cells or cell compartment the deamidation occurs. Duodenal dendritic cells (DCs) can be directly involved in gluten-reactive T-cell activation. Here we use blood monocyte-derived dendritic cells (iDC) and macrophages (MPhi) as a model for intestinal antigen-presenting cells (APCs) and show that they contain large amounts of TG2. We found that TG100, a commercial TG2-specific monoclonal antibody can recognize TG2 on the surface of these cells, that is monocyte-derived APCs express surface-associated TG2. TG2 expression was found on the surface of individual tunica propria cells in frozen small bowel tissue sections from both normal and celiac subjects. We also demonstrate that the pool of TG2 on the surface of iDCs can be catalytically active, hence it might directly be involved in the deamidation of gliadin peptides. Bacterial lipopolysaccharide (LPS) increased the level of TG2 on the surface of maturing DCs, supporting the hypothesis that an unspecific inflammatory process in the gut may expose more transglutaminase activity.}, }
@article {pmid19995377, year = {2009}, author = {Moran, MS and Yang, Q and Haffty, BG}, title = {The Yale University experience of early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) treated with breast conservation treatment (BCT): analysis of clinical-pathologic features, long-term outcomes, and molecular expression of COX-2, Bcl-2, and p53 as a function of histology.}, journal = {The breast journal}, volume = {15}, number = {6}, pages = {571-578}, doi = {10.1111/j.1524-4741.2009.00833.x}, pmid = {19995377}, issn = {1524-4741}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/chemistry/pathology/*surgery ; Carcinoma, Lobular/chemistry/pathology/*surgery ; Cyclooxygenase 2/*analysis ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Proto-Oncogene Proteins c-bcl-2/*analysis ; Treatment Outcome ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {To evaluate our experience of the clinical-pathologic features and outcomes of early-stage Invasive Lobular (ILC) versus Invasive Ductal (IDC) carcinoma treated with breast conservation treatment (BCT). 142 ILC and 1,760 IDC patients were treated with BCT at our institution. All patients underwent breast conserving surgery and radiation therapy (median total dose: 64 Gy). Clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. In addition, COX-2, Bcl-2, and p-53 expression was analyzed from our existing tissue micro-array database. Median follow-up was 6.8 years. A higher percentage of ILC patients presented at >40 years of age (94% ILC versus 89% IDC, p = 0.0353) and had more mammographically occult tumors (p < 0.002). There were no significant differences in T stage, nodal status, family history, final margin, ER/PR/HER-2 status or triple negative tumors (all p-values >0.05). From the immuno-histochemical analysis, expression of p53, COX-2, and Bcl-2 did not differ significantly (all p-values >0.05) between the two cohorts. At 10 years, there was no difference in breast relapse (20% versus 13%, p = 0.25), distant relapse (26% versus 20%, p = 0.28), cause-specific survival (72% versus 84%, p = 0.09) and OS (68% versus 78%, p = 0.08). Patients with ILC had higher contralateral breast relapses (26% versus 12%, p = 0.0006). Patients with early-stage ILC have comparable outcomes to IDC when treated with BCT. Because of the higher risk of contralateral breast cancers for ILC patients, careful evaluation of the contralateral breast will be important in the follow-up of these patients. Future investigations of chemo-preventive strategies to decrease contralateral breast cancers are warranted.}, }
@article {pmid19968660, year = {2010}, author = {Peiró, G and Adrover, E and Guijarro, J and Ballester, I and Jimenez, MJ and Planelles, M and Catasús, L}, title = {Synchronous bilateral breast carcinoma in a patient with cowden syndrome: a case report with morphologic, immunohistochemical and genetic analysis.}, journal = {The breast journal}, volume = {16}, number = {1}, pages = {77-81}, doi = {10.1111/j.1524-4741.2009.00846.x}, pmid = {19968660}, issn = {1524-4741}, mesh = {Adult ; Axilla ; Biopsy, Needle ; Breast Neoplasms/drug therapy/*pathology/surgery ; Breast Self-Examination ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Genetic Testing ; Hamartoma Syndrome, Multiple/*diagnosis ; Humans ; Immunohistochemistry ; Lymph Node Excision/*methods ; Lymph Nodes/pathology/surgery ; Magnetic Resonance Imaging ; Mammography/methods ; Mastectomy/*methods ; Neoplasm Staging ; Neoplasms, Multiple Primary/drug therapy/*pathology/surgery ; Treatment Outcome ; }, abstract = {Synchronous bilateral breast carcinoma (SBBC) and early onset are important characteristics of hereditary cases. The lifetime risk for breast carcinoma in Cowden syndrome (CS) is estimated to be 25-50%. We reported a 44-year-old woman presenting SBBC and characteristic mucocutaneous lesions of CS, confirmed by PTEN gene mutation analysis. Bilateral modified mastectomy and axillary dissection were performed. Histopathologic examination revealed a moderate-differentiated invasive ductal carcinoma with mixed features of luminal A immunophenotype (Estrogen and/or Progesterone Receptors >50% and/or Ki67 < 30% of positive cells). The skin lesions showed the characteristic findings of tricholemmoma. Lack of PTEN expression was observed in all specimens. Sequencing analysis confirmed the presence of PTEN splice-acceptor site mutation in intron 8 (c.1027-2A>G), a germline mutation which had not been previously reported in CS. The patient received adjuvant chemotherapy and tamoxifen for 5 years. After 5 years of follow-up, she persists recurrence-free. SBBC with early onset suggests a hereditary predisposition. Thus, analysis of PTEN expression abnormality, easily assessed by immunohistochemistry, may be of clinical value to screen those patients with CS.}, }
@article {pmid19967723, year = {2010}, author = {Germain, M and De Arcangelis, A and Robinson, SD and Baker, M and Tavora, B and D'Amico, G and Silva, R and Kostourou, V and Reynolds, LE and Watson, A and Jones, JL and Georges-Labouesse, E and Hodivala-Dilke, K}, title = {Genetic ablation of the alpha 6-integrin subunit in Tie1Cre mice enhances tumour angiogenesis.}, journal = {The Journal of pathology}, volume = {220}, number = {3}, pages = {370-381}, doi = {10.1002/path.2654}, pmid = {19967723}, issn = {1096-9896}, support = {12007/CRUK_/Cancer Research UK/United Kingdom ; 2003:602/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Animals ; Breast Neoplasms/*blood supply/metabolism ; Carcinoma, Ductal, Breast/blood supply ; Carcinoma, Lewis Lung/blood supply/metabolism/pathology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Genotype ; Humans ; Integrin alpha6/*genetics/metabolism/physiology ; Melanoma/blood supply/metabolism/pathology ; Mice ; Mice, Knockout ; Neoplasm Proteins/*genetics/metabolism/physiology ; Neoplasm Transplantation ; Neoplasms, Experimental/*blood supply/metabolism ; Neovascularization, Pathologic/chemically induced/*genetics/metabolism ; Polymerase Chain Reaction/methods ; Vascular Endothelial Growth Factor A/toxicity ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; }, abstract = {Laminins are expressed highly in blood vessel basement membranes and have been implicated in angiogenesis. alpha6beta1- and alpha6beta4-integrins are major receptors for laminins in endothelial cells, but the precise role of endothelial alpha6-integrin in tumour angiogenesis is not clear. We show that blood vessels in human invasive ductal carcinoma of the breast have decreased expression of the alpha6-integrin-subunit when compared with normal breast tissue. These data suggest that a decrease in alpha6-integrin-subunit expression in endothelial cells is associated with tumour angiogenesis. To test whether the loss of the endothelial alpha6-integrin subunit affects tumour growth and angiogenesis, we generated alpha6fl/fl-Tie1Cre+ mice and showed that endothelial deletion of alpha6-integrin is sufficient to enhance tumour size and tumour angiogenesis in both murine B16F0 melanoma and Lewis cell lung carcinoma. Mechanistically, endothelial alpha6-integrin deficiency elevated significantly VEGF-mediated angiogenesis both in vivo and ex vivo. In particular, alpha6-integrin-deficient endothelial cells displayed increased levels of VEGF-receptor 2 (VEGFR2) and VEGF-mediated downstream ERK1/2 activation. By developing the first endothelial-specific alpha6-knockout mice, we show that the expression of the alpha6-integrin subunit in endothelial cells acts as a negative regulator of angiogenesis both in vivo and ex vivo.}, }
@article {pmid19949854, year = {2010}, author = {Sharma, M and Beck, AH and Webster, JA and Espinosa, I and Montgomery, K and Varma, S and van de Rijn, M and Jensen, KC and West, RB}, title = {Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ.}, journal = {Breast cancer research and treatment}, volume = {123}, number = {2}, pages = {397-404}, pmid = {19949854}, issn = {1573-7217}, support = {R01 CA129927/CA/NCI NIH HHS/United States ; R01 CA129927-01A2/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/*genetics/pathology ; Carcinoma, Ductal, Breast/*chemistry/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/*genetics/pathology ; Disease Progression ; Female ; Fibroblasts/chemistry ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Genotype ; Humans ; Immunohistochemistry ; Macrophages/chemistry ; Neoplasm Invasiveness ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Stromal Cells/*chemistry/pathology ; Tissue Array Analysis ; }, abstract = {Recent advances in the study of the tumor microenvironment have revealed significant interaction between tumor cells and their surrounding stroma in model systems. We have previously shown that two distinct stromal signatures derived from a macrophage (CSF1) response and a fibroblastic (DTF-like) response are present in subsets of invasive breast cancers and show a correlation with clinical outcome. In the present study we explore whether these signatures also exist in the stroma of ductal carcinoma in situ (DCIS). We studied the signatures by both gene expression profile analysis of a publically available data set of DCIS and by immunohistochemistry (IHC) on a tissue microarray of DCIS and invasive breast cancer cases. Both the gene expression and immunohistochemical data show that the macrophage response and fibroblast expression signatures are present in the stroma of subsets of DCIS cases. The incidence of the stromal signatures in DCIS is similar to the incidence in invasive breast cancer that we have previously reported. We also find that the macrophage response signature is associated with higher grade DCIS and cases which are ER and PR negative, whereas the fibroblast signature was not associated with any clinicopathologic features in DCIS. A comparison of 115 matched cases of DCIS and invasive breast cancer found a correlation between the type of stromal response in DCIS and invasive ductal carcinoma (IDC) within the same patient for both the macrophage response and the fibroblast stromal signatures (P = 0.03 and 0.08, respectively). This study is a first characterization of these signatures in DCIS. These signatures have significant clinicopathologic associations and tend to be conserved as the tumor progresses from DCIS to invasive breast cancer.}, }
@article {pmid19945859, year = {2011}, author = {Elliott, RL and DeLand, M and Head, JF and Elliott, MC}, title = {Accelerated partial breast irradiation: initial experience with the Intrabeam System.}, journal = {Surgical oncology}, volume = {20}, number = {2}, pages = {73-79}, doi = {10.1016/j.suronc.2009.11.001}, pmid = {19945859}, issn = {1879-3320}, mesh = {*Brachytherapy ; Breast Neoplasms/pathology/*radiotherapy ; Female ; Humans ; Intraoperative Care ; Mastectomy, Segmental ; }, abstract = {Failure after breast conserving surgery (BCS) and total breast irradiation usually occurs at the site of the original tumor. This has caused an increased interest in accelerated partial breast irradiation (APBI), because if radiation is delivered directly to the tumor bed there should be better local control. Patients greater than age 50 with core biopsy confirmed invasive ductal carcinoma were enrolled. They had preoperative ultrasound defining margins of less than 3.5 cm. Intraoperative ultrasound was also performed in an effort to ensure good surgical margins. After excision of the tumor, intraoperative radiotherapy (IORT) with the Intrabeam System was delivered to the tumor bed. The procedure has been performed on 67 patients. Sixty-one patients had it with the original surgery, while 6 had the procedure after re-exploration of the segmental mastectomy site. Because of the final pathology (surgical margins, tumor biology, and nodal status) 4 patients later had total mastectomy and 11 received total breast irradiation. When total breast irradiation is done the IORT serves as the radiation boost. The cosmetic results have been good to excellent, and there have been no serious surgical or radiation complications. To date there have been no local failures. IORT with the Intrabeam System is feasible, user friendly, versatile, with few complications, good cosmetic results, and great patient acceptance. It is practical and excellent for breast IORT in the community setting.}, }
@article {pmid19944674, year = {2010}, author = {Prasad, CP and Rath, G and Mathur, S and Bhatnagar, D and Ralhan, R}, title = {Expression analysis of maspin in invasive ductal carcinoma of breast and modulation of its expression by curcumin in breast cancer cell lines.}, journal = {Chemico-biological interactions}, volume = {183}, number = {3}, pages = {455-461}, doi = {10.1016/j.cbi.2009.11.019}, pmid = {19944674}, issn = {1872-7786}, mesh = {Antineoplastic Agents/*pharmacology ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Curcumin/*pharmacology ; Female ; Humans ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Serpins/genetics/*metabolism ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation ; }, abstract = {In breast cancer, maspin, a serine protease inhibitor, can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. The clinical significance of maspin expression in breast cancer, especially in the sequence of ductal carcinoma in situ (DCIS)-invasive cancer-lymph node metastasis is well known in the Western countries, but its status in the rapidly increasing breast cancers in India remains unknown. The present study was designed to determine the clinical significance of maspin expression in invasive ductal carcinomas of breast (IDCs) in North Indian population and modulation of its expression by curcumin. Immunohistochemical analysis of maspin showed loss or reduced cytoplasmic expression in 36 of 59 (61%) tumors. Furthermore, breast cancer cells (MCF-7 (wild type p53) and MDA-MB-231 (mutant p53)) were treated with curcumin and the effect on expression of maspin gene at transcription and translation levels was analyzed by RT-PCR, immunofluorescence and Western blotting. Maspin expression was also correlated with p53 and Bcl-2 levels. Curcumin inhibited cell growth, induced apoptosis and upregulated maspin gene expression in MCF-7 cells and these findings were further correlated with the upregulation of p53 protein and downregulation of Bcl-2, suggesting maspin mediated apoptosis in MCF-7 cells. To our knowledge this is the first report showing the upregulation of maspin expression by curcumin in breast cancer cells and taken together with the clinical data suggests a potential therapeutic role for curcumin in inducing maspin mediated inhibition of invasion of breast carcinoma cells.}, }
@article {pmid19932795, year = {2009}, author = {Dimas, VV and Denfield, SW and Friedman, RA and Cannon, BC and Kim, JJ and Smith, EO and Clunie, SK and Price, JF and Towbin, JA and Dreyer, WJ and Kertesz, NJ}, title = {Frequency of cardiac death in children with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {104}, number = {11}, pages = {1574-1577}, doi = {10.1016/j.amjcard.2009.07.034}, pmid = {19932795}, issn = {1879-1913}, mesh = {Adolescent ; Arrhythmias, Cardiac/mortality ; Cardiomyopathy, Dilated/diagnosis/epidemiology/*mortality ; Child ; Child, Preschool ; Death, Sudden, Cardiac/*epidemiology/prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Medical Records ; Prognosis ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Texas/epidemiology ; }, abstract = {The prognosis in children with idiopathic dilated cardiomyopathy (IDC) is guarded, with the 5-year mortality rate ranging from 14% to 50%, owing to sudden cardiac death (SCD) or pump failure. The risk factors for SCD in adults with IDC include asymptomatic nonsustained ventricular tachycardia and poor left ventricular function. It is unclear whether these findings can be extrapolated to the pediatric population. A retrospective review of all patients with the diagnosis of IDC seen at a single institution from 1990 to 2004 was performed. A total of 85 patients (46 males), with a median age of 3.8 years (0 days to 17.3 years) were studied. The mean left ventricular ejection fraction was 25 +/- 12% (median 23%, range 45% to 45%) at presentation. The following arrhythmias occurred at presentation or during the initial hospitalization: nonsustained ventricular tachycardia in 6, sustained ventricular tachycardia or fibrillation in 1, supraventricular arrhythmias in 6, and both atrial and ventricular arrhythmias in 1. During a subsequent hospitalization or outpatient follow-up, 7 patients had the following arrhythmias: supraventricular arrhythmias in 2, nonsustained ventricular tachycardia in 4, and both atrial and ventricular arrhythmias in 1. The cumulative survival rate was 40% at a mean follow-up of 6.2 years (95% confidence interval 4.4 to 8.1). One single episode of SCD occurred in 1 patient without a history of sustained arrhythmias. In conclusion, in children with IDC, despite the low left ventricular ejection fraction and presence of ventricular arrhythmias, only one episode of SCD occurred in this group of patients. Given the 1% incidence of SCD in this cohort, the use of implantable cardioverter-defibrillators as primary prevention in children with IDC might not be indicated.}, }
@article {pmid19932096, year = {2010}, author = {García-Becerra, R and Díaz, L and Camacho, J and Barrera, D and Ordaz-Rosado, D and Morales, A and Ortiz, CS and Avila, E and Bargallo, E and Arrecillas, M and Halhali, A and Larrea, F}, title = {Calcitriol inhibits Ether-à go-go potassium channel expression and cell proliferation in human breast cancer cells.}, journal = {Experimental cell research}, volume = {316}, number = {3}, pages = {433-442}, doi = {10.1016/j.yexcr.2009.11.008}, pmid = {19932096}, issn = {1090-2422}, mesh = {Adult ; Aged ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/*pathology ; Calcitriol/*pharmacology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Ether-A-Go-Go Potassium Channels/*antagonists &amp; inhibitors/genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunohistochemistry ; Middle Aged ; Receptors, Calcitriol/metabolism ; }, abstract = {Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-à-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.}, }
@article {pmid19922592, year = {2009}, author = {Geyer, FC and Kushner, YB and Lambros, MB and Natrajan, R and Mackay, A and Tamber, N and Fenwick, K and Purnell, D and Ashworth, A and Walker, RA and Reis-Filho, JS}, title = {Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma.}, journal = {Histopathology}, volume = {55}, number = {6}, pages = {732-743}, doi = {10.1111/j.1365-2559.2009.03432.x}, pmid = {19922592}, issn = {1365-2559}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Adenoma/*diagnosis/*genetics ; Aged ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*diagnosis/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease/*diagnosis/*genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Oligonucleotide Array Sequence Analysis ; }, abstract = {AIMS: Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non-obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER-2 overexpression (triple-negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC-NST).<br><br>METHODS AND RESULTS: We report on a case comprising MGA, AMGA and a high-grade IDC-NST. The three components were separately microdissected and subjected to genetic analysis with high-resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant profiles across all components, characterized by triple-negative phenotype and variable positivity for basal markers.<br><br>CONCLUSIONS: Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non-obligate precursor of a subgroup of high-grade triple-negative and basal-like breast carcinomas.}, }
@article {pmid19915892, year = {2010}, author = {Chang, RK and Chen, AY}, title = {Impact of palivizumab on RSV hospitalizations for children with hemodynamically significant congenital heart disease.}, journal = {Pediatric cardiology}, volume = {31}, number = {1}, pages = {90-95}, pmid = {19915892}, issn = {1432-1971}, mesh = {Antibodies, Monoclonal/economics/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antiviral Agents/economics/*therapeutic use ; Bronchiolitis/epidemiology/*prevention &amp; control/virology ; California/epidemiology ; Case-Control Studies ; Chemoprevention ; Cost-Benefit Analysis ; Drug Costs ; Heart Defects, Congenital/*virology ; Hospitalization/statistics &amp; numerical data ; Humans ; Incidence ; Infant ; Infant, Newborn ; Palivizumab ; Respiratory Syncytial Virus Infections/epidemiology/*prevention &amp; control ; }, abstract = {The objective of this study was to evaluate the impact of palivizumab prophylaxis on respiratory syncytial virus (RSV) hospitalizations among children with hemodynamically significant congenital heart disease (CHD). In 2003, the American Academy of Pediatrics (AAP) revised the bronchiolitis policy statement and recommended the use of palivizumab in children <24 months old with hemodynamically significant CHD (HS-CHD). California statewide hospital discharge data from years 2000-2002 (pre-AAP policy revision) were compared to those from years 2004-2006 (post-AAP policy revision). Hospitalizations due to RSV bronchiolitis for children <2 years of age were identified by IDC-9 CM codes 4661.1, 480.1, and 079.6 as the Principal Diagnosis. Children with CHD and children with HS-CHD were identified by the codiagnoses. The overall RSV hospitalization rate was 71 per 10,000 children <2 years of age. Of all RSV hospitalizations, 3.0% were among children with CHD, and 0.50% among children with HS-CHD. HS-CHD patients accounted for 0.56% of RSV hospitalizations in 2000-2002, compared to 0.46% RSV hospitalizations in 2004-2006. That represents a 19% reduction in RSV hospitalizations among HS-CHD patients after 2003. The 19% decrease in RSV hospitalizations equates to seven fewer hospitalizations (76 hospital days) per year among HS-CHD patients. We conclude that, since the recommendation of palivizumab for children with HS-CHD in 2003, the impact on RSV hospitalizations in California among HS-CHD patients has been limited. Considering the high cost of palivizumab administration, the cost-benefit of RSV prophylaxis with palivizumab warrants further investigation.}, }
@article {pmid19906927, year = {2010}, author = {Kather, A and Raftery, MJ and Devi-Rao, G and Lippmann, J and Giese, T and Sandri-Goldin, RM and Schönrich, G}, title = {Herpes simplex virus type 1 (HSV-1)-induced apoptosis in human dendritic cells as a result of downregulation of cellular FLICE-inhibitory protein and reduced expression of HSV-1 antiapoptotic latency-associated transcript sequences.}, journal = {Journal of virology}, volume = {84}, number = {2}, pages = {1034-1046}, pmid = {19906927}, issn = {1098-5514}, support = {R37 AI021515/AI/NIAID NIH HHS/United States ; }, mesh = {Apoptosis/*physiology ; CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/*metabolism ; Cell Line ; *Dendritic Cells/cytology/physiology/virology ; *Down-Regulation ; Herpesvirus 1, Human/genetics/*pathogenicity/physiology ; Humans ; MicroRNAs/*metabolism ; Virus Latency ; }, abstract = {Herpes simplex virus type 1 (HSV-1) is one of the most frequent and successful human pathogens. It targets immature dendritic cells (iDCs) to interfere with the antiviral immune response. The mechanisms underlying apoptosis of HSV-1-infected iDCs are not fully understood. Previously, we have shown that HSV-1-induced apoptosis of iDCs is associated with downregulation of the cellular FLICE-inhibitory protein (c-FLIP), a potent inhibitor of caspase-8-mediated apoptosis. In this study, we prove that HSV-1 induces degradation of c-FLIP in a proteasome-independent manner. In addition, by using c-FLIP-specific small interfering RNA (siRNA) we show for the first time that downregulation of c-FLIP expression is sufficient to drive uninfected iDCs into apoptosis, underlining the importance of this molecule for iDC survival. Surprisingly, we also observed virus-induced c-FLIP downregulation in epithelial cells and many other cell types that do not undergo apoptosis after HSV-1 infection. Microarray analyses revealed that HSV-1-encoded latency-associated transcript (LAT) sequences, which can substitute for c-FLIP as an inhibitor of caspase-8-mediated apoptosis, are much less abundant in iDCs as compared to epithelial cells. Finally, iDCs infected with an HSV-1 LAT knockout mutant showed increased apoptosis when compared to iDCs infected with the corresponding wild-type HSV-1. Taken together, our results demonstrate that apoptosis of HSV-1-infected iDCs requires both c-FLIP downregulation and diminished expression of viral LAT.}, }
@article {pmid19900584, year = {2010}, author = {Noori, S and Hassan, ZM and Taghikhani, M and Rezaei, B and Habibi, Z}, title = {Dihydroartemisinin can inhibit calmodulin, calmodulin-dependent phosphodiesterase activity and stimulate cellular immune responses.}, journal = {International immunopharmacology}, volume = {10}, number = {2}, pages = {213-217}, doi = {10.1016/j.intimp.2009.11.002}, pmid = {19900584}, issn = {1878-1705}, mesh = {Animals ; Antineoplastic Agents/adverse effects/*pharmacology ; Artemisinins/adverse effects/*pharmacology ; Calmodulin/*antagonists &amp; inhibitors ; Carcinoma, Ductal/*metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 1/*antagonists &amp; inhibitors ; Erythrocytes/immunology ; Female ; Hypersensitivity, Delayed/chemically induced/immunology ; Immunity, Cellular/drug effects ; Mammary Neoplasms, Animal/*metabolism ; Mice ; Mice, Inbred BALB C ; }, abstract = {Calmodulin (CaM) is a ubiquitous, calcium-binding protein that regulates several important aspects of cellular metabolism. A number of enzymes such as phosphodiesterase (PDE-1) are stimulated by CaM. In previous studies, our results showed that artemisinin (ART) is a potent inhibitor of CaM and PDE-1 activity. In this study, the effects of dihydroartemisinin (DHA) that is a semisynthesized agent from the ART on CaM structure were investigated. The result showed that DHA increased fluorescence emission of CaM in higher amounts compared with the ART. Also, the effect of DHA on CaM-dependent PDE-1 activity was studied. Kinetic analysis of the DHA-CaM interaction showed that this agent competitively inhibited the activation of PDE-1 without affecting Vmax. Km values of PDE-1 in the presence of ART and DHA were 10 and 15 microM, respectively; DHA increased Km value in higher amounts compared with the ART. The Ki constants for ART and DHA were 10 microM and 7.3 microM, respectively. As a conclusion, CaM and CaM-dependent PDE-1 were inhibited by DHA more than ART. The data indicated that DHA could stimulate the delayed type hypersensitivity (DTH) against sheep blood cells in Balb/c mice and reduced the tumor growth in vivo against invasive ductal carcinoma in Balb/c mice.}, }
@article {pmid19896695, year = {2010}, author = {Macher-Goeppinger, S and Marme, F and Goeppert, B and Penzel, R and Schirmacher, P and Sinn, HP and Aulmann, S}, title = {Invasive ductal breast cancer within a malignant phyllodes tumor: case report and assessment of clonality.}, journal = {Human pathology}, volume = {41}, number = {2}, pages = {293-296}, doi = {10.1016/j.humpath.2009.08.006}, pmid = {19896695}, issn = {1532-8392}, mesh = {Aged ; Breast Neoplasms/genetics/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Loss of Heterozygosity/genetics ; Neoplasms, Multiple Primary/genetics/*pathology/surgery ; Phyllodes Tumor/genetics/*pathology/surgery ; Polymerase Chain Reaction ; }, abstract = {Invasive carcinomas arising within fibroepithelial tumors represent an uncommon manifestation of breast cancer. We report the case of a 70-year-old woman who underwent mastectomy for a malignant phyllodes tumor measuring 6 cm. Histological workup of the specimen revealed a high-grade invasive ductal carcinoma 2.5 cm in diameter within the phyllodes tumor. DNA was isolated from microdissected epithelial and stromal components of the phyllodes tumor as well as from the invasive ductal carcinoma cells. Using multiplex polymerase chain reaction, a comparative allelotyping was performed with a panel of 11 microsatellite markers. The malignant stroma of the phyllodes tumor showed loss of heterozygosity at chromosome 16q23, 17q12, 17q25, and 22q13; the epithelial tumor component shared the loss of 16q23; whereas the invasive carcinoma had lost divergent alleles at 16q23, 17q12, and 17q25, indicating a lack of clonality between phyllodes tumor and invasive ductal carcinoma. Although our data are compatible with a previously postulated common origin of epithelial and stromal components of phyllodes tumors, the coexisting invasive ductal carcinoma appears to represent a true collision tumor.}, }
@article {pmid19895711, year = {2009}, author = {Sui, W and Ou, M and Chen, J and Wan, Y and Peng, H and Qi, M and Huang, H and Dai, Y}, title = {Comparison of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assessment for Her-2 status in breast cancer.}, journal = {World journal of surgical oncology}, volume = {7}, number = {}, pages = {83}, pmid = {19895711}, issn = {1477-7819}, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism ; China ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2/*genetics ; Humans ; *Immunohistochemistry ; *In Situ Hybridization, Fluorescence ; Predictive Value of Tests ; Prospective Studies ; Receptor, ErbB-2/*metabolism ; Reproducibility of Results ; Tissue Fixation ; }, abstract = {BACKGROUND: The concordance rate between IHC and FISH according to clinical performance is still controversial. We report a prospective study to reflect the concordance between IHC and FISH in Guilin city, People's Republic of China.<br><br>METHODS: Fifty cases of invasive ductal carcinoma of breast tested by IHC and scored as 0, 1+, 2+ and 3+ by pathologists were further analyzed by FISH using a commercially available double-color probe, and the FISH findings were compared with IHC test results.<br><br>RESULTS: A total concordance of 82.0% was observed with a Kappa coefficient of 0.640 (P<0.001). A high discordance was observed in 30.0% of the patients with IHC 2+, 7.1% in IHC 3+, 19.2% overall in IHC 0 and 1+.<br><br>CONCLUSION: The IHC can be used firstly to screen the HER-2 status, and FISH can be used as a supplementary role to IHC and 2+ and some negative cases. And only those cases with Her-2 status of IHC 3+ or FISH positive should be treated with Herceptin.}, }
@article {pmid19893985, year = {2009}, author = {Makdissi, FB and Machado, LV and Oliveira, AG and Benvenuti, TT and Katayama, ML and Brentani, MM and Osório, CA and Mourão Netto, M and Lyra, EC and Carvalho, F and Góes, JC and Folgueira, MA}, title = {Expression of E-cadherin, Snail and Hakai in epithelial cells isolated from the primary tumor and from peritumoral tissue of invasive ductal breast carcinomas.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {42}, number = {12}, pages = {1128-1137}, doi = {10.1590/s0100-879x2009001200002}, pmid = {19893985}, issn = {1414-431X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Epithelial Cells/chemistry ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Snail Family Transcription Factors ; Transcription Factors/genetics/*metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism ; }, abstract = {Epithelial intercellular cohesion, mainly mediated by E-cadherin (CDH1) expression and function, may be deregulated during cancer cell invasion of adjacent tissues and lymphatic and vascular channels. CDH1 expression is down-modulated in invasive lobular breast carcinomas but its regulation in invasive ductal carcinomas (IDC) is less clear. CDH1 expression is repressed by transcription factors such as Snail (SNAI1) and its product is degraded after Hakai ubiquitination. We compared CDH1, SNAI1 and HAKAI mRNA expression in IDC and paired adjacent normal breast tissue and evaluated its relation with node metastasis and circulating tumor cells. Matched tumor/peritumoral and blood samples were collected from 30 patients with early IDC. Epithelial cells from each compartment (tumor/peritumoral) were recovered by an immunomagnetic method and gene expression was determined by real time RT-PCR. There were no differences in CDH1, SNAI1 and HAKAI mRNA expression between tumor and corresponding peritumoral samples and no differential tumoral gene expression according to nodal involvement. Another 30 patients with a long-term follow-up (at least 5 years) and a differential prognosis (good or poor, as defined by breast cancer death) had E-cadherin and Snail protein detected by immunohistochemistry in tumor samples. In this group, E-cadherin-positive expression, but not Snail, may be associated with a better prognosis. This is the first report simultaneously analyzing CDH1, SNAI1 and HAKAI mRNA expression in matched tumor and peritumoral samples from patients with IDC. However, no clear pattern of their expression could distinguish the invasive tumor compartment from its adjacent normal tissue.}, }
@article {pmid19889514, year = {2010}, author = {Christodoulou, MI and Kapsogeorgou, EK and Moutsopoulos, HM}, title = {Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome.}, journal = {Journal of autoimmunity}, volume = {34}, number = {4}, pages = {400-407}, doi = {10.1016/j.jaut.2009.10.004}, pmid = {19889514}, issn = {1095-9157}, mesh = {Adult ; Aged ; Biopsy ; Cell Count ; Cell Movement/*immunology ; Humans ; Immune System/cytology ; Immunohistochemistry ; Leukocytes, Mononuclear ; Middle Aged ; Salivary Glands, Minor/immunology/*pathology ; Sjogren's Syndrome/immunology/*pathology ; Young Adult ; }, abstract = {Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable degree of lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations. Minor salivary gland (MSG) lesions mainly consist of T and B cells, while antigen-presenting cells have been reported in heavy infiltrates. Evidence suggests that the infiltrate composition differs according to lesion severity; however, these differences are not well-defined. To investigate the differential distribution of the major infiltrating mononuclear cell (MNC) types in SS-lesions of variable severity, total-T, CD4(+)-T, CD8(+)-T, Treg, and B cell, macrophage (MPhi), interdigitating (iDC) and follicular dendritic cell (fDC), and natural-killer (NK)-cell incidence (%-total infiltrating MNC) was analyzed in MSG biopsies with mild (n = 11), intermediate (n = 13) or severe (n = 15) lesions. T cells, CD4(+)-T cells and Tregs, B lymphocytes, MPhis and iDCs were significantly different among MSG tissues with mild, intermediate or severe inflammatory lesions, while CD8(+)-T cell, fDC and NK cell incidence was not correlated with lesion severity. T cell, CD4(+)-T cell, T/B cell ratio and iDC incidence was negatively, whereas B cell and MPhi incidence was positively correlated with infiltration grade and biopsy focus score. Tregs predominated in intermediate lesions. Multivariate analysis revealed several associations between the incidence of each infiltrating MNC-type and disease manifestations, implying an involvement of local immune responses in systemic disease features. Our findings support that the distribution of infiltrating MNCs at the SS-lesions varies according to lesion severity and correlates with disease manifestations. The significance of this differential distribution and the underlying aetiopathogenic factors need to be elucidated.}, }
@article {pmid19889214, year = {2009}, author = {Provatopoulou, X and Gounaris, A and Kalogera, E and Zagouri, F and Flessas, I and Goussetis, E and Nonni, A and Papassotiriou, I and Zografos, G}, title = {Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {390}, pmid = {19889214}, issn = {1471-2407}, mesh = {Acute-Phase Proteins/genetics/*metabolism ; Adult ; Aged ; Breast Neoplasms/blood/genetics/*metabolism/pathology ; Carcinoma/blood/genetics/*metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Lipocalin-2 ; Lipocalins/blood/genetics/*metabolism ; Matrix Metalloproteinase 9/blood/genetics/*metabolism ; Middle Aged ; Protein Binding ; Proto-Oncogene Proteins/blood/genetics/*metabolism ; }, abstract = {BACKGROUND: Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.<br><br>METHODS: The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.<br><br>RESULTS: Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.<br><br>CONCLUSION: These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.}, }
@article {pmid19889024, year = {2010}, author = {Tuettenberg, A and Fondel, S and Steinbrink, K and Enk, AH and Jonuleit, H}, title = {CD40 signalling induces IL-10-producing, tolerogenic dendritic cells.}, journal = {Experimental dermatology}, volume = {19}, number = {1}, pages = {44-53}, doi = {10.1111/j.1600-0625.2009.00975.x}, pmid = {19889024}, issn = {1600-0625}, mesh = {Adenoviridae ; Autocrine Communication ; CD4-Positive T-Lymphocytes/immunology ; CD40 Antigens/*metabolism ; CD40 Ligand/genetics/*metabolism ; CD8-Positive T-Lymphocytes/immunology ; Cell Proliferation ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/*immunology/metabolism ; Gene Transfer Techniques ; Genetic Vectors ; Humans ; *Immunomodulation ; Interleukin-10/*metabolism ; Phenotype ; Receptors, Interleukin-10/metabolism ; Signal Transduction ; }, abstract = {Dendritic cells (DC) are potent antigen-presenting cells capable to induce efficient antigen-specific T cell responses in vitro and in vivo. Herein, the maturation process is of great significance, as immature DC (iDC) are known to induce rather regulatory than effector T cell differentiation. This study was designed to characterize the role of the CD40-CD40L pathway for differentiation and function of human DC. Therefore, iDC were stimulated through CD40-CD40L interaction by transduction of DC with adenoviral vectors encoding for CD40L (Ad-CD40L). Resulting DC (CD40L-DC) were analysed concerning their phenotype, cytokine profile and T cell stimulatory capacity. Transduction induced a DC phenotype comparable to stimulation with proinflammatory cytokines as revealed by upregulation of CD83 and the costimulatory molecules CD80 and CD86. Additionally, Ad-CD40L-induced strong production of IL-12p70 not observed in cytokine-matured DC. Surprisingly, the T cell stimulatory capacity was markedly reduced in CD40L-DC. Furthermore, stimulation of CD8(+) T cells by peptide-loaded CD40L-DC resulted in a substantial reduction of antigen-specific IFN-gamma production. This phenomenon is due to an enhanced IL-10 production of CD40L-DC in DC-T cell coculture as well as a stabilization of the IL-10 receptor expression on activated T cells. These data demonstrate that DC stimulated through CD40-CD40L interaction differentiate into tolerogenic DC with immunomodulatory function.}, }
@article {pmid19880290, year = {2010}, author = {Charbonnier, LM and Han, WG and Quentin, J and Huizinga, TW and Zwerina, J and Toes, RE and Jorgensen, C and Louis-Plence, P}, title = {Adoptive transfer of IL-10-secreting CD4+CD49b+ regulatory T cells suppresses ongoing arthritis.}, journal = {Journal of autoimmunity}, volume = {34}, number = {4}, pages = {390-399}, doi = {10.1016/j.jaut.2009.10.003}, pmid = {19880290}, issn = {1095-9157}, mesh = {Adoptive Transfer/*methods ; Animals ; Arthritis/*therapy ; CD4 Antigens ; Cell Movement ; Dendritic Cells/immunology ; Integrin alpha2 ; Interleukin-10/*metabolism ; Lymph Nodes ; Mice ; T-Lymphocytes, Regulatory/immunology/*transplantation ; Treatment Outcome ; }, abstract = {We have previously demonstrated, in the collagen-induced arthritis model (CIA), that repetitive injections of immature bone-marrow-derived dendritic cells (iDCs) induce the expansion of a population of CD4CD49b-expressing cells, and that their adoptive transfer results in protection against CIA in a prophylactic setting. However, the in vivo mechanism responsible for their expansion, as well as their therapeutic potential in established disease remains to be defined. In the present study, we show that expression of the MHC class II molecules on iDCs is required for their expansion thus identifying these cells as MHC class II-restricted T cells. Using adoptive transfer of Thy1.1 positive cells, it is shown that iDC-induced CD4(+)CD49b(+) T cells home to the lymph nodes draining the inflamed tissue. The high immunomodulatory potential of these cells was underscored following their adoptive transfer in a model of contact hypersensitivity. Finally, we assessed and compared the therapeutic potential of iDC-inducible CD4(+)CD49b(+) T cells with that of iDCs in established CIA. Repetitive injections of iDCs in arthritic mice failed to decrease the severity of established disease. In contrast however, a single injection of iDC-induced CD4(+)CD49b(+) T cells reversed clinical symptoms of arthritis and provided long-lasting protection. Together, our data indicate that iDC-induced CD4(+)CD49b(+) T cells are bona fide T regulatory cells with strong immunomodulatory properties that are not only able to prevent disease onset, but also to interfere with an ongoing inflammatory immune response.}, }
@article {pmid19879256, year = {2010}, author = {Sharma, G and Mirza, S and Parshad, R and Srivastava, A and Datta Gupta, S and Pandya, P and Ralhan, R}, title = {CpG hypomethylation of MDR1 gene in tumor and serum of invasive ductal breast carcinoma patients.}, journal = {Clinical biochemistry}, volume = {43}, number = {4-5}, pages = {373-379}, doi = {10.1016/j.clinbiochem.2009.10.009}, pmid = {19879256}, issn = {1873-2933}, mesh = {ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/*genetics/metabolism ; Adult ; Aged ; Breast Neoplasms/*blood/*genetics/pathology ; Carcinoma, Ductal, Breast/*blood/*genetics/pathology ; CpG Islands/*genetics ; DNA Methylation/*genetics ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Polymerase Chain Reaction ; Survival Analysis ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVES: Multidrug resistance 1 (MDR1) gene encodes P-glycoprotein (P-gp), a transmembrane calcium-dependent efflux pump, implicated in drug resistance. In this prospective study, methylation status of MDR1 promoter and its correlation with clinicopathological parameters were evaluated in tumor and serum of breast cancer patients.<br><br>DESIGN AND METHODS: Methylation-specific PCR was carried out to investigate the promoter methylation status of MDR1 in tumor and serum of 100 patients with invasive ductal carcinomas of breast (IDCs). The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.<br><br>RESULTS: MDR1 was hypomethylated in 47% tumors and 44% paired sera of IDC patients and correlated significantly with increased tumor size and advanced tumor stage. Promoter hypomethylation of MDR1 in serum DNA showed 98% specificity and 50% sensitivity.<br><br>CONCLUSIONS: Hypomethylation of MDR1 promoter in IDCs accounted for P-gp overexpression and aggressive biologic behavior in a subset of patients. Detection of these epigenetic changes in circulating DNA may not only enhance insight into the biological behavior of the primary tumor of an individual but may also provide valuable information regarding prognosis that can be readily monitored throughout the disease course.}, }
@article {pmid19877191, year = {2010}, author = {Lott, DG and Dan, O and Lu, L and Strome, M}, title = {Decoy NF-kappaB fortified immature dendritic cells maintain laryngeal allograft integrity and provide enhancement of regulatory T cells.}, journal = {The Laryngoscope}, volume = {120}, number = {1}, pages = {44-52}, doi = {10.1002/lary.20667}, pmid = {19877191}, issn = {1531-4995}, mesh = {Animals ; Dendritic Cells/*immunology ; Immunosuppression Therapy/*methods ; Larynx/*transplantation ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; NF-kappa B/*physiology ; T-Lymphocytes, Regulatory/*immunology ; Transplantation, Homologous ; }, abstract = {OBJECTIVES/HYPOTHESIS: The increased risk of malignancy associated with post-transplant immunosuppression limits the potential of laryngeal transplantation as a reconstructive option. This risk may be mitigated by utilizing decoy nuclear factor kappa B (NF-kappaB) immature dendritic cells (iDC) to provide donor-specific tolerance. The purpose of this study was to explore whether tolerogenic properties of iDC can be applied to composite tissue transplantation.<br><br>STUDY DESIGN: Animal study.<br><br>METHODS: Five iDC-injected mice were euthanized at 15, 30, and 60 days post-laryngeal transplant. Control groups included five transplanted mice without immunosuppression, one iDC-injected mouse euthanized prior to transplantation, one mouse without injection or transplantation, and one mouse administered mature DC to serve as an accelerated rejection control. Larynges were graded for rejection severity according to a grading scale. Draining lymph nodes and spleens were evaluated by flow cytometry to determine immunogenic activity of iDC and T cells locally and peripherally.<br><br>RESULTS: Each time group demonstrated moderate allograft rejection (rejection severity scores: 4.38, 5.10, 5.29). NF-kappaB iDC-treated mice had significantly less rejection at all time points compared to nonimmunosuppressed mice. Flow cytometry showed inhibition of cytotoxic T cell infiltration and expansion of regulatory T cells at the allograft site.<br><br>CONCLUSIONS: iDC immunosuppression maintains laryngeal allograft integrity up to 60 days post-transplantation. Regulatory T cells are enhanced at the allograft site, which serves to suppress immune cell activation and induce self-antigen tolerance. iDC injection may lessen post-transplant comorbidities by decreasing the systemic immune response and favorably affecting concurrent immunosuppressive dose sequencing for laryngeal allograft preservation.}, }
@article {pmid19812188, year = {2009}, author = {Miksa, M and Wu, R and Dong, W and Komura, H and Amin, D and Ji, Y and Wang, Z and Wang, H and Ravikumar, TS and Tracey, KJ and Wang, P}, title = {Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor-factor VIII [corrected].}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {183}, number = {9}, pages = {5983-5990}, pmid = {19812188}, issn = {1550-6606}, support = {R01 AG028352/AG/NIA NIH HHS/United States ; R01 GM062508/GM/NIGMS NIH HHS/United States ; R01 GM057468/GM/NIGMS NIH HHS/United States ; R01 GM053008/GM/NIGMS NIH HHS/United States ; R01 GM053008-15/GM/NIGMS NIH HHS/United States ; R01 GM057468-12/GM/NIGMS NIH HHS/United States ; R01//PHS HHS/United States ; R01 GM062508-07/GM/NIGMS NIH HHS/United States ; R01 AG028352-04/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Antigens, Surface/administration &amp; dosage/*physiology ; Apoptosis Regulatory Proteins/administration &amp; dosage/antagonists &amp; inhibitors/physiology ; Cell Differentiation/*immunology ; Cells, Cultured ; Dendritic Cells/*cytology/*immunology/pathology ; Exosomes/*immunology/*metabolism ; Inflammation Mediators/administration &amp; dosage/antagonists &amp; inhibitors/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Milk Proteins/administration &amp; dosage/antagonists &amp; inhibitors ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/administration &amp; dosage ; Sepsis/immunology/*metabolism/pathology/*therapy ; }, abstract = {Sepsis, a highly lethal systemic inflammatory syndrome, is associated with increases of proinflammatory cytokines (e.g., TNF-alpha, HMGB1) and the accumulation of apoptotic cells that have the potential to be detrimental. Depending on the timing and tissue, prevention of apoptosis in sepsis is beneficial; however, thwarting the development of secondary necrosis through the active removal of apoptotic cells by phagocytosis may offer a novel anti-sepsis therapy. Immature dendritic cells (IDCs) release exosomes that contain milk fat globule EGF factor VIII (MFGE8), a protein required to opsonize apoptotic cells for phagocytosis. In an experimental sepsis model using cecal ligation and puncture, we found that MFGE8 levels decreased in the spleen and blood, which was associated with impaired apoptotic cell clearance. Administration of IDC-derived exosomes promoted phagocytosis of apoptotic cells and significantly reduced mortality. Treatment with recombinant MFGE8 was equally protective, whereas MFGE8-deficient mice suffered from increased mortality. IDC exosomes also attenuated the release of proinflammatory cytokines in septic rats. Liberation of HMGB1, a nuclear protein that contributes to inflammation upon release from unengulfed apoptotic cells, was prevented by MFGE8-mediated phagocytosis in vitro. We conclude that IDC-derived exosomes attenuate the acute systemic inflammatory response in sepsis by enhancing apoptotic cell clearance via MFGE8.}, }
@article {pmid19811434, year = {2009}, author = {Cruz-Robles, D and Chávez-González, JP and Cavazos-Quero, MM and Pérez-Méndez, O and Reyes, PA and Vargas-Alarcón, G}, title = {Association between IL-1B and IL-1RN gene polymorphisms and Chagas' disease development susceptibility.}, journal = {Immunological investigations}, volume = {38}, number = {3-4}, pages = {231-239}, doi = {10.1080/08820130902729637}, pmid = {19811434}, issn = {1532-4311}, mesh = {Cardiomyopathy, Dilated/genetics ; Chagas Cardiomyopathy/*genetics ; Chagas Disease/genetics ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein/*genetics ; Interleukin-1beta/*genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; }, abstract = {Though it is known that the immune system exerts some influence on the resistance against T. cruzi infection its precise role in this process is not well-understood. Some IL-1B alleles and haplotypes have been associated with susceptibility to inflammatory, autoimmune and infectious diseases. The objective of this study was to determine and compare the distribution of IL-1B and IL-1 receptor antagonist (IL-1RN) polymorphisms among T. cruzi seropositive patients, patients with idiopathic dilated cardiomyopathy (IDC) and healthy individuals. We studied 86 individuals seropositive for T. cruzi (58 patients with chronic chagasic cardiomyopathy (CCC) and 28 asymptomatics), 50 seronegative individuals with IDC and 109 healthy individuals. IL-1B-511, IL-1F10.3 IL-1RN.4, IL-1RN 6/1, and IL-1RN 6/2 polymorphisms were analyzed using real-time PCR allelic discrimination technology. Infected patients presented an increased frequency of the CC genotype of the IL-1RN.4 polymorphism when compared to IDC (pC = 0.028; OR = 11.46). The C allele of this polymorphism was found increased in CCC when compared with IDC (pC = 0.036; OR = 0.5) and with controls (pC = 0.035; OR = 1.87). CC genotype of IL-1RN.4 polymorphism was increased in patients with CCC when compared to IDC (pC = 0.0018; OR = 16.74) and healthy individuals (pC = 0.011; OR = 3.6). There is an evident association between the IL1RN.4 polymorphism, T. cruzi infection and CCC development.}, }
@article {pmid19811289, year = {2009}, author = {Fehr, EM and Kierschke, S and Max, R and Gerber, A and Lorenz, HM and Schiller, M}, title = {Apototic cell-derived membrane vesicles induce CD83 expression on human mdDC.}, journal = {Autoimmunity}, volume = {42}, number = {4}, pages = {322-324}, doi = {10.1080/08916930902832173}, pmid = {19811289}, issn = {1607-842X}, mesh = {Antigens, CD/*biosynthesis/immunology ; Apoptosis/*immunology ; Autoantigens/immunology ; Cell Communication/immunology ; Cell Membrane/*immunology ; Cytoplasmic Vesicles/immunology ; Dendritic Cells/*immunology/metabolism ; Humans ; Immunoglobulins/*biosynthesis/immunology ; Membrane Glycoproteins/*biosynthesis/immunology ; Phagocytes/immunology ; }, abstract = {A characteristic of apo cell death is the shedding of membrane vesicles from the dying cell. This process is also referred to as apo membrane blebbing. These apo particles contain various autoantigens and are effectively engulfed by phagocytes. A defective phagocytosis has been described in autoimmune diseases like systemic lupus erythematosus and this defect might lead to an accumulation of apo cells and bodies. Thus, we investigated the interactions between apototic cell-derived membrane vesicles (ACdMV), and myeloid dendritic cell (DC). ACdMV were isolated from the supernatant of apo lymphocytes. These isolated ACdMV were morphologically characterized as membrane coated vesicles of an average size of 500 nm. Coincubating isolated ACdMV with iDC we observed CD83 surface expression of the latter. Accumulation of ACdMV may contribute to an inflammatory immune response in autoimmune diseases.}, }
@article {pmid19806450, year = {2010}, author = {Kim, HS and Yom, CK and Kim, HJ and Lee, JW and Sohn, JH and Kim, JH and Park, YL and Ahn, SH}, title = {Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy.}, journal = {Breast cancer research and treatment}, volume = {121}, number = {3}, pages = {777-788}, doi = {10.1007/s10549-009-0560-5}, pmid = {19806450}, issn = {1573-7217}, mesh = {Adult ; Age Distribution ; Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/*metabolism/pathology/secondary ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; Tamoxifen/*therapeutic use ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed data from 4,683 patients with cancer enrolled in two institutions between 1997 and 2006. We analyzed the correlation between p53 overexpression and relapse, response to adjuvant therapy, breast cancer-specific survival (BCSS), and relapse-free survival (RFS) in patients with primary breast cancer. Overexpression of p53 was noted in 1,091 patients (23.3%). A significant correlation existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, visceral metastasis, and worse BCSS and RFS. Based upon subgroup analyses, combined age (<35, 35-50, and >50 years) and adjuvant therapy (hormone therapy only, chemotherapy only, and hormone therapy following chemotherapy), the greatest reduction of survival based on p53 overexpression was noted in patients 35-50 years of age who received hormone therapy following chemotherapy (P < 0.05). Multivariate analysis showed that p53 overexpression is an independent prognostic factor in patients treated with hormone therapy and chemotherapy (relative risk for BCSS, 2.003; 95% CI, 1.105-3.631; P = 0.022). The p53-overexpressing patients with breast cancer between 35 and 50 years of age who received tamoxifen following chemotherapy had the greatest adverse effect on outcome. Overexpression of p53 is significantly associated with tamoxifen resistance in premenopausal women with breast cancer.}, }
@article {pmid19804500, year = {2010}, author = {Takaki, A and Tatsukawa, M and Iwasaki, Y and Koike, K and Noguchi, Y and Shiraha, H and Sakaguchi, K and Nakayama, E and Yamamoto, K}, title = {Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells.}, journal = {Journal of viral hepatitis}, volume = {17}, number = {8}, pages = {555-562}, pmid = {19804500}, issn = {1365-2893}, mesh = {Adult ; Cell Polarity/immunology ; Cytokines/immunology ; Dendritic Cells/cytology/*immunology ; Flow Cytometry ; Hepacivirus/*immunology ; Hepatitis C, Chronic/*immunology/virology ; Humans ; Lymphocyte Activation/immunology ; Male ; Plasmids/immunology ; Recombinant Proteins/*immunology ; Statistics, Nonparametric ; Th1 Cells/*immunology ; Viral Nonstructural Proteins/*immunology ; }, abstract = {Dendritic cells (DCs) in chronic hepatitis C patients display impaired function, although the details remain unclear. To investigate the hepatitis C virus (HCV) protein that has the most impact on DC function, we compared five recombinant proteins and seven HCV protein genes in modulating DC phenotype and function. Immature DCs (iDCs) were established from healthy donor peripheral blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4. Lipopolysaccharide was used to establish mature DCs (mDCs). Cells were then pulsed with HCV recombinant proteins or transfected with HCV plasmids and subsequently assayed for cell surface marker expression by flow cytometry. For cytokine and proliferative T-cell response analysis, DCs were cultured with autologous CD4 T cells and tuberculin purified protein derivative (PPD). Mean fluorescent intensity of CD86 was reduced in HCV protein-pulsed iDCs. Proliferative T-cell responses and Th1 cytokine concentrations were reduced with HCV nonstructural proteins (NS), particularly with HCV NS4. HCV nonstructural proteins, particularly NS4, change the iDC phenotype and reduce antigen-specific T-cell stimulatory function with Th1 cytokine reductions.}, }
@article {pmid19802703, year = {2009}, author = {Csankovszki, G and Petty, EL and Collette, KS}, title = {The worm solution: a chromosome-full of condensin helps gene expression go down.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {17}, number = {5}, pages = {621-635}, pmid = {19802703}, issn = {1573-6849}, support = {R01 GM079533/GM/NIGMS NIH HHS/United States ; R01 GM079533-02/GM/NIGMS NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; T32 GM07544/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/*genetics ; Animals ; Caenorhabditis elegans/*genetics ; DNA-Binding Proteins/*genetics ; Dosage Compensation, Genetic ; Female ; *Gene Expression Regulation ; Male ; Multiprotein Complexes/*genetics ; *X Chromosome ; }, abstract = {Dosage compensation in the nematode Caenorhabditis elegans is achieved by the binding of a condensin-like dosage compensation complex (DCC) to both X chromosomes in hermaphrodites to downregulate gene expression two-fold. Condensin I(DC), a sub-part of the DCC, differs from the mitotic condensin I complex by a single subunit, strengthening the connection between dosage compensation and mitotic chromosome condensation. The DCC is targeted to X chromosomes by initial binding to a number of recruiting elements, followed by dispersal or spreading to secondary sites. While the complex is greatly enriched on the X chromosomes, many sites on autosomes also bind the complex. DCC binding does not correlate with DCC-mediated repression, suggesting that the complex acts in a chromosome-wide manner, rather than on a gene-by-gene basis. Worm dosage compensation represents an excellent model system to study how condensin-mediated changes in higher order chromatin organization affect gene expression.}, }
@article {pmid19801514, year = {2009}, author = {Turner, MS and Kane, LP and Morel, PA}, title = {Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {183}, number = {8}, pages = {4895-4903}, pmid = {19801514}, issn = {1550-6606}, support = {R01 GM080398-02/GM/NIGMS NIH HHS/United States ; T32 CA082084-10/CA/NCI NIH HHS/United States ; 5T32CA82084-10/CA/NCI NIH HHS/United States ; R01 GM080398-03/GM/NIGMS NIH HHS/United States ; R01 GM080398/GM/NIGMS NIH HHS/United States ; T32 CA082084/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies/immunology ; Antigens/*immunology ; CD28 Antigens/drug effects/immunology/metabolism ; CD3 Complex/drug effects/immunology/metabolism ; CD4-Positive T-Lymphocytes/*immunology/metabolism ; Carrier Proteins/immunology/metabolism ; Coculture Techniques ; Cytokines/biosynthesis/immunology ; Dendritic Cells/*immunology/metabolism ; Diabetes Mellitus, Type 1/*immunology ; Dose-Response Relationship, Immunologic ; Forkhead Transcription Factors/immunology ; Interleukin-6/genetics/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Oncogene Protein v-akt/immunology/metabolism ; Ovalbumin/immunology ; Peptides/immunology ; Phosphotransferases (Alcohol Group Acceptor)/immunology/metabolism ; Receptors, Antigen, T-Cell/immunology/metabolism ; Signal Transduction/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; TOR Serine-Threonine Kinases ; }, abstract = {The definitions of tolerogenic vs immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allogeneic Ags. However, we have previously reported that mature DC (mDC) prevented the onset of autoimmune diabetes, whereas immature DC (iDC) were therapeutically ineffective. In this study, islet-specific CD4(+) T cells from BDC2.5 TCR-transgenic mice were stimulated in the absence of exogenous cytokine with iDC or mDC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both iDC and mDC presenting low peptide doses induced weak TCR signaling via the Akt/mammalian target of rapamycin (mTOR) pathway, resulting in significant expansion of Foxp3(+) Treg. Furthermore, unpulsed mDC, but not iDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3(neg) Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-transgenic T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with Ag dose and inversely with Treg expansion. Studies with T cells or DC from IL-6(-/-) mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low Ag doses. These studies indicate that the strength of Akt/mTOR signaling, a critical T cell-intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production.}, }
@article {pmid19789948, year = {2013}, author = {Yamashita, M and Ogawa, T and Hanamura, N and Kashikura, Y and Mitsui, T and Zhang, X and Fujii, K and Shiraishi, T}, title = {An uncommon case of T1b breast cancer with diabetic mastopathy in type II diabetes mellitus.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {20}, number = {1}, pages = {92-96}, doi = {10.1007/s12282-009-0172-2}, pmid = {19789948}, issn = {1880-4233}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Calcinosis ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Diabetes Mellitus, Type 2/*complications/drug therapy ; Female ; Fibrocystic Breast Disease/diagnosis/*etiology/pathology ; Humans ; Magnetic Resonance Imaging, Interventional ; Middle Aged ; Radiography ; Ultrasonography, Mammary ; }, abstract = {A 64-year-old postmenopausal female had been treated with insulin therapy for type 2 diabetes mellitus for 18 years, but her diabetes mellitus was not well controlled and she developed retinopathy. Her screening mammography showed abnormal findings, and thus she consulted a hospital. A physical examination showed her mammary glands to be hard on both sides and no palpable mass was observed. Mammography revealed an amorphous calcification in the middle outer portion of the left breast. Ultrasonography showed an irregular hypoechoic mass measuring about 11 mm in size in the upper outer portion of the left breast. Although a core-needle biopsy specimen of the hypoechoic mass showed hyalinizing fibrosis without any evidence of malignancy, a stereotactic guided vacuum-assisted biopsy was performed because magnetic resonance imaging revealed an enhanced area in the region of the amorphous calcification that could not be distinguished from breast cancer. The histological findings indicated noninvasive ductal carcinoma, and therefore a quardrantectomy with a sentinel lymph node biopsy was performed. The pathological diagnosis was invasive ductal carcinoma (0.7 × 0.3 cm) with a predominant intraductal component accompanying diabetic mastopathy. The sentinel lymph nodes demonstrated no metastasis. The surgical margin was positive for carcinoma and the patient later underwent a mastectomy. No malignant cells were observed in the specimen. The patient has so far experienced no recurrence after surgery.}, }
@article {pmid19785482, year = {2009}, author = {Mikulincer, M and Shaver, PR and Sapir-Lavid, Y and Avihou-Kanza, N}, title = {What's inside the minds of securely and insecurely attached people? The secure-base script and its associations with attachment-style dimensions.}, journal = {Journal of personality and social psychology}, volume = {97}, number = {4}, pages = {615-633}, doi = {10.1037/a0015649}, pmid = {19785482}, issn = {0022-3514}, mesh = {Adaptation, Psychological ; Adolescent ; Adult ; Anxiety Disorders/complications/psychology ; Cognition ; Dreams/psychology ; Female ; Humans ; Israel ; Judgment ; Male ; Middle Aged ; *Object Attachment ; Personality Disorders/complications/psychology ; *Social Behavior ; Social Support ; Stress, Psychological/complications/psychology ; Students/psychology ; Task Performance and Analysis ; Young Adult ; }, abstract = {In 8 studies the authors explored the procedural knowledge (secure-base script; H. S. Waters &amp; E. Waters, 2006) associated with secure attachment (i.e., low scores on attachment anxiety and avoidance). The studies assessed the accessibility, richness, and automaticity of the secure-base script and the extent to which it guided the processing of attachment-relevant information. Secure attachment (lower scores on anxiety and avoidance) was associated with greater secure-base "scriptedness" of attachment narratives, greater accessibility of the secure-base script in narratives and dreams about distressing experiences, deeper processing of script-relevant information, and faster and more confident script-relevant judgments. In addition, secure participants' tendency to process secure-base information more deeply was evident even 5 days after being exposed to it and was impervious to the depletion of cognitive resources, indicating automatic processing. The discussion focuses on implications of the findings for understanding the cognitive bases of secure people's affect-regulation strategies and behavior in social relationships.}, }
@article {pmid19783719, year = {2009}, author = {Chang, H and Mohabir, N and Done, S and Hamel, PA}, title = {Loss of ALX4 expression in epithelial cells and adjacent stromal cells in breast cancer.}, journal = {Journal of clinical pathology}, volume = {62}, number = {10}, pages = {908-914}, doi = {10.1136/jcp.2009.067298}, pmid = {19783719}, issn = {1472-4146}, mesh = {Animals ; Breast/cytology/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; DNA-Binding Proteins/*metabolism ; Epithelial Cells/metabolism ; Female ; Homeodomain Proteins/metabolism ; Humans ; Mammary Glands, Animal/cytology/metabolism ; Mice ; Mice, Inbred C57BL ; Neoplasm Proteins/metabolism ; Species Specificity ; Stromal Cells/metabolism ; Tissue Array Analysis/methods ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Loss of the stromally-restricted homeodomain transcription factor, Alx4, causes defective mouse mammary epithelial morphogenesis.<br><br>AIMS: To begin to define the role of ALX4 in the human breast and in breast cancer, the expression pattern of ALX4 in the normal human breast and changes in expression in breast cancer were determined.<br><br>METHODS: Cells expressing ALX4 in the human breast were identified by co-immunofluorescence using alpha-ALX4 antibodies and markers of specific mammary cell types. ALX4 expression in breast cancer was then determined by immunohistochemistry on tumour sections that also harboured regions of normal breast tissue. Using criteria that required ALX4 staining in both stromal and epithelial cells, changes in ALX4 expression in tumours on a tissue microarray were determined.<br><br>RESULTS: ALX4 was expressed in both stromal and luminal epithelial cells in the human breast. Scoring tissue sections of duct carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC) that also harboured regions of normal breast tissue, a loss of ALX4 (p<0.001) in stromal and epithelial cells in breast tumours was observed. Analysis of ALX4 expression in 123 sections on a tissue microarray confirmed a highly significant loss (p<0.001) of ALX4 in breast cancer in the tumours themselves and in adjacent stromal cells.<br><br>CONCLUSIONS: These data show a distinct pattern of expression of ALX4 in the human breast relative to the murine mammary gland. Furthermore, characterisation of ALX4 in breast cancer showed that loss of ALX4 in tumours and the surrounding untransformed stroma is a basic characteristic of DCIS and IDC.}, }
@article {pmid19760610, year = {2009}, author = {Wang, C and Iakovlev, VV and Wong, V and Leung, S and Warren, K and Iakovleva, G and Arneson, NC and Pintilie, M and Miller, N and Youngson, B and McCready, DR and Done, SJ}, title = {Genomic alterations in primary breast cancers compared with their sentinel and more distal lymph node metastases: an aCGH study.}, journal = {Genes, chromosomes &amp; cancer}, volume = {48}, number = {12}, pages = {1091-1101}, doi = {10.1002/gcc.20711}, pmid = {19760610}, issn = {1098-2264}, support = {STP-53912//Canadian Institutes of Health Research/Canada ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/secondary ; Chromosomes, Human, Pair 17/genetics ; *Comparative Genomic Hybridization ; Female ; Genome, Human ; Humans ; Immunoenzyme Techniques ; Lymph Nodes ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Prognosis ; Sentinel Lymph Node Biopsy ; }, abstract = {Metastatic potential of breast cancer may be associated with specific genomic alterations and the earliest metastases are likely to be found in the sentinel lymph nodes (SLN). Using array comparative genomic hybridization (aCGH), we compared the genomes of primary breast invasive duct carcinomas (IDCs), their sentinel and more distal lymph node metastases, and IDCs without nodal metastasis. Thirty-three samples from 22 patients with IDC were subjected to aCGH: 8 IDC samples from patients without lymph node metastasis, 11 IDCs associated with SLN metastases out of which 7 had paired samples of metastases, and 14 samples of lymph node metastases out of which 8 were sentinel-distal pairs from 4 patients. aCGH data were analyzed by correlation of genomic profiles, cluster analysis, segmentation, and peak identification. Quantitative real-time PCR was used for data validation. We observed high genomic similarity between primary tumors and their nodal metastases as well as between metastases to the sentinel and distal lymph nodes. Several recurrent alterations were detected preferentially in IDC associated with SLN metastases compared to IDCs without metastasis. Amplification within the 17q24.1-24.2(59.96-62.76 Mb) region was associated with presence of sentinel or distal lymph node metastases; larger tumor size and higher histological grade. In our samples, there were genomic events associated with metastatic progression, which could be detected in both primary tumors and LN metastases. Gain on 17q24.1-24.2 is a candidate region for further testing as a predictor of nodal metastasis.}, }
@article {pmid19751508, year = {2009}, author = {Prasad, CP and Rath, G and Mathur, S and Bhatnagar, D and Parshad, R and Ralhan, R}, title = {Expression analysis of E-cadherin, Slug and GSK3beta in invasive ductal carcinoma of breast.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {325}, pmid = {19751508}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Glycogen Synthase Kinase 3/*metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Middle Aged ; Signal Transduction ; Snail Family Transcription Factors ; Transcription Factors/*metabolism ; Wnt1 Protein/metabolism ; beta Catenin/metabolism ; }, abstract = {BACKGROUND: Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-beta and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/beta-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast.<br><br>METHODS: In the current study, we analyzed the expression patterns and relationships between the key Wnt/beta-catenin signaling components- E-cadherin, Slug and GSK3beta in IDCs of breast.<br><br>RESULTS: Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3beta expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3beta. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear beta-catenin (p = 0.001), and cytoplasmic beta-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/beta-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3beta nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression.<br><br>CONCLUSION: The present study for the first time provided the clinical evidence in support of Wnt/beta-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3beta with beta-catenin in implementing EMT in these cells.}, }
@article {pmid19749460, year = {2009}, author = {Gupta, S and Joshi, K and Wig, JD and Arora, SK}, title = {High frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in advanced breast tumors associated with aggressiveness of the tumor.}, journal = {Indian journal of cancer}, volume = {46}, number = {4}, pages = {303-310}, doi = {10.4103/0019-509X.55550}, pmid = {19749460}, issn = {1998-4774}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; *Genes, Wilms Tumor ; Humans ; Insulin-Like Growth Factor II/biosynthesis ; Loss of Heterozygosity ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Receptor, IGF Type 1/biosynthesis ; Transforming Growth Factor beta1/biosynthesis ; Vascular Endothelial Growth Factor A/biosynthesis ; }, abstract = {BACKGROUND: The product of Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis and are known to facilitate angiogenesis. In the present study, WT1 allelic integrity was examined by Loss of Heterozygosity (LOH) studies in infiltrating breast carcinoma (n=60), ductal carcinoma in situ (DCIS) (n=10) and benign breast disease (n=5) patients, to determine its possible association with tumor progression.<br><br>METHODS: LOH at the WT1 locus (11p13) as determined by PCR-RFLP for Hinf1 restriction site and was subsequently examined for its association with intratumoral expression of various growth factors i.e. TGF-beta1, IGF-II, IGF-1R and angiogenesis (VEGF and Intratumoral micro-vessel density) in breast carcinoma.<br><br>RESULTS: Six of 22 (27.2%) genetically heterozygous of infiltrating breast carcinoma and 1 of 4 DCIS cases showed loss of one allele at WT1 locus. Histologically, the tumors with LOH at WT1 were Intraductal carcinoma (IDC) and were of grade II and III. There was no correlation in the appearance of LOH at WT1 locus with age, tumor stage, menopausal status, chemotherapy status and lymph node metastasis. The expression of factor IGF-II and its receptor, IGF-1R was significantly higher in carcinoma having LOH at WT1 locus. A positive correlation was observed between the TGF-beta1, VEGF expression and IMD scores in infiltrating carcinoma.<br><br>CONCLUSIONS: The current study indicates that the high frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in high-graded breast tumors is associated with aggressiveness of the tumor.}, }
@article {pmid19745684, year = {2009}, author = {Lahey, T and Shah, R and Gittzus, J and Schwartzman, J and Kirkland, K}, title = {Infectious diseases consultation lowers mortality from Staphylococcus aureus bacteremia.}, journal = {Medicine}, volume = {88}, number = {5}, pages = {263-267}, pmid = {19745684}, issn = {1536-5964}, support = {K08 AI069915/AI/NIAID NIH HHS/United States ; K08 AI069915-04/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteremia/epidemiology/*mortality/prevention &amp; control ; Central Nervous System Diseases/microbiology/mortality ; Endocarditis/microbiology/mortality ; Female ; Hospital Mortality ; Humans ; Lebanon/epidemiology ; Male ; Middle Aged ; Osteomyelitis/microbiology/mortality ; Prevalence ; *Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/epidemiology/*mortality/prevention &amp; control ; Staphylococcus aureus/*isolation &amp; purification ; Survival Analysis ; }, abstract = {Staphylococcus aureus bacteremia (SAB) is a lethal and increasingly common infection in hospitalized patients. We assessed the impact of infectious diseases consultation (IDC) on clinical management and hospital mortality of SAB in 240 hospitalized patients in a retrospective cohort study. Patients who received IDC were older than those who did not (57.9 vs. 51.7 yr; p = 0.05), and were more likely to have a health care-associated infection (63% vs. 45%; p < 0.01). In patients who received IDC, there was a higher prevalence of severe complications of SAB such as central nervous system involvement (5% vs. 0%, p = 0.01), endocarditis (20% vs. 2%; p < 0.01), or osteomyelitis (15.6% vs. 3.4%; p < 0.01). Patients who received IDC had closer blood culture follow-up and better antibiotic selection, and were more likely to have pus or prosthetic material removed. Hospital mortality from SAB was lower in patients who received IDC than in those who did not (13.9% vs. 23.7%; p = 0.05). In multivariate survival analysis, IDC was associated with substantially lower hazard of hospital mortality during SAB (hazard 0.46; p = 0.03). This mortality benefit accrued predominantly in patients with methicillin-resistant SAB (hazard 0.3; p < 0.01), and in patients who did not require ICU admission (hazard 0.15; p = 0.01). In conclusion, IDC is associated with reduced mortality in patients with staphylococcal bacteremia.}, }
@article {pmid19740438, year = {2009}, author = {Bloise, E and Couto, HL and Massai, L and Ciarmela, P and Mencarelli, M and Borges, LE and Muscettola, M and Grasso, G and Amaral, VF and Cassali, GD and Petraglia, F and Reis, FM}, title = {Differential expression of follistatin and FLRG in human breast proliferative disorders.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {320}, pmid = {19740438}, issn = {1471-2407}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Nucleus/genetics/metabolism ; Cytoplasm/genetics/metabolism ; Female ; Follistatin/*genetics/metabolism ; Follistatin-Related Proteins/*genetics/metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Protein Transport ; }, abstract = {BACKGROUND: Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG) bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases.<br><br>METHODS: Paraffin embedded specimens of normal breast (NB - n = 8); florid hyperplasia without atypia (FH - n = 17); fibroadenoma (FIB - n = 17); ductal carcinoma in situ (DCIS - n = 10) and infiltrating ductal carcinoma (IDC - n = 15) were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively.<br><br>RESULTS: Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed.<br><br>CONCLUSION: The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the present findings indicate that an increased FST and FLRG expression in breast proliferative diseases might counteract the anti-proliferative effects of activin in human breast cancer.}, }
@article {pmid19740355, year = {2009}, author = {Kamdar, A and Yahya, A and Thangaraj, L}, title = {Retrospective observational study of the incidence of short-term indwelling urinary catheters in elderly patients with neck of femur fractures.}, journal = {Geriatrics &amp; gerontology international}, volume = {9}, number = {2}, pages = {131-134}, doi = {10.1111/j.1447-0594.2008.00490.x}, pmid = {19740355}, issn = {1447-0594}, mesh = {Aged ; Aged, 80 and over ; Catheters, Indwelling/adverse effects/*statistics &amp; numerical data ; Device Removal/adverse effects ; England/epidemiology ; Female ; Femoral Fractures/complications/*epidemiology ; Hospitals/statistics &amp; numerical data ; Humans ; Incidence ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Urinary Catheterization/adverse effects/*statistics &amp; numerical data ; Urinary Incontinence/complications/*epidemiology ; Urinary Retention/complications/*epidemiology ; }, abstract = {BACKGROUND: 15-25% of general hospital admissions tend to involve patients that have had a short-term indwelling urinary catheter (IDC) inserted some time during their stay. There is little data on the specific incidence and complications of short-term urinary catheterization in elderly patients with neck of femur fractures.<br><br>METHODS: Data was collected from the notes of 50 patients at Hemel Hempstead General Hospital with neck of femur fractures retrospectively from 31 August 2007. Specific information on patient demographics, premorbid status, record and reason for urethral catheterization, place of insertion, gentamicin cover pre- and post-removal of IDC, residual volumes, duration of catheter insertion, catheter clamping prior to removal of IDC, urinary tract infection with IDC, post-IDC removal newly incontinent/in retention were collated from patient notes. Patients with prior chronic catheterization were excluded from the study.<br><br>RESULTS: 78% of the patients had an IDC insertion (95% confidence interval, 64-88.4%). Most of the catheters were inserted on the ward (75%) with the rest being inserted mostly in theatre and recovery. Only approximately one-third of the sample that had IDC inserted had residual volume documented in the notes. Of these patients, the majority had residual volume above 300 mL. The main reasons for IDC insertion were urinary retention (50%), incontinence (30.8%) and fluid monitoring (11.5%). Of the patients, 31.4% had documented urinary tract infection as a result of IDC insertion.<br><br>CONCLUSION: This study revealed a higher incidence of short-term IDC insertion (approximately 75%) in elderly patients with neck of femur fractures in comparison to general hospital admissions of 15-25%. There is a role for more effective documentation in patient notes on the reasons behind urinary IDC insertion and increased clinical vigilance in preventing unnecessary catheterizations.}, }
@article {pmid19729831, year = {2009}, author = {Yoon, NK and Seligson, DB and Chia, D and Elshimali, Y and Sulur, G and Li, A and Horvath, S and Maresh, E and Mah, V and Bose, S and Bonavida, B and Goodglick, L}, title = {Higher expression levels of 14-3-3sigma in ductal carcinoma in situ of the breast predict poorer outcome.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {5}, number = {4}, pages = {215-224}, pmid = {19729831}, issn = {1875-8592}, support = {CA-86366/CA/NCI NIH HHS/United States ; U24 CA086366/CA/NCI NIH HHS/United States ; U24 CA086366-06/CA/NCI NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; P30 CA016042-29/CA/NCI NIH HHS/United States ; 2 P30 CA16042-29/CA/NCI NIH HHS/United States ; }, mesh = {14-3-3 Proteins ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Exonucleases/*biosynthesis/genetics ; Exoribonucleases ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/*biosynthesis/genetics ; Prognosis ; Survival Analysis ; }, abstract = {The protein 14-3-3sigma is involved in the regulation of cellular processes such as apoptosis, cell cycle progression and proliferation. Disruption of protein expression has been implicated in a number of malignancies. Here we examine the expression pattern of 14-3-3sigma in breast cancer and specifically consider whether expression in ductal carcinoma in situ (DCIS) lesions is predictive of disease outcome. We examined 14-3-3sigma protein expression and localization using immunohistochemical staining on a high-density tissue microarray consisting of 157 invasive breast cancer patients. Statistical analyses were used to assess the correlation of 14-3-3sigma expression with clinico-pathological parameters and patient outcome. We observed a statistically significant increase in 14-3-3sigma protein expression in ductal hyperplasia, DCIS, and invasive ductal carcinoma (IDC) as compared normal glandular epithelium. In IDC, lower expression of 14-3-3sigma tended to predicted poorer survival time while in DCIS lesions, there was a stronger correlation between relatively higher levels of 14-3-3sigma predicting shorter survival time. Further, of patients who had concurrent DCIS and IDC lesions, those that exhibited a decrease of 14-3-3sigma expression from DCIS to IDC had significantly shorter survival time. Our findings indicate that 14-3-3sigma expression may be a useful prognostic indicator for survival in patients with breast cancer with an elevated 14-3-3sigma in earlier disease predicting a less favorable disease outcome. To our knowledge this is the first published study associating 14-3-3sigma protein expression with breast cancer survival.}, }
@article {pmid19722158, year = {2009}, author = {Safwat, MD and Habib, F and Elayat, A and Oweiss, N and Reffat, S and Algaidi, S}, title = {Morphometric and immunohistochemical study of angiogenic marker expressions in invasive ductal carcinoma of human breast.}, journal = {Folia morphologica}, volume = {68}, number = {3}, pages = {144-155}, pmid = {19722158}, issn = {0015-5659}, mesh = {Adult ; Antigens, CD/analysis/metabolism ; Antigens, CD34/analysis/metabolism ; Biomarkers, Tumor/analysis/*metabolism ; Blood Vessels/metabolism/pathology ; Breast Neoplasms/*blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/*blood supply/*metabolism/pathology ; Disease Progression ; Endoglin ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic/*metabolism/pathology/physiopathology ; Predictive Value of Tests ; Receptors, Cell Surface/analysis/metabolism ; Sensitivity and Specificity ; Vascular Endothelial Growth Factor A/analysis/metabolism ; }, abstract = {Breast cancer is the leading cause of cancer deaths among women. Results from experimental studies suggest that tumour progression and metastasis in breast cancer are angiogenesis dependant. The College of American Pathologists has stated that further study of quantification of tumour angiogenesis is still required to demonstrate its prognostic value in breast cancer. In this study, not only the microvascular density (MVD), but also the vascular area ratio (VAR), and the vascular count in different grades of invasive ductal breast carcinoma were assessed using a pan-endothelial marker, CD34, and monoclonal antibody to CD105, by employing computer assisted morphometric measurements. In addition, quantitative expression of vascular endothelial growth factor (VEGF) was detected. Correlation of the vascular parameters and VEGF expression with the different grades of invasive ductal breast carcinoma was clarified. Immunohistochemical staining for the CD105, CD34, and VEGF antibodies were performed in 25 patients with invasive ductal carcinoma in King Fahd Hospital, Saudi Arabia. Normal breast tissue samples comprised 15 specimens detected at the safety margin of the malignant breast cases were collected. Positive CD34 stained blood-vessel endothelial cells were observed in all normal breast tissues. In contrast, CD105 and VEGF expression were not expressed in the normal breast ducts and lobules. Widespread staining for CD34, to a lesser extent CD105, and VEGF expression were seen in all tumour specimens with different grades. Significant differences in the vascular parameters, stained with antiCD34, were observed between normal breast tissues and invasive ductal carcinoma. In addition, the vascular parameters stained with antiCD34 and antiCD105, and the percentage of VEGF expression in the three grades of invasive ductal carcinomas showed significant differences with positive correlations. In conclusion, MVD as well as VAR are considered to reflect the final result of the tumour angiogenesis cascade. In addition, VEGF expression was found to be a useful angiogenic marker. However, few cases were VEGF negatively stained. Thus, the expression of MVD, VAR, and to a lesser extent VEGF might be reference predictors for the biological behaviour and prognosis of breast carcinoma.}, }
@article {pmid19719774, year = {2009}, author = {Hasebe, T and Okada, N and Tamura, N and Houjoh, T and Akashi-Tanaka, S and Tsuda, H and Shibata, T and Sasajima, Y and Iwasaki, M and Kinoshita, T}, title = {p53 expression in tumor stromal fibroblasts is associated with the outcome of patients with invasive ductal carcinoma of the breast.}, journal = {Cancer science}, volume = {100}, number = {11}, pages = {2101-2108}, doi = {10.1111/j.1349-7006.2009.01307.x}, pmid = {19719774}, issn = {1349-7006}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/genetics/*pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/*pathology ; Female ; Fibroblasts/chemistry ; Genes, p53 ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Staging ; Stromal Cells/chemistry ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {The purpose of this study was to determine whether p53 protein expression in tumor stromal fibroblasts assessed immunohistochemically by the Allred score system is significantly associated with nodal metastasis by invasive ductal carcinoma (IDC), and significantly associated with the outcome of 1042 IDC patients according to adjuvant therapy status, UICC pTNM stage, and triple-negative IDC status, in multivariate analyses with well-known clinicopathological factors. The Allred scores for p53 expression in tumor stromal fibroblasts were significantly associated with the number of nodal metastases, and Allred scores of 4-8 for p53 in tumor stromal fibroblasts significantly increased the hazard rate for distant organ metastasis or for tumor death in the triple-negative IDC patients, and the UICC pTNM stage I, II, and III patients. The results indicated that p53 protein expression in tumor stromal fibroblasts is closely associated with the number of nodal metastases and the outcome of IDC patients.}, }
@article {pmid21475903, year = {2009}, author = {Portela De Melo, M and Bittelbrunn, AC and Menke, CH and De Mendonça Uchoa, D and Grazziotin Rossato, L and Lucena Kortmann, G and Leistner-Segal, S}, title = {Analysis of the R72P polymorphism of the TP53 gene in patients with invasive ductal breast carcinoma.}, journal = {Molecular medicine reports}, volume = {2}, number = {5}, pages = {793-797}, doi = {10.3892/mmr_00000174}, pmid = {21475903}, issn = {1791-3004}, abstract = {Breast cancer is the most common neoplasia as well as the main cause of cancer-related death among women, experiencing a 0.5% increase in incidence per year. The disease results from a series of mutations in the DNA development and repair genes. Approximately 50% of human carcinomas present mutations in the TP53 gene. Polymorphisms of TP53 include codon 72 containing either arginine (CGC) or proline (CCC). Such polymorphisms may be involved in the susceptibility and predisposition to cancer, presenting a widely variable ethnic and geographic distribution. The arginine homozygous genotype seems to be a significant risk factor for breast cancer. The purpose of this study was to determine the frequency of the R72P polymorphism of the TP53 gene in patients with invasive ductal breast cancer from southern Brazil, where this type of cancer has a high incidence, as well as its association with breast carcinoma and clinicopathological characteristics. Seventy-six patients suffering from invasive ductal breast cancer and 80 controls were analyzed, and samples were evaluated by PCR followed by restriction enzyme digestion. No statistical differences in terms of the genotype frequency (P=0.707) or the arginine and proline allele frequencies (P=0.469) involving codon 72 were found in patients compared to controls. Thus, statistical analysis did not suggest any association between the R72P polymorphism of the TP53 gene and invasive ductal carcinoma in the population studied. Additionally, no significant association with the clinicopathological characteristics presented by the breast carcinoma patients was found.}, }
@article {pmid19700666, year = {2009}, author = {Anand, AR and Prasad, A and Bradley, RR and Deol, YS and Nagaraja, T and Ren, X and Terwilliger, EF and Ganju, RK}, title = {HIV-1 gp120-induced migration of dendritic cells is regulated by a novel kinase cascade involving Pyk2, p38 MAP kinase, and LSP1.}, journal = {Blood}, volume = {114}, number = {17}, pages = {3588-3600}, pmid = {19700666}, issn = {1528-0020}, support = {R01 HL087576/HL/NHLBI NIH HHS/United States ; HL087576/HL/NHLBI NIH HHS/United States ; }, mesh = {Blotting, Western ; *Cell Movement ; Chemotaxis ; Dendritic Cells/*metabolism ; Flow Cytometry ; Focal Adhesion Kinase 2/antagonists &amp; inhibitors/genetics/*metabolism ; HIV Envelope Protein gp120/genetics/*metabolism ; Humans ; Microfilament Proteins/antagonists &amp; inhibitors/genetics/*metabolism ; Phosphorylation/drug effects ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering/pharmacology ; Receptors, CCR5/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tyrphostins/pharmacology ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism ; }, abstract = {Targeting dendritic cell (DC) functions such as migration is a pivotal mechanism used by HIV-1 to disseminate within the host. The HIV-1 envelope protein is the most important of the virally encoded proteins that exploits the migratory capacity of DCs. In the present study, we elucidated the signaling machinery involved in migration of immature DCs (iDCs) in response to HIV-1 envelope protein. We observed that M-tropic HIV-1 glycoprotein 120 (gp120) induces phosphorylation of the nonreceptor tyrosine kinase, Pyk2. Inhibition of Pyk2 activity using a pharmacologic inhibitor, kinase-inactive Pyk2 mutant, and Pyk2-specific small interfering RNA blocked gp120-induced chemotaxis, confirming the role of Pyk2 in iDC migration. In addition, we also illustrated the importance of Pyk2 in iDC migration induced by virion-associated envelope protein, using aldithriol-2-inactivated M-tropic HIV-1 virus. Further analysis of the downstream signaling mechanisms involved in gp120-induced migration revealed that Pyk2 activates p38 mitogen-activated protein kinase, which in turn activates the F-actin-binding protein, leukocyte-specific protein 1, and enhances its association with actin. Taken together, our studies provide an insight into a novel gp120-mediated pathway that regulates DC chemotaxis and contributes to the dissemination of HIV-1 within an infected person.}, }
@article {pmid19699526, year = {2009}, author = {van Stijn, CM and van den Broek, M and van de Weerd, R and Visser, M and Taşdelen, I and Tefsen, B and van Die, I}, title = {Regulation of expression and secretion of galectin-3 in human monocyte-derived dendritic cells.}, journal = {Molecular immunology}, volume = {46}, number = {16}, pages = {3292-3299}, doi = {10.1016/j.molimm.2009.07.026}, pmid = {19699526}, issn = {1872-9142}, mesh = {Animals ; Apoptosis/drug effects/physiology ; Cell Differentiation/drug effects/*physiology ; Cells, Cultured ; Dendritic Cells/cytology/immunology/*metabolism ; Galectin 3/*biosynthesis/immunology ; Gene Expression Regulation/drug effects/*physiology ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology/metabolism/pharmacology ; Humans ; Interleukin-4/immunology/metabolism/pharmacology ; Monocytes/cytology/immunology/*metabolism ; Phosphatidylserines/genetics/immunology/metabolism ; RNA, Messenger/biosynthesis/immunology ; Schistosoma mansoni/immunology ; Schistosomiasis mansoni/immunology/metabolism ; Th2 Cells/immunology/metabolism ; }, abstract = {Galectin-3 (Gal-3) is a beta-galactoside binding lectin displaying both intracellular and extracellular immune functions. In Schistosoma mansoni infection, Gal-3 has been associated with the induction of a T helper 2 response. Whereas dendritic cells (DCs) play a pivotal role in the regulation of T cell differentiation, little is known about the regulation of Gal-3 expression in DCs. In this study we determined Gal-3 mRNA and protein levels during in vitro differentiation of human monocytes into immature DCs (iDCs), by culturing monocytes in the presence of interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Gal-3 mRNA levels show a moderate, transient increase during iDC generation, accompanied by elevated cell-associated Gal-3 protein. Our data show that culturing monocytes with IL-4 alone strongly increases Gal-3 mRNA levels, whereas GM-CSF induces a low increase in Gal-3 mRNA. The combined data indicate that GM-CSF reduces IL-4 induced Gal-3 mRNA levels during the generation of iDC. Remarkably, stimulation of monocytes with GM-CSF results in secretion of significant amounts of Gal-3 in the medium, whereas iDCs do not release detectable amounts of Gal-3, indicating a suppressive role of IL-4 on GM-CSF induced Gal-3 secretion. Finally, our data demonstrate that all differentiated cell types tested show a significantly lower capacity to bind Gal-3 on the cell surface than monocytes. In conclusion, Gal-3 expression in iDCs is restricted, and Gal-3 protein is localized mainly intracellular, due to the opposite actions of IL-4 and GM-CSF. By these properties, the DCs may be protected against Gal-3 induced phosphatidylserine (PS) exposure and/or apoptosis.}, }
@article {pmid19664142, year = {2009}, author = {Sidhu, M and Griffiths, MM and Bradley, DS}, title = {Vaccination with collagen-pulsed dendritic cells prevents the onset and reduces the disease severity in the mouse model of spontaneous polychondritis.}, journal = {Clinical and experimental immunology}, volume = {157}, number = {3}, pages = {350-358}, pmid = {19664142}, issn = {1365-2249}, support = {R01 AR030752/AR/NIAMS NIH HHS/United States ; R56 AR030752/AR/NIAMS NIH HHS/United States ; AR30752/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Collagen/pharmacology ; Cytokines/analysis/blood ; Dendritic Cells/drug effects/immunology/*transplantation ; HLA Antigens/genetics ; HLA-DQ Antigens/genetics ; Humans ; Immunoglobulin G/blood ; Immunohistochemistry ; Male ; Mice ; Mice, Transgenic ; Models, Animal ; Polychondritis, Relapsing/genetics/immunology/*therapy ; Treatment Outcome ; Vaccination ; }, abstract = {Immature dendritic cells (iDCs) have a tolerogenic potential due to low expression of important co-stimulatory cell surface molecules required for antigen presentation and induction of an effective immune response. We report here that injection of iDCs pulsed with chick type II collagen (CII) delayed the onset significantly and suppressed the severity of spontaneous polychondritis (SP) in the human leucocyte antigen (HLA)-DQ6alphabeta8alphabeta transgenic mouse model. Bone marrow-derived iDCs were pulsed in vitro with CII and transferred into 6-week-old HLA-DQ6alphabeta8alphabeta transgenic mice. Mice receiving CII-pulsed iDCs did not display any clinical signs of disease until 5.5 months of age, indicating the ability of the DC vaccine to delay significantly the onset of SP. Control groups receiving unpulsed iDCs or phosphate-buffered saline (PBS) developed polyarthritis at 3.5 months, as we have reported previously. The severity and incidence of disease was reduced in mice injected with CII-pulsed iDCs. Proinflammatory cytokines were in low to undetectable levels in the serum and tissue in the CII-pulsed iDC mice, correlating with the protection. This is the first evidence of iDC therapy controlling SP and suggests that iDC vaccination may provide a tool to reducing clinical manifestations in human inflammatory autoimmune disease such as relapsing polychondritis and rheumatoid arthritis.}, }
@article {pmid19663185, year = {2009}, author = {Lisitsyna, TA and Vel'tishchev, DIu and Seravina, OF and Kovalevskaia, OB and Marchenko, AS and Novikova, DS and Novikov, AA and Aleksandrova, EN and Nasonov, EL}, title = {[Prevalence of mental disorders in SLE patients: correlations with the disease activity and comorbid chronic conditions].}, journal = {Terapevticheskii arkhiv}, volume = {81}, number = {6}, pages = {10-16}, pmid = {19663185}, issn = {0040-3660}, mesh = {Adult ; Antiphospholipid Syndrome/complications/drug therapy ; C-Reactive Protein/analysis ; Cytokines/blood ; Female ; Glucocorticoids/administration &amp; dosage/*therapeutic use ; Heart Diseases/complications/diagnosis/drug therapy ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Lupus Erythematosus, Systemic/*complications/diagnosis/drug therapy ; Male ; Mental Disorders/diagnosis/*epidemiology ; Middle Aged ; Prevalence ; Russia/epidemiology ; Young Adult ; }, abstract = {AIM: To study effects of the disease activity and comorbid chronic conditions on the incidence of mental disorders in patients with systemic lupus erythematosus (SLE) treated in the State Institute of Rheumatology, RAMS.<br><br>MATERIAL AND METHODS: A total of 115 patients with documented SLE (age 24-45 years, median 34 years, SLE duration 4-17, median 8 years) participated in the study. SLE activity was evaluated by SLEDAI scale, atherosclerosis--by ultrasonic arterial dopplerography, mental disorders--by psychological and psychic scales according to IDC-10.<br><br>RESULTS: Mental disorders were detected in 76 of 115 (66%) patients: anxiety and depression (83%), depression episodes (40%), maladaptation (24%), generalized anxiety (10%), dysthymia (9%). Manifest cognitive disorders were seen in 7% of examinees. SLE patients with and without mental disorders did not differ by age, gender, SLE duration and activity, cumulative doses of glucocorticoids and cytotoxic drugs, but differed by diagnosed atherosclerosis (23 and 8%, respectively). All SLE patients with the history of myocardial infarction had mental disorders. SLE patients with antiphospholipid syndrome had mental disorders in 85%, while controls--in 49%.<br><br>CONCLUSION: Mental disorders are found frequently in SLE patients (66%). 83% of these disorders are anxiodepressive. Incidence of mental disorders in SLE patients do not correlate with age, gender, SLE duration and activity, doses of glucocorticoids and cytotoxic drugs, but correlate with comorbid diseases (atherosclerosis, myocardial infarction, acute cerebral attacks, antiphospholipid syndrome and Sjogren's syndrome.}, }
@article {pmid19662489, year = {2011}, author = {Scally, N and Campbell, W and Hall, S and McCusker, G and Stirling, WJ}, title = {Invasive ductal carcinoma arising within a breast hamartoma.}, journal = {Irish journal of medical science}, volume = {180}, number = {3}, pages = {767-768}, pmid = {19662489}, issn = {1863-4362}, mesh = {Aged ; Biopsy, Needle ; Breast Diseases/diagnostic imaging/*pathology ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Hamartoma/diagnostic imaging/*pathology ; Humans ; Lymph Nodes/pathology ; Mammography ; }, abstract = {INTRODUCTION: Malignant transformation within hamartoma of the breast is uncommon. Invasive ductal or lobular carcinoma of the breast with this aetiology has been noted rarely in the literature.<br><br>CONCLUSION: We discuss the diagnosis, radiology and pathology of a 79-year-old lady with an invasive ductal carcinoma arising within a breast hamartoma.}, }
@article {pmid19657752, year = {2010}, author = {Liu, C and Zhang, H and Shuang, C and Lu, Y and Jin, F and Xu, H and Lu, P}, title = {Alterations of ER, PR, HER-2/neu, and P53 protein expression in ductal breast carcinomas and clinical implications.}, journal = {Medical oncology (Northwood, London, England)}, volume = {27}, number = {3}, pages = {747-752}, pmid = {19657752}, issn = {1559-131X}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Transformation, Neoplastic/genetics ; Disease Progression ; *Estrogens ; Female ; *Gene Expression Regulation, Neoplastic ; Genes, erbB-2 ; Genes, p53 ; Humans ; Middle Aged ; Neoplasm Proteins/*biosynthesis/genetics ; Neoplasms, Hormone-Dependent/*metabolism/pathology ; *Progesterone ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/*biosynthesis/genetics ; Receptors, Progesterone/*biosynthesis/genetics ; Tumor Suppressor Protein p53/*biosynthesis ; }, abstract = {The aim of the study is to investigate the alterations in expression of estrogen receptor alpha (ER), progesterone receptor (PgR), c-erbB2 gene (HER-2/neu), and P53 protein in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDC), and the association between their expression and clinicopathologic findings. The mastectomy specimens of 520 cases containing both DCIS and IDC were examined. The expression of ER, PgR, HER-2/neu, and P53 proteins were examined by immunohistochemistry. Linear regression was used to investigate the correlation among ER, PgR, HER-2/neu, P53 protein expression, and the clinicopathologic factors. There was a significant decrease of ER and PgR expression in IDC compared to DCIS (32.81 vs. 21.05%, chi(2) = 4.45, P = 0.035; 26.56 vs. 15.57%, chi(2) = 4.82, P = 0.028, respectively). In contrast, there was a significant increase of HER-2/neu expression in IDC compared to DCIS (10.94 vs. 21.27%, chi(2) = 3.88, P = 0.049). However, there was no significant difference in expression of p53 between DCIS and IDC. In both DCIS and IDC, a significant positive correlation was observed between ER and PgR receptor expression (r = 0.67, P = 0.00; r = 0.56, P = 0.00, respectively). In conclusion, these findings substantiate the notion that breast cancer progression is often associated with alterations in expressions of ER, PgR, and HER-2/neu. The underlying mechanisms of these alterations need further investigation.}, }
@article {pmid19653048, year = {2009}, author = {Ikenaga, N and Ohuchida, K and Mizumoto, K and Yu, J and Fujita, H and Nakata, K and Ueda, J and Sato, N and Nagai, E and Tanaka, M}, title = {S100A4 mRNA is a diagnostic and prognostic marker in pancreatic carcinoma.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {13}, number = {10}, pages = {1852-1858}, pmid = {19653048}, issn = {1873-4626}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Carcinoma, Pancreatic Ductal/*diagnosis/*genetics ; Female ; Gene Expression ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/*diagnosis/*genetics ; Prognosis ; RNA, Messenger ; S100 Calcium-Binding Protein A4 ; S100 Proteins/*genetics ; Survival Analysis ; }, abstract = {OBJECTIVE: The aim of this study is to evaluate the clinical significance of S100A4 mRNA expression in pancreatic cancer.<br><br>MATERIALS AND METHODS: We obtained invasive ductal carcinoma (IDC) cells from ten lesions, intraductal papillary mucinous neoplasm (IPMN) cells from 20 lesions, and normal ductal cells from 20 normal pancreatic tissues by laser microdissection of frozen tissues. S100A4 expression was examined in the microdissected cells and in formalin-fixed paraffin-embedded (FFPE) samples of 87 pancreatic cancers by quantitative reverse transcription-polymerase chain reaction.<br><br>RESULTS: IDC cells expressed higher levels of S100A4 than IPMN cells (P = 0.002) and normal ductal cells (P < 0.001), although the difference between IPMN cells and normal ductal cells was not statistically significant (P = 0.070). Analysis of FFPE samples revealed that high S100A4 expression was significantly associated with a shorter overall survival (P = 0.023). In immunohistochemical analysis, the extent of S100A4 mRNA expression was significantly correlated with the expression of S100A4 protein (P = 0.028).<br><br>CONCLUSION: S100A4 could be a marker for malignancy in pancreatic tumors and for poor prognosis in patients with pancreatic cancer.}, }
@article {pmid19652229, year = {2009}, author = {Wong, CS and Chu, YC and Wong, KW and Yeung, TH and Ma, KF}, title = {Is ultrasonography-guided modified coaxial core biopsy of the breast a better technique?.}, journal = {Hong Kong medical journal = Xianggang yi xue za zhi}, volume = {15}, number = {4}, pages = {246-248}, pmid = {19652229}, issn = {1024-2708}, mesh = {Adult ; Aged ; Biopsy, Needle/*methods ; Breast/*pathology ; Breast Neoplasms/diagnostic imaging/*pathology ; Female ; Hong Kong ; Humans ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Risk Factors ; Ultrasonography, Interventional ; Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: To compare the diagnostic rate, patient comfort, and complications of ultrasonography-guided breast biopsy using a modified coaxial technique with ultrasonography-guided fine needle aspiration and traditional core biopsy. A secondary objective was to describe the use of the coaxial technique for the biopsy of breast lesions and our initial experience.<br><br>DESIGN: Retrospective study.<br><br>SETTING: A regional hospital in Hong Kong.<br><br>PATIENTS: Patients, who were referred for ultrasonography-guided fine needle aspiration or biopsy from 23 November 2007 to 19 March 2008, were divided into three groups. For breast lesions of 8 mm or smaller, fine needle aspirations were performed. For breast lesions larger than 8 mm, the patients were randomly divided into groups receiving traditional core biopsies and coaxial biopsies. The pathological reports were reviewed.<br><br>MAIN OUTCOME MEASURES: Diagnostic rate, patient comfort assessed in terms of pain, and any procedural complications.<br><br>RESULTS: A total of 45 ultrasonography-guided fine needle aspirations or biopsies of breast lesions were performed. All core biopsies using the traditional core technique (n=15) and coaxial technique (n=16) were diagnostic. While for fine needle aspirations, three (21%) of 14 were not diagnostic and repeat biopsies were undertaken for the corresponding patients. Except for one breast lesion biopsied with the coaxial technique that revealed invasive ductal carcinoma, all others yielded benign lesions. The average pain score for coaxial biopsies was 2.2, while for traditional core biopsies and fine needle aspirations, average scores were 3.7 and 3.8, respectively (P=0.022). No procedure-related complication was documented with either of the three techniques.<br><br>CONCLUSION: Modified coaxial core biopsy of the breast has an optimal diagnostic rate and hence avoids the need for repeat biopsies. It is associated with better patient comfort and no increase in the risk of complications.}, }
@article {pmid19648285, year = {2009}, author = {Poole, JA and Thiele, GM and Alexis, NE and Burrell, AM and Parks, C and Romberger, DJ}, title = {Organic dust exposure alters monocyte-derived dendritic cell differentiation and maturation.}, journal = {American journal of physiology. Lung cellular and molecular physiology}, volume = {297}, number = {4}, pages = {L767-76}, pmid = {19648285}, issn = {1522-1504}, support = {K08 ES015522-02/ES/NIEHS NIH HHS/United States ; K08: ES015522-01/ES/NIEHS NIH HHS/United States ; K08 ES015522-03/ES/NIEHS NIH HHS/United States ; 1R01OH008539-01/OH/NIOSH CDC HHS/United States ; K08 ES015522/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/*immunology ; Cells, Cultured ; Cytokines/immunology/*metabolism ; Dendritic Cells/*immunology/metabolism ; Dust/*immunology ; Flow Cytometry ; Housing, Animal ; Humans ; Lymphocytes/*immunology/metabolism ; Monocytes/*immunology/metabolism ; Phagocytosis ; Swine ; }, abstract = {Organic dust exposure in agricultural animal environments results in airway diseases. Dendritic cells (DCs) orchestrate inflammatory immune response in the airways, but little is known about how organic dust affects differentiation and maturation of monocyte-derived immature and mature DCs (iDCs, mDCs). Peripheral blood monocytes were differentiated in vitro into iDCs with granulocyte-macrophage colony stimulating factor + IL-4 (6 days) with and without swine facility organic dust extract (ODE, 0.1%). Unlike control iDCs, ODE-conditioned iDCs maintained key monocyte properties (increased mCD14, increased phagocytic ability) while expressing DC features [increased mCD83, HLA-DR, CD80, CD86, diminished cytokine (TNF-alpha, IL-6) responsiveness]. At day 6, iDCs were cultured for an additional 48 h (days 7 and 8) with lipopolysaccharide (LPS) to induce mDCs. ODE-conditioned mDCs maintained high expression of mCD14(+) and elevated phagocytosis while their DC features weakened as evidenced by decreased CD11c, CD83, HLA-DR, CD86, and CCR7 expression and reduced lymphocyte-stimulating capacity. Similar results were observed when monocytes were exposed to ODE for only the first 48 h and with ODE depleted of endotoxin. Control iDCs exposed to ODE during the final 2 days of iDC maturation (days 7 and 8) did not differ from control (no ODE) iDCs in surface marker expression and phagocytic ability, but exhibited enhanced lymphocyte-stimulating capacity. Dust exposure alters monocyte differentiation to iDCs and prevents maturation of iDC to mDCs. The first 48 h of monocyte differentiation appears to be the susceptible period to exposure. Environmental exposures present during early monocyte differentiation may impact the critical balance of DCs in the lung.}, }
@article {pmid19635920, year = {2009}, author = {Tanaka, M and Krutzik, SR and Sieling, PA and Lee, DJ and Rea, TH and Modlin, RL}, title = {Activation of Fc gamma RI on monocytes triggers differentiation into immature dendritic cells that induce autoreactive T cell responses.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {183}, number = {4}, pages = {2349-2355}, pmid = {19635920}, issn = {1550-6606}, support = {A122553//PHS HHS/United States ; R37 AI047868/AI/NIAID NIH HHS/United States ; R37 AI047868-09/AI/NIAID NIH HHS/United States ; AR40312/AR/NIAMS NIH HHS/United States ; R01 AI022553-24/AI/NIAID NIH HHS/United States ; R01 AR040312/AR/NIAMS NIH HHS/United States ; R01 AI022553/AI/NIAID NIH HHS/United States ; R01 AR040312-19/AR/NIAMS NIH HHS/United States ; }, mesh = {Antigens, CD1/biosynthesis/genetics ; Autoimmune Diseases/blood/*immunology/pathology ; Cell Adhesion Molecules/metabolism ; Cell Differentiation/genetics/*immunology ; Cells, Cultured ; Dendritic Cells/*immunology/*metabolism/pathology ; Granulocyte-Macrophage Colony-Stimulating Factor/physiology ; Humans ; Immune Complex Diseases/blood/immunology/pathology ; Inflammation Mediators/blood/physiology ; Lectins, C-Type/metabolism ; Lymphocyte Activation/genetics/immunology ; Monocytes/cytology/*immunology/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, IgG/biosynthesis/*blood/genetics ; T-Lymphocyte Subsets/*immunology/metabolism/pathology ; }, abstract = {The formation of immune complexes results in activation of the innate immune system and subsequent induction of host inflammatory responses. In particular, the binding of IgG immune complexes to FcgammaR on monocytes triggers potent inflammatory responses leading to tissue injury in disease. We investigated whether activation of monocytes via FcgammaR induced cell differentiation, imparting specific inflammatory functions of the innate immune response. Human IgG alone induced monocytes to differentiate into cells with an immature dendritic cell (iDC) phenotype, including up-regulation of CD1b, CD80, CD86, and CD206. Differentiation into CD1b(+) iDC was dependent on activation via CD64 (FcgammaRI) and induction of GM-CSF. The human IgG-differentiated iDC were phenotypically different from GM-CSF-derived iDC at the same level of CD1b expression, with higher cell surface CD86, but lower MHC class II, CD32, CD206, and CD14. Finally, in comparison to GM-CSF-derived iDC, IgG-differentiated iDC were more efficient in activating T cells in both autologous and allogeneic mixed lymphocyte reactions but less efficient at presenting microbial Ag to T cells. Therefore, activation of FcgammaRI on monocytes triggers differentiation into specialized iDC with the capacity to expand autoreactive T cells that may contribute to the pathogenesis of immune complex-mediated tissue injury.}, }
@article {pmid19633015, year = {2009}, author = {Hombach, V and Merkle, N and Torzewski, J and Kraus, JM and Kunze, M and Zimmermann, O and Kestler, HA and Wöhrle, J}, title = {Electrocardiographic and cardiac magnetic resonance imaging parameters as predictors of a worse outcome in patients with idiopathic dilated cardiomyopathy.}, journal = {European heart journal}, volume = {30}, number = {16}, pages = {2011-2018}, pmid = {19633015}, issn = {1522-9645}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/diagnosis/*mortality/physiopathology ; *Electrocardiography ; Female ; Humans ; Kaplan-Meier Estimate ; *Magnetic Resonance Angiography ; Male ; Middle Aged ; Prognosis ; Risk Factors ; }, abstract = {AIMS: Clinical parameters are weak predictors of outcome in patients with idiopathic dilated cardiomyopathy (IDC). We assessed the prognostic value of cardiac magnetic resonance (CMR) parameters in addition to conventional clinical and electrocardiographic characteristics.<br><br>METHODS AND RESULTS: One hundred and forty-one IDC patients were studied. QRS and QTc intervals were measured in 12-lead surface electrocardiogram. Patients were followed for median 1339 days, including 483 patient-years. The primary endpoint-cardiac death or sudden death-occurred in 25 (18%) patients, including 16 patients with cardiac death, 3 patients with sudden cardiac death (SCD), and 6 patients with ICD shock. Late gadolinium enhancement (LGE) was detected in 36 patients (26%). Kaplan-Meier survival analysis displayed QRS >110 ms (P = 0.010), the presence of LGE (P = 0.037), and diabetes mellitus (P < 0.001) as significant parameters for a worse outcome. Multivariable analysis revealed cardiac index (P < 0.001), right ventricular end-diastolic volume index (RVEDVI) (P = 0.006) derived from CMR imaging, the presence of diabetes mellitus (P = 0.006), and QRS >110 ms (P = 0.045) as significant predictors for the primary endpoint.<br><br>CONCLUSION: Cardiac index and RVEDVI derived from CMR imaging in addition to QRS duration >110 ms from conventional surface ECG and diabetes mellitus provide prognostic impact for cardiac death and SCD in patients with IDC.}, }
@article {pmid19632522, year = {2009}, author = {Ogimoto, A and Okayama, H and Nagai, T and Ohtsuka, T and Suzuki, J and Inoue, K and Nishimura, K and Shigematsu, Y and Tabara, Y and Kohara, K and Miki, T and Higaki, J}, title = {Association of monocyte chemoattractant protein 1 gene polymorphism with susceptibility to nonfamilial idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiology}, volume = {54}, number = {1}, pages = {66-70}, doi = {10.1016/j.jjcc.2009.04.001}, pmid = {19632522}, issn = {1876-4738}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cardiomyopathy, Dilated/*genetics ; Chemokine CCL2/*genetics ; Child ; Female ; Genetic Markers ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Male ; Middle Aged ; *Polymorphism, Genetic ; Young Adult ; }, abstract = {BACKGROUND: The cytotoxic action of leukocytes is known to be a probable cause of the cardiac myocyte damage seen in idiopathic dilated cardiomyopathy (IDC). Monocyte chemoattractant protein 1 (MCP-1) contributes to enhanced leukocyte recruitment and activation resulting in chronic damage of cardiomyocytes. MCP-1 has been reported to be dynamically regulated in IDC and may contribute to the deterioration of left ventricular function. In addition, a polymorphism at -2518 (G/A) in the MCP-1 gene affects the level of MCP-1 expression in response to an inflammatory stimulus.<br><br>METHODS AND RESULTS: We genotyped the polymorphism at -2518 G/A in the MCP-1 gene in 73 Japanese patients with nonfamilial IDC and 349 healthy controls. The distribution of the MCP-1 genotypes in the IDC patients differed significantly from the controls (p=0.016). In a dominant G allele model, there was a significant difference in the distribution of genotypes between the two groups (p<0.01). The odds ratio for nonfamilial IDC associated with the GG vs. non-GG genotype was 10.4 (95% CI=1.7-64.5) after adjustment for the confounding factors.<br><br>CONCLUSIONS: These findings suggest that the G allele at -2518 in the MCP-1 gene may be a novel genetic marker of susceptibility to nonfamilial IDC.}, }
@article {pmid19628225, year = {2010}, author = {Pappo, I and Spector, R and Schindel, A and Morgenstern, S and Sandbank, J and Leider, LT and Schneebaum, S and Lelcuk, S and Karni, T}, title = {Diagnostic performance of a novel device for real-time margin assessment in lumpectomy specimens.}, journal = {The Journal of surgical research}, volume = {160}, number = {2}, pages = {277-281}, doi = {10.1016/j.jss.2009.02.025}, pmid = {19628225}, issn = {1095-8673}, mesh = {Adult ; Biopsy ; Breast/pathology/surgery ; Breast Neoplasms/*pathology/*surgery ; Female ; Humans ; Intraoperative Care/instrumentation/standards ; *Mastectomy, Segmental ; Pathology, Clinical/*instrumentation/standards ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity ; Spectroscopy, Near-Infrared/*instrumentation/standards ; }, abstract = {BACKGROUND: Margin status in breast lumpectomy procedures is a prognostic factor for local recurrence and the need to obtain clear margins is often a cause for repeated surgical procedures. A recently developed device for real-time intraoperative margin assessment (MarginProbe; Dune Medical Devices, Caesarea, Israel), was clinically tested. The work presented here looks at the diagnostic performance of the device.<br><br>METHODS: The device was applied to freshly excised lumpectomy and mastectomy specimens at specific tissue measurement sites. These measurement sites were accurately marked, cut out, and sent for histopathologic analysis. Device readings (positive or negative) were compared with histology findings (namely malignant, containing any microscopically detected tumor, or nonmalignant) on a per measurement site basis. The sensitivity and specificity of the device was computed for the full dataset and for additional relevant subgroups.<br><br>RESULTS: A total of 869 tissue measurement sites were obtained from 76 patients, 753 were analyzed, of which 165 were cancerous and 588 were nonmalignant. Device performance on relatively homogeneous sites was: sensitivity 1.00 (95% CI: 0.85-1), specificity 0.87 (95% CI: 0.83-0.90). Performance for the full dataset was: sensitivity 0.70 (95% CI: 0.63-0.77), specificity 0.70 (95% CI: 0.67-0.74). Device sensitivity was estimated to change from 56% to 97% as the cancer feature size increased from 0.7 mm to 6.6 mm. Detection rate of samples containing pure DCIS clusters was not different from rates of samples containing IDC.<br><br>CONCLUSIONS: The device has high sensitivity and specificity in distinguishing between normal and cancer tissue even down to small cancer features.}, }
@article {pmid19622106, year = {2009}, author = {Turpeinen, AK and Vanninen, E and Magga, J and Tuomainen, P and Kuusisto, J and Sipola, P and Punnonen, K and Vuolteenaho, O and Peuhkurinen, K}, title = {Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy.}, journal = {Clinical physiology and functional imaging}, volume = {29}, number = {6}, pages = {414-419}, doi = {10.1111/j.1475-097X.2009.00887.x}, pmid = {19622106}, issn = {1475-097X}, mesh = {Cardiomyopathy, Dilated/complications/*physiopathology ; Female ; Humans ; Interleukin-6/*blood ; Male ; Middle Aged ; Myocarditis/complications/*physiopathology ; Natriuretic Peptide, Brain/*blood ; Neurotransmitter Agents/*blood ; Peptide Fragments/*blood ; Sympathetic Nervous System/*physiopathology ; Ventricular Dysfunction, Left/etiology/*physiopathology ; }, abstract = {BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood.<br><br>METHODS AND RESULTS: We studied 99 patients with IDC (age 54 +/- 1 years, left ventricular ejection fraction (EF) 40 +/- 1%, maximum oxygen uptake (VO(2)max) 20 +/- 1 ml kg(-1) min(-2), mean +/- SEM) by using (123)I-metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)-ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)-6 and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL-6 (r = 0.42, P<0.001 and r = -0.31, P<0.01) and NT-proBNP (r = 0.48, P<0.001 and r = -0.40, P<0.001). During a median follow-up of 4.1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter-defibrillator). In these patients, MIBG washout was higher (53 +/- 4 versus 40 +/- 2%, P = 0.01) and H/M ratio lower (1.38 +/- 0.04 versus 1.51 +/- 0.02, P = 0.01) than in patients without an event.<br><br>CONCLUSIONS: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.}, }
@article {pmid19616675, year = {2009}, author = {Gimeno, JR and Lacunza, J and García-Alberola, A and Cerdán, MC and Oliva, MJ and García-Molina, E and López-Ruiz, M and Castro, F and González-Carrillo, J and de la Morena, G and Valdés, M}, title = {Penetrance and risk profile in inherited cardiac diseases studied in a dedicated screening clinic.}, journal = {The American journal of cardiology}, volume = {104}, number = {3}, pages = {406-410}, doi = {10.1016/j.amjcard.2009.03.055}, pmid = {19616675}, issn = {1879-1913}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cardiomyopathies/diagnosis/epidemiology/*genetics ; Child ; Consanguinity ; Echocardiography ; Electrocardiography ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mass Screening ; Middle Aged ; *Penetrance ; Risk Assessment ; Risk Factors ; }, abstract = {Genetically transmitted cardiomyopathies can affect several members in a family. Identification of high-risk patients could lead to a preventive treatment. We report the results of a 5-year experience of a dedicated clinic. Family screening was offered to 493 consecutive unrelated patients; 2,328 subjects (40 +/- 19 years old, 52% men) were evaluated (mean 4.4 relatives/family). Electrocardiography and echocardiography were performed in all cases; additional tests were indicated depending on the disease. Familial study was recommended because of a proband with hypertrophic cardiomyopathy (HC) in 57%, idiopathic dilated cardiomyopathy (IDC) in 14%, arrhythmogenic right ventricular cardiomyopathy (ARVC) in 2%, left ventricular noncompaction in 2%, Brugada syndrome (BS) in 15%, long QT syndrome (LQTS) in 3%, and other conditions in 6%. Familial disease was confirmed in 164 (39%); 43% with HC, 47% with IDC, 25% with ARVC, 33% with left ventricular noncompaction, 28% with BS, and 30% with LQTS. Two hundred twenty-two (44 +/- 20 years old, 60% men) affected relatives were identified (129 of whom were newly diagnosed). Sixty-four patients were newly diagnosed with HC, 40 with IDC, 2 with ARVC, 5 with left ventricular noncompaction, 14 with BS, and 2 with LQTS, in whom appropriate risk stratification and medication, if needed, were initiated (specific medication in 40, 31.0%). Cardioverter-defibrillator implantation was indicated in 4 relatives for primary prevention. Ninety-two (18.7%) had a family history of sudden death (FHSCD). Consanguinity was rare but significantly associated to a higher percentage of family disease (75.0% vs 38.3%, p = 0.003) and family history of sudden death (42.1% vs 17.8, p <0.001). In conclusion, the prevalence of familial disease in inherited cardiac conditions is high. Systematic familial study identified many asymptomatic affected patients who could benefit from early treatment to prevent complications. Dedicated clinics and multidisciplinary teams are needed for proper screening programs.}, }
@article {pmid19606195, year = {2009}, author = {Mukhtar-Yola, M and Gwarzo, GD and Galadanci, HS and Tukur, J and Farouk, ZL and Adeleke, SI}, title = {HIV exposed infants: a preliminary report of the Aminu Kano Teaching Hospital experience.}, journal = {The Nigerian postgraduate medical journal}, volume = {16}, number = {2}, pages = {143-148}, pmid = {19606195}, issn = {1117-1936}, mesh = {Bottle Feeding ; Breast Feeding ; *Counseling ; Female ; HIV Infections/epidemiology/*prevention &amp; control/*transmission ; HIV Seropositivity/epidemiology/transmission ; HIV-1 ; Hospitals, Teaching ; Humans ; Infant ; Infant Formula ; Infant, Newborn ; Infectious Disease Transmission, Vertical/*prevention &amp; control ; Male ; Mothers ; Nigeria/epidemiology ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology/*prevention &amp; control ; Socioeconomic Factors ; }, abstract = {UNLABELLED: To determine the Sociodemographic characteristics, infant feeding choices and outcome of HIV exposed neonates attending the paediatric infectious disease clinic (IDC) of Aminu Kano Teaching Hospital Kano.<br><br>PATIENTS AND METHODS: The records of all HIV exposed babies were reviewed. One hundred and ninety HIV exposed babies were seen between October 2003-December 2005. Of these 121 were part of the PMTCT programme while 69 were not. A total of 179(94.2%) babies were delivered at term while 11(5.8%) were delivered prematurely, with M: F ratio of 1.2:1.<br><br>RESULTS: A substantial number of mothers in the non PMTCT group were diagnosed antenataly or even prior to conception yet they did not avail themselves of the interventions in the PMTCT programme. Reasons given were ignorance, inaccessibility to PMTCT centres and fear of stigmatisation. Breast milk substitute, was the leading choice of mothers in the PMTCT group while breast milk and mixed feeding was practised more in the non-PMTCT group.<br><br>CONCLUSION: PMTCT remains the best way of preventing paediatric HIV infection and infant feeding counselling should be family oriented. Provision of free infant formula, PCR machines to enable early diagnosis, waiving of fees, and home visits would greatly improve infant follow up.}, }
@article {pmid19580475, year = {2009}, author = {Cummings, RJ and Mitra, S and Foster, TH and Lord, EM}, title = {Migration of skin dendritic cells in response to ionizing radiation exposure.}, journal = {Radiation research}, volume = {171}, number = {6}, pages = {687-697}, pmid = {19580475}, issn = {0033-7587}, support = {R01 CA028332-24/CA/NCI NIH HHS/United States ; R01 CA028332-28/CA/NCI NIH HHS/United States ; R01 CA068409-14/CA/NCI NIH HHS/United States ; R01 CA028332-27/CA/NCI NIH HHS/United States ; R01 CA028332-29/CA/NCI NIH HHS/United States ; R01 CA028332-21A1/CA/NCI NIH HHS/United States ; R01 CA068409/CA/NCI NIH HHS/United States ; R01 CA068409-07/CA/NCI NIH HHS/United States ; R01 CA028332/CA/NCI NIH HHS/United States ; U19AI067733/AI/NIAID NIH HHS/United States ; R01 CA028332-19/CA/NCI NIH HHS/United States ; R01CA28332/CA/NCI NIH HHS/United States ; CA68409/CA/NCI NIH HHS/United States ; R01 CA068409-05/CA/NCI NIH HHS/United States ; R01 CA028332-22/CA/NCI NIH HHS/United States ; U19 AI067733/AI/NIAID NIH HHS/United States ; R01 CA068409-11/CA/NCI NIH HHS/United States ; R01 CA068409-13A1/CA/NCI NIH HHS/United States ; R01 CA068409-06/CA/NCI NIH HHS/United States ; R01 CA028332-20/CA/NCI NIH HHS/United States ; R01 CA068409-12/CA/NCI NIH HHS/United States ; R01 CA068409-15/CA/NCI NIH HHS/United States ; R01 CA028332-26/CA/NCI NIH HHS/United States ; R01 CA028332-25/CA/NCI NIH HHS/United States ; R01 CA068409-10/CA/NCI NIH HHS/United States ; R01 CA028332-23/CA/NCI NIH HHS/United States ; R01 CA068409-09/CA/NCI NIH HHS/United States ; R01 CA068409-08/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Count ; Cell Movement/physiology/*radiation effects ; Dendritic Cells/metabolism/pathology/*radiation effects ; Dose-Response Relationship, Radiation ; Female ; Fluorescence ; *Gamma Rays ; Histocompatibility Antigens Class II/metabolism ; Interleukin-12/administration &amp; dosage/metabolism ; Langerhans Cells/metabolism/pathology/*radiation effects ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Microscopy, Confocal ; Microscopy, Fluorescence ; Receptors, Interleukin-12/genetics ; Recombinant Proteins/administration &amp; dosage/metabolism ; Skin/immunology/metabolism/radiation effects ; Time Factors ; }, abstract = {We describe an imaging assay that monitors the migration of two unique subsets of immune dendritic cells (DC), interstitial dendritic cells (iDC) and Langerhans cells (LC), found in the dermal and epidermal layers of skin, respectively. Using this assay, we study responses of these cells to ionizing radiation. Results obtained using whole-mount histology and fluorescence microscopy suggest that ionizing radiation triggered the migration of both major histocompatibility complex (MHC) class II(+) iDC and Langerin(+) LC in a dose- and time-dependent manner. Migration appeared to be limited by local administration of recombinant IL-12, a potent immunostimulatory cytokine known to induce DNA repair. Those findings were extended to an in vivo model by injecting fluorescently conjugated anti-MHC class II antibodies intradermally into the ears of live, anesthetized mice and visualizing the DC population in the same ear before and after radiation exposure using confocal microscopy.}, }
@article {pmid19569713, year = {2009}, author = {Lu, WG and Jiang, L and Feng, XL and Lu, TB}, title = {Three-dimensional lanthanide anionic metal-organic frameworks with tunable luminescent properties induced by cation exchange.}, journal = {Inorganic chemistry}, volume = {48}, number = {15}, pages = {6997-6999}, doi = {10.1021/ic900506z}, pmid = {19569713}, issn = {1520-510X}, abstract = {Three 3D lanthanide anionic metal-organic frameworks {K(5)[Ln(5)(IDC)(4)(ox)(4)]}(n) x (20H(2)O)(n) with 1D channels were synthesized under hydrothermal conditions [Ln = Gd (1), Tb (2), and Dy (3)]. The K(+) ions within the 1D channel are easily exchanged with various cations. The emission intensities of Tb(III) in 2 increased significantly upon the addition of Ca(2+) ions, while the introduction of other metal ions caused the intensities to be either unchanged or weakened.}, }
@article {pmid19568416, year = {2009}, author = {Nakata, K and Ohuchida, K and Nagai, E and Hayashi, A and Miyasaka, Y and Kayashima, T and Yu, J and Aishima, S and Oda, Y and Mizumoto, K and Tanaka, M and Tsuneyoshi, M}, title = {LMO2 is a novel predictive marker for a better prognosis in pancreatic cancer.}, journal = {Neoplasia (New York, N.Y.)}, volume = {11}, number = {7}, pages = {712-719}, pmid = {19568416}, issn = {1476-5586}, mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma in Situ/genetics/metabolism/pathology ; Carcinoma, Pancreatic Ductal/genetics/metabolism/*pathology ; DNA-Binding Proteins/*genetics/metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; LIM Domain Proteins ; Male ; Metalloproteins/*genetics/metabolism ; Middle Aged ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Prognosis ; Proto-Oncogene Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {PURPOSE: LIM domain only 2 (LMO2) has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors. We investigate the involvement of LMO2 in pancreatic cancer.<br><br>EXPERIMENTAL DESIGN: We evaluated LMO2 expression in cultured cells, bulk tissues, and microdissected cells from pancreatic cancers by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry.<br><br>RESULTS: Of 164 pancreatic cancers, 98 (60%) were positive for LMO2 expression. LMO2 was more frequently detected in high-grade pancreatic intraepithelial neoplasia (PanIN) lesions (PanIN-2 and -3) than in low-grade PanIN lesions (PanIN-1A and -1B; P < .001) and was not detected in normal pancreatic ductal epithelium. The LMO2 messenger RNA levels were significantly higher in invasive ductal carcinoma cells than in normal pancreatic cells as evaluated by quantitative reverse transcription-polymerase chain reaction analyses of microdissected cells (P = .036). We also found higher incidence of LMO2 expression in histologic grade G1/G2 cancers than in grade G3 cancers (P < .001). The median survival time of LMO2-positive patients was significantly longer than that of LMO2-negative patients (P < .001), and multivariate analyses revealed that high LMO2 expression was an independent predictor of longer survival (risk ratio, 0.432, P < .001). Even among patients with a positive operative margin, LMO2-positive patients had a significant survival benefit compared with LMO2-negative patients. We further performed a large cohort study (n = 113) to examine the LMO2 messenger RNA levels in formalin-fixed paraffin-embedded samples and found similar results.<br><br>CONCLUSIONS: LMO2 is a promising marker for predicting a better prognosis in pancreatic cancer.}, }
@article {pmid19568168, year = {2010}, author = {Schorr, MC and Pedrini, JL and Savaris, RF and Zettler, CG}, title = {Are the pure in situ breast ductal carcinomas and those associated with invasive carcinoma the same?.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {18}, number = {1}, pages = {51-54}, doi = {10.1097/PAI.0b013e3181acaded}, pmid = {19568168}, issn = {1533-4058}, mesh = {Adult ; Aged ; Antigens, Neoplasm/*analysis ; Biomarkers, Tumor/analysis ; Carcinoma, Ductal, Breast/*diagnosis/immunology/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Middle Aged ; Neoplasm Invasiveness/*diagnosis/immunology ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tumor Suppressor Protein p53/analysis ; Young Adult ; }, abstract = {It has been reported that pure ductal carcinoma in situ of the breast has morphologic differences from the in situ component of the invasive ductal carcinoma, as well estrogen and progesterone receptors expression according to their cytokeratin expression. However, there is no data comparing other tumor markers without using the cytokeratin expression. The objective of this study is to compare the expression of estrogen receptor (ER) and progesterone receptor (PR), HER-2/neu, p53, and Ki67 between pure ductal in situ carcinoma (pDCIS) and the in situ component of the invasive ductal carcinoma (DCIS + IDC) of the breast, and the in situ component to the invasive component of the same tumor (DCIS + IDC). The immunohistochemistry expression of the tumor markers was performed in 45 cases of pDCIS and DCIS + IDC, yielding a total of 90 cases. Statistical analysis was carried out using Fisher exact test, having a P < 0.05, and Kappa index (kappa) to assess intratumoral concordance. In DCIS + IDC, the in situ and invasive components did not show a significant difference and Kappa index (kappa) was high (0.7-1) for positive and negative expression. ER and PR were significantly different between the pDCIS and DCIS + IDC (ER: 86.7 vs. 66.7% P = 0.04; PR: 80% vs. 55.6% P = 0.02). These findings suggest that in situ component of DCIS + IDC and pDCIS are distinct conditions.}, }
@article {pmid19567399, year = {2009}, author = {Perrone, G and Altomare, V and Zagami, M and Vulcano, E and Muzii, L and Battista, C and Rabitti, C and Muda, AO}, title = {Breast-like vulvar lesion with concurrent breast cancer: a case report and critical literature review.}, journal = {In vivo (Athens, Greece)}, volume = {23}, number = {4}, pages = {629-634}, pmid = {19567399}, issn = {0258-851X}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*secondary ; Diagnosis, Differential ; Female ; Humans ; Vulvar Neoplasms/*secondary ; }, abstract = {In the current report, we describe an intriguing case of a breast-like cancer lesion located in the vulvar region in a woman lacking a remarkable past medical or family history of breast cancer but with concurrent breast cancer. Consequently, a differential diagnosis between a primary synchronous breast and vulvar cancer or a metastatic breast carcinoma to the vulva is a key point in terms of the clinical approach. In a review of the literature, 39 cases of breast-like cancer lesion have been described: 23 cases of primary infiltrating carcinoma of the vulva and 16 cases of vulvar metastases of breast carcinoma. To the best of our knowledge, this is the first report of a clinically synchronous vulvar metastasis from an invasive ductal carcinoma. The main diagnostic criteria for differential diagnosis between primary or metastatic breast-like vulvar carcinoma are also discussed.}, }
@article {pmid19566361, year = {2009}, author = {Alamsamimi, M and Mirkheshti, N and Mohajery, MR and Abdollahi, M}, title = {Bilateral invasive ductal carcinoma in a woman with neurofibromatosis type 1.}, journal = {Archives of Iranian medicine}, volume = {12}, number = {4}, pages = {412-414}, pmid = {19566361}, issn = {1735-3947}, mesh = {Breast Neoplasms/*etiology/pathology/therapy ; Carcinoma, Ductal, Breast/*etiology/pathology/therapy ; Female ; Humans ; Middle Aged ; Neurofibromatosis 1/*complications/pathology ; }, abstract = {A 51-year-old woman with neurofibromatosis type 1 presented to our department for investigation of a left breast lump (50 x 50 x 30 mm); a mass in the right breast (40 x 40 x 20 mm) was also detected on physical examination. The lumps were suspected to be malignant based on physical examination and ultrasonography. Biopsy and frozen sections subsequently confirmed a diagnosis of bilateral invasive ductal carcinoma. A standard bilateral radical mastectomy was performed, followed by postoperative chemoendocrine therapy. Tumor recurrence has not been observed within the first 23 months following the surgery.}, }
@article {pmid19514014, year = {2009}, author = {Barone, P and Antonini, A and Colosimo, C and Marconi, R and Morgante, L and Avarello, TP and Bottacchi, E and Cannas, A and Ceravolo, G and Ceravolo, R and Cicarelli, G and Gaglio, RM and Giglia, RM and Iemolo, F and Manfredi, M and Meco, G and Nicoletti, A and Pederzoli, M and Petrone, A and Pisani, A and Pontieri, FE and Quatrale, R and Ramat, S and Scala, R and Volpe, G and Zappulla, S and Bentivoglio, AR and Stocchi, F and Trianni, G and Dotto, PD and , }, title = {The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {24}, number = {11}, pages = {1641-1649}, doi = {10.1002/mds.22643}, pmid = {19514014}, issn = {1531-8257}, mesh = {Aged ; Antiparkinson Agents/therapeutic use ; Anxiety/epidemiology/etiology/psychology ; Cognition Disorders/epidemiology/etiology/psychology ; Depression/epidemiology/etiology/psychology ; Fatigue/epidemiology/etiology/psychology ; Female ; Gastrointestinal Diseases/epidemiology/etiology/psychology ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Olfaction Disorders/epidemiology/etiology/psychology ; Pain/epidemiology/etiology/psychology ; Parkinson Disease/complications/drug therapy/*psychology ; *Quality of Life ; Sleep Disorders, Intrinsic/epidemiology/etiology/psychology ; Urination Disorders/epidemiology/etiology/psychology ; }, abstract = {We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales.}, }
@article {pmid19489232, year = {2009}, author = {Zhang, RJ and Niu, Y and Gao, YX}, title = {[Recent advances in studies on in-situ and invasive ductal carcinoma].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {1}, pages = {63-65}, pmid = {19489232}, issn = {0529-5807}, mesh = {Aneuploidy ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma in Situ/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; *Cell Movement ; DNA Methylation ; DNA, Neoplasm/genetics ; Female ; Humans ; Membrane Proteins/metabolism ; Neoplasm Invasiveness ; }, }
@article {pmid19483464, year = {2009}, author = {Csankovszki, G}, title = {Condensin function in dosage compensation.}, journal = {Epigenetics}, volume = {4}, number = {4}, pages = {212-215}, doi = {10.4161/epi.8957}, pmid = {19483464}, issn = {1559-2308}, support = {R01 GM079533/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/genetics/*physiology ; Animals ; Caenorhabditis elegans/*genetics ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; DNA-Binding Proteins/genetics/*physiology ; *Dosage Compensation, Genetic ; Evolution, Molecular ; Female ; Humans ; Male ; Models, Genetic ; Multiprotein Complexes/genetics/*physiology ; }, abstract = {Dosage compensation is an essential process that equalizes X-linked gene dosage between the sexes. In the worm Caenorhabditis elegans, a complex of proteins called the dosage compensation complex (DCC) binds both X chromosomes in hermaphrodites to downregulate gene expression two-fold and hence to reduce X-linked gene expression levels equal to that in males. Five subunits of the DCC form the condensin I(DC) complex, a homolog of the evolutionarily conserved condensin complex required for chromosome segregation and compaction during mitosis and meiosis. How related complexes can perform such diverse functions remains a mystery. Nevertheless, it is believed that the mitotic and interphase functions of condensin are mechanistically related and understanding one process will reveal new insights into the other. We discuss how during worm dosage compensation a condensin-mediated function may guide the organization of the interphase chromatin fibers, leading to the formation of a repressive nuclear compartment.}, }
@article {pmid19479727, year = {2009}, author = {Marchiò, C and Iravani, M and Natrajan, R and Lambros, MB and Geyer, FC and Savage, K and Parry, S and Tamber, N and Fenwick, K and Mackay, A and Schmitt, FC and Bussolati, G and Ellis, I and Ashworth, A and Sapino, A and Reis-Filho, JS}, title = {Mixed micropapillary-ductal carcinomas of the breast: a genomic and immunohistochemical analysis of morphologically distinct components.}, journal = {The Journal of pathology}, volume = {218}, number = {3}, pages = {301-315}, doi = {10.1002/path.2572}, pmid = {19479727}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Papillary/*genetics/metabolism/pathology ; Chromosome Aberrations ; Comparative Genomic Hybridization ; Female ; Humans ; Immunophenotyping ; Neoplasm Proteins/metabolism ; Neoplasms, Complex and Mixed/*genetics/metabolism/pathology ; Oligonucleotide Array Sequence Analysis ; }, abstract = {Micropapillary carcinomas (MPCs) can present as a rare histological special type of breast cancer; however, this histological type is more frequently found admixed with invasive ductal carcinomas of no special type (IDC-NSTs). We have previously demonstrated that pure MPCs constitute a distinct entity at the morphological and genetic levels. Here, we sought to determine whether mixed MPCs have genomic aberrations similar to those found in pure MPCs, and to investigate whether the distinct morphological components of MPCs harbour different genetic aberrations. Using high-resolution microarray comparative genomic hybridization (aCGH), we profiled a series of 10 MPCs of mixed histology and 20 IDC-NSTs matched for grade and oestrogen receptor (ER) status. In addition, we generated tissue microarrays containing a series of 24 pure and 40 mixed MPCs and performed immunohistochemical analysis with ER, progesterone receptor (PR), Ki-67, HER2, cytokeratin (CK) 5/6, CK14, CK17, EGFR, topoisomerase-IIalpha, cyclin D1, caveolin-1 and E-cadherin antibodies. In situ hybridization was employed to evaluate the prevalence of HER2, TOP2A, EGFR, CCND1, MYC and FGFR1 gene amplification. Our results demonstrate that mixed MPCs harbour similar patterns of genomic aberrations and phenotype (82.5% luminal and 17.5% HER2) compared to pure MPCs. A comparison between the distinct morphological components of mixed MPCs in a pairwise fashion revealed that both components harbour strikingly similar genomic profiles. When compared to grade- and ER-matched IDC-NSTs, mixed MPCs significantly more frequently harboured amplification of multiple regions on 8q (adjusted Fisher's p value < 0.05). Furthermore, mixed MPCs displayed higher proliferative rates than grade- and ER-matched IDC-NSTs. Our results suggest that micropapillary differentiation in breast cancer may identify a subgroup of more aggressive ER-positive breast carcinomas, even in those featuring a mixed histology, and that mixed MPCs are more closely related to pure MPCs than to IDC-NSTs.}, }
@article {pmid19473551, year = {2009}, author = {Qi, L and Bart, J and Tan, LP and Platteel, I and Sluis, Tv and Huitema, S and Harms, G and Fu, L and Hollema, H and Berg, Av}, title = {Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {163}, pmid = {19473551}, issn = {1471-2407}, mesh = {Apoptosis Regulatory Proteins/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Epithelium/*metabolism ; Female ; *Gene Expression ; Humans ; MicroRNAs/*genetics/metabolism ; Neoplasm Invasiveness ; PTEN Phosphohydrolase/*genetics/metabolism ; RNA-Binding Proteins/*genetics/metabolism ; Tropomyosin/*genetics/metabolism ; }, abstract = {BACKGROUND: Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA expression changes associated with invasive breast cancer, like miR-21, have not been studied in FEA.<br><br>METHODS: We performed miRNA in-situ hybridization (ISH) on 15 cases with simultaneous presence of normal breast tissue, FEA and/or DCIS and 17 additional cases with IDC. Expression of the miR-21 targets PDCD4, TM1 and PTEN was investigated by immunohistochemistry.<br><br>RESULTS: Two out of fifteen cases showed positive staining for miR-21 in normal breast ductal epithelium, seven out of fifteen cases were positive in the FEA component and nine out of twelve cases were positive in the DCIS component. A positive staining of miR-21 was observed in 15 of 17 IDC cases. In 12 cases all three components were present in one tissue block and an increase of miR-21 from normal breast to FEA and to DCIS was observed in five cases. In three cases the FEA component was negative, whereas the DCIS component was positive for miR-21. In three other cases, normal, FEA and DCIS components were negative for miR-21 and in the last case all three components were positive. Overall we observed a gradual increase in percentage of miR-21 positive cases from normal, to FEA, DCIS and IDC. Immunohistochemical staining for PTEN revealed no obvious changes in staining intensities in normal, FEA, DCIS and IDC. Cytoplasmic staining of PDCD4 increased from normal to IDC, whereas, the nuclear staining decreased. TM1 staining decreased from positive in normal breast to negative in most DCIS and IDC cases. In FEA, the staining pattern for TM1 was similar to normal breast tissue.<br><br>CONCLUSION: Upregulation of miR-21 from normal ductal epithelial cells of the breast to FEA, DCIS and IDC parallels morphologically defined carcinogenesis. No clear relation was observed between the staining pattern of miR-21 and its previously reported target genes.}, }
@article {pmid19461184, year = {2009}, author = {Sawada, Y and Fujii, T and Takahashi, H and Yokoyama, G and Matsubayashi, RN and Inoue, Y and Uesugi, N and Momosaki, S and Toh, U and Shirouzu, K}, title = {[A case of triple negative chest wall recurrent breast cancer treated with capecitabine and docetaxel combination therapy (XT therapy)].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {36}, number = {5}, pages = {815-817}, pmid = {19461184}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*drug therapy/*pathology/surgery ; Capecitabine ; Deoxycytidine/*analogs &amp; derivatives/therapeutic use ; Docetaxel ; Female ; Fluorouracil/*analogs &amp; derivatives/therapeutic use ; Humans ; Middle Aged ; Positron-Emission Tomography ; Taxoids/*therapeutic use ; Thoracic Neoplasms/blood/*drug therapy/pathology/*secondary ; Thoracic Wall/pathology ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {A 59-year-old woman underwent modified radical mastectomy for left breast cancer 9 years earlier. This time, a chest wall recurrence was found. A chest CT showed a chest wall tumor and lymph node metastases. PET images showed increased uptake in chest wall tumor and lymph nodes. The serum tumor markers have also elevated. Open biopsy of chest wall tumor was performed, and the tumor was diagnosed as invasive ductal carcinoma[ER(-), Pg R (-), HER2 score(0)]. Combination chemotherapy with capecitabine and docetaxel was initiated. After 7 courses of treatment, a marked response has been seen. Capecitabine and docetaxel combination therapy are considered useful for treatment of triple negative recurrent breast cancer.}, }
@article {pmid19461183, year = {2009}, author = {Morohashi, S and Morohashi, H and Saito, C and Odagiri, H}, title = {[A case of recurrent breast cancer with liver metastasis responding to exemestane].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {36}, number = {5}, pages = {811-814}, pmid = {19461183}, issn = {0385-0684}, mesh = {Adult ; Androstadienes/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*drug therapy/*pathology/surgery ; Female ; Humans ; Liver Neoplasms/blood/diagnostic imaging/*drug therapy/*secondary ; Recurrence ; Tomography, X-Ray Computed ; }, abstract = {We report a woman in her 30s who developed a right breast tumor 10 years after undergoing mastectomy for invasive ductal carcinoma of the left breast. She underwent modified radical mastectomy for the right breast cancer, which was diagnosed histologically as invasive ductal carcinoma with metastasis to the axillary lymph nodes. Because of the risk of recurrence, she received postoperative systemic adjunctive chemotherapy using CMF, but this had to be withdrawn because of liver toxicity. The patient therefore received hormonal therapy with goserelin and tamoxifen for 24 months. During this period, however, she became menopausal, necessitating withdrawal of the goserelin. After a disease-free interval of 34 months, liver metastasis appeared, and so tamoxifen was changed to exemestane. After 3 months, the metastasis showed a marked response, and this has been subsequently maintained for 48 months. Because the patient's menstrual cycle then returned, goserelin was restarted after consultation with a gynecologist. This case illustrates that exemestane and goserelin combination therapy is effective for recurrent breast cancer.}, }
@article {pmid19448591, year = {2009}, author = {Yeh, IT and Martin, MA and Robetorye, RS and Bolla, AR and McCaskill, C and Shah, RK and Gorre, ME and Mohammed, MS and Gunn, SR}, title = {Clinical validation of an array CGH test for HER2 status in breast cancer reveals that polysomy 17 is a rare event.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {22}, number = {9}, pages = {1169-1175}, doi = {10.1038/modpathol.2009.78}, pmid = {19448591}, issn = {1530-0285}, support = {P30 CA54174/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Chromosomes, Artificial, Bacterial ; Chromosomes, Human, Pair 17/*genetics ; Comparative Genomic Hybridization/*methods ; Female ; *Gene Dosage ; Genes, erbB-2/*genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Reproducibility of Results ; }, abstract = {The HER2 gene is an important prognostic and therapeutic marker in newly diagnosed breast cancer. Currently, HER2 status is most frequently determined by immunohistochemical detection of HER2 protein expression on the cellular membrane surface or by fluorescence in situ hybridization analysis of HER2 gene copy number in fixed tissue using locus-specific probes for the HER2 gene and chromosome 17 centromere. However, these methods are problematic because of issues with intra- and inter-laboratory reproducibility and preanalytic variables, such as fixation time. In addition, the commonly used HER2/chromosome 17 ratio presumes that chromosome 17 polysomy is present when the centromere is amplified, even though analysis of the rest of the chromosome is not included in the assay. In this study, 97 frozen samples of invasive lobular and invasive ductal carcinoma, with known immunohistochemistry and fluorescence in situ hybridization results for HER2, were analyzed by comparative genomic hybridization to a commercially available bacterial artificial chromosome whole-genome array containing 99 probes targeted to chromosome 17 and the HER2/TOP2 amplicon. Results were 97% concordant for HER2 status, meeting the College of American Pathologists/American Society of Clinical Oncology's validation requirements for HER2 testing. Surprisingly, not a single case of complete polysomy 17 was detected even though multiple breast cancer cases showed clear polysomies of other chromosomes. We conclude that array comparative genomic hybridization is an accurate and objective DNA-based alternative for clinical evaluation of HER2 gene copy number, and that polysomy 17 is a rare event in breast cancer.}, }
@article {pmid19438749, year = {2009}, author = {Liu, F and Lang, R and Wei, J and Fan, Y and Cui, L and Gu, F and Guo, X and Pringle, GA and Zhang, X and Fu, L}, title = {Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast.}, journal = {Histopathology}, volume = {54}, number = {6}, pages = {741-750}, doi = {10.1111/j.1365-2559.2009.03289.x}, pmid = {19438749}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology ; Carcinoma/metabolism/pathology ; Carcinoma, Papillary/metabolism/*pathology ; Chemokine CXCL12/*genetics/metabolism ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Receptors, CXCR4/*genetics/metabolism ; Tissue Array Analysis ; }, abstract = {AIMS: Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are implicated in tumour chemotaxis and metastasis. The aim was to examine their roles in the metastasis of invasive micropapillary carcinoma (IMPC) of the breast, a tumour with a high propensity for nodal spread.<br><br>METHODS AND RESULTS: We compared the expression of SDF-1 and CXCR4 in 103 cases of breast cancer containing IMPC components with a control group of 96 cases of invasive ductal carcinoma (IDC), not otherwise specified type by immunohistochemistry and chemical in situ hybridization (CISH). The results showed that the predominant cytoplasmic expression of both SDF-1 and CXCR4 was greater in tumour cells of the IMPC components than in those of the non-IMPC components and the control IDC cases, and was correlated significantly with the number of positive lymph nodes (P < 0.05). SDF-1 expression on cell membranes was less frequently identified in IMPC than IDC (P = 0.021). Immunohistochemical detection of SDF-1 in endothelial cells of lymphatic vessels was more common in IMPC (P = 0.007) and correlated significantly with lymph node status (P = 0.002), although SDF-1 mRNA was rarely detected by CISH.<br><br>CONCLUSIONS: This study suggests that up-regulation of cytoplasmic expression of SDF-1/CXCR4 might be one of the molecular mechanisms facilitating lymph node metastasis of IMPC.}, }
@article {pmid19414985, year = {2009}, author = {Mohammadizadeh, F and Naimi, A and Rajabi, P and Ghasemibasir, H and Eftekhari, A}, title = {Expression of basal and luminal cytokeratins in breast cancer and their correlation with clinicopathological prognostic variables.}, journal = {Indian journal of medical sciences}, volume = {63}, number = {4}, pages = {152-162}, pmid = {19414985}, issn = {0019-5359}, mesh = {Adult ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal/diagnosis/*genetics/pathology ; ErbB Receptors/genetics ; Female ; Gene Expression ; Humans ; Keratin-5/*genetics ; Keratin-6/*genetics ; Keratin-7/*genetics ; Middle Aged ; Phenotype ; Prognosis ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND: Normal breast ducts contain at least 3 types of epithelial cells: luminal (glandular) cells, basal/myoepithelial cells and stem cells. Myoepithelial and luminal epithelia can be distinguished by their different cytokeratin expression patterns. The aim of this study is to evaluate the expression of some prognostic biomarkers (ER, PR and HER2), as well as histological grading and lymph node status in cytokeratin-based groups of breast cancer.<br><br>OBJECTIVE: To evaluate the correlation between expression of basal and luminal markers and hormonal receptors, HER2/neu, age, grade and lymph node status in breast-invasive ductal carcinoma.<br><br>MATERIALS AND METHODS: Sixty-seven formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma, 'NOS' type) which had already been studied for ER, PR and HER2/neu were selected. Data concerning age, tumor grade and lymph node status were also obtained from archives. Expression of basal (CK5/6) and luminal (CK7) cytokeratins was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of stained cells.<br><br>RESULTS: We categorized the cases into 3 distinct phenotype groups: pure luminal, basal phenotype and null. Pure basal, mixed basal and luminal groups were classified as expressing a basal phenotype. There was a significant difference in the ER and/or PR expression between those 3 groups and a significant association between ER and/or PR negativity and basal phenotype expression. There was no significant difference in HER2/neu expression, age of the patients, tumor grade and lymph node status between the 3 cytokeratin-based groups and no significant association between lymph node status and basal phenotype expression.<br><br>CONCLUSION: We found that to gain a real association between basal phenotype and prognostic markers, we should use a cocktail or a panel of different biomarkers to correctly determine basal-like phenotype of breast cancers. This approach guarantees more concordance with gene expression-based studies.}, }
@article {pmid19412328, year = {2008}, author = {Hershberger, RE and Parks, SB and Kushner, JD and Li, D and Ludwigsen, S and Jakobs, P and Nauman, D and Burgess, D and Partain, J and Litt, M}, title = {Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy.}, journal = {Clinical and translational science}, volume = {1}, number = {1}, pages = {21-26}, pmid = {19412328}, issn = {1752-8062}, support = {M01 RR000334-380409/RR/NCRR NIH HHS/United States ; R01 HL058626-08/HL/NHLBI NIH HHS/United States ; R01-HL58626/HL/NHLBI NIH HHS/United States ; 5 M01 RR000334/RR/NCRR NIH HHS/United States ; R01 HL058626/HL/NHLBI NIH HHS/United States ; M01 RR000334/RR/NCRR NIH HHS/United States ; N01-HV-48194/HV/NHLBI NIH HHS/United States ; }, mesh = {Cardiac Myosins/*genetics ; Cardiomyopathy, Dilated/*genetics ; Connectin ; *DNA Mutational Analysis ; Ethnicity ; Exons ; Family Health ; Humans ; Introns ; LIM Domain Proteins ; Muscle Proteins/*genetics ; *Mutation ; Myosin Heavy Chains/*genetics ; NAV1.5 Voltage-Gated Sodium Channel ; Protein Structure, Tertiary ; Sodium Channels/*genetics ; Troponin T/*genetics ; }, abstract = {BACKGROUND: More than 20 genes have been reported to cause idiopathic and familial dilated cardiomyopathy (IDC/FDC), but the frequency of genetic causation remains poorly understood.<br><br>METHODS AND RESULTS: Blood samples were collected and DNA prepared from 313 patients, 183 with FDC and 130 with IDC. Genomic DNA underwent bidirectional sequencing of six genes, and mutation carriers were followed up by evaluation of additional family members. We identified in 36 probands, 31 unique protein-altering variants (11.5% overall) that were not identified in 253 control subjects (506 chromosomes). These included 13 probands (4.2%) with 12 beta-myosin heavy chain (MYH7) mutations, nine probands (2.9%) with six different cardiac troponin T (TNNT2) mutations, eight probands (2.6%) carrying seven different cardiac sodium channel (SCN5A) mutations, three probands (1.0%) with three titin-cap or telethonin (TCAP) mutations, three probands (1.0%) with two LIM domain binding 3 (LDB3) mutations, and one proband (0.3%) with a muscle LIM protein (CSRP3) mutation. Four nucleotide changes did not segregate with phentoype and/or did not alter a conserved amino acid and were therefore considered unlikely to be disease-causing. Mutations in 11 probands were assessed as likely disease-causing, and in 21 probands were considered possibly disease-causing. These 32 probands included 14 of the 130 with IDC (10.8%) and 18 of 183 with FDC (9.8%)<br><br>CONCLUSIONS: Mutations of these six genes each account for a small fraction of the genetic cause of FDC/IDC. The frequency of possible or likely disease-causing mutations in these genes is similar for IDC and FDC.}, }
@article {pmid19404978, year = {2009}, author = {Taylor, K and Rolfe, M and Reynolds, N and Kilanowski, F and Pathania, U and Clarke, D and Yang, D and Oppenheim, J and Samuel, K and Howie, S and Barran, P and Macmillan, D and Campopiano, D and Dorin, J}, title = {Defensin-related peptide 1 (Defr1) is allelic to Defb8 and chemoattracts immature DC and CD4+ T cells independently of CCR6.}, journal = {European journal of immunology}, volume = {39}, number = {5}, pages = {1353-1360}, pmid = {19404978}, issn = {1521-4141}, support = {MC_U127527201/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; Chemotaxis/*immunology ; Dendritic Cells/*immunology ; Flow Cytometry ; Humans ; Immunity, Innate/*immunology ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Receptors, CCR6/*immunology ; Reverse Transcriptase Polymerase Chain Reaction ; beta-Defensins/genetics/*immunology ; }, abstract = {Beta-defensins comprise a family of cationic, antimicrobial and chemoattractant peptides. The six cysteine canonical motif is retained throughout evolution and the disulphide connectivities stabilise the conserved monomer structure. A murine beta-defensin gene (Defr1) present in the main defensin cluster of C57B1/6 mice, encodes a peptide with only five of the canonical six cysteine residues. In other inbred strains of mice, the allele encodes Defb8, which has the six cysteine motif. We show here that in common with six cysteine beta-defensins, defensin-related peptide 1 (Defr1) displays chemoattractant activity for CD4(+) T cells and immature DC (iDC), but not mature DC cells or neutrophils. Murine Defb2 replicates this pattern of attraction. Defb8 is also able to attract iDC but not mature DC. Synthetic analogues of Defr1 with the six cysteines restored (Defr1 Y5C) or with only a single cysteine (Defr1-1c(V)) chemoattract CD4(+) T cells with reduced activity, but do not chemoattract DC. Beta-defensins have previously been shown to attract iDC through CC receptor 6 (CCR6) but neither Defr1 or its related peptides nor Defb8, chemoattract cells overexpressing CCR6. Thus, we demonstrate that the canonical six cysteines of beta-defensins are not required for the chemoattractant activity of Defr1 and that neither Defr1 nor the six cysteine polymorphic variant allele Defb8, act through CCR6.}, }
@article {pmid19403322, year = {2009}, author = {Lapierre-Combes, M and Rousset, J and Combes, E and Chinelatto, S and Dupré, PF and André, V}, title = {[Retrospective study conducted in northern Finistère about the role of breast MRI in normal breast screening, experience in 51 patients].}, journal = {Gynecologie, obstetrique &amp; fertilite}, volume = {37}, number = {5}, pages = {401-409}, doi = {10.1016/j.gyobfe.2009.02.013}, pmid = {19403322}, issn = {1297-9589}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/diagnosis/pathology ; Carcinoma/diagnosis/pathology ; Carcinoma, Ductal/diagnosis/pathology ; Female ; France ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography ; Mass Screening/*methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVES: To study the role and indications of breast MRI in normal breast screening.<br><br>PATIENTS AND METHODS: Retrospective study of 51 patients (mean age of 51 years) conducted in northern Finist&#xe8;re. Each patient had a normal (BI-RADS 1 or 2) breast screening (mammography and echography). Four indications for MRI were chosen: screening of high-risk patients, high-density breasts, radio-clinical discordance, and breasts prostheses. Breast MRI were reviewed according to BI-RADS classification. Abnormalities categorized in BI-RADS 4 or 5 were confirmed histologically.<br><br>RESULTS: Thirteen patients underwent histological analysis. Nine invasive carcinomas were identified (six invasive lobular carcinomas (ILC), two mixed carcinomas, one invasive ductal carcinoma). For these patients, the reason for performing MRI was a radio-clinical discordance.<br><br>DISCUSSION AND CONCLUSION: The study demonstrates the breast MRI value for radio-clinical discordance and the key role of MRI in diagnostic challenge of ILC. In literature review, MRI has a role even if breast screening is normal: radio-clinical discordance, screening of patients with high-risk, breasts prostheses in certain cases. Breast density comes as an additional criteria to perform this exam.}, }
@article {pmid19396698, year = {2009}, author = {Tokyol, C and Ersoz, G and Dilek, FH and Gencer, E and Kosar, MN and Dilek, ON}, title = {Thrombospondin 1 expression and angiogenesis in breast carcinoma and their relation with platelet activity.}, journal = {Upsala journal of medical sciences}, volume = {114}, number = {2}, pages = {108-115}, pmid = {19396698}, issn = {2000-1967}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Platelets/*cytology ; Breast Neoplasms/blood/*metabolism/physiopathology ; Case-Control Studies ; Cyclic GMP/metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Immunohistochemistry ; Middle Aged ; *Neovascularization, Pathologic ; Thrombospondin 1/*metabolism ; }, abstract = {This study investigates angiogenesis and the expression of thrombospondin 1 in invasive ductal carcinoma of the breast and their possible relation to platelet counts and platelet activity. The study included 20 cases of invasive ductal carcinoma. Platelet activity was evaluated by determining thromboxane B2 and cyclic guanosine monophosphate (cGMP) levels by enzyme immunoassay (EIA).Thrombospondin (TSP) 1 and CD34 expression was studied immunohistochemically. Mean platelet count of the patient group was significantly greater than the mean platelet count of the control group (P < 0.05). The platelet counts were positively correlated with tumour size (r=0.609; P < 0.01). Platelet counts were higher in the patients who had grade 3 microvessel density (P < 0.05). The mean basal platelet cGMP level in the patient group was significantly lower than it was in the control group (P < 0.05). Focal TSP immunoreactivity was detectable in 5 (20%) cases in the tumour cells, and in 9 (45%) cases in the stroma. We did not find any correlation between TSP-1 staining and angiogenesis, platelet counts, platelet activity, and the histological prognostic parameters. Our study confirms the essential role of platelets in tumour growth and angiogenesis. Decreased levels of cGMP in the patient group may cause platelet hyperreactivity. Although thrombospondin 1 may be upregulated in malignant breast tissue, this is not sufficient for tumour growth and dissemination according to our results.}, }
@article {pmid19396029, year = {2009}, author = {Jaafar, H and Mohamad Idris, F and Mohd Nafi, SN}, title = {The association between phenotype and size of breast tumors induced by 1-methyl-1-nitrosourea (MNU) injection in rats.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {15}, number = {5}, pages = {BR129-34}, pmid = {19396029}, issn = {1643-3750}, mesh = {Animals ; Carcinogens/*toxicity ; Female ; Mammary Neoplasms, Experimental/chemically induced/*pathology ; Methylnitrosourea/*toxicity ; Phenotype ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Administration of 1-methyl-1-nitrosourea (MNU) is considered a simple and rapid method for inducing breast tumors in rats. While most studies focus on the time frame of tumor development, there are little data on the development of breast tumor in relation to tumor size. Thus the current study was carried out to analyze the phenotype of MNU-induced tumors in relation to tumor size.<br><br>MATERIAL/METHODS: Twenty-one 21-day-old female Sprague Dawley rats were administered intraperitoneally with MNU at a dose of 70 mg/kg body weight. The entire palpable tumor was excised when the tumor size reached the diameters of 4.0+/-0.5 mm, 8.0+/-0.5 mm, 12.0+/-0.5 mm, and 16.0+/-0.5 mm and then subjected to histopathological assessment.<br><br>RESULTS: Epithelial inclusion cysts and mammary adenomas made up most of the benign tumors, with four cases occurring together with malignant lesions. Ductal carcinoma in situ was seen in tumor sizes of 4.0+/-0.5 mm or less. Among the malignant tumors, the cribriform type was seen predominantly at tumor sizes of less than 12.0+/-0.5 mm, while those with sizes of 12.0+/-0.5 mm or greater were of papillary type. Infiltrating ductal carcinoma-no special type (IDC-NST) commonly seen in humans was also observed at tumor sizes greater than 12.0+/-0.5 mm.<br><br>CONCLUSIONS: The tumors were found to be mainly of malignant type and the histological features of the induced tumors underwent changes as the tumor grew in size.}, }
@article {pmid19391212, year = {2009}, author = {Pai, RK and West, RB}, title = {MOC-31 exhibits superior reactivity compared with Ber-EP4 in invasive lobular and ductal carcinoma of the breast: a tissue microarray study.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {17}, number = {3}, pages = {202-206}, doi = {10.1097/pai.0b013e31818c0f42}, pmid = {19391212}, issn = {1533-4058}, mesh = {Antibodies/immunology ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Lobular/*diagnosis/pathology ; Cell Adhesion Molecules/*metabolism ; Diagnosis, Differential ; Epithelial Cell Adhesion Molecule ; Female ; Humans ; Tissue Array Analysis ; }, abstract = {Distinguishing between reactive mesothelial proliferations and adenocarcinoma is often very difficult. Ancillary studies, in particular immunohistochemistry, are often critical in detecting malignant epithelial cells, especially in serous effusion specimens. MOC-31 and Ber-EP4 are antibodies which target the epithelial cell adhesion molecule (Ep-CAM, TACSTD1) expressed in epithelial cells, and both are useful in distinguishing metastatic adenocarcinoma from reactive mesothelial cells. However, the reactivity of MOC-31 and Ber-EP4 with breast carcinoma, one of the more common carcinomas involving serous effusions, has not been extensively studied. We analyzed the immunohistochemical expression of MOC-31 and Ber-EP4 using tissue microarrays containing invasive ductal carcinoma (191 cases), invasive lobular carcinoma (44 cases), and 102 other carcinoma types comprising primary carcinomas of lung, gynecologic tract, pancreas, colon, gastric, esophageal, prostate, head and neck, hepatic, and renal origin. For MOC-31, 184 of 191 (96%) invasive ductal carcinomas and 39 of 44 (89%) invasive lobular carcinomas exhibited diffuse positive staining. In contrast, for Ber-EP4, 121 of 183 (66%) invasive ductal carcinomas and 11 of 40 (27.5%) invasive lobular carcinomas exhibited diffuse positive staining. With the exception of 1 case of esophageal adenocarcinoma, all other adenocarcinomas (86 of 87 cases) exhibited diffuse staining with both Ber-EP4 and MOC-31. MOC-31 and Ber-EP4 exhibited identical staining with all other carcinoma types. Our findings indicate that MOC-31 is superior to Ber-EP4 in detecting both invasive lobular and ductal carcinoma of the breast.}, }
@article {pmid19386432, year = {2009}, author = {Liu, GF and Yang, Q and Haffty, BG and Moran, MS}, title = {Clinical-pathologic features and long-term outcomes of tubular carcinoma of the breast compared with invasive ductal carcinoma treated with breast conservation therapy.}, journal = {International journal of radiation oncology, biology, physics}, volume = {75}, number = {5}, pages = {1304-1308}, doi = {10.1016/j.ijrobp.2008.12.070}, pmid = {19386432}, issn = {1879-355X}, mesh = {Adenocarcinoma/*drug therapy/mortality/pathology/*radiotherapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*drug therapy/mortality/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/*drug therapy/mortality/pathology/*radiotherapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Treatment Outcome ; }, abstract = {PURPOSE: To evaluate our institutional experience of treating tubular carcinoma of the breast (TC) and invasive ductal carcinoma (IDC) with conservative surgery and radiation therapy, to compare clinical-pathologic features and long-term outcomes.<br><br>METHODS AND MATERIALS: A review of our institution's tumor registry from 1975 to 2007, followed by a central pathology review of available slides, yielded 71 cases of Stage I/II TC and 2,238 cases of Stage I/II IDC treated with breast conservation therapy. Clinical-pathologic features and outcomes were analyzed by subtype to detect significant differences.<br><br>RESULTS: The median follow-up was 7 years. The TC cohort presented more frequently with pT1 disease (97% vs. 80%, p = 0.0007), pN0 disease (95% vs. 74%, p = 0.0004), hormone-receptor positivity (ER+, 89% vs. 62%, p = 0.0001; PR+, 81% vs. 52%, p = 0.0001), and HER-2 negativity (89% vs. 71%, p = 0.04). Clinical outcomes also favored the TC cohort, with lower rates of breast cancer-related death (1% vs. 10%; p = 0.0109) and distant metastasis (1% vs. 13%; p = 0.0028) and higher rates of 10-year overall (90% vs. 80%; p = 0.033), cause-specific (99% vs. 86%; p = 0.011), and disease-free (99% vs. 82%; p = 0.003) survival. There was a nonsignificant trend toward improved breast cancer relapse-free survival for the TC cohort (95% vs. 87%; p = 0.062) but no difference in nodal relapse-free survival or contralateral breast cancer relapse-free survival (all p values >0.05) between the cohorts.<br><br>CONCLUSION: Our institutional experience suggests that TC, when compared with IDC, is associated with more favorable clinical-pathologic features and comparable, if not superior, outcomes after breast conservation therapy, suggesting the appropriateness of a conservative approach to this rare subtype.}, }
@article {pmid19384208, year = {2009}, author = {Badjatia, N and Strongilis, E and Prescutti, M and Fernandez, L and Fernandez, A and Buitrago, M and Schmidt, JM and Mayer, SA}, title = {Metabolic benefits of surface counter warming during therapeutic temperature modulation.}, journal = {Critical care medicine}, volume = {37}, number = {6}, pages = {1893-1897}, doi = {10.1097/CCM.0b013e31819fffd3}, pmid = {19384208}, issn = {1530-0293}, support = {GRANT KL2 RR024157/RR/NCRR NIH HHS/United States ; }, mesh = {Brain Injuries/complications/metabolism/therapy ; Calorimetry, Indirect ; *Energy Metabolism ; Female ; *Heating ; Humans ; Hyperthermia, Induced/*methods ; Hypothermia/etiology/*metabolism/*therapy ; Hypothermia, Induced/adverse effects ; Male ; Middle Aged ; Prospective Studies ; *Shivering ; Skin ; }, abstract = {OBJECTIVE: To determine the impact of counter warming (CW) with an air circulating blanket on shivering and metabolic profile during therapeutic temperature modulation (TTM).<br><br>DESIGN: A prospective observational study.<br><br>SETTING: An 18-bed neurologic intensive care unit.<br><br>PATIENTS: Fifty mechanically ventilated patients with brain injury undergoing TTM with automated surface and intravascular devices.<br><br>INTERVENTIONS: Fifty indirect calorimetry (IDC) measurements with and without CW during TTM.<br><br>MEASUREMENTS AND MAIN RESULTS: IDC was continuously performed for 10-15 minutes at baseline with CW (phase I), off CW (phase II), and again after the return of CW (phase III). Shivering severity during each phase was scored on a scale of 0-3 using the Bedside Shivering Assessment Scale (BSAS). Resting energy expenditure (REE), oxygen consumption, and carbon dioxide production were determined by IDC; 56% were women, with mean age 61 +/- 15 years. At the time of IDC, 72% of patients had signs of shivering (BSAS >0). All measures of basal metabolism increased after removal of the air warming blanket (from phases I and II); REE increased by 27% and oxygen consumption by 29% (both p < 0.002). A one-point increase in baseline BSAS was noted in 55% (n = 23/42) of patients from phase I to phase II. In a multivariate analysis, sedative use (p = 0.03), baseline moderate to severe shivering (p = 0.04), and lower serum magnesium levels (p = 0.01) were associated with greater increases in REE between phase I and phase II of CW. Phase III of CW was associated with a reversal in the increases in all metabolic variables.<br><br>CONCLUSIONS: Surface CW provides beneficial control of shivering and improves the metabolic profile during TTM.}, }
@article {pmid19384070, year = {2009}, author = {Cangelosi, JJ and Nash, JW and Prieto, VG and Ivan, D}, title = {Cutaneous adnexal tumor with an unusual presentation--discussion of a potential diagnostic pitfall.}, journal = {The American Journal of dermatopathology}, volume = {31}, number = {3}, pages = {278-281}, doi = {10.1097/DAD.0b013e31819ddccf}, pmid = {19384070}, issn = {1533-0311}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/secondary/surgery ; Carcinoma, Ductal, Breast/secondary/surgery ; Cell Differentiation ; Diagnosis, Differential ; Diagnostic Errors/*prevention &amp; control ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Adnexal and Skin Appendage/chemistry/*pathology/therapy ; *Neoplasms, Second Primary ; Skin Neoplasms/chemistry/*pathology/therapy ; }, abstract = {The clinical presentation of skin adnexal tumors is nonspecific, and histologically; the differential diagnosis between primary cutaneous adnexal malignant carcinomas and metastatic tumors with a visceral origin can be challenging. We report a patient with history of invasive ductal carcinoma of the breast who presented with a 1-cm erythematous palpable lesion on her right calf. The biopsy showed an intradermal proliferation of malignant epithelioid cells with ductal differentiation, histologically compatible with metastatic breast carcinoma. However, the tumor cells labeled strongly and diffusely not only for pancytokeratin and cytokeratin (CK7) but also with p63 and CK5/6; carcinoembryonic antigen highlighted the ductal structures. No labeling was seen for mammoglobin, estrogen/progesterone, Her2-neu, S-100 protein, CK20, thyroid transcription factor-1 (TTF-1), and CDX-2. Based on the p63 and CK5/6 positivity, the differential diagnosis also included the possibility of a primary adnexal neoplasm and a complete excision was advised. The reexcision specimen revealed residual infiltrating dermal tumor and an overlying intraepithelial component with marked cytologic atypia and focal duct formation, diagnostic of a primary cutaneous adnexal tumor with ductal differentiation (porocarcinoma). Immunohistochemical studies (like p63 and CK5/6) can help to differentiate a primary cutaneous neoplasm from a metastatic lesion. This discrimination is of a paramount importance because a diagnostic error can result in profound implications for patient's assumed prognosis and subsequently applied therapy.}, }
@article {pmid19351366, year = {2009}, author = {Koo, JS and Jung, W}, title = {Xanthogranulomatous mastitis: clinicopathology and pathological implications.}, journal = {Pathology international}, volume = {59}, number = {4}, pages = {234-240}, doi = {10.1111/j.1440-1827.2009.02356.x}, pmid = {19351366}, issn = {1440-1827}, mesh = {Adult ; Aged ; Breast Neoplasms/complications ; Carcinoma in Situ/complications ; Carcinoma, Ductal, Breast/complications ; Female ; Granuloma/complications/metabolism/*pathology ; Humans ; Immunohistochemistry ; Mastitis/metabolism/*pathology ; Middle Aged ; Xanthomatosis/complications/metabolism/*pathology ; }, abstract = {Xanthogranulomatous inflammation is an uncommon finding in the breast. Sixteen cases of xanthogranulomatous mastitis were reviewed to determine the characteristic clinicopathological features. Xanthogranulomatous mastitis involved foamy histiocyte clusters interspersed with inflammatory cells. Foamy histiocytes were bland with small pyknotic nuclei. Xanthogranulomatous mastitis was associated with fat necrosis in five cases (31%), multinucleated giant-cell reactions in six cases (38%), and cholesterol crystals in five cases (31%). In three cases (19%), xanthogranulomatous mastitis coincided with ductal carcinoma in situ or invasive ductal carcinoma. Duct ectasia with foamy histiocyte aggregates were noted in five cases (31%). It is suggested that the etiology of xanthogranulomatous mastitis is obstruction and rupture of the ectatic duct with foamy histiocyte aggregates. In breast core biopsy, granular cell tumor and invasive carcinoma such as histiocytoid carcinoma and lipid-rich carcinoma could demonstrate similar pathological features to xanthogranulomatous mastitis. In conclusion, xanthogranulomatous mastitis could be encountered in breast core biopsy and surgical excision tissue. Diagnosis of xanthogranulomatous mastitis can be made by excluding other diseases that elicit xanthogranulomatous inflammation in the breast. In breast core biopsy, xanthogranulomatous mastitis could be distinguished from granular cell tumor, histiocytoid carcinoma and lipid-rich carcinoma by using cytokeratin and histiocytic marker such as alpha1-anti-trypsin and CD68 stain.}, }
@article {pmid19349195, year = {2009}, author = {Li, ZD and Wu, Y and Bao, YL and Yu, CL and Guan, LL and Wang, YZ and Meng, XY and Li, YX}, title = {Identification and characterization of human ARIP2 and its relation to breast cancer.}, journal = {Cytokine}, volume = {46}, number = {2}, pages = {251-259}, doi = {10.1016/j.cyto.2009.02.009}, pmid = {19349195}, issn = {1096-0023}, mesh = {Activin Receptors, Type II/genetics/*metabolism ; Activins/genetics/metabolism ; Adaptor Proteins, Signal Transducing/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carrier Proteins/genetics/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Membrane Proteins/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Protein Isoforms/genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; Transcription, Genetic ; Two-Hybrid System Techniques ; }, abstract = {Activin, a member of the TGF-beta superfamily, inhibits the proliferation of breast cancer cells. Activin interacts with its type I and type II receptors to induce phosphorylation of intracellular signaling molecules known as Smads. Previous studies showed that mouse ARIP2 can reduce activin signaling by interacting with activin type II receptors (ActRIIs); however, the activity of ARIP2 in breast cancer is still unclear. In this study, we used RT-PCR to obtain a human homologue of mouse ARIP2, human activin receptor-interacting protein 2 (hARIP2). Like murine ARIP2, hARIP2 has a PDZ domain in its NH2-terminal region and can interact specifically with ActRIIs. Overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human breast adenocarcinoma MCF-7 cells and MDA-MB-231 cells. However, down-regulation of hARIP2 expression by RNAi enhanced activin-induced transcriptional activity and reduced cell proliferation and colony formation. Immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant breast tissues such as simple carcinoma, invasive ductal carcinoma and mucinous adenocarcinoma than in benign hyperplasia or fibroadenoma cases. These results suggest that hARIP2 is a putative growth-promoting factor involved in breast tumorigenesis and tumor development.}, }
@article {pmid19345064, year = {2009}, author = {Meluzin, J and Spinarova, L and Hude, P and Krejci, J and Poloczkova, H and Podrouzkova, H and Pesl, M and Orban, M and Dusek, L and Korinek, J}, title = {Left ventricular mechanics in idiopathic dilated cardiomyopathy: systolic-diastolic coupling and torsion.}, journal = {Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography}, volume = {22}, number = {5}, pages = {486-493}, doi = {10.1016/j.echo.2009.02.022}, pmid = {19345064}, issn = {1097-6795}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*diagnostic imaging ; Echocardiography, Doppler/*methods ; Elasticity Imaging Techniques/*methods ; Female ; Humans ; Male ; Middle Aged ; Torsion Abnormality/complications/*diagnostic imaging ; Ventricular Dysfunction, Left/complications/*diagnostic imaging ; }, abstract = {BACKGROUND: In idiopathic dilated cardiomyopathy (IDC), myocardial deformational parameters and their mutual relationships remain incompletely characterized.<br><br>METHODS: Thirty-seven patients with IDC underwent two-dimensional speckle-tracking echocardiography (2D-STE) to assess left ventricular rotation, torsion, and longitudinal, circumferential, and radial systolic and diastolic strains and strain rates. Additionally, 2D-STE was performed in 14 controls.<br><br>RESULTS: All deformational parameters on 2D-STE were significantly lower in patients with IDC compared with controls. Seven patients exhibited opposite basal (positive, counterclockwise) and 11 patients exhibited opposite apical (negative, clockwise) rotation at end-systole. Circumferential, radial, and longitudinal early diastolic strain rates were correlated most strongly with the corresponding spatial components of systolic deformation.<br><br>CONCLUSION: In patients IDC, all torsional, systolic, and diastolic deformational parameters were decreased. Corresponding three-dimensional components of systolic and diastolic deformations were closely coupled. Considerable variation in the direction of basal and apical rotation exists in a subset of patients with IDC.}, }
@article {pmid19344495, year = {2009}, author = {Schedin, P and Borges, V}, title = {Breaking down barriers: the importance of the stromal microenvironment in acquiring invasiveness in young women's breast cancer.}, journal = {Breast cancer research : BCR}, volume = {11}, number = {2}, pages = {102}, pmid = {19344495}, issn = {1465-542X}, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Disease Progression ; Epithelial Cells/pathology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Neoplasm Invasiveness ; Stromal Cells/*pathology ; }, abstract = {Gene expression profiling was performed on laser captured breast stroma and epithelium obtained from 14 breast cancer patients. As with breast epithelium, of the stromal gene expression changes observed between normal tissue and invasive ductal carcinoma, greater than 90% occurred early, at the normal to ductal carcinoma in situ transition. Only 10% of stromal and 0% of epithelial genes were differentially regulated between non-invasive ductal carcinoma in situ and invasive disease. These data suggest that the majority of gene expression changes required for transformation occur early, prior to histological evidence of an invasive phenotype, the stroma cooperates closely with epithelium in this transformation, and for acquisition of the invasive phenotype, the stroma is dominant over the epithelium.}, }
@article {pmid21495363, year = {2009}, author = {Matei, M and Azoicăi, D}, title = {[Histopathological characteristics of genital and breast cancer included in epidemiologic study cohort].}, journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi}, volume = {113}, number = {2}, pages = {540-548}, pmid = {21495363}, issn = {0048-7848}, mesh = {Adenocarcinoma/epidemiology/pathology ; Adult ; Aged ; Breast Neoplasms/diagnosis/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Carcinoma, Squamous Cell/epidemiology/pathology ; Cohort Studies ; Endometrial Neoplasms/epidemiology/pathology ; Female ; Genital Neoplasms, Female/diagnosis/*epidemiology/*pathology ; Humans ; Incidence ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/epidemiology/pathology ; Prognosis ; Risk Factors ; Romania/epidemiology ; Uterine Neoplasms/epidemiology/pathology ; }, abstract = {UNLABELLED: The correct management of genitals and breast cancers and the improving of the preventional and therapeutical successes ratio involve the knowledge of the histopathological features of these nosological entities which have different origins, different risk factors, different simptomatology and also different prognosis.<br><br>AIM: The descriptive evaluation of the histopathological features of the genitals and breast cancers to women from North-Eastern region of Romania.<br><br>MATERIAL AND METHOD: We have been included in the study 96 women (age range 23-77 years, mean 54,49) diagnosed with breast cancer, ovarian cancer, endometrial cancer and cervical cancer at the hospital admission, residency in the Obstetrics and Gynecology Clinics within 23 months. The following main parameters were assessed: histological types, stage at diagnosis, Pap test. After data collection, these have been codified and included in a MS Excel Database, in order to be processed with SPSS 16 and EpiInfo 3.5.1. (2008) Softwares.<br><br>RESULTS: The following cases' repartition on diagnostic types was observed: breast cancer (44 cases), cervical cancer (24 cases), endometrial cancer (16 cases) and ovarian cancer (12 cases). In our study, the most affected range of age was 40-69 years for breast cancer, 30-59 years for cervical cancer, over 6 years for endometrial cancer and 50-59 years for ovarian cancer. For the cervical neoplasia, 40% of analyzed cases were in incipient stages (in situ to IB stage lessions). More than 50% of breast cancer cases have been diagnosed in advances stages (IIB to IIIC stages). For the endometrium carcinoma, 45% of cases have been identified in incipient stages (in situ to IC). The ovarian neoplasia cases have been detected, most frequently, in advanced stages (III and IV). 25% of women which participated in our study had showed cervical changes.<br><br>CONCLUSION: From a histopathological point of view, for cervical neoplasia, squamous carcinoma was the most frequent type (87%), for breast neoplasia--invasive ductal carcinoma (80%) and for ovary and endometrium malignant tumors--adenocarcinoma (69%, respectively 83%).}, }
@article {pmid19332930, year = {2009}, author = {Pervatikar, SK and Rao, R and Dinesh, US and Parameswaraiah, S}, title = {Large mammary hamartoma with focal invasive ductal carcinoma.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {52}, number = {2}, pages = {249-251}, doi = {10.4103/0377-4929.48935}, pmid = {19332930}, issn = {0974-5130}, mesh = {Adult ; Breast Neoplasms/*diagnosis/*pathology/surgery ; Carcinoma, Ductal/*complications/*diagnosis/pathology/surgery ; Female ; Hamartoma/*complications/*diagnosis/pathology/surgery ; Humans ; Mastectomy ; }, abstract = {Mammary hamartomas are uncommon benign lesions rarely associated with malignancy. We report a case of a 25-year-old female patient presenting with a lump in the left breast. Fine needle aspiration cytology showed features of invasive ductal carcinoma along with normal benign glands that were mistaken for normal breast tissue. However, the mastectomy specimen revealed the malignant mass within a larger hamartomatous mass. Mammary hamartomas are benign lesions but, on exceedingly rare occasions, they may be involved by incidental, coexisting carcinoma, as illustrated in this case report.}, }
@article {pmid19318578, year = {2009}, author = {Neal, CL and Yao, J and Yang, W and Zhou, X and Nguyen, NT and Lu, J and Danes, CG and Guo, H and Lan, KH and Ensor, J and Hittelman, W and Hung, MC and Yu, D}, title = {14-3-3zeta overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival.}, journal = {Cancer research}, volume = {69}, number = {8}, pages = {3425-3432}, pmid = {19318578}, issn = {1538-7445}, support = {R01 CA109570-02/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA109570-05/CA/NCI NIH HHS/United States ; P01 CA099031-010004/CA/NCI NIH HHS/United States ; R01-CA109570/CA/NCI NIH HHS/United States ; P50 CA116199/CA/NCI NIH HHS/United States ; R01 CA109570-03/CA/NCI NIH HHS/United States ; P50 CA116199-040004/CA/NCI NIH HHS/United States ; P01 CA099031/CA/NCI NIH HHS/United States ; P01-CA099031/CA/NCI NIH HHS/United States ; R01-CA119127/CA/NCI NIH HHS/United States ; R01 CA109570-01/CA/NCI NIH HHS/United States ; P50-CA116199/CA/NCI NIH HHS/United States ; R01 CA109570-04/CA/NCI NIH HHS/United States ; R01 CA109570/CA/NCI NIH HHS/United States ; P30-CA 16672/CA/NCI NIH HHS/United States ; }, mesh = {14-3-3 Proteins/*biosynthesis/genetics ; Apoptosis/physiology ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Adhesion/physiology ; Cell Growth Processes/physiology ; Cell Line, Tumor ; Cell Survival/physiology ; Female ; Gene Amplification ; Humans ; Mitochondria/genetics/metabolism ; Neoplasm Recurrence, Local/genetics/*metabolism/pathology ; Prognosis ; Risk Factors ; }, abstract = {The ubiquitously expressed 14-3-3 proteins are involved in numerous important cellular functions. The loss of 14-3-3sigma is a common event in breast cancer; however, the role of other 14-3-3s in breast cancer is unclear. Recently, we found that 14-3-3zeta overexpression occurs in early stage breast diseases and contributes to transformation of human mammary epithelial cells. Here, we show that 14-3-3zeta overexpression also persisted in invasive ductal carcinoma and contributed to the further progression of breast cancer. To examine the clinical effect of 14-3-3zeta overexpression in advanced stage breast cancer, we performed immunohistochemical analysis of 14-3-3zeta expression in primary breast carcinomas. 14-3-3zeta overexpression occurred in 42% of breast tumors and was determined to be an independent prognostic factor for reduced disease-free survival. 14-3-3zeta overexpression combined with ErbB2 overexpression and positive lymph node status identified a subgroup of patients at high risk for developing distant metastasis. To investigate whether 14-3-3zeta overexpression causally promotes breast cancer progression, we overexpressed 14-3-3zeta by stable transfection or reduced 14-3-3zeta expression by siRNA in cancer cell lines. Increased 14-3-3zeta expression enhanced anchorage-independent growth and inhibited stress-induced apoptosis, whereas down-regulation of 14-3-3zeta reduced anchorage-independent growth and sensitized cells to stress-induced apoptosis via the mitochondrial apoptotic pathway. Transient blockade of 14-3-3zeta expression by siRNA in cancer cells effectively reduced the onset and growth of tumor xenografts in vivo. Therefore, 14-3-3zeta overexpression is a novel molecular marker for disease recurrence in breast cancer patients and may serve as an effective therapeutic target in patients whose tumors overexpress 14-3-3zeta.}, }
@article {pmid19304743, year = {2009}, author = {Chae, BJ and Bae, JS and Lee, A and Park, WC and Seo, YJ and Song, BJ and Kim, JS and Jung, SS}, title = {p53 as a specific prognostic factor in triple-negative breast cancer.}, journal = {Japanese journal of clinical oncology}, volume = {39}, number = {4}, pages = {217-224}, doi = {10.1093/jjco/hyp007}, pmid = {19304743}, issn = {1465-3621}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/drug therapy/*genetics/mortality ; Carcinoma, Ductal/drug therapy/*genetics/mortality/secondary ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration &amp; dosage ; Disease-Free Survival ; Doxorubicin/administration &amp; dosage ; Epirubicin/administration &amp; dosage ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {OBJECTIVE: A recent suggestion is that the predictive value of a single biomarker may rely on the genetic background on the tumor and that different breast cancer subgroups may have different predictive markers of response to chemotherapy. The prognostic value of p53 in the outcome of adjuvant anthracycline-containing chemotherapy was evaluated according to molecular subclasses defined using the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2.<br><br>METHODS: Subjects were patients (n = 135) with invasive ductal carcinoma treated with adjuvant anthracycline-based chemotherapy between 1994 and 2000 in our hospital. Clinico-pathological features were reviewed by retrospective examination of medical records.<br><br>RESULTS: Overall survival rate was not independently predictive by p53 status (P = 0.182). However, in triple-negative cases, there was statistically significant survival difference (P = 0.034) and no statistically significant difference (P = 0.783) in non-triple-negative cases by p53 status. In the Cox proportional hazard analysis, p53 was also strongly predictive for relapse-free survival (P = 0.013) and overall survival (P = 0.049) in triple-negative patients.<br><br>CONCLUSIONS: p53 status could be a specific prognostic factor in triple-negative breast cancer patients treated by adjuvant anthracycline-based regimen. When p53 is positive in triple-negative breast cancer, we could expect poor survival, prompting aggressive or alternative treatment.}, }
@article {pmid19295274, year = {2009}, author = {Rai, Y and Sagara, Y and Ooi, Y and Sagara, Y and Sagara, Y and Baba, S and Tamada, S and Matsuyama, Y and Ando, M}, title = {[Preoperative therapy using trastuzumab and weekly paclitaxel in a stage IIIB inoperable locally advanced HER2- positive breast cancer with complete pathologic response].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {36}, number = {3}, pages = {471-473}, pmid = {19295274}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/*immunology/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/immunology/*therapeutic use ; Breast Neoplasms/*drug therapy/immunology/metabolism/*pathology ; Combined Modality Therapy ; Female ; Humans ; Immunotherapy ; Middle Aged ; Neoplasm Staging ; Paclitaxel/*therapeutic use ; Receptor, ErbB-2/*metabolism ; Trastuzumab ; Treatment Outcome ; }, abstract = {A 63-year-old woman had a 12 cm tumor on her right breast with broad skin redness, satellite lesions and 8 cm ipsilateral lymph nodes swelling(T4bN2aM0, Stage IIIB). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor(ER-, PgR-)and overexpression of HER2 (HercepTest 3+). She was treated with weekly paclitaxel(80 mg/m(2), 4 administrations with a week rest)and a com- bination with weekly trastuzumab(initially 4 mg/kg followed by 2 mg/kg every week, totally 11 administrations). After 3courses of administration, the breast tumor, skin redness and axillary swelling were completely disappeared(clinical complete response), then mastectomy with axillary dissection was performed. Histopathology of the breast and lymph nodes showed complete disappear of invasive cancer cells with only 2x1 mm residue of ductal component(pCR, grade 3, DC+). We conclude that the combination of weekly paclitaxel and trastuzumab is a promising neoadjuvant therapy regimen for HER2 positive, ER-negative breast cancer.}, }
@article {pmid19293840, year = {2009}, author = {Møller, DV and Andersen, PS and Hedley, P and Ersbøll, MK and Bundgaard, H and Moolman-Smook, J and Christiansen, M and Køber, L}, title = {The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy.}, journal = {European journal of human genetics : EJHG}, volume = {17}, number = {10}, pages = {1241-1249}, pmid = {19293840}, issn = {1476-5438}, mesh = {Adult ; Amino Acid Sequence ; Cardiomyopathy, Dilated/*genetics ; Cohort Studies ; Denmark ; Echocardiography/methods ; Electrophoresis, Capillary/methods ; Female ; Humans ; Male ; Molecular Sequence Data ; *Mutation ; Pedigree ; Phenotype ; Polymorphism, Single-Stranded Conformational ; Sarcomeres/*genetics/*metabolism ; Sequence Analysis, DNA ; }, abstract = {We investigated a Danish cohort of 31 unrelated patients with idiopathic dilated cardiomyopathy (IDC), to assess the role that mutations in sarcomere protein genes play in IDC. Patients were genetically screened by capillary electrophoresis single strand conformation polymorphism and subsequently by bidirectional DNA sequencing of conformers in the coding regions of MYH7, MYBPC3, TPM1, ACTC, MYL2, MYL3, TNNT2, CSRP3 and TNNI3. Eight probands carried disease-associated genetic variants (26%). In MYH7, three novel mutations were found; in MYBPC3, one novel variant and two known mutations were found; and in TNNT2, a known mutation was found. One proband was double heterozygous. We find evidence of phenotypic plasticity: three mutations described earlier as HCM causing were found in four cases of IDC, with no history of a hypertrophic phase. Furthermore, one pedigree presented with several cases of classic DCM as well as one case with left ventricular non-compaction. Disease-causing sarcomere gene mutations were found in about one-quarter of IDC patients, and seem to play an important role in the causation of the disease. The genetics is as complex as seen in HCM. Thus, our data suggest that a genetic work-up should include screening of the most prominent sarcomere genes even in the absence of a family history of the disease.}, }
@article {pmid19287511, year = {2009}, author = {Pavicic, WH and Laguens, M and Richard, SM}, title = {Analysis association between mitochondrial genome instability and xenobiotic metabolizing genes in human breast cancer.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {15}, number = {5-6}, pages = {160-165}, pmid = {19287511}, issn = {1528-3658}, mesh = {Arylamine N-Acetyltransferase/*genetics ; Breast Neoplasms/*genetics ; DNA, Mitochondrial/genetics ; *Genetic Predisposition to Disease ; Genome, Mitochondrial/*genetics ; *Genomic Instability ; Genotype ; Glutathione Transferase/*genetics ; Humans ; Polymorphism, Genetic/genetics ; }, abstract = {The aim of this study was to determine the existence of association between the genetic polymorphisms of metabolizing genes GSTM-1, GSTT-1, and NAT-2, and the presence of mitochondrial genome instability (mtGI) in breast cancer cases. Ninety-four pairs of tumoral/nontumoral breast cancer samples were analyzed. Our samples showed 40.42% of mtGI by analysis of two D-loop region markers, a (CA)n mtMS starting at the 514-bp position, and four informative MnlI sites between the 16,108-16,420-bp. GSTM-1 null genotype has shown a significant association with mtGI presence (chi(2) = 7.62; P = 0.006) in breast cancer cases; moreover, these genotypes also are related to an increased risk for mtDNA damage (odds ratio [OR] = 3.71 [1.41-9.88]; 95% Cornfield confidence interval [CI]). These results suggest that the absence of GSTM-1 enzymatic activity favors chemical actions in damaging the mtDNA. Analysis of GSTT-1 and NAT-2 polymorphisms showed no association with mtGI (chi(2) = 0.03; P = 0.87 and chi(2) = 2.76; P = 0.09, respectively). The analysis of invasive breast cancer cases showed mtGI in 74.36% of ILC cases (29 of 39 samples), and in only 18.75% (9 out of 48) IDC cases; this result suggests a possible relation between mtDNA mutations and variations in molecular pathways of tumor development.}, }
@article {pmid19283332, year = {2009}, author = {Plehn, G and Vormbrock, J and Lefringhausen, L and van Bracht, M and Plehn, A and Butz, T and Trappe, HJ and Meissner, A}, title = {Prevalence of ventricular discordance and its relation to functional capacity in idiopathic dilated cardiomyopathy.}, journal = {Clinical research in cardiology : official journal of the German Cardiac Society}, volume = {98}, number = {6}, pages = {371-378}, pmid = {19283332}, issn = {1861-0692}, mesh = {Cardiomyopathy, Dilated/*diagnosis/*epidemiology ; Comorbidity ; Female ; Germany/epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Assessment ; Risk Factors ; Ventricular Dysfunction, Left/*diagnosis/*epidemiology ; }, abstract = {INTRODUCTION: Although left ventricular (LV) dilatation is the most distinguishing morphologic feature of idiopathic dilated cardiomyopathy (IDC), right ventricular (RV) dilatation may variably contribute to total cardiac enlargement. The prevalence and functional importance of the relative degree of left and right ventricular dilatation has not been comprehensively studied using cardiac magnetic resonance imaging (MRI).<br><br>METHODS: Our prospective study included 58 consecutive IDC patients with a LV ejection fraction <40% and NYHA functional class > or =2. MRI was performed with a 1.5 Tesla scanner for RV and LV dimensional and functional analysis. Cardiopulmonary exercise testing was used for evaluation of exercise capacity. Patients were grouped into tertiles based on the distribution of LV end-diastolic volume.<br><br>RESULTS: Compared to control subjects a considerable heterogeneity in the relative degree of left and right ventricular dilatation was noted in IDC patients. Within the entire patient group, a strong correlation between the degree of ventricular volume discordance and the extent of LV enlargement was observed (r = 0.8; P < 0.001). Tertile analysis revealed that the LV/RV volume ratio significantly differed in the three subgroups of patients (1.0 +/- 0.3 vs. 1.5 +/- 0.4 vs. 2.1 +/- 0.9; P < 0.001). Only weak correlations between MRI data and patients' functional capacity were found. LV ejection fraction was identified as the only independent predictor of maximum oxygen consumption in our setting.<br><br>CONCLUSION: In IDC patients the degree of ventricular volume discordance is strongly related to the extent of left ventricular enlargement. However, comprehensive biventricular assessment of cardiac function by MRI adds little to our understanding of the cardiac mechanisms limiting exercise tolerance when compared to exclusive left ventricular measurements.}, }
@article {pmid19282847, year = {2009}, author = {Ilett, EJ and Prestwich, RJ and Kottke, T and Errington, F and Thompson, JM and Harrington, KJ and Pandha, HS and Coffey, M and Selby, PJ and Vile, RG and Melcher, AA}, title = {Dendritic cells and T cells deliver oncolytic reovirus for tumour killing despite pre-existing anti-viral immunity.}, journal = {Gene therapy}, volume = {16}, number = {5}, pages = {689-699}, pmid = {19282847}, issn = {1476-5462}, support = {R01 CA107082/CA/NCI NIH HHS/United States ; R01 CA175386/CA/NCI NIH HHS/United States ; R01130878//PHS HHS/United States ; CA RO1107082-02/CA/NCI NIH HHS/United States ; R01 CA130878/CA/NCI NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; Cell Death ; Cytotoxicity, Immunologic ; Dendritic Cells/*transplantation ; Lymph Nodes/virology ; Lymphatic Metastasis ; Melanoma, Experimental/immunology/pathology/*secondary/*therapy ; Mice ; Mice, Inbred C57BL ; Oncolytic Virotherapy/*methods ; Oncolytic Viruses/*immunology ; Reoviridae/immunology/isolation &amp; purification ; T-Lymphocytes/*transplantation ; Treatment Outcome ; Tumor Cells, Cultured ; Viral Load ; }, abstract = {Reovirus is a naturally occurring oncolytic virus currently in early clinical trials. However, the rapid induction of neutralizing antibodies represents a major obstacle to successful systemic delivery. This study addresses, for the first time, the ability of cellular carriers in the form of T cells and dendritic cells (DC) to protect reovirus from systemic neutralization. In addition, the ability of these cellular carriers to manipulate the subsequent balance of anti-viral versus anti-tumour immune response is explored. Reovirus, either neat or loaded onto DC or T cells, was delivered intravenously into reovirus-naive or reovirus-immune C57Bl/6 mice bearing lymph node B16tk melanoma metastases. Three and 10 days after treatment, reovirus delivery, carrier cell trafficking, metastatic clearance and priming of anti-tumour/anti-viral immunity were assessed. In naive mice, reovirus delivered either neat or through cell carriage was detectable in the tumour-draining lymph nodes 3 days after treatment, though complete clearance of metastases was only obtained when the virus was delivered on T cells or mature DC (mDC); neat reovirus or loaded immature DC (iDC) gave only partial early tumour clearance. Furthermore, only T cells carrying reovirus generated anti-tumour immune responses and long-term tumour clearance; reovirus-loaded DC, in contrast, generated only an anti-viral immune response. In reovirus-immune mice, however, the results were different. Neat reovirus was completely ineffective as a therapy, whereas mDC--though not iDC--as well as T cells, effectively delivered reovirus to melanoma in vivo for therapy and anti-tumour immune priming. Moreover, mDC were more effective than T cells over a range of viral loads. These data show that systemically administered neat reovirus is not optimal for therapy, and that DC may be an appropriate vehicle for carriage of significant levels of reovirus to tumours. The pre-existing immune status against the virus is critical in determining the balance between anti-viral and anti-tumour immunity elicited when reovirus is delivered by cell carriage, and the viral dose and mode of delivery, as well as the immune status of patients, may profoundly affect the success of any clinical anti-tumour viral therapy. These findings are therefore of direct translational relevance for the future design of clinical trials.}, }
@article {pmid19274027, year = {2009}, author = {Leone, A and Laudani, R and Definite, G and Martini, R and Andreozzi, GM}, title = {Unbalanced risk factors, could compromise the effectiveness of physical training in patients with intermittent claudication?.}, journal = {Minerva cardioangiologica}, volume = {57}, number = {2}, pages = {165-174}, pmid = {19274027}, issn = {0026-4725}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Analysis of Variance ; Cohort Studies ; Exercise Therapy/*methods ; Exercise Tolerance ; Female ; Humans ; Intermittent Claudication/diagnosis/physiopathology/*rehabilitation ; Male ; Middle Aged ; Multivariate Analysis ; Program Evaluation ; Recovery of Function ; Resistance Training ; Risk Factors ; Secondary Prevention ; Severity of Illness Index ; Smoking/adverse effects ; Treatment Outcome ; Walking ; }, abstract = {AIM: The correction of atherosclerotic risk factors is the unavoidable assumption to assure the maximal effectiveness and duration of the results of any therapeutic intervention (pharmacological and surgical) for the treatment of intermittent claudication. Aim of this study has been to verify if the presence/absence of risk factors and the degree of their correction could compromise the responsiveness of claudicant patients to the supervised physical training.<br><br>METHODS: Initial (IDC), absolute (ACD) claudication distance, and recovery time (RT) have been measured by maximal treadmill exercise in 74 claudicants. The measurements have been repeated after 18 days of supervised physical training consisting of a daily walk reaching either a distance goal of 1-2 km or a time goal of at least 30 min. The working load of each single training session has been tailored at 60-70% of the ACD measured by a non-maximal treadmill exercise. The patients' cohort has been stratified in 7 groups and 18 sub-groups (no smokers, smokers in the past, still smokers, no-diabetics, well balanced and unbalanced diabetes, absent, well balanced and unbalanced hypercholesterolemia, normal weight, over weight and light obesity, hypertensive and no-hypertensive, with and without previous myocardial infarction and TIAs or stroke). The mean and standard error of ICD, ACD and RT before and after 18 days of physical training have been calculated and compared with Student's t test in each group and sub-group. On the data before and after training of ICD, ACD and RT of each group of risk factors the multivariate analysis of the variance has been carried out by analysis of variance (ANOVA). All the analyses were considered significant when the P value was less than 0.05.<br><br>RESULTS: ICD values increased from 55.12 to 121.86 m, ACD from 103.16 to 191.58 m, RT reduced from 204.04 to 87.46 s, confirming the relevant (P<0.0001) effectiveness of supervised physical training on the walking capacity of claudicant patients. The comparison between the deltas (value after minus value before) of each sub-group did not show any significant difference. The multivariate ANOVA of before and after ICD ACD and RT of each risk factor groups showed values relevantly lesser than 0.05, indicating that risk factors did not influence the result of physical training.<br><br>CONCLUSIONS: The supervised physical training is confirmed as an effective tool for the treatment of claudicant patient. We did not find any significant difference in the response to the programme related with the presence, absence or balance degree of risk factors, and we conclude that physical training effectiveness is independent from the their presence, absence or balance degree. This statement is very important because highlights the physical training as the only therapeutic tool for peripheral arterial disease (PAD) independent from the results of the risk factors' treatment.}, }
@article {pmid19267929, year = {2009}, author = {Seniski, GG and Camargo, AA and Ierardi, DF and Ramos, EA and Grochoski, M and Ribeiro, ES and Cavalli, IJ and Pedrosa, FO and de Souza, EM and Zanata, SM and Costa, FF and Klassen, G}, title = {ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {80}, pmid = {19267929}, issn = {1471-2407}, mesh = {ADAM Proteins/*genetics ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Lobular/*genetics/pathology ; Cell Line, Tumor ; DNA Methylation ; Female ; Gene Expression/genetics ; *Gene Silencing ; Humans ; Middle Aged ; Promoter Regions, Genetic/genetics ; }, abstract = {BACKGROUND: ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer.<br><br>METHODS: First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test.<br><br>RESULTS: The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this difference was statistically significant (p = 0.0002).<br><br>CONCLUSION: ADAM33 gene silencing may be related to the discohesive histological appearance of ILCs. We suggest that ADAM33 promoter methylation may be a useful molecular marker for differentiating ILC and IDC.}, }
@article {pmid19267401, year = {2009}, author = {Chen, C and Zhou, Z and Sheehan, CE and Slodkowska, E and Sheehan, CB and Boguniewicz, A and Ross, JS}, title = {Overexpression of WWP1 is associated with the estrogen receptor and insulin-like growth factor receptor 1 in breast carcinoma.}, journal = {International journal of cancer}, volume = {124}, number = {12}, pages = {2829-2836}, doi = {10.1002/ijc.24266}, pmid = {19267401}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/pharmacology ; Biomarkers, Tumor/metabolism ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Carcinoma, Lobular/drug therapy/*metabolism/secondary ; Cell Proliferation/drug effects ; Estrogen Receptor alpha/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Small Interfering/pharmacology ; Receptor, IGF Type 1/*metabolism ; Tamoxifen/pharmacology ; Tumor Cells, Cultured ; Ubiquitin-Protein Ligases/antagonists &amp; inhibitors/genetics/*metabolism ; Up-Regulation ; }, abstract = {WWP1, a HECT type E3 ubiquitin ligase frequently amplified and overexpressed in breast cancer, has the potential to become a useful clinical biomarker and therapeutic target in breast cancer. Here, we performed immunohistochemical staining in formalin-fixed and paraffin-embedded tissue sections from 187 cases of primary invasive mammary carcinoma [137 ductal carcinomas (IDC) and 50 lobular carcinomas (ILC)] by using a monoclonal anti-WWP1 antibody. The normal breast epithelium and adjacent benign epithelium are essentially negative for WWP1. Cytoplasmic WWP1 immunoreactivity was observed in 76/187 (40.6%) tumors and showed a positive correlation with ERalpha (p = 0.05) and IGF-1R proteins (p = 0.001) in this cohort. The positive correlations between WWP1 and ER/IGF-1R were also observed in a panel of 12 breast cancer cell lines by Western blot. Interestingly, the ER levels are decreased when WWP1 is silenced in ER positive MCF7 and T47D breast cancer cell lines. Finally, WWP1 ablation collectively inhibits cell proliferation with tamoxifen in MCF7 and T47D, as measured by (3)H-thymidine incorporation assays. These findings suggest that WWP1 may play an important role in ER positive breast cancer.}, }
@article {pmid19266279, year = {2010}, author = {Chen, DT and Nasir, A and Culhane, A and Venkataramu, C and Fulp, W and Rubio, R and Wang, T and Agrawal, D and McCarthy, SM and Gruidl, M and Bloom, G and Anderson, T and White, J and Quackenbush, J and Yeatman, T}, title = {Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue.}, journal = {Breast cancer research and treatment}, volume = {119}, number = {2}, pages = {335-346}, pmid = {19266279}, issn = {1573-7217}, support = {R01 CA112215/CA/NCI NIH HHS/United States ; R01 CA098522-05/CA/NCI NIH HHS/United States ; P30 CA076292/CA/NCI NIH HHS/United States ; R01CA112215/CA/NCI NIH HHS/United States ; R01 CA 098522/CA/NCI NIH HHS/United States ; R01 CA112215-03/CA/NCI NIH HHS/United States ; R01 CA098522/CA/NCI NIH HHS/United States ; P30 CA076292-07/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*genetics/pathology/surgery ; Case-Control Studies ; *Cell Proliferation ; Female ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; *Genetic Testing ; Humans ; Mastectomy ; *Oligonucleotide Array Sequence Analysis ; Precancerous Conditions/chemistry/*genetics/pathology ; Principal Component Analysis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Risk Factors ; }, abstract = {Historical data have indicated the potential for the histologically-normal breast to harbor pre-malignant changes at the molecular level. We postulated that a histologically-normal tissue with "tumor-like" gene expression pattern might harbor substantial risk for future cancer development. Genes associated with these high-risk tissues were considered to be "malignancy-risk genes". From a total of 90 breast cancer patients, we collected a set of 143 histologically-normal breast tissues derived from patients harboring breast cancer who underwent curative mastectomy, as well as a set of 42 invasive ductal carcinomas (IDC) of various histologic grades. All samples were assessed for global gene expression differences using microarray analysis. For the purpose of this study we defined normal breast tissue to include histologically normal and benign lesions. Here we report the discovery of a "malignancy-risk" gene signature that may portend risk of breast cancer development in benign, but molecularly-abnormal, breast tissue. Pathway analysis showed that the malignancy-risk signature had a dramatic enrichment for genes with proliferative function, but appears to be independent of ER, PR, and HER2 status. The signature was validated by RT-PCR, with a high correlation (Pearson correlation = 0.95 with P < 0.0001) with microarray data. These results suggest a predictive role for the malignancy-risk signature in normal breast tissue. Proliferative biology dominates the earliest stages of tumor development.}, }
@article {pmid19256762, year = {2008}, author = {Nurismah, MI and Noriah, O and Suryati, MY and Sharifah, NA}, title = {E-cadherin expression correlates with histologic type but not tumour grade in invasive breast cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {9}, number = {4}, pages = {699-702}, pmid = {19256762}, issn = {2476-762X}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Breast Neoplasms/*chemistry/*pathology ; Cadherins/*analysis ; Carcinoma, Ductal, Breast/*chemistry/*pathology ; Carcinoma, Lobular/*chemistry/*pathology ; Chi-Square Distribution ; Cohort Studies ; Diagnosis, Differential ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness/genetics/*pathology ; Neoplasm Staging ; Probability ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {The traditional classification of infiltrating breast carcinomas into ductal and lobular can be diagnostically challenging in a small proportion of cases with equivocal histological features and in in-situ lesions with overlapping features. Distinguishing between the infiltrating ductal (IDC) and lobular (ILC) carcinomas is clinically important because of the different pattern of systemic metastases and prognostic evaluation. E-cadherin is a potentially useful immunohistochemical marker which may serve to differentiate between the two tumour types. We therefore studied E-cadherin expression in 32 cases of breast carcinomas comprising 16 IDCs and 16 ILCs. The correlation between E-cadherin expression and the histological grade of IDCs was also analysed. Our results showed complete loss of E-cadherin expression in all ILCs, while the IDCs consistently showed variable E-cadherin positivity. No significant correlation was found between E- cadherin expression and the histological grade of IDCs. We conclude from this study that E-cadherin is a useful marker to differentiate between IDC and ILC of the breast. A larger study of IDCs is now needed to further evaluate the correlation between E-cadherin and tumour grade to estimate its prognostic potential.}, }
@article {pmid19242778, year = {2009}, author = {Rokutanda, N and Horiguchi, J and Koibuchi, Y and Nagaoka, R and Sato, A and Odawara, H and Tokiniwa, H and Iino, Y and Hirato, J and Takeyoshi, I}, title = {Isolated retromammary lymph node metastasis of breast cancer without axillary lymph node involvement: a case report with a false-negative sentinel lymph node biopsy.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {2}, pages = {162-165}, doi = {10.1007/s12282-008-0089-1}, pmid = {19242778}, issn = {1880-4233}, mesh = {Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; False Negative Reactions ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Sentinel Lymph Node Biopsy ; }, abstract = {A 54-year-old woman visited our hospital with a palpable tumor in her left breast, which was diagnosed as invasive ductal carcinoma. Breast-conserving surgery was performed, in association with a sentinel lymph node (SLN) biopsy and back-up dissection of the axillary lymph nodes. One dyed axillary lymph node with high radioactivity was defined as an SLN, and intraoperative frozen-section analysis of the SLN was negative for metastasis. The final pathological diagnosis of the tumor was invasive ductal carcinoma, and one small lymph node, located in the retromammary space, just under the tumor, was positive for metastasis. The backup axillary lymph nodes were not metastatic. This patient was diagnosed false-negative by SLN biopsy, despite being positive for retroMLN metastasis. It should be recognized that retroMLNs are difficult to detect preoperatively, or intra-operatively, using dye or radiocolloid, if they are located in the post-tumoral retro-mammary space. RetroMLNs may be a pitfall in SLN biopsies.}, }
@article {pmid19242056, year = {2009}, author = {Mohammadizadeh, F and Ghasemibasir, H and Rajabi, P and Naimi, A and Eftekhari, A and Mesbah, A}, title = {Correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {5}, number = {1}, pages = {1-8}, doi = {10.3233/CBM-2009-0551}, pmid = {19242056}, issn = {1574-0153}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Female ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/metabolism ; Middle Aged ; Paraffin Embedding ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {BACKGROUND: Down-regulation of the epithelial cell-cell adhesion molecule E-cadherin is frequently associated with tumor formation and progression in breast cancer. The aim of this study is the assessment of relationship between E-cadherin expression and routine prognostic biomarkers as well as grading and lymph node status in breast invasive ductal carcinomas. . The associations between co-expression of E-cadherin and other biomarkers on one hand and grading, proliferating index and lymph node status on the other have also been evaluated.<br><br>OBJECTIVE: To evaluate the correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma.<br><br>METHODS: 108 formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma "NOS" type) from the pathology archive of Alzahra hospital(Isfahan, Iran) which had been studied for expression of routine molecular biomarkers were selected. E-cadherin expression was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing E-cadherin staining.<br><br>RESULTS: No association was found between E-cadherin alteration and ER, PR, p53, Ki67 and HER2/neu status of breast cancer. However, E-cadherin alteration showed a significant difference between grading and also lymph node groups. There was no association between co-expression of E-cadherin/ER, E-cadherin/PR, E-cadherin/Her-2neu, E-cadherin/p53 and Her-2neu/p53 on one hand and Ki67 status and tumor grade on the other. Co-expressions of E-cadherin/Her-2neu and E-cadherin/p53 showed significant difference in lymph node groups.<br><br>CONCLUSION: We found that E-cadherin alteration in breast cancer has an association with other important prognostic factors. Evaluation of E-cadherin status can help, independently or in addition to conventional biological prognostic markers, to identify prognosis of breast cancer.}, }
@article {pmid19239320, year = {2009}, author = {Cholujova, D and Jakubikova, J and Sedlak, J}, title = {BioBran-augmented maturation of human monocyte-derived dendritic cells.}, journal = {Neoplasma}, volume = {56}, number = {2}, pages = {89-95}, doi = {10.4149/neo_2009_02_89}, pmid = {19239320}, issn = {0028-2685}, mesh = {B7-1 Antigen/analysis ; B7-2 Antigen/analysis ; Cell Differentiation/drug effects ; Dendritic Cells/*drug effects/immunology/physiology ; Endocytosis/drug effects ; Humans ; Interleukin-3 Receptor alpha Subunit/analysis ; Monocytes/*cytology ; Receptors, Interleukin-3/analysis ; Xylans/*pharmacology ; }, abstract = {UNLABELLED: BioBran, enzymatically modified arabinoxylan from rice bran was tested for its possible effects on in vitro maturation of human dendritic cells (DC). Immature DC (iDC) derived from plastic-adhered, IL-4 and GM-CSF treated peripheral monocytes (Mo) were further cultured with cytokine maturation mix 1 (CMM1; TNF-alpha, IL-1beta and IL-6) or CMM2 (LPS and IFN-gamma) to induce their maturation into mature DC (matDC1 or matDC2, respectively). Different concentrations of BioBran (10, 100, 400 and 1000 microg/ml) were applied in the presence or absence of relevant CMM to assess the effects of BioBran on DC maturation processes. BioBran induced maturation of iDC, as these cells cultured with IL-4/GM-CSF/BioBran down-regulated CD14 and CD1a antigens on cell surface and significantly increased expression of maturation marker CD83. The increase of surface density of costimulatory molecules CD80 and CD86 on iDC in the presence of BioBran was also observed. In addition, BioBran induced functional maturation of iDC, confirmed by decreased endocytic activity of iDC. Further emore, BioBran enhanced maturation potential of cytokine mixes, as both matDC1 and matDC2 exposed to BioBran completely lost CD14 and upregulated CD83, CD80 and CD86 antigens, in comparison to DC matured with the relevant CMM alone. BioBran also increased CD123 antigen expression on all DC subsets. Interestingly, matDC2 matured in the presence of BioBran (400microg/ml) expressed higher levels of CD123 and lower levels of CD11c cell surface antigens, the phenotype represented by CD11c[dim] CD123[bright] plasmacytoid DC population. These data demonstrate that BioBran is a potent enhancer of DC maturation and suggest that BioBran might be a useful agent to create the environment that favours DC maturation.<br><br>KEYWORDS: Dendritic cell, maturation, BioBran, buffy coat.}, }
@article {pmid19225570, year = {2009}, author = {Keriel, A and Mahuteau-Betzer, F and Jacquet, C and Plays, M and Grierson, D and Sitbon, M and Tazi, J}, title = {Protection against retrovirus pathogenesis by SR protein inhibitors.}, journal = {PloS one}, volume = {4}, number = {2}, pages = {e4533}, pmid = {19225570}, issn = {1932-6203}, mesh = {Animals ; Animals, Newborn ; Indoles/*pharmacology ; Leukemia Virus, Murine/genetics/*pathogenicity ; Leukemia, Erythroblastic, Acute/drug therapy/*prevention &amp; control ; Mice ; Nuclear Proteins/*antagonists &amp; inhibitors ; RNA Splicing ; RNA-Binding Proteins ; Retroviridae ; Serine-Arginine Splicing Factors ; }, abstract = {Indole derivatives compounds (IDC) are a new class of splicing inhibitors that have a selective action on exonic splicing enhancers (ESE)-dependent activity of individual serine-arginine-rich (SR) proteins. Some of these molecules have been shown to compromise assembly of HIV infectious particles in cell cultures by interfering with the activity of the SR protein SF2/ASF and by subsequently suppressing production of splicing-dependent retroviral accessory proteins. For all replication-competent retroviruses, a limiting requirement for infection and pathogenesis is the expression of the envelope glycoprotein which strictly depends on the host splicing machinery. Here, we have evaluated the efficiency of IDC on an animal model of retroviral pathogenesis using a fully replication-competent retrovirus. In this model, all newborn mice infected with a fully replicative murine leukemia virus (MLV) develop erythroleukemia within 6 to 8 weeks of age. We tested several IDC for their ability to interfere ex vivo with MLV splicing and virus spreading as well as for their protective effect in vivo. We show here that two of these IDC, IDC13 and IDC78, selectively altered splicing-dependent production of the retroviral envelope gene, thus inhibiting early viral replication in vivo, sufficiently to protect mice from MLV-induced pathogenesis. The apparent specificity and clinical safety observed here for both IDC13 and IDC78 strongly support further assessment of inhibitors of SR protein splicing factors as a new class of antiretroviral therapeutic agents.}, }
@article {pmid19224162, year = {2009}, author = {Liu, C and Pan, H and Li, Z and Shi, L and Huang, T}, title = {Histopathological features of invasion of breast invasive ductal carcinoma and safety of breast-conserving surgery.}, journal = {Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban}, volume = {29}, number = {1}, pages = {50-52}, pmid = {19224162}, issn = {1672-0733}, mesh = {Adolescent ; Adult ; Aged ; Axilla ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy/methods ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics/*metabolism ; Young Adult ; }, abstract = {In order to investigate the relationship between the extent of tumor invasion and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery, the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed. The correlation analysis on invasive extent, which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre, and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading was processed. There was a significant correlation between invasive extent and tumor size (r=0.766, P<0.01), and lymph nodes metastases (r=0.574, P<0.01), but there was no significant correlation between invasive extent and Her-2 expression (r=0.106, P>0.05), and histologic grading (r=0.228, P>0.05). The 100% negative rate of infiltration in patients without nipple discharge with tumor size <2, 2-3 and >3 cm was obtained at 1.5, 2.0 and 2.5 cm away from the tumor respectively. It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.}, }
@article {pmid19215229, year = {2009}, author = {Niu, Y and Liu, T and Tse, GM and Sun, B and Niu, R and Li, HM and Wang, H and Yang, Y and Ye, X and Wang, Y and Yu, Q and Zhang, F}, title = {Increased expression of centrosomal alpha, gamma-tubulin in atypical ductal hyperplasia and carcinoma of the breast.}, journal = {Cancer science}, volume = {100}, number = {4}, pages = {580-587}, doi = {10.1111/j.1349-7006.2008.01075.x}, pmid = {19215229}, issn = {1349-7006}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Centrosome/metabolism ; Female ; Humans ; Immunohistochemistry ; Precancerous Conditions/genetics/metabolism/*pathology ; Tubulin/genetics/*metabolism ; }, abstract = {Centrosomal abnormalities have been found in various cancer types. We sought to determine whether centrosomal dysfunctions occur in the atypical ductal hyperplasia (ADH)-carcinoma sequence of breast cancer. As alpha and gamma-tubulins are the structural components of centrosomes, we performed real time quantitative polymerase chain reaction (qPCR), in situ hybridization (ISH) and immunnohistochemistry (IHC) to determine the DNA copy levels, messenger RNA (mRNA) expression, and protein expression of alpha and gamma-tubulins respectively. Gamma-tubulin staining was used for the localization and quantification of centrosomes. We found that alpha-tubulin or gamma-tubulin mRNA was increasingly expressed from normal breast tissue (NBT) to ADH, ductal carcinoma in situ (DCIS), and infiltrative ductal carcinoma (IDC), respectively, with the highest expressions being found in DCIS. The expression profiles of alpha, gamma-tubulin proteins were concordant with that of mRNA, except that the highest expression was found in IDC. Similarly, DNA copies of alpha, gamma-tubulins showed a rising tendency, with the highest level for gamma-tubulin attained in IDC and that for alpha-tubulin was found in DCIS. However, there was no significant difference of alpha, gamma-tubulin DNA copy levels, mRNA expression, and protein expression between DCIS and IDC. Our results demonstrate that centrosomal aberrations may play key roles in the early stage of breast tumorogenesis. The malignant transformation sequence is probably attributable to the amplification of centrosomal DNA leading to mRNA and protein over-expression of these centrosomal proteins. Furthermore, determination of alpha, gamma-tubulins using combined qPCR with ISH may be useful in assisting the diagnosis of premalignant lesions of the breast.}, }
@article {pmid19212625, year = {2009}, author = {Huang, GL and Zhang, XH and Guo, GL and Huang, KT and Yang, KY and Shen, X and You, J and Hu, XQ}, title = {Clinical significance of miR-21 expression in breast cancer: SYBR-Green I-based real-time RT-PCR study of invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {21}, number = {3}, pages = {673-679}, pmid = {19212625}, issn = {1021-335X}, mesh = {Benzothiazoles ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Diamines ; Female ; Humans ; Immunohistochemistry ; MicroRNAs/*biosynthesis ; Neoplasm Staging ; Organic Chemicals ; PTEN Phosphohydrolase/*biosynthesis ; Quinolines ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Growing evidence suggests microRNAs (miRNAs) have an important role in tumorigenesis. MicroRNA-21 (miR-21) is up-regulated in many malignant tumors, including breast cancer. Its association with clinicopathologic features and expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10), one of its target genes, in breast cancer has not been reported systematically. To further determine the potential involvement of miR-21 in breast cancer, we have evaluated the expression level of miR-21 by stem-loop real-time RT-PCR based on SYBR-Green I in human invasive ductal carcinoma of the breast, and we have correlated the results with clinicopathologic features and PTEN protein expression. Matched non-tumor and tumor tissues of 40 human invasive ductal carcinoma of the breast were analyzed for miR-21 expression by stem-loop real-time RT-PCR based on SYBR-Green I. Immunohistochemistry (IHC) was used to estimate PTEN expression in tumor tissue. The expression levels of miR-21 were correlated with PTEN and commonly used clinicopathologic features of breast cancer. The stem-loop real-time RT-PCR based on SYBR-Green I was sensitive and specific enough to detect miR-21. Expression levels of miR-21 were significantly higher in tumor tissues than the levels in matched non-tumor tissues (P=0.000). Expression of miR-21 was negatively correlated with expression of PTEN (P=0.013). Up-regulated miR-21 expression was associated with lymph node positivity (P=0.01), higher proliferation index (ki67>10%) (P=0.03) and advanced breast cancer TNM clinical stage (P=0.021). These findings suggest that PTEN is possibly one of the targets of miR-21 in breast cancer and high expression of mir-21 indicates a more aggressive phenotype.}, }
@article {pmid19207951, year = {2009}, author = {Faratian, D and Munro, A and Twelves, C and Bartlett, JM}, title = {Membranous and cytoplasmic staining of Ki67 is associated with HER2 and ER status in invasive breast carcinoma.}, journal = {Histopathology}, volume = {54}, number = {2}, pages = {254-257}, doi = {10.1111/j.1365-2559.2008.03191.x}, pmid = {19207951}, issn = {1365-2559}, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cell Membrane/metabolism ; Cytoplasm/metabolism ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/*metabolism ; Prognosis ; Receptor, ErbB-2/*genetics/metabolism ; Receptors, Estrogen/*metabolism ; }, abstract = {AIMS: Membranous and cytoplasmic Ki67 immunoreactivity has recently been observed in a number of histopathological entities, but frequency of occurrence and relationship to prognosis in more common cancers have not been described. The aim was to describe the pattern and frequency of membranous/cytoplasmic Ki67 in a cohort of invasive breast carcinomas, and their associations with grade, HER2 amplification and oestrogen receptor (ER) expression.<br><br>METHODS AND RESULTS: Three hundred and twenty-two cases of invasive ductal carcinoma were assessed for histological grade, Ki67 (MIB-1 clone) proliferation index and pattern of immunoreactivity, ER expression by immunohistochemistry, and HER2 amplification status by fluorescence in situ hybridization. Overall, 26/322 (8%) breast carcinomas showed membranous/cytoplasmic Ki67, and expression was significantly associated with grade 3, HER2-amplified and ER- tumours. Membranous/cytoplasmic Ki67 was not, however, an independent prognostic factor on multivariate analysis.<br><br>CONCLUSIONS: Membranous/cytoplasmic Ki67 identifies a group of breast carcinomas that may be important to consider separately in prognostic and predictive studies. The mechanism of subcellular Ki67 relocalization remains elusive and further studies are required to establish both the cause and effect of this unusual pattern of Ki67 immunoreactivity.}, }
@article {pmid19205420, year = {2008}, author = {Sarcević, B}, title = {[Histopathologic diagnosis of luminal and basal type breast cancer].}, journal = {Acta medica Croatica : casopis Hravatske akademije medicinskih znanosti}, volume = {62}, number = {4}, pages = {427-430}, pmid = {19205420}, issn = {1330-0164}, mesh = {Breast Neoplasms/diagnosis/genetics/*pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/*pathology ; Female ; Gene Expression Profiling ; Humans ; Oligonucleotide Array Sequence Analysis ; Prognosis ; }, abstract = {Despite tremendous advances in breast cancer characterization and therapy over the last 20 years, clinicians still have difficulty to accurately predict the prognosis in individual breast cancer patients. Patients with identical histologic tumor characteristics can have markedly different outcome in terms of distant metastasis-free and overall survival. The most common breast cancer is invasive ductal carcinoma, which is heterogeneous and according to immunohistochemical markers is divided in the luminal and basal type, as also identified by the recent expression profiling method. Microarray expression profiling is a novel method to further characterize breast cancer tumors at the gene expression level. Breast cancer subtypes have been described which display different biological behaviors. In addition, groups of genes known as gene-signatures have been identified, which provide more accurate prognostic factors than current clinical and histologic features. Future clinical decisions may rely on expression profiling of breast tumors.}, }
@article {pmid19201736, year = {2009}, author = {Lester, T and Wang, J and Bourne, P and Yang, Q and Fu, L and Tang, P}, title = {Different panels of markers should be used to predict mammary Paget's disease associated with in situ or invasive ductal carcinoma of the breast.}, journal = {Annals of clinical and laboratory science}, volume = {39}, number = {1}, pages = {17-24}, pmid = {19201736}, issn = {1550-8080}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*complications/pathology ; Carcinoma, Ductal, Breast/*complications/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/metabolism ; Nipples/pathology ; Paget's Disease, Mammary/*complications/*diagnosis/pathology ; }, abstract = {Mammary Paget's disease (MPD) is a rare manifestation of breast carcinoma involving the nipple. Our objective was to identify molecular markers and molecular subtypes that may predict patients at high risk of developing MPD. Immunohistochemical (IHC) analyses were performed with antibodies to estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, epidermal growth factor receptor (EGFR), and several cytokeratins (CK5/6, CK14, CK17, CK8, CK18) on representative sections of 121 cases of ductal carcinoma of the breast, including 28 cases with MPD, 81 cases with neither MPD nor nipple involvement, and 12 cases of non-MPD with nipple involvement. The rates of receptor expression and subtype distributions of 3 IHC-based molecular classifications were compared among these groups. The results showed that: (1) MPD is more likely to be associated with ER- and PR-negative ductal carcinoma in situ (DCIS), but not invasive ductal carcinoma (IDC); (2) MPD is more likely to be associated with HER2-over expression subtype DCIS, but not IDC; and (3) carcinomas with non-MPD nipple involvement differ from those with MPD, since they are more likely to be ER- and PR-positive, HER2-negative, and luminal A subtype. In summary, different panels of markers should be used to predict MPD associated with different underlying lesions; for DCIS, the ER-negative, PR-negative, and HER2-subtype and not basal-like subtype is most predictive of MPD; for IDC, the luminal B-subtype is most predictive of MPD.}, }
@article {pmid19190531, year = {2009}, author = {McGonagle, D and Aziz, A and Dickie, LJ and McDermott, MF}, title = {An integrated classification of pediatric inflammatory diseases, based on the concepts of autoinflammation and the immunological disease continuum.}, journal = {Pediatric research}, volume = {65}, number = {5 Pt 2}, pages = {38R-45R}, doi = {10.1203/PDR.0b013e31819dbd0a}, pmid = {19190531}, issn = {1530-0447}, mesh = {Adaptation, Physiological/immunology ; Child ; Humans ; Immune System Diseases/*immunology ; Immunity, Innate ; Inflammation/*classification/immunology ; }, abstract = {Historically, pediatric inflammatory diseases were viewed as autoimmune but developments in genetics of monogenic disease have supported our proposal that "inflammation against self" be viewed as an immunologic disease continuum (IDC), with genetic disorders of adaptive and innate immunity at either end. Innate immune-mediated diseases may be associated with significant tissue destruction without evident adaptive immune responses and are designated as autoinflammatory due to distinct immunopathologic features. However, the majority of pediatric inflammatory disorders are situated along this IDC. Innate immunity has been demonstrated in polygenic disorders, particularly Crohn's disease (CD). A genetic overlap exists between CD and some major histocompatibility complex (MHC) class I-associated diseases, including psoriasis; these diseases seem to represent a true intermediate between autoinflammation and autoimmunity. Conversely, classical autoimmune diseases, with autoantibody and MHC class II associations, including celiac disease and rheumatoid arthritis (RA), have adaptive immune genetic associations, including Cytotoxic T-Lymphocyte Antigen-4 (CTLA4) and PTPN22. This proposed classification is clinically relevant, because innate immune-mediated disorders may respond to cytokine antagonism whereas autoimmune-mediated diseases respond better to anti-T and B cell therapies. Furthermore, the etiopathogenesis of poorly defined "autoimmune" diseases, such as juvenile idiopathic arthritis, may be inferred to have substantial innate immune involvement, based on response to IL-1 antagonism.}, }
@article {pmid19190350, year = {2009}, author = {Nagasaki, S and Suzuki, T and Miki, Y and Akahira, J and Kitada, K and Ishida, T and Handa, H and Ohuchi, N and Sasano, H}, title = {17Beta-hydroxysteroid dehydrogenase type 12 in human breast carcinoma: a prognostic factor via potential regulation of fatty acid synthesis.}, journal = {Cancer research}, volume = {69}, number = {4}, pages = {1392-1399}, doi = {10.1158/0008-5472.CAN-08-0821}, pmid = {19190350}, issn = {1538-7445}, mesh = {17-Hydroxysteroid Dehydrogenases/genetics/*metabolism ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal/*enzymology/genetics/pathology ; Cell Division ; Estradiol/metabolism ; Fatty Acids/biosynthesis ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; Prognosis ; RNA Interference ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; }, abstract = {17beta-Hydroxysteroid dehydrogenase type 12 (17beta-HSD12) has been shown to be involved in elongation of very long chain fatty acid (VLCFA) as well as in biosynthesis of estradiol (E2). 17beta-HSD12 expression was also reported in breast carcinomas but its functions have remained unknown. In this study, we examined the correlation between mRNA expression profiles determined by microarray analysis and tissue E2 concentrations obtained from 16 postmenopausal breast carcinoma cases. No significant correlations were detected between 17beta-HSD12 expression and E2 concentration. We then immunolocalized this enzyme in 110 cases of invasive ductal carcinoma. 17beta-HSD12 immunoreactivity in breast carcinoma cells was significantly associated with poor prognosis of the patients. We further examined the biological significance of 17beta-HSD12 using cell-based studies. Small interfering RNA-mediated knockdown of 17beta-HSD12 in SK-BR-3 (estrogen receptor-negative breast carcinoma cell line) resulted in significant growth inhibition, which was recovered by the addition of VLCFAs such as arachidonic acid. The status of 17beta-HSD12 immunoreactivity was also correlated with adverse clinical outcome in cyclooxygenase 2 (COX2)-positive breast cancer patients but not in COX2-negative patients. Therefore, these findings indicated that 17beta-HSD12 was not necessarily related to intratumoral E2 biosynthesis, at least in human breast carcinoma, but was rather correlated with production of VLCFAs such as arachidonic acid, which may subsequently be metabolized to prostaglandins by COX2 and result in tumor progression of the patients.}, }
@article {pmid19187537, year = {2009}, author = {Ma, XJ and Dahiya, S and Richardson, E and Erlander, M and Sgroi, DC}, title = {Gene expression profiling of the tumor microenvironment during breast cancer progression.}, journal = {Breast cancer research : BCR}, volume = {11}, number = {1}, pages = {R7}, pmid = {19187537}, issn = {1465-542X}, support = {R01 CA112021/CA/NCI NIH HHS/United States ; R01-CA 112021-01/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Disease Progression ; Epithelial Cells/*metabolism/pathology ; Extracellular Matrix/metabolism/pathology ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*physiology ; Humans ; Immunoenzyme Techniques ; Lasers ; Microdissection ; Middle Aged ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stromal Cells/*metabolism/pathology ; }, abstract = {INTRODUCTION: The importance of the tumor microenvironment in breast cancer has been increasingly recognized. Critical molecular changes in the tumor stroma accompanying cancer progression, however, remain largely unknown. We conducted a comparative analysis of global gene expression changes in the stromal and epithelial compartments during breast cancer progression from normal to preinvasive to invasive ductal carcinoma.<br><br>METHODS: We combined laser capture microdissection and gene expression microarrays to analyze 14 patient-matched normal epithelium, normal stroma, tumor epithelium and tumor-associated stroma specimens. Differential gene expression and gene ontology analyses were performed.<br><br>RESULTS: Tumor-associated stroma undergoes extensive gene expression changes during cancer progression, to a similar extent as that seen in the malignant epithelium. Highly upregulated genes in the tumor-associated stroma include constituents of the extracellular matrix and matrix metalloproteases, and cell-cycle-related genes. Decreased expression of cytoplasmic ribosomal proteins and increased expression of mitochondrial ribosomal proteins were observed in both the tumor epithelium and the stroma. The transition from preinvasive to invasive growth was accompanied by increased expression of several matrix metalloproteases (MMP2, MMP11 and MMP14). Furthermore, as observed in malignant epithelium, a gene expression signature of histological tumor grade also exists in the stroma, with high-grade tumors associated with increased expression of genes involved in immune response.<br><br>CONCLUSIONS: Our results suggest that the tumor microenvironment participates in tumorigenesis even before tumor cells invade into stroma, and that it may play important roles in the transition from preinvasive to invasive growth. The immune cells in the tumor stroma may be exploited by the malignant epithelial cells in high-grade tumors for aggressive invasive growth.}, }
@article {pmid19181339, year = {2009}, author = {Masannat, YA and Hanby, A and Horgan, K and Hardie, LJ}, title = {DNA damaging effects of the dyes used in sentinel node biopsy: possible implications for clinical practice.}, journal = {The Journal of surgical research}, volume = {154}, number = {2}, pages = {234-238}, doi = {10.1016/j.jss.2008.07.039}, pmid = {19181339}, issn = {1095-8673}, mesh = {Breast Neoplasms/*pathology ; Cell Line, Transformed ; Cell Line, Tumor ; Coloring Agents/*toxicity ; *DNA Damage ; Epithelial Cells/drug effects/*pathology ; Humans ; In Vitro Techniques ; Indigo Carmine/toxicity ; Methylene Blue/toxicity ; Rosaniline Dyes/toxicity ; *Sentinel Lymph Node Biopsy ; }, abstract = {OBJECTIVE: This study investigates whether methylene blue (MB), patent blue V (PBV), and indigo carmine (IDC) commonly used in sentinel node biopsy cause DNA damage to breast epithelial cells in vitro.<br><br>METHODS: MCF-7 and HB-2 cells were exposed for 5 minutes to the above dyes at the same concentrations used in clinical practice. Following exposure, the comet assay was performed to detect DNA damage. The enzyme, Fapy-DNA glycosylase (FpG) was incorporated to enable the detection of additional oxidative damage.<br><br>RESULTS: Both PBV and MB stimulated DNA strand breaks in both MCF-7 and HB2 cell lines (P < 0.05). Levels were elevated over 3-fold (P < 0.05) in MCF-7 and HB2 cells treated with 2.5% PBV and 1% MB, compared with untreated control cells. In contrast, IDC did not stimulate DNA strand break damage at clinically relevant concentrations in either cell line. Addition of Fapy-DNA glycosylase enzyme also revealed significantly (P < 0.05) increased levels of oxidative DNA lesions (ODL) in MCF-7 cells treated with PBV (17.6% ODL) compared with control cells (5.9% ODL).<br><br>CONCLUSIONS: This study shows, for the first time, that certain dyes (MB and PBV) commonly used in SLNB have genotoxic effects on breast cells at clinically relevant concentrations in vitro. In vivo studies are now warranted to assess and minimize DNA damage caused by these dyes during SLNB.}, }
@article {pmid19173804, year = {2008}, author = {Bi, Y and Wei, L and Mao, HT and Zhang, L and Zuo, WS}, title = {[Expressions of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma and their relationship with clinicopathological factors].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {30}, number = {10}, pages = {749-753}, pmid = {19173804}, issn = {0253-3766}, mesh = {Adult ; Aged ; Antigens, CD/genetics/*metabolism ; Breast/metabolism ; Breast Neoplasms/*metabolism/pathology ; CTLA-4 Antigen ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Female ; GTP-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; RNA, Messenger/metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; fas Receptor/genetics/*metabolism ; }, abstract = {OBJECTIVE: The purpose of this study was to explore the clinical significance of expression of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma.<br><br>METHODS: Semi-quantitative reverse transcriptive polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression levels of the three genes in tumor tissues from 60 patients with primary breast cancer and normal breast tissues of 30 cases. The relationship between gene expression and clinicopathological factors were analyzed and determined.<br><br>RESULTS: The relative expression levels (gray scale ratio between target gene and internal reference gene) of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma tissues were 0.699 +/- 0.285, 1.045 +/- 0.302 and 0.625 +/- 0.160, respectively. In the normal breast tissues, they were 0.502 +/- 0.178, 0.418 +/- 0.140 and 0.843 +/- 0.218, respectively. There were statistically significant differences of the expression of those three genes between carcinoma tissues and normal breast tissues (P < 0.01). The expression level of Fas in carcinoma tissues was significantly higher in lymph node matastasis positive patients (0.782 +/- 0.313) than that in node-negative patients (0.557 +/- 0.146, P < 0.01). The expression level of CTLA-4 gene in carcinoma tissues was lower in II stage patients (0.978 +/- 0.330) than that in III stage patients (1.134 +/- 0.240, P < 0.05). The expression level of RhoBTB2 gene was lower in invasive ductal carcinoma (0.597 +/- 0.157) than that in invasive lobular carcinoma (0.717 +/- 0.145, P < 0.05). There were no correlations of expression of the three genes at mRNA level and age, ER, PR, HER2 status and survival time. Furthermore, no correlation was seen among the three genes expression (P > 0.05).<br><br>CONCLUSION: The expression of all the three genes at mRNA level is involved in genesis and progression of breast cancer. There exist correlations between Fas expression and axillary lymph node matastasis, CTLA-4 expression and disease stage, and RhoBTB2 expression and pathological type of breast cancer.}, }
@article {pmid19156836, year = {2009}, author = {Natrajan, R and Lambros, MB and Geyer, FC and Marchio, C and Tan, DS and Vatcheva, R and Shiu, KK and Hungermann, D and Rodriguez-Pinilla, SM and Palacios, J and Ashworth, A and Buerger, H and Reis-Filho, JS}, title = {Loss of 16q in high grade breast cancer is associated with estrogen receptor status: Evidence for progression in tumors with a luminal phenotype?.}, journal = {Genes, chromosomes &amp; cancer}, volume = {48}, number = {4}, pages = {351-365}, doi = {10.1002/gcc.20646}, pmid = {19156836}, issn = {1098-2264}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/*metabolism/pathology ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 16/*genetics ; Cluster Analysis ; Comparative Genomic Hybridization ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Genomic Instability ; Humans ; Immunohistochemistry ; Male ; Receptors, Estrogen/genetics/*metabolism ; }, abstract = {Loss of the long arm of chromosome 16 (16q) is observed in the vast majority of low grade/grade I (GI) invasive ductal carcinomas of no special type (IDC-NSTs), whereas this event is uncommonly seen in high grade/grade III (GIII) IDC-NSTs. Together with data on the pathology and genetics of breast cancer recurrences, this has led to the proposal that GI and GIII breast cancers evolve through distinct genetic pathways and that progression from GI to GIII is an unlikely biological phenomenon. We compared the genomic profiles of GIII-IDC-NSTs with 16q whole arm loss (16qWL) according to estrogen receptor (ER) status. 16qWL was found in 36.5% of cases and was significantly associated with ER expression and luminal phenotype. ER+ GIII-IDC-NSTs with 16qWL displayed significantly higher levels of genomic instability than ER+ IDC-NSTs without 16qWL. Furthermore, ER+ and ER- IDC-NSTs stratified according to the presence of 16qWL harbored distinct patterns of genetic aberrations. Interestingly, ER+/16qWL tumors displayed genetic features usually found in tumors with homologous DNA repair defects and significantly more frequently harbored heterozygous loss of BRCA2 than the remaining ER+ cancers. Our results demonstrate that approximately one third of GIII tumors harbor 16qWL, confirming that progression from low to high grade breast cancer is not found in the majority of breast cancers. 16qWL was significantly more prevalent in ER+/luminal GIII-IDC-NSTs. Given that GI breast cancers harbor a luminal phenotype, our results suggest that if progression from GI to GIII breast cancer does happen, it may preferentially occur in breast cancers of luminal phenotype.}, }
@article {pmid19153424, year = {2008}, author = {Irawan, C and Hukom, R and Prayogo, N}, title = {Factors associated with bone metastasis in breast cancer: a preliminary study in an Indonesian population.}, journal = {Acta medica Indonesiana}, volume = {40}, number = {4}, pages = {178-180}, pmid = {19153424}, issn = {0125-9326}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Bone Neoplasms/epidemiology/genetics/*secondary ; Breast Neoplasms/epidemiology/genetics/*pathology ; Cathepsin D/metabolism ; Chi-Square Distribution ; Cross-Sectional Studies ; Estrogen Replacement Therapy ; Female ; Humans ; Indonesia/epidemiology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Factors ; }, abstract = {AIM: to know the characteristics of breast cancer patients with bone metastasis and its risk factors.<br><br>METHODS: this was a cross-sectional study on breast cancer patients in Dharmais Cancer Hospital between 1998 and 2002. Data were retrieved from medical records and consisted of age, history of hormonal contraceptive use, histopathological type, estrogen receptor (ER) and progesteron receptor (PR) expression, c-erbB-2 and cathepsin D expressions.<br><br>RESULTS: a total of 197 cases were recruited between the study period. Almost all patients were women with a mean age of 47 years old. The majority of patients were between 36 and 55 years old (69.1%) with a peak between 46 and 50 years. About 70% of the patients had already had advanced diseases (III and IV). Invasive ductal carcinoma was the commonest histopathological type (80%). The expression of ER, PR, c-erbB-2, and cathepsin D were evaluated in 55 patients. Metastases were found to occur in bone (24.4%), lungs (20.8%), and liver (10.7%). Among patients with bone metastasis, 36 patients ((75%) were more than 40 years old and 32 (66.7%) had invasive ductal carcinomas. There was a significant correlation (p=0.011) between bone metastasis and histopathological type. No significant correlation was found between the use of hormonal contraceptives, ER/PR expression, c-erbB-2 and cathepsin D and bone metastasis.<br><br>CONCLUSION: most breast cancer patients came in an already advanced stage, either locally or distant metastasis. The most common site of metastasis was the bone, followed by lungs and liver. Histopathological type of invasive ductal carcinoma was associated to the higher incidence of bone metastasis. Further studies are needed to identify patients with high risk of bone metastasis. There is also a need to evaluate predictive factors for the occurrence of bone metastasis at earlier stage.}, }
@article {pmid19153192, year = {2009}, author = {Dietrich, D and Lesche, R and Tetzner, R and Krispin, M and Dietrich, J and Haedicke, W and Schuster, M and Kristiansen, G}, title = {Analysis of DNA methylation of multiple genes in microdissected cells from formalin-fixed and paraffin-embedded tissues.}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, volume = {57}, number = {5}, pages = {477-489}, pmid = {19153192}, issn = {0022-1554}, mesh = {Adipose Tissue/chemistry/pathology ; Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/chemistry/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/pathology ; *DNA Methylation ; Female ; Fibrocystic Breast Disease/chemistry/pathology ; *Fixatives ; *Formaldehyde ; Humans ; Indicators and Reagents ; Lasers ; Lymphocytes, Tumor-Infiltrating/chemistry ; Microdissection ; *Paraffin Embedding ; Polymerase Chain Reaction/methods ; Promoter Regions, Genetic ; Sequence Analysis, DNA/methods ; Stromal Cells/chemistry ; Sulfites ; }, abstract = {A procedure for simultaneous quantification of DNA methylation of several genes in minute amounts of sample material was developed and applied to microdissected formalin-fixed and paraffin-embedded breast tissues. The procedure is comprised of an optimized bisulfite treatment protocol suitable for samples containing only few cells, a multiplex preamplification and subsequent locus specific reamplification, and a novel quantitative bisulfite sequencing method based on the incorporation of a normalization domain into the PCR product. A real-time PCR assay amplifying repetitive elements was established to quantify low amounts of bisulfite-treated DNA. Ten prognostic and diagnostic epigenetic breast cancer biomarkers (PITX2, RASSF1A, PLAU, LHX3, PITX3, LIMK1, SLITRK1, SLIT2, HS3ST2, and TFF1) were analyzed in tissue samples obtained from two patients with invasive ductal carcinoma of the breast. The microdissected samples were obtained from several areas within the tumor tissue, including intraductal and invasive carcinoma, adenosis, and normal ductal epithelia of adjacent normal tissue, as well as stroma, tumor infiltrating lymphocytes, and adipose tissue. Overall, reliable quantification was possible for all genes. For most genes, increased DNA methylation in invasive and intraductal carcinoma cells compared with other tissue components was observed. For TFF1, decreased methylation levels were observed in tumor cells.}, }
@article {pmid19152796, year = {2009}, author = {Heo, YJ and Son, CH and Chung, JS and Park, YS and Son, JH}, title = {The cryopreservation of high concentrated PBMC for dendritic cell (DC)-based cancer immunotherapy.}, journal = {Cryobiology}, volume = {58}, number = {2}, pages = {203-209}, doi = {10.1016/j.cryobiol.2008.12.006}, pmid = {19152796}, issn = {1090-2392}, mesh = {Cell Differentiation ; Cell Survival ; Cells, Cultured ; Cryopreservation/instrumentation/*methods ; Dendritic Cells/*cytology/*immunology ; Humans ; Immunotherapy ; Leukocytes, Mononuclear/*cytology/immunology ; Lymphocyte Activation/immunology ; Time Factors ; }, abstract = {Peripheral blood mononuclear cells (PBMC) have been accepted as a unique material for cancer immunotherapy using dendritic cells (DC) or activated lymphocytes that are being developed as an alternative or adjuvant to conventional therapies such as surgery, chemotherapy and radiation treatment. Although successful cryopreservation of large numbers of PBMC is critical for the immunotherapy, subsequent functional study of the effects of PBMC cryopreservation on differentiation into immune cells has not been well defined. In this study, over 1.0 x 10(8)cells/ml PBMC were cryopreserved as long as 52 weeks using a controlled-rate freezer (CRF) and stored in a vapor phase of liquid nitrogen tank. The effect of PBMC cryopreservation on differentiation into DC was studied by comparing the phenotypic and functional properties of immature DC (iDC) and mature DC (mDC) derived from cryopreserved PBMC to those from fresh PBMC. The results show that cryopreservation of PBMC at a fairly high cell concentration does not significantly affect cell recovery, viability, or phenotypes of PBMC. After differentiation into DC, iDC and mDC derived from cryopreserved PBMC had their typical phenotypes and function equivalent to those derived from fresh PBMC. Therefore, the improved cryopreservation process of PBMC described in this study is available for DC-based cancer immunotherapy.}, }
@article {pmid19151330, year = {2009}, author = {Sims, JS and Militello, KT and Sims, PA and Patel, VP and Kasper, JM and Wirth, DF}, title = {Patterns of gene-specific and total transcriptional activity during the Plasmodium falciparum intraerythrocytic developmental cycle.}, journal = {Eukaryotic cell}, volume = {8}, number = {3}, pages = {327-338}, pmid = {19151330}, issn = {1535-9786}, support = {F32 AI050303/AI/NIAID NIH HHS/United States ; R01 GM061351/GM/NIGMS NIH HHS/United States ; GM61351-03/GM/NIGMS NIH HHS/United States ; AI050303-01/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Erythrocytes/*parasitology ; *Gene Expression Regulation, Developmental ; Humans ; Malaria, Falciparum/*parasitology ; Plasmodium falciparum/genetics/*growth &amp; development/metabolism ; Protozoan Proteins/*genetics/metabolism ; *Transcription, Genetic ; }, abstract = {The relationships among gene regulatory mechanisms in the malaria parasite Plasmodium falciparum throughout its asexual intraerythrocytic developmental cycle (IDC) remain poorly understood. To investigate the level and nature of transcriptional activity and its role in controlling gene expression during the IDC, we performed nuclear run-on on whole-transcriptome samples from time points throughout the IDC and found a peak in RNA polymerase II-dependent transcriptional activity related to both the number of nuclei per parasite and variable transcriptional activity per nucleus over time. These differential total transcriptional activity levels allowed the calculation of the absolute transcriptional activities of individual genes from gene-specific nuclear run-on hybridization data. For half of the genes analyzed, sense-strand transcriptional activity peaked at the same time point as total activity. The antisense strands of several genes were substantially transcribed. Comparison of the transcriptional activity of the sense strand of each gene to its steady-state RNA abundance across the time points assayed revealed both correlations and discrepancies, implying transcriptional and posttranscriptional regulation, respectively. Our results demonstrate that such comparisons can effectively indicate gene regulatory mechanisms in P. falciparum and suggest that genes with diverse transcriptional activity levels and patterns combine to produce total transcriptional activity levels tied to parasite development during the IDC.}, }
@article {pmid19144278, year = {2008}, author = {Buttari, B and Profumo, E and Mancinelli, R and Cesta Incani, U and Tosti, ME and Attilia, ML and Ceccanti, M and Riganò, R}, title = {Chronic and acute alcohol exposure prevents monocyte-derived dendritic cells from differentiating and maturing.}, journal = {International journal of immunopathology and pharmacology}, volume = {21}, number = {4}, pages = {929-939}, doi = {10.1177/039463200802100417}, pmid = {19144278}, issn = {0394-6320}, mesh = {Adolescent ; Adult ; Alcoholism/*immunology ; Cell Differentiation/*drug effects ; Dendritic Cells/*drug effects/immunology/metabolism ; Endocytosis ; Ethanol/*administration &amp; dosage/toxicity ; Female ; Flow Cytometry ; Humans ; Lipopolysaccharides/pharmacology ; Male ; Middle Aged ; Monocytes/*cytology ; NF-kappa B/metabolism ; }, abstract = {Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics inverted exclamation mark| monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-alpha and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.}, }
@article {pmid19128816, year = {2009}, author = {Le Nouën, C and Munir, S and Losq, S and Winter, CC and McCarty, T and Stephany, DA and Holmes, KL and Bukreyev, A and Rabin, RL and Collins, PL and Buchholz, UJ}, title = {Infection and maturation of monocyte-derived human dendritic cells by human respiratory syncytial virus, human metapneumovirus, and human parainfluenza virus type 3.}, journal = {Virology}, volume = {385}, number = {1}, pages = {169-182}, pmid = {19128816}, issn = {1096-0341}, support = {Z99 AI999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {ADP-ribosyl Cyclase 1/metabolism ; Adult ; Animals ; Apoptosis ; Cell Line ; Cells, Cultured ; Chlorocebus aethiops ; Cytokines/metabolism ; Dendritic Cells/cytology/*virology ; Gene Expression Regulation ; Humans ; Metapneumovirus/*physiology ; Monocytes/immunology/virology ; Parainfluenza Virus 3, Human/*physiology ; Paramyxoviridae Infections/*virology ; RNA, Viral/metabolism ; Respiratory Syncytial Virus Infections/*virology ; Respiratory Syncytial Virus, Human/*physiology ; Respirovirus Infections/*virology ; Vero Cells ; Viral Fusion Proteins/genetics/immunology/metabolism ; }, abstract = {Human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza virus type 3 (HPIV3) are common, important respiratory pathogens, but HRSV has a substantially greater impact with regard to acute disease, long-term effects on airway function, and frequency of re-infection. It has been reported to strongly interfere with the functioning of dendritic cells (DC). We compared HRSV to HMPV and HPIV3 with regard to their effects on human monocyte-derived immature DC (IDC). Side-by-side analysis distinguished between common effects versus those specific to individual viruses. The use of GFP-expressing viruses yielded clear identification of robustly infected cells and provided the means to distinguish between direct effects of robust viral gene expression versus bystander effects. All three viruses infected inefficiently based on GFP expression, with considerable donor-to donor-variability. The GFP-negative cells exhibited low, abortive levels of viral RNA synthesis. The three viruses induced low-to-moderate levels of DC maturation and cytokine/chemokine responses, increasing slightly in the order HRSV, HMPV, and HPIV3. Infection at the individual cell level was relatively benign, such that in general GFP-positive cells were neither more nor less able to mature compared to GFP-negative bystanders, and cells were responsive to a secondary treatment with lipopolysaccharide, indicating that the ability to mature was not impaired. However, there was a single exception, namely that HPIV3 down-regulated CD38 expression at the RNA level. Maturation by these viruses was anti-apoptotic. Inefficient infection of IDC and sub-optimal maturation might result in reduced immune responses, but these effects would be common to all three viruses rather than specific to HRSV.}, }
@article {pmid19122965, year = {2008}, author = {Padungchaichote, W and Kongmebhol, P and Muttarak, M}, title = {Clinics in diagnostic imaging (125). Diagnosis: Suspicious right breast carcinoma with axillary node metastases.}, journal = {Singapore medical journal}, volume = {49}, number = {12}, pages = {1062-5; quiz 1066}, pmid = {19122965}, issn = {2737-5935}, mesh = {Axilla ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/pathology/secondary ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*diagnostic imaging/pathology ; Lymphatic Metastasis ; *Mammography ; Middle Aged ; Neoplasms, Second Primary/diagnostic imaging ; Ovarian Neoplasms/pathology ; }, abstract = {A 61-year-old woman who had a known history of ovarian carcinoma presented with a palpable painless mass in the right axilla. Mammograms showed segmental-distributed pleomorphic microcalcifications in the upper outer quadrant of the right breast with marked enlargement of the right axillary nodes. The biggest node contained microcalcifications. Right axillary node dissection showed metastatic adenocarcinoma which was likely to be metastasis from the primary breast carcinoma. Unfortunately, she was then lost to follow-up and came back again with a right breast mass. Histopathology of the right breast mass revealed invasive ductal carcinoma. The causes and differential diagnosis of axillary adenopathy are discussed. In a patient with known primary extramammary malignancy and axillary adenopathy, it is important to differentiate if it is metastasis from the primary breast carcinoma or extramammary malignancy to provide proper management.}, }
@article {pmid19121212, year = {2009}, author = {Shen, C and Gu, M and Liang, D and Miao, L and Hu, L and Zheng, C and Chen, J}, title = {Establishment and characterization of three new human breast cancer cell lines derived from Chinese breast cancer tissues.}, journal = {Cancer cell international}, volume = {9}, number = {}, pages = {2}, pmid = {19121212}, issn = {1475-2867}, abstract = {BACKGROUND: Breast cancer is a major malignancy affecting females worldwide. It is the most common cause of death from cancer in women. Cell lines are widely used in laboratory research and particularly as in vitro models in cancer research. But we found that the routinely used breast cancer cell lines were mostly derived from Caucasians or African-Americans. There were few standard models to study the pathogenic mechanism at molecular level and cell signaling pathway of breast cancer for Asian patients. It is quite necessary to establish new breast cancer cell lines from xanthoderm to study the pathogenic mechanism and therapeutic methods.<br><br>RESULTS: Three new breast cancer cell lines, designated BC-019, BC-020 and BC-021, were successfully established and characterized from breast invasive ductal carcinoma tissues of three Chinese female patients. These new cell lines growing as adherent monolayer with characteristic epithelial morphology could be maintained continuously in vitro, and they were ER-, PR- and C-erbB-2-positive. Their chromosomes showed high hyperdiploidy and complex rearrangements, and they displayed aggressive tumorigencity in tumorigenesis test.<br><br>CONCLUSION: The three newly established breast cancer cell lines from Chinese patients were tested for a number of, and the results indicate that the cell lines were in good quality and could be served as new cell models in breast cancer study.}, }
@article {pmid19121206, year = {2009}, author = {Gujral, DM and Quante, M and Simcock, RA}, title = {An unusual cause of dysphagia in ductal breast cancer due to submucosal oropharyngeal metastatic spread: a case report.}, journal = {Cases journal}, volume = {2}, number = {1}, pages = {3}, pmid = {19121206}, issn = {1757-1626}, abstract = {INTRODUCTION: Invasive ductal and lobular carcinomas represent 67.9% and 6.3% of breast carcinoma, respectively. Metastatic breast cancer typically involves the lungs, bones, brain, and liver. Studies have shown differing patterns of metastatic spread between ductal and lobular carcinoma. Lobular carcinoma is more likely to metastasise to the gastrointestinal tract.<br><br>CASE PRESENTATION: We report the case of a 49 year old white woman with invasive ductal carcinoma with lobular differentiation who developed submucosal oropharyngeal metastases nearly two years after her original diagnosis after presenting with odynophagia and dysphagia. The patient's symptoms preceded any associated radiological or endoscopic abnormalities by at least 9 months. Repeat computed tomography scan and eventual oropharyngeal biopsy confirmed submucosal metastatic invasive ductal carcinoma, suggesting occult submucosal spread.<br><br>CONCLUSION: This case illustrates the importance of maintaining a high index of suspicion for metastatic disease in patients with invasive breast cancer who present with unusual symptoms and a careful search for metastatic sites.}, }
@article {pmid19121176, year = {2008}, author = {Bubenik, L and Hosgood, G}, title = {Urinary tract infection in dogs with thoracolumbar intervertebral disc herniation and urinary bladder dysfunction managed by manual expression, indwelling catheterization or intermittent catheterization.}, journal = {Veterinary surgery : VS}, volume = {37}, number = {8}, pages = {791-800}, doi = {10.1111/j.1532-950X.2008.00452.x}, pmid = {19121176}, issn = {1532-950X}, mesh = {Animals ; Dog Diseases/*therapy ; Dogs ; Female ; Intervertebral Disc Displacement/complications/therapy/*veterinary ; Male ; Risk Factors ; Time Factors ; Treatment Outcome ; Urinary Bladder Diseases/complications/therapy/*veterinary ; Urinary Catheterization/adverse effects/methods/*veterinary ; Urinary Tract Infections/epidemiology/etiology/*veterinary ; Urination/physiology ; }, abstract = {OBJECTIVE: To evaluate risk factors for lower urinary tract infection (UTI) in dogs with intervertebral disc disease (IVDD) that had manual expression (ME), indwelling catheterization (IDC) or intermittent catheterization (ITC) for urinary bladder management.<br><br>STUDY DESIGN: Randomized-clinical trial.<br><br>ANIMALS: Dogs (n=62) treated with urinary bladder dysfunction requiring surgery for IVDD and control dogs (n=30) that had surgery for reasons other than IVDD.<br><br>METHODS: Treated dogs were randomly assigned to ME, IDC, or ITC. Urine was collected for culture and antimicrobial susceptibility testing before and after treatment. Incidence and risk factors for UTI were evaluated. Bacterial isolates and antimicrobial resistance patterns were described.<br><br>RESULTS: Mean (+/-SD) time to urination was significantly longer for IDC dogs (7.4+/-2.75 days) than ME dogs (4.2+/-2.63) and ITC dogs (4.9+/-3.12). Thirteen treated dogs (21%) and no control dogs developed UTI: 4/25 (16%) ME, 8/25 (32%) IDC, and 1/12 (8%) ITC. Enterobacter sp. was most frequently isolated (4/13; 31%). Duration of treatment was the only risk factor for UTI and each additional day of treatment increased the risk of UTI 1.5 times.<br><br>CONCLUSION: For dogs with acute IVDD, the duration of required urinary bladder management establishes the risk of UTI, not the urinary bladder management technique.<br><br>CLINICAL RELEVANCE: Duration of treatment for urinary bladder dysfunction is a risk factor for UTI in dogs recovering from acute IVDD. Treatment for urinary bladder management should be limited where possible and no method of treatment is preferred. For dogs managed by IDC, voluntary urination might occur before clinically suspected.}, }
@article {pmid19119011, year = {2009}, author = {Csankovszki, G and Collette, K and Spahl, K and Carey, J and Snyder, M and Petty, E and Patel, U and Tabuchi, T and Liu, H and McLeod, I and Thompson, J and Sarkeshik, A and Yates, J and Meyer, BJ and Hagstrom, K}, title = {Three distinct condensin complexes control C. elegans chromosome dynamics.}, journal = {Current biology : CB}, volume = {19}, number = {1}, pages = {9-19}, pmid = {19119011}, issn = {1879-0445}, support = {R01 GM079533/GM/NIGMS NIH HHS/United States ; R01 GM030702/GM/NIGMS NIH HHS/United States ; T32 GM07544/GM/NIGMS NIH HHS/United States ; P41 RR011823/RR/NCRR NIH HHS/United States ; R01 GM076378/GM/NIGMS NIH HHS/United States ; R01 GM30702/GM/NIGMS NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; R01 GM030702-28/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adenosine Triphosphatases/*genetics/metabolism/*physiology ; Animals ; Caenorhabditis elegans/*genetics/physiology ; Cell Nucleus Division/physiology ; Chromosome Segregation/*physiology ; Chromosomes/*genetics/metabolism ; DNA-Binding Proteins/*genetics/metabolism/*physiology ; Dosage Compensation, Genetic/*genetics/physiology ; Evolution, Molecular ; Gene Expression Regulation/*genetics/physiology ; Immunoprecipitation ; *Models, Biological ; Multiprotein Complexes/*genetics/metabolism/*physiology ; Proteomics/methods ; RNA Interference ; }, abstract = {BACKGROUND: Condensin complexes organize chromosome structure and facilitate chromosome segregation. Higher eukaryotes have two complexes, condensin I and condensin II, each essential for chromosome segregation. The nematode Caenorhabditis elegans was considered an exception, because it has a mitotic condensin II complex but appeared to lack mitotic condensin I. Instead, its condensin I-like complex (here called condensin I(DC)) dampens gene expression along hermaphrodite X chromosomes during dosage compensation.<br><br>RESULTS: Here we report the discovery of a third condensin complex, condensin I, in C. elegans. We identify new condensin subunits and show that each complex has a conserved five-subunit composition. Condensin I differs from condensin I(DC) by only a single subunit. Yet condensin I binds to autosomes and X chromosomes in both sexes to promote chromosome segregation, whereas condensin I(DC) binds specifically to X chromosomes in hermaphrodites to regulate transcript levels. Both condensin I and II promote chromosome segregation, but associate with different chromosomal regions during mitosis and meiosis. Unexpectedly, condensin I also localizes to regions of cohesion between meiotic chromosomes before their segregation.<br><br>CONCLUSIONS: We demonstrate that condensin subunits in C. elegans form three complexes, one that functions in dosage compensation and two that function in mitosis and meiosis. These results highlight how the duplication and divergence of condensin subunits during evolution may facilitate their adaptation to specialized chromosomal roles and illustrate the versatility of condensins to function in both gene regulation and chromosome segregation.}, }
@article {pmid22059352, year = {2009}, author = {Ghoneim, HM and Maher, S and Abdel-Aty, A and Saad, A and Kazem, A and Demian, SR}, title = {Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping.}, journal = {The Egyptian journal of immunology}, volume = {16}, number = {2}, pages = {37-48}, pmid = {22059352}, issn = {1110-4902}, mesh = {Age Factors ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/*immunology/pathology/physiopathology ; Carcinoma/*diagnosis/*immunology/pathology/physiopathology ; Chemokine CCL2/metabolism ; Disease Progression ; Female ; Humans ; Immune Evasion ; Interleukin-8/metabolism ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Microenvironment ; }, abstract = {Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand-2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings.}, }
@article {pmid21686476, year = {2009}, author = {Garas, G and Stacey-Clear, A and Whitaker, S and Collyer, J}, title = {An atypical presentation of breast cancer metastasis.}, journal = {BMJ case reports}, volume = {2009}, number = {}, pages = {}, pmid = {21686476}, issn = {1757-790X}, abstract = {A 78-year-old woman heard a crack in her left mandible while eating a biscuit and reported to her dentist, who urgently referred her to the oral and maxillofacial surgery department. On examination she had a lesion in the body of her left mandible, which had eroded through the lower border and caused a pathological fracture. Her past medical history included a left mastectomy and level II axillary lymph node dissection for a 27 mm grade III invasive ductal carcinoma of the left breast 9 months prior to her mandibular fracture. A transoral incisional biopsy was performed which confirmed the mandibular lesion to be an osteolytic metastasis from the breast. The metastasis was subsequently surgically removed and the remaining mandible repaired with a reconstruction plate followed by postoperative radiotherapy. The patient regained full function of her mandible and is now eating normally. She is being closely followed-up in the oncology outpatient department.}, }
@article {pmid20635772, year = {2009}, author = {Doron, G and Moulding, R}, title = {Cognitive behavioral treatment of obsessive compulsive disorder: a broader framework.}, journal = {The Israel journal of psychiatry and related sciences}, volume = {46}, number = {4}, pages = {257-263}, pmid = {20635772}, issn = {0333-7308}, mesh = {Cognitive Behavioral Therapy/*methods ; Combined Modality Therapy ; Cross-Sectional Studies ; Culture ; Health Education/methods ; Humans ; Implosive Therapy/methods ; Obsessive-Compulsive Disorder/epidemiology/psychology/*therapy ; Professional-Patient Relations ; Reality Testing ; Secondary Prevention ; Self Concept ; }, abstract = {Obsessive Compulsive Disorder (OCD) is rated as a leading cause of disability by the World Health Organization (1996). OCD is a heterogeneous and complex anxiety disorder characterized by the occurrence of repeated and distressing intrusive thoughts, and compulsive actions that are performed in order to lessen distress or prevent the negative outcome associated with the intrusions. Over the last several decades, cognitive behavioral treatments (CBT) of OCD have dramatically improved the prognosis for the disorder. However, a significant proportion of individuals presenting with OCD may still fail to benefit from treatment. In this paper, we present current CBT treatment models of OCD. We then propose several ways of enhancing CBT for OCD by targeting clients' attachment anxiety and dysfunctional self perceptions.}, }
@article {pmid19116033, year = {2008}, author = {Gur-Dedeoglu, B and Konu, O and Kir, S and Ozturk, AR and Bozkurt, B and Ergul, G and Yulug, IG}, title = {A resampling-based meta-analysis for detection of differential gene expression in breast cancer.}, journal = {BMC cancer}, volume = {8}, number = {}, pages = {396}, pmid = {19116033}, issn = {1471-2407}, mesh = {Breast/metabolism ; Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism ; Carcinoma, Lobular/genetics/metabolism ; Databases, Genetic ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures.<br><br>METHODS: A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis.<br><br>RESULTS: The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively). The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real-time qRT-PCR supported the meta-analysis results.<br><br>CONCLUSION: The proposed meta-analysis approach has the ability to detect a set of differentially expressed genes with the least amount of within-group variability, thus providing highly stable gene lists for class prediction. Increased statistical power and stringent filtering criteria used in the present study also make identification of novel candidate genes possible and may provide further insight to improve our understanding of breast cancer development.}, }
@article {pmid19115704, year = {2008}, author = {Aydin, O and Bagci, P and Akyildiz, EU and Ozguroglu, M and Ilvan, S}, title = {Metastasis from breast carcinoma to endometrial polyp.}, journal = {European journal of gynaecological oncology}, volume = {29}, number = {6}, pages = {666-668}, pmid = {19115704}, issn = {0392-2936}, mesh = {Bone Neoplasms/*secondary ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Endometrial Neoplasms/*secondary ; Fatal Outcome ; Female ; Humans ; Middle Aged ; }, abstract = {Metastasis of a breast carcinoma to an endometrial polyp is extremely rare, with only ten cases having been reported in the literature up to now. We present the case of a 60-year-old woman with invasive ductal carcinoma who complained of vaginal bleeding. She underwent hysteroscopy with biopsy. Microscopic examination revealed an endometrial polyp which contained foci of adenocarcinoma. The morphologic features of the tumor were identical to the original breast carcinoma.}, }
@article {pmid19101238, year = {2009}, author = {Chen, CA and Hsiao, CH and Wang, JK and Lin, MT and Wu, ET and Chiu, SN and Chiu, HH and Wu, MH}, title = {Implication of QRS prolongation and its relation to mechanical dyssynchrony in idiopathic dilated cardiomyopathy in childhood.}, journal = {The American journal of cardiology}, volume = {103}, number = {1}, pages = {103-109}, doi = {10.1016/j.amjcard.2008.08.044}, pmid = {19101238}, issn = {1879-1913}, mesh = {Adolescent ; Cardiomyopathy, Dilated/*drug therapy/epidemiology/physiopathology ; Cardiotonic Agents/administration &amp; dosage/*therapeutic use ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; *Electrocardiography ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Injections, Intravenous ; Male ; Morbidity/trends ; Retrospective Studies ; Risk Factors ; Survival Rate/trends ; Taiwan/epidemiology ; Time Factors ; Treatment Outcome ; Ventricular Function, Left/drug effects/physiology ; }, abstract = {We explored the role of QRS prolongation (>or=120 ms) and its relation to mechanical dyssynchrony and outcomes in childhood idiopathic dilated cardiomyopathy (IDC). A total of 89 patients <or=18 years old diagnosed as having IDC (21 days to 26 years of follow-up) were investigated. In 20 survivors with residual left ventricular (LV) dysfunction, mechanical (interventricular and intra-LV) dyssynchrony was assessed. The SD of time from the beginning of QRS prolongation to peak systolic contraction was measured in 12 LV segments by tissue Doppler imaging. A cut-off value >32.6 ms was used to define intra-LV dyssynchrony. The 1- and 5-year survivals were 70% and 53%, respectively. Requirement of intravenous inotropes at follow-up (hazard ratio 3.10) and initial LV ejection fraction (hazard ratio 0.95) were major prognostic factors. QRS prolongation, primarily left bundle branch block, was identified in 16 patients (18%) and tended to increase the risk of requiring inotropes. Moreover, none of those with QRS prolongation regained normal cardiac function at follow-up. Two patients with QRS prolongation showed marked improvement in cardiac function after cardiac resynchronization therapy. Mechanical dyssynchrony was noted in all patients with QRS prolongation and in 8% (interventricular) or 38% (intra-LV) of those without. In conclusion, QRS prolongation was common in childhood IDC and was possibly associated with persistent LV dysfunction and worse cardiac outcome. Mechanical (inter- and intraventricular) dyssynchrony was highly prevalent in those with QRS prolongation and was still often observed in those without.}, }
@article {pmid19099607, year = {2008}, author = {Yu, J and Ohuchida, K and Nakata, K and Mizumoto, K and Cui, L and Fujita, H and Yamaguchi, H and Egami, T and Kitada, H and Tanaka, M}, title = {LIM only 4 is overexpressed in late stage pancreas cancer.}, journal = {Molecular cancer}, volume = {7}, number = {}, pages = {93}, pmid = {19099607}, issn = {1476-4598}, mesh = {AMP-Activated Protein Kinase Kinases ; Adaptor Proteins, Signal Transducing ; Analysis of Variance ; Carcinoma, Pancreatic Ductal/genetics/pathology ; Carcinoma, Papillary/genetics/pathology ; Cell Line, Tumor ; *Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/*genetics ; Humans ; LIM Domain Proteins ; Neoplasm Staging ; Pancreatic Neoplasms/*genetics/pathology ; Protein Serine-Threonine Kinases/genetics ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: LIM-only 4 (LMO4), a member of the LIM-only (LMO) subfamily of LIM domain-containing transcription factors, was initially reported to have an oncogenic role in breast cancer. We hypothesized that LMO4 may be related to pancreatic carcinogenesis as it is in breast carcinogenesis. If so, this could result in a better understanding of tumorigenesis in pancreatic cancer.<br><br>METHODS: We measured LMO4 mRNA levels in cultured cells, pancreatic bulk tissues and microdissected target cells (normal ductal cells; pancreatic intraepithelial neoplasia-1B [PanIN-1B] cells; PanIN-2 cells; invasive ductal carcinoma [IDC] cells; intraductal papillary-mucinous adenoma [IPMA] cells; IPM borderline [IPMB] cells; and invasive and non-invasive IPM carcinoma [IPMC]) by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR).<br><br>RESULTS: 9 of 14 pancreatic cancer cell lines expressed higher levels of LMO4 mRNA than did the human pancreatic ductal epithelial cell line (HPDE). In bulk tissue samples, expression of LMO4 was higher in pancreatic carcinoma than in intraductal papillary-mucinous neoplasm (IPMN) or non-neoplastic pancreas (p < 0.0001 for both). We carried out microdissection-based analyses. IDC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia or PanIN-1B cells (p < 0.001 for both) or PanIN-2 cells (p = 0.014). IPMC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia (p < 0.001), IPMA (p < 0.001) and IPMB cells (p = 0.003).<br><br>CONCLUSION: Pancreatic carcinomas (both IDC and IPMC) expressed significantly higher levels of LMO4 mRNA than did normal ductal epithelia, PanIN-1B, PanIN-2, IPMA and IPMB. These results suggested that LMO4 is overexpressed at late stages in carcinogenesis of pancreatic cancer.}, }
@article {pmid19095807, year = {2009}, author = {Oztoprak, I and Oztoprak, B and Gümüş, C and Eğilmez, H and Erkoç, MF}, title = {An abdominal muscular fold mimicking tumour.}, journal = {The British journal of radiology}, volume = {82}, number = {973}, pages = {e1-2}, doi = {10.1259/bjr/25402966}, pmid = {19095807}, issn = {1748-880X}, mesh = {Abdominal Muscles/*diagnostic imaging ; Abdominal Neoplasms/diagnosis/*secondary ; Aged ; *Breast Neoplasms ; Carcinoma, Ductal, Breast/diagnosis/*secondary ; Diagnosis, Differential ; Female ; Humans ; Muscular Atrophy/*diagnostic imaging ; Tomography, X-Ray Computed ; }, abstract = {Mass-like lesions and anatomical variations sometimes create challenges for diagnosis in both clinical and radiology practice. We present a "pseudomass" originating from the right abdominal wall in a 75-year-old patient with invasive ductal carcinoma of the breast. Age-related structural changes in the abdominal wall, as well as anatomical variations, should be kept in mind in order to establish the correct radiological diagnosis and to avoid unnecessary procedures.}, }
@article {pmid19086167, year = {2008}, author = {Wei, G and Kalaitzakis, E and Bergquist, A and Björnsson, E}, title = {Long-term follow-up of patients with acute liver failure of indeterminate aetiology.}, journal = {Scandinavian journal of gastroenterology}, volume = {43}, number = {8}, pages = {984-991}, doi = {10.1080/00365520801965399}, pmid = {19086167}, issn = {0036-5521}, mesh = {Acetaminophen/*adverse effects ; Adult ; Analgesics, Non-Narcotic/adverse effects ; Budd-Chiari Syndrome/*complications ; Disease Progression ; Female ; Follow-Up Studies ; Hepatitis, Viral, Human/*complications ; Humans ; Liver Failure, Acute/diagnosis/*etiology/surgery ; *Liver Transplantation ; Male ; Middle Aged ; Mushroom Poisoning/*complications ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; }, abstract = {OBJECTIVE: To determine the clinical characteristics of patients with acute liver failure of indeterminate cause and their long-term outcome in comparison with patients with acute liver failure of obvious aetiology (acetaminophen and mushroom poisoning, Budd-Chiari syndrome, acute viral hepatitis) and other controls (idiosyncratic drug reactions, autoimmune hepatitis and Wilson's disease).<br><br>MATERIAL AND METHODS: All patients with acute liver failure and listed for liver transplantation in Sweden between 1984 and 2006 were included in a retrospective analysis.<br><br>RESULTS: A total of 71 patients with acute liver failure were identified, 33 with indeterminate cause (IDC group), 23 with obvious aetiology (OE group) and 15 other controls (OC group). Before admission to the transplant centre, IDC patients were hospitalized in the referring hospital for 9 days (4-15) versus 1.5 days (1-3) in the OE group (p<0.001) and 7 days (2-14) in the OC group (NS). Serum bilirubin was higher (p<0.001), whereas peak creatinine was lower (p=0.001) in the IDC group compared with the OE group but was not significantly different from the OC group. There were no significant differences in 1-, 3-, 5- and 10-year patient and graft survival rates between the IDC group and the OE or the OC group.<br><br>CONCLUSIONS: Patients with acute liver failure of indeterminate cause seem to differ from those with obvious aetiology in clinical and biochemical presentation but are similar to other controls. The overall long-term outcome seems to be similar in patients with an unknown aetiology as in those with a specific aetiology.}, }
@article {pmid19085710, year = {2008}, author = {Ikeda, Y and Morita, N and Ikeda, T}, title = {Metachronous rectal metastasis from invasive ductal carcinoma of the male breast.}, journal = {Endoscopy}, volume = {40 Suppl 2}, number = {}, pages = {E108-9}, doi = {10.1055/s-2007-995392}, pmid = {19085710}, issn = {1438-8812}, mesh = {Breast Neoplasms, Male/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Humans ; Liver Neoplasms/*secondary ; Male ; Middle Aged ; Rectal Neoplasms/pathology/*secondary ; }, }
@article {pmid19080492, year = {2008}, author = {Huang, GL and Zhang, XH and Guo, GL and Huang, KT and Yang, KY and Hu, XQ}, title = {[Expression of microRNA-21 in invasive ductal carcinoma of the breast and its association with phosphatase and tensin homolog deleted from chromosome expression and clinicopathologic features].}, journal = {Zhonghua yi xue za zhi}, volume = {88}, number = {40}, pages = {2833-2837}, pmid = {19080492}, issn = {0376-2491}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Gene Expression ; Humans ; MicroRNAs/*biosynthesis/genetics ; Middle Aged ; Neoplasm Invasiveness ; PTEN Phosphohydrolase/*genetics ; }, abstract = {OBJECTIVE: To investigate the expression of microRNA-21 (mir-21) in invasive ductal carcinoma (IDC) of the breast and its association with phosphatase and tensin homologue deleted from chromosome (PTEN)-10 protein expression and the clinicopathologic features of IDC.<br><br>METHODS: Specimens of IDC and normal tissues more than 5 cm away from the tumor tissues were collected from 40 IDC patients, all female, aged 53 (35-77). Stem-loop real-time RT-PCR was used to examine the mir-21 expression. Immunohistochemistry was used to examine the PTEN protein expression in the tumor tissue. The association of mir-21 expression with the PTEN expression and the clinicopathologic features of the breast IDC were analyzed.<br><br>RESULTS: Compared with the nontumor control samples, the median (M) of relative expression of mir-21 (2(-DeltadeltaCt)) was 5.770 (25th-75th percentile, 3.605-7.255) in the tumor samples, significantly higher than that of the nontumor control samples (set at 1.000, P<0.001). Reduced PTEN protein expression was seen in 45% (18/22) of all cases. The expression of mir-21 was higher in the group of reduced PTEN expression (with an M of 6.800) than in the group of high PTEN expression (with an M of 4.850, P=0.013). The up-regulated expression of mir-21 was positively correlated with the TNM clinical stage, lymph node positivity, and proliferation index (P=0.021, 0.010, and 0.030 respectively).<br><br>CONCLUSION: mir-21 plays an important role in the development and progression of breast cancer. PTEN is possibly one of the targets of mir-21.}, }
@article {pmid19080258, year = {2008}, author = {Wang, TT and Frezza, EE and Ma, R and Hu, SY and Liu, CZ and Zhang, GY and Wachtel, MS and Lü, XM and Feng, JB and Lü, CX}, title = {Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities.}, journal = {Chinese medical journal}, volume = {121}, number = {20}, pages = {1969-1974}, pmid = {19080258}, issn = {0366-6999}, mesh = {Acid Anhydride Hydrolases/analysis/*genetics ; Breast/*pathology ; Breast Neoplasms/*genetics ; *Chromosome Fragile Sites ; Female ; *Genes, Tumor Suppressor ; Humans ; Hyperplasia ; Neoplasm Proteins/analysis/*genetics ; Oxidoreductases/analysis/*genetics ; Tumor Suppressor Proteins/analysis/*genetics ; WW Domain-Containing Oxidoreductase ; }, abstract = {BACKGROUND: WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.<br><br>METHODS: Reverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.<br><br>RESULTS: Compared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).<br><br>CONCLUSION: Expression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.}, }
@article {pmid19066611, year = {2009}, author = {Millar, EK and Anderson, LR and McNeil, CM and O'Toole, SA and Pinese, M and Crea, P and Morey, AL and Biankin, AV and Henshall, SM and Musgrove, EA and Sutherland, RL and Butt, AJ}, title = {BAG-1 predicts patient outcome and tamoxifen responsiveness in ER-positive invasive ductal carcinoma of the breast.}, journal = {British journal of cancer}, volume = {100}, number = {1}, pages = {123-133}, pmid = {19066611}, issn = {1532-1827}, mesh = {Breast Neoplasms/chemistry/*drug therapy/pathology ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/pathology ; Cell Line, Tumor ; DNA-Binding Proteins/analysis/genetics/*physiology ; Estrogen Antagonists/*therapeutic use ; Female ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; RNA, Messenger/analysis ; Receptors, Estrogen/*analysis ; Tamoxifen/*therapeutic use ; Transcription Factors/analysis/genetics/*physiology ; }, abstract = {BAG-1 (bcl-2-associated athanogene) enhances oestrogen receptor (ER) function and may influence outcome and response to endocrine therapy in breast cancer. We determined relationships between BAG-1 expression, molecular phenotype, response to tamoxifen therapy and outcome in a cohort of breast cancer patients and its influence on tamoxifen sensitivity in MCF-7 breast cancer cells in vitro. Publically available gene expression data sets were analysed to identify relationships between BAG-1 mRNA expression and patient outcome. BAG-1 protein expression was assessed using immunohistochemistry in 292 patients with invasive ductal carcinoma and correlated with clinicopathological variables, therapeutic response and disease outcome. BAG-1-overexpressing MCF-7 cells were treated with antioestrogens to assess its effects on cell proliferation. Gene expression data demonstrated a consistent association between high BAG-1 mRNA and improved survival. In ER+ cancer (n=189), a high nuclear BAG-1 expression independently predicted improved outcome for local recurrence (P=0.0464), distant metastases (P=0.0435), death from breast cancer (P=0.009, hazards ratio 0.29, 95% CI: 0.114-0.735) and improved outcome in tamoxifen-treated patients (n=107; P=0.0191). BAG-1 overexpression in MCF-7 cells augmented antioestrogen-induced growth arrest. A high BAG-1 expression predicts improved patient outcome in ER+ breast carcinoma. This may reflect both a better definition of the hormone-responsive phenotype and a concurrent increased sensitivity to tamoxifen.}, }
@article {pmid19052036, year = {2009}, author = {Gao, D and Du, J and Cong, L and Liu, Q}, title = {Risk factors for initial lung metastasis from breast invasive ductal carcinoma in stages I-III of operable patients.}, journal = {Japanese journal of clinical oncology}, volume = {39}, number = {2}, pages = {97-104}, doi = {10.1093/jjco/hyn133}, pmid = {19052036}, issn = {1465-3621}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; ErbB Receptors/*analysis ; Female ; Humans ; Lung Neoplasms/*secondary ; Mastectomy, Radical ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate high-risk factors for initial lung metastases from breast invasive ductal carcinomas in operable patients with Stages I-III invasive ductal carcinoma.<br><br>METHODS: Data of all patients who underwent radical mastectomy were reviewed retrospectively, and they were confirmed with invasive ductal breast cancer between January 2003 and December 2007. Routine clinical examination data of patients included in the study at primary diagnosis, adjuvant modes and first metastasis sites were recorded. Possible risk factors were easily identified from patients. Twenty-eight potential risk factors were investigated. Finally, 78 patients with complete data in the potential factors were found eligible, and univariate and multivariate analyses were conducted.<br><br>RESULTS: Univariate analyses showed that the status of estrogen receptor (ER) and progesterone receptor (PR) and the status of the epidermal growth factor receptor-2 (Her2) were high-risk factors for invasive ductal breast cancer metastasis to the lung as the first organ. P values were, respectively, 0.045, 0.049 and 0.026. Multivariate analyses showed that the pN3 stage needs to be combined with vascular invasion to predict initial lung metastasis. The status of ER and PR was also viewed in combination with p53 negative to predict lung metastasis. Further analyses demonstrated that a subtype of four negative in breast cancer was significantly associated with initial lung metastasis.<br><br>CONCLUSIONS: Patients with pN3 stage and vascular invasion were more likely to develop lung metastasis. A new subtype with Her2 negative, both ER-negative and PR negative combination with p53 negative, had a great tendency to develop initial lung metastasis in breast invasive ductal cancer patients.}, }
@article {pmid19047898, year = {2009}, author = {Downs-Kelly, E and Nayeemuddin, KM and Albarracin, C and Wu, Y and Hunt, KK and Gilcrease, MZ}, title = {Matrix-producing carcinoma of the breast: an aggressive subtype of metaplastic carcinoma.}, journal = {The American journal of surgical pathology}, volume = {33}, number = {4}, pages = {534-541}, doi = {10.1097/PAS.0b013e31818ab26e}, pmid = {19047898}, issn = {1532-0979}, mesh = {Adenocarcinoma/*secondary/therapy ; Adult ; Aged ; Breast Neoplasms/*pathology/therapy ; Calcinosis ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Chondrogenesis ; Disease-Free Survival ; Extracellular Matrix/*pathology ; Female ; Humans ; Lymph Nodes/pathology ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local ; }, abstract = {Matrix-producing carcinoma (MPC) of the breast is a subtype of metaplastic carcinoma defined as an invasive breast carcinoma with a direct transition of carcinoma to cartilaginous or osseous matrix without an intervening spindle cell component. Our aims were (1) to evaluate specific histologic characteristics of MPC and correlate these with disease recurrence; and (2) to determine whether rates of locoregional and distant recurrence for MPC are significantly different from those of invasive ductal carcinoma. Thirty-two cases of MPC were identified. Fourteen patients (44%) were < or =50 years of age; 10 (31%) had tumors of size < or =2 cm, and 6 (19%) had tumors > or =5 cm. In this series, all tumors contained chondromyxoid or chondroid matrix, and 1 (3.1%) also contained focal (<5%) osseous matrix. High-grade matrix was present in 9 cases (28%), and low-grade matrix was present in 23 (72%). Matrix comprised < or =10% of the tumor in 14 cases (44%), >10% but <40% in 9 (28%), and > or =40% in 9 (28%). The carcinomatous component was high grade in 30 cases (94%), and 19 tumors (59%) had central necrosis. Seven patients (22%) had positive axillary lymph nodes, and 8 (25%) had lymphovascular space invasion (LVSI). LVSI was the only factor independently associated with locoregional recurrence-free survival in multivariate analysis (P=0.043). Although > or =40% matrix was associated with improved distant recurrence-free (DFS) survival in univariate analysis (P=0.044), only LVSI and tumor stage were independently associated with DFS survival in multivariate analysis (P=0.027 and P=0.001, respectively). Compared with matched controls with invasive ductal carcinoma, patients with MPC had decreased locoregional recurrence-free survival (P=0.001) and decreased DRF survival (P=0.001). In summary, MPC is an aggressive subtype of metaplastic carcinoma with a worse clinical outcome than invasive ductal carcinoma.}, }
@article {pmid19047897, year = {2009}, author = {Shin, SJ and Simpson, PT and Da Silva, L and Jayanthan, J and Reid, L and Lakhani, SR and Rosen, PP}, title = {Molecular evidence for progression of microglandular adenosis (MGA) to invasive carcinoma.}, journal = {The American journal of surgical pathology}, volume = {33}, number = {4}, pages = {496-504}, doi = {10.1097/PAS.0b013e31818af361}, pmid = {19047897}, issn = {1532-0979}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/genetics/*pathology ; Carcinoma in Situ/chemistry/genetics/*pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/genetics/*pathology ; *Chromosome Aberrations ; Comparative Genomic Hybridization ; DNA, Neoplasm/analysis ; Disease Progression ; Female ; Fibrocystic Breast Disease/chemistry/genetics/*pathology ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization ; Karyotyping ; Microdissection ; Middle Aged ; }, abstract = {Microglandular adenosis (MGA) is an uncommon, benign breast lesion that is characterized by a proliferation of small uniform, round glands lined by a single layer of epithelial cells around open lumina with haphazard infiltrative growth in fibrous and fatty breast tissue. Although MGA usually has an indolent course, there is morphologic evidence that MGA can be a precursor for the development of intraductal and invasive ductal carcinoma. To investigate the possibility of such a transition, we studied 17 cases of MGA or atypical MGA some of which had given rise to carcinoma in situ (CIS) and/or invasive ductal carcinoma using the reticulin stain, immunohistochemistry (S-100, p63, Ki-67, and p53), and a molecular approach involving microdissection and high-resolution comparative genomic hybridization and MYC chromogenic in situ hybridization. MGA and carcinomas arising from MGA were typically negative for p63 and positive for S-100 and Ki-67 and occasionally positive for p53. High-resolution comparative genomic hybridization identified recurrent gains and losses in MGA (2q+, 5q-, 8q+, and 14q-) and atypical MGA (1q+, 5q-, 8q+, 14q-, and 15q-). Some examples of MGA and carcinomas arising from MGA harbored few gross chromosomal abnormalities whereas others had considerable genetic instability with widespread aberrations affecting numerous chromosomal arms. Such widespread genetic changes, together with recurrent loss of 5q and gain of 8q were reminiscent of those reported specifically for basal-like, estrogen receptor-negative, and BRCA1-associated breast tumors. Concordant genetic alterations were identified between MGA, atypical MGA, and higher risk lesions (CIS and invasive ductal carcinoma) and in some cases there was an accumulation of genetic alterations as cases "progressed" from MGA to atypical MGA, CIS, and invasive ductal carcinoma. The molecular data suggests that MGA, atypical MGA, and carcinoma arising in MGA in a single case were clonally related. This result implicates MGA as a nonobligate precursor for the development of intraductal and invasive ductal carcinoma.}, }
@article {pmid19047097, year = {2008}, author = {Farrell, CJ and Zaupa, C and Barnard, Z and Maley, J and Martuza, RL and Rabkin, SD and Curry, WT}, title = {Combination immunotherapy for tumors via sequential intratumoral injections of oncolytic herpes simplex virus 1 and immature dendritic cells.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {14}, number = {23}, pages = {7711-7716}, pmid = {19047097}, issn = {1078-0432}, support = {R01 NS032677/NS/NINDS NIH HHS/United States ; R01 NS032677-16/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/immunology/therapeutic use ; Combined Modality Therapy ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; Herpesvirus 1, Human/immunology ; Immunohistochemistry ; Immunotherapy/*methods ; Interferon-gamma/biosynthesis ; Mice ; Neoplasms, Experimental/*therapy ; Oncolytic Virotherapy/*methods ; }, abstract = {PURPOSE: Oncolytic herpes simplex virus 1 (oHSV) vectors treat tumors in preclinical models and have been used safely in phase I clinical trials for patients with cancer. Infection of tumors with oHSV also induces specific antitumor immunity. We investigated whether this immunotherapeutic effect is enhanced by combining oHSV infection with intratumoral administration of immature myeloid dendritic cells (iDC).<br><br>EXPERIMENTAL DESIGN: Subcutaneous neuroblastoma tumors were established in syngeneic immunocompetent mice and sequentially treated with oHSV(G47Delta) and intratumoral iDCs. Tumor volumes and survival were monitored. Antitumor immune responses were evaluated by immunohistochemistry, IFN-gamma ELISPOT, and CTL assay. Treatment was also evaluated in immunodeficient NOD-SCID mice.<br><br>RESULTS: We observed significant reductions in tumor volumes in mice receiving G47Delta + iDCs compared with those treated with G47Delta or iDC monotherapy. Survival was prolonged, with approximately 90% of tumors eradicated in the combination group. Combination therapy led to enhancement of antitumor immune responses, confirmed by increases in IFN-gamma expression by splenocytes harvested from G47Delta + iDC-treated mice. Splenocytes harvested from G47Delta + iDC-treated mice were effective against neuroblastoma tumor cells in a CTL assay. Immunohistochemistry of combination-treated tumors revealed robust lymphocytic infiltrates. Adding iDCs to G47Delta infection in tumors in NOD-SCID mice did not reduce the rate of growth. Substitution of lipopolysaccharide-matured dendritic cells abrogated the enhanced tumor volume reduction seen with combination therapy with iDCs.<br><br>CONCLUSIONS: Combination treatment of murine tumors with oHSV and iDCs reduces the volume of established tumors and prolongs survival via enhancement of antitumor immunity.}, }
@article {pmid19037993, year = {2009}, author = {Tamaki, K and Moriya, T and Sato, Y and Ishida, T and Maruo, Y and Yoshinaga, K and Ohuchi, N and Sasano, H}, title = {Vasohibin-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis.}, journal = {Cancer science}, volume = {100}, number = {1}, pages = {88-94}, doi = {10.1111/j.1349-7006.2008.01015.x}, pmid = {19037993}, issn = {1349-7006}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/mortality ; Cell Cycle Proteins/analysis/*physiology ; Feedback, Physiological ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic/*etiology ; Platelet Endothelial Cell Adhesion Molecule-1/analysis ; Vascular Endothelial Growth Factor A/analysis/antagonists &amp; inhibitors ; }, abstract = {Vasohibin-1 is a recently identified negative feedback inhibitor or suppressor of angiogenesis induced by vascular endothelial growth factor (VEGF)-A. The status of vasohibin-1 in human breast carcinoma has not been examined. We examined 151 breast specimens including 98 cases of invasive ductal carcinoma (IDC), 12 of ductal carcinoma in situ (DCIS), 16 of fibroadenoma (FA), six of inflammatory lesion, nine of fibrocystic change and seven of non-pathological breast tissue. We immunolocalized vasohibin-1 and compared its immunoreactivity to that of VEGF-A, basic fibroblastic growth factor (bFGF), VEGF receptor 2 (Flk-1), CD31, CD34 and Ki-67/MIB-1. The correlation of vasohibin-1 immunoreactivity with overall survival (OS), and disease-free survival (DFS) of the patients with breast carcinoma was also evaluated. In addition, we evaluated Ki-67 and CD31, and Ki-67 and vasohibin-1 double-immunostaining for further characterization of neovascularization. Vasohibin-1 was detected in endothelial cells of human breast and its immunodensity was significantly higher in IDC and inflammatory lesions than the other types (P<0.001). In addition, a significant positive correlation was detected between vasohibin-1 and VEGF-A, bFGF or Flk-1 (P<0.001). There was also positive associations between vasohibin-1 and OS (P=0.004) and between vasohibin-1 and DFS (P<or=0.001) in carcinoma cases. Results of double-immunostaining demonstrated the ratio of Ki-67-positive cells among vasohibin-1-positive endothelial cells (46.5%) was significantly higher than those among CD31-positive cells (23.5%). This is the first study demonstrating the status of vasohibin-1 in human breast lesions, which indicates that vasohibin-1 is associated with neovascularization and may especially play important roles in the regulation of intratumoral angiogenesis in human breast cancer.}, }
@article {pmid19035318, year = {2008}, author = {Harnack, U and Pecher, G}, title = {Impact of antigen-unloaded immature dendritic cells on antileukemic T-cell cytotoxicity.}, journal = {Anticancer research}, volume = {28}, number = {5A}, pages = {2831-2835}, pmid = {19035318}, issn = {0250-7005}, mesh = {Animals ; B7-1 Antigen/immunology ; B7-2 Antigen/immunology ; CD11c Antigen/immunology ; Cell Line, Tumor ; Coculture Techniques ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology/pharmacology ; Leukemia, B-Cell/immunology/*therapy ; Mice ; Mice, Inbred BALB C ; T-Cell Antigen Receptor Specificity ; T-Lymphocytes/*immunology ; }, abstract = {BACKGROUND: Immature dendritic cells (iDC) loaded with antigens are able to induce tolerance in antigen-specific T-cells. The potential of antigen-unloaded iDC to regulate the antileukemic cytotoxicity of autologous T-cells was determined.<br><br>MATERIALS AND METHODS: iDC generated with 50 U/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) and very immature DC (viDC) generated with 10 U/ml GM-CSF from the bone marrow of Balb/c mice were used for T-cell co-culture.<br><br>RESULTS: The measurement of cellular cytotoxicity against the syngeneic murine B-cell leukemia line A20 revealed that T-cells without co-culture or after co-culture with iDC exerted a similar cytotoxicity, whereas T-cells co-incubated with viDC showed a significantly diminished lysis of A20 cells (p<0.05).<br><br>CONCLUSION: Antigen-unloaded iDC in contrast to antigen-loaded iDC may not affect antileukemic T-cell cytotoxicity, whereas antigen-unloaded DC cultures generated with a low dose of GM-CSF are able to impair the T-cell-mediated cytolysis of leukemic cells.}, }
@article {pmid19032762, year = {2008}, author = {Schobesberger, M and Baltzer, A and Oberli, A and Kappeler, A and Gugger, M and Burger, H and Jaggi, R}, title = {Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores.}, journal = {BMC cancer}, volume = {8}, number = {}, pages = {343}, pmid = {19032762}, issn = {1471-2407}, mesh = {Breast ; Breast Neoplasms/*diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology ; Cell Proliferation ; Female ; Genes, erbB-2 ; Genetic Variation ; Humans ; *Oligonucleotide Array Sequence Analysis ; Paraffin Embedding ; Polymerase Chain Reaction ; Prognosis ; RNA, Neoplasm/analysis/isolation &amp; purification ; Receptors, Estrogen/genetics ; }, abstract = {BACKGROUND: Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection.<br><br>METHODS: In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR.<br><br>RESULTS: Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan(R) Low Density Arrays (16 invasive ductal carcinoma (IDC), 8 ductal carcinoma in situ (DCIS) and 6 normal tissue), and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO), the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores than cores derived from IDC or DCIS of the same block or from different blocks of the same patient.<br><br>CONCLUSION: We have developed optimized protocols for RNA isolation from histologically distinct areas. RNA prepared from FFPE tissue cores is suitable for gene expression measurement by quantitative PCR. Distinct molecular scores could be determined from different cores of the same tumor specimen.}, }
@article {pmid19031084, year = {2009}, author = {Da Silva, L and Buck, L and Simpson, PT and Reid, L and McCallum, N and Madigan, BJ and Lakhani, SR}, title = {Molecular and morphological analysis of adenoid cystic carcinoma of the breast with synchronous tubular adenosis.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {454}, number = {1}, pages = {107-114}, pmid = {19031084}, issn = {0945-6317}, mesh = {Actins/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*complications/genetics/*pathology ; Carcinoma, Adenoid Cystic/*complications/genetics/*pathology ; Cell Proliferation ; DNA, Neoplasm ; Female ; Fibrocystic Breast Disease/*complications/genetics/*pathology ; Genomic Instability/genetics ; Humans ; Keratin-19/metabolism ; Keratin-7/metabolism ; Middle Aged ; S100 Proteins/metabolism ; }, abstract = {Adenoid cystic carcinoma (ACC) of the breast is a rare tumour. Its recognition as a special type of breast carcinoma is very important because its prognosis is better than the not-otherwise-specified invasive ductal carcinoma and its treatment may not include axillary dissection. Tubular adenosis (TA) is a very rare condition of the breast that is histologically benign; however, it has been described in association with invasive ductal carcinoma. There are scant data regarding the molecular genomic alterations in ACC of the breast and no data has been presented on TA. Herein, we provide a morphological characterisation of TA arising synchronically with ACC in the breast. To characterise these lesions, we performed ultrastructural analysis, three-dimensional reconstruction and molecular analysis using immunohistochemistry and comparative genomic hybridisation. The copy number alterations found in ACC were restricted to small deletions on 16p and 17q only, whereas the TA harboured gains on 1q, 5p, 8q, 10q, 11p and 11q and losses on 1p, 10q, 11q, 12q, 14q, 15q and 16q. These molecular data highlight the genomic instability of TA, a benign florid proliferation intermingled with ACC, and do not provide evidence of molecular evolution from TA to ACC.}, }
@article {pmid18997986, year = {2008}, author = {Brooksbank, R and Badenhorst, D and Sliwa, K and Norton, G and Woodiwiss, A}, title = {The G-308A polymorphism of the TNF-alpha gene does not predict changes in cardiac function in response to medical therapy for idiopathic dilated cardiomyopathy.}, journal = {Cardiovascular journal of Africa}, volume = {19}, number = {5}, pages = {254-258}, pmid = {18997986}, issn = {1995-1892}, mesh = {Alleles ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiomyopathy, Dilated/drug therapy/*genetics/physiopathology ; Cardiotonic Agents ; Cardiovascular Agents/*therapeutic use ; Case-Control Studies ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Female ; Genotype ; Heart Ventricles ; Humans ; Male ; Middle Aged ; *Polymorphism, Genetic ; Prospective Studies ; Risk Factors ; Tumor Necrosis Factor-alpha/*genetics ; }, abstract = {The G-308A polymorphism of the tumour necrosis factor-alpha (TNF-alpha) gene, a variant that influences TNF-alpha transcription, may contribute to non-ischaemic dilated cardiomyopathy. To evaluate whether TNF-alpha genotyping may assist in identifying a subset of patients who could potentially benefit from immunomodulatory therapy, we assessed the relationship between the G-308A polymorphism of the TNF-alpha gene and changes in left ventricular (LV) chamber dimensions and systolic function in patients with idiopathic dilated cardiomyopathy (IDC) before and six months after diuretic, digoxin and angiotensin-converting enzyme inhibitor (ACEI) therapy. In 331 patients with IDC and 349 controls, the TNF-2 (A) allele (odds ratio = 1.509, 95% CI = 1.130-2.015, p < 0.01) and the TNF-12/22 (AG/GG) genotype (odds ratio = 1.620, 95% CI = 1.159-2.266, p < 0.01) were associated with IDC. However, in 122 patients with IDC, the TNF-alpha genotype was not associated with plasma TNF-alpha concentrations. In 133 patients with IDC, the TNF-alpha genotype failed to predict either the severity of pump dysfunction and cardiac dilatation at baseline, or changes in pump function and cardiac dimensions after six months of medical treatment. We conclude therefore that although the TNF-alpha gene G-308A polymorphism may contribute to the development of IDC, it does not influence pump function or adverse cardiac remodelling in patients with IDC. Genotyping for this variant is therefore unlikely to assist in identifying patients with heart failure who may be particularly susceptible to novel immunomodulatory therapeutic strategies.}, }
@article {pmid18987550, year = {2009}, author = {Zhang, MQ and Lennerz, JK and Dehner, LP and Brunt, LM and Wang, HL}, title = {Granulomatous inflammatory pseudotumor of the spleen: association with Epstein-Barr virus.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {17}, number = {3}, pages = {259-263}, doi = {10.1097/PAI.0b013e318189f10f}, pmid = {18987550}, issn = {1533-4058}, mesh = {Aged ; Epstein-Barr Virus Infections/complications/*diagnosis/pathology ; Female ; Granuloma/*diagnosis/pathology/virology ; Granuloma, Plasma Cell/*diagnosis/pathology/virology ; Herpesvirus 4, Human/*isolation &amp; purification ; Humans ; RNA, Viral/analysis ; Splenic Diseases/*diagnosis/pathology/virology ; }, abstract = {A 74-year-old woman with a clinical history of invasive ductal carcinoma of the breast was found to have a splenic mass during a routine radiographic survey. Splenectomy revealed a 3-cm well-demarcated lesion, which on histopathologic examination consisted of heterogeneous inflammatory cells. A striking feature of the lesion was the presence of innumerable well-formed non-necrotizing granulomas. Immunohistochemical studies confirmed the lesion to be composed mainly of mixed T and B lymphocytes, histiocytes, and plasma cells. No spindle cell component was evident on light microscopic examination or by immunohistochemical staining for smooth muscle actin, anaplastic lymphoma kinase, or follicular dendritic cell markers CD21 and CD35. Interestingly, Epstein-Barr virus-encoded RNA and latent membrane protein were detected by in situ hybridization and immunohistochemistry in numerous lymphohistiocytic cells within the lesion, but not in surrounding uninvolved splenic tissue. To our knowledge, this case represents a rare example of splenic inflammatory pseudotumor with exuberant granulomatous reaction in association with Epstein-Barr viral infection.}, }
@article {pmid18982746, year = {2008}, author = {Mustać, E and Zamolo, G and Petković, M and Dordević, G and Radić, J and Grgurević, E and Batinac, T}, title = {Breast infiltrating ductal carcinoma: analysis of hormone, HER-2 receptors and Ki-67 proliferation marker.}, journal = {Collegium antropologicum}, volume = {32}, number = {3}, pages = {741-746}, pmid = {18982746}, issn = {0350-6134}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/*genetics/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/*pathology ; Female ; Gene Expression ; Humans ; Ki-67 Antigen/*analysis ; Menopause ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*analysis ; }, abstract = {The aim of this study was to analyse breast carcinomas with discordant receptor status, probably hormonal dependent (estrogen receptor (ER) positive, progesterone receptor (PR) negative or ER-PR + subgroup profile) infiltrating ductal breast carcinomas not otherwise specified (IDC NOS). Specimens from 90 IDC NOS were grouped into three categories according to hormonal status: dependent (D) (ER +PR +), probably dependent (PD) (ER +PR- or ER-PR +) and non-dependent (ND) (ER-PR-); they were evaluated considering some established prognostic parameters in breast carcinomas. Statistically significant difference was found between tumor receptor status distribution and menopausal status (p = 0.0235), age of the patients (p = 0.000467), histological grade (p = 0.000003), vascular invasion (p = 0.006), HER-2 status (p = 0.0039) and Ki-67 proliferation rate (p = 0.000311). D tumors were found exclusively in post-menopausal patients (average age 68.9 years), most of which had intermediate (II) grade, without vascular invasion, with HER-2 status score predominantly 0 or 1 + and lower Ki-67 proliferation rate. PD tumors were found predominantly in younger post-menopausal patients (average age 57.5 years), with vascular invasion found in 23% of the cases. ND tumors mostly had higher histological grade, showed the highest percentage of the Ki-67 positive tumor cells and vascular invasion in 30% of the cases. We conclude that the patients with PD breast carcinomas were younger post-menopausal women with the tumors moderately differentiated, HER-2 score 0 or 1+ and with lower Ki-67 proliferation rate.}, }
@article {pmid18982439, year = {2009}, author = {Nodari, S and Metra, M and Milesi, G and Manerba, A and Cesana, BM and Gheorghiade, M and Dei Cas, L}, title = {The role of n-3 PUFAs in preventing the arrhythmic risk in patients with idiopathic dilated cardiomyopathy.}, journal = {Cardiovascular drugs and therapy}, volume = {23}, number = {1}, pages = {5-15}, doi = {10.1007/s10557-008-6142-7}, pmid = {18982439}, issn = {1573-7241}, mesh = {Aged ; Anti-Arrhythmia Agents/*pharmacology ; Arrhythmias, Cardiac/etiology/*prevention &amp; control ; Cardiomyopathy, Dilated/*complications ; Catecholamines/blood ; Cytokines/blood/drug effects ; Docosahexaenoic Acids/*pharmacology ; Double-Blind Method ; Drug Combinations ; Eicosapentaenoic Acid/*pharmacology ; Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Heart Rate/drug effects ; Humans ; Male ; Middle Aged ; Risk Factors ; }, abstract = {BACKGROUND: N-3 polyunsaturated fatty acids (n-3 PUFAs) intake is associated with a reduction in sudden cardiac death in patients with ischemic heart disease. Their effects in patients with heart failure caused by idiopathic dilated cardiomyopathy (IDC) are unknown.<br><br>METHODS: We compared with placebo the effects of n-3 PUFAs administration in 44 patients with IDC and with frequent or repetitive ventricular arrhythmias at Holter monitoring using a randomized, double-blind design. Arrhythmic risk was assessed by microvolt T-wave analysis (MTWA), signal averaged ECG (SAECG), Holter monitoring, power spectral analysis of heart rate (HR) variability, catecholamine and cytokine plasma levels, at baseline and after 6 months.<br><br>RESULTS: At MTWA, 7/12 patients (58%) initially positive became negative after n-3 PUFAs while one patient became positive after placebo (p = 0.019). N-3 PUFAs administration was also associated to normalization of SAECG (11/15 patients, p < 0.0015), decrease in non-sustained ventricular tachycardia (NSVT) episodes (p = 0.0002) and NSVT HR (p = 0.0003), improvement in HR variability and decrease in catecholamine and cytokine plasma levels. The ratio of plasma n-6 PUFAs to n-3 PUFAs decreased from 12.01 to 3.48 after n-3 PUFAs.<br><br>CONCLUSIONS: N-3 PUFAs administration is associated with favorable effects on parameters related to arrhythmic risk in patients with idiopathic dilated cardiomyopathy. These results are consistent with antiarrhythmic activity independent from their antiischemic effects.}, }
@article {pmid18972942, year = {2008}, author = {Busch, M and Wall, JR and Koch, SM and Anderson, C}, title = {Addressing the disproportionate representation of children of color: a collaborative community approach.}, journal = {Child welfare}, volume = {87}, number = {2}, pages = {255-278}, pmid = {18972942}, issn = {0009-4021}, mesh = {Black or African American/*statistics &amp; numerical data ; Child ; Child Abuse/*ethnology/statistics &amp; numerical data ; Child Custody/statistics &amp; numerical data ; Child Welfare/*ethnology/statistics &amp; numerical data ; *Cooperative Behavior ; Cross-Sectional Studies ; Data Collection/statistics &amp; numerical data ; Foster Home Care/statistics &amp; numerical data ; Hispanic or Latino/statistics &amp; numerical data ; Humans ; Incidence ; Indiana ; Outcome Assessment, Health Care/statistics &amp; numerical data ; *Prejudice ; Risk Factors ; *Social Welfare ; White People/statistics &amp; numerical data ; }, abstract = {The state of Indiana recommended a committee be formed to address the disproportional representation of black youth in out-of-home placements. In response, the Indiana Disproportionality Committee (IDC) was established. This article presents the development, objectives and future of the IDC. One of the objectives, research, will be offered as an example of the committee's collaborative strategies. The IDC, in partnership with another organization, has begun exploring relationships between ethnicity, risk factors and treatment outcomes. The results of this research effort have examined disproportion and disparity, leading the IDC to identify needs for change within the state. Barriers and successes of the IDC will be shared, so that others can use these efforts to guide their own strategies to reduce disproportionality.}, }
@article {pmid18949740, year = {2008}, author = {Brankovic-Magic, MV and Jankovic, RN and Dobricic, JD and Borojevic, ND and Magic, ZM and Radulovic, SS}, title = {TP53 mutations in breast cancer: association with ductal histology and early relapse of disease.}, journal = {The International journal of biological markers}, volume = {23}, number = {3}, pages = {147-153}, doi = {10.1177/172460080802300303}, pmid = {18949740}, issn = {0393-6155}, mesh = {Adult ; Aged ; Breast Neoplasms/ethnology/*genetics/*pathology ; Case-Control Studies ; Disease-Free Survival ; Female ; *Genes, p53 ; Humans ; Middle Aged ; *Mutation ; Polymorphism, Single-Stranded Conformational ; Receptors, Steroid/metabolism ; Recurrence ; Serbia ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {PURPOSE: This study aimed to investigate the incidence of core domain TP53 mutations in Serbian breast cancer patients in view of their possible correlation with prognostic parameters, tumor characteristics and clinical disease course.<br><br>METHODS: 145 breast cancer patients were included. Data on clinical disease course were available for 100 patients including 30 node-negative and 70 node-positive patients. After surgery, node-positive patients underwent adjuvant chemotherapy, mostly CMF. TP53 mutations were detected by PCR-SSCP.<br><br>RESULTS: 31 mutations were found in 27/145 patients including 4/59 node-negative patients and 23/83 node-positive patients (4 double mutations). 26/31 TP53 mutations were found in patients with invasive ductal carcinoma and only 2 in patients with invasive lobular carcinoma. The presence of TP53 mutations was correlated with clinical disease course in premenopausal node-positive patients (n=70). 11/20 patients with TP53 mutations relapsed. Within the first 24 months of follow-up, significantly shorter disease-free intervals were observed in TP53-mutated patients.<br><br>CONCLUSIONS: TP53 mutations correlated only with nodal status and ductal histology. The significance of the predominant distribution of TP53 mutations in tumors with a ductal histology for the aggressive behavior of these tumors has yet to be proved, since the favorable biological features of tumors with a lobular histology do not result in a better prognosis. Early relapse in mutated-TP53 carriers may support data on its predictive value with respect to adjuvant CMF.}, }
@article {pmid18942291, year = {2008}, author = {Al-Joudi, FS and Iskandar, ZA and Rusli, J}, title = {The expression of p53 in invasive ductal carcinoma of the breast: a study in the North-East States of Malaysia.}, journal = {The Medical journal of Malaysia}, volume = {63}, number = {2}, pages = {96-99}, pmid = {18942291}, issn = {0300-5283}, mesh = {Biomarkers/analysis ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; DNA-Binding Proteins/*analysis ; Female ; Humans ; Malaysia/epidemiology ; Middle Aged ; }, abstract = {The p53 gene is a tumour suppressor gene that encodes a 393-amino-acid nuclear DNA-binding phosphoprotein. The significance of p53 detection is that p53 mutation is linked with chemo-resistance and transformation to more aggressive disease in a large number of tumour types and it was confirmed that mutant p53 is involved in neoplastic transformations. In addition, the expression of p53 has been closely correlated with clinicopathological findings. Since breast cancer has been reported as one of the most frequent malignancies in women in Malaysia, the expression of p53 was studied in 382 cases of invasive ductal carcinoma of the breast, obtained from three major hospitals in the North-East States of Malaysia. The study utilized an enzyme immunohistochemistry assay for the detection of p53. It was found that p53 was expressed in 29.6% of all the study cases. Furthermore, its expression was significantly correlated with the age and the clinical grading of the disease. No significant statistical correlations were depicted with lymph node status, tumour size, side of tumour, and expression of estrogen and progesterone receptors. Nevertheless, knowledge of the p53 status may be valuable in making clinical decisions regarding diagnosis, prognosis and therapy.}, }
@article {pmid18936904, year = {2009}, author = {Gao, Y and Niu, Y and Wang, X and Wei, L and Lu, S}, title = {Genetic changes at specific stages of breast cancer progression detected by comparative genomic hybridization.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {87}, number = {2}, pages = {145-152}, pmid = {18936904}, issn = {1432-1440}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Chromosome Aberrations ; Chromosome Banding/methods ; Comparative Genomic Hybridization/*methods ; Disease Progression ; Gene Dosage ; Humans ; Hyperplasia ; Neoplasm Staging ; }, abstract = {Although a simple linear progression model for breast cancer has already been proposed, its validity still remains controversial. Especially, the genetic and molecular features of breast cancer at different stages during the development and progression, as well as their relationship, have rarely been studied under the same experimental conditions simultaneously. According to these limitations in this research area, the current study applied comparative genomic hybridization technique to investigate genomic changes in 15 cases of breast atypical ductal hyperplasia (ADH), 15 cases of ductal carcinomas in situ (DCIS), and 15 cases of invasive ductal carcinomas (IDC) and the relationship among the genetic changes. Thirty commonly altered regions that were identified included known (gains of 1q,8q, 17q,20q,Xq and losses of 8p,13q,16q,17p,22q) and several uncharacterized (gains of 2q,5p, 10p,12q,16p,18q, etc. and losses of 11p13-pter,11q,14q,Xp, etc). The overall frequency of copy number losses was higher in IDC than that in DCIS (P = 0.013). ADH showed more frequent gain of 17q than that in IDC (P = 0.007), and IDC exhibited a higher frequency for the loss of 22q than that in ADH (P = 0.018). On one hand, several common genomic changes shared by ADH, DCIS, and IDC make a linear relationship for these three lesions possible. On the other hand, the heterogeneity has also showed clonal diversification and different pathways of breast cancer progression. The regions of chromosomal copy number alterations may bring new insights into the strategy for tumor progression blocking and the discovery of new potential targets for breast cancer treatment.}, }
@article {pmid18936692, year = {2009}, author = {Subhawong, AP and Subhawong, T and Nassar, H and Kouprina, N and Begum, S and Vang, R and Westra, WH and Argani, P}, title = {Most basal-like breast carcinomas demonstrate the same Rb-/p16+ immunophenotype as the HPV-related poorly differentiated squamous cell carcinomas which they resemble morphologically.}, journal = {The American journal of surgical pathology}, volume = {33}, number = {2}, pages = {163-175}, pmid = {18936692}, issn = {1532-0979}, support = {P50 CA088843/CA/NCI NIH HHS/United States ; P50 CA088843-06A19005/CA/NCI NIH HHS/United States ; P50 CA 88843/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Squamous Cell/metabolism/pathology ; Cyclin-Dependent Kinase Inhibitor p16/biosynthesis/*genetics ; Female ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization ; Middle Aged ; Papillomavirus Infections ; Phenotype ; Retinoblastoma Protein/biosynthesis/*genetics ; Tissue Array Analysis ; Tumor Suppressor Protein p53/biosynthesis/genetics ; }, abstract = {Basal-like carcinomas (BLCs) of the breast share discriminatory morphologic features with poorly differentiated high-risk human papilloma virus (HPV)-related squamous cell carcinomas of the oropharynx, penis, and vulva. Because HPV E7 protein inactivates the retinoblastoma (Rb) protein, diffuse p16 expression is a surrogate marker for these high-risk HPV-related carcinomas. HPV E6 protein also inactivates p53, further compromising the G1-S cell cycle checkpoint. The Rb/p16/p53 immunohistochemical profile of BLC of the breast has not been well characterized. Tissue microarrays containing 71 invasive ductal carcinomas (IDCs) of the breast were immunolabeled for p16, Rb, p53, and Ki-67. The cases included 4 distinct groups of IDCs having surrogate immunohistochemical profiles corresponding to categories defined by gene expression profiling (17 luminal A, 7 luminal B, 14 HER-2+, and 21 BLC), along with 12 unclassifiable triple negative carcinomas (UTNCs). Twenty-five of the 71 IDC were Rb negative/p16 diffuse positive (Rb-/p16+). These included 15 of 21 BLC and 9 of 12 UTNC, but only 1 of 14 HER-2 positive cases and none of the 17 luminal A or 7 luminal B cases (P<0.01, BLC or UTNC vs. others). Six of the Rb-/p16+ IDC also had a significant ductal carcinoma in situ component. The ductal carcinoma in situ in 4 of these 6 cases showed the same Rb-/p16+ phenotype as the associated IDC. BLC and UTNC had the highest Ki-67 indices of the 5 groups, even when matched for grade. The Rb-/p16+ phenotype and the Rb-/p16+/p53 overexpressing phenotype correlated with increased proliferation within the BLC group. In conclusion, BLC and UTNC, but not HER-2, luminal A, or luminal B carcinomas, frequently demonstrate an Rb-/p16+ phenotype, similar to the HPV-related squamous cell carcinomas that BLC resemble morphologically. This subset may represent a more homogenous group than BLC as defined currently.}, }
@article {pmid18928525, year = {2008}, author = {Castro, NP and Osório, CA and Torres, C and Bastos, EP and Mourão-Neto, M and Soares, FA and Brentani, HP and Carraro, DM}, title = {Evidence that molecular changes in cells occur before morphological alterations during the progression of breast ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {10}, number = {5}, pages = {R87}, pmid = {18928525}, issn = {1465-542X}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/genetics/*pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/genetics/*pathology ; Disease Progression ; Female ; *Gene Expression Profiling ; *Genes, Neoplasm ; Humans ; Microdissection ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Proteins/*biosynthesis/genetics ; Oligonucleotide Array Sequence Analysis ; Protein-Lysine 6-Oxidase/genetics ; RNA, Messenger/biosynthesis/genetics ; RNA, Neoplasm/biosynthesis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfotransferases/genetics ; Time Factors ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast includes a heterogeneous group of preinvasive tumors with uncertain evolution. Definition of the molecular factors necessary for progression to invasive disease is crucial to determining which lesions are likely to become invasive. To obtain insight into the molecular basis of DCIS, we compared the gene expression pattern of cells from the following samples: non-neoplastic, pure DCIS, in situ component of lesions with co-existing invasive ductal carcinoma, and invasive ductal carcinoma.<br><br>METHODS: Forty-one samples were evaluated: four non-neoplastic, five pure DCIS, 22 in situ component of lesions with co-existing invasive ductal carcinoma, and 10 invasive ductal carcinoma. Pure cell populations were isolated using laser microdissection. Total RNA was purified, DNase treated, and amplified using the T7-based method. Microarray analysis was conducted using a customized cDNA platform. The concept of molecular divergence was applied to classify the sample groups using analysis of variance followed by Tukey's test.<br><br>RESULTS: Among the tumor sample groups, cells from pure DCIS exhibited the most divergent molecular profile, consequently identifying cells from in situ component of lesions with co-existing invasive ductal carcinoma as very similar to cells from invasive lesions. Additionally, we identified 147 genes that were differentially expressed between pure DCIS and in situ component of lesions with co-existing invasive ductal carcinoma, which can discriminate samples representative of in situ component of lesions with co-existing invasive ductal carcinoma from 60% of pure DCIS samples. A gene subset was evaluated using quantitative RT-PCR, which confirmed differential expression for 62.5% and 60.0% of them using initial and partial independent sample groups, respectively. Among these genes, LOX and SULF-1 exhibited features that identify them as potential participants in the malignant process of DCIS.<br><br>CONCLUSIONS: We identified new genes that are potentially involved in the malignant transformation of DCIS, and our findings strongly suggest that cells from the in situ component of lesions with co-existing invasive ductal carcinoma exhibit molecular alterations that enable them to invade the surrounding tissue before morphological changes in the lesion become apparent.}, }
@article {pmid18852879, year = {2008}, author = {Simhadri, VR and Reiners, KS and Hansen, HP and Topolar, D and Simhadri, VL and Nohroudi, K and Kufer, TA and Engert, A and Pogge von Strandmann, E}, title = {Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function.}, journal = {PloS one}, volume = {3}, number = {10}, pages = {e3377}, pmid = {18852879}, issn = {1932-6203}, mesh = {Cell Line ; Dendritic Cells/*metabolism/ultrastructure ; Exosomes/chemistry/metabolism/*physiology ; Flow Cytometry ; Humans ; Killer Cells, Natural/chemistry/*immunology ; Ligands ; Microscopy, Electron ; Molecular Chaperones ; Natural Cytotoxicity Triggering Receptor 3/*metabolism ; Proteins/*metabolism ; }, abstract = {NKp30, a natural cytotoxicity receptor expressed on NK cells is critically involved in direct cytotoxicity against various tumor cells and directs both maturation and selective killing of dendritic cells. Recently the intracellular protein BAT3, which is involved in DNA damage induced apoptosis, was identified as a ligand for NKp30. However, the mechanisms underlying the exposure of the intracellular ligand BAT3 to surface NKp30 and its role in NK-DC cross talk remained elusive. Electron microscopy and flow cytometry demonstrate that exosomes released from 293T cells and iDCs express BAT3 on the surface and are recognized by NKp30-Ig. Overexpression and depletion of BAT3 in 293T cells directly correlates with the exosomal expression level and the activation of NK cell-mediated cytokine release. Furthermore, the NKp30-mediated NK/DC cross talk resulting either in iDC killing or maturation was BAT3-dependent. Taken together this puts forward a new model for the activation of NK cells through intracellular signals that are released via exosomes from accessory cells. The manipulation of the exosomal regulation may offer a novel strategy to induce tumor immunity or inhibit autoimmune diseases caused by NK cell-activation.}, }
@article {pmid18848858, year = {2008}, author = {Brusa, D and Garetto, S and Chiorino, G and Scatolini, M and Migliore, E and Camussi, G and Matera, L}, title = {Post-apoptotic tumors are more palatable to dendritic cells and enhance their antigen cross-presentation activity.}, journal = {Vaccine}, volume = {26}, number = {50}, pages = {6422-6432}, doi = {10.1016/j.vaccine.2008.08.063}, pmid = {18848858}, issn = {0264-410X}, mesh = {Antigen Presentation/*immunology ; Apoptosis/*physiology ; Cell Line, Tumor ; Cross-Priming/*immunology ; Dendritic Cells/cytology/*immunology ; Flow Cytometry ; HMGB1 Protein/genetics/metabolism ; HSP70 Heat-Shock Proteins/genetics/metabolism ; Humans ; Neoplasms/*immunology ; Oligonucleotide Array Sequence Analysis ; Phagocytosis ; T-Lymphocytes/immunology ; }, abstract = {Critical issues for cytotoxic lymphocyte (CTL) cross-priming are (a) the maturation state of dendritic cells (DC), (b) the source of the tumor-associated antigens (TAA) and (c) the context in which they are delivered to DCs. Drug-induced apoptosis has recently been implicated in CTL cross-priming. However, since drug-treatment produces in vivo more tumor cells than the DC default apoptotic clearance program can cope with, they are expected to proceed to secondary necrosis and change their molecular pattern. Here we have addressed this issue on renal carcinoma cells (RCC) by using different apoptotic stimuli. UVC, but not gamma-irradiation or anthracyclins, induced after 4h treatment of the RCC cell line K1 a combination of apoptotic (phosphatydilserine and calreticulin plasma membrane mobilization) and necrotic (membrane incompetence) features. Heat shock protein (Hsp)-70 and chromatin-bound high mobility box 1 HMGB1 protein, typical of necrosis, were released during the further 20h and thus made accessible to co-cultured monocyte-derived immature (i) DC. UVC-treated, secondary necrotic RCC cell lines were cross-presented with higher efficiency by cytokine-matured (m) DC than their early apoptotic (i.e. gamma-irradiated) counterpart. Upstream events such as increased tumor uptake, activation of genes involved in the antigen-processing machinery, and increased expression of costimulatory and maturation molecules were also observed after loading iDC with secondary necrotic, but not apoptotic, tumor cells. These data offer a description of the molecular and immunogenic characteristics of post-apoptotic tumors which can be exploited to increase the efficiency of in vivo and ex vivo TAA delivery to the DC cross-presentation pathway.}, }
@article {pmid18837432, year = {2009}, author = {Kabay, SC and Kabay, S and Yucel, M and Ozden, H}, title = {Acute urodynamic effects of percutaneous posterior tibial nerve stimulation on neurogenic detrusor overactivity in patients with Parkinson's disease.}, journal = {Neurourology and urodynamics}, volume = {28}, number = {1}, pages = {62-67}, doi = {10.1002/nau.20593}, pmid = {18837432}, issn = {1520-6777}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscle Contraction ; Parkinson Disease/*complications/physiopathology/therapy ; *Tibial Nerve ; *Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Urinary Bladder/innervation/*physiopathology ; Urinary Bladder, Neurogenic/etiology/physiopathology/*therapy ; Urinary Bladder, Overactive/etiology/physiopathology/*therapy ; *Urodynamics ; }, abstract = {AIMS: Lower urinary tract dysfunction is often occurs in patients with Parkinson's disease (PD), that is primarily induced by neurogenic detrusor overactivity (NDO) and negatively effect the quality of the patient's life. The aim of this study is to evaluate the acute effects of posterior tibial nerve stimulation (PTNS) on the urodynamic findings in the PD patients with NDO.<br><br>METHODS: Thirty-two patients with PD (19 [59.3%] men and 13 [40.6%] women) with NDO were included in the study. Mean age of the patients was 64.2 +/- 8.7 years (range 44-78). Urodynamic studies before and during PTNS were performed. Electrical stimulation was applied unilaterally from the medial malleolus and posterior to the edge of the tibia by using charge-compensated 200 microsec pulses with a pulse rate of 20 Hz. Mean first involuntary detrusor (1st IDCV) contractions and means maximum cystometric capacity (MCC) before and during PTNS was compared.<br><br>RESULTS: Mean 1st IDCV on standard cystometry was 145.2 +/- 41.1 (55-265) ml, while it was 244.7 +/- 51.7 (145-390) ml during PTNS. MCC on standard cystometry was 204.8 +/- 40.5 (115-320) ml, while it was 301.2 +/- 51.5 (230-395) ml during stimulation. Mean 1st IDC and mean MCC were significantly improved during PTNS.<br><br>CONCLUSIONS: These results have demonstrated the objective acute effect of PTNS on urodynamic parameters. PTNS is acutely effective to suppress detrusor overactivity in PD patients.}, }
@article {pmid18828272, year = {2008}, author = {Yagmurdur, MC and Atac, FB and Tutar, NU and Verdi, H and Isiklar, I and Ozdemir, BH and Ozbek, N and Karakayali, H and Haberal, M}, title = {Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.}, journal = {International surgery}, volume = {93}, number = {3}, pages = {163-168}, pmid = {18828272}, issn = {0020-8868}, mesh = {Alleles ; Breast Neoplasms/*genetics/surgery ; Carcinoma, Ductal, Breast/*genetics/surgery ; Disease-Free Survival ; Female ; Genotype ; Humans ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics ; Plasminogen Activator Inhibitor 1/*genetics ; *Polymorphism, Genetic ; Prognosis ; Retrospective Studies ; Statistics, Nonparametric ; Turkey ; }, abstract = {The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.}, }
@article {pmid18826393, year = {2008}, author = {Qadura, M and Othman, M and Waters, B and Chegeni, R and Walker, K and Labelle, A and Ozelo, M and Hough, C and Lillicrap, D}, title = {Reduction of the immune response to factor VIII mediated through tolerogenic factor VIII presentation by immature dendritic cells.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {6}, number = {12}, pages = {2095-2104}, doi = {10.1111/j.1538-7836.2008.03165.x}, pmid = {18826393}, issn = {1538-7836}, mesh = {Animals ; *Antigen Presentation ; Dendritic Cells/*immunology/transplantation ; Dogs ; Factor VIII/*immunology ; Hemophilia A/*immunology ; Immune System Phenomena ; *Immune Tolerance ; Interleukin-10 ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta ; Treatment Outcome ; }, abstract = {BACKGROUND: The development of neutralizing antibodies to factor FVIII (FVIII) represents the most serious complication in the treatment of hemophilia A.<br><br>OBJECTIVE: We have explored the potential of using immature dendritic cells (iDCs) to present FVIII in a tolerogenic manner to T cells.<br><br>METHODS: The iDCs were isolated from hemophilic murine bone marrow and pulsed with canine cFVIII (cFVIII-iDCs) in the presence or absence of the NFkappaB pathway blocking compound Andrographolide (Andro-cFVIII-iDCs). Three weekly intravenous infusions of one million cFVIII pulsed-iDCs were administered to a group of five hemophilic Balb/c mice. Anti-FVIII antibody levels were monitored by functional Bethesda assay after four weekly intravenous challenges with 2 IU of cFVIII.<br><br>RESULTS: We have shown that cFVIII in the presence or absence of Andro is efficiently taken up by iDCs and that this process does not result in the maturation of DCs or the activation of co-cultured T cells. Following repeated infusion of the cFVIII-iDCs and Andro-cFVIII-iDCs into hemophilic mice, which were subsequently challenged with cFVIII, long-term reductions of FVIII inhibitors of 25% and 40%, respectively, were documented. Studies of cytokine release and T-cell phenotypes indicate that the mechanisms responsible for reducing immunologic responsiveness to cFVIII appear to involve an expansion of Foxp3 T regulatory cells in the case of cFVIII-iDC infusion and the elaboration of the immunosuppressive cytokines IL-10 and TGF-beta following andrographolide-treated cFVIII-iDCs.<br><br>CONCLUSIONS: This study shows that tolerogenic presentation of cFVIII to the immune system can significantly reduce immunogenicity of the protein.}, }
@article {pmid19999196, year = {2008}, author = {Naeem, M and Khan, N and Aman, Z and Nasir, A and Samad, A and Khattak, A}, title = {Pattern of breast cancer: experience at Lady Reading Hospital, Peshawar.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {20}, number = {4}, pages = {22-25}, pmid = {19999196}, issn = {1025-9589}, mesh = {Adult ; Age Distribution ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology ; Female ; Hospitals, Teaching/*statistics &amp; numerical data ; Humans ; Male ; Middle Aged ; Pakistan/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Breast Cancer is the commonest malignancy of females all over the world and second leading cause of death due to cancer among females. The aim of this Descriptive study was to see the various features of breast cancer in order to know the pattern of disease in the recent time. The study was conducted from Jan. 2007 to Dec. 2007 in Surgical C Unit, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, Pakistan.<br><br>METHODS: Study included all patients presenting to and admitted in Surgical C Unit LRH, with carcinoma of breast during the above mentioned period. Name, age, sex, other relevant data, history and examination findings and results of histopathology and other investigations were recorded.<br><br>RESULTS: Total of 46 patients was included in the study, out of which there were 46 female and 1 male patients. Most common age group was 40-49 years with 14 patients, followed by 50-59 years with 12 patients. Most common type of carcinoma was infiltrating ductal carcinoma with no specific features with 38 patients. Other types included 2 infiltrating ductal carcinomas of papillary type, 1 mucinous type and 1 medullary type; 3 invasive lobular carcinomas, and 1 mixed lobular and ductal carcinoma. The disease was left sided in 24 cases, right sided in 20 cases while it was bilateral in 2 cases. Upper outer quadrant of the breast was most commonly involved (n = 26). There were 2 cases of stage I, 16 stage II, 20 stage III and 08 cases of stage IV disease. There were 2 cases of grade I, 16 grade II, and 28 cases of grade III.<br><br>CONCLUSION: Carcinoma breast is still a common problem presenting at a young to middle age group with invasive ductal carcinoma being the commonest variant with a high grade and a late stage of presentation due to lack of screening and awareness programs.}, }
@article {pmid18814924, year = {2009}, author = {Branca, S and Bennati, E and Ferlito, L and Spallina, G and Cardillo, E and Malaguarnera, M and Motta, M and , }, title = {The health-care in the extreme longevity.}, journal = {Archives of gerontology and geriatrics}, volume = {49}, number = {1}, pages = {32-34}, doi = {10.1016/j.archger.2008.04.012}, pmid = {18814924}, issn = {1872-6976}, mesh = {Aged, 80 and over ; Female ; Health Services Needs and Demand ; Health Services for the Aged/*organization &amp; administration ; Hospices ; Humans ; *Longevity ; Male ; }, abstract = {The increase in life expectancy, the decrease of birth rate, and of the death rate in advanced ages caused, particularly in the industrialized countries, a progressive demographic transformation of the society, characterized by an increased proportion of the elderly. We assist an inevitable increase of morbidity and disability, not only due to the global aging of the population, but mainly to the increase of the age class above 80 years. For this reason, it is necessary to create and/or effort, especially in the Western countries, an adequate health-caring network. This should integrate and interact between the hospitals and the territories, offering all sanitary services (e.g., assisted sanitary residences, day hospitals (DHs), hospices, Alzheimer centers, diurnal centers, integrated domiciliary care (IDC), general practitioners), required by the elderly, and particularly by the oldest old people. All this should be maintained by an adequate financial support of the social-economic sources, which are necessary not only to activate the health-care services, but also to favor the economic and fiscal stimulation toward the families maintaining the elderly patients.}, }
@article {pmid18813127, year = {2009}, author = {Chadwick, B and Willmore-Payne, C and Tripp, S and Layfield, LJ and Hirschowitz, S and Holden, J}, title = {Histologic, immunohistochemical, and molecular classification of 52 IPMNs of the pancreas.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {17}, number = {1}, pages = {31-39}, doi = {10.1097/PAI.0b013e31817c02c6}, pmid = {18813127}, issn = {1533-4058}, mesh = {Biomarkers, Tumor/*analysis ; Carcinoma, Pancreatic Ductal/diagnosis/etiology/genetics/*pathology ; Classification ; Epithelial Cells/chemistry/pathology ; Epithelium/chemistry/*pathology ; Gene Expression Profiling ; Genes, Neoplasm ; Humans ; Immunohistochemistry ; Intestinal Neoplasms/pathology ; Mucins/chemistry ; Mutation ; Neoplasm Proteins/analysis ; }, abstract = {BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas account for approximately 5% of pancreatic neoplasms. Prognosis is superior to that of pancreatic invasive ductal carcinoma. IPMNs reveal a variety of epithelial linings expressing different mucin staining patterns and may progress along different oncogenic pathways.<br><br>MATERIALS AND METHODS: Fifty-two IPMNs were studied for expression of MUC1, MUC2, p16, p21, HER2, cyclin D1, and p53 protein and for mutations in K-ras, HER2, p53, EGFR, and BRAF genes. The cases were evaluated for dysplasia, presence of invasion, and morphology of lining epithelium.<br><br>RESULTS: Twenty-six IPMNs appeared intestinal (IN). Five were low, 12 moderate, and 9 high grade. K-ras mutations were found in 15, EGFR mutations in 2, and BRAF mutation in 1. Seven cases were pancreaticobiliary (PB) and all showed moderate to high-grade dysplasia. Six K-ras mutations and 2 p53 mutations were found in PB tumors. p53 mutations were in cases with high-grade dysplasia. Nineteen IPMNs demonstrated a gastric foveolar (GF) pattern. The majority of GF cases had low or moderate dysplasia. Sixteen revealed K-ras mutations and 1 case each demonstrated a HER2 or p53 mutation. Five IPMNs revealed invasive adenocarcinoma, including a colloid carcinoma from an IN type epithelium.<br><br>CONCLUSIONS: IN pattern IPMNs were the most common. Mixed histology was common. K-ras mutations were most common, but did not correlate with dysplasia. p53 mutations were seen in 6% of cases (only in GF and PB subtypes). A HER2 mutation was found in a GF IPMN. EGFR and BRAF mutations were restricted to IN IPMNs. These findings suggest the possibility of alternate pathways for carcinogenesis between epithelial subtypes of IPMNs.}, }
@article {pmid18801081, year = {2008}, author = {Kunju, LP and Ding, Y and Kleer, CG}, title = {Tubular carcinoma and grade 1 (well-differentiated) invasive ductal carcinoma: comparison of flat epithelial atypia and other intra-epithelial lesions.}, journal = {Pathology international}, volume = {58}, number = {10}, pages = {620-625}, doi = {10.1111/j.1440-1827.2008.02280.x}, pmid = {18801081}, issn = {1440-1827}, support = {CA090876/CA/NCI NIH HHS/United States ; CA107469/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/metabolism/*pathology ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Carcinoma, Intraductal, Noninfiltrating/metabolism ; Cell Nucleus/metabolism/pathology ; Epithelial Cells/pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {The distinction between tubular carcinomas (TC) and invasive well-differentiated (grade 1) ductal carcinoma (IDC) is important given treatment and prognostic differences. Studies have described a strong association between flat epithelial atypia (FEA) and TC. The incidence of FEA associated with grade 1 IDC is not well established. The aim of the present study was to assess morphology and intra-epithelial lesions between 14 TC and 18 grade 1 IDC matched for size. Of 14 TC, eight (57%) had associated FEA, seven (50%) had micropapillary atypical ductal hyperplasia (ADH), three (21%) had low nuclear grade ductal carcinoma in situ (DCIS), and four (29%) had lobular neoplasia. Notably, only two of 18 (11%) grade 1 IDC had associated FEA. Three of 18 (16%) grade 1 IDC had ADH, two (11%) had lobular neoplasia, and seven (39%) had DCIS. All tubular carcinomas were estrogen receptor (ER) positive and negative for Her-2/neu overexpression. All grade 1 IDC were ER positive but 5% also overexpressed Her-2/neu. Axillary lymph node metastasis was present in 11% of grade 1 IDC and absent in TC. A strong association was found between TC, FEA, and micropapillary ADH, which may reflect a biological progression. Despite matching for tumor size, grade 1 IDC have a higher incidence of lymph node metastasis and may have Her-2-neu overexpression compared to TC.}, }
@article {pmid18801076, year = {2008}, author = {Lee, SH and Chaung, CR}, title = {Mucinous metaplasia of breast carcinoma with macrocystic transformation resembling ovarian mucinous cystadenocarcinoma in a case of synchronous bilateral infiltrating ductal carcinoma.}, journal = {Pathology international}, volume = {58}, number = {9}, pages = {601-605}, doi = {10.1111/j.1440-1827.2008.02278.x}, pmid = {18801076}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Cystadenocarcinoma, Mucinous/chemistry/*pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lymph Node Excision ; Mastectomy, Radical ; Metaplasia ; Middle Aged ; Neoplasms, Second Primary/*pathology/surgery ; Ovarian Neoplasms/*pathology/secondary ; }, abstract = {Mammary mucinous cystadenocarcinoma (MCA) is a rare, invasive ductal carcinoma (IDC) of the breast that is virtually identical morphologically to MCA of the ovary, pancreas or appendix. Synchronous bilateral breast tumors, not uncommonly encountered in fibroadenoma and lobular carcinoma, are unusual in IDC. Reported herein is a primary MCA of the right breast coexisting with a bilateral ordinary IDC in a 55-year-old Taiwanese woman who underwent modified radical mastectomy of both breasts with bilateral axillary level I and II lymph node dissection. In the right breast a 2.5 cm unilocular mucus-filled cyst was found. It had complex papillae, some of which were supported by delicate fibrovascular stroma, lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin and an abundance of intracystic extracellular mucin, coexisting with a low-grade ordinary IDC. In the left breast a high-grade ordinary IDC was discovered. The patient had undergone simple abdominal total hysterectomy for myoma uteri along with bilateral salpingo-oophorectomy 10 years previously. Based on pathological studies and a literature review, it is suggested that mammary MCA arises from mucinous metaplasia and macrocystic transformation of ordinary breast carcinoma. A brief discussion of bilateral breast cancers is also given.}, }
@article {pmid18795615, year = {2008}, author = {Fu, BM and He, XS and Yu, S and Hu, AB and Ma, Y and Huang, JF}, title = {[Culture and identification of mouse myeloid semimature dendritic cells].}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {30}, number = {4}, pages = {430-435}, pmid = {18795615}, issn = {1000-503X}, mesh = {Animals ; *Cell Culture Techniques ; *Cell Differentiation ; Cells, Cultured ; Cytokines/immunology ; Dendritic Cells/*cytology/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Monocytes/*cytology/immunology ; }, abstract = {OBJECTIVE: To investigate the methods of culturing and identifying mouse myeloid semimature dendritic cell (smDC) in vitro.<br><br>METHODS: Myeloid monocytes derived from 6-week-old C57 BL/6 mice were cultured in RPMI-1640 medium containing 10% fetal bovine serum, 2 ng/ml recombinant murine granulocyte macrophage-colony stimulating factor (GM-CSF), and 20 ng/ml recombinant murine interleukin (IL)-4 for 9 days. Then cells were incubated with 40 ng/ml tumor necrosis factor-alpha (TNF-alpha) for 24 hours to obtain smDC. Meanwhile, smDC was differentiated into mature dendritic cell (mDC) or immature dendritic cell (iDC) by treatment with 1 micro/m1 lipopolysaccharide (LPS) or without LPS. The morphological features of smDC were assayed by inverted microscopy and scanning electron microscopy. Surface markers such as CD11c, CD4O, CD8O, CD86, and MHC-II were tested by flow cytometry. IL-1beta, IL-6, IL-12, and IL-10 in the supernatant were tested by ELISA. The activation of allogene lymphocyte (BALB/c mice) stimulated by C57BL/6 myeloid smDC in mixed lymphocyte reaction was examined by Cell Counting Kit-8 in vitro.<br><br>RESULTS: The shape of smDC was round or oval-shaped, and the diameter of smDC was about 15 microm. The length of smDC dendrite was between 5 to 10 microm. smDC, iDC, and mDC all expressed high level of CD11 c. The expressions of MHC-II, CD40, CD80, and CD86 on smDC were higher than those of iDC and lower than those of mDC. IL-1beta, IL-6, and IL-12 secretion of smDC was significantly lower than that of mDC (P < 0.01), and IL-12 was significantly lower than that of iDC (P < 0.05), while no significant difference of IL-1beta and IL-6 secretion was found between smDC and iDC (P > 0.05). Furthermore, IL-10 secretion was not significantly different among these three kinds of DCs (P > 0.05). The effect of allogene lymphocytes activation on smDC was significantly lower than that of mDC and positive control (P < 0.01), but had no significant difference when compared with that of iDC and negative control (P > 0.05).<br><br>CONCLUSIONS: smDC may be a relatively independent dendritic cell sub-population in terms of function and morphology. It is a feasible way to induce myeloid monocytes to differentiate into smDC using GM-CSF, IL-4, and TNF-alpha in vitro.}, }
@article {pmid18779730, year = {2008}, author = {Sepehr, A and Mino-Kenudson, M and Ogawa, F and Brugge, WR and Deshpande, V and Lauwers, GY}, title = {IgG4+ to IgG+ plasma cells ratio of ampulla can help differentiate autoimmune pancreatitis from other "mass forming" pancreatic lesions.}, journal = {The American journal of surgical pathology}, volume = {32}, number = {12}, pages = {1770-1779}, doi = {10.1097/PAS.0b013e318185490a}, pmid = {18779730}, issn = {1532-0979}, mesh = {Adult ; Aged ; Aged, 80 and over ; Ampulla of Vater/*immunology/metabolism/pathology ; Autoimmune Diseases/*immunology/metabolism ; Carcinoma, Pancreatic Ductal/pathology ; Diagnosis, Differential ; Female ; Humans ; *Immunoglobulin G ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/pathology ; Pancreatitis/*immunology/metabolism/pathology ; Plasma Cells/*immunology/metabolism ; ROC Curve ; Sensitivity and Specificity ; }, abstract = {Autoimmune pancreatitis (AIP) shows a unique spectrum of histologic features and commonly presents with an abundant IgG4-positive (IgG4+) plasma cell infiltration. However, differentiating AIP from other mass lesions, particularly pancreatic cancer [invasive ductal carcinoma (IDC)] can be clinically challenging. In this study, we evaluated the validity of IgG4 and IgG immunohistochemistry of ampullary and periampullary tissue for the diagnosis of AIP. Our study group consisted of 14 resected AIP cases with appropriate ampullary sections. Superficial ampullary tissue and "shouldering" duodenal mucosa were evaluated for several histologic variables. Immunohistochemistry for IgG4 and IgG was performed. The number of IgG4 and IgG-positive plasma cells was counted and an IgG4+ to IgG+ plasma cells ratio (IgG4/IgG ratio) was evaluated. A control cohort was composed of IDC (n=30) and chronic pancreatitis (CP) (n=29). Although an overlap was present between the groups, the overall inflammation and number of plasma cells in and around the ampulla was significantly increased in AIP compared with CP and IDC. Furthermore, although there was some overlap in the crude number of IgG4+ plasma cells of the ampullary and duodenal tissue between AIP, IDC, and CP, an IgG4/IgG ratio, especially of the ampulla, seems diagnostically useful in differentiating AIP from other "mass forming" lesions. When a cut-off of 0.10 was applied, the diagnostic sensitivity and specificity of the ampullary IgG4/IgG ratio was 86% and 95%, respectively. In conclusion, evaluation of ampullary histology and IgG4/IgG ratio might be proven beneficial in discriminating AIP from other mass forming pancreatic lesions.}, }
@article {pmid18776959, year = {2008}, author = {Woodiwiss, AJ and Badenhorst, D and Sliwa, K and Brooksbank, R and Essop, R and Sareli, P and Norton, GR}, title = {Beta1- and alpha2c-adrenoreceptor variants as predictors of clinical aspects of dilated cardiomyopathy in people of African ancestry.}, journal = {Cardiovascular journal of Africa}, volume = {19}, number = {4}, pages = {188-193}, pmid = {18776959}, issn = {1995-1892}, mesh = {Black People/*genetics ; Cardiomyopathy, Dilated/drug therapy/ethnology/*genetics/pathology/physiopathology ; Cardiovascular Agents/therapeutic use ; Case-Control Studies ; Disease Progression ; Drug Therapy, Combination ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Homozygote ; Humans ; Male ; Middle Aged ; *Polymorphism, Genetic ; Prospective Studies ; Receptors, Adrenergic, alpha-2/*genetics ; Receptors, Adrenergic, beta-1/*genetics ; Risk Factors ; Severity of Illness Index ; South Africa ; Stroke Volume/drug effects/genetics ; Treatment Outcome ; Ventricular Function, Left/drug effects/genetics ; }, abstract = {BACKGROUND: Although the beta1-adrenoreceptor (AR) Gly389Arg and alpha2c-AR Del322-325 gene variants are associated with the response to beta-AR-blocker therapy, whether this effect is associated with the risk for heart failure, or the severity or progression of heart failure is uncertain.<br><br>AIMS: To assess the relationship between Gly389Arg and Del322-325 variants and the presence, severity and progression of idiopathic dilated cardiomyopathy (IDC) in 403 black South African patients.<br><br>METHODS: Genotypes were identified using a restriction fragment length polymorphism-based technique and automated sequencing. Left ventricular ejection fraction (LVEF) and dimensions were determined at baseline and in 132 patients after six months of standard medical therapy excluding beta-AR-blockers (not indicated as standard care at the time of completing this study).<br><br>RESULTS: All patients and controls genotyped for the alpha2c-AR variant were homozygous for the Del322-325 (risk) allele. The Gly389Arg polymorphism was not associated with IDC (control n = 429) (Arg389 allele homozygosity: odds ratio = 1.03, confidence limits = 0.78-1.35), nor did it predict LVEF and cavity dimensions either before or after therapy.<br><br>CONCLUSION: In patients homozygous for the risk allele of the alpha2c-AR variant, the beta1-AR variant neither increased the risk for IDC nor predicted its severity or progression in patients not receiving beta-AR-blockers.}, }
@article {pmid18774496, year = {2008}, author = {Reena, RM and Mastura, M and Siti-Aishah, MA and Munirah, MA and Norlia, A and Naqiyah, I and Rohaizak, M and Sharifah, NA}, title = {Minichromosome maintenance protein 2 is a reliable proliferative marker in breast carcinoma.}, journal = {Annals of diagnostic pathology}, volume = {12}, number = {5}, pages = {340-343}, doi = {10.1016/j.anndiagpath.2008.04.001}, pmid = {18774496}, issn = {1532-8198}, mesh = {Adenocarcinoma/*metabolism/secondary ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/secondary ; Carcinoma, Intraductal, Noninfiltrating/metabolism/secondary ; Carcinoma, Lobular/metabolism/secondary ; Cell Cycle Proteins/*metabolism ; Cell Nucleus/metabolism/pathology ; Cell Proliferation ; Female ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Nuclear Proteins/*metabolism ; Receptors, Estrogen/metabolism ; }, abstract = {This is a study aimed to examine the distribution pattern of a specific minichromosome maintenance protein 2 (MCM2) in benign and malignant breast tissue. We also aim to correlate the frequency of expression of MCM2 with the degree of tumor differentiation. We used immunohistochemistry to examine the distribution and expression pattern of MCM2 on formalin-fixed paraffin-embedded tissue sections of benign (n = 30) and malignant breast tissue (n = 70) (IDC 56, DCIS 4, ILC 2, nonductal 4, mixed type 4). We quantified MCM2 expression by calculating a labeling index, which represents the percentage of epithelial nuclei that stained positively. Immunoreactivity was heterogenous in all the 70 malignant cases examined. Epithelial cells in cycle are most frequent at the tumor periphery. Labeling index of MCM2 was greatest in grade 3 (poorly differentiated) and lowest in grade 1 tumors (well differentiated). Minichromosome maintenance protein 2 expression in breast cancer showed a positive association with histologic grade (P < .05). In all the benign breast tissue examined, no proliferating compartments could be characterized. Minichromosome maintenance protein 2 is a useful proliferative marker of breast carcinoma. The frequency of expression of MCM2 showed an inverse correlation with the degree of tumor differentiation.}, }
@article {pmid18771601, year = {2008}, author = {Ismail, NI and Kaur, G and Hashim, H and Hassan, MS}, title = {S100A4 overexpression proves to be independent marker for breast cancer progression.}, journal = {Cancer cell international}, volume = {8}, number = {}, pages = {12}, pmid = {18771601}, issn = {1475-2867}, abstract = {BACKGROUND: Breast cancer is the most common cancer and cause of deaths in women around the world. Oncogene amplification usually occurs late in tumor progression and correlates well with aggressiveness of tumor. In fact the function of the S100A4 protein and its role in metastasis is unclear at present. The purpose of the study was to determine the expression of S100A4 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of S100A4 gene product.<br><br>METHODS: S100A4 protein expression was examined by immunohistochemistry (IHC) using commercially available tissue microarray containing malignant and normal breast tissue cores from 216 patients.<br><br>RESULTS: S100A4 was absent in normal breast tissues while positive in 45.1% of infiltrating ductal carcinoma (IDC) node negative and 48.8% of infiltrating lobular carcinoma node negative. In paired samples, S100A4 protein was expressed in 13.5% of IDC node positive cases and 35.1% of matched lymph node metastasis.<br><br>CONCLUSION: S100A4 protein expression appears widely expressed in early and advanced breast cancer stages compared with normal breast. Our study suggests S100A4 may play a role in breast cancer progression and may prove to be an independent marker of breast cancer which appears to be down regulated in more advanced stages of breast cancer.}, }
@article {pmid18765526, year = {2008}, author = {Kikuchi, S and Honda, K and Tsuda, H and Hiraoka, N and Imoto, I and Kosuge, T and Umaki, T and Onozato, K and Shitashige, M and Yamaguchi, U and Ono, M and Tsuchida, A and Aoki, T and Inazawa, J and Hirohashi, S and Yamada, T}, title = {Expression and gene amplification of actinin-4 in invasive ductal carcinoma of the pancreas.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {14}, number = {17}, pages = {5348-5356}, doi = {10.1158/1078-0432.CCR-08-0075}, pmid = {18765526}, issn = {1078-0432}, mesh = {Actinin/antagonists &amp; inhibitors/*genetics ; Aged ; Animals ; Carcinoma, Pancreatic Ductal/*genetics ; Cell Line, Tumor ; Female ; *Gene Amplification ; Gene Expression ; Humans ; Male ; Mice ; Mice, SCID ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Pancreatic Neoplasms/*genetics ; Transfection ; }, abstract = {PURPOSE: An invasive growth pattern is one of the hallmarks of pancreatic ductal carcinoma. Actinin-4 is an actin-binding protein associated with enhanced cell motility, invasive growth, and lymph node metastasis. Actinin-4 might play an important role in the development and progression of pancreatic cancer.<br><br>EXPERIMENTAL DESIGN: The expression of actinin-4 was examined immunohistochemically in 173 cases of invasive pancreatic ductal carcinoma. The copy number of the actinin-4 (ACTN4) gene was calculated by fluorescence in situ hybridization. The expression of actinin-4 was stably knocked down by short hairpin RNA, and tumorigenicity was evaluated by orthotopic implantation into mice with severe combined immunodeficiency.<br><br>RESULTS: The expression level of actinin-4 was increased in 109 (63.0%) of 173 cases of pancreatic cancer. Kaplan-Meier survival curves revealed that patients with increased expression of actinin-4 had a significantly poorer outcome (P=0.00001, log-rank test). Multivariate analysis by the Cox proportional hazard model showed that high expression of actinin-4 was the most significant independent negative predictor of survival (hazard ratio, 2.33; P=0.000009). Amplification (defined as more than four copies per interphase nucleus) of the ACTN4 gene was detected in 11 (37.9%) of 29 cases showing increased expression of actinin-4. Knockdown of actinin-4 expression inhibited the destructive growth of cancer cells in the pancreatic parenchyma.<br><br>CONCLUSION: Recurrent amplification of chromosome 19q13.1-2 has been reported in pancreatic cancer, but the exact target gene has not been identified. Actinin-4 contributes to the invasive growth of pancreatic ductal carcinoma, and ACTN4 is one of the candidate oncogenes in this chromosome locus.}, }
@article {pmid18763593, year = {2008}, author = {Vybornykh, DE and Ivanov, SV and Savchenko, VG and Gemdzhian, EG}, title = {[Somatogenic and somatogenically provoked psychoses in blood diseases].}, journal = {Terapevticheskii arkhiv}, volume = {80}, number = {7}, pages = {38-43}, pmid = {18763593}, issn = {0040-3660}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Hematologic Diseases/*complications ; Humans ; Incidence ; Male ; Middle Aged ; Psychotic Disorders/epidemiology/*etiology ; Retrospective Studies ; Risk Factors ; Russia/epidemiology ; Surveys and Questionnaires ; }, abstract = {AIM: To detect risk factors (RF) to develop somatogenic psychoses (SP) in blood diseases.<br><br>MATERIAL AND METHODS: A total of 107 SP patients were examined with the disease corresponding to diagnostic points F05 or F06 (IDC-10).<br><br>RESULTS: The following RF were identified: cytostatic drugs with or without glucocorticosteroids, glucocorticosteroids alone, interferon-alpha, viral encephalitis, neuroleukemia. Single obligatory specific factors which bring manifestation of certain psychoses were not identified. SP in each of the considered hematological malignancies are related with various factors.<br><br>CONCLUSION: The findings suggest polyfactor etiology of SP including some schemes of chemotherapy, some type of blood disease, specific premorbid features and mental disease burden. We suggest that the clinical picture, dynamics and prognosis of SP in blood diseases may be caused by a profile of factors typical for each disease.}, }
@article {pmid20424657, year = {2008}, author = {Hamed, ST and Abdo, MH and Ahmed, HH}, title = {Breast discharge: ultrasound and Doppler evaluation.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {20}, number = {3}, pages = {262-270}, pmid = {20424657}, issn = {1110-0362}, abstract = {BACKGROUND: Nipple discharge causes discomfort and anxiety to many women. Nipple discharge is most commonly associated with endocrine alterations and/or medications. These often result in duct ectasia and/or fibrocystic changes that may lead to discharge from one or several ducts. The most common cause of clinically significant discharge is intraductal growth of the ductal epithelium, due to hyperplasia, micropapillary proliferation, solitary papillomas and/or ductal carcinoma (both in situ and invasive). The aim of the study was to evaluate the role of the gray-scale ultrasound and colour Doppler in the diagnosis of intraductal pathology in patients with nipple discharge.<br><br>PATIENTS AND METHODS: One hundred &amp; seven patients were included in the study, (age range 23-65years). Standard mammographic views were taken. Ultrasound evaluation was performed for all cases; ductography for 20 cases and ductoscopy for 3 cases. US guided fine needle biopsy was done in 7 cases; microducectomy of affected duct was done in 20 cases and major duct excision in 5cases. Fibro-optic Ductoscopy is performed for 3 cases.<br><br>RESULTS: Revision of biopsy specimens of 17 cases with intraluminal masses detected by US revealed: Six cases with intraductal carcinoma, intraductal papilloma in 7 cases, 1 case of ductal papillomatosis. Three cases showed atypical cells: Intraductal papilloma with atypia in 2 cases, proliferative hyperplasia with atypia in one case. Eighty eight cases had simple duct ectasia (51 bilateral multiple and 37 focal duct ectasia). No dilated ducts were detected in 2 cases. Fibro-optic Ductoscopy confirmed the presence of intraductal papilloma in one case, carcinoma in one case, no intraductal masses in the third case. A 6 months follow-up was requested for all cases with no detected intra luminal pathology. Ultrasound examination is highly sensitive (100%) but less specific (82.4%) in diagnosis of intraductal pathology. Colour &amp; power Doppler are sensitive (94%) in detecting flow in intraductal echogenic masses to differentiate them from insipissated secretions. Colour and power Doppler raises specificity and diagnostic accuracy to 100%. Ductography is an underused procedure that is sensitive (100%) but less specific (60%) in characterization of intraductal filling defects.<br><br>CONCLUSION: Ultrasonography is a mandatory complement to mammography in these cases, US guided fine needle biopsy is minimally invasive technique in confirming the diagnosis of suspicious mass. Ultrasound may also be a guide to fibro-optic ductoscope.<br><br>KEY WORDS: Ductography - Nipple discharge - Intraductal carcinoma - Intraductal papilloma - In situ ductal carcinoma - Invasive ductal carcinoma - Duct ectasia - Breast ductoscopy.}, }
@article {pmid18751874, year = {2009}, author = {Kondo, NI and Yoshida, S and Kajiyama, H and Nagasaka, T and Uematsu, T}, title = {Metastasis of breast cancer to a uterine leiomyoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {2}, pages = {157-161}, doi = {10.1007/s12282-008-0069-5}, pmid = {18751874}, issn = {1880-4233}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Hysterectomy ; Leiomyoma/*pathology/surgery ; Middle Aged ; Tomography, X-Ray Computed ; Treatment Outcome ; Uterine Neoplasms/pathology/*secondary/surgery ; }, abstract = {Metastasis of breast cancer to a uterine leiomyoma is rare. We review the clinicopathological features of breast cancer metastasis to a uterine leiomyoma and discuss possible effective treatment. We describe a case of a woman who presented with abdominal discomfort after undergoing mastectomy for breast cancer. At the time of mastectomy, imaging showed osseous metastases involvement to the right kidney. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Microscopic examination disclosed carcinoma of breast origin localized within the leiomyoma. To date, the patient is alive and asymptomatic after treatment with anastozole and capecitabine for 11 months. Per reports in the literature, abnormal uterine bleeding or a rapidly growing leiomyoma may be symptomatic of breast cancer metastasis to a uterine leiomyoma, especially if a patient has a previous diagnosis of invasive ductal carcinoma of the breast. Palliative hysterectomy can potentially improve prognosis in patients whose cancer is restricted to a uterine leiomyoma with or without involvement of lymph nodes, and may offer relief of genital tract symptoms in patients who have widespread involvement of non-life-threatening metastases.}, }
@article {pmid18720524, year = {2008}, author = {Loo, LW and Ton, C and Wang, YW and Grove, DI and Bouzek, H and Vartanian, N and Lin, MG and Yuan, X and Lawton, TL and Daling, JR and Malone, KE and Li, CI and Hsu, L and Porter, PL}, title = {Differential patterns of allelic loss in estrogen receptor-positive infiltrating lobular and ductal breast cancer.}, journal = {Genes, chromosomes &amp; cancer}, volume = {47}, number = {12}, pages = {1049-1066}, pmid = {18720524}, issn = {1098-2264}, support = {R01 CA095717-01/CA/NCI NIH HHS/United States ; R01 CA095717/CA/NCI NIH HHS/United States ; R01 CA085913/CA/NCI NIH HHS/United States ; R01 CA085913-05/CA/NCI NIH HHS/United States ; R01 CA085913-01/CA/NCI NIH HHS/United States ; R01 CA095717-04/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics/pathology ; Case-Control Studies ; DNA, Neoplasm/metabolism ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; *Loss of Heterozygosity ; Polymorphism, Single Nucleotide ; Receptors, Estrogen/*analysis/genetics ; Tissue Array Analysis ; }, abstract = {The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct. To assess the molecular alterations associated with these breast cancer subtypes, we conducted a whole-genome study of 166 archival estrogen receptor (ER)-positive tumors (89 IDC and 77 ILC) using the Affymetrix GeneChip(R) Mapping 10K Array to identify sites of loss of heterozygosity (LOH) that either distinguished, or were shared by, the two phenotypes. We found single nucleotide polymorphisms (SNPs) of high-frequency LOH (>50%) common to both ILC and IDC tumors predominately in 11q, 16q, and 17p. Overall, IDC had a slightly higher frequency of LOH events across the genome than ILC (fractional allelic loss = 0.186 and 0.156). By comparing the average frequency of LOH by chromosomal arm, we found IDC tumors with significantly (P < 0.05) higher frequency of LOH on 3p, 5q, 8p, 9p, 20p, and 20q than ILC tumors. We identified additional chromosomal arms differentiating the subtypes when tumors were stratified by tumor size, mitotic rate, or DNA content. Of 5,754 informative SNPs (>25% informativity), we identified 78 and 466 individual SNPs with a higher frequency of LOH (P < 0.05) in ILC and IDC tumors, respectively. Hierarchical clustering of these 544 SNPs grouped tumors into four major groups based on their patterns of LOH and retention of heterozygosity. LOH in chromosomal arms 8p and 5q was common in higher grade IDC tumors, whereas ILC and low-grade IDC grouped together by virtue of LOH in 16q.}, }
@article {pmid18720457, year = {2008}, author = {Weigelt, B and Horlings, HM and Kreike, B and Hayes, MM and Hauptmann, M and Wessels, LF and de Jong, D and Van de Vijver, MJ and Van't Veer, LJ and Peterse, JL}, title = {Refinement of breast cancer classification by molecular characterization of histological special types.}, journal = {The Journal of pathology}, volume = {216}, number = {2}, pages = {141-150}, doi = {10.1002/path.2407}, pmid = {18720457}, issn = {1096-9896}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*classification/genetics/pathology ; Carcinoma, Ductal, Breast/*classification/genetics/pathology ; Cluster Analysis ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; Signal Transduction/genetics ; Statistics, Nonparametric ; }, abstract = {Most invasive breast cancers are classified as invasive ductal carcinoma not otherwise specified (IDC NOS), whereas about 25% are defined as histological 'special types'. These special-type breast cancers are categorized into at least 17 discrete pathological entities; however, whether these also constitute discrete molecular entities remains to be determined. Current therapy decision-making is increasingly governed by the molecular classification of breast cancer (luminal, basal-like, HER2+). The molecular classification is derived from mainly IDC NOS and it is unknown whether this classification applies to all histological subtypes. We aimed to refine the breast cancer classification systems by analysing a series of 11 histological special types [invasive lobular carcinoma (ILC), tubular, mucinous A, mucinous B, neuroendocrine, apocrine, IDC with osteoclastic giant cells, micropapillary, adenoid cystic, metaplastic, and medullary carcinoma] using immunohistochemistry and genome-wide gene expression profiling. Hierarchical clustering analysis confirmed that some histological special types constitute discrete entities, such as micropapillary carcinoma, but also revealed that others, including tubular and lobular carcinoma, are very similar at the transcriptome level. When classified by expression profiling, IDC NOS and ILC contain all molecular breast cancer types (ie luminal, basal-like, HER2+), whereas histological special-type cancers, apart from apocrine carcinoma, are homogeneous and only belong to one molecular subtype. Our analysis also revealed that some special types associated with a good prognosis, such as medullary and adenoid cystic carcinomas, display a poor prognosis basal-like transcriptome, providing strong circumstantial evidence that basal-like cancers constitute a heterogeneous group. Taken together, our results imply that the correct classification of breast cancers of special histological type will allow a more accurate prognostication of breast cancer patients and facilitate the identification of optimal therapeutic strategies.}, }
@article {pmid18681321, year = {2008}, author = {Li, J and Yang, SJ and Zhao, XL and Zhang, YQ and Li, KN and Cui, JH and Li, J}, title = {[Significant increase of glucose transport activity in breast cancer].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {37}, number = {2}, pages = {103-108}, pmid = {18681321}, issn = {0529-5807}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Glucose/*physiology ; Glucose Transport Proteins, Facilitative/genetics/metabolism ; Glucose Transporter Type 1/genetics/*metabolism ; Humans ; Prognosis ; }, abstract = {OBJECTIVE: To study the expression level and significance of glucose transporter 1 (Glut-1) in normal breast tissue, adenosis, adenoma and breast carcinoma.<br><br>METHODS: A total of 147 cases of female breast tissue samples, including 92 cases of invasive ductal carcinoma, 26 cases of breast fibroadenoma, 24 cases of breast adenosis and 5 cases of normal breast tissues, were collected for quantitative detection of the expression of Glut-1 protein by immunohistochemistry (EnVision method) and Western blot, and its mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).<br><br>RESULTS: In normal breast tissue and benign lesions of the breast, Glut-1 was undetectable or only weakly detectable in cytoplasm of ductal and acinar epithelia. In contrast, the intensity of Glut-1 staining was significantly higher in invasive ductal carcinomas (P = 0.0002) with protein expression predominantly in cellular membrane and lesser in cytoplasm. Western blot and RT-PCR analyses showed that the expression of Glut-1 protein and mRNA were significantly increased in invasive ductal carcinoma than fibroadenoma (P =0.001 for protein; P <0.05 for mRNA) and adenosis (P =0.001 for protein; P < 0.05 for mRNA). There was a significant difference among groups (P = 0.0002 for protein; P = 0.0001 for mRNA).<br><br>CONCLUSIONS: Glucose transport activity, as indicated by Glut-1 protein and its mRNA expression, significantly increases in breast carcinoma than non-cancerous lesions. The over-expression of Glut-1 in breast carcinoma is tightly coupled with tumor cell proliferation, invasion and metastasis, implying that Glut-1 may serve as a new marker in the early diagnosis and prognostication of breast malignancy as well as a new therapeutic target.}, }
@article {pmid18681318, year = {2008}, author = {Lü, YL and Zhong, M and Liu, L and Wei, LX and Zhao, P}, title = {[Clinicopathologic significance of chromosome 17 polysomy in breast cancer].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {37}, number = {2}, pages = {88-91}, pmid = {18681318}, issn = {0529-5807}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics ; *Chromosome Aberrations ; Chromosomes, Human, Pair 17/*genetics ; *Gene Amplification ; Gene Dosage ; Gene Expression Regulation, Neoplastic/genetics ; Genes, erbB-2/*genetics ; Humans ; }, abstract = {OBJECTIVE: To investigate the clinicopathological significance of chromosome 17 polysomy in breast cancer.<br><br>METHODS: Retrospective study of 200 cases of breast cancer including 106 cases of invasive ductal carcinoma and 94 cases of in-situ carcinoma was performed by fluorescence in-situ hybridization (FISH) to explore the relationship between chromosome 17 polysomy and age, nuclear atypia, lymphatic metastasis, HER2 gene amplification and HER2 protein expression.<br><br>RESULTS: Twenty-six percent (52/200) of chromosome 17 polysomy was detected in 200 cases of breast ductal carcinoma, all of which were invasive ductal carcinoma. Overall 52. 8% (52/180) of invasive ductal carcinoma cases showed chromosome 17 polysomy, which was correlated to HER2 gene amplification (P = 0.000) and HER-2 protein expression (P=0.000), and to HER2 expression combined with HER2 gene amplification (P=0.001). Chromosome 17 polysomy with or without HER2 gene amplification was also associated with high-grade nuclear atypia (P = 0.012 or P = 0.010) and lymphatic metastasis (P = 0.002 or P = 0.009). However, chromosome 17 polysomy with or without HER2 gene amplification was not correlative with the age of patients (P = 1. 000 or P = 0. 415).<br><br>CONCLUSION: Chromosome 17 polysomy may be related to the nuclear atypia, metastasis, HER2 gene amplification of invasive ductal carcinoma and thus a worse prognosis of the patients.}, }
@article {pmid18681317, year = {2008}, author = {Gao, LX and Yang, GZ and Ding, HY and Li, L}, title = {[Morphological features of basal-like subtype invasive carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {37}, number = {2}, pages = {83-87}, pmid = {18681317}, issn = {0529-5807}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Basal Cell/*pathology ; ErbB Receptors/genetics ; Female ; Genes, erbB-2/physiology ; Humans ; Immunohistochemistry ; Keratin-5/analysis ; Magnetic Resonance Imaging ; Male ; Mammography/instrumentation/methods ; Neoplasm Invasiveness/physiopathology ; Prognosis ; Receptor, ErbB-2/*analysis/genetics ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/analysis ; Ultrasonography/methods ; }, abstract = {OBJECTIVE: To summarize the morphological features of basal-like subtype of invasive breast carcinoma (BLSIBC), and to look for diagnostic clues for its recognition.<br><br>METHODS: Immunohistochemistry was performed in 109 cases of invasive ductal carcinoma, with CK5/6, CK14, CK8/ 18, 34betaE12, calponin, p63, CD10, ER, PR and c-erbB-2 monoclonal antibodies. Five subtypes were classified according to immunophenotypes: luminal A subtype (ER+/HER2-), luminal B subtype (ER+/ HER2+), normal breast-like subtype (ER/HER2-), HER2-overexpressing subtype and BLSIBC which was identified with at least one kind of basal-like cytokeratins or markers of myoepithelium and ER/HER2. The microscopic features of basal-like subtype were also analyzed.<br><br>RESULTS: The number of luminal A case was 48 (44.0%), luminal B 15 (13.8%), HER2 over-expressing 15 (13.6%), normal breast-like 10 (9.1%), basal-like subtype 19 (17.4%). Besides, the other two cases expressed c-erbB-2 or/and ER plus markers for myoepithelium, thus were excluded from all the five mentioned subtypes. Of the 19 basal-like subtype, CK5/6 was expressed in 16 cases, CK8/18 in 17 cases, CK14 in 11 cases, 34betaE12 in 18 cases, p63 in 5 cases, CD10 in 6 cases, and calponin in 1 case. The diameter of the BLSIBC cases was 1.2-7 cm (averagely 3.9 cm) , and in 6 cases, the tumor diameter was >5 cm. Only one case displayed extensive in situ component, 9 cases were grade 2, and 9 cases were grade 3. Compared to non basal subtype, there were significantly more high grade cases (P <0.01). The morphological features of basal-like subtype were summarized as the followings: pushing margin (13 cases), lymphocytic tissue hyperplasia (18 cases), nest or sheet arrangement (18 cases), nucleus grade 3 and scattered giant or bizarre nuclei (17 cases), syncytial growth (7 cases), and comedo-like necrosis (17 cases). The frequency of these features were significantly more common than non basal subtype (P <0.01).<br><br>CONCLUSION: The morphologic diagnostic features of BLSIBC are pushing margins, lymphocyte infiltration, comedo-like necrosis, gigantic cell and syncytial growth.}, }
@article {pmid18678310, year = {2008}, author = {Yamano, T and Nakatani, S and Kanzaki, H and Toh, N and Amaki, M and Tanaka, J and Abe, H and Hasegawa, T and Sawada, T and Matsubara, H and Kitakaze, M}, title = {Exercise-induced changes of functional mitral regurgitation in asymptomatic or mildly symptomatic patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {102}, number = {4}, pages = {481-485}, doi = {10.1016/j.amjcard.2008.03.086}, pmid = {18678310}, issn = {0002-9149}, mesh = {Cardiomyopathy, Dilated/diagnostic imaging/*physiopathology ; Echocardiography, Doppler, Color ; *Exercise ; Exercise Test ; *Exercise Tolerance ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Mitral Valve/*pathology ; Mitral Valve Insufficiency/diagnostic imaging/*etiology/physiopathology ; Prognosis ; Prospective Studies ; Risk Factors ; Stroke Volume ; Systole ; Time Factors ; }, abstract = {It has remained unclear why functional mitral regurgitation (MR), even if it is of a mild degree, has prognostic importance in patients with idiopathic dilated cardiomyopathy (IDC). Exercise-induced changes in functional MR, which might be a clue to this question, have not been fully clarified. Thus, in this study, semisupine exercise echocardiography was performed on 32 asymptomatic or mildly symptomatic patients with IDC (29 men, mean age 45 +/- 14 years). The mean ejection fraction was 28 +/- 10% (range 13% to 45%). The effective regurgitant orifice (ERO) area of MR was measured, as well as echocardiographic parameters including mitral valve geometry. ERO at rest was associated best with systolic mitral tenting area (r(S) = 0.85, p <0.001). Functional MR did not newly appear during exercise in 9 subjects without MR at rest. In the remaining 23 subjects with functional MR at rest, all showed exacerbations of MR, with a median ERO of 10.5 mm(2) (interquartile range 6.3 to 16.5) to 18.7 mm(2) (interquartile range 9.5 to 29.3) (p <0.001). An increase in ERO was correlated best with the enlargement of tenting area (r(S) = 0.90, p <0.001) and was the strongest independent determinant of exercise duration (beta = -0.55, p = 0.002, multiple R(2) = 0.46). In conclusion, functional MR complicated with IDC was significantly exacerbated during exercise, with mitral valve deformation, which was strongly related to exercise intolerance; thus, the clinical impact of functional MR in patients with IDC could be more serious than can be expected by its degree at rest.}, }
@article {pmid18677762, year = {2008}, author = {Monaco, SE and Dabbs, DJ and Kanbour-Shakir, A}, title = {Pleomorphic lobular carcinoma in pleural fluid: diagnostic pitfall for atypical mesothelial cells.}, journal = {Diagnostic cytopathology}, volume = {36}, number = {9}, pages = {657-661}, doi = {10.1002/dc.20866}, pmid = {18677762}, issn = {1097-0339}, mesh = {Biopsy ; Breast Neoplasms/complications/*diagnosis/*pathology ; Cadherins/metabolism ; Carcinoma, Lobular/complications/*diagnosis/*pathology ; *Diagnostic Errors ; Epithelium/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Pleural Effusion/complications/*pathology ; }, abstract = {Pleomorphic lobular carcinoma (PLC) is a subtype of infiltrating lobular carcinoma because of its dyscohesiveness, linear infiltration pattern, and lack of membranous E-cadherin staining. However, it differs from classic lobular carcinoma because of its high-grade cytology and more aggressive clinical behavior. In breast fine-needle aspiration biopsies, PLC can be confused with invasive ductal carcinoma, particularly the apocrine variant. In this report, we illustrate how metastatic PLC in body fluid specimens shows many of the same cytomorphologic changes that occur in reactive/atypical mesothelial cells. Fortunately, the immunohistochemical staining pattern of PLC can help to distinguish it from other possible diagnoses in the differential, such as reactive/atypical mesothelial cells and other metastatic neoplasms. However, the frequent apocrine features seen in this variant of breast carcinoma can cause nonspecific immunohistochemical positivity that may make the interpretation difficult. This is the first report illustrating the cytopathology and immunohistochemical findings of pleomorphic lobular carcinoma in body cavity fluid cytology. Our case highlights the important issues and pitfalls to be aware of when making this diagnosis.}, }
@article {pmid18662704, year = {2008}, author = {Prasad, CP and Mirza, S and Sharma, G and Prashad, R and DattaGupta, S and Rath, G and Ralhan, R}, title = {Epigenetic alterations of CDH1 and APC genes: relationship with activation of Wnt/beta-catenin pathway in invasive ductal carcinoma of breast.}, journal = {Life sciences}, volume = {83}, number = {9-10}, pages = {318-325}, doi = {10.1016/j.lfs.2008.06.019}, pmid = {18662704}, issn = {0024-3205}, mesh = {Adenomatous Polyposis Coli Protein/genetics/metabolism ; Antigens, CD ; Breast Neoplasms/*genetics/metabolism/pathology ; Cadherins/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Cell Line, Tumor ; DNA Methylation ; *Epigenesis, Genetic ; Female ; *Genes, APC ; Humans ; Kaplan-Meier Estimate ; Prospective Studies ; *Signal Transduction ; Wnt Proteins/genetics/*metabolism ; beta Catenin/genetics/*metabolism ; }, abstract = {Activation of canonical Wnt/beta-catenin pathway in Invasive Ductal Carcinoma of Breast (IDCs) was recently reported from our laboratory. Herein, we analyzed promoter methylation status of CDH1 and Adenomatous polyposis coli (APC) genes in 50 IDCs and correlated with expression of E-cadherin (E-CD) and APC proteins and with activation of oncogenic Wnt/beta-catenin signaling pathway components, Dvl, beta-catenin and CyclinD1. Further, Wnt/beta-catenin driven epithelial mesenchymal transition (EMT) was investigated by correlating the expression of Dvl, beta-catenin and CyclinD1 with vimentin expression in these IDCs. Promoter hypermethylation was observed in 25/50 (50%) IDCs for CDH1 and in 11/50 (22%) tumors for APC, associated with loss of expression of E-CD and APC proteins; concordant hypermethylation of these genes was observed in paired patients' sera. Further, 57% of tumors harboring CDH1 methylation and 50% tumors harboring the methylated APC gene showed nuclear localization of beta-catenin, suggesting activation of the canonical Wnt/beta-catenin pathway. Our study demonstrates significant association between vimentin expression and nuclear beta-catenin (p=0.001; Odds ratio (OR)=25.6) and Dvl (p=0.023; OR=8.0), suggesting that EMT may be driven by Wnt/beta-catenin activation in IDCs. In conclusion, we demonstrate correlation of CDH1 and APC promoter methylation with loss of E-CD and APC proteins and with activation of Wnt/beta-catenin signaling pathway. Association of nuclear Dvl and beta-catenin with vimentin expression suggests the importance of Wnt/beta-catenin pathway driven EMT in IDCs. The concordance between CDH1 and APC methylation in IDCs and paired circulating DNA underscores the utility of serum DNA as a non-invasive tool for methylation analysis in IDC patients.}, }
@article {pmid18660445, year = {2008}, author = {Jerosch-Herold, M and Sheridan, DC and Kushner, JD and Nauman, D and Burgess, D and Dutton, D and Alharethi, R and Li, D and Hershberger, RE}, title = {Cardiac magnetic resonance imaging of myocardial contrast uptake and blood flow in patients affected with idiopathic or familial dilated cardiomyopathy.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {295}, number = {3}, pages = {H1234-H1242}, pmid = {18660445}, issn = {0363-6135}, support = {5 M01 RR000334/RR/NCRR NIH HHS/United States ; R01-HL-58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Cardiomyopathy, Dilated/genetics/metabolism/*pathology ; Computer Simulation ; Contrast Media/metabolism ; Coronary Circulation/*physiology ; Extracellular Space/metabolism ; Female ; Gadolinium DTPA/pharmacokinetics ; Heart/*physiology ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Models, Statistical ; Mutation/genetics ; Myocardium/metabolism/*pathology ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular (LV) enlargement with systolic dysfunction, other causes excluded. When inherited, it represents familial dilated cardiomyopathy (FDC). We hypothesized that IDC or FDC would show with cardiac magnetic resonance (CMR) increased myocardial accumulation of gadolinium contrast at steady state and decreased baseline myocardial blood flow (MBF) due to structural alterations of the extracellular matrix compared with normal myocardium. CMR was performed in nine persons affected with IDC/FDC. Healthy controls came from the general population (n = 6) or were unaffected family members of FDC patients (n = 3) without signs or symptoms of IDC/FDC or any structural cardiac abnormalities. The myocardial partition coefficient for gadolinium contrast (lambda(Gd)) was determined by T1 measurements. LV shape and function and MBF were assessed by standard CMR methods. lambda(Gd) was elevated in IDC/FDC patients vs. healthy controls (lambda(Gd) = 0.56 +/- 0.15 vs. 0.41 +/- 0.06; P = 0.002), and correlated with LV enlargement (r = 0.61 for lambda(Gd) vs. end-diastolic volume indexed by height; P < 0.01) and with ejection fraction (r = -0.80; P < 0.001). The extracellular volume fraction was higher in IDC patients than in healthy controls (0.31 +/- 0.05 vs. 0.24 +/- 0.03; P = 0.002). Resting MBF was lower in IDC patients (0.64 +/- 0.13 vs. 0.91 +/- 0.22; P = 0.01) than unaffected controls and correlated with both the partition coefficient (r = -0.57; P = 0.012) and the extracellular volume fraction (r = -0.56; P = 0.019). The expansion of the extracellular space correlated with reduced MBF and ventricular dilation. Expansion of the extracellular matrix may be a key contributor to contractile dysfunction in IDC patients.}, }
@article {pmid18643929, year = {2008}, author = {Zhou, X and Coad, J and Ducatman, B and Agazie, YM}, title = {SHP2 is up-regulated in breast cancer cells and in infiltrating ductal carcinoma of the breast, implying its involvement in breast oncogenesis.}, journal = {Histopathology}, volume = {53}, number = {4}, pages = {389-402}, doi = {10.1111/j.1365-2559.2008.03103.x}, pmid = {18643929}, issn = {1365-2559}, support = {R01 CA124940/CA/NCI NIH HHS/United States ; 2P20RR016440/RR/NCRR NIH HHS/United States ; CA124940/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*enzymology/genetics ; Carcinoma, Ductal, Breast/*enzymology/genetics/metabolism ; Cell Transformation, Neoplastic/genetics/metabolism ; Female ; Fluorescent Antibody Technique ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/*metabolism ; Tumor Cells, Cultured ; *Up-Regulation ; }, abstract = {AIMS: To determine whether Src homology phosphotyrosyl phosphatase 2 (SHP2) is up-regulated in breast cancer and, if so, to determine whether its up-regulation has any relationship with clinical variables of breast cancer.<br><br>METHODS AND RESULTS: Immunoblotting, immunohistochemistry and immunofluorescence microscopy were used to assess the state of SHP2 expression in breast cancer cells and in infiltrating ductal carcinoma (IDC) of breast. The possible role of SHP2 in breast cancer cell transformation was determined by dominant-negative expression and anchorage-independent growth assays. All of the breast cancer cell lines tested and 72% of IDC breast tumours analysed had increased amounts of the SHP2 protein. In support of its positive role, dominant-negative SHP2 blocked anchorage-independent growth of breast cancer cells. Furthermore, overexpression of SHP2 seemed to have a positive relationship to HER2 overexpression, nuclear accumulation of hormone receptors, higher tumour grade and lymph node metastasis, but not to age of breast cancer patients.<br><br>CONCLUSION: SHP2 is a widely overexpressed signalling protein in IDC breast tumours. Given SHP2's positive role in cell growth, transformation and stem cell survival, the positive relationship of its overexpression to lymph node metastasis, nuclear accumulation of hormone receptors and higher tumour grade suggests that SHP2 promotes breast oncogenesis.}, }
@article {pmid18636275, year = {2009}, author = {Xuan, Y and Lin, Z}, title = {Expression of Indian Hedgehog signaling molecules in breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {135}, number = {2}, pages = {235-240}, pmid = {18636275}, issn = {1432-1335}, mesh = {Adult ; Aged, 80 and over ; Breast/cytology/*physiology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology ; Disease Progression ; Female ; Hedgehog Proteins/genetics/*physiology ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Middle Aged ; Neoplasm Invasiveness ; Patched Receptors ; Patched-1 Receptor ; Receptors, Cell Surface/genetics ; Receptors, Estrogen/analysis ; Receptors, G-Protein-Coupled/genetics ; Receptors, Progesterone/analysis ; Smoothened Receptor ; }, abstract = {PURPOSE: To investigate the clinicopathological significance and expression pattern of Hedgehog (Hh) signaling molecules in breast normal glands and invasive ductal carcinoma.<br><br>MATERIALS AND METHODS: A total of 142 cases, including 21 of normal breast and 121 of invasive ductal carcinoma of the breast, were immunohistochemically analyzed for Ihh, Ptch, Smo, Gli-1, Gli-2, and Gli-3 protein expression.<br><br>RESULTS: All of Hh signaling molecules were greatly enhanced in invasive ductal carcinoma compared with the normal breast epithelia. The expressions of Ihh, Smo, and Gli-2 were increased in PR negative cases, and the expressions of Ihh, Ptch, and Gli-1/2/3 were statistically correlated with increased proliferating index of Ki-67 in invasive ductal carcinoma. Ihh and Gli-1/2/3 expressions were correlated with node metastasis. Additionally, the protein expressions of Ihh, Ptch, and Gli-2 were correlated with the clinical stage of breast cancer.<br><br>CONCLUSIONS: Hedgehog signaling molecules play an important role in the progression of invasive ductal carcinoma of breast.}, }
@article {pmid18628458, year = {2008}, author = {Iakovlev, VV and Arneson, NC and Wong, V and Wang, C and Leung, S and Iakovleva, G and Warren, K and Pintilie, M and Done, SJ}, title = {Genomic differences between pure ductal carcinoma in situ of the breast and that associated with invasive disease: a calibrated aCGH study.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {14}, number = {14}, pages = {4446-4454}, doi = {10.1158/1078-0432.CCR-07-4960}, pmid = {18628458}, issn = {1078-0432}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Chromosomes, Human, Pair 17/*genetics ; Female ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {PURPOSE: In the quest for new targets, genomes of ductal carcinoma in situ (DCIS) and infiltrating duct carcinoma (IDC) have been compared previously; however, genomic alterations associated with cancer progression were difficult to identify. We hypothesized that significant events can be detected by comparing lesions with a broader range of behavior: from pure DCIS to IDC associated with lymph node metastasis.<br><br>EXPERIMENTAL DESIGN: Array comparative genomic hybridization, calibrated by self-self hybridization tests, was used to study 6 cases of pure DCIS and 17 cases of DCIS paired with IDC where 8 tumors had spread to the local lymph nodes.<br><br>RESULTS: Pure DCIS exhibited a marginally higher degree of genomic complexity than DCIS and IDC components of invasive tumors. The latter two showed similarity between tumors and between components of the same tumor with several regions detected preferentially compared with pure DCIS. IDC associated with lymph node metastases showed similarity of genomic profiles as a group. Gain on 17q22-24.2 was associated with higher histologic grade, large IDC size, lymphatic/vascular invasion, and lymph node metastasis (P < 0.05).<br><br>CONCLUSIONS: Our findings suggest that DCIS and IDC are associated with specific genomic events. DCIS associated with IDC is genomically similar to the invasive component and therefore may represent either a clone with high invasive potential or invasive cancer spreading through the ducts. Specifically, gain on 17q22-24.2 is a candidate region for further testing as a predictor of invasion when detected in DCIS and predictor of nodal metastasis when detected in DCIS or IDC.}, }
@article {pmid18612038, year = {2008}, author = {Tykocinski, OE}, title = {Insurance, risk, and magical thinking.}, journal = {Personality &amp; social psychology bulletin}, volume = {34}, number = {10}, pages = {1346-1356}, doi = {10.1177/0146167208320556}, pmid = {18612038}, issn = {0146-1672}, mesh = {Accidents, Traffic/economics/psychology/statistics &amp; numerical data ; Adult ; Female ; Health Services Accessibility ; Humans ; Insurance/economics/*statistics &amp; numerical data ; Insurance Coverage/statistics &amp; numerical data ; Insurance Selection Bias ; Insurance, Health ; *Intuition ; Judgment ; *Magic ; Male ; Medically Uninsured/psychology ; Mental Disorders ; Middle Aged ; Models, Psychological ; Probability ; Risk ; *Risk Assessment ; Risk Factors ; Travel ; Volition ; }, abstract = {The possession of an insurance policy may not only affect the severity of a potential loss but also its perceived probability. Intuitively, people may feel that if they are insured nothing bad is likely to happen, but if they do not have insurance they are at greater peril. In Experiment 1, respondents who were reminded of their medical insurance felt they were less likely to suffer health problems in the future compared to people who were not reminded of their medical insurance. In Experiment 2a, participants who were unable to purchase travel insurance judged the probability of travel-related calamities higher compared to those who were insured. These results were replicated in Experiment 3a in a simulation of car accident insurance. The findings are explained in terms of intuitive magical thinking, specifically, the negative affective consequences of "tempting fate" and the sense of safety afforded by the notion of "being covered."}, }
@article {pmid18611928, year = {2010}, author = {Wei, J and Cui, L and Liu, F and Fan, Y and Lang, R and Gu, F and Guo, X and Tang, P and Fu, L}, title = {E-selectin and Sialyl Lewis X expression is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast.}, journal = {International journal of surgical pathology}, volume = {18}, number = {3}, pages = {193-200}, doi = {10.1177/1066896908320832}, pmid = {18611928}, issn = {1940-2465}, mesh = {Adenocarcinoma, Papillary/blood supply/metabolism/*secondary ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/*secondary ; Cell Polarity ; E-Selectin/*metabolism ; Female ; Humans ; Lymph Nodes/*metabolism/pathology ; Lymphatic Metastasis ; Microvessels/pathology ; Neoplasm Invasiveness ; Oligosaccharides/*metabolism ; Sialyl Lewis X Antigen ; }, abstract = {To investigate the possible roles of E-selectin and its ligand, Sialyl Lewis X, in lymph node metastasis of invasive micropapillary carcinoma of the breast, 100 cases of invasive micropapillary carcinoma and 97 cases of invasive ductal carcinoma were analyzed immunohistochemically for the expression of E-selectin and Sialyl Lewis X, along with CD34, to measure the microvessel density of invasive micropapillary carcinoma. We found that the number of E-selectin-positive vessels was greater in invasive micropapillary carcinoma than in invasive ductal carcinoma, and it was significantly correlated with the histological grade, the number of positive lymph nodes, and the microvessel density of invasive micropapillary carcinoma. The Sialyl Lewis X expression of invasive micropapillary carcinoma was higher than that of invasive ductal carcinoma, which was also associated with lymph node metastasis. In invasive micropapillary carcinoma, the Sialyl Lewis X expression was predominantly in the stroma-facing surface of the cell clusters and the adjacent stroma, while in invasive ductal carcinoma it was largely intracytoplasmic or intercellular. These findings suggested that E-selectin and Sialyl Lewis X might play an important role in lymph node metastasis in invasive micropapillary carcinoma. The expression pattern of Sialyl Lewis X in invasive micropapillary carcinoma suggested that the reversal of cell polarity of invasive micropapillary carcinoma might be as an important factor for the morphogenesis and possibly the pathogenesis, especially their higher rates of lymph node metastasis.}, }
@article {pmid18593679, year = {2008}, author = {Wilson, NM and Espirito, JL and Valero, V and Pusztai, L}, title = {Paclitaxel-induced sickle cell crisis.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {65}, number = {14}, pages = {1333-1336}, doi = {10.2146/ajhp070432}, pmid = {18593679}, issn = {1535-2900}, mesh = {Black or African American ; *Anemia, Sickle Cell ; Antineoplastic Agents, Phytogenic/administration &amp; dosage/*adverse effects/pharmacology ; Breast Neoplasms/drug therapy ; Female ; Humans ; Middle Aged ; Paclitaxel/administration &amp; dosage/*adverse effects/pharmacology ; Pain/*chemically induced ; }, abstract = {PURPOSE: A case of paclitaxel-induced painful crisis in a patient with breast cancer and hemoglobin sickle cell disease (SCD) is reported.<br><br>SUMMARY: A 55-year-old postmenopausal African-American woman had stage IIB invasive ductal carcinoma of the left breast. She was not taking any medications and did not report a history of cancer or other diseases. She had mild microcytic anemia, but the rest of her blood counts and liver function test values were normal. Bone scans and computed tomography scans of her chest and abdomen did not reveal any metastatic disease. She underwent a routine left segmental mastectomy and axillary lymph node dissection that revealed a 4-cm invasive cancer with 1 of 10 axillary lymph nodes positive for metastatic disease. Her treatment plan included chemotherapy with weekly paclitaxel, followed by fluorouracil, epirubicin, and cyclophosphamide and radiation. The first cycle of paclitaxel was well tolerated until one week after initiation when the patient woke up in the middle of the night with a sudden onset of excruciating back pain and muscle spasms. Other symptoms that developed included fatigue, left-sided rib pain, and shortness of breath. The patient recalled being told that she had sickle cell trait but said that she never had a sickle cell crisis. Laboratory tests during her 13-day hospitalization revealed hemolysis. The patient was diagnosed with hemoglobin SCD and later discharged with as-needed, low-dose oxycodone and baclofen, antibiotics, and folic acid.<br><br>CONCLUSION: A patient with breast cancer and SCD had a painful crisis after receiving paclitaxel as part of her chemotherapy regimen.}, }
@article {pmid18592167, year = {2008}, author = {Kuroda, N and Fujishima, N and Inoue, K and Ohara, M and Hirouchi, T and Mizuno, K and Hayashi, Y and Lee, GH}, title = {Basal-like carcinoma of the breast: further evidence of the possibility that most metaplastic carcinomas may be actually basal-like carcinomas.}, journal = {Medical molecular morphology}, volume = {41}, number = {2}, pages = {117-120}, pmid = {18592167}, issn = {1860-1480}, mesh = {Adult ; Breast Neoplasms/*pathology ; Carcinoma, Basal Cell/*pathology ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/secondary ; Middle Aged ; Neoplasm Metastasis/*pathology ; }, abstract = {Some investigators have previously suggested that basal-like carcinoma may consist of components of invasive ductal carcinoma, not otherwise specified, metaplastic carcinoma, and medullary carcinoma. We report here two cases of breast carcinoma showing basal cell/myoepithelial differentiation. The first case was a 58-year-old Japanese woman and the second case was a 39-year-old Japanese woman. The two tumors were composed of the proliferation of epithelial cells and/or spindle-or stellate-shaped cells on the background of mucinous materials. Additionally, chondroid matrix was observed in the metastatic lesion of the first case and the primary lesion of the second case. Immunohistochemically, epithelial neoplastic cells were positive for E-cadherin and cytokeratin CAM5.2, and epithelial and spindle-or stellate-shaped cells were positive for cytokeratins 5, 14, or 17, alpha-smooth muscle actin, S-100, and p63. Our results supply further evidence that most metaplastic carcinomas may be actually be basallike carcinomas.}, }
@article {pmid18585512, year = {2008}, author = {Parks, SB and Kushner, JD and Nauman, D and Burgess, D and Ludwigsen, S and Peterson, A and Li, D and Jakobs, P and Litt, M and Porter, CB and Rahko, PS and Hershberger, RE}, title = {Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.}, journal = {American heart journal}, volume = {156}, number = {1}, pages = {161-169}, pmid = {18585512}, issn = {1097-6744}, support = {R01 HL058626-08/HL/NHLBI NIH HHS/United States ; 5 M01 RR000334/RR/NCRR NIH HHS/United States ; R01 HL058626/HL/NHLBI NIH HHS/United States ; M01 RR000334/RR/NCRR NIH HHS/United States ; R01- HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Cardiomyopathy, Dilated/epidemiology/*genetics/pathology ; Cohort Studies ; DNA Mutational Analysis ; Female ; Gene Expression Regulation ; Genetic Predisposition to Disease/*epidemiology ; *Heterozygote ; Humans ; Lamin Type A/genetics ; Male ; Middle Aged ; *Mutation, Missense ; Nuclear Lamina/genetics ; Pedigree ; Polymerase Chain Reaction ; Prognosis ; Severity of Illness Index ; Survival Analysis ; }, abstract = {BACKGROUND: Lamin A/C mutations are a well-established cause of dilated cardiomyopathy (DCM), although their frequency has not been examined in a large cohort of patients. We sought to examine the frequency of mutations in LMNA, the gene encoding lamin A/C, in patients with idiopathic (IDC) or familial dilated cardiomyopathy (FDC).<br><br>METHODS: Clinical cardiovascular data, family histories, and blood samples were collected from 324 unrelated IDC probands, of whom 187 had FDC. DNA samples were sequenced for nucleotide alterations in LMNA. Likely protein-altering mutations were followed up by evaluating additional family members, when possible.<br><br>RESULTS: We identified 18 protein-altering LMNA variants in 19 probands or 5.9% of all cases (7.5% of FDC; 3.6% of IDC). Of the 18 alterations, 11 were missense (one present in 2 kindreds), 3 were nonsense, 3 were insertion/deletions, and 1 was a splice site alteration. Conduction system disease and DCM were common in carriers of LMNA variants. Unexpectedly, in 6 of the 19 kindreds with a protein-altering LMNA variant (32%), at least one affected family member was negative for the LMNA variant.<br><br>CONCLUSIONS: Lamin A/C variants were observed with a frequency of 5.9% in probands with DCM. The novel observation of FDC pedigrees in which not all affected individuals carry the putative disease-causing LMNA mutation suggests that some protein-altering LMNA variants are not causative or that some proportion of FDC may be because of multiple causative factors. These findings warrant increased caution in FDC research and molecular diagnostics.}, }
@article {pmid18584413, year = {2008}, author = {Schubert, A and Schulz, H and Emons, G and Gründker, C}, title = {Expression of osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in HCC70 breast cancer cells and effects of treatment with gonadotropin-releasing hormone on RANKL expression.}, journal = {Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology}, volume = {24}, number = {6}, pages = {331-338}, doi = {10.1080/09513590802095845}, pmid = {18584413}, issn = {1473-0766}, mesh = {Antineoplastic Agents, Hormonal/*pharmacology ; Blotting, Western ; Breast Neoplasms/*drug therapy/genetics/*metabolism ; Cell Line, Tumor ; Coculture Techniques ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunohistochemistry ; Osteoblasts/cytology/metabolism ; Osteoprotegerin/*biosynthesis/genetics ; RANK Ligand/*biosynthesis/genetics ; RNA, Messenger/biosynthesis/genetics ; Receptors, LHRH/biosynthesis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Triptorelin Pamoate/*pharmacology ; }, abstract = {BACKGROUND: The majority of human breast cancers and in addition most breast-cancer cell lines express gonadotropin-releasing hormone (GnRH) receptors. Their proliferation and in addition their bone-directed invasion is time- and dose-dependently reduced by GnRH. Osteolytic metastases are characteristic for breast cancer-derived metastasis. Since the osteolytic activity depends on the receptor activator of nuclear factor-kappaB (NFkappaB) ligand (RANKL)/osteoprotegerin (OPG) ratio, we analyzed RANKL and OPG expression in different breast-cancer cell lines.<br><br>METHODS: Different human breast-cancer cell lines were tested for expression of GnRH receptor, OPG and RANKL. Using a co-culture system of breast-cancer cell lines and human primary osteoblasts (hOB), we analyzed the expression of OPG and RANKL in the GnRH receptor-positive breast-cancer cell line HCC70 co-cultured with or without hOB. In addition, we assessed the effects of GnRH analog treatment on OPG and RANKL mRNA and protein levels.<br><br>RESULTS: All tested breast-cancer cell lines were GnRH receptor-positive. The majority of these cell lines expressed OPG but not RANKL. The HCC70 breast-cancer cell line derived from an invasive ductal carcinoma with metastases was positive for both OPG and RANKL. The expression of RANKL by HCC70 cells was increased when co-cultured with hOB. Treatment with GnRH analogs reduced the expression of RANKL by HCC70 cells co-cultured with hOB. No effects were observed on breast cancer OPG expression.<br><br>CONCLUSIONS: These data show that the majority of human breast-cancer cell lines express OPG but not RANKL. The HCC70 breast-cancer cell line is RANKL-positive. Co-culture of HCC70 breast cancer cells with hOB increases RANKL expression. Activation of tumor GnRH receptors reduces RANKL expression. These experiments demonstrate that HCC70 breast cancer cells are able to activate osteoclasts directly via RANKL. The interaction between HCC70 breast cancer cells and osteoblasts induces osteoclastogenesis through an increase of RANKL expression. GnRH seems to play an important role by modulating the RANKL expression in HCC70 breast cancer cells.}, }
@article {pmid18580238, year = {2008}, author = {Borkar, S and Pandit-Taskar, N}, title = {F-18 FDG uptake in cutaneous metastases from breast cancer.}, journal = {Clinical nuclear medicine}, volume = {33}, number = {7}, pages = {488-489}, doi = {10.1097/RLU.0b013e318177934e}, pmid = {18580238}, issn = {1536-0229}, mesh = {Aged ; Biopsy ; Breast Neoplasms/*complications/*diagnostic imaging ; Diagnostic Imaging/methods ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/*pharmacokinetics ; Skin Neoplasms/*diagnostic imaging/*secondary ; }, abstract = {Cutaneous metastases from internal malignancies are rare with a reported incidence between 0.7% and 10%. Among all malignancies the highest incidence of cutaneous metastasis is seen in breast cancer. We report the detection of distant dermal metastases from breast cancer on F-18 FDG PET imaging. A 73-year-old woman with metastatic left breast cancer was referred for F-18 FDG PET/CT scan, which showed multiple FDG avid lesions along cutaneous and subcutaneous nodules in the posterior neck, bilateral proximal arms, anterior chest wall, and trunk. A punch biopsy of a right lower chest wall lesion revealed invasive ductal carcinoma involving the deep dermis.}, }
@article {pmid18575275, year = {2008}, author = {Miller-Graziano, CL and De, A and Laudanski, K and Herrmann, T and Bandyopadhyay, S}, title = {HSP27: an anti-inflammatory and immunomodulatory stress protein acting to dampen immune function.}, journal = {Novartis Foundation symposium}, volume = {291}, number = {}, pages = {196-208; discussion 208-11, 221-4}, doi = {10.1002/9780470754030.ch15}, pmid = {18575275}, issn = {1528-2511}, support = {R01-GM036214/GM/NIGMS NIH HHS/United States ; }, mesh = {Anti-Inflammatory Agents/*pharmacology ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Dendritic Cells/cytology/drug effects/immunology ; Heat-Shock Proteins/*pharmacology ; Humans ; Immunity/*drug effects ; Immunologic Factors/*pharmacology ; Macrophages/cytology/drug effects/immunology ; Monocytes/cytology/drug effects/immunology ; Phagocytosis/drug effects ; Phenotype ; T-Lymphocytes/cytology/drug effects/immunology ; Thrombospondin 1/immunology ; }, abstract = {The effects of HSP27 on human monocytes (MO) are predominantly antiinflammatory through preferential interleukin (IL)10 induction and by alteration of MO to immature dendritic cells (iDCs) or MO to macrophage (Mac) differentiation. Initial HSP27 inclusion in IL4+GM-CSF MO to iDC induction cultures allows Mac differentiation (CD14++, CD16+), decreases iDC (CD1a+) differentiation, and depresses DC induction of allogeneic T lymphocyte proliferation (MLR). HSP27 increased MO IL10 and M-CSF production but subsequent increased Mac differentiation isn't responsible for depressed MO to iDC differentiation and function. Mac function after IL10 induced MO to Mac differentiation is also altered by HSP27 inclusion so that Mac phagocytic activity and scavenger receptor expression (CD163) are depressed. HSP27, in addition to immature DCs, doesn't increase Mac differentiation but instead generates inhibitory DCs, which depress rather than stimulate T cell proliferation even during anti CD3+CD28 induction. Upon maturation, these HSP27-altered inhibitory DCs have increased production of the T cell and DC suppressive mediator, thrombospondin 1. HSP27's anti-inflammatory and immunodepressive effects include deranging MO differentiation to both Mac and DCs, altering their receptor expression, and inducing production of inhibitory mediators such as thrombospondin-1 as well as IL10. These data suggest HSP27 belongs to a new group of 'anti-danger signals'.}, }
@article {pmid18564057, year = {2009}, author = {Othman, MI and Majid, MI and Singh, M and Subathra, S and Seng, L and Gam, LH}, title = {Proteomics of Grade 3 infiltrating ductal carcinoma in Malaysian Chinese breast cancer patients.}, journal = {Biotechnology and applied biochemistry}, volume = {52}, number = {Pt 3}, pages = {209-219}, doi = {10.1042/BA20070271}, pmid = {18564057}, issn = {1470-8744}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; China ; Chromatography, Liquid ; Electrophoresis, Polyacrylamide Gel ; Female ; Gene Expression ; Humans ; Malaysia ; Neoplasm Proteins/*analysis ; *Proteomics ; Tandem Mass Spectrometry ; }, abstract = {Breast cancer is the leading cause of cancer-related mortality and morbidity among women worldwide and IDC (infiltrating ductal carcinoma) is the most common type of invasive breast cancer. The changes in the biological behaviour of cancer tissue can be predicted by measuring the differential protein expression of normal and cancerous tissues. Using a combination of SDS/PAGE and LC (liquid chromatography)-MS/MS (tandem MS), we identified 82 common and differentially expressed proteins from normal and cancerous breast tissues in 20 Malaysian Chinese patients with IDC. These proteins are extracted from the normal and cancerous tissue of patients and therefore represent the actual proteins involved in cancer development. Proteins identified possibly have significant roles in the development of breast cancer in Malaysian Chinese patients in view of their consistent expression in most of the patients, although some of the proteins had not been detected in earlier studies that were mostly carried out in Western countries. This observation suggests that molecular mechanisms leading to breast cancer development in this region may not be identical with those leading to IDC in Western regions.}, }
@article {pmid18548321, year = {2009}, author = {Hayashi, H and Kimura, M and Yoshimoto, N and Tsuzuki, M and Tsunoda, N and Fujita, T and Yamashita, T and Iwata, H}, title = {A case of HER2-positive male breast cancer with lung metastases showing a good response to trastuzumab and paclitaxel treatment.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {2}, pages = {136-140}, doi = {10.1007/s12282-008-0060-1}, pmid = {18548321}, issn = {1880-4233}, mesh = {Aged ; Antibodies, Monoclonal/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms, Male/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/*drug therapy/metabolism/secondary ; Male ; Paclitaxel/administration &amp; dosage ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tomography, X-Ray Computed ; Trastuzumab ; Treatment Outcome ; }, abstract = {We present a case of advanced HER2-positive male breast cancer, which showed a good response to a combined treatment of trastuzumab and paclitaxel. A 78-year-old man was diagnosed with invasive ductal carcinoma (T4d N3 M1, stage IV). He had advanced breast cancer consisting of multiple tumors with skin involvement and redness over the entire left chest region. A computed tomography (CT) scan of the chest revealed a metastatic tumor in the left lung. Histologically, both the primary breast cancer and the metastatic lung tumor were identified as invasive ductal carcinoma that was estrogen receptor-negative (ER)(-) and progesterone receptor-negative (PgR)(-), with a HER2 score of 3+ (IHC). The patient received a combination chemotherapy using trastuzumab and paclitaxel. Two months later, a follow-up chest CT scan showed that the left lung tumor had disappeared, suggesting a good response to trastuzumab and paclitaxel. During trastuzumab treatment, no severe adverse events above grade 3 were observed. This is the first reported case of advanced HER2-positive male breast cancer in which a good response to trastuzumab and paclitaxel was demonstrated at both primary breast cancer and metastatic sites.}, }
@article {pmid18546481, year = {2007}, author = {Alexe, G and Dalgin, GS and Scanfeld, D and Tamayo, P and Mesirov, JP and Ganesan, S and Delisi, C and Bhanot, G}, title = {Breast cancer stratification from analysis of micro-array data of micro-dissected specimens.}, journal = {Genome informatics. International Conference on Genome Informatics}, volume = {18}, number = {}, pages = {130-140}, pmid = {18546481}, issn = {0919-9454}, mesh = {Breast Neoplasms/*classification/genetics/pathology ; Case-Control Studies ; Disease Progression ; Gene Expression Profiling ; Genes, erbB-2 ; Humans ; *Oligonucleotide Array Sequence Analysis ; Receptors, Estrogen/genetics ; }, abstract = {We describe a new method based on principal component analysis and robust consensus ensemble clustering to identify and elucidate the subtypes of breast cancer disease. The method was applied to microarray gene expression data using micro-dissection of samples from 36 breast cancer patients with at least two of three pathological stages of disease. Controls were normal breast epithelial cells from 3 disease free patients. Our method identified an optimum set of genes and strong, stable clusters which correlated well with clinical classification into Luminal, Basal and Her2+ subtypes based on ER, PR and Her2 status. It also revealed a hierarchical portrait of disease progression through various grades and stages and identified genes and functional pathways for each stage, grade and disease subtype. We found that gene expression heterogeneity across subtypes is much greater than the heterogeneity of progression from DCIS to IDC within a subtype, suggesting that the disease subtypes are distinct disease processes. The averaging over data perturbations and clustering methods is critical in the robust identification of subtypes and gene markers for grade and progression.}, }
@article {pmid18538170, year = {2008}, author = {Kojima, Y and Akimoto, K and Nagashima, Y and Ishiguro, H and Shirai, S and Chishima, T and Ichikawa, Y and Ishikawa, T and Sasaki, T and Kubota, Y and Inayama, Y and Aoki, I and Ohno, S and Shimada, H}, title = {The overexpression and altered localization of the atypical protein kinase C lambda/iota in breast cancer correlates with the pathologic type of these tumors.}, journal = {Human pathology}, volume = {39}, number = {6}, pages = {824-831}, doi = {10.1016/j.humpath.2007.11.001}, pmid = {18538170}, issn = {1532-8392}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*enzymology/*pathology/therapy ; Carcinoma, Ductal, Breast/enzymology/secondary/therapy ; Carcinoma, Intraductal, Noninfiltrating/enzymology/secondary/therapy ; Cell Polarity ; Combined Modality Therapy ; Epithelial Cells/metabolism/pathology ; Female ; Humans ; Immunoenzyme Techniques ; Isoenzymes/*metabolism ; Middle Aged ; Neoplasm Staging ; Protein Kinase C/*metabolism ; Signal Transduction ; }, abstract = {Breast cancer is one of the common malignant diseases among women in Japan as well as in western countries, and its incidence continues to increase. Normal mammary duct epithelial cells exhibit a well-organized apicobasal polarity, which forms the basis for their specific structure and function. Although the loss of epithelial cell polarity is one of the major changes that occur during the progression of tumor cells, including breast cancer, the underlying molecular mechanisms for this, as well as their relationship to other changes such as increased proliferation and metastasis, remain to be elucidated. The atypical protein kinase C lambda/iota (aPKC lambda/iota) is involved in several signal transduction pathways, including the establishment of epithelial cell polarity. In this study we evaluated the expression and localization of aPKC lambda/iota in breast cancer by immunohistochemistry and compared our findings with the clinicopathologic factors associated with the tumor specimens. We detected aPK Clambda/iota protein overexpression in 88 of the 110 breast cancer cases (80.0%) under study, expect for decreased expression in a few cases. The immunoreactivity of aPK Clambda/iota was generally weak in ductal carcinoma in situ, but strong in invasive ductal carcinoma (IDC; P = .022). The correlation between apical or cytoplasmic aPKC lambda/iota localization and tumor pathologic type (ie, atypical ductal hyperplasia, ductal carcinoma in situ. or IDC) was also demonstrated (P < .001). These results thus indicate that the normal apicobasal polarity is lost upon the progression of a breast lesion to IDC. This is also the first evidence to show aPKC lambda/iota overexpression in breast cancer and demonstrates that its localization is associated with the trend of pathologic type of the tumor.}, }
@article {pmid18524845, year = {2008}, author = {Yan, Z and Zou, H and Tian, F and Grandis, JR and Mixson, AJ and Lu, PY and Li, LY}, title = {Human rhomboid family-1 gene silencing causes apoptosis or autophagy to epithelial cancer cells and inhibits xenograft tumor growth.}, journal = {Molecular cancer therapeutics}, volume = {7}, number = {6}, pages = {1355-1364}, pmid = {18524845}, issn = {1535-7163}, support = {P50 CA097190/CA/NCI NIH HHS/United States ; CA097190/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Apoptosis/drug effects ; *Autophagy/drug effects ; Breast Neoplasms/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Epithelial Cells/drug effects/*pathology ; ErbB Receptors/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; *Gene Silencing/drug effects ; Head and Neck Neoplasms/genetics/pathology ; Humans ; Membrane Proteins ; Mice ; Mice, Nude ; Nanoparticles ; Neoplasms/genetics/*pathology ; Neoplasms, Squamous Cell/genetics/pathology ; Polymers ; RNA, Small Interfering/pharmacology ; Signal Transduction/drug effects ; *Xenograft Model Antitumor Assays ; }, abstract = {The rhomboid family of genes carry out a wide range of important functions in a variety of organisms. Little is known, however, about the function of the human rhomboid family-1 gene (RHBDF1). We show here that RHBDF1 function is essential to epithelial cancer cell growth. RHBDF1 mRNA level is significantly elevated in clinical specimens of invasive ductal carcinoma of the breast, and the protein is readily detectable in human breast cancer or head and neck cancer cell lines. Silencing the RHBDF1 gene with short interfering RNA (siRNA) results in apoptosis in breast cancer MDA-MB-435 cells and autophagy in head and neck squamous cell cancer 1483 cells. The treatment also leads to significant down-modulation of activated AKT and extracellular signal-regulated kinase in the cells, suggesting that critically diminished strength of these growth signals may be the key attributes of the induction of cell death. Furthermore, silencing the RHBDF1 gene in MDA-MB-435 or 1483 xenograft tumors on athymic nude mice by using i.v. administered histidine-lysine polymer nanoparticle-encapsulated siRNA results in marked inhibition of tumor growth. Our findings indicate that RHBDF1 has a pivotal role in sustaining growth signals in epithelial cancer cells and thus may serve as a therapeutic target for treating epithelial cancers.}, }
@article {pmid18505551, year = {2008}, author = {Scholz, M and Fraunholz, MJ}, title = {A computational model of gene expression reveals early transcriptional events at the subtelomeric regions of the malaria parasite, Plasmodium falciparum.}, journal = {Genome biology}, volume = {9}, number = {5}, pages = {R88}, pmid = {18505551}, issn = {1474-760X}, mesh = {Animals ; DNA, Protozoan/*genetics ; Models, Genetic ; Plasmodium falciparum/*genetics ; Principal Component Analysis ; Telomere/*genetics ; *Transcription, Genetic ; }, abstract = {BACKGROUND: The malaria parasite, Plasmodium falciparum, replicates asexually in a well-defined infection cycle within human erythrocytes (red blood cells). The intra-erythrocytic developmental cycle (IDC) proceeds with a 48 hour periodicity.<br><br>RESULTS: Based on available malaria microarray data, which monitored gene expression over one complete IDC in one-hour time intervals, we built a mathematical model of the IDC using a circular variant of non-linear principal component analysis. This model enables us to identify rates of expression change within the data and reveals early transcriptional events at the subtelomeres of the parasite's nuclear chromosomes.<br><br>CONCLUSION: A delay between subtelomeric and central gene activities suggests that key events of the IDC are initiated at the subtelomeric regions of the P. falciparum nuclear chromosomes.}, }
@article {pmid18497952, year = {2008}, author = {Xu, S and Wei, B and Zhang, H and Qing, M and Bu, H}, title = {Evidence of chromosomal alterations in pure usual ductal hyperplasia as a breast carcinoma precursor.}, journal = {Oncology reports}, volume = {19}, number = {6}, pages = {1469-1475}, pmid = {18497952}, issn = {1021-335X}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; *Chromosome Aberrations ; Chromosomes, Human/*genetics ; DNA, Neoplasm/genetics ; Female ; Humans ; Hyperplasia/genetics/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Precancerous Conditions/*genetics/pathology ; }, abstract = {Previous studies have shown the chromosomal alterations in usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) in the breast with bilateral ductal hyperplasia or adjacent to invasive ductal carcinoma (IDC). However, the role of UDH as a putative precursor of breast IDC is not clear and has not been fully addressed. The aim of this study was to clarify the role of UDH in breast carcinoma pathogenesis. To investigate chromosomal imbalances and commonality, samples of pure unilateral UDH (n=20) were obtained by laser capture microdissection and analyzed by comparative genomic hybridization. Other ductal lesions, including ADH (n=2), high-grade DCIS (n=3), and grade III IDC (n=5), were assessed at the same time for comparison. The mean values of alteration were 1.95 (39/20) in UDH, 9.5 (19/2) in ADH, 11.0 (33/3) in DCIS and 18.2 (89/5) in IDC, respectively. Some common predisposition regions for the deletions were at chromosomes 1p36-pter, 13q11-14, and 16q11-23, while the high frequency amplification regions were 1q31-qter, 3p21-pter, 6p21-pter, 11q11-14, 12q11-qter, 13q21-qter, 16p12-pter, 17q12-22, and 20q. The genetic abnormalities in the spectrum of breast ductal hyperplasia revealed that the deletion of DNA copy in UDH was the lowest, and gradually increased in the lineages of ADH, DCIS and IDC. Results showed that a significant portion of UDH shares common genetic alterations with ADH, DCIS and IDC, indicating UDH as a precursor of invasive breast ductal carcinoma.}, }
@article {pmid18490762, year = {2008}, author = {Woszczek, G and Chen, LY and Nagineni, S and Shelhamer, JH}, title = {IL-10 inhibits cysteinyl leukotriene-induced activation of human monocytes and monocyte-derived dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {180}, number = {11}, pages = {7597-7603}, pmid = {18490762}, issn = {0022-1767}, support = {Z01 CL008071-04/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Cell Migration Inhibition ; Chemokine CCL5/immunology/metabolism ; Chemotaxis ; Chemotaxis, Leukocyte ; Cysteine/immunology/*metabolism ; Dendritic Cells/*immunology/metabolism ; Humans ; Interleukin-10/immunology/*metabolism ; Leukotriene D4/immunology/metabolism ; Leukotrienes/immunology/*metabolism ; Monocytes/*immunology/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering ; Receptors, Leukotriene/deficiency/genetics/*metabolism ; }, abstract = {The immunoregulatory cytokine IL-10 plays an essential role in down-modulating adaptive and innate immune responses leading to chronic inflammatory diseases. In contrast, cysteinyl leukotrienes (cysLTs), important proinflammatory mediators of cell trafficking and innate immune responses, are thought to enhance immune reactions in the pathogenesis of diseases, such as bronchial asthma, atherosclerosis, and pulmonary fibrosis. The aim of this study was to determine the IL-10 regulatory role in cysLT-induced activation of human monocytes and monocyte-derived dendritic cells. Herein we show that cysLT-induced activation and chemotaxis of human monocytes and monocyte-derived immature dendritic cells (iDC) are inhibited by IL-10 pretreatment. IL-10 down-regulated cysLT type 1 and 2 receptors' mRNA in a time- and concentration-dependent fashion. cysLT-induced activation of monocytes and iDCs measured by intracellular calcium flux and immediate-early gene expression (FBJ murine osteosarcoma viral oncogen homolog B and early growth response-2) was potently decreased by IL-10 and by the cysLT antagonist MK571. Chemotaxis of monocytes and iDCs to increasing concentrations of leukotriene D(4) (LTD(4)) was also inhibited by IL-10. LTD(4) enhanced iDC migration in response to CCL5. IL-10 selectively inhibited LTD(4)-induced chemotaxis without affecting migration to CCL5. These data indicate that cysLT-induced activation of human monocytes and dendritic cells may be specifically inhibited by IL-10, suggesting a direct link between the 5-lipoxygenase proinflammatory pathway and IL-10 regulatory mechanisms. Antileukotriene therapies may reproduce some regulatory mechanisms played by IL-10 in inflammatory processes.}, }
@article {pmid18488218, year = {2009}, author = {Vujanovic, L and Whiteside, TL and Potter, DM and Chu, J and Ferrone, S and Butterfield, LH}, title = {Regulation of antigen presentation machinery in human dendritic cells by recombinant adenovirus.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {58}, number = {1}, pages = {121-133}, pmid = {18488218}, issn = {1432-0851}, support = {P01 CA109688/CA/NCI NIH HHS/United States ; R01 CA110249/CA/NCI NIH HHS/United States ; R01 CA110249-03/CA/NCI NIH HHS/United States ; R01 CA138188/CA/NCI NIH HHS/United States ; }, mesh = {Adenoviridae/*genetics/physiology ; *Antigen Presentation/genetics/immunology/physiology ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Dendritic Cells/*immunology/metabolism ; Flow Cytometry ; *Genetic Vectors ; Humans ; Lymphocyte Activation ; Recombinant Proteins/genetics ; Transduction, Genetic ; }, abstract = {Recombinant adenoviral vectors (AdV) are potent vehicles for antigen engineering of dendritic cells (DC). DC engineered with AdV to express full length tumor antigens are capable stimulators of antigen-specific polyclonal CD8+ and CD4+ T cells. To determine the impact of AdV on the HLA class I antigen presentation pathway, we investigated the effects of AdV transduction on antigen processing machinery (APM) components in human DC. Interactions among AdV transduction, maturation, APM regulation and T cell activation were investigated. The phenotype and cytokine profile of DC transduced with AdV was intermediate, between immature (iDC) and matured DC (mDC). Statistically significant increases in expression were observed for peptide transporters TAP-1 and TAP-2, and HLA class I peptide-loading chaperone ERp57, as well as co-stimulatory surface molecule CD86 due to AdV transduction. AdV transduction enhanced the expression of APM components and surface markers on mDC, and these changes were further modulated by the timing of DC maturation. Engineering of matured DC to express a tumor-associated antigen stimulated a broader repertoire of CD8+ T cells, capable of recognizing immunodominant and subdominant epitopes. These data identify molecular changes in AdV-transduced DC (AdV/DC) that could influence T cell priming and should be considered in design of cancer vaccines.}, }
@article {pmid18484683, year = {2008}, author = {Marchiò, C and Iravani, M and Natrajan, R and Lambros, MB and Savage, K and Tamber, N and Fenwick, K and Mackay, A and Senetta, R and Di Palma, S and Schmitt, FC and Bussolati, G and Ellis, LO and Ashworth, A and Sapino, A and Reis-Filho, JS}, title = {Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast.}, journal = {The Journal of pathology}, volume = {215}, number = {4}, pages = {398-410}, doi = {10.1002/path.2368}, pmid = {18484683}, issn = {0022-3417}, mesh = {Breast Neoplasms/*genetics/immunology ; Carcinoma, Ductal, Breast/*genetics/immunology ; Cyclin D1/genetics ; Disease Progression ; Female ; Gene Amplification ; Gene Expression Profiling/*methods ; Genetic Markers ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; *Oligonucleotide Array Sequence Analysis ; Oncogenes ; }, abstract = {Pure invasive micropapillary carcinoma (MPC) is a special histological type that accounts for 0.7-3% of all breast cancers. MPC has a distinctive growth pattern and a more aggressive clinical behaviour than invasive ductal carcinomas of no special type (IDC-NSTs). To define the molecular characteristics of MPCs, we profiled a series of 12 MPCs and 24 grade and oestrogen receptor (ER)-matched IDC-NSTs using high-resolution microarray comparative genomic hybridization (aCGH). In addition, we generated a tissue microarray containing a series of 24 MPCs and performed immunohistochemical analysis with ER, PR, Ki-67, HER2, CK5/6, CK14, CK17, EGFR, topoisomerase-IIalpha, cyclin D1, caveolin-1, E-cadherin, and beta-catenin antibodies. In situ hybridization probes were employed to evaluate the prevalence of amplification of HER2, TOP2A, EGFR, CCND1, MYC, ESR1, and FGFR1 genes. aCGH analysis demonstrated that MPCs significantly differed from IDC-NSTs at the genomic level. Gains of 1q, 2q, 4p, 6p, 6q23.2-q27, 7p, 7q, 8p, 8q, 9p, 10p, 11q, 12p, 12q, 16p, 17p, 17q, 19p, 20p, 20q, and 21q, and losses of 1p, 2p, 6q11.1-q16.3, 6q21-q22.1, 9p, 11p, 15q, and 19q were more prevalent in MPCs. High-level gains/amplifications of 8p12-p11, 8q12, 8q13, 8q21, 8q23, 8q24, 17q21, 17q23, and 20q13 were significantly associated with MPCs. A comparison between 24 MPCs and a series of 48 grade and ER-matched IDC-NSTs revealed that high cyclin D1 expression, high proliferation rates, and MYC (8q24) amplification were significantly associated with MPCs. Our results demonstrate that MPCs have distinct histological features and molecular genetic profiles supporting the contention that they constitute a distinct pathological entity.}, }
@article {pmid18473330, year = {2008}, author = {Simpson, PT and Reis-Filho, JS and Lambros, MB and Jones, C and Steele, D and Mackay, A and Iravani, M and Fenwick, K and Dexter, T and Jones, A and Reid, L and Da Silva, L and Shin, SJ and Hardisson, D and Ashworth, A and Schmitt, FC and Palacios, J and Lakhani, SR}, title = {Molecular profiling pleomorphic lobular carcinomas of the breast: evidence for a common molecular genetic pathway with classic lobular carcinomas.}, journal = {The Journal of pathology}, volume = {215}, number = {3}, pages = {231-244}, doi = {10.1002/path.2358}, pmid = {18473330}, issn = {0022-3417}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*genetics ; Carcinoma, Ductal, Breast/chemistry/genetics ; Carcinoma, Lobular/chemistry/*genetics ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Loss of Heterozygosity ; Oligonucleotide Array Sequence Analysis ; }, abstract = {Pleomorphic lobular carcinomas (PLC) of the breast display histological features associated with classic invasive lobular carcinoma (ILC), yet they also exhibit more conspicuous nuclear atypia and pleomorphism, and an aggressive clinical behaviour. From a breast cancer progression perspective, it is unclear whether PLC is a variant of ILC or is a high-grade invasive ductal carcinoma (IDC) that has lost E-cadherin. The molecular features of 26 PLC were studied using immunohistochemistry [oestrogen receptor (ER), progesterone receptor (PR), HER2, p53 and E-cadherin], 0.9 Mb resolution, microarray-based comparative genomic hybridization (aCGH), fluorescent (FISH) and chromogenic (CISH) in situ hybridization and loss of heterozygosity. Comparative analysis was performed with aCGH data from PLC with classic ILC (16 cases) and high grade IDC (35 cases). PLCs were frequently ER- and PR-positive, E-cadherin-negative and occasionally HER2- and p53-positive. Recurrent copy number changes identified by aCGH included gains on 1q, 8q, 11q, 12q, 16p and 17q and losses on 8p, 11q, 13q, 16q and Xq. Highly recurrent 1q+ (100% of cases), 16p+ (93%), 11q- (53%) and 16q- (93%) and evidence of the der(1;16)/der(16)t(1;16) rearrangement, as detected by FISH, suggested that PLC had a 'lobular genotype'. Focal amplifications were evident at 8p12-p11, 8q24, 11q13.1-q14.1, 12q14, 17q12 and 20q13. Loss of BRCA2 was detected in 40% of PLC by LOH. Comparative analysis of aCGH data suggested the molecular features of PLC (ER/PR-positive, E-cadherin-negative, 1q+, 11q(-), 16p+ and 16q(-)) were more closely related to those of ILC than IDC, implicating an overlapping developmental pathway for these lobular tumour types. Molecular alterations found in PLC that are more typical of high-grade IDC than ILC (p53 and HER2 positivity, 8q+, 17q24-q25+, 13q(-) and amplification of 8q24, 12q14, 17q12 and 20q13) are likely to drive the high-grade and more aggressive biology of PLC.}, }
@article {pmid18460206, year = {2008}, author = {Segerer, SE and Müller, N and Brandt, Jv and Kapp, M and Dietl, J and Reichardt, HM and Rieger, L and Kämmerer, U}, title = {The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation.}, journal = {Reproductive biology and endocrinology : RB&amp;E}, volume = {6}, number = {}, pages = {17}, pmid = {18460206}, issn = {1477-7827}, mesh = {Actins/analysis ; Activins/pharmacology/*physiology ; Adult ; Antigens, CD/biosynthesis/genetics ; B7-2 Antigen/biosynthesis/genetics ; CD40 Antigens/biosynthesis/genetics ; Cell Differentiation/drug effects ; Cells, Cultured/drug effects/metabolism ; Cytoskeleton/drug effects/ultrastructure ; Dendritic Cells/cytology/*drug effects/metabolism ; Dexamethasone/pharmacology ; Female ; HLA-DR Antigens/biosynthesis ; Humans ; Immune Tolerance/physiology ; Immunoglobulins/biosynthesis/genetics ; Inhibins/pharmacology/*physiology ; Interleukin-1beta/pharmacology ; Interleukin-6/pharmacology ; Male ; Membrane Glycoproteins/biosynthesis/genetics ; Monocytes/cytology/drug effects ; Recombinant Proteins/pharmacology ; T-Lymphocyte Subsets/immunology ; Transforming Growth Factor beta1/pharmacology ; }, abstract = {BACKGROUND: Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta) family including activin A (ActA) and inhibin A (InA) are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype.<br><br>METHODS: To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex) as controls.<br><br>RESULTS: Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected.<br><br>CONCLUSION: These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.}, }
@article {pmid18454879, year = {2008}, author = {Ismail, NI and Kaur, G and Hashim, H and Hassan, MS}, title = {Nuclear localization and intensity of staining of nm23 protein is useful marker for breast cancer progression.}, journal = {Cancer cell international}, volume = {8}, number = {}, pages = {6}, pmid = {18454879}, issn = {1475-2867}, abstract = {BACKGROUND: Breast cancer is the most common cause of cancer death in the western world. The expression differences of many proteins are associated with breast cancer progression or suppression. The purpose of the study was to determine the expression of nm23 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of nm23 gene product.<br><br>METHOD: nm23 protein expression was examined by immunohistochemistry (IHC) using commercially available tissue microarray containing malignant and normal breast tissues from 216 patients.<br><br>RESULTS: a similar percentage of cases showed positive cytoplasmic/nuclear staining for nm23 in normal breast tissue (85.7%), primary breast carcinoma node negative (97.5%) and carcinoma with lymph node metastasis (92.1%). Nuclear localization of staining for nm23 protein was higher in infiltrating ductal carcinoma (IDC) node positive (24.3%) and in matched lymph mode metastasis (18.9%) compared to IDC node negative (4.9%). Strong intensity of cytoplasmic/nucleus staining was observed in IDC node negative (42.6%), in IDC node positive (57.1%), and Infiltrating lobular carcinoma (ILC) node negative (44%) compared to normal breast tissue (16.7%).<br><br>CONCLUSION: nm23 protein expression appears widely expressed in normal breast, early and advanced breast cancer stages. Interestingly our study found that strong staining intensity and nuclear localization of nm23 protein may prove to be a useful marker of breast cancer progression.}, }
@article {pmid18452239, year = {2008}, author = {Shin, O and Kim, SJ and Lee, WI and Kim, JY and Lee, H}, title = {Effective transduction by self-complementary adeno-associated viruses of human dendritic cells with no alteration of their natural characteristics.}, journal = {The journal of gene medicine}, volume = {10}, number = {7}, pages = {762-769}, doi = {10.1002/jgm.1204}, pmid = {18452239}, issn = {1521-2254}, mesh = {DNA Primers/genetics ; Dendritic Cells/*cytology ; Dependovirus ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; *Gene Transfer Techniques ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Interleukin-4 ; Propidium ; Transduction, Genetic/*methods ; }, abstract = {BACKGROUND: Effective gene delivery techniques are required to genetically manipulate dendritic cells (DCs). We therefore investigated the feasibility of using various self-complementary recombinant adeno-associated virus (scAAV) serotypes to deliver genes to human DCs.<br><br>METHODS: Monocytes isolated from healthy volunteers were differentiated to immature DCs (iDC) by incubation with interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor. The iDCs were transduced with scAAV1, 2, 3, 4, 5, 6 or 8 at various multiplicities of infection (MOIs). Transduction efficiency (TE), cell viability and functional characteristics of the transduced DCs were evaluated.<br><br>RESULTS: TE of scAAV was three-fold greater than TE of conventional recombinant adeno-associated virus with a single-stranded genome. The TEs of scAAV2, 5, and 6 were much higher than those of the other scAAVs; at 1000 MOI, the TEs were 22.2% +/- 9.5%, 27.0% +/- 8.8% and 28.4% +/- 6.0%, respectively. Exposure of iDCs to 5000 MOI of these viruses increased their TEs, leading to the transduction of nearly the entire DC population. In addition, gene transfer by scAAV did not cause any cytotoxicity. Flow cytometric analysis of scAAV-transduced DCs showed no changes in surface marker profiles. Moreover, transduced cells maintained their functional properties, as represented by active antigen uptake. These cells could efficiently differentiate into mature DCs, as shown by their release of IL-12, the substantial loss of antigen-uptake activity, and the ability of T-cell stimulation.<br><br>CONCLUSIONS: These findings strongly indicate that scAAVs, especially subtypes 2, 5 and 6, hold a promising potential as gene delivery tools in human DCs.}, }
@article {pmid18442377, year = {2008}, author = {Myerson, JS and Nicum, S and Sharma, B and O'Brien, ME}, title = {Malignant mesothelioma with unexpected contralateral mediastinal shift: a case report.}, journal = {Journal of medical case reports}, volume = {2}, number = {}, pages = {125}, pmid = {18442377}, issn = {1752-1947}, abstract = {INTRODUCTION: Contralateral mediastinal shift due to pleural mesothelioma tissue, rather than a pleural effusion, is an unusual clinical feature of mesothelioma.<br><br>CASE PRESENTATION: A 63-year-old woman with a past history of treated invasive ductal carcinoma of the breast presented with breathlessness and chest pain. Her chest radiograph revealed contralateral mediastinal shift and drainage of over 3 litres of pleural fluid relieved her symptoms. She underwent further investigations which revealed pleural mesothelioma, rather than the expected metastatic breast cancer. When she represented with breathlessness a few months later, a chest radiograph again demonstrated contralateral mediastinal shift. A thoracic ultrasound on this occasion revealed only a small loculated pleural effusion and, unexpectedly, a large volume of malignant tissue, thereby explaining the chest radiograph appearances.<br><br>CONCLUSION: This case illustrates mediastinal shift away from the affected side which was caused by mesothelioma tissue itself, rather than by a pleural effusion which is the more usual cause of contralateral mediastinal shift in mesothelioma.}, }
@article {pmid18441844, year = {2008}, author = {Lehman, JS and Benacci, JC}, title = {Cutaneous metastasis of invasive ductal carcinoma of the breast to an infusaport site.}, journal = {Cutis}, volume = {81}, number = {3}, pages = {223-226}, pmid = {18441844}, issn = {0011-4162}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; *Catheters, Indwelling ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Skin Neoplasms/*secondary ; Subclavian Vein ; }, abstract = {Cutaneous metastasis of a primary internal malignancy is a relatively common phenomenon, occurring in up to 10% of patients with noncutaneous cancer. Cutaneous metastasis can occur via direct extension, hematologic or lymphatic dissemination, or surgical implantation. The most common internal malignancy associated with the development of cutaneous metastases in females is breast cancer. We present a patient with widely metastatic invasive ductal carcinoma of the breast, status postpalliative mastectomy and chest wall coverage with a vertical rectus abdominus myocutaneous flap, who acquired cellulitis and, subsequently, noncontiguous cutaneous metastasis of her breast cancer to the site of her central venous access device (ie, infusaport). We hypothesize that the local inflammation associated with her recent bout of cellulitis and operations, in conjunction with the presence of a foreign body, may have predisposed the infusaport site to seeding by metastatic tumor cells. This case highlights the importance of considering cutaneous metastasis in the differential diagnosis of new skin eruptions in patients with cancer.}, }
@article {pmid18439077, year = {2008}, author = {Ghaffari, SR and Sabokbar, T and Pour, PN and Dastan, J and Mehrkhani, F and Shoraka, S and Mohagheghi, MA and Tirgari, F and Mosavi-Jarrahi, A}, title = {Comparative genomic hybridization (CGH) analysis of chromosomal aberrations in Iranian patients with invasive ductal carcinoma breast cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {9}, number = {1}, pages = {66-70}, pmid = {18439077}, issn = {2476-762X}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1/genetics ; Chromosomes, Human, Pair 13/genetics ; Chromosomes, Human, Pair 17/genetics ; Chromosomes, Human, Pair 8/genetics ; Comparative Genomic Hybridization/*methods ; DNA, Neoplasm/genetics ; Female ; Humans ; Image Processing, Computer-Assisted ; In Situ Hybridization, Fluorescence ; Iran/epidemiology ; Lymphatic Metastasis ; Middle Aged ; Polymerase Chain Reaction ; Prognosis ; }, abstract = {INTRODUCTION: Breast cancer is one of the most common cancers in women; however, due to the complexity of chromosomal changes, limited data are available regarding chromosomal constitution.<br><br>MATERIALS AND METHODS: In this study, Comparative Genomic Hybridization (CGH) was used on 16 Iranian patients diagnosed with invasive ductal breast carcinomas.<br><br>RESULTS: 12 samples had abnormal CGH results (75%), including 21 types of chromosomal imbalance. The most prevalent were chromosomal gain of +1q, +17q, +8q and chromosomal loss of -13q. All three cases with DNA loss at chromosome 13q (-13q) had lymph node metastasis.<br><br>CONCLUSIONS: CGH is able to detect chromosomal abnormalities which are difficult to identify by conventional cytogenetic techniques. More studies on a larger sample size may help to confirm or rule out any possible correlation between 13q monosomy and lymph node metastasis, which could result in establishing new strategies for prevention and early detection of invasive breast tumors.}, }
@article {pmid18437416, year = {2008}, author = {Turashvili, G and Hayes, M and Gilks, B and Watson, P and Aparicio, S}, title = {Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer?.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {452}, number = {6}, pages = {589-598}, pmid = {18437416}, issn = {0945-6317}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/classification/genetics/*pathology ; Carcinoma in Situ/pathology ; Epithelial Cells/*pathology ; Estrogen Receptor alpha/analysis ; Female ; Humans ; Immunohistochemistry ; Mammary Glands, Human/*pathology ; Mammography ; Precancerous Conditions/*pathology ; Receptors, Androgen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {Columnar cell lesions (CCLs) are one of the most common abnormalities in the adult female human breast, characterized by the presence of columnar-shaped epithelial cells lining enlarged terminal-duct lobular units. CCLs are being seen increasingly in core biopsies taken for the non-palpable calcifications. The increased incidence may reflect improved delineation and recognition of CCLs by pathologists or a true increase in incidence related to biological and/or environmental factors. Columnar cell-like lesions have been described under a variety of names such as blunt duct adenosis, flat epithelial atypia, and ductal intraepithelial neoplasia type DIN1a. The current histologic classification used by some pathologists divides them into simple columnar cell change and columnar cell hyperplasia, both of which can occur with or without atypia. Columnar cells lack mature luminal or basal/myoepithelial phenotype markers, but they are usually positive for estrogen receptor-alpha. The cellular origin of CCLs and their possible relationship to either expansion or metaplasia of a preexisting normal cell phenotype remains unclear. CCLs are frequently associated with lobular and ductal in situ tumors and invasive lobular and tubular carcinomas. The relationship and natural history of CCLs to invasive ductal carcinoma is enigmatic, but they may prove of clinical relevance when detected by screening mammography.}, }
@article {pmid18432005, year = {2008}, author = {de Carsalade, GY and Receveur, MC and Ezzedine, K and Saget, J and Achirafi, A and Bobin, P and Malvy, D}, title = {[Delayed home screening of leprosy; experience of the screening team in Mayotte].}, journal = {Bulletin de la Societe de pathologie exotique (1990)}, volume = {101}, number = {1}, pages = {32-35}, pmid = {18432005}, issn = {0037-9085}, mesh = {Adolescent ; Adult ; Attitude to Health ; Child ; Comoros ; Contact Tracing ; Early Diagnosis ; Endemic Diseases ; *Family ; Female ; Health Education ; Humans ; Leprosy/*diagnosis/psychology/transmission ; Leprosy, Lepromatous/diagnosis ; Leprosy, Tuberculoid/diagnosis ; Male ; Mass Screening/*methods ; Middle Aged ; Self Care ; Self Concept ; }, abstract = {Mayotte, a French territory island located in the Indian Ocean near Madagascar, remains a leprosy endemic area. In 2006, leprosy was still a problem of public health with a prevalence of 3.94 per 10,000 inhabitants. There is practically no formal consensus about active screening (AS) on an index case. According to teams and their related staffs, the AS concerns intradomicilary contact individuals (IDC) restrictively or extended to extra-domicilary social and professional contacts. Date, number and frequency of these investigations depend on each team. Between 1997 and 2003, there was no AS planned in Mayotte, but all index case individuals have been encouraged to propose a screening to their relatives through specific campaign information and education. This procedure allowed to identify 10 new cases of leprosy infection among the IDC. Concurrently 12 IDC cases have been diagnosed by health workers. In 2003, we performed a postponed AS within IDC of every Mahorais case registered by passive detection between 1997 and 2003. 325 IDC have been examined and 15 new cases have been detected. All these new cases showed early leprosy features: 14 were paucibacillary forms, among which 9 cases with an isolated cutaneous lesion (7 had an infracentimetric lesion). One patient had multibacillary disease although he presented with an isolated skin lesion which developed within the 6 previous months. None presented with disability. Our results suggest that passive detection even reinforced by repeated individual information and education about leprosy is neither appropriate nor effective. The postponed AS seems to favour an increased self-esteem and a better involvement of the index patient in sanitary education together with the screening of his relatives. In the Mayotte background, the postponed AS has not been associated with a significant delay for diagnosis. Although WHO recommandations are to abandon immediate AS of IDC and to promote self-screening for leprosy our study suggests an intermediate position, namely delayed active screening for an enhanced effective detection.}, }
@article {pmid18429832, year = {2008}, author = {Yasuhara, Y and Mikami, Y and Ishiguro, S}, title = {Metastatic breast carcinoma identified in a uterine leiomyosarcoma.}, journal = {Pathology international}, volume = {58}, number = {5}, pages = {317-321}, doi = {10.1111/j.1440-1827.2008.02230.x}, pmid = {18429832}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/*secondary/therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Hysterectomy ; Leiomyosarcoma/chemistry/*pathology/surgery ; Liver Neoplasms/secondary ; Middle Aged ; Neoplasm Metastasis ; *Neoplasms, Second Primary ; Uterine Neoplasms/chemistry/*pathology/*secondary/surgery ; }, abstract = {A rare example is described of an advanced invasive ductal carcinoma of the breast with concomitant metastatic foci in a uterine leiomyosarcoma. Both tumors arose in a 48-year-old woman, without any evidence of distant metastases as assessed on imaging at the time of diagnosis. The double diagnosis in this particular case was established on a combination of microscopic appearance of the uterine tumors in the hysterectomy specimen, immunophenotype assessment, and clinical information on the breast carcinoma. But the association between the two malignancies can be challenging and potentially difficult to prove.}, }
@article {pmid18426675, year = {2008}, author = {Liu, YY and Fan, HH and Ren, YN and Yang, J and Nie, XX and Zhao, LH and Lin, JJ}, title = {[Immune tolerance induced by exosomes derived from regulatory dendritic cells of mice].}, journal = {Zhongguo shi yan xue ye xue za zhi}, volume = {16}, number = {2}, pages = {406-410}, pmid = {18426675}, issn = {1009-2137}, mesh = {Animals ; Dendritic Cells/cytology/*immunology/*transplantation ; Exosomes/immunology/*transplantation ; Female ; Graft Enhancement, Immunologic/*methods ; Graft Survival ; Immune Tolerance/*immunology ; Lymphocyte Culture Test, Mixed ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Skin Transplantation ; Transplantation Immunology ; Transplantation, Homologous ; }, abstract = {The study was aimed to explore the roles of exosomes derived from regulatory dendritic cells of mice in the induction of immune tolerance. Immature DC (iDC) from mouse bone marrow cells and regulatory DCs (rDC) were induced by treating iDC with TGF-beta1 and IL-10. The phenotype of regulatory DCs and normal DCs were assayed by flow cytometry. Exosomes from immature DCs (iDex) and regulatory DCs (rDex) were isolated by ultracentrifugation and ultrafiltration. A skin transplantation model was established with the recipients BALB/c mice and the donor C57BL/6 mice. Recipients were divided into PBS control group, iDex group (injection 10 microg iDex of donor C57BL/6 mice via tail vein at days 7 and 3 before skin transplantation), rDex group (injection 10 microg rDex of donor C57BL/6 mice via tail vein at days 7 and 3 before skin transplantation). The capacity of the donor mice and the unrelated allogeneic donor mice to stimulate allogeneic T lymphocyte proliferation was examined by mixed lymphocyte culture (MLR). The results showed that TGF-beta1 and IL-10 could down-regulate the expressions of costimulatory molecules, including CD80, CD86 and CD40. The graft mean survival time (MST) in control group, iDex group and rDex group was 7.8, 10.7 and 18.8 days, respectively. There was significant difference in MST between iDex group and control group (p<0.05), and between rDex group and iDex group (p<0.01). The results of MLR assays indicated donor-specific hyporeactivity especially in rDex group, while the tolerant B/C mice were still immunocompetent to unrelated allogeneic DBA mouse. It is concluded that injection iDex or rDex of donor mice via tail vein before skin transplantation induces immunotolerance, and the effect of rDex is more significant.}, }
@article {pmid18425387, year = {2008}, author = {Castellano, I and Sapino, A and Arisio, R and Viale, G and Bussolati, G and Bandelloni, R and Barresi, G and Bersiga, A and Bordi, C and Botti, G and Cosimi, F and D'Amore, E and Doglioni, C and Marchetti, A and Nappi, O and Romeo, F and Roncalli, M and Russo, R and Santinelli, A and Spagnoli, LG and Tanda, F and Tricomi, P and Trentini, G and Zanconati, F and Iurlaro, M}, title = {Fluorescent in situ hybridization as a screening test for HER2 amplification in G2 and G3 breast cancers of lobular and ductal histotype and metastases.}, journal = {Oncology reports}, volume = {19}, number = {5}, pages = {1271-1275}, pmid = {18425387}, issn = {1021-335X}, mesh = {Female ; Genes, erbB-2/*genetics ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Mass Screening/methods ; Medical Oncology/methods ; Models, Statistical ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging/methods ; Receptor, ErbB-2/*biosynthesis ; Reproducibility of Results ; Time Factors ; }, abstract = {The aim of the present study was to evaluate the effectiveness of fluorescence in situ hybridisation (FISH), as a screening test, in moderately- (G2) or poorly- (G3) differentiated breast cancers of the ductal (IDC) and lobular (ILC) histotypes and distant metastases. HER2 FISH was performed on 486 G2 and 477 G3 both of IDC and ILC histotypes and in 241 metastases. A significant difference in the HER2 amplification was observed between G2 (14.8%) and G3 (31.9%), with no difference according to the histotype. However, the rate of amplification increased to 36% in the G2/hormone receptor-negative cases as compared to 10.6% in the G2/receptor-positive cases (p<0.0001). HER2 was amplified in 17% of metastases with some differences depending on the location. These data suggest that the HER2 FISH analysis may be an effective screening test in breast cancer metastases and G3 tumors, irrespective of the hormone receptor status or presence of lymphovascular invasion.}, }
@article {pmid18425347, year = {2008}, author = {Calaf, GM and Echiburú-Chau, C and Zhao, YL and Hei, TK}, title = {BigH3 protein expression as a marker for breast cancer.}, journal = {International journal of molecular medicine}, volume = {21}, number = {5}, pages = {561-568}, pmid = {18425347}, issn = {1107-3756}, support = {NAG2 1637//PHS HHS/United States ; P30 ES 09089/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*metabolism/pathology ; Extracellular Matrix Proteins/genetics/*metabolism ; Female ; Humans ; Mammary Glands, Human/cytology/metabolism/pathology ; Microarray Analysis ; Middle Aged ; Transforming Growth Factor beta/genetics/*metabolism ; }, abstract = {The current hypothesis of tumorigenesis in humans suggests that cancer cells acquire their hallmarks of malignancy through the accumulation of advantageous gene activation and inactivation events over long periods of time. For breast cancer development, this multistep process may manifest itself as a sequence of pathologically defined stages. It is widely held that breast cancer originates at the premalignant stage of atypical ductal hyperplasia, progresses to the preinvasive stage of ductal carcinoma in situ, and culminates in the potentially lethal stage of invasive ductal carcinoma. Tumor grade has been a highly valuable prognostic factor for breast cancer, and high-grade ductal carcinoma in situ lesions are associated with poor clinical outcome. The aim of this work was to investigate the BigH3 protein expression changes associated with various stages of breast cancer progression in comparison to benign specimens using tissue microarray technology. Pathological characteristics of breast tissues ranged from benign lesions to breast cancers either of lobular or ductal carcinomas in origin, and included in situ ductal carcinomas, lobular carcinomas, infiltrating ductal carcinomas, carcinomas, scirrhous carcinomas, adenocarcinomas and infiltrating colloid carcinomas. BigH3 protein expression was analyzed by immunohistochemistry in 192 cases of breast tumors. Results indicated a decrease in BigH3 protein expression from benign tissues to in situ ductal carcinoma, lobular carcinoma, infiltrating ductal carcinomas, carcinomas, scirrhous carcinoma, adenocarcinomas to infiltrating colloid carcinomas. We observed that the benign tissue had a 23-fold increase in BigH3 protein expression compared to the infiltrating colloid carcinoma which was the most malignant tissue analyzed. In summary, these studies confirmed the suppressor effect of the BigH3 gene expressed as protein expression in those processes related to the progression of breast tumorigenesis. We conclude that this protein can be used as a marker for breast cancer progression.}, }
@article {pmid18419605, year = {2008}, author = {Cools, N and Van Tendeloo, VF and Smits, EL and Lenjou, M and Nijs, G and Van Bockstaele, DR and Berneman, ZN and Ponsaerts, P}, title = {Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells.}, journal = {Journal of cellular and molecular medicine}, volume = {12}, number = {2}, pages = {690-700}, pmid = {18419605}, issn = {1582-1838}, mesh = {CD4-Positive T-Lymphocytes/*immunology ; Cell Differentiation ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology/*immunology ; Humans ; Immunomagnetic Separation ; Immunophenotyping ; *Immunosuppression Therapy ; Interleukin-10/*immunology ; Models, Immunological ; Monocytes/cytology ; T-Lymphocytes, Regulatory/*immunology ; Transforming Growth Factor beta/*immunology ; }, abstract = {Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)-beta and interleukin (IL)-10 double-positive CD4(+) T cells within 1 week of autologous DC/T cell co-cultures. In iDC/T cell cultures, where antigen-specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF-beta and IL-10 secreted by CD4(+)CD25(-)FOXP3(-) T cells. In addition, the suppressive capacity of CD4(+) T cells conditioned by iDC was transferable to already primed antigen-specific CD8(+) T cell cultures. In contrast, addition of CD4(+) T cells conditioned by mDC to primed antigen-specific CD8(+) T cells resulted in enhanced CD8(+) T cell responses, notwithstanding the presence of TGF-beta(+)/IL-10(+) T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine-secreting regulatory T cells. We show that iDC-conditioned CD4(+) T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4(+) T cells. Furthermore, TGF-beta(+)/IL-10(+) T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.}, }
@article {pmid18408445, year = {2008}, author = {Sugie, T and Nagai, T and Ohgaki, K}, title = {[A case of HER2-positive metastatic breast cancer responding to trastuzumab plus gemcitabine combination therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {35}, number = {4}, pages = {683-686}, pmid = {18408445}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/*immunology/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Breast Neoplasms/*drug therapy/*immunology/metabolism/pathology ; Carcinoembryonic Antigen/blood ; Combined Modality Therapy ; Deoxycytidine/*analogs &amp; derivatives/therapeutic use ; Female ; Humans ; Immunotherapy ; Middle Aged ; Neoplasm Metastasis/diagnostic imaging/pathology ; Positron-Emission Tomography ; Radiography ; Receptor, ErbB-2/*immunology/*metabolism ; Tomography Scanners, X-Ray Computed ; Trastuzumab ; Gemcitabine ; }, abstract = {A 60-year-old woman was admitted to the hospital with left thigh pain. She had undergone mastectomy and axillary lymph node dissection for right breast cancer (T3N2M0) five years and two months earlier. The pathological diagnosis then was invasive ductal carcinoma with axillaryly mph node metastases. Hormone receptors and HER2 status were negative and positive (3+), respectively. The patient received adjuvant chemotherapy and radiotherapy, but bone metastases appeared 18 months after surgery. Although trastuzumab-combination chemotherapy with taxane and/or capecitabine was given, bone metastases in thoracic vertebra resulted in incomplete paralysis in both legs. She underwent thoraco-lumbar vertebral fixation 10 months before admission. A PET/CT revealed multiple bone metastases in the left femur as well as vertebrae, and CEA rose markedly. She received radiotherapy and trastuzumab monotherapy in addition to bisphosphonate. Temporarily, CEA decreased, but because recurrence nests were recognized in the supraclavicle and mediastinum after the eight-month treatment, trastuzumab monotherapy was followed by trastuzumab plus vinorelbine combined therapy. This regimen markedly reduced CEA after three months, but it rose again over the following three months. As S-1-combined therapy was not effective, trastuzumab+gemcitabine (1 g/week and two weeks on/one week off) combined therapy was started. CEA decreased markedly after 4 cycles, and FDG accumulation in the recurrence region was markedly improved. The adverse event during this treatment was minor, and PS was sufficiently maintained. These results suggest that trastuzumab plus gemcitabine combination therapy is effective for HER2-positive metastatic breast cancer.}, }
@article {pmid18394338, year = {2008}, author = {Tu, SF and Guo, KY and Hu, LS and Mei, JZ and Zhou, J and Sun, M}, title = {[Expression of NKG2D ligands on dendritic cells at different development stages and its effect on cytotoxicity of NK cells].}, journal = {Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology}, volume = {24}, number = {4}, pages = {341-3, 347}, pmid = {18394338}, issn = {1007-8738}, mesh = {Antibodies/immunology/pharmacology ; Cells, Cultured ; Cytotoxicity, Immunologic/drug effects ; Dendritic Cells/*metabolism/ultrastructure ; Flow Cytometry ; GPI-Linked Proteins ; Gene Expression Regulation, Developmental/drug effects ; Histocompatibility Antigens Class I/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Killer Cells, Natural/*immunology/*metabolism ; Membrane Proteins/metabolism ; Microscopy, Electron, Transmission ; NK Cell Lectin-Like Receptor Subfamily K/immunology ; }, abstract = {AIM: To investigate the expression of NKG2D ligands on dendritic cells(DC) at different development stages and its effect on cytotoxicity of natural killer(NK) cells.<br><br>METHODS: The monocytes were cultured into immature dendritic cells(iDC) and mature dendritic cells(mDC) with cytokines. NK cells were obtained from normal peripheral blood by CD56 antibody magnetic isolation.The expression of NKG2D ligands (MICA/B, ULBP1-3) was detected by flow cytometry. Cytotoxicity of NK cells and the NK cells blocked with anti-NKG2D mAbs against iDC and mDC was tested using LDH-releasing method.<br><br>RESULTS: IDC and mDC were of typical morphology and phenotypes. MICA, MICB, ULBP1, and ULBP3 were expressed on iDC and their expression rate was (32.39+/-8.30)%, (17.75+/-3.40)%, (26.71+/-6.48)%, (38.37+/-6.89)%, respectively. MICA and ULBP3 were expressed on mDC and their expression rate was (7.81+/-3.33)% and (8.36+/-2.42)%, respectively, which was lower than that on mDC (P<0.01). At the each E:T ratio cytotoxicity of NK cells against iDC was stronger than that against mDC (P<0.01). cytotoxicity of NK cells blocked with anti-NKG2D mAb against iDC was decreased compared with that of NK cells unblocked (P<0.05) while cytotoxicity of NK cells blocked with anti-NKG2D mAb against mDC showed no decrease compared with that of NK cells unblocked (P>0.05).<br><br>CONCLUSION: The expression of NKG2D ligands on iDC is higher than that on mDC, which plays an important role in the cytotoxic effect of NK cells against iDC, but has no effect on that against mDC. NKG2D-NKG2D ligands shows one of the molecular mechanisms that NK cells kill iDC selectively.}, }
@article {pmid18383208, year = {2008}, author = {Bettendorf, O and Schmidt, H and Staebler, A and Grobholz, R and Heinecke, A and Boecker, W and Hertle, L and Semjonow, A}, title = {Chromosomal imbalances, loss of heterozygosity, and immunohistochemical expression of TP53, RB1, and PTEN in intraductal cancer, intraepithelial neoplasia, and invasive adenocarcinoma of the prostate.}, journal = {Genes, chromosomes &amp; cancer}, volume = {47}, number = {7}, pages = {565-572}, doi = {10.1002/gcc.20560}, pmid = {18383208}, issn = {1098-2264}, mesh = {Adenocarcinoma/genetics/metabolism/pathology ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; *Chromosomal Instability ; Humans ; Immunoenzyme Techniques ; *Loss of Heterozygosity ; Male ; Middle Aged ; Neoplasm Invasiveness ; PTEN Phosphohydrolase/*metabolism ; Prognosis ; Prostatic Intraepithelial Neoplasia/genetics/metabolism/pathology ; Prostatic Neoplasms/*genetics/*metabolism/pathology ; Retinoblastoma Protein/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {Recent studies have shown that intraductal prostate carcinoma (IDC-P) should be considered as a separate lesion distinct from prostatic intraepithelial neoplasia (PIN). The purpose of the present study was to analyze the genetic relationship between benign prostatic tissue, PIN, invasive cancer, IDC-P, and extracapsular tumor tissue to get further information about the role of IDC-P in the development of prostate cancer. One hundred five radical prostatectomy specimens were investigated immunohistochemically, 77 cases were analyzed by PCR for LOH of the tumor suppressor genes TP53 and RB1, and 11 cases of IDC-P and 10 cases of PIN were investigated using comparative genomic hybridization (CGH). At CGH analysis, IDC-P showed several chromosomal imbalances in contrast to PIN, where no changes were found. We could demonstrate a significant increase of LOH for TP53 or RB1 from benign tissue to PIN. LOH of both TP53 and RB1 were frequently found in IDC-P (52%), followed by extracapsular tumor tissue (44%), invasive cancer (24%), PIN (19%), and benign prostatic tissue (17%). Increased immunohistochemical expression was found in invasive cancer for TP53, RB1, and for PTEN. Decreased expression could be demonstrated in extracapsular tumor tissue and in IDC-P. Our results indicate that IDC-P in general follows the genetic pathway from normal epithelium over PIN lesion. IDC-P represents a separate prostatic lesion and should be graded as a poorly differentiated carcinoma.}, }
@article {pmid18358477, year = {2008}, author = {Caliskan, M and Erdogan, D and Gullu, H and Muderrisoglu, H}, title = {Higher serum gamma-glutamyltransferase levels are independently associated with impaired coronary microvascular function in patients with dilated cardiomyopathy.}, journal = {Atherosclerosis}, volume = {201}, number = {1}, pages = {163-167}, doi = {10.1016/j.atherosclerosis.2008.01.010}, pmid = {18358477}, issn = {1879-1484}, mesh = {Adult ; Aged ; C-Reactive Protein/metabolism ; Cardiomyopathy, Dilated/diagnostic imaging/*enzymology/*physiopathology ; Cohort Studies ; Echocardiography, Doppler ; Female ; Fractional Flow Reserve, Myocardial/*physiology ; Humans ; Male ; Microcirculation/*physiology ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Risk Factors ; gamma-Glutamyltransferase/*blood ; }, abstract = {BACKGROUND: Patients with idiopathic dilated cardiomyopathy (IDC) have impaired coronary flow reserve (CFR) and reduced CFR has been reported to be a poor prognostic indicator and independent predictor of subsequent cardiac events in patients with IDC. Serum gamma-glutamyltransferase (GGT) level is an independent risk factor for cardiovascular disease. Therefore, we aimed to determine whether serum GGT level is associated with CFR impairment in patients with IDC.<br><br>METHODS: We examined 32 patients with IDC. The patients were divided into two groups based on serum GGT levels.<br><br>RESULTS: There were no significant differences between the lower and higher GGT groups regarding clinical data, baseline hemodynamics, medications and biochemical data except GGT and hsCRP levels. Subjects with higher GGT had significantly impaired CFR as compared to those with lower GGT (1.86+/-0.28 vs. 2.27+/-0.38, P=0.002). After adjusting for potential confounders, including age, sex, body mass index, blood pressure, lipids and glucose, we found that serum GGT levels were independently associated with CFR impairment (beta=-0.48, P=0.001). We also found that GGT level was a good predictor of low CFR at the receiver-operating characteristic curve. Area under the curve was 81% (95% CI: 0.66-0.95), and GGT level was significantly predictive of low CFR (P=0.003).<br><br>CONCLUSION: These results showed that there was an independent association between serum GGT level and CFR in patients with IDC.}, }
@article {pmid18354176, year = {2008}, author = {Santegoets, SJ and Bontkes, HJ and Stam, AG and Bhoelan, F and Ruizendaal, JJ and van den Eertwegh, AJ and Hooijberg, E and Scheper, RJ and de Gruijl, TD}, title = {Inducing antitumor T cell immunity: comparative functional analysis of interstitial versus Langerhans dendritic cells in a human cell line model.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {180}, number = {7}, pages = {4540-4549}, doi = {10.4049/jimmunol.180.7.4540}, pmid = {18354176}, issn = {0022-1767}, mesh = {Cell Line ; Cell Movement ; Cytokines/metabolism ; Dendritic Cells/cytology/*immunology/metabolism ; HLA-A2 Antigen/immunology ; Humans ; Islets of Langerhans/cytology/*immunology/metabolism ; Lymph Nodes/cytology/immunology ; *Models, Immunological ; Neoplasms/*immunology ; Peptides/immunology ; Phenotype ; Skin/immunology ; T-Lymphocytes/*immunology ; }, abstract = {Dendritic cells (DC) are increasingly applied as a cellular adjuvant in immunotherapy of cancer. Two major myeloid DC subsets are recognized: interstitial DC (IDC) that infiltrate connective tissues and Langerhans cells (LC) that line epithelial surfaces. Yet, functional differences between IDC and LC remain to be defined. We recently showed that the CD34(+) acute myeloid leukemia cell line MUTZ-3 supports differentiation of both DC-SIGN(+) IDC and Langerin-positive Birbeck granule-expressing LC. By comparative functional characterization of MUTZ-3 IDC and MUTZ-3 LC, we aimed to elucidate the relative abilities of these two DC subsets to induce a specific T cell response and reveal the more suitable candidate for use as a clinical vehicle of tumor vaccines. Although mature LC and IDC displayed comparable lymph node-homing potential, mature LC showed higher allogeneic T cell stimulatory capacity. Nevertheless, IDC supported the induction of tumor Ag-specific CD8(+) T cells at an overall higher efficiency. This might be related to the observed inability of LC to release T cell stimulatory cytokines such as IL-12p70, IL-23, and IL-15. Although this inability did not result in a detectable deviation in the cytokine expression profile of primed T cells, transduction with IL-12p70 significantly improved priming efficiency of LC, and ensured a functional equivalence with IDC in this regard. In conclusion, except for the inability of LC to release distinct type 1 T cell stimulatory cytokines, in vitro function of LC and IDC suggests comparable abilities of both subsets for the in vivo induction of antitumor T cells.}, }
@article {pmid18329692, year = {2008}, author = {Hasebe, T and Imoto, S and Yokose, T and Ishii, G and Iwasaki, M and Wada, N}, title = {Histopathologic factors significantly associated with initial organ-specific metastasis by invasive ductal carcinoma of the breast: a prospective study.}, journal = {Human pathology}, volume = {39}, number = {5}, pages = {681-693}, doi = {10.1016/j.humpath.2007.09.012}, pmid = {18329692}, issn = {0046-8177}, mesh = {Adult ; Aged ; Bone Neoplasms/mortality/pathology/secondary ; Breast Neoplasms/mortality/*pathology/secondary ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology/secondary ; Chemotherapy, Adjuvant ; Female ; Fibrosis ; Humans ; Liver Neoplasms/mortality/pathology/secondary ; Lung Neoplasms/mortality/pathology/secondary ; Middle Aged ; Multivariate Analysis ; Neoplasm Metastasis/pathology ; Prospective Studies ; }, abstract = {The purpose of this study was to identify histologic factors significantly associated with initial organ-specific metastasis by 1044 invasive ductal carcinomas (IDCs) of the breast with and without adjuvant therapy, separately, according to nodal status and pathologic TNM stage status. The following histologic factors were prospectively analyzed by multivariate analyses for distant organ metastasis and bone metastasis in patients with IDC who did not receive adjuvant therapy, and for distant organ metastasis, bone metastasis, liver metastasis, and lung metastasis in patients with IDC who received adjuvant therapy: (1) invasive tumor size, (2) histologic grade, (3) tumor necrosis, (4) fibrotic focus (FF), (5) lymphatic invasion, (6) blood vessel invasion, (7) adipose tissue invasion, (8) skin invasion, (9) muscle invasion, (10) age, (11) estrogen (ER)/progesterone (PR) status, and (12) nodal status. The results showed that FF diameter greater than 8 mm and FF fibrosis grade 1 were the factors that most accurately predicted distant organ metastasis and bone metastasis in patients with IDC who did not receive adjuvant therapy. In patients with IDC who received adjuvant therapy, FF diameter greater than 8 mm was the factor that most accurately predicted bone metastasis, and the presence of tumor necrosis and ER-/PR- were very important predictive factors for metastasis to the lung. Ten or more nodal metastases (N3) were the factor that most accurately predicted liver metastasis. Based on these findings, FF characteristics can be concluded to be the most important histologic factors for predicting metastasis to the bone, the presence of tumor necrosis and ER-/PR- for predicting metastasis to the lung, and N3 for predicting metastasis to the liver.}, }
@article {pmid18314615, year = {2007}, author = {Dietrich, D and Schuster, M and Lesche, R and Haedicke, W and Kristiansen, G}, title = {[Multiplexed methylation analysis--a new technology to analyse the methylation pattern of laser microdissected cells of normal breast tissue, DCIS and invasive ductal carcinoma of the breast].}, journal = {Verhandlungen der Deutschen Gesellschaft fur Pathologie}, volume = {91}, number = {}, pages = {197-207}, pmid = {18314615}, issn = {0070-4113}, mesh = {Breast/*cytology/physiology ; Breast Neoplasms/*genetics/*pathology ; *DNA Methylation ; DNA, Neoplasm/*genetics ; Dissection ; Female ; Gene Amplification ; Humans ; Polymerase Chain Reaction ; Reference Values ; }, abstract = {AIMS: DNA methylation has been shown to play an important role in breast cancer pathogenesis, but up until now it is not clear how the tissue components contribute to the overall methylation of the sample, because microdissection does not provide sufficient material for most standard methylation assays.<br><br>METHODS: We developed a technology to analyse several methylation markers in a limited number of cells dissected from tissue sections. To evaluate the technology, we analysed, among others, the methylation markers PITX2, RASSF1A and TFF1 in 79 samples of three PITX2 methylation positive invasive ductal carcinomas. The microdissected samples were from the invasive part, the intraductal part, the stroma, tumor infiltrating lymphocytes, chest wall muscle, adipose tissue and healthy ducts.<br><br>RESULTS: The multiplexed methylation analysis allows for the quantitative analysis of methylation patterns in microdissected samples with as few as 100 genome copies. In all analysed patients PITX2 and RASSF1A were highly methylated in invasive and intraductal carcinoma cells compared to other tissue components. TFF1 behaved inversely. PITX2 showed some methylation in normal adjacent breast tissue. The methylation of the individual markers varied little within one tissue type and between blocks.<br><br>CONCLUSIONS: This technology is a powerful tool to analyse the methylation of multiple markers in different microdissected tissue components. Methylation patterns may differ significantly between different markers and tissue components. This technology may help to analyse different transitions states of breast and other cancers.}, }
@article {pmid18314479, year = {2008}, author = {Ricciardi, A and Elia, AR and Cappello, P and Puppo, M and Vanni, C and Fardin, P and Eva, A and Munroe, D and Wu, X and Giovarelli, M and Varesio, L}, title = {Transcriptome of hypoxic immature dendritic cells: modulation of chemokine/receptor expression.}, journal = {Molecular cancer research : MCR}, volume = {6}, number = {2}, pages = {175-185}, doi = {10.1158/1541-7786.MCR-07-0391}, pmid = {18314479}, issn = {1541-7786}, support = {N01 CO 12400/CO/NCI NIH HHS/United States ; }, mesh = {Cell Hypoxia ; Cell Movement ; Chemokines/*genetics ; Dendritic Cells/*cytology/*metabolism ; *Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Receptors, Chemokine/*genetics ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues. Dendritic cells (DC) are professional antigen-presenting cells whose differentiation, migration, and activities are intrinsically linked to the microenvironment. DCs will home and migrate through pathologic tissues before reaching their final destination in the lymph node. We studied the differentiation of human monocytes into immature DCs (iDCs) in a hypoxic microenvironment. We generated iDC in vitro under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and examined the hypoxia-responsive element in the promoter, gene expression, and biochemical KEGG pathways. Hi-DCs had an interesting phenotype represented by up-regulation of genes associated with cell movement/migration. In addition, the Hi-DC cytokine/receptor pathway showed a dichotomy between down-regulated chemokines and up-regulated chemokine receptor mRNA expression. We showed that CCR3, CX3CR1, and CCR2 are hypoxia-inducible genes and that CCL18, CCL23, CCL26, CCL24, and CCL14 are inhibited by hypoxia. A strong chemotactic response to CCR2 and CXCR4 agonists distinguished Hi-DCs from iDCs at a functional level. The hypoxic microenvironment promotes the differentiation of Hi-DCs, which differs from iDCs for gene expression profile and function. The most prominent characteristic of Hi-DCs is the expression of a mobility/migratory rather than inflammatory phenotype. We speculate that Hi-DCs have the tendency to leave the hypoxic tissue and follow the chemokine gradient toward normoxic areas where they can mature and contribute to the inflammatory process.}, }
@article {pmid18310280, year = {2008}, author = {Shibuya, R and Suzuki, T and Miki, Y and Yoshida, K and Moriya, T and Ono, K and Akahira, J and Ishida, T and Hirakawa, H and Evans, DB and Sasano, H}, title = {Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast.}, journal = {Endocrine-related cancer}, volume = {15}, number = {1}, pages = {113-124}, doi = {10.1677/ERC-07-0092}, pmid = {18310280}, issn = {1351-0088}, mesh = {17-Hydroxysteroid Dehydrogenases/genetics/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Aromatase/genetics/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Chromatography, Liquid ; Dihydrotestosterone/*metabolism ; Estradiol/*metabolism ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Spectrometry, Mass, Electrospray Ionization ; Steryl-Sulfatase/genetics/*metabolism ; Stromal Cells/metabolism/pathology ; Survival Rate ; }, abstract = {It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5alpha-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1)), and androgen-producing enzymes (17betaHSD5 and 5alpha-reductase type 1 (5alphaRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5alphaRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast.}, }
@article {pmid18306351, year = {2008}, author = {Itoh, H and Miyajima, Y and Umemura, S and Osamura, RY}, title = {Lower HER-2/chromosome enumeration probe 17 ratio in cytologic HER-2 fluorescence in situ hybridization for breast cancers: three-dimensional analysis of intranuclear localization of centromere 17 and HER-2 signals.}, journal = {Cancer}, volume = {114}, number = {2}, pages = {134-140}, doi = {10.1002/cncr.23367}, pmid = {18306351}, issn = {0008-543X}, mesh = {Breast Neoplasms/*genetics ; Carrier Proteins/genetics ; Cell Nucleus/genetics/metabolism ; Centromere/*genetics ; Chromosomes, Human, Pair 17/*genetics ; DNA Probes/*genetics ; Female ; Gene Amplification ; Humans ; *In Situ Hybridization, Fluorescence ; Receptor, ErbB-2/*genetics ; }, abstract = {BACKGROUND: Fluorescence in situ hybridization (FISH) is the gold standard for assessing HER-2 status for breast cancers, and paraffin-embedded tissue sections are used routinely for HER-2 FISH. Cytologic samples also are used, but to the authors' knowledge, little is known regarding the reliability of these samples. The objective of this study was to elucidate the usefulness of cytologic specimens for HER-2 FISH testing.<br><br>METHODS: Histologic and cytologic specimens from 32 patients with invasive ductal carcinoma of the breast were subjected to comparative analysis of HER-2 status by FISH. FISH was performed by using a PathVysion HER-2 DNA Probe Kit according the manufacturer's instructions. The signal ratios of chromosome enumeration probe 17 (CEP17) and HER-2 were estimated and compared. In 15 cytologic specimens, the distance between signals (HER-2 and CEP17) and the nearest nuclear membrane were measured by using 3-dimensional image analysis and confocal microscopy.<br><br>RESULTS: Cytologic and histologic FISH results were compared. Signal ratios of HER-2/CEP17 were lower in cytologic specimens from 26 of 32 patients compared with the histologic material. Three-dimensional image analysis demonstrated that the distance between the CEP17 signal and the nuclear membrane was shorter than the distance between the HER-2 gene and the nuclear membrane.<br><br>CONCLUSIONS: The current results demonstrated that CEP17 could be lost more easily through histologic sectioning compared with the cytology results, because CEP17 is closer to the nuclear membrane. FISH analysis in cytologic specimens produced more accurate HER-2/CEP17 ratios, because the whole nucleus was subjected to FISH testing, compared with matched histologic specimens.}, }
@article {pmid18292984, year = {2008}, author = {Wang, J and McClean, PE and Lee, R and Goos, RJ and Helms, T}, title = {Association mapping of iron deficiency chlorosis loci in soybean (Glycine max L. Merr.) advanced breeding lines.}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {116}, number = {6}, pages = {777-787}, pmid = {18292984}, issn = {0040-5752}, mesh = {Biomarkers ; *Breeding ; *Chromosome Mapping ; Chromosomes, Plant ; *Iron Deficiencies ; Minisatellite Repeats/*genetics ; Models, Genetic ; Plant Diseases/*genetics ; *Quantitative Trait Loci ; Soybeans/*genetics/*metabolism ; }, abstract = {Association mapping is an alternative to mapping in a biparental population. A key to successful association mapping is to avoid spurious associations by controlling for population structure. Confirming the marker/trait association in an independent population is necessary for the implementation of the marker in other genetic studies. Two independent soybean populations consisting of advanced breeding lines representing the diversity within maturity groups 00, 0, and I were screened in multi-site, replicated field trials to discover molecular markers associated with iron deficiency chlorosis (IDC), a major yield-limiting factor in soybean. Lines with extreme phenotypes were initially screened to identify simple sequence repeat (SSR) markers putatively associated with the IDC. Marker data collected from all lines were used to control for population structure and kinship relationships. Single factor analysis of variance (SFA) and mixed linear model (MLM) analyses were used to discover marker/trait associations. The MLM analyses, which include population structure, kinship or both factors, reduced the number of markers significantly associated with IDC by 50% compared with SFA. With the MLM approach, three markers were found to be associated with IDC in the first population. Two of these markers, Satt114 and Satt239, were also found to be associated with IDC in the second confirmation population. For both populations, those lines with the tolerance allele at both these two marker loci had significantly lower IDC scores than lines with one or no tolerant alleles.}, }
@article {pmid18286776, year = {2007}, author = {Ratnatunga, N and Liyanapathirana, LV}, title = {Hormone receptor expression and Her/2neu amplification in breast carcinoma in a cohort of Sri Lankans.}, journal = {The Ceylon medical journal}, volume = {52}, number = {4}, pages = {133-136}, doi = {10.4038/cmj.v52i4.916}, pmid = {18286776}, issn = {0009-0875}, mesh = {Adult ; Age Factors ; Breast Neoplasms/epidemiology/*genetics/pathology ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; Middle Aged ; Prevalence ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/*genetics/physiology ; Receptors, Progesterone/*genetics/physiology ; Retrospective Studies ; Sri Lanka/epidemiology ; }, abstract = {OBJECTIVE: 1) To determine the profile of estrogen and, progesterone receptors (ER, PR) expression and Her/2neu amplification in carcinoma of breast of Sri Lankan women. 2) To determine their inter-relationships, and associations with age at diagnosis and histological grade.<br><br>DESIGN: Retrospective analysis of data.<br><br>SETTING: Department of Pathology, Faculty of Medicine, University of Peradeniya.<br><br>MATERIALS: 124 samples of invasive ductal carcinoma of breast, stained for steroid receptors and Her/2neu amplification with immunohistochemistry.<br><br>MEASUREMENTS: 1) Semiquantative scores of steroid receptors and Her/2neu amplification. 2) Correlations of ER, PR, Her/2neu amplification, age at diagnosis and histological grade.<br><br>RESULTS: The prevalence of ER, PR and Her/2neu amplification were 53.2%, 50% and 14.6% respectively. The expression of ER and PR were significantly correlated (p < 0.001). and had a significant negative correlation with Her/2neu amplification (p0.003 each). Lower grade of the tumour was significantly related to the expression of ER (p0.000) and PR (p0.000) but not to Her/2neu amplification (p0.331). Age at diagnosis was significantly correlated to the expression of ER (p0.004), but not to PR (p0.365) or Her/2neu amplification (p0.456).<br><br>CONCLUSION: Prevalence or ER, PR and Her/2neu amplification in carcinoma of breast among Sri Lankans is similar to that described internationally. The correlations of ER, PR, Her/2neu amplification, to each other, age at diagnosis and grade of tumour is as reported in other countries.}, }
@article {pmid18284499, year = {2008}, author = {Nogami, A and Sugiyasu, A and Tada, H and Kurosaki, K and Sakamaki, M and Kowase, S and Oginosawa, Y and Kubota, S and Usui, T and Naito, S}, title = {Changes in the isolated delayed component as an endpoint of catheter ablation in arrhythmogenic right ventricular cardiomyopathy: predictor for long-term success.}, journal = {Journal of cardiovascular electrophysiology}, volume = {19}, number = {7}, pages = {681-688}, doi = {10.1111/j.1540-8167.2008.01104.x}, pmid = {18284499}, issn = {1540-8167}, mesh = {Adult ; Aged ; Cardiomyopathies/*etiology/*surgery ; Catheter Ablation/*methods ; Electrocardiography/*methods ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prognosis ; Tachycardia, Ventricular/*complications/*surgery ; Treatment Outcome ; Ventricular Dysfunction, Right/*etiology/*surgery ; }, abstract = {INTRODUCTION: Although successful ablation of ventricular tachycardia (VT) is feasible in arrhythmogenic right ventricular cardiomyopathy (ARVC), long-term recurrence is common. The aim of this study was to assess the usefulness of a change in the isolated delayed component (IDC) as an endpoint of the catheter ablation in ARVC.<br><br>METHODS AND RESULTS: Eighteen patients (48 +/- 11 years) with ARVC were studied. Detailed endocardial mapping of the right ventricle (RV) was performed during sinus rhythm. IDCs were recorded in 16 patients and the latest IDCs were related to the VT circuit. Catheter ablation was carried out in the areas with the IDCs. At the end of the session, the IDC was electrically dissociated in one, disappeared in five, exhibited second-degree block in one, was significantly delayed (>or=50 ms) in three, and remained unchanged in six. The change in the IDC was correlated with the change in the type II/III late potentials in the signal-averaged electrocardiography (ECG) and the inducibility of the clinical VT after the ablation. During a follow-up of 61 +/- 38 months, VT recurred in six. The patients with a changed IDC had a significantly lower VT recurrence than those with no IDC or an unchanged IDC (P < 0.02).<br><br>CONCLUSION: In patients with ARVC, (1) the IDCs during sinus rhythm are related to the clinical VT and can be a target for the ablation, (2) a change in the IDC can be used as an endpoint, and (3) qualitative analyses of the serial signal-averaged ECGs may be useful for the long-term follow-up.}, }
@article {pmid18271465, year = {2008}, author = {Menke-van der Houven van Oordt, CW and Fliervoet, HJ and Mandigers, CM and van Spronsen, DJ}, title = {[Cardiotoxicity of trastuzumab of significance in the adjuvant treatment of breast cancer].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {152}, number = {3}, pages = {158-163}, pmid = {18271465}, issn = {0028-2162}, mesh = {Adult ; Antibodies, Monoclonal/*adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*adverse effects/therapeutic use ; Breast Neoplasms/drug therapy ; Cardiomyopathies/*chemically induced ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Trastuzumab ; Ventricular Dysfunction, Left/*chemically induced ; }, abstract = {Three women aged 53, 52 and 36 years, respectively, underwent surgery for breast cancer, i.e. right-sided grade II invasive ductal carcinoma, left-sided grade III invasive ductal carcinoma, and left-sided multifocal grade III invasive ductal carcinoma, respectively. All 3 received adjuvant anthracycline-containing chemotherapy followed by trastuzumab. They developed significant cardiac dysfunction, as determined by a decrease in left ventricular ejection fraction (LVEF), which necessitated trastuzumab discontinuation. Trastuzumab therapy was resumed in the third patient after LVEF recovery but was stopped definitively when the LVEF decreased again. Trastuzumab has been shown to improve both disease-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, symptomatic cardiac failure due to cardiomyopathy has been observed in 0.6-4.1% of patients treated with trastuzumab after adjuvant anthracycline-based chemotherapy, whereas in 5-19% of the patients the decline in cardiac function led to permanent discontinuation of trastuzumab therapy. Cardiac function should be monitored regularly during trastuzumab therapy. An LVEF less than 50% or an absolute reduction of more than 10% warrant treatment discontinuation and close follow-up. Cardiac dysfunction is usually reversible; however, the long-term consequences of LVEF reduction following trastuzumab therapy are still unknown and warrant close attention, given the relatively young age and long life expectancy of these patients.}, }
@article {pmid18260729, year = {2007}, author = {Chariyalertsak, S and Purisa, W and Thisuphakorn, P and Karalak, A and Pakeetoot, T and Petmitr, S}, title = {Real-time quantitative PCR analysis of amplified DNA on chromosomes 4p15.2 and 6q23-24 from formalin-fixed, paraffin-embedded breast cancer tissues.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {8}, number = {4}, pages = {561-566}, pmid = {18260729}, issn = {2476-762X}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/secondary ; Chromosome Aberrations ; Chromosomes, Human, Pair 4/*genetics ; Chromosomes, Human, Pair 6/*genetics ; DNA Mutational Analysis ; DNA, Neoplasm/genetics ; Disease Progression ; Female ; Gene Amplification ; Humans ; Lymphatic Metastasis ; Middle Aged ; Paraffin Embedding ; Polymerase Chain Reaction/*methods ; Tissue Fixation ; }, abstract = {This study was performed to detect amplification of DNA sequences on chromosomes 4p15.2 and 6q23-24, obtained from formalin-fixed, paraffin-embedded, breast-cancer tissues. The prognostic relevance of the amplification was also demonstrated. DNA from formalin-fixed, paraffin-embedded tumor and corresponding normal tissues of 53 patients with breast cancer was extracted and amplified by real-time quantitative PCR technique. Amplification of the DNA sequences on chromosomes 4p15.2 and 6q23-24 was detected in 23 (43%) and 32 (60%) cases, respectively. Thirty-six (68%) cases showed amplification on both or one of the chromosomes. These frequencies are similar to that obtained from fresh samples in our previous study. In addition, amplification of the DNA on chromosomes 4p15.2 and / or 6q23-24 was predominantly observed in tumors with invasive ductal carcinoma. The findings in this study demonstrate that DNA extracted from formalin-fixed, paraffin-embedded breast tumors can be used to determine amplification of DNA sequences on selective chromosomal regions. We also suggest that the amplified DNA on chromosomal regions 4p15.2 and 6q23-24 might be involved in the development and progression of breast cancer.}, }
@article {pmid18260722, year = {2007}, author = {Leong, BD and Chuah, JA and Kumar, VM and Yip, CH}, title = {Breast cancer in Sabah, Malaysia: a two year prospective study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {8}, number = {4}, pages = {525-529}, pmid = {18260722}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/metabolism/pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Carcinoma, Lobular/epidemiology/pathology ; Female ; Humans ; Incidence ; Malaysia/epidemiology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prospective Studies ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Factors ; Time Factors ; Young Adult ; }, abstract = {INTRODUCTION: Malaysian women have a 1 in 20 chance of developing breast cancer in their lifetime. Sabah, formerly known as North Borneo, is part of East Malaysia with a population of 3.39 million and more than 30 ethnic groups. We conducted a 2 year prospective epidemiological study to provide unreported data of breast cancer from this part of the world and to recognise which particular group of patients are more likely to present with advanced disease.<br><br>METHODS: All newly diagnosed breast cancers seen at the Queen Elizabeth Hospital, Kota Kinabalu, from January 2005 to December 2006 were included in the study. Patient and tumour characteristics, including age, race, education, socioeconomic background, parity, practice of breast feeding, hormonal medication intake, menopausal status, family history, mode of presentation, histology, grade, stage of disease and hormonal receptors status were collected and analysed.<br><br>RESULTS: A total of 186 patients were seen. The commonest age group was 40 to 49 years old (32.3%). Chinese was the commonest race (30.6%) followed by Kadazan-Dusun (24.2%). The commonest histology was invasive ductal carcinoma (88.4%). Stages at presentation were Stage 0- 4.8%, Stage I- 12.9%, Stage II- 30.1%, Stage III- 36.6% and Stage IV- 15.6%. The estrogen and progesterone receptor status was positive in 59.1% and 54.8% of cases, respectively. 73.7% of Chinese patients presented with early cancer compared to 36.4% of the other races. Patients who presented with advanced disease were also poor, non-educated and from rural areas. 20.4% of patients defaulted treatment; most of them opted for traditional alternatives.<br><br>CONCLUSIONS: Sabahan women with breast cancer present late. Great efforts are needed to improve public awareness of breast cancer, especially among those who have higher risk of presenting with advanced disease.}, }
@article {pmid18256927, year = {2009}, author = {Subramaniam, MM and Chan, JY and Soong, R and Ito, K and Ito, Y and Yeoh, KG and Salto-Tellez, M and Putti, TC}, title = {RUNX3 inactivation by frequent promoter hypermethylation and protein mislocalization constitute an early event in breast cancer progression.}, journal = {Breast cancer research and treatment}, volume = {113}, number = {1}, pages = {113-121}, doi = {10.1007/s10549-008-9917-4}, pmid = {18256927}, issn = {1573-7217}, mesh = {Breast Neoplasms/*genetics/mortality/*pathology/surgery ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Core Binding Factor Alpha 3 Subunit/*antagonists &amp; inhibitors/*genetics ; DNA Methylation ; DNA Primers ; DNA, Neoplasm/genetics ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Microdissection ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Polymerase Chain Reaction ; *Promoter Regions, Genetic ; }, abstract = {BACKGROUND: We had previously established that inactivation of RUNX3 occurs by frequent promoter hypermethylation and protein mislocalization in invasive ductal carcinomas (IDC) of breast. Here, we hypothesize that inactivation of RUNX3 occurring in ductal carcinoma in situ (DCIS) represent early event in breast carcinogenesis.<br><br>METHODS: The study cohort of 40 patients included 17 pure DCIS cases and 23 cases of DCIS with associated IDC (DCIS-IDC). The DCIS and IDC components of mixed cases were manually microdissected to permit separate evaluation. All the 63 samples including 17 pure DCIS, 23 samples each of DCIS and IDC of DCIS-IDC cases were analyzed for RUNX3 protein expression using R3-6E9 monoclonal antibody as well as promoter methylation status by methylation specific PCR.<br><br>RESULTS: Compared to matched normal breast samples (4 of 40, 10%), DCIS (35 of 40, 88%) and IDC (21 of 23, 91%) exhibited significant RUNX3 inactivation (P<0.001) in the form of negative or weak nuclear staining. In contrast to normal breast tissues (1/10, 10%), promoter hypermethylation of RUNX3 was significantly higher in the neoplastic breast samples (46 of total 61, 75%) including 30 of 40 (75%) DCIS and 16 of 21 (76%) IDC samples (P=0.009). Overall, promoter hypermethylation correlated with RUNX3 inactivation in 42 of 46 (91%) methylated samples (P=0.03). Mislocalized cytoplasmic expression also accounted for RUNX3 inactivation in majority of DCIS (33/40, 83%) and IDC (20/23, 87%) samples independent of promoter hypermethylation.<br><br>CONCLUSION: Our data suggest that RUNX3 inactivation by promoter hypermethylation and protein mislocalization constitute an early event in breast cancer progression.}, }
@article {pmid18242371, year = {2008}, author = {Trigo Rocha, F and Gomes, CM and Mitre, AI and Arap, S and Srougi, M}, title = {A prospective study evaluating the efficacy of the artificial sphincter AMS 800 for the treatment of postradical prostatectomy urinary incontinence and the correlation between preoperative urodynamic and surgical outcomes.}, journal = {Urology}, volume = {71}, number = {1}, pages = {85-89}, doi = {10.1016/j.urology.2007.09.009}, pmid = {18242371}, issn = {1527-9995}, mesh = {Aged ; Humans ; Male ; Middle Aged ; Prospective Studies ; Prostatectomy/*adverse effects ; Quality of Life ; Treatment Outcome ; Urinary Incontinence/etiology/*physiopathology/*surgery ; *Urinary Sphincter, Artificial ; Urodynamics ; }, abstract = {OBJECTIVES: We have evaluated prospectively the long-term efficacy of the artificial urinary sphincter (AUS) AMS 800 for the treatment postradical prostatectomy urinary incontinence (PRPUI) patients. We also evaluated the correlation between preoperative urodynamic findings and surgical outcomes.<br><br>METHODS: From May 1997 to April 2003, 40 consecutive patients with PRPUI caused by intrinsic sphincter deficiency (ISD) were treated with the AMS 800. Mean age was 68.3 +/- 6.3 years. Continence status was evaluated on the basis of pad count, impact of urinary incontinence on the quality of life, complications, and surgical revisions. Preoperative urodynamic findings were correlated with surgical outcomes.<br><br>RESULTS: Follow-up ranged from 27 to 132 months (mean = 53.4 +/- 21.4 months). There was a significant reduction in pad count from 4.0 +/- 0.9 to 0.62 +/- 1.07 diapers per day (P <0.001) leading to continence in 90%. There was a significant reduction on the impact of incontinence decreasing from 5.0 +/- 0.7 to 1.4 +/- 0.93 (P <0.001) in a visual analogue scale (VAS). Surgical revision rate was 20%. Preoperative urodynamics was useful to identify sphincter deficiency. Except by a tendency of worse results in patients with reduced bladder compliance (RBC), other urodynamic parameters did not correlate with a worse surgical outcome.<br><br>CONCLUSIONS: The AMS 800 offers good long-term continence to most PRPUI patients. Preoperative findings like detrusor hyperactivity (DH), impaired detrusor contraction (IDC), low Valsalva leak point pressure, bladder outlet obstruction (BOO), and mild RBC were not associated with worse surgical outcomes.}, }
@article {pmid18227005, year = {2008}, author = {Trabelsi, A and Rammeh, S and Stita, W and Mokni, M and Mourou, A and Korbi, S}, title = {[Detection of Epstein-Barr virus in breast cancers with lymphoid stroma].}, journal = {Annales de biologie clinique}, volume = {66}, number = {1}, pages = {59-62}, doi = {10.1684/abc.2008.0191}, pmid = {18227005}, issn = {0003-3898}, mesh = {Breast Neoplasms/*pathology/*virology ; Carcinoma, Medullary/pathology/virology ; Female ; Herpesvirus 4, Human/*isolation &amp; purification ; Humans ; Immunohistochemistry ; *Lymphatic Metastasis ; Retrospective Studies ; }, abstract = {OBJECTIVE: the purpose of our work is to detect Epstein-Barr virus (EBV) in 2 types of breast cancer: medullary carcinoma and high grade invasive ductal carcinoma with lymphoid stroma.<br><br>PATIENTS AND METHODS: we proceeded to a retrospective study of 18 medullary carcinoma and 18 high grade invasive ductal carcinoma with lymphoid stroma. The detection of the virus was carried out by immunohistochemistry with anti-LMP2 antibody and by hybridization in situ by oligonucleotides EBER1 and EBER1. LMP1 as well as hybridization in situ were positive in 5 tumors (3 medullary carcinoma and 2 high grade invasive ductal carcinoma with lymphoid stroma).<br><br>RESULTS: positivity was observed in tumor cells and neither in epithelial non tumoral ones nor in lymphoid cells.<br><br>DISCUSSION AND CONCLUSIONS: during numerous years, correlations between the replication of EBV and the appearance of a malignant phenotype were limited to nasopharyngeal carcinoma and to lymphoid cells. A controversy regarding the association of EBV with breast cancers has recently been reported in the literature. This cancer being very frequent, the involvement of EBV even in a small proportion of breast cancers could have important implications. Our results suggest a possible implication of EBV in these tumours but other studies are necessary.}, }
@article {pmid18186882, year = {2008}, author = {Steinman, S and Bourne, P and Yang, Q and Tang, P and Wang, J}, title = {Some DCIS is different molecularly from DCIS with co-existing IDC.}, journal = {The breast journal}, volume = {14}, number = {1}, pages = {122-123}, doi = {10.1111/j.1524-4741.2007.00536.x}, pmid = {18186882}, issn = {1524-4741}, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism ; Estrogen Receptor alpha/biosynthesis/genetics ; Female ; Gene Expression ; Humans ; Receptor, ErbB-2/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; }, }
@article {pmid18165279, year = {2008}, author = {Melnikov, AA and Scholtens, DM and Wiley, EL and Khan, SA and Levenson, VV}, title = {Array-based multiplex analysis of DNA methylation in breast cancer tissues.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {10}, number = {1}, pages = {93-101}, pmid = {18165279}, issn = {1525-1578}, mesh = {Breast Neoplasms/*genetics ; Cell Line, Tumor ; *DNA Methylation ; Female ; Genes, Neoplasm ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis/*methods/*standards ; Reproducibility of Results ; }, abstract = {Abnormal DNA methylation is well established for cancer cells, but a methylation-based diagnostic test is yet to be developed. One of the problems is insufficient accuracy of cancer detection in heterogeneous clinical specimens when only a single gene is analyzed. A new technique was developed to produce a multigene methylation signature in each sample, and its potential for selection of informative genes was tested using DNA from formalin-fixed, paraffin-embedded breast cancer tissues. Fifty-six promoters were analyzed in each of 138 clinical specimens by a microarray-based modification of the previously developed technique. Specific methylation signatures were identified for atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Informative promoters selected by Fisher's exact test were used for composite biomarker design using naïve Bayes algorithm. All informative promoters were unmethylated in disease compared with normal tissue. Cross-validation showed 72.4% sensitivity and 74.7% specificity for detection of ductal carcinoma in situ and invasive ductal carcinoma, and 87.5% sensitivity and 95% specificity for detection of atypical ductal hyperplasia. These results indicate that informative cancer-specific methylation signatures can be detected in heterogeneous tissue specimens, suggesting that a diagnostic assay can then be developed.}, }
@article {pmid18154662, year = {2007}, author = {O'Rourke, JA and Charlson, DV and Gonzalez, DO and Vodkin, LO and Graham, MA and Cianzio, SR and Grusak, MA and Shoemaker, RC}, title = {Microarray analysis of iron deficiency chlorosis in near-isogenic soybean lines.}, journal = {BMC genomics}, volume = {8}, number = {}, pages = {476}, pmid = {18154662}, issn = {1471-2164}, mesh = {Cluster Analysis ; DNA, Complementary/genetics ; Expressed Sequence Tags ; FMN Reductase/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Plant/*genetics ; Genes, Plant/genetics ; Hydroponics ; Iron/*metabolism ; *Iron Deficiencies ; Multigene Family/genetics ; *Oligonucleotide Array Sequence Analysis ; Phenotype ; Plant Diseases/*genetics ; Plant Roots/genetics/metabolism ; Polymerase Chain Reaction ; RNA, Plant/analysis/genetics ; Soybeans/enzymology/*genetics/*metabolism ; }, abstract = {BACKGROUND: Iron is one of fourteen mineral elements required for proper plant growth and development of soybean (Glycine max L. Merr.). Soybeans grown on calcareous soils, which are prevalent in the upper Midwest of the United States, often exhibit symptoms indicative of iron deficiency chlorosis (IDC). Yield loss has a positive linear correlation with increasing severity of chlorotic symptoms. As soybean is an important agronomic crop, it is essential to understand the genetics and physiology of traits affecting plant yield. Soybean cultivars vary greatly in their ability to respond successfully to iron deficiency stress. Microarray analyses permit the identification of genes and physiological processes involved in soybean's response to iron stress.<br><br>RESULTS: RNA isolated from the roots of two near isogenic lines, which differ in iron efficiency, PI 548533 (Clark; iron efficient) and PI 547430 (IsoClark; iron inefficient), were compared on a spotted microarray slide containing 9,728 cDNAs from root specific EST libraries. A comparison of RNA transcripts isolated from plants grown under iron limiting hydroponic conditions for two weeks revealed 43 genes as differentially expressed. A single linkage clustering analysis of these 43 genes showed 57% of them possessed high sequence similarity to known stress induced genes. A control experiment comparing plants grown under adequate iron hydroponic conditions showed no differences in gene expression between the two near isogenic lines. Expression levels of a subset of the differentially expressed genes were also compared by real time reverse transcriptase PCR (RT-PCR). The RT-PCR experiments confirmed differential expression between the iron efficient and iron inefficient plants for 9 of 10 randomly chosen genes examined. To gain further insight into the iron physiological status of the plants, the root iron reductase activity was measured in both iron efficient and inefficient genotypes for plants grown under iron sufficient and iron limited conditions. Iron inefficient plants failed to respond to decreased iron availability with increased activity of Fe reductase.<br><br>CONCLUSION: These experiments have identified genes involved in the soybean iron deficiency chlorosis response under iron deficient conditions. Single linkage cluster analysis suggests iron limited soybeans mount a general stress response as well as a specialized iron deficiency stress response. Root membrane bound reductase capacity is often correlated with iron efficiency. Under iron-limited conditions, the iron efficient plant had high root bound membrane reductase capacity while the iron inefficient plants reductase levels remained low, further limiting iron uptake through the root. Many of the genes up-regulated in the iron inefficient NIL are involved in known stress induced pathways. The most striking response of the iron inefficient genotype to iron deficiency stress was the induction of a profusion of signaling and regulatory genes, presumably in an attempt to establish and maintain cellular homeostasis. Genes were up-regulated that point toward an increased transport of molecules through membranes. Genes associated with reactive oxidative species and an ROS-defensive enzyme were also induced. The up-regulation of genes involved in DNA repair and RNA stability reflect the inhospitable cellular environment resulting from iron deficiency stress. Other genes were induced that are involved in protein and lipid catabolism; perhaps as an effort to maintain carbon flow and scavenge energy. The under-expression of a key glycolitic gene may result in the iron-inefficient genotype being energetically challenged to maintain a stable cellular environment. These experiments have identified candidate genes and processes for further experimentation to increase our understanding of soybeans' response to iron deficiency stress.}, }
@article {pmid18154115, year = {2007}, author = {Kriuchkov, AN}, title = {[Extent of destructive changes in tumor parenchyma of breast cancer patients of various age].}, journal = {Voprosy onkologii}, volume = {53}, number = {5}, pages = {531-534}, pmid = {18154115}, issn = {0507-3758}, mesh = {Adult ; Age Factors ; Aged ; Apoptosis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/secondary ; Female ; Humans ; Middle Aged ; Necrosis ; }, abstract = {Extent of viable tumor parenchyma and necrotic tissue as well as grade of tumor cell apoptosis were assessed using histological samples from 377 patients with invasive ductal carcinoma of the breast. No preoperative chemo- or radiotherapy was given. Patients of varying age were examined for destructive changes in tumor nodes both in absence and presence of regional metastases. The highest viability was registered in patients aged 30-39 years. There was a reverse correlation between age, on the one hand, and extent of intact tumor parenchyma, on the other. Similarly, the same age group revealed relatively pronounced destructive changes such as necrosis and apoptosis which are generally characteristic of younger age. There was a significant relationship between extent of destructive changes and malignant anaplasia.}, }
@article {pmid18087220, year = {2007}, author = {Signorino, E and Brusa, D and Granata, R and Malavasi, F and Ferrone, S and Matera, L}, title = {Contribution of dendritic cells' FcgammaRI and FcgammaRIII to cross-presentation of tumor cells opsonized with the anti-MHC class I monoclonal antibodies.}, journal = {Cancer biology &amp; therapy}, volume = {6}, number = {12}, pages = {1932-1937}, doi = {10.4161/cbt.6.12.4973}, pmid = {18087220}, issn = {1555-8576}, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; Antibody Specificity ; Antigen Presentation/*immunology ; Antigens, Neoplasm/*immunology/metabolism ; Carcinoma/immunology/pathology ; Cell Differentiation/immunology ; Cell Line, Tumor/immunology ; Coculture Techniques ; Cytokines/pharmacology ; Dendritic Cells/drug effects/*immunology ; GPI-Linked Proteins ; HLA-A2 Antigen/*immunology/metabolism ; Humans ; Interferon-gamma/biosynthesis ; K562 Cells/immunology ; Mice ; Opsonin Proteins/*immunology ; Receptors, IgG/*immunology ; Stomach Neoplasms/immunology/pathology ; T-Lymphocytes, Cytotoxic/immunology ; }, abstract = {Dendritic cells (DC) operate through an immature (iDC) step (where tumor antigens are internalized) and a mature step (mDC) (where tumor antigens (TA) are cross-presented to naive TA-specific cytotoxic T lymphocyte (CTL) progenitors). Receptors by which cellbound antigens can access the DC cross-presentation pathway include the Fcgamma receptors (FcgammaR). This route has been exploited to deliver opsonized tumors to DC and promising results have been obtained with mAbs raised against overexpressed or specific tumor antigens. In order to extend this strategy to tumor for which no antigens have been described, we have exploited the ubiquitous molecule MHC Class I as target antigen. The low membrane expression of tumor antigens on KATO cells, a previously studied human gastric carcinoma cell line, suggested its use here as a model. The IgG1 TP25.99 and the IgG2a W6/32 anti-MHC Class I mAbs, which strongly reacted with KATO cells, where employed as tumor coating mAbs. Since these mAbs recognize the FcgammaRI (CD64) and FcgammaRIII (CD16), respectively on DCs, the frequencies of the two classes of FcgammaRI on DCs was evaluated. CD64 was expressed on 35% of iDCs compared to 11% expression of CD16, the two molecules being co-expressed. IgG1 mAb-opsonized KATO (KATO(TP25)) cells were taken up by iDCs with the same efficiency as KATO cells opsonized with IgG2a mAb (KATO(W6/32)), but induced a higher expression of the maturation marker CD83. CTL cross-priming by KATO(TP25) (but not KATO(W6/32))-loaded and cytokine-matured DCs was also higher than cross-priming induced by uncoated- or FcgammaRI-targeted KATO(W6/32)-DC. Together the present results indicate that: (i) MHC Class I antigens are advantageous antigens for targeting tumor cells to the FcgammaR-mediated cross-presentation pathway and (ii) immunogenic signals seem to be prevalently conveyed by FcgammaRIII.}, }
@article {pmid18056365, year = {2007}, author = {Bax, M and García-Vallejo, JJ and Jang-Lee, J and North, SJ and Gilmartin, TJ and Hernández, G and Crocker, PR and Leffler, H and Head, SR and Haslam, SM and Dell, A and van Kooyk, Y}, title = {Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {179}, number = {12}, pages = {8216-8224}, doi = {10.4049/jimmunol.179.12.8216}, pmid = {18056365}, issn = {0022-1767}, support = {081882/WT_/Wellcome Trust/United Kingdom ; GM62116/GM/NIGMS NIH HHS/United States ; }, mesh = {Dendritic Cells/*immunology ; Galectins/*immunology ; Gene Expression Profiling ; Glycosylation ; Glycosyltransferases/genetics ; Humans ; Lectins/*immunology ; Oligonucleotide Array Sequence Analysis ; Polysaccharides/*biosynthesis/genetics ; Sialic Acid Binding Immunoglobulin-like Lectins ; }, abstract = {Dendritic cells (DC) are the most potent APC in the organism. Immature dendritic cells (iDC) reside in the tissue where they capture pathogens whereas mature dendritic cells (mDC) are able to activate T cells in the lymph node. This dramatic functional change is mediated by an important genetic reprogramming. Glycosylation is the most common form of posttranslational modification of proteins and has been implicated in multiple aspects of the immune response. To investigate the involvement of glycosylation in the changes that occur during DC maturation, we have studied the differences in the glycan profile of iDC and mDC as well as their glycosylation machinery. For information relating to glycan biosynthesis, gene expression profiles of human monocyte-derived iDC and mDC were compared using a gene microarray and quantitative real-time PCR. This gene expression profiling showed a profound maturation-induced up-regulation of the glycosyltransferases involved in the expression of LacNAc, core 1 and sialylated structures and a down-regulation of genes involved in the synthesis of core 2 O-glycans. Glycosylation changes during DC maturation were corroborated by mass spectrometric analysis of N- and O-glycans and by flow cytometry using plant lectins and glycan-specific Abs. Interestingly, the binding of the LacNAc-specific lectins galectin-3 and -8 increased during maturation and up-regulation of sialic acid expression by mDC correlated with an increased binding of siglec-1, -2, and -7.}, }
@article {pmid18045769, year = {2008}, author = {Kijima, Y and Yoshinaka, H and Koriyama, C and Funasako, Y and Natsugoe, S and Aikou, T}, title = {Ultrasound examination is useful for prediction of histologic type in invasive ductal carcinoma of the breast.}, journal = {Ultrasound in medicine &amp; biology}, volume = {34}, number = {4}, pages = {517-524}, doi = {10.1016/j.ultrasmedbio.2007.09.017}, pmid = {18045769}, issn = {0301-5629}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/secondary ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Risk Factors ; Ultrasonography, Mammary/methods ; }, abstract = {The aim of this study was to estimate the histologic type of invasive ductal carcinoma of the breast according to the ultrasound (US) criteria and to identify the high-risk patients for lymph node metastases. An acceptable preoperative diagnosis of lymph node metastasis is essential when performing the reduction of lymphadenectomy. The positive relationship between histology and prognosis has been reported in breast cancer. However, few reports have examined the relationship between preoperative US findings and histology. Ultrasound examination was performed in 252 patients with invasive ductal carcinoma (91 papillotubular, 54 solid-tubular and 107 scirrhous carcinoma). Risk factors for nodal metastasis were analyzed in clinicopathological findings. After nine criteria were defined based on US findings, all tumors were classified into US histologic type. According to the multivariate analysis, lymph node metastases was significantly associated with tumor size (p < 0.001), histology (p < 0.001) and age (p = 0.038). Histology was an important risk factor for nodal metastasis, especially in scirrhous carcinoma. When comparing the US classification and histology, the accuracy rate of US for papillotubular, solid-tubular and scirrhous type was 75%, 78% and 75%, respectively. To predict the scirrhous carcinoma with frequent nodal metastasis, US criteria such as the larger ratio of depth-to-width, boundary echo and attenuation of the back echo was important. It is important to preoperatively estimate the histologic type by tumor property using US. Our US classifications may be useful to pick up high-risk patients for nodal metastasis in invasive breast cancer.}, }
@article {pmid18041310, year = {2007}, author = {Al-Joudi, FS and Iskandar, ZA and Imran, AK}, title = {Correlations in survivin expression with the expression of p53 and bcl-2 in invasive ductal carcinoma of the breast.}, journal = {The Southeast Asian journal of tropical medicine and public health}, volume = {38}, number = {5}, pages = {904-910}, pmid = {18041310}, issn = {0125-1562}, mesh = {Adult ; Apoptosis/physiology ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins/*biosynthesis/genetics ; Middle Aged ; Neoplasm Proteins/*biosynthesis/genetics ; Survivin ; Tumor Suppressor Protein p53/*biosynthesis/genetics ; }, abstract = {This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.}, }
@article {pmid18028418, year = {2008}, author = {Aessopos, A and Tsironi, M and Polonifi, K and Baltopoulos, P and Vaiopoulos, G}, title = {Intervertebral disc calcification in thalassemia intermedia.}, journal = {European journal of haematology}, volume = {80}, number = {2}, pages = {164-167}, doi = {10.1111/j.1600-0609.2007.00987.x}, pmid = {18028418}, issn = {1600-0609}, mesh = {Adult ; Calcinosis/*complications/etiology ; Female ; Hemochromatosis/complications/etiology ; Humans ; Intervertebral Disc/*physiopathology ; Intervertebral Disc Displacement/*complications/etiology ; Lumbar Vertebrae/diagnostic imaging ; Male ; Middle Aged ; Prevalence ; Radiography, Thoracic ; Treatment Outcome ; X-Rays ; beta-Thalassemia/*complications ; }, abstract = {OBJECTIVES: Intervertebral disc calcification, an age-related phenomenon of variable clinical significance is described in hemochromatosis. As beta-thalassemia is characterized by excessive tissue iron deposition and secondary hemosiderosis, and skeletal abnormalities are often observed in these patients, this study is conducted to identify the prevalence of Intervertebral Disc Calcification (IDC) in thalassemia intermedia population.<br><br>METHODS: We investigated all the elder than 30 years beta-thalassemia intermedia patients of our Department thalassemia unit. Patients underwent thoracic and lumbar spinal X-rays for IDC presence. Patients presenting IDC were compared to those not presenting, regarding back pain anamnesis, presence of back pain, extramedullary hemopoiesis, sex, age, Hb levels, ferritin levels, reticulocytes, bilirubin values, thyroid-parathyroid abnormalities. Student's t-test was used to compare variables between patients with and without IDC. A P-value under 0.05 was considered statistically significant.<br><br>RESULTS: We investigated 30 beta-thalassemia intermedia patients (19 women) with an age range 38-61 yr (42.5 +/- 11.46 yr). Intervertebral disc calcifications were observed in seven patients (23.33%). No sex and laboratory parameters statistically significant differences were observed differences for IDC prevalence, while mean age and back pain history was statistically significantly different between the two groups.<br><br>CONCLUSIONS: In thalassemia patients, the big variety of spinal deformities may hide the presence of IDC and thus, this entity may be overlooked or underestimated. The clinical significance of IDC development as well as the possible prevention by early transfusion chelation therapy should be further investigated.}, }
@article {pmid18026874, year = {2008}, author = {Di Saverio, S and Gutierrez, J and Avisar, E}, title = {A retrospective review with long term follow up of 11,400 cases of pure mucinous breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {111}, number = {3}, pages = {541-547}, doi = {10.1007/s10549-007-9809-z}, pmid = {18026874}, issn = {0167-6806}, mesh = {Adenocarcinoma, Mucinous/*epidemiology/mortality/pathology/therapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/mortality/pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; }, abstract = {BACKGROUND: Pure mucinous breast carcinoma (PMBC) is a rare histologic type of mammary neoplasm. It has been associated with a better short-term prognosis than infiltrating ductal carcinoma (IDC) but identical long-term survival curves have been reported. The value of tumor size for TNM staging has been challenged because of the mucin content of the lesions. This study presents a large PMBC series with 20 years follow up as compared to IDC. The relative significance of a variety of common prognostic factors is calculated for this uncommon histology.<br><br>MATERIALS AND METHODS: A retrospective analysis of all PMBC cases reported in the SEER database between 1973 and 2002 was conducted. Overall survival (OS) and disease specific survival (DSS) were calculated at 5, 10, 15 and 20 years of follow up. Those curves were compared with all the IDC cases reported into the database during the same period. The prognostic significance of gender, race, laterality, age at diagnosis, T and N status, estrogen and progesterone receptors and administration of radiation therapy was calculated by univariate and multivariate analysis.<br><br>RESULTS: There were 11,422 PMBC patients reported. The median age at diagnosis was 71 years (Range 25-85). Fifty three percent of the tumors were well differentiated, 38% were moderately differentiated and the remaining 9% were poorly differentiated or anaplastic. The majority of the tumors were located in the upper outer quadrant (44%) the other 56% were roughly evenly divided between the upper inner, lower inner, lower outer and central quadrants. Eighty six percent of the patients had only localized disease at the time of surgery without nodal or distant disease while 12% had regional nodal involvement and 2% had distant metastases. The PMBC cases showed a better differentiation with lesions of lesser grade and more frequent ER/PR expression, smaller size and lesser nodal involvement when compared to the IDC cases of the same period. Kaplan Meier survival curves revealed a 5 years. breast cancer specific survival rate of 94%. Although slowly decreasing with time, 10, 15 and 20 years survival were 89%, 85% and 81% respectively compared to 82% (5 year), 72% (10 year), 66% (15 year) and 62% (20 year) for IDC. There were no significant differences in overall survival. Multivariate analysis by Cox regression revealed the nodal status (N) to be the most significant prognostic factor followed by age, tumor size (T), progesterone receptors and nuclear grade. Disease specific survival curves stratified for nodal status revealed a highly significant difference between node negative and node positive patients. The addition of radiation therapy after surgery did not significantly improve overall survival.<br><br>CONCLUSIONS: This large retrospective comparative analysis confirms the less aggressive behavior of PMBC compared to IDC. This favorable outcome is maintained after 20 years. This tumor presents typically in older patients and is rarely associated with nodal disease. Positive nodal status appears to be the most significant predictor of worse prognosis.}, }
@article {pmid18024331, year = {2007}, author = {Lee, Y and Cho, S and Seo, JH and Shin, BK and Kim, HK and Kim, I and Kim, A}, title = {Correlated expression of erbB-3 with hormone receptor expression and favorable clinical outcome in invasive ductal carcinomas of the breast.}, journal = {American journal of clinical pathology}, volume = {128}, number = {6}, pages = {1041-1049}, doi = {10.1309/GA5VRFQFY5D0MVKD}, pmid = {18024331}, issn = {0002-9173}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/secondary ; Disease-Free Survival ; ErbB Receptors/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/pathology ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-3/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Survival Rate ; }, abstract = {The prognostic impact of epidermal growth factor receptor (EGFR) family members in breast carcinoma was evaluated through the analysis of 378 cases of invasive ductal carcinoma to determine the relationship between EGFR family members and clinical outcome. It was found that 13.8% of the cases were positive for erbB-3. Expression of erbB-3 was inversely correlated with EGFR and erbB-4 expression (P = .012 and P = .046). Expression of erbB-3 was correlated with positive estrogen and progesterone receptor status and inversely correlated with histologic grade. Expression of erbB-3 was correlated with longer disease-free survival (DFS; P = .028). Within the erbB-3-expressing group, there was a tendency for the coexpressing group to have shorter DFS compared with the single-expressing group. This study revealed that erbB-3 expression was associated with better prognosis. In an era of personalized targeted therapy, erbB-3 expression and its coexpressive pattern with other EGFR family members could be an important determinant for therapeutic plans for breast cancer treatment.}, }
@article {pmid18022074, year = {2007}, author = {Rasmusson, KD and Stehlik, J and Brown, RN and Renlund, DG and Wagoner, LE and Torre-Amione, G and Folsom, JW and Silber, DH and Kirklin, JK and , }, title = {Long-term outcomes of cardiac transplantation for peri-partum cardiomyopathy: a multiinstitutional analysis.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {26}, number = {11}, pages = {1097-1104}, doi = {10.1016/j.healun.2007.08.002}, pmid = {18022074}, issn = {1557-3117}, mesh = {Adult ; Cardiomyopathies/etiology/*surgery ; Female ; Follow-Up Studies ; Graft Rejection ; *Heart Transplantation ; Humans ; Incidence ; Longitudinal Studies ; Male ; Outcome Assessment, Health Care/*statistics &amp; numerical data ; *Postpartum Period ; Pregnancy ; Pregnancy Complications, Cardiovascular/*surgery ; Registries ; Survivors/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Outcomes of patients with a prior diagnosis of peri-partum cardiomyopathy (PPCM) undergoing heart transplantation are not well described but may be worse than for women who undergo transplantation for other etiologies.<br><br>METHODS: Between 1999 and 2005, 69 women aged younger than 40 underwent transplantation for PPCM in 29 institutions participating in the Cardiac Transplant Research Database. Patients with PPCM were compared with 90 female recipients of similar age with idiopathic dilated cardiomyopathy (IDC) and history of pregnancy (P+), 53 with no prior pregnancy (P-), and with 459 men of a similar age with IDC. Rejection, infection, cardiac allograft vasculopathy, and survival were compared.<br><br>RESULTS: Recipients with PPCM accounted for 1% of all transplants and 5% of transplants in women. Comparisons of the 4 patient groups were made. The risk of cumulative rejection was higher in the PPCM Group compared with the P- Group (p < 0.04) and the men (p < 0.0001). Cumulative risk of infection was lowest in the PPCM Group. Freedom from cardiac allograft vasculopathy was similar or higher in the PPCM Group compared with the other groups. Finally, the long-term survival of PPCM patients was comparable with the survival of men (p = 0.9), and there was a trend toward improved survival compared with the P+ Group (p = 0.07) and improved survival compared with the P- Group (p = 0.05).<br><br>CONCLUSIONS: Heart transplantation for PPCM remains relatively infrequent. Survival and freedom from cardiac allograft vasculopathy in patients who receive a transplant for PPCM are no worse than in women who require a transplant for other indications, regardless of parity.}, }
@article {pmid18001417, year = {2007}, author = {McLean, SR and Shousha, S and Francis, N and Lim, A and Eccles, S and Nathan, M and Brock, CS and Palmieri, C}, title = {Metastatic ductal eccrine adenocarcinoma masquerading as an invasive ductal carcinoma of the male breast.}, journal = {Journal of cutaneous pathology}, volume = {34}, number = {12}, pages = {934-938}, doi = {10.1111/j.1600-0560.2007.00749.x}, pmid = {18001417}, issn = {0303-6987}, mesh = {Adenocarcinoma/metabolism/*pathology/therapy ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis ; Bone Density Conservation Agents/therapeutic use ; Bone Neoplasms/secondary/therapy ; Breast Neoplasms, Male/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Cyclophosphamide/therapeutic use ; Diphosphonates/therapeutic use ; Eccrine Glands/*pathology ; Epirubicin/therapeutic use ; Fluorouracil/therapeutic use ; Humans ; Ibandronic Acid ; Immunohistochemistry ; Lung Neoplasms/secondary/therapy ; Lymphatic Metastasis/pathology ; Male ; Radiotherapy ; Sweat Gland Neoplasms/metabolism/*pathology/therapy ; Tamoxifen/therapeutic use ; Tomography, X-Ray Computed ; }, abstract = {We report the case of a 38-year-old man with metastatic ductal eccrine adenocarcinoma (DEA) of the left breast responding to 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. He initially presented with a 2-week history of difficulty walking because of bilateral hip and lower back pain. Examination showed an ulcerating cutaneous mass over the left anterior chest wall, left axillary lymphadenopathy and tenderness over the spine. A punch biopsy of the breast lesion resulted in a diagnosis of metastatic invasive ductal carcinoma (IDC) of the breast. He received palliative radiotherapy to the spine and also received six cycles of FEC chemotherapy and was subsequently commenced on tamoxifen and ibandronate. There was a symptomatic and radiological response to the FEC chemotherapy. Referral was subsequently made to our institution where the original punch biopsy was reviewed. This showed tumor cells that were polygonal with darkly stained pleomorphic nuclei and abundant eosinophilic cytoplasm and were also localized to areas of fibrotic stroma containing eccrine glands and ducts but did not appear to involve mammary tissue. Immunohistochemical studies showed the tumors to be cytokeratin 7 and gross cystic disease fluid protein-15/prolactin inducible protein negative and estrogen receptor alpha positive. Both the morphological and the immunohistochemical characteristics of the tumor were consistent with a revised diagnosis of DEA rather than IDC. When last reviewed, the patient remains pain free and his disease stable 17 months after his original presentation. This case emphasizes the challenge in discriminating histopathologically between two rare tumors of the male breast, namely DEA and IDC. In addition, clinical response to FEC by metastatic DEA has not been previously documented, and this therapeutic regimen warrants further investigation.}, }
@article {pmid17986805, year = {2007}, author = {Horii, R and Akiyama, F and Ito, Y and Matsuura, M and Miki, Y and Iwase, T}, title = {Histological features of breast cancer, highly sensitive to chemotherapy.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {4}, pages = {393-400}, doi = {10.2325/jbcs.14.393}, pmid = {17986805}, issn = {1880-4233}, mesh = {Adenocarcinoma/*drug therapy/secondary ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/secondary ; Chemotherapy, Adjuvant ; Epirubicin/administration &amp; dosage ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Paclitaxel/administration &amp; dosage ; }, abstract = {BACKGROUND: To establish tailor-made therapy for breast cancer, we investigated the possibility of predicting chemotherapy sensitive cases based on pre-therapeutic histological features.<br><br>METHODS: A total of 87 breast cancer patients underwent neoadjuvant chemotherapy with a paclitaxel (80 mg/m(2)/q1w, 12 courses)or an epirubicin regimen (90 mg/m(2)/q3wks, 4 courses). We investigated the chemo-sensitivity of invasive ductal carcinoma, solid-tubular carcinoma consisting of highly malignant cancer cells with many mitoses. We refer to this type of carcinoma as " chemo-sensitive carcinoma " and compared the histological therapeutic effects of chemo-sensitive and chemo-insensitive carcinomas.<br><br>RESULTS: 1) Out of 87 patients, 20 cases (23%) showed the histological features of chemo-sensitive carcinomas on pre-therapeutic needle biopsy specimens. The remaining 67 cases (77%) were classified as chemo-insensitive carcinoma. 2) Histologically marked or complete response were observed in 50% (10/20) of chemo-sensitive carcinomas and 10% (7/67) of chemo-insensitive carcinomas (chi(2)=15.33, p=0.0001). Multivariate analysis of chemo-sensitive carcinoma, including HER2, hormone receptor and p53 status, revealed that chemo-sensitive carcinoma had a significant correlation with the histological therapeutic effects (p=0.01119). 3) Pathological complete response (pCR) was achieved in 35% (7/20) of chemo-sensitive carcinomas and 1.5% (1/67)of chemo-insensitive carcinomas (chi(2)=20.71, p<0.0001). Multivariate analysis revealed that chemo-sensitive carcinoma had a significant correlation with pCR (p=0.0091).<br><br>CONCLUSION: The histological features of chemo-sensitive carcinoma were significant predictive factors for chemotherapeutic efficacy.}, }
@article {pmid17985332, year = {2008}, author = {Parker, BS and Ciocca, DR and Bidwell, BN and Gago, FE and Fanelli, MA and George, J and Slavin, JL and Möller, A and Steel, R and Pouliot, N and Eckhardt, B and Henderson, MA and Anderson, RL}, title = {Primary tumour expression of the cysteine cathepsin inhibitor Stefin A inhibits distant metastasis in breast cancer.}, journal = {The Journal of pathology}, volume = {214}, number = {3}, pages = {337-346}, doi = {10.1002/path.2265}, pmid = {17985332}, issn = {0022-3417}, support = {R01 CA90291/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biomarkers, Tumor/analysis ; Bone Neoplasms/genetics/*metabolism/*secondary ; Breast Neoplasms/drug therapy/genetics/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/genetics/*metabolism ; Case-Control Studies ; Cystatin A ; Cystatins/*analysis/genetics/metabolism ; Cysteine Proteinase Inhibitors/*analysis/genetics/metabolism ; Disease-Free Survival ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Injections, Intralesional ; Mice ; Neoplasm Invasiveness/pathology ; Prognosis ; Proportional Hazards Models ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Using the clinically relevant 4T1-derived syngeneic murine model of spontaneous mammary metastasis to bone, we have identified the cysteine cathepsin inhibitor Stefin A as a gene differentially expressed in primary and metastatic mammary tumours. In primary tumours, Stefin A expression correlated inversely with metastatic potential in 4T1-derived lines and was not detected in tumour cells in culture, indicating induction only within the tumour microenvironment. Enforced expression of Stefin A in the highly metastatic 4T1.2 cell line significantly reduced spontaneous bone metastasis following orthotopic injection into the mammary gland. Consistent with the mouse data, Stefin A expression correlated with disease-free survival (absence of distant metastasis) in a cohort of 142 primary tumours from breast cancer patients. This was most significant for patients with invasive ductal carcinoma expressing Stefin A, who were less likely to develop distant metastases (log rank test, p = 0.0075). In a multivariate disease-free survival analysis (Cox proportional hazards model), Stefin A expression remained a significant independent prognostic factor in patients with invasive ductal carcinoma (p = 0.0014), along with grade and progesterone receptor (PR) status. In human lung and bone metastases, we detected irregular Stefin A staining patterns, with expression often localizing to micrometastases (<0.2 mm) in direct contact with the stroma. We propose that Stefin A, as a cysteine cathepsin inhibitor, may be a marker of increased cathepsin activity in metastases. Using immunohistology, the cathepsin inhibitor was detected co-expressed with cathepsin B in lung and bone metastases in both the murine model and human tissues. We conclude that Stefin A expression reduces distant metastasis in breast cancer and propose that this may be due to the inhibition of cysteine cathepsins, such as cathepsin B.}, }
@article {pmid17983059, year = {2007}, author = {Bremner, AK and Recabaren, J}, title = {The efficacy of MRI as an adjuvant to traditional mammography.}, journal = {The American surgeon}, volume = {73}, number = {10}, pages = {970-972}, pmid = {17983059}, issn = {0003-1348}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/*statistics &amp; numerical data ; Male ; Mammography/*statistics &amp; numerical data ; Middle Aged ; }, abstract = {The objective of our study is to assess the utility of breast Magnetic Resonance Imaging (MRI) when used for indications other than those published in peer-reviewed studies. A retrospective chart review was conducted of the records of 588 women who underwent both mammography and breast MRI. Patients excluded from the study were those who had breast MRI for accepted indications based on published peer-review studies. Included on the study were the remaining 122 patients. An evaluation was then made in each case as to whether the MRI finding caused a change in the patient's management. In this review, subject age ranged from 27- to 85-years-old. The mean age of the sample was 54.5 years. Of the positive MRI results, 29 (27.7%) had additional findings. There were 25 (20.3%) subjects with a treatment change and 97 (79.5%) without. In conclusion, breast MRI affected the clinical management in 25 (20.3%) of 122 patients. The majority of the 25 patients have invasive ductal carcinoma, followed by ductal carcinoma in situ. We believe this is a significant percentage positively affected by the additional use of breast MRI. We suggest that indications for the use of breast MRI in addition to traditional breast imaging should include all patients with invasive ductal carcinoma.}, }
@article {pmid17982621, year = {2007}, author = {Wen, YH and Shi, X and Chiriboga, L and Matsahashi, S and Yee, H and Afonja, O}, title = {Alterations in the expression of PDCD4 in ductal carcinoma of the breast.}, journal = {Oncology reports}, volume = {18}, number = {6}, pages = {1387-1393}, pmid = {17982621}, issn = {1021-335X}, support = {K12CA01713/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis Regulatory Proteins/*genetics/metabolism ; Breast/cytology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/genetics/pathology ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; RNA-Binding Proteins/*genetics/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Programmed cell death 4 gene (PDCD4), an in vivo repressor of transformation, was originally isolated from a human glioma library by screening it with an antibody against a nuclear antigen in proliferating cells. PDCD4 functions as a transformation repressor by inhibiting the activity of the RNA helicase, eIF4A. We previously showed that retinoids, anti-estrogens and HER2/neu antagonist induce PDCD4 expression in human breast cancer cell lines. Very little is known about the expression of PDCD4 in human breast cancer tissues or the significance of the PDCD4 expression in breast cancer. To gain insight into the pattern of the PDCD4 expression in breast tissues, we performed an immunohistochemical analysis of the PDCD4 expression in 80 archived, normal and ductal breast carcinoma tissues (invasive and carcinoma in situ) (DCIS) and correlated PDCD4 expression with expression of known prognostic markers in breast cancer (ER, PR and HER2/neu). To assess the role of methylation on PDCD4 expression in breast cancer cells, breast cancer cell lines were treated with the demethylating agent 5-deoxy-azacytidine and analyzed for PDCD4 expression. We observed primarily nuclear localization of PDCD4 in ductal carcinoma in situ compared to normal breast tissues where the PDCD4 expression was predominantly cytoplasmic. This was seen more frequently in DCIS cases that were ER positive and HER2/neu negative samples. PDCD4 expression was markedly decreased in the invasive ductal carcinoma. We did not observe any significant relationship between PDCD4 expression and the expression of RAR or PR. In T-47D, MDA-MB-435 and MDA-MB-231 cells, treatment with 5-deoxy-azacytidine did not result in an increased expression of PDCD4. The present study demonstrated altered cellular localization of PDCD4 when comparing normal breast to neoplastic breast tissues. In addition, there was a decreased expression of PDCD4 in breast cancer when compared with normal breast tissue. A loss of the PDCD4 expression in breast cancer cell lines does not appear to result from hypermethylation of the PDCD4 promoter.}, }
@article {pmid17954264, year = {2007}, author = {Walker, LC and Harris, GC and Holloway, AJ and McKenzie, GW and Wells, JE and Robinson, BA and Morris, CM}, title = {Cytokeratin KRT8/18 expression differentiates distinct subtypes of grade 3 invasive ductal carcinoma of the breast.}, journal = {Cancer genetics and cytogenetics}, volume = {178}, number = {2}, pages = {94-103}, doi = {10.1016/j.cancergencyto.2007.06.002}, pmid = {17954264}, issn = {0165-4608}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics ; Cohort Studies ; DNA, Complementary ; Female ; Humans ; Keratin-18/*genetics ; Keratin-8/*genetics ; Middle Aged ; Neoplasm Invasiveness/*genetics ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Invasive ductal carcinomas of the breast (IDC) are routinely assessed on hematoxylin and eosin stained paraffin sections, with limited use of immunohistochemistry (IHC). Most IDC are regarded as a single diagnostic entity, IDC of no special type (IDC-NST), which is subdivided further only by grading. However, recent research suggests that there is high clinical relevance in differentiating IDC subtypes. Here, we ascertain whether tumor histology alone can predict basal or luminal cell phenotype in high-grade IDC-NST, and whether IHC and molecular characteristics are associated with the observed morphologies. A total of 29 grade 3 IDC-NST samples were studied, 10 tumors from a selected pilot cohort A and 19 tumors from an unselected validation cohort B. Along with histopathological assessment, the expression of ESR1, PGR, ERBB2 (HER-2), the basal/myoepithelial marker TP73L (p63), cytokeratins 5/6 (KRT5/6) and 14 (KRT14), and the luminal-specific cytokeratins 8/18 (KRT 8/18) and 19 (KRT19) was assessed by IHC. Hierarchical cluster analysis of clinicopathological variables and, separately, microarray expression profiles showed that the phenotypically distinctive basaloid and luminal tumors of cohort A fell into two main groups, defined by heterogeneous or uniformly positive expression of KRT8/18. The 38 genes differentially expressed between these two classes included ERBB2, KRT8, and six other genes previously associated with ERBB2-positive or luminal phenotypes. Tumor histology was not predictive for validation cohort B, but quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed two molecularly defined clusters that again aligned with the KRT8/18 staining phenotypes. Metaphase comparative genomic hybridization revealed 10q, 16q, and 20q copy-number imbalances that associated recurrently with KRT8/18 staining patterns.}, }
@article {pmid17949231, year = {2007}, author = {Kamali-Sarvestani, E and Aliparasti, MR and Atefi, S}, title = {Association of interleukin-8 (IL-8 or CXCL8) -251T/A and CXCR2 +1208C/T gene polymorphisms with breast cancer.}, journal = {Neoplasma}, volume = {54}, number = {6}, pages = {484-489}, pmid = {17949231}, issn = {0028-2685}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Case-Control Studies ; Disease Progression ; Female ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-8/*genetics ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, Interleukin-8B/*genetics ; }, abstract = {A case-control study involving 257 breast cancer patients with invasive ductal carcinoma and 233 healthy women was carried out to explore if the IL-8 -251T/A polymorphism and the CXCR2 +1208 C/T polymorphism have a role in breast cancer susceptibility. Genotypic analysis showed an increased frequency of high producer IL-8 -251AA genotype (p=0.016) in the patient group as compared to controls while CXCR2 +1208 C/T polymorphism did not show any differences between studied groups. However, in contrast to IL-8 -251 polymorphism, the percentage of CXCR2 +1208 TT genotype was significantly lower in patients with NPI<or=3.4 compared to NPI>3.4 (2% and 12%, respectively; p=0.03). Also, ER- tumors showed an approximately significant higher CXCR2 +1208 TT genotype compared to ER+ tumors (18.6% and 7.1%, respectively; p=0.07). In conclusion, IL-8 -251T/A polymorphism is associated with development of invasive ductal carcinoma type of breast cancer while CXCR2 +1208C/T polymorphism may affect the disease progression.}, }
@article {pmid17945020, year = {2007}, author = {Arkadianos, I and Valdes, AM and Marinos, E and Florou, A and Gill, RD and Grimaldi, KA}, title = {Improved weight management using genetic information to personalize a calorie controlled diet.}, journal = {Nutrition journal}, volume = {6}, number = {}, pages = {29}, pmid = {17945020}, issn = {1475-2891}, mesh = {Adult ; Analysis of Variance ; Blood Glucose/analysis/*metabolism ; Body Mass Index ; Diet, Mediterranean ; Diet, Reducing ; Exercise/physiology ; Female ; Genetic Predisposition to Disease ; Genotype ; Glycemic Index ; Humans ; Male ; Middle Aged ; Nutrigenomics/*methods ; Nutritional Requirements ; Obesity/*diet therapy/*genetics ; Patient Compliance ; Time Factors ; Treatment Outcome ; *Weight Loss ; }, abstract = {BACKGROUND: Gene-environment studies demonstrate variability in nutrient requirements depending upon individual variations in genes affecting nutrient metabolism and transport. This study investigated whether the inclusion of genetic information to personalize a patient's diet (nutrigenetics) could improve long term weight management.<br><br>METHODS: Patients with a history of failures at weight loss were offered a nutrigenetic test screening 24 variants in 19 genes involved in metabolism. 50 patients were in the nutrigenetic group and 43 patients attending the same clinic were selected for comparison using algorithms to match the characteristics: age, sex, frequency of clinical visits and BMI at initial clinic visit. The second group of 43 patients did not receive a nutrigenetic test. BMI reduction at 100 and > 300 days and blood fasting glucose were measured.<br><br>RESULTS: After 300 days of follow-up individuals in the nutrigenetic group were more likely to have maintained some weight loss (73%) than those in the comparison group (32%), resulting in an age and gender adjusted OR of 5.74 (95% CI 1.74-22.52). Average BMI reduction in the nutrigenetic group was 1.93 kg/m2(5.6% loss) vs. an average BMI gain of 0.51 kg/m2(2.2% gain) (p < 0.023). Among patients with a starting blood fasting glucose of > 100 mg/dL, 57% (17/30) of the nutrigenetic group but only 25% (4/16) of the non-tested group had levels reduced to < 100 mg/dL after > 90 days of weight management therapy (OR for lowering glucose to < 100 mg/dL due to diet = 1.98 95%CI 1.01, 3.87, p < 0.046).<br><br>CONCLUSION: Addition of nutrigenetically tailored diets resulted in better compliance, longer-term BMI reduction and improvements in blood glucose levels.}, }
@article {pmid17940995, year = {2007}, author = {Ohuchida, K and Mizumoto, K and Miyasaka, Y and Yu, J and Cui, L and Yamaguchi, H and Toma, H and Takahata, S and Sato, N and Nagai, E and Yamaguchi, K and Tsuneyoshi, M and Tanaka, M}, title = {Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis.}, journal = {The Journal of pathology}, volume = {213}, number = {3}, pages = {275-282}, doi = {10.1002/path.2250}, pmid = {17940995}, issn = {0022-3417}, mesh = {Biomarkers, Tumor/analysis ; Carcinoma, Pancreatic Ductal/metabolism/*pathology ; Cell Differentiation ; Cell Line, Tumor ; Chemotactic Factors/analysis/*genetics/metabolism ; Gene Expression ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; Pancreas/chemistry ; Pancreatic Neoplasms/metabolism/*pathology ; Paraffin Embedding ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; S100 Proteins/analysis/*genetics/metabolism ; }, abstract = {Controversy exists regarding the clinical significance of S100A2 in the progression of tumours. In pancreatic cancer, little is known about the role of S100A2. The aim of this study was to clarify the clinical significance of S100A2 expression in pancreatic carcinogenesis. We microdissected invasive ductal carcinoma (IDC) cells from 22 lesions, pancreatic intraepithelial neoplasia (PanIN) cells from five lesions, intraductal papillary mucinous neoplasm (IPMN) cells from 38 lesions, pancreatitis-affected epithelial (PAE) cells from 16 lesions, and normal ductal cells from 18 normal pancreatic tissues. S100A2 expression in 14 pancreatic cancer cell lines, microdissected cells and formalin-fixed paraffin-embedded (FFPE) samples was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Microdissection analyses revealed that IDC cells expressed higher levels of S100A2 than did IPMN, PAE or normal cells (all comparisons, p < 0.007). Cell lines from metastatic sites expressed higher levels of S100A2 than those from primary sites. PanIN cells expressed higher levels of S100A2 than normal cells (p = 0.018). IDC cells associated with poorly differentiated adenocarcinoma expressed higher levels of S100A2 than did IDC cells without poorly differentiated adenocarcinoma (p = 0.006). Analyses of FFPE samples revealed that levels of S100A2 were higher in samples from patients who survived < 1000 days after surgery than in those from patients who survived > 1000 days (p = 0.043). Immunohistochemical analysis was consistent with qRT-PCR. S100A2 may be a marker of tumour progression or prognosis in pancreatic carcinogenesis and pancreatic cancer.}, }
@article {pmid17940391, year = {2007}, author = {Murakami, K and Sakata, H and Miyazawa, Y and Matsushita, K and Akutsu, Y and Nishimori, T and Yoneyama, Y and Usui, A and Kano, M and Matsubara, H and Ochiai, T}, title = {[Two cases treated with trastuzumab as primary chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {34}, number = {10}, pages = {1683-1687}, pmid = {17940391}, issn = {0385-0684}, mesh = {Adult ; Antibodies, Monoclonal/*administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*administration &amp; dosage ; Antineoplastic Agents, Phytogenic/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Female ; Humans ; Paclitaxel/administration &amp; dosage ; Trastuzumab ; }, abstract = {We report two cases treated with primary chemotherapy containing trastuzumab with a review of some important papers. The first patient was a 43-year-old female. A 33-mm left breast invasive ductal carcinoma (ER (-), PgR (-), HER2 3+(IHC)) with several lymph node metastases in the Ax, Ic and Sc was found. After primary chemotherapy with 6 courses of EC and 4 courses of weekly paclitaxel + trastuzumab, the efficacy for the local tumor was judged as PR. However, brain metastases appeared, so the operation was canceled. Brain metastases were then treated by gamma-knife three times, but systemic chemotherapy was not administered. Eight months later, carcinomatous meningitis appeared. Intrathecal chemotherapy with MTX+Ara-C was started, but the patient died after 20 months from the beginning of the treatment. Local efficacy was judged as CR. The second patient was a 41-year-old female. A 39-mm right breast invasive ductal carcinoma (ER (-), PgR (-), HER2 3+(IHC)) with two lymph node metastases in the Ax was found. After primary chemotherapy with 6 courses of FEC and 4 courses of weekly paclitaxel + trastuzumab, the efficacy was judged as PR. The operation was scheduled, but he patient wished to continue chemotherapy for cosmetic reasons. Later, because of mild tumor regrowth, we used 2 courses of vinorelbine in combination with trastuzumab. The tumor grew more, so Bp + Ax was done. The woman is alive at this writing with no recurrence.}, }
@article {pmid17936526, year = {2007}, author = {Cluzel-Tailhardat, M and Bonnet-Duquennoy, M and de Queral, DP and Vocanson, M and Kurfürst, R and Courtellemont, P and Le Varlet, B and Nicolas, JF}, title = {Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells.}, journal = {Toxicology letters}, volume = {174}, number = {1-3}, pages = {98-109}, doi = {10.1016/j.toxlet.2007.08.015}, pmid = {17936526}, issn = {0378-4274}, mesh = {Allergens/*toxicity ; Cells, Cultured ; Dendritic Cells/*drug effects/immunology ; Dinitrofluorobenzene/analogs &amp; derivatives/toxicity ; Eugenol/analogs &amp; derivatives/toxicity ; Gene Expression Profiling ; Haptens/*toxicity ; Humans ; Oligonucleotide Array Sequence Analysis ; Sodium Dodecyl Sulfate/toxicity ; Terpenes/toxicity ; }, abstract = {A critical step in the induction of allergic contact dermatitis is the interaction of haptens with immature dendritic cells (iDC) leading to their activation. Therefore iDC appear as suitable targets for the evaluation of the sensitizing properties of haptens with the aim of developing in vitro toxicologic methods. Here, using a low-density cDNA-array, we analyzed the expression of 165 genes related to dendritic cell biology in human iDC following a 24h incubation with four haptens representative of strong (DNBS), moderate (isoeugenol) and weak (eugenol, hydroxycitronellal) contact sensitizers and with one irritant sodium dodecyl sulphate (SDS). Results show that 21/165 iDC genes were significantly modulated by hapten treatment. Some genes were preferentially modulated by a given chemical. Thus, DNBS, isoeugenol, eugenol and hydroxycitronellal consistently modulated CCR5, CCL27, CCL2 and CCR7, respectively, whereas the CXCL10 gene was regulated by SDS. When subjected to principal component analysis, the 21 target genes fell into four groups associated with a particular type of chemical endowed with distinct sensitizing or irritant properties. Thus, gene profiling of iDC using low-density microarray allows, for screening of chemicals, the indentification of weak haptens with potential skin sensitizing properties. These results suggest that gene profiling of iDC using low-density microarrays may be useful to identify chemicals with weak skin sensitizing properties.}, }
@article {pmid17933706, year = {2007}, author = {Bölke, E and Peiper, M and Budach, W and Matuschek, C and Schwarz, A and Orth, K and Gripp, S}, title = {Unilateral keloid formation after bilateral breast surgery and unilateral radiation.}, journal = {European journal of medical research}, volume = {12}, number = {7}, pages = {320-322}, pmid = {17933706}, issn = {0949-2321}, mesh = {Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Female ; Humans ; Keloid/*etiology/radiotherapy/surgery ; Mastectomy, Segmental/*adverse effects ; Middle Aged ; *Postoperative Complications ; Radiotherapy, Adjuvant ; }, abstract = {BACKGROUND: Keloid is a hypertrophic scar that may arise within 6 months after injury in susceptible individuals. Different therapies like surgical excision, intralesional steroid injections, local application of pressure, or postoperative irradiation with x-rays or electrons are reported. Although an immediate starting of therapy after surgery is usually recommended, delayed radiotherapy may also be effective.<br><br>CASE REPORT: We report on a 48 year old women with a history of an invasive ductal carcinoma in the upper lateral quadrant of the left breast. A breast conserving tumor resection with axillary dissection was performed. An adapting reduction mammaplasty was carried out on the right breast for cosmetic reasons at the same time. 5 weeks after surgery, adjuvant radiotherapy was applied with a total dose of 59 Gy to the left breast. 10 weeks after surgery and by the end of radiotherapy, a keloid had developed on the right breast with reduction mammaplasty, but not on the left irradiated one. 8 months after initial surgery the patient's keloid formation on the right mamma was removed by surgical resection and a keloid prevention with postoperative radiotherapy with 20 Gy was performed.<br><br>CONCLUSION: Postoperative radiation of the scar prevented effectively keloid formation while simultaneously a hypertrophic scar developed in the non-irradiated scar.}, }
@article {pmid17914245, year = {2007}, author = {Alexe, G and Dalgin, GS and Ganesan, S and Delisi, C and Bhanot, G}, title = {Analysis of breast cancer progression using principal component analysis and clustering.}, journal = {Journal of biosciences}, volume = {32}, number = {5}, pages = {1027-1039}, pmid = {17914245}, issn = {0250-5991}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*metabolism/pathology ; Cluster Analysis ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Neoplasm Invasiveness/genetics ; Oligonucleotide Array Sequence Analysis ; Predictive Value of Tests ; *Principal Component Analysis ; Signal Transduction/genetics ; }, abstract = {We develop a new technique to analyse microarray data which uses a combination of principal components analysis and consensus ensemble k-clustering to find robust clusters and gene markers in the data. We apply our method to a public microarray breast cancer dataset which has expression levels of genes in normal samples as well as in three pathological stages of disease; namely, atypical ductal hyperplasia or ADH, ductal carcinoma in situ or DCIS and invasive ductal carcinoma or IDC. Our method averages over clustering techniques and data perturbation to find stable, robust clusters and gene markers. We identify the clusters and their pathways with distinct subtypes of breast cancer (Luminal,Basal and Her2+). We confirm that the cancer phenotype develops early (in early hyperplasia or ADH stage) and find from our analysis that each subtype progresses from ADH to DCIS to IDC along its own specific pathway, as if each was a distinct disease.}, }
@article {pmid17914088, year = {2007}, author = {Biglia, N and Mariani, L and Sgro, L and Mininanni, P and Moggio, G and Sismondi, P}, title = {Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications for diagnosis, surgical and medical treatment.}, journal = {Endocrine-related cancer}, volume = {14}, number = {3}, pages = {549-567}, doi = {10.1677/ERC-06-0060}, pmid = {17914088}, issn = {1351-0088}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Fine-Needle ; Breast Neoplasms/*chemically induced/diagnosis/*epidemiology/therapy ; Carcinoma, Lobular/*chemically induced/diagnosis/*epidemiology/therapy ; Combined Modality Therapy ; Estrogen Replacement Therapy/*adverse effects ; Feasibility Studies ; Female ; Humans ; Incidence ; Intraoperative Period ; Magnetic Resonance Imaging ; Mammography ; Mastectomy, Segmental ; Mastectomy, Simple ; Neoplasm Invasiveness/diagnosis ; Prognosis ; Risk Assessment ; Sentinel Lymph Node Biopsy ; Ultrasonography, Mammary ; }, abstract = {A growing body of evidence support the association between the use of hormone replacement therapy (HRT) and a higher risk of both invasive lobular carcinoma (ILC) and invasive ductal-lobular mixed carcinoma (IDLC). Overall biological and clinical features of ILC entail a more cautious diagnostic and therapeutic approach as compared with invasive ductal carcinoma (IDC). ILCs are more frequently multifocal, multicentric and/or bilateral. Mammography and ultrasound show, therefore, significant limitations, while the higher sensitivity of magnetic resonance imaging in the detection of multifocal and/or multicentric lesions seems to improve the accuracy of preoperative staging of ILCs. Early diagnosis is even more challenging because the difficult in the localization and the sparse cellularity of lobular tumours may determine a false negative core biopsy. ILC is characterized by low proliferative activity, C-ErbB-2 negativity, bcl-2 positivity, p53 and VEGF negativity, oestrogen and progesterone positive receptors, low grade and low likelihood of lymphatic-vascular invasion. However, this more favourable biological behaviour does not reflect into a better disease-free and overall survival as compared with IDC. Since lobular histology is associated with a higher risk of positive margins, mastectomy is often preferred to breast conservative surgery. Moreover, only few patients with ILC achieve a pathologic response to preoperative chemotherapy and, therefore, in most patients mastectomy can be regarded as the safer surgical treatment. The preoperative staging and the follow-up of patients with ILC are also complicated by the particular metastatic pattern of such histotype. In fact, metastases are more frequently distributed to the gastrointestinal tract, peritoneum/retroperitoneum and gynaecological organs than in IDC.}, }
@article {pmid17899367, year = {2008}, author = {Putignani, L and Raffa, S and Pescosolido, R and Aimati, L and Signore, F and Torrisi, MR and Grammatico, P}, title = {Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria.}, journal = {Breast cancer research and treatment}, volume = {110}, number = {3}, pages = {439-452}, doi = {10.1007/s10549-007-9738-x}, pmid = {17899367}, issn = {0167-6806}, mesh = {Blotting, Western ; Breast Neoplasms/*enzymology ; Female ; Fluorescent Antibody Technique ; Humans ; Microscopy, Electron, Transmission ; Microscopy, Immunoelectron ; Mitochondria/*enzymology/ultrastructure ; Multienzyme Complexes/*biosynthesis ; *Oxidative Phosphorylation ; Tumor Cells, Cultured ; }, abstract = {Mitochondria are dynamic intracellular organelles playing a central role in cell metabolism by generating ATP, through the oxidative phosphorylation system (OXPHOS). Altered mitochondrial functions have been identified as causative or contributing factors in some degenerative diseases and are becoming crucial to understanding cancer mechanisms. We report on distinct expression differences between mitochondria of normal and breast-infiltrating ductal carcinoma (IDC) cells. Mitochondria isolated from HMC (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures were assayed for expression levels of the multi-protein OXPHOS complexes using Western blot and densitometric analyses. Depressed expression levels were detected for all HMC OXPHOS complexes. Drastic signal reduction was observed for the succinate-dehydrogenase complex II iron-sulphur protein SDH-B (3.38%), while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I Fe-S protein 3 NDUFS3 (32.78%) and the ubiquinol-cytochrome c reductase complex III protein 2 UQCRC2 (50.34%). A significant signal dropping was detected for the ATP-synthase complex V F(1)beta subunit (18.07%). For the cytochrome-oxidase complex IV (CO), near-depletion of the mitochondrial-encoded COI (4.37%) and no apparent variation of the COIV (97.26%) subunits were observed. CO and ATP-synthase were also assayed by cryo-immunoelectron microscopy (CIEM) on unfractionated HMC and HEMC cell mitochondria. COI and F(1)beta differential expression, invariance of COIV levels were corroborated, while HMC mitochondria morphology deterioration was highlighted. MitoTracker Red and fluorescence immunolabelling merging confirmed CIEM data. MitoTracker Red and Green co-staining showed mitochondria membrane property modulation. These data describe bioenergetic and phenotypic alterations of IDC cell mitochondria, possibly providing new cancer hallmarks.}, }
@article {pmid17898060, year = {2007}, author = {Herschke, F and Plumet, S and Duhen, T and Azocar, O and Druelle, J and Laine, D and Wild, TF and Rabourdin-Combe, C and Gerlier, D and Valentin, H}, title = {Cell-cell fusion induced by measles virus amplifies the type I interferon response.}, journal = {Journal of virology}, volume = {81}, number = {23}, pages = {12859-12871}, pmid = {17898060}, issn = {1098-5514}, mesh = {Animals ; Cell Fusion ; Cell Line ; Cell Nucleus/chemistry ; Chlorocebus aethiops ; Dendritic Cells/immunology/*virology ; Epithelial Cells/immunology/*virology ; Giant Cells/cytology/immunology/*virology ; Humans ; Interferon Regulatory Factor-3/analysis ; Interferon Regulatory Factor-7/analysis ; Interferon Type I/*biosynthesis ; Measles virus/genetics/*immunology/*physiology ; Microscopy, Video ; Viral Fusion Proteins/immunology/physiology ; Viral Proteins/immunology/physiology ; }, abstract = {Measles virus (MeV) infection is characterized by the formation of multinuclear giant cells (MGC). We report that beta interferon (IFN-beta) production is amplified in vitro by the formation of virus-induced MGC derived from human epithelial cells or mature conventional dendritic cells. Both fusion and IFN-beta response amplification were inhibited in a dose-dependent way by a fusion-inhibitory peptide after MeV infection of epithelial cells. This effect was observed at both low and high multiplicities of infection. While in the absence of virus replication, the cell-cell fusion mediated by MeV H/F glycoproteins did not activate any IFN-alpha/beta production, an amplified IFN-beta response was observed when H/F-induced MGC were infected with a nonfusogenic recombinant chimerical virus. Time lapse microscopy studies revealed that MeV-infected MGC from epithelial cells have a highly dynamic behavior and an unexpected long life span. Following cell-cell fusion, both of the RIG-I and IFN-beta gene deficiencies were trans complemented to induce IFN-beta production. Production of IFN-beta and IFN-alpha was also observed in MeV-infected immature dendritic cells (iDC) and mature dendritic cells (mDC). In contrast to iDC, MeV infection of mDC induced MGC, which produced enhanced amounts of IFN-alpha/beta. The amplification of IFN-beta production was associated with a sustained nuclear localization of IFN regulatory factor 3 (IRF-3) in MeV-induced MGC derived from both epithelial cells and mDC, while the IRF-7 up-regulation was poorly sensitive to the fusion process. Therefore, MeV-induced cell-cell fusion amplifies IFN-alpha/beta production in infected cells, and this indicates that MGC contribute to the antiviral immune response.}, }
@article {pmid17885501, year = {2007}, author = {Kazakov, DV and Nemcova, J and Mikyskova, I and Belousova, IE and Vazmitel, M and Michal, M}, title = {Human papillomavirus in lesions of anogenital mammary-like glands.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {26}, number = {4}, pages = {475-480}, doi = {10.1097/pgp.0b013e31803104af}, pmid = {17885501}, issn = {0277-1691}, mesh = {Adult ; Aged ; Anus Neoplasms/*virology ; Exocrine Glands/*pathology ; Female ; Genital Neoplasms, Female/*virology ; Humans ; Male ; Middle Aged ; Papillomaviridae/isolation &amp; purification ; Papillomavirus Infections/*epidemiology ; Polymerase Chain Reaction ; Tumor Virus Infections/*epidemiology ; }, abstract = {Long considered as ectopic breast tissue, anogenital mammary-like glands (MLGs) have recently been suggested to represent distinctive structures located in the anogenital area. We studied 16 neoplasms of anogenital MLG for human papillomavirus (HPV) DNA using INNO-line probe assay (LiPA) HPV Genotyping kit, GP5+/6+, CP(SGB), and FAP 6085-6319 primer sets. The lesions included 3 fibroadenomas, 2 adenosis tumors, 1 invasive ductal carcinoma, 1 tubulolobular carcinoma, 2 hidradenoma papilliferum with prominent cystic change rendering a cystadenoma appearance and oxyphilic metaplasia, and 7 cases of extramammary Paget disease. All 3 fibroadenomas, both adenosis tumors, both hidradenoma papilliferum, and the tubulolobular carcinoma proved negative for HPV DNA. HPV-31 was detected by LiPA in the case of invasive ductal carcinoma. In 2 of the 7 patients with extramammary Paget disease, there was HPV DNA present in the lesional tissue, typed as HPV-6 (LiPA) and a type which was closely related to HPV-21 and HPV-24 (FAP 6085-6319), whereas the remaining 5 cases tested negative. These results coupled with those obtained from literature review suggest that HPV plays no causative role in lesions of anogenital MLG.}, }
@article {pmid17867594, year = {2006}, author = {Hungermann, D and Korsching, E and Bürger, H and Röser, K and Löning, T and Herbst, H}, title = {[Salivary duct carcinomas comprise phenotypically and genotypically diverse high grade neoplasms].}, journal = {Verhandlungen der Deutschen Gesellschaft fur Pathologie}, volume = {90}, number = {}, pages = {168-176}, pmid = {17867594}, issn = {0070-4113}, mesh = {Genotype ; Humans ; Keratins/analysis ; Phenotype ; Salivary Ducts/*pathology ; Salivary Gland Neoplasms/*genetics/*pathology ; }, abstract = {Salivary duct carcinomas (SDC) are high grade neoplasms morphologically reminiscent of breast ductal carcinomas. Whereas the latter are well characterized, the body of immunophenotypic and cytogenetic data on SDC is limited. We studied 23 SDC by conventional histology, immunohistology, in situ hybridization, and comparative genomic hybridization (CGH). Data were subjected to biomathematical analysis in comparison to previously characterized breast ductal carcinomas in situ and invasive ductal carcinoma cases. Most SDC stained for cytokeratins (Ck) Ck 8/18 (77 %) or Ck 5/6 (30 %), 30 % of cases expressed the androgen receptor (AR), 14 cases (63 %) expressed c-erbB2, and one case stained for prostate specific antigen. Except for two cases, Ck 8/18 and Ck 5/6 were not coexpressed. Ck 8/18 expression positively correlated with presence of c-erbB2 and AR. At variance, Ck 5/6 correlated positively with p63 and inversely with both AR and c-erbB2 expression. Ck 5/6 and p 63 co-expression was also found in a distinct population of ductal epithelial cells of normal salivary glands. CGH analysis of SDC revealed increasing numbers of alterations in correlation with advanced diseases, but no recurrent alterations. Cluster analysis of phenotypic and genotypic markers assigned both salivary and breast carcinomas to numerous clusters independent of the primary tumour site. Although undistinguishable by conventional histology, SDC are heterogeneous, comprising at least two immunophenotypically distinct subgroups of neoplasms. Cluster analysis suggests several distinct patterns of gene expression common to both primary sites explaining morphologic parallels between SDC and high grade breast cancer.}, }
@article {pmid17854427, year = {2007}, author = {Lin, A and Yan, WH and Xu, HH and Tang, LJ and Chen, XF and Zhu, M and Zhou, MY}, title = {14 bp deletion polymorphism in the HLA-G gene is a risk factor for idiopathic dilated cardiomyopathy in a Chinese Han population.}, journal = {Tissue antigens}, volume = {70}, number = {5}, pages = {427-431}, doi = {10.1111/j.1399-0039.2007.00926.x}, pmid = {17854427}, issn = {0001-2815}, mesh = {Adult ; Aged ; Asian People ; Autoimmune Diseases/*genetics ; Base Sequence ; Cardiomyopathy, Dilated/*genetics ; China ; Female ; *Genetic Predisposition to Disease ; HLA Antigens/*genetics ; HLA-G Antigens ; Histocompatibility Antigens Class I/*genetics ; Humans ; *INDEL Mutation ; Male ; Middle Aged ; Mutagenesis, Insertional ; *Polymorphism, Genetic ; Risk Factors ; Sequence Deletion ; }, abstract = {Human leukocyte antigen (HLA) has been reported to be associated with the pathogenesis of autoimmune-associated idiopathic dilated cardiomyopathy (IDC). However, the HLA-G in this context is limited. In the current study, a total of 117 IDC patients and age and sex matched 401 unrelated healthy controls in a Chinese Han population were HLA-G genotyped for the 14 bp insertion and deletion polymorphism. IDC patients showed markedly increased frequencies of -14 bp/-14 bp genotype [Pc = 0.00049, odds ratio (OR) = 2.17] and -14 bp alleles (Pc = 4.1 x 10(-5), OR = 1.97) when compared with healthy controls. Whereas the frequencies of +14 bp/+14 bp genotype (Pc = 0.0036, OR = 0.35) and +14 bp alleles (Pc = 4.1 x 10(-5), OR = 0.51) were significantly lower in IDC. These data, for the first time, indicated that 14 bp insertion/deletion polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to IDC.}, }
@article {pmid17851087, year = {2007}, author = {Streitner, F and Kuschyk, J and Veltmann, C and Brueckmann, M and Streitner, I and Brade, J and Neumaier, M and Bertsch, T and Schumacher, B and Borggrefe, M and Wolpert, C}, title = {Prospective study of interleukin-6 and the risk of malignant ventricular tachyarrhythmia in ICD-recipients--a pilot study.}, journal = {Cytokine}, volume = {40}, number = {1}, pages = {30-34}, doi = {10.1016/j.cyto.2007.07.187}, pmid = {17851087}, issn = {1096-0023}, mesh = {Aged ; Cardiomyopathy, Dilated/blood/complications/*therapy ; Cohort Studies ; Coronary Artery Disease/blood/complications/*therapy ; *Defibrillators, Implantable ; Female ; Follow-Up Studies ; Humans ; Interleukin-6/biosynthesis/*blood ; Male ; Pilot Projects ; Prospective Studies ; Risk Assessment ; Tachycardia, Ventricular/blood/*etiology ; Ventricular Fibrillation/blood/*etiology ; }, abstract = {OBJECTIVE: We investigated the relationship between interleukin-6 (IL-6) and the risk of experiencing spontaneous ventricular tachyarrhythmia (VT/VF) in patients with an implantable cardioverter-defibrillator (ICD).<br><br>BACKGROUND: Cytokine levels predict outcome in patients with advanced heart failure and are elevated in patients with coronary artery disease (CAD). Regarding heart rhythm disturbances, proinflammatory activity could predict the occurrence of atrial fibrillation. There is no data on cytokine levels and the risk of spontaneous VT/VF.<br><br>METHODS: IL-6 serum concentrations were determined at baseline and follow-up in 47 consecutive ICD-patients with CAD and idiopathic dilated cardiomyopathy (IDC). Data were prospectively correlated with VT/VF-incidence.<br><br>RESULTS: Thirty-six patients (76.6%) suffered from CAD and 11 (23.4%) from IDC. Mean serum concentrations of IL-6 at baseline and at 9 months follow-up were 6.12+/-4.98 and 4.63+/-6.97. 88 spontaneous VT/VF-events occurred in 13/47 patients (27.7%). Patients with VT/VF had significantly higher IL-6 levels as compared to patients without VT/VF (8.96+/-5.97 vs. 5.04+/-4.16pg/ml at baseline (p =0.03), 7.8+/-4.88 vs. 3.42+/-6.32pg/ml at follow-up (p =0.01)).<br><br>CONCLUSIONS: Elevated IL-6 serum concentrations were prospectively associated with an increased risk of spontaneous VT/VF-events in ICD-patients with CAD or IDC. These preliminary findings support a possible association of proinflammatory activity and an increased susceptibility to spontaneous VT/VF-events.}, }
@article {pmid17848197, year = {2007}, author = {Zagouri, F and Sergentanis, TN and Koulocheri, D and Nonni, A and Bousiotou, A and Domeyer, P and Michalopoulos, NV and Dardamanis, D and Konstadoulakis, MM and Zografos, GC}, title = {Bilateral synchronous breast carcinomas followed by a metastasis to the gallbladder: a case report.}, journal = {World journal of surgical oncology}, volume = {5}, number = {}, pages = {101}, pmid = {17848197}, issn = {1477-7819}, mesh = {Biopsy, Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/pathology/*secondary/therapy ; Carcinoma, Lobular/pathology/*secondary/therapy ; Chemotherapy, Adjuvant ; Cholecystectomy/methods ; Female ; Follow-Up Studies ; Gallbladder Neoplasms/pathology/*secondary/surgery ; Humans ; Immunohistochemistry ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Staging ; Neoplasms, Multiple Primary/*pathology/therapy ; Radiotherapy, Adjuvant ; Risk Assessment ; Treatment Outcome ; }, abstract = {BACKGROUND: Breast cancer is usually associated with metastases to lungs, bones and liver. Breast carcinoma metastasizing to the gallbladder is very rare.<br><br>CASE PRESENTATION: A 59-year-old woman presented with bilateral synchronous breast lesions. A palpable, retroareolar solid lesion of diameter equal to 5 cm was present in the right breast, and a newly developed, non-palpable lesion with microcalcifications (diameter equal to 0.7 cm) was present in the upper outer quadrant of the left breast. Modified radical mastectomy was performed on the right breast and lumpectomy after hook-wire localization was performed on the left breast, combined with lymph node dissection in both sides. The pathological examination revealed invasive lobular carcinoma grade II in the right breast and invasive ductal carcinoma grade I in the left breast. Chemotherapy, radiation therapy, trastuzumab and letrozole were appropriately administered. At her 18-month follow-up, the patient was free of symptoms; the imaging tests (chest CT, abdominal U/S, bone scan), biochemical tests, blood cell count and tumor markers were also normal. At the 20th month after surgery however, the patient developed symptoms of cholecystitis and underwent cholecystectomy. The histopathological examination revealed metastasis of the lobular carcinoma to the gallbladder.<br><br>CONCLUSION: This extremely rare case confirms on a single patient the results of large series having demonstrated the preferential metastasis of lobular breast cancer to the gallbladder. Symptoms of cholecystitis should not be neglected in such patients, as they might indicate metastasis to the gallbladder.}, }
@article {pmid17826642, year = {2007}, author = {Sarzani, R and Forleo, C and Pietrucci, F and Capestro, A and Soura, E and Guida, P and Sorrentino, S and Iacoviello, M and Romito, R and Dessì-Fulgheri, P and Pitzalis, M and Rappelli, A}, title = {The 212A variant of the APJ receptor gene for the endogenous inotrope apelin is associated with slower heart failure progression in idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {13}, number = {7}, pages = {521-529}, doi = {10.1016/j.cardfail.2007.04.002}, pmid = {17826642}, issn = {1532-8414}, mesh = {Adenine ; Adult ; Alleles ; Apelin ; Apelin Receptors ; Cardiomyopathy, Dilated/genetics/*physiopathology ; Cytosine ; DNA Mutational Analysis ; Disease Progression ; Female ; Follow-Up Studies ; Gene Dosage ; *Genetic Variation ; Genotype ; Guanine ; Haplotypes ; Homozygote ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Linkage Disequilibrium ; Male ; Middle Aged ; Myocardial Contraction ; Polymorphism, Genetic ; Prognosis ; Prospective Studies ; Receptors, G-Protein-Coupled/*genetics ; }, abstract = {BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) has multiple genetic and acquired causes. Apelin is an endogenous peptide that increases cardiac inotropism through his APJ receptor. No data are available concerning the APJ gene mutations responsible for IDC or on the role of APJ receptor gene variants in predicting heart failure (HF) progression.<br><br>METHODS AND RESULTS: We prospectively evaluated 202 consecutive patients with IDC and 202 matched controls: 90 were screened for APJ gene mutations and all 202 were genotyped for G212A and A445C APJ receptor polymorphisms. No mutations were found within the coding or untranslated regions of the APJ receptor, and no differences in allelic or genotype frequencies were observed comparing patients with a healthy control population. The correlations between APJ receptor polymorphisms and HF progression were assessed. During a median follow-up of 37 months, 35 patients experienced HF progression. Univariate analysis showed that patients carrying at least 1 copy of 212A had a significantly lower risk for HF-related events than those who were homozygous for the G212 variant, and multivariate analysis confirmed that it was significantly related to a more favorable prognosis.<br><br>CONCLUSIONS: APJ is unlikely to be a gene causing IDC, but the independent correlation between the 212A allele and a better prognosis suggests that it might act as a modifier gene.}, }
@article {pmid17823891, year = {2007}, author = {Laudanski, K and De, A and Miller-Graziano, C}, title = {Exogenous heat shock protein 27 uniquely blocks differentiation of monocytes to dendritic cells.}, journal = {European journal of immunology}, volume = {37}, number = {10}, pages = {2812-2824}, doi = {10.1002/eji.200636993}, pmid = {17823891}, issn = {0014-2980}, support = {GM36214/GM/NIGMS NIH HHS/United States ; GM65237/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/immunology/*physiology ; Cells, Cultured ; Dendritic Cells/*cytology/immunology ; Growth Inhibitors/*pharmacology ; HSP27 Heat-Shock Proteins ; Heat-Shock Proteins/*pharmacology ; Humans ; Macrophages/cytology/immunology ; Molecular Chaperones ; Monocytes/*cytology/immunology ; Neoplasm Proteins/*pharmacology ; Rabbits ; Receptors, Immunologic/antagonists &amp; inhibitors/biosynthesis ; Signal Transduction/immunology ; }, abstract = {Circulating heat shock protein (HSP)-27 is associated with tumor progression and increased post-injury infection. Extracellular HSP-27 might alter monocyte (MO)-derived DC and/or MPhi function to mediate immunosuppression. HSP-27 treatment inhibited expression of CD1a and CD1b/c, antigen uptake, and allogeneic T cell induction (MLR) by IL-4 + GM-CSF-differentiated human DC while increasing some MPhi characteristics (upward arrowCD14, upward arrowCD16, upward arrowCD163). MO cytokine receptor profiles elicited by 24-h exogenous HSP-27 treatment remained supportive of immature DC (iDC) emergence (upward arrowIL-4R, downward arrowIL-6R, downward arrowM-CSFR). IL-10, IL-6, and M-CSF (which promote MPhi differentiation) were significantly increased in IL-4 + GM-CSF + HSP-27 MO-->iDC differentiation cultures. However, HSP-27 treatment during MO differentiation to DC increased programmed cell death ligand 1 coinhibitor and depressed CD86 costimulator expression in parallel to decreased iDC MLR activity. This suggested that increased MPhi differentiation was not solely responsible for HSP-27 reduction of differentiating DC activity. HSP-27 treatment actually depressed the phagocytic capacity of MO differentiated to MPhi by IL-10 or M-CSF culture. CD163 (hemoglobin receptor) expression was depressed on M-CSF + HSP-27 MO-derived MPhi. HSP-27-mediated inhibition of MO-->iDC differentiation was reversed by p38alpha &amp; beta inhibitor (SB202190) addition or TLR4 receptor modulation. HSP-27 impaired appropriate MO-->iDC and MO-->MPhi differentiation modulating expression of receptors necessary for their proper functions. This suggests that endogenous HSP-27 has immunoregulatory activities which could contribute to immunopathology.}, }
@article {pmid17822781, year = {2007}, author = {Cirone, M and Lucania, G and Bergamo, P and Trivedi, P and Frati, L and Faggioni, A}, title = {Human herpesvirus 8 (HHV-8) inhibits monocyte differentiation into dendritic cells and impairs their immunostimulatory activity.}, journal = {Immunology letters}, volume = {113}, number = {1}, pages = {40-46}, doi = {10.1016/j.imlet.2007.07.013}, pmid = {17822781}, issn = {0165-2478}, mesh = {Cell Differentiation/*immunology ; Cells, Cultured ; Dendritic Cells/cytology/*immunology/*virology ; Herpesvirus 8, Human/*immunology ; Humans ; *Immunosuppression Therapy ; Lymphocyte Activation/*immunology ; Monocytes/cytology/*immunology/*virology ; Stem Cells/cytology/immunology/virology ; Virus Activation/immunology ; }, abstract = {Several viruses interfere with the host immune response by infecting dendritic cells and by altering their functional activity. Here, we report that exposure to Human herpesvirus 8 (HHV-8) of human dendritic cell (DC) monocyte precursors resulted in impaired immature DC (iDC) formation as indicated by a reduced CD1a expression. In accordance, the immunostimulatory ability of such iDC was significantly reduced, as indicated by mixed lymphocyte culture (MLR) assays. The immunostimulatory functions of DCs were similarly inhibited by the UV inactivated viral stocks, suggesting that the virus binding is sufficient to determine the observed effect. Furthermore, HHV8 mediated inhibition of the DC allostimulatory function was present in lipopolysaccharide (LPS) matured DCs. A strong reduction of the expression of the costimulatory molecule CD80 on the surface of the virus-exposed cells was observed as well. Impairment of dendritic cell development and function might represent an important strategy used by HHV-8 to escape from the host defense mechanisms.}, }
@article {pmid17711977, year = {2007}, author = {Cools, N and Ponsaerts, P and Van Tendeloo, VF and Berneman, ZN}, title = {Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells.}, journal = {Journal of leukocyte biology}, volume = {82}, number = {6}, pages = {1365-1374}, doi = {10.1189/jlb.0307166}, pmid = {17711977}, issn = {0741-5400}, mesh = {Animals ; Cell Differentiation ; Cell- and Tissue-Based Therapy ; Dendritic Cells/cytology/*immunology ; Humans ; Immune Tolerance/*immunology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Dendritic cells (DC), professional antigen-presenting cells of the immune system, exert important functions both in induction of T cell immunity, as well as tolerance. It is well established that the main function of immature DC (iDC) in their in vivo steady-state condition is to maintain peripheral tolerance to self-antigens and that these iDC mature upon encounter of so-called danger signals and subsequently promote T cell immunity. Previously, it was believed that T cell unresponsiveness induced after stimulation with iDC is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. Moreover, several reports indicate that traditional DC maturation can no longer be used to distinguish tolerogenic and immunogenic properties of DC. This review will focus on the complementary role of dendritic cells in inducing both tolerance and immunity, and we will discuss the clinical implications for dendritic cell-based therapies.}, }
@article {pmid17690565, year = {2007}, author = {Connolly, N and Riddler, S and Stanson, J and Gooding, W and Rinaldo, CR and Ferrone, S and Whiteside, TL}, title = {Levels of antigen processing machinery components in dendritic cells generated for vaccination of HIV-1+ subjects.}, journal = {AIDS (London, England)}, volume = {21}, number = {13}, pages = {1683-1692}, doi = {10.1097/QAD.0b013e32825eabbc}, pmid = {17690565}, issn = {0269-9370}, support = {UL1 TR000005/TR/NCATS NIH HHS/United States ; R01 CA 110249/CA/NCI NIH HHS/United States ; P01 AI 55794/AI/NIAID NIH HHS/United States ; R01 CA 67108/CA/NCI NIH HHS/United States ; P01 DE 12321/DE/NIDCR NIH HHS/United States ; R01 CA 113861/CA/NCI NIH HHS/United States ; }, mesh = {AIDS Vaccines/*immunology ; Adult ; Antigen Presentation/*immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation/immunology ; Dendritic Cells/*immunology ; Epitopes, T-Lymphocyte/immunology ; HIV Infections/*immunology ; HIV-1/*immunology ; HLA-A2 Antigen/analysis ; Humans ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Interleukin-12/biosynthesis ; Middle Aged ; Monocytes/immunology ; Vaccination ; }, abstract = {OBJECTIVE: To evaluate expression of the antigen processing machinery (APM) components and HLA molecules by monocyte-derived dendritic cells (DC) generated from chronically HIV-1 infected subjects on antiretroviral therapy (ART) and to assess their ability to ex vivo induce HIV-1 specific T cells.<br><br>METHODS: DC generated in 16 HLA-A2 positive patients were matured in cytokines, pulsed with HIV-1 or other viral peptides and tested in interferon (IFN)-gamma ELISPOT assays. Immature (i)DC, mature (m)DC and viral peptide-pulsed DC were studied by multiparameter quantitative flow cytometry for intracellular APM component expression and for HLA class I and II, beta-2 microglobulin and co-stimulatory molecule surface expression. DC from 13 normal donors served as controls.<br><br>RESULTS: Marked heterogeneity in APM component expression levels in iDC and mDC from HIV-1 positive subjects was observed. Nevertheless, the median levels were comparable to those in iDC and mDC, respectively, from normal donors. Patients' mDC pulsed with the HIV-1, influenza A, cytomegalovirus (CMV) or Epstein-Barr virus peptides induced IFN-gamma production by T cells specific for these peptides in ELISPOT assays. The frequency of T cells responsive to influenza A, cytomegalovirus or Epstein-Barr virus peptides was comparable in the patients and normal donors.<br><br>CONCLUSIONS: The APM component expression profiles of iDC and mDC were more heterogeneous in subjects with chronic HIV-1 infection on ART, than those in normal donors, although not statistically different. Ex vivo, patients' DC pulsed with HIV-1 peptides induced IFN-gamma production from autologous T cells. Thus, DC obtained from HIV-1 infected subjects on ART were phenotypically and functionally competent.}, }
@article {pmid17690509, year = {2007}, author = {Sato, T and Muto, I and Hasegawa, M and Aono, T and Okada, T and Tamura, T and Sakai, T}, title = {A rare case of invasive ductal carcinoma with hyperprolactinemia.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {3}, pages = {302-306}, doi = {10.2325/jbcs.14.302}, pmid = {17690509}, issn = {1340-6868}, mesh = {Adult ; Breast Neoplasms/complications/*diagnosis/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/complications/*diagnosis/diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Hyperprolactinemia/*etiology ; Magnetic Resonance Imaging ; Mammography ; Nipples/*pathology ; Ultrasonography ; }, abstract = {We report here a rare form of invasive ductal carcinoma composed of a mass protruding from the tip of the nipple in a 43-year-old woman with hyperprolactinemia. She had been amenorrheic for 15 years following an incomplete pituitary adenomectomy for prolactinoma. She presented with a mass on the left nipple that had been growing for 6 months. Morphologically, the mass resembled adenoma of the nipple. Another mass was located in the subareolar region. She underwent mastectomy after invasive ductal carcinoma was diagnosed. Histopathologically, the tumor of the nipple was invasive ductal carcinoma, which had extended intraductally from another invasive ductal carcinoma in the subareolar region, and had infiltrated the epidermis of the nipple (Paget's disease). MR mammography successfully detected the relationship between the tumors. Postoperatively, the plasma prolactin level was abnormally high, while the plasma estradiol level was quite low, although macro-pituitary adenoma was not detected by MRI. The patient was treated with bromocriptine mesilate, in addition to adjuvant chemotherapy for breast cancer, and the plasma prolactin level has since normalized.}, }
@article {pmid17690508, year = {2007}, author = {Morohashi, S and Odagiri, H and Morohashi, H and Kimura, Y and Sasaki, M}, title = {Complete remission of recurrent breast cancer with multiple liver metastases after oral capecitabine and injected trastuzumab.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {3}, pages = {297-301}, doi = {10.2325/jbcs.14.297}, pmid = {17690508}, issn = {1340-6868}, mesh = {Administration, Oral ; Adult ; Antibodies, Monoclonal/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/diagnostic imaging/*drug therapy/pathology ; Capecitabine ; Carcinoma, Ductal, Breast/diagnostic imaging/*drug therapy/secondary ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Female ; Fluorouracil/administration &amp; dosage/analogs &amp; derivatives ; Humans ; Injections, Intravenous ; Liver Neoplasms/diagnostic imaging/*drug therapy/secondary ; Neoplasm Recurrence, Local/diagnostic imaging/*drug therapy/pathology ; Radiography ; Trastuzumab ; }, abstract = {A 32-year-old woman underwent modified radical mastectomy for right breast cancer (invasive ductal carcinoma, f, INF beta, v0, ly1, pT2, pN1, M0, Stage II B ER (+/-), PR (-), Her2 (3+)) in June 2003, and received postoperative systemic adjunctive chemotherapy using epirubicin combined with cyclophosphamide, followed by paclitaxel. In August 2004, after a disease-free interval of 14 months, liver metastasis appeared, and therefore from September 2004, combination chemotherapy with oral capecitabine (2,400 mg/day) and injected trastuzumab (120 mg/week) was started. After 3 cycles, all the metastases responded and this marked response has been maintained for 16 months. This therapy is currently being continued (19 cycles), and no serious side effects have been encountered. Capesitabine and trastuzumab combination therapy is effective for recurrent breast cancer showing overexpression of HER2 and resistance to taxane, and can be considered as a first-line therapy for this purpose. It is anticipated that many cases treated with this regimen will be reported and discussed in the near future.}, }
@article {pmid17685448, year = {2008}, author = {Postovit, LM and Abbott, DE and Payne, SL and Wheaton, WW and Margaryan, NV and Sullivan, R and Jansen, MK and Csiszar, K and Hendrix, MJ and Kirschmann, DA}, title = {Hypoxia/reoxygenation: a dynamic regulator of lysyl oxidase-facilitated breast cancer migration.}, journal = {Journal of cellular biochemistry}, volume = {103}, number = {5}, pages = {1369-1378}, doi = {10.1002/jcb.21517}, pmid = {17685448}, issn = {1097-4644}, support = {5 P50 CA089018/CA/NCI NIH HHS/United States ; AR047713/AR/NIAMS NIH HHS/United States ; RR003061/RR/NCRR NIH HHS/United States ; }, mesh = {Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; Cell Hypoxia ; Cell Line, Tumor ; *Cell Movement ; Female ; *Gene Expression Regulation, Enzymologic ; *Gene Expression Regulation, Neoplastic ; Humans ; Hydrogen Peroxide/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Protein-Lysine 6-Oxidase/*biosynthesis/genetics ; }, abstract = {Fluctuating oxygen levels characterize the microenvironment of many cancers and tumor hypoxia is associated with increased invasion and metastatic potential concomitant with a poor prognosis. Similarly, the expression of lysyl oxidase (LOX) in breast cancer facilitates tumor cell migration and is associated with estrogen receptor negative status and reduced patient survival. Here we demonstrate that hypoxia/reoxygenation drives poorly invasive breast cancer cells toward a more aggressive phenotype by up-regulating LOX expression and catalytic activity. Specifically, hypoxia markedly increased LOX protein expression; however, catalytic activity (beta-aminopropionitrile inhibitable hydrogen peroxide production) was significantly reduced under hypoxic conditions. Moreover, poorly invasive breast cancer cells displayed a marked increase in LOX-dependent FAK/Src activation and cell migration following hypoxia/reoxygenation, but not in response to hypoxia alone. Furthermore, LOX expression is only partially dependent on hypoxia inducible factor-1 (HIF-1alpha) in poorly invasive breast cancer cells, as hypoxia mimetics and overexpression of HIF-1alpha could not up-regulate LOX expression to the levels observed under hypoxia. Clinically, LOX expression positively correlates with tumor progression and co-localization with hypoxic regions (defined by HIF-1alpha expression) in ductal carcinoma in situ and invasive ductal carcinoma primary tumors. However, positive correlation is lost in metastatic tumors, suggesting that LOX expression is independent of a hypoxic environment at later stages of tumor progression. This work demonstrates that both hypoxia and reoxygenation are necessary for LOX catalytic activity which facilitates breast cancer cell migration through a hydrogen peroxide-mediated mechanism; thereby illuminating a potentially novel mechanism by which poorly invasive cancer cells can obtain metastatic competency.}, }
@article {pmid17676086, year = {2007}, author = {McFadden, AM and Wang, J and Mackereth, GF and Clough, RR and Loth, LH and Vermunt, JJ and King, CM and Alley, MR}, title = {Non-systemic erosive stomatitis of unknown aetiology in a dairy cow herd in New Zealand.}, journal = {New Zealand veterinary journal}, volume = {55}, number = {4}, pages = {198-202}, doi = {10.1080/00480169.2007.36768}, pmid = {17676086}, issn = {0048-0169}, mesh = {Animals ; Bacterial Infections/diagnosis/pathology/veterinary ; Cattle ; Cattle Diseases/*etiology/*pathology ; Diagnosis, Differential ; Female ; Immunohistochemistry/veterinary ; New Zealand ; Polymerase Chain Reaction/methods/veterinary ; Stomatitis/etiology/pathology/*veterinary ; Virus Diseases/diagnosis/pathology/veterinary ; }, abstract = {CASE HISTORY: Veterinarians from the Investigation and Diagnostic Centre (IDC), Wallaceville, New Zealand, investigated a novel vesicular disease in a 397-cow dairy herd, characterised by erosive stomatitis.<br><br>The investigation commenced with a report of erosive stomatitis in four dairy cows. The herd was examined that day and 30/397 (8%) adult cows were found to be affected. Two weeks later, the oral cavity of 180 cows from one management group were re-examined, and it was estimated that 80% of this group had healing erosive lesions. During the course of the investigation, intact vesicles were observed on the muzzle of two affected animals. None of the affected animals was systemically ill and there was no decrease in milk production.<br><br>DIAGNOSIS: No infectious aetiological agent was detected using virus isolation, polymerase chain reaction (PCR), electron microscopy (EM) and serological tests, for any exotic infectious vesicular disease or any endemic cause of vesicular disease.<br><br>CLINICAL RELEVANCE: Lesions of erosive stomatitis occurring in cattle must be differentiated from vesicular disease during exotic disease investigations.}, }
@article {pmid17666645, year = {2007}, author = {Sekar, R and Stone, PR}, title = {Trastuzumab use for metastatic breast cancer in pregnancy.}, journal = {Obstetrics and gynecology}, volume = {110}, number = {2 Pt 2}, pages = {507-510}, doi = {10.1097/01.AOG.0000267133.65430.44}, pmid = {17666645}, issn = {0029-7844}, mesh = {Adult ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Brachial Plexus Neuropathies/drug therapy ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Chemotherapy, Adjuvant ; Docetaxel ; Female ; Humans ; Infant, Newborn ; Lung Neoplasms/drug therapy/secondary ; Neoplasm Staging ; Oligohydramnios/*chemically induced ; Pregnancy ; Pregnancy Complications, Neoplastic/*drug therapy/pathology ; Pregnancy Outcome ; Taxoids/adverse effects/therapeutic use ; Trastuzumab ; }, abstract = {BACKGROUND: Trastuzumab is approved for first-line treatment for breast cancer in combination with docetaxel for stage 2 tumors positive for human epidermal growth factor receptor 2. The effects of trastuzumab on the fetus are mostly unknown.<br><br>CASE: Our case report focuses on a woman who was treated for invasive ductal carcinoma 1 year before pregnancy. She presented at 20 weeks of gestation with metastases and was treated with docetaxel and trastuzumab. She underwent two cycles of chemotherapy, and an ultrasound scan at 30 weeks showed anhydramnios. There was no history of ruptured membranes. Reappearance of amniotic fluid was noted at 33 weeks of gestation, 7 weeks after cessation of treatment.<br><br>CONCLUSION: Treatment with trastuzumab during midgestation may be associated with anhydramnios.}, }
@article {pmid17664621, year = {2007}, author = {Palacios, M and Friedrich, H and Götze, C and Vallverdú, M and de Luna, AB and Caminal, P and Hoyer, D}, title = {Changes of autonomic information flow due to idiopathic dilated cardiomyopathy.}, journal = {Physiological measurement}, volume = {28}, number = {6}, pages = {677-688}, doi = {10.1088/0967-3334/28/6/006}, pmid = {17664621}, issn = {0967-3334}, mesh = {Adult ; Autonomic Nervous System/*physiopathology ; Cardiomyopathy, Dilated/*physiopathology ; Case-Control Studies ; Heart Rate/physiology ; Humans ; Risk Factors ; Statistics, Nonparametric ; }, abstract = {Risk stratification of patients with idiopathic dilated cardiomyopathy (IDC) is an epidemiologically relevant question. But the results based on conventional heart rate variability (HRV) analysis are still unsatisfactory. The adjustments within the cardiovascular system incorporate nonlinear and complex mechanisms of information exchange which may have additional prognostic value. It is an objective of the present work to evaluate the prognostic value of autonomic information flow (AIF) measures in IDC patients compared to conventional HRV measures in a first explorative study. Holter recordings of 32 patients with idiopathic dilated cardiomyopathy (IDC) and 12 normal subjects (NRM) were analyzed. The IDC patients consisted of two groups: 10 high risk (HR) patients, after aborted sudden cardiac death (SCD); 22 low risk (LR) patients, without SCD. Sensitivity, specificity, positive predictive value, negative predictive value and ROC characteristics of a comprehensive set of AIF measures, organized according to the conventional HRV standards, and conventional HRV measures were investigated. The significant risk predictors were evaluated by Spearman's rank correlation. While the only traditional HRV measure discriminating IDC patients from NRM was ln(LF) most of the AIF measures had a discriminatory value. Concerning the prognosis of the IDC patients by conventional HRV we found that SDNN and all frequency band measures (lnHF, lnLF, lnVLF) significantly discriminated HR from LR. Among the AIF measures the time shift related peak decay (PD(dHF)) reflecting the HF band information flow had a prognostic value. PD(dHF) was identified as a promising candidate which might improve the predictive value of traditional HRV analysis, predominantly represented by SDNN. A subsequent comprehensive clinical study is necessary to validate this hypothesis.}, }
@article {pmid17659933, year = {2007}, author = {Fukunaga, T and Soejima, H and Irie, A and Sugamura, K and Oe, Y and Tanaka, T and Nagayoshi, Y and Kaikita, K and Sugiyama, S and Yoshimura, M and Nishimura, Y and Ogawa, H}, title = {Relation between CD4+ T-cell activation and severity of chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {100}, number = {3}, pages = {483-488}, doi = {10.1016/j.amjcard.2007.03.052}, pmid = {17659933}, issn = {0002-9149}, mesh = {Aged ; C-Reactive Protein/analysis ; CD4-Positive T-Lymphocytes/*immunology/metabolism ; Cardiomyopathy, Dilated/*complications ; Female ; Flow Cytometry ; Heart Failure/blood/etiology/*immunology/physiopathology ; Heart Rate ; Humans ; Interferon-gamma/metabolism ; Interleukin-4/metabolism ; Male ; Middle Aged ; Myocardial Ischemia/*complications ; Natriuretic Peptide, Brain/blood ; Stroke Volume ; Tumor Necrosis Factor-alpha/analysis ; }, abstract = {The percentage of CD4(+) T cells in blood is correlated with left ventricular dysfunction and decreased ejection fraction in heart disease. The aim of this study was to determine the relation between activation of CD4(+) T cells and New York Heart Association functional classes in chronic heart failure (HF) and differences in inflammatory activation between ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Blood samples were obtained from 47 patients with HF and 20 controls. Percentages of interferon-gamma-positive CD4(+) T cells (representative type 1 T-helper cells) and interleukin-4-positive CD4(+) T cells (representative type 2 T-helper cells) were analyzed using 3-color flow cytometry. The proportion of interferon-gamma-positive CD4(+) T cells was higher in patients with HF (28.96 +/- 12.90%) than in controls (18.12 +/- 5.28, p = 0.0006), but there was no difference in percentage of interleukin-4-positive CD4(+) T cells between the 2 groups. The proportion of interferon-gamma-positive CD4(+) T cells and plasma B-type natriuretic peptide levels increased with worsening of New York Heart Association functional class in the IC and IDC groups. The proportion of interferon-gamma-positive CD4(+) T cells in the IC group (33.88 +/- 13.33%) was higher than in the IDC group (22.33 +/- 8.88%, p = 0.002); however, plasma B-type natriuretic peptide levels were higher in the IDC group (358.0 pg/ml, 327.5 to 1,325.7) than in the IC group (82.7 pg/ml, 34.7 to 252.9, p = 0.019). In conclusion, we demonstrated pronounced type 1 T-helper cell activation in patients with HF in proportion to severity of HF and that the specificity of T-cell activation differs between patients with IC and those with IDC.}, }
@article {pmid17658224, year = {2007}, author = {Oka, K and Sando, N and Moriya, T and Yatabe, Y}, title = {Malignant adenomyoepithelioma of the breast with matrix production may be compatible with one variant form of matrix-producing carcinoma: a case report.}, journal = {Pathology, research and practice}, volume = {203}, number = {8}, pages = {599-604}, doi = {10.1016/j.prp.2007.04.004}, pmid = {17658224}, issn = {1618-0631}, mesh = {Adenocarcinoma, Mucinous/pathology/surgery ; Adenomyoepithelioma/metabolism/*pathology ; Aged ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/pathology/surgery ; Extracellular Matrix ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Multiple Primary/metabolism/*pathology ; Rectal Neoplasms/pathology/surgery ; Stroke/complications ; }, abstract = {We examined a 77-year-old woman who suffered from a left breast tumor. She had undergone right mastectomy for invasive ductal carcinoma at 68 years of age, and rectal resection for mucinous carcinoma at the age of 74 years. The left breast tumor measured 3.8 x 2.5 x 1.6 cm. Neoplastic cells consisted of atypical epithelial and myoepithelial cells. The former cells were polygonal and large. They were located in the periphery of the tumor, arranged in a ductal pattern, and expressed cytokeratins, S-100 protein, maspin, and MIC2. The latter cells were composed of dark cells which proliferated in a periductal pattern, and stellate cells which were located in the center of the tumor. They invaded the chondromyxoid tissues, and proliferated in a lace-like pattern. Atypical myoepithelial cells expressed vimentin, S-100 protein, maspin, and MIC2. We conclude that malignant adenomyoepithelioma of the breast with matrix production might be compatible with a variant form of matrix-producing carcinoma.}, }
@article {pmid17652893, year = {2007}, author = {Ohta, S and Shinke, T and Hata, K and Takaoka, H and Shite, J and Kijima, Y and Murata, T and Yoshikawa, R and Masai, H and Hirata, K and Yokoyama, M}, title = {Inhibition of endogenous nitric oxide synthase augments contractile response to adenylyl cyclase stimulation without altering mechanical efficiency in patients with idiopathic dilated cardiomyopathy.}, journal = {Circulation journal : official journal of the Japanese Circulation Society}, volume = {71}, number = {8}, pages = {1268-1273}, doi = {10.1253/circj.71.1268}, pmid = {17652893}, issn = {1346-9843}, mesh = {Adenylyl Cyclases/*pharmacology ; Adrenergic beta-Agonists ; Aged ; Biomechanical Phenomena ; Cardiomyopathy, Dilated/*complications ; Colforsin/administration &amp; dosage/analogs &amp; derivatives ; Female ; Heart Failure/etiology ; Heart Function Tests ; Humans ; Male ; Middle Aged ; Myocardial Contraction/*drug effects ; Nitric Oxide Synthase Type III/*antagonists &amp; inhibitors ; omega-N-Methylarginine/administration &amp; dosage/pharmacology ; }, abstract = {BACKGROUND: Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to beta-adrenergic receptor stimulation. However, the physiological effects of NO on the beta-adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure.<br><br>METHODS AND RESULTS: The study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV external work (EW), pressure-volume area (PVA), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during colforsin daropate infusion, and during concurrent infusion of colforsin daropate with the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA; 200 micromol). Colforsin daropate increased Emax by 53% and EW by 18%, and reduced PVA by 14%, without altering MVO2 or mechanical efficiency. The combination of colforsin daropate with L-NMMA further increased Emax by 26% and reduced PVA by 9%, without altering MVO2 or mechanical efficiency.<br><br>CONCLUSIONS: These findings suggest endogenous NO may modulate beta-adrenergic post-receptor pathways and preserve myocardial efficiency in patients with IDC.}, }
@article {pmid17652529, year = {2007}, author = {Khilko, N and Bourne, P and Qi Yang,  and Ping Tang, }, title = {Mismatch repair genes hMLH1 and hMSH2 may not play an essential role in breast carcinogenesis.}, journal = {International journal of surgical pathology}, volume = {15}, number = {3}, pages = {233-241}, doi = {10.1177/1066896907302116}, pmid = {17652529}, issn = {1066-8969}, mesh = {Adaptor Proteins, Signal Transducing/*genetics/physiology ; Breast Neoplasms/*genetics/pathology/physiopathology ; Carcinoma, Ductal, Breast/*genetics/pathology/physiopathology ; *DNA Mismatch Repair ; DNA, Neoplasm/genetics ; ErbB Receptors/genetics/physiology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Keratins/genetics/physiology ; Microsatellite Instability ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein/*genetics/physiology ; Nuclear Proteins/*genetics/physiology ; Receptor, ErbB-2/genetics/physiology ; Receptors, Estrogen/genetics/physiology ; Receptors, Progesterone/genetics/physiology ; }, abstract = {Breast carcinoma is one of the most common malignancies in women, and its carcinogenesis is still unknown. The role of microsatellite instability (MSI) in breast carcinogenesis has been inconsistent in the literature. Here we studied the expression of 2 mismatch repair genes, hMLH1 and hMSH2, in 211 cases of intraductal (DCIS; 90 cases) and invasive ductal carcinoma (121 cases) of the breast by immunohistochemical analysis; and evaluated its relationship with cytokeratin (CK) subtypes, along with expression of ER-alpha (138 cases positive, 73 cases negative); PR (118 cases positive, 93 cases negative), and HER-2/neu (47 cases positive, 164 cases negative); and clinical features such as patient age (157 cases>50 years, 54 cases<50 years), tumor size (31 cases of IDC>2 cm, 90 cases of IDC<2 cm), tumor grade (87 cases high nuclear grade, 124 case non-high grade), and lymph node metastasis (38 cases of IDC positive, 74 cases of IDC negative, 9 cases of IDC with no available data on lymph node status). For CK subtypes, 167 cases were classified as luminal subtype (expressing CK8 and/or CK18, negative for CK5/6, CK14, and CK17) and 44 cases were classified as nonluminal (most of them belonged to basal/stem subtype, expressing CK5/6, and/or CK14, and/or CK17). No typical or atypical medullary carcinoma was included in this study. Our results showed that no loss of nuclear expression of either hMLH1 or hMSH2 was identified in any of the 211 cases of DCIS or IDC regardless of the various pathological and clinical factors, suggesting that hMLH1 or hMSH2 may not play an essential role in the majority of cases of the breast carcinoma.}, }
@article {pmid17645766, year = {2007}, author = {Zaguri, R and Verbovetski, I and Atallah, M and Trahtemberg, U and Krispin, A and Nahari, E and Leitersdorf, E and Mevorach, D}, title = {'Danger' effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells.}, journal = {Clinical and experimental immunology}, volume = {149}, number = {3}, pages = {543-552}, pmid = {17645766}, issn = {0009-9104}, mesh = {Antigens, CD/blood ; Apoptosis/drug effects ; B7-2 Antigen/blood ; Cell Differentiation/drug effects/immunology ; Cells, Cultured ; Dendritic Cells/*drug effects ; HLA-DR Antigens/blood ; Humans ; Immunoglobulins/blood ; Lipoproteins, LDL/*pharmacology ; Membrane Glycoproteins/blood ; Phagocytosis/immunology ; Receptors, CCR7 ; Receptors, Chemokine/blood ; }, abstract = {Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous 'dangerous' signals that can induce dendritic cell maturation. We have found that autologous plasma contains danger signals that induce up-regulation of major histocompatibility complex (MHC) class II and co-stimulatory molecules in immature DCs (iDCs). The objective of this study was to determine whether low-density lipoprotein (LDL) and/or oxidized LDL (oxLDL) constitute danger signals, and to assess the effect of exposure to LDL and oxLDL following monocyte differentiation into iDCs in lipoprotein-deficient serum (LPDS). IDCs were generated in the presence of autologous plasma or LPDS. Expression of maturation and migration molecules was evaluated using flow cytometry, and morphology was assessed by light microscopy. Pro- or anti-apoptotic effect was determined using annexin V and propidium iodide binding. Phagocytosis of apoptotic cells was evaluated using autologous plasma or LPDS. LDL and oxLDL were clearly able to slightly up-regulate levels of HLA-DR and co-stimulatory molecule CD86. High oxLDL concentrations (50-100 microg/ml) were associated with expression of additional maturation molecules. Moreover, iDCs that were prepared in LPDS showed partial maturation following exposure to LDL and oxLDL, and improved tolerogenic apoptotic cell uptake. This study suggests that oxLDL, and to some extent LDL, are at least partly responsible for the iDC 'danger' response induced by autologous plasma.}, }
@article {pmid17617471, year = {2007}, author = {Wang, YS and Chi, KH and Chu, RM}, title = {Cytokine profiles of canine monocyte-derived dendritic cells as a function of lipopolysaccharide- or tumor necrosis factor-alpha-induced maturation.}, journal = {Veterinary immunology and immunopathology}, volume = {118}, number = {3-4}, pages = {186-198}, doi = {10.1016/j.vetimm.2007.05.010}, pmid = {17617471}, issn = {0165-2427}, mesh = {Animals ; Cell Differentiation/*drug effects ; Cytokines/*genetics/*metabolism ; Dendritic Cells/cytology/*drug effects/*metabolism ; Dogs ; Flow Cytometry/veterinary ; Gene Expression Regulation/drug effects ; Interferons/genetics/metabolism ; Interleukins/genetics/metabolism ; Lipopolysaccharides/*pharmacology ; Monocytes/cytology/drug effects ; Th1 Cells/drug effects/metabolism ; Th2 Cells/drug effects/metabolism ; Tumor Necrosis Factor-alpha/*pharmacology ; }, abstract = {In response to exogenous as well as endogenous signals, dendritic cells (DC) undergo programmed maturation to become efficient, antigen-presenting cells and mediate innate and adaptive immune responses. Very little is known, however, about the differential maturation responses of canine DC to endogenous and exogenous stimuli, especially the concomitant events related to the specific expression of cytokine genes. Canine monocyte-derived immature DC (iDC) were treated with an exogenous signal, bacterial lipopolysaccharide (LPS), or an endogenous signal, tumor necrosis factor-alpha (TNF-alpha), to generate mature DC (mDC). The mDC generated from either stimuli were characterized by significant increases in the expression of surface molecules, including CD11c, MHC class II, CD80, CD83, and CD86. Using real-time reverse transcriptase polymerase chain reactions, the cytokine expression profiles generated by these two stimuli were studied. Compared with the iDC, the LPS-stimulated mDC exhibited a significantly increased expression of IL-1 beta, IL-10, IL-12p40, IL-13, and TNF-alpha. Using the mixed lymphocyte reaction and cytokine intracellular staining, it was shown that the array of cytokines from LPS-generated mDC contributed to T cell priming and T helper cell type 1 (Th1) polarization. TNF-alpha-generated mDC increased the expression of a distinctly different panel of cytokines, namely IL-2, IL-4, IL-12p40, IL-13, TNF-alpha, TGF-beta, IFN-gamma, and MCP-2, and shifted naïve T cell differentiation to T helper cell type 2 (Th2) polarization. IL-13 expression was dramatically increased in canine TNF-alpha-generated mDC, which does not occur in other mammalian species, including humans. Because IL-13 is functionally similar to IL-4, IL-13 may contribute to the observed Th2 polarization. Thus, canine DC maturing from different stimuli release different cytokine profiles that in turn promote different immune responses and activate innate and adaptive immune responses.}, }
@article {pmid17607371, year = {2007}, author = {Sanada, Y and Yoshida, K and Ohara, M and Tsutani, Y}, title = {Expression of orotate phosphoribosyltransferase (OPRT) in hepatobiliary and pancreatic carcinoma.}, journal = {Pathology oncology research : POR}, volume = {13}, number = {2}, pages = {105-113}, pmid = {17607371}, issn = {1219-4956}, mesh = {Adenocarcinoma/*enzymology/pathology ; Aged ; Carcinoma in Situ/*enzymology/pathology ; Carcinoma, Hepatocellular/*enzymology/pathology ; Female ; Gallbladder/enzymology/pathology ; Gallbladder Neoplasms/*enzymology/pathology ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Liver/enzymology/pathology ; Liver Neoplasms/*enzymology/pathology ; Male ; Middle Aged ; Orotate Phosphoribosyltransferase/genetics/*metabolism ; Pancreas/enzymology/pathology ; Pancreatic Neoplasms/*enzymology/pathology ; Retrospective Studies ; }, abstract = {The purpose of this study was to clarify the role of orotate phosphoribosyltransferase (OPRT) in the progression of hepatobiliary and pancreatic carcinomas. Representative sections from 8 surgically resected pancreatic carcinomas, 5 gallbladder carcinomas and 19 hepatocellular carcinomas (HCCs) were examined microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma of the pancreas (IDC) were determined. Gallbladder carcinomas and HCCs were examined histologically, and the subtypes and spread patterns were assessed. Expression of OPRT was examined immunohistochemically. A total of 75 PanINs were identified. Expression of OPRT increased as lesions progressed from early to high-grade PanINs (PanIN-1A and -1B versus PanIN-2 and -3, p=0.0004). Three (37.5%) of the 8 pancreatic IDCs were positive for OPRT. In the remaining 5 cases, OPRT was expressed only in the neoplastic ducts adjacent to PanIN-3s. In gallbladder carcinomas, mucosal neoplastic epithelium showed dense cytoplasmic expression in 4 of the 5 cases, but expression was absent in the deeply invasive lesions. Among HCCs, 15 of the 19 cases were negative for OPRT in the central area of the tumor, but 8 of the 19 cases expressed OPRT in vascularly invasive lesions. Our data suggest that OPRT is involved in early events of pancreatic and gallbladder carcinogenesis and invasion of HCC.}, }
@article {pmid17599361, year = {2007}, author = {Mirza, S and Sharma, G and Prasad, CP and Parshad, R and Srivastava, A and Gupta, SD and Ralhan, R}, title = {Promoter hypermethylation of TMS1, BRCA1, ERalpha and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients.}, journal = {Life sciences}, volume = {81}, number = {4}, pages = {280-287}, doi = {10.1016/j.lfs.2007.05.012}, pmid = {17599361}, issn = {0024-3205}, mesh = {Adult ; Aged ; Aged, 80 and over ; BRCA1 Protein/*metabolism ; Biomarkers, Tumor/blood/genetics ; Breast Neoplasms/*blood/genetics/pathology ; CARD Signaling Adaptor Proteins ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Cohort Studies ; Cytoskeletal Proteins/*metabolism ; DNA Methylation ; DNA, Neoplasm/*blood ; Epigenesis, Genetic ; Estrogen Receptor alpha/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Genes, Tumor Suppressor ; Humans ; Middle Aged ; Promoter Regions, Genetic/genetics ; Receptors, Progesterone/*metabolism ; Tumor Cells, Cultured ; }, abstract = {Breast cancer is fast emerging as the leading cancer amongst females, especially in younger age group in India; a large proportion of these tumors are often aggressive and ER and/or PR negative. Promoter methylation of genes involved in DNA repair and hormonal regulation may, in part, account for this behavior. To test this hypothesis methylation status of tumor suppressor genes TMS1, BRCA1, ERalpha and PRB was determined in invasive ductal carcinoma of breast and paired serum DNA. Of the 50 breast cancer patients investigated, 36/50 (72%) tumors and 32/50 (64%) paired sera showed methylation of at least one of these genes, while 17/50 (34%) tumors and 12/50 (24%) sera showed methylation of three genes. Methylation frequencies ranged from 24% for TMS1 to 63% for ERalpha. Significant association was observed between ERalpha and PRB methylation (p< or =0.001) and there was concordance between DNA methylation in tumor and serum for each gene. Immunohistochemical analysis showed no detectable expression of ERalpha, PRB and BRCA1 in 21/36 (58%), 20/36 (56%) and 23/36 (64%) tumors respectively; significant correlation was observed between promoter methylation and loss of protein expression confirming our hypothesis that promoter methylation is an important mechanism for transcriptional silencing of these genes in breast cancer in this population. This study also underscores the potential utility of DNA methylation based screening of serum (a surrogate for tumor DNA methylation) as a tool for detection of breast cancer.}, }
@article {pmid17597348, year = {2007}, author = {King, TA and Li, W and Brogi, E and Yee, CJ and Gemignani, ML and Olvera, N and Levine, DA and Norton, L and Robson, ME and Offit, K and Borgen, PI and Boyd, J}, title = {Heterogenic loss of the wild-type BRCA allele in human breast tumorigenesis.}, journal = {Annals of surgical oncology}, volume = {14}, number = {9}, pages = {2510-2518}, doi = {10.1245/s10434-007-9372-1}, pmid = {17597348}, issn = {1068-9265}, support = {R01 CA71840/CA/NCI NIH HHS/United States ; }, mesh = {*Alleles ; Breast Neoplasms/*genetics ; Female ; Gene Frequency ; *Genes, BRCA1 ; *Genes, BRCA2 ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Haplotypes ; Humans ; *Loss of Heterozygosity ; Ovarian Neoplasms/genetics ; Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: For individuals genetically predisposed to breast and ovarian cancer through inheritance of a mutant BRCA allele, somatic loss of heterozygosity affecting the wild-type allele is considered obligatory for cancer initiation and/or progression. However, several lines of evidence suggest that phenotypic effects may result from BRCA haploinsufficiency.<br><br>METHODS: Archival fixed and embedded tissue specimens from women with germ line deleterious mutations in BRCA1 or BRCA2 were identified. After pathologic review, focal areas of normal breast epithelium, atypical ductal hyperplasia, ductal carcinoma-in-situ, and invasive ductal carcinoma were identified from 14 BRCA1-linked and 9 BRCA2-linked breast cancers. Ten BRCA-linked prophylactic mastectomy specimens and 12 BRCA-linked invasive ovarian carcinomas were also studied. Laser catapult microdissection was used to isolate cells from the various pathologic lesions and corresponding normal tissues. After DNA isolation, real-time polymerase chain reaction assays were used to quantitate the proportion of wild-type to mutant BRCA alleles in each tissue sample.<br><br>RESULTS: Quantitative allelotyping of microdissected cells revealed a high level of heterogeneity in loss of heterozygosity within and between preinvasive lesions and invasive cancers from BRCA1 and BRCA2 heterozygotes with breast cancer. In contrast, all BRCA-associated ovarian cancers displayed complete loss of the wild-type BRCA allele.<br><br>CONCLUSIONS: These data suggest that loss of the wild-type BRCA allele is not required for BRCA-linked breast tumorigenesis, which would have important implications for the genetic mechanism of BRCA tumor suppression and for the clinical management of this patient population.}, }
@article {pmid17595678, year = {2007}, author = {Soederholm, A and Bánki, Z and Wilflingseder, D and Gassner, C and Zwirner, J and López-Trascasa, M and Falkensammer, B and Dierich, MP and Stoiber, H}, title = {HIV-1 induced generation of C5a attracts immature dendriticcells and promotes infection of autologous T cells.}, journal = {European journal of immunology}, volume = {37}, number = {8}, pages = {2156-2163}, doi = {10.1002/eji.200636820}, pmid = {17595678}, issn = {0014-2980}, mesh = {Chemotaxis, Leukocyte/*immunology ; Coculture Techniques ; Complement C5a/*immunology ; Dendritic Cells/immunology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; HIV Infections/*immunology ; HIV-1/*immunology/pathogenicity ; Humans ; T-Lymphocytes/immunology/*virology ; Transplantation, Autologous ; }, abstract = {For the recruitment of dendritic cells (DC) to the site of infection, DC express several sensors for danger signals, such as receptors for C5a. This anaphylatoxin is generated upon complement activation. As HIV-1 triggers the complement cascade, we determined whether C5a is generated by the virus and tested the functional activity of C5a in migration and infection assays. The immature (i)DC responded in migration assays to recombinant C5a and native C5a, which was generated in situ upon activation of the complement system by HIV-1. In combined migration and infection assays, a C5a-dependent enhancement of HIV-1 infection in DC-T cell cocultures was observed. These results indicate that HIV induces generation of C5a and thereby attracts iDC, which in turn promote the productive infection of autologous primary T cells.}, }
@article {pmid17593048, year = {2007}, author = {Cheung, KJ and Tam, W and Chuang, E and Osborne, MP}, title = {Concurrent invasive ductal carcinoma and chronic lymphocytic leukemia manifesting as a collision tumor in breast.}, journal = {The breast journal}, volume = {13}, number = {4}, pages = {413-417}, doi = {10.1111/j.1524-4741.2007.00451.x}, pmid = {17593048}, issn = {1075-122X}, mesh = {Breast Neoplasms/*pathology/radiotherapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/radiotherapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology/radiotherapy ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Lymphoma/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*pathology ; Sentinel Lymph Node Biopsy ; }, abstract = {Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement in the same site. The occurrence of these tumors in the breast is extremely rare. Here, we present a case of a patient with both invasive ductal carcinoma and chronic lymphocytic leukemia in the breast. Wide excision with sentinel lymph node biopsy revealed palpably abnormal lymph nodes negative for breast carcinoma on frozen section. Histopathological examination of these lymph nodes showed extensive involvement by lymphoma and review of the breast specimen demonstrated the same lymphoma at the periphery of the ductal carcinoma. We review the literature and discuss possible etiologies for the dual presentation of both cancers.}, }
@article {pmid17590131, year = {2007}, author = {Sánchez Muñoz, LA and Castiella Herrero, J and Sanjuán Portugal, FJ and Naya Manchado, J and Alfaro Alfaro, MJ}, title = {[Usefulness of MBDS in detection of adverse drug events].}, journal = {Anales de medicina interna (Madrid, Spain : 1984)}, volume = {24}, number = {3}, pages = {113-119}, doi = {10.4321/s0212-71992007000300003}, pmid = {17590131}, issn = {0212-7199}, mesh = {Adult ; *Adverse Drug Reaction Reporting Systems ; Aged ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Spain ; }, abstract = {OBJECTIVE: To analyze the incidence of adverse drug events (ADE) as noted in hospital discharge reports, as well as their potential avoidability, drugs involved, clinical symptoms and the type of medication errors that led to the preventable ADE.<br><br>MATERIAL AND METHODS: A retrospective study for the January- December 2005 period of time, at a district hospital. ADE were detected in which patients with discharge reports including event codes as defined by the IDC-9-CM system, using the minimum basic data set (MBDS).<br><br>RESULTS: ADEs were detected in 4.01% of all discharge reports in the study period (n = 160). 45% of ADEs were were detected at the Emergency Department (n = 72) and 55% (n = 88) were detected during hospitalization.62.3% of ADEs were considered potentially avoidable (n = 109). 38.1% of ADEs were serious, 40.0% moderate and 21.9% mild. Drugs most commonly involved in the ADEs sample studied included: antimicrobials (24.0%), systemic corticoids (15.4%), NSAIDs (11.4%), diuretics (10.3%), digoxin (9.1%), insulin and oral hypoglycaemic agents (5.7%), anticoagulants and heparin (5.7%). Inadequate therapy monitoring (47.7%), excessive dosage (28.5%), drug-drug interactions (10.1%) were the most common identified type of errors leading to preventable ADE.<br><br>CONCLUSIONS: 3.2% of admissions was caused by ADEs. 2.2% of hospitalized patients experienced ADEs. 62% of ADEs were potentially preventable. A high proportion of preventable ADEs were around a small number of drugs. Effective safety practices directed to reduce the incidence of medication errors are needed.}, }
@article {pmid17587091, year = {2007}, author = {Black, D and Specht, M and Lee, JM and Dominguez, F and Gadd, M and Hughes, K and Rafferty, E and Smith, B}, title = {Detecting occult malignancy in prophylactic mastectomy: preoperative MRI versus sentinel lymph node biopsy.}, journal = {Annals of surgical oncology}, volume = {14}, number = {9}, pages = {2477-2484}, doi = {10.1245/s10434-007-9356-1}, pmid = {17587091}, issn = {1068-9265}, mesh = {Adult ; Axilla ; Breast Neoplasms/*diagnosis/genetics/pathology/surgery ; Costs and Cost Analysis ; Diagnostic Errors/economics ; Female ; Genetic Predisposition to Disease ; Humans ; Intraoperative Care/economics ; Lymph Node Excision ; Lymphatic Metastasis ; Magnetic Resonance Imaging/economics/*methods ; Mastectomy ; Middle Aged ; Neoplasm Staging ; Preoperative Care/economics ; Primary Prevention ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; *Sentinel Lymph Node Biopsy/economics ; }, abstract = {BACKGROUND: High-risk patients undergoing prophylactic mastectomy (PM) may have unsuspected cancers identified on pathology. The optimum way to identify and manage them is controversial. Magnetic resonance imaging (MRI) may identify occult cancer preoperatively. Sentinel lymph node biopsy (SLNB) allows intraoperative staging and axillary dissection during the same operation. We determined the efficacy and cost of MRI and/or SLNB in managing high-risk PM patients.<br><br>METHODS: We reviewed 192 PMs in 173 patients from 1999 to 2005. Costs were estimated for MRI and SLNB during PM by the 2005 Medicare Resource-Based Relative Value Scale. We also estimated costs and procedures for the four strategies in a larger hypothetical cohort.<br><br>RESULTS: A total of 19 (10%) of 192 PMs contained occult cancers, 14 ductal carcinoma-in-situ (DCIS) and 5 invasive ductal carcinoma (IDC). In 59 patients, MRI detected an IDC but missed two DCIS and an IDC. Positive MRIs generated an additional average cost of $1,207 per patient. In 56 PMs with SLNB, 6 occult cancers were found, 5 DCIS and 1 IDC, all with negative SLNBs. Adding a SLNB costs an additional average of $644. A theoretical analysis demonstrated that PM alone costs $808 per patient, PM with SLNB costs $1,420, PM with MRI and selective SLNB costs $1,774, and PM with routine MRI and SLNB costs $2,379.<br><br>CONCLUSIONS: MRI adds great cost and misses most occult cancers in PMs. SLNB allows the rare patient with occult IDC to avoid axillary dissection but adds cost. Given the low rate of unsuspected invasive cancers and the costs of MRI and SLNB, neither is recommended as standard practice for PM patients.}, }
@article {pmid17576158, year = {2007}, author = {Breckpot, K and Emeagi, P and Dullaers, M and Michiels, A and Heirman, C and Thielemans, K}, title = {Activation of immature monocyte-derived dendritic cells after transduction with high doses of lentiviral vectors.}, journal = {Human gene therapy}, volume = {18}, number = {6}, pages = {536-546}, doi = {10.1089/hum.2007.006}, pmid = {17576158}, issn = {1043-0342}, mesh = {Cell Adhesion ; Cytokines/metabolism ; Dendritic Cells/*immunology ; Flow Cytometry ; *Gene Transfer Techniques ; Genetic Vectors ; Humans ; Lentivirus/*genetics ; Monocytes/*immunology ; Phenotype ; Toll-Like Receptors/genetics/metabolism ; *Transduction, Genetic ; eIF-2 Kinase/genetics/metabolism ; }, abstract = {Dendritic cells (DCs) are an attractive tool for immunomodulation, targeting mature DCs (mDCs) for immunization or immature/semimature DCs (iDCs) for tolerization. Therefore, introducing antigens into DCs has become a prime topic in various immunological disciplines. Numerous studies have shown that lentiviruses are an efficient vehicle for this purpose. This study evaluates the effects of lentiviral transduction on iDC activation. Immature DCs are efficiently transduced with increasing doses of lentivirus without affecting cell viability. Transduction at low multiplicities of infection (MOIs) did not result in phenotypical or functional maturation. Higher doses of lentivirus, however, resulted in upregulation of adhesion, costimulatory, and HLA molecules, as well as in increased allostimulatory capacity and secretion of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha. Production of IL-12 p70, IL-10, and interferon-alpha was observed only at extremely high doses. Protein kinase R phosphorylation on transduction at an MOI of 150 was demonstrated by Western blotting. A Toll-like receptor (TLR)-driven luciferase reporter assay showed dose-dependent activation of TLR2, TLR3, and TLR8, which was independent of the pseudotype, production, or transduction protocol and was abrogated on heat inactivation. These data show that lentiviral vectors provide not only the antigen but also appropriate activation signals to iDCs, favoring their use for immunotherapy and vaccine development.}, }
@article {pmid17568853, year = {2006}, author = {Dos Reis, FJ and de Sousa, TA and Oliveira, MS and Dantas, N and Silveira, M and Braghiroly, MI and Paraná, R}, title = {Is hepatitis C virus a cause of idiopathic dilated cardiomyopathy? A systematic review of literature.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {10}, number = {3}, pages = {199-202}, doi = {10.1590/s1413-86702006000300009}, pmid = {17568853}, issn = {1413-8670}, mesh = {Cardiomyopathy, Dilated/*virology ; Hepatitis C/*complications ; Humans ; }, abstract = {Recent studies have suggested that some patients with idiopathic dilated cardiomyopathy (IDC) are also afflicted with insidious forms of viral myocarditis. Participation of hepatitis C virus (HCV) in this process has been postulated. The objective of this study was to evaluate a possible association between hepatitis C virus and idiopathic dilated cardiomyopathy. Systematic review of the literature using electronic databases (MEDLINE, EMBASES, LILACS and COCHRANE) for the period from 1995 to 2005, limited to papers published in English, Spanish and Portuguese. Sixty-two papers were found, of which six were in accordance with the proposed methodology. After selection, the articles were classified by quality of data and number of variables studied. Most of the patients were male adults from 31 and 75 years old, who had ischemic cardiopathy excluded as etiology of the dilated cardiomyopathy. A significant association between dilated cardiomyopathy and hepatitis C virus was found in only two papers, both from Japan and by the same author. Most of the papers received low classifications, as they did not fulfill the systematization criteria.}, }
@article {pmid17567699, year = {2007}, author = {Wang, JH and Janas, AM and Olson, WJ and Wu, L}, title = {Functionally distinct transmission of human immunodeficiency virus type 1 mediated by immature and mature dendritic cells.}, journal = {Journal of virology}, volume = {81}, number = {17}, pages = {8933-8943}, pmid = {17567699}, issn = {0022-538X}, support = {R01 AI068493/AI/NIAID NIH HHS/United States ; R01 AI068493-02/AI/NIAID NIH HHS/United States ; }, mesh = {Cells, Cultured ; Dendritic Cells/immunology/ultrastructure/*virology ; Endocytosis ; HIV-1/*growth &amp; development/physiology ; Humans ; Lectins, C-Type/physiology ; Microscopy, Electron, Transmission ; Virus Internalization ; }, abstract = {Dendritic cells (DCs) potently stimulate the transmission of human immunodeficiency virus type 1 (HIV-1) to CD4(+) T cells. Immature DCs (iDCs) located in submucosal tissues can capture HIV-1 and migrate to lymphoid tissues, where they become mature DCs (mDCs) for effective antigen presentation. DC maturation promotes HIV-1 transmission; however, the underlying mechanisms remain unclear. Here we have compared monocyte-derived iDCs and mDCs for their efficiencies and mechanisms of HIV-1 transmission. We have found that mDCs significantly facilitate HIV-1 endocytosis and efficiently concentrate HIV-1 at virological synapses, which contributes to mDC-enhanced viral transmission, at least in part. mDCs were more efficient than iDCs in transferring HIV-1 to various types of target cells independently of C-type lectins, which partially accounted for iDC-mediated HIV-1 transmission. Efficient HIV-1 trans-infection mediated by iDCs and mDCs required contact between DCs and target cells. Moreover, rapid HIV-1 degradation occurred in both iDCs and mDCs, which correlated with the lack of HIV-1 retention-mediated long-term viral transmission. Our results provide new insights into the mechanisms underlying DC-mediated HIV-1 transmission, suggesting that HIV-1 exploits mDCs to facilitate its dissemination within lymphoid tissues.}, }
@article {pmid17557561, year = {2007}, author = {Piccirilli, M and Sassun, TE and Brogna, C and Giangaspero, F and Salvati, M}, title = {Late brain metastases from breast cancer: clinical remarks on 11 patients and review of the literature.}, journal = {Tumori}, volume = {93}, number = {2}, pages = {150-154}, doi = {10.1177/030089160709300207}, pmid = {17557561}, issn = {0300-8916}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Aged ; Brain Neoplasms/mortality/*secondary/*therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Cranial Irradiation ; Female ; Humans ; Middle Aged ; Palliative Care ; Radiosurgery ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; }, abstract = {AIMS AND BACKGROUND: Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor.<br><br>PATIENTS AND METHODS: Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30).<br><br>RESULTS: Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years).<br><br>CONCLUSIONS: Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.}, }
@article {pmid17554196, year = {2007}, author = {Kim, MJ and Kim, EK and Lee, JY and Youk, JH and Park, BW and Kim, H and Oh, KK}, title = {Breast cancer from the excisional scar of a benign mass.}, journal = {Korean journal of radiology}, volume = {8}, number = {3}, pages = {254-257}, pmid = {17554196}, issn = {1229-6929}, mesh = {Breast Neoplasms/*etiology/pathology/surgery ; Carcinoma, Ductal, Breast/*etiology ; Cicatrix/*complications ; Female ; Foreign-Body Reaction/pathology ; Giant Cells/pathology ; Humans ; Middle Aged ; Papilloma, Intraductal/pathology/surgery ; }, abstract = {Breast cancer developing from a surgical scar is rare; this type of malignancy has been reported in only 12 cases to date. Herein, we report on a 52-year-old female who developed infiltrating ductal carcinoma in a surgical scar following excision of a benign mass. Two years previously, the patient underwent surgery and radiotherapy for invasive ductal carcinoma of the contralateral breast. The initial appearance of the scar was similar to fat necrosis; it was observed to be progressively shrinking on follow-up sonography. On the two year follow-up ultrasound, the appearance changed, an angular margin and vascularity at the periphery of the scar were noted. A biopsy and subsequent excision of the scar were performed; the diagnosis of infiltrating ductal carcinoma of the scar was confirmed.}, }
@article {pmid17540213, year = {2007}, author = {Sugioka, K and Hozumi, T and Takemoto, Y and Ehara, S and Ogawa, K and Iwata, S and Oe, H and Matsumura, Y and Otsuka, R and Yoshiyama, M and Yoshikawa, J}, title = {Relation of early improvement in coronary flow reserve to late recovery of left ventricular function after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.}, journal = {American heart journal}, volume = {153}, number = {6}, pages = {1080.e1-6}, doi = {10.1016/j.ahj.2007.03.014}, pmid = {17540213}, issn = {1097-6744}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Blood Flow Velocity ; Carbazoles/*therapeutic use ; Cardiomyopathy, Dilated/*complications/diagnostic imaging/*drug therapy ; Carvedilol ; Coronary Vessels/diagnostic imaging ; Echocardiography ; Female ; Follow-Up Studies ; Fractional Flow Reserve, Myocardial/*drug effects ; Humans ; Male ; Middle Aged ; Propanolamines/*therapeutic use ; Stroke Volume/*drug effects ; Ventricular Dysfunction, Left/etiology/*prevention &amp; control ; }, abstract = {BACKGROUND: Beta-blocker therapy reverses left ventricular (LV) remodeling in patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary circulation by beta-blocker could play a role in these circumstances. This study investigated the relationship between change in coronary flow reserve (CFR), as a marker of coronary circulation, and subsequent improvement in LV ejection fraction (LVEF) at follow-up during carvedilol therapy in patients with IDC.<br><br>METHODS: Eighteen patients with IDC underwent CFR measurements by transthoracic Doppler echocardiography at baseline and after 1 month of treatment with carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 +/- 6 months of treatment. The patients were classified by the degree of improvement in LVEF in the follow-up study, as group A (LVEF change > or = 10%) and group B (LVEF change < 10%).<br><br>RESULTS: Although there was no significant difference in CFR between the 2 groups at baseline, CFR was significantly higher in group A than in group B at 1 month of therapy (3.7 +/- 0.5 vs 2.5 +/- 0.9; P < .01). Coronary flow reserve change after 1 month was significantly greater in group A than in group B (1.3 +/- 0.6 vs 0.4 +/- 0.5; P < .01). Logistic regression analysis revealed that CFR change predicted a significant improvement in LVEF at follow-up (P < .05). Furthermore, a significant correlation was found between the change in CFR after 1 month and that in LVEF on follow-up (r = 0.65, P < .01).<br><br>CONCLUSIONS: This study demonstrated that early change in CFR is associated with subsequent improvement in LVEF, suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with IDC.}, }
@article {pmid17532057, year = {2007}, author = {Yao, Q and Doan, LX and Zhang, R and Bharadwaj, U and Li, M and Chen, C}, title = {Thymosin-alpha1 modulates dendritic cell differentiation and functional maturation from human peripheral blood CD14+ monocytes.}, journal = {Immunology letters}, volume = {110}, number = {2}, pages = {110-120}, pmid = {17532057}, issn = {0165-2478}, support = {R01 HL083471/HL/NHLBI NIH HHS/United States ; R21 AT003094-02/AT/NCCIH NIH HHS/United States ; EB-002436/EB/NIBIB NIH HHS/United States ; R01 EB002436/EB/NIBIB NIH HHS/United States ; R01 HL072716/HL/NHLBI NIH HHS/United States ; R01 DE015543-04/DE/NIDCR NIH HHS/United States ; HL083471/HL/NHLBI NIH HHS/United States ; R01 DE015543/DE/NIDCR NIH HHS/United States ; R01 HL065916/HL/NHLBI NIH HHS/United States ; AT003094/AT/NCCIH NIH HHS/United States ; R21 AT003094/AT/NCCIH NIH HHS/United States ; DE15543/DE/NIDCR NIH HHS/United States ; HL65916/HL/NHLBI NIH HHS/United States ; HL72716/HL/NHLBI NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic ; Cell Differentiation ; Cytokines/*immunology/metabolism ; Dendritic Cells/cytology/*immunology/metabolism ; Flow Cytometry ; Humans ; *Lipopolysaccharide Receptors/blood/immunology ; Lymphocyte Culture Test, Mixed ; Monocytes/cytology/*immunology/metabolism ; T-Lymphocytes/*immunology/metabolism ; Thymalfasin ; Thymosin/*analogs &amp; derivatives/immunology/metabolism ; }, abstract = {Although thymosins have been demonstrated to have immunomodulatory effects, it is still not clear whether they could affect dendritic cells (DCs), the most professional antigen-presenting cells. The objective of this study was to determine the effect and potential mechanisms of thymosin-alpha1 (Talpha1) on DC differentiation and functional maturation. Human peripheral blood CD14(+) monocytes were purified by using a magnetic separation column and cultured with GM-CSF and IL-4 to differentiate into immature DCs (iDCs). In the presence of Talpha1, iDC surface markers CD40, CD80, MHC class I and class II molecules were significantly upregulated as measured by flow cytemotry analysis. However, Tbeta4 or Tbeta10 did not show these effects on iDCs. There was an approximately 30% reduction in antigen (FITC-conjugated dextran)-uptake by Talpha1-treated iDCs as compared with non-Talpha1-treated iDCs. In addition, Talpha1-treated matured DCs (mDCs) showed an increased stimulation of allogeneic CD3(+) T-cell proliferation as measured by a mixed-lymphocyte reaction assay. Talpha1-treated mDCs also increased the production of several Th1- and Th2-type cytokines as measured by a Bio-Plex cytokine assay. Furthermore, rapid activation of p38 MAPK and NFkappaB was seen in Talpha1-treated iDCs as measured by a Bio-Plex phosphoprotein assay. Thus, Talpha1 significantly enhances DC differentiation, activation, and functions from human peripheral blood CD14(+) monocytes possibly through a mechanism of the activation of p38 MAPK and NFkappaB pathways. This study provides a basis to further evaluate Talpha1 as a possible adjuvant for a DC-directed vaccine or therapy.}, }
@article {pmid17525722, year = {2007}, author = {Smits, EL and Ponsaerts, P and Van de Velde, AL and Van Driessche, A and Cools, N and Lenjou, M and Nijs, G and Van Bockstaele, DR and Berneman, ZN and Van Tendeloo, VF}, title = {Proinflammatory response of human leukemic cells to dsRNA transfection linked to activation of dendritic cells.}, journal = {Leukemia}, volume = {21}, number = {8}, pages = {1691-1699}, doi = {10.1038/sj.leu.2404763}, pmid = {17525722}, issn = {0887-6924}, mesh = {Acute Disease ; Cells, Cultured ; Coculture Techniques ; Cytokines/metabolism ; Dendritic Cells/*immunology ; Electroporation ; Flow Cytometry ; Humans ; Interferon Type I/immunology ; Interferon-gamma/immunology ; Leukemia, Myeloid/*genetics/immunology/pathology ; Lymphocyte Activation ; Poly I-C/metabolism ; RNA, Double-Stranded/*genetics ; T-Lymphocytes/*immunology ; Th1 Cells/immunology ; Toll-Like Receptor 3/genetics/*metabolism ; *Transfection ; }, abstract = {Leukemic cells exert immunosuppressive effects that interfere with dendritic cell (DC) function and hamper effective antileukemic immune responses. Here, we sought to enhance the immunogenicity of leukemic cells by loading them with the double-stranded (ds) RNA Toll-like receptor 3 (TLR3) ligand polyriboinosinic polyribocytidylic acid (poly(I:C)), mimicking viral infection of the tumor cells. Given the responsiveness of DC to TLR ligands, we hypothesized that the uptake of poly(I:C)-loaded leukemic cells by immature DC (iDC) would lead to DC activation. Primary acute myeloid leukemia (AML) cells and AML cell lines markedly responded to poly(I:C) electroporation by apoptosis, upregulation of TLR3 expression, enhanced expression of major histocompatibility complex (MHC) and costimulatory molecules and by production of type I interferons (IFN). Upon phagocytosis of poly(I:C)-electroporated AML cells, DC maturation and activation were induced as judged by an increased expression of MHC and costimulatory molecules, production of proinflammatory cytokines and an increase of T helper 1 (T(H)1)-polarizing capacity. These immune effects were suboptimal when AML cells were passively pulsed with poly(I:C), indicating the superiority of poly(I:C) transfection over pulsing. Our results demonstrate that poly(I:C) electroporation is a promising strategy to increase the immunogenicity of AML cells and to convert iDC into activated mature DC following the phagocytosis of AML cells.}, }
@article {pmid17520199, year = {2007}, author = {Nagata, K and Horinouchi, M and Saitou, M and Higashi, M and Nomoto, M and Goto, M and Yonezawa, S}, title = {Mucin expression profile in pancreatic cancer and the precursor lesions.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {14}, number = {3}, pages = {243-254}, doi = {10.1007/s00534-006-1169-2}, pmid = {17520199}, issn = {0944-1166}, mesh = {Adenocarcinoma, Mucinous/genetics/*metabolism/pathology ; Biomarkers, Tumor/biosynthesis/genetics ; DNA, Neoplasm/*genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; Mucins/biosynthesis/*genetics ; Pancreatic Neoplasms/genetics/*metabolism/pathology ; Precancerous Conditions/genetics/*metabolism/pathology ; }, abstract = {In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary-mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.}, }
@article {pmid17516241, year = {2007}, author = {Cejas, P and García-Cabezas, MA and Casado, E and Belda-Iniesta, C and De Castro, J and Fresno, JA and Sereno, M and Barriuso, J and Espinosa, E and Zamora, P and Feliu, J and Redondo, A and Hardisson, DA and Renart, J and González-Barón, M}, title = {Phospholipid hydroperoxide glutathione peroxidase (PHGPx) expression is downregulated in poorly differentiated breast invasive ductal carcinoma.}, journal = {Free radical research}, volume = {41}, number = {6}, pages = {681-687}, doi = {10.1080/10715760701286167}, pmid = {17516241}, issn = {1071-5762}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; *Cell Differentiation ; Down-Regulation ; Female ; *Gene Expression Regulation, Enzymologic ; Glutathione Peroxidase/genetics/*metabolism ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Phospholipid Hydroperoxide Glutathione Peroxidase ; RNA, Messenger/genetics/metabolism ; RNA, Neoplasm/genetics/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) is the only known enzyme able to reduce lipid peroxides bound to cell membranes. Moreover it has been involved in apoptosis and can influence intracellular signaling. To investigate the possible relationship between PHGPx and human cancer we have quantified PHGPx expression levels by real-time quantitative PCR and immunohistochemistry in tissue samples of human breast invasive ductal carcinoma from 34 patients compared with their own controls of benign breast tissue. PHGPx expression levels were compared with the clinical and pathological data of these patients. The results showed that PHGPx expression levels are downregulated in poorly differentiated (grade 3) breast invasive ductal carcinoma (P = 0.0043). PHGPx expression levels decreased gradually with tumor grade from grade 1 to grade 3. We also found a downregulation of PHGPx in cases that showed p53 accumulation compared with cases without p53 immunostaining (P = 0.0011). PHGPx was also downregulated in cases without progesterone receptors (PR) immunostaining compared with cases with PR immunostaining (P = 0.0165). Grade 3, p53 immunostaining and absence of PR immunostaining are poor prognostic factors. These results suggest that PHGPx downregulation could be related with a poorer prognosis in breast invasive ductal carcinoma.}, }
@article {pmid17506030, year = {2007}, author = {Alemán, M and de la Barrera, S and Schierloh, P and Yokobori, N and Baldini, M and Musella, R and Abbate, E and Sasiain, M}, title = {Spontaneous or Mycobacterium tuberculosis-induced apoptotic neutrophils exert opposite effects on the dendritic cell-mediated immune response.}, journal = {European journal of immunology}, volume = {37}, number = {6}, pages = {1524-1537}, doi = {10.1002/eji.200636771}, pmid = {17506030}, issn = {0014-2980}, mesh = {Adult ; Antibodies, Monoclonal/immunology/pharmacology ; Antigens, CD/metabolism ; Apoptosis/*immunology ; B7-2 Antigen/metabolism ; CD36 Antigens/immunology ; Cell Adhesion Molecules/metabolism ; Cell Differentiation/immunology ; Coculture Techniques ; Cytochalasin D/pharmacology ; Dendritic Cells/drug effects/*immunology/metabolism ; Enzyme Inhibitors/pharmacology ; HLA-DR Antigens/metabolism ; Humans ; Imidazoles/pharmacology ; Immunoglobulins/metabolism ; Integrins/immunology ; Interferon-gamma/metabolism ; Interleukin-12/metabolism ; Kinetics ; Lectins, C-Type/metabolism ; Lipopolysaccharides/pharmacology ; Membrane Glycoproteins/metabolism ; Middle Aged ; Mycobacterium tuberculosis/*immunology ; Neutrophils/*immunology ; Pyridines/pharmacology ; Receptors, Cell Surface/metabolism ; Receptors, Vitronectin/immunology ; p38 Mitogen-Activated Protein Kinases/antagonists &amp; inhibitors/metabolism ; }, abstract = {Polymorphonuclear neutrophils (PMN) modulate the adaptive immune response through interactions with immature dendritic cells (iDC) while spontaneous apoptotic neutrophils PMNapo (PMNapo) may have an inhibitory effect on DC functions. We investigate the effect exerted by PMNapo in DC maturation and the role of Mycobacterium tuberculosis (Mtb)-induced PMNapo in the cross-presentation of mycobacterial antigens. We demonstrate that Mtb triggers the maturation of iDC while it is impaired by the presence of PMNapo, which abrogate Mtb-induced expression of costimulatory and HLA class II molecules, reducing IL-12 and IFN-gamma release by DC and partially inhibiting Mtb-driven lymphocyte proliferation. This inhibitory effect is not observed in already Mtb-matured DC, and it involves a direct interaction between DC and PMNapo, as supernatants from PMNapo cultures do not reveal this effect. Although PMNapo do not alter Mtb/DC-SIGN interaction, they affect the intracellular signals leading to DC maturation without requiring their entry into DC. Phagocytosis of Mtb-induced PMNapo by iDC leads to lymphoproliferation, which is significantly reduced by blocking CD36 and not DC-SIGN on iDC. Therefore, cross-presentation of Mtb antigens is taking place. Our findings suggest that the inflammatory milieu is subjected to a fine balance between non-infected and Mtb-induced PMNapo: non-infected PMNapo limiting inflammation and Mtb-induced PMNapo generating a specific immune activity.}, }
@article {pmid17493477, year = {2007}, author = {Domanski, M and Coady, S and Fleg, J and Tian, X and Sachdev, V}, title = {Effect of statin therapy on survival in patients with nonischemic dilated cardiomyopathy (from the Beta-blocker Evaluation of Survival Trial [BEST]).}, journal = {The American journal of cardiology}, volume = {99}, number = {10}, pages = {1448-1450}, doi = {10.1016/j.amjcard.2006.12.080}, pmid = {17493477}, issn = {0002-9149}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Cardiomyopathy, Dilated/complications/*drug therapy/*mortality/physiopathology ; Female ; Follow-Up Studies ; Heart Failure/etiology/mortality/physiopathology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Research Design ; Risk Factors ; Stroke Volume ; Survival Analysis ; Treatment Outcome ; }, abstract = {To determine whether statin therapy improves survival in patients with heart failure (HF) secondary to nonischemic dilated cardiomyopathy (non-IDC), data from 1,024 patients with non-IDC (New York Heart Association functional class III and IV HF) and left ventricular ejection fraction < or =0.35 who were enrolled in the BEST were analyzed. The association of statin therapy at the initial screening visit with all-cause and cardiovascular mortality was evaluated using multivariate Cox proportional hazards models. After adjusting for age, gender, race, systolic blood pressure, total cholesterol, New York Heart Association functional class IV, estimated glomerular filtration rate, current cigarette smoking, left ventricular ejection fraction, angiotensin-converting enzyme inhibitor use, antiplatelet therapy, diabetes mellitus, treatment group (beta blocker or placebo), and hypertension, statin use was independently associated with decreased all-cause mortality (hazard ratio 0.38, confidence interval 0.18 to 0.82, p = 0.0134) and also with decreased cardiovascular death (hazard ratio 0.42, confidence interval 0.18 to 0.95, p = 0.037). In conclusion, in patients with moderate or severe HF due to non-IDC entered into BEST, statin therapy at entry was independently associated with a decrease in all-cause and cardiovascular mortality.}, }
@article {pmid17479284, year = {2007}, author = {Lee, JS}, title = {GSTP1 promoter hypermethylation is an early event in breast carcinogenesis.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {450}, number = {6}, pages = {637-642}, pmid = {17479284}, issn = {0945-6317}, support = {P50 CA88843/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; *DNA Methylation ; Female ; Glutathione S-Transferase pi/*genetics/metabolism ; Humans ; Immunohistochemistry/methods ; Neoplasm Invasiveness ; Precancerous Conditions/*genetics/metabolism/pathology ; *Promoter Regions, Genetic ; Staining and Labeling ; Time Factors ; Tissue Distribution ; }, abstract = {Promoter hypermethylation in precursor lesions of the breast cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. Pi-class glutathione-S-transferases (GSTP1) is inactivated by promoter hypermethylation in invasive breast cancers. However, little is known about epigenetic silencing of GSTP1 gene by promoter hypermethylation in precursor lesions. To determine the significance of GSTP1 promoter hypermethylation in breast carcinogenesis, methylation status of GSTP1 gene was studied by nested methylation-specific polymerase chain reaction, and GSTP1 expression was studied by immunohistochemistry in invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), usual ductal hyperplasia (UDH), and normal breast tissue. GSTP1 promoter hypermethylation was detected in 4/24 (16.7%) of UDH, 18/49 (36.7%) of DCIS, and 14/36 (38.9%) of IDC. No hypermethylation was detected in normal breast tissues. GSTP1 promoter hypermethylation was found to be progressively elevated during breast carcinogenesis (p < 0.01). GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.01 for UDH, p < 0.001 for DCIS and IDC). Our results suggest that GSTP1 promoter hypermethylation is an early event in breast carcinogenesis and appears to functionally silence GSTP1 expression. GSTP1 promoter hypermethylation in the precursor lesions of breast cancer may be used as a target for cancer chemoprevention.}, }
@article {pmid17466527, year = {2007}, author = {O'Rourke, JA and Graham, MA and Vodkin, L and Gonzalez, DO and Cianzio, SR and Shoemaker, RC}, title = {Recovering from iron deficiency chlorosis in near-isogenic soybeans: a microarray study.}, journal = {Plant physiology and biochemistry : PPB}, volume = {45}, number = {5}, pages = {287-292}, doi = {10.1016/j.plaphy.2007.03.008}, pmid = {17466527}, issn = {0981-9428}, mesh = {Adaptation, Physiological/genetics ; DNA, Plant/genetics ; *Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Iron Deficiencies ; *Oligonucleotide Array Sequence Analysis ; Plant Diseases/*genetics ; Plant Proteins/metabolism ; Soil/analysis ; Soybeans/*genetics/*metabolism ; }, abstract = {Iron deficiency chlorosis (IDC) in soybeans has proven to be a perennial problem in the calcareous soils of the U.S. upper Midwest. A historically difficult trait to study in fields, the use of hydroponics in a controlled greenhouse environment has provided a mechanism to study genetic variation while limiting environmental complications. IDC susceptible plants growing in calcareous soils and in iron-controlled hydroponic experiments often exhibit a characteristic chlorotic phenotype early in the growing season but are able to re-green later in the season. To examine the changes in gene expression of these plants, near-isogenic lines, iron efficient PI548553 (Clark) and iron inefficient PI547430 (IsoClark), developed for their response to iron deficiency stress [USDA, ARS, National Genetic Resources Program, Germplasm Resources Information Network - GRIN. (Online Database) National Germplasm Resources Laboratory, Beltsville, MD, 2004. Available: http://www.ars.grin.gov/cgi-bin/npgs/html/acc_search.pl?accid=PI+547430. [22] were grown in iron-deficient hydroponic conditions for one week, then transferred to iron sufficient conditions for another week. This induced a phenotypic response mimicking the growth of the plants in the field; initial chlorosis followed by re-greening. RNA was isolated from root tissue and transcript profiles were examined between the two near-isogenic lines using publicly available cDNA microarrays. By alleviating the iron deficiency stress our expectation was that plants would return to baseline expression levels. However, the microarray comparison identified four cDNAs that were under-expressed by a two-fold or greater difference in the iron inefficient plant compared to the iron efficient plant. This differential expression was re-examined and confirmed by real time PCR experimentation. Control experiments showed that these genes are not differentially expressed in plants grown continually under iron rich hydroponic conditions. The expression differences suggest potential residual effects of iron deficiency on plant health.}, }
@article {pmid17462982, year = {2007}, author = {Perez-Fidalgo, JA and Chirivella, I and Laforga, J and Colio, JM and Blanes, MD and Baydal, R and Roselló, S and De-la-Morena, E and Lluch, A}, title = {Parotid gland metastasis of a breast cancer.}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {9}, number = {4}, pages = {264-265}, doi = {10.1007/s12094-007-0051-2}, pmid = {17462982}, issn = {1699-048X}, mesh = {Anastrozole ; Antibiotics, Antineoplastic/administration &amp; dosage/therapeutic use ; Antimetabolites, Antineoplastic/administration &amp; dosage/therapeutic use ; Antineoplastic Agents, Alkylating/administration &amp; dosage/therapeutic use ; Antineoplastic Agents, Hormonal/administration &amp; dosage/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/therapeutic use ; *Breast Neoplasms/diagnosis/drug therapy/surgery ; Capecitabine ; *Carcinoma, Ductal, Breast/drug therapy/pathology/radiotherapy/secondary/surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/administration &amp; dosage/therapeutic use ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives/therapeutic use ; Doxorubicin/administration &amp; dosage/therapeutic use ; Female ; Fluorouracil/administration &amp; dosage/analogs &amp; derivatives/therapeutic use ; Humans ; Immunohistochemistry ; Mastectomy, Radical ; Middle Aged ; Nitriles/administration &amp; dosage/therapeutic use ; Parotid Gland/pathology/surgery ; Parotid Neoplasms/diagnosis/drug therapy/pathology/radiotherapy/*secondary/surgery ; Receptors, Estrogen/analysis ; Time Factors ; Treatment Outcome ; Triazoles/administration &amp; dosage/therapeutic use ; }, abstract = {Parotid gland metastases from malignant tumors are extremely rare. A 61-year-old woman was diagnosed with an early breast cancer with no expression of oestrogen and progesterone receptors. Five years later the patient presented a tumour in parotid gland. After total parotidectomy, microscopic analysis of the gland demonstrated an invasive duct carcinoma (IDC) with positive expression of oestrogen receptor. The patient was treated with chemotherapy followed by complementary local radiotherapy. Diagnosis of a metastasic tumour in parotid gland poses a challenge. In our case an immunohistochemical study of oestrogen receptor was fundamental to establish a diagnosis.}, }
@article {pmid17460770, year = {2007}, author = {Rashid-Kolvear, F and Pintilie, M and Done, SJ}, title = {Telomere length on chromosome 17q shortens more than global telomere length in the development of breast cancer.}, journal = {Neoplasia (New York, N.Y.)}, volume = {9}, number = {4}, pages = {265-270}, pmid = {17460770}, issn = {1476-5586}, mesh = {Breast Neoplasms/etiology/*genetics/pathology ; Carcinoma, Ductal, Breast/etiology/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/etiology/*genetics/pathology ; Chromosomal Instability/genetics ; Chromosomes, Human, Pair 17/*genetics ; Female ; Humans ; Telomere/*genetics ; }, abstract = {It is known that total telomere length is shorter in invasive breast cancer than in normal breast tissue but the status of individual telomere lengths has not been studied. Part of the difficulty is that usually telomere length in interphase cells is measured on all chromosomes together. In this study we compared normal breast epithelium, duct carcinoma in situ (DCIS), and invasive duct carcinoma (IDC) from 18 patients. Telomere length was specifically measured on chromosome 17q and was found to be shorter in DCIS and IDC than in normal breast epithelial cells, with more heterogeneity in telomere length in DCIS associated with IDC than in DCIS alone. More importantly, we found that the shortening of telomere on chromosome 17q is greater than the average shortening of all telomeres. This finding indicates that telomere shortening is not simply the result of the end replication problem; otherwise, all telomeres should be subjected to the same rate of telomere shortening. It seems there are mechanisms that preferentially erode some telomeres more than others or preferentially protect some chromosome ends. Our results suggest that the increased level of telomere shortening on 17q may be involved in chromosome instability and the progression of DCIS.}, }
@article {pmid17448240, year = {2007}, author = {von Euw, EM and Barrio, MM and Furman, D and Bianchini, M and Levy, EM and Yee, C and Li, Y and Wainstok, R and Mordoh, J}, title = {Monocyte-derived dendritic cells loaded with a mixture of apoptotic/necrotic melanoma cells efficiently cross-present gp100 and MART-1 antigens to specific CD8(+) T lymphocytes.}, journal = {Journal of translational medicine}, volume = {5}, number = {}, pages = {19}, pmid = {17448240}, issn = {1479-5876}, mesh = {Antigens, Neoplasm/*immunology ; *Apoptosis/drug effects/radiation effects ; CD8-Positive T-Lymphocytes/cytology/drug effects/*immunology/radiation effects ; Cell Differentiation/drug effects/radiation effects ; Cell Line, Tumor ; Cell Movement/drug effects/radiation effects ; Chemokine CCL19/pharmacology ; Coculture Techniques ; Cross-Priming/drug effects/*immunology/radiation effects ; Dendritic Cells/cytology/drug effects/*immunology/ultrastructure ; Epitopes/immunology ; Gamma Rays ; Humans ; Interleukin-10/immunology ; Interleukin-12/immunology ; MART-1 Antigen ; Melanoma/immunology/*pathology/ultrastructure ; Membrane Glycoproteins/*immunology ; Monocytes/cytology/immunology ; Necrosis ; Neoplasm Proteins/*immunology ; Phagocytosis/drug effects/immunology/radiation effects ; Receptors, CCR7/immunology ; Time Factors ; gp100 Melanoma Antigen ; }, abstract = {BACKGROUND: In the present study, we demonstrate, in rigorous fashion, that human monocyte-derived immature dendritic cells (DCs) can efficiently cross-present tumor-associated antigens when co-cultured with a mixture of human melanoma cells rendered apoptotic/necrotic by gamma irradiation (Apo-Nec cells).<br><br>METHODS: We evaluated the phagocytosis of Apo-Nec cells by FACS after PKH26 and PKH67 staining of DCs and Apo-Nec cells at different times of coculture. The kinetics of the process was also followed by electron microscopy. DCs maturation was also studied monitoring the expression of specific markers, migration towards specific chemokines and the ability to cross-present in vitro the native melanoma-associated Ags MelanA/MART-1 and gp100.<br><br>RESULTS: Apo-Nec cells were efficiently phagocytosed by immature DCs (iDC) (55 +/- 10.5%) at 12 hs of coculture. By 12-24 hs we observed digested Apo-Nec cells inside DCs and large empty vacuoles as part of the cellular processing. Loading with Apo-Nec cells induced DCs maturation to levels achieved using LPS treatment, as measured by: i) the decrease in FITC-Dextran uptake (iDC: 81 +/- 5%; DC/Apo-Nec 33 +/- 12%); ii) the cell surface up-regulation of CD80, CD86, CD83, CCR7, CD40, HLA-I and HLA-II and iii) an increased in vitro migration towards MIP-3beta. DC/Apo-Nec isolated from HLA-A*0201 donors were able to induce >600 pg/ml IFN-gamma secretion of CTL clones specific for MelanA/MART-1 and gp100 Ags after 6 hs and up to 48 hs of coculture, demonstrating efficient cross-presentation of the native Ags. Intracellular IL-12 was detected in DC/Apo-Nec 24 hs post-coculture while IL-10 did not change.<br><br>CONCLUSION: We conclude that the use of a mixture of four apoptotic/necrotic melanoma cell lines is a suitable source of native melanoma Ags that provides maturation signals for DCs, increases migration to MIP-3beta and allows Ag cross-presentation. This strategy could be exploited for vaccination of melanoma patients.}, }
@article {pmid17403919, year = {2007}, author = {Fiore, F and Castella, B and Nuschak, B and Bertieri, R and Mariani, S and Bruno, B and Pantaleoni, F and Foglietta, M and Boccadoro, M and Massaia, M}, title = {Enhanced ability of dendritic cells to stimulate innate and adaptive immunity on short-term incubation with zoledronic acid.}, journal = {Blood}, volume = {110}, number = {3}, pages = {921-927}, doi = {10.1182/blood-2006-09-044321}, pmid = {17403919}, issn = {0006-4971}, mesh = {Adjuvants, Immunologic/*pharmacology ; Bone Density Conservation Agents/pharmacology ; Cancer Vaccines/immunology ; Cell Proliferation/drug effects ; Cells, Cultured ; Dendritic Cells/*immunology ; Diphosphonates/*pharmacology ; Histocompatibility Antigens/immunology ; Humans ; Imidazoles/*pharmacology ; Immunity, Innate/*drug effects ; Immunologic Memory/drug effects ; Immunotherapy, Adoptive ; Lymphocyte Activation/drug effects ; Monocytes/*immunology ; Neoplasms/immunology/therapy ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; T-Lymphocytes/immunology ; Time Factors ; Zoledronic Acid ; }, abstract = {Vgamma9/Vdelta2 (gammadelta) T cells play a major role in innate immunity against microbes, stressed, and tumor cells. They represent less than 5% of peripheral blood lymphocytes but can be activated and expanded in vitro by aminobisphosphonates (ABP)-treated monocytes. The aim of this work was to determine whether ABP-treated dendritic cells (DCs) can also activate gammadelta T cells and regulate immune responses mediated by conventional alphabeta T cells. Highly purified immature (iDC) and mature DC (mDC) were generated from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol-treated iDC and mDC retained their immunostimulatory properties and induced the vigorous expansion of central memory and effector memory gammadelta T cells. gammadelta T cells displayed antitumor activity and appropriate cell surface antigens to target secondary lymphoid organs and exert costimulatory activity. Antigen-specific MHC-restricted immune responses, mediated by conventional alphabeta T cells, were improved by the concurrent gammadelta T-cell activation. In conclusion, large numbers of gammadelta T cells with effector and costimulatory activities are rapidly generated by Zol-treated iDC/mDC. This strategy is worthy of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.}, }
@article {pmid17389037, year = {2007}, author = {Turashvili, G and Bouchal, J and Baumforth, K and Wei, W and Dziechciarkova, M and Ehrmann, J and Klein, J and Fridman, E and Skarda, J and Srovnal, J and Hajduch, M and Murray, P and Kolar, Z}, title = {Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis.}, journal = {BMC cancer}, volume = {7}, number = {}, pages = {55}, pmid = {17389037}, issn = {1471-2407}, support = {F31 NR007844/NR/NINR NIH HHS/United States ; R01 NR008425/NR/NINR NIH HHS/United States ; }, mesh = {Biomarkers ; Breast/metabolism ; Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Collagen Type III/genetics ; Extracellular Matrix Proteins/genetics ; Female ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lasers ; Microdissection/*methods ; Tissue Array Analysis/*methods ; }, abstract = {BACKGROUND: Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells.<br><br>METHODS: We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR.<br><br>RESULTS: Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC.<br><br>CONCLUSION: IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.}, }
@article {pmid17385712, year = {2007}, author = {Ogura, S and Ohdaira, T and Hozumi, Y and Omoto, Y and Nagai, H}, title = {Metastasis-related factors expressed in pT1 pN0 breast cancer: assessment of recurrence risk.}, journal = {Journal of surgical oncology}, volume = {96}, number = {1}, pages = {46-53}, doi = {10.1002/jso.20805}, pmid = {17385712}, issn = {0022-4790}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*secondary/surgery ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*metabolism ; Logistic Models ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinases/*metabolism ; Middle Aged ; *Neoplasm Recurrence, Local/etiology ; Postoperative Period ; Predictive Value of Tests ; Prognosis ; Risk Factors ; Tissue Inhibitor of Metalloproteinase-2/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {OBJECTIVES: Previous reports have indicated that small breast cancers without lymph node metastasis present a favorable prognosis. However, 10-20% of patients with T1 N0 invasive ductal carcinoma experience recurrence and have a poor prognosis. The objective of this study was to examine whether certain metastasis-related factors are prognostic of cancer recurrence in such patients at risk for relapse.<br><br>METHODS: Nineteen patients with the carcinoma who had recurrence 1-15 years after margin-free resection were examined. The control group consisted of 20 patients with pT1 pN0 invasive ductal carcinoma who had no recurrence for > or =10 years after radical surgery. The two groups were compared with respect to clinical profiles, conventional neoplastic features, and immunohistochemical expressions of 16 metastasis-related factors.<br><br>RESULTS: No significant difference was found between the two groups in clinical profiles and conventional neoplastic features. However, six factors (MMP-2, MT1-MMP, T1MP-2, VEGF, cMET, and PCNA) were significantly expressed in the recurrence group against the control group. MMP-9 was significantly less expressed in the recurrence group. Of these factors, MMP-2, MT1-MMP, and VEGF showed the highest adjusted odds ratios.<br><br>CONCLUSION: MMP family and growth factors may be promising predictors of recurrence risk of early stage breast cancer.}, }
@article {pmid17383681, year = {2007}, author = {Sharma, G and Mirza, S and Prasad, CP and Srivastava, A and Gupta, SD and Ralhan, R}, title = {Promoter hypermethylation of p16INK4A, p14ARF, CyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients.}, journal = {Life sciences}, volume = {80}, number = {20}, pages = {1873-1881}, doi = {10.1016/j.lfs.2007.02.026}, pmid = {17383681}, issn = {0024-3205}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/*blood/diagnosis ; Cyclin-Dependent Kinase 2/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism ; DNA Methylation ; DNA, Neoplasm/*metabolism ; Female ; Humans ; Immunohistochemistry/methods ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Middle Aged ; Nerve Tissue Proteins/genetics/metabolism ; Promoter Regions, Genetic/*physiology ; Serum/chemistry ; Tumor Suppressor Protein p14ARF/*genetics/metabolism ; }, abstract = {Epigenetic mechanisms such as DNA methylation play important role in cancer. Epigenetic alterations involved in the onset and progression of breast cancer may serve as biomarkers for early detection and prediction of disease prognosis. Furthermore, using body fluids such as serum offers a non-invasive method to procure multiple samples for biomarker analyses. The aim of this study is to determine the correlation between methylation status of multiple cancer genes, p16(INK4A), p14(ARF), Cyclin D2 and Slit2 in invasive ductal carcinoma of the breast and paired serum DNA and clinicopathological parameters. Of the 36 breast cancer patients investigated, 31 (86%) tumors and 30 (83%) paired sera showed methylation of at least one of these 4 genes. Methylation frequencies varied from 27% for CyclinD2, 44% for p16(INK4A), 47% for p14(ARF) to 58% for Slit2. There was concordance between DNA methylation in tumor and paired serum DNA of each gene. This study underscores the potential utility of DNA methylation based screening of serum as a surrogate marker for tumor DNA methylation status of these genes in breast cancer. Further, expression profile of p16(INK4A) could be linked to epigenetic events, thus suggesting this pathway as a potential target for therapeutic strategies based on reversal of epigenetic silencing.}, }
@article {pmid17380381, year = {2008}, author = {Aulmann, S and Penzel, R and Longerich, T and Funke, B and Schirmacher, P and Sinn, HP}, title = {Clonality of lobular carcinoma in situ (LCIS) and metachronous invasive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {107}, number = {3}, pages = {331-335}, doi = {10.1007/s10549-007-9557-0}, pmid = {17380381}, issn = {0167-6806}, mesh = {Adult ; Breast Neoplasms/genetics/*pathology ; Cadherins/analysis ; Carcinoma in Situ/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; DNA, Mitochondrial/genetics ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasms, Second Primary/genetics/*pathology ; }, abstract = {Lobular carcinoma in situ (LCIS) of the breast is generally considered an indicator for a bilaterally increased risk of invasive breast cancer (IBC). However, as recent studies suggested a clonal relationship between a subset of synchronous LCIS and invasive lobular carcinomas (ILC), we aimed to examine a possible precursor role for LCIS and IBC occurring in the same breast at a later time. Out of a consecutive series of 88 LCIS, nine patients developed IBC (5 ILC and 4 invasive ductal carcinomas) between 2 and 10 years after initial biopsy. For each case, mitochondrial DNA heteroplasmy was analyzed in normal mammary gland epithelia, LCIS and IBC by PCR, direct DNA sequencing and phylogenetic tree clustering. Two cases of LCIS and ILC showed identical patterns of heteroplasmy. In one further case, additional mtDNA mutations were present in the ILC following LCIS. The remaining two cases of ILC and all 4 IDC were clonally unrelated to the previously diagnosed LCIS. While the overall risk for the development of invasive breast cancer following LCIS is relatively low and the majority of cases are clonally unrelated, our data clearly show that some LCIS eventually do progress to ILC. Thus, LCIS represents both an indicator lesion for an increased risk of subsequent invasive breast cancer and in some cases a precursor of ILC.}, }
@article {pmid17365021, year = {2007}, author = {Jin, Y and Fuller, L and Esquenazi, V and Blomberg, BB and Burke, GW and Ciancio, G and Tzakis, AG and Ricordi, C and Miller, J}, title = {Induction of auto-reactive regulatory T cells by stimulation with immature autologous dendritic cells.}, journal = {Immunological investigations}, volume = {36}, number = {2}, pages = {213-232}, doi = {10.1080/08820130601015775}, pmid = {17365021}, issn = {0882-0139}, support = {5 R01-DK25243-25/DK/NIDDK NIH HHS/United States ; }, mesh = {CD4-Positive T-Lymphocytes/immunology ; Cell Communication/immunology ; Dendritic Cells/*immunology ; Down-Regulation ; Epstein-Barr Virus Infections/immunology ; Forkhead Transcription Factors/biosynthesis/immunology ; Herpesvirus 4, Human/immunology ; Humans ; Immunity, Cellular ; Interleukin-2 Receptor alpha Subunit/biosynthesis/immunology ; Kidney Transplantation/immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {We have shown in ex vivo studies in donor bone marrow-infused kidney transplant recipients, that chimeric cells of either donor or recipient origin taken from the recipient's bone marrow down-regulated the recipient's cellular immune responses. In the present study, we have now induced regulatory T cells from peripheral blood mononuclear cells (PBMC) of renal transplant recipients or laboratory volunteers by multi-stimulation with autologous immature dendritic cell (iDC) enriched populations derived from either bone marrow cells (BMC) of the (immunosuppressed) kidney transplant recipients or PBMC of the laboratory volunteers (i.e., ibDC and ipDC, respectively). These regulatory T cells, induced by ibDC and ipDC, were autoreactive and designated as TAb and TAp with similar phenotypes and functional profiles. They were largely CD4 + CD25high, CD45RA low and CD45RO high, and uniformly expressed intracellular CTLA-4, and message of IL-4, IL-10, Foxp3, and differentially expressed TGFbeta. Their proliferative responses to autologous mature dendritic stimulating cells (mDC) were approximately two-fold stronger than to allogeneic mDC, and to allogeneic mDC were significantly lower than those of (control) autologous TPBL, suggesting an anergic state. TAb and TAp were not cytotoxic to autologous cells expressing Epstein-Barr virus (EBV) antigens, but were able to inhibit (regulate) the effector phase of this TPBL response to both autologous and allogeneic EBV lymphoblasts. This regulation appeared to require cell-to-cell contact.}, }
@article {pmid17363347, year = {2007}, author = {Reynolds, JL and Mahajan, SD and Sykes, DE and Schwartz, SA and Nair, MP}, title = {Proteomic analyses of methamphetamine (METH)-induced differential protein expression by immature dendritic cells (IDC).}, journal = {Biochimica et biophysica acta}, volume = {1774}, number = {4}, pages = {433-442}, pmid = {17363347}, issn = {0006-3002}, support = {R01 DA12366/DA/NIDA NIH HHS/United States ; R01 DA021537/DA/NIDA NIH HHS/United States ; R01 DA012366-09/DA/NIDA NIH HHS/United States ; R01 DA14218/DA/NIDA NIH HHS/United States ; R01 DA15628/DA/NIDA NIH HHS/United States ; R01 DA014218/DA/NIDA NIH HHS/United States ; R01 DA012366/DA/NIDA NIH HHS/United States ; R01 DA014218-06/DA/NIDA NIH HHS/United States ; F32 DA021535/DA/NIDA NIH HHS/United States ; R01 DA021537-02/DA/NIDA NIH HHS/United States ; 1 F32 DA02153501/DA/NIDA NIH HHS/United States ; F32 DA021535-01/DA/NIDA NIH HHS/United States ; R01 DA015628/DA/NIDA NIH HHS/United States ; }, mesh = {Dendritic Cells/drug effects/immunology/*metabolism/virology ; Gene Expression Regulation/drug effects ; HIV-1/physiology ; Humans ; Methamphetamine/*pharmacology ; Peroxidases/biosynthesis ; Peroxiredoxins ; Proteomics/methods ; Virus Replication/drug effects ; }, abstract = {In the US, the increase in methamphetamine (METH) use has been associated with increased human immunodeficiency virus (HIV-1) infection. Dendritic cells (DC) are the first line of defense against HIV-1. DC play a critical role in harboring HIV-1 and facilitate the infection of neighboring T cells. However, the role of METH on HIV-1 infectivity and the expression of the proteome of immature dendritic cells (IDC) has not been elucidated. We hypothesize that METH modulates the expression of a number of proteins by IDC that foster the immunopathogenesis of HIV-1 infection. We utilized LTR amplification, p24 antigen assay and the proteomic method of difference gel electrophoresis (DIGE) combined with protein identification through high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze the effects of METH on HIV-1 infectivity (HIV-1 IIIB; CXCR4-tropic, X4 strain) and the proteomic profile of IDC. Our results demonstrate that METH potentiates HIV-1 replication in IDC. Furthermore, METH significantly differentially regulates the expression of several proteins including CXCR3, protein disulfide isomerase, procathepsin B, peroxiredoxin and galectin-1. Identification of unique, METH-induced proteins may help to develop novel markers for diagnostic, preventive and therapeutic targeting in METH using subjects.}, }
@article {pmid17348440, year = {2007}, author = {Grenier, J and Soria, JC and Mathieu, MC and Andre, F and Abdelmoula, S and Velasco, V and Morat, L and Besse, B and Dunant, A and Spielmann, M and Delaloge, S}, title = {Differential immunohistochemical and biological profile of squamous cell carcinoma of the breast.}, journal = {Anticancer research}, volume = {27}, number = {1B}, pages = {547-555}, pmid = {17348440}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alphapapillomavirus/genetics ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology/virology ; Carcinoma, Ductal, Breast/metabolism/*pathology/virology ; Carcinoma, Squamous Cell/metabolism/*pathology/virology ; Cohort Studies ; DNA-Binding Proteins/analysis ; ErbB Receptors/analysis ; Female ; Humans ; Immunohistochemistry ; Keratin-5/analysis ; Keratin-6/analysis ; Ki-67 Antigen/analysis ; Middle Aged ; Papillomavirus Infections/metabolism/pathology/virology ; Polymerase Chain Reaction ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Survival Analysis ; Trans-Activators/analysis ; Transcription Factors ; Tumor Suppressor Proteins/analysis ; }, abstract = {BACKGROUND: Pure or metaplastic squamous cell carcinoma (SCC) of the breast is a rare entity with an unclear pathogeny and aggressive clinical behaviour. An attempt was made to characterize its differential immunohistochemical and biological profile.<br><br>PATIENTS AND METHODS: Twenty-seven cases of SCC (pure or not) of the breast were matched with 27 ductal invasive carcinomas (IDC) for age, tumour size, nodal involvement and year of diagnosis. The expression levels of oestrogen receptor (ER), progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), HER2, Cyclin Bl, hTERT, cytokeratins (CK) 5/6 and p63 were determined immunohistochemically in both cohorts. The presence of the human papilloma virus (HPV) genome was investigated by polymerase chain reaction (PCR).<br><br>RESULTS: Pure and metaplastic SCC displayed common profiles typifying a basal origin: they never expressed ER or PR, were HER2-negative in 93% of cases, exhibited positivity for CK5/6 or EGF-R in 75% and 85%, and for p63 in 70% of cases and were highly proliferative. These profiles were markedly different from those of matched controls (p<0.001 for five markers) except for HER2 and hTERT. The HPVgenome was detected in 2 out of 14 cases (14%) of SCC.<br><br>CONCLUSION: The expression profile of SCC of the breast was markedly different from that of IDC. A typical "basal-like" phenotype was displayed that may explain part of their behaviour and justify specific therapeutic approaches. HPV infection was not a leading oncogenic event in SCC of the breast.}, }
@article {pmid17319852, year = {2007}, author = {Hanna, W and Nofech-Mozes, S and Kahn, HJ}, title = {Intratumoral heterogeneity of HER2/neu in breast cancer--a rare event.}, journal = {The breast journal}, volume = {13}, number = {2}, pages = {122-129}, doi = {10.1111/j.1524-4741.2007.00396.x}, pmid = {17319852}, issn = {1075-122X}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; *Genes, erbB-2 ; *Genetic Heterogeneity ; Humans ; Immunohistochemistry ; In Situ Hybridization/methods ; Receptor, ErbB-2/*genetics ; }, abstract = {HER2/neu is overexpressed in about 20% of invasive breast carcinomas. Numerous studies have shown that there is high level of concordance between the HER2/neu status of the primary breast cancer and the metastases of a given patient. Recently, changes in HER2/neu status with tumor progression have been reported, suggesting the possibility of an emerging different tumor clone. Little is known about intratumoral heterogeneity with regard to HER2/neu oncoprotein overexpression. We identified nine cases of invasive ductal carcinoma that showed intratumoral variation in HER2/neu oncoprotein expression by immunohistochemistry. This was confirmed by the intratumoral variation in the amplification status of the HER2/neu gene by fluorescence in situ hybridization and by chromogenic in situ hybridization. The results of this study suggest that some cases of primary breast carcinoma are heterogeneous in regard to HER2/neu gene amplification or protein overexpression. Heterogeneity of HER2/neu status in a tumor may be a rare event or underestimated. This phenomenon should be examined as it may contribute to a better understanding of the variation in therapeutic responses and the conflicting data in studies about the prognostic and predictive role of HER2/neu status in subsets of breast cancer patients.}, }
@article {pmid17316413, year = {2007}, author = {Millar, EK and Tran, K and Marr, P and Graham, PH}, title = {p27KIP-1, cyclin A and cyclin D1 protein expression in ductal carcinoma in situ of the breast: p27KIP-1 correlates with hormone receptor status but not with local recurrence.}, journal = {Pathology international}, volume = {57}, number = {4}, pages = {183-189}, doi = {10.1111/j.1440-1827.2007.02079.x}, pmid = {17316413}, issn = {1320-5463}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cyclin A/genetics/*metabolism ; Cyclin D1/genetics/*metabolism ; Cyclin-Dependent Kinase Inhibitor p27/genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; }, abstract = {Using whole sections of formalin-fixed paraffin-embedded material the expression of p27(KIP-1), cyclin A and cyclin D1 was examined in 60 cases of ductal carcinoma in situ (DCIS) using routine immunohistochemistry with a median follow up of 95 months (range 10-139 months) to identify any association with disease recurrence. Fifty-six patients were treated by local excision and radiotherapy and four by mastectomy without radiotherapy. There was a highly significant positive association between p27(KIP-1) and estrogen receptor/progesterone receptor (ER/PR) status (P = 0.002, P = 0.02) and with p27(KIP-1) and cyclin D1 expression (P = 0.002). A trend between cyclin A and PR status (P = 0.08) was also identified. These findings mirror those described in invasive ductal carcinoma, but there were no associations of any biomarker with histological parameters such as nuclear grade or with local recurrence on univariate analysis, which was present in four of the 56 locally excised group (7.1%). Further examination of a larger cohort may be worthwhile to explore the possible role as adjunctive predictive markers to aid clinical decision making.}, }
@article {pmid17314521, year = {2007}, author = {Rebbapragada, A and Wachihi, C and Pettengell, C and Sunderji, S and Huibner, S and Jaoko, W and Ball, B and Fowke, K and Mazzulli, T and Plummer, FA and Kaul, R}, title = {Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract.}, journal = {AIDS (London, England)}, volume = {21}, number = {5}, pages = {589-598}, doi = {10.1097/QAD.0b013e328012b896}, pmid = {17314521}, issn = {0269-9370}, mesh = {Adult ; Cervix Uteri/immunology/virology ; Chronic Disease ; Cross-Sectional Studies ; Dendritic Cells/immunology ; Female ; Genitalia, Female/*immunology/virology ; HIV Infections/complications/*immunology/transmission/virology ; HIV-1/*isolation &amp; purification ; Herpes Genitalis/complications/*immunology/transmission/virology ; Humans ; Immunity, Mucosal ; Middle Aged ; Mucous Membrane/immunology ; Sex Work ; T-Lymphocyte Subsets/immunology ; Vagina/immunology/virology ; Virus Shedding/immunology ; }, abstract = {OBJECTIVE: There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80% of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract.<br><br>METHODS: Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined.<br><br>RESULTS: HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels.<br><br>CONCLUSIONS: The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.}, }
@article {pmid17290405, year = {2007}, author = {Nielsen, BS and Rank, F and Illemann, M and Lund, LR and Danø, K}, title = {Stromal cells associated with early invasive foci in human mammary ductal carcinoma in situ coexpress urokinase and urokinase receptor.}, journal = {International journal of cancer}, volume = {120}, number = {10}, pages = {2086-2095}, doi = {10.1002/ijc.22340}, pmid = {17290405}, issn = {0020-7136}, mesh = {Breast Neoplasms/enzymology/genetics/*metabolism/*pathology ; Carcinoma in Situ/enzymology/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/metabolism/*pathology ; Fluorescent Antibody Technique/methods ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization ; Matrix Metalloproteinase 13/metabolism ; RNA, Messenger/biosynthesis/genetics ; Receptors, Cell Surface/*biosynthesis/metabolism ; Receptors, Urokinase Plasminogen Activator ; Stromal Cells/enzymology/metabolism/pathology ; Urokinase-Type Plasminogen Activator/*biosynthesis/genetics/metabolism ; }, abstract = {The transition from ductal carcinoma in situ (DCIS) of the breast to invasive ductal carcinoma is facilitated by proteolytic degradation of basement membrane. The transition can be identified as microinvasive foci in a small proportion of DCIS lesions. We have previously found that MMP-13 is frequently expressed in such foci. To establish whether plasmin-directed proteolysis is likely to be involved in early invasion, we have here studied the expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) in human DCIS lesions with and without microinvasion. uPA mRNA was detected in periductal stromal cells in all of 9 DCIS lesions with microinvasion and in 2 of 9 DCIS lesions without microinvasion by in situ hybridization. The uPA mRNA signal was seen in numerous stromal cells in microinvasive areas together with MMP-13 mRNA expressing cells. Double immunofluorescence analyses, using emission fingerprinting, showed that the uPA expressing stromal cells included both myofibroblasts and macrophages. The early invasive carcinoma cells were negative for uPA. uPAR immunoreactivity was focally upregulated in periductal stromal cells in all of the 9 DCIS lesions with microinvasion and in only 2 of the 9 DCIS lesions without microinvasion. uPAR was seen in both macrophages and myofibroblasts in microinvasive areas, and it was evident that uPA and uPAR colocalized in both fibroblast-like cells and macrophage-like cells. We conclude that periductal macrophages and myofibroblasts are strongly involved in the initial steps of breast cancer invasion by focally upregulating the expression of the plasminogen activation system and MMP-13.}, }
@article {pmid17288765, year = {2006}, author = {Huang, J and Zheng, Z and Hu, SS and Yang, YJ and Zhao, H and Song, LF and Song, YH and Zhu, J and Zhao, SH}, title = {[Comparison between pre- and post-transplant diagnosis of end-stage dilated cardiomyopathy].}, journal = {Zhonghua xin xue guan bing za zhi}, volume = {34}, number = {11}, pages = {1005-1008}, pmid = {17288765}, issn = {0253-3758}, mesh = {Adolescent ; Adult ; Cardiomyopathy, Dilated/*diagnosis/pathology/surgery ; Heart Failure/diagnosis/pathology ; *Heart Transplantation ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Stroke Volume ; }, abstract = {OBJECTIVE: To evaluate the discrepancy between pre- and post-transplant diagnosis of end-stage dilated cardiomyopathy, a pre-transplantation diagnosis was compared with the diagnosis made after macroscopic and microscopic examination of the explanted hearts in 40 cardiac transplant recipients who had undergone cardiac transplantation at our institute.<br><br>METHODS: Pre-operation echocardiograms were obtained in all patients and coronary angiogram was obtained in 9 patients who had significant risk factors for coronary heart disease (CHD). CHD was considered present when there was a 75% reduction in cross-sectional luminal area of >or= 1 major coronary artery. Idiopathic dilated cardiomyopathy (IDC) was diagnosed when ventricular dilation and global reduction in ventricular systolic function were present in the absence of any identifiable cause. IDC patients with an alcohol consumption of > 100 g/day during the last 12 months before the onset of congestive heart failure were classified as having alcoholic cardiomyopathy. The pathological diagnosis of arrhythmogenic right ventricular cardiomyopathy was formulated in the presence of gross/or histological evidence of regional or diffuse transmural fatty or fibrofatty infiltration of the right ventricular free wall.<br><br>RESULTS: Before transplantation, 45.0%, 17.5%, 17.5% and 7.5% of patients were classified as IDC, CHD, alcoholic cardiomyopathy and hypertrophic cardiomyopathy. Post-transplant CHD diagnosis was made in all patients with a pre-transplant diagnosis of CHD. Post-transplant CHD diagnosis was also established in 4 patients with a pre-transplant diagnosis of IDC, in 4 patients with presumptive alcoholic cardiomyopathy, in 1 patient with hypertensive cardiomyopathy and in 1 patient with a pre-transplant diagnosis of aortic valve disease. Post-transplant arrhythmogenic right ventricular cardiomyopathy diagnosis was made in 6 patients with a pre-transplant diagnosis of IDC or KaShan disease. Post-transplant giant cell myocarditis diagnosis was made in 1 patient with a pre-transplant diagnosis of IDC.<br><br>CONCLUSION: Post-transplant CHD diagnosis is significantly higher than that of pre-transplant (42.5% vs. 17.5%, P < 0.05). Part of these patients might benefit from bypass surgery or PCI. Therefore, "in-depth" search for a heart failure cause, especially the coronary angiography examination, should be conducted in all heart transplantation candidates due to heart failure, regardless of their clinical presentation.}, }
@article {pmid17283573, year = {2007}, author = {Rampey, AM and Lathers, DM and Woodworth, BA and Schlosser, RJ}, title = {Immunolocalization of dendritic cells and pattern recognition receptors in chronic rhinosinusitis.}, journal = {American journal of rhinology}, volume = {21}, number = {1}, pages = {117-121}, doi = {10.2500/ajr.2007.21.2998}, pmid = {17283573}, issn = {1050-6586}, mesh = {Biomarkers/metabolism ; Biopsy ; Chronic Disease ; Dendritic Cells/immunology/*pathology ; Humans ; Immunohistochemistry ; Receptors, Pattern Recognition/*metabolism ; Rhinitis/complications/*immunology/pathology ; Sinusitis/*immunology/pathology ; }, abstract = {BACKGROUND: Dendritic cell (DC) activation and antigen presentation to T cells are critical to innate and adaptive immunity. Toll-like receptors (TLRs) are known to bind pathogen-associated molecular patterns in addition to sinonasally secreted surfactant proteins (SP) such as SP-A and SP-D. TLR binding is known to activate DCs. Based on these observations, we sought to establish the presence, in sinonasal mucosa, of DC and the pattern recognition receptors (PRRs), CD14, TLR2, and TLR4.<br><br>METHODS: Sinonasal biopsy specimens were taken from patients with eosinophilic nonatopic nasal polyposis (n = 4), allergic fungal sinusitis (n = 1), and nondiseased patients undergoing cerebrospinal fluid leak repair or pituitary tumor resection (n = 2). Tissue samples were stained immunohistochemically for PRR (CD14, TLR2, and TLR4), mature DC marker (CD208), iDC marker (CD209), or isotype controls.<br><br>RESULTS: Immature and mature DC were immunolocalized to the subepithelial stroma and ciliated epithelial surface, respectively. Diffuse staining of CD14 was observed throughout the stroma with additional staining in the ciliated epithelium. The TLR markers showed no staining in the ciliated epithelium. TLR2 primarily localized in stroma immediately deep to the ciliated epithelial surface. TLR4 immunolocalized to submucosal seromucinous gland ductal epithelium. Data from nondiseased patients were mixed, with one patient showing minimal staining of any of the tested cellular markers.<br><br>CONCLUSION: This study indicates progressive DC activation and emigration of mature antigen-presenting cells from the epithelial surfaces of sinonasal mucosa. The presence of TLR known to bind SP-A and SP-D suggests a link between SP expression and immune response in sinonasal mucosa.}, }
@article {pmid17265021, year = {2007}, author = {Bergmann, C and Strauss, L and Zeidler, R and Lang, S and Whiteside, TL}, title = {Expansion and characteristics of human T regulatory type 1 cells in co-cultures simulating tumor microenvironment.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {56}, number = {9}, pages = {1429-1442}, doi = {10.1007/s00262-007-0280-9}, pmid = {17265021}, issn = {0340-7004}, support = {P0-1 DE12321/DE/NIDCR NIH HHS/United States ; }, mesh = {*Carcinoma, Squamous Cell/immunology ; Cell Line, Tumor ; Cell Proliferation ; Coculture Techniques ; Cytokines/metabolism/pharmacology ; Dendritic Cells/immunology ; Enzyme-Linked Immunosorbent Assay ; *Head and Neck Neoplasms/immunology ; Humans ; *Interleukin-10 ; *Lymphocyte Activation ; Sirolimus/pharmacology ; T-Lymphocytes, Regulatory/drug effects/*immunology ; }, abstract = {OBJECTIVE: Chronic inflammation and cancer development are associated with dysregulated immune responses and the presence of regulatory T cells (T(reg)). To study the role of T(reg) in tumor cell escape from immune surveillance, an in vitro model simulating the tumor microenvironment and promoting the induction and expansion of IL-10(+) T(reg)type 1 (Tr1) was established.<br><br>METHODS: An in vitro co-culture system (IVA) included an irradiated head and neck squamous cell carcinoma cell line, immature dendritic cells (iDC), CD4(+)CD25(-)T cells and cytokines, IL-2 (10 IU/ml), IL-10 (20 IU/ml), IL-15 (20 IU/ml) +/- 1 nM rapamycin. Autologous iDC and CD4(+)CD25(-) T cells were obtained from the peripheral blood of 15 normal donors. Co-cultures were expanded for 10 days. Proliferating lymphocytes were phenotyped by multi-color flow cytometry. Their suppressor function was measured in CFSE inhibition assays +/- neutralizing anti-IL-10 mAb and using transwell cultures. Culture supernatants were tested for IL-4, IL-10, TGF-beta and IFN-gamma in ELISA.<br><br>RESULTS: In the IVA, low doses of IL-2, IL-10 and IL-15 promoted induction and expansion of CD3(+)CD4(+)CD25(-)IL2Rbeta(+)IL2Rgamma(+)FoxP3(+)CTLA-4(+)IL-10(+) cells with suppressor activity (mean suppression +/- SD = 58 +/- 12%). These suppressor cells produced IL-10 (mean +/- SD = 535 +/- 12 pg/ml) and TGF-beta (mean +/- SD = 512 +/- 38 pg/ml), but no IL-4 or IFN-gamma. Suppressor function of co-cultures correlated with the percent of expanding IL-10(+) Tr1 cells (r (2)=()0.9; P < 0.001). The addition of rapamycin enriched Tr1 cells in all co-cultures. Neutralizing anti-IL-10 mAb abolished suppressive activity. Suppression was cell-contact independent.<br><br>CONCLUSION: The tumor microenvironment promotes generation of Tr1 cells which have the phenotype distinct from that of CD4(+)CD25(high)FoxP3(+) nTreg and mediate IL-10 dependent immune suppression in a cell-contact independent manner. Tr1 cells may play a critical role in cancer progression.}, }
@article {pmid17236203, year = {2007}, author = {Ohuchida, K and Mizumoto, K and Ohhashi, S and Yamaguchi, H and Konomi, H and Nagai, E and Yamaguchi, K and Tsuneyoshi, M and Tanaka, M}, title = {Twist, a novel oncogene, is upregulated in pancreatic cancer: clinical implication of Twist expression in pancreatic juice.}, journal = {International journal of cancer}, volume = {120}, number = {8}, pages = {1634-1640}, doi = {10.1002/ijc.22295}, pmid = {17236203}, issn = {0020-7136}, mesh = {Adenocarcinoma, Mucinous/genetics/metabolism ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Pancreatic Ductal/genetics/metabolism ; Carcinoma, Papillary/genetics/metabolism ; Cells, Cultured ; Epithelial Cells/metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Nuclear Proteins/*genetics ; Pancreas/metabolism/pathology ; Pancreatic Juice/*physiology ; Pancreatic Neoplasms/*genetics/metabolism ; Pancreatitis/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Twist-Related Protein 1/*genetics ; Up-Regulation ; }, abstract = {Despite evidence that Twist, a highly conserved basic helix-loop-helix transcription factor, is a novel oncogene, there are no reports describing Twist expression in pancreatic cancer. Intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia (PanIN) are precursor lesions of pancreatic cancer. To clarify involvement of Twist expression in pancreatic cancer, we used quantitative reverse transcription-polymerase chain reaction and examined Twist expression in pancreatic cancer, IPMN, and non-neoplastic pancreas using bulk tissues (11 cancers, 18 IPMNs, and 15 non-neoplastic pancreata), microdissected cells (cancer from 22 sections, IPMN from 19 sections, PanIN from 6 sections, and pancreatitis-affected epithelial cells from 14 sections), and pancreatic juice (16 from cancer, 28 from IPMN, and 17 from pancreatitis). Twist expression differed significantly between cancer and IPMN bulk tissues (p < 0.0001) but not between cancer and non-neoplastic tissues. Twist expressions differed significantly between microdissected cancer cells, IPMN cells, and pancreatitis-affected cells (all comparisons, p < 0.017). PanIN cells expressed significantly lower levels of Twist than did IDC cells (p = 0.016). Twist expression differed significantly between cancer and IPMN juice samples (p = 0.0002) but not between cancer and pancreatitis juice samples. Receiver operation characteristic curve analyses revealed that measurement of Twist was more useful for discriminating cancer from IPMN than from chronic pancreatitis (p = 0.009). Our results suggest that Twist is involved in tumor progression of pancreatic cancer and that measurement of Twist in pancreatic juice may be useful to differentiate pancreatic cancer from nonmalignant neoplasms such as IPMN.}, }
@article {pmid17223209, year = {2007}, author = {Miettinen, KH and Magga, J and Vuolteenaho, O and Vanninen, EJ and Punnonen, KR and Ylitalo, K and Tuomainen, P and Peuhkurinen, KJ}, title = {Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy.}, journal = {Regulatory peptides}, volume = {140}, number = {3}, pages = {178-184}, doi = {10.1016/j.regpep.2006.12.004}, pmid = {17223209}, issn = {0167-0115}, mesh = {Adult ; Apelin ; Biomarkers/blood ; Cardiomyopathy, Dilated/blood/*diagnosis ; Carrier Proteins/*blood ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*blood ; Interleukin-6/blood ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Norepinephrine/blood ; Peptide Fragments/blood ; Predictive Value of Tests ; Radioimmunoassay ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {Apelin is a recently discovered peptide ligand reported to be involved in the regulation of cardiovascular homeostasis. The exact role of apelin in the pathophysiology of congestive heart failure has remained obscure, and the reported circulating levels of apelin in patients with heart failure have been contradictory. To establish the role of apelin in the assessment of cardiac dysfunction we measured plasma apelin levels in 65 patients with congestive heart failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy volunteers by specific radioimmunoassay. IDC patients were carefully examined including echocardiography, both-sided cardiac catheterization and cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), epinephrine and norepinephrine were determined. Plasma apelin levels were similar in IDC patients (median 26.5 pg/ml, range<3.40-97.6 pg/ml) and in control subjects (median 24.1 pg/ml, range 19.0-28.7 pg/ml; p=NS). Unlike the levels of NT-proBNP, IL-6, TNF-alpha, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure. Our study demonstrates that although disturbed apelin-APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction.}, }
@article {pmid17218854, year = {2007}, author = {Tang, P and Hajdu, SI and Lyman, GH}, title = {Ductal carcinoma in situ: a review of recent advances.}, journal = {Current opinion in obstetrics &amp; gynecology}, volume = {19}, number = {1}, pages = {63-67}, doi = {10.1097/GCO.0b013e3280114a3a}, pmid = {17218854}, issn = {1040-872X}, mesh = {Biomarkers ; Breast Neoplasms/genetics/pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/*therapy ; Female ; Humans ; *Mastectomy, Segmental ; Neoplasm Recurrence, Local/prevention &amp; control ; Prognosis ; }, abstract = {PURPOSE OF REVIEW: This review summarizes recent findings on ductal carcinoma in situ of the breast and their impact on prognosis and management of the disease.<br><br>RECENT FINDINGS: Great advances have been made in our understanding of ductal carcinoma in situ. Nuclear grading is probably the most important pathological factor that affects clinical outcome and correlates with distinct genetic pathways. Identifying key molecules in each pathway may provide better markers for prognostic, predictive and therapeutic purposes. Not all cases of ductal carcinoma in situ will progress to invasive ductal carcinoma, and identifying this subgroup of patients should lead to a reduction of overtreatment. Progenitor cell theory at the cellular level and sick lobe theory at the architectural level may help provide a better understanding of ductal carcinoma in situ from a different perspective and facilitate the development of individualized therapy. Prevention of local recurrence is the primary goal for treatment. Debate continues, however, on the use of radiotherapy, hormonal therapy, and sentinel lymph node biopsy. A panel of molecular markers may be needed for accurately predicting clinical outcome for the disease.<br><br>SUMMARY: Understanding the carcinogenesis of ductal carcinoma in situ at the molecular level may lead to an optimal individualized therapy with minimal over or undertreatment.}, }
@article {pmid17212145, year = {2006}, author = {Sakurai, K and Amano, S and Enomoto, K and Matsuo, S}, title = {[A case of advanced breast cancer with meningeal carcinomas and orbital metastasis successfully treated with multi-disciplinary therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {33}, number = {12}, pages = {1913-1915}, pmid = {17212145}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Breast Neoplasms/*pathology/*therapy ; Carcinoma, Ductal/*pathology/*therapy ; Combined Modality Therapy ; Female ; Humans ; Meningeal Neoplasms/drug therapy/radiotherapy/*secondary ; Middle Aged ; Orbital Neoplasms/drug therapy/radiotherapy/*secondary ; Paclitaxel/therapeutic use ; Quality of Life ; Tegafur/therapeutic use ; Trastuzumab ; }, abstract = {We report a case of advanced breast cancer with meningeal metastasis and orbital metastasis (T4bN3cM1, Stage IV) achieving a significant improvement in QOL by multi-disciplinary therapy. The patient was a 51-year-old woman who had headaches and an ulcerative breast lump with meningeal metastasis and orbital metastasis. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for HER2/neu protein expression. She received 9 cycles of weekly trastuzumab and radiation therapy for meningeal metastasis and orbital metastasis. Although the size of breast tumor, orbital metastasis lesion, and meningeal metastasis lesion exhibited no change, clinical symptoms were improved. One year later, she received paclitaxel so that the sensitivity of HER2/neu dropped. However, the tumor markers relapsed and we then changed paclitaxel to TS-1. Eighteen-months later, she had no neurological symptoms. Multi disciplinary therapy can improve patient's QOL and the clinical outcomes in Stage IV advanced breast cancer.}, }
@article {pmid17210616, year = {2007}, author = {Kim, HJ and Yang, JS and Woo, SS and Kim, SK and Yun, CH and Kim, KK and Han, SH}, title = {Lipoteichoic acid and muramyl dipeptide synergistically induce maturation of human dendritic cells and concurrent expression of proinflammatory cytokines.}, journal = {Journal of leukocyte biology}, volume = {81}, number = {4}, pages = {983-989}, doi = {10.1189/jlb.0906588}, pmid = {17210616}, issn = {0741-5400}, mesh = {Acetylmuramyl-Alanyl-Isoglutamine/*pharmacology ; Cell Differentiation ; Cytokines/*metabolism ; Dendritic Cells/drug effects/metabolism/*physiology ; Drug Synergism ; Endocytosis ; Histocompatibility Antigens Class II/metabolism ; Humans ; Inflammation/*metabolism ; Interleukin-10/immunology/metabolism ; Interleukin-12/metabolism ; Lipopolysaccharides/*pharmacology ; Monocytes/drug effects/metabolism/physiology ; Teichoic Acids/*pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Maturation is an important process by which dendritic cells (DC) develop the potent antigen-presentation capacity necessary for efficient activation of adaptive immunity. Here, we have investigated the ability of lipoteichoic acid (LTA) and muramyl dipeptide (MDP; the minimal structural unit of peptidoglycan with immunostimulating activity) to induce maturation of human immature DC (iDC), derived from peripheral blood CD14-positive cells, and the production of proinflammatory cytokines. Exposure of iDC to staphylococcal LTA (StLTA) at 1 or 10 microg/ml or MDP at 0.1 or 1 microg/ml alone had little effect on the expression of CD80 and CD83, with a minor increase in expression of CD86, all of which are indicative of cell surface markers for maturation. However, there was a synergistic expression of these molecules when iDC were stimulated with StLTA and MDP together. It is interesting that selective induction of MHC Class II expression was observed during the DC maturation, only when costimulated with LTA plus MDP, and Escherichia coli LPS induced dramatic expression of MHC Classes I and II. Endocytosis assay using Dextran-FITC showed that costimulation with StLTA and MDP attenuated the endocytic capacity of the DC, which is a typical phenomenon of DC maturation. Concomitantly, increased expression of DEC-205, but decreased expression of CD206, was observed under the same costimulating condition. Furthermore, ELISA showed that secretions of TNF-alpha and IL-12 p40, but not IL-10, were induced in iDC by the costimulation. These results suggest that StLTA and MDP synergistically induce maturation and activation of human DC.}, }
@article {pmid17205249, year = {2007}, author = {Munhoz, AM and Filassi, JR and Aldrighi, C and Ricci, MD and Martella, E and de Barros, AC and Gemperli, R and Ferreira, MC}, title = {Bilateral reduction mammaplasty for immediate breast conservation surgery reconstruction and intraoperative radiotherapy: a preliminary report.}, journal = {Aesthetic plastic surgery}, volume = {31}, number = {1}, pages = {94-100}, doi = {10.1007/s00266-006-0200-y}, pmid = {17205249}, issn = {0364-216X}, mesh = {Adult ; Breast Neoplasms/*radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; *Intraoperative Period ; *Mammaplasty ; *Mastectomy, Segmental ; }, abstract = {BACKGROUND: Breast conservation surgery and postoperative radiotherapy are widely accepted as the treatment of choice for patients with early breast cancer. Despite its oncologic benefits, the radiotherapy may cause unpredictable outcomes in soft tissues, especially in patients undergoing breast reconstruction. Described recently, intraoperative irradiation (IORT) has been indicated for selected patients as an alternative to radiotherapy with fewer adverse local effects. Clinical use of reduction mammaplasty (RM) techniques in oncologic breast surgery has been described previously. However, no previous studies have mentioned its application after breast conservation surgery and IORT.<br><br>METHODS: The authors used RM to reconstruct a partial breast tissue defect secondary to breast conservation surgery followed by IORT treatment in a 46-year-old patient with an 11-mm invasive ductal carcinoma between the superior internal quadrants of the right breast.<br><br>RESULTS: Satisfactory breast volume and shape were achieved, and no immediate or late complications were observed. After 2 postoperative years, no evidence of fat necrosis, tumor recurrence, or tissue volume loss was observed.<br><br>CONCLUSION: The initial data indicate that RM in the setting of breast conservation surgery reconstruction and IORT is feasible. With appropriate patient selection, respecting indications and limitations, RM has its place among the various reconstructive techniques. Additional studies with larger clinical series and longer follow-up periods are necessary to analyze the precise IORT effects in patients submitted to immediate breast conservation surgery reconstruction.}, }
@article {pmid17198087, year = {2007}, author = {Zhang, R and Bharadwaj, U and Li, M and Chen, C and Yao, Q}, title = {Effects of pentoxifylline on differentiation, maturation, and function of human CD14+ monocyte-derived dendritic cells.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {30}, number = {1}, pages = {89-95}, doi = {10.1097/01.cji.0000211323.53396.38}, pmid = {17198087}, issn = {1524-9557}, support = {AT003094/AT/NCCIH NIH HHS/United States ; DE15543/DE/NIDCR NIH HHS/United States ; EB-002436/EB/NIBIB NIH HHS/United States ; HL083471/HL/NHLBI NIH HHS/United States ; HL65916/HL/NHLBI NIH HHS/United States ; HL72716/HL/NHLBI NIH HHS/United States ; }, mesh = {Cell Differentiation/drug effects/immunology ; Dendritic Cells/*drug effects/*immunology ; Humans ; Interferon-gamma/biosynthesis/immunology ; Lipopolysaccharide Receptors/*immunology ; Lymphocyte Activation/drug effects/immunology ; Monocytes/*drug effects/immunology ; Pentoxifylline/*pharmacology ; T-Lymphocytes/drug effects/immunology ; Tumor Necrosis Factor-alpha/biosynthesis/immunology ; }, abstract = {Pentoxifylline (PTX) is a nonspecific phosphodiesterase inhibitor which has potent immunoregulatory and antiinflammatory effects. Although its immunomodulation property has been recognized, it is not clear whether PTX could affect dendritic cells (DCs), the most efficient antigen-presenting cells. The purpose of this study was to determine whether PTX could suppress DC differentiation, maturation, and its associated functions. Immature DCs (iDCs) were generated from human peripheral blood mononuclear cell CD14+ monocytes cultured with granulocyte macrophage colony stimulating factor and interleukin-4 for 5 days. PTX concentration-dependently suppressed the expression of iDC differentiation markers including CD54, CD80, CD86, and human leukocyte antigen-DR. In addition, PTX also inhibited DC maturation marker CD83 expression after stimulating DCs with lipopolysaccharide. Furthermore, PTX inhibited the antigen-uptake ability of DCs when tested by fluorescein isothiocyanate-dextran endocytosis assay. PTX significantly reduced the production of TNF-alpha and IFN-gamma in mature DCs (mDCs). Consequently, PTX-treated mDCs showed a reduced activity of mDC-induced T-cell allostimulation and proliferation by mixed-lymphocyte reaction (MLR) assay. Therefore, PTX significantly inhibits CD14+ monocyte-derived DC differentiation, maturation, antigen-uptake ability of iDCs, and antigen-presentation ability of mDCs possibly due to the suppression of TNF-alpha and IFN-gamma production. These results suggested that inhibitory effects of PTX on DCs may contribute its antiinflammatory and immunoregulatory functions.}, }
@article {pmid21475451, year = {2007}, author = {Younis, LK and El Sakka, H and Haque, I}, title = {The Prognostic Value of E-cadherin Expression in Breast Cancer.}, journal = {International journal of health sciences}, volume = {1}, number = {1}, pages = {43-51}, pmid = {21475451}, issn = {1658-3639}, abstract = {BACKGROUND: Breast cancer continues to be a major cause of morbidity and mortality throughout the world. The behavior of breast cancer varies widely. Several parameters have been investigated to predict the prognosis in breast cancer. But still there is no single parameter that can predict prognosis in an individual patient. Among the novel prognostic markers is E-cadherin; a calcium-dependent epithelial cell adhesion molecule. Its loss has been associated with metastases, thereby providing evidence for its role as an invasion suppressor. The objective of the present study was to assess the prognostic value of E-cadherin expression in breast cancer cases, and its correlations with the other studied prognostic parameters.<br><br>METHODS: The study comprised 54 breast cancer patients admitted at King Fahd Specialist Hospital, Qassim during the period 2001-2006. The median tumor size was 3cms. Fifty cases (92.6%) had invasive ductal carcinoma, four cases had lobular carcinomas, and most were grade II (82%), stage II (48%), and the majority of cases had positive axillary lymph nodes (70.3%). Representative sections from formalin-fixed paraffin embedded tissue blocks were taken from the 54 cases of breast cancer, and were stained for E-cadherin expression by immunohistochemical technique (monoclonal E-cadherin (NCL-E-cad), Novocastra). All the lobular carcinoma cases were negative for membranous expression of E-cadherin while 72% of invasive ductal carcinomas were positive for the marker.<br><br>RESULTS: A significant correlation was found between strong E-cadherin expression and node negative cases. Node negative cases were found to be an independent predictor of strong E-cadherin expression while node positive cases predicted negative expression of E-cadherin (P = 0 .026). Also loss of E-cadherin was noted in advanced stages of breast cancer supporting the view that loss of E-cadherin expression is a marker of aggressiveness. However, there was no correlation between the E-cadherin and other prognostic parameters as tumor size, tumor grade, ER, PR, and HER-2 expression.<br><br>CONCLUSION: A significant correlation was found between strong E-cadherin expression and node negative cases.}, }
@article {pmid20306655, year = {2007}, author = {Zeiwar, MM and Zaki, SM and Mohammad, LA and Zidan, AA and El Nagar, MR}, title = {HER-2 gene amplification, serum nucleosomes, CEA and CA15.3 tumor markers in breast cancer patients.}, journal = {The Egyptian journal of immunology}, volume = {14}, number = {2}, pages = {29-41}, pmid = {20306655}, issn = {1110-4902}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/genetics/*pathology ; Carcinoembryonic Antigen/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; *Gene Amplification ; Genes, erbB-2/*genetics ; Humans ; Middle Aged ; Mucin-1/*blood ; Nucleosomes/*metabolism ; Polymerase Chain Reaction ; Predictive Value of Tests ; Prognosis ; ROC Curve ; }, abstract = {Breast cancer is the most frequently diagnosed cancer in women in the world, for which tumor markers are needed for early detection, clinical prognistication and monitoring. The study was designed to assess the usefulness of HER-2 gene amplification, serum nucleosomes, CEA and CA15.3 tumor markers in the diagnosis of invasive ductal carcinoma and analyze whether their levels correlate with the clinicopathological features. The study was carried out on fifty patients with invasive ductal carcinoma and 25 age matched women with benign breast diseases (BBD). Cancer patients were categorised into three subgroups according to absence (-) or presence (+) of axillary lymph nodes (N) or presence of distant metastasis (M+) into: subgroup I (N-) included 15 patients, subgroup II (N+) included 20 patients and subgroup III (M+) included 15 patients. All individuals were subjected to CBC, fasting blood sugar, liver &amp; kidney function tests, CEA and CA15.3 by electrochemiluminescence, serum nucleosomes by cell death detection ELISA and amplification of HER-2 gene by differential PCR. The HER-2 gene PCR results were + ve in 28% of cancer patients; 20% of subgroup I, 25% of subgroup II and 40% of subgroup III, but in none of the BBD patients. HER-2 gene amplification results showed significant positive correlation with tumor grade. Serum nucleosomes showed significant increase in cancer patients as compared to that of BBD group, significant negative correlation with HER-2 gene amplification and significant positive correlation with CA15.3. Serum nucleosomes was the most sensitive marker (76% versus 32% and 50% for CEA &amp; CA15.3 respectively) but the least specific (72% versus 92% and 96% for CEA &amp; CA15.3 respectively). Elevated CEA and CA15.3 levels were detected in 13.3% and 33.3% respectively in node negative patients, these percentage increased in node positive patients to 20% and 40% and in metastatic patients to 66.7% and 80% respectively. In conclusion, serum nucleosomes is more sensitive but less specific marker than CEA and CA15.3 for diagnosis of early-stage breast cancer. HER-2 gene amplification is a potential prognostic marker for advanced stage breast cancer.}, }
@article {pmid17189983, year = {2006}, author = {Sahin, FI and Yilmaz, Z and Yagmurdur, MC and Atac, FB and Ozdemir, BH and Karakayali, H and Demirhan, B and Haberal, M}, title = {Clinical findings and HER-2/neu gene amplification status of breast carcinoma patients.}, journal = {Pathology oncology research : POR}, volume = {12}, number = {4}, pages = {211-215}, pmid = {17189983}, issn = {1219-4956}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/secondary ; Carcinoma, Lobular/genetics/secondary ; Female ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Prognosis ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; }, abstract = {The study group was derived from the archival materials of 48 invasive intraductal breast cancer patients who had undergone partial mastectomy/ axillary dissection. All patients included in the study had clinically T1-2N0M0 invasive ductal carcinoma. To detect HER-2/neu status, fluorescent in situ hybridization was performed using a HER-2/neu locus-specific probe. Signals were counted and patients were classified in three groups according to signal ratios: signal ratio <2, group 1 (n=31); signal ratio 2-4, group 2 (n=11); signal ratio >4, group 3 (n=6). Ratios of axillary metastatic lymph nodes to dissected total lymph nodes were 17%, 23% and 83% in groups 1, 2 and 3 respectively (P=0.003). The number of metastatic axillary lymph nodes, and the ratio of microscopic metastatic lymph nodes were highest in group 3 (P=0.001 and P=0.008, respectively). No significant difference was observed between groups for distant metastasis in a 5-year follow-up period. Signal ratios decreased with estrogen receptor expression (P=0.03). Histopathologically, an irregular growth pattern of the tumor was observed in 100% of the patients in group 3, and in 54% and 60% in groups 1 and 2, respectively (P=0.04). Lymphovascular invasion of the tumor was significantly higher in group 3 compared to the other two groups (P=0.01). The extensive intraductal component ratio was the highest in group 3 (P=0.04). The appearance of desmoplastic reaction and lymphocyte infiltration did not show significant difference between the groups. Our results show that HER-2/neu signal ratio increases with lymphovascular invasion, an extensive intraductal component, irregular growth pattern and axillary metastasis in clinically T1-2N0M0 invasive ductal carcinoma of the breast.}, }
@article {pmid17184588, year = {2007}, author = {Zhang, CL and Zou, XL and Peng, JB and Xiang, M}, title = {Immune tolerance induced by adoptive transfer of dendritic cells in an insulin-dependent diabetes mellitus murine model.}, journal = {Acta pharmacologica Sinica}, volume = {28}, number = {1}, pages = {98-104}, doi = {10.1111/j.1745-7254.2007.00467.x}, pmid = {17184588}, issn = {1671-4083}, mesh = {Adoptive Transfer/*methods ; Animals ; CD4 Antigens/immunology ; Cell Proliferation ; Cytokines/blood ; Dendritic Cells/*immunology/transplantation ; Diabetes Mellitus, Type 1/chemically induced/*immunology/therapy ; Flow Cytometry ; *Immune Tolerance ; Interleukin-2 Receptor alpha Subunit/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Streptozocin ; T-Lymphocytes/immunology/pathology ; }, abstract = {AIM: To investigate the effect and underlying mechanisms of immune-tolerance induced by the adoptive transfer of bone marrow (BM)-derived dendritic cells (DC) in insulin-dependent diabetes mellitus (IDDM) mice.<br><br>METHODS: The IDDM model was established by a low dose of streptozotocin (STZ) in Balb/c mice. Two DC subpopulations were generated from the BM cells with granulocyte-macrophage colony-stimulating factor with or without interleukin-4. The purity and the T cell stimulatory capability of DC were identified. These cells were used to modulate autoimmune response in pre-diabetic mice. Blood glucose was examined weekly; pancreas tissues were taken for histopathological analysis, and CD4(+) T cells were isolated to detect lymphocyte proliferation by MTT assay and the ratio of CD4(+)CD25(+) T cells by fluorescence-activated cell sorting (FACS). The cytokine secretion was determined by ELISA analysis.<br><br>RESULTS: Two DC subsets were generated from BM, which have phenotypes of mature DC (mDC) and immature DC (iDC), respectively. The level of blood glucose decreased significantly by transferring iDC (P< 0.01) rather than mDC. Less lymphocyte infiltration was observed in the islets, and pancreatic structure was intact. In vitro, proliferation of lymphocytes decreased and the proportion of CD4(+)CD25(+) T cells increased remarkably, compared with the mDC-treated groups (P< 0.05), which were associated with increased level of the Th2 cytokine and reduced level of the Th1 cytokine after iDC transfer.<br><br>CONCLUSION: Our data showed that iDC transfer was able to confer protection to mice from STZ-induced IDDM. The immune-tolerance to IDDM may be associated with promoting the production of CD4(+)CD25(+) T cells and inducing regulatory Th2 responses in vivo.}, }
@article {pmid17178859, year = {2006}, author = {Yang, C and Trent, S and Ionescu-Tiba, V and Lan, L and Shioda, T and Sgroi, D and Schmidt, EV}, title = {Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression.}, journal = {Cancer research}, volume = {66}, number = {24}, pages = {11649-11658}, doi = {10.1158/0008-5472.CAN-06-1645}, pmid = {17178859}, issn = {0008-5472}, support = {P50 CA89393/CA/NCI NIH HHS/United States ; R01 CA69069/CA/NCI NIH HHS/United States ; }, mesh = {3T3 Cells ; Animals ; Breast/cytology/pathology/physiology/physiopathology ; Breast Neoplasms/*genetics/*pathology ; Cyclin D1/*genetics ; Disease Progression ; Estrogens/*physiology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia ; Mice ; Mice, Transgenic ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Reference Values ; }, abstract = {Tumors can become lethal when they progress from preinvasive lesions to invasive carcinomas. Here, we identify candidate tumor progression genes using gene array analysis of preinvasive and invasive tumors from mice, which were then evaluated in human cancers. Immediate early response protein IEX-1, small stress protein 1 (HSPB8), and tumor necrosis factor-associated factor-interacting protein mRNAs displayed higher expression levels in invasive lesions than in preinvasive lesions using samples obtained by laser capture microdissection (LCM) from transgenic erbB2, ras, and cyclin D1 mice. LCM-isolated tissues from patient-matched normal, ductal carcinoma in situ, and invasive ductal carcinoma revealed similar increased expression in invasive human cancers compared with preinvasive and normal samples. These genes induced anchorage independence, increased cell proliferation, and protected against apoptosis, singly or in collaboration with erbB2. Surprisingly, they were all up-regulated by 17beta-estradiol and cyclin D1, and cyclin D1 overexpression increased p300/CBP binding to their promoters, supporting the model that cyclin D1-estrogen receptor (ER) coactivator interactions may be important to its role in ER-positive breast cancer. Additionally, an irreversible dual kinase inhibitor of ErbB signaling inhibited expression of the same genes. The up-regulation of genes contributing to increased invasiveness of ER-positive cancers offers a novel explanation for the contribution of cyclin D1 to a worse prognosis in ER-positive cancers. As targets of estrogen, cyclin D1, and erbB2 signaling, these candidates offer insights into the nature of the second events involved in breast cancer progression, regulatory events contributing to invasion, and potential targets of combined inhibition of hormone and growth factor signaling pathways.}, }
@article {pmid17169608, year = {2007}, author = {Gullu, H and Erdogan, D and Caliskan, M and Tok, D and Kulaksizoglu, S and Yildirir, A and Muderrisoglu, H}, title = {Elevated serum uric acid levels impair coronary microvascular function in patients with idiopathic dilated cardiomyopathy.}, journal = {European journal of heart failure}, volume = {9}, number = {5}, pages = {466-468}, doi = {10.1016/j.ejheart.2006.10.019}, pmid = {17169608}, issn = {1388-9842}, mesh = {Adult ; Aged ; Biomarkers/blood ; Blood Flow Velocity ; Cardiomyopathy, Dilated/*blood/etiology/*physiopathology ; *Coronary Circulation ; Endothelium, Vascular/metabolism/physiopathology ; Female ; Humans ; Hyperuricemia/blood/complications/physiopathology ; Logistic Models ; Male ; *Microcirculation ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Stroke Volume ; Uric Acid/*blood ; }, abstract = {In patients with idiopathic dilated cardiomyopathy (IDC), attenuated coronary flow reserve (CFR) and elevated serum uric acid levels have been reported. In this study, we investigated whether increased uric acid levels correlate with the degree of coronary microvascular dysfunction. Serum uric acid levels were measured in 29 patients with IDC (mean age: 57.0+/-10.8 years, 10 female), and each patient also underwent transthoracic echocardiographic examination including CFR measurement. The study population was divided into two groups according to the median CFR value (lower CFR group and higher CFR group). Uric acid levels were significantly higher in the lower CFR group than in the higher CFR group (7.59+/-2.56 vs 4.80+/-0.80 mg/dL, P=0.000). CFR correlated significantly and inversely to serum uric acid (r=-0.570, P=0.001). Logistic regression analysis revealed that uric acid level was the only independent predictor of CFR (B=-1080, P=0.015). We found a possibly clinically important negative association between serum uric acid levels and CFR in patients with IDC.}, }
@article {pmid17165026, year = {2007}, author = {Mrhalova, M and Kodet, R}, title = {A modified approach for I-FISH evaluation of ERBB2 (HER-2) gene copy numbers in breast carcinomas: comparison with HER-2/CEP17 ratio system.}, journal = {Journal of cancer research and clinical oncology}, volume = {133}, number = {5}, pages = {321-329}, pmid = {17165026}, issn = {0171-5216}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; *Gene Dosage ; *Genes, erbB-2 ; Humans ; In Situ Hybridization, Fluorescence ; Interphase ; Receptor, ErbB-2/*metabolism ; }, abstract = {PURPOSE: The evaluation of ERBB2 gene copy numbers and ERBB-2 protein expression in invasive duct carcinomas of the mammary gland (IDC) has been introduced as a part of a regular investigation protocol. Amplification of the ERBB2 gene detected by fluorescence in situ hybridization on interphasic nuclei (I-FISH) is used as a criterion for Herceptin administration. To improve characterization of cases with a borderline ERBB2 gene amplification, we applied a modified evaluation of the ERBB2 gene copy numbers. The results were compared with a commonly used HER-2/CEP17 ratio calculation.<br><br>METHODS: We investigated 175 patients with primary IDCs in histological sections from paraffin embedded tissue with PathVysion HER-2 DNA Probe Kit (Vysis). Tumor cells of each case were sorted according to the number of ERBB2 signals into groups of tumor cells without amplification, with moderate amplification (< or =10 signals) and with strong amplification (>10 signals). If >10% of tumor cells had moderate or strong amplification of the ERBB2 gene, the case was reported as "moderately" or "strongly" amplified.<br><br>RESULTS: The groups of patients classified by the proposed system as "without" and as with "strong" amplification had the HER-2/CEP17 ratio <1.91 (median 1.22, n = 33) and >2.3 (median 6.85, n = 115), respectively. Thus, the findings using the two systems of evaluation yielded similar results for these groups of patients. In cases, classified as with "moderate" amplification, the HER-2/CEP17 ratio varied from 1.3 to 4.77 (median 2.11, n = 27). Twelve of these 27 patients were according to the HER-2/CEP17 ratio system "not amplified" (1.3-1.93, median 1.72). Median percentage of the tumor cells with amplification of the ERBB2 gene was 14.5% in this subgroup. Of these 12 cases, 10 were ERBB-2 protein positive, and would be candidates for Herceptin therapy.<br><br>CONCLUSION: The criteria for evaluation of the ERBB2 gene copy number proposed for this study separate gray zone cases with a borderline HER-2/CEP17 finding. The proposed system is easy to apply and characterizes a heterogeneity of the ERBB2 gene copy number in IDC tumor cell population more precisely than the currently used HER-2/CEP17 ratio system.}, }
@article {pmid17163418, year = {2007}, author = {Wolf, I and Bose, S and Williamson, EA and Miller, CW and Karlan, BY and Koeffler, HP}, title = {FOXA1: Growth inhibitor and a favorable prognostic factor in human breast cancer.}, journal = {International journal of cancer}, volume = {120}, number = {5}, pages = {1013-1022}, doi = {10.1002/ijc.22389}, pmid = {17163418}, issn = {0020-7136}, mesh = {Breast/chemistry/metabolism/pathology ; Breast Neoplasms/chemistry/genetics/*pathology ; Carcinoma, Ductal/chemistry/genetics/*pathology ; Estrogen Receptor alpha/genetics ; Gene Expression Regulation, Neoplastic ; Hepatocyte Nuclear Factor 3-alpha/*analysis/genetics/*physiology ; Humans ; Prognosis ; Proliferating Cell Nuclear Antigen/genetics ; RNA, Messenger/analysis/metabolism ; RNA, Small Interfering/pharmacology ; Tissue Array Analysis ; Transcriptional Activation ; Tumor Cells, Cultured ; }, abstract = {The transcription factor Forkhead-box A1 (Foxa1), a member of the FOX class of transcription factors, has been implicated in the pathogenesis of lung, esophageal and prostate cancers. We have recently identified transcriptional activation of p27 by FOXA1. In this study, we analyzed the activities and expression pattern of FOXA1 in breast cancer. Forced expression of FOXA1 inhibited clonal growth of breast cancer cell lines, and FOXA1 levels inversely correlated with growth stimuli. In the estrogen receptor (ER)-positive MCF-7 cells, FOXA1 increased p27 promoter activity and inhibited the ER pathway activity. Analysis of FOXA1 expression in breast tissue arrays revealed significantly higher expression in pure ductal carcinomas in situ compared to invasive ductal carcinomas (IDC); and in IDC, high expression of FOXA1 was associated with favorable prognostic factors. Yet, FOXA1 expression was noted in a subset of the ER-negative tumors. Taken together, our findings suggest a growth inhibitory role for FOXA1, and identify it as a novel, potential prognostic factor in breast cancer.}, }
@article {pmid17159656, year = {2007}, author = {Shire, NJ and Rouster, SD and Stanford, SD and Blackard, JT and Martin, CM and Fichtenbaum, CJ and Sherman, KE}, title = {The prevalence and significance of occult hepatitis B virus in a prospective cohort of HIV-infected patients.}, journal = {Journal of acquired immune deficiency syndromes (1999)}, volume = {44}, number = {3}, pages = {309-314}, doi = {10.1097/QAI.0b013e31802e29a9}, pmid = {17159656}, issn = {1525-4135}, support = {AI 25897/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; DNA, Viral/blood/genetics ; Female ; HIV Infections/*complications ; Hepatitis B/*complications/*epidemiology/virology ; Hepatitis B Antibodies/blood ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/analysis ; Hepatitis B virus/isolation &amp; purification ; Humans ; Male ; Multivariate Analysis ; Ohio/epidemiology ; Polymerase Chain Reaction ; Prevalence ; Risk Factors ; }, abstract = {BACKGROUND: Occult hepatitis B virus (HBV) is defined as low-level HBV DNA without hepatitis B surface antigen (HBsAg). Prevalence estimates vary widely. We determined the prevalence of occult HBV at the University of Cincinnati Infectious Diseases Center (IDC).<br><br>METHODS: Patients in the IDC HIV database (n = 3867) were randomly selected using a 25% sampling fraction. Samples were pooled for HBV nucleic acid extraction. Pools were tested for HBV DNA by a real-time polymerase chain reaction (PCR) assay to co-amplify core/surface protein regions. The PCR assay was run on all individual samples from each DNA pool. DNA samples were tested for HBV serologic markers.<br><br>RESULTS: A total of 909 patients without known HBV were selected. The mean CD4 count was 384 cells/mm. Forty-three patients were HBV DNA. Twelve of 43 were DNA/HBsAg (95% confidence interval for database: 0.58% to 1.90%). Five of 12 were negative for all serologic markers. Alanine aminotransferase, aspartate aminotransferase, and HBV DNA titers were elevated in HBsAg patients versus occult patients and versus HIV-monoinfected patients. No other significant differences were detected. No occult HBV patient was on treatment with anti-HBV activity.<br><br>CONCLUSIONS: Forty-three percent of those with HBV were not previously identified as HBV, indicating the need for ongoing screening in high-risk populations. Occult HBV may occur in persons with all negative serologic markers, representing a challenge for identification.}, }
@article {pmid17156488, year = {2006}, author = {Basu, GD and Liang, WS and Stephan, DA and Wegener, LT and Conley, CR and Pockaj, BA and Mukherjee, P}, title = {A novel role for cyclooxygenase-2 in regulating vascular channel formation by human breast cancer cells.}, journal = {Breast cancer research : BCR}, volume = {8}, number = {6}, pages = {R69}, pmid = {17156488}, issn = {1465-542X}, mesh = {Animals ; Blood Vessels/*drug effects/physiopathology ; Breast Neoplasms/*metabolism ; Celecoxib ; Cell Line, Tumor ; Cyclooxygenase 2/*biosynthesis ; Cyclooxygenase 2 Inhibitors/pharmacology ; Female ; Humans ; Male ; Mice ; Mice, Nude ; Neovascularization, Pathologic/genetics/*metabolism/physiopathology ; Pyrazoles/pharmacology ; Sulfonamides/pharmacology ; }, abstract = {INTRODUCTION: Cyclo-oxygenase (COX)-2 expression correlates directly with highly aggressive and metastatic breast cancer, but the mechanism underlying this correlation remains obscure. We hypothesized that invasive human breast cancer cells that over-express COX-2 have the unique ability to differentiate into extracellular-matrix-rich vascular channels, also known as vasculogenic mimicry. Vascular channels have been associated with angiogenesis without involvement of endothelial cells, and may serve as another mechanism by which tumor cells obtain nutrients to survive, especially in less vascularized regions of the tumor.<br><br>METHODS: To determine whether COX-2 regulates vascular channel formation, we assessed whether treatment with celecoxib (a selective COX-2 inhibitor) or silencing COX-2 synthesis by siRNA inhibits vascular channel formation by breast cancer cell lines. Cell lines were selected based on their invasive potential and COX-2 expression. Additionally, gene expression analysis was performed to identify candidate genes involved in COX-2-induced vascular channel formation. Finally, vascular channels were analyzed in surgically resected human breast cancer specimens that expressed varying levels of COX-2.<br><br>RESULTS: We found that invasive human breast cancer cells that over-express COX-2 develop vascular channels when plated on three-dimensional matigel cultures, whereas non-invasive cell lines that express low levels of COX-2 did not develop such channels. Similarly, we identified vascular channels in high-grade invasive ductal carcinoma of the breast over-expressing COX-2, but not in low-grade breast tumors. Vascular channel formation was significantly suppressed when cells were treated with celecoxib or COX-2 siRNA. Inhibition of channel formation was abrogated by addition of exogenous prostaglandin E2. In vitro results were corroborated in vivo in tumor-bearing mice treated with celecoxib. Using gene expression profiling, we identified several genes in the angiogenic and survival pathways that are engaged in vascular channel formation.<br><br>CONCLUSION: Antivascular therapies targeting tumor cell vasculogenic mimicry may be an effective approach to the treatment of patients with highly metastatic breast cancer.}, }
@article {pmid17146166, year = {2006}, author = {Tsutani, Y and Ohsumi, S and Aogi, K and Taira, N and Kataoka, M and Hamamoto, Y and Nishimura, R and Takashima, S}, title = {A case of metastatic breast cancer with HER2 gene amplification that responded completely to single agent trastuzumab.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {4}, pages = {374-377}, doi = {10.2325/jbcs.13.374}, pmid = {17146166}, issn = {1340-6868}, mesh = {Aged, 80 and over ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Ductal, Breast/*drug therapy/genetics/pathology ; Female ; *Gene Amplification ; *Genes, erbB-2 ; Humans ; Lymphatic Metastasis ; Trastuzumab ; }, abstract = {An 80-year-old woman visited our hospital with a massive ulcerated tumor in the upper lateral quadrant of the right breast. Her performance status was 2. Histopathologically, a mass consisting of a huge primary tumor and metastatic axillary lymph nodes was seen and invasive ductal carcinoma was diagnosed. Both estrogen and progesterone receptors were negative. Herceptest (DakoCytomation, Glostrup, Denmark) showed 2 + staining and HER2 amplification was detected by fluorescent in situ hybridization. CT revealed multiple lung metastases. Her old age and performance status of 2 made aggressive chemotherapy difficult. After receiving 5'-DFUR 600 mg/day as the first line treatment for two months, the tumors progressed. As second-line treatment, single agent therapy with a loading dose, a trastuzumab 4 mg/kg followed by 2 mg/kg weekly was recommended. The patient also received 60 Gy radiotherapy. Six months after the second line treatment, the breast tumor disappeared and only a scar remained on the chest wall and axilla. CT showed no lung tumors. During the trastuzumab treatment, no adverse effect was observed. Her performance status improved to zero, and she is alive and free from the disease 24 months after the disappearance of the tumor.}, }
@article {pmid17145955, year = {2006}, author = {Pion, M and Granelli-Piperno, A and Mangeat, B and Stalder, R and Correa, R and Steinman, RM and Piguet, V}, title = {APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection.}, journal = {The Journal of experimental medicine}, volume = {203}, number = {13}, pages = {2887-2893}, pmid = {17145955}, issn = {0022-1007}, support = {N01AI40045/AI/NIAID NIH HHS/United States ; AI40045/AI/NIAID NIH HHS/United States ; }, mesh = {APOBEC-3G Deaminase ; Antiviral Restriction Factors ; Base Sequence ; Carrier Proteins/genetics/metabolism/physiology ; Cell Differentiation/drug effects/genetics ; Cell Line ; Cytidine Deaminase ; Cytosine Deaminase/genetics/metabolism/*physiology ; DNA, Viral/genetics ; Dendritic Cells/drug effects/metabolism/*virology ; Flow Cytometry ; Gene Expression ; Green Fluorescent Proteins/genetics/metabolism ; HIV-1/genetics/*growth &amp; development ; HeLa Cells ; Humans ; Jurkat Cells ; Lipopolysaccharides/pharmacology ; Membrane Glycoproteins/genetics ; Molecular Sequence Data ; Monocytes/*cytology ; Nucleoside Deaminases/genetics/metabolism/*physiology ; Point Mutation ; RNA, Small Interfering/genetics ; Repressor Proteins/genetics/metabolism/*physiology ; Sequence Homology, Nucleic Acid ; Transfection ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases ; Viral Envelope Proteins/genetics ; Virus Replication/genetics ; }, abstract = {HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA-mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5alpha, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry.}, }
@article {pmid17139431, year = {2006}, author = {Naito, Y and Suda, K and Nobukawa, B and Kinoshita, H and Kojiro, M}, title = {Histopathological study of invasive ductal carcinoma (IDC) of the pancreas without associated cancerous occlusion of the main pancreatic duct.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {13}, number = {6}, pages = {556-561}, doi = {10.1007/s00534-006-1112-6}, pmid = {17139431}, issn = {0944-1166}, mesh = {Adult ; Aged ; Carcinoma, Pancreatic Ductal/immunology/*pathology ; Constriction, Pathologic ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/immunology ; Male ; Middle Aged ; Pancreatic Ducts/*pathology ; Pancreatic Neoplasms/immunology/*pathology ; }, abstract = {BACKGROUND/PURPOSE: [corrected] Invasive ductal carcinoma (IDC) of the pancreas may be associated with cancerous occlusion of the main pancreatic duct (MPD) in its growth process, but at quite low a frequency; there are patients who do not develop this occlusion.<br><br>METHODS: This study examined the histological features of surgical specimens from 8 patients with IDC without MPD occlusion, in comparison to 32 patients with IDC with this occlusion (controls). The pancreatic duct was identified by confirming the presence of mural elastic fibers on the wall of the pancreatic duct. Immunohistochemical staining was done with Ki-67 antibody.<br><br>RESULTS: The frequency of IDC without MPD occlusion was very low (5.0% [2/40] patients at Kurume University and 3.1% [4/126] patients at Juntendo University). The number of intraductal carcinoma components was 1.5 +/- 1.1 per specimen in the IDCs without occlusion and 5.9 +/- 2.4 in the controls (P < 0.001). The Ki-67 labeling index was 18.0 +/- 11.7% in the IDCs without occlusion and 30.0 +/- 12.1% in the controls (P < 0.05). The number of intraductal carcinoma components and the Ki-67 labeling index were significantly lower in the IDCs without occlusion than in the controls.<br><br>CONCLUSIONS: Our findings suggested that these two types of IDC could have different biological features.}, }
@article {pmid17130547, year = {2006}, author = {Lo, J and Peng, RH and Barker, T and Xia, CQ and Clare-Salzler, MJ}, title = {Peptide-pulsed immature dendritic cells reduce response to beta cell target antigens and protect NOD recipients from type I diabetes.}, journal = {Annals of the New York Academy of Sciences}, volume = {1079}, number = {}, pages = {153-156}, doi = {10.1196/annals.1375.023}, pmid = {17130547}, issn = {0077-8923}, mesh = {*Adoptive Transfer ; Animals ; Antigens/*immunology ; Cell Division/drug effects/immunology ; Cells, Cultured ; Dendritic Cells/*immunology/transplantation ; Diabetes Mellitus, Type 1/*immunology/*prevention &amp; control ; Female ; Glutamate Decarboxylase/immunology ; Immune Tolerance ; Insulin/pharmacology ; Islets of Langerhans/*immunology/pathology ; Mice ; Mice, Inbred NOD ; Peptide Fragments/chemistry/immunology/pharmacology ; Spleen/cytology/metabolism ; T-Lymphocytes/immunology/physiology ; }, abstract = {Our previous work demonstrated peptide-pulsed mature myeloid dendritic cells (DC) presenting beta cell antigens induce tolerance. Here we determine whether immature DC (iDC) presenting dominant (insulin beta9-23 chain, proinsulin C19-A3) or ignored (glutamic acid decarboxylase 65(78-97)) antigen determinants promote tolerance. Nonobese diabetic (NOD) mice were given injections of either unpulsed or peptide-pulsed myeloid iDC beginning at 9 weeks of age for 3 consecutive weeks. Diabetes incidence in recipients of unpulsed iDC was comparable to unmanipulated animals (approximately 80%), whereas GAD65(78-97) pulsed iDC recipients were protected from the disease (P = 0.05). We also analyzed splenic T cell proliferation responses to the panel of studied peptides in diabetic and nondiabetic recipients. When stimulated with insulin or proinsulin peptide, nondiabetic mice receiving the peptide-pulsed iDC had a 21- to 31-fold or 3.9- to 9.0-fold reduction in T cell response, respectively, as compared to the response of diabetic unpulsed recipients. However, only a 2.6- to 3.1-fold reduction in response to beta chain peptide, and a 1.5- to 3.4-fold reduction in proinsulin response were observed in diabetic mice receiving peptide-pulsed iDC. The reduction was not specific to the immunizing peptide, as reduced proliferation was observed to other diabetes-target peptides. We conclude that protective iDC-based therapies require target antigen presentation, and ignored determinants may be preferable perhaps due to an available naïve T cell repertoire. In addition, iDC presenting peptides induce a nonspecific reduction in T cell responses to beta cell antigens, possibly through the induction of regulatory T cells.}, }
@article {pmid17126830, year = {2007}, author = {Rodríguez-Pérez, JM and Fragoso, JM and Alvarez-León, E and Martínez-Rodríguez, N and Gallardo, GJ and Inés-Real, S and Granados, J and Reyes, PA and Vargas-Alarcón, G}, title = {MHC class II genes in Mexican patients with idiopathic dilated cardiomyopathy.}, journal = {Experimental and molecular pathology}, volume = {82}, number = {1}, pages = {49-52}, doi = {10.1016/j.yexmp.2006.10.002}, pmid = {17126830}, issn = {0014-4800}, mesh = {Cardiomyopathy, Dilated/*genetics ; *Genes, MHC Class II ; *Genetic Predisposition to Disease ; Humans ; Mexico ; Polymerase Chain Reaction ; }, abstract = {The purpose of the present study was to evaluate the relationship between class II major histocompatibility complex (MHC) genes (HLA-DR and HLA-DQB) and the genetic susceptibility to idiopathic dilated cardiomyopathy (IDC) in Mexican patients. The HLA-DR and DQB alleles were analyzed in 53 patients with IDC and 99 ethnically matched healthy controls using the polymerase chain reaction-sequence specific oligonucleotides (PCR-SSO) technique. IDC patients showed increased frequencies of HLA-DR4 (pC=0.02, OR=1.87), HLA-DQB1*0301 (pC=0.02, OR=1.92) and HLA-DQB1*0302 (pC=0.02, OR=1.87) when compared to healthy controls. On the other hand, IDC patients also showed decreased frequencies of HLA-DR11 allele (pC=0.03, OR=0.26) and HLA-DQB1*0201 (pC=0.04, OR=0.41). These data suggest that variation in class II HLA alleles could be a genetic factor involved in the susceptibility to IDC of the Mexican Mestizo population.}, }
@article {pmid17125718, year = {2006}, author = {Fernández-Portales, J and Valdesuso, R and Carreras, R and Jiménez-Candil, J and Serrador, A and Romaní, S}, title = {[Right versus left radial artery approach for coronary angiography. Differences observed and the learning curve].}, journal = {Revista espanola de cardiologia}, volume = {59}, number = {10}, pages = {1071-1074}, doi = {10.1157/13093986}, pmid = {17125718}, issn = {0300-8932}, mesh = {Age Factors ; Aged ; Cardiac Catheterization/*methods ; Coronary Angiography/adverse effects/*methods ; Female ; Fluoroscopy ; Humans ; Learning ; Logistic Models ; Male ; Prospective Studies ; *Radial Artery/anatomy &amp; histology ; Risk Factors ; }, abstract = {There are anatomical differences between right and left radial artery approaches for coronary catheterization that could influence application of the technique. We present the results of a randomized study that compared the effectiveness of the two approaches and identified factors associated with failure of the procedure. The study involved 351 consecutive patients: a left radial approach was used in 180, and a right radial approach, in 171. The procedure could not be completed using the initial approach selected in 15 patients (11 right radial vs. 4 left radial; P=.007). Use of a right radial approach, lack of catheterization experience, patient age >70 years, and the absence of hypertension were found to be independently associated with prolonged fluoroscopy duration and failure using the initial approach. Use of the right radial approach in patients aged over 70 years was associated with a 6-fold increase in the risk of an adverse event. Consequently, use of the right radial approach should be avoided in patients aged over 70 years when trainee practitioners are on the learning curve.}, }
@article {pmid17117186, year = {2007}, author = {Badenhorst, D and Norton, GR and Sliwa, K and Brooksbank, R and Essop, R and Sareli, P and Woodiwiss, AJ}, title = {Impact of beta2-adrenoreceptor gene variants on cardiac cavity size and systolic function in idiopathic dilated cardiomyopathy.}, journal = {The pharmacogenomics journal}, volume = {7}, number = {5}, pages = {339-345}, doi = {10.1038/sj.tpj.6500426}, pmid = {17117186}, issn = {1470-269X}, mesh = {Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiomyopathy, Dilated/drug therapy/*genetics/pathology/physiopathology ; Cardiotonic Agents/therapeutic use ; Cardiovascular Agents/pharmacology/*therapeutic use ; Case-Control Studies ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Drug Therapy, Combination ; Female ; Furosemide/therapeutic use ; Gene Frequency ; Genetic Predisposition to Disease ; Haplotypes ; Heart Ventricles/pathology ; Humans ; Male ; Middle Aged ; *Polymorphism, Restriction Fragment Length ; Prospective Studies ; Receptors, Adrenergic, beta-2/*genetics ; Risk Factors ; Stroke Volume/drug effects/genetics ; Systole ; Time Factors ; Treatment Outcome ; Ventricular Function, Left/drug effects/*genetics ; Ventricular Remodeling/drug effects/*genetics ; }, abstract = {In heart failure, the Arg16Gly and Gln27Glu polymorphisms of the beta2-adrenoreceptor (beta2-AR) gene are associated with exercise-capacity, clinical outcomes and response to beta-AR blocker therapy. Whether beta2-AR gene variants mediate these effects in-part through an impact on cardiac structural remodeling and pump function independent of the effects of beta-blockers is uncertain. We evaluated whether the Arg16Gly and Gln27Glu variants of the beta2-AR gene predict left ventricular ejection fraction (LVEF) and LV end diastolic diameter (LVEDD) in patients with idiopathic dilated cardiomyopathy (IDC) before and 6 months after receiving standard medical therapy other than beta-AR blockers. In all, 394 patients with IDC and 393 age and gender-matched controls were genotyped for the beta2-AR gene variants using restriction-fragment length polymorphism-based techniques. LVEF and dimensions were determined in 132 patients (of whom 71 were newly diagnosed) both at baseline and after 6 months. Genotype of neither variant was associated with the presence of IDC. Moreover, beta2-AR genotype did not determine LVEF or LV dimensions prior to initiating therapy. After 6 months of therapy, LVEF increased by 7.1+/-1.0 absolute units (P<0.0001) and LVEDD decreased by 0.27+/-0.06 cm (P<0.02). Adjusting for baseline values as well as gender, age, and type of angiotensin-converting enzyme inhibitor therapy received, genotype was associated with neither final LVEF and LVEDD, nor change in LVEF and LVEDD. In conclusion, these data suggest that in heart failure, the functional Arg16Gly and Gln27Glu variants of the beta2-AR gene have no independent effect on adverse structural remodeling and pump function.}, }
@article {pmid17090707, year = {2007}, author = {Sydnor, MK and Wilson, JD and Hijaz, TA and Massey, HD and Shaw de Paredes, ES}, title = {Underestimation of the presence of breast carcinoma in papillary lesions initially diagnosed at core-needle biopsy.}, journal = {Radiology}, volume = {242}, number = {1}, pages = {58-62}, doi = {10.1148/radiol.2421031988}, pmid = {17090707}, issn = {0033-8419}, mesh = {Adult ; Aged ; Biopsy, Needle/statistics &amp; numerical data ; Breast Neoplasms/diagnosis/*epidemiology/*pathology ; Carcinoma, Papillary/diagnosis/*epidemiology/*pathology ; False Negative Reactions ; Female ; Humans ; Mammography/statistics &amp; numerical data ; Middle Aged ; Observer Variation ; Prevalence ; Reproducibility of Results ; Risk Assessment/*methods ; Risk Factors ; Sensitivity and Specificity ; Ultrasonography, Mammary/statistics &amp; numerical data ; Virginia/epidemiology ; }, abstract = {PURPOSE: To retrospectively determine the degree of underestimation of breast carcinoma diagnosis in papillary lesions initially diagnosed at core-needle biopsy.<br><br>MATERIALS AND METHODS: Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. Mammographic database review (1994-2003) revealed core biopsy diagnoses of benign papilloma (n=38), atypical papilloma (n=15), sclerotic papilloma (n=6), and micropapilloma (n=4) in 57 women (mean age, 57 years). Excisional or mammographic follow-up (>or=2 years) findings were available. Patients with in situ or invasive cancer in the same breast or patients without follow-up were excluded. Findings were collected from mammography, ultrasonography, core technique, core biopsy, excision, and subsequent mammography. Reference standard was excisional findings or follow-up mammogram with no change at 2 years. Associations were examined with regression methods.<br><br>RESULTS: In 38 of 63 lesions, surgical excision was performed; in 25 additional lesions (considered benign), follow-up mammography (24-month minimum) was performed, with no interval change. In 15 lesions, 14-gauge core needle was used; in 48, vacuum assistance (mean cores per lesion, 8.7). Carcinoma was found at excision in 14 of 38 lesions. Core pathologic findings associated with malignancy were benign papilloma (n=1), sclerotic papilloma (n=1), micropapilloma (n=2), and atypical papilloma (n=10). Frequency of malignancy was one (3%) of 38 benign papillomas, 10 (67%) of 15 atypical papillomas, two (50%) of four micropapillomas, and one (17%) of six sclerotic papillomas. Excisional findings included lobular carcinoma in situ (n=2), ductal carcinoma in situ (n=7), papillary carcinoma (n=2), and invasive ductal carcinoma (n=3). Low-risk group (micropapillomas and sclerotic and benign papillomas) was compared with high-risk atypical papilloma group. Core findings were associated with malignancy at excision for atypical papilloma (P=.006). Lesion location, mammographic finding, core number, or needle type were not associated (P>.05) with underestimation of malignancy at excision.<br><br>CONCLUSION: Benign papilloma diagnosed at core biopsy is infrequently (3%) associated with malignancy; mammographic follow-up is reasonable. Because of the high association with malignancy (67%), diagnosis of atypical papilloma at core biopsy should prompt excision for definitive diagnosis.}, }
@article {pmid17081394, year = {2006}, author = {Li, WM and Liu, W and Gao, C and Zhou, BG and Wang, Z and Zhang, RH and Kong, YH and Li, Y and Han, W and Gan, RT and Xue, HJ and Geng, JQ and Yang, SS and Shao, Q and Zhang, M}, title = {[IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis].}, journal = {Zhonghua xin xue guan bing za zhi}, volume = {34}, number = {8}, pages = {703-707}, pmid = {17081394}, issn = {0253-3758}, mesh = {Animals ; Animals, Genetically Modified ; Autoimmune Diseases/*immunology ; Bone Marrow Cells ; Cell Line ; Dendritic Cells/*immunology ; Genetic Therapy ; *Immune Tolerance ; Interleukin-10/*genetics/immunology ; Myocarditis/*immunology ; Rats ; Rats, Inbred Lew ; }, abstract = {OBJECTIVE: To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).<br><br>METHODS: EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.<br><br>RESULTS: EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.<br><br>CONCLUSION: Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.}, }
@article {pmid17065184, year = {2007}, author = {Erdogan, D and Gullu, H and Caliskan, M and Ciftci, O and Baycan, S and Yildirir, A and Muderrisoglu, H}, title = {Nebivolol improves coronary flow reserve in patients with idiopathic dilated cardiomyopathy.}, journal = {Heart (British Cardiac Society)}, volume = {93}, number = {3}, pages = {319-324}, pmid = {17065184}, issn = {1468-201X}, mesh = {Benzopyrans/*administration &amp; dosage ; Cardiomyopathy, Dilated/diagnostic imaging/*drug therapy/physiopathology ; Case-Control Studies ; Coronary Circulation/*drug effects ; Dose-Response Relationship, Drug ; Echocardiography ; Echocardiography, Doppler, Color ; Ethanolamines/*administration &amp; dosage ; Female ; Humans ; Male ; Middle Aged ; Nebivolol ; Treatment Outcome ; Vasodilator Agents/*administration &amp; dosage ; }, abstract = {BACKGROUND: Impaired coronary flow reserve (CFR) is a significant predictor of poor prognosis in patients with idiopathic dilated cardiomyopathy (IDC). Nebivolol reduces mortality and morbidity in patients with heart failure and left ventricular dysfunction, including cases caused by IDC.<br><br>OBJECTIVE: To assess the effects of nebivolol on CFR in patients with IDC.<br><br>METHODS: CFR was measured in 21 clinically stable patients with IDC (mean (SD) ejection fraction 35.7 (6.2)) at baseline and after 1 month of treatment with nebivolol once daily. A control group of apparently healthy subjects who were matched for age and sex was used for comparison. Resting and hyperaemic coronary flows were measured using transthoracic second-harmonic Doppler echocardiography. None of the subjects had any systemic disease.<br><br>RESULTS: After 1 month of treatment, heart rate was reduced significantly (p<0.001). The blood pressure was decreased significantly (p<0.001). The left ventricular end-diastolic diameter and stroke volume were not changed significantly, but end-systolic diameter was decreased significantly (p<0.05). Resting rate-pressure product was lower after treatment with nebivolol, but dipyridamole-induced change was not influenced by the treatment. Nebivolol treatment reduced significantly coronary velocities at rest (p<0.02) and also caused a significant increase in coronary velocities after dipyridamole (p<0.02), leading to a greater CFR (2.02 (0.35) vs 2.61 (0.43), p<0.001). Nebivolol induced an absolute increase of 6% in the CFR in 17 of 21 patients (80.9%).<br><br>CONCLUSIONS: In patients with IDC, 1 month of treatment with nebivolol induces a marked increase in CFR.}, }
@article {pmid17062971, year = {2006}, author = {Koike, A and Hoshimoto, M and Tajima, A and Nagayama, O and Yamaguchi, K and Goda, A and Yamashita, T and Sagara, K and Itoh, H and Aizawa, T}, title = {Critical level of cerebral oxygenation during exercise in patients with left ventricular dysfunction.}, journal = {Circulation journal : official journal of the Japanese Circulation Society}, volume = {70}, number = {11}, pages = {1457-1461}, doi = {10.1253/circj.70.1457}, pmid = {17062971}, issn = {1346-9843}, mesh = {Aged ; Blood Pressure/physiology ; Brain/*metabolism ; Cardiomyopathy, Dilated/physiopathology ; Cerebral Arteries/*physiology ; Consciousness/physiology ; Exercise/*physiology ; Exercise Test ; Female ; Humans ; Male ; Middle Aged ; Oxygen/*blood ; Regional Blood Flow/physiology ; Retrospective Studies ; Tachycardia, Ventricular/physiopathology ; Ventricular Dysfunction, Left/*metabolism/*physiopathology ; }, abstract = {BACKGROUND: In a recent study the indexes of cerebral oxygenation decreased during maximal exercise in nearly half of all patients with left ventricular dysfunction. Whether these levels decrease severely enough to influence mental status or level of consciousness was evaluated in the present study.<br><br>METHODS AND RESULTS: Forty-two patients with idiopathic dilated cardiomyopathy (IDC) and 29 healthy subjects underwent a symptom-limited maximal exercise test. The cerebral oxyhemoglobin (O(2)Hb) and tissue oxygenation index (TOI) were continuously monitored using near-infrared spectroscopy. The changes in O(2)Hb and TOI were also measured in 7 subjects: 2 who experienced episodes of reduced consciousness caused by sudden decreases in blood pressure during exercise recovery and 5 who exhibited sustained ventricular tachycardia during an electrophysiological study. The change in cerebral O(2)Hb during exercise in patients with IDC averaged 0.38+/-3.39 micromol/L, significantly lower than in the normal subjects (4.30+/-4.47 micromol/L, p<0.0001). The cerebral O(2)Hb decreased during exercise in 18 of 42 patients with IDC. The change in cerebral TOI in the IDC patients during exercise was significantly less than that in the normal subjects (-2.0+/-4.7 vs 2.1+/-5.8%, p=0.002). The mean decreases in cerebral O(2)Hb and TOI were -5.34 micromol/L and -9.7%, respectively, in the patients with reduced consciousness during exercise recovery, and -2.52 micromol/L and -16.5%, respectively, in those with ventricular tachycardia.<br><br>CONCLUSION: The indexes of cerebral oxygenation may drop severely enough during maximal exercise in some patients with severe IDC that consciousness is affected.}, }
@article {pmid17061934, year = {2006}, author = {Hoyer, D and Frank, B and Götze, C and Schmidt, H and Baranowski, R and Zebrowski, JJ and Vallverdú, M and Caminal, P and Bayés De Luna, A and Falkenhahn, K and Bär, KJ and Stein, PK}, title = {Complex autonomic dysfunction in cardiovascular, intensive care, and schizophrenic patients assessed by autonomic information flow.}, journal = {Biomedizinische Technik. Biomedical engineering}, volume = {51}, number = {4}, pages = {182-185}, doi = {10.1515/BMT.2006.032}, pmid = {17061934}, issn = {0013-5585}, mesh = {Autonomic Nervous System/*physiopathology ; Autonomic Nervous System Diseases/complications/diagnosis/*physiopathology ; *Biological Clocks ; Critical Care ; Diagnosis, Computer-Assisted/methods ; Electrocardiography/methods ; Heart Failure/complications/diagnosis/*physiopathology ; *Heart Rate ; Humans ; Information Storage and Retrieval/methods ; Male ; Multiple Organ Failure/complications/diagnosis/*physiopathology ; Schizophrenia/complications/diagnosis/*physiopathology ; }, abstract = {BACKGROUND: The cardiovascular control system is mediated by mechanisms acting at different time scales, such as heart period, vagal, sympathetic, and other slower controllers. Since these elements are interrelated in a complex manner, classical control theory fails and information-based description, based on autonomic information flow (AIF) functions, is appropriate. We investigated the hypothesis that AIF functions of typical time scales specifically characterize autonomic dysfunction and prognosis.<br><br>MATERIALS AND METHODS: Holter recordings of patients with multiple organ dysfunction syndrome (MODS) (26 survivors, 10 non-survivors), heart failure (13 low risk, 13 high risk of cardiac arrest), idiopathic dilated cardiomyopathy (IDC) (26 low risk, 11 high risk), after abdominal aorta surgery (AAS) [32 with length of stay in hospital (LOS) >7 days; 62 with LOS < or =7 days] or with schizophrenia (n=20) were assessed and compared to 20 control subjects.<br><br>RESULTS: We found different AIF time scales discriminating risk. AIF measures of heart beat period had predominant prognostic value in heart failure patients, those of vagal communication in MODS and IDC, and those of long-term communication after AAS. Schizophrenic patients were discriminated from controls by vagally mediated communication.<br><br>CONCLUSION: Different time scales of AIF represent specific pathophysiological aspects of altered complex autonomic control (communication) and consequently have predictive implications.}, }
@article {pmid17060025, year = {2006}, author = {Liu, W and Li, WM and Yang, SS and Gao, C and Li, SJ and Li, Y and Kong, YH and Gan, RT}, title = {Association of HLA class II DRB1, DPA1 and DPB1 polymorphism with genetic susceptibility to idiopathic dilated cardiomyopathy in Chinese Han nationality.}, journal = {Autoimmunity}, volume = {39}, number = {6}, pages = {461-467}, doi = {10.1080/08916930600893709}, pmid = {17060025}, issn = {0891-6934}, mesh = {Alleles ; Asian People ; Cardiomyopathy, Dilated/*genetics/immunology ; Case-Control Studies ; China ; Female ; *Genetic Predisposition to Disease ; Genotype ; HLA-DP Antigens/*genetics/immunology ; HLA-DR Antigens/*genetics/immunology ; Humans ; Male ; *Polymorphism, Genetic ; }, abstract = {Although the aetiology of idiopathic dilated cardiomyopathy (IDC) remains unclear, many immunological abnormalities involving changes in cell-mediated and humoral immunity may be associated with cardiac impairment in IDC. Autoimmune mechanisms are likely to participate in the pathogenesis of at least a subgroup of IDC and components of the major histocompatibility complex may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, which are highly polymorphic, play an important role in the activating of immune responses and thus control the predisposition for or protection from IDC. This study explores the possible contribution of HLA-DRB and DP polymorphisms to IDC susceptibility. DNA genotyping for HLA-DRB1, DPA1 and DPB1 was performed using polymerase chain reaction-sequencing based typing (PCR-SBT) method in 198 IDC patients and 136 random selected healthy Han ethnic individuals living in Northern China. IDC patients were, sub-grouped into asymptomatics (subgroup A), with arrhythmia (subgroup B) and with overt congestive heart failure (subgroup C) according to the clinical manifestations and electrocardiogram or echocardiographic characteristics. ADP/ATP autoantibody was detected in IDC group by immunoblot analysis. The results revealed that HLA-DR15, -DPB*0601 frequencies were significantly elevated in IDC group compared with normal control. The DPB1*0601 allele in homozygous form or in combination with allele DPB1*2301 or *3901, was found present more often in IDC patients. The predominance of HLA-DR4 allele was observed in subgroup B after stratification. However, the frequency of DPB1*0101 allele increased in the control than in the IDC group. The frequency of HLA-DPB1*0601 allele was significantly higher in IDC patients with positive autoantibody against ADP/ATP carrier of myocardial mitochondria in contrast to those with negative autoantibody. We conclude that HLA-DR4, -DR15, -DPB1*0601 alleles confers susceptibility to, while DPB1*0101 allele confers protection from IDC among individuals of northern Chinese Han nationality. The glutamate at position 69 in the second exon of DPB1*0601, as a key residue for special conformation of HLA-DP, may confer predisposition to IDC. HLA-DR and -DP alleles polymorphisms may serve as genetic markers for IDC and be involved in the regulation of the immune specific response to auto or exterior anti-myocardium antibodies.}, }
@article {pmid17047060, year = {2006}, author = {Chen, D and Kennedy, A and Wang, JY and Zeng, W and Zhao, Q and Pearl, M and Zhang, M and Suo, Z and Nesland, JM and Qiao, Y and Ng, AK and Hirashima, N and Yamane, T and Mori, Y and Mitsumata, M and Ghersi, G and Chen, WT}, title = {Activation of EDTA-resistant gelatinases in malignant human tumors.}, journal = {Cancer research}, volume = {66}, number = {20}, pages = {9977-9985}, pmid = {17047060}, issn = {0008-5472}, support = {R01 CA039077/CA/NCI NIH HHS/United States ; R01EB002065/EB/NIBIB NIH HHS/United States ; R01 EB002065/EB/NIBIB NIH HHS/United States ; M01 RR010710/RR/NCRR NIH HHS/United States ; M01RR10710/RR/NCRR NIH HHS/United States ; R01CA0039077/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism ; Edetic Acid/*pharmacology ; Endopeptidases ; Enzyme Activation ; Gelatinases/biosynthesis/genetics/isolation &amp; purification/*metabolism ; Haplorhini ; Humans ; Membrane Proteins/biosynthesis/genetics/isolation &amp; purification/*metabolism ; Models, Molecular ; Neoplasms/*enzymology/pathology ; Protein Conformation ; Recombinant Proteins/genetics/isolation &amp; purification/metabolism ; Serine Endopeptidases/biosynthesis/genetics/isolation &amp; purification/*metabolism ; }, abstract = {Among the many proteases associated with human cancer, seprase or fibroblast activation protein alpha, a type II transmembrane glycoprotein, has two types of EDTA-resistant protease activities: dipeptidyl peptidase and a 170-kDa gelatinase activity. To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to generate a soluble recombinant seprase (r-seprase). In the presence of putative EDTA-sensitive activators, r-seprase was converted into 70- to 50-kDa shortened forms of seprase (s-seprase), which exhibited a 7-fold increase in gelatinase activity, whereas levels of dipeptidyl peptidase activity remained unchanged. In malignant human tumors, seprase is expressed predominantly in tumor cells as shown by in situ hybridization and immunohistochemistry. Proteins purified from experimental xenografts and malignant tumors using antibody- or lectin-affinity columns in the presence of 5 mmol/L EDTA were assayed for seprase activation in vivo. Seprase expression and activation occur most prevalently in ovarian carcinoma but were also detected in four other malignant tumor types, including adenocarcinoma of the colon and stomach, invasive ductal carcinoma of the breast, and malignant melanoma. Together, these data show that, in malignant tumors, seprase is proteolytically activated to confer its substrate specificity in collagen proteolysis and tumor invasion.}, }
@article {pmid17045008, year = {2006}, author = {Zhao, WH and Xu, BH and Li, Q and Zhang, P and Sun, Y}, title = {[Clinical features and prognosis in breast cancer patients over 70 years of age].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {28}, number = {5}, pages = {385-388}, pmid = {17045008}, issn = {0253-3766}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/complications/pathology/*surgery ; Carcinoma, Ductal, Breast/complications/pathology/*surgery ; Coronary Disease/complications ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy/*methods ; Neoplastic Cells, Circulating/pathology ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVE: To investigate the clinical characteristics and prognostic factors in breast cancer patients over 70 years of age.<br><br>METHODS: From 1980 to 2003, 280 female breast cancer patients over 70 years old were treated and the data were retrospectively reviewed. The clinical features including age, comorbidity, initial symptom, tumor size and location, pathological type, lymph node status, hormonal receptor status, treatment approaches and overall survival were analyzed.<br><br>RESULTS: These 280 patients accounted for 2.9% of all breast cancer patients registered in our institution during the same period. Presentation of breast lump as initial symptom accounted for 92.5% of the patients. The median time from the presentation of initial symptom to initial diagnosis was 4 months. Major pathological type was invasive ductal carcinoma (74.3%). Estrogen or progesterone receptor was found to be positive in 72.9% by immunohistochemical staining. 165 patients (58.9%) had comorbidity such as coronary heart disease, hypertension, diabetes, etc. 256 patients underwent surgery consisting of 162 modified mastectomies, 46 mastectomies, 38 lumpectomies, 7 lumpectomies plus lymph node dissection, 2 lymph node resection and 1 with unavailable surgery record. The cumulative 5- and 10-year overall survival was 69.9% and 40.6%, respectively. Factors affecting the prognosis were tumor size, lymph node status, pathological stage, vascular invasion and endocrine therapy by univariate analysis. The lymph node status and vascular invasion were found to be two independent prognostic factors affecting significantly the prognosis by multivariate analysis.<br><br>CONCLUSION: Female breast cancer patients over 70 years of age exhibit distinctive clinical and pathological characteristics. Surgery and endocrine therapy are important to achieve good clinical outcome. Lymph node status and vascular invasion are two independent prognostic factors.}, }
@article {pmid17044772, year = {2006}, author = {Eason, RR and Till, SR and Frank, JA and Badger, TM and Korourian, S and Simmen, FA and Simmen, RC}, title = {Tumor-protective and tumor-promoting actions of dietary whey proteins in an N-methyl-N-nitrosourea model of rat mammary carcinogenesis.}, journal = {Nutrition and cancer}, volume = {55}, number = {2}, pages = {171-177}, doi = {10.1207/s15327914nc5502_8}, pmid = {17044772}, issn = {0163-5581}, mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Animals ; Anticarcinogenic Agents/administration &amp; dosage/*pharmacology ; Caseins/administration &amp; dosage/pharmacology ; Cell Differentiation/drug effects ; Disease Models, Animal ; Female ; Genetic Predisposition to Disease ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Experimental/*epidemiology/pathology/*prevention &amp; control ; Milk Proteins/administration &amp; dosage/*pharmacology ; Pregnancy ; Prenatal Exposure Delayed Effects ; Proliferating Cell Nuclear Antigen/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Whey Proteins ; }, abstract = {The mammary tumor-protective effects of dietary factors are considered to be mediated by multiple signaling pathways, consistent with the heterogeneous nature of the disease and the distinct genetic profiles of tumors arising from diverse mammary cell populations. In a 7,12-dimethylbenz(a)anthracene-induced model of carcinogenesis, we showed previously that female Sprague-Dawley rats exposed to AIN-93G diet containing whey protein hydrolysate (WPH) beginning at gestation Day 4 had reduced tumor incidence than those exposed to diet containing casein (CAS), due partly to increased mammary differentiation and reduced activity of phase I metabolic enzymes. Here, we evaluated the tumor-protective effects of these same dietary proteins to the direct-acting carcinogen N-methyl-N-nitrosourea (NMU). We found that lifetime exposure to WPH, relative to CAS, decreased mammary tumor incidence and prolonged the appearance of tumors in NMU-treated female rats, with no corresponding effects on tumor multiplicity. At 115 days post-NMU, histologically normal mammary glands from WPH-fed tumor-bearing rats had increased gene expression for the tumor suppressor BRCA1 and the differentiation marker kappa-casein than those of CAS-fed tumor-bearing rats. Tumor-bearing rats from the WPH group had more advanced tumors, with a greater incidence of invasive ductal carcinoma than ductal carcinoma in situ and higher serum C-peptide levels than corresponding rats fed CAS. WPH-fed tumor-bearing rats were also heavier after NMU administration than CAS tumor-bearing rats, although no correlation was noted between body weight and C-peptide levels for either diet group. Results demonstrate the context-dependent tumor-protective and tumor-promoting effects of WPH; provide support for distinct signaling pathways underlying dietary effects on development of mammary carcinoma; and raise provocative questions on the role of diet in altering the prognosis of existing breast tumors.}, }
@article {pmid17042978, year = {2006}, author = {Li, WM and Liu, W and Gao, C and Zhou, BG and Yang, SS and Wang, Z and Zhang, RH and Gan, RT and Kong, YH and Li, Y}, title = {Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats.}, journal = {Chinese medical journal}, volume = {119}, number = {19}, pages = {1646-1652}, pmid = {17042978}, issn = {0366-6999}, mesh = {Animals ; Autoimmune Diseases/*immunology ; Dendritic Cells/*physiology ; *Immune Tolerance ; Interleukin-10/*genetics ; Lymphocyte Activation ; Male ; Myocarditis/*immunology ; Myosins/*immunology ; NF-kappa B/physiology ; Rats ; Rats, Inbred Lew ; Signal Transduction ; Transfection ; }, abstract = {BACKGROUND: Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.<br><br>METHODS: EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the inhibitor of NF-kappaB pathway, was determined by Western blot.<br><br>RESULTS: BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m) DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IkappaB protein was up-regulated significantly in the IL-10 gene modified iDC group.<br><br>CONCLUSIONS: IL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-kappaB pathway inhibition.}, }
@article {pmid17041796, year = {2006}, author = {Hikino, H and Yasui, K and Ozaki, N and Nagaoka, S}, title = {Significance of preoperative lymphoscintigraphy and thin-slice computed tomography on sentinel node assessment: metastatic sentinel node in a lateral paramammary lesion out of axillary nodes from breast cancer.}, journal = {Radiation medicine}, volume = {24}, number = {8}, pages = {583-586}, pmid = {17041796}, issn = {0288-2043}, mesh = {Adult ; Axilla ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*secondary/surgery ; Female ; Humans ; *Lymph Node Excision ; Lymph Nodes/*diagnostic imaging/pathology/surgery ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Mammography ; Neoplasm Staging ; Radionuclide Imaging ; Sentinel Lymph Node Biopsy ; *Tomography, X-Ray Computed ; Ultrasonography, Interventional ; }, abstract = {Sentinel node status was evaluated using preoperative lymphoscintigraphy in a 43-year-old woman who presented with an invasive ductal carcinoma in the lower outer quadrant of the right breast. Two strong hot nodules were visualized in the affected axillary basin on an early image, and a faint accumulation of radioactive tracer was lying between the cancer in the right lower outer quadrant and the axillary hot nodules on the lymphoscintigram taken at 90 min. The faint accumulation was considered to represent a small paramammary node on thin-slice computed tomography (CT) and was confirmed by node biopsy to be a sentinel node grossly involved with tumor cells. Immediate axillary dissection and adjuvant chemotherapy was subsequently performed. Careful evaluation using lymphoscintigraphy and thin-slice CT may be associated with increased localization of true sentinel nodes.}, }
@article {pmid17019712, year = {2006}, author = {Schneider, J and Ruschhaupt, M and Buness, A and Asslaber, M and Regitnig, P and Zatloukal, K and Schippinger, W and Ploner, F and Poustka, A and Sültmann, H}, title = {Identification and meta-analysis of a small gene expression signature for the diagnosis of estrogen receptor status in invasive ductal breast cancer.}, journal = {International journal of cancer}, volume = {119}, number = {12}, pages = {2974-2979}, doi = {10.1002/ijc.22234}, pmid = {17019712}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Cation Transport Proteins/genetics ; Cluster Analysis ; Female ; GATA3 Transcription Factor/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*genetics ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Middle Aged ; Neoplasm Proteins/genetics ; Oligonucleotide Array Sequence Analysis/methods ; Receptors, Estrogen/genetics/*metabolism ; Reproducibility of Results ; }, abstract = {In breast cancer, the determination of estrogen receptor (ER) expression is crucial for the decision on therapeutic strategies. Current ER expression analysis is based on immunohistochemical (IHC) staining of ER on formalin fixed tissue sections. However, low levels of ER expression frequently escape detection because of varying sensitivities of routine histopathological laboratories. Moreover, in estimating ER by IHC the receptor protein only is tested instead of the complex underlying ER pathway, which reflects its biological activity. To overcome this limitation, we have used the microarray technology to study 56 samples of invasive ductal carcinoma. We infer a robust and reliable signature of 10 genes, which is associated with ER expression and presumably therapeutically relevant biological processes. In a meta-analysis, the signature was tested on 3 further independent microarray gene expression data sets, covering different laboratories, array platforms, and clinics. The classification based on the signature showed a very low misclassification rate. In summary, the expression of few genes is sufficient to determine ER status. Future decisions on antiestrogen based therapy in breast cancer could be based on this signature rather than on immunostaining alone.}, }
@article {pmid16997856, year = {2006}, author = {Joshi, PS and Liu, JQ and Wang, Y and Chang, X and Richards, J and Assarsson, E and Shi, FD and Ljunggren, HG and Bai, XF}, title = {Cytokine-induced killer T cells kill immature dendritic cells by TCR-independent and perforin-dependent mechanisms.}, journal = {Journal of leukocyte biology}, volume = {80}, number = {6}, pages = {1345-1353}, doi = {10.1189/jlb.0506305}, pmid = {16997856}, issn = {0741-5400}, support = {R21AI166T8/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Cytotoxicity, Immunologic ; Dendritic Cells ; Interferon-gamma/*immunology ; Killer Cells, Lymphokine-Activated/*immunology ; Lymphocyte Activation/*immunology ; Membrane Glycoproteins/*immunology ; Mice ; Neoplasms/immunology ; Perforin ; Pore Forming Cytotoxic Proteins/*immunology ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/*immunology ; }, abstract = {Cytokine-induced killer (CIK) cells are ex vivo, expanded T cells with proven anticancer activity in vitro and in vivo. However, their functional properties with the exception of their cancer cell-killing activity are largely unclear. Here, we show that CIK T cells recognize dendritic cells (DC), and although mature DC (mDC) induce CIK T cells to produce IFN-gamma, immature DC (iDC) are killed selectively by them. Moreover, CIK T cell activation by mDC and their destruction of iDC are independent of the TCR. The cytotoxicity of CIK T cells to iDC is perforin-dependent. Our data have revealed an important regulatory role of CIK cells.}, }
@article {pmid16978974, year = {2006}, author = {Vo, TN and Meric-Bernstam, F and Yi, M and Buchholz, TA and Ames, FC and Kuerer, HM and Bedrosian, I and Hunt, KK}, title = {Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma.}, journal = {American journal of surgery}, volume = {192}, number = {4}, pages = {552-555}, doi = {10.1016/j.amjsurg.2006.06.020}, pmid = {16978974}, issn = {0002-9610}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/mortality/secondary/*therapy ; Carcinoma, Lobular/mortality/secondary/*therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: Breast-conservation therapy (BCT), including wide local excision and postoperative irradiation, is considered standard treatment for early-stage invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular carcinoma (ILC) has been questioned because of concerns regarding ipsilateral breast recurrence and risk of bilateral breast cancer. We evaluated our institutional experience with BCT and compared treatment outcomes for ILC with those for IDC.<br><br>METHODS: A review of our BCT database revealed 84 patients with ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation between 1976 and 1999. We evaluated local-regional recurrence, disease-specific survival, and contralateral breast cancer rates in both groups.<br><br>RESULTS: The 5- and 10-year local-regional recurrence rates for the ILC group were 1% and 7%, respectively, and 4% and 9%, respectively, for the IDC group (P = .70). There were no significant differences in the 5- and 10-year disease-specific survival rates between the groups. Contralateral breast cancer occurred in 11.3% of patients with IDC and 11.9% of patients with ILC.<br><br>CONCLUSIONS: BCT achieves similar local-regional control and survival outcomes in selected patients with ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for patients with early-stage invasive lobular carcinoma.}, }
@article {pmid16978959, year = {2006}, author = {Greene, T and Tartter, PI and Smith, SR and Estabrook, A}, title = {The significance of surgical margins for patients with atypical ductal hyperplasia.}, journal = {American journal of surgery}, volume = {192}, number = {4}, pages = {499-501}, doi = {10.1016/j.amjsurg.2006.06.024}, pmid = {16978959}, issn = {0002-9610}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*etiology ; Carcinoma, Ductal, Breast/*etiology ; Carcinoma, Intraductal, Noninfiltrating/*etiology ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/surgery ; Mammary Glands, Human/*pathology/*surgery ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: The significance of surgical margins for patients with atypical ductal hyperplasia is unknown.<br><br>PATIENTS AND METHODS: We reviewed our experience with atypical ductal hyperplasia and correlated the margin status of the specimens removed with the risk of recurrence as atypical ductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma. Seven hundred forty-seven patients were identified between February 1995 and September 2005 as having biopsy proven atypical ductal hyperplasia (ADH). One hundred fifty-five of these patients were found to have "pure" atypical ductal hyperplasia without associated premalignant or malignant breast disease or a history of ipsilateral disease. Margin status of the initial excisional biopsy was noted and was correlated with the risk of recurrence.<br><br>RESULTS: Of the 155 patients whose excisional biopsy specimens were "pure" atypical ductal hyperplasia, 44% (68) had negative margins, 5% (7) had positive margins, and 52% (80) were not reported. No patient underwent re-excision for close or positive margins. Follow-up ranged from 0 to 119 months, with a mean of 26 months. Seven patients (5%) presented with new findings at the site of their initial excisional biopsy, 1 of whom was found to have an invasive ductal carcinoma and 6 of whom had benign findings. Of the 87 patients with margins positive or unknown for ADH at surgical excision, none went on to develop malignancy.<br><br>CONCLUSION: Our results suggest that clear surgical margins at surgical excision for atypical ductal hyperplasia did not affect the risk of subsequently developing a malignancy.}, }
@article {pmid16972643, year = {2006}, author = {Iwasaki, T and Nakagawa, K and Katsura, H and Nakane, S and Kawahara, K and Fukuda, H}, title = {Pulmonary suture abscess with false-positive 18F-fluorodeoxyglucose positron emission scan mimicking lung cancer recurrence.}, journal = {The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyobu Geka Gakkai zasshi}, volume = {54}, number = {8}, pages = {351-355}, pmid = {16972643}, issn = {1344-4964}, mesh = {Adenocarcinoma/surgery ; Breast Neoplasms/surgery ; Carcinoma, Ductal, Breast/surgery ; Diagnosis, Differential ; False Positive Reactions ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lung Abscess/diagnostic imaging/*etiology/pathology ; Lung Neoplasms/surgery ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/*diagnostic imaging ; *Pneumonectomy ; *Positron-Emission Tomography/methods ; Radiopharmaceuticals ; Sutures/*adverse effects ; }, abstract = {We present the case of a 57-year-old woman with pulmonary suture abscess. She had undergone right S3 segmentectomy for early lung adenocarcinoma 7 years before and right breast-conserving surgery for invasive ductal carcinoma 5 months previously, followed by irradiation plus endocrine therapy. Chest radiography and computed tomography revealed an irregular mass (3.5 cm in diameter) between the residual S1 segment and the middle lobe, neighboring the staple line of the segmentectomy. 18F-fluorodeoxyglucose uptake into the mass increased, seen by positron emission scans. Therefore, we could not rule out the possibility of local recurrence of lung cancer and resected it. Pathologically and microbiologically, the mass was a suture abscess arising around the nylon suture of the previous segmentectomy. This lesion was the result of a foreign-body reaction, as confirmed by polarized microscopy. Moreover, titanium staples at the segmentectomy and breast-conserving surgery may also have contributed to this condition.}, }
@article {pmid16969029, year = {2006}, author = {Ohsako, T and Inoue, K and Nagamoto, N and Yoshida, Y and Nakahara, O}, title = {[Two cases of recurrent breast cancer with regional lymph node metastases showing a complete response to trastuzumab and paclitaxel treatment].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {33}, number = {9}, pages = {1301-1303}, pmid = {16969029}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Drug Administration Schedule ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Paclitaxel/administration &amp; dosage ; Receptor, ErbB-2/biosynthesis ; Remission Induction ; Trastuzumab ; }, abstract = {We report two cases of recurrent breast cancer with regional lymph node metastases that responded completely to treatment with trastuzumab and paclitaxel. Case 1: A 52-year-old woman, who presented with left breast cancer, underwent mastectomy and axillary lymph node dissection in July 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 2.2 cm in size, histological grade 3, positive invasion to the lymphatic and blood vessels, negative nodal status (0/11), negative ER/PgR status, and overexpression of HER 2/neu. Left axillary lymph node metastasis was noted after five months, ie, in December 2002. Four cycles of chemotherapy with doxorubicin and cyclophosphamide were administered from January 2003; however, they were not effective. The patient showed a complete response after three months of chemotherapy with trastuzumab and paclitaxel. This treatment was stopped in September 2003. She has maintained a complete response for two and a half years and was not administered any further treatment as of February 2006. Case 2: A 59-year-old woman, who presented with right breast cancer, underwent mastectomy and axillary lymph node dissection in May 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 1.8 cm in size, histological grade 2, positive invasion to the lymphatic and blood vessels, negative nodal status (0/5), positive ER and uncertain PgR status, and overexpression of HER 2/neu. She had received adjuvant hormonal therapy with tamoxifen; however, a right supraclavicular lymph node metastasis was noted in October 2004. Treatment with exemestane was not effective. However, a complete response was observed with trastuzumab and paclitaxel for four months. She has maintained a complete response for six months and was not administered any further treatment as of February 2006.}, }
@article {pmid16969028, year = {2006}, author = {Rai, Y and Takahama, T and Sagara, Y and Sagara, Y and Matsuyama, Y and Ando, M and Sagara, Y and Ooi, Y}, title = {[Markedly effective regimen using bi-weekly trastuzumab and paclitaxel in an advanced breast cancer with multiple liver metastases].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {33}, number = {9}, pages = {1297-1300}, pmid = {16969028}, issn = {0385-0684}, mesh = {Aged ; Antibodies, Monoclonal/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary ; Drug Administration Schedule ; Female ; Humans ; Liver Neoplasms/*secondary ; Paclitaxel/administration &amp; dosage ; Receptor, ErbB-2/biosynthesis ; Remission Induction ; Trastuzumab ; }, abstract = {A 69-year-old woman had a 7 x 6 cm tumor on her left breast with ipsilateral axillary lymph node swelling and multiple liver metastases as detected on CT scan (T 3 N 2 M 1 b, Stage IV). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor and overexpression of HER 2. After a treatment failure of 3 months weekly trastuzumab monotherapy, a combination of bi-weekly trastuzumab and paclitaxel (weekly 6, bi-weekly 9 courses), was given. Tumor markers became negative 4 months later, and multiple liver nodules, breast tumor and axillary nodes completely disappeared 9 months later. Breast surgery was avoided, and CR was maintained more than 8 months only with bi-weekly trastuzumab. From the standpoint of the patient's convenience,a bi-weekly schedule of trastuzumab and paclitaxel could be a promising treatment choice for metastatic breast cancer.}, }
@article {pmid16959899, year = {2006}, author = {Santegoets, SJ and Masterson, AJ and van der Sluis, PC and Lougheed, SM and Fluitsma, DM and van den Eertwegh, AJ and Pinedo, HM and Scheper, RJ and de Gruijl, TD}, title = {A CD34(+) human cell line model of myeloid dendritic cell differentiation: evidence for a CD14(+)CD11b(+) Langerhans cell precursor.}, journal = {Journal of leukocyte biology}, volume = {80}, number = {6}, pages = {1337-1344}, doi = {10.1189/jlb.0206111}, pmid = {16959899}, issn = {0741-5400}, mesh = {Antigens, CD/biosynthesis/immunology ; Antigens, CD34/*immunology/metabolism ; CD11b Antigen/*immunology/metabolism ; Cell Differentiation/*immunology ; Cell Line, Tumor ; Cell Proliferation ; Cytoplasmic Granules/immunology/metabolism ; Gene Expression Regulation/immunology ; Humans ; Langerhans Cells/*immunology/metabolism ; Lectins, C-Type/biosynthesis/immunology ; Lipopolysaccharide Receptors/*immunology/metabolism ; Mannose-Binding Lectins/biosynthesis/immunology ; *Models, Immunological ; Myeloid Progenitor Cells/immunology/metabolism ; }, abstract = {The study of early events in dendritic cell (DC) differentiation is hampered by the lack of homogeneous primary cell systems that allow the study of cytokine-driven, transitional DC differentiation steps. The CD34(+) acute myeloid leukemia cell line MUTZ-3 displays a unique ability to differentiate into interstitial DC (IDC) and Langerhans cells (LC) in a cytokine-dependent manner. Phenotypic characterization revealed MUTZ-3 to consist of three distinct subpopulations. Small CD34(+)CD14(-)CD11b(-) progenitors constitute the proliferative compartment of the cell line with the ability to differentiate through a CD34(-)CD14(-)CD11b(+) stage to ultimately give rise to a morphologically large, nonproliferating CD14(+)CD11b(hi) progeny. These CD14(+)CD11b(hi) cells were identified as common, immediate myeloid DC precursors with the ability to differentiate into LC and IDC, exhibiting characteristic and mutually exclusive expression of Langerin and DC-specific ICAM-grabbing nonintegrin, respectively. The identity of the MUTZ-3-derived LC subset was confirmed further by the presence of Birbeck granules. We conclude that the MUTZ-3 cell line provides a ready and continuous supply of common myeloid precursors, which should facilitate further study of the ontogeny of myeloid DC lineages.}, }
@article {pmid16951894, year = {2006}, author = {de Moraes, AB and Zanini, RR and Turchiello, MS and Riboldi, J and de Medeiros, LR}, title = {[Survival study of breast cancer patients treated at the hospital of the Federal University in Santa Maria, Rio Grande do Sul, Brazil].}, journal = {Cadernos de saude publica}, volume = {22}, number = {10}, pages = {2219-2228}, doi = {10.1590/s0102-311x2006001000028}, pmid = {16951894}, issn = {0102-311X}, mesh = {Adult ; Biomarkers, Tumor/blood ; Brazil/epidemiology ; Breast Neoplasms/*mortality/pathology/therapy ; Cohort Studies ; Female ; Humans ; Lymph Nodes/*pathology/surgery ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; }, abstract = {This retrospective hospital-based study aimed to describe health conditions and to estimate the survival of 252 patients diagnosed with breast cancer and treated at the Mastology Outpatient Clinic at the University Hospital of the Federal University in Santa Maria, Rio Grande do Sul, Brazil, from 1980 to 2000. Analysis followed the Kaplan-Meier and Cox model. Mean age was 54, and 73.4% of the patients had a histological diagnosis of invasive ductal carcinoma, 63.9% showed no lymph node involvement, and 57.6% were clinical stage II. At the end of the study, 64.7% were alive and free of breast cancer and 5.1% had died of other causes. Five-year survival was 87.7% for all women, and prognostic factors associated with survival were tumor size (HR = 12.03; > 5cm), lymph node involvement (HR = 3.08; N1) and number (HR = 4.66; None), and estrogen (HR = 0.34) and c-erbB-2 (HR = 2.51) receptors. Based on the results, intensive awareness-raising campaigns are vitally important for implementing breast cancer screening to achieve early diagnosis.}, }
@article {pmid16951342, year = {2006}, author = {Charbonnier, LM and van Duivenvoorde, LM and Apparailly, F and Cantos, C and Han, WG and Noël, D and Duperray, C and Huizinga, TW and Toes, RE and Jorgensen, C and Louis-Plence, P}, title = {Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {177}, number = {6}, pages = {3806-3813}, doi = {10.4049/jimmunol.177.6.3806}, pmid = {16951342}, issn = {0022-1767}, mesh = {Adoptive Transfer ; Animals ; Arthritis, Experimental/*immunology/pathology/*prevention &amp; control ; B-Lymphocyte Subsets/immunology/metabolism ; Cell Differentiation/immunology ; *Cell Proliferation ; Cells, Cultured ; Dendritic Cells/*cytology/*immunology/transplantation ; Injections, Intraperitoneal ; Integrin alpha2/*biosynthesis ; Interleukin-10/biosynthesis/metabolism ; Lymph Nodes/cytology/immunology/metabolism ; Lymphocyte Activation/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; T-Lymphocytes, Regulatory/*immunology/metabolism/*pathology ; }, abstract = {Dendritic cells (DCs) are specialized APCs with an important role in the initiation and regulation of immune responses. Immature DCs (iDCs) reportedly mediate tolerance in the absence of maturation/inflammatory stimuli, presumably by the induction of regulatory T cells. In this study, we show for the first time that repetitive iDC injections trigger the expansion of a novel regulatory population with high immunomodulatory properties, able to protect mice from collagen-induced arthritis. These regulatory T cells are characterized by the expression of the CD49b molecule and correspond to a CD4+ alpha-galactosylceramide/CD1d-nonrestricted T cell population producing IL-10. Adoptive transfer of < 10(5) TCRbeta+ CD49b+ cells isolated from the liver of iDCs-vaccinated mice, conferred a complete protection against arthritis. This protection was associated with an attenuation of the B and T cell response associated with a local secretion of IL-10. Thus, together these data demonstrate that iDCs can expand and activate a novel regulatory population of CD49b+ T cells, with high immunosuppressive potential able to mediate protection against a systemic autoimmune disease.}, }
@article {pmid16942646, year = {2006}, author = {Lopes, G and DeCesare, T and Ghurani, G and Vincek, V and Jorda, M and Glück, S and Silva, O}, title = {Primary ectopic breast cancer presenting as a vulvar mass.}, journal = {Clinical breast cancer}, volume = {7}, number = {3}, pages = {278-279}, doi = {10.3816/CBC.2006.n.041}, pmid = {16942646}, issn = {1526-8209}, mesh = {Adenocarcinoma/*diagnosis/secondary/therapy ; Adult ; *Breast ; Breast Neoplasms/*diagnosis/pathology/therapy ; Choristoma/*diagnosis/pathology/therapy ; Diagnosis, Differential ; Female ; Humans ; Neoplasms, Hormone-Dependent/*diagnosis/pathology/therapy ; Vulvar Neoplasms/*diagnosis/secondary/therapy ; }, abstract = {Ectopic breast tissue is found along the primitive embryonic milk lines, which extend from the axilla to the groin. Rarely, its occurrence has been described in the vulva. We report a patient who developed primary adenocarcinoma of ectopic breast tissue in such a location and present a review of the pertinent medical literature. The predominant pathology is that of invasive ductal carcinoma; however, other tumor types have also been reported in accessory breast tissue. Its treatment usually entails surgical resection with lymph node dissection. Adjuvant therapy should be guided by the same principles as in orthotopic breast carcinoma.}, }
@article {pmid16941124, year = {2007}, author = {Igyártó, BZ and Magyar, A and Oláh, I}, title = {Origin of follicular dendritic cell in the chicken spleen.}, journal = {Cell and tissue research}, volume = {327}, number = {1}, pages = {83-92}, doi = {10.1007/s00441-006-0250-0}, pmid = {16941124}, issn = {0302-766X}, mesh = {Animals ; B-Lymphocytes/cytology/immunology ; Cell Differentiation ; Cell Movement ; Chickens/*physiology ; Dendritic Cells, Follicular/*cytology/enzymology/immunology ; Fluorescent Antibody Technique, Indirect ; Immunoenzyme Techniques ; Spleen/*cytology ; T-Lymphocytes/cytology/immunology ; beta-Galactosidase/immunology/metabolism ; }, abstract = {The ellipsoid-associated cell (EAC) is a blood-borne phagocytic cell, residing in the antigen trapping zone of the chicken spleen. Binding and endocytosis of betaGalactosidase (betaGal) are independent from the Fc and complement receptors, because sulfated polysaccharides, in a concentration manner, inhibit the bacterial antigen uptake. The betaGal-positive cells migrate to the periarterial lymphatic sheath (PALS), the preexisting germinal centers (GC), and form clusters with B- and T-cells. betaGal, E5G12 double positive cells on the surface of the ellipsoid and in the PALS, GC and clusters prove that the EACs carry the enzyme. The EAC and the follicular dendritic cell (FDC) express, 68.2 and E5G12 and, 74.3 and E5G12, antigens, respectively. During migration the cessation of 68.2 and expression of 74.3 indicate the differentiation of EAC to FDC. By day 14 the clusters had disappeared, and in several GC the presence of double positive cells (74.3 and betaGal; E5G12 and betaGal) showed that the clusters had developed to GC. The presence of betaGal(+) cells in the PALS, where interdigitating dendritic cells (IDC) cooperate with the T-cells, suggests that in the spleen alternate routes exist for the EAC differentiation to FDC: EAC to FDC: betaGal-loaded cells in the preexisting GC; and EAC through IDC to FDC: betaGal(+) EAC in the PALS and clusters. The EAC-FDC axis works exclusively inside the spleen; therefore; this system may be operated in pneumococcus infection.}, }
@article {pmid16937310, year = {2006}, author = {Hikino, H and Kawashima, M and Yamada, T and Ozaki, N}, title = {Motor dominant neuropathy induced by adjuvant therapy with adriamycin and cyclophosphamide followed by dose-dense paclitaxel in a breast cancer patient.}, journal = {International journal of clinical oncology}, volume = {11}, number = {4}, pages = {332-335}, pmid = {16937310}, issn = {1341-9625}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Chemotherapy, Adjuvant/adverse effects ; Cyclophosphamide/*administration &amp; dosage ; Dose-Response Relationship, Drug ; Doxorubicin/*administration &amp; dosage ; Female ; Humans ; Motor Neuron Disease/chemically induced ; Paclitaxel/*administration &amp; dosage ; Peripheral Nervous System Diseases/*chemically induced ; }, abstract = {A 38-year-old woman underwent mastectomy and axillary lymph node dissection for invasive ductal carcinoma with multiple lymph node involvement. The patient received adriamycin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) followed by weekly paclitaxel 80 mg/m(2) (without interruption) as adjuvant treatment. After receiving ten courses of paclitaxel, the patient developed motor neuropathy, with difficulty in ascending stairs and rising from a chair. A nerve conduction study demonstrated impairment of bilateral peroneal nerve function, although the sural sensory nerves were intact. After 2 weeks of withholding paclitaxel treatment, the motor neuropathy was alleviated and the scheduled doses were completed. A pharmacokinetic study of paclitaxel showed the possibility of elimination delay at the last infusion. We suggest that a dose-dense schedule of paclitaxel may be a significant risk factor for this kind of motor neuropathy.}, }
@article {pmid16932086, year = {2006}, author = {La Vecchia, L and Varotto, L and Zanolla, L and Spadaro, GL and Fontanelli, A}, title = {Right ventricular function predicts transplant-free survival in idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiovascular medicine (Hagerstown, Md.)}, volume = {7}, number = {9}, pages = {706-710}, doi = {10.2459/01.JCM.0000243006.90170.ce}, pmid = {16932086}, issn = {1558-2027}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/mortality/*physiopathology ; Coronary Angiography ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Stroke Volume ; Ventricular Dysfunction, Left/etiology ; Ventricular Dysfunction, Right/*etiology ; }, abstract = {BACKGROUND: Right ventricular function may be reduced in patients with idiopathic dilated cardiomyopathy (IDC). The prognostic implications of right ventricular dysfunction have not been investigated in this group of patients.<br><br>METHODS: In a series of 120 consecutive patients with IDC [defined as a left ventricular ejection fraction (LVEF) < 55%, normal coronary arteries and no other causes for left ventricular dysfunction], right ventricular function was prospectively evaluated by means of angiocardiography at the time of catheterization. A head-to-head comparison of ventricular volumes, ejection fraction, end-diastolic pressure, stroke work index and end-systolic pressure/volume ratio of the left and right ventricle was performed according to the Cox's proportional hazard method for the pre-defined end-point of transplant-free survival.<br><br>RESULTS: In the study population, LVEF was 31 +/- 11% and right ventricular ejection fraction (RVEF) was 34 +/- 10%. After a mean follow-up of 30 months (range 12-120 months), 26 patients died (22%) and 14 (12%) underwent heart transplantation. At univariate analysis, all the above mentioned parameters were significantly (P < 0.0001) associated with outcome except left and right ventricular end-systolic pressure/volume ratio. At multivariate analysis, independent predictors of transplant-free survival were RVEF (P = 0.001), right ventricular stroke work index (P = 0.015), right ventricular end-diastolic volume (P = 0.034) and left ventricular end-diastolic volume (P = 0.048), but not LVEF. The same relation holds true considering the end point of total mortality.<br><br>CONCLUSIONS: Parameters of right ventricular function are strong predictors of survival in IDC, even in patients enrolled over a wide range of LVEFs. The present study suggests that right ventricular function should be evaluated in patients with IDC. A large non-invasive based study on right ventricular function in IDC appears to be warranted.}, }
@article {pmid16932083, year = {2006}, author = {Barbieri, A and Grigioni, F and Bursi, F and Reggianini, L and Bonatti, S and Ricci, C and Boriani, G and Russo, A and Magelli, C and Branzi, A and Modena, MG}, title = {Role of severe functional mitral regurgitation in predicting electrical remodeling in idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiovascular medicine (Hagerstown, Md.)}, volume = {7}, number = {9}, pages = {691-695}, doi = {10.2459/01.JCM.0000243003.05418.d4}, pmid = {16932083}, issn = {1558-2027}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*physiopathology ; Electrocardiography ; Female ; Heart Conduction System/*physiopathology ; Heart Ventricles/physiopathology ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency/complications/*physiopathology ; Multivariate Analysis ; Myocardial Contraction/physiology ; Prognosis ; Risk Assessment ; }, abstract = {OBJECTIVE: To investigate incidence and predictors of clinically relevant QRS widening (predefined as > or = 10% with respect to baseline) in idiopathic dilated cardiomyopathy (IDC) and particularly the prognostic role of functional mitral regurgitation (MR). Although QRS widening in left ventricular systolic dysfunction carries relevant prognostic and therapeutic implications, its incidence and predictors in patients with IDC remain unknown.<br><br>METHODS: We analyzed 114 patients with IDC receiving optimized medical treatment (age 52 +/- 10 years; 44% males; 36% New York Heart Association class III-IV) who underwent clinical, echocardiographic, hemodynamic, and laboratory evaluations and at least two electrocardiograms > or = 6 months after the index evaluation.<br><br>RESULTS: During follow-up (median 20 months), 19 (17%) patients developed clinically relevant QRS widening, corresponding to an incidence of 8% per year. At multivariable analysis, the presence of echocardiographically detected severe MR (P = 0.029) and mean right atrial pressure (RAP) by right heart catheterization (P = 0.021) independently predicted clinically relevant QRS widening.<br><br>CONCLUSIONS: Clinically relevant QRS widening is relatively frequent in IDC despite optimized medical treatment, and is independently predicted by MR severity and high RAP. IDC patients presenting either of these risk-factors might benefit from strict follow-up, which could also allow timely detection of the onset of indications for cardiac resynchronization therapy.}, }
@article {pmid16929128, year = {2006}, author = {Kijima, Y and Umekita, Y and Ehi, K and Yoshinaka, H and Funasako, Y and Owaki, T and Yoshida, H and Aikou, T}, title = {Sudden hemorrhage without skin invasion in a patient with breast cancer: a case report and literature review.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {3}, pages = {317-321}, doi = {10.2325/jbcs.13.317}, pmid = {16929128}, issn = {1340-6868}, mesh = {Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/*complications/diagnostic imaging ; Carcinoma, Ductal, Breast/complications/diagnostic imaging ; Female ; Hemorrhage/*etiology ; Humans ; Mammography ; Mastectomy ; Neoplasm Invasiveness/*pathology ; Skin/*pathology ; Tomography, X-Ray Computed ; }, abstract = {We report a rare case of sudden hemorrhage caused by breast cancer. A 70-year-old Japanese woman noted fresh bleeding from her left breast. On physical examination, continuous hemorrhage accompanied by an open cavity was observed in the left breast. Mammography and ultrasonography revealed a well-circumscribed mass, with solid and cystic components, that was highly suggestive of intracystic breast carcinoma with direct skin invasion. Computed tomography and bone scintigraphy showed no distant metastasis. Aspiration biopsy of the lesion showed several clusters of adenocarcinoma cells. Modified radical mastectomy was performed with a presumptive diagnosis of stage III B left breast cancer. Invasive ductal carcinoma without skin invasion was diagnosed histologically. To the best of our knowledge, only 6 other cases of sudden hemorrhage caused by breast cancer without skin invasion have been reported in Japan. We review the literature and discuss the clinical characteristics of this unusual phenomenon.}, }
@article {pmid16911908, year = {2006}, author = {Kushner, JD and Nauman, D and Burgess, D and Ludwigsen, S and Parks, SB and Pantely, G and Burkett, E and Hershberger, RE}, title = {Clinical characteristics of 304 kindreds evaluated for familial dilated cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {12}, number = {6}, pages = {422-429}, doi = {10.1016/j.cardfail.2006.03.009}, pmid = {16911908}, issn = {1532-8414}, support = {5 M01 RR000334/RR/NCRR NIH HHS/United States ; R01-HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Cardiomyopathy, Dilated/diagnosis/*genetics/physiopathology/surgery ; Cardiovascular System/*physiopathology ; Child ; Child, Preschool ; Death ; Female ; Heart Transplantation ; Humans ; Infant ; Male ; Medical Records ; Middle Aged ; Pedigree ; Time Factors ; }, abstract = {BACKGROUND: Familial dilated cardiomyopathy (FDC) is dilated cardiomyopathy of unknown cause occurring in 2 or more closely related family members.<br><br>METHODS AND RESULTS: Members of 304 families suspected to have FDC were evaluated by family history (FH) and medical record review and were categorized as affected with idiopathic dilated cardiomyopathy (IDC), unaffected, unknown, or no data. Pedigrees were categorized with confirmed FDC, probable FDC, possible FDC or IDC based on strength of evidence. Of the 304 pedigrees, 125 were categorized as confirmed FDC, 48 were probable FDC, 72 were possible FDC, and 59 had sporadic, nonfamilial IDC. Numbers of living first- and second-degree family members, and median number of relatives available for FH was greatest with confirmed FDC, and diminished for probable and possible FDC, and IDC categories. LV dimensions increased and LV function worsened in index patients along the spectrum from confirmed FDC, probable FDC, possible FDC and IDC, and a greater proportion of IDC patients underwent heart transplant. However, the age of onset, duration of disease, the time to death or heart transplant, and most other findings were similar among the 4 categories.<br><br>CONCLUSION: Clinical characteristics of IDC and FDC are similar, precluding an FDC diagnosis from clinical features only.}, }
@article {pmid16904443, year = {2006}, author = {Monoski, MA and Gonzalez, RR and Sandhu, JS and Reddy, B and Te, AE}, title = {Urodynamic predictors of outcomes with photoselective laser vaporization prostatectomy in patients with benign prostatic hyperplasia and preoperative retention.}, journal = {Urology}, volume = {68}, number = {2}, pages = {312-317}, doi = {10.1016/j.urology.2006.02.020}, pmid = {16904443}, issn = {1527-9995}, mesh = {Humans ; *Laser Therapy ; Male ; Prostatectomy/*methods ; Prostatic Hyperplasia/complications/*physiopathology/*surgery ; Retrospective Studies ; Treatment Outcome ; Urinary Retention/etiology/*physiopathology/*surgery ; *Urodynamics ; }, abstract = {OBJECTIVES: To determine whether preoperative urodynamic parameters can predict the outcome in men in urinary retention and aid in counseling these men.<br><br>METHODS: Forty men in urinary retention due to benign prostatic hyperplasia underwent photoselective laser vaporization prostatectomy (PVP). Preoperative urodynamic studies were used to identify the men with detrusor overactivity (DO) and impaired detrusor contractility (IDC). The International Prostate Symptom Score (IPSS), maximal flow rate, and postvoid residual urine volume were collected at 1, 3, 6, and 12 months after PVP.<br><br>RESULTS: Of the 40 men, 8 (20%) had IDC and 30 had DO (75%) preoperatively. The men without preoperative DO had a significantly lower IPSS than those with preoperative DO at 1 month of follow-up. Men without preoperative IDC had a significantly lower IPSS and postvoid residual urine volume at the same point compared with men with preoperative IDC. The flow rate in men with preoperative IDC 1 and 6 months postoperatively was significantly lower than in men without preoperative IDC.<br><br>CONCLUSIONS: Preoperative urodynamic parameters predict for outcome in men in urinary retention undergoing PVP. Men in urinary retention benefit from PVP with an improvement in both subjective and objective voiding function, regardless of the presence of DO or IDC. Postoperatively, patients with DO have more voiding symptoms than those without DO, and are almost twice as likely to require anticholinergics. Men without IDC have better IPSS, flow rates, and postvoid residual urine volumes compared with men with IDC. Of the 8 men with IDC, 3 required reoperation within the first year.}, }
@article {pmid16904381, year = {2006}, author = {Yang, S and Li, W and Liu, W and Gao, C and Zhou, B and Li, S and Li, Y and Kong, Y}, title = {IL-10 gene modified dendritic cells induced antigen-specific tolerance in experimental autoimmune myocarditis.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {121}, number = {1}, pages = {63-73}, doi = {10.1016/j.clim.2006.06.009}, pmid = {16904381}, issn = {1521-6616}, mesh = {Adoptive Transfer ; Animals ; Autoantigens/immunology ; Autoimmune Diseases/*genetics/therapy ; Bone Marrow Cells/immunology/metabolism ; Cells, Cultured ; Dendritic Cells/*immunology/*metabolism/transplantation ; Disease Models, Animal ; Epitopes/*immunology ; Immune Tolerance/*genetics ; Interleukin-10/*genetics/physiology ; Male ; Myocarditis/*genetics/*immunology/therapy ; Rats ; Rats, Inbred Lew ; }, abstract = {Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder, and the involvement of Th1/Th2 unbalance has been demonstrated. The induction of antigen-specific tolerance is critical for the treatment of EAM and maintenance of immune tolerance. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to explore the effects of IL-10 gene modified bone-marrow-derived immature dendritic cells (iDCs) on the in vitro and in vivo immune response to cardiac myosin in EAM. EAM was induced using the classic methods of cardiac myosin immunization on day 0 and day 7. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously for treatment 5 days after the first immunization. On day 21, transthoracic echocardiogram and HE staining were performed to detect the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen-specific tolerance induced by IL-10 gene modified iDCs. IL-10 gene modified iDC-treated EAM rats showed improved cardiac function and reduced infiltration of inflammatory cell into myocardium. Serum cytokines data indicated lower Th1 while higher Th2-type responses were induced in the pcDNA3-IL-10-iDC-treated group, suggesting a Th2 polarization. Moreover, IL-10 gene modified iDCs down-regulated MHC-II and costimulatory molecules on the surface of splenocytes and inhibited the antigen-specific immunological responses towards cardiac myosin. Adoptive transfer of IL-10 producing DCs prevented EAM induction. IL-10 gene modified iDCs ameliorates EAM histopathologically and functionally. The underlying mechanisms may be related to the IL-10 induced Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecules expression.}, }
@article {pmid16888913, year = {2003}, author = {Diallo, R and Tognon, C and Knezevich, SR and Sorensen, P and Poremba, C}, title = {Secretory carcinoma of the breast: a genetically defined carcinoma entity.}, journal = {Verhandlungen der Deutschen Gesellschaft fur Pathologie}, volume = {87}, number = {}, pages = {193-203}, pmid = {16888913}, issn = {0070-4113}, mesh = {3T3 Cells ; Adult ; Aged ; Animals ; Breast Neoplasms/classification/*genetics/*pathology ; Child ; Female ; Gene Fusion ; Humans ; In Situ Hybridization, Fluorescence ; Mice ; Middle Aged ; Nucleic Acid Hybridization ; Proto-Oncogene Proteins c-ets/genetics ; Receptor, trkC/genetics ; Repressor Proteins/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; }, abstract = {Secretory carcinomas (SBC) are characterized by their characteristic histomorphology and more favorable prognosis compared to invasive ductal carcinoma of usual type (IDC). On this basis, 13 SBCs are evaluated by molecular and immunohistochemical (IH) methods. 13 SBCs and 4 IDCs were analyzed for ETV6-NTRK3 gene fusion by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Fluorescence in situ Hybridization (FISH). 8 of 13 microdissected SBCs with evaluable DNA were evaluated for genetic alterations (GA) by comparative genomic hybridization (CGH). IH included estrogen-receptor (ER), progesterone-receptor (PR), Her-2/neu and Ki-67 (MIB-1) in all 13 cases. Molecular and immunohistochemical results in SBCs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. 12 of 13 (92 %) SBC cases, but not IDCs expressed the ETV6-NTRK3 fusion gene which encodes a chimeric tyrosine kinase. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary epithelial cells resulted in transformed cells that readily formed epithelial tumors in nude mice. CGH revealed an average of 2.0 GAs (range 0-6), including recurrent gains of chromosome 8q and 1q and losses of 22q. Four SBCs were positive for ER and 2 were positive for PR. The mean MIB-1-labeling index was 11.4% (range: <1-34%). Her-2/ neu protein overexpression was detected in 1 case (score 3+). Compared to previous findings in IDCs, SBCs are characterized by the recurrent expression of ETV6-NTRK3 fusion gene, a relatively low number of GAs, low proliferative rate, infrequent Her-2/ neu protein overexpression and a lower rate of steroid hormone receptor expression. These results support the hypothesis that SBCs have immunohistochemical and genetic features that specifically distinguish them from IDCs.}, }
@article {pmid16882710, year = {2006}, author = {Krispin, A and Bledi, Y and Atallah, M and Trahtemberg, U and Verbovetski, I and Nahari, E and Zelig, O and Linial, M and Mevorach, D}, title = {Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states.}, journal = {Blood}, volume = {108}, number = {10}, pages = {3580-3589}, doi = {10.1182/blood-2006-03-013334}, pmid = {16882710}, issn = {0006-4971}, mesh = {Antigens, CD/physiology ; Apoptosis/*immunology ; Binding Sites ; Dendritic Cells/*physiology ; Gene Expression Regulation ; Heparin ; Humans ; *Immune Tolerance ; Monocytes/cytology/*metabolism ; *Phagocytosis ; Proteomics/methods ; Thrombospondin 1/*biosynthesis/isolation &amp; purification/metabolism ; }, abstract = {Apoptotic cells were shown to induce dendritic cell immune tolerance. We applied a proteomic approach to identify molecules that are secreted from apoptotic monocytes, and thus may mediate engulfment and immune suppression. Supernatants of monocytes undergoing apoptosis were collected and compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and differentially expressed proteins were identified using tandem mass spectrometry. Thrombospondin-1 (TSP-1) and its cleaved 26-kDa heparin-binding domain (HBD) were identified. We show that TSP-1 is expressed upon induction of monocyte apoptosis in a caspase-dependent pattern and the HBD is cleaved by chymotrypsin-like serine protease. We further show that CD29, CD36, CD47, CD51, and CD91 simultaneously participate in engulfment induction and generation of an immature dendritic cell (iDC) tolerogenic and phagocytic state. We conclude that apoptotic cell TSP-1, and notably its HBD, creates a signalosome in iDCs to improve engulfment and to tolerate engulfed material prior to the interaction with apoptotic cells.}, }
@article {pmid16875603, year = {2006}, author = {Tang, F and Gu, DH and Wang, H and Zhu, TF and Zhu, HG and Xu, ZD and Hu, XQ}, title = {[Expression and significance of hTERT mRNA in breast carcinoma and its relation to p53].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {28}, number = {3}, pages = {192-195}, pmid = {16875603}, issn = {0253-3766}, mesh = {Adult ; Breast/metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Diagnosis, Differential ; Disease Progression ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Middle Aged ; RNA, Messenger/biosynthesis/genetics ; Telomerase/*biosynthesis/genetics ; Tumor Suppressor Protein p53 ; }, abstract = {OBJECTIVE: This study was designed to investigate the significance of hTERT mRNA in breast carcinogenesis and to explore the diagnostic efficacy, and to study the effect of tumor suppressor gene p53 on the expression of hTERT mRNA.<br><br>METHODS: The expression of hTERT mRNA was examined by in situ hybridization in 12 cases of normal breast tissue nearby cancer, 7 of simple ductal hyperplasia, 20 of atypical hyperplasia, 18 of ductal carcinoma in situ and 25 with invasive ductal carcinoma. The expression of p53 protein were examined by immunohistochemistry in 43 carcinomas.<br><br>RESULTS: hTERT was not detected in normal breast tissue nearby cancer and simple ductal hyperplasia. The positive rate of hTERT mRNA in atypical hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma were 25.0%, 83.3% and 88.0%, respectively. The prevalence and intensity of hTERT mRNA expression were much greater in carcinoma than those in simple or atypical hyperplasia and normal breast tissue nearby cancer (P < 0.05). The expression of hTERT was not correlated with tumor size and lymph node metastasis (P > 0.05). The positive correlation between hTERT mRNA and p53 was found in breast carcinoma (r = 0.5540, P < 0.01).<br><br>CONCLUSION: hTERT mRNA expression is closely related to the malignant transformation of breast tissue. Semi-quantitative detection of hTERT mRNA expression in situ is helpful in differentiated diagnosis of carcinoma in situ and atypical hyperplasia. Inactivation of p53 may play a role in the transcriptive activation of hTERT gene in breast carcinoma.}, }
@article {pmid16872435, year = {2006}, author = {Umekita, Y and Souda, M and Ohi, Y and Sagara, Y and Rai, Y and Takahama, T and Yoshida, H}, title = {Expression of wild-type estrogen receptor beta protein in human breast cancer: specific correlation with HER2/neu overexpression.}, journal = {Pathology international}, volume = {56}, number = {8}, pages = {423-427}, doi = {10.1111/j.1440-1827.2006.01983.x}, pmid = {16872435}, issn = {1320-5463}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/secondary/surgery ; Cell Nucleus/metabolism/pathology ; Estrogen Receptor beta/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Mammary Glands, Human/metabolism ; Middle Aged ; Neoplasm Staging ; Reagent Kits, Diagnostic ; Receptor, ErbB-2/*metabolism ; Receptors, Progesterone/metabolism ; Trastuzumab ; }, abstract = {Expression of estrogen receptor beta (ERbeta) protein in human breast cancer and correlation with clinicopathological factors have been reported by many investigators, but many of them used ERbeta antibodies that react with both wild-type ERbeta (ERbetawt) and splicing variant isoform. Therefore, the frequency and correlation with clinicopathological factors of ERbetawt expression remain to be established. In the present study a monoclonal antibody EMR02, specific for ERbetawt, was used in formalin-fixed paraffin-embedded sections from 225 female primary breast cancer patients diagnosed as having invasive ductal carcinoma. Expression of ERalpha, progesterone receptor (PgR) and HER2/neu were also investigated by immunohistochemistry. For ERbetawt, ERalpha and PgR, positivity was defined as nuclear staining in >10% of the cancer cells. HER2/neu overexpression was defined as a Hercep test score 3+. Positivity for ERbetawt, ERalpha, PgR and HER2/neu overexpression was 55%, 74%, 61% and 25%, respectively. The expression of ERbetawt had a positive correlation with ERalpha (P=0.018) and PgR (P=0.02). There was significant positive correlation between ERbetawt expression and HER2/neu overexpression (P<0.0001). According to multivariate logistic regression analysis the most significant association was between ERbetawt expression and HER2/neu overexpression (P<0.0001). These results suggest that clinical significances of ERbetawt expression in human breast cancer patients may be more complex.}, }
@article {pmid16848850, year = {2006}, author = {Ruiz-Tovar, J and Reguero-Callejas, ME and Aláez, AB and Ramiro, C and Rojo, R and Collado, MV and González-Palacios, F and Muñoz, J and García-Villanueva, A}, title = {Infiltrating ductal carcinoma and ductal carcinoma in situ associated with mammary hamartoma.}, journal = {The breast journal}, volume = {12}, number = {4}, pages = {368-370}, doi = {10.1111/j.1075-122X.2006.00279.x}, pmid = {16848850}, issn = {1075-122X}, mesh = {Adult ; Breast Diseases/*complications/pathology/surgery ; Breast Neoplasms/*complications/pathology/surgery ; Carcinoma, Ductal, Breast/*complications/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*complications/pathology/surgery ; Female ; Hamartoma/*complications/pathology/surgery ; Humans ; Mastectomy ; }, abstract = {Mammary hamartoma is a rare nonmalignant lesion. Only 11 cases of carcinoma associated with hamartoma have been previously described in the literature. We describe a case of infiltrating ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) associated with hamartoma in a 35-year-old woman. Mammography showed the features of a typical hamartoma with suspicious microcalcifications arising in it. The patient underwent a radical modified mastectomy. It is likely that hamartoma is a coincidental finding. The identification of suspicious microcalcifications in a typical mammographic image of a hamartoma should prompt continued examination to exclude an underlying tumor.}, }
@article {pmid16846989, year = {2006}, author = {Wood, CE and Usborne, AL and Starost, MF and Tarara, RP and Hill, LR and Wilkinson, LM and Geisinger, KR and Feiste, EA and Cline, JM}, title = {Hyperplastic and neoplastic lesions of the mammary gland in macaques.}, journal = {Veterinary pathology}, volume = {43}, number = {4}, pages = {471-483}, doi = {10.1354/vp.43-4-471}, pmid = {16846989}, issn = {0300-9858}, support = {AT00639/AT/NCCIH NIH HHS/United States ; P51RR000167/RR/NCRR NIH HHS/United States ; P51RR000169/RR/NCRR NIH HHS/United States ; T32 RR07009/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Carcinoma in Situ/genetics/metabolism/pathology/*veterinary ; Carcinoma, Ductal/genetics/metabolism/pathology/*veterinary ; Female ; Gene Expression ; Genes, erbB-2 ; Immunohistochemistry/veterinary ; Ki-67 Antigen/metabolism ; *Macaca fascicularis ; *Macaca mulatta ; Male ; Mammary Glands, Animal/metabolism/pathology ; Mammary Neoplasms, Animal/genetics/metabolism/*pathology ; Monkey Diseases/genetics/metabolism/*pathology ; Oncogenes ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Retrospective Studies ; }, abstract = {Macaques provide an important animal model for the study of hormonal agents and their effects on risk biomarkers for breast cancer. A common criticism of this model is that spontaneous breast cancer has rarely been described in these animals. In this report, we characterize 35 mammary gland lesions ranging from ductal hyperplasia to carcinoma in situ and invasive ductal carcinoma in cynomolgus and rhesus macaques. Based on a retrospective analysis, we estimated the lifetime incidence of mammary gland neoplasia in aged female macaques to be about 6%. Hyperplastic lesions (n = 19) occurred segmentally along ducts and included such features as columnar alteration, micropapillary atypia, and fibroadenomatous change. In situ carcinomas (n = 8) included solid, comedo, cribriform, and micropapillary elements, encompassing 4 of the major architectural patterns seen in human lesions. Invasive ductal carcinomas (n = 8) were generally solid, with prominent central necrosis and mineralization, often on a background of micropapillary ductal hyperplasia and in situ carcinoma. Cytologic changes of invasive lesions included increased mitoses, nuclear pleomorphism, extensive microinvasion, and stromal desmoplasia. Axillary lymph-node metastases were confirmed in 5 of the 8 invasive carcinomas. On immunohistochemistry, intraductal and invasive carcinomas had increased Ki67/MIB1 and HER2 expression and selective loss of estrogen and progesterone receptors. These findings suggest that breast cancer is an underreported lesion in macaques and highlight unique morphologic and molecular similarities in breast cancer between human and macaque species.}, }
@article {pmid16846613, year = {2006}, author = {Marrero, A and Mallorquí-Fernández, G and Guevara, T and García-Castellanos, R and Gomis-Rüth, FX}, title = {Unbound and acylated structures of the MecR1 extracellular antibiotic-sensor domain provide insights into the signal-transduction system that triggers methicillin resistance.}, journal = {Journal of molecular biology}, volume = {361}, number = {3}, pages = {506-521}, doi = {10.1016/j.jmb.2006.06.046}, pmid = {16846613}, issn = {0022-2836}, mesh = {Acylation ; Amino Acid Sequence ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/*chemistry/metabolism ; Binding Sites ; Methicillin/*pharmacology ; Methicillin Resistance/*physiology ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Signal Transduction ; Staphylococcus aureus/drug effects/*metabolism ; }, abstract = {Methicillin-resistant Staphylococcus aureus (MRSA) strains are responsible for most hospital-onset bacterial infections. Lately, they have become a major threat to the community through infections of skin, soft tissue and respiratory tract, and subsequent septicaemia or septic shock. MRSA strains are resistant to most beta-lactam antibiotics (BLAs) as a result of the biosynthesis of a penicillin-binding protein with low affinity for BLAs, called PBP2a, PBP2' or MecA. This response is regulated by the chromosomal mec-divergon, which encodes a signal-transduction system including a transcriptional repressor, MecI, and a sensor/transducer, MecR1, as well as the structural mecA gene. This system is similar to those encoded by bla divergons in S. aureus and Bacillus licheniformis. MecR1 comprises an integral-membrane latent metalloprotease domain facing the cytosol and an extracellular sensor domain. The latter binds BLAs and transmits a signal through the membrane that eventually triggers activation of the metalloprotease moiety, which in turn switches off MecI-induced repression of mecA transcription. The MecR1 sensor domain, MecR1-PBD, reveals a two-domain structure of alpha/beta-type fold reminiscent of penicillin-binding proteins and beta-lactamases, and a catalytic serine residue as the ultimate cause for BLA-binding. Covalent complexes with benzylpenicillin and oxacillin provide evidence that serine acylation does not entail significant structural changes, thus supporting the hypothesis that additional extracellular segments of MecR1 are involved in signal transmission. The chemical nature of the residues shaping the active-site cleft favours stabilisation of the acyl enzyme complexes in MecR1-PBD, in contrast to the closely related OXA beta-lactamases, where the cleft is more likely to promote subsequent hydrolysis. The present structural data provide insights into the mec-encoded BLA-response mechanism and an explanation for kinetic differences in signal transmission with the related bla-encoded systems.}, }
@article {pmid16826579, year = {2006}, author = {Tham, YL and Sexton, K and Kramer, R and Hilsenbeck, S and Elledge, R}, title = {Primary breast cancer phenotypes associated with propensity for central nervous system metastases.}, journal = {Cancer}, volume = {107}, number = {4}, pages = {696-704}, doi = {10.1002/cncr.22041}, pmid = {16826579}, issn = {0008-543X}, support = {P01 CA 30195/CA/NCI NIH HHS/United States ; P20 CA 1033698/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/metabolism ; Brain Neoplasms/metabolism/mortality/*secondary ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*secondary ; Carcinoma, Intraductal, Noninfiltrating/metabolism/mortality/*secondary ; Carcinoma, Lobular/metabolism/mortality/*secondary ; ErbB Receptors/metabolism ; Female ; Humans ; Incidence ; Middle Aged ; Neoplasm Recurrence, Local/metabolism/pathology ; Neoplasm Staging ; Phenotype ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {BACKGROUND: There is anecdotal evidence that the incidence of central nervous system (CNS) metastases in breast cancer patients is increasing. It is unclear whether specific tumor biological properties or the use of systemic therapies influence this risk.<br><br>METHODS: Using a database of 10,782 patients, 2685 patients were identified who experienced recurrence distantly. Clinical and biological features were analyzed in 2 ways: (1) patients who ever had versus those who never had CNS metastases, and (2) CNS metastases as the first site of recurrence versus those who had other sites. Correlations of survival after CNS metastasis with clinical and biologic features were also analyzed.<br><br>RESULTS: In the ever versus never analysis, CNS metastases were significantly associated with younger age, premenopausal status, infiltrating ductal carcinoma histology (IDC), estrogen receptor (ER) and progesterone receptor (PR) negativity, low Bcl-2, high S-phase, aneuploidy, and altered p53. Tumor size, lymph node status, and use of adjuvant systemic therapy played little role. HER-2 overexpression was not associated with an increased risk in these patients (none of whom were treated with trastuzumab) (P = .91). However, epidermal growth factor receptor (EGFR) overexpression was associated with increased risk (P = .02). A multivariate analysis revealed ER negativity (odds ratio [OR] 2.8, P < .001), IDC histology (OR 2.5, P = .02), and young age (P < .001) as independent factors for CNS metastases. The clinical and biologic profiles of primary tumors with CNS metastases at first recurrence did not differ from those with CNS metastases after recurrence to other sites, except for HER-2 status. HER-2-positive tumors were not more likely to undergo recurrence initially in the CNS (P =.04). The median survival after CNS metastases was 5.5 months and HER-2-positive patients had a shorter survival.<br><br>CONCLUSIONS: Younger patients with hormone receptor-negative, highly proliferative, genomically unstable, and p53-altered tumors were at increased relative risk for CNS metastases. HER-2 expression and adjuvant systemic therapies did not increase this risk.}, }
@article {pmid16807982, year = {2006}, author = {Kim, HJ and Park, CI and Park, BW and Lee, HD and Jung, WH}, title = {Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast.}, journal = {Yonsei medical journal}, volume = {47}, number = {3}, pages = {333-342}, pmid = {16807982}, issn = {0513-5796}, mesh = {Breast Neoplasms/genetics/*physiopathology ; Carcinoma in Situ/genetics/*physiopathology ; Carcinoma, Ductal, Breast/genetics/*physiopathology ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Matrix Metalloproteinase 1/genetics ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinases/*genetics ; Matrix Metalloproteinases, Membrane-Associated ; RNA, Messenger/metabolism ; Tissue Inhibitor of Metalloproteinase-2/genetics ; }, abstract = {We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta1 were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta1 expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.}, }
@article {pmid16800732, year = {2006}, author = {Zhang, Y and Bhat, I and Zeng, M and Jayal, G and Wazer, DE and Band, H and Band, V}, title = {Human kallikrein 10, a predictive marker for breast cancer.}, journal = {Biological chemistry}, volume = {387}, number = {6}, pages = {715-721}, doi = {10.1515/BC.2006.090}, pmid = {16800732}, issn = {1431-6730}, support = {CA 76118/CA/NCI NIH HHS/United States ; CA 87986/CA/NCI NIH HHS/United States ; CA 99163/CA/NCI NIH HHS/United States ; CA 99900/CA/NCI NIH HHS/United States ; CA81076/CA/NCI NIH HHS/United States ; CA94143/CA/NCI NIH HHS/United States ; CA96844/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/diagnosis/genetics/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; In Vitro Techniques ; Kallikreins/*analysis/genetics ; Neoplasms ; Prognosis ; RNA, Messenger/analysis ; }, abstract = {Our laboratory is involved in identifying genes that can be used as early diagnostic or prognostic markers in breast cancer. We previously identified a gene (NES1) that is expressed in normal but not in transformed mammary epithelial cells (MECs). NES1 is located on chromosome 19q13.4 within the kallikrein locus and thus was designated as human kallikrein 10 (hK10), although we have been unable to detect any protease activity. Importantly, hK10 expression is decreased in a majority of breast cancer cell lines. Transfection of hK10 into hK10-negative breast cancer cells reduces the tumorigenicity. Using methylation-specific PCR and subsequent sequencing, we demonstrate a strong correlation between hypermethylation of hK10 and loss of mRNA expression. Further analysis showed that essentially 100% of normal breast specimens had hK10 expression, whereas 46% of ductal carcinoma in situ (DCIS) and the majority of infiltrating ductal carcinoma (IDC) samples lacked the hK10 mRNA. Importantly, hK10-negative DCIS diagnosed at the time of biopsy were subsequently diagnosed as IDC at the time of definitive surgery. It has been shown that hK10 protein expression is regulated by steroids. In addition to breast cancers, hK10 is downregulated in cervical cancer, prostate cancer and acute lymphocytic leukemia, whereas it is upregulated in ovarian cancers. These results point to the paradoxical role of hK10 in human cancers and underscore the importance of further studies of this kallikrein.}, }
@article {pmid16786469, year = {2006}, author = {Wieczorek, M and Hoeltgen, R and Djajadisastra, I}, title = {[Avoidance of intermittent T-wave oversensing with device programming].}, journal = {Herzschrittmachertherapie &amp; Elektrophysiologie}, volume = {17}, number = {2}, pages = {106-111}, pmid = {16786469}, issn = {0938-7412}, mesh = {Adult ; Defibrillators, Implantable/*adverse effects ; Electrocardiography/*methods ; Humans ; Male ; Tachycardia, Ventricular/*etiology/*prevention &amp; control ; Therapy, Computer-Assisted/*methods ; }, abstract = {We report the case of a 35-year-old man who was suffering from severe heart failure due to cardiomyopathy. He underwent heart transplantation years ago and developed complex ventricular arrhythmias in the following months in combination with recurrent episodes of syncope due to hypertrophic non-obstructive cardiomyopathy in the transplanted heart, so a dual chamber ICD was implanted. Months later repetitive episodes of intermittent T-wave oversensing with consecutive activation of the ICD could be observed. Surgical revision of the electrode was performed and the patient was closely followed up. One year later, further episodes of T-wave oversensing led to multiple inappropriate IDC-shocks. A very short AV-conduction time was programmed to allow ventricular capture whenever possible, because T-wave oversense after ventricular capture would be annotated as single ventricular ectopy not resulting in antitachycardia pacing. As a consequence, the patient was free from inappropriate ICD-shocks, but showed several shorter episodes of T-wave oversensing. They were all initiated by atrial activity that was seen in the refractory period, thus leading to a loss of AV synchrony. Programming a very short post ventricular atrial refractory period (PVARP) in addition to a short AV-delay led to the complete disappearance of T-wave oversensing in this patient. During a 9-month follow-up, no further tachycardia episodes were detected by the device.}, }
@article {pmid16786147, year = {2006}, author = {Kalfoglou, EA and Faikoglu, R and Ozcan, S and Petridis, G and Yükseloglu, H and Atasoy, S}, title = {DNA analysis as a tool for breast cancer malpractice determination: an interdisciplinary approach.}, journal = {Oncology reports}, volume = {16}, number = {1}, pages = {203-206}, pmid = {16786147}, issn = {1021-335X}, mesh = {Biopsy ; Breast Neoplasms/*genetics/surgery ; DNA/metabolism ; Female ; Humans ; *Malpractice ; Medical Oncology/*legislation &amp; jurisprudence ; Middle Aged ; Polymorphism, Genetic ; *Sequence Analysis, DNA ; Tandem Repeat Sequences/genetics ; }, abstract = {Malpractice in breast cancer can be seen as false-negative or false-positive findings which may result in either late or incorrect therapies. Biopsy material can be unintentionally interchanged, leading to incorrect treatment, and psychological damage to the patient. There is an obvious need for individualization of the tissue samples in such cases. In this study we used a multidisciplinary approach to integrate DNA technology that has been standardized and used in forensic science for other purposes, mainly to prove malpractice that has been the result of interchanging tissue samples in breast cancer. The main focus of the study was to evaluate the applicability of the technique, therefore we studied the samples of a 58-year-old female for whom the result of pathological analysis was reported as 'invasive ductal carcinoma'. The patient was surgically treated by a modified mastectomy technique and referred for chemotherapy. Prior to chemotherapy we found that the tissue samples analyzed did not belong to the patient in question. We used a battery of 15 polymorphic STR loci to identify the sample and we had strong evidence for exclusion of the patient. The analysis was done on both blood and buccal swab of the patient and on the tissue sample. We concluded that the technique is applicable and useful; however care should be taken in the interpretation of the results because the mutations in the tumoral tissues are very well known. Therefore, the maximum of informative loci should be studied and loss of heterozygosity should always be considered. We should also have in mind the possibility of intentional interchange which gives the results value in medico-legal investigations.}, }
@article {pmid16785780, year = {2006}, author = {Vogl, G and Bartel, H and Dietze, O and Hauser-Kronberger, C}, title = {HER2 is unlikely to be involved in directly regulating angiogenesis in human breast cancer.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {14}, number = {2}, pages = {138-145}, doi = {10.1097/01.pai.0000168591.58721.a6}, pmid = {16785780}, issn = {1541-2016}, mesh = {Angiogenesis Inducing Agents/analysis/*metabolism ; Breast Neoplasms/*etiology ; Carcinoma, Ductal, Breast/*etiology ; Female ; Humans ; Immunohistochemistry/methods ; Neovascularization, Pathologic/*etiology ; Prognosis ; Receptor, ErbB-2/*physiology ; Receptors, Growth Factor/analysis/classification/*metabolism ; Up-Regulation ; }, abstract = {Angiogenesis is a fundamental component of oncogenesis. Angiogenic factors such as vascular endothelial growth factor (VEGF) and platelet derived-endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) are generated from tumor cells to provide tumor growth and are thought to be regulated via the HER2 oncogene, whose amplification is the most common genetic alteration in breast cancer. The present study aimed to evaluate the immunoreactivity of angiogenic factors (VEGF, PD-ECGF/TP) and microvessel density (MVD) via epidermal growth factor receptor (EGFR) and HER2, and to correlate their expression with clinicopathologic features. Two hundred one invasive human breast cancer specimens were tested immunohistochemically for the expression of these proteins. In addition, MVD was examined using computerized image analysis. VEGF could be an additional interesting prognostic variable, as it was significantly associated with tumor grade (P=0.002), stage (P=0.018), and negative estrogen receptor status (P=0.011). EGFR was significantly related to invasive ductal carcinoma (P=0.030), tumor grade (P=0.009), VEGF expression (P=0.013), PD-ECGF/TP expression (P=0.024), and MVD (P=0.050). The finding that VEGF is not correlated to MVD does not rule out a crucial role of VEGF as a key factor in angiogenesis. HER2 could not be correlated to MVD, VEGF expression, or PD-ECGF/TP expression, indicating that this factor is unlikely to be involved in directly regulating angiogenesis, whereas the significant correlations between EGFR and histologic tumor type, tumor grade, the angiogenic factors VEGF and PD-ECGF/TP, and MVD point out that EGF is the major modulating growth factor for angiogenesis in breast cancer.}, }
@article {pmid16782429, year = {2006}, author = {Eguchi, H and Ishikawa, O and Ohigashi, H and Tomimaru, Y and Sasaki, Y and Yamada, T and Tsukuma, H and Nakaizumi, A and Imaoka, S}, title = {Patients with pancreatic intraductal papillary mucinous neoplasms are at high risk of colorectal cancer development.}, journal = {Surgery}, volume = {139}, number = {6}, pages = {749-754}, doi = {10.1016/j.surg.2005.11.008}, pmid = {16782429}, issn = {0039-6060}, mesh = {Adenocarcinoma, Mucinous/*complications ; Aged ; Carcinoma, Pancreatic Ductal/*complications ; Carcinoma, Papillary/*complications ; Colorectal Neoplasms/*etiology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Pancreatic Neoplasms/*complications ; Risk ; }, abstract = {BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been recognized recently and is being diagnosed with increasing frequency. Although IPMN has a more favorable prognosis than standard invasive ductal carcinoma (IDC) of the pancreas, recent reports suggest that IPMN patients are at higher risks of synchronous or metachronous primary cancers arising from various organs other than the pancreas (extrapancreatic cancers).<br><br>METHODS: Records of 370 patients (69 of IPMN, 301 of IDC) who underwent surgery were used to assess risk factors for preoperative or postoperative extrapancreatic cancers. To calculate the rate of increase of extrapancreatic cancers in IPMN patients, compared with the normal population, the observed/expected ratio (O/E ratio) was calculated by using the Osaka Cancer Registry, one of the world largest cancer databases.<br><br>RESULTS: The incidence of preoperative extrapancreatic cancers was significantly higher in IPMN patients (28%, 19 patients) than that in IDC (9%, 27 patients). In the IPMN-group, the preoperative incidence of colorectal cancer was 12% followed by gastric cancer at 4%. Logistic regression analysis showed IPMN and age to be independent risk factors for preoperative colorectal cancer development. The O/E ratio of preoperative colorectal cancer was significantly high in IPMN patients (5.37; 95% confidence interval, 2.31-10.58) but not in IDC patients (1.24; 95% confidence interval, 0.46-2.70). The incidence of postoperative extrapancreatic cancers also was significantly higher in IPMN patients (15%, 10 patients) than that in IDC (4%, 12 patients). During the postoperative follow-up, 4% of IPMN (3 patients) and 0.7% of IDC (2 patients) died from extrapancreatic cancers.<br><br>CONCLUSIONS: Our results indicate that IPMN patients are at significantly higher risks of extrapancreatic cancers including colorectal cancer. A careful systemic checkup is therefore required for preoperative screening and postoperative follow-up for IPMN patients.}, }
@article {pmid16762512, year = {2006}, author = {Gong, N and Zhao, Y and Dong, C and Chen, ZK}, title = {Negative costimulatory molecules: the proximal of regulatory T cells?.}, journal = {Medical hypotheses}, volume = {67}, number = {4}, pages = {841-847}, doi = {10.1016/j.mehy.2006.04.013}, pmid = {16762512}, issn = {0306-9877}, mesh = {Abatacept ; Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; CD28 Antigens/immunology ; CD4 Antigens/immunology ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Humans ; Immunoconjugates/immunology ; L-Selectin/immunology ; Leukocyte Common Antigens/immunology ; Ligands ; Lymphocyte Activation ; Models, Immunological ; Receptors, Interleukin-2/immunology ; Signal Transduction ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Regulatory T cells (Tregs) are a central mechanism of immune regulation. It is well known that their regulatory effect is antigen-specific and depends on cell-cell contact. In addition, some immunological phenomenon such as linked suppression and iDC-induced tolerance are related with Tregs. But the surface markers, which reliably distinguish Treg from other T cell populations, and the regulatory mechanism still remain to be further revealed. Negative costimulatory molecule (NCM) family is one natural intrinsic mechanism that delivers the negative signal into cytoplasma to modulate immunoresponse and its expression can be induced not only on the immune cells but also on the parenchymal cells. Based on the present knowledge, we hypothesize NCMs are the specific surface markers to define Tregs. Tregs are one kind of activated T cells with high expression of NCM receptor and have the capability to induce NCM ligands expression on the membrane of APCs and the target cells of the activated cells. The NCM receptor-ligand complexes deliver negative signal into lymphocytes to regulate the immune response. This hypothesis remains to be fully elucidated.}, }
@article {pmid16762272, year = {2006}, author = {Ruibal, A and Garrido Pumar, M and Arias, JI}, title = {[Preoperative serum CA15.3 and CEA levels and clinical-biological parameters in breast tumors].}, journal = {Revista espanola de medicina nuclear}, volume = {25}, number = {3}, pages = {180-183}, doi = {10.1157/13088414}, pmid = {16762272}, issn = {0212-6982}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Biomarkers, Tumor/analysis/*blood ; Breast Neoplasms/*blood/chemistry/pathology/surgery ; Carcinoembryonic Antigen/*analysis ; Carcinoma, Ductal, Breast/*blood/chemistry/secondary/surgery ; Cathepsin D/analysis ; Cytosol/chemistry ; ErbB Receptors/analysis ; Female ; Humans ; Hyaluronic Acid/analysis ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Mucin-1/*blood ; Neoplasm Proteins/analysis/blood ; Receptors, Estrogen/analysis ; Sensitivity and Specificity ; Trefoil Factor-1 ; Tumor Burden ; Tumor Suppressor Proteins/analysis ; }, abstract = {OBJECTIVE: To study the possible associations between preoperative serum CEA and CA15.3 levels and different clinical-biological parameters of infiltrating ductal carcinomas of the breast (IDC).<br><br>PATIENTS AND METHOD: Preoperative serum CA15.3 and CEA levels were determined in 255 and 224 females, respectively, having IDC. We assayed the cytosolic levels of estrogen receptor, pS2, cathepsin D and hyaluronic acid, as well as the levels of epidermal growth factor receptor in cell surfaces. Tumor size, axillary involvement (N), distant metastasis (M), histological grade (HG) and cellular S-phase (SP) were taken into account.<br><br>RESULTS: 22 IDC were positive for CA15.3 (> 40 U/ml) and they had greater global tumor size (p < 0.001), > 2 cm (p: 0.005) and distant metastasis (p < 0.001). 19 IDC were positive for CEA (> 4 ng/ml) and they had greater global tumor size (p < 0.001), > 2 cm (p < 0.001), > 5 cm (p: 0.052) and global S-phase values (p: 0.062), and were more frequently N + (p: 0.045), > 3N + (p: 0.001) and > 10N + (p < 0.001), M + (p: 0.004), HG3 (p: 0.091) and SP > 7 % (p: 0.006).<br><br>CONCLUSIONS: Our results led us to the following: In patients having IDC of the breast, preoperative serum CA15.3 levels are associated with greater tumor size and distant metastasis, while pre-treatment CEA serum levels are associated moreover with axillary involvement; we have not observed any correlation between serum levels of both antigens and the hormonal status of the tumor; these results had physiopathological interest but reduced clinical value in pretreatment breast carcinomas due to their low sensitivity of both markers. However, they are useful in the follow-up of the patients when assessing serum concentrations of both markers, since they contribute to knowing the patients' clinical status better.}, }
@article {pmid16755121, year = {2006}, author = {Kijima, Y and Umekita, Y and Yoshinaka, H and Owaki, T and Sakamoto, A and Yoshida, H and Aikou, T}, title = {A case of breast carcinoma with cartilaginous and osseous metaplasia.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {2}, pages = {214-219}, doi = {10.2325/jbcs.13.214}, pmid = {16755121}, issn = {1340-6868}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Biopsy, Needle ; Bone Neoplasms/pathology/*secondary ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology/*secondary/surgery ; Carcinosarcoma/pathology/*secondary/surgery ; Diagnosis, Differential ; Disease Progression ; Fatal Outcome ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/pathology/*secondary ; Magnetic Resonance Imaging ; Mammography ; Mastectomy, Segmental ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/*pathology ; Risk Assessment ; }, abstract = {We report a case of a 49-year-old Japanese woman diagnosed with breast carcinoma with osseous and cartilaginous metaplasia with a poor outcome. Histological examination revealed invasive ductal carcinoma with undifferentiated sarcomatous components including chondrosarcomatous areas. Osseous metaplasia was also noted in a very limited area. Neither axillary lymph node metastases nor vessel invasion were observed. Immunohistochemical examination was negative for estrogen receptor, progesterone receptor and HER2 overexpression. Stage II A T2N0M0 carcinoma was diagnosed postoperatively. Five months after the operation, she developed lung metastases. Although she received systemic chemotherapy, the lesions increased in number and grew rapidly. She died of pulmonary distress 5 months after relapse.}, }
@article {pmid16753605, year = {2006}, author = {Oakley, GJ and Tubbs, RR and Crowe, J and Sebek, B and Budd, GT and Patrick, RJ and Procop, GW}, title = {HER-2 amplification in tubular carcinoma of the breast.}, journal = {American journal of clinical pathology}, volume = {126}, number = {1}, pages = {55-58}, doi = {10.1309/E0YE-KHBP-3YYQ-YUBD}, pmid = {16753605}, issn = {0002-9173}, mesh = {Adenocarcinoma/*genetics/metabolism/secondary ; Axilla ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Female ; *Gene Amplification ; Gene Dosage ; *Genes, erbB-2 ; Humans ; In Situ Hybridization, Fluorescence ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Receptor, ErbB-2/*genetics/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {The prognostic and therapeutic implications of HER-2 gene amplification and estrogen and progesterone receptor status in breast cancer are well described. To address the relative paucity of information concerning HER-2 amplification for tubular carcinomas, we assessed the frequency of gene amplification in 55 tubular carcinomas of the breast from 54 patients, 5 of which had axillary node metastases. The HER-2 gene copy number was assessed by fluorescence in situ hybridization for the majority of tumors analyzed, whereas estrogen and progesterone receptor status was achieved by immunohistochemical analysis. HER-2 gene amplification was not observed in any of the tumors examined, and most were estrogen receptor-positive. This HER-2 gene amplification frequency was significantly lower than the frequency of gene amplification previously reported for all invasive ductal carcinoma of no special type (P < .01). HER-2 gene amplification likely occurs infrequently, or not at all, in tubular carcinomas of the breast, whereas most express estrogen receptors.}, }
@article {pmid16731957, year = {2006}, author = {Holl, V and Peressin, M and Decoville, T and Schmidt, S and Zolla-Pazner, S and Aubertin, AM and Moog, C}, title = {Nonneutralizing antibodies are able to inhibit human immunodeficiency virus type 1 replication in macrophages and immature dendritic cells.}, journal = {Journal of virology}, volume = {80}, number = {12}, pages = {6177-6181}, pmid = {16731957}, issn = {0022-538X}, support = {R01 AI036085/AI/NIAID NIH HHS/United States ; AI36085/AI/NIAID NIH HHS/United States ; R01 HL059725/HL/NHLBI NIH HHS/United States ; HL59725/HL/NHLBI NIH HHS/United States ; AI27742/AI/NIAID NIH HHS/United States ; P30 AI027742/AI/NIAID NIH HHS/United States ; }, mesh = {Cell Line ; Dendritic Cells/*virology ; HIV Antibodies/*pharmacology ; HIV-1/*immunology ; Humans ; Immunoglobulin Fab Fragments/pharmacology ; Macrophages/*virology ; Neutralization Tests ; Receptors, IgG ; Virus Replication/drug effects/*immunology ; }, abstract = {Only five monoclonal antibodies (MAbs) neutralizing a broad range of primary isolates (PI) have been identified up to now. We have found that some MAbs with no neutralizing activities according to the "conventional" neutralization assay, involving phytohemagglutinin-stimulated peripheral blood mononuclear cells as targets, efficiently inhibit the replication of human immunodeficiency virus type 1 (HIV-1) PI in macrophages and immature dendritic cells (iDC). The mechanism of inhibition is distinct from the neutralization of infectivity occurring via Fab fragments and involves the interaction of the F portion with the FcgammaRs present on macrophages and iDC. We propose that, if such nonneutralizing inhibitory antibodies limit mucosal HIV transmission, they should be induced by vaccination.}, }
@article {pmid16707453, year = {2006}, author = {Schuetz, CS and Bonin, M and Clare, SE and Nieselt, K and Sotlar, K and Walter, M and Fehm, T and Solomayer, E and Riess, O and Wallwiener, D and Kurek, R and Neubauer, HJ}, title = {Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis.}, journal = {Cancer research}, volume = {66}, number = {10}, pages = {5278-5286}, doi = {10.1158/0008-5472.CAN-05-4610}, pmid = {16707453}, issn = {0008-5472}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Cell Movement/genetics ; Cluster Analysis ; Disease Progression ; Epithelial Cells/pathology ; Female ; Gene Amplification ; Gene Expression Profiling ; Humans ; Microdissection/methods ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; Protein Biosynthesis/genetics ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Becoming invasive is a crucial step in breast cancer oncogenesis. At this point, a lesion carries the potential for spreading and metastasis--a process, whose molecular characteristics still remain poorly understood. In this article, we describe a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of nine breast ductal carcinomas to identify novel molecular markers characterizing the transition from DCIS to IDC. The purpose of this study was to better understand the molecular biology of this transition and to identify candidate genes whose products might serve as prognostic markers and/or as molecular targets for treatment. To obtain cellular-based gene expression profiles from epithelial tumor cells, we combined laser capture microdissection with a T7-based two-round RNA amplification and Affymetrix oligonucleotide microarray analysis. Altogether, a set of 24 tumor samples was analyzed, comprised of nine matched DCIS/IDC and replicate DCIS/IDC preparations from three of the nine tumors. Cluster analysis on expression data shows the robustness and reproducibility of the techniques we established. Using multiple statistical methods, 546 significantly differentially expressed probe sets were identified. Eighteen candidate genes were evaluated by RT-PCR. Examples of genes already known to be associated with breast cancer invasion are BPAG1, LRRC15, MMP11, and PLAU. The expression of BPAG1, DACT1, GREM1, MEF2C, SART2, and TNFAIP6 was localized to epithelial tumor cells by in situ hybridization and/or immunohistochemistry, confirming the accuracy of laser capture microdissection sampling and microarray analysis.}, }
@article {pmid16702952, year = {2006}, author = {Roylance, R and Gorman, P and Papior, T and Wan, YL and Ives, M and Watson, JE and Collins, C and Wortham, N and Langford, C and Fiegler, H and Carter, N and Gillett, C and Sasieni, P and Pinder, S and Hanby, A and Tomlinson, I}, title = {A comprehensive study of chromosome 16q in invasive ductal and lobular breast carcinoma using array CGH.}, journal = {Oncogene}, volume = {25}, number = {49}, pages = {6544-6553}, pmid = {16702952}, issn = {0950-9232}, support = {/WT_/Wellcome Trust/United Kingdom ; 077008/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; Chromosome Aberrations ; Chromosome Breakage ; *Chromosomes, Human, Pair 16 ; Cluster Analysis ; DNA, Neoplasm ; Gene Amplification ; Gene Deletion ; Genetic Linkage ; Humans ; Loss of Heterozygosity ; Models, Statistical ; Neoplasm Invasiveness/*genetics ; Neoplasm Staging ; Nucleic Acid Hybridization/*methods ; Tissue Array Analysis/*methods ; }, abstract = {We analysed chromosome 16q in 106 breast cancers using tiling-path array-comparative genomic hybridization (aCGH). About 80% of ductal cancers (IDCs) and all lobular cancers (ILCs) lost at least part of 16q. Grade I (GI) IDCs and ILCs often lost the whole chromosome arm. Grade II (GII) and grade III (GIII) IDCs showed less frequent whole-arm loss, but often had complex changes, typically small regions of gain together with larger regions of loss. The boundaries of gains/losses tended to cluster, common sites being 54.5-55.5 Mb and 57.4-58.8 Mb. Overall, the peak frequency of loss (83% cancers) occurred at 61.9-62.9 Mb. We also found several 'minimal' regions of loss/gain. However, no mutations in candidate genes (TRADD, CDH5, CDH8 and CDH11) were detected. Cluster analysis based on copy number changes identified a large group of cancers that had lost most of 16q, and two smaller groups (one with few changes, one with a tendency to show copy number gain). Although all morphological types occurred in each cluster group, IDCs (especially GII/GIII) were relatively overrepresented in the smaller groups. Cluster groups were not independently associated with survival. Use of tiling-path aCGH prompted re-evaluation of the hypothetical pathways of breast carcinogenesis. ILCs have the simplest changes on 16q and probably diverge from the IDC lineage close to the stage of 16q loss. Higher-grade IDCs probably develop from low-grade lesions in most cases, but there remains evidence that some GII/GIII IDCs arise without a GI precursor.}, }
@article {pmid16698952, year = {2006}, author = {Lawson, JS and Tran, DD and Carpenter, E and Ford, CE and Rawlinson, WD and Whitaker, NJ and Delprado, W}, title = {Presence of mouse mammary tumour-like virus gene sequences may be associated with morphology of specific human breast cancer.}, journal = {Journal of clinical pathology}, volume = {59}, number = {12}, pages = {1287-1292}, pmid = {16698952}, issn = {0021-9746}, mesh = {Animals ; Breast Neoplasms/pathology/*virology ; Carcinoma, Ductal, Breast/pathology/*virology ; Carcinoma, Intraductal, Noninfiltrating/pathology/*virology ; DNA, Viral/analysis ; Female ; Humans ; Mammary Neoplasms, Animal/pathology/virology ; Mammary Tumor Virus, Mouse/genetics/*isolation &amp; purification ; Mice ; Mice, Inbred C3H ; Polymerase Chain Reaction/methods ; Retroviridae Infections/complications ; Tumor Virus Infections/complications ; Viral Envelope Proteins/analysis ; }, abstract = {BACKGROUND: Mouse mammary tumour virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible in-bred mice. MMTV-like env gene sequences, which indicate the presence of a replication-competent MMTV-like virus, have been identified in some human breast cancers, but rarely in normal breast tissues. However, no evidence for a causal role of an MMTV-like virus in human breast cancer has emerged, although there are precedents for associations between specific histological characteristics of human cancers and the presence of oncogenic viruses.<br><br>AIM: To investigate the possibility of an association between breast cancer and MMTV-like viruses.<br><br>METHODS: Histological characteristics of invasive ductal human breast cancer specimens were compared with archival MMTV-associated mammary tumours from C3H experimental mice. The presence of MMTV-like env DNA sequences in the human breast cancer specimens was determined by polymerase chain reaction and confirmed by Southern hybridisation.<br><br>RESULTS: MMTV-like env gene sequences were identified in 22 of 59 (37.3%) human breast cancer specimens. Seventeen of 43 (39.5%) invasive ductal carcinoma breast cancer specimens and 4 of 16 (25%) ductal carcinoma in situ specimens had some histological characteristics, which were similar to MMTV-associated mouse mammary tumours. However, these similarities were not associated with the presence or absence of MMTV-like gene sequences in the human breast tumour specimens. A significant (p = 0.05) correlation was found between the grade of the human breast cancer and similarity to the mouse mammary tumours. The lower the grade, the greater the similarity.<br><br>CONCLUSION: Some human breast cancer specimens, in which MMTV-like env DNA sequences have been identified, were shown to have histological characteristics (morphology) similar to MMTV-associated mouse mammary tumours. These observations are compatible with, but not conclusive of, an association between the presence of MMTV-like env DNA sequences and some human breast cancers.}, }
@article {pmid16698674, year = {2006}, author = {Eigenbrod, S and Derwand, R and Jakl, V and Endres, S and Eigler, A}, title = {Sphingosine kinase and sphingosine-1-phosphate regulate migration, endocytosis and apoptosis of dendritic cells.}, journal = {Immunological investigations}, volume = {35}, number = {2}, pages = {149-165}, doi = {10.1080/08820130600616490}, pmid = {16698674}, issn = {0882-0139}, mesh = {Apoptosis/immunology ; Cell Movement/*immunology ; Cell Survival/immunology ; Chemokines/immunology ; Dendritic Cells/cytology/enzymology/*immunology ; Endocytosis/immunology ; Humans ; Immunotherapy, Adoptive ; Lysophospholipids/*immunology/pharmacology ; Phosphotransferases (Alcohol Group Acceptor)/antagonists &amp; inhibitors/biosynthesis/*immunology/metabolism ; RNA, Messenger/biosynthesis/genetics ; Receptors, Lysosphingolipid/biosynthesis/genetics ; Sphingosine/*analogs &amp; derivatives/immunology/pharmacology ; Statistics, Nonparametric ; }, abstract = {Dendritic cells (DC) are inducers of primary immune responses and represent an attractive vector for cancer immunotherapy. Sphingosine kinase (SphK) and its product sphingosine-1-phosphate (S1P) play an important role in the regulation of immune cells and cancer, affecting processes such as differentiation, growth or migration. We studied the role of SphK and S1P on migration of DC. RT-PCR showed mRNA expression of SphK in DC, declining from immature (iDC) to mature DC (mDC) to antigen-loaded mDC. Expression of S1P receptors was S1P(1) > S1P(2) = S1P(3), unrelated to maturation or antigen uptake. In transwell assays, iDC migrated towards SDF-1, MIP-1alpha, MCP and S1P, whereby S1P combined with a chemokine had a synergistic effect. mDC migrated towards 6Ckine and MIP-3beta, but not towards S1P. The SphK-inhibitor dihydro-sphingosine (DHS) reduced migration of iDC but not of mDC. In addition S1P(3)-inhibitor suramin inhibited DC migration in response to S1P. DHS had a reverse effect on endocytosis, enhancing the uptake of FITC dextran. We also observed an anti-apoptotic effect of S1P on mDC for the first time. This indicates that SphK/S1P may play a role in accumulation of peripheral iDC at the location of antigen and subsequent antigen-uptake. These findings may help to optimise DC-based cancer immunotherapy by modulation of SphK/S1P.}, }
@article {pmid16681686, year = {2006}, author = {Park, K and Han, S and Kim, HJ and Kim, J and Shin, E}, title = {HER2 status in pure ductal carcinoma in situ and in the intraductal and invasive components of invasive ductal carcinoma determined by fluorescence in situ hybridization and immunohistochemistry.}, journal = {Histopathology}, volume = {48}, number = {6}, pages = {702-707}, doi = {10.1111/j.1365-2559.2006.02403.x}, pmid = {16681686}, issn = {0309-0167}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Male ; Middle Aged ; Receptor, ErbB-2/analysis/*genetics ; }, abstract = {AIM: To determine the HER2 status of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. The increased prevalence of HER2 amplification and overexpression in DCIS is considered to be maintained in the intraductal component of IDC; however, HER2 amplification and overexpression are detected much less in IDC.<br><br>METHODS AND RESULTS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed to detect HER2 in 270 IDCs with an intraductal component and in 50 pure DCIS samples; IHC was also performed in 116 metastatic nodes. HER2 was found to be amplified in 77 cases (28.5%) and overexpressed in 79 (29.3%) of the 270 IDCs. HER2 amplification was similar between intraductal and invasive components of the same tumour. The concordance for HER2 status between invasive and intraductal components of individual tumours was 98.5% and 99.3% by FISH and IHC, respectively. HER2 was amplified in 25 (50%) of the 50 pure DCIS samples. HER2 overexpression in metastatic nodes resembled the HER2 status in the primary tumour for 108 (93.1%) of 116 cases (kappa =0.831).<br><br>CONCLUSION: Our study indicates that the intraductal component of IDC may differ biologically when compared with pure DCIS. HER2 appears to lack a critical role in the progression from DCIS to IDC and HER2 status is maintained in metastatic lesions.}, }
@article {pmid16670630, year = {2006}, author = {Einama, T and Kagata, Y and Tsuda, H and Morita, D and Ogata, S and Ueda, S and Takigawa, T and Kawarabayashi, N and Fukatsu, K and Sugiura, Y and Matsubara, O and Hatsuse, K}, title = {High-level Skp2 expression in pancreatic ductal adenocarcinoma: correlation with the extent of lymph node metastasis, higher histological grade, and poorer patient outcome.}, journal = {Pancreas}, volume = {32}, number = {4}, pages = {376-381}, doi = {10.1097/01.mpa.0000220862.78248.c4}, pmid = {16670630}, issn = {1536-4828}, mesh = {Adenocarcinoma/mortality/*pathology ; Carcinoma, Pancreatic Ductal/mortality/*pathology ; Chromosomes, Human, Pair 5 ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatic Neoplasms/mortality/*pathology ; Prognosis ; S-Phase Kinase-Associated Proteins/*analysis/genetics ; Survival Rate ; }, abstract = {OBJECTIVES: Recent studies have shown that overexpression of S-phase kinase-associated protein 2 (Skp2) occurs in many cancers at an advanced stage. We examined the clinicopathologic significance and prognostic implication of Skp2 expression in pancreatic invasive ductal carcinoma.<br><br>METHODS: Tissue samples from 46 pancreatic carcinomas were examined immunohistochemically for Skp2. The proportion of constituent tumor cells with Skp2 expression was analyzed and classified as high-level nuclear expression when more than 20% of the cancer cells were positive, or low-level nuclear expression otherwise.<br><br>RESULTS: High-level Skp2 overexpression was detected in 13 (28.3%) of the 46 tumors. The incidence of high-level Skp2 was correlated with higher histological grade (P = 0.0056), the extent of lymph node metastasis (P = 0.0086), the level of lymphatic permeation (P = 0.0024), and poorer patient outcome (P = 0.0189). Multivariate analysis showed that high-level Skp2 expression was an independent predictor of overall patient survival (P = 0.0140).<br><br>CONCLUSIONS: It is suggested that examination of Skp2 expression might be clinically useful for prognostication in patients with pancreatic carcinoma and that Skp2 protein might be a novel therapeutic molecular target.}, }
@article {pmid16648106, year = {2006}, author = {Ruiz Tovar, J and Reguero Callejas, ME and Aláez Chillarón, AB and Ramiro Pérez, C and Collado Guirao, MV and Rojo Blanco, R and Muñoz Martín-Cámara, J and González-Palacios, F and García Villanueva, A}, title = {Mammary hamartoma.}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {8}, number = {4}, pages = {290-293}, pmid = {16648106}, issn = {1699-048X}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Biopsy, Needle ; Breast Diseases/complications/diagnosis/diagnostic imaging/*pathology/surgery ; Breast Neoplasms/complications/diagnosis ; Carcinoma, Ductal, Breast/complications/diagnosis ; Female ; Hamartoma/complications/diagnosis/diagnostic imaging/*pathology/surgery ; Humans ; Mammography ; Middle Aged ; Recurrence ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {INTRODUCTION: Mammary hamartomas are rare benign breast lumps. They are usually painless, wellcircumscribed, mobile and with no adherence to skin or muscle, composed of varying amounts of fat, glandular and fibrous tissue. Mammary hamartoma has been classically considered as an underdiagnosed pathology, but with the increasing use of diagnostic procedures in breast tumours, the number of hamartomas has increased in the last years. Because there is no distinct pathological feature, a correlation with the clinical findings and image techniques is necessary in order to achieve a correct diagnosis of the pathology.<br><br>MATERIALS AND METHODS: The clinicopathological features of 8 mammary hamartomas are reported here.<br><br>RESULTS: The patients are ranged in age from 34 to 67 years. The initial manifestation was in all cases a well-circumscribed, soft, palpable breast lump. Mammography was performed in all patients. Other diagnostic procedures used in the diagnosis were Ultrasound, Fine Needle Aspiration Cytology and Needle Core Biopsy. Treatment was tumorectomy. We describe a case of recurrence after excision of the lump in a more aggressive histological form and one patient who presented the coexistence of a mammary hamartoma and an invasive ductal carcinoma.<br><br>CONCLUSION: Mammary hamartoma is an uncommon breast tumour. It is necessary the correlation between pathology and clinical and radiological findings. We express our management plan for these lesions.}, }
@article {pmid16647957, year = {2006}, author = {Strauss, BL and Bratthauer, GL and Tavassoli, FA}, title = {STAT 5a expression in the breast is maintained in secretory carcinoma, in contrast to other histologic types.}, journal = {Human pathology}, volume = {37}, number = {5}, pages = {586-592}, doi = {10.1016/j.humpath.2006.01.009}, pmid = {16647957}, issn = {0046-8177}, mesh = {Adenocarcinoma/*metabolism/pathology ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; STAT5 Transcription Factor/*metabolism ; Tumor Suppressor Proteins ; }, abstract = {The 7 signal transducer and activator of transcription (STAT) molecules are responsible for the transcription of a variety of regulatory and differentiation proteins. STAT 5a is activated through a variety of mechanisms; in the breast, this is predominantly through binding of prolactin to its receptor. Previously, we showed that STAT 5a expression is decreased in atypical and malignant breast ductal epithelial cells. Interestingly, STAT 5a overexpression was observed in cells undergoing secretory change. In this study, secretory carcinomas were examined by immunohistochemistry for the presence of STAT 5a. In contrast to usual in situ or invasive ductal carcinoma, which lacked STAT 5a expression, all secretory carcinomas (11 invasive and 7 in situ, including 4 cases with both) expressed STAT 5a. No expression was seen in apocrine metaplasia or in other specialized breast carcinomas, such as mucinous or clear cell carcinoma. This retention of signal in the secretory carcinomas may be explained by the higher STAT 5a concentration present in cells undergoing secretory changes in general. Alternatively, STAT 5a expression may be related to the t(12;15)(p13;q25) chromosomal translocation, associated with certain pediatric tumors and recently demonstrated in many secretory carcinomas of the breast, which results in the expression of a tyrosine kinase through ETV6 and NTRK3 fusion. ETV6 also has been associated with the STAT 5a signaling pathway in another gene translocation and may be altering STAT 5a expression in secretory carcinomas. Breast cancer causes significant morbidity and mortality, and, regardless of the mechanism for retention of STAT 5a expression in this uncommon variant, the examination of STAT 5a will aid our understanding of normal and abnormal breast tissues.}, }
@article {pmid16645950, year = {2006}, author = {Neubauer, H and Clare, SE and Kurek, R and Fehm, T and Wallwiener, D and Sotlar, K and Nordheim, A and Wozny, W and Schwall, GP and Poznanović, S and Sastri, C and Hunzinger, C and Stegmann, W and Schrattenholz, A and Cahill, MA}, title = {Breast cancer proteomics by laser capture microdissection, sample pooling, 54-cm IPG IEF, and differential iodine radioisotope detection.}, journal = {Electrophoresis}, volume = {27}, number = {9}, pages = {1840-1852}, doi = {10.1002/elps.200500739}, pmid = {16645950}, issn = {0173-0835}, mesh = {Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*chemistry/drug therapy/genetics ; Cell Extracts/chemistry ; Cryopreservation ; Drug Resistance, Neoplasm ; Electrophoresis, Gel, Two-Dimensional/*methods ; Female ; Humans ; Hydrogen-Ion Concentration ; Iodine Radioisotopes/analysis ; *Lasers ; Microdissection/*methods ; Mutation ; Neoplasm Proteins/*analysis ; Proteomics/*methods ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tamoxifen/therapeutic use ; }, abstract = {The presence of progesterone receptor (PR) in estrogen receptor (ER)-positive breast cancer is associated with a good prognosis, and indicates that tumors are likely to respond to tamoxifen. However, ER+/PR- tumors respond less well. To reveal the potential molecular mechanism of this phenomenon, we sought to identify differential protein abundances between invasive ductal carcinoma cells from cryopreserved ER+/PR+ and ER+/PR- mammary tumor specimens. Because current proteomics methods are hampered in the examination of most primary human tumor samples by the extreme tissue heterogeneity, we used laser capture microdissection (LCM) to isolate tumor cells and developed a sample pooling strategy to analyze small sample protein lysates. Proteins from LCM-harvested tumors were pooled into four sub-pools from each condition of three tumors/sub-pool, and proteins from respective paired sub-pools were co-electrophoresed by 2-DE using 54-cm IEF over pH 4-9. Abundance ratios were accurately quantified by a differential multiplex radioactive ProteoTope method at low attomole levels (approximately 3.6 microg protein per labeling reaction, <180 ng per multiplex protein sample per 54-cm gel). Applying this approach, differentially displayed proteins were identified by MS using comigrating non-radioactively labeled tumor proteins. They include decreased cytochrome b5 and transgelin, and more abundant CRABP-II, cyclophilin A, Neudesin, and hemoglobin in ER+/PR+ tumors versus ER+/PR- providing a possible explanation for differential susceptibility against tamoxifen as a result of deregulated cytochrome b5-dependent metabolism. This study demonstrates the potential of ProteoTope and LCM to enable extremely sensitive and precise differential analyses from well-defined primary clinical specimen.}, }
@article {pmid16642558, year = {2006}, author = {Kim, YJ and Shim, HS and Lee, H and Jung, WH}, title = {Metaplastic carcinoma with extensive chondroid differentiation in the breast (chondroid carcinoma).}, journal = {Yonsei medical journal}, volume = {47}, number = {2}, pages = {259-263}, pmid = {16642558}, issn = {0513-5796}, mesh = {Actins/metabolism ; Antigens, CD34/biosynthesis ; Breast Neoplasms/complications/metabolism/*pathology ; Carcinoma/*complications/metabolism/pathology ; Cell Differentiation ; Female ; Humans ; Immunohistochemistry ; Keratins/metabolism ; Metaplasia ; Middle Aged ; Mucin-1/metabolism ; Muscle, Smooth/pathology ; Neoplasm Metastasis ; S100 Proteins/chemistry ; }, abstract = {Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with chondroid differentiation is even rarer. Here, we report a case of metaplastic carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that was challenging to diagnose. The tumor was characterized by an abundant chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma was minimal. The peripheral portion of the tumor showed increased cellularity with pleomorphism and definitive invasive growth. Tumor cells in the chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy positive for cytokeratin, but negative for epithelial membrane antigen (EMA). Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100 protein, and patchy positive for EMA. In both areas, tumor cells were negative for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed. When pathologists encounter breast tumors with chondroid differentiation, careful sampling and immunohistochemistry for cytokeratin and SMA are most helpful to differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant adenomyoepithelioma.}, }
@article {pmid16628084, year = {2006}, author = {Shimada, K and Sakamoto, Y and Sano, T and Kosuge, T and Hiraoka, N}, title = {Invasive carcinoma originating in an intraductal papillary mucinous neoplasm of the pancreas: a clinicopathologic comparison with a common type of invasive ductal carcinoma.}, journal = {Pancreas}, volume = {32}, number = {3}, pages = {281-287}, doi = {10.1097/01.mpa.0000202955.33483.e2}, pmid = {16628084}, issn = {1536-4828}, mesh = {Adenocarcinoma, Mucinous/*pathology ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*pathology ; Carcinoma, Papillary/*pathology ; Female ; Humans ; Liver Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatic Neoplasms/*pathology ; }, abstract = {OBJECTIVES: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is an indolent neoplasm by nature; however, it sometimes acquires invasive potential and has been classified as invasive IPMN. The aim of the present study was to investigate the clinicopathologic difference between invasive IPMN and a common type of invasive ductal carcinoma of the pancreas.<br><br>METHODS: Eighteen patients with invasive IPMN underwent pancreatectomy between 1992 and 2004. Clinical, biochemical, and histopathologic factors were retrospectively analyzed. The resulting data were compared with those of 274 patients with a common type of pancreatic ductal carcinoma who underwent surgery during the same period.<br><br>RESULTS: The total size of tumor of invasive IPMN, including cystic and invasive components, was statistically larger than that of a common type of invasive ductal carcinoma (62 vs 40 mm, P < 0.001), but the size of invasive component of invasive IPMN was smaller than that of a common type of invasive ductal carcinoma (21 vs 40 mm, P < 0.001). Negative lymph node metastases and relatively limited local tumor spreading were frequently observed in patients with invasive IPMN. On microscopic examination, the tumors infiltrating the surrounding tissue had a less invasive growth pattern, and a lower frequency of lymphatic invasion, venous invasion, and intrapancreatic neural invasion was also observed in patients with invasive IPMN. The 5-year survival rate of invasive IPMN was significantly higher than that of common-type invasive ductal carcinoma (42% vs 20%, P = 0.04).<br><br>CONCLUSIONS: An increased awareness of invasive IPMN has enabled pancreatectomies to be performed at an earlier stage, relative to that for ordinary pancreatic cancer. The less frequent detection of pathological factors concerned with tumor invasiveness in patients with invasive IPMN suggested the lower aggressive behavior of this tumor.}, }
@article {pmid16627986, year = {2006}, author = {Zhong, D and Morikawa, A and Guo, L and Colpaert, C and Xiong, L and Nassar, A and Chen, C and Lamb, N and Dong, JT and Zhou, W}, title = {Homozygous deletion of SMAD4 in breast cancer cell lines and invasive ductal carcinomas.}, journal = {Cancer biology &amp; therapy}, volume = {5}, number = {6}, pages = {601-607}, doi = {10.4161/cbt.5.6.2660}, pmid = {16627986}, issn = {1538-4047}, mesh = {Base Sequence ; Breast Neoplasms/*genetics ; Carcinoma, Ductal/*genetics/pathology ; Cell Line, Tumor ; DNA Primers ; Female ; *Gene Deletion ; Homozygote ; Humans ; Neoplasm Invasiveness ; Smad4 Protein/*genetics ; }, abstract = {Inactivation of TGF-beta/SMAD4 signaling was postulated to play an important role in breast cancer development. Even though SMAD4 is located on 18q21, a region frequently lost in breast cancers, point mutations of SMAD4 were rarely observed, implying that biallelic inactivation of SMAD4 was not necessary in the process. In this study, a novel homozygous deletion of SMAD4 was identified in breast cancer cell line SW527 during a screening of 31 breast cancer cell lines. As several breast cancer cell lines were shown to contain SMAD4 homozygous deletion, we sought to develop a reliable method to access such lesions in archived primary tumor specimens. First, a DNA quantification method was developed to measure as few as 5 copies of DNA templates so that the amount of genomic DNA isolated by laser-capture microdissection can be accurately determined. Next, accurate DNA quantitation allowed sufficient DNA templates to be included in the homozygous deletion assay for the robust amplification of SMAD4 genetic markers. Two out of 24 primary infiltrative ductal carcinomas (IDC) with 18q allelic imbalance were determined to contain SMAD4 homozygous deletions, and these samples are also negative for Smad4 protein expression by immunohistochemistry. Our data suggest that biallelic inactivation of SMAD4 through homozygous deletion does occur in a small percentage of IDCs, and support the hypothesis that inactivation of TGF-beta/SMAD4 signaling plays in a role in the development of a subset of IDC.}, }
@article {pmid16627203, year = {2006}, author = {Kuzmiak, CM and Dancel, R and Pisano, E and Zeng, D and Cole, E and Koomen, MA and McLelland, R}, title = {Consensus review: A method of assessment of calcifications that appropriately undergo a six-month follow-up.}, journal = {Academic radiology}, volume = {13}, number = {5}, pages = {621-629}, doi = {10.1016/j.acra.2006.01.042}, pmid = {16627203}, issn = {1076-6332}, mesh = {Breast Diseases/diagnostic imaging/epidemiology ; Breast Neoplasms/*diagnostic imaging/*epidemiology ; Calcinosis/*diagnostic imaging/*epidemiology ; *Consensus ; Female ; Humans ; Incidence ; Mammography/*statistics &amp; numerical data ; Outcome Assessment, Health Care/methods ; Precancerous Conditions/diagnostic imaging/epidemiology ; Prognosis ; Radiographic Image Interpretation, Computer-Assisted/*methods ; Retrospective Studies ; Risk Assessment/methods ; Risk Factors ; Severity of Illness Index ; United States/epidemiology ; }, abstract = {RATIONALE AND OBJECTIVES: Breast calcifications seen on mammography may be associated with benign conditions or malignancies. Accurate characterization of these calcifications is crucial to providing optimal care that may spare women unnecessary biopsies and appropriately allow interval mammography. The purpose of this study is to determine if consensus characterization of calcifications by two breast imaging experts using standardized criteria can establish that follow-up is a safe option.<br><br>MATERIALS AND METHODS: For this retrospective study, our breast imaging database was reviewed and the cases imaged between the years 1999 and 2001 were used to identify patients with calcifications who were recommended for a six-month follow-up or biopsy. All cases had been prospectively assessed by at least two expert breast imagers using standardized features to assess the findings before a recommendation for follow-up or a biopsy was made. A retrospective chart review examining the radiology reports was done to determine the percentage of women from each of the two groups who developed malignancies.<br><br>RESULTS: Of 744 patients who had mammographically identified clusters of calcifications, 490 clusters (409 single and 81 multiple) were diagnosed as probably-benign, and a short-interval 6-month follow-up was recommended. Of these calcifications followed for three years, only two (0.5%) of the single clusters proved to be malignant, and malignancy was diagnosed at the 12-month follow-up examination. In both cases, the women were diagnosed with ductal carcinoma in situ (DCIS). Of 254 clusters recommended for biopsy, 242 (215 single and 27 multiple) underwent biopsy. A total of 70 cancers were diagnosed: 54 (77.1%) were DCIS and 16 (22.9%) were primary invasive mammary carcinoma (10 cases of invasive ductal carcinoma, 3 cases of invasive lobular carcinoma, 2 cases of invasive ductal carcinoma with DCIS, and one case of invasive mucinous carcinoma with DCIS). Twenty-nine percent of women who had a biopsy performed had calcifications associated with malignancy. In contrast, in the women whose calcifications were followed by mammography, only 0.5% went on to develop malignancies.<br><br>CONCLUSION: Consensus review of calcifications by two breast imagers using standardized criteria is a safe follow-up option.}, }
@article {pmid16619488, year = {2006}, author = {Seth, RM and Burger, AM and Kahn, HJ}, title = {Analysis of the HER2/neu gene amplification in microdissected breast cancer tumour samples.}, journal = {Anticancer research}, volume = {26}, number = {2A}, pages = {927-931}, pmid = {16619488}, issn = {0250-7005}, mesh = {Base Sequence ; Breast Neoplasms/*genetics/metabolism/pathology ; Female ; *Gene Amplification ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; Microdissection ; Molecular Sequence Data ; Polymerase Chain Reaction ; Receptor, ErbB-2/biosynthesis/genetics ; }, abstract = {The HER2/neu oncogene has been reported to be amplified in > 20% of invasive ductal carcinomas. In order to investigate the HER2/neu status in pure populations of breast cancer cells, a laser capture microdissection (LCM) system was used. Formalin-fixed paraffin-embedded breast tissue areas corresponding to normal ducts, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were microdissected and genomic DNA was isolated by a modified proteinase K- phenol extraction method and subjected to PCR for HER2/neu analysis. One hundred % concordance for detection of the HER2/neu gene amplification was found between immunohistochemistry and PCR used in combination with LCM. Our results indicated that LCM is a powerful technique for isolating pure populations of cells from paraffin-embedded tissue sections and that these cells can be used to study genomic alterations at the DNA level.}, }
@article {pmid16614520, year = {2006}, author = {Lee, MJ and Suh, CH and Li, ZH}, title = {Clinicopathological significance of maspin expression in breast cancer.}, journal = {Journal of Korean medical science}, volume = {21}, number = {2}, pages = {309-314}, pmid = {16614520}, issn = {1011-8934}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/mortality/pathology ; DNA, Neoplasm/analysis/genetics ; Female ; Genes, Tumor Suppressor ; Humans ; Middle Aged ; Ploidies ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Serpins/*metabolism ; Survival Rate ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Maspin is a unique serine proteinase inhibitor that has tumor suppressor activity. It has been reported that maspin is expressed in normal human mammary epithelial cells and it is down-regulated during the progression of cancer. However, to date, there is very limited data on the clinical significance of maspin expression in human breast cancer. In this study, maspin expression was assessed immunohistochemically from 80 invasive ductal carcinoma (IDC) specimens of the breast. Also, maspin expression was compared with the clinicopathological factors (age, grade, tumor size and lymph node status), the expression of estrogen receptor (ER), progesterone receptor (PR) and p53, DNA ploidy and the overall survival in an attempt to assess its prognostic value. The maspin expression was positive in 25 IDC cases (31.3%). The maspin expression in IDC was significantly correlated with a higher histologic grade, a larger tumor size, a positive p53 status and shorter survival. There was an inverse association with maspin expression and the PR status. These findings suggest that maspin expression is not down-regulated with the progression of cancer and maspin expression may be associated with a poor prognosis. The immunohistochemical detection of maspin in breast cancers may be helpful for predicting an aggressive phenotype.}, }
@article {pmid16606540, year = {2006}, author = {Niu, Y and Wang, Y and Yu, Y and Ding, XM and Lü, SH and Xiao, XQ}, title = {[Expression of alpha-tubulin and gamma-tubulin in premalignant lesion and carcinoma of breast and the significance thereof].}, journal = {Zhonghua yi xue za zhi}, volume = {86}, number = {1}, pages = {56-60}, pmid = {16606540}, issn = {0376-2491}, mesh = {Blotting, Western ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Centrosome/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Precancerous Conditions/genetics/metabolism/*pathology ; RNA, Messenger/genetics/metabolism ; Survival Analysis ; Tubulin/genetics/*metabolism ; }, abstract = {OBJECTIVE: To investigate the expression of alpha-tubulin and gamma-tubulin, 2 kinds of centrosome proteins, in premalignant lesion and carcinoma of breast and the significance thereof.<br><br>METHODS: Forty specimens of premalignant lesions of breast, 40 specimens of infiltrating ductal carcinoma of breast, 40 specimens of intraductal carcinoma (IDC), and 30 specimens of normal breast tissues were obtained during operation. Immunohistochemistry was used to analyze the protein expression of alpha-tubulin and gamma-tubulin, and the percentages of ki67 positive cells. Western blotting was used to examine the mRNA expression of alpha-tubulin and gamma-tubulin.<br><br>RESULTS: The protein and mRNA expression values of alpha-tubulin and gamma-tubulin in breast carcinoma were higher than those in the premalignant lesions and normal breast tissues with significant differences between the premalignant lesions and normal breast torques and without significant differences between infiltrating ductal carcinoma of breast and IDC. The ki67 positive rates of the infiltrating ductal carcinoma of breast group, IDC group, premalignant lesion group, and normal breast tissues group were 16.0%, 37.0%, 53.6%, and 67.8% (P = 0.001). A positive correlation existed between the expression of alpha-tubulin and the expression of gamma-tubulin in the same case and the same group (all P = 0.00) and there was no significant correlation between the expression of alpha-tubulin and the expression of gamma-tubulin in the same case and the same group (all P > 0.05). Both the expression of alpha-tubulin and the expression of gamma-tubulin were significantly associated with the prognosis.<br><br>CONCLUSIONS: Centrosome protein is one of the distinct phenotypes of breast cancer cells. Aberration of centrosome proteins may be used to screen high risk cases of breast carcinoma and to estimate the prognosis.}, }
@article {pmid16604511, year = {2006}, author = {Larson, PS and de las Morenas, A and Cerda, SR and Bennett, SR and Cupples, LA and Rosenberg, CL}, title = {Quantitative analysis of allele imbalance supports atypical ductal hyperplasia lesions as direct breast cancer precursors.}, journal = {The Journal of pathology}, volume = {209}, number = {3}, pages = {307-316}, doi = {10.1002/path.1973}, pmid = {16604511}, issn = {0022-3417}, support = {CA81078/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; *Allelic Imbalance ; Breast/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; Humans ; Hyperplasia/genetics ; Microdissection ; Microsatellite Repeats ; Middle Aged ; Polymerase Chain Reaction/methods ; Precancerous Conditions/*genetics ; }, abstract = {It remains unclear whether hyperplastic breast lesions, especially with atypia, are cancer precursors or markers of increased cancer risk. Quantified comparisons of genomic alterations in coexisting lesions could address this question. Therefore, we examined allele imbalance (AI), also known as loss of heterozygosity (LOH), at 20 microsatellite markers on nine chromosome arms, in DNA from 106 samples microdissected from 17 randomly selected cancer-containing breast specimens: 13 simple (DH) and 45 atypical ductal hyperplastic (ADH) lesions, 30 in situ (DCIS) and 18 invasive ductal carcinomas (IDC). Data were analysed using regression models and generalized estimating equations. We found that AI increased as histology became more aberrant and varied with histology across the chromosome arms (p<0.0001). ADH had more AIs on 1q (p=0.03) and 16q (p=0.02) and fewer AIs on 17p (p=0.06) and 17q (p<0.0001) than on other arms. In cancers, AIs remained high on 1q and 16q, and became frequent on 17p and 17q. Concordance between AIs in ADHs and cancers exceeded the 50% expected if the lesions were separate clones in 16/20 (80%) ADHs (p=0.05), from 9/11 (82%) cases (p=0.03), and involved 41/51 (80%) evaluable markers (p=0.05). The occurrence of any AI in ADH predicted greater AI (p=0.009) and possibly lower grade (p=0.05) in coexisting cancers. Nevertheless, ADHs were not genetically identical to cancers or to each other. We found AIs discordant between ADHs and cancers (always on 1q and 16q), AIs unique to ADH (usually on 11q) and some genetic heterogeneity among coexisting ADHs. We conclude that ADH lesions are genetically advanced, with frequent alterations on 1q and 16q, and are often direct cancer precursors. Their global genetic characteristics predict features of cancers in the same breast. Nevertheless, the genetic heterogeneity detected suggests that hyperplasias and cancers may arise on a field at generalized increased cancer risk.}, }
@article {pmid16604497, year = {2006}, author = {Liu, W and Li, WM and Gao, C and Li, Y and Kong, YH}, title = {[The research on associating the single nucleotide polymorphism of CTLA-4 gene promoter region with idiopathic dilated cardiomyopathy].}, journal = {Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics}, volume = {23}, number = {2}, pages = {198-201}, pmid = {16604497}, issn = {1003-9406}, mesh = {Antigens, CD/*genetics ; CTLA-4 Antigen ; Cardiomyopathy, Dilated/*genetics ; Female ; Haplotypes ; Humans ; Male ; *Polymorphism, Single Nucleotide ; Promoter Regions, Genetic/*genetics ; }, abstract = {OBJECTIVE: To investigate the expression of cytotoxic T lymphocyte associated antigen-4 (CTLA-4) in patients with idiopathic dilated cardiomyopathy (IDC) and to explore genetic susceptibility to IDC caused possibly by single nucleotide polymorphism (SNP) of CTLA-4 gene promoter.<br><br>METHODS: PCR-restriction fragment length polymorphism techniques were used to analyze the SNPs of CTLA-4 gene at position -1772, -1661 and -318 in the promoter region. Serum sCTLA-4, IFN-gamma and IL-4 were tested by ELISA.<br><br>RESULTS: sCTLA-4 levels of IDC patients were associated with the haplotype and genotype. Patients with -1772 TC genotype or -1772 TC -1661 AA, -1772 TC -1661 AG haplotypes had higher sCTLA-4 levels than patients with other haplotypes did. The frequency of -1772 TC genotype was significantly high in patients with low ejection factor(EF) values. Whereas the frequencies of -1661 G allele and -1661 GG genotype were lower in IDC patients. Levels of IL-4 were increased in IDC group.<br><br>CONCLUSION: Patients with IDC have an aberrant expression of the CTLA-4 products, and the -1772 C/T and -1661 A/G polymorphisms. The two SNPs may function as genetic markers for disease susceptibility.}, }
@article {pmid16598321, year = {2006}, author = {Hussain, SS and Qattan, AT and Nirmal, MS and Al-Malik, OA and Al-Tweigeri, TA and Tulba, AM and Bin Amer, SM}, title = {Gene expression profiles of the fibroblasts from breast tumors and normal tissue compared with the tumor expression profiles.}, journal = {Saudi medical journal}, volume = {27}, number = {4}, pages = {463-469}, pmid = {16598321}, issn = {0379-5284}, mesh = {Adult ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Case-Control Studies ; Female ; Fibroblasts/*physiology ; Gene Expression Profiling ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; }, abstract = {OBJECTIVE: The study was designed to examine whether the gene expression profiles of fibroblast cell lines, established from the tumor and the normal tissue from the same breast, exhibit any similarities with the profiles of the original tissues.<br><br>METHODS: Fibroblast cell lines were established from invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) of the breast and the adjacent normal tissues. Isolated total RNA from the cell lines and tissues were used to prepare labeled cDNA which was hybridized to Becton Dickinson Atlas microarrays for obtaining profiles of expressed genes. The profiles of tumors and cell lines were compared. This study was carried out at King Faisal specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, during 2004 and 2005.<br><br>RESULTS: Alterations of expression of most of the genes in the tissues were not detectable in the cell lines. The expression of a lower number of genes was altered in DCIS compared with that in IDC tumors.<br><br>CONCLUSION: Although the fibroblasts discharge important functions, their gene expression profiles do not represent the breast tissue to the extent that any prognostic decisions could be made.}, }
@article {pmid16569492, year = {2006}, author = {Broekhuizen, LN and Wijsman, JH and Peterse, JL and Rutgers, EJ}, title = {The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {32}, number = {5}, pages = {502-506}, doi = {10.1016/j.ejso.2006.02.006}, pmid = {16569492}, issn = {0748-7983}, mesh = {Adenocarcinoma/pathology/secondary ; Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma/pathology/*secondary ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/pathology/*secondary ; Carcinoma, Lobular/pathology/secondary ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplastic Cells, Circulating/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Survival Rate ; }, abstract = {AIM: To report the incidence and predictive value of positive axillary nodes in ductal carcinoma in situ (DCIS) and T1a carcinoma of the breast.<br><br>METHODS: Cases from The Netherlands Cancer Institute were used to determine the incidence of lymph-node metastases. All consecutive patients with primary breast cancer that were treated between 1989 and 1998 and who had undergone axillary dissection were selected. Patients were identified with pure DCIS (n = 71), DCIS with small invasion (n = 12), invasive ductal/lobular carcinoma (IDC/ILC) < or =5 mm (n = 18) or tubular carcinoma < or =10 mm (n = 17). All archived lymph nodes of these patients were re-evaluated using immunohistochemistry (IHC).<br><br>RESULTS: In DCIS the incidence increased from 1.4% with routine staining to 11% with IHC. For DCIS with small invasion it was 0 vs 27%, respectively. In IDC/ILC sized 2-5 mm the incidence rose from 6 to 12% and in tubular carcinoma < or =10 mm from 0 to 12%. All but one of the immunohistochemically detected metastases were isolated tumour cells (n = 9) or small (micro)metastases (n = 4). Maximally two nodes per patient were affected. None of the patients with positive lymph nodes died during follow-up (mean 102 months).<br><br>CONCLUSIONS: Survival of our patients appeared not to be influenced by the finding of micrometastases in the lymph nodes by IHC. Immunohistochemistry of the sentinel node seems not contributive to further treatment in these patients.}, }
@article {pmid16552336, year = {2006}, author = {Sanada, Y and Yoshida, K and Ohara, M and Oeda, M and Konishi, K and Tsutani, Y}, title = {Histopathologic evaluation of stepwise progression of pancreatic carcinoma with immunohistochemical analysis of gastric epithelial transcription factor SOX2: comparison of expression patterns between invasive components and cancerous or nonneoplastic intraductal components.}, journal = {Pancreas}, volume = {32}, number = {2}, pages = {164-170}, doi = {10.1097/01.mpa.0000202947.80117.a0}, pmid = {16552336}, issn = {1536-4828}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/genetics/pathology/physiopathology/surgery ; Disease Progression ; Female ; Gastric Mucosa/*pathology ; HMGB Proteins/*genetics ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mucin 5AC ; Mucins ; Neoplasm Invasiveness ; Pancreatic Ducts/pathology ; Pancreatic Neoplasms/genetics/*pathology/physiopathology/surgery ; Retrospective Studies ; SOXB1 Transcription Factors ; Transcription Factors/*genetics ; }, abstract = {OBJECTIVES: The purpose of this study was to perform histopathologic and immunohistochemical analyses of gastric transcription factor SOX2 and gastric mucin MUC5AC to better understand the stepwise progression of pancreatic carcinoma.<br><br>METHODS: Twenty-eight representative sections from 14 surgically resected pancreatic carcinomas were assessed microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma (IDC) were determined. The expression of SOX2 and MUC5AC in PanIN and IDC was examined immunohistochemically.<br><br>RESULTS: One hundred thirty-eight PanINs were identified. In 4 of the 14 cases, gradual transition from PanIN-1A to PanIN-3 was observed in a single duct, suggesting stepwise progression. The expression of MUC5AC increased with the progression of lesions from PanIN-1A to PanIN-3. SOX2 was expressed in only 6 of 107 early PanINs (5.8%). Out of 31 PanIN-3s, 7 were positive (22.6%), and SOX2 protein was localized in the nuclei of cells of the basal epithelium or in the vicinity of luminal necrosis. In addition, SOX2 was frequently and strongly expressed in poorly differentiated (57.1%) and neurally invasive (63.6%) components.<br><br>CONCLUSIONS: The results of our histopathologic examinations suggest that PanIN progresses stepwise to IDC. Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis.}, }
@article {pmid16552071, year = {2006}, author = {Dionne, SO and Podany, AB and Ruiz, YW and Ampel, NM and Galgiani, JN and Lake, DF}, title = {Spherules derived from Coccidioides posadasii promote human dendritic cell maturation and activation.}, journal = {Infection and immunity}, volume = {74}, number = {4}, pages = {2415-2422}, pmid = {16552071}, issn = {0019-9567}, support = {P01 AI061310/AI/NIAID NIH HHS/United States ; IP01AI061310-01/AI/NIAID NIH HHS/United States ; }, mesh = {Cell Adhesion/immunology ; Cell Differentiation/*immunology ; Cells, Cultured ; Coccidioides/cytology/*immunology/metabolism ; Dendritic Cells/*cytology/*immunology/metabolism ; Dose-Response Relationship, Immunologic ; Fungal Vaccines/immunology ; Humans ; Leukocytes, Mononuclear/immunology ; }, abstract = {Previous studies have shown that dendritic cells (DC) pulsed with T27K, an antigenic preparation derived from spherules (of Coccidioides posadasii), activate peripheral blood mononuclear cells (PBMC) from nonimmune subjects as well as from patients with disseminated coccidioidomycosis. In this study, we have assessed the interaction between human DC and C. posadasii spherules in order to better understand the initial response between Coccidioides and the human host. Whole autoclaved spherules induced lymphocyte transformation in PBMC obtained from immune but not from nonimmune donors. Immature DC (iDC) bound fluorescein isothiocyanate-labeled spherules in a time- and temperature-dependent manner. This binding was blocked by the addition of mannan, suggesting mannose receptor involvement in the DC-Coccidioides interaction. Binding was subsequently associated with ingestion and intracellular processing of spherules. Coculturing of spherules with iDC was associated with the development of mature DC that were morphologically, phenotypically, and functionally similar to those induced by tumor necrosis factor alpha and prostaglandin E2. Finally, spherules incubated with iDC induced activation of PBMC from nonimmune donors. These data indicate that human DC are capable of binding, internalizing, and presenting antigens from Coccidioides spherules and suggest that DC may play a critical early role in the formation of a cellular immune response in human coccidioidomycosis.}, }
@article {pmid16527609, year = {2006}, author = {Corzo, C and Corominas, JM and Tusquets, I and Salido, M and Bellet, M and Fabregat, X and Serrano, S and Solé, F}, title = {The MYC oncogene in breast cancer progression: from benign epithelium to invasive carcinoma.}, journal = {Cancer genetics and cytogenetics}, volume = {165}, number = {2}, pages = {151-156}, doi = {10.1016/j.cancergencyto.2005.08.013}, pmid = {16527609}, issn = {0165-4608}, mesh = {Breast Neoplasms/*genetics/pathology ; Chromosomes, Human, Pair 8 ; Disease Progression ; Female ; *Genes, myc ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Invasiveness ; Paraffin Embedding ; }, abstract = {One hypothesis for breast cancer development suggests that breast carcinogenesis involves a progression of events leading from benign epithelium to hyperplasia (with or without atypia) to carcinoma in situ and then invasive carcinoma. The MYC gene (alias c-Myc) is a transcriptional regulator whose expression is strongly associated with cell proliferation and cell differentiation. The present study is a descriptive analysis of MYC status throughout the hypothesized stages of invasive ductal carcinoma progression. A tissue microarray (TMA) was constructed including representative selected areas (normal cells, hyperplasia, in situ carcinoma, and invasive carcinoma) from each of 15 patients. Fluorescence in situ hybridization (FISH) with the LSI c-MYC/CEN8/IgH probe was performed. Two cases displayed MYC amplification (13%), showing this amplification only in the invasive carcinoma zones selected. Five cases displayed polysomy of chromosome 8 (33%), detected only in ductal in situ and invasive zones selected. Benign lesions and normal adjacent cells were classified as normal. None of the hyperplasia specimens and normal specimens analyzed showed any alterations in MYC status or any aneusomies of chromosome 8. The presence of MYC amplification only in invasive cells suggests that the finding of MYC amplification could reflect an advanced tumor progression.}, }
@article {pmid16523261, year = {2006}, author = {Takahashi, K and Nishikawa, Y and Sato, H and Oka, T and Yoshino, T and Miyatani, K}, title = {Dendritic cells interacting mainly with B cells in the lymphoepithelial symbiosis of the human palatine tonsil.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {448}, number = {5}, pages = {623-629}, pmid = {16523261}, issn = {0945-6317}, mesh = {B-Lymphocytes/cytology/*immunology ; Carrier Proteins/metabolism ; Cell Communication/*immunology ; Cell Differentiation ; Dendritic Cells/cytology/*immunology ; Humans ; Immunohistochemistry ; Microfilament Proteins/metabolism ; Palatine Tonsil/*cytology/*immunology ; }, abstract = {The lymphoepithelial symbiosis (LES) of the human palatine tonsil is composed of spindle- or star-shaped epithelial cells forming a loose meshwork, containing numerous lymphocytes and dendritic cells (DCs). In the present study, we immunohistochemically characterized DCs in the LES (LES-DCs). LES-DCs were phenotypically immature DCs that were S100beta+, fascin-, HLA-DR+, CD1a-, CD80-, CD83-, CD86-, and CD123-. The most characteristic feature of LES-DCs was that they contacted many B cells, which were mostly IgM+ IgD+ resting naive B cells. Langerhans cells (LCs) located in the nonsymbiotic squamous epithelium were immature DCs that were S100beta+, fascin-, and CD1a+ and did not contact lymphocytes. In contrast to LES-DCs, interdigitating dendritic cells (IDCs) in the T zone were mature DCs that were HLA-DR+, CD1a-, fascin+, CD80+, CD83+, and CD86+ and contacted numerous CD4+ T cells. Two subsets of IDC, S100beta+ fascin+ IDC (IDC-1) and S100beta- fascin+ IDC (IDC-2), were identified, and the majority of IDCs are IDC-2. In contrast to IDCs, which were distributed in the T-cell area in groups, LES-DCs were distributed along the crypt as if forming a barrier. These findings suggest that LES-DCs are a novel type of DC playing an important role in the induction of humoral immune response against incoming air- or food-borne pathogenic antigens.}, }
@article {pmid16518063, year = {2006}, author = {Li, YS and Kaneko, M and Sakamoto, DG and Takeshima, Y and Inai, K}, title = {The reversed apical pattern of MUC1 expression is characteristics of invasive micropapillary carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {1}, pages = {58-63}, doi = {10.2325/jbcs.13.58}, pmid = {16518063}, issn = {1340-6868}, mesh = {Antigens, Neoplasm ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Carcinoma, Papillary/*metabolism/secondary ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Mucin-1 ; Mucins/*metabolism ; Neoplasm Invasiveness ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a special subtype of invasive ductal carcinoma (IDC), which is known to have a high potential to metastasize to the axillary lymph node. However, it is sometimes difficult to differentiate IMPC from conventional IDC showing an IMPC-like pattern due to artifact (pseudo-IMPC). In the present study, we investigated the usefulness of immunohistochemical expression of MUC1 for distinguishing IMPC from pseudo-IMPC, and analyzed several clinicopathological parameters of IMPC and pseudo-IMPC cases.<br><br>METHODS: Eighty cases showing IMPC or IMPC-like pattern were selected from our surgical files of 1,240 cases of IDC. We examined the expression of MUC1, D2-40 and CD34 by immunohistochemistry.<br><br>RESULTS: Eighty cases were classified into 9 cases (0.7%) of pure-IMPC, 31 cases (2.5%) of mixed-IMPC, and 40 cases of pseudo-IMPC, according to the expression pattern of MUC1. In pure-IMPC cases, MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters, while in pseudo-IMPC, MUC1 expression was present in the whole cytoplasmic membrane and/or cytoplasm. There were no significant differences among the three groups in patient age, tumor size and nuclear grade of neoplastic cells. However, lymphatic invasion and lymph node metastasis in the pure-IMPC or mixed-IMPC cases were higher than those in pseudo-IMPC cases with statistically significant values. Pure-IMPC has a higher recurrence rate and lower overall survival compared to pseudo-IMPC [P = 0.0165(DFS) P = 0.025(OS)].<br><br>CONCLUSIONS: This study demonstrated that immunohistochemistry of MUC1 is useful for the diagnosis of IMPC. The pure-IMPC cases had higher incidences of lymphatic invasion and lymph node metastasis, and also showed a poorer prognosis.}, }
@article {pmid16507410, year = {2005}, author = {Lui, EL and Loo, WT and Zhu, L and Cheung, MN and Chow, LW}, title = {DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {59 Suppl 2}, number = {}, pages = {S363-5}, doi = {10.1016/s0753-3322(05)80079-4}, pmid = {16507410}, issn = {0753-3322}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; *DNA Methylation ; DNA, Neoplasm/biosynthesis/genetics ; Female ; Humans ; Lymphatic Metastasis/pathology ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Inhibitor of Metalloproteinase-3/*genetics ; }, abstract = {BACKGROUND: Neoplastic cells often display aberrant methylation and silencing of multiple genes, including tumor suppressor genes (TSGs) that regulate critical processes such as cell cycle control, DNA repair and angiogenesis. Tissue inhibitor of metalloproteinase-3 (TIMP3) is an extracellular matrix-bound protein which regulates matrix composition and affects tumor growth, invasion and angiogenesis. It mediates vascular endothelial growth factor (VEGF) by blocking the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling. This study focused on the hypermethylation status of the TIMP3 gene with clinical parameters in invasive breast ductal carcinoma (IDC) samples.<br><br>MATERIALS AND METHODS: DNA extraction and methylation specific PCR (MSP) was performed on 173 patients with invasive breast carcinoma. Both specific methylated and unmethylated primers for each gene were used for PCR and the products were visualized on agarose gel. The methylation status of TIMP3 was then compared with corresponding patients' clinicopathologic characteristics.<br><br>RESULTS: Methylation frequencies of TIMP3 in the breast cancer samples were 20.81 %. Among the hypermethylated cancers, 50% were tumor grade II-III, 44.44% were positive in lymph node involvement (LN), 36.11% were positive in lymphovascular permeation (LVP); 44.44%, 22.22% and 47.22% for the overexpressions in estrogen receptor (ER), progesterone receptor(PR) and c-erbB2, respectively.<br><br>CONCLUSION: The result demonstrated that hypermethylation of TIMP3 in IDC might be associated with high tumor grading and lymph nodes metastasis, and overexpression of ER, PR and c-erbB2, respectively.}, }
@article {pmid16507397, year = {2005}, author = {Chow, LW and Loo, WT and Wai, CC and Lui, EL and Zhu, L and Toi, M}, title = {Study of COX-2, Ki67, and p53 expression to predict effectiveness of 5-flurouracil, epirubicin and cyclophosphamide with celecoxib treatment in breast cancer patients.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {59 Suppl 2}, number = {}, pages = {S298-301}, doi = {10.1016/s0753-3322(05)80050-2}, pmid = {16507397}, issn = {0753-3322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibiotics, Antineoplastic/administration &amp; dosage ; Antimetabolites, Antineoplastic/administration &amp; dosage ; Antineoplastic Agents, Alkylating/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Apoptosis/drug effects ; Breast Neoplasms/*drug therapy/enzymology ; Celecoxib ; Cell Proliferation/drug effects ; Cyclooxygenase 2/*biosynthesis ; Cyclooxygenase 2 Inhibitors/*therapeutic use ; Cyclophosphamide/administration &amp; dosage ; Epirubicin/administration &amp; dosage ; Female ; Fluorouracil/administration &amp; dosage ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, p53/*genetics ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*biosynthesis ; Middle Aged ; Pyrazoles/*therapeutic use ; Sulfonamides/*therapeutic use ; }, abstract = {BACKGROUND: Cyclooxygenase-2 (COX-2) affects cell proliferation, apoptosis, and metastasis of breast cancer, and may also be involved in tumor angiogenesis through vascular endothelial growth factor. Ki67 and p53 are common markers of proliferation and apoptosis in tumor cells. This study investigated the change in expression of COX-2, Ki67, and p53 in solid tumors after the administration of chemotherapeutic drugs.<br><br>MATERIALS AND METHODS: Fifty patients were eligible to be treated with preoperative 5-fluorouracil, epirubicin, and cyclophosphamide, with celecoxib (FECC). Tumor tissue samples from 10 patients who, diagnosed with invasive ductal carcinoma, completed chemotherapy were examined immunohistochemically for COX-2, Ki67, and p53.<br><br>RESULTS: From the 60% of patients who expressed COX-2 and 90% who expressed Ki67 and p53 before treatment, 90% of patients revealed a lower intensity staining for each marker after FECC treatment. However, changes in expression of the three markers did not significantly correlate with tumor size, grade, axillary lymph node status. Immunostained slides clearly showed that the diaminobenzidine intensity was markedly reduced after the three-cycle FECC treatment, which implied the combined regimens be effective to the cancer patients.<br><br>CONCLUSIONS: This study demonstrates a novel relationship between COX-2, Ki67, and p53 expression of human breast invasive ductal carcinomas. This functional relationship provides support for a potential therapeutic role of COX-2 inhibitors in human breast cancer.}, }
@article {pmid16493140, year = {2006}, author = {Llinás, M and Bozdech, Z and Wong, ED and Adai, AT and DeRisi, JL}, title = {Comparative whole genome transcriptome analysis of three Plasmodium falciparum strains.}, journal = {Nucleic acids research}, volume = {34}, number = {4}, pages = {1166-1173}, pmid = {16493140}, issn = {1362-4962}, support = {U01 AI053862/AI/NIAID NIH HHS/United States ; AI53862/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigenic Variation ; Antigens, Protozoan/genetics ; Drug Resistance ; Erythrocytes/parasitology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome, Protozoan ; Phenotype ; Plasmodium falciparum/drug effects/*genetics/growth &amp; development ; RNA, Messenger/metabolism ; RNA, Protozoan/*metabolism ; Species Specificity ; Transcription, Genetic ; }, abstract = {Gene expression patterns have been demonstrated to be highly variable between similar cell types, for example lab strains and wild strains of Saccharomyces cerevisiae cultured under identical growth conditions exhibit a wide range of expression differences. We have used a genome-wide approach to characterize transcriptional differences between strains of Plasmodium falciparum by characterizing the transcriptome of the 48 h intraerythrocytic developmental cycle (IDC) for two strains, 3D7 and Dd2 and compared these results to our prior work using the HB3 strain. These three strains originate from geographically diverse locations and possess distinct drug sensitivity phenotypes. Our goal was to identify transcriptional differences related to phenotypic properties of these strains including immune evasion and drug sensitivity. We find that the highly streamlined transcriptome is remarkably well conserved among all three strains, and differences in gene expression occur mainly in genes coding for surface antigens involved in parasite-host interactions. Our analysis also detects several transcripts that are unique to individual strains as well as identifying large chromosomal deletions and highly polymorphic regions across strains. The majority of these genes are uncharacterized and have no homology to other species. These tractable transcriptional differences provide important phenotypes for these otherwise highly related strains of Plasmodium.}, }
@article {pmid16487965, year = {2006}, author = {Fragoso, JM and Rodríguez-Pérez, JM and González, J and Cruz, D and Pérez-Méndez, O and de Jesus García, J and de la Peña, A and Arce, M and Reyes, PA and Vargas-Alarcón, G}, title = {Beta1-adrenergic receptor gene polymorphisms in Mexican patients with idiopathic dilated cardiomyopathy.}, journal = {Experimental and molecular pathology}, volume = {80}, number = {3}, pages = {279-282}, doi = {10.1016/j.yexmp.2005.12.005}, pmid = {16487965}, issn = {0014-4800}, mesh = {Cardiomyopathy, Dilated/*genetics ; Gene Frequency ; *Genetic Predisposition to Disease ; Humans ; Mexico ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, Adrenergic, beta-1/*genetics ; }, abstract = {The objective of the study was to evaluate the role of beta1-adrenergic receptor gene polymorphisms (Ser49Gly and Arg389Gly) as susceptibility markers for idiopathic dilated cardiomyopathy (IDC) in Mexican patients. The polymorphisms were analyzed in 47 patients with IDC and 93 ethnically matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The Ser49Gly allele and genotype frequencies were similar in patients and healthy controls. On the other hand, the analysis of the Arg389Gly polymorphism showed an increased frequencies of the *Gly allele (pC = 0.022, OR = 2.16) and *Arg/*Gly genotype (pC = 0.027, OR = 2.70) in the group of IDC patients when compared to healthy controls. The data suggest that Arg389Gly polymorphism could be involved in the genetic susceptibility to develop IDC in Mexicans.}, }
@article {pmid16471119, year = {2005}, author = {Sampatanukul, P and Chaiwun, B and Wongwaisayawan, S and Suwanagool, P and Vinyuvat, S and Karalak, A and Praditphol, N and Paueksakon, P and Ruangvejvorachai, P and Field, AS and Wannakrairot, P}, title = {A two-phase study model for the standardization of HER2 immunohistochemical assay on invasive ductal carcinoma of the breast.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {88}, number = {11}, pages = {1680-1688}, pmid = {16471119}, issn = {0125-2208}, mesh = {Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Clinical Protocols ; Coloring Agents ; Female ; Genes, erbB-2/*immunology ; Humans ; Immunohistochemistry/methods/*standards ; Models, Theoretical ; Pathology, Clinical/methods/*standards ; Receptor, ErbB-2/*immunology ; Thailand ; }, abstract = {OBJECTIVES: To develop and verify a standardized protocol for HER2 immunohistochemical assays on invasive ductal carcinoma of the breast in Thailand.<br><br>MATERIAL AND METHOD: A two-phase study approach was employed. In the Phase One, after verifying the proposed protocol that adopted the HercepTest procedure using readily available primary antibodies, CB11 and A0485, Lab 1 performed the HER2 immunohistochemical staining for 137 cases of invasive ductal carcinoma twice with two types of the antibody. Nine pathologists from 8 centers independently examined and scored all the 2 x 137 stained slides that were blinded for antibody type. Interobserver reliability was calculated using pair-wise kappa. Following discussion of the results, the Phase Two study was planned. Lab 2 and Lab 3 independently performed the HER2 staining according to the protocol for 60 invasive breast carcinoma cases. The same group of pathologists scored 2 x 60 stained slides that were masked for laboratories. Interobserver reliability and interlaboratory agreement from each pathologist were calculated using kappa statistics. Three interpreted categories--namely negative, equivocal and positive tests were used in the analyses.<br><br>RESULTS: Phase One study showed interobserver agreement between pairs varied from kappa 0.75 (95%CI, 0.68-0.82) to 0.06 (95%CI, 0-0.14) while Phase Two study obtained pair-wise kappa scores ranged from 0.84 (95%CI, 0. 80-0.89) to 0. 65 (95%CI, 0.59-0.71). Interlaboratory kappa for each pathologist was 0.67 (95%CI, 0.61-0.73).<br><br>CONCLUSION: The standardization of HER2 immunohistochemical assay was achieved through this two-phase study model. It had added benefits of improving pathologists' expertise and verifying the HER2 testing protocol to be used in Thailand.}, }
@article {pmid16457686, year = {2005}, author = {Morikawa, A and Williams, TY and Dirix, L and Colpaert, C and Goodman, M and Lyles, RH and Zhong, D and Zhou, W}, title = {Allelic imbalances of chromosomes 8p and 18q and their roles in distant relapse of early stage, node-negative breast cancer.}, journal = {Breast cancer research : BCR}, volume = {7}, number = {6}, pages = {R1051-7}, pmid = {16457686}, issn = {1465-542X}, mesh = {Adult ; Aged ; *Allelic Imbalance ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Case-Control Studies ; Chromosomes, Human, Pair 18/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Metastasis/genetics ; Neoplasm Staging ; }, abstract = {INTRODUCTION: Identification of breast cancer patients at risk for postoperative distant relapse is an important clinical issue. Existing pathological markers can predict disease recurrence only to a certain extent, and there is a need for more accurate predictors.<br><br>METHODS: Using 'counting alleles', a novel experimental method, we determined allelic status of chromosomes 8p and 18q in a case-control study with 65 early stage, node negative, invasive ductal carcinomas (IDCs). The association between allelic imbalance (AI) of both chromosomal markers and distant relapses was examined.<br><br>RESULTS: Eighty percent of tumors contained 8pAI and sixty-eight percent of tumors contained 18qAI. However, none of the tumor samples retained both chromosome 8p and 18q alleles. More importantly, tumors with 8pAI but not 18qAI were more likely to have distant relapse compared to tumors with 18qAI but not 8pAI.<br><br>CONCLUSION: Our finding suggests that differential allelic loss of chromosomes 8p and 18q may represent subtypes of early stage IDC with different tumor progression behaviors.}, }
@article {pmid16455138, year = {2006}, author = {Metharom, P and Velten, FW and Goerdt, S}, title = {Highly phagocytic, CD4hi, CD14hi and CD16hi antigen-presenting cells modulated by tumour-conditioned media retain the capacity to mature and induce TH1 T-cell proliferation.}, journal = {Molecular immunology}, volume = {43}, number = {13}, pages = {2070-2082}, doi = {10.1016/j.molimm.2005.12.008}, pmid = {16455138}, issn = {0161-5890}, mesh = {Antigen-Presenting Cells/cytology/*immunology ; Antigens, CD/*immunology ; CD4 Antigens/*immunology ; Cell Differentiation/drug effects/immunology ; Cell Line, Tumor ; *Cell Proliferation/drug effects ; Culture Media, Conditioned/pharmacology ; Cytokines/immunology ; GPI-Linked Proteins ; Humans ; Lipopolysaccharide Receptors/*immunology ; Neoplasms/immunology ; Receptors, IgG/*immunology ; Th1 Cells/*immunology ; }, abstract = {The tumour microenvironment down-modulates antigen-presentation by dendritic cells (DC), presumably due to inhibition of DC maturation. Here, we sought to examine (1) whether monocyte-derived cells cultivated with tumour-conditioned media under conditions that are conducive to DC generation (APCTCM) resemble immature DC (iDC), IL-10-induced regulatory DC (DCIL10) or display other distinctive features; (2) whether APCTCM are convertible to immunostimulatory DC (DCims) upon proper activation and (3) whether APCTCM and activated APCTCM are functionally defective. Four tumour cell lines expressing different cytokines were used to mimic different tumour microenvironments. As compared to iDC, DCims or DCIL10, APCTCM exhibited the highest levels of expression for CD14, CD16 and CD4. These markers and a high phagocytic capacity were unique features of these cells. When APCTCM were activated by a maturation cocktail, CD83, CD86, HLA-DR and CD25 were up-regulated to levels considerably higher than in DCIL10 and comparable to DCims while CD14, CD16, CD4 and dextran-uptake were down-modulated. Activated APCTCM induced 50-60% of the proliferative response of DCims in the allogeneic T-cell proliferation assay while DCIL10 mounted a 20-30% response (iDC elicited approximately 10%). Activated APCTCM induced secretion of almost equal amounts of IFN-gamma, TNF-alpha and IL-2 as DCims indicating induction of Th1 differentiation. When mature DCims were exposed to TCM, their immunostimulatory function was not significantly altered. However, when TCM were added to the co-cultures of DCims and CD4 T-cells the proliferative outcome was dependent on the TCM. In summary, APCTCM display special features but can mature into DCims-like cells.}, }
@article {pmid16442403, year = {2006}, author = {Fauchier, L and Poret, P and Robin, I and de Labriolle, A and Giraudeau, C and Cosnay, P and Babuty, D}, title = {Different criteria of cardiac resynchronization therapy and their prognostic value for worsening heart failure or major arrhythmic events in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {97}, number = {3}, pages = {393-399}, doi = {10.1016/j.amjcard.2005.08.059}, pmid = {16442403}, issn = {0002-9149}, mesh = {Adult ; Arrhythmias, Cardiac/*etiology ; Cardiomyopathy, Dilated/complications/*therapy ; Clinical Trials as Topic ; Defibrillators, Implantable ; Disease Progression ; Electric Countershock/*adverse effects/instrumentation ; Female ; Heart Failure/*etiology ; Humans ; Male ; Middle Aged ; *Patient Selection ; Prognosis ; }, abstract = {There are still controversies about pertinent criteria for cardiac resynchronization therapy (CRT) and prophylactic indications for biventricular cardioverter-defibrillators, particularly in idiopathic dilated cardiomyopathy (IDC). This study compared several criteria for resynchronization therapy in IDC among those of several completed trials. In 201 patients with IDC, the relative risk for (1) death from heart failure (HF) or heart transplantation and (2) sudden death or sustained ventricular tachyarrhythmia were calculated separately according to the inclusion criteria of the Multisite Stimulation in Cardiomyopathy (MUSTIC), InSync, Multicenter InSync Randomized Clinical Evaluation (MIRACLE), Pacing Therapies for Congestive Heart Failure (PATH-CHF), Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION), and CONTAK studies. The percentage of patients meeting the criteria ranged from 6% for those of MUSTIC to 23% for those of CONTAK. In a follow-up of 51 +/- 42 months, 28 patients died (15 from progressive HF, 13 from sudden death), 20 underwent heart transplantation, and 12 had sustained ventricular tachyarrhythmia. Relative risks of worsening HF ranged from 3.14 (95% confidence interval [CI] 1.41 to 6.99, p = 0.005) for the MIRACLE criteria to 4.63 (95% CI 1.76 to 12.2, p = 0.0019) for the MUSTIC criteria. Only the CONTAK criteria were significantly associated with a risk for major arrhythmic events (2.65, 95% CI 1.19 to 5.95, p = 0.018). Arrhythmic events constituted 16% of all cardiac events for the MUSTIC patients, 11% for InSync patients, 31% for PATH-CHF patients, 36% for MIRACLE patients, 38% for COMPANION patients, and 42% for CONTAK patients. In conclusion, in IDC, the less restrictive criteria for CRT were associated with the greatest risk for arrhythmic events. In contrast, patients with the MUSTIC criteria for CRT mainly had a risk for worsening HF and may not benefit from biventricular cardioverter-defibrillators.}, }
@article {pmid16434695, year = {2006}, author = {Chabot, V and Reverdiau, P and Iochmann, S and Rico, A and Sénécal, D and Goupille, C and Sizaret, PY and Sensebé, L}, title = {CCL5-enhanced human immature dendritic cell migration through the basement membrane in vitro depends on matrix metalloproteinase-9.}, journal = {Journal of leukocyte biology}, volume = {79}, number = {4}, pages = {767-778}, doi = {10.1189/jlb.0804464}, pmid = {16434695}, issn = {0741-5400}, mesh = {Antibodies/pharmacology ; Basement Membrane/immunology/*metabolism ; Cell Membrane/drug effects/immunology ; Cell Movement/drug effects/*immunology ; Chemokine CCL5 ; Chemokines, CC/antagonists &amp; inhibitors/immunology/*pharmacology ; Collagen/immunology ; Dendritic Cells/drug effects/metabolism/*physiology ; Dose-Response Relationship, Drug ; Drug Combinations ; Humans ; In Vitro Techniques ; Laminin/immunology ; Matrix Metalloproteinase 9/drug effects/*metabolism ; Monocytes/drug effects/immunology ; Proteoglycans/immunology ; RNA, Messenger/biosynthesis/drug effects ; Reference Values ; Time Factors ; Tissue Inhibitor of Metalloproteinases/pharmacology ; }, abstract = {The proinflammatory chemokine CC chemokine ligand 5 (CCL5) is a potent chemoattractant of immature dendritic cells (iDCs). It remains to be elucidated whether CCL5 may also enhance iDC migration through the basement membrane by affecting matrix metalloproteinase (MMP)-9 secretion. In this study, iDCs were differentiated in vitro from human monocytes of healthy donors. Zymographic analysis of cellular membranes of nontreated iDCs revealed a basal secretion of the pro- and active MMP-9, whereas only pro-MMP-9 was detected in conditioned media. Increasing concentrations of CCL5 significantly enhanced MMP-9 secretion by iDCs, peaking at 100 ng/ml, which optimally increased iDC migration through a reconstituted basement membrane (Matrigel) in vitro. The CCL5-enhanced secretion of MMP-9 occurred early (2 h) and was maintained at least for 10 h. A significant increase in MMP-9 mRNA synthesis was detected by reverse transcriptase-polymerase chain reaction, only at 6 h of CCL5 treatment, which suggests that the early effect of CCL5 (0-4 h) on MMP-9 secretion was independent of mRNA synthesis, whereas the more delayed effect (6-10 h) could be mediated through an increase in MMP-9 gene expression. In a Matrigel migration assay, the CCL5-enhanced iDC migration was reduced significantly by specific inhibitors of MMP-9, such as tissue inhibitor of metalloproteinase-1 or an anti-MMP-9 antibody, which indicates that iDC migration through the basement membrane depends on MMP-9. These results suggest that under inflammatory conditions, the chemokine CCL5 may enhance iDC migration through the basement membrane by rapidly increasing their MMP-9 secretion.}, }
@article {pmid16428471, year = {2006}, author = {Stange, DE and Radlwimmer, B and Schubert, F and Traub, F and Pich, A and Toedt, G and Mendrzyk, F and Lehmann, U and Eils, R and Kreipe, H and Lichter, P}, title = {High-resolution genomic profiling reveals association of chromosomal aberrations on 1q and 16p with histologic and genetic subgroups of invasive breast cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {12}, number = {2}, pages = {345-352}, doi = {10.1158/1078-0432.CCR-05-1633}, pmid = {16428471}, issn = {1078-0432}, mesh = {Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; *Chromosome Aberrations ; Chromosomes, Artificial, Bacterial ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 16/*genetics ; Cluster Analysis ; DNA, Neoplasm ; *Genome, Human ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Invasiveness/pathology ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; }, abstract = {PURPOSE: Invasive ductal carcinoma and invasive lobular carcinoma (ILC) represent the major histologic subtypes of invasive breast cancer. They differ with regard to presentation, metastatic spread, and epidemiologic features. To elucidate the genetic basis of these differences, we analyzed copy number imbalances that differentiate the histologic subtypes.<br><br>EXPERIMENTAL DESIGN: High-resolution genomic profiling of 40 invasive breast cancers using matrix-comparative genomic hybridization with an average resolution of 0.5 Mb was conducted on bacterial artificial chromosome microarrays. The data were subjected to classification and unsupervised hierarchical cluster analyses. Expression of candidate genes was analyzed in tumor samples.<br><br>RESULTS: The highest discriminating power was achieved when combining the aberration patterns of chromosome arms 1q and 16p, which were significantly more often gained in ILC. These regions were further narrowed down to subregions 1q24.2-25.1, 1q25.3-q31.3, and 16p11.2. Located within the candidate gains on 1q are two genes, FMO2 and PTGS2, known to be overexpressed in ILC relative to invasive ductal carcinoma. Assessment of four candidate genes on 16p11.2 by real-time quantitative PCR revealed significant overexpression of FUS and ITGAX in ILC with 16p copy number gain. Unsupervised hierarchical cluster analysis identified three molecular subgroups that are characterized by different aberration patterns, in particular concerning gain of MYC (8q24) and the identified candidate regions on 1q24.2-25.1, 1q25.3-q31.3, and 16p11.2. These genetic subgroups differed with regard to histology, tumor grading, frequency of alterations, and estrogen receptor expression.<br><br>CONCLUSIONS: Molecular profiling using bacterial artificial chromosome arrays identified DNA copy number imbalances on 1q and 16p as significant classifiers of histologic and molecular subgroups.}, }
@article {pmid16427184, year = {2006}, author = {Miki, Y and Clyne, CD and Suzuki, T and Moriya, T and Shibuya, R and Nakamura, Y and Ishida, T and Yabuki, N and Kitada, K and Hayashi, S and Sasano, H}, title = {Immunolocalization of liver receptor homologue-1 (LRH-1) in human breast carcinoma: possible regulator of insitu steroidogenesis.}, journal = {Cancer letters}, volume = {244}, number = {1}, pages = {24-33}, doi = {10.1016/j.canlet.2005.11.038}, pmid = {16427184}, issn = {0304-3835}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; DNA-Binding Proteins/*metabolism ; Female ; Gene Expression Profiling ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins/genetics/*metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Transcription Factors/*metabolism ; }, abstract = {Liver receptor homologue-1 (LRH-1) belongs to a class of nuclear orphan receptor. We examined immunolocalization of LRH-1 in 106 breast carcinomas. LRH-1 immunoreactivity was detected in 43% of the invasive ductal carcinoma. It was negatively correlated with clinical stage, histological grade and HER2 status, and positively associated with sex-steroid receptors, steroidogenic acute regulatory protein, P450 side-chain cleavage, and 3beta-hydroxysteroid dehydrogenase. LRH-1 immunoreactivity was also detected in 28% of the ductal carcinoma in situ. These results suggest that LRH-1 is frequently detected in breast carcinoma tissues, and plays important roles including the regulation of in situ steroidogenesis.}, }
@article {pmid16425085, year = {2006}, author = {Furuyama, K and Doi, R and Mori, T and Toyoda, E and Ito, D and Kami, K and Koizumi, M and Kida, A and Kawaguchi, Y and Fujimoto, K}, title = {Clinical significance of focal adhesion kinase in resectable pancreatic cancer.}, journal = {World journal of surgery}, volume = {30}, number = {2}, pages = {219-226}, pmid = {16425085}, issn = {0364-2313}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Blotting, Western ; Female ; Focal Adhesion Kinase 1/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatectomy/*methods ; Pancreatic Neoplasms/mortality/*pathology/*surgery ; Probability ; Prognosis ; RNA, Neoplasm ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Sensitivity and Specificity ; Statistics, Nonparametric ; Survival Analysis ; }, abstract = {Focal adhesion kinase (FAK) is a non-receptor, cytoplasmic protein tyrosine kinase that is involved in the regulation of cellular signaling, migration, apoptosis, and cell cycle progression. Previous reports have shown that FAK is expressed in various kinds of cancer tissues and cancer cell lines; however, no information is available about human pancreatic carcinoma specimens. Tissue such specimens were obtained from 50 patients who underwent pancreatic resection for pancreatic invasive ductal carcinoma at our institute from 1996 to 2002. Immunohistochemical analysis of FAK was performed in the resected specimens. Focal adhesion kinase expression in seven human pancreatic cancer cell lines was analyzed by reverse transcription polymerase chain reaction (PCR) analysis and Western blot analysis. Focal adhesion kinase expression was detected in 24 of 50 cases (48%). There was a statistically significant correlation between FAK expression and tumor size (P=0.004), although FAK expression did not significantly correlate with other factors such as tumor histological grade, lymph node metastasis, distant metastasis, histological stage, and overall survival. Reverse transcription PCR analysis and Western blot analysis showed that FAK was expressed in all seven pancreatic cancer cell lines. Focal adhesion kinase expression was not directly related to clinicopathological factors except tumor size in pancreatic carcinoma. Focal adhesion kinase expression may not be a prognostic marker for pancreatic cancer patients.}, }
@article {pmid16424165, year = {2006}, author = {Devilder, MC and Maillet, S and Bouyge-Moreau, I and Donnadieu, E and Bonneville, M and Scotet, E}, title = {Potentiation of antigen-stimulated V gamma 9V delta 2 T cell cytokine production by immature dendritic cells (DC) and reciprocal effect on DC maturation.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {176}, number = {3}, pages = {1386-1393}, doi = {10.4049/jimmunol.176.3.1386}, pmid = {16424165}, issn = {0022-1767}, mesh = {Antigens/immunology ; Antineoplastic Agents/pharmacology ; Calcium/metabolism ; Cell Adhesion/immunology ; Cell Differentiation/*immunology ; Cells, Cultured ; Coculture Techniques ; Cytokines/*biosynthesis ; Dendritic Cells/*cytology/drug effects/*immunology/microbiology ; Diphosphates/pharmacology ; Diphosphonates/pharmacology ; Humans ; Kinetics ; Mycobacterium bovis/immunology ; Pamidronate ; Receptors, Antigen, T-Cell, gamma-delta/*immunology/metabolism ; T-Lymphocytes/*immunology/metabolism ; Th1 Cells/immunology/metabolism ; Th2 Cells/immunology/metabolism ; Tumor Necrosis Factor-alpha/biosynthesis ; }, abstract = {Vgamma9Vdelta2 T cells, a major gammadelta PBL subset in human adults, have been previously implicated in dendritic cell (DC) licensing, owing to their high frequency in peripheral tissues and their ability to produce inflammatory cytokines upon recognition of a broad array of conserved Ags. Although these observations implied efficient recognition of Ag-expressing immature DC (iDC) by Vgamma9Vdelta2 T cells, the role played by DC subsets in activation of these lymphocytes has not been carefully studied so far. We show that iDC, and to a lesser extent mature DC, potentiated Th1 and Th2 cytokine, but not cytolytic or proliferative responses, of established Vgamma9Vdelta2 T cell clones and ex vivo memory Vgamma9Vdelta2 PBL stimulated by synthetic agonists. The ability of iDC to potentiate Vgamma9Vdelta2 production of inflammatory cytokines required for their own maturation suggested that Vgamma9Vdelta2 T cells, despite their strong lytic activity, could promote efficient iDC licensing without killing at suboptimal Ag doses. Accordingly Vgamma9Vdelta2 cells induced accelerated maturation of Ag-expressing iDC but not "bystander" DC, even within mixed cell populations comprising both Ag-expressing and nonexpressing iDC. Furthermore Vgamma9Vdelta2 cells induced full differentiation into IL-12-producing cells of iDC infected by Vgamma9Vdelta2-stimulating mycobacteria that were otherwise unable to induce complete DC maturation. In conclusion the ability of iDC to selectively potentiate cytokine response of memory Vgamma9Vdelta2 T cells could underlie the adjuvant effect of these lymphocytes, and possibly other natural memory T cells, on conventional T cell responses.}, }
@article {pmid16417224, year = {2006}, author = {Isomura, I and Tsujimura, K and Morita, A}, title = {Antigen-specific peripheral tolerance induced by topical application of NF-kappaB decoy oligodeoxynucleotide.}, journal = {The Journal of investigative dermatology}, volume = {126}, number = {1}, pages = {97-104}, doi = {10.1038/sj.jid.5700027}, pmid = {16417224}, issn = {0022-202X}, mesh = {Animals ; CD4 Antigens/immunology ; Cell Movement/drug effects ; Dendritic Cells/drug effects/immunology ; Hypersensitivity, Delayed/immunology/*prevention &amp; control ; Immune Tolerance ; *Immunosuppression Therapy ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Ointments ; Oligodeoxyribonucleotides/*administration &amp; dosage ; Ovalbumin/immunology ; Receptors, Interleukin-2/immunology ; Skin/drug effects ; T-Lymphocytes, Regulatory/*drug effects/immunology ; }, abstract = {Activation and maturation of dendritic cells (DC) are crucial for the establishment of delayed-type hypersensitivity (DTH). However, antigen presentation by immature DC (iDC) might lead to antigen-specific peripheral tolerance. NF-kappaB plays significant roles in upregulation of co-stimulatory molecules and cytokines in DC and therefore we investigated whether NF-kappaB decoy oligodeoxynucleotide (ODN) might induce tolerance to DTH. NF-kappaB decoy ODN suppressed ovalbumin (OVA)-induced DTH responses not only in naïve but also in presensitized mice. The suppressive effect was found to be antigen-specific. NF-kappaB decoy ODN-induced tolerance involved CD4(+)CD25(+) regulatory T cells (Treg), because in vivo depletion of CD25(+) T cells abrogated the tolerance, whereas adoptive transfer of such T cell population from tolerant mice induced tolerance. Furthermore, the induction of Treg was related to insufficient migration and/or maturation of DC, because a sizable DC population still remained in peripheral tissue even after exposure to exogenous antigen in NF-kappaB decoy ODN-treated mice. Even if they migrated into lymph nodes, they showed insufficient upregulation of co-stimulatory molecules and impaired antigen-specific activation of T cells. Topical application of NF-kappaB decoy ODN might thus be a new approach to induce antigen-specific peripheral tolerance.}, }
@article {pmid16410723, year = {2006}, author = {Lo, PK and Mehrotra, J and D'Costa, A and Fackler, MJ and Garrett-Mayer, E and Argani, P and Sukumar, S}, title = {Epigenetic suppression of secreted frizzled related protein 1 (SFRP1) expression in human breast cancer.}, journal = {Cancer biology &amp; therapy}, volume = {5}, number = {3}, pages = {281-286}, doi = {10.4161/cbt.5.3.2384}, pmid = {16410723}, issn = {1538-4047}, support = {P50 CA88843/CA/NCI NIH HHS/United States ; }, mesh = {Acetylation ; Azacitidine/analogs &amp; derivatives/pharmacology ; Breast/metabolism ; Breast Neoplasms/*genetics ; Cell Line ; Cell Line, Tumor ; *DNA Methylation/drug effects ; Decitabine ; Down-Regulation ; *Epigenesis, Genetic ; Genes, Tumor Suppressor ; Histones/*metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Intracellular Signaling Peptides and Proteins ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Proteins/*genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {Expression of Secreted frizzled related protein 1 (SFRP1), a recently identified tumor suppressor gene encoding a WNT signaling antagonist, has been found to be frequently down-regulated in breast cancer and is associated with disease progression and poor prognosis. Here, we investigated the role of epigenetic silencing of SFRP1 in breast cancer cell lines and primary breast tumors. Through analyses by methylation-specific PCR and bisulfite sequencing, promoter methylation of SFRP1 was detected in 88% (7/8) of breast cancer cell lines, 17% (1/6) of grade 1 of ductal carcinoma in situ (DCIS), 69% (9/13) of grade 2 and 3 of DCIS, 68% (19/28) of invasive ductal carcinomas (IDC) and 33% (6/18) of lobular carcinomas but not in any (0/14) of normal mammoplasty specimens and mammary epithelial organoids examined. Real-time RT-PCR studies indicated that loss or downregulation of SFRP1 expression in tumors is frequently associated with promoter hypermethylation. In addition, breast cancer cell lines with SFRP1 promoter hypermethylation reexpressed SFRP1 mRNA after treatment with 5-azaC, implying that DNA methylation is the predominant epigenetic mechanism for SFRP1 gene silencing. These findings suggest that frequent downregulation of SFRP1 expression in breast cancer can be attributed, in large part, to aberrant promoter hypermethylation in conjunction with or without histone deacetylation. Based on the frequency of tumor-specific hypermethylation in this gene, SFRP1 could provide a valuable marker for breast cancer.}, }
@article {pmid16406060, year = {2006}, author = {Goth, SR and Chu, RA and Pessah, IN}, title = {Oxygen tension regulates the in vitro maturation of GM-CSF expanded murine bone marrow dendritic cells by modulating class II MHC expression.}, journal = {Journal of immunological methods}, volume = {308}, number = {1-2}, pages = {179-191}, doi = {10.1016/j.jim.2005.10.012}, pmid = {16406060}, issn = {0022-1759}, support = {P01 ES11269/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antigen Presentation ; Bone Marrow Cells/*cytology/*drug effects/immunology/metabolism ; CD11c Antigen/metabolism ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cell Separation ; Dendritic Cells/*cytology/*drug effects/immunology/metabolism ; Female ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology ; Histocompatibility Antigens Class II/*metabolism ; In Vitro Techniques ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Oxygen/metabolism ; Recombinant Proteins ; }, abstract = {Conventional culture conditions for GM-CSF expanded murine bone marrow derived dendritic cells (BMDCs) uses ambient (hyperoxic) oxygen pressure (20% v/v, 152 Torr) and medium supplemented with the thiol 2-mercaptoethanol (2-Me). Given the redox activities of O2 and 2-Me, the effects of 2%, 5%, 10%, and 20% v/v O2 atmospheres and omitting 2-Me from the medium were tested upon the generation of GM-CSF expanded BMDCs. DC yield, phenotype and function were compared to BMDCs grown using conventional conditions. All cultures yielded DC subsets with CD11c+ MHC II(NEG), CD11c+ MHC II(INT), CD11c+ MHC II(HI) expression phenotypes, classed as precursor, immature, and mature DCs (IDC, MDC). Low O2 tensions generated significantly fewer precursor DCs, and more IDCs and MDCs. Cytometer sorted precursor DCs expressed surface class II MHC after transfer to low, but not high O2 atmospheres. Expression of myeloid markers was similar between BMDC cultures generated in 5% O2 or conventional conditions, and MDCs from low O2 cultures had the morphology typical of mature myeloid DCs. IDCs and MDCs from low O2 and conventional culture conditions were similarly potent allostimulatory APCs. The O2 tension (but not 2-Me addition) in vitro significantly influences overall DC subset frequencies and yield, and governs DC maturation by regulating the surface class II MHC expression of GM-CSF expanded BMDC cultures.}, }
@article {pmid16405845, year = {2005}, author = {Liu, W and Li, WM and Gao, C and Wang, XR and Li, DM and Sun, NL}, title = {[Relationship of CTLA-4 exon 1 A49--&gt;G polymorphism with sCTLA-4 and Th1/Th2 bias in idiopathic dilated cardiomyopathy].}, journal = {Zhonghua yi xue za zhi}, volume = {85}, number = {45}, pages = {3221-3224}, pmid = {16405845}, issn = {0376-2491}, mesh = {Antigens, CD/blood/*genetics ; Antigens, Differentiation/blood/*genetics ; CTLA-4 Antigen ; Cardiomyopathy, Dilated/blood/*genetics/*immunology ; Case-Control Studies ; Exons ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interferon-gamma/blood ; Interleukin-4/blood ; Male ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; *Polymorphism, Single Nucleotide ; T-Lymphocytes, Helper-Inducer/*immunology ; Th1 Cells/immunology ; Th2 Cells/immunology ; }, abstract = {OBJECTIVE: To investigate the association of cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene exon 1 A49-->G polymorphism with the genetic susceptibility to idiopathic dilated cardiomyopathy (IDC) in Chinese Han nationality.<br><br>METHODS: Peripheral blood samples were collected from 48 patients with IDC, 31 males and 17 females, and 50 sex- and age-matched normal controls. ELISA was used to examine the cytokines: sCTLA-4, gamma-interferon (IFN-gamma), and interleukin-4 (IL-4)with the ratio of IFN-gamma/IL-4 as an indicator for Th1/Th2 bias. PCR-RFLP was used to analyze the A/G polymorphism of CTLA-4 exon 1 A49-->G. The relationship of CTLA-4 genotype and alleles frequencies with sCTLA-4, IFN-gamma and IFN-gamma/IL-4 was evaluated by linear regression analysis.<br><br>RESULTS: Compared with the normal controls, the frequencies of GG genotype (0.6042 and 0.7396, P = 0.012) and the G allele (0.36 and 0.56, P = 0.008) were significantly increased in the patients with IDC. Increased serum sCTLA-4 was found in the IDC group compared with the controls (1.87 microg/L +/- 1.06 microg/L vs. 0.54 microg/L +/- 0.19 microg/L, P < 0.05). IFN-gamma was significantly lower in the IDC group than in the control group (16 ng/L +/- 6 ng/L vs. 30 ng/L +/- 10 ng/L, P < 0.05). The ratio of IFN-gamma/IL-4 was significantly in the IDC group than in the control group (1.63 +/- 0.50 vs. 3.01 +/- 0.89, P < 0.05). No statistically difference was found in the IL-4 level between the two groups. Linear regression analysis manifested significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4 (r = 0.57, P = 0.021), IFN-gamma/IL-4 ratio (r = 0.42, P = 0.028) in the IDC group. While no correlation was found for AA, AG genotype and the A allele frequency.<br><br>CONCLUSION: CTLA-4 gene exon 1 A49-->G substitution is associated with an increased IDC genetic susceptibility, which implicates that the CTLA-4 gene may have a significant role in IDC, possibly via a Thr-->Ala change in CTLA-4 signal peptide, with a result of functional change of sCTLA-4. The bias of Th1/Th2 paradigm is associated with the increased sCTLA-4 level under certain background of immunogenicity.}, }
@article {pmid16402338, year = {2006}, author = {Vanden Bempt, I and Vanhentenrijk, V and Drijkoningen, M and De Wolf-Peeters, C}, title = {Comparative expressed sequence hybridization reveals differential gene expression in morphological breast cancer subtypes.}, journal = {The Journal of pathology}, volume = {208}, number = {4}, pages = {486-494}, doi = {10.1002/path.1911}, pmid = {16402338}, issn = {0022-3417}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Chromosomes, Human, Pair 8 ; Diagnosis, Differential ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genes, erbB-2 ; Humans ; In Situ Hybridization/methods ; Oligonucleotide Array Sequence Analysis ; }, abstract = {In this study, comparative expressed sequence hybridization (CESH) has been used to compare gene expression patterns in three morphologically different breast cancer subtypes: classic-type invasive lobular carcinoma (ILC), poorly differentiated ERBB2-negative invasive ductal carcinoma-not otherwise specified (IDC-NOS), and poorly differentiated ERBB2-positive IDC-NOS. CESH allows global detection of chromosomal regions with differential gene expression in a way similar to that of comparative genomic hybridization (CGH). Eight cases of each breast cancer subtype were included in the study. For each subtype, two pools of four cases each were constructed. CESH was used to compare both pools within the same morphological subtype, followed by a comparison of pools belonging to different subtypes. This revealed three chromosomal regions that were differentially expressed in ductal and lobular carcinomas, including relative overexpression at 8q13-q23 and 16q22, and relative underexpression at 8p21-p22. In addition, an expression signature characterized by relative overexpression at 3q24-q26.3, 14q23-31, 17q12, and 20q12-13 was identified for ERBB2-positive IDC-NOS. In summary, CESH analysis highlights chromosomal regions of differential gene expression that are associated with morphologically defined breast cancer subtypes and suggests that regions on chromosome 8 are of interest in the discrimination between ductal and lobular carcinomas. In addition, using CESH, it was possible to identify an ERBB2 expression signature, comprising four chromosomal regions with potential significance in the aggressive behaviour of ERBB2-positive IDC-NOS.}, }
@article {pmid16397925, year = {2005}, author = {Izgi, C and Cevik, C and Ozdemir, N and Kaymaz, C and Ozkan, M}, title = {Serum anti-p53 antibodies do not occur in patients with heart failure due to idiopathic dilated and ischemic cardiomyopathies.}, journal = {European journal of heart failure}, volume = {7}, number = {7}, pages = {1095-1098}, doi = {10.1016/j.ejheart.2005.01.015}, pmid = {16397925}, issn = {1388-9842}, mesh = {Adolescent ; Adult ; Aged ; Autoantibodies/*blood ; Biomarkers/blood ; Cardiomyopathy, Dilated/*complications ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Heart Failure/blood/*etiology/immunology ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*complications ; Tumor Suppressor Protein p53/*immunology ; }, abstract = {BACKGROUND: P53 is a key protein which controls cell cycle arrest and apoptosis in response to DNA damage. Auto-antibodies against p53 have been detected in some cancer patients and also in patients with autoimmune diseases. In these patients, the main cause of anti-p53 antibody occurrence was considered to be increased intracellular p53 protein in cancer cells and autoreactive lymphocytes, respectively. Intracellular p53 also increases with cardiomyocyte apoptosis during heart failure and autoreactive lymphocytes play a role in the course of idiopathic dilated cardiomyopathy (IDC) and ischemic cardiomyopathy (ICM). Based on these observations, we hypothesized that anti-p53 antibody response may also occur in patients with heart failure due to ICM and IDC.<br><br>AIM: The aim of this study was to evaluate anti-p53 antibodies in the serum of patients with heart failure due to IDC and ICM.<br><br>METHODS: 70 eligible patients with heart failure and severe left ventricular systolic dysfunction (mean fractional shortening 12.03 +/- 3.93%) were included in the study. The aetiology of heart failure was IDC in 26 patients and ICM in 44 patients, according to the angiographic and echocardiographic findings.<br><br>RESULTS: Anti-p53 antibodies were not detected in any of the patients.<br><br>CONCLUSION: Anti-p53 antibodies do not occur in patients with heart failure due to IDC and ICM, possible explanations are discussed in the text.}, }
@article {pmid16381010, year = {2006}, author = {Yeh, YT and Hou, MF and Chung, YF and Chen, YJ and Yang, SF and Chen, DC and Su, JH and Yuan, SS}, title = {Decreased expression of phosphorylated JNK in breast infiltrating ductal carcinoma is associated with a better overall survival.}, journal = {International journal of cancer}, volume = {118}, number = {11}, pages = {2678-2684}, doi = {10.1002/ijc.21707}, pmid = {16381010}, issn = {0020-7136}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Case-Control Studies ; Cell Transformation, Neoplastic ; Female ; Gene Expression Profiling ; Humans ; Immunoblotting ; Mitogen-Activated Protein Kinase 1/biosynthesis ; Mitogen-Activated Protein Kinase 3/biosynthesis ; Mitogen-Activated Protein Kinase 8/*biosynthesis/genetics ; Mitogen-Activated Protein Kinase 9/*biosynthesis/genetics ; Phosphorylation ; Prognosis ; Survival Analysis ; p38 Mitogen-Activated Protein Kinases/biosynthesis ; }, abstract = {Phosphorylation/activation of c-jun NH2-terminal kinase (JNK) has an ambivalent role, pro-proliferation or antiproliferation, in human cancers, which is determined by different cell types and by its crosstalk with other kinases. So far, the role of phosphorylated JNK (p-JNK) in breast cancer is mostly undefined. In this study, we analyzed the expression of p-JNK, as well as p-ERK1/2 and p-38, in the pair of cancer and noncancer breast tissues, by using immunoblotting techniques. These results were further correlated with the clinicopathological characteristics and overall survival. Decreased p-JNK1/2 expression in cancer tissues was observed in 48.5% of breast infiltrating ductal carcinoma (IDC) cases and was correlated significantly with the increased tumor grade and the decreased age at diagnosis (p = 0.030 and 0.029). Interestingly, the Kaplan-Meier survival curve showed that the decreased p-JNK1/2 expression was associated with a better overall survival of IDC (p = 0.004). The expression of p-JNK1/2 was positively correlated with p-p38 (p = 0.002), but not p-ERK1/2. Furthermore, co-expressed p-JNK1/2 and p-p38 was associated with a poor overall survival of IDC (p = 0.007). In conclusion, our results indicate that the aberrant p-JNK1/2 expression and the co-expressed p-JNK1/2 and p-p38 in breast tissues may play a role in the carcinogenesis of breast IDC.}, }
@article {pmid16380768, year = {2005}, author = {Meteoglu, I and Dikicioglu, E and Erkus, M and Culhaci, N and Kacar, F and Ozkara, E and Uyar, M}, title = {Breast carcinogenesis. Transition from hyperplasia to invasive lesions.}, journal = {Saudi medical journal}, volume = {26}, number = {12}, pages = {1889-1896}, pmid = {16380768}, issn = {1658-3175}, mesh = {Adult ; Aged ; Apoptosis/physiology ; Biopsy, Needle ; Breast/*pathology ; Breast Neoplasms/*pathology/*physiopathology ; Carcinoma, Ductal, Breast/pathology/physiopathology ; Carcinoma, Intraductal, Noninfiltrating/pathology/physiopathology ; Cell Proliferation ; Cell Transformation, Neoplastic/*pathology ; Female ; Humans ; Hyperplasia/pathology/physiopathology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Neoplasm Staging ; Probability ; Sampling Studies ; Statistics, Nonparametric ; Tissue Culture Techniques ; }, abstract = {OBJECTIVES: To examine the balance loss between proliferation and apoptosis that play a role in breast cancer development, and to explore the places of various genes and molecules within this process in this supposed multistep process.<br><br>METHODS: We obtained the specimens from 40 patients between 2002 and 2004 at the Department of Pathology, Medical Faculty, Adnan Menderes University, Aydin, Turkey. We categorized the lesions ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), in situ ductal carcinoma (DCIS), and invasive ductal carcinoma (IDC). We determined the tumor size, histological grade and lymph node status of invasive cases and we used nottingham prognostic index (NPI). We applied ER, PR, c-erbB2, p53, Ki-67, bcl-2, dUTP nick end labeling (TUNEL), breast cancer gene-1, matrix metalloproteinases-1 and tissue inhibitor matrix metalloproteinases-1 stains to each lesion using the immunohistochemical method.<br><br>RESULTS: We observed that ER and PR decreased in ADH when compared with DH (p=0.0001 and p=0.019). However, we determined that in DCIS as c-erbB2 (p=0.005) and Ki-67 (p=0.004) increase, TUNEL (p=0.04) and bcl-2 (p=0.005) decrease, when compared with ADH. When compared with DCIS lesions, we observed the existence of a higher c-erbB2 (p=0.003) and a lower TUNEL (p=0.012) in invasive tumors. Furthermore, we found that there is a higher MMP-1 (p=0.04) in invasive lesions, when compared with non-invasive lesions. We detected higher PR (p=0.049), lower TUNEL and c-erbB2 (p=0.017) in low grade group of NPI, when compared with high grade group of NPI.<br><br>CONCLUSION: As a result, it has been shown that together with increase in proliferation, decrease in apoptosis, too, contributes to the proliferation/apoptosis imbalance that occurs in breast carcinogenesis. Increase in proliferation and decrease in apoptosis are parallel with the progression of lesions. We also showed that the changes, beginning with loss of ER and PR in ADH step, can cause malign transformation, which is especially notable both in DCIS step due to Ki-67 and c-erbB2 increase, and also with bcl-2 and TUNEL decrease.}, }
@article {pmid16372244, year = {2006}, author = {García-Caballero, T and Menéndez, MD and Vázquez-Boquete, A and Gallego, R and Forteza, J and Fraga, M}, title = {HER-2 status determination in breast carcinomas. A practical approach.}, journal = {Histology and histopathology}, volume = {21}, number = {3}, pages = {227-236}, doi = {10.14670/HH-21.227}, pmid = {16372244}, issn = {1699-5848}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/*chemistry/drug therapy/genetics ; Carcinoma, Ductal, Breast/*chemistry/drug therapy/genetics ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2/genetics ; Humans ; Immunohistochemistry/*methods ; In Situ Hybridization, Fluorescence/*methods ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*analysis/genetics ; Reproducibility of Results ; Trastuzumab ; }, abstract = {Accurate evaluation of HER-2 status is crucial in the selection of breast carcinoma patients for trastuzumab (Herceptin) treatment. Various laboratory methods have been used for this purpose. The aim of the present work was to analyse the results obtained in the routine practice by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in determination of HER-2 status. Five hundred and three cases of breast invasive ductal carcinoma were selected to analyse the HER-2 overexpression by immunohistochemistry (HercepTest, Dako). HercepTest 2+ equivocal cases (60) were studied by FISH (PathVysion, Vysis) to determine HER-2 gene amplification. HER-2 overexpression determined by Herceptest was shown in 97/503 cases (19%). FISH performed on equivocal cases demonstrated HER-2 amplification in 11/60 tumours (18%). IHC and FISH together showed HER-2 overexpression/gene amplification in 21% of breast invasive carcinomas. Immunohistochemical determination of HER-2 status represents an easy and standardized method that (in contrast to FISH) can be performed in all pathology laboratories without need of any special microscope and enabling to check the morphologic features of the cells analysed. However, in order to assure the reliability of the results, standardization of fixation protocols, automation of the immunohistochemical procedure, and training of pathologists in the interpretation of the results (scoring criteria) should be a priority. Equivocal HercepTest cases must be analysed by FISH preferably in a reference laboratory.}, }
@article {pmid16364645, year = {2006}, author = {Haraguchi, M and Kuroki, T and Tsuneoka, N and Furui, J and Kanematsu, T}, title = {Management of chylous leakage after axillary lymph node dissection in a patient undergoing breast surgery.}, journal = {Breast (Edinburgh, Scotland)}, volume = {15}, number = {5}, pages = {677-679}, doi = {10.1016/j.breast.2005.11.004}, pmid = {16364645}, issn = {0960-9776}, mesh = {Aged ; Axilla ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Chylous Ascites/*diagnosis/etiology/surgery ; Diagnosis, Differential ; Female ; Humans ; Lymph Node Excision/*adverse effects ; Lymphatic Vessels/*surgery ; Mastectomy/adverse effects ; Postmenopause ; Postoperative Complications/*diagnosis/etiology/surgery ; Reoperation ; Suction ; }, abstract = {A 71-year old woman who underwent a modified radical mastectomy for invasive ductal carcinoma of the left breast, developed postoperative chylous leakage. Though conservative management was uneffective, a direct surgical repair led to good results. Because the morbidity of a reoperation to the superficial chest wall is low, timely surgical treatment is therefore strongly recommended in cases of high output chylous leakage following a mastectomy.}, }
@article {pmid16360363, year = {2005}, author = {Sampietro, T and Neglia, D and Bionda, A and Dal Pino, B and Bigazzi, F and Puntoni, M and Startari, U and Morales, A and Minichilli, F and Bianchi, F and L'Abbate, A}, title = {Inflammatory markers and serum lipids in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {96}, number = {12}, pages = {1718-1720}, doi = {10.1016/j.amjcard.2005.07.093}, pmid = {16360363}, issn = {0002-9149}, mesh = {Adult ; Aged ; Biomarkers/blood ; C-Reactive Protein/*metabolism ; Cardiomyopathy, Dilated/*blood/complications/immunology ; Ceruloplasmin/metabolism ; Cholesterol, HDL/*blood ; Complement C3/metabolism ; Complement C4/metabolism ; Disease Progression ; Dyslipidemias/blood/complications/immunology ; E-Selectin/blood ; Female ; Haptoglobins/metabolism ; Humans ; Immunity, Innate/physiology ; Inflammation/blood ; Intercellular Adhesion Molecule-1/blood ; Male ; Middle Aged ; Prognosis ; Risk Factors ; Triglycerides/*blood ; }, abstract = {Coronary microcirculation is impaired in idiopathic dilated cardiomyopathy (IDC), possibly because of endothelial dysfunction. High-density lipoproteins (HDLs) have the potential to regulate endothelial function and modulate inflammation and the innate immune response. This study investigated whether reduced HDLs, concomitantly with the activation of inflammation, are associated with IDC. Fifty-five patients with IDC, without evidence of other organ or systemic, chronic, or recurrent diseases, were compared with 55 healthy controls for HDLs and complete lipid profiles, C-reactive protein, C3 and C4 complement fractions, soluble intercellular adhesion molecule-1 and soluble endothelial leukocyte adhesion molecule-1, haptoglobin, and ceruloplasmin. Patients with IDC differed from controls, with lower HDL levels, lower apolipoprotein A-I and A-II levels, and higher triglyceride levels, but not on total and low-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein(a). In addition, all measured inflammation markers were significantly greater in patients with IDC than in controls and were negatively correlated with HDLs. A strong and independent association with IDC was found for age, soluble intercellular adhesion molecule-1, and HDLs that, when categorized as <40 or >40 mg/dl, showed the strongest association (prevalence odds ratio 0.10, p <0.0005) with the disease. In conclusion, the data here reported on reduced HDLs and increased endothelial inflammatory activation and the linear negative correlation between HDLs and inflammation markers, particularly soluble intercellular adhesion molecule-1, could suggest a role for HDLs in the endothelial-microvascular dysfunction seen in IDC.}, }
@article {pmid16338494, year = {2005}, author = {Chang, CC and Satwani, P and Oberfield, N and Vlad, G and Simpson, LL and Cairo, MS}, title = {Increased induction of allogeneic-specific cord blood CD4+CD25+ regulatory T (Treg) cells: a comparative study of naïve and antigenic-specific cord blood Treg cells.}, journal = {Experimental hematology}, volume = {33}, number = {12}, pages = {1508-1520}, doi = {10.1016/j.exphem.2005.09.002}, pmid = {16338494}, issn = {0301-472X}, support = {5P-30CA13697/CA/NCI NIH HHS/United States ; }, mesh = {Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; Cell Proliferation ; Coculture Techniques ; Dendritic Cells/immunology ; Fetal Blood/*immunology ; Graft vs Host Disease/etiology/immunology ; Humans ; Isoantigens/*immunology ; Lymphocyte Activation/*immunology ; Models, Biological ; T-Cell Antigen Receptor Specificity/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Transplantation Immunology ; }, abstract = {OBJECTIVE: The genetic and immunological mechanism(s) responsible for the significant decrease in the incidence of graft-vs-host disease (GVHD) following HLA-disparate unrelated cord blood transplantation remains largely unknown. In this study, we investigated if cord blood (CB) CD4(+)CD25(+) T cells play a significant role in reducing the immune responses of allo-reactive CD4(+)CD25(-) T lymphocytes.<br><br>METHODS: We compared CB CD4(+)CD25(-) and CD4(+)CD25(+) T cells, either na&#xef;ve or antigenic stimulated, to their counterparts in unmobilized adult peripheral blood (APB) with respect to genetic expression patterns, immunophenotype, suppressive activity, and mechanism(s) of suppression.<br><br>RESULTS: Both na&#xef;ve CB and APB CD4(+)CD25(+) T cells expressed similarly elevated mRNA levels of CTLA-4, GITR, Foxp3, CD25, and elevated protein levels of CTLA-4 (p < 0.001) and GITR (p < 0.001). However, only na&#xef;ve APB but not CB CD4(+)CD25(+) T cells showed suppression of allogeneic responses. Stimulation of CD4(+)CD25(-) T cells by MUTZ-iDC (MUTZ-3-specific immature dendritic cells) elicited amplification of these genes and potent suppression (69% +/- 5% and 71% +/- 3% suppression, p < 0.001, CB and APB, respectively) on CD4(+)CD25(-) T cell proliferation induced by MUTZ-iDC but not by unrelated stimulators. Compared to that from unmobilized APB, a significantly higher percentage (2.7-fold +/- 0.5-fold; p < 0.002) of CD4(+)CD25(+)CTLA-4(+) T regulatory (Treg) cell subsets were induced from CB CD4(+)CD25(-) T cells following allogeneic stimulation.<br><br>CONCLUSION: Our results suggest that CB CD4(+)CD25(+) Treg cells, which are induced at a higher rate by allogeneic stimulation when compared to unmobilized APB, can readily function as potent allogeneic immune suppressors and may in part contribute to the decrease in CB alloantigen recognition and activation of CB CD4(+)CD25(-) T cells.}, }
@article {pmid16328121, year = {2005}, author = {Haberstich, R and Tuech, JJ and Wilt, M and Rodier, JF}, title = {Anal localization as first manifestation of metastatic ductal breast carcinoma.}, journal = {Techniques in coloproctology}, volume = {9}, number = {3}, pages = {237-238}, doi = {10.1007/s10151-005-0235-0}, pmid = {16328121}, issn = {1123-6337}, mesh = {Aged ; Anastrozole ; Anus Neoplasms/pathology/*secondary/*therapy ; Biopsy, Needle ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology/*secondary/surgery ; Chemotherapy, Adjuvant ; Colectomy/methods ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Nitriles/*administration &amp; dosage ; Rare Diseases ; Risk Assessment ; Treatment Outcome ; Triazoles/*administration &amp; dosage ; }, abstract = {The incidence of extrahepatic gastrointestinal metastases from breast cancer is reported in the literature only as necroscopy studies (6-18%); they usually originate from lobular or a mixed ductal-lobular subtype. Nonspecific presenting symptoms, death of the patients caused by other more frequent metastases, and variable radiographic features mimicking primary neoplasms cause a clinical underestimation of this pathology. We report here a case of rectal metastasis from an invasive ductal carcinoma (IDC). This is to our knowledge, the first recorded instance of an anal metastasis from IDC.}, }
@article {pmid16324201, year = {2005}, author = {Park, SS and Kim, JE and Kim, YA and Kim, YC and Kim, SW}, title = {Caveolin-1 is down-regulated and inversely correlated with HER2 and EGFR expression status in invasive ductal carcinoma of the breast.}, journal = {Histopathology}, volume = {47}, number = {6}, pages = {625-630}, doi = {10.1111/j.1365-2559.2005.02303.x}, pmid = {16324201}, issn = {0309-0167}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Cadherins/analysis/metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Case-Control Studies ; Caveolin 1/*analysis/genetics/metabolism ; *Down-Regulation ; ErbB Receptors/analysis/metabolism ; Female ; Genes, erbB-1 ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis/metabolism ; Microarray Analysis ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Tumor Suppressor Protein p53/analysis/metabolism ; beta Catenin/analysis/metabolism ; }, abstract = {AIMS: To evaluate the caveolin-1 status of invasive ductal carcinoma and its correlation with other important parameters of breast carcinogenesis. Caveolin-1, the main structural protein of caveolae, is involved in the regulation of several intracellular signalling pathways and also functions as a tumour suppressor in breast carcinogenesis.<br><br>METHODS AND RESULTS: One hundred and thirty cases of invasive ductal carcinomas with matched normal breast tissue were evaluated immunohistochemically for caveolin-1 expression. Using a tissue microarray, caveolin-1 expression was also correlated with the expression of other antigens such as eostrogen receptor, progesterone receptor, epidermal growth factor receptor (EGFR), HER2, beta-catenin, E-cadherin, p53, Ki67 and with clinicopathological parameters. Immunohistochemical results showed strong expression of caveolin-1 in all normal breast epithelial cells, but a reduction of caveolin-1 expression in 56 cases (43.1%) of invasive ductal carcinoma. Furthermore, a statistically significant inverse correlation between caveolin-1 and EGFR and HER2 was noted (P < 0.001).<br><br>CONCLUSIONS: Our results indicate a reduction in caveolin-1 expression in invasive ductal carcinoma of the breast, which supports in vitro studies of its role as a tumour suppressor. Caveolin-1 also shows an inverse correlation with EGFR and HER2, which fits with its function as a negative regulator of signal transduction.}, }
@article {pmid16315943, year = {2005}, author = {Sakurai, K and Enomoto, K and Amano, S and Kitajima, A and Suzuki, M and Matsuo, S and Sakamoto, A and Kashio, M and Tani, M and Negishi, N}, title = {[A case of advanced breast cancer with multiple lung and liver metastases successfully treated with multi-disciplinary therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {32}, number = {11}, pages = {1792-1794}, pmid = {16315943}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/administration &amp; dosage ; Antineoplastic Agents, Phytogenic/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal/pathology/secondary/*therapy ; Combined Modality Therapy ; Docetaxel ; Female ; Humans ; Liver Neoplasms/*secondary/*therapy ; Lung Neoplasms/*secondary/*therapy ; Middle Aged ; Taxoids/administration &amp; dosage ; Trastuzumab ; Treatment Outcome ; }, abstract = {We report a case of advanced breast cancer with multiple lung and liver metastases (T4bN1M1) achieving a significant improvement of QOL by multi-disciplinary therapy. The patient was a 63-year-old woman with slight jaundice who had ascites and an ulcerative breast lump with multiple lung and liver metastases. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for HER2/neu protein expression. She received 6 cycles of tri-weekly docetaxel (60 mg/m2) and weekly trastuzumab. Although the ascites and the jaundice disappeared after chemotherapy, the response for breast tumor, metastatic sites in the lung and the liver were less satisfactory. Fifteen-months later, she received radiation therapy so that metastasis in the brain was recognized. But she had no neurological symptoms. Multi-disciplinary therapy can improve patient's QOL and the clinical outcomes in Stage IV advanced breast cancer.}, }
@article {pmid16295319, year = {2004}, author = {Stăvaru, C and Caplanus, A and Radu, DL}, title = {Phenotypical changes during in vitro cultivation of monocytes derived immature dendritic cells.}, journal = {Roumanian archives of microbiology and immunology}, volume = {63}, number = {1-2}, pages = {35-46}, pmid = {16295319}, issn = {1222-3891}, mesh = {Antigens, CD/metabolism ; *Cell Differentiation ; Cells, Cultured ; Dendritic Cells/*cytology/*physiology ; Flow Cytometry ; Granulocytes/immunology/metabolism ; HLA-DR Antigens/metabolism ; Humans ; Luminescence ; Monocytes/*cytology ; Phenotype ; Reactive Oxygen Species/metabolism ; }, abstract = {Dendritic cells (DC) form a link between the first line of host defence and cellular immunity. In the present study we investigated the effect of cultivation time in generation of immature dendritic cells (iDCs) in vitro from human peripheral blood (PB) monocytes and the influence of iDCs on the oxygen free radicals (OFR) release by polymorphonuclear granulocytes (PMN) stimulated with opsonized zymozan (OZ) and concanavalin A (ConA). Our data suggest that the differentiation in vitro of PB monocytes in iDCs is influenced by the health status of the cell donor, and more by the concentration of cytokines GM-CSF and IL-4 in the system than by the time of cultivation. The in vitro experiments performed demonstrated the interactions between iDC and PMN granulocytes, evaluated by enhanced release of OFR.}, }
@article {pmid16288397, year = {2005}, author = {Perencevich, EN and Harris, AD and Kaye, KS and Bradham, DD and Fisman, DN and Liedtke, LA and Strausbaugh, LJ and , }, title = {Physicians' acceptable treatment failure rates in antibiotic therapy for coagulase-negative staphylococcal catheter-associated bacteremia: implications for reducing treatment duration.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {41}, number = {12}, pages = {1734-1741}, doi = {10.1086/498116}, pmid = {16288397}, issn = {1537-6591}, support = {K23 AI01752-01A1/AI/NIAID NIH HHS/United States ; U50/CCU112346/CC/ODCDC CDC HHS/United States ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/*microbiology ; *Catheterization ; *Equipment Contamination ; Humans ; *Practice Patterns, Physicians' ; Staphylococcal Infections/*drug therapy/*microbiology ; Surveys and Questionnaires ; Time Factors ; Treatment Failure ; }, abstract = {BACKGROUND: Decreasing the duration of antimicrobial therapy is an attractive strategy for delaying the emergence of antimicrobial resistance. Limited data regarding optimal treatment durations for most clinical infections hinder the adoption of this approach and impair optimal physician-patient communication under the shared decision-making model. We aimed to identify acceptable failure rates among infectious disease consultants (IDCs) for treatment of central venous catheter-associated bacteremia.<br><br>METHODS: A case scenario involving a representative patient who developed central venous catheter-associated bacteremia caused by coagulase-negative staphylococci and who received standard-of-care therapy was distributed to all nonpediatric IDC members of the Infectious Diseases Society of America's Emerging Infections Network in August 2003. Each member was suggested 1 of 10 treatment failure rates and asked whether he or she would accept or reject the given value. Logistic regression was used to evaluate the relationship between specific failure rates offered to respondents and their willingness to accept them using a methodology derived from contingent valuation.<br><br>RESULTS: Among the 374 respondents (response rate, 54%), the median acceptable failure rate was 6.8%. Thus, one-half of the IDCs would have found a failure rate of 6.8% to be acceptable. Seventy-five percent of IDCs would have found a failure rate of 1.6% to be acceptable, and 25% of IDCs would have found a failure rate as high as 11.9% to be acceptable.<br><br>CONCLUSIONS: The quantified acceptable failure rates, when used to interpret clinical trial or cohort study results, will help select optimal antimicrobial therapy durations for this specific condition. These findings are a critical step in the development of effective shared decision-making models.}, }
@article {pmid16276696, year = {2005}, author = {Gukas, ID and Jennings, BA and Mandong, BM and Igun, GO and Girling, AC and Manasseh, AN and Ugwu, BT and Leinster, SJ}, title = {Clinicopathological features and molecular markers of breast cancer in Jos, Nigeria.}, journal = {West African journal of medicine}, volume = {24}, number = {3}, pages = {209-213}, doi = {10.4314/wajm.v24i3.28220}, pmid = {16276696}, issn = {0189-160X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Black People/genetics ; Breast Neoplasms/*diagnosis/ethnology/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; *Neoplasm Staging ; Nigeria ; Prognosis ; }, abstract = {BACKGROUND: Several studies have suggested that breast cancer in black women is associated with aggressive features and poor survival. This study examines molecular markers along with clinical stage and pathological grade in breast cancer material from Jos, Nigeria.<br><br>STUDY DESIGN: The histological diagnoses of 178 consecutive Nigerian patients with breast cancer were retrieved from their hospital records. A subset of 36 patients was staged and their tumours typed and graded. Immunohistochemical staining of sections from paraffin wax embedded tissues from these cases for the expression of oestrogen receptor (ER), progesterone receptor (PGR), Human ERBB2 (or HER2/neu), p53 and cyclin D1 (CCND1) was carried out using the avidin biotin complex (ABC) procedure.<br><br>RESULTS: A majority of the cases were invasive ductal carcinoma (92.7%), high grade (grade 3, 70.6%) and of late clinical stage (stages III and IV, 58.3%). Only 25% and 27.8% of cases expressed ER and PGR respectively. The ERBB2 and CCND1 antigens were expressed in 25%, and 5.7% of cases respectively. The p53 protein was the most frequently expressed in this study (47.2% of cases). High grade tumours were significantly more likely to be ER and PGR negative (P = 0.006 and P = 0.002 respectively). CONLCLUSION: There is predominance of high grade, invasive ductal carcinomas which are likely to be ER and PGR negative but p53 positive. These features suggest a biologically aggressive form of breast cancer in Nigerian women with the possibility of poor response to both hormonal therapy and chemotherapy.}, }
@article {pmid16264937, year = {2005}, author = {Katz, MS and Schapira, L and Harisinghani, MG and Hughes, KS}, title = {Palpable right breast mass in a pregnant woman.}, journal = {Nature clinical practice. Oncology}, volume = {2}, number = {4}, pages = {218-21; quiz 1 p following 222}, doi = {10.1038/ncponc0135}, pmid = {16264937}, issn = {1743-4254}, mesh = {Adult ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Combined Modality Therapy ; Diagnosis, Differential ; Female ; Gestational Age ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Mastectomy ; Pregnancy ; Pregnancy Complications, Neoplastic/*pathology/therapy ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: A 29-year-old female presented with a palpable right breast mass at a 12-week prenatal visit. She had no family history of breast or ovarian cancer. Ultrasound revealed a 3 cm lobulated mass, which was confirmed to be malignant by a core biopsy. Postmastectomy pathology at 15 weeks' gestation demonstrated this mass to be a stage T2N0M0 high-grade invasive ductal carcinoma with 0/20 axillary nodes involved. A staging CT scan postpartum showed an enlarged right internal mammary lymph node, confirmed by MRI as suspicious for malignancy.<br><br>INVESTIGATIONS: Physical examination, breast ultrasound, core biopsy, mastectomy, CT scan, MRI.<br><br>DIAGNOSIS: Pregnancy-associated breast carcinoma.<br><br>MANAGEMENT: Mastectomy, chemotherapy and radiotherapy.}, }
@article {pmid16261396, year = {2006}, author = {Marshall, C and Blackburn, E and Clark, M and Humphreys, S and Gullick, WJ}, title = {Neuregulins 1-4 are expressed in the cytoplasm or nuclei of ductal carcinoma (in situ) of the human breast.}, journal = {Breast cancer research and treatment}, volume = {96}, number = {2}, pages = {163-168}, doi = {10.1007/s10549-005-9073-z}, pmid = {16261396}, issn = {0167-6806}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Female ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Neuregulins/immunology/*metabolism ; }, abstract = {A new family of epidermal growth factor-like proteins, the Neuregulins (NRGs), have recently been identified and are expressed in a range of normal tissues and in some forms of cancer including breast cancer. In this study we examined using immunohistochemical staining expression of NRG1alpha, NRG1beta, NRG2alpha, NRG2beta, NRG3 and NRG4 in sixty cases of pre-invasive ductal carcinoma in situ of the breast representing different degrees of differentiation. Each protein was expressed in a high proportion of these cases showing a predominantly homogenous cytoplasmic staining pattern. Nuclear expression of NRG1alpha, NRG1beta, and NRG3 was however also observed in a significant fraction of cases. High levels of expression of NRG2beta and NRG4 were associated with high-grade tumours (p< or =0.005), NRG2beta staining was associated with tumour size >25 mm (p=0.005) while NRG3 nuclear staining was present more often in low-grade tumours (p=0.039). This data demonstrates that each member of the NRG family of ligands is present in pre-invasive ductal breast cancer and that they may be involved in regulating cell behaviour. The significance of intranuclear expression remains to be determined but suggests a novel mechanism of action for some of these proteins.}, }
@article {pmid16258702, year = {2005}, author = {Nagi, C and Guttman, M and Jaffer, S and Qiao, R and Keren, R and Triana, A and Li, M and Godbold, J and Bleiweiss, IJ and Hazan, RB}, title = {N-cadherin expression in breast cancer: correlation with an aggressive histologic variant--invasive micropapillary carcinoma.}, journal = {Breast cancer research and treatment}, volume = {94}, number = {3}, pages = {225-235}, doi = {10.1007/s10549-005-7727-5}, pmid = {16258702}, issn = {0167-6806}, support = {5 R24 CA 88282-04/CA/NCI NIH HHS/United States ; R01 CA90872/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD ; Breast Neoplasms/*pathology ; Cadherins/*biosynthesis/genetics ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Papillary/*pathology ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; *Neoplasm Invasiveness ; Phenotype ; Up-Regulation ; }, abstract = {Upregulation of N-cadherin in epithelial tumor cells has been shown to contribute to the invasive/metastatic phenotype. It remains however to be determined whether N-cadherin is increased in human breast cancers with enhanced malignant potential. We examined a large number of invasive breast cancer specimens (n = 114) for N- and E-cadherin. These specimens compared invasive duct carcinomas (IDCs) of varying histologic grades with an aggressive subtype, invasive micropapillary carcinoma of the breast (MPAP), which has a high propensity for lymphatic invasion and lymph node metastasis. Staining scores for N- and E-cadherin were compared between non-MPAP and MPAP IDCs, and between the invasive and ductal carcinoma in situ (DCIS) of each IDC using statistical analysis. We found that N-cadherin was expressed in 76% of MPAP and 52% of non-MPAP carcinomas, and E-cadherin in 57% of MPAP and 36% of non-MPAP tumors. More MPAP (25%) compared to non-MPAP (5%) tumors expressed both cadherins. Of the two cadherins, N-cadherin was significantly associated with MPAP tumors (p = 0.033) compared to E-cad (p = 0.171). Moreover, in the majority of tumors that were positive for N-cadherin, the staining scores were increased in the IDC relative to intraductal components, and this effect was more dramatic in the MPAP carcinomas. This difference for N-cadherin was greater than the corresponding difference for E-cadherin in the MPAP group (p = 0.005), whereas such changes were not significant in the non-MPAP group (p = 0.10). Thus, N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression.}, }
@article {pmid16257133, year = {2006}, author = {Zhang, Y and Ma, QY and Dang, CX and Moureau-Zabotto, M and Chen, WK}, title = {Quantitative molecular diagnosis of axillary drainage fluid for prediction of locoregional failure in patients with one to three positive axillary nodes after mastectomy without adjuvant radiotherapy.}, journal = {International journal of radiation oncology, biology, physics}, volume = {64}, number = {2}, pages = {505-511}, doi = {10.1016/j.ijrobp.2005.07.984}, pmid = {16257133}, issn = {0360-3016}, mesh = {Adult ; Analysis of Variance ; Axilla ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/mortality/*pathology/surgery ; Carcinoembryonic Antigen/*analysis ; Carcinoma, Ductal, Breast/mortality/*secondary/surgery ; Female ; Humans ; Keratins/*analysis ; Lymph Nodes/*metabolism/pathology ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Models, Biological ; Neoplasm Recurrence, Local/metabolism/pathology ; Neoplasm, Residual ; Radiotherapy, Adjuvant ; Reverse Transcriptase Polymerase Chain Reaction/*methods/standards ; Sensitivity and Specificity ; }, abstract = {PURPOSE: A quantitative multiple-marker reverse transcriptase (RT)-polymerase chain reaction (PCR) assay for sensitive detection of cancer cells in axillary drainage fluid was developed to examine whether the presence of cancer cells in axillary drainage fluid can be used as a predictor of locoregional recurrence (LRR) in patients with breast cancer who had T1/2 primary tumors and one to three positive axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy.<br><br>METHODS AND MATERIALS: Axillary drainage fluid was collected from 126 patients with invasive ductal carcinoma of the breast who were treated with modified radical mastectomy and were found to have one to three positive axillary nodes. Cancer cells in axillary drainage fluid were detected by RT-PCR assay using primers specific for carcinoembryonic antigen (CEA) and cytokeratin-19 (CK-19) together with numerous clinicopathologic and treatment-related factors and were analyzed for their impact on LRR.<br><br>RESULTS: A total of 38 patients suffered LRR during follow-up and the multimarker RT-PCR assays for CEA and CK-19 in the axillary drainage fluid both were positive in 34 patients (27.0%), of which 29 patients had LRR. In univariate analysis, the 5-year LRR-free survival showed higher rates in patients with PCR-negative findings in axillary drainage fluid (p<0.0001), age>or=40 years old (p<0.0001), tumor size<2.5 cm (p<0.0001), negative lymph-vascular space invasion (p=0.026), and T1 status (<0.0001); in multivariate analysis, PCR-positive findings together with age and tumor size were found to be independent predictors of LRR (all p<0.05).<br><br>CONCLUSION: Multiplex RT-PCR assay for CEA and CK-19 was highly sensitive for detection and might be useful for prediction of LRR in such subgroup breast cancer patients.}, }
@article {pmid16246429, year = {2006}, author = {Leong, PP and Mohammad, R and Ibrahim, N and Ithnin, H and Abdullah, M and Davis, WC and Seow, HF}, title = {Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast.}, journal = {Immunology letters}, volume = {102}, number = {2}, pages = {229-236}, doi = {10.1016/j.imlet.2005.09.006}, pmid = {16246429}, issn = {0165-2478}, mesh = {Adult ; Breast Neoplasms/*immunology ; CD28 Antigens/analysis ; CD4-CD8 Ratio ; Carcinoma, Ductal/*immunology ; Estrogen Receptor alpha/analysis ; Female ; Forkhead Transcription Factors/analysis ; Humans ; *Immunophenotyping ; Lymphocytes, Tumor-Infiltrating/*classification/immunology ; Middle Aged ; Receptors, Interleukin-2/analysis ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Dysfunction of the host immune system in cancer patients can be due to a number of reasons including suppression of tumour associated antigen reactive lymphocytes by regulatory T (Treg) cells. In this study, we used flow cytometry to determine the phenotype and relative abundance of the tumour infiltrating lymphocytes (TILs) from 47 enzymatically dissociated tumour specimens from patients with infiltrating ductal carcinoma (IDC) of the breast. The expression of both effector and regulatory markers on the TILs were determined by using a panel of monoclonal antibodies. Analysis revealed CD8(+) T cells (23.4+/-2.1%) were predominant in TILs, followed by CD4(+) T cells (12.6+/-1.7%) and CD56(+) natural killer cells (6.4+/-0.7%). The CD4(+)/CD8(+) ratio was 0.8+/-0.9%. Of the CD8(+) cells, there was a higher number (68.4+/-3.5%) that expressed the effector phenotype, namely, CD8(+)CD28(+) and about 46% of this subset expressed the activation marker, CD25. Thus, a lower number of infiltrating CD8(+) T cells (31.6+/-2.8%) expressed the marker for the suppressor phenotype, CD8(+)CD28(-). Of the CD4(+) T cells, 59.6+/-3.9% expressed the marker for the regulatory phenotype, CD4(+)CD25(+). About 43.6+/-3.8% CD4(+)CD25(+) subset co-expressed both the CD152 and FOXP3, the Treg-associated molecules. A positive correlation was found between the presence of CD4(+)CD25(+) subset and age (> or =50 years old) (r=0.51; p=0.045). However, no significant correlation between tumour stage and CD4(+)CD25(+) T cells was found. In addition, we also found that the CD4(+)CD25(-) subset correlated with the expression of the nuclear oestrogen receptor (ER)-alpha in the tumour cells (r=0.45; p=0.040). In conclusion, we detected the presence of cells expressing the markers for Tregs (CD4(+)CD25(+)) and suppressor (CD8(+)CD28(-)) in the tumour microenvironment. This is the first report of the relative abundance of Treg co-expressing CD152 and FOXP3 in breast carcinoma.}, }
@article {pmid16236472, year = {2006}, author = {Cárdaba, B and del Pozo, V and Gallardo, S and Palomino, P and Posada, M and Lahoz, C}, title = {Genetic approaches in the understanding of Toxic Oil Syndrome.}, journal = {Toxicology letters}, volume = {161}, number = {1}, pages = {83-88}, doi = {10.1016/j.toxlet.2005.09.027}, pmid = {16236472}, issn = {0378-4274}, mesh = {Adult ; Case-Control Studies ; Chromosomes, Human, Pair 6/genetics ; Eosinophilia/etiology ; Fatty Acids, Monounsaturated ; Female ; Gene Frequency/genetics ; Genetic Markers/genetics ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Liver Diseases/etiology ; Logistic Models ; Lung Diseases/etiology ; Male ; Microsatellite Repeats/genetics ; Odds Ratio ; Plant Oils/administration &amp; dosage/*poisoning ; Rapeseed Oil ; Scleroderma, Systemic/etiology ; Sex Factors ; Spain ; Syndrome ; }, abstract = {The Toxic Oil Syndrome (TOS) is a multisystemic disease that occurred in Spain in 1981 due to the ingestion of rapeseed oil denatured with 2% aniline. Female prevalence and the different clinical evolution even inside the same family (similar exposition), pointed to genetic implications. Furthermore, HLA-DR2 was increased in patients dead because of TOS. Th2 activation and eosinophilia implicated immunological mechanisms. For those reasons we firstly decided, to do a genome-wide search by linkage mapping set along the chromosome 6 (where HLA loci are located), to identify loci associated to the TOS development. The design was case-control-matched (n = 328). By this procedure, microsatellite (near to HLA) was related with the patients. After fine-mapping around this marker, we defined four more closely related to TOS-, , and . Secondly, we analysed in 420 patients, the association of these four markers with 14 TOS clinical phenotypes. We demonstrated that alveolar infiltration, liver disease and scleroderma are clearly associated with . As conclusion, we have identified in chromosome 6, a region where are located some genes related with autoimmune diseases, associated with certain TOS phenotypes, pointing out the possible role of autoimmune reactions in the pathogenesis of the disease.}, }
@article {pmid16225776, year = {2004}, author = {Liu, W and Li, W and Sun, N}, title = {Association of HLA-DQ with idiopathic dilated cardiomyopathy in a northern Chinese Han population.}, journal = {Cellular &amp; molecular immunology}, volume = {1}, number = {4}, pages = {311-314}, pmid = {16225776}, issn = {1672-7681}, mesh = {Adolescent ; Adult ; Aged ; Asian People/*genetics ; Autoimmune Diseases/genetics ; Cardiomyopathy, Dilated/*genetics ; Case-Control Studies ; China ; Ethnicity/*genetics ; Female ; Gene Frequency ; *Genes, MHC Class II ; Genotype ; HLA-DQ Antigens/*genetics ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; Humans ; Male ; Middle Aged ; }, abstract = {Autoimmune mechanisms are likely involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC) and components of MHC may serve as markers for the propensity to develop immune-mediated myocardial damage. This study was conducted to investigate the possible association between HLA-DQA1, -DQB1 alleles and IDC in Han population from northern China by using PCR-based sequence-specific primer (PCR-SSP) technique for HLA genotyping. Among 68 unrelated IDC patients, 4 probands of IDC pedigrees and 100 healthy controls, we found that the alleles of HLA-DQA1*0501 and HLA-DQB1*0303 conferred susceptibility to IDC while HLA-DQA1*0201 and HLA-DQB1*0502, *0504 alleles were in negative association with IDC. The serine at position 57 (SER57) in the exon of HLA-DQB1*0502 and *0504 was confirmed in our experiment as a marker for resistance to IDC. The results suggest that HLA-DQ polymorphism may be involved in the pathogenesis of IDC.}, }
@article {pmid16224211, year = {2005}, author = {Agarwal, B and Saxena, R and Morimiya, A and Mehrotra, S and Badve, S}, title = {Lymphangiogenesis does not occur in breast cancer.}, journal = {The American journal of surgical pathology}, volume = {29}, number = {11}, pages = {1449-1455}, doi = {10.1097/01.pas.0000174269.99459.9d}, pmid = {16224211}, issn = {0147-5185}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal, Murine-Derived ; Biomarkers ; Biomarkers, Tumor ; Breast/pathology/*physiology ; Breast Neoplasms/pathology/*physiopathology ; Carcinoma, Ductal, Breast/pathology/physiopathology ; Carcinoma, Intraductal, Noninfiltrating/pathology/*physiopathology ; Carcinoma, Lobular/pathology/*physiopathology ; Female ; Homeodomain Proteins/immunology ; Humans ; Lymphangiogenesis/*physiology ; Lymphatic Metastasis ; Membrane Glycoproteins/immunology ; Middle Aged ; Proliferating Cell Nuclear Antigen/immunology ; Tumor Suppressor Proteins ; }, abstract = {Breast cancer metastasis predominantly occurs via lymphatic vessels. However, the study of lymphatic vessels and lymphangiogenesis has been hampered by lack of specific markers. Recently, antibodies directed against M2A (D2-40), Podoplanin, and Prox-1 that specifically mark lymphatic vessels in paraffin-embedded sections have become available. These were used to study lymphangiogenesis in archival paraffin sections of normal breast (n = 23), fibrocystic disease (n = 7), ductal carcinoma in situ (n = 32), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 5). In addition, endothelial proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and proliferating cell nuclear antigen (PCNA). Expression of D2-40, Prox-1, and Podoplanin was seen in lymphatic vessels but not in blood vessels. Lymphatic vessels were seen in the peritumoral area and as "entrapped" intratumoral vessels adjacent to preexisting normal lobules and ducts. Unlike angiogenesis, there was no increase of lymphatic vessel density in association with neoplastic transformation. On the contrary, a marked reduction in intratumoral lymphatic vessel density was seen in comparison to normal breast tissue, fibrocystic disease, and ductal carcinoma in situ (P = 0.0001). There was an increase in peritumoral lymphatic vessel density as compared with normal breast (P = 0.0001). However, the endothelial cells in the "entrapped" or the peritumoral lymphatic vessels did not show any expression of PCNA indicating minimal or no proliferative activity. This was in contrast to the strong expression seen in adjacent tumor cells and blood vessel endothelial cells. Thus, lymphangiogenesis was not evident when studied by lymphatic vessel density or by lymph vessel endothelial proliferation.}, }
@article {pmid16212073, year = {2005}, author = {Zecchin, M and Di Lenarda, A and Gregori, D and Moretti, M and Driussi, M and Aleksova, A and Chersevani, D and Sabbadini, G and Sinagra, G}, title = {Prognostic role of non-sustained ventricular tachycardia in a large cohort of patients with idiopathic dilated cardiomyopathy.}, journal = {Italian heart journal : official journal of the Italian Federation of Cardiology}, volume = {6}, number = {9}, pages = {721-727}, pmid = {16212073}, issn = {1129-471X}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*diagnosis/mortality/physiopathology ; Echocardiography ; Electrocardiography, Ambulatory ; Follow-Up Studies ; Humans ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Stroke Volume ; Survival Analysis ; Tachycardia, Ventricular/complications/*diagnosis/mortality/physiopathology ; Ventricular Dysfunction, Left/diagnosis ; }, abstract = {BACKGROUND: The identification of patients with idiopathic dilated cardiomyopathy (IDC) at higher risk of sudden death (SD) is still an unsolved issue, and the role of non-sustained ventricular tachycardia (NSVT) uncertain.<br><br>METHODS: The effect of NSVT on total mortality, SD and life-threatening arrhythmias was evaluated in 554 patients with IDC on optimal medical treatment and at long-term follow-up (81 +/- 58 months).<br><br>RESULTS: At diagnosis, 240 patients (43%) had NSVT at Holter monitoring and 314 (57%) did not. During follow-up, 189 patients (5/100 patients-year) died or underwent heart transplantation; SD occurred in 53 patients (1.4/100 patients-year); SD + non-fatal ventricular arrhythmias occurred in 75 patients (2/100 patients-year). Patients with and without NSVT at diagnosis had the same 5-year transplant-free survival rate (76 vs 76%, p = NS) and a similar incidence of SD (10 vs 7%, p = NS). The length and rate of NSVT did not show any significant relationship with the outcome. Only heart failure symptoms (NYHA class III-IV) (hazard ratio [HR] 1.9, p = 0.015) and severe left ventricular impairment (left ventricular ejection fraction < or = 0.30 and left ventricular end-diastolic diameter > or = 70 mm) (HR 2.7, p < 0.0001) were independently associated with higher SD risk. At multivariate analysis the presence of frequent NSVT episodes (> or = 3 runs/day) was associated with an increased risk of total mortality (HR 1.68, p = 0.041) and of major ventricular arrhythmias (HR 2.11, p = 0.037), but only in the subgroup of patients with severe left ventricular impairment.<br><br>CONCLUSIONS: Patients with advanced heart failure symptoms, severe left ventricular dysfunction and dilation had a higher risk of SD independently of NSVT. The finding of more frequent NSVT was associated with an increased risk of all-cause mortality and of major ventricular arrhythmias in patients with severe left ventricular impairment.}, }
@article {pmid16207355, year = {2005}, author = {Huang, S and Li, Y and Chen, Y and Podsypanina, K and Chamorro, M and Olshen, AB and Desai, KV and Tann, A and Petersen, D and Green, JE and Varmus, HE}, title = {Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice.}, journal = {Genome biology}, volume = {6}, number = {10}, pages = {R84}, pmid = {16207355}, issn = {1474-760X}, support = {P01 CA094060/CA/NCI NIH HHS/United States ; P01 CA94060-02/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm/genetics ; Genotype ; Hyperplasia ; Mammary Glands, Animal/cytology/pathology ; Mammary Neoplasms, Animal/*genetics ; Mammary Tumor Virus, Mouse/*genetics ; Mice ; Mice, Transgenic ; Wnt1 Protein/*genetics ; }, abstract = {BACKGROUND: In human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ, invasive cancer, and metastasis. The changes in gene expression associated with this stepwise progression are unclear. Mice transgenic for mouse mammary tumor virus (MMTV)-Wnt-1 exhibit discrete steps of mammary tumorigenesis, including hyperplasia, invasive ductal carcinoma, and distant metastasis. These mice might therefore be useful models for discovering changes in gene expression during cancer development.<br><br>RESULTS: We used cDNA microarrays to determine the expression profiles of five normal mammary glands, seven hyperplastic mammary glands and 23 mammary tumors from MMTV-Wnt-1 transgenic mice, and 12 mammary tumors from MMTV-Neu transgenic mice. Adipose tissues were used to control for fat cells in the vicinity of the mammary glands. In these analyses, we found that the progression of normal virgin mammary glands to hyperplastic tissues and to mammary tumors is accompanied by differences in the expression of several hundred genes at each step. Some of these differences appear to be unique to the effects of Wnt signaling; others seem to be common to tumors induced by both Neu and Wnt-1 oncogenes.<br><br>CONCLUSION: We described gene-expression patterns associated with breast-cancer development in mice, and identified genes that may be significant targets for oncogenic events. The expression data developed provide a resource for illuminating the molecular mechanisms involved in breast cancer development, especially through the identification of genes that are critical in cancer initiation and progression.}, }
@article {pmid16196516, year = {2005}, author = {Kim, MJ and Gong, G and Joo, HJ and Ahn, SH and Ro, JY}, title = {Immunohistochemical and clinicopathologic characteristics of invasive ductal carcinoma of breast with micropapillary carcinoma component.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {129}, number = {10}, pages = {1277-1282}, doi = {10.5858/2005-129-1277-IACCOI}, pmid = {16196516}, issn = {1543-2165}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary ; Carcinoma, Papillary/chemistry/mortality/*secondary ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Survival Rate ; Tissue Array Analysis/methods ; }, abstract = {CONTEXT: A micropapillary carcinoma (MC) component is generally considered to behave aggressively. Although several reports have described the prognostic significance of MC in breast carcinomas, immunohistochemical findings of MC, especially as compared to non-MC, are rarely described.<br><br>OBJECTIVE: We compared clinicopathologic and immunohistochemical findings between 38 cases of invasive breast carcinoma with an MC component (IMC) and 217 cases of invasive breast carcinoma without an MC component (NIMC).<br><br>DESIGN: We constructed a tissue microarray from 38 cases of IMC and performed immunohistochemical stainings for cytokeratin (CK) 7, CK20, estrogen receptor, progesterone receptor, p53, c-Erb-B2, CD34, CK5, epidermal growth factor receptor, and c-Kit in both MC and non-MC components.<br><br>RESULTS: Cases with IMC were associated with greater tumor size, more frequent lymphovascular invasion, nodal metastases, greater mean numbers of positive lymph nodes, and higher stage than those with NIMC, but were not associated with poorer survival rates. On immunohistochemistry, only p53 reactivity was statistically different between MC and non-MC components in IMC cases. Estrogen receptor positivity tended to be lower in MC than non-MC, but the difference was not significant. Most of the MCs and non-MCs in IMC cases were positive for CK7, but none of them were positive for CK20, CK5, epidermal growth factor receptor, or c-Kit.<br><br>CONCLUSIONS: Based on the frequent nodal metastases and association with higher stage found in IMC as compared with NIMC cases, as well as higher p53 positivity and lower frequency of estrogen receptor expression, MC could be considered an aggressive histologic type of breast carcinoma. In both MC and non-MC components in IMC cases, no basallike immunostaining pattern was detected.}, }
@article {pmid16195769, year = {2005}, author = {Behjati, F and Atri, M and Najmabadi, H and Nouri, K and Zamani, M and Mehdipour, P}, title = {Prognostic value of chromosome 1 and 8 copy number in invasive ductal breast carcinoma among Iranian women: an interphase FISH analysis.}, journal = {Pathology oncology research : POR}, volume = {11}, number = {3}, pages = {157-163}, pmid = {16195769}, issn = {1219-4956}, mesh = {Aneuploidy ; Biomarkers/analysis ; Breast Neoplasms/*genetics/mortality/pathology/surgery ; Carcinoma, Ductal/*genetics/mortality/pathology/surgery ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Diploidy ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Iran ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; }, abstract = {Breast cancer is amongst the leading causes of death in women worldwide and the most common cancer amongst Iranian women. Unfortunately, the current clinical and histological criteria can only help 60 percent of women with breast cancer in diagnosis and long-term treatment. Therefore, genetic markers both at single gene and chromosomal level can play an important role in improving the diagnosis and prognosis of breast cancer patients. The aim of this retrospective study was to investigate the role of chromosome 1 and 8 copy number assessed by interphase fluorescence in situ hybridization (FISH), as prognostic parameters in 50 Iranian women, aged 35 to 64 years, with sporadic invasive ductal breast carcinoma. Chromosome 1 and 8 copy numbers were evaluated in relation to established clinicopathological parameters, the immunohistochemical markers ER, PR, P53 and cathepsin D, DNA index by flow cytometry, age and survival status of the patients. FISH using centromeric probes for chromosomes 1 and 8 was applied to interphase cell suspensions prepared from archived, Carnoyfixed tumor cells and selected paraffin-embedded tumor sections. Aneusomy for chromosomes 1 and 8 was present in all 50 patients to different levels. The total abnormality rate for chromosome 1 was 33.92 percent (4.24 percent monosomy and 29.68 percent polysomy), whereas for chromosome 8 this rate was 28.30 percent (6.48 percent monosomy and 21.82 percent polysomy). Statistically significant association (p<0.05) was demonstrated between monosomy 1 and patients' age below 50 years, and between monosomy 1 and poor survival, respectively. Disomy 8 was significantly associated with P53 expression. A borderline significant correlation was demonstrated between polysomy 8 and diploid DNA content, as well as between disomy 1 and disease-free status of the patients. Chromosome 1 and 8 copy numbers may be considered as useful prognostic markers in invasive ductal carcinoma of the breast.}, }
@article {pmid16187283, year = {2006}, author = {Zafrakas, M and Chorovicer, M and Klaman, I and Kristiansen, G and Wild, PJ and Heindrichs, U and Knüchel, R and Dahl, E}, title = {Systematic characterisation of GABRP expression in sporadic breast cancer and normal breast tissue.}, journal = {International journal of cancer}, volume = {118}, number = {6}, pages = {1453-1459}, doi = {10.1002/ijc.21517}, pmid = {16187283}, issn = {0020-7136}, mesh = {Breast/*metabolism ; Breast Neoplasms/*genetics/pathology ; Cell Line ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization/methods ; Protein Subunits/*genetics ; RNA, Messenger/genetics/metabolism ; Receptors, GABA-A/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {The GABRP gene has been previously identified by in silico analysis of four million ESTs as a candidate gene differentially expressed in breast cancer. GABRP is located on chromosome 5q34 and it encodes the pi-subunit of the gamma-aminobutyric acid (GABA) receptor, a transmembrane protein expressed in the brain and several nonneuronal tissues. Using cDNA dot blot hybridisation (cancer profiling array), quantitative RT-PCR and non-radioisotopic in situ hybridisation (ISH), we have analysed GABRP expression in breast cancer and normal breast tissues as well as in nontumorigenic and tumorigenic breast cell lines. Analysis of the cancer profiling array revealed a more than 2-fold downregulation of GABRP (p < 0.001) in 76% of primary breast carcinomas (n = 50) compared to corresponding normal tissues. Quantitative RT-PCR in a panel of 23 normal human tissues showed that the GABRP expression level was most abundant in the normal breast tissues compared to other human tissues. GABRP downregulation in breast cancer was confirmed by quantitative RT-PCR in cryopreserved breast tumour and normal breast tissue specimens (n = 22), in archival formalin-fixed, paraffin-embedded tissue specimens (n = 32), as well as in breast cancer cell lines (n = 8). Furthermore, a significant downregulation of GABRP was noted in large (pT3-pT4) (p = 0.044) primary breast tumours. Non-radioisotopic ISH showed strong GABRP expression in normal epithelial and benign papilloma breast cells, but no signal could be detected in invasive ductal carcinoma. Altogether, these data suggest that GABRP is progressively down-regulated with tumour-progression, and that it may be useful as a prognostic marker in breast cancer.}, }
@article {pmid16187230, year = {2005}, author = {Gao, RJ and Bao, HZ and Yang, Q and Cong, Q and Song, JN and Wang, L}, title = {The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters.}, journal = {Breast cancer research and treatment}, volume = {93}, number = {2}, pages = {111-115}, doi = {10.1007/s10549-005-4321-9}, pmid = {16187230}, issn = {0167-6806}, mesh = {Antibodies, Neoplasm/*blood ; Biomarkers, Tumor/analysis/*blood ; Breast Neoplasms/*blood/metabolism/pathology ; Carcinoma, Ductal/*blood/metabolism/pathology ; China ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tumor Suppressor Protein p53/analysis/*immunology ; }, abstract = {Breast cancer has been the most common malignant tumor among women in many large cities of China. The aim of this study was to clarify the prognostic significance of serum anti-p53 antibodies (p53 Abs) in Chinese patients of breast cancer. One hundred and forty-four patients with invasive ductal carcinoma of breast were involved in this study. The expressions of ER, PR, c-erbB-2 and p53 were immunostained in tumor tissues and serum p53 Abs were assayed using ELISA method. The correlations between p53 Abs and other clinical and biological markers were analyzed. Among 144 patients, 31 (21.5%) had positive p53 Abs, which was associated with several poor prognostic parameters including higher clinical stage (p = 0.0233), lymph nodes metastasis (p = 0.0033), negative ER expression (p = 0.0250) and positive c-erbB-2 status (p = 0.0227). There was also a strong correlation between p53 Abs and tumor p53 positivity (p < 0.0001). These results indicated that the presence of p53 Abs is probably triggered by the accumulation of tumor p53 protein, and it could be a useful marker to complement routine prognostic factors in breast cancer patients.}, }
@article {pmid16184928, year = {2005}, author = {Rai, Y and Ando, M and Sagara, Y and Takahama, T and Matsuyama, Y and Ooi, Y and Sagara, Y}, title = {[Neoadjuvant endocrine therapy with anastrozole significantly downstaged an elderly breast cancer woman with locally-advanced breast cancer which became operable].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {32}, number = {9}, pages = {1301-1305}, pmid = {16184928}, issn = {0385-0684}, mesh = {Aged ; Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Bone Neoplasms/secondary ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; *Mastectomy ; Neoadjuvant Therapy ; Nitriles/*therapeutic use ; Postmenopause ; Preoperative Care ; Sternum ; Triazoles/*therapeutic use ; }, abstract = {A 73-year-old postmenopausal woman had a 13 cm-sized huge tumor in her left breast with an extensive purple skin color change. She had sternal destruction, axillary and supraclavicular lymph node metastases (T4bN3M1, Stage IV). Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+++, PgR+++). She was treated with 1 mg per day of anastrozole. The tumor decreased in size gradually and became operable after 7.5 months of the anastrozole monotherapy. She underwent mastectomy and axillary node clearance. The resected specimen showed a 3.5 cm sized tumor with significant fibrosis and scanty viable tumor cells. We concluded that neoadjuvant therapy with anastrozole is a good choice for receptor-positive postmenopausal breast cancer, especially for elderly or poor risk women.}, }
@article {pmid16183152, year = {2006}, author = {Nanas, JN and Tsagalou, EP and Nanas, SN and Terrovitis, JV and Tsolakis, EJ and Toumanidis, S and Papazoglou, PD and Alexopoulos, GP and Kanakakis, J and Anastasiou-Nana, MI}, title = {Reverse left ventricular remodeling by intermittent dobutamine infusions and amiodarone in end-stage heart failure due to idiopathic dilated cardiomyopathy.}, journal = {International journal of cardiology}, volume = {108}, number = {2}, pages = {237-243}, doi = {10.1016/j.ijcard.2005.05.010}, pmid = {16183152}, issn = {0167-5273}, mesh = {Administration, Oral ; Adult ; Aged ; Amiodarone/*administration &amp; dosage ; Cardiomyopathy, Dilated/complications/physiopathology ; Cardiovascular Agents/*administration &amp; dosage ; Dobutamine/*administration &amp; dosage ; Female ; Heart Failure/*drug therapy/etiology/physiopathology ; Hemodynamics/drug effects ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Prospective Studies ; Stroke Volume/drug effects ; Ventricular Remodeling/*drug effects ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the long-term effect of combined intermittent dobutamine infusions (IDI) and oral amiodarone on reverse left ventricular (LV) remodeling and hemodynamics of patients with idiopathic dilated cardiomyopathy (IDC) and end-stage congestive heart failure (CHF).<br><br>METHODS: This non-randomized, prospective, clinical trial included sixteen consecutive patients suffering from dyspnea for a mean of 76+/-43 months, who presented with acute cardiac decompensation and were weaned from dobutamine therapy after an initial 72-h infusion. They were then placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. The long-term clinical outcomes and the effects of treatment on reverse LV remodeling (echocardiographic parameters) and hemodynamics were evaluated at 3, 6, and 12 months of follow up.<br><br>RESULTS: A significant degree of reverse LV remodeling, hemodynamic improvements, and survivals >1.5 years were observed in 9 of the 16 patients (56%). In addition, 5 patients (31% of entire cohort) were weaned from IDI after a mean of 61+/-41 weeks, and 4 remained clinically stable for 116+/-66 weeks thereafter. At 12 months of follow-up, LV end-diastolic and end-systolic volume indices had decreased from 231+/-91 to 206+/-80 ml/m2 (P=0.002) and from 137+/-65 to 110+/-50 ml/m2 (P=0.003), respectively, right atrial pressure from 16+/-6 to 5.6+/-4 mm Hg, (P=0.031), and pulmonary capillary wedge pressure from 29+/-4 to 16+/-5.4 mm Hg, P=0.000, while LV ejection fraction had increased from 22+/-6% to 27.3+/-8% (P=0.006).<br><br>CONCLUSIONS: In end-stage CHF due to IDC, long-term treatment with IDI and oral amiodarone caused reverse LV remodeling, and allowed permanent and successful weaning from IDI in 1/4 of patients.}, }
@article {pmid16163035, year = {2005}, author = {Woodhams, R and Matsunaga, K and Iwabuchi, K and Kan, S and Hata, H and Kuranami, M and Watanabe, M and Hayakawa, K}, title = {Diffusion-weighted imaging of malignant breast tumors: the usefulness of apparent diffusion coefficient (ADC) value and ADC map for the detection of malignant breast tumors and evaluation of cancer extension.}, journal = {Journal of computer assisted tomography}, volume = {29}, number = {5}, pages = {644-649}, doi = {10.1097/01.rct.0000171913.74086.1b}, pmid = {16163035}, issn = {0363-8715}, mesh = {Adult ; Aged ; Aged, 80 and over ; Artifacts ; Breast Neoplasms/*diagnosis/pathology/surgery ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; Statistics, Nonparametric ; }, abstract = {The authors used breast diffusion-weighted imaging (DWI) to diagnose breast cancer and identify cancer extension. Isotropic DWI was performed with EPI. The apparent diffusion coefficient (ADC) value was calculated and displayed on an ADC map. The authors compared between the distribution of low ADC values and pathologic cancer extension. The mean ADC value of breast cancer was 1.12 +/- 0.24 x 10(-3) mm/s, which was lower than that of normal breast tissue. The ADC value for invasive ductal carcinoma was lower than that of noninvasive ductal carcinoma. The sensitivity of the ADC value for breast cancer using a threshold of less than 1.6 x 10(-3) mm/s was 95%. Seventy-five percent of all cases showed precise distribution of low ADC value as cancer extension. The causes of underestimation were susceptibility artifact from bleeding and the limit of spatial resolution. Benign proliferative change showed a low ADC value. The authors conclude that DWI has a potential for clinical appreciation in detecting breast cancer.}, }
@article {pmid16154043, year = {2005}, author = {Huck, B and Steck, T and Habersack, M and Dietl, J and Kämmerer, U}, title = {Pregnancy associated hormones modulate the cytokine production but not the phenotype of PBMC-derived human dendritic cells.}, journal = {European journal of obstetrics, gynecology, and reproductive biology}, volume = {122}, number = {1}, pages = {85-94}, doi = {10.1016/j.ejogrb.2005.02.017}, pmid = {16154043}, issn = {0301-2115}, mesh = {Cytokines/*biosynthesis ; Dendritic Cells/*drug effects/metabolism ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Estradiol/administration &amp; dosage/*pharmacology ; Female ; Humans ; Lymphocyte Activation/drug effects ; Male ; Monocytes/drug effects/metabolism ; Phenotype ; Pregnancy ; Progesterone/administration &amp; dosage/*pharmacology ; T-Lymphocytes/immunology ; }, abstract = {OBJECTIVE: Dendritic cells (DC) play a central role in initiating and polarizing immune responses. As effects of pregnancy associated hormones on phenotype and function of DC are unknown, our objective was to test the influence of progesterone, beta-estradiol and betaHCG on immature (iDC) and mature (mDC) DC.<br><br>STUDY DESIGN: DC generated from peripheral-blood-monocytes were exposed to different doses of hormones. DC phenotype was determined by FACS-analysis of surface marker expression (CD40, CD86, CD83 and HLA-DR). Modifications in the secretion of cytokines (IL12p70, IL-18, IL-10, IL-6, TNFalpha) and chemokines (MDC, IL-8) were analysed by ELISA. T cell stimulatory capacity of mDC was assessed by mixed lymphocyte reaction.<br><br>RESULTS: Incubation with progesterone or estradiol resulted in a significant upregulation of IL-10 production by iDC and mDC. Combinations of progesterone and betaHCG or estradiol respectively induced a significant decrease in production of IL-18 by mDC. No significant changes could be observed in surface marker expression or T cell stimulatory capacity, neither in cultures of DC matured under influence of progesterone, estradiol nor betaHCG.<br><br>CONCLUSIONS: PBMC-derived DC seem to be relatively stable against the influence of pregnancy associated hormones apart from particular effects on cytokine production which partly could contribute to the modification of immune responses observed in normal early pregnancy.}, }
@article {pmid16127252, year = {2005}, author = {Woodhams, R and Matsunaga, K and Kan, S and Hata, H and Ozaki, M and Iwabuchi, K and Kuranami, M and Watanabe, M and Hayakawa, K}, title = {ADC mapping of benign and malignant breast tumors.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {4}, number = {1}, pages = {35-42}, doi = {10.2463/mrms.4.35}, pmid = {16127252}, issn = {1347-3182}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Artifacts ; *Artificial Intelligence ; Breast Neoplasms/*diagnosis ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Information Storage and Retrieval/methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {PURPOSE: The purpose of this study was to investigate the utility of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) value in differentiating benign and malignant breast lesions and evaluating the detection accuracy of the cancer extension.<br><br>MATERIALS AND METHODS: We used DWI to obtain images of 191 benign and malignant lesions (24 benign, 167 malignant) before surgical excision. The ADC values of the benign and malignant lesions were compared, as were the values of noninvasive ductal carcinoma (NIDC) and invasive ductal carcinoma (IDC). We also evaluated the ADC map, which represents the distribution of ADC values, and compared it with the cancer extension.<br><br>RESULTS: The mean ADC value of each type of lesion was as follows: malignant lesions, 1.22+/-0.31 x 10(-3) mm2/s; benign lesions, 1.67+/-0.54 x 10(-3) mm2/s; normal tissues, 2.09+/-0.27 x 10(-3) mm2/s. The mean ADC value of the malignant lesions was statistically lower than that of the benign lesions and normal breast tissues. The ADC value of IDC was statistically lower than that of NIDC. The sensitivity of the ADC value for malignant lesions with a threshold of less than 1.6 x 10(-3) mm2/s was 95% and the specificity was 46%. A full 75% of all malignant cases exhibited a near precise distribution of low ADC values on ADC maps to describe malignant lesions. The main causes of false negative and underestimation of cancer spread were susceptibility artifact because of bleeding and tumor structure. Major histologic types of false-positive lesions were intraductal papilloma and fibrocystic diseases. Fibrocystic diseases also resulted in overestimation of cancer extension.<br><br>CONCLUSIONS: DWI has the potential in clinical appreciation to detect malignant breast tumors and support the evaluation of tumor extension. However, the benign proliferative change remains to be studied as it mimics the malignant phenomenon on the ADC map.}, }
@article {pmid16110288, year = {2005}, author = {Kuroda, H and Sakamoto, G and Ohnisi, K and Itoyama, S}, title = {Clinical and pathological features of glycogen-rich clear cell carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {12}, number = {3}, pages = {189-195}, doi = {10.2325/jbcs.12.189}, pmid = {16110288}, issn = {1340-6868}, mesh = {Adenocarcinoma, Clear Cell/genetics/*metabolism/pathology ; Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Genes, erbB-2 ; Glycogen/*metabolism ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; }, abstract = {BACKGROUND: Twenty cases of invasive ductal carcinoma of the breast with a pure or partial glycogen-rich clear cell carcinoma(GRCC)component are reported. GRCC of the breast is composed almost entirely of polygonal cells with clear cytoplasm. These contain large amounts of partly water-soluble glycogen.<br><br>METHODS: The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, axillary lymph node and Her2/neu status.<br><br>RESULTS: Between 1990 and 2004, 723 patients with primary breast carcinomas were treated and clinicopathologic analysis was performed. 20 cases were identified as GRCC among the 723 cases. The patients' age at presentation ranged from 33 to 68 years (mean, 52 years). Tumor size ranged from 1 to 6.5 cm (mean, 2.6 cm); 35% (7 of 20) of cases that underwent axillary dissection had positive lymph nodes. Among 15 of 20 cases who were followed for 1-72 months, 5 cases died from their breast carcinoma within 5 years following the diagnosis.<br><br>CONCLUSION: Our series included more small size carcinomas than did previous series. Lymph node status does not appear to be markedly different from that of the usual invasive ductal carcinomas. Her2/neu expression was similar to that found in common breast carcinomas.}, }
@article {pmid16107908, year = {2005}, author = {Demirbag, R and Yilmaz, R and Erel, O and Gultekin, U and Asci, D and Elbasan, Z}, title = {The relationship between potency of oxidative stress and severity of dilated cardiomyopathy.}, journal = {The Canadian journal of cardiology}, volume = {21}, number = {10}, pages = {851-855}, pmid = {16107908}, issn = {0828-282X}, mesh = {Age Distribution ; Aged ; Analysis of Variance ; Antioxidants/*metabolism ; Cardiomyopathy, Dilated/*epidemiology/*etiology/physiopathology ; Case-Control Studies ; Cohort Studies ; Female ; Heart Function Tests ; Humans ; Incidence ; Male ; Middle Aged ; Oxidation-Reduction ; Oxidative Stress/*physiology ; Probability ; Prognosis ; Reference Values ; Risk Assessment ; Sensitivity and Specificity ; Severity of Illness Index ; Sex Distribution ; Survival Rate ; }, abstract = {BACKGROUND: It has been suggested that oxidative stress may have a role in the etiopathogenesis of congestive heart failure.<br><br>OBJECTIVES: To investigate and compare the oxidative-antioxidative status and oxidative stress index (OSI) of patients with idiopathic dilated cardiomyopathy (IDC) with those of healthy volunteers, and to determine the relationship between total antioxidant capacity (TAC) and ejection fraction (EF).<br><br>METHODS: Twenty-eight patients with IDC and 24 control subjects were enrolled in the study. Antioxidative status was evaluated by measuring the TAC and the vitamin C and thiol levels in the plasma. Oxidative status was evaluated by measuring the total peroxide level. The per cent ratio of TAC to total peroxide level was accepted as the OSI. EF was measured using Simpson's method.<br><br>RESULTS: TAC and vitamin C and thiol levels of plasma were found to be significantly lower in patients with IDC than in control subjects (P < 0.001). In contrast, total peroxide levels and OSIs were significantly higher in patients with IDC than in control subjects (P = 0.002 and P = 0.002, respectively). An important positive correlation was found between TAC and EF (r = 0.772; P < 0.001). On the other hand, significant negative correlations were found between EF and OSI and between EF and total peroxide levels in patients.<br><br>CONCLUSIONS: Oxidants are increased and antioxidants are decreased in patients with IDC; as a result, the oxidative-antioxidative balance is shifted to the oxidative side. There is a significant correlation between the potency of oxidative stress and the severity of IDC. It is believed that supplementation of antioxidants in the treatment of IDC may be helpful to these patients.}, }
@article {pmid16102447, year = {2005}, author = {Moloney, ED and Egan, JJ and Kelly, P and Wood, AE and Cooper, LT}, title = {Transplantation for myocarditis: a controversy revisited.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {24}, number = {8}, pages = {1103-1110}, doi = {10.1016/j.healun.2004.06.015}, pmid = {16102447}, issn = {1053-2498}, mesh = {Adult ; Biopsy, Needle ; Echocardiography, Transesophageal ; Follow-Up Studies ; Graft Survival ; Heart Failure/*complications/diagnosis ; Heart Function Tests ; Heart Transplantation/adverse effects/*methods ; Humans ; Immunohistochemistry ; Immunosuppressive Agents/*therapeutic use ; Male ; Myocarditis/diagnostic imaging/etiology/*pathology/*surgery ; Postoperative Complications/drug therapy/pathology ; Risk Assessment ; Severity of Illness Index ; }, abstract = {Myocarditis is a major cause of end-stage heart failure and is responsible for up to 10% of cases of idiopathic dilated cardiomyopathy (IDC). Worldwide, approximately 45% of all heart transplants are performed for IDC and up to 8% for myocarditis. Early reports suggested that survival after transplantation for myocarditis was poor and patients had an increased risk of rejection. More recently, larger case series suggest that overall survival after transplantation for myocarditis is similar to survival after transplantation for other causes. However, certain disorders, including cardiac sarcoidosis and giant cell myocarditis (GCM), require heightened surveillance for post-transplantation disease recurrence. We present the case of a 42-year-old man with recurrence of GCM 8 years after transplantation and review the literature on the role of cardiac transplantation for patients with myocarditis.}, }
@article {pmid16094691, year = {2005}, author = {Pruenster, M and Wilflingseder, D and Bánki, Z and Ammann, CG and Muellauer, B and Meyer, M and Speth, C and Dierich, MP and Stoiber, H}, title = {C-type lectin-independent interaction of complement opsonized HIV with monocyte-derived dendritic cells.}, journal = {European journal of immunology}, volume = {35}, number = {9}, pages = {2691-2698}, doi = {10.1002/eji.200425940}, pmid = {16094691}, issn = {0014-2980}, mesh = {Antibodies, Monoclonal/immunology/pharmacology ; CD4 Antigens/immunology ; Cell Adhesion Molecules/immunology ; Coculture Techniques ; Complement C3/*immunology ; Dendritic Cells/*immunology/*virology ; HIV/*immunology ; HIV Envelope Protein gp120/*immunology ; HIV Infections/*immunology ; Humans ; Immunity, Innate/immunology ; Intercellular Adhesion Molecule-1/immunology ; Lectins, C-Type/immunology ; Mannans/immunology ; Protein Binding ; Receptors, Cell Surface/immunology ; T-Lymphocytes/immunology ; }, abstract = {HIV directly activates the complement cascade and is, therefore, opsonized with C3-cleavage products in vivo. This cloud of C3 fragments on the viral surface may impair the interaction of the HIV envelope glycoproteins gp120/gp41 with C-type lectins expressed on immature dendritic cells (iDC). Therefore, we determined the accessibility of gp120 after opsonization and compared the interaction of DC with non-opsonized or complement-opsonized HIV. The recognition of native gp120 was drastically impaired when the virus was covered by complement. Independent of opsonization, similar amounts of HIV bound to DC. The interaction of iDC and the infection of DC-PBL co-cultures with non-opsonized virus was significantly reduced by mannan and antibodies which inhibit the ICAM-1-CR3 interaction. The binding of opsonized virus to iDC was reduced by an anti-CR3-antibody, which interferes with the binding of C3 fragments, but was not affected by mannan. Complement enhanced the HIV infection of DC and DC-PBL co-cultures significantly. Mannan did not inhibit the complement-dependent enhancement of infection. Thus, non-opsonized and opsonized HIV interacted with iDC, although the binding mechanisms seemed to differ. As HIV is opsonized in vivo, the C-type lectin-independent interaction of opsonized viruses with iDC has to be taken into account.}, }
@article {pmid16086078, year = {2005}, author = {Bassarova, AV and Nesland, JM and Sedloev, T and Lilleby, W and Hristova, SL and Trifonov, DY and Torlakovic, E}, title = {Simultaneous bilateral breast carcinomas: a category with frequent coexpression of HER-2 and ER-alpha, high Ki-67 and bcl-2, and low p53.}, journal = {International journal of surgical pathology}, volume = {13}, number = {3}, pages = {239-246}, doi = {10.1177/106689690501300302}, pmid = {16086078}, issn = {1066-8969}, mesh = {Adenocarcinoma/metabolism/*secondary ; Adult ; Aged ; Axilla ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Ki-67 Antigen/metabolism ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Proteins/*metabolism ; *Neoplasms, Multiple Primary ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {The aim of this study was to evaluate clinicopathological characteristics and immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and their axillary metastases. Immunohistochemical analysis and in situ hybridization were performed using formalin-fixed/paraffin-embedded tissues. In total, 15 primary and 9 metastatic tumors from 8 patients were evaluated. The expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), Ki 67, p53, bcl-2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was evaluated by chromogenic in situ hybridization (CISH). Four patients were younger that 40 years of age (mean 47 years). Six patients had pleomorphic lobular carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the contralateral breast. One patient had atypical medullary carcinoma in both breasts and 1 patient had atypical medullary carcinoma in 1 breast and pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors and corresponding metastatic tumors was similar for the expression of ER-alpha (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2 and ER-alpha is exceptional in hereditary breast carcinoma and sporadic breast carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression of HER-2 and ER-alpha. P53 protein expression was found in only 2/15 (13%) primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast carcinomas, which often express p53 protein. Most of the patients presented with axillary metastases and had very aggressive course. Characteristically, the tumors showed high levels of expression of ER-alpha and Her2 amplification, were bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical medullary carcinoma there was no expression of ER-alpha or amplification of Her-2.}, }
@article {pmid16084677, year = {2006}, author = {Tang, MW and Kwok, TC and Hui, E and Woo, J}, title = {Intermittent versus indwelling urinary catheterization in older female patients.}, journal = {Maturitas}, volume = {53}, number = {3}, pages = {274-281}, doi = {10.1016/j.maturitas.2005.05.014}, pmid = {16084677}, issn = {0378-5122}, mesh = {Aged ; Aged, 80 and over ; Bacteriuria/epidemiology/etiology ; Catheters, Indwelling ; Female ; Humans ; Prospective Studies ; Treatment Outcome ; Urinary Catheterization/instrumentation/*methods ; Urinary Retention/*therapy ; }, abstract = {OBJECTIVES: To compare the use of intermittent and indwelling catheterization in older female patients with urinary retention.<br><br>METHODS: A randomized, 2-week prospective study in a geriatric rehabilitation ward. Female patients of age 65 years and older with post-voiding residual urine volume (PVRU) persistently > or = 300 ml were randomly assigned to one of the two groups: intermittent catheterization (IMC group, n=36) and indwelling catheterization (IDC group, n=45). The primary outcome was the proportion of subjects being catheter-free and had a PVRU < 150 ml on day 14. The secondary outcomes were the time to become catheter-free and the rate of bacteriuria on day 14.<br><br>RESULTS: Sixteen out of 27 (59.3%) in the IMC group versus 27 out of 39 (69.2%) in the IDC group achieved the primary outcome on day 14 (P=.403) without significant difference in the PVRU. The IMC and IDC groups took a mean of 8.6+/-3.3 and 9.2+/-4.0 days to become catheter-free, respectively (P=.609). Fourteen out of 22 (63.6%) in the IMC group versus 21 out of 34 (61.8%) in the IDC group had bacteriuria on day 14 (P=.888).<br><br>CONCLUSION: Given the similar success rate of regaining bladder voiding function, the similar rate of bacteriuria and considering that the IMC group only underwent a median of 3 times of intermittent catheterization, we believe that the approach of intermittent urinary catheterization when required would be justified in managing elderly female urinary retention in rehabilitation ward as the presence of indwelling catheters would hinder rehabilitation and adversely affect patient quality of life.}, }
@article {pmid16053511, year = {2005}, author = {Peng, DF and Kanai, Y and Sawada, M and Ushijima, S and Hiraoka, N and Kosuge, T and Hirohashi, S}, title = {Increased DNA methyltransferase 1 (DNMT1) protein expression in precancerous conditions and ductal carcinomas of the pancreas.}, journal = {Cancer science}, volume = {96}, number = {7}, pages = {403-408}, doi = {10.1111/j.1349-7006.2005.00071.x}, pmid = {16053511}, issn = {1347-9032}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Pancreatic Ductal/*chemistry/genetics ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases/*analysis ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/*chemistry/genetics ; Precancerous Conditions/*chemistry/genetics ; Prognosis ; Up-Regulation ; }, abstract = {Aberrant DNA methylation has been shown to play an important role during multistage carcinogenesis in various human organs. The aim of the present study was to evaluate the significance of DNA methyltransferase 1 (DNMT1) protein expression during pancreatic carcinogenesis. Immunohistochemical analysis of DNMT1 in 48 peripheral pancreatic duct epithelia showing no remarkable histological findings without an inflammatory background (DE), 54 peripheral pancreatic duct epithelia with an inflammatory background (DEI), 188 pancreatic intraepithelial neoplasias (PanIN), and 220 areas of invasive ductal carcinoma from surgical specimens resected from 100 patients, was carried out. The average incidence of DNMT1 immunoreactivity increased progressively from DE to DEI (P = 0.003), from DE and DEI to PanIN (P < 0.0001), among PanIN with different grades of dysplasia (from PanIN I to PanIN II, P = 0.0012), from PanIN to invasive ductal carcinomas (P < 0.0001) and among invasive ductal carcinomas with different grades of histological differentiation (from well or moderately to poorly differentiated adenocarcinomas, P < 0.0001). High-level DNMT1 protein expression in invasive ductal carcinomas was correlated significantly with an advanced t category (P = 0.0224) and an advanced stage (P = 0.0294). Moreover, patients with invasive ductal carcinomas showing high-level DNMT1 protein expression had a poorer outcome (P = 0.0469). These data suggest that increased DNMT1 protein expression participates in multistage pancreatic carcinogenesis from the precancerous stage to malignant progression of ductal carcinomas and may be a biological predictor of poor prognosis.}, }
@article {pmid16052519, year = {2006}, author = {Ohuchida, K and Mizumoto, K and Yamada, D and Fujii, K and Ishikawa, N and Konomi, H and Nagai, E and Yamaguchi, K and Tsuneyoshi, M and Tanaka, M}, title = {Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer.}, journal = {International journal of cancer}, volume = {118}, number = {2}, pages = {405-411}, doi = {10.1002/ijc.21317}, pmid = {16052519}, issn = {0020-7136}, mesh = {Biomarkers, Tumor/analysis ; Case-Control Studies ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Mucin 5AC ; Mucin-1/*analysis/biosynthesis/genetics ; Mucins/*analysis/biosynthesis/genetics ; Pancreatic Juice/chemistry ; Pancreatic Neoplasms/*diagnosis ; Polymerase Chain Reaction ; Preoperative Care ; RNA, Messenger/analysis ; Tumor Cells, Cultured ; }, abstract = {Pancreatic juice is a promising type of diagnostic sample for pancreatic cancer, and members of the mucin (MUC) family are diagnostic candidates. To evaluate the utility of MUC family members as diagnostic markers, we measured MUC mRNA expression in pancreatic tissues and pancreatic juice obtained from patients with different pancreatic diseases as well as in pancreatic cancer cell lines by real-time PCR. Furthermore, to support the possibility of early diagnosis by quantification of MUC1 and MUC5AC, immunohistochemistry and microdissection-based quantitative analysis of mRNA were carried out. There was no significant correlation between MUC1 and MUC5AC expression in cell lines. When beta-actin was used as a reference gene, median MUC1 and MUC5AC mRNA expression levels were remarkably greater in tumoral tissues than in non-tumoral tissues, but median MUC4 and MUC6 mRNA expression levels were not. Receiver operating characteristic curve analysis showed that quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice is better diagnostic modality than that of MUC4 and MUC6 mRNA. Immunohistochemistry showed that MUC1 and MUC5AC were highly expressed in invasive ductal carcinomas (IDC) and moderately expressed in high-grade pancreatic intraepithelial neoplasia (PanIN); no staining was observed in normal ducts. Analysis of cells isolated by microdissection showed stepwise upregulation of MUC1 and MUC5AC in the development of high-grade PanIN to IDC. Our results suggest that MUC1 and MUC5AC are upregulated stepwise in pancreatic carcinogenesis and that quantitative assessment of MUC1 and MUC5AC mRNA in pancreatic juice has high potential for preoperative diagnosis of pancreatic cancer.}, }
@article {pmid16049287, year = {2005}, author = {Saitou, M and Goto, M and Horinouchi, M and Tamada, S and Nagata, K and Hamada, T and Osako, M and Takao, S and Batra, SK and Aikou, T and Imai, K and Yonezawa, S}, title = {MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas.}, journal = {Journal of clinical pathology}, volume = {58}, number = {8}, pages = {845-852}, pmid = {16049287}, issn = {0021-9746}, support = {R01 CA078590/CA/NCI NIH HHS/United States ; CA 78590/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Pancreatic Ductal/*metabolism/pathology/secondary ; Disease Progression ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Male ; Middle Aged ; Mucin-4 ; Mucins/*metabolism ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Pancreas/metabolism ; Pancreatic Neoplasms/*metabolism/pathology ; Prognosis ; Risk Factors ; Survival Analysis ; }, abstract = {BACKGROUND: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC.<br><br>AIMS: To investigate the prognostic significance of MUC4 expression in IDC.<br><br>METHODS: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry.<br><br>RESULTS: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors.<br><br>CONCLUSIONS: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.}, }
@article {pmid16043406, year = {2005}, author = {Mocelin, AO and Issa, VS and Bacal, F and Guimarães, GV and Cunha, E and Bocchi, EA}, title = {The influence of aetiology on inflammatory and neurohumoral activation in patients with severe heart failure: a prospective study comparing Chagas' heart disease and idiopathic dilated cardiomyopathy.}, journal = {European journal of heart failure}, volume = {7}, number = {5}, pages = {869-873}, doi = {10.1016/j.ejheart.2004.10.014}, pmid = {16043406}, issn = {1388-9842}, mesh = {Adult ; Cardiomyopathy, Dilated/*blood/mortality/physiopathology ; Chagas Cardiomyopathy/*blood/mortality/physiopathology ; Female ; Humans ; Interleukin-6/*blood ; Male ; Middle Aged ; Natriuretic Peptide, Brain/*blood ; Neurotransmitter Agents/blood ; Prospective Studies ; Receptors, Tumor Necrosis Factor/*blood ; Survival Analysis ; Tumor Necrosis Factor-alpha/*analysis ; fas Receptor/*blood ; }, abstract = {Patients with Chagas' cardiomyopathy have the worst prognosis when compared to other aetiologies. It has been suggested that a more intense inflammatory activation could be responsible for this excessive mortality. We studied 35 patients with idiopathic dilated cardiomyopathy (IDC group) and 28 patients with Chagas' heart disease (Chagas' group) and 12 control subjects. We compared plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptor type 1 (sTNF-R1), soluble Fas (sFas), interleukin 6 (IL-6), and brain natriuretic peptide type B (BNP) concentrations between the groups. TNF-alpha and IL-6 concentrations were higher in the IDC and Chagas groups as compared to controls (p<0.001 and p=0.001, respectively). sTNF-R1 concentration was higher in IDC after stratification for functional class (p=0.039), and there was a trend toward higher plasma TNF-alpha concentration in the Chagas' group (p=0.092). IL-6 concentration was higher in Chagas than in IDC (p=0.005). Higher IL-6 levels were associated with worse outcome (p=0.03 for Chagas; p=0.003 for IDC). sFas concentration was similar among groups. BNP concentrations were higher in IDC (350 pg/ml) and in Chagas (444.6 pg/ml) as compared to the controls (20.3 pg/ml; p<0.01). Higher BNP levels were associated with death and heart transplantation in both aetiologies. Inflammatory activation in Chagas heart disease differs from IDC and is associated with heart failure severity.}, }
@article {pmid16024247, year = {2005}, author = {Sasano, H and Anderson, TJ and Silverberg, SG and Santen, RJ and Conway, M and Edwards, DP and Krause, A and Bhatnagar, AS and Evans, DB and Miller, WR}, title = {The validation of new aromatase monoclonal antibodies for immunohistochemistry--a correlation with biochemical activities in 46 cases of breast cancer.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {95}, number = {1-5}, pages = {35-39}, doi = {10.1016/j.jsbmb.2005.04.027}, pmid = {16024247}, issn = {0960-0760}, mesh = {*Antibodies, Monoclonal ; Aromatase/*analysis/immunology ; Breast Neoplasms/diagnosis/*enzymology ; Female ; Humans ; *Immunohistochemistry ; }, abstract = {Intratumoral aromatase is a therapeutic target for the treatment of post-menopausal estrogen-dependent breast cancers. Therefore, reliable methods should be developed for routine application for the detection of intratumoral aromatase. Immunohistochemistry (IHC) is considered one of the most suitable methods in this regard. A multi-centre collaborative group has been established to generate and validate new aromatase monoclonal antibodies. We have selected two monoclonal antibodies, #677 against native aromatase protein and F2 against formalin-fixed protein for this purpose. With these two monoclonal antibodies 43 cases of invasive ductal carcinoma, which had been previously assayed for aromatase activity by product isolation methodology, were immunostained in three laboratories in UK, USA and Japan and independently evaluated by three pathologists (H.S., T.A. and S.G.S.). Staining of malignant epithelium, adipose tissue, normal/benign and stromal compartments of the tumors were assessed by estimating the proportion of positive staining cells and the relative intensity of staining in this fashion. Immunoreactivity could be detected in each component of the tissue specimens but a significant positive correlation with biochemical activity was detected only in malignant epithelium stained with 677 not in other components with #677 and not in any of the components. Staining using F2 as a primary antibody did not produce a positive correlation in any components with aromatase activity. These results suggest that we now have a monoclonal antibody against aromatase (#677) which may be used to stain archival materials. A methodology and scoring system is recommended whereby staining significantly correlates with aromatase activity of the resected tissue specimens of breast cancer.}, }
@article {pmid16023232, year = {2006}, author = {Tsagalou, EP and Anastasiou-Nana, MI and Terrovitis, JV and Nanas, SN and Alexopoulos, GP and Kanakakis, J and Nanas, JN}, title = {The long-term survival benefit conferred by intermittent dobutamine infusions and oral amiodarone is greater in patients with idiopathic dilated cardiomyopathy than with ischemic heart disease.}, journal = {International journal of cardiology}, volume = {108}, number = {2}, pages = {244-250}, doi = {10.1016/j.ijcard.2005.05.012}, pmid = {16023232}, issn = {0167-5273}, mesh = {Administration, Oral ; Aged ; Amiodarone/administration &amp; dosage/*therapeutic use ; Cardiomyopathy, Dilated/*drug therapy/mortality ; Dobutamine/administration &amp; dosage/*therapeutic use ; Female ; Hemodynamics/drug effects ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Myocardial Ischemia/*drug therapy/mortality ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Intermittent dobutamine infusions (IDI) combined with oral amiodarone improve the survival of patients with end-stage congestive heart failure (CHF). The purpose of the present study was to evaluate whether the response to long-term treatment with IDI+amiodarone is different in patients with ischemic heart disease (IHD) versus idiopathic dilated cardiomyopathy (IDC).<br><br>METHODS: The prospective study population consisted of 21 patients with IHD (the IHD Group) and 16 patients with IDC (the IDC Group) who presented with decompensated CHF despite optimal medical therapy, and were successfully weaned from an initial 72-h infusion of dobutamine. They were placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h.<br><br>RESULTS: There were no differences in baseline clinical and hemodynamic characteristics between the 2 groups. The probability of 2-year survival was 44% in the IDC Group versus 5% in the IHD Group (long-rank, P=0.004). Patients with IDC had a 77% relative risk reduction in death from all causes compared to patients with IHD (odd ratio 0.27, 95% confidence interval 0.13 to 0.70, P=0.007). In contrast, no underlying disease-related difference in outcomes was observed in a retrospectively analyzed historical Comparison Group of 29 patients with end stage CHF treated by standard methods.<br><br>CONCLUSIONS: Patients with end stage CHF due to IDC derived a greater survival benefit from IDI and oral amiodarone than patients with IHD.}, }
@article {pmid16008586, year = {2005}, author = {Edwards, JL and Apicella, MA}, title = {I-domain-containing integrins serve as pilus receptors for Neisseria gonorrhoeae adherence to human epithelial cells.}, journal = {Cellular microbiology}, volume = {7}, number = {8}, pages = {1197-1211}, doi = {10.1111/j.1462-5822.2005.00547.x}, pmid = {16008586}, issn = {1462-5814}, support = {5-T32-AI07511-07/AI/NIAID NIH HHS/United States ; AI45728/AI/NIAID NIH HHS/United States ; }, mesh = {Asialoglycoprotein Receptor/metabolism ; Bacterial Adhesion ; Cells, Cultured ; Epithelial Cells/metabolism/microbiology/*physiology ; Humans ; Immunoprecipitation ; Integrin alpha Chains/*metabolism ; Male ; Neisseria gonorrhoeae/metabolism/*physiology ; Pili, Sex/metabolism/*physiology ; Protein Structure, Tertiary ; Urethra/cytology/*microbiology ; }, abstract = {Two pilus receptors are identified for the pathogenic Neisseria, CD46 and complement receptor 3. An intimate association between the asialoglycoprotein receptor and gonococcal lipooligosaccharide mediates invasion of primary, male urethral epithelial cells (UECs); however, studies to identify pilus receptors on these cells have not been performed. Based on our previous studies we reasoned that the I-domain-containing (IDC), alpha(1)- and alpha(2)-integrins might serve as pilus receptors on UECs and on urethral tissue. Confocal microscopy revealed colocalization of pilus with alpha(1) and alpha(2) integrins on UECs and tissue. We found that recombinant I-domain and antibodies directed against the alpha(1)- and alpha(2)-integrins inhibited gonococcal association with UECs and with immortal cell lines of variable origin. Gonococcus-integrin colocalization occurred at early time points post infection, but this interaction dissociated with extended infection. Similarly, Western Blot analyses revealed that gonococcal pilin coimmunoprecipitates with alpha(1)- and alpha(2)-integrins. However, studies performed in parallel and that were designed to capture CD46-pilus immune complexes indicated that a CD46-pilus interaction did not occur. Collectively, these data suggest that while CD46 might be able to bind gonococcal pilus, IDC integrins are preferentially used as the initial docking site for gonococci on UECs, on urethral tissue and on some immortal cell lines.}, }
@article {pmid15999153, year = {2005}, author = {Simsa, P and Teillaud, JL and Stott, DI and Tóth, J and Kotlan, B}, title = {Tumor-infiltrating B cell immunoglobulin variable region gene usage in invasive ductal breast carcinoma.}, journal = {Pathology oncology research : POR}, volume = {11}, number = {2}, pages = {92-97}, pmid = {15999153}, issn = {1219-4956}, mesh = {B-Lymphocytes/*immunology ; Brain Stem Neoplasms/immunology/pathology ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; *Genes, Immunoglobulin ; Humans ; Immunoglobulin Variable Region/*genetics ; Lymphocytes, Tumor-Infiltrating/*immunology ; Neoplasm Invasiveness/*pathology ; Retrospective Studies ; }, abstract = {A major focus of tumor immunology is to reveal the potential role and capacity of immunocompetent cells found in different solid tumor tissues. The most abundant infiltrating cells (TIL), the T lymphocytes have been investigated in details concerning T-cell receptor usage and specificity. However, B cells have hardly been investigated in this respect, although high cellular B-cell infiltration has been correlated with improved patients' survival in some breast carcinomas. This led to our objectives to study variable region gene usage of the tumor-infiltrating B cells in different breast carcinoma types. By defining the immunoglobulin repertoire of the tumor-infiltrating B lymphocytes in the most common invasive ductal carcinoma (IDC) of the breast we compared it to the rare medullary breast carcinoma (MBC). After phenotyping infiltrating ductal carcinomas, B cells were obtained from tumor tissue by microdissection technique. Numerous rearranged TIL-B immunoglobulin heavy chain V genes (VH) were amplified, cloned, sequenced, and comparatively analyzed. Some characteristics were found for both breast carcinoma types. The immunoglobulins produced by TIL-B in ductal carcinoma are highly matured and oligoclonal. We conclude that Ig variable region gene usage reveals similar and distinguishable characteristics of TIL-B immunoglobulin repertoires, which are representative of the nature of the immune responses in invasive ductal and medullary breast carcinomas.}, }
@article {pmid15998374, year = {2005}, author = {Guler, G and Uner, A and Guler, N and Han, SY and Iliopoulos, D and McCue, P and Huebner, K}, title = {Concordant loss of fragile gene expression early in breast cancer development.}, journal = {Pathology international}, volume = {55}, number = {8}, pages = {471-478}, doi = {10.1111/j.1440-1827.2005.01855.x}, pmid = {15998374}, issn = {1320-5463}, support = {CA53036/CA/NCI NIH HHS/United States ; CA77738/CA/NCI NIH HHS/United States ; }, mesh = {Acid Anhydride Hydrolases/*biosynthesis/genetics ; Adult ; Aged ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Chi-Square Distribution ; Chromosome Fragile Sites/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*biosynthesis/genetics ; Oxidoreductases/*biosynthesis/genetics ; Receptor, ErbB-2/analysis ; Tumor Suppressor Protein p53/analysis ; Tumor Suppressor Proteins ; WW Domain-Containing Oxidoreductase ; }, abstract = {The FHIT and WWOX genes encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. Reduced Fhit and Wwox expression has been reported in approximately two-thirds of invasive breast tumors. Expression of these fragile gene products, as well as ErbB2 and p53, were evaluated immunohistochemically in 44 pure and 31 adjacent-to-invasive ductal carcinoma in-situ (DCIS) cases. Reduced Fhit and Wwox expression were observed in (i) 70% and 68% of pure DCIS; (ii) 52% and 55% of DCIS adjacent-to-invasive tumor cases; and (iii) 20% and 50% of adjacent normal tissue in pure DCIS cases. Reduced Wwox expression in adjacent normal tissue was observed in 30% of cases in the DCIS adjacent-to-invasive group. Reduced Fhit and Wwox expression was observed in 61% of adjoining invasive tumors. In all normal, pure DCIS, and DCIS adjacent-to-invasive lesions, Fhit and Wwox expression was positively associated (P = 0.034, P = 0.042, P = 0.004, respectively) and in the invasive component there was a positive trend toward association (P = 0.075). Fhit and Wwox were more frequently reduced in high-grade lesions in the DCIS adjacent-to-invasive (P = 0.025, P = 0.004, respectively). In the pure DCIS group, there was a statistically significant negative association between Fhit and ErbB2 expression in DCIS (P = 0.035). In summary, reduced Fhit and Wwox expression in in-situ breast cancer was associated, which may contribute to the high-grade DCIS-invasive tumor pathway.}, }
@article {pmid15996865, year = {2006}, author = {Yamaguchi, H and Ishikawa, M and Hatanaka, K and Uekusa, T and Ishimaru, M and Nagawa, H}, title = {Occult breast cancer presenting as axillary metastases.}, journal = {Breast (Edinburgh, Scotland)}, volume = {15}, number = {2}, pages = {259-262}, doi = {10.1016/j.breast.2005.04.018}, pmid = {15996865}, issn = {0960-9776}, mesh = {Axilla ; Breast Neoplasms/*diagnosis/secondary ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Metastasis ; Neoplasms, Unknown Primary/*diagnosis/pathology ; }, abstract = {We report the case of a 52-year-old woman with occult breast cancer who presented with a hard metastatic nodule in the left axilla. Although histology identified a metastatic adenocarcinoma in the lymph nodes, numerous tests failed to detect the primary tumor. Immunohistochemistry showed that the resected lymph node was positive for both estrogen and progesterone receptors, suggesting the breast as the site of the primary tumor. Left modified radical mastectomy was performed. Pathology revealed an invasive ductal carcinoma (1.5x1 mm in size) with extensive lymphatic involvement, which strongly expressed both vascular endothelial growth factor-C (VEGF-C) and VEGF-D.}, }
@article {pmid15996167, year = {2005}, author = {Liu, W and Li, WM and Sun, NL}, title = {HLA-DQA1, -DQB1 polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy in Hans of northern China.}, journal = {Annals of human genetics}, volume = {69}, number = {Pt 4}, pages = {382-388}, doi = {10.1111/j.1529-8817.2005.00166.x}, pmid = {15996167}, issn = {0003-4800}, mesh = {Adult ; Alleles ; Asian People/genetics ; Cardiomyopathy, Dilated/epidemiology/*genetics/immunology ; Case-Control Studies ; China/epidemiology ; Female ; *Genetic Predisposition to Disease ; Genotype ; HLA-DQ Antigens/*genetics/immunology ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; Humans ; Lod Score ; Male ; *Polymorphism, Genetic ; }, abstract = {Autoimmune mechanisms are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the major histocompatibility complex (MHC) may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, especially HLA-DQ genes, which are highly polymorphic, play an important role in the activation of immune responses and thus control the predisposition to, or protection from, IDC. This study was conducted to investigate the association of HLA-DQA1, -DQB1 allele polymorphisms with an autoantibody against the myocardial mitochondria ADP/ATP carrier, and to explore susceptibility to idiopathic dilated cardiomyopathy (IDC) among the Han ethnic group in northern China and the immunological mechanisms and hereditary susceptibility to IDC. Polymerase chain reaction sequence-specific primer (PCR-SSP) techniques were used to analyze polymorphisms of the second exon of HLA-DQA1 and -DQB1 alleles among 68 unrelated IDC patients, 4 probands of IDC pedigrees, and 100 healthy controls, all of Han nationality and having lived in northern China for a long time. Following echocardiography examination the IDC subjects were stratified according to ejection fraction (EF) values. Those with EF values higher than 50% were placed in subgroup 1, subgroup 2 included the patients with an EF value of 15-35%, and subgroup 3 consisted of those whose EF values were less than 15%. An autoantibody against the myocardial mitochondria ADP/ATP carrier was examined using immunoblot analysis. The frequencies of HLA-DQA1*0501 and HLA-DQB1*0303 were 0.3889 and 0.1806 in the IDC group, significantly higher than those of the healthy controls (0.0900 and 0.0364 respectively, both P < 0.05). The OR was 5.20 (95% CI: 3.60-8.50) and 4.85 (95% CI: 2.56-9.39) respectively. Further analysis of the three subgroups showed a higher frequency of HLA-DQA1*0501 among patients whose EF was less than 15% than those whose EF values were > or =15%. Conversely, the frequencies of HLA-DQA1*0201 and -DQB1*0502, *0504 were significantly lower in the IDC group (0.0139, 0.0139 and 0.0417 respectively) than in the control group (0.2000, 0.0727 and 0.1091 respectively) (P < 0.05). The frequency of the HLA-DQA1*0501 allele was significantly higher in IDC patients whose autoantibody is positive in contrast with those whose autoantibody is negative (18.57% vs. 5.86%, P < 0.05); the relative risk (RR) was 4.32. The other frequencies of HLA-DQA1 and -DQB1 alleles showed no significant difference in the antibody positive and negative groups of IDC patients. The alleles of HLA-DQA1*0501 and HLA-DQB1*0303 were closely associated with poor EF values in the IDC group, and may be involved in susceptibility to the disease. The DQA1*0201 and DQB1*0502, *0504 alleles may confer protection to IDC among individuals of northern Chinese Han nationality. The SER(57) residue in the second exon of DQB1*0502 and *0504 may confer resistance to IDC, and defects or substitution of this amino acid residue at position 57 of the DQbeta chain may be associated with IDC susceptibility. HLA-DQ allele polymorphisms may serve as genetic markers for IDC and be involved in the regulation of the immune specific response to auto or exterior anti-myocardium antibodies.}, }
@article {pmid15995634, year = {2005}, author = {Tokatli, F and Altaner, S and Uzal, C and Ture, M and Kocak, Z and Uygun, K and Bilgi, S}, title = {Association of HER-2/neu overexpression with the number of involved axillary lymph nodes in hormone receptor positive breast cancer patients.}, journal = {Experimental oncology}, volume = {27}, number = {2}, pages = {145-149}, pmid = {15995634}, issn = {1812-9269}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/*metabolism/pathology ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Survival Rate ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {AIM: To evaluate the prognostic significance of HER-2/neu overexpression in hormone receptor and axillary lymph node positive breast cancer patients treated in a single institution.<br><br>METHODS: Paraffin-embedded primary breast cancers from 40 patients with invasive ductal carcinoma were studied immunohistochemically. HER-2/neu staining was classified as negative (0, 1+), weak/moderate positive (2+), or moderate/strong positive (3+) and was assessed for effectiveness as a predictor of outcome in univariate and Cox model multivariate analyses.<br><br>RESULTS: 20% of patients were positive for HER-2/neu. Significant associations were observed between HER-2/neu and increasing number of involved nodes (p = 0.014), p53 positivity (p = 0.039), the presence of vascular invasion (p = 0.029) and metastases (p = 0.01). Multivariate analysis demonstrated that HER-2/neu overexpression (p = 0.016) and age (p = 0.005) were independent predictors for disease-free survival (DFS) where the number of involved nodes (p = 0.032) was shown to be independent predictor for overall survival. In the HER-2/neu positively stained tumors, significant number of patients developed distant metastases than the patients with HER-2/neu negatively stained tumors (87.5% vs 34.4%, p = 0.01).<br><br>CONCLUSION: For node positive patients, HER-2/neu overexpression was a significant predictor of DFS.}, }
@article {pmid15990453, year = {2005}, author = {Pellegrini, P and Totaro, R and Contasta, I and Berghella, AM and Carolei, A and Adorno, D}, title = {CD30 antigen and multiple sclerosis: CD30, an important costimulatory molecule and marker of a regulatory subpopulation of dendritic cells, is involved in the maintenance of the physiological balance between TH1/TH2 immune responses and tolerance. The role of IFNbeta-1a in the treatment of multiple sclerosis.}, journal = {Neuroimmunomodulation}, volume = {12}, number = {4}, pages = {220-234}, doi = {10.1159/000085654}, pmid = {15990453}, issn = {1021-7401}, mesh = {Adult ; Biomarkers/metabolism ; Cytokines/immunology ; Dendritic Cells/drug effects/*immunology ; Down-Regulation/drug effects/immunology ; Female ; Humans ; Immune Tolerance/immunology ; Immunity, Cellular/drug effects/immunology ; Immunologic Factors/*immunology/metabolism ; Interferon beta-1a ; Interferon-beta/pharmacology/therapeutic use ; Ki-1 Antigen/*immunology ; Male ; Multiple Sclerosis/drug therapy/*immunology/physiopathology ; Principal Component Analysis ; Severity of Illness Index ; Th1 Cells/*immunology ; Th2 Cells/*immunology ; }, abstract = {OBJECTIVES: The immunological effect of CD30 on dendritic cells (DCs) was examined in a comparative study of patients with relapsing-remitting multiple sclerosis (RRMS). The patients were divided into two groups on the basis of interferon (IFN)beta-1a treatment: IFNbeta-1a-treated patients and untreated patients. We have already shown that CD30 is a marker of cells involved in the regulation of the balance between TH1 and TH2 immune responses and so the aim of this study was to confirm this role in DCs and, consequently, to clarify the immunopathological mechanisms of MS and the causes of immunosuppressive drug failure.<br><br>METHODS: We studied network interactions between soluble (s) CD30 and TH1/TH2 cytokines in the supernatants of CD14+-derived immature DC (IDC) and DC cultures from treated and untreated patients. Network interactions between the sCD30 and cytokines in IDC and DC supernatants were also evaluated in relation to TH1/TH2 cytokine serum levels.<br><br>RESULTS: Our overall results show that CD30 is expressed on IDCs and DCs, indicating an immunological role in resting and activated physiological conditions. This role would appear to be the regulation of the resting and activated physiological balance between the TH1/TH2 immune functions as abnormal increases in sCD30 levels result in impaired regulation. Further studies are undoubtedly required to clarify this situation. IFNbeta-1a treatment was found to determine a fall in sCD30 levels, leading to the restoration of the normal functional selection of IDCs from progenitor cells and the regulation of the TH1/TH2 network balance. However, IFNbeta-1a treatment may also be responsible for the in vivo suppression of CD30-mediated TH1-DC functions in immune activation. TH1-DC functions are involved in the induction of T-regulatory cells for the physiological deletion of self-aggressive cells.<br><br>CONCLUSION: We conclude that CD30 is an important costimulatory molecule and marker of a regulatory subpopulation of DCs which induces and modulates immune cells involved in the maintenance of the physiological balance between TH1/TH2 immune responses and tolerance. Elucidating the mechanisms restoring DC and T-regulatory cell function could lead to more effective therapy and strategies for the prevention and treatment of immunopathological conditions such as autoimmunity, transplant rejection, allergy and tumors.}, }
@article {pmid15986450, year = {2005}, author = {Kasper, G and Weiser, AA and Rump, A and Sparbier, K and Dahl, E and Hartmann, A and Wild, P and Schwidetzky, U and Castaños-Vélez, E and Lehmann, K}, title = {Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients.}, journal = {International journal of cancer}, volume = {117}, number = {6}, pages = {961-973}, doi = {10.1002/ijc.21235}, pmid = {15986450}, issn = {0020-7136}, mesh = {Base Sequence ; Breast Neoplasms/chemistry/*genetics/pathology ; Cation Transport Proteins/analysis/*genetics ; DNA, Complementary/chemistry ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Endoplasmic Reticulum/chemistry ; *Gene Expression ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Middle Aged ; Molecular Sequence Data ; Neoplasm Proteins/analysis/*genetics ; Neoplasm Recurrence, Local ; Prognosis ; RNA, Messenger/analysis ; Receptors, Estrogen/analysis ; Survival Rate ; Tamoxifen ; }, abstract = {We investigated the expression pattern of the breast cancer associated gene LIV-1 on mRNA and protein level in 111 human breast cancer patients by in situ hybridization as well as immunohistochemistry and focused on the unknown potential of LIV-1 expression levels as a prognostic marker. To our knowledge, this is the first study on endogenous LIV-1 protein expression. Results of our study indicate that LIV-1 mRNA and protein expression levels are only weakly correlated, suggesting posttranscriptional regulatory mechanisms. Furthermore, LIV-1 mRNA quantity in combination with a positive ER status seem to represent a better marker than the progesterone receptor status according to the prognostic significance for relapse free survival (RFS). A negative correlation of LIV-1 protein levels with tumor size, grade and stage reflects an association of LIV-1 protein expression with less aggressive tumors. High LIV-1 protein expression seems to be associated with a longer relapse free and overall survival in breast cancer patients with invasive ductal carcinoma. This association, however, seems to be dependent from other prognostic markers. Our data suggest that LIV-1 is a promising candidate for a novel marker for breast cancer patients with better outcome. Furthermore, our study presents a revised cDNA sequence of LIV-1 and demonstrates the localization of endogenous LIV-1 in the endoplasmic reticulum.}, }
@article {pmid15983632, year = {2005}, author = {Rossini, M and Piscitelli, P and Fitto, F and Camboa, P and Angeli, A and Guida, G and Adami, S}, title = {[Incidence and socioeconomic burden of hip fractures in Italy].}, journal = {Reumatismo}, volume = {57}, number = {2}, pages = {97-102}, doi = {10.4081/reumatismo.2005.97}, pmid = {15983632}, issn = {0048-7449}, mesh = {Aged ; Arthroplasty, Replacement, Hip/economics ; Diagnosis-Related Groups ; Female ; Femoral Fractures/economics/*epidemiology/rehabilitation/surgery ; Fractures, Spontaneous/economics/epidemiology/etiology/rehabilitation/surgery ; Health Expenditures/statistics &amp; numerical data ; Hip Fractures/economics/*epidemiology/rehabilitation/surgery ; Hospitalization/economics/statistics &amp; numerical data ; Humans ; Incidence ; Italy/epidemiology ; Male ; Middle Aged ; National Health Programs/economics ; Orthopedic Procedures/economics ; Osteoporosis/complications/economics ; Rehabilitation/economics ; Sick Leave/economics ; }, abstract = {OBJECTIVES: The aim of this study was to evaluate the trend of the incidence and costs of hip fractures in Italy.<br><br>METHODS: The incidence of hip fractures after 45 years of age in both females and males during the years 1999-2002 was obtained by analyzing the Italian Ministry of Health national hospitalization database, according to the diagnosis codes of International Classification of Diseases, Clinical Modification, 9th edition (IDC-9-CM) that indicate femoral fracture. We have computed all direct costs sustained by the National Health Service for hospitalization and treatment of hip fractures on the basis of the value of the Diagnosis Related Groups (DRG) referring to hip fractures. The expenses of rehabilitation and indirect expenses were based on estimates.<br><br>RESULTS: In 2002, more than 86,000 hip fractures were registered in Italy in male and female patients over 45 years old, with 9% progression compared to 1999; 77% were female and 80% were over 75 years of age. In 2002 the direct costs of hospitalization, in the patients over 65 years alone, were almost 400 million euros, with an increase of 15% as compared to 1999. Considering also estimated rehabilitation costs, social aid and indirect costs, we estimate that hip fractures due to age-related osteoporosis created over a billion euros in expenses in 2002.<br><br>CONCLUSIONS: Preventive intervention regarding the risk of hip fracture in elderly patients is urgent.}, }
@article {pmid15979827, year = {2005}, author = {Gallardo, S and Cárdaba, B and Posada, M and del Pozo, V and Messeguer, A and David, CS and Lahoz, C}, title = {Toxic oil syndrome: genetic restriction and immunomodulatory effects due to adulterated oils in a model of HLA transgenic mice.}, journal = {Toxicology letters}, volume = {159}, number = {2}, pages = {173-181}, doi = {10.1016/j.toxlet.2005.05.009}, pmid = {15979827}, issn = {0378-4274}, support = {AI-14764/AI/NIAID NIH HHS/United States ; }, mesh = {Aniline Compounds/*toxicity ; Animals ; Eosinophils/*drug effects/immunology ; Fatty Acids, Monounsaturated ; Female ; *Genetic Predisposition to Disease ; Histocompatibility Antigens Class II/genetics ; Humans ; Immunoglobulin E/blood ; Interleukin-4/biosynthesis ; Interleukin-5/biosynthesis ; Lung/drug effects/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Plant Oils/*toxicity ; Propylene Glycols/toxicity ; RNA, Messenger/biosynthesis ; Rapeseed Oil ; Syndrome ; Th2 Cells/*drug effects/immunology ; }, abstract = {Toxic oil syndrome (TOS) was described in Spain in 1981, due to the ingestion of contaminated rapeseed oil denatured with 2% aniline. More than 20,000 persons were affected, causing over 2500 deaths. Immunological findings were: eosinophilia, mRNA for Th2 cytokines (IL-4 and IL-5) in lungs, elevated total IgE and sIL-2R and increase of DR2 HLA class II phenotypic frequency in patients died by TOS. Our objective is to test the genetic restriction found in humans using HLA transgenic mice. Results show that mice expressing human DR2 and DQ6 (both in linkage disequilibrium), had higher percentage of eosinophils (DQ6) and IgE (DR2) than other transgenic mice tested (DR3 and DR4). Also, a Th2 shift was found in DR2 transgenic mice when toxic oil was administered with OVA. This has been corroborated by the IL-5 mRNA expression in 4 out of 6 lung tissues from TOS oil treated BALB/c mice. These data indicate that an immunological response was induced as consequence of the toxic administration. These results correlate with those found in TOS patients and reinforce the implication of genetic restrictions in the acquisition of toxic-mediated disease.}, }
@article {pmid15958055, year = {2005}, author = {Tsuda, H and Tani, Y and Weisenberger, J and Kitada, S and Hasegawa, T and Murata, T and Tamai, S and Hirohashi, S and Matsubara, O and Natori, T}, title = {Frequent KIT and epidermal growth factor receptor overexpressions in undifferentiated-type breast carcinomas with 'stem-cell-like' features.}, journal = {Cancer science}, volume = {96}, number = {6}, pages = {333-339}, doi = {10.1111/j.1349-7006.2005.00060.x}, pmid = {15958055}, issn = {1347-9032}, mesh = {Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma/*genetics/*pathology ; Carcinoma, Ductal/*genetics/*pathology ; Cell Differentiation ; ErbB Receptors/*biosynthesis/genetics ; Female ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; Proto-Oncogene Proteins c-kit/*biosynthesis/genetics ; Receptor, ErbB-2/biosynthesis ; *Stem Cells ; }, abstract = {It was hypothesized that four histopathological types or subtypes of breast carcinoma were undifferentiated types characterized by bidirectional differentiation toward both luminal epithelial and myoepithelial cells and had characteristic molecular changes: invasive ductal carcinoma (IDC) with a large central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid-tubular carcinoma), matrix-producing carcinoma, and spindle-cell carcinoma (or carcinoma with spindle-cell metaplasia). In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types, we immunohistochemically examined the expressions of myoepithelial markers and KIT, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoproteins. Vimentin, S-100, and alpha-smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the undifferentiated types, but were positive in seven (19%), one (3%), and one (3%) of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions were detected more frequently in the undifferentiated types (34 and 88%, respectively) than in relatively differentiated types (3 and 3%, respectively) (P < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR overexpression concurred. c-erbB-2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types, and did not correlate with KIT or EGFR overexpression. Phosphotyrosine was detected in 16 (67%) of 24 cases with KIT, EGFR, and/or c-erbB-2 overexpression but only in six (18%) of 34 cases without KIT, EGFR, or c-erbB-2 overexpression (P = 0.0002). The undifferentiated-type breast carcinomas appeared to show mammary epithelial stem cell-like features, and they could be identified by KIT and/or EGFR overexpressions.}, }
@article {pmid15942148, year = {2005}, author = {Sezgin, N and Sezgin, AT and Gullu, H and Karabulut, A and Barutcu, I and Topal, E and Yalcintas, D and Temel, I}, title = {Decreased serum lipoprotein levels as a guide for clinical severity in patients with idiopathic dilated cardiomyopathy.}, journal = {The Tohoku journal of experimental medicine}, volume = {206}, number = {3}, pages = {219-224}, doi = {10.1620/tjem.206.219}, pmid = {15942148}, issn = {0040-8727}, mesh = {Adult ; Aged ; Apolipoprotein A-I/metabolism ; Apolipoproteins/metabolism ; Cardiomyopathy, Dilated/*blood/diagnosis ; Cholesterol/metabolism ; Cholesterol, HDL/metabolism ; Cholesterol, LDL/metabolism ; Cytokines/metabolism ; Echocardiography ; Female ; Glucose/metabolism ; Humans ; Interleukin-6/metabolism ; Lipoproteins/*blood/metabolism ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Hyperlipidemia is a cardiovascular risk factor. In patients with idiopathic dilated cardiomyopathy (IDC), prognostic roles of endogenous lipoproteins are not fully clarified. It has been known that there is a direct relationship between the levels of cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6]) and deteriorating functional classes of heart failure and mortality. The present study compared the levels of circulating TNF-alpha, IL-6, lipoproteins, and apolipoproteins in patients with stable IDC (n = 28) with those of patients with unstable IDC (n = 26) and controls (n = 24). Mean serum total cholesterol (TC) was significantly lower in stable IDC patients than controls (p < 0.05). In unstable IDC patients, mean serum TC was also lower than controls but not statistically significant. The IDC patients had significantly higher concentrations of IL-6 and TNF-alpha than the controls (p < 0.01). Serum IL-6 and Apo AI levels were significantly different between stable and unstable IDC patients (p = 0.021 and p = 0.012, respectively). Increased levels of IL-6 were associated with decreased levels of TC (r = -0.266, p = 0.019), LDL-C (r = -0.376, p = 0.001) and apolipoprotein AI (apo AI) (r = -0.495, p < 0.001) in all IDC patients. TNF-alpha was also inversely related to apo AI (r = -0.455, p < 0.001) and LDL-C (r = -0.364, p = 0.001) in all patients. Thus, elevated serum levels of cytokines in patients with IDC are associated with decreased lipoprotein concentrations, which may indicate impaired prognosis.}, }
@article {pmid15923404, year = {2005}, author = {Peter, JC and Tugler, J and Eftekhari, P and Maurice, D and Hoebeke, J and Roegel, JC}, title = {Effects on heart rate of an anti-M2 acetylcholine receptor immune response in mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {19}, number = {8}, pages = {943-949}, doi = {10.1096/fj.04-3042com}, pmid = {15923404}, issn = {1530-6860}, mesh = {Allosteric Regulation ; Amino Acid Sequence ; Animals ; Antibodies/blood/*immunology/physiology ; Atropine/pharmacology ; CHO Cells ; Carbachol/pharmacology ; Cricetinae ; Cricetulus ; Cyclic AMP/analysis ; Electrocardiography ; Female ; Gallamine Triethiodide/pharmacology ; Heart Rate/drug effects/*physiology ; Humans ; Immunization ; Isoproterenol/pharmacology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Parasympathetic Nervous System/physiology ; Peptide Fragments/chemistry/immunology ; Receptor, Muscarinic M2/genetics/*immunology/physiology ; Transfection ; }, abstract = {Autoantibodies in vitro modulating the M2 acetylcholine receptor (M2ACh-R) were observed in patients with idiopathic dilated cardiomyopathy (IDC) or Chagas' cardiomyopathy (ChC). We investigated the in vivo consequences on heart rate of such antibodies in mice immunized with a peptide derived from the second extracellular loop of the M2ACh-R compared with mice immunized with an irrelevant peptide. Sera of mice immunized with the M2ACh-R-derived peptide recognized the M2ACh-R on immunoblots and enhanced agonist activity of carbachol toward the M2AChR transfected in CHO cells. In vivo, no difference could be shown in heart rate or heart rate variability between the two groups of mice. The decrease in heart rate induced by carbachol was more pronounced, however, in the M2ACh-R immunized mice. The increase in heart rate induced by atropine, gallamine, and isoproterenol was significantly attenuated in the M2ACh-R immunized mice. Analysis of heart rate variability further argued for an increased parasympathetic response to different drugs in the M2ACh-R immunized mice. Antibodies raised against the M2AChR can behave as positive M2AChR allosteric modulators in vivo. They might be protective in boosting the activity of the parasympathetic drive to the heart, especially in patients with a high sympathetic tone.}, }
@article {pmid15917448, year = {2005}, author = {Oppenheim, JJ and Dong, HF and Plotz, P and Caspi, RR and Dykstra, M and Pierce, S and Martin, R and Carlos, C and Finn, O and Koul, O and Howard, OM}, title = {Autoantigens act as tissue-specific chemoattractants.}, journal = {Journal of leukocyte biology}, volume = {77}, number = {6}, pages = {854-861}, doi = {10.1189/jlb.1004623}, pmid = {15917448}, issn = {0741-5400}, support = {N01-CO-12400/CO/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, Neoplasm/*immunology ; Autoantigens/*immunology ; Autoimmune Diseases/*immunology ; Chemotactic Factors/*immunology ; Chemotaxis, Leukocyte/immunology ; Dendritic Cells/immunology ; Humans ; Leukocytes, Mononuclear/immunology ; Mice ; Neoplasms/*immunology ; }, abstract = {We have investigated the chemoattractant properties of self-antigens associated with autoimmune diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi-protein-coupled receptors (GiPCR). Our initial observation that myositis-associated autoantigens, histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, were chemotactic for CC chemokine receptor 5 (CCR5)- and CCR3-expressing leukocytes, while other nonautoantigenic aminoacyl-tRNA synthesases were not, suggested that only self-antigens capable of interacting with receptors on antigen-presenting cells were immunogenic. We next determined that self-antigens associated with autoimmune diseases, e.g., multiple sclerosis or experimental autoimmune encephalomyelitis, type I diabetes, scleroderma, systemic lupus erythematosus, autoimmune uveitis, or experimental autoimmune uveitis (EAU), were chemotactic for GiPCR expressed by iDC. The majority of autoantigens were DC chemoattractants at 10-100 ng/ml, but did not induce DC maturation until they reached 1000-fold higher concentrations. Interphotoreceptor retinoid-binding protein and retinal arrestin (S-antigen) are targets of autoantibodies in human uveitis and are chemotactic for CXC chemokine receptor 5 (CXCR5)- and/or CXCR3-expressing iDC. However, although S-antigen does not induce EAU in wild-type mice, it is nevertheless a chemoattractant for murine iDC. These unexpected observations suggested that the chemotactic activity of these tissue-specific self-antigens could be involved in promotion of tissue repair and restoration. Thus, the primary role of autoantigens may be to alert the immune system to danger signals from invaded and damaged tissues to facilitate repair, and autoimmune responses subsequently develop only in subjects with impaired immunoregulatory function.}, }
@article {pmid15915241, year = {2005}, author = {Granizo Martínez, JJ}, title = {[Resistance to penicillin and erythromycin of Streptococcus pneumoniae and Streptococcus pyogenes isolated from community-acquired respiratory infections in Spain between 1986-1999 and its relationship with the use of beta-lactams and macrolides].}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {18}, number = {1}, pages = {83-85}, pmid = {15915241}, issn = {0214-3429}, mesh = {Community-Acquired Infections/microbiology ; Drug Resistance, Bacterial ; Drug Utilization/statistics &amp; numerical data ; Erythromycin/*pharmacology ; Humans ; Macrolides/*therapeutic use ; *Penicillin Resistance ; Pneumonia, Bacterial/microbiology ; Pneumonia, Pneumococcal/*microbiology ; Spain ; Streptococcal Infections/*microbiology ; Streptococcus pneumoniae/*drug effects/isolation &amp; purification ; Streptococcus pyogenes/*drug effects/isolation &amp; purification ; beta-Lactams/*therapeutic use ; }, }
@article {pmid15899192, year = {2005}, author = {Sitges, M and Roig, E and Morales, M and Azqueta, M and Pérez Villa, F and Paré, C and Orús, J and Heras, M and Sanz, G}, title = {[Impaired endothelium-dependent forearm vasodilation in idiopathic dilated cardiomyopathy is related to severe left ventricular dysfunction and elevated serum tumor necrosis factor levels].}, journal = {Revista espanola de cardiologia}, volume = {58}, number = {5}, pages = {477-483}, pmid = {15899192}, issn = {0300-8932}, mesh = {Arm/blood supply ; Cardiomyopathy, Dilated/*blood/complications/*physiopathology ; Endothelium, Vascular/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Severity of Illness Index ; Tumor Necrosis Factor-alpha/*analysis ; Vasodilation ; Ventricular Dysfunction, Left/*blood/complications/*physiopathology ; }, abstract = {INTRODUCTION AND OBJECTIVES: Endothelial dysfunction has been found in patients with idiopathic dilated cardiomyopathy (IDC), but its mechanism remains unknown. Our aim was to investigate whether forearm endothelium-dependent vasoreactivity correlates with cardiac disease severity or neurohormonal activation.<br><br>PATIENTS AND METHOD: We studied 23 patients with IDC and 10 healthy sex- and age-matched controls using brachial artery ultrasound to assess flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NIV). In the IDC group, we determined plasma neurohormone and cytokine levels at the same time.<br><br>RESULTS: FMD was significantly less in the IDC group compared with the control group [--0.06 (2.8)% vs 4.4 (4.6)%, respectively; P<.01], whereas NIV was similar in both groups [15.0 (6.4)% vs 14.0 (7.4)%, respectively; P=NS]. FMD was significantly less in patients with poorer left ventricular (LV) function and more severe LV dilatation, and in those with a higher tumor necrosis factor-alpha (TNF-alpha) level. NIV was similar in all patient subgroups. There was a significant inverse correlation between the TNF-alpha plasma level and FMD (r=-0.75; P<.01). No correlation was found between the plasma levels of other neurohormones and FMD.<br><br>CONCLUSIONS: FMD, but not NIV, was impaired in patients with IDC compared with control subjects. In patients, there were significant associations between FMD impairment and the severity of LV dilatation, the severity of LV systolic dysfunction, and the plasma TNF-alpha level. The strongest correlation was observed between TNF-alpha plasma level and FMD. These data suggest that TNF-alpha may be implicated in endothelial dysfunction in patients with IDC.}, }
@article {pmid15892087, year = {2005}, author = {Schimke, I and Müller, J and Dandel, M and Gremmels, HD and Bayer, W and Wallukat, B and Wallukat, G and Hetzer, R}, title = {Reduced oxidative stress in parallel to improved cardiac performance one year after selective removal of anti-beta 1-adrenoreceptor autoantibodies in patients with idiopathic dilated cardiomyopathy: data of a preliminary study.}, journal = {Journal of clinical apheresis}, volume = {20}, number = {3}, pages = {137-142}, doi = {10.1002/jca.20050}, pmid = {15892087}, issn = {0733-2459}, mesh = {Adsorption ; Adult ; *Autoantibodies/blood/immunology ; Cardiomyopathy, Dilated/blood/immunology/*therapy ; Female ; *Hemodiafiltration/methods ; Humans ; Male ; Middle Aged ; *Oxidative Stress ; Pilot Projects ; *Receptors, Adrenergic, beta-1/blood/immunology ; *Recovery of Function ; Ventricular Function, Left ; }, abstract = {Patients with idiopathic dilated cardiomyopathy (IDC) were treated with selective immunoadsorption to remove anti-beta 1-adrenoreceptor autoantibodies (anti-beta1A-AB). After one year, the effect on cardiac performance and oxidative stress was tested. Extracorporeal immunoadsorption of the whole IgG class in IDC patients for the removal of anti-beta1A-AB reduced oxidative stress in parallel to an improvement of cardiac performance. However, the non-specificity of IgG adsorption means that these beneficial effects cannot be attributed exclusively to anti-beta1A-AB removal. In an open clinical pilot study enrolling 8 patients with IDC prior to and one year after selective immunoadsorption of anti-beta1A-AB, plasma markers for oxidative stress--thiobarbituric acid-reactive substances (TBARS), lipid peroxides (LPO) and anti-oxidized low-density lipoprotein autoantibodies (anti-oxLDL-AB)--were measured in parallel to evaluation of the left ventricular function using conventional echocardiography and wall motion analysis by tissue Doppler imaging. After one year, TBARS (Wilcoxon test with bootstrapping simulation for paired data: 95% confidence interval of the P value 0.020 to 0.029) and anti-oxLDL-AB (P = 0.025 to 0.035) were decreased in parallel to an improvement of the peak systolic wall motion velocity (P = 0.006 to 0.01) and left ventricular ejection fraction (P = 0.002 to 0.02). For changes over the study period, a direct correlation with borderline significance (P = 0.076) was calculated for TBARS to the left ventricular diameter in the diastole. One year after selective immunoadsorption for anti-beta1A-AB removal, patients with ICD show a reduction in oxidative stress and a parallel improvement in cardiac performance.}, }
@article {pmid15887223, year = {2005}, author = {Santiago, RJ and Harris, EE and Qin, L and Hwang, WT and Solin, LJ}, title = {Similar long-term results of breast-conservation treatment for Stage I and II invasive lobular carcinoma compared with invasive ductal carcinoma of the breast: The University of Pennsylvania experience.}, journal = {Cancer}, volume = {103}, number = {12}, pages = {2447-2454}, doi = {10.1002/cncr.21071}, pmid = {15887223}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/pathology/*therapy ; Carcinoma, Lobular/pathology/*therapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Humans ; Lymph Node Excision ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: The objective of the current study was to determine the long-term results of breast-conservation treatment in women with early-stage, invasive lobular carcinoma of the breast.<br><br>METHODS: Between 1977 and 1995, 1093 women with Stage I and II invasive ductal carcinoma of the breast and 55 women with invasive lobular carcinoma of the breast underwent lumpectomy, axillary lymph node dissection, and radiation treatment. Overall, 49% of the women received adjuvant systemic therapy (chemotherapy and/or hormones).<br><br>RESULTS: The median age was 52 years for patients in the invasive ductal group and 54 years for patients in the invasive lobular group. The median follow-up was 8.7 years and 10.2 years for patients in the invasive ductal and invasive lobular groups, respectively. A comparison of patients who had invasive lobular carcinoma with patients who had invasive ductal carcinoma showed no difference in the 10-year actuarial rates of overall survival (85% vs. 79%, respectively; P = 0.73), cause-specific survival (93% vs. 84%, respectively; P = 0.85), or freedom from distant metastases (81% vs. 80%, respectively; P = 0.76). The 10-year rates of local failure were 18% for patients with invasive lobular carcinoma and 12% for patients with invasive ductal carcinoma (P = 0.24), and the 10-year rates of contralateral breast carcinoma development for the 2 groups were 12% and 8%, respectively (P = 0.40).<br><br>CONCLUSIONS: Breast-conservation treatment yielded similar long-term results for women with early-stage, invasive lobular carcinoma and women with the more prevalent invasive ductal carcinoma.}, }
@article {pmid15879625, year = {2005}, author = {Moriya, T and Kimura, W and Semba, S and Sakurai, F and Hirai, I and Ma, J and Fuse, A and Maeda, K and Yamakawa, M}, title = {Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.}, journal = {International journal of gastrointestinal cancer}, volume = {35}, number = {2}, pages = {111-119}, pmid = {15879625}, issn = {1537-3649}, mesh = {Aged ; Bile Duct Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Papillary/*genetics/*pathology ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/*genetics/*pathology ; }, abstract = {BACKGROUND: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail.<br><br>AIMS: PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two.<br><br>METHODOLOGY: A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2.<br><br>RESULTS: Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015).<br><br>CONCLUSIONS: In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.}, }
@article {pmid15871723, year = {2005}, author = {Yamasaki, T and Tsuda, H and Imazeki, N and Matsubara, O}, title = {Vascular endothelial growth factor mRNA levels quantified by reverse transcription-polymerase chain reaction in microdissected breast carcinoma tissues are correlated with histological type and grade of both invasive and intraductal components.}, journal = {Pathology international}, volume = {55}, number = {5}, pages = {255-263}, doi = {10.1111/j.1440-1827.2005.01822.x}, pmid = {15871723}, issn = {1320-5463}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Microdissection ; Middle Aged ; Neoplasm Invasiveness ; RNA, Messenger/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A/*genetics/metabolism ; }, abstract = {In breast cancer, vascular endothelial growth factor (VEGF) is a prognostic factor, but the relationship of VEGF mRNA levels with various parameters or tumor progression is unclear. VEGF mRNA levels were measured in 48 cases of invasive ductal carcinoma by using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean VEGF mRNA levels were compared among different histological types and grades in 41 and 29 samples of invasive and intraductal components, respectively. VEGF mRNA levels were always higher in cancerous cells than in non-cancerous cells, but mean VEGF mRNA levels were not significantly different between invasive component (3.24 +/- 3.18-fold the value of non-cancerous tissue) and intraductal component (4.14 +/- 4.43-fold). They were higher in papillotubular type than in other types, and higher in grade 2 carcinomas than in grade 3 carcinomas of invasive component, and higher in comedo type than in other types of intraductal component. Mean VEGF mRNA levels were higher in the VEGF-immunopositive group than in the VEGF-immunonegative group. There was no correlation between VEGF mRNA levels and tumor size, nodal status, or hormone receptor status. VEGF expression may play an important role in the development of both invasive and intraductal carcinoma components, especially those carcinoma components of less aggressive histological features.}, }
@article {pmid15864214, year = {2005}, author = {Fernandez, C and Chetaille, B and Tasei, AM and Sastre, B and Sahel, J and Payan-Defais, MJ}, title = {From pancreatic intraepithelial neoplasia to cancer: a dramatic progression with K-ras status analysis.}, journal = {Gastroenterologie clinique et biologique}, volume = {29}, number = {4}, pages = {465-468}, doi = {10.1016/s0399-8320(05)80818-8}, pmid = {15864214}, issn = {0399-8320}, mesh = {Carcinoma in Situ/diagnosis/*genetics/*physiopathology ; Cell Transformation, Neoplastic/*genetics ; Disease Progression ; Female ; Genes, ras/*genetics ; Humans ; Immunohistochemistry ; Middle Aged ; Pancreatic Neoplasms/diagnosis/*genetics/*physiopathology ; }, abstract = {Pancreatic ductal carcinomas are thought to arise from precursor ductal lesions called pancreatic intra-epithelial neoplasias or PanINs. We report the case of a woman suffering from idiopathic chronic pancreatitis associated with PanINs lesions who developed six years later an invasive ductal carcinoma. Immunohistochemistry for p53, HER-2/neu and genetic analysis of K-ras oncogene were performed at different stages of disease and revealed that the PanINs and the carcinoma did not express p53 and HER-2/neu gene products whereas a K-ras mutation was present at the carcinoma stage. The relationship between cancer and chronic pancreatitis and the main difficulties concerning the early diagnostic of pancreatic cancer are discussed.}, }
@article {pmid15846392, year = {2005}, author = {Ogbagabriel, S and Fernando, M and Waldman, FM and Bose, S and Heaney, AP}, title = {Securin is overexpressed in breast cancer.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {18}, number = {7}, pages = {985-990}, doi = {10.1038/modpathol.3800382}, pmid = {15846392}, issn = {0893-3952}, mesh = {Analysis of Variance ; Blotting, Northern ; Blotting, Western ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/chemistry ; Cytoplasm/chemistry ; Estrogen Receptor alpha/analysis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Mitotic Index ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/*biosynthesis/genetics ; RNA, Messenger/genetics/metabolism ; Securin ; }, abstract = {Securin regulates sister chromatid separation during mitosis, induces bFGF-mediated angiogenesis, and securin overexpression causes in vitro transformation and in vivo tumor formation in nude mice. As estrogen administration to oophorectomized rats increased pituitary securin expression, we used immunohistochemistry to examine securin and estrogen receptor alpha (ER-alpha) expression in 90 breast tumors and 18 normal breast tissues. Breast tumor securin and ER-alpha expression were quantitated by image analysis and expressed as fold difference relative to securin expression in normal breast tissue. Low cytoplasmic securin expression was seen in the normal breast epithelium, whereas abundant cytoplasmic and nuclear securin expression was demonstrated in all 90 breast tumors. Highest securin expression was seen in brain metastatic breast tumors (4.3-fold, P<0.01), cells derived from metastatic breast cancers (6.5-fold, P<0.001), and in invasive ductal carcinoma (mean+/-s.e.: 3.8-fold, P<0.001). Highly pleomorphic (4.1-fold) or highly proliferative breast tumors (1.6-fold) exhibited high immunohistochemical securin expression compared to low-grade breast tumors (P<0.05). Northern blot analysis in 12 of the breast tumors confirmed the immunohistochemical findings demonstrating increased securin mRNA expression compared to normal breast mucosa (2.5-fold, P=0.03), with highest securin evident in invasive (3.5-fold) vs noninvasive tumors (1.9-fold, P=0.03). In addition, some tumors that exhibited high securin expression also expressed high ER-alpha levels (P<0.0001). These results demonstrate that the estrogen-induced transforming gene, securin is abundantly expressed in breast carcinoma, and is associated with the presence of metastatic spread, and lymph node invasion. We propose immunohistochemical tumor securin expression as a potential invasive marker, and novel therapeutic target in breast cancer.}, }
@article {pmid15844251, year = {2004}, author = {Tamiolakisl, D and Venizelos, I and Lambropoulou, M and Jivannakis, T and Seliniotakis, E and Tsikouras, P and Limberis, V and Tsalkidis, A and Papadopoulos, N}, title = {Gains and losses of HLA class II (DR) and CD4 in atypical hyperplasia, carcinoma in situ and infiltrating ductal carcinoma of the breast.}, journal = {Acta medica (Hradec Kralove)}, volume = {47}, number = {4}, pages = {257-262}, pmid = {15844251}, issn = {1211-4286}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*immunology ; CD4 Antigens/analysis ; *CD4 Lymphocyte Count ; Carcinoma, Ductal, Breast/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*immunology ; Female ; HLA-DR Antigens/*analysis ; Humans ; Hyperplasia/immunology ; Middle Aged ; }, abstract = {AIM: Breast cancer is a frequent cause of death among women with gynaecologic malignancies despite the introduction of combination chemotherapy. There is therefore a need for new therapeutic strategies for patients with breast cancer, such as cellular immunotherapy. In this immunohistochemical study we analyzed the epithelial expression of major histocompatibility complex (MHC) class II (HLA-DR) on atypical and malignant primary mammary epithelial cells, as well as the magnitude of the stromal T lymphocytes (T4 subset) at the tumor site.<br><br>EXPERIMENTAL DESIGN: The study was carried out retrospectively in tumor tissue from 82 patients with mammary lesions (31 cases of atypical ductal hyperplasia -ADH-, 12 cases of ductal carcinoma in situ -DCIS- and 39 cases of infiltrating ductal carcinoma not otherwise specified -IDC-NOS). Medullary carcinomas were not included in our investigation. Material used had been formalin fixed and paraffin embedded.<br><br>RESULTS: HLA class II (DR) was expressed in 20 of 31 ADHs (64.5%), in 4 of 12 DCISs (33.3%), and in 10 of 39 IDC-NOSs (25.6%). CD4 was expressed in 9 of 31 ADHs (29%), in 5 of 12 DCISs (42%), and in 26 of 39 IDC-NOSs (67%).<br><br>CONCLUSIONS: The results showed decreased epithelial expression of HLA class II (DR) and increased stromal expression of CD4, as the lesion progressed to malignancy. Gradual loss of epithelial HLA class II expression might be a manifestation of cellular differentiation from the atypical form versus the malignant one, signaling simultaneously a selective effect on the response capacity of the immune system.}, }
@article {pmid15840906, year = {2005}, author = {Liesmaa, I and Kuoppala, A and Shiota, N and Kokkonen, JO and Kostner, K and Mäyränpää, M and Kovanen, PT and Lindstedt, KA}, title = {Increased expression of bradykinin type-1 receptors in endothelium of intramyocardial coronary vessels in human failing hearts.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {288}, number = {5}, pages = {H2317-22}, doi = {10.1152/ajpheart.00815.2004}, pmid = {15840906}, issn = {0363-6135}, mesh = {Adult ; Cardiomyopathy, Dilated/physiopathology ; Coronary Disease/physiopathology ; Coronary Vessels/*physiology ; Endothelium, Vascular/*physiology ; Female ; Heart Failure/*physiopathology ; Humans ; Male ; Middle Aged ; RNA, Messenger/analysis ; Receptor, Bradykinin B1/*genetics ; Receptor, Bradykinin B2/genetics ; Tumor Necrosis Factor-alpha/genetics ; }, abstract = {In experimental animals, bradykinin type-1 receptors (BK-1Rs) are induced during inflammation and ischemia, and, by exerting either cardioprotective or cardiotoxic effects, they may contribute to the pathogenesis of heart failure. Nothing is known about the expression of BK-1Rs in human heart failure. Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13), due to idiopathic dilated cardiomyopathy (IDC; n = 7) or to coronary heart disease (CHD; n = 6), and from normal hearts (n = 6). The expression of BK-1Rs was analyzed by means of competitive RT-PCR, Western blot analysis, and immunohistochemistry. Expression of BK-1R mRNA was increased in both IDC (2.8-fold) and CHD (2.1-fold) hearts compared with normal hearts. The observed changes were verified at the protein level. Expression of BK-1Rs in failing hearts localized to the endothelium of intramyocardial coronary vessels and correlated with an increased expression of TNF-alpha in the vessel wall. Treatment of human coronary artery endothelial cells with TNF-alpha increases their BK-1R expression. These novel results show that BK-1Rs are induced in the endothelium of intramyocardial coronary vessels in failing human hearts and so may participate in the pathogenesis of heart failure.}, }
@article {pmid15840262, year = {2005}, author = {Mao, GY and Yang, J and Chen, HB and Guo, W and Nie, HX}, title = {[A study of phenotype and function of dendritic cells and secretory cytokine in allergic asthmatic patients].}, journal = {Zhonghua nei ke za zhi}, volume = {44}, number = {3}, pages = {206-209}, pmid = {15840262}, issn = {0578-1426}, mesh = {Adolescent ; Adult ; Asthma/*immunology ; Cytokines/*metabolism ; Dendritic Cells/*immunology/metabolism ; Female ; Humans ; Immunophenotyping ; Interleukin-10/metabolism ; Interleukin-12/metabolism ; Male ; T-Lymphocytes/immunology ; }, abstract = {OBJECTIVE: To investigate the deficiency of the expression of the phenotypes (CD(1a), CD(83), CD(40), CD(86)) and cytokines (IL-12 and IL-10) by human peripheral blood monocyte (PBMC)-derived dendritic cell (DCs) from asthmatic subjects, and their influence on naive T cell polarization.<br><br>METHODS: Adherent cells were isolated from peripheral blood samples in asthmatic patients and in healthy volunteers, and were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 as immature DC (iDC). iDCs were stimulated with lipopolysaccharide as mature DC (mDCs). Nonadherent cells were obtained from umbilical cord blood by idem methods, and na&#xef;ve T cells were sorted by adding anti-CD(4) and anti-CD(45RA) in nonadherent cells respectively and magnetic microbeads. Na&#xef;ve T cells and mDCs from two groups were co-cultured in complete RPMI1640 media respectively, and naive T cells polarized as T helper cells 1 (Th1) and Th2. The expression of the CD(1a), CD(83), CD(40) and CD(86) on mature DCs were examined by fluorescent activated cell sorter. IL-12 and IL-10 released by mDCs and IL-4 and IFNgamma produced by Th cells were measured by ELISA.<br><br>RESULTS: (1) The expression of CD(86) on dendritic cells from atopic asthmatics was higher than that from healthy control subjects (40.75 +/- 3.99 vs 29.88 +/- 1.25, P < 0.01). (2) The levels of IL-12, IL-12p40 and IL-10 produced by DCs from asthmatic subjects were all significantly lower than those from healthy control group (217.79 +/- 118.65 vs 905.66 +/- 495.32, P < 0.01; 2072.22 +/- 1496.37 vs 5569.43 +/- 2922.75, P < 0.01; 336.89 +/- 261.52 vs 1425.00 +/- 1148.87, P < 0.05, respectively). (3) IL-4 production by Th2 cells which were primed by DCs from asthmatics was significantly increased as compared to that from control group (368.56 +/- 190.72 vs 584.91 +/- 290.13, P < 0.01); On the contrary, IFNgamma in the patient group was reduced as compared to that in the control group (425.33 +/- 164.94 vs 49.86 +/- 18.14, P < 0.05). (4) In the patient group, the level of IL-12 was positively correlated to that of IFNgamma (P < 0.05), negatively correlated to that of IL-4 (P < 0.05); IL-10 was negatively correlated to IL-4 (P < 0.05). (5) There was a positive correlation between IL-12 and IL-10 in the two groups (P < 0.01).<br><br>CONCLUSION: Because of DC deficiency, na&#xef;ve T cells preferentially polarize to Th2 which synthesize more Th2-type cytokine (i.e. IL-4) and T cell tolerance cannot be induced, which may be one of the important pathogenic mechanisms for allergic asthma.}, }
@article {pmid15837543, year = {2005}, author = {Parrella, P and Scintu, M and Prencipe, M and Poeta, ML and Gallo, AP and Rabitti, C and Rinaldi, M and Tommasi, S and Paradiso, A and Schittulli, F and Valori, VM and Toma, S and Altomare, V and Fazio, VM}, title = {HIC1 promoter methylation and 17p13.3 allelic loss in invasive ductal carcinoma of the breast.}, journal = {Cancer letters}, volume = {222}, number = {1}, pages = {75-81}, doi = {10.1016/j.canlet.2004.08.026}, pmid = {15837543}, issn = {0304-3835}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Chromosome Deletion ; Chromosomes, Human, Pair 17/genetics ; *DNA Methylation ; DNA Mutational Analysis ; DNA, Neoplasm/analysis ; DNA-Binding Proteins ; Female ; Humans ; Kruppel-Like Transcription Factors ; Microsatellite Repeats ; *Promoter Regions, Genetic ; Transcription Factors/*genetics ; }, abstract = {The HIC1 gene is a transcriptional regulator commonly methylated in a variety of human cancer. Thirty-three invasive ductal carcinomas of the breast and 21 matched normal breast tissues were analysed for HIC1 promoter methylation, and allelic loss of a 700 kb region spanning the gene locus. At least one genetic or epigenetic abnormality was found in 27 of the carcinomas tested (82%). Promoter methylation was demonstrated in 21 carcinomas (64%), and nine normal tissues (43%), whereas 18 malignant tumors (54%) showed allelic loss. Concomitant loss of heterozigosity and promoter hypermethylation in the region spanning HIC1 was detected in eight carcinomas (24%) suggesting that in this subset of tumors both copies of the gene are functionally lost. These observations support a role for the HIC1 gene in the pathogenesis of breast ductal carcinomas.}, }
@article {pmid15832194, year = {2005}, author = {Furukawa, T and Fujisaki, R and Yoshida, Y and Kanai, N and Sunamura, M and Abe, T and Takeda, K and Matsuno, S and Horii, A}, title = {Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {18}, number = {8}, pages = {1034-1042}, doi = {10.1038/modpathol.3800383}, pmid = {15832194}, issn = {0893-3952}, mesh = {Adenocarcinoma, Mucinous/genetics/metabolism/*pathology ; Adenocarcinoma, Papillary/genetics/metabolism/*pathology ; Carcinoma, Pancreatic Ductal/genetics/metabolism/*pathology ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; DNA Mutational Analysis/methods ; DNA-Binding Proteins/metabolism ; Disease Progression ; Dual Specificity Phosphatase 6 ; Humans ; Immunohistochemistry ; Mutation ; Pancreatic Ducts/metabolism/pathology ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Precancerous Conditions/metabolism/*pathology ; Protein Tyrosine Phosphatases/*metabolism ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Signal Transduction ; Smad4 Protein ; Trans-Activators/metabolism ; Tumor Suppressor Protein p53/metabolism ; ras Proteins ; }, abstract = {DUSP6/MKP-3 is identified as a candidate tumor suppressor gene for pancreatic cancer. The aim of this study was to elucidate the roles of DUSP6 in the pancreatic carcinogenesis through the pancreatic intraepithelial neoplasia and/or intraductal papillary-mucinous neoplasms, both of which are considered to be precursor lesions of invasive carcinoma of the pancreas, by comparing with involvements of other major tumor suppressive pathways. Expressions of DUSP6, CDKN2A, TP53, and SMAD4 were investigated by immunohistochemistry in a total of 206 lesions of dysplastic ductal precursors and carcinomas retrieved from 52 pancreata with invasive ductal carcinomas and 51 of those with intraductal papillary-mucinous neoplasms. The intensity of staining was evaluated in lesions at different atypical grades and statistically compared among them. Mutations of KRAS2 were analyzed by methods of the allele-specific oligonucleotide hybridization and nucleotide sequencing. In pancreata with invasive ductal carcinomas, expressions of DUSP6 were abrogated exclusively in the invasive carcinoma cells in contrast to its fairly preserved expressions in pancreatic intraepithelial neoplasia. In pancreata with intraductal papillary-mucinous neoplasms, abrogated expressions of DUSP6 were observed in a relatively small fraction of intraductal adenoma/borderlines and intraductal carcinomas. Most of the intraductal adenoma/borderline lesions with abrogation of DUSP6 harbored mutations of KRAS2. None of the molecules was associated with each other in any grade of lesions. Morphological variations of papillae of the intraductal papillary-mucinous neoplasms were evaluated and analyzed for their associations with abrogations of the molecules, which resulted in finding of no significant associations. Our results suggest that the abrogation of DUSP6 is associated exclusively with progression from pancreatic intraepithelial neoplasia to the invasive ductal carcinoma while it is potentially associated with initiation of intraductal papillary-mucinous neoplasms with mutated KRAS2, which is independent of other major tumor suppressive pathways in both types of neoplasms.}, }
@article {pmid15830137, year = {2005}, author = {Man, YG and Fu, SW and Schwartz, A and Pinzone, JJ and Simmens, SJ and Berg, PE}, title = {Expression of BP1, a novel homeobox gene, correlates with breast cancer progression and invasion.}, journal = {Breast cancer research and treatment}, volume = {90}, number = {3}, pages = {241-247}, doi = {10.1007/s10549-004-4492-9}, pmid = {15830137}, issn = {0167-6806}, support = {CA 91149/CA/NCI NIH HHS/United States ; K08 CA 101875/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*pathology ; Case-Control Studies ; Disease Progression ; Female ; *Gene Expression Profiling ; Homeodomain Proteins/*biosynthesis ; Humans ; Neoplasm Invasiveness/*genetics ; RNA, Messenger/biosynthesis ; Transcription Factors/*biosynthesis ; }, abstract = {BACKGROUND: Our previous studies revealed that the mRNA encoded by BP1, a member of the homeobox gene superfamily of transcription factors, was expressed in leukemia and infiltrating breast ductal carcinoma (IDC). This study investigated the immunohistochemical profile of BP1, to determine whether the expression of BP1 protein correlated with breast tumor progression and invasion and whether BP1 was co-localized with erbB2.<br><br>DESIGN: Paraffin sections from normal reduction mammoplasties (n = 34) and a variety of in situ and invasive breast cancers (n = 270) were either singly immunostained for BP1, or doubly immunostained for BP1 plus either erbB2 or Ki-67.<br><br>RESULTS: The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and carcinogenesis. BP1 expression was barely detectable in normal reduction mammoplasties compared to distinct staining in 21, 46, and 81% of hyperplastic, in situ, and infiltrating lesions, respectively. In cases with co-existing normal, hyperplastic, in situ, and invasive lesions, the tumor cells of the invasive lesions consistently showed the highest frequency and the highest intensity of BP1 immunostaining, followed by in situ tumor cells. Double immunostaining revealed that BP1 co-localized with a subset of erbB2 positive cells in all 15 in situ and IDC tumors examined, and that BP1 positive cells had a substantially higher proliferation rate than morphologically similar cells without BP1 expression.<br><br>CONCLUSION: These findings suggest that BP1 is an important upstream factor in an oncogenic pathway, and that expression of BP1 may reliably reflect or directly contribute to tumor progression and/or invasion.}, }
@article {pmid15812230, year = {2005}, author = {Feder-Mengus, C and Schultz-Thater, E and Oertli, D and Marti, WR and Heberer, M and Spagnoli, GC and Zajac, P}, title = {Nonreplicating recombinant vaccinia virus expressing CD40 ligand enhances APC capacity to stimulate specific CD4+ and CD8+ T cell responses.}, journal = {Human gene therapy}, volume = {16}, number = {3}, pages = {348-360}, doi = {10.1089/hum.2005.16.348}, pmid = {15812230}, issn = {1043-0342}, mesh = {Animals ; Antibodies, Monoclonal/metabolism ; Antigen-Presenting Cells/*immunology/metabolism ; Antigens, Neoplasm ; CD4-Positive T-Lymphocytes/*immunology ; CD40 Antigens/*immunology/metabolism ; CD40 Ligand/immunology/metabolism ; CD8-Positive T-Lymphocytes/*immunology ; Cell Line ; Chlorocebus aethiops ; Cytokines/genetics/metabolism ; Cytotoxicity Tests, Immunologic ; DNA Primers ; Flow Cytometry ; Genetic Vectors ; Immunity, Cellular/*immunology ; Immunotherapy/*methods ; Interleukin-12/metabolism ; Interleukin-12 Subunit p40 ; Ligands ; Lymphocyte Activation/immunology ; MART-1 Antigen ; Neoplasm Proteins/metabolism ; Neoplasms/immunology/*therapy ; Protein Subunits/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vaccinia virus/genetics/*immunology ; }, abstract = {Recombinant poxviruses expressing immunomodulatory molecules together with specific antigens represent powerful vaccines for cancer immunotherapy. Recently, we and others have demonstrated, in vitro and in vivo, that coexpression of CD80 and CD86 costimulatory molecules enhances the immunogenic capacity of a recombinant vaccinia virus (rVV) encoding different tumor-associated antigens. To further investigate the capacity of these vectors to provide ligands for different costimulatory pathways relevant in the generation of T cell responses, we constructed a recombinant virus (rVV) expressing CD40 ligand or CD154 (CD154rVV). Upon binding the CD40 receptor expressed on antigen presenting cells (APC), this molecule, physiologically expressed on activated CD4+ T cells, increases their antigen presentation and immunostimulatory capacities. Therefore, we evaluated the effects of CD154rVV infection on APC activation and its consequences on T cell stimulation. CD154rVV infection of autologous fibroblasts, monocytes, or iDC promoted the expression of a number of cytokines, including GM-CSF, TNF-alpha, and IL-15 in iDC. Most importantly, IL-12 p40 gene expression and protein secretion were induced by CD154rVV but not by wild-type VV (WT VV) in either CD14+ cells or iDC, and these effects could be blocked by anti-CD40 monoclonal antibodies. Furthermore, phenotypic characterization of CD154rVV infected iDC revealed enhanced expression of CD83 and CD86 surface markers as compared with wild-type vaccinia virus infection. As expected, VV infection triggered cytokines gene expression in cultures including APC and T cells from VV immune donors. However, cytokine genes typically expressed by T cell receptor triggered T cells such as those encoding IL-2 and IFN-gamma, or T cell proliferation, were detectable to a significantly higher extent in CD154rVV infected cultures, as compared with WT VV. Activation of specific CD8+ T cells was then investigated using MART-1/Melan-A(27-35) epitope as the model of tumor-associated antigen (TAA). In the presence of CD154rVV activated APCs, significantly higher numbers of specific cytotoxic CD8+ T cells were detected, as compared with cultures performed in the presence of WT VV or in the absence of virus. Taken together, these data indicate that functional CD154 expression from rVV infected cells promotes APC activation, thereby enhancing antigen-specific T cell generation. Such a recombinant vector might help bypass the requirement for activated helper cells during CTL priming, thus qualifying as a potentially relevant vector in the generation of CD8+ T cell responses in cancer immunotherapy.}, }
@article {pmid15808750, year = {2005}, author = {Burkett, EL and Hershberger, RE}, title = {Clinical and genetic issues in familial dilated cardiomyopathy.}, journal = {Journal of the American College of Cardiology}, volume = {45}, number = {7}, pages = {969-981}, doi = {10.1016/j.jacc.2004.11.066}, pmid = {15808750}, issn = {0735-1097}, support = {NIH R01 HL 58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Cardiomyopathy, Dilated/diagnostic imaging/*genetics ; Echocardiography ; Electrocardiography ; Family ; Genetic Counseling ; Genetic Testing ; Humans ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular dilatation and systolic dysfunction after known causes have been excluded. Idiopathic dilated cardiomyopathy occurring in families, or familial dilated cardiomyopathy (FDC), may occur in 20% to 50% of IDC cases. Sixteen genes have been shown to cause autosomal dominant FDC, but collectively may account for only a fraction of genetic causation; it is anticipated that additional genes causative of FDC will be discovered. Familial dilated cardiomyopathy demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making clinical and genetic diagnosis complex. Echocardiographic and electrocardiographic screening of first-degree relatives of individuals with IDC and FDC is indicated, as detection and treatment are possible before the onset of advanced symptomatic disease. Genetic counseling for IDC and FDC is also indicated to assist with family evaluations for genetic disease and with the uncertainty and anxiety surrounding the significance of clinical and genetic evaluation. Genetic testing is not yet commonly available, but its emergence will provide new opportunities for presymptomatic diagnosis.}, }
@article {pmid15802534, year = {2005}, author = {Semino, C and Angelini, G and Poggi, A and Rubartelli, A}, title = {NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1.}, journal = {Blood}, volume = {106}, number = {2}, pages = {609-616}, doi = {10.1182/blood-2004-10-3906}, pmid = {15802534}, issn = {0006-4971}, mesh = {Calcium Signaling ; Cell Communication/immunology ; Cell Differentiation ; Cell Polarity ; Cytokines/biosynthesis ; Cytotoxicity, Immunologic ; Dendritic Cells/cytology/*immunology/metabolism ; HMGB1 Protein/*biosynthesis ; Humans ; In Vitro Techniques ; Interleukin-18/*biosynthesis/pharmacology ; Killer Cells, Natural/drug effects/*immunology/metabolism ; Recombinant Proteins/pharmacology ; Tubulin/metabolism ; }, abstract = {Interaction of natural killer (NK) cells with autologous immature dendritic cells (DCs) results in reciprocal activation; however, the underlying mechanisms are so far elusive. We show here that NK cells trigger immature DCs to polarize and secrete interleukin 18 (IL-18), a cytokine lacking a secretory leader sequence. This occurs through a Ca2+-dependent and tubulin-mediated recruitment of IL-18-containing secretory lysosomes toward the adhering NK cell. Lysosome exocytosis and IL-18 secretion are restricted at the synaptic cleft, thus allowing activation of the interacting NK cells without spreading of the cytokine. In turn, DC-activated NK cells secrete the proinflammatory cytokine high mobility group B1 (HMGB1), which induces DC maturation and protects DCs from lysis. Also HMGB1 is a leaderless cytokine that undergoes regulated secretion. Differently from IL-18, soluble HMGB1 is consistently detected in NK/DC supernatants. These data point to secretion of leaderless cytokines as a key event for the reciprocal activation of NK cells and DCs. DCs initiate NK cell activation by targeted delivery of IL-18, thus instructing NK cells in the absence of adaptive-type cytokines; in turn, activated NK cells release HMGB1, which promotes inflammation and induces DC maturation, thus favoring the onset of the adaptive immune response.}, }
@article {pmid15799760, year = {2005}, author = {Zheng, W and Zheng, J and Ma, L and Meng, F and Huang, L and Ma, D}, title = {Comparison of HER-2/neu, ER and PCNA expression in premenopausal and postmenopausal patients with breast carcinoma.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {113}, number = {3}, pages = {175-181}, doi = {10.1111/j.1600-0463.2005.apm1130304.x}, pmid = {15799760}, issn = {0903-4641}, mesh = {Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/*diagnosis/immunology/pathology ; Carcinoma, Ductal, Breast/*diagnosis/immunology/pathology ; Cell Membrane/chemistry/immunology ; Cell Nucleus/chemistry/immunology ; Cell Proliferation ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; *Postmenopause ; *Premenopause ; Proliferating Cell Nuclear Antigen/analysis/*metabolism ; Receptor, ErbB-2/analysis/*metabolism ; Receptors, Estrogen/analysis/*metabolism ; }, abstract = {We attempted to compare the pattern of HER-2/neu, ER and PCNA in premenopausal and postmenopausal patients with breast carcinoma to identify potential biological differences. Five hundred and forty-eight samples from 318 premenopausal and 230 postmenopausal women with invasive ductal carcinoma of the breast were evaluated for HER-2/neu, ER and PCNA expression by immunohistochemistry. HER-2/neu expression showed 27.4% positivity in premenopausal and 24.8% in postmenopausal women; there was no significant difference between the two groups (p>0.05). In contrast, HER-2/neu expression was found to be significantly associated with ER negativity in the two groups (p<0.05 in premenopausal, p<0.001 in postmenopausal patients). However, it was significantly associated with PCNA expression only in the postmenopausal group (p<0.001). 54.4% showed premenopausal tumor cell ER positivity, whereas 64.3% of the postmenopausal group showed positivity. ER expression showed a significant correlation with patient menopausal status (p<0.05). The prevalence of PCNA positivity in the tumor cell components is slightly higher in postmenopausal compared to premenopausal women (p>0.20). The current study is consistent with reports from other groups regarding the correlation of HER-2/neu with adverse pathologic features and with expression of other markers in carcinoma. We also observed there was no trend toward increased HER-2/neu expression in either premenopausal or postmenopausal patients, i.e. there was similar HER-2/neu expression in the two groups. This suggests that HER-2/neu status could be used to determine assignment to specific intensive adjuvant therapy and evaluation of biological behavior in both pre- and postmenopausal patients with breast carcinoma.}, }
@article {pmid15790698, year = {2005}, author = {Busund, LT and Richardsen, E and Busund, R and Ukkonen, T and Bjørnsen, T and Busch, C and Stalsberg, H}, title = {Significant expression of IGFBP2 in breast cancer compared with benign lesions.}, journal = {Journal of clinical pathology}, volume = {58}, number = {4}, pages = {361-366}, pmid = {15790698}, issn = {0021-9746}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/pathology ; Carcinoma in Situ/chemistry/pathology ; Epithelial Cells/metabolism/pathology ; Female ; Humans ; Hyperplasia/metabolism ; Image Processing, Computer-Assisted/methods ; Immunohistochemistry/methods ; Insulin-Like Growth Factor Binding Protein 2/*analysis ; Mammary Glands, Human/chemistry/pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Proteins/*analysis ; Precancerous Conditions/chemistry/pathology ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {BACKGROUND/AIM: Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) play a role in the normal development of breast tissue, and possibly in breast cancer aetiology. IGFBP2, one of six members of the IGFBP superfamily, acts as regulator of the IGFs and has pleiotropic effects in normal and neoplastic tissues. Because IGFs have mitogenic effects on mammary epithelia, this study investigated IGFBP2 expression in mammary tissues of different benign and malignant entities.<br><br>METHODS: Immunohistochemistry was used to study correlations between the presence and intensity of IGFBP2 staining and tumour type and grade, in addition to steroid hormone receptor status, in 120 breast specimens. Expression was measured by quantitative colour video image analysis and semiquantitative evaluation, and the measurements correlated well (r = 0.92; p<0.05).<br><br>RESULTS: Both methods found no significant expression of IGFBP2 in normal glandular cells and hyperplasia (group I). Atypical hyperplasia showed a slightly increased cytoplasmic expression of IGFBP2, and carcinoma in situ showed a distinctive, membrane associated and cytoplasmic expression (group II). Infiltrating carcinomas strongly expressed cytoplasmic IGFBP2 (group III). There were significant differences between group I and II, and between group II and III. There were no significant differences between invasive lobular and invasive ductal carcinoma, or between grades I, II, and III within these entities. There was no significant correlation between IGFBP2 immunostaining and oestrogen or progesterone receptor positivity within the malignant group.<br><br>CONCLUSIONS: IGFBP2 mitogenic signals of autocrine/paracrine regulatory mechanisms may be responsible for the growth of breast carcinomas and IGFBP2 may be an independent indicator of malignancy.}, }
@article {pmid15778382, year = {2005}, author = {Buettner, M and Meinken, C and Bastian, M and Bhat, R and Stössel, E and Faller, G and Cianciolo, G and Ficker, J and Wagner, M and Röllinghoff, M and Stenger, S}, title = {Inverse correlation of maturity and antibacterial activity in human dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {174}, number = {7}, pages = {4203-4209}, doi = {10.4049/jimmunol.174.7.4203}, pmid = {15778382}, issn = {0022-1767}, mesh = {Bacteria/growth &amp; development/*immunology ; Bronchoalveolar Lavage ; *Cell Differentiation ; Cells, Cultured ; Dendritic Cells/*cytology/*immunology ; Humans ; *Immunity, Innate ; Immunophenotyping ; Macrophages, Alveolar/immunology ; Mycobacterium tuberculosis/growth &amp; development/immunology ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Dendritic cells (DCs) are a key part of host defense against microbial pathogens, being part of the innate immune system, but also instructing the adaptive T cell response. This study was designed to evaluate whether human DCs directly contribute to innate immunity by killing intracellular bacteria, using tuberculosis as a model. DCs were detected in bronchoalveolar lavage samples indicating that DCs are available for immediate interaction with Mycobacterium tuberculosis (M. Tb) after inhalation of the pathogen. The phenotype of DC in bronchoalveolar lavage closely resembles monocyte-derived immature DC (iDC) according to the expression of CD1a, CD83, and CCR7. The antimicrobial activity of iDC against intracellular M. Tb inversely correlated with TNF-alpha-release and was enhanced by treatment with anti-TNF-alpha Abs. Differentiation of iDC into mature DC by addition of TNF-alpha or activation via Toll-like receptors further reduced killing of M. Tb. The antibacterial activity against intracellular M. Tb of all DCs was significantly lower than alveolar macrophages. Therefore, the maintenance of a pool of DCs at the site of disease activity in tuberculosis, and the maturation of these DC by TNF-alpha provides a mechanism by which M. Tb escapes the innate immune system.}, }
@article {pmid15770294, year = {2005}, author = {Agarwal, AK and Venugopalan, P and Meharali, A and de Bono, D}, title = {Survival analysis of patients with idiopathic dilated cardiomyopathy in Oman.}, journal = {Saudi medical journal}, volume = {26}, number = {2}, pages = {220-224}, pmid = {15770294}, issn = {0379-5284}, mesh = {Adolescent ; Adult ; Aged ; Arrhythmias, Cardiac/epidemiology ; Cardiomyopathy, Dilated/epidemiology/*mortality/physiopathology ; Comorbidity ; Female ; Humans ; Male ; Oman/epidemiology ; Prospective Studies ; Stroke Volume ; Survival Analysis ; }, abstract = {OBJECTIVE: To study the 10-year survival of adults with idiopathic dilated cardiomyopathy (IDC) in Oman.<br><br>METHODS: Ninety-seven patients aged >13 years with IDC attending the Cardiology Unit, Sultan Qaboos University Hospital, Muscat, Oman from 1992-1995 were prospectively studied, in order to identify the outcome and factors contributing to death.<br><br>RESULTS: Among 97 patients, 2 died from acute heart failure at presentation. The remaining 95 patients were followed up for periods ranging from 1-10 years (median 7 years). Twenty-four out of 95 patients exhibited clinical deterioration with reduced left ventricular ejection fraction (LVEF), by 5-11%, and 17 of them expired due to resistant heart failure. The remaining 71 patients remained stable and did not show deterioration in LVEF; however, 7 of them died suddenly at home possibly from ventricular arrhythmia. The survival rates were 94% at one year (95% confidence interval [CI] 88% to 99%), 86% at 3 years (95% CI 79% to 93%), and 64% at 10 years (95% CI 51% to 78%). Mean survival was 6.5 years (95% CI 6 to 7 years). Multivariate regression analysis revealed that factors related to death were LVEF <30% (p<0.001) and presence of severe mitral regurgitation (p=0.01).<br><br>CONCLUSION: Outcome of dilated cardiomyopathy has improved due to greater understanding of this condition leading to better therapeutic approach. Resistant heart failure and cardiac arrhythmias remain the main causes of mortality. Poor outcome was related to low LVEF and presence of severe mitral regurgitation.}, }
@article {pmid15746244, year = {2005}, author = {Klein, E and Koch, S and Borm, B and Neumann, J and Herzog, V and Koch, N and Bieber, T}, title = {CD83 localization in a recycling compartment of immature human monocyte-derived dendritic cells.}, journal = {International immunology}, volume = {17}, number = {4}, pages = {477-487}, doi = {10.1093/intimm/dxh228}, pmid = {15746244}, issn = {0953-8178}, mesh = {Antigens, CD ; Dendritic Cells/*immunology ; Endosomes/immunology ; Golgi Apparatus/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunoglobulins/*immunology ; Membrane Glycoproteins/*immunology ; Time Factors ; }, abstract = {Dendritic cells (DC) change their phenotype and functional properties during maturation. CD83 cell surface expression is induced on mature DC (mDC). In this study, we investigated intracellular CD83 localization and transport in human monocyte-derived DC. The enhanced level of CD83 cell surface expression in mDC resulted predominantly from increased protein synthesis, and in addition from regulated intracellular transport of CD83 protein. An internal pool of CD83 protein is present in immature DC (iDC). Although CD83 protein in iDC and in mDC was localized in the Golgi compartment and in recycling endosomes, only in mature cells did CD83 co-localize with MHC class II molecules in endocytic vesicles. CD83 cell surface expression on iDC was induced by inhibition of endocytosis. This result could be explained by CD83 cycling between endosomes and the cell surface in iDC. The mDC also rapidly internalized membrane-bound CD83 protein. Furthermore, a thiol protease inhibitor and specific cathepsin inhibitors impaired CD83 up-regulation in DC, indicating a role of endosomal proteases in the maturation-induced exposure of CD83 on the plasma membrane.}, }
@article {pmid15736718, year = {2004}, author = {Ozbilgin, MK and Polat, S and Mete, UO and Tap, O and Kaya, M}, title = {Antigen-presenting cells in the hypertrophic pharyngeal tonsils: a histochemical, immunuhistochemical and ultrastructural study.}, journal = {Journal of investigational allergology &amp; clinical immunology}, volume = {14}, number = {4}, pages = {320-328}, pmid = {15736718}, issn = {1018-9068}, mesh = {Antigen-Presenting Cells/*physiology ; Child ; Child, Preschool ; Dendritic Cells, Follicular/physiology ; HLA-DR Antigens/analysis ; Humans ; Hypertrophy ; Immunohistochemistry ; Microscopy, Electron ; Palatine Tonsil/immunology/*pathology/ultrastructure ; Pharynx/immunology/*pathology/ultrastructure ; }, abstract = {The antigen presenting cells (APCs) with special interest to dendritic cells (DC), were investigated in 28 hypertrophic and 10 control pharyngeal tonsils of children by histochemistry, immunohistochemistry and electron microscopy. In this study, we are trying to clarify the function and classification of APC in pharyngeal tonsils using morphologic criteria, Human Leukocyte Antigen Monoclonal Antibody (HLA-DR MoAb), which is specific for APCs, and acid phosphatase (APh) reacting with both phagosomes and lysosomes. The surface epithelium of the patient group examined by light microscopy, heavy infiltration of lymphocytes, degenerated columnar cells and a few HLA-DR MoAb (+) columnar cells was observed. Additionally, a significant number of APCs which were Langerhans cells (LCs), interdigitating dendritic cell (IDC), follicular dendritic cell (FDC) and macrophages were stained with both HLA-DR MoAb and APh in the epithelial, interfollicular-subepithelial and follicular areas. Ultrastructural examinations revealed that lymphocytes, macrophages, LC and M cells were found among the surface columnar epithelial cells of the patient group. The interactions between M cells and LC suggested that M cells probably passed antigens from surface to LC. In the interfollicular-subepithelial areas of the hypertrophic pharyngeal tonsil, IDCs were in close contact with lymphocytes, macrophages and plasma cells. Seven types of FDCs (FDC-1 - FDC-7) were recognised according to their ultrastructural appearances. Differentiated FDCs (FDC-4) were also in close contact with each active subtype of FDCs in follicular areas besides lymphocytes. These findings supported the idea that although the pharyngeal tonsils contained several types of active APCs, only DC were in close contact with immunocompetent cells and the other APC's. Therefore, these morphologic appearances of DC could be a sign of function to initiate the immune response of the pharyngeal tonsil.}, }
@article {pmid15723402, year = {2005}, author = {Li, X and Huang, W and Yankeelov, TE and Tudorica, A and Rooney, WD and Springer, CS}, title = {Shutter-speed analysis of contrast reagent bolus-tracking data: Preliminary observations in benign and malignant breast disease.}, journal = {Magnetic resonance in medicine}, volume = {53}, number = {3}, pages = {724-729}, doi = {10.1002/mrm.20405}, pmid = {15723402}, issn = {0740-3194}, support = {R01 EB 00422/EB/NIBIB NIH HHS/United States ; R01 NS 40801/NS/NINDS NIH HHS/United States ; }, mesh = {Breast Diseases/*metabolism ; Breast Neoplasms/metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Contrast Media/*pharmacokinetics ; Female ; Fibroadenoma/*metabolism ; Gadolinium DTPA/*pharmacokinetics ; Humans ; Image Processing, Computer-Assisted ; }, abstract = {The standard pharmacokinetic model applied to contrast reagent (CR) bolus-tracking (B-T) MRI (dynamic-contrast-enhanced) data makes the intrinsic assumption that equilibrium transcytolemmal water molecule exchange is effectively infinitely fast. Theory and simulation have suggested that this assumption can lead to significant errors. Recent analyses of animal model experimental data have confirmed two predicted signature inadequacies: a specific temporal mismatch with the B-T time-course and a CR dose-dependent underestimation of model parameters. The most parsimonious adjustment to account for this aspect leads to the "shutter-speed" pharmacokinetic model. Application of the latter to the animal model data mostly eliminates the two signature inadequacies. Here, the standard and shutter-speed models are applied to B-T data obtained from routine human breast examinations. The signature standard model temporal mismatch is found for each of the three invasive ductal carcinoma (IDC) cases and for each of the three fibroadenoma (FA) cases studied. It is effectively eliminated by use of the shutter-speed model. The size of the mismatch is considerably greater for the IDC lesions than for the FA lesions, causing the shutter-speed model to exhibit improved discrimination of malignant IDC tumors from the benign FA lesions compared with the standard model. Furthermore, the shutter-speed model clearly reveals focal "hot spots" of elevated CR perfusion/permeation present in only the malignant tumors.}, }
@article {pmid15711412, year = {2005}, author = {Cocquyt, V and Van Belle, S}, title = {Lobular carcinoma in situ and invasive lobular cancer of the breast.}, journal = {Current opinion in obstetrics &amp; gynecology}, volume = {17}, number = {1}, pages = {55-60}, doi = {10.1097/00001703-200502000-00010}, pmid = {15711412}, issn = {1040-872X}, mesh = {Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/drug therapy/epidemiology/pathology/*surgery ; Carcinoma in Situ/drug therapy/epidemiology/pathology/*surgery ; Carcinoma, Lobular/drug therapy/epidemiology/pathology/*surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Incidence ; Magnetic Resonance Imaging ; Mastectomy, Radical ; Mastectomy, Segmental ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/epidemiology/etiology/pathology ; Neoplasm Staging ; Preoperative Care ; Prognosis ; Risk Factors ; Sentinel Lymph Node Biopsy ; Survival Rate ; }, abstract = {PURPOSE OF REVIEW: The incidence of lobular carcinoma in situ and invasive lobular carcinoma of the breast is increasing. Recent data suggest that lobular carcinoma in situ is an indolent precursor for breast cancer, rather than a pure risk factor. This could imply free surgical margins become important. The risk of contralateral carcinoma and of multifocality of invasive lobular carcinoma is higher than for invasive ductal carcinoma. Therefore, the need for mastectomy, or even for preventative contralateral mastectomy is questioned. Conventional mammography or ultrasonography cannot always give useful preoperative information about the extent of lobular cancers. The value of dynamic contrast-enhanced magnetic resonance imaging needs to be established for these patients.<br><br>RECENT FINDINGS: The risk of invasive carcinoma after lobular carcinoma in situ is increased. Invasive carcinoma is usually located at the index point of lobular carcinoma in situ and is of lobular histology. Dynamic contrast-enhanced magnetic resonance imaging can be useful in the detection and preoperative staging of invasive lobular carcinoma. The risk of local recurrence is high in patients with invasive lobular carcinoma. Mastectomy and breast reconstruction could be an option in selected patients. The response to preoperative chemotherapy is worse for invasive lobular carcinoma compared with invasive ductal carcinoma, with a greater need for rescue mastectomy.<br><br>SUMMARY: Lobular carcinoma in situ and invasive lobular carcinoma are different entities from ductal carcinoma in situ and invasive lobular carcinoma. Their biological profile should be studied further in order to make the fine tuning of treatment possible.}, }
@article {pmid15701478, year = {2005}, author = {Fauchier, L and Douglas, J and Babuty, D and Cosnay, P and Fauchier, JP}, title = {QT dispersion in nonischemic dilated cardiomyopathy. A long-term evaluation.}, journal = {European journal of heart failure}, volume = {7}, number = {2}, pages = {277-282}, doi = {10.1016/j.ejheart.2004.07.009}, pmid = {15701478}, issn = {1388-9842}, mesh = {Adult ; Aged ; Arrhythmias, Cardiac/*etiology ; Cardiomyopathy, Dilated/complications/*mortality/*physiopathology ; Death, Sudden, Cardiac/*etiology ; Disease-Free Survival ; *Electrocardiography ; Female ; Follow-Up Studies ; Heart Rate/physiology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Severity of Illness Index ; Ventricular Function, Left/*physiology ; }, abstract = {BACKGROUND: In idiopathic dilated cardiomyopathy (IDC), the predictive value of QT dispersion is still under debate.<br><br>AIMS: This study assessed the role of QT dispersion for the long-term risk of cardiac death and of major arrhythmic events in IDC.<br><br>METHODS AND RESULTS: In 162 patients with IDC (age 52+/-12 years), the QT interval on a 12-lead ECG was measured manually. QT dispersion was evaluated with QT range and QT standard deviation, for both QT and QTc (Bazett formula). With a follow-up of 53+/-41 months, QT dispersion was not a predictor of cardiac death in univariate or in multivariate analysis, and was of similar value for patients with or without bundle branch block. Using multivariate analysis, increased pulmonary capillary wedge pressure (p=0.003), decreased heart rate variability (Standard deviation of all NN intervals, p=0.01) and non-sustained ventricular tachycardia (NSVT) (p=0.03) were predictors of cardiac death. Sudden death and/or major arrhythmic events were independently predicted by NSVT (p=0.005), decreased heart rate variability (p=0.01) and late ventricular potentials on signal averaged ECG (p=0.02).<br><br>CONCLUSION: This study confirms the poor prognostic value of QT dispersion in patients with IDC. Other methods to assess repolarization abnormalities need to be evaluated in such patients.}, }
@article {pmid15690336, year = {2005}, author = {Gutmann, EJ and Cates, JM}, title = {Initial diagnosis of breast cancer via cytological examination of a pleural effusion: a rare event facilitated by recognition of an unusual morphological pattern.}, journal = {Diagnostic cytopathology}, volume = {32}, number = {3}, pages = {177-181}, doi = {10.1002/dc.20207}, pmid = {15690336}, issn = {8755-1039}, mesh = {Adenocarcinoma/diagnosis ; Aged ; Biopsy, Needle ; Breast Neoplasms/complications/*diagnosis/pathology ; Carcinoma, Ductal, Breast/complications/*diagnosis/pathology ; Diagnosis, Differential ; Dyspnea/etiology ; Female ; Humans ; Lung Neoplasms/diagnosis ; Pleural Effusion, Malignant/pathology ; Pulmonary Disease, Chronic Obstructive/complications ; }, abstract = {It is uncommon for breast carcinoma to present as a malignant serous effusion. Here, we describe a case in which the initial diagnosis of an occult invasive ductal carcinoma of the breast was made via cytological examination of a pleural effusion. Recognition of a cribriform architecture with intraluminal necrosis and microcalcifications in a cell block preparation was critical in making that diagnosis. To our knowledge, this specific morphological pattern of breast carcinoma in a cell block preparation from an effusion has not been reported previously.}, }
@article {pmid15683503, year = {2005}, author = {Lamparter, S and Grimm, W}, title = {Predictive value of high-sensitivity C-reactive protein in patients with idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {28 Suppl 1}, number = {}, pages = {S233-6}, doi = {10.1111/j.1540-8159.2005.00034.x}, pmid = {15683503}, issn = {0147-8389}, mesh = {Arrhythmias, Cardiac/epidemiology/*etiology ; C-Reactive Protein/*analysis ; Cardiomyopathy, Dilated/*blood/*complications ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; }, abstract = {We analyzed the serum concentrations of high-sensitivity C-reactive protein (hsCRP) at the time of diagnostic cardiac catheterization in 198 patients with idiopathic dilated cardiomyopathy (IDC) to evaluate its prognostic value. Patients were dichotomized according to a median value of hsCRP of 2 mg/dL. Predefined study endpoints over 69 +/- 33 months of follow-up included major arrhythmic events and transplant-free survival. Major arrhythmic events during follow-up occurred in 20 of 98 patients (20%) with low, compared to 22 of 100 patients (22%) with high hsCRP (ns). By multivariate analysis, a depressed left ventricular ejection fraction (LVEF) was the only significant predictor of arrhythmic risk. Death or cardiac transplantation was observed in 36% of patients with high, versus 22% of patients with low hsCRP (P < 0.05). By multivariate analysis, hsCRP and LVEF were independent predictors of transplant-free survival. Thus, in this patient population with IDC, hsCRP had independent prognostic value with regard to transplant-free survival, but did not contribute in the stratification with regard to arrhythmic risk.}, }
@article {pmid15683498, year = {2005}, author = {Grimm, W and Christ, M and Maisch, B}, title = {Long runs of non-sustained ventricular tachycardia on 24-hour ambulatory electrocardiogram predict major arrhythmic events in patients with idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {28 Suppl 1}, number = {}, pages = {S207-10}, doi = {10.1111/j.1540-8159.2005.00035.x}, pmid = {15683498}, issn = {0147-8389}, mesh = {Arrhythmias, Cardiac/diagnosis/etiology ; Cardiomyopathy, Dilated/*complications ; *Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Tachycardia, Ventricular/*diagnosis/etiology ; Time Factors ; }, abstract = {This study examined the prognostic significance of the rate and length of non-sustained (NS) ventricular tachycardia (VT) on 24-hour ambulatory electrocardiograms (ECG) recorded in 343 patients with idiopathic dilated cardiomyopathy (IDC) in the prospective Marburg Cardiomyopathy study. NSVT was defined as >/=3 consecutive ventricular premature beats at >120 bpm. During 52 +/- 21 months of follow-up, major arrhythmic events defined as sustained VT, VF, or sudden cardiac death occurred in 46 of 343 patients (13%). Patients with 3-4 beat runs of NSVT had a similar arrhythmia-free survival as patients without NSVT on baseline 24-hour ambulatory ECG. The incidence of major arrhythmic events during follow-up increased significantly from 2% per year in patients without NSVT, to 5% per year in patients with 5-9 beat runs of NSVT, to 10% per year in patients with >/=10 beat runs of NSVT (P < 0.05). Unlike the length, the rate of NSVT was similar in patients with versus without subsequent major arrhythmic events (163 +/- 23 vs 160 +/- 24 bpm). Thus, the length but not the rate of NSVT on 24-hour ambulatory ECG was a predictor of major arrhythmic events in patients with IDC. The presence of NSVT with >/=10 beat runs on ambulatory ECG was associated with a particularly high risk of major arrhythmic events.}, }
@article {pmid15683497, year = {2005}, author = {Grimm, W and Christ, M and Sharkova, J and Maisch, B}, title = {Arrhythmia risk prediction in idiopathic dilated cardiomyopathy based on heart rate variability and baroreflex sensitivity.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {28 Suppl 1}, number = {}, pages = {S202-6}, doi = {10.1111/j.1540-8159.2005.00033.x}, pmid = {15683497}, issn = {0147-8389}, mesh = {Arrhythmias, Cardiac/epidemiology/*etiology ; Baroreflex/*physiology ; Cardiomyopathy, Dilated/*complications/*physiopathology ; Female ; Heart Rate/*physiology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Risk Factors ; }, abstract = {UNLABELLED: This study examined the relation between heart rate variability (HRV) and baroreflex sensitivity (BRS) and subsequent major arrhythmic events (MAE), defined as sustained VT, VF or sudden death, in 263 patients with idiopathic dilated cardiomyopathy (IDC) in sinus rhythm. The predefined measure of HRV was the standard deviation of all normal-to-normal RR intervals (SDNN) on baseline 24-hour ambulatory ECG. BRS was determined by the phenylephrine method. Over 52 +/- 21 months of follow-up, MAE occurred in 38 patients (14%). SDNN at baseline 24-hour ambulatory ECG (106 +/- 46 vs 109 +/- 45, ns) and BRS (7.9 +/- 5.5 vs 7.7 +/- 5.3 ms/mmHg, ns) were both similar in patients with versus without MAE during follow-up. In contrast, left ventricular ejection fraction was significantly lower in patients with versus without MAE (24%+/- 7% vs 31%+/- 10%, P < 0.019.<br><br>CONCLUSIONS: Neither HRV nor BRS predicted MAE in patients with IDC.}, }
@article {pmid15657525, year = {2005}, author = {Kijima, Y and Yoshinaka, H and Higuchi, I and Owaki, T and Aikou, T}, title = {A case of amyotrophic lateral sclerosis and breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {12}, number = {1}, pages = {57-59}, doi = {10.2325/jbcs.12.57}, pmid = {15657525}, issn = {1340-6868}, mesh = {Amyotrophic Lateral Sclerosis/*complications ; Breast Neoplasms/*complications/surgery ; Carcinoma, Ductal, Breast/*complications/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; }, abstract = {We report a case of breast cancer occurring in a patient with amyotrophic lateral sclerosis (ALS). A 58-year-old Japanese woman diagnosed with ALS 6 years previously noticed a mass in the left breast. We performed a modified radical mastectomy for the mass lesion. Invasive ductal carcinoma without lymph node metastasis was diagnosed. During the operation, she had no worsening of her neurological symptoms. The patient has been cancer-free for 11 months since her operation and no improvement has been seen in her neurological condition. To the best of our knowledge, this is the first case of breast cancer occurring in a patient with ALS in Japan.}, }
@article {pmid15645698, year = {2004}, author = {Glaser, NS and Iden, SB and Green-Burgeson, D and Bennett, C and Hood-Johnson, K and Styne, DM and Goodlin-Jones, B}, title = {Benefits of an insulin dosage calculation device for adolescents with type 1 diabetes mellitus.}, journal = {Journal of pediatric endocrinology &amp; metabolism : JPEM}, volume = {17}, number = {12}, pages = {1641-1651}, doi = {10.1515/jpem.2004.17.12.1641}, pmid = {15645698}, issn = {0334-018X}, mesh = {Adolescent ; Adult ; Child ; Cross-Over Studies ; Diabetes Mellitus, Type 1/complications/*drug therapy ; Dose-Response Relationship, Drug ; Female ; Humans ; Hypoglycemia/complications ; Insulin/*administration &amp; dosage ; Male ; Patient Satisfaction ; }, abstract = {OBJECTIVE: Multiple daily injection insulin regimens (MDI) and continuous subcutaneous insulin infusion (CSII) allow adolescents with type 1 diabetes mellitus (DM) meal flexibility, and may improve metabolic control. The insulin dosage calculations, however, involve ratios of insulin to carbohydrate and corrections for high blood glucose values, and are labor-intensive and prone to error. We evaluated the impact of an insulin dosage calculation device (IDC) on metabolic control, treatment satisfaction, regimen adherence and quality of life in adolescents using MDI or CSII.<br><br>RESEARCH DESIGN AND METHODS: We conducted a randomized control trial using the IDC in 83 adolescents on MDI or CSII. At enrollment, patients received training on dosage calculation using either the IDC or conventional methods, and performed sample calculations. At enrollment, 6 months and 12 months, we recorded HbA1c and frequency of hypoglycemia, and patients completed questionnaires assessing treatment satisfaction, regimen adherence and quality of life. After 6 months, patients in the control group were also given the IDC.<br><br>RESULTS: We observed a higher frequency of errors with conventional calculations (53-67% incorrect calculations) than with the IDC (25-32% incorrect). At 6 months, there was a trend toward improved HbA1c in the IDC group overall (9.3 vs 8.9, p = 0.07) and a significant improvement in the subset (42%) who used the IDC consistently (9.7 vs 8.8, p = 0.03). There was no change in HbA1c in the control group during this interval (9.0 vs 8.9, p = 0.90). During months 6-12, when both groups were combined, there was a significant increase in HbA1c in patients using the IDC inconsistently or not at all (8.9 vs 9.4, p = 0.005), but no change in HbA1c in those using the IDC consistently (9.1 vs 8.9, p = 0.57). Treatment satisfaction, adherence and quality of life improved throughout the study in both groups.<br><br>CONCLUSIONS: Errors in calculation of insulin dosage by adolescents occur frequently. Consistent use of an insulin dosage calculation device may help to improve metabolic control in adolescents using MDI or CSII.}, }
@article {pmid15608061, year = {2004}, author = {Zucchi, I and Mento, E and Kuznetsov, VA and Scotti, M and Valsecchi, V and Simionati, B and Vicinanza, E and Valle, G and Pilotti, S and Reinbold, R and Vezzoni, P and Albertini, A and Dulbecco, R}, title = {Gene expression profiles of epithelial cells microscopically isolated from a breast-invasive ductal carcinoma and a nodal metastasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {101}, number = {52}, pages = {18147-18152}, pmid = {15608061}, issn = {0027-8424}, mesh = {Breast/metabolism ; Breast Neoplasms/*genetics/*pathology ; Carcinoma/genetics/*pathology ; DNA, Complementary/metabolism ; Down-Regulation ; Epithelial Cells/*metabolism ; Epithelium/metabolism ; *Gene Expression Regulation, Neoplastic ; Gene Library ; Humans ; In Situ Hybridization ; *Lymphatic Metastasis ; Up-Regulation ; }, abstract = {Expression profiles of breast carcinomas are difficult to interpret when they are obtained from tissue in toto, which may contain a large proportion of non-cancer cells. To avoid this problem, we microscopically isolated cells from a primary invasive ductal carcinoma of the breast and from an axillary node harboring a metastatic breast carcinoma, to obtain pure populations of carcinoma cells (approximately 500) and used them for serial analysis of gene expression. The expression profiles generated from both populations of cells were compared with the profile of a disease-free mammary epithelium. We showed that the expression profiles obtained are exclusive of carcinoma cells with no contribution of non-epithelial cells. From a total of 16,939 unique tags analyzed, we detected 559 statistically significant changes in gene expression; some of these genes have not been previously associated with breast cancer. We observed that many of the down-regulated genes are the same in both cancers, whereas the up-regulated genes are completely different, suggesting that the down-regulation of a set of genes may be the basic mechanism of cancer formation, while the up-regulation may characterize and possibly control the state of evolution of individual cancers. The results obtained may help in characterizing the neoplastic process of breast cancer.}, }
@article {pmid15583806, year = {2005}, author = {Mylonas, I and Jeschke, U and Shabani, N and Kuhn, C and Friese, K and Gerber, B}, title = {Inhibin/activin subunits (inhibin-alpha, -betaA and -betaB) are differentially expressed in human breast cancer and their metastasis.}, journal = {Oncology reports}, volume = {13}, number = {1}, pages = {81-88}, pmid = {15583806}, issn = {1021-335X}, mesh = {Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/diagnosis/*metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/*metabolism/pathology ; Female ; Humans ; Inhibin-beta Subunits/analysis/*metabolism ; Inhibins/analysis/*metabolism ; Lymphatic Metastasis ; Prognosis ; Recurrence ; }, abstract = {Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH-alpha) and one of two possible beta-subunits (INH-betaA or -betaB). Aims of this study were to determine the frequency and tissue distribution of INH-alpha, -betaA and -betaB in breast cancer tissue. Paraffin-fixed ductal carcinoma in situ (DCIS; n=7), invasive ductal carcinomas without lymph node metastases (IDC; n=8), infiltrating ductal carcinomas with their lymph node metastases (IDC/LN; n=8), primary ductal carcinomas with their subsequent recurrence (n=7) were analyzed by immunohistochemical means with monoclonal antibodies against inhibin-alpha, -betaA and -betaB subunits. INH-alpha was observed in DCIS (5/7), while its expression was significantly higher in DCIS than IDC (1/7; p<0.05) and IDC/LN (0/8; p<0.005) and recurrent breast cancer tissue (0/7; p<0.005). The INH-betaA subunit was also demonstrated in all DCIS cases with a significantly higher intensity compared to IDC (p<0.05), IDC/LN (p<0.01) and primary carcinoma with subsequent recurrence (p<0.05). INH-betaA expression was significant higher in primary tumors with subsequent recurrence compared to IDC/LN (p<0.05). The metastatic lymph nodes expressed the lowest inhibin-betaA compared to all other groups (p<0.01). INH-betaB was also demonstrated in all mammary carcinoma tissues, but without any statistical differences. The differential expression of INH-alpha in DCIS might suggest a function as a tumor suppressor in breast tissue, suggesting a useful marker for recognizing patients with subsequent risk of developing invasive ductal cancer. The higher INH-betaA expression in DCIS than invasive cancer suggests an important role in mammary carcinogenesis. Interestingly, primary breast tumor with a subsequent recurrence expressed a higher intensity of the inhibin-betaA subunit, suggesting an important role in metastatic pathogenesis, and utilization as a tumor marker. The immunoreactivity of inhibin-betaA was significantly higher in DCIS than invasive ductal carcinomas, suggesting an important role in mammary carcinogenesis. The metastatic lymph nodes expressed lower INH-betaA and -betaB than the primary tumor, which might be the cause of less differentiated and aggressive tumor cells within the primary tumor. Therefore, inhibin/activin subunits might be useful prognostic markers for breast cancer.}, }
@article {pmid15578708, year = {2005}, author = {Yankeelov, TE and Rooney, WD and Huang, W and Dyke, JP and Li, X and Tudorica, A and Lee, JH and Koutcher, JA and Springer, CS}, title = {Evidence for shutter-speed variation in CR bolus-tracking studies of human pathology.}, journal = {NMR in biomedicine}, volume = {18}, number = {3}, pages = {173-185}, doi = {10.1002/nbm.938}, pmid = {15578708}, issn = {0952-3480}, support = {P01-CA05826-038A1/CA/NCI NIH HHS/United States ; R01-CA62556/CA/NCI NIH HHS/United States ; R01-EB00422/EB/NIBIB NIH HHS/United States ; R01-HL50139/HL/NHLBI NIH HHS/United States ; R01-NS40801/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; *Algorithms ; Breast Neoplasms/*diagnosis ; Computer Simulation ; *Contrast Media ; Evidence-Based Medicine ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; *Models, Biological ; Multiple Sclerosis/*diagnosis ; Osteosarcoma/*diagnosis ; Reproducibility of Results ; Sample Size ; Sensitivity and Specificity ; }, abstract = {The standard pharmacokinetic model for the analysis of MRI contrast reagent (CR) bolus-tracking (B-T) data assumes that the mean intracellular water molecule lifetime (tau(i)) is effectively zero. This assertion is inconsistent with a considerable body of physiological measurements. Furthermore, theory and simulation show the B-T time-course shape to be very sensitive to the tau(i) magnitude in the physiological range (hundreds of milliseconds to several seconds). Consequently, this standard model aspect can cause significant underestimations (factors of 2 or 3) of the two parameters usually determined: K(trans), the vascular wall CR transfer rate constant, and v(e), the CR distribution volume (the extracellular, extravascular space fraction). Analyses of animal model data confirmed two predicted behaviors indicative of this standard model inadequacy: (1) a specific temporal pattern for the mismatch between the best-fitted curve and data; and (2) an inverse dependence of the curve's K(trans) and v(e) magnitudes on the CR dose. These parameters should be CR dose-independent. The most parsimonious analysis allowing for realistic tau(i) values is the 'shutter-speed' model. Its application to the experimental animal data essentially eliminated the two standard model signature inadequacies. This paper reports the first survey for the extent of this 'shutter-speed effect' in human data. Retrospective analyses are made of clinical data chosen from a range of pathology (the active multiple sclerosis lesion, the invasive ductal carcinoma breast tumor, and osteosarcoma in the leg) that provides a wide variation, particularly of K(trans). The signature temporal mismatch of the standard model is observed in all cases, and is essentially eliminated by use of the shutter-speed model. Pixel-by-pixel maps show that parameter values from the shutter-speed analysis are increased by more than a factor of 3 for some lesion regions. This endows the lesions with very high contrast, and reveals heterogeneities that are often not seen in the standard model maps. Normal muscle regions in the leg allow validation of the shutter-speed model K(trans), v(e), and tau(i) magnitudes, by comparison with results of previous careful rat leg studies not possible for human subjects.}, }
@article {pmid15578430, year = {2005}, author = {Katayama, S and Nakayama, T and Ito, M and Naito, S and Sekine, I}, title = {Expression of the ets-1 proto-oncogene in human breast carcinoma: differential expression with histological grading and growth pattern.}, journal = {Histology and histopathology}, volume = {20}, number = {1}, pages = {119-126}, doi = {10.14670/HH-20.119}, pmid = {15578430}, issn = {0213-3911}, mesh = {Breast/metabolism ; Breast Neoplasms/genetics/*metabolism/physiopathology ; Carcinoma/genetics/*metabolism/physiopathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Metastasis/genetics ; Proto-Oncogene Mas ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins/biosynthesis/*genetics ; Proto-Oncogene Proteins c-ets ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/biosynthesis/*genetics ; }, abstract = {The proto-oncogene, ets-1, is a transcription factor known to control the expression of a number of genes and has been postulated to play a role in cell growth, differentiation and tumour invasion. We examined 137 cases of breast carcinoma by immunohistochemistry and compared the degree of Ets-1 expression among the different histological types of invasive carcinomas. Ets-1 was not expressed in the normal breast epithelium nor in noninvasive carcinomas. Among the 137 breast carcinoma cases, 104 (83.2%) showed positive staining for the Ets-1 protein. Histologically, invasive ductal carcinomas expressed immunopositivity with intense staining for Ets-1 in the tumour cells. Ets-1 expression correlated with Bloom-Richardson grading in invasive ductal carcinoma (p<0.01). However, there was no correlation between Ets-1 expression and lymph node metastasis, "t" classification or TNM staging. In situ hybridization confirmed the presence of Ets-1 mRNA in breast carcinomas. The expression of Ets-1 mRNA was detected in two of three different kinds of cultured human breast carcinoma cell lines and one of three human breast carcinoma tissues by the reverse transcription polymerase chain reaction method. These findings suggest that ets-1 is overexpressed in ductal cells of the breast that have undergone malignant conversion and that ets-1 is one of the factors associated with tumour growth and histological differentiation of breast carcinomas.}, }
@article {pmid15554925, year = {2004}, author = {Mehrotra, S and Chhabra, A and Chakraborty, A and Chattopadhyay, S and Slowik, M and Stevens, R and Zengou, R and Mathias, C and Butterfield, LH and Dorsky, DI and Economou, JS and Mukherji, B and Chakraborty, NG}, title = {Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized human monocyte-derived dendritic cells.}, journal = {Immunology}, volume = {113}, number = {4}, pages = {472-481}, pmid = {15554925}, issn = {0019-2805}, support = {R01 CA077623/CA/NCI NIH HHS/United States ; CA88059/CA/NCI NIH HHS/United States ; CA77623/CA/NCI NIH HHS/United States ; R01 CA088059/CA/NCI NIH HHS/United States ; R01 CA083130/CA/NCI NIH HHS/United States ; R01 CA079976/CA/NCI NIH HHS/United States ; CA83130/CA/NCI NIH HHS/United States ; CA79976/CA/NCI NIH HHS/United States ; CA61398/CA/NCI NIH HHS/United States ; }, mesh = {Adenoviridae/genetics ; Antigen Presentation/*immunology ; Antigens, Neoplasm/*immunology ; CD8-Positive T-Lymphocytes/immunology ; Cytotoxicity, Immunologic/immunology ; Dendritic Cells/*immunology ; Genetic Vectors ; Humans ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Interleukin-10/genetics/*immunology ; Lymphocyte Activation/immunology ; MART-1 Antigen ; Melanoma/immunology ; Neoplasm Proteins/genetics/*immunology ; Transduction, Genetic ; }, abstract = {Dendritic cells (DC) play critical roles in generating an immune response and in inducing tolerance. Diverse microenvironmental factors can 'polarize' DC toward an immunogenic or non-immunogenic phenotype. Among the various microenvironmental factors, interleukin-10 (IL-10) exhibits a potent immunosuppressive effect on antigen-presenting cells (APC). Here, we show that monocyte-derived DC generated in the presence of IL-10 exhibit a profound down-regulation of many genes that are associated with immune activation and show that the IL-10-grown DC are poor stimulators of CD8(+) T cells in a strictly autologous and major histocompatibility complex (MHC) class I-restricted melanoma antigen recognized by T cells (MART-1) epitope presentation system. However, these IL-10-grown DC can efficiently activate the epitope-specific CD8(+) T cells when they are made to present the epitope following transduction with an adenoviral vector expressing the MART-1 antigen. In addition, we show that the MART-1 protein colocalizes with the MHC class I protein, equally well, in the iDC and in the DC cultured in presence of IL-10 when both DC types are infected with the viral vector. We also show that the vector transduced DC present the MART-1(27-35) epitope for a sustained period compared to the peptide pulsed DC. These data suggest that although DCs generated in the presence of IL-10 tend to be non-immunogenic, they are capable of processing and presenting an antigen when the antigen is synthesized within the DC.}, }
@article {pmid15553762, year = {2004}, author = {Sengoku, N and Kuranami, M and Handa, K and Hayashi, K and Enomoto, T and Watanabe, M}, title = {[A case of local advanced breast cancer with multiple lung metastases successfully treated with multimodal therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {31}, number = {11}, pages = {1927-1929}, pmid = {15553762}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Phytogenic/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage ; Breast Neoplasms/*pathology/*therapy ; Carcinoma, Ductal/*pathology/*therapy ; Combined Modality Therapy ; Docetaxel ; Female ; Humans ; Lung Neoplasms/*secondary/*therapy ; Mastectomy ; Middle Aged ; Palliative Care ; Quality of Life ; Taxoids/administration &amp; dosage ; Trastuzumab ; Ulcer/pathology ; }, abstract = {We report a case of local advanced breast cancer with multiple lung metastases (T4bN2M1) achieving a significant improvement of QOL by multimodal therapy with chemotherapy, antibody therapy, radiation therapy and surgery. The patient was a 47-year-old woman with mental deterioration who had an ulcerative breast cancer with multiple lung metastases. Breast biopsy led to a diagnosis of an invasive ductal carcinoma positive for erbB2 protein expression. She received 6 cycles of tri-weekly docetaxel (60 mg/m2) and weekly trastuzumab. Although metastases in the lung disappeared after chemotherapy, the response of breast ulceration was less satisfactory. Simple mastectomy followed by radiation therapy (50 Gy) to the axilla was performed as a palliative treatment. No signs of recurrence were observed for more than 14 months of treatment by trastuzumab. Multimodal therapy can improve patient QOL and the clinical outcomes in Stage IV local advanced breast cancer.}, }
@article {pmid15551757, year = {2004}, author = {Jin, GS and Kondo, E and Miyake, T and Shibata, M and Takashima, T and Liu, YX and Hayashi, K and Akagi, T and Yoshino, T}, title = {Expression and intracellular localization of FKHRL1 in mammary gland neoplasms.}, journal = {Acta medica Okayama}, volume = {58}, number = {4}, pages = {197-205}, doi = {10.18926/AMO/32088}, pmid = {15551757}, issn = {0386-300X}, mesh = {Adult ; Animals ; Antibodies ; Breast Neoplasms/pathology/*physiopathology ; Carcinoma, Ductal, Breast/physiopathology/secondary ; DNA-Binding Proteins/*genetics/immunology/metabolism ; Female ; Fibroadenoma/pathology/physiopathology ; Forkhead Box Protein O1 ; Forkhead Box Protein O3 ; Forkhead Transcription Factors ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Papilloma, Intraductal/*physiopathology/secondary ; Paraffin Embedding ; Rabbits ; Transcription Factors/*genetics/immunology/metabolism ; }, abstract = {FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast.}, }
@article {pmid15547078, year = {2004}, author = {Radstake, TR and Blom, AB and Slöetjes, AW and van Gorselen, EO and Pesman, GJ and Engelen, L and Torensma, R and van den Berg, WB and Figdor, CG and van Lent, PL and Adema, GJ and Barrera, P}, title = {Increased FcgammaRII expression and aberrant tumour necrosis factor alpha production by mature dendritic cells from patients with active rheumatoid arthritis.}, journal = {Annals of the rheumatic diseases}, volume = {63}, number = {12}, pages = {1556-1563}, pmid = {15547078}, issn = {0003-4967}, mesh = {Antigen-Antibody Complex/immunology ; Arthritis, Rheumatoid/*immunology ; Cell Differentiation/immunology ; Cells, Cultured ; Dendritic Cells/*immunology ; Gene Expression ; Humans ; RNA, Messenger/genetics ; Receptors, IgG/genetics/*metabolism ; Synovial Membrane/immunology ; Tumor Necrosis Factor-alpha/*biosynthesis ; Up-Regulation/immunology ; }, abstract = {OBJECTIVES: To investigate potential differences in phenotype and behaviour of immature (iDC) and mature dendritic cells (mDC) from patients with RA and healthy subjects.<br><br>METHODS: iDC and mDC were derived from blood monocytes of patients with RA and healthy controls following standardised protocols. FACS was used to analyse expression of FcgammaRI, II, and III and molecules to characterise DC. Discrimination between FcgammaRIIa and FcgammaRIIb was achieved by RT-PCR. Immunohistochemistry was performed on synovial biopsy specimens of three patients with RA and three healthy controls. TNFalpha production by iDC and mDC upon FcgammaR dependent stimulation was compared between patients with RA and controls by ELISA.<br><br>RESULTS: iDC from patients with active RA but not from patients with inactive RA or healthy controls markedly up regulated FcgammaRII. mDC from patients with active RA also lacked the physiological down regulation of FcgammaRII that occurs upon maturation in both control groups. RT-PCR analysis confirmed the increased expression of FcgammaRII in RA-especially marked for FcgammaRIIb. FcgammaR dependent stimulation of DC using antigen-IgG immune complexes (IC) significantly increased TNFalpha production by DC from healthy subjects, but significantly decreased TNFalpha by DC from patients with RA. Overlapping expression patterns between FcgammaRII and DC-LAMP in the synovial tissue of patients with RA imply that in vivo, also, mature DC express increased levels of FcgammaRIIb.<br><br>CONCLUSION: The presence and altered characteristics of DC during active RA suggest that DC help to modulate autoimmunity in RA. Further studies should elucidate the role of local factors in altering the function of DC in RA and in increasing expression of FcgammaRII.}, }
@article {pmid15539129, year = {2004}, author = {Perez-Villa, F and Leivas, A and Roig, E and Jiménez, W and Sanz, G}, title = {Adrenomedullin messenger RNA expression is increased in myocardial tissue of patients with idiopathic dilated cardiomyopathy.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {23}, number = {11}, pages = {1297-1300}, doi = {10.1016/j.healun.2003.09.002}, pmid = {15539129}, issn = {1053-2498}, mesh = {Adrenomedullin ; Cardiomyopathy, Dilated/*genetics ; Female ; Humans ; Male ; Middle Aged ; Myocardium/chemistry ; Peptides/*genetics ; RNA, Messenger/analysis/*biosynthesis ; }, abstract = {Increased plasma levels of adrenomedullin (ADM) have been reported in patients with congestive heart failure Immunohistochemical ADM has been identified in failing human ventricle, but the gene expression pattern of ADM messenger RNA (mRNA) in myocardial tissue of patients with heart failure has not been elucidated. In this study, gene expression of ADM mRNA (analyzed by northern blot) and tissue concentration of ADM (measured by radioimmunoassay) were assessed in the explanted hearts of 17 patients with idiopathic dilated cardiomyopathy (IDC) and in 7 organ donors with no cardiopathy (controls). Myocardial tissue samples of patients with IDC showed increased ADM mRNA gene expression (p < 0.05) and decreased immunoreactive ADM protein content (p < 0.02) compared with controls.}, }
@article {pmid15535846, year = {2004}, author = {Kitayama, J and Shida, D and Sako, A and Ishikawa, M and Hama, K and Aoki, J and Arai, H and Nagawa, H}, title = {Over-expression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {6}, pages = {R640-6}, pmid = {15535846}, issn = {1465-542X}, mesh = {Antibodies, Monoclonal/chemistry ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; RNA, Messenger/biosynthesis/genetics ; Receptors, Lysophosphatidic Acid/*biosynthesis/genetics/immunology ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {INTRODUCTION: Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse effects on various cells. It interacts with at least three G-protein-coupled transmembrane receptors, namely LPA1, LPA2 and LPA3, whose expression in various tumours has not been fully characterized. In the present study we characterized the expression profile of LPA receptors in human breast cancer tissue and assessed the possible roles of each receptor.<br><br>METHODS: The relative expression levels of each receptor's mRNA against beta-actin mRNA was examined in surgically resected invasive ductal carcinomas and normal gland tissue using real-time RT-PCR. LPA2 expression was also examined immunohistochemically using a rat anti-LPA2 monoclonal antibody.<br><br>RESULTS: In 25 cases normal and cancer tissue contained LPA1 mRNA at similar levels, whereas the expression level of LPA2 mRNA was significantly increased in cancer tissue as compared with its normal counterpart (3479.0 +/- 426.6 versus 1287.3 +/- 466.8; P < 0.05). LPA3 was weakly expressed in both cancer and normal gland tissue. In 48 (57%) out of 84 cases, enhanced expression of LPA2 protein was confirmed in carcinoma cells as compared with normal mammary epithelium by immunohistochemistry. Over-expression of LPA2 was detected in 17 (45%) out of 38 premenopausal women, as compared with 31 (67%) out of 46 postmenopausal women, and the difference was statistically significant (P < 0.05).<br><br>CONCLUSION: These findings suggest that upregulation of LPA2 may play a role in carcinogenesis, particularly in postmenopausal breast cancer.}, }
@article {pmid15502381, year = {2004}, author = {Miura, K and Nakagawa, H and Toyoshima, H and Kodama, K and Nagai, M and Morikawa, Y and Inaba, Y and Ohno, Y}, title = {Environmental factors and risk of idiopathic dilated cardiomyopathy: a multi-hospital case-control study in Japan.}, journal = {Circulation journal : official journal of the Japanese Circulation Society}, volume = {68}, number = {11}, pages = {1011-1017}, doi = {10.1253/circj.68.1011}, pmid = {15502381}, issn = {1346-9843}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacterial Infections/complications ; Cardiomyopathy, Dilated/*etiology ; Case-Control Studies ; Education ; *Environment ; Fatigue/complications ; Female ; Humans ; Japan ; Male ; Medical Records ; Middle Aged ; Occupational Exposure ; Odds Ratio ; Risk Factors ; Temperature ; Tobacco Smoke Pollution/adverse effects ; }, abstract = {BACKGROUND: Detailed epidemiological investigations on the relationship of environmental factors, especially occupational and microbiological factors, to the development of idiopathic dilated cardiomyopathy (IDC) are scarce.<br><br>METHODS AND RESULTS: A multi-hospital case-control study was conducted in 38 hospitals throughout Japan in order to survey IDC cases and age, sex-matched outpatient controls at each hospital. Crude and adjusted odds ratios (ORs) by various environmental factors were calculated in 135 pairs of cases and controls. Univariate analyses revealed significantly increased ORs for lower education, passive smoking in the workplace, cold and/or hot workplace, symptoms of fatigue and history of bacterial infection; in contrast, decreased ORs were associated with a history of rubella and gastroduodenal diseases. Based on multivariate adjusted analyses, lower education (OR 1.96, 95% confidence interval (CI) 1.13-3.40), cold or hot workplace (OR 1.84, 95%CI 1.08-3.12) and history of measles (OR 1.78, 95%CI 1.01-3.08) exhibited a significant positive relationship with IDC risk. History of rubella (OR 0.17, 95%CI 0.06-0.52) and gastroduodenal diseases (OR 0.14, 95%CI 0.07-0.29) were inversely related to the risk.<br><br>CONCLUSIONS: Some occupational and microbiological factors appear to relate independently to the development of IDC and further investigation is required to establish their respective mechanisms.}, }
@article {pmid15498363, year = {2004}, author = {Liu, W and Li, WM and Sun, NL}, title = {Relationship between HLA-DQA1 polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy.}, journal = {Chinese medical journal}, volume = {117}, number = {10}, pages = {1449-1452}, pmid = {15498363}, issn = {0366-6999}, mesh = {Adolescent ; Adult ; Aged ; Cardiomyopathy, Dilated/*genetics ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; HLA-DQ Antigens/*genetics ; HLA-DQ alpha-Chains ; Humans ; Male ; Middle Aged ; *Polymorphism, Genetic ; }, abstract = {BACKGROUND: Autoimmune mechanisms are likely to participate in the pathogenesis of subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the major histocompatibility complex may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, especially highly polymorphic HLA-DQ genes, play an important role in the activation of immune responses, and thus control the predisposition for or protect from IDC. This study was conducted to investigate the HLA-DQA1 allele polymorphisms in IDC patients and to explore the underlying immunological mechanism and the hereditary susceptibility to IDC.<br><br>METHODS: The polymerase chain reaction sequence-specific primers (PCR-SSP) technique was used to analyze the polymorphisms in the second exon of DQA1 in three groups: 72 IDC patients diagnosed according to the criteria of World Health Organization (IDC group); 100 end-stage heart failure patients suffering from a disease of known etiology (HF group); and 100 healthy subjects enrolled for the study during a routine health survey (control group). Patients in the IDC group were stratified according to ejection fraction (EF). Those with EF values were higher than 35% were placed into subgroup 1; subgroup 2 included patients with an EF value of 15% - 35%; and subgroup 3 consisted of those whose EF values less than 15%.<br><br>RESULTS: The frequency of HLA-DQA1 *0501 alleles was significantly higher in the IDC group (0.39) than that in the HF group (0.12) and the control group (0.09) (both P < 0.05). Further analysis of the three IDC subgroups showed a higher frequency of DQA1 *0501 among patients with lower EF values (both P < 0.05, compared with subgroups 1 and 2). The frequency of DQA1 *0201 was higher in the control group than that in the IDC group (P < 0.05).<br><br>CONCLUSIONS: The HLA-DQA1 *0501 allele confers susceptibility to IDC, while the DQA1 *0201 allele confers protection against it, which indicates that genetic background involved in IDC and heart failure is different. HLA-DQA1 genes are involved in the regulation of specific immune responses by auto- or foreign anti-myocardium antibody.}, }
@article {pmid15480266, year = {2004}, author = {Frachon, S and Pasquier, D and Treilleux, I and Seigneurin, D and Ringeisen, F and Rosier, P and Bolla, M and Boutonnat, J}, title = {[Breast carcinoma with predominant neuroendocrine differentiation].}, journal = {Annales de pathologie}, volume = {24}, number = {3}, pages = {278-283}, doi = {10.1016/s0242-6498(04)93966-1}, pmid = {15480266}, issn = {0242-6498}, mesh = {Biomarkers, Tumor/analysis ; Bone Neoplasms/chemistry/*secondary ; Breast Neoplasms/chemistry/drug therapy/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Carcinoma, Neuroendocrine/chemistry/pathology/*secondary ; Cell Differentiation ; Chemotherapy, Adjuvant ; Chromogranin A ; Chromogranins/analysis ; Combined Modality Therapy ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Proteins/analysis ; Neoplastic Stem Cells/*pathology ; Neural Cell Adhesion Molecules/analysis ; Radiotherapy, Adjuvant ; Sternum/chemistry/*pathology ; Synaptophysin/analysis ; }, abstract = {Neuroendocrine differentiation can be identified in a subset of human breast carcinomas, either as scattered cells or as a predominant neuroendocrine component. We report a case of an invasive breast carcinoma largely composed of neuroendocrine cells. Eight years after a left mammary lumpectomy for a pT2N1MO SBR III invasive ductal carcinoma, a 67-years-old woman presented with a metastastic neuroendocrine sternal mass. To establish a relationship between mammary carcinoma and bone metastasis, histological slides of both the breast tumor and axillary lymph nodes were reviewed, and an immunohistochemical study was performed. They showed that: a) the mammary carcinoma was composed of a majority of small and large neuroendocrine cells synaptophysin +, NCAM+, chromogranin - (80%), associated with 2 other differentiated non endocrine components, one of metaplastic squamous carcinoma (10%) and the other of ductal carcinoma (10%); b) 4 axillary lymph nodes were involved by the ductal component which contained few NCAM + but synaptophysin - cells; c) Estrogen and progesterone receptors and HER2 were negative in the breast tumor and the metastatic nodes. We discuss the histogenesis of composite mammary carcinomas with neuroendocrine differentiation, the outcome of each component and the prognostic relevance of such a diagnosis.}, }
@article {pmid15466187, year = {2004}, author = {Zhang, J and Shridhar, R and Dai, Q and Song, J and Barlow, SC and Yin, L and Sloane, BF and Miller, FR and Meschonat, C and Li, BD and Abreo, F and Keppler, D}, title = {Cystatin m: a novel candidate tumor suppressor gene for breast cancer.}, journal = {Cancer research}, volume = {64}, number = {19}, pages = {6957-6964}, doi = {10.1158/0008-5472.CAN-04-0819}, pmid = {15466187}, issn = {0008-5472}, support = {CA36481/CA/NCI NIH HHS/United States ; CA91785/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Division/physiology ; Cell Line, Tumor ; Cystatin M ; Cystatins/biosynthesis/*genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Liver Neoplasms, Experimental/pathology/secondary ; Lung Neoplasms/pathology/secondary ; Mice ; Mice, Inbred ICR ; Mice, SCID ; Neoplasm Staging ; Transfection ; }, abstract = {The contribution of pericellular proteolysis to tumor progression is well documented. To better understand protease biology and facilitate clinical translation, specific proteolytic systems need to be better defined. In particular, the precise role of endogenous protease inhibitors still needs to be deciphered. We reported previously that cystatin M, a potent endogenous inhibitor of lysosomal cysteine proteases, significantly suppressed in vitro cell proliferation, migration, and Matrigel invasion. Here, we show that scid mice orthotopically implanted with breast cancer cells expressing cystatin M show significantly delayed primary tumor growth and lower metastatic burden in the lungs and liver when compared with mice implanted with mock controls. The incidence of metastasis, however, appeared to be unaltered between the cystatin M group and the control group. Experimental metastasis assays suggest that cystatin M suppressed tumor cell proliferation at the secondary site. By using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction, we found consistent expression of cystatin M in normal human breast epithelial cells, whereas expression was decreased by 86% in invasive ductal carcinoma (IDC) cells of stage I to IV patients. Complete loss of expression of cystatin M was observed in two of three IDCs from stage IV patients. Immunohistochemical studies confirmed that expression of cystatin M in IDCs was partially or completely lost. We propose cystatin M as a novel candidate tumor suppressor gene for breast cancer.}, }
@article {pmid15459534, year = {2004}, author = {Tomasini, C and Grassi, M and Pippione, M}, title = {Cutaneous angiosarcoma arising in an irradiated breast. Case report and review of the literature.}, journal = {Dermatology (Basel, Switzerland)}, volume = {209}, number = {3}, pages = {208-214}, doi = {10.1159/000079891}, pmid = {15459534}, issn = {1018-8665}, mesh = {Aged ; Breast Neoplasms/*radiotherapy ; Female ; Hemangiosarcoma/*etiology/pathology ; Humans ; Neoplasms, Radiation-Induced/*etiology/pathology ; Radiotherapy/adverse effects ; Skin Neoplasms/*etiology/pathology ; }, abstract = {Angiosarcoma (AS) is a rare, aggressive tumour of endothelial origin occurring in various clinical settings, including idiopathic AS on the head and neck in elderly people, lymphoedema-associated AS, post-irradiation AS, soft-tissue AS, and various others. Despite the widespread use of radiation therapy in the treatment of breast carcinoma, AS developing in the wake of a radiation therapy is extremely infrequent. Although there is little doubt that radiation in therapeutic doses can induce sarcomas, quantification of that risk is complicated by many variables, among them chronic lymphoedema. We describe a 70-year-old woman in generally good health who presented with a 2-year history of a maculo-papular eruption on the skin of her right breast. There was no lymphoedema of the thoracic area. The lesions developed 3 years after she had undergone ipsilateral quadrantectomy for an invasive ductal carcinoma followed by 25 tangent field radiotherapy sessions on the breast. The oncological follow-up did not disclose local recurrence of the tumour or metastases of breast carcinoma. Histopathologic examination of a papule was diagnostic for AS. In addition, signs of chronic radiation dermatitis were found in the biopsy specimens. The patient underwent monthly cycles of chemotherapy with intravenous doxorubicin with partial remission of the affected area after 24 months, followed by the occurrence of liver metastases and exitus 30 months after diagnosis. From the review of the literature, it appears that post-irradiation mammary AS mainly affects women over 60 who have undergone breast-sparing surgery and that it is usually associated with axillary lymphadenectomy. Whereas the role of lymphoedema does not seem relevant to the pathogenesis of this malignancy, the association with chronic radiation dermatitis in our case reinforces the supposed role of radiation in the development of this tumour. Onset of AS should be taken into consideration when treating patients who develop multiple lesions on the skin above the irradiated area, even many years after the therapy.}, }
@article {pmid15455373, year = {2005}, author = {Yuan, Y and Liu, H and Sahin, A and Dai, JL}, title = {Reactivation of SYK expression by inhibition of DNA methylation suppresses breast cancer cell invasiveness.}, journal = {International journal of cancer}, volume = {113}, number = {4}, pages = {654-659}, doi = {10.1002/ijc.20628}, pmid = {15455373}, issn = {0020-7136}, support = {R01CA100278/CA/NCI NIH HHS/United States ; }, mesh = {Antimetabolites, Antineoplastic/pharmacology ; Azacitidine/*analogs &amp; derivatives/pharmacology ; Breast/metabolism ; Breast Neoplasms/genetics/*prevention &amp; control ; Carcinoma, Ductal/genetics/prevention &amp; control ; Carcinoma, Intraductal, Noninfiltrating/genetics/prevention &amp; control ; Cell Proliferation/drug effects ; *DNA Methylation ; DNA Modification Methylases/antagonists &amp; inhibitors ; Decitabine ; Enzyme Precursors/*antagonists &amp; inhibitors/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Intracellular Signaling Peptides and Proteins ; Neoplasm Invasiveness/*prevention &amp; control ; Phenotype ; Protein-Tyrosine Kinases/*antagonists &amp; inhibitors/*genetics/metabolism ; Stilbenes/pharmacology ; Syk Kinase ; }, abstract = {The gene product of spleen tyrosine kinase (SYK) has been implicated in the suppression of breast cancer invasion. We previously reported that SYK expression is lost in a subset of breast cancer; primarily by methylation-mediated gene silencing. In our study, we explored the possibility of using a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (AZA), to suppress breast cancer cell invasion by restoring SYK expression. We found that AZA treatment reestablished the expression of SYK(L) that was accompanied by suppression of the invasion capacity of SYK-negative cells. This invasion inhibition was not due to global cellular toxicity since this treatment did not affect overall cell proliferation. This decreased invasiveness by AZA treatment was diminished by piceatannol, a SYK inhibitor, suggesting that SYK play a significant role in AZA-inducible invasion suppression. SYK promoter hypermethylation was found infrequent in pathologically normal mammary tissues or benign lesions (<5%). In contrast, SYK methylation was frequently identified in ductal carcinoma in situ (approximately 45%) and invasive ductal carcinoma (47% in node-negative and 40% in node-positive cases), indicating that the hypermethylation of SYK occurs at a stage prior to the development of invasion phenotypes. All these results suggested a potential use of SYK methylation as a valuable biomarker to detect early cancerous lesions and support the use of AZA as a new reagent to the management of advanced breast cancer.}, }
@article {pmid15452174, year = {2004}, author = {Adams, SA and Smith, ME and Cowley, GP and Carr, LA}, title = {Reversal of glandular polarity in the lymphovascular compartment of breast cancer.}, journal = {Journal of clinical pathology}, volume = {57}, number = {10}, pages = {1114-1117}, pmid = {15452174}, issn = {0021-9746}, mesh = {Animals ; Antibodies, Monoclonal/analysis ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Female ; Humans ; Immunohistochemistry/methods ; Laminin/analysis ; Lymphatic System/pathology ; Mice ; Platelet Endothelial Cell Adhesion Molecule-1/analysis ; }, abstract = {AIM: To investigate the polarity of breast invasive ductal carcinoma cells by comparing the polarity of the tumour located within lymphovascular spaces with that located in the extravascular compartment.<br><br>METHODS: An immunohistochemical study identifying the apical HMFG-1, basolateral AUA-1, and basal laminin polarity markers of 11 cases of invasive ductal carcinoma (grades 1 or 2) metastatic to lymph nodes, all of which contained areas of tumour within and outside of lymphovascular spaces.<br><br>RESULTS: Only one of 11 tumours had a focus of apparent reversed glandular polarity in the larger extravascular tumour compartment (with AUA-1 present internally and HMFG-1 expressed externally on tumour clumps), but six of the 11 tumours showed reversed glandular polarity (either with AUA-1, or HMFG-1, or both) within the very much smaller lymphovascular space tumour compartment. Laminin was not identified in association with lymphovascular tumour.<br><br>CONCLUSIONS: Reversed glandular polarity in invasive ductal breast carcinomas was identified and was significantly more frequent within vessels than outside of them. Reversal of tumour glandular polarity within lymphovascular spaces allows direct interaction between apical domain-type molecules-which are then aberrantly expressed on the external surface of tumour clumps-and lymphovascular endothelium. Such interactions may affect the establishment of metastatic disease.}, }
@article {pmid15377846, year = {2004}, author = {Lawson, JS and Tran, DD and Ford, C and Rawlinson, WD}, title = {Elevated expression of the tumor suppressing protein p53 is associated with the presence of mouse mammary tumor-like env gene sequences (MMTV-like) in human breast cancer.}, journal = {Breast cancer research and treatment}, volume = {87}, number = {1}, pages = {13-17}, doi = {10.1023/B:BREA.0000041573.09142.00}, pmid = {15377846}, issn = {0167-6806}, mesh = {Animals ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*genetics/*virology ; Carcinoma, Ductal, Breast/*genetics/*virology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*virology ; *Gene Expression Profiling ; Genes, env/*genetics ; Humans ; Mammary Neoplasms, Animal/virology ; Mammary Tumor Virus, Mouse/*genetics/pathogenicity ; Mice ; Polymerase Chain Reaction ; Tumor Suppressor Protein p53/*biosynthesis ; }, abstract = {Mouse mammary tumor virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible laboratory inbred mice. The carcinogenic characteristics of this virus are enhanced by estrogen and other steroid hormones. MMTV-like envelope gene sequences, with 95% homology to MMTV have been identified in approximately 40% of breast cancers in US, Australian and Argentinian women. The presence of such sequences indicates the presence of a replication competent MMTV-like virus in human breast tumors. Whether an MMTV-like virus contributes to human breast cancer remains to be demonstrated. Non-statistically significant differences in p53 expression between MMTV-like positive and negative human breast cancers have previously been observed. As high p53 protein expression is associated with aggressive breast carcinogenesis we sought to determine if there were associations between the presence of MMTV-like gene sequences and elevated p53 expression in both invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS). We also investigated the expression of other biomarkers which are commonly associated with human breast cancer. These included estrogen receptor, progesterone receptor, Ki67, Cyclin D1, Bcl-2 and HER-2. Using polymerase chain reaction (PCR) analyses, MMTV-like envelope gene sequences were detected in 15 (75%) of 20 IDC specimens and 5 (23%) of 22 DCIS specimens. The average percentage of p53 positive cells in MMTV-like positive IDC specimens was 69% as compared to 44% in MMTV-like negative specimens (p for difference = 0.067). The average percentage of p53 positive cells in MMTV-like positive DCIS specimens was 93% as compared to 35% in MMTV-like negative specimens (numbers too few for statistical analysis). There was an increased intensity of p53 expression in IDC and DCIS specimens that were MMTV-like positive compared to those that were MMTV-like negative. There were no statistically significant differences in age, grade, and percentage of average positive cells for ERa, PR, Ki67, cyclin D1, Bcl-2, and HER-2, between MMTV-like positive and negative breast cancer specimens. Although these observations do not provide evidence of causality, they are consistent with a role for MMTV-like viruses in some human breast cancers.}, }
@article {pmid15375712, year = {2004}, author = {Abe, H and Hanasawa, K and Naitoh, H and Endo, Y and Tani, T and Kushima, R}, title = {Invasive ductal carcinoma within a fibroadenoma of the breast.}, journal = {International journal of clinical oncology}, volume = {9}, number = {4}, pages = {334-338}, doi = {10.1007/s10147-004-0401-9}, pmid = {15375712}, issn = {1341-9625}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Fine-Needle ; Breast Neoplasms/etiology/*pathology/therapy ; Carcinoma, Ductal, Breast/etiology/*pathology/therapy ; Combined Modality Therapy ; Cyclophosphamide/therapeutic use ; Female ; Fibroadenoma/complications/*pathology/therapy ; Fluorouracil/therapeutic use ; Humans ; Lymphatic Metastasis ; Mastectomy/methods ; Methotrexate/therapeutic use ; Treatment Outcome ; }, abstract = {A rare case of invasive ductal carcinoma within a fibroadenoma of the breast in a 42-year-old woman is reported. The patient had a well-defined mass, measuring 6.0 x 5.0 cm, in the upper lateral quadrant of the left breast. Physical examination suggested fibroadenoma. Ultrasonography and mammography revealed some malignant findings. Needle biopsy demonstrated fibroadenoma. Frozen section revealed invasive ductal carcinoma, scirrhous type, arising in a fibroadenoma; muscle-preserving mastectomy was performed. Only 16 cases of carcinoma within a fibroadenoma of the breast have been reported in the literature in Japan. Carcinoma in a fibroadenoma should be treated on the basis of the therapeutic criteria for ordinary carcinoma.}, }
@article {pmid15375528, year = {2004}, author = {Nishidate, T and Katagiri, T and Lin, ML and Mano, Y and Miki, Y and Kasumi, F and Yoshimoto, M and Tsunoda, T and Hirata, K and Nakamura, Y}, title = {Genome-wide gene-expression profiles of breast-cancer cells purified with laser microbeam microdissection: identification of genes associated with progression and metastasis.}, journal = {International journal of oncology}, volume = {25}, number = {4}, pages = {797-819}, pmid = {15375528}, issn = {1019-6439}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Disease Progression ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lasers ; Lymphatic Metastasis ; Microdissection ; Middle Aged ; Multigene Family ; }, abstract = {Breast carcinoma is a complex disease characterized by accumulation of multiple genetic alterations, and the understanding of the molecular basis of mammary tumorigenesis is still incomplete. In this study we analyzed gene-expression profiles of 81 surgical specimens of 12 ductal carcinoma in situ (DCIS) and 69 invasive ductal carcinoma (IDC). After applying laser-microbeam micro-dissection to all samples we achieved 98-99% pure populations of breast cancer cells, and of normal breast epithelial cells used as controls. A cDNA-microarray analysis of 23,040 genes in these samples and a subsequent unsupervised hierarchical clustering distinguished two tumor groups, mainly in terms of estrogen-receptor (ER) status. We then undertook a supervised analysis and identified 325 genes that were commonly either up- or down-regulated in both pathologically discrete stages (DCIS and IDC), indicating that these genes might play important roles in malignant transformation of breast ductal cells. In addition, we searched invasion-associated gene candidates whose expression was altered in IDC, but not in DCIS, and identified 24 up-regulated genes and 41 down-regulated genes. Furthermore, we identified 34 genes that were expressed differently in tumors from patients with lymph node metastasis as opposed to no metastasis. On that basis we developed a scoring system that correlated well with the metastatic status. Tumors from all of the 37 test patients with lymph-node metastasis yielded positive scores by our definition, whereas 38 of the 40 tumors (95%) without lymph node metastasis had negative scores. Our data should provide useful information for identifying predictive markers for invasion or metastasis, and suggest potential target molecules for treatment of breast cancers.}, }
@article {pmid15368805, year = {2004}, author = {Stöllberger, C and Leitner, S and Kopsa, W and Finsterer, J}, title = {Left ventricular hypertrabeculation/noncompaction and neuromuscular disorders in idiopathic dilated cardiomyopathy.}, journal = {Acta cardiologica}, volume = {59}, number = {4}, pages = {425-430}, doi = {10.2143/AC.59.4.2005209}, pmid = {15368805}, issn = {0001-5385}, mesh = {Aged ; Austria ; Cardiomyopathy, Dilated/*diagnosis/*etiology/metabolism ; Coronary Angiography ; Echocardiography ; Electrocardiography ; Electromyography ; Female ; Follow-Up Studies ; Heart Ventricles/diagnostic imaging/pathology ; Humans ; Hypertrophy, Left Ventricular/*diagnosis/*etiology/metabolism ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Myocardium/enzymology/pathology/ultrastructure ; Neuromuscular Diseases/*diagnosis/*etiology/metabolism ; Prospective Studies ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Our aim was to assess 1) the association of idiopathic dilative cardiomyopathy (IDC) and left ventricular hypertrabeculation/noncompaction (LVHT), 2) the use of cardiac magnetic resonance imaging (CMRI) in IDC and 3) the association of IDC and neuromuscular disorders (NMD).<br><br>METHODS: Patients in whom coronary heart disease had been excluded by coronary angiography and whose left ventricular end diastolic diameter was > 59 mm and fractional shortening < 25% with no other causes of cardiac dysfunction, were invited to participate.<br><br>RESULTS: Among 25 patients, 18 refused CMRI (claustrophobia n = 13, inability to lie flat n = 5), thus 7 patients (2 female, 47-66 years) were included. LVHT was found in 5/7 cases. In 4/5 patients who were neurologically investigated, a NMD was found. In 2/7 cases echocardiography failed to visualise the ventricular apex.<br><br>CONCLUSIONS: Patients with IDC should be investigated neurologically. In IDC patients with poor echocardiographic quality CMRI should be applied.}, }
@article {pmid15368253, year = {2004}, author = {Yoshida, M and Babensee, JE}, title = {Poly(lactic-co-glycolic acid) enhances maturation of human monocyte-derived dendritic cells.}, journal = {Journal of biomedical materials research. Part A}, volume = {71}, number = {1}, pages = {45-54}, doi = {10.1002/jbm.a.30131}, pmid = {15368253}, issn = {1549-3296}, mesh = {Animals ; Antigens, CD/immunology ; Biocompatible Materials/*pharmacology ; Biomarkers ; Cell Culture Techniques/methods ; Cell Shape ; Cells, Cultured ; Dendritic Cells/cytology/*drug effects/immunology/physiology ; Glycolates/immunology/*pharmacology ; Humans ; Hypersensitivity, Delayed ; Lactic Acid ; Lymphocyte Culture Test, Mixed ; Materials Testing ; Mice ; Monocytes/cytology/*drug effects/immunology/physiology ; Phenotype ; Polyglycolic Acid ; Polylactic Acid-Polyglycolic Acid Copolymer ; }, abstract = {Immature dendritic cells (iDCs) were derived from human peripheral blood monocytes, and treated with 75:25 poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) or film to assess the resultant dendritic cell (DC) maturation as compared to positive control of lipopolysaccharide (LPS) treatment for DC maturation or negative control of untreated iDCs. The effect of PLGA contact on DC maturation was examined as one possible explanation for the PLGA adjuvant effect we have observed in the enhancement of an immune response to codelivered model antigen, as adjuvants act through the maturation of DCs. Culturing iDCs with PLGA MPs or PLGA film resulted in morphology similar to that of LPS-matured DCs and the association, or possible internalization, of PLGA MPs. Furthermore, biomaterial-treated iDCs demonstrated an increase in MHC class II and costimulatory molecule expression compared to iDCs but to a lower level than that of LPS-matured DCs. Direct iDC contact with PLGA MPs was necessary for maturation. Immature DCs exposed to PLGA MPs were stimulatory of allogeneic T-cell proliferation, whereas cells exposed to PLGA film were not. Further, PLGA MPs supported a moderate delayed type hypersensitivity reaction in mice indicative of in vivo DC maturation. Taken together, these results suggest that PLGA is a DC maturation stimulus and that the form of the biomaterial may influence the extent of DC maturation.}, }
@article {pmid15363312, year = {2004}, author = {Fan, Y and Lang, RG and Wang, Y and Sun, BC and Fu, L}, title = {[Relationship between expression of cell adhesion molecules and metastatic potential in invasive micropapillary carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {33}, number = {4}, pages = {308-311}, pmid = {15363312}, issn = {0529-5807}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/metabolism/secondary ; Carcinoma, Papillary/*metabolism/secondary ; Cell Membrane/*metabolism ; Cytoskeletal Proteins/metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Trans-Activators/metabolism ; alpha Catenin ; beta Catenin ; }, abstract = {OBJECTIVE: To investigate the expression of cell adhesion molecules and Their significance in invasive micropapillary carcinoma (IMPC) of the breast.<br><br>METHODS: Immunohistochemical study for E-cadherin was performed on 64 cases of IMPC and 57 cases of invasive ductal carcinoma (IDC).<br><br>RESULTS: E-cadherin was mainly expressed on the cell membrane of tumor cells. The expression of E-cadherin in IMPC (85.9%, 55/64) was significantly higher than that in IDC (43.9%, 25/57). E-cadherin expressed in the intercellular contact surface of IMPC cells. In contrast, it was weakly positive/not expressed on the outer membranous surface of the tumor clusters in IMPC. The rate of lymph node metastasis in IMPC (85.9%, 55/64) was significantly higher than that in IDC (52.6%, 30/57), the rate of alpha-catenin and beta-catenin coexpression in IMPC (45.1%, 26/51) with lymph node metastasis and E-cadherin normal expression was also significantly higher than that in IDC (15.4%, 2/13).<br><br>CONCLUSION: Weak cell adhesion molecule expression on the outer surface of IMPC cell clusters, in contrast to strong cohesion in intercellular contact surface, may help to explain the high metastatic potential of this type of breast cancer.}, }
@article {pmid15358256, year = {2004}, author = {Llinás, M and DeRisi, JL}, title = {Pernicious plans revealed: Plasmodium falciparum genome wide expression analysis.}, journal = {Current opinion in microbiology}, volume = {7}, number = {4}, pages = {382-387}, doi = {10.1016/j.mib.2004.06.014}, pmid = {15358256}, issn = {1369-5274}, mesh = {Animals ; Erythrocytes/*parasitology ; Gene Expression Profiling/methods ; *Gene Expression Regulation ; *Genome, Protozoan ; Humans ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/*growth &amp; development ; *Proteome ; Protozoan Proteins/genetics/*metabolism ; }, abstract = {The asexual intraerythrocytic developmental cycle (IDC) of Plasmodium falciparum is responsible for the majority of the clinical manifestations of malaria in humans. Although malaria has been studied for over a century, the elucidation of the full genome sequence of P. falciparum has now allowed for in-depth studies of gene expression throughout the entire intraerythrocytic stage. As the mainstays of anti-malarial chemotherapy become increasingly ineffective, we need a deeper understanding of fundamental plasmodial bioregulatory mechanisms to successfully subvert them. Recent gene expression studies have begun to examine different aspects of the IDC and are providing key insights into the basic mechanisms of Plasmodium gene regulation and are helping to define gene functions. However, to date, no transcription factor has been fully characterized from Plasmodium and the definitive identification of cis-acting regulatory elements along with their corresponding trans-acting partners is still lacking. The characterization of the transcriptome of P. falciparum is the first major step towards the understanding of the genome wide regulation of gene expression in this parasite. IDC expression data for almost every gene in the P. falciparum genome can now be publicly queried at and. The results of these studies suggest promising leads for identifying novel targets for anti-malarial therapeutics and vaccines in addition to providing a solid foundation for the ongoing elucidation of plasmodial gene expression.}, }
@article {pmid15356156, year = {2004}, author = {Skorokhod, OA and Alessio, M and Mordmüller, B and Arese, P and Schwarzer, E}, title = {Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: a peroxisome proliferator-activated receptor-gamma-mediated effect.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {173}, number = {6}, pages = {4066-4074}, doi = {10.4049/jimmunol.173.6.4066}, pmid = {15356156}, issn = {0022-1767}, mesh = {Aldehydes/metabolism/pharmacology ; Animals ; Antigens, CD ; Antigens, CD1/biosynthesis ; Antigens, Surface/biosynthesis ; Apoptosis/immunology ; Biotransformation ; Cell Differentiation/immunology ; Dendritic Cells/*immunology/metabolism/parasitology/pathology ; Growth Inhibitors/metabolism/pharmacology/*physiology ; Hemeproteins/metabolism/*physiology ; Humans ; Hydroxyeicosatetraenoic Acids/metabolism/physiology ; Immunoglobulins/biosynthesis/genetics ; Immunosuppressive Agents/metabolism/*pharmacology ; Leukocyte Count ; Ligands ; Membrane Glycoproteins/antagonists &amp; inhibitors/biosynthesis/genetics ; Monocytes/*immunology/metabolism/parasitology/pathology ; NF-kappa B/metabolism ; Peroxisomes/immunology/metabolism/parasitology/pathology ; Phagocytosis/immunology ; Pigments, Biological/metabolism/*physiology ; Plasmodium falciparum/*immunology ; RNA, Messenger/antagonists &amp; inhibitors/biosynthesis ; Receptors, Cytoplasmic and Nuclear/biosynthesis/genetics/metabolism/*physiology ; Transcription Factors/biosynthesis/genetics/metabolism/*physiology ; Up-Regulation/immunology ; }, abstract = {Acute and chronic Plasmodium falciparum malaria are accompanied by severe immunodepression possibly related to subversion of dendritic cells (DC) functionality. Phagocytosed hemozoin (malarial pigment) was shown to inhibit monocyte functions related to immunity. Hemozoin-loaded monocytes, frequently found in circulation and adherent to endothelia in malaria, may interfere with DC development and play a role in immunodepression. Hemozoin-loaded and unloaded human monocytes were differentiated in vitro to immature DC (iDC) by treatment with GM-CSF and IL-4, and to mature DC (mDC) by LPS challenge. In a second setting, hemozoin was fed to iDC further cultured to give mDC. In both settings, cells ingested large amounts of hemozoin undegraded during DC maturation. Hemozoin-fed monocytes did not apoptose but their differentiation and maturation to DC was severely impaired as shown by blunted expression of MHC class II and costimulatory molecules CD83, CD80, CD54, CD40, CD1a, and lower levels of CD83-specific mRNA in hemozoin-loaded iDC and mDC compared with unfed or latex-loaded DC. Further studies indicated activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in hemozoin-loaded iDC and mDC, associated with increased expression of PPAR-gamma mRNA, without apparent involvement of NF-kappaB. Moreover, expression of PPAR-gamma was induced and up-regulation of CD83 was inhibited by supplementing iDC and mDC with plausible concentrations of 15(S)-hydroxyeicosatetraenoic acid, a PPAR-gamma ligand abundantly produced by hemozoin via heme-catalyzed lipoperoxidation.}, }
@article {pmid15354746, year = {2004}, author = {Vassallo, J and Pinto, GA and Alvarenga, JM and Zeferino, LC and Chagas, CA and Metze, K}, title = {Comparison of immunoexpression of 2 antibodies for estrogen receptors (1D5 and 6F11) in breast carcinomas using different antigen retrieval and detection methods.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {12}, number = {2}, pages = {177-182}, doi = {10.1097/00129039-200406000-00014}, pmid = {15354746}, issn = {1541-2016}, mesh = {*Antibodies, Monoclonal ; Antigen-Antibody Reactions ; Antigens, Neoplasm/*analysis/immunology ; Carcinoma, Ductal, Breast/*diagnosis ; Female ; Humans ; Immunohistochemistry/methods ; Receptors, Estrogen/*analysis/immunology ; }, abstract = {The importance of in situ immunodetection of hormone receptors for therapy planning and prognostic evaluation in patients with breast carcinoma is well established. Sensitive detection methods are of utmost importance, especially in poorly fixed tissues, which are not uncommon in routine pathologic practice. The purpose of the present study is to compare immunoexpression of estrogen receptors in 20 cases of invasive ductal carcinoma using two antibodies, 1D5 and 6F11, and to verify the effect of different antigen retrieval solutions and detection systems. Immunoperoxidase was performed on paraffin sections using 1D5 and 6F11 as primary antibodies. Heat-induced antigen retrieval was performed using citrate buffer (pH 6.0) or Tris-EDTA buffer (pH 8.9). Detection was achieved using the following systems: EnVision, EnVision Plus, and labeled streptavidin-biotin peroxidase complex. Reaction was semiquantified from 0 to 4. There were no differences between the two markers, 1D5 and 6F11, except when 6F11 was used with EnVision and citrate buffer, in which case weaker reactivity was observed. Only in this combination (6F11/EnVision) was EDTA buffer significantly better than citrate. Labeled streptavidin-biotin peroxidase complex presented the best results, followed by EnVision Plus.}, }
@article {pmid15342290, year = {2004}, author = {Fujioka, S and Kitaura, Y and Deguchi, H and Shimizu, A and Isomura, T and Suma, H and Sabbah, HN}, title = {Evidence of viral infection in the myocardium of American and Japanese patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {94}, number = {5}, pages = {602-605}, doi = {10.1016/j.amjcard.2004.05.023}, pmid = {15342290}, issn = {0002-9149}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*ethnology/*virology ; Coxsackievirus Infections ; Enterovirus ; Female ; Heart/*virology ; Humans ; Japan/epidemiology ; Male ; Middle Aged ; Myocarditis/*complications/*ethnology/virology ; United States/epidemiology ; Virus Diseases/complications ; }, abstract = {Enteroviruses have been implicated in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Recently, the association of adenovirus or parvovirus with IDC has been reported. Viral infection in the myocardium of American and Japanese patients with end-stage IDC was evaluated. Myocardial specimens from 30 American patients with IDC and 47 Japanese patients with IDC were analyzed for the presence of cardiotropic viruses. The strand-specific detection of enteroviral ribonucleic acid (RNA) was performed to determine viral activity in hearts with IDC. Established reverse transcription-polymerase chain reaction (PCR) or PCR techniques were used to detect genomic sequences of influenza viruses, mumps virus, adenovirus, parvovirus, herpes simplex viruses, varicella-zoster virus, and Epstein-Barr virus. Enteroviral RNA was detected in 7 of the 30 American patients (23%) and in 15 of the 47 Japanese patients (32%). Minus-strand enteroviral RNA, an indicator of active enteroviral RNA replication, was demonstrated in 5 of 7 plus-strand-positive American patients (71%) and in 12 of 15 plus-strand-positive Japanese patients (80%). Sequence analysis revealed that the viruses detected were Coxsackie B viruses. No genomic sequences of other viruses were detected in the myocardium of either American or Japanese patients with IDC. Therefore, active group B Coxsackie virus RNA replication in the myocardium was demonstrated in a significant proportion of American and Japanese patients with end-stage IDC. There was no evidence of persistent infection by other viruses in hearts with IDC. Specific therapy should be designed for Coxsackie virus positive patients with IDC.}, }
@article {pmid15338348, year = {2004}, author = {Kijima, Y and Yoshinaka, H and Owaki, T and Nozaki, T and Hamada, T and Yasumoto, Y and Aikou, T}, title = {Breast cancer with nephrotic syndrome: report of two cases.}, journal = {Surgery today}, volume = {34}, number = {9}, pages = {755-759}, doi = {10.1007/s00595-004-2811-8}, pmid = {15338348}, issn = {0941-1291}, mesh = {Breast Neoplasms/*complications/diagnosis/surgery ; Carcinoma, Ductal, Breast/*complications/diagnosis/surgery ; Female ; Glomerulonephritis, Membranous/*etiology ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Nephrotic Syndrome/*etiology ; Treatment Outcome ; }, abstract = {We report two cases of women found to have breast cancers within a few months of being diagnosed with nephrotic syndrome. Case 1 was a 53-year-old Japanese woman in whom breast cancer was diagnosed 14 months after the onset of nephrotic syndrome. The histological diagnosis was invasive ductal carcinoma with no lymph node metastasis. We performed a modified radical mastectomy, after which the proteinuria and hypoproteinemia resolved almost completely, and the patient has been disease-free for 5 years since. Case 2 was a 61-year-old Japanese woman in whom breast cancer was diagnosed 2 months after the onset of membranous nephropathy. We performed a modified radical mastectomy and the histological diagnosis was invasive ductal carcinoma with marked lymphatic vessel permeation and involvement of five axillary lymph nodes. Proteinuria and hypoproteinemia did not resolve postoperatively and there is a high possibility of remnant or recurrent cancer. To our knowledge, there are only four other reported cases of paraneoplastic membranous nephropathy complicating breast cancer. However, we speculate that the postoperative resolution of nephrotic syndrome might be a measure of cancer control.}, }
@article {pmid15334643, year = {2004}, author = {Weizman, DA and Leong, WL}, title = {Anti-Ri antibody opsoclonus-myoclonus syndrome and breast cancer: a case report and a review of the literature.}, journal = {Journal of surgical oncology}, volume = {87}, number = {3}, pages = {143-145}, doi = {10.1002/jso.20103}, pmid = {15334643}, issn = {0022-4790}, mesh = {Aged ; Antigens, Neoplasm/*immunology ; Autoantibodies/analysis ; Breast Neoplasms/*complications/surgery ; Carcinoma, Ductal, Breast/*complications/surgery ; Female ; Humans ; Nerve Tissue Proteins/*immunology ; Neuro-Oncological Ventral Antigen ; Paraneoplastic Syndromes, Nervous System/complications/*immunology ; Purkinje Cells/immunology ; RNA-Binding Proteins/*immunology ; }, abstract = {Opsoclonus-myoclonus is a rare neurological paraneoplastic syndrome associated with breast cancer and the presence of anti-Ri antibody. We presented a case of a 79-year-old woman with this syndrome and a small invasive ductal carcinoma [pT1aN0(sn)M0], whose symptoms improved 3 months following her simple mastectomy without any adjuvant therapy. Based on the 15 previously reported cases in the literature, there is no uniform treatment option available, and the response to such treatments is mixed.}, }
@article {pmid15331393, year = {2005}, author = {Radstake, TR and van der Voort, R and ten Brummelhuis, M and de Waal Malefijt, M and Looman, M and Figdor, CG and van den Berg, WB and Barrera, P and Adema, GJ}, title = {Increased expression of CCL18, CCL19, and CCL17 by dendritic cells from patients with rheumatoid arthritis, and regulation by Fc gamma receptors.}, journal = {Annals of the rheumatic diseases}, volume = {64}, number = {3}, pages = {359-367}, pmid = {15331393}, issn = {0003-4967}, mesh = {Arthritis, Rheumatoid/*blood ; Cells, Cultured ; Chemokine CCL17 ; Chemokine CCL19 ; Chemokines, CC/biosynthesis/*blood/genetics ; Dendritic Cells/*metabolism ; Gene Expression Regulation ; Humans ; Monocytes/metabolism ; Polymerase Chain Reaction/methods ; RNA, Messenger/genetics ; Receptors, IgG/*physiology ; Severity of Illness Index ; Synovial Membrane/metabolism ; }, abstract = {BACKGROUND: Dendritic cells (DC) have a role in the regulation of immunity and tolerance, attracting inflammatory cells by the production of various chemokines (CK). Fc gamma receptors (Fc gamma R) may be involved in regulation of the DC function.<br><br>OBJECTIVE: To assess the expression of CK by immature (iDC) and mature DC (mDC) and its regulation by Fc gamma R in patients with RA and healthy donors (HC).<br><br>METHODS: Expression of CK by DC from patients with RA and from HC was determined by real time quantitative PCR and ELISA. DC were derived from monocytes following standardised protocols. To study the potential regulation by Fc gamma R, iDC were stimulated with immune complexes (IC) during lipopolysaccharide (LPS) induced maturation. The presence of CK was studied in synovial tissue from patients with RA, osteoarthritis, and healthy subjects by RT-PCR and immunohistochemistry.<br><br>RESULTS: iDC from patients with RA had markedly increased mRNA levels of the CK CCL18 and CXCL8. Upon maturation with LPS, expression of CCL18, CCL19, CXCL8, CCL3, and CCL17 increased dramatically, reaching significantly higher levels in patients with RA. Monocytes failed to express these CK, except for CXCL8 and CCL3. IC-mediated triggering of the Fc gamma R on DC from patients with highly active RA down regulated all CK, whereas the reverse was seen when DC from patients with low disease activity and healthy donors were stimulated. CCL18 was significantly increased in RA synovial tissue.<br><br>CONCLUSION: Increased CK expression by DC was found in patients with RA. This expression is partly regulated by Fc gamma R triggering and results in an inhibitory DC subtype in RA upon Fc gamma R-mediated triggering.}, }
@article {pmid15330252, year = {2004}, author = {Castriconi, R and Della Chiesa, M and Moretta, A}, title = {Shaping of adaptive immunity by innate interactions.}, journal = {Comptes rendus biologies}, volume = {327}, number = {6}, pages = {533-537}, doi = {10.1016/j.crvi.2003.12.001}, pmid = {15330252}, issn = {1631-0691}, mesh = {Animals ; Cell Communication/immunology ; Dendritic Cells/*immunology ; *Immunity, Innate ; Killer Cells, Natural/*immunology ; Lymphocyte Activation ; Monocytes/immunology ; }, abstract = {In inflamed tissues, the reciprocal interaction between Natural Killer (NK) cells and Dendritic Cells (DC) results in a potent activating cross talk that leads to DC maturation and NK cell activation with acquisition of NK-mediated cytotoxicity against immature DC (iDC). We focused our studies on NK-mediated killing of monocyte-derived iDC and we provided evidence that NK cells that express CD94/NKG2A but not killer Ig-like receptors (KIR) are able to kill autologous iDC. Indeed HLA-E (i.e. the cellular ligand of CD94/NKG2A) is sharply reduced in iDC, whereas it is partially recovered in mDC. The latter are lysed only by a small fraction of NK clones characterized by low levels of CD94/NKG2A expression. Another NK receptor, whose surface density is crucial for the ability to kill iDC, is represented by NKp30, a member of the NCR (Natural Cytotoxicity Receptor) family. We showed that transforming growth factor beta1 (TGFbeta1) treatment results in specific downregulation of NKp30 expression. This effect profoundly inhibits the NK-mediated killing of DC suggesting a possible mechanism by which TGFbeta1-producing DC may acquire resistance to the NK-mediated attack.}, }
@article {pmid15322200, year = {2004}, author = {Giese, A and Stuhlsatz, S and Däubener, W and MacKenzie, CR}, title = {Inhibition of the growth of Toxoplasma gondii in immature human dendritic cells is dependent on the expression of TNF-alpha receptor 2.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {173}, number = {5}, pages = {3366-3374}, doi = {10.4049/jimmunol.173.5.3366}, pmid = {15322200}, issn = {0022-1767}, mesh = {Animals ; Cell Differentiation/*immunology ; Dendritic Cells/*immunology/microbiology ; Humans ; Receptors, Tumor Necrosis Factor/antagonists &amp; inhibitors/genetics/immunology/*metabolism ; Toxoplasma/growth &amp; development/*immunology ; Toxoplasmosis/*immunology ; Tumor Necrosis Factor-alpha/immunology/metabolism ; }, abstract = {An effective immunity to Toxoplasma gondii in humans is dependent on the cellular immune response. Toxoplasma can infect and replicate in almost all nucleated cells, and the most important cytokine regulating the growth in humans is IFN-gamma; however, the role of TNF-alpha has to date been largely described to be synergistic. We show that, compared with mature human dendritic cells (mDC), immature human DC (iDC) demonstrate a reduced parasite proliferation when infected with Toxoplasma. This toxoplasmostasis was only present in iDC after 11 days of culture and was not present in DC that had been matured ex vivo using a cytokine mixture (mDC). Spontaneous toxoplasmostatic activity has previously only been described in fresh human monocytes, and the mechanism involved is as yet unclear. We show that, in comparison with an absence of expression in mDC, TNF-R2 is expressed in both iDC and monocytes infected with Toxoplasma, and furthermore, that blocking the TNF-R2 with Abs abrogates the toxoplasmostasis in the iDC. These findings demonstrate a functional role for TNF-R2 in the newly described spontaneous toxoplasmostasis of iDC.}, }
@article {pmid15318940, year = {2004}, author = {Madrid, MA and Lo, RW}, title = {Chromogenic in situ hybridization (CISH): a novel alternative in screening archival breast cancer tissue samples for HER-2/neu status.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {5}, pages = {R593-600}, pmid = {15318940}, issn = {1465-542X}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization/*methods ; Nucleic Acid Amplification Techniques ; Receptor, ErbB-2/metabolism ; }, abstract = {BACKGROUND: Chromogenic in situ hybridization (CISH) is emerging as a practical, cost-effective, and valid alternative to fluorescent in situ hybridization in testing for gene alteration, especially in centers primarily working with immunohistochemistry (IHC).<br><br>METHODS: We assessed Her-2/neu alteration using CISH on formalin-fixed paraffin-embedded primary invasive ductal carcinoma tumors in which IHC (CB11 antibody) had previously been performed, and we compared the results with IHC. The 160 selected cases were equally stratified randomly into the four IHC categories (scores of 0, 1+, 2+, and 3+). We also compared age at diagnosis and tumor histologic grade with IHC and CISH Her-2/neu.<br><br>RESULTS: We were able to perform and evaluate CISH successfully on all cases. The agreement between 3+ IHC and CISH-amplified cases as well as between all IHC and CISH Her-2/neu negative cases was 100%, and the concordance on all positive cases was 72.50%, with an overall agreement of 86.25%. All the discordant cases had 2+ IHC scores. Although we noted Her-2/neu positivity more in premenopausal women, the age at diagnosis was not significantly associated with IHC or CISH results. Similarly, although the small group of well-differentiated tumors was apparently Her-2/neu negative in both tests, no significant association was noted between any tumor histologic grade and either IHC or CISH results.<br><br>CONCLUSIONS: CISH is easily integrated into routine testing in our laboratory. It is a necessary adjunct in determining the subset of non-amplified IHC-positive invasive tumors that will not benefit from trastuzumab therapy. Those cases with 2+ IHC results will be triaged and subjected to CISH. Her-2/neu testing should be done on all breast cancer cases regardless of age at presentation and tumor histologic grade.}, }
@article {pmid15318932, year = {2004}, author = {Abba, MC and Drake, JA and Hawkins, KA and Hu, Y and Sun, H and Notcovich, C and Gaddis, S and Sahin, A and Baggerly, K and Aldaz, CM}, title = {Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {5}, pages = {R499-513}, pmid = {15318932}, issn = {1465-542X}, support = {U19 CA084978/CA/NCI NIH HHS/United States ; 1U19 CA84978/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Cycle ; Cell Division ; Extracellular Matrix ; Gene Expression ; *Gene Expression Profiling ; Gene Library ; Humans ; NF-kappa B ; Neoplasm Invasiveness/genetics ; Neoplasm Metastasis/genetics ; Tumor Necrosis Factor-alpha ; }, abstract = {INTRODUCTION: Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution.<br><br>METHODS: In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed.<br><br>RESULTS: We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01).<br><br>CONCLUSION: A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions with fully invasive lesions, a much more heterogeneous group, clearly identified as the most importantly deregulated group of transcripts those encoding for various families of proteins in charge of extracellular matrix remodeling, invasion and cell motility functions.}, }
@article {pmid15307010, year = {2004}, author = {DeJesus, E and McCarty, D and Farthing, CF and Shortino, DD and Grinsztejn, B and Thomas, DA and Schrader, SR and Castillo, SA and Sension, MG and Gough, K and Madison, SJ and , }, title = {Once-daily versus twice-daily lamivudine, in combination with zidovudine and efavirenz, for the treatment of antiretroviral-naive adults with HIV infection: a randomized equivalence trial.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {39}, number = {3}, pages = {411-418}, doi = {10.1086/422143}, pmid = {15307010}, issn = {1537-6591}, mesh = {Adolescent ; Adult ; Aged ; Alkynes ; Anti-HIV Agents/administration &amp; dosage ; Antiretroviral Therapy, Highly Active/*methods ; Benzoxazines ; CD4 Lymphocyte Count ; Cyclopropanes ; Disease Progression ; Double-Blind Method ; Drug Administration Schedule ; Drug Resistance, Viral ; Female ; HIV Infections/*drug therapy/virology ; HIV-1/drug effects/isolation &amp; purification ; Humans ; Lamivudine/*administration &amp; dosage/adverse effects ; Male ; Middle Aged ; Oxazines/administration &amp; dosage ; RNA, Viral/blood ; Reverse Transcriptase Inhibitors/*administration &amp; dosage/adverse effects ; Viral Load ; Zidovudine/administration &amp; dosage ; }, abstract = {A randomized, double-blind, double-dummy controlled, multicenter trial was conducted that involved 554 antiretroviral-naive human immunodeficiency virus-infected adults (plasma HIV type 1 [HIV-1] RNA level, >or=400 copies/mL; CD4(+) cell count, >100 cells/mm(3)) and compared a 300-mg once-daily (q.d.) regimen of lamivudine (3TC) versus a 150-mg twice-daily (b.i.d.) regimen of 3TC, combined with zidovudine (300 mg b.i.d.) and efavirenz (600 mg q.d.), during a 48-week period. Treatments were considered equivalent if the 95% confidence interval (CI) for the difference in proportions of patients achieving an HIV-1 RNA level of <400 copies/mL was within the bound of -12% to 12%. At week 48 of the study, an intent-to-treat analysis in which patients with missing data were considered to have experienced treatment failure showed that the 3TC q.d. and 3TC b.i.d. regimens were equivalent (HIV-1 RNA level <400 copies/mL, 178 [64%] of 278 vs. 174 [63%] of 276; treatment difference, 1% [95% CI, -7.1% to 8.9%]; HIV-1 RNA level <50 copies/mL, 165 [59%] of 278 vs. 168 [61%] of 276; treatment difference, 1.7% [95% CI, -9.7% to 6.6%]). Median increase above baseline in CD4(+) cell count was similar (q.d. group, +144 cells/mm(3); b.i.d. group, +146 cells/mm(3)), and the incidences of adverse events, disease progression, and HIV-associated conditions were comparable.}, }
@article {pmid15295005, year = {2004}, author = {Cignetti, A and Vallario, A and Roato, I and Circosta, P and Allione, B and Casorzo, L and Ghia, P and Caligaris-Cappio, F}, title = {Leukemia-derived immature dendritic cells differentiate into functionally competent mature dendritic cells that efficiently stimulate T cell responses.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {173}, number = {4}, pages = {2855-2865}, doi = {10.4049/jimmunol.173.4.2855}, pmid = {15295005}, issn = {0022-1767}, mesh = {CD40 Ligand/pharmacology ; Cell Differentiation/drug effects/*immunology ; Cell Movement/immunology ; Cells, Cultured ; Cytokines/biosynthesis/immunology ; Dendritic Cells/cytology/drug effects/*immunology ; Female ; Flow Cytometry ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute/*immunology ; Lipopolysaccharide Receptors/immunology ; Lymphocyte Activation/drug effects/*immunology ; Male ; Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/*immunology ; }, abstract = {Primary acute myeloid leukemia cells can be induced to differentiate into dendritic cells (DC). In the presence of GM-CSF, TNF-alpha, and/or IL-4, leukemia-derived DC are obtained that display features of immature DC (i-DC). The aim of this study was to determine whether i-DC of leukemic origin could be further differentiated into mature DC (m-DC) and to evaluate the possibility that leukemic m-DC could be effective in vivo as a tumor vaccine. Using CD40L as maturating agent, we show that leukemic i-DC can differentiate into cells that fulfill the phenotypic criteria of m-DC and, compared with normal counterparts, are functionally competent in vitro in terms of: 1) production of cytokines that support T cell activation and proliferation and drive Th1 polarization; 2) generation of autologous CD8(+) CTLs and CD4(+) T cells that are MHC-restricted and leukemia-specific; 3) migration from tissues to lymph nodes; 4) amplification of Ag presentation by monocyte attraction; 5) attraction of naive/resting and activated T cells. Irradiation of leukemic i-DC after CD40L stimulation did not affect their differentiating and functional capacity. Our data indicate that acute myeloid leukemia cells can fully differentiate into functionally competent m-DC and lay the ground for testing their efficacy as a tumor vaccine.}, }
@article {pmid15289310, year = {2004}, author = {Fernández-Madrid, F and Tang, N and Alansari, H and Granda, JL and Tait, L and Amirikia, KC and Moroianu, M and Wang, X and Karvonen, RL}, title = {Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer.}, journal = {Cancer research}, volume = {64}, number = {15}, pages = {5089-5096}, doi = {10.1158/0008-5472.CAN-03-0932}, pmid = {15289310}, issn = {0008-5472}, mesh = {Annexins/*immunology ; Antibodies, Monoclonal ; Autoantibodies/*blood ; Autoantigens/*immunology ; Autoimmune Diseases/immunology/metabolism/pathology ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/diagnosis ; Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Female ; Humans ; Middle Aged ; Peptide Library ; }, abstract = {We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput method involved the assembly of 938 T7 phages encoding potential breast cancer autoantigens. Microarrays of positive phages were probed with sera from 90 patients with breast cancer [15 patients with ductal carcinoma in situ (DCIS) and 75 patients with IDC of the breast], with 51 non-cancer control sera and with sera from 21 patients with systemic autoimmune diseases. A 12-phage breast cancer predictor group was constructed with phage inserts recognized by sera from patients with breast cancer and not by non-cancer or autoimmune control sera (P < 0.0001). Several autoantigens including annexin XI-A, the p80 subunit of the Ku antigen, ribosomal protein S6, and other unknown autoantigens could significantly discriminate between breast cancer and non-cancer control sera. Biopanning with three different sera led to the cloning of partial cDNA sequences identical to annexin XI-A. IgG autoantibodies reacting with the amino acid 41-74 sequence of annexin XI-A were found in 19% of all women with breast cancer but in 60% of sera from women with DCIS of the breast. In addition, partial sequences identical to annexin XI-A, nucleolar protein interacting with the forkhead-associated (FHA) domain of pKi-67, the KIAA1671 gene product, ribosomal protein S6, cyclin K, elongation factor-2, Grb2-associated protein 2, and other unknown proteins could distinguish DCIS from IDC of the breast and appear to be potential biomarkers for the diagnosis of breast cancer.}, }
@article {pmid15279632, year = {2004}, author = {Sastre-Garau, X and Genin, P and Rousseau, A and Al Ghuzlan, A and Nicolas, A and Fréneaux, P and Rosty, C and Sigal-Zafrani, B and Couturier, J and Thiery, JP and Magdelénat, H and Vincent-Salomon, A}, title = {Increased cell size and Akt activation in HER-2/neu-overexpressing invasive ductal carcinoma of the breast.}, journal = {Histopathology}, volume = {45}, number = {2}, pages = {142-147}, doi = {10.1111/j.1365-2559.2004.01899.x}, pmid = {15279632}, issn = {0309-0167}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Case-Control Studies ; Cell Membrane/metabolism/pathology ; Cell Nucleus ; Cell Size ; DNA, Neoplasm/analysis ; Female ; Humans ; Image Processing, Computer-Assisted ; In Situ Hybridization, Fluorescence ; Protein Serine-Threonine Kinases/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-akt ; Receptor, ErbB-2/*metabolism ; }, abstract = {AIMS: To determine whether cell size is related to HER-2/neu status and/or to Akt activation in breast carcinomas. HER-2/neu overexpression is observed in 20-30% of invasive breast carcinomas with poor pronostic features, but little is known about the cell phenotype associated with HER-2/neu activation. Akt has been found to be involved in the HER-2/neu signal transduction pathway and Akt activation has been associated with increased cell size in various models.<br><br>METHODS AND RESULTS: A case-control study of invasive ductal carcinoma of the breast was carried out, including 21 cases displaying HER-2/neu overexpression and 20 HER-2/neu negative controls. Cytoplasmic and nuclear sizes were measured on digitized histological pictures using cell image analysis software. Akt expression analysis was performed by immunohistochemistry on formalin-fixed histological sections using an anti-phosphorylated-Akt (Ser473) antibody.<br><br>RESULTS: HER-2/neu-overexpressing carcinomas had a mean nuclear size of 75 +/- 22.2 micro m(2) and a mean cytoplasmic size of 187 +/- 52.3 micro m(2). Both values were higher than the nuclear and cytoplasmic size of HER-2/neu-negative cases (nucleus = 58 +/- 24.5 micro m(2), cytoplasm = 133 +/- 56.6 micro m(2); P = 0.02 and P =0.003, respectively). Up to 75% of the tumours with a cell size over 140 micro m(2) were HER-2/neu-positive. Immunohistochemical Akt expression was observed in 19/40 (47.5%) cases. The immunoreactivity was localized in the cytoplasm in eight cases, on the cell membrane in four cases and at both sites in seven cases. One case was not interpretable. Comparison between HER-2/neu and Akt status showed that Akt was detectable at the cell membrane in 43% (9/21) of HER-2/neu-positive and in 10% (2/19) of HER-2/neu-negative cases (P = 0.02).<br><br>CONCLUSIONS: HER-2/neu overexpression was consistently associated with increased cell size in invasive ductal carcinoma of the breast. This increase may be related to concomitant Akt activation. The assessment of activated pathways in HER-2/neu-overexpressing breast carcinomas may provide useful information for optimized individual HER-2/neu-targeted therapy.}, }
@article {pmid15277404, year = {2004}, author = {Rivas-Carvalho, A and Meraz-Ríos, MA and Santos-Argumedo, L and Bajaña, S and Soldevila, G and Moreno-García, ME and Sánchez-Torres, C}, title = {CD16+ human monocyte-derived dendritic cells matured with different and unrelated stimuli promote similar allogeneic Th2 responses: regulation by pro- and anti-inflammatory cytokines.}, journal = {International immunology}, volume = {16}, number = {9}, pages = {1251-1263}, doi = {10.1093/intimm/dxh127}, pmid = {15277404}, issn = {0953-8178}, mesh = {Cytokines/*physiology ; Dendritic Cells/*physiology ; Humans ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Interleukin-10/biosynthesis ; Interleukin-12/biosynthesis ; Interleukin-4/biosynthesis ; Lymphocyte Activation ; Monocytes/*cytology ; Receptors, IgG/*analysis ; Th2 Cells/*immunology ; }, abstract = {We previously demonstrated that tumor necrosis factor (TNF)-alpha-matured CD16- and CD16+ human monocyte-derived dendritic cells (16-mDC and 16+mDC) differentially stimulate naive CD4+ lymphocytes by inducing Th1- and Th2-like responses, respectively. Here, we further characterized the role of different DC maturation factors on Th polarization. Immature 16+mDC and 16-mDC (iDC) obtained by culture of purified monocytes with GM-CSF and IL-4 were maturated with (i) Toll-like receptor (TLR) ligands [lipopolysaccharide (LPS)], (ii) lymphocyte-derived (soluble CD40 ligand, IFN-gamma) and (iii) endogenous inflammatory stimuli [TNF-alpha, prostaglandin (PG)E2]. After activation with these stimuli, DC secrete IL-12 only in presence of LPS, and 16+mDC produced lower amounts of IL-12 and IL-10 than 16-mDC. Allogeneic CD4+CD45RO- lymphocytes co-cultured with 16+mDC secreted higher levels of IL-4 and IL-10 than those co-cultured with 16-mDC, regardless of the maturation stimuli. Results were similar when DC were activated with TLR-2 or TLR-3 ligands. The higher induction of IL-4 by 16+mDC was primarily dependent on IL-12, IL-4 and IL-10. IFN-gamma production by CD4+ T cells was similar with all the conditions except with LPS-16+mDC, which induced reduced amounts of this cytokine. Those differences were totally eliminated by neutralization of IL-12, IL-4 or IL-10. Finally, 16-mDC could reverse the Th2 phenotype of already committed lymphocytes toward a Th1 pattern in short-term cultures, whereas 16+mDC had less ability to skew this phenotype. These results indicate that 16+mDC elicit superior Th2 responses independently of the maturation factors that they received, and suggest that they could represent an important population of regulatory DC.}, }
@article {pmid15256443, year = {2004}, author = {Ford, CE and Faedo, M and Crouch, R and Lawson, JS and Rawlinson, WD}, title = {Progression from normal breast pathology to breast cancer is associated with increasing prevalence of mouse mammary tumor virus-like sequences in men and women.}, journal = {Cancer research}, volume = {64}, number = {14}, pages = {4755-4759}, doi = {10.1158/0008-5472.CAN-03-3804}, pmid = {15256443}, issn = {0008-5472}, mesh = {Adult ; Aged ; Animals ; Breast/cytology ; Breast Neoplasms/genetics/*virology ; Breast Neoplasms, Male/genetics/*virology ; Carcinoma in Situ/genetics/virology ; Carcinoma, Ductal/genetics/virology ; Cell Transformation, Viral/*genetics ; Cohort Studies ; Disease Progression ; Female ; Humans ; Longitudinal Studies ; Male ; Mammary Tumor Virus, Mouse/*genetics ; Mice ; Middle Aged ; NIH 3T3 Cells ; Precancerous Conditions/genetics/*virology ; Sex Factors ; }, abstract = {Mouse mammary tumor virus (MMTV)-like sequences have been found in up to 40% of breast cancer samples but in <2% of normal breast tissue samples from Australian women studied by our group. Screening of a larger and more diverse cohort of female breast cancer samples has now shown a correlation of MMTV-like sequences with the severity (grade) of breast cancer. Thirty-two percent (43 of 136) of female breast cancer samples were positive for MMTV-like sequences when screened using PCR. A significant gradient of MMTV positivity was observed with increasing severity of cancer from 23% of infiltrating ductal carcinoma (IDC) grade I tumors to 34% of IDC grade II tumors (P = 0.00034) and 38% of IDC grade III tumors (P = 0.00002). We also report for the first time the detection of MMTV-like sequences in 62% (8 of 13) of male breast cancer samples and 19% (10 of 52) of male gynecomastia samples screened. MMTV-like sequences were demonstrated in various premalignant breast lesions of females, including fibroadenoma (20%) and fibrocystic disease (28%) samples, at a significantly higher prevalence than that seen in normal breast tissue (1.8%; P = 0.00001). Study of a longitudinal cohort of female breast cancer patients indicated that MMTV was co-incident with tumor but was not present when tumor was absent on histology. These results support the association of MMTV-like sequences with development of breast tumors in men and women and suggest association of MMTV with increasing severity of cancer.}, }
@article {pmid15256368, year = {2004}, author = {Del Corsso, C and de Carvalho, AC and Martino, HF and Varanda, WA}, title = {Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {287}, number = {5}, pages = {H1928-36}, doi = {10.1152/ajpheart.00044.2004}, pmid = {15256368}, issn = {0363-6135}, mesh = {Action Potentials ; Adrenergic beta-Agonists/pharmacology ; Adult ; Aged ; Animals ; Autoantibodies/*blood ; Calcium Channels, L-Type/drug effects/*metabolism ; Cardiomyopathy, Dilated/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Isoproterenol/pharmacology ; Male ; Middle Aged ; Myocytes, Cardiac/*metabolism ; Patch-Clamp Techniques ; Rabbits ; Reaction Time ; Receptor, Muscarinic M2/*immunology ; Receptors, Adrenergic, beta-1/*immunology ; }, abstract = {Autoantibodies against muscarinic and adrenergic receptors have been found in the sera of patients with idiopathic dilated cardiomyopathy (IDC) and Chagas disease, but it is still unclear whether they can functionally interact with their respective receptors to modulate cardiac functions. In this study, our goal was to detect the presence of those antibodies in the sera of patients with IDC and characterize their electrophysiological effects on cardiomyocytes from rabbits. By using ELISA immunoassays, we detected high titers of antibodies against muscarinic M2 receptors in the sera of all IDC patients, whereas the detection of antibodies against the beta1-receptor occurred in 50% of them. Electrophysiological experiments using the whole cell configuration of the patch-clamp technique showed that sera from 43% of IDC patients induced a significant decrease (approximately 26%) in isoproterenol-stimulated L-type Ca2+ currents in rabbit ventricular myocytes, whereas the sera from healthy blood donors failed to do so. As expected, IDC sera also decreased the action potential duration (by 10.5%) due to a shortening of the plateau phase. Sera that reduced isoproterenol-stimulated L-type Ca2+ currents did not cause any effect on K+ currents. We conclude that sera from IDC patients have autoantibodies, which interact with muscarinic M2 receptors of rabbit cardiomyocytes, acting in an agonist-like fashion. This action results in changes in electrogenesis, which, as often observed in patients with IDC, could initiate ventricular arrhythmias that lead to sudden death.}, }
@article {pmid15239795, year = {2004}, author = {Pelte, MF and Schwaller, J and Cerrato, C and Meier, CA}, title = {Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion.}, journal = {The breast journal}, volume = {10}, number = {4}, pages = {350-354}, doi = {10.1111/j.1075-122X.2004.21467.x}, pmid = {15239795}, issn = {1075-122X}, mesh = {ACTH Syndrome, Ectopic/*complications ; Adrenocorticotropic Hormone/analysis/blood/metabolism ; Arrhythmias, Cardiac/etiology ; Biopsy, Needle ; Bone Neoplasms/secondary ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/*secondary ; Cushing Syndrome/*complications ; Fatal Outcome ; Female ; Gene Expression Regulation, Neoplastic ; Heart Failure/etiology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Liver Neoplasms/secondary ; Lung Neoplasms/metabolism/secondary ; Middle Aged ; Pro-Opiomelanocortin/*biosynthesis/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.}, }
@article {pmid15235131, year = {2003}, author = {Jinfeng, M and Kimura, W and Hirai, I and Sakurai, F and Moriya, T and Mizutani, M}, title = {Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis.}, journal = {International journal of gastrointestinal cancer}, volume = {34}, number = {1}, pages = {9-18}, pmid = {15235131}, issn = {1537-3649}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*genetics/*pathology ; Female ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Mucin 5AC ; Mucin-6 ; Mucins/*biosynthesis ; Pancreatic Neoplasms/*genetics/*pathology ; Prognosis ; Survival Analysis ; }, abstract = {AIM/BACKGROUND: MUC5AC and MUC6 are two major types of mucin that are abundantly present in the stomach; both of them form a gel of high viscosity that provides protection and lubrication. Expressions of MUC5AC and MUC6 are seen in pancreatic neoplasms, whereas the relationships between MUC5AC/MUC6 expression and clinicopathological factors and patient prognosis in invasive ductal carcinoma (IDC) of the pancreas have not been investigated. The aim of this study was to investigate MUC5AC and MUC6 expressions in IDC with special reference to clinicopathological factors and patient prognosis.<br><br>METHODS: Tissue samples were taken from 33 patients with IDC of the pancreas after radical surgical treatment. MUC5AC and MUC6 expressions were examined immunohistochemically.<br><br>RESULTS: The expressions of MUC5AC and MUC6 were observed in the cytoplasm of the tumor cells. MUC5AC and MUC6 immunoreactivities in the cancer tissues were found in 21 (63.6%) and 15 (45.5%) of 33 cases of IDC of the pancreas, respectively. MUC5AC-negative expression was associated significantly with lymphatic invasion, venous invasion, lymph node metastasis, and MUC5AC-positive patients showed significant better survival than those MUC5AC-negative patients. MUC6 expression was significantly related to tumor location, whereas MUC6 expression did not show significant relationship with patient survival.<br><br>CONCLUSION: The results indicate that MUC5AC expression plays an important role in impacting tumor progression in IDC of the pancreas. MUC5AC expression is a benefit to better survival of patients with IDC of the pancreas. MUC6 expression is not involved in tumor progression in IDC of the pancreas.}, }
@article {pmid15226612, year = {2004}, author = {Mieda, J and Ohaki, Y and Oguro, T and Shimizu, H and Akasaka, K and Kyomoto, A and Kurokawa, M and Arai, S and Mori, O and Okada, S and Kyono, S and Tanaka, N}, title = {Breast cancer with neuroendocrine differentiation detected by unique staining pattern of neoplastic cells in hercep test.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {71}, number = {3}, pages = {203-208}, doi = {10.1272/jnms.71.203}, pmid = {15226612}, issn = {1345-4676}, mesh = {Aged ; Aged, 80 and over ; *Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/pathology ; Carcinoma, Neuroendocrine/*diagnosis/genetics/pathology ; Female ; Humans ; Immunohistochemistry/*methods ; *Neoplasms, Multiple Primary ; Reagent Kits, Diagnostic ; Receptor, ErbB-2/*analysis ; Trastuzumab ; }, abstract = {Hercep Test (DAKO) is an immunohistological screening kit to select cases of advanced breast cancer with indication for treatment with a humanized mouse monoclonal antibody to human epidermal growth factor receptor-2, trasthzumab (Herceptin). We report a case of an 84-year-old female with invasive ductal carcinoma of the right breast, whose neoplastic cells showed a unique staining pattern in Hercep Test. The cells showed an intracytoplasmic fine granular staining pattern, instead of the membranous pattern of typical breast cancer cells. This unique staining pattern suggested some special features of the neoplastic cells. This case was finally diagnosed as invasive ductal carcinoma with focal neuroendocrine differentiation by subsequent imunohistochemical and electron microscopic examinations. The neoplastic cells showed positive reactivity for grimelius stain, chromogranin A, synaptophysin, and neuronspecific enolase, as well as electron-dense neurosecretory granules (up to 150 nm in diameter). This unique staining pattern of the neoplastic cells with Hercep Test is a useful clue to detect breast cancer with neuroendocrine differentiation, which is likely to be missed in routine examination. Clinical and pathologic findings including immunohistochemical and ultrastructural findings of this case are reported, together with a brief review of the literature.}, }
@article {pmid15222110, year = {2004}, author = {Yoshida, T and Horiguchi, J and Koibuchi, Y and Kanoh, T and Iijima, K and Yoshida, M and Kikuchi, M and Takata, D and Oyama, T and Iino, Y and Morishita, Y}, title = {[Metastatic breast cancer treated with trastuzumab and paclitaxel--a case report with clinically complete response].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {31}, number = {6}, pages = {907-910}, pmid = {15222110}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Drug Administration Schedule ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/surgery ; Paclitaxel/administration &amp; dosage ; Receptor, ErbB-2/biosynthesis ; Remission Induction ; Trastuzumab ; }, abstract = {A 60-year-old woman who had undergone a total glandectomy for non-invasive ductal carcinoma of the left breast at the age of 56 in another hospital had a local recurrence in the left preserved breast. The patient was referred to our hospital and underwent a mastectomy. After surgery, treatment of UFT and CPA was started. Seven months after surgery, metastasis occurred at the left supraclavicular lymph node, and CPA, THP-adriamycine and 5-FU therapy was started. Fourteen months after surgery, skin redness of the left upper arm, the left chest wall and contralateral breast, and a contralateral axillary lymph node swelling were recognized. Neither docetaxel nor mitoxantrone-combined therapy was effective. Trastuzumab therapy was started because of HER2 overexpression by immunohistochemistry, and partial response was received after 7 weeks. Four months later, multiple nodules in the chest wall were recognized, and weekly treatment of trastuzumab and paclitaxel was started. Skin redness and multiple nodules in the chest wall completely disappeared after 3 months. No recurrence has been found for 14 months.}, }
@article {pmid15215807, year = {2004}, author = {Smilde, TD and Hillege, HL and Navis, G and Boomsma, F and de Zeeuw, D and van Veldhuisen, DJ}, title = {Impaired renal function in patients with ischemic and nonischemic chronic heart failure: association with neurohormonal activation and survival.}, journal = {American heart journal}, volume = {148}, number = {1}, pages = {165-172}, doi = {10.1016/j.ahj.2004.02.007}, pmid = {15215807}, issn = {1097-6744}, mesh = {Aged ; Cardiomyopathy, Dilated/*blood/complications/mortality ; Coronary Artery Disease/complications ; Female ; Glomerular Filtration Rate ; Heart Failure/*blood/etiology/mortality ; Humans ; Kidney Diseases/blood/*complications/physiopathology ; Male ; Middle Aged ; Multivariate Analysis ; Natriuretic Peptides/*blood ; Neurotransmitter Agents/*blood ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Survival Analysis ; }, abstract = {BACKGROUND: Renal dysfunction is a strong predictor of mortality in chronic heart failure (CHF). Most patients with CHF have atherosclerotic vascular disease, and several authors have suggested that impaired renal function is only a marker of advanced atherosclerosis. We compared renal function in patients with ischemic and nonischemic CHF and examined associations with prognosis and extent of neurohormonal activation.<br><br>METHODS: In a large survival study (1906 patients), patients with documented coronary artery disease (CAD, n = 995), were compared with patients with idiopathic dilated cardiomyopathy (IDC, n = 429). In a smaller substudy, plasma neurohormones were determined in 270 patients and 37 patients (CAD and IDC, respectively). All patients had advanced CHF (New York Heart Association functional class III-IV). At baseline, the mean patient age was 64 +/- 10 years, and the mean left ventricular ejection fraction was 0.26 +/- 0.08. The baseline glomerular filtration rate was calculated with the Cockcroft-Gault equation (GFRc).<br><br>RESULTS: GFRc was a strong predictor for mortality in both groups on multivariate analysis. The relative risk was 3.04 for patients with IDC (P < or =.01, for the lowest quartile < or =53 mL/min), and the relative risk for patients with CAD was 1.81 (P =.01 for the lowest quartile < or =42 mL/min). Plasma neurohormones showed a relation with GFRc in both groups.<br><br>CONCLUSIONS: GFRc is related to survival and plasma neurohormones in both patient groups. In patients with IDC, this association appears to be at least as strong as in patients with CAD.}, }
@article {pmid15182249, year = {2004}, author = {Chen, L and Jondal, M}, title = {Endolysosomal processing of exogenous antigen into major histocompatibility complex class I-binding peptides.}, journal = {Scandinavian journal of immunology}, volume = {59}, number = {6}, pages = {545-552}, doi = {10.1111/j.1365-3083.2004.01426.x}, pmid = {15182249}, issn = {0300-9475}, mesh = {Animals ; Antigen Presentation/*immunology ; Dendritic Cells/*cytology/immunology ; Egg Proteins/immunology ; Endosomes/*immunology ; Female ; Flow Cytometry ; Histocompatibility Antigens Class I/*immunology ; Lysosomes/*immunology ; Ovalbumin/immunology ; Peptide Fragments ; }, abstract = {An alternative endolysosomal pathway has recently been suggested for the processing of MHC-I-binding peptides, and peptide/MHC-I complexes have been demonstrated in this compartment. However, it remains unclear where in the antigen-presenting cells such peptides are processed, in the endolysosomes themselves or in the proteasomal complex. Here, we have investigated this using monoclonal antibodies specific for the immunodominant SIINFEKL/Kb complex (25-D1) or for the carbohydrate part of Db- or Kb-binding glycopeptides in combination with inhibitors for classical and endolysosomal MHC-I-processing pathways. Alternative processing was detected in both wt and TAP1(-/-) immature DC (iDC) as the expression of SIINFEKL/Kb complexes on the surface of OVA-treated cells in the presence of Brefeldin A (BFA) or lactacystin and their absence in the presence of the lysosomotropic amines ammonium chloride, chloroquine and methylamine. Internalized Db- and Kb-binding glycopeptides, detected with high specificity using an anti-galabiose (Gal2) monoclonal antibody, were found to appear on the cell surface of BFA-treated cells after intracellular MHC-I-binding. Peptide exchange in Kb was demonstrated as the gradual appearance of SIINFEKL/Kb complexes on BFA-treated cells which earlier had been saturated with another Kb-binding peptide. Our data support the presence of a fully functional endolysosomal processing pathway in iDC guided by the chaperone function of MHC-I molecules.}, }
@article {pmid15162424, year = {2004}, author = {Zehn, D and Cohen, CJ and Reiter, Y and Walden, P}, title = {Extended presentation of specific MHC-peptide complexes by mature dendritic cells compared to other types of antigen-presenting cells.}, journal = {European journal of immunology}, volume = {34}, number = {6}, pages = {1551-1560}, doi = {10.1002/eji.200324355}, pmid = {15162424}, issn = {0014-2980}, mesh = {Antigen Presentation/*immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cell Line, Tumor/immunology ; Cell Membrane/immunology ; Dendritic Cells/*immunology ; Epitopes/immunology ; HLA-A Antigens/*immunology ; Humans ; Kinetics ; Microscopy, Confocal ; Monocytes/immunology ; Peptide Fragments/immunology ; Receptors, Antigen, T-Cell/*immunology ; Recombinant Proteins/immunology ; Sodium Azide ; }, abstract = {Dendritic cells are known as the most potent antigen-presenting cells for the induction of T cell-mediated immune responses. To discriminate between the presentation of antigens and the co-stimulatory aspects of this high immunostimulatory capacity, we used recombinant antibodies with T cell receptor-like specificity to detect defined MHC-peptide complexes on living cells. Mature human dendritic cells (mDC) were compared with immature DC (iDC), monocytes, CD4(+) T lymphocytes, melanoma cells, T2 cells and B lymphoblastoid cells for their capacity to present MHC class I-restricted tumor-associated T cell epitopes and were found to display the specific peptides two to six times longer than other cells. The most short-lived peptide had an average half-life of 8.7 h on mDCvs. 3.5 h on B lymphoblastoid cells, while the most long-lived peptide had a half-life of 118.5 h vs. 20.7 h on these two cell types. The decay kinetics of specific MHC-peptide complexes on iDC were among the fastest observed. The high potency of dendritic cells to induce specific T cell responses is thus based, in addition to the expression of co-stimulatory molecules, on an extended antigenic memory, which increases the likelihood and the extent of contacts between dendritic cells and antigen-specific T cells.}, }
@article {pmid15154643, year = {2004}, author = {Toga, T and Nio, Y and Hashimoto, K and Higami, T and Maruyama, R}, title = {The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome.}, journal = {Anticancer research}, volume = {24}, number = {2C}, pages = {1173-1178}, pmid = {15154643}, issn = {0250-7005}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/genetics/*metabolism/pathology/surgery ; Chemotherapy, Adjuvant ; DNA-Binding Proteins/*biosynthesis/genetics ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pancreatic Neoplasms/genetics/*metabolism/pathology/surgery ; RNA, Messenger/*biosynthesis/genetics ; Smad4 Protein ; Trans-Activators/*biosynthesis/genetics ; Treatment Outcome ; }, abstract = {BACKGROUND: The loss of expression of Dpc4 protein (pDpc4) has been demonstrated in about half of invasive ductal carcinoma (IDC) of the pancreas, but the expression of DPC4-mRNA remains to be evaluated. The present study assessed the comparative expression of pDpc4 and DPC4-mRNA in pancreatic IDC and their implication for patient outcome.<br><br>MATERIALS AND METHODS: In the freshly separated specimens of 21 IDCs and the paraffin-embedded specimens of 88 resectable IDCs, the expression of mRNA was assessed by in situ hybridization and the expression of pDpc4 was assessed by immunohistochemistry.<br><br>RESULTS: In the freshly separated specimens, DPC4-mRNA was expressed in 71% of the IDC, but pDpc4 expression was lost in 76% of the IDC. In 88 resectable IDCs, pDpc4 expression was lost in 75 (85.2%) and loss of pDpc4 expression was significantly correlated with the grade of nodal involvement (p =0.0265). Furthermore, the survival rate of the pDpc4 (-) group was significantly lower than that of the pDpc4 (+) group (p=0.0391). Adjuvant chemotherapy (ACT) significantly improved the survival rate and, in the ACT group, pDpc4 (-) patients had a significantly lower survival rate than the pDpc4 (+) patients.<br><br>CONCLUSION: In human pancreatic IDC, although DPC4-mRNA was usually expressed, the expression of pDpc4 was lost. The expression of pDpc-4 is an indicator of better prognosis and response to ACT.}, }
@article {pmid15151696, year = {2004}, author = {Goulter, AB and Goddard, MJ and Allen, JC and Clark, KL}, title = {ACE2 gene expression is up-regulated in the human failing heart.}, journal = {BMC medicine}, volume = {2}, number = {}, pages = {19}, pmid = {15151696}, issn = {1741-7015}, mesh = {Adolescent ; Adult ; Aged ; Analysis of Variance ; Angiotensin-Converting Enzyme 2 ; Carboxypeptidases/*genetics ; Cardiomyopathy, Dilated/*enzymology ; Child, Preschool ; Female ; *Gene Expression ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*enzymology ; Myocardium/*enzymology ; Peptidyl-Dipeptidase A ; *Up-Regulation ; }, abstract = {BACKGROUND: ACE2 is a novel homologue of angiotensin converting enzyme (ACE). ACE2 is highly expressed in human heart and animal data suggest that ACE2 is an essential regulator of cardiac function in vivo. Since overactivity of the renin-angiotensin system contributes to the progression of heart failure, this investigation assessed changes in gene expression of ACE2, ACE, AT1 receptor and renin in the human failing heart.<br><br>METHODS: The sensitive technique of quantitative reverse transcriptase polymerase chain reaction was used to determine the level of mRNA expression of ACE and ACE2 in human ventricular myocardium from donors with non-diseased hearts (n = 9), idiopathic dilated cardiomyopathy (IDC, n = 11) and ischemic cardiomyopathy (ICM, n = 12). Following logarithmic transformation of the data, a one-way analysis of variance was performed for each target gene followed by a Dunnett's test to compare the two disease groups IDC and ICM versus control.<br><br>RESULTS: As anticipated, ACE mRNA was found to be significantly increased in the failing heart with a 3.1 and 2.4-fold up-regulation found in IDC and ICM relative to non-diseased myocardium. Expression of ACE2 mRNA was also significantly up-regulated in IDC (2.4-fold increase) and ICM (1.8-fold increase) versus non-diseased myocardium. No change in angiotensin AT1 receptor mRNA expression was found in failing myocardium and renin mRNA was not detected.<br><br>CONCLUSIONS: These data suggest that ACE2 is up-regulated in human IDC and ICM and are consistent with the hypothesis that differential regulation of this enzyme may have important functional consequences in heart failure. This strengthens the hypothesis that ACE2 may be a relevant target for the treatment of heart failure and will hopefully spur further studies to clarify the functional effects in human myocardium of ACE2 derived peptides.}, }
@article {pmid15142882, year = {2004}, author = {Bengtsson, AK and Ryan, EJ and Giordano, D and Magaletti, DM and Clark, EA}, title = {17beta-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells.}, journal = {Blood}, volume = {104}, number = {5}, pages = {1404-1410}, doi = {10.1182/blood-2003-10-3380}, pmid = {15142882}, issn = {0006-4971}, support = {AI 44257/AI/NIAID NIH HHS/United States ; DE 13061/DE/NIDCR NIH HHS/United States ; RR 00166/RR/NCRR NIH HHS/United States ; }, mesh = {CD40 Antigens/metabolism ; Cell Movement/drug effects/immunology ; Cell Survival/drug effects/immunology ; Cells, Cultured ; Chemokine CCL17 ; Chemokine CCL19 ; Chemokine CCL2/metabolism ; Chemokine CCL22 ; Chemokines, CC/metabolism/pharmacology ; Cytokines/*metabolism ; Dendritic Cells/cytology/*drug effects/*metabolism ; Estradiol/*immunology/*pharmacology ; Glycoproteins/metabolism ; Humans ; Immunophenotyping ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Lipopolysaccharides/pharmacology ; Monocytes/cytology ; Osteoprotegerin ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Tumor Necrosis Factor ; }, abstract = {The effects of estrogen on the immune system are still largely unknown. We have investigated the effect of 17beta-estradiol (E(2)) on human monocyte-derived immature dendritic cells (iDCs). Short-term culture in E(2) had no effect on iDC survival or the expression of cell surface markers. However, E(2) treatment significantly increased the secretion of interleukin 6 (IL-6) in iDCs and also increased secretion of osteoprotegerin (OPG) by DCs. Furthermore, E(2) significantly increased secretion of the inflammatory chemokines IL-8 and monocyte chemoattractant protein 1 (MCP-1) by iDCs, but not the production of the constitutive chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). However, after E(2) pretreatment the lipopolysaccharide (LPS)-induced production of MCP-1, TARC, and MDC by DCs was clearly enhanced. Moreover, mature DCs pretreated with E(2) stimulated T cells better than control cells. Finally, we found that E(2) provides an essential signal for migration of mature DCs toward CCL19/macrophage inflammatory protein 3beta (MIP3beta). In summary, E(2) may affect DC regulation of T-cell and B-cell responses, as well as help to sustain inflammatory responses. This may explain, in part, the reason serum levels of estrogen correlate with the severity of certain autoimmune diseases.}, }
@article {pmid15140777, year = {2004}, author = {Radstake, TR and van Lent, PL and Pesman, GJ and Blom, AB and Sweep, FG and Rönnelid, J and Adema, GJ and Barrera, P and van den Berg, WB}, title = {High production of proinflammatory and Th1 cytokines by dendritic cells from patients with rheumatoid arthritis, and down regulation upon FcgammaR triggering.}, journal = {Annals of the rheumatic diseases}, volume = {63}, number = {6}, pages = {696-702}, pmid = {15140777}, issn = {0003-4967}, mesh = {Arthritis, Rheumatoid/immunology/*metabolism ; Cytokines/*biosynthesis ; Dendritic Cells/*metabolism ; Down-Regulation/immunology ; Enzyme-Linked Immunosorbent Assay/methods ; Flow Cytometry/methods ; Humans ; Interferon-gamma/biosynthesis ; Interleukins/biosynthesis ; Radioimmunoassay/methods ; Receptors, IgG/*immunology ; Tumor Necrosis Factor-alpha/biosynthesis ; }, abstract = {OBJECTIVE: To assess whether DC from RA produce altered cytokine levels and whether this is regulated by triggering of Fc gamma receptors (FcgammaR).<br><br>METHODS: The production of proinflammatory (TNFalpha, IL1, IL6), Th1 (IL12, IFNgamma), and Th2 (IL10) cytokine profiles of immature DC (iDC) from patients with RA and healthy subjects upon triggering of FcgammaR dependent and independent pathways was investigated. iDC, derived from blood monocytes by standardised protocols, were stimulated with immune complexes (IC) at day 6 for 48 hours and, subsequently, for 2 days with LPS in the presence or absence of IC or IFNgamma, resulting in fully matured DC (mDC). IL1, IL6, TNFalpha, IFNgamma, IL12, and IL10 levels in supernatants were measured by ELISA and RIA.<br><br>RESULTS: mDC from patients with RA showed a markedly increased production of IL1, IL6, TNFalpha, and IL10 compared with DC from healthy donors. Triggering of FcgammaR decreased the production of proinflammatory cytokines IL1, IL12, and IFNgamma by iDC and mDC in RA and controls. The production of IL6 and TNFalpha decreased in patients with RA, whereas it was increased in controls. Triggering of FcgammaR independent mechanisms using IFNgamma increased the production of proinflammatory and Th1 cytokines, which was more pronounced in RA.<br><br>CONCLUSION: FcgammaR dependent pathways influence cytokine production by DC. A skewed balance towards proinflammatory and Th1 cytokines in RA can, at least partly, be restored by triggering FcgammaR on DC in RA. Insight into the mechanism which determines the FcgammaR balance might lead to new strategies to abrogate Th1 driven inflammatory processes in RA.}, }
@article {pmid15123465, year = {2004}, author = {Sabel, MS and Kaufman, CS and Whitworth, P and Chang, H and Stocks, LH and Simmons, R and Schultz, M}, title = {Cryoablation of early-stage breast cancer: work-in-progress report of a multi-institutional trial.}, journal = {Annals of surgical oncology}, volume = {11}, number = {5}, pages = {542-549}, doi = {10.1245/ASO.2004.08.003}, pmid = {15123465}, issn = {1068-9265}, mesh = {Adult ; Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Cryosurgery/adverse effects/*methods ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; *Neoplasm Staging ; *Pain, Postoperative ; Treatment Outcome ; }, abstract = {BACKGROUND: With recent improvements in breast imaging, our ability to identify small breast tumors has markedly improved, prompting significant interest in the use of ablation without surgical excision to treat early-stage breast cancer. We conducted a multi-institutional pilot safety study of cryoablation in the treatment of primary breast carcinomas.<br><br>METHODS: Twenty-nine patients with ultrasound-visible primary invasive breast cancer </=2.0 cm were enrolled. Twenty-seven (93%) successfully underwent ultrasound-guided cryoablation with a tabletop argon gas-based cryoablation system with a double freeze/thaw cycle. Standard surgical resection was performed 1 to 4 weeks after cryoablation. Patients were monitored for complications, and pathology data were used to assess efficacy.<br><br>RESULTS: Cryoablation was successfully performed in an office-based setting with only local anesthesia. There were no complications to the procedure or postprocedural pain requiring narcotic pain medications. Cryoablation successfully destroyed 100% of cancers <1.0 cm. For tumors between 1.0 and 1.5 cm, this success rate was achieved only in patients with invasive ductal carcinoma without a significant ductal carcinoma-in-situ (DCIS) component. For unselected tumors >1.5 cm, cryoablation was not reliable with this technique. Patients with noncalcified DCIS were the cause of most cryoablation failures.<br><br>CONCLUSIONS: Cryoablation is a safe and well-tolerated office-based procedure for the ablation of early-stage breast cancer. At this time, cryoablation should be limited to patients with invasive ductal carcinoma </=1.5 cm and with <25% DCIS in the core biopsy. A multicenter phase II clinical trial is planned.}, }
@article {pmid15113399, year = {2004}, author = {Cao, W and Epstein, C and Liu, H and DeLoughery, C and Ge, N and Lin, J and Diao, R and Cao, H and Long, F and Zhang, X and Chen, Y and Wright, PS and Busch, S and Wenck, M and Wong, K and Saltzman, AG and Tang, Z and Liu, L and Zilberstein, A}, title = {Comparing gene discovery from Affymetrix GeneChip microarrays and Clontech PCR-select cDNA subtraction: a case study.}, journal = {BMC genomics}, volume = {5}, number = {1}, pages = {26}, pmid = {15113399}, issn = {1471-2164}, mesh = {Dendritic Cells/*metabolism ; Gene Expression Profiling/*methods ; Gene Library ; Humans ; Monocytes/*metabolism ; Nucleic Acid Hybridization/methods ; Oligonucleotide Array Sequence Analysis/*methods ; RNA/genetics/metabolism ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; }, abstract = {BACKGROUND: Several high throughput technologies have been employed to identify differentially regulated genes that may be molecular targets for drug discovery. Here we compared the sets of differentially regulated genes discovered using two experimental approaches: a subtracted suppressive hybridization (SSH) cDNA library methodology and Affymetrix GeneChip technology. In this "case study" we explored the transcriptional pattern changes during the in vitro differentiation of human monocytes to myeloid dendritic cells (DC), and evaluated the potential for novel gene discovery using the SSH methodology.<br><br>RESULTS: The same RNA samples isolated from peripheral blood monocyte precursors and immature DC (iDC) were used for GeneChip microarray probing and SSH cDNA library construction. 10,000 clones from each of the two-way SSH libraries (iDC-monocytes and monocytes-iDC) were picked for sequencing. About 2000 transcripts were identified for each library from 8000 successful sequences. Only 70% to 75% of these transcripts were represented on the U95 series GeneChip microarrays, implying that 25% to 30% of these transcripts might not have been identified in a study based only on GeneChip microarrays. In addition, about 10% of these transcripts appeared to be "novel", although these have not yet been closely examined. Among the transcripts that are also represented on the chips, about a third were concordantly discovered as differentially regulated between iDC and monocytes by GeneChip microarray transcript profiling. The remaining two thirds were either not inferred as differentially regulated from GeneChip microarray data, or were called differentially regulated but in the opposite direction. This underscores the importance both of generating reciprocal pairs of SSH libraries, and of real-time RT-PCR confirmation of the results.<br><br>CONCLUSIONS: This study suggests that SSH could be used as an alternative and complementary transcript profiling tool to GeneChip microarrays, especially in identifying novel genes and transcripts of low abundance.}, }
@article {pmid15108046, year = {2004}, author = {Lamy, O and Elmiger, H and Fiche, M and Bauer, J and Livio, F}, title = {Acquired hemophilia as first manifestation of breast carcinoma in a man under long-term spironolactone therapy.}, journal = {International journal of clinical oncology}, volume = {9}, number = {2}, pages = {130-133}, doi = {10.1007/s10147-003-0372-2}, pmid = {15108046}, issn = {1341-9625}, mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Biopsy, Needle/methods ; Breast Neoplasms, Male/*chemically induced/diagnosis/therapy ; Carcinoma, Ductal, Breast/*chemically induced/diagnosis/therapy ; Diuretics/*adverse effects ; Hemophilia A/*etiology/therapy ; Humans ; Male ; Mammography ; Mastectomy/methods ; Paraneoplastic Syndromes/etiology ; Spironolactone/*adverse effects ; Tamoxifen/therapeutic use ; Treatment Outcome ; }, abstract = {A 69-year-old man under long-term spironolactone therapy (16 years) was hospitalized with spontaneous hematoma on the trunk and extremities. Coagulation studies disclosed an acquired hemophilia that was successfully treated with human factor VIII for a few days and immunosuppressive agents for several months. Physical examination revealed bilateral gynecomastia and an upper left quadrant breast nodule. Complete staging was unremarkable. Complete left mastectomy was performed. Histopathology showed invasive ductal carcinoma, expressing positivity for estrogen and progesterone receptors. The acquired hemophilia was considered to be a paraneoplasic syndrome. The question of a linkage between long-term spironolactone therapy and breast carcinoma is discussed.}, }
@article {pmid15084238, year = {2004}, author = {Arpino, G and Bardou, VJ and Clark, GM and Elledge, RM}, title = {Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {3}, pages = {R149-56}, pmid = {15084238}, issn = {1465-542X}, support = {P01 CA030195/CA/NCI NIH HHS/United States ; P50 CA058183/CA/NCI NIH HHS/United States ; P01 CA30195/CA/NCI NIH HHS/United States ; P50 CA58183/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/mortality/pathology/secondary ; Carcinoma, Lobular/chemistry/mortality/*pathology/secondary ; Disease-Free Survival ; ErbB Receptors/analysis ; Female ; Follow-Up Studies ; Humans ; Life Tables ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Proteins/analysis ; Neoplasms, Hormone-Dependent/chemistry/mortality/pathology ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Survival Analysis ; Survival Rate ; Treatment Outcome ; Tumor Suppressor Protein p53/analysis ; }, abstract = {INTRODUCTION: Invasive lobular carcinoma (ILC) comprises approximately 10% of breast cancers and appears to have a distinct biology. Because it is less common than infiltrating ductal carcinoma (IDC), few data have been reported that address the biologic features of ILC in the context of their clinical outcome. In the present study we undertook an extensive comparison of ILC and IDC using a large database to provide a more complete and reliable assessment of their biologic phenotypes and clinical behaviors.<br><br>METHODS: The clinical and biological features of 4140 patients with ILC were compared with those of 45,169 patients with IDC (not otherwise specified). The median follow-up period was 87 months.<br><br>RESULTS: In comparison with IDC, ILC was significantly more likely to occur in older patients, to be larger in size, to be estrogen and progesterone receptor positive, to have lower S-phase fraction, to be diploid, and to be HER-2, p53, and epidermal growth factor receptor negative. It was more common for ILC than for IDC to metastasize to the gastrointestinal tract and ovary. The incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (20.9% versus 11.2%; P < 0.0001). Breast preservation was modestly less frequent in ILC patients than in IDC patients. The 5-year disease-free survival was 85.7% for ILC and 83.5% for IDC (P = 0.13). The 5-year overall survival was 85.6% for ILC and 84.1% for IDC (P = 0.64).<br><br>CONCLUSION: Despite the fact that the biologic phenotype of ILC is quite favorable, these patients do not have better clinical outcomes than do patients with IDC. At present, management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.}, }
@article {pmid15073245, year = {2004}, author = {Fukuchi, K and Yasumura, Y and Kiso, K and Hayashida, K and Miyatake, K and Ishida, Y}, title = {Gated myocardial SPECT to predict response to beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {45}, number = {4}, pages = {527-531}, pmid = {15073245}, issn = {0161-5505}, mesh = {Adrenergic beta-Antagonists/administration &amp; dosage ; Adult ; Age Factors ; Aged ; Bisoprolol/*administration &amp; dosage ; Carbazoles/*administration &amp; dosage ; Cardiomyopathy, Dilated/complications/diagnosis/*diagnostic imaging/*drug therapy ; Carvedilol ; Drug Therapy, Combination ; Feasibility Studies ; Female ; Gated Blood-Pool Imaging/*methods ; Humans ; Male ; Middle Aged ; Prognosis ; Propanolamines/*administration &amp; dosage ; Reproducibility of Results ; Risk Assessment/methods ; Sensitivity and Specificity ; Sex Factors ; Tomography, Emission-Computed, Single-Photon/*methods ; Treatment Outcome ; Ventricular Dysfunction, Left/diagnosis/*diagnostic imaging/*drug therapy/etiology ; }, abstract = {UNLABELLED: Because of the difficulty of predicting the response of patients with idiopathic dilated cardiomyopathy (IDC) to beta-blocker therapy, this study was performed to evaluate whether gated myocardial SPECT (gated SPECT) could be useful for predicting that response.<br><br>METHODS: We performed gated SPECT with (99m)Tc-sestamibi on 38 patients with IDC before treatment with a beta-blocker and standard medication. Perfusion abnormalities, left ventricular (LV) function, and spheric distortion were assessed by a quantitative software program.<br><br>RESULTS: We classified patients into 2 groups according to improvement in LV function after 4 mo of therapy. The groups consisted of 16 poor responders whose LV ejection fraction (LVEF) increased less than 10% and 22 good responders whose LVEF increased by 10% or more. The patient characteristics before therapy, including LV volume and LVEF, did not significantly differ between the 2 groups, but the size of the myocardial perfusion defect and spheric distortion were significantly greater in poor responders than in good responders.<br><br>CONCLUSION: Gated SPECT, by allowing simultaneous assessment of perfusion, function and geometry, might be useful for predicting the response of patients with IDC to beta-blocker therapy.}, }
@article {pmid15059899, year = {2004}, author = {Grimshaw, MJ and Hagemann, T and Ayhan, A and Gillett, CE and Binder, C and Balkwill, FR}, title = {A role for endothelin-2 and its receptors in breast tumor cell invasion.}, journal = {Cancer research}, volume = {64}, number = {7}, pages = {2461-2468}, doi = {10.1158/0008-5472.can-03-1069}, pmid = {15059899}, issn = {0008-5472}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma in Situ/genetics/metabolism/*pathology ; Carcinoma, Ductal/genetics/metabolism/*pathology ; Cell Line, Tumor ; Chemotaxis/drug effects/physiology ; Coculture Techniques ; Endothelin-1/pharmacology/physiology ; Endothelin-2/biosynthesis/genetics/pharmacology/*physiology ; Humans ; Isoenzymes/biosynthesis ; MAP Kinase Signaling System/physiology ; Macrophages/cytology/drug effects/enzymology ; Matrix Metalloproteinases/biosynthesis ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/metabolism ; Neoplasm Invasiveness ; RNA, Messenger/biosynthesis/genetics ; Receptor, Endothelin A/biosynthesis/genetics/*physiology ; Receptor, Endothelin B/biosynthesis/genetics/*physiology ; }, abstract = {We have studied the role of endothelins (ET-1, ET-2 and ET-3) and ET receptors (ET-RA and ET-RB) in the invasive capacity of breast tumor cells, which express ET-1 and ET-2 as well as ET-RA and ET-RB. Of five human breast tumor cell lines tested, all expressed mRNAs for ET-1, ET-2, and ET-RB. ET-RA mRNA was expressed by four of five tumor cell lines. Breast tumor cells migrated toward ET-1 and ET-2 but not toward ET-3. Chemotaxis involved signaling via both receptors, and a pertussis toxin-sensitive p42/p44 mitogen-activated protein kinase (MAPK)-mediated pathway that could be inhibited by MAPK kinase (MEK)1/2 antagonists. Chemotaxis toward ETs did not involve p38 or stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) and was not inhibited by hypoxia. Incubation of tumor cells with ET-2 also increased chemotaxis toward the chemokines CXCL12 and CCL21. As well as inducing chemotaxis of tumor cells, ET-1 and ET-2 increased tumor cell invasion through Matrigel. Furthermore, stimulation of macrophage/tumor cell cocultures with ETs led to increased matrix metalloproteinase (MMP)-2 and -9 production by macrophages and a marked increase in invasion of tumor cells. Antagonism of either ET-RA or ET-RB decreased the invasion seen in ET-stimulated cocultures, as did a broad-spectrum MMP inhibitor. Immunohistochemical staining of human breast tumor sections showed increased ET and ET receptor protein expression by tumor cells in invasive ductal carcinoma compared with normal breast tissue or ductal carcinoma in situ. Furthermore, tumor cell ET and receptor expression was stronger at the invasive margin of invasive ductal carcinomas, in the lymphovascular space, and in lymph node metastases. ET expression often colocalized with ET-RB expression in all neoplastic tissue indicating a possible autocrine action of ETs. We suggest that expression of ETs and their receptors by human breast tumors, particularly in conjunction with a high macrophage infiltrate, may have a role in the progression of breast cancer and the invasion of tumor cells.}, }
@article {pmid15050489, year = {2004}, author = {Molhoek, SG and Bax, JJ and van Erven, L and Bootsma, M and Boersma, E and Steendijk, P and van der Wall, EE and Schalij, MJ}, title = {Comparison of benefits from cardiac resynchronization therapy in patients with ischemic cardiomyopathy versus idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {93}, number = {7}, pages = {860-863}, doi = {10.1016/j.amjcard.2003.12.024}, pmid = {15050489}, issn = {0002-9149}, mesh = {Aged ; Cardiac Output/*physiology ; *Cardiac Pacing, Artificial ; Cardiomyopathy, Dilated/*mortality/physiopathology/*therapy ; Exercise Tolerance/physiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*mortality/physiopathology/*therapy ; Patient Selection ; Quality of Life ; Survival Rate ; Treatment Outcome ; }, abstract = {Cardiac resynchronization therapy (CRT) is a recently introduced therapeutic option for patients with severe heart failure and intraventricular conduction disturbances. However, it is estimated that 20% to 30% of patients may not respond to CRT. Patients with ischemic cardiomyopathy (IC) may respond less favorably to CRT compared with patients with idiopathic dilated cardiomyopathy (IDC). Accordingly, the beneficial effects of CRT were evaluated in 2 subsets of patients (IC and IDC). Seventy-four patients with end-stage heart failure, New York Heart Association (NYHA) class III or IV, left ventricular (LV) ejection fraction <35%, QRS >120ms, and left bundle branch block received a biventricular pacemaker. At baseline and 6 months after implantation these parameters were evaluated: NYHA class, Minnesota quality-of-life score, QRS duration, and 6-minute walking distance. LV ejection fraction and severity of mitral regurgitation were assessed before and 6 months after CRT using 2-dimensional echocardiography. Long-term follow-up and hospitalization rates were obtained up to 2 years. Of the 74 patients, 46% (n = 34) had IC and 54% (n = 40) IDC. At 6 months follow-up all clinical parameters, QRS duration, LV ejection fraction, and mitral regurgitation improved significantly in both groups. Long-term (2-year) follow-up showed a survival rate of 87.5% for patients with IDC and 88.3% for patients with IC. The percentages of responders to CRT (defined as an improvement in NYHA class >or=1 grade) were comparable in both groups (65% vs 71%). Therefore, the underlying etiology of heart failure (IC vs IDC) was not related to the response to CRT.}, }
@article {pmid15050488, year = {2004}, author = {Seghatol, FF and Shah, DJ and Diluzio, S and Bello, D and Johnson, MR and Cotts, WG and O'Donohue, JA and Bonow, RO and Gheorghiade, M and Rigolin, VH}, title = {Relation between contractile reserve and improvement in left ventricular function with beta-blocker therapy in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {93}, number = {7}, pages = {854-859}, doi = {10.1016/j.amjcard.2003.12.023}, pmid = {15050488}, issn = {0002-9149}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiomyopathy, Dilated/complications/drug therapy/*physiopathology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Contraction/*physiology ; Myocardial Ischemia/complications/drug therapy/*physiopathology ; Predictive Value of Tests ; Prospective Studies ; Time Factors ; Ventricular Dysfunction, Left/complications/*drug therapy/*physiopathology ; }, abstract = {Beta blockers improve left ventricular (LV) ejection fraction but patient responses are heterogenous. We investigated the role of contractile reserve (CR) in predicting beta-blocker response in ischemic and nonischemic cardiomyopathy. Resting and low-dose dobutamine echocardiograms were recorded in 32 patients with heart failure (LV ejection fraction <or=35%), 18 with ischemic cardiomyopathy (IC), and 14 with idiopathic dilated cardiomyopathy (IDC). A segment was defined as CR positive (CR+) or negative (CR-) based on response to dobutamine. Patients were then classified as CR+ or CR- based on number of improved segments (IC group) or ejection fraction improvement (IDC group) in response to dobutamine. During follow-up (2, 6, and 14 months after beta-blocker initiation), response was measured by the percent of segments showing improved contractility from baseline, ejection fraction, and wall motion score index. In the IC group, the percent of improved segments was greater at 2 and 6 months in CR+ versus CR- (70% vs 15% and 39% vs 17%, p <0.05), whereas it was greater at all periods in the patients with IDC (36% vs 9% at 2 months, 50% vs 19% at 6 months, and 63% vs 42% at 14 months, p <0.05). Findings for ejection fraction and wall motion score index were similar. Therefore, time course and magnitude of improvement in LV function in patients with heart failure receiving beta blockers are related to CR status. CR predicts a greater early response in IC, whereas it predicts a greater response at all time periods in IDC. However, even patients without CR showed improvement in LV function at 14 months.}, }
@article {pmid15048705, year = {2004}, author = {Chen, L and Jondal, M}, title = {Alternative processing for MHC class I presentation by immature and CpG-activated dendritic cells.}, journal = {European journal of immunology}, volume = {34}, number = {4}, pages = {952-960}, doi = {10.1002/eji.200324359}, pmid = {15048705}, issn = {0014-2980}, mesh = {Acetylcysteine/*analogs &amp; derivatives/pharmacology ; Animals ; Antigen Presentation/drug effects/*immunology ; Bone Marrow/immunology ; Brefeldin A/pharmacology ; Cells, Cultured ; CpG Islands/*immunology ; Cysteine Proteinase Inhibitors/pharmacology ; Dendritic Cells/drug effects/*immunology ; Female ; Flow Cytometry ; Histocompatibility Antigens Class I/*immunology ; Mice ; Ovalbumin/immunology ; Protein Synthesis Inhibitors/pharmacology ; }, abstract = {Exogenous proteins can be processed by antigen-presenting cells for the generation of MHC class I-restricted T cell responses. Where this occurs is not clear, although both transfer of internalized antigen into the cytosol and alternative processing in endolysosomes and phagosomes have been reported. Here we have studied the capacity of bone marrow-derived mouse myeloid dendritic cells (DC) to process the OVA protein for peptide presentation by H2-K(b). We have found that immature DC (iDC), both wild-type and transporter associated with antigen processing (TAP)-deficient cells, can transiently process OVA in a pathway which is resistant to inhibitors of the classical MHC class I pathway including the Golgi inhibitor Brefeldin A (BFA) and the proteasome inhibitor lactacystin. This alternative pathway is not found in subcultured DC with an intermediate maturity (imDC) or in resting, IL-3 expanded macrophages but can be re-expressed in imDC if these are activated by an immunostimulatory CpG oligonucleotide. Both iDC and CpG-activated DC were found to process OVA by regurgitation. In addition, we found that iDC secrete proteolytic enzymes into the supernatant, which can process OVA in the extracellular phase. These results suggest that multiple pathways exist for the processing of exogenous protein antigens into MHC class I-binding peptides.}, }
@article {pmid15048136, year = {2004}, author = {Ishikawa, A and Sasaki, M and Ohira, S and Ohta, T and Oda, K and Nimura, Y and Chen, MF and Jan, YY and Yeh, TS and Nakanuma, Y}, title = {Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {84}, number = {5}, pages = {629-638}, doi = {10.1038/labinvest.3700087}, pmid = {15048136}, issn = {0023-6837}, mesh = {Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Bile Duct Neoplasms/genetics/metabolism/pathology ; Bile Ducts, Intrahepatic/metabolism/pathology ; CDX2 Transcription Factor ; Cholangiocarcinoma/genetics/metabolism/pathology ; Cholelithiasis/*complications ; DNA, Complementary/genetics ; Female ; Gene Expression ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Immunohistochemistry ; Intestinal Mucosa/metabolism ; Intestines/pathology ; Liver Neoplasms/*complications/*genetics/metabolism/pathology ; Male ; Metaplasia ; Middle Aged ; Mucin 5AC ; Mucin-2 ; Mucins/*genetics/metabolism ; Pancreatic Neoplasms/genetics/metabolism/pathology ; RNA, Messenger/genetics/metabolism ; RNA, Neoplasm/genetics/metabolism ; Trans-Activators ; }, abstract = {Intraductal papillary neoplasia of the liver (IPNL) frequently presents gastrointestinal metaplasia with aberrant expression of MUC2 and MUC5AC and oversecretion of mucin into the ductal lumen. In this study, the involvement of CDX2, a homeodomain protein involved in the regulation of intestinal development and differentiation, in the expression of MUC2 was examined in mucinous intrahepatic cholangiocarcinoma (ICC) (n=7) and IPNL with hepatolithiasis (n=19) with comparison to conventional ICC (n=11), and intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas (n=9 and 11, respectively). A total of 33 cases of hepatolithiasis, extrahepatic biliary obstruction and normal livers were used as the control. Immunohistochemically, both MUC2 and MUC5AC were frequently expressed in mucinous ICC and IPNL, while expression of MUC2 was not seen in conventional ICC. The nuclear expression of CDX2 was closely associated with the expression of MUC2 in mucinous ICC and IPNL. This intimate association of MUC2 and CDX2 was confirmed by double immunostaining. The cytoplasmic CDX2 expression was frequent in the mucinous and the conventional ICC and pancreatic carcinoma, irrespective of MUC2 and MUC5AC expression. CDX2 mRNA was detected in neoplastic cells showing cytoplasmic as well as nuclear expression of CDX2 by reverse transcriptase-polymerase chain reaction. One IPMT expressed MUC2 associated with nuclear CDX2 expression, while the other IPMT and conventional pancreatic carcinoma expressed MUC5AC only. Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous ICC and IPNL associated with hepatolithiasia, suggesting its role in intestinal differentiation and its association with carcinogenesis in these tumors.}, }
@article {pmid15034139, year = {2004}, author = {Zhao, H and Langerød, A and Ji, Y and Nowels, KW and Nesland, JM and Tibshirani, R and Bukholm, IK and Kåresen, R and Botstein, D and Børresen-Dale, AL and Jeffrey, SS}, title = {Different gene expression patterns in invasive lobular and ductal carcinomas of the breast.}, journal = {Molecular biology of the cell}, volume = {15}, number = {6}, pages = {2523-2536}, pmid = {15034139}, issn = {1059-1524}, support = {U01 CA085129/CA/NCI NIH HHS/United States ; U01CA85129/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; RNA/genetics/metabolism ; }, abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological types of breast cancer worldwide. Whereas IDC incidence has remained stable, ILC is the most rapidly increasing breast cancer phenotype in the United States and Western Europe. It is not clear whether IDC and ILC represent molecularly distinct entities and what genes might be involved in the development of these two phenotypes. We conducted comprehensive gene expression profiling studies to address these questions. Total RNA from 21 ILCs, 38 IDCs, two lymph node metastases, and three normal tissues were amplified and hybridized to approximately 42,000 clone cDNA microarrays. Data were analyzed using hierarchical clustering algorithms and statistical analyses that identify differentially expressed genes (significance analysis of microarrays) and minimal subsets of genes (prediction analysis for microarrays) that succinctly distinguish ILCs and IDCs. Eleven of 21 (52%) of the ILCs ("typical" ILCs) clustered together and displayed different gene expression profiles from IDCs, whereas the other ILCs ("ductal-like" ILCs) were distributed between different IDC subtypes. Many of the differentially expressed genes between ILCs and IDCs code for proteins involved in cell adhesion/motility, lipid/fatty acid transport and metabolism, immune/defense response, and electron transport. Many genes that distinguish typical and ductal-like ILCs are involved in regulation of cell growth and immune response. Our data strongly suggest that over half the ILCs differ from IDCs not only in histological and clinical features but also in global transcription programs. The remaining ILCs closely resemble IDCs in their transcription patterns. Further studies are needed to explore the differences between ILC molecular subtypes and to determine whether they require different therapeutic strategies.}, }
@article {pmid15020654, year = {2004}, author = {Delgado, M and Reduta, A and Sharma, V and Ganea, D}, title = {VIP/PACAP oppositely affects immature and mature dendritic cell expression of CD80/CD86 and the stimulatory activity for CD4(+) T cells.}, journal = {Journal of leukocyte biology}, volume = {75}, number = {6}, pages = {1122-1130}, doi = {10.1189/jlb.1203626}, pmid = {15020654}, issn = {0741-5400}, support = {2 R25 GM060826-05/GM/NIGMS NIH HHS/United States ; AI052306/AI/NIAID NIH HHS/United States ; AI47325/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD/genetics/*metabolism ; B7-1 Antigen/genetics/*metabolism ; B7-2 Antigen ; Bone Marrow/metabolism ; CD4-Positive T-Lymphocytes/*immunology ; Cell Differentiation/immunology ; Cell Division/immunology ; Cytokines/metabolism ; Dendritic Cells/*drug effects/metabolism ; Dual Specificity Phosphatase 2 ; Immunity, Innate/physiology ; Lipopolysaccharides/pharmacology ; Membrane Glycoproteins/genetics/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Neuropeptides/*pharmacology ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Protein Phosphatase 2 ; Protein Tyrosine Phosphatases/genetics/metabolism ; Receptors, Vasoactive Intestinal Peptide/genetics/metabolism ; Receptors, Vasoactive Intestinal Peptide, Type II ; Receptors, Vasoactive Intestinal Polypeptide, Type I ; Reverse Transcriptase Polymerase Chain Reaction ; Spleen/immunology/metabolism ; Th1 Cells/immunology ; Th2 Cells/immunology ; Vasoactive Intestinal Peptide/*pharmacology ; }, abstract = {The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) released within lymphoid organs from nerve terminals and/or immune cells play a significant, anti-inflammatory role by inhibiting macrophage-induced inflammatory reactions and promoting T helper cell type 2 (Th2) responses. However, dendritic cells (DC) and not macrophages often are the major antigen-presenting cells and link between innate and adaptive immunity. The role of VIP/PACAP in DC development and function is mostly unknown. Here, we report that bone marrow-derived DC express VIP/PACAP receptors and that VIP and PACAP exert a differential effect on immature DC (iDC) and lipopolysaccharide (LPS)-treated DC. In iDC, VIP/PACAP up-regulates CD86 expression and enables them to stimulate T cell proliferation and differentiation into Th2 effectors in vivo and in vitro. In contrast, VIP/PACAP down-regulates CD80/CD86 expression in LPS-stimulated DC and strongly reduces their capacity to stimulate T cell proliferation and secretion of Th1 and Th2 cytokines. The VIP/PACAP effects on iDC and LPS-stimulated DC are mediated primarily through the VIP receptor 1. These results indicate that neuropeptides such as VIP and PACAP can differentially affect the function of iDC and mature DC. In the absence of an ongoing immune response, VIP/PACAP contributes to the initiation of Th2-type immunity, whereas in the presence of a full-blown, inflammatory reaction, VIP/PACAP act as anti-inflammatory agents.}, }
@article {pmid15017585, year = {2004}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Histological characteristics of tumor in vessels and lymph nodes are significant predictors of progression of invasive ductal carcinoma of the breast: a prospective study.}, journal = {Human pathology}, volume = {35}, number = {3}, pages = {298-308}, doi = {10.1016/j.humpath.2003.05.004}, pmid = {15017585}, issn = {0046-8177}, mesh = {Adult ; Aged ; Apoptosis ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/metabolism/*pathology ; Lymphatic Metastasis/pathology ; Lymphatic System/pathology ; Middle Aged ; Mitosis ; Neoplastic Cells, Circulating/*pathology ; Predictive Value of Tests ; Prospective Studies ; Survival Rate ; }, abstract = {Invasive ductal carcinomas (IDCs) of the breast are composed of primary invasive tumors as well as tumor cells in blood vessels and lymph nodes. The purpose of this study was to determine whether the histological characteristics of tumor in the vessels and nodes are significantly associated with outcome. In a series of 393 patients, multivariate analyses showed that in IDCs without nodal metastasis and with fibrotic focus dimension, lymph vessel tumor emboli with >6 apoptotic figures and those invading >3 mm from the tumor margin had significantly higher hazard rates (HRs) for recurrence (P<0.05). In IDCs with 1 to 3 nodal metastases, >2 apoptotic figures in tumor emboli in blood vessels and >5 invaded lymph vessels were associated with significantly higher HRs for tumor recurrence and death (P<0.005). In IDCs with 4 or more nodal metastases, nodal tumors with >5 mitotic figures and >5 nodes with extranodal extension were associated with significantly higher HRs for tumor recurrence or death (P<0.05). We conclude that several histological characteristics of tumors in vessels and nodes have significant implications for the progression of IDCs.}, }
@article {pmid14984725, year = {2004}, author = {Fauchier, L and Babuty, D and Melin, A and Bonnet, P and Cosnay, P and Paul Fauchier, J}, title = {Heart rate variability in severe right or left heart failure: the role of pulmonary hypertension and resistances.}, journal = {European journal of heart failure}, volume = {6}, number = {2}, pages = {181-185}, doi = {10.1016/j.ejheart.2003.09.007}, pmid = {14984725}, issn = {1388-9842}, mesh = {Adult ; Arrhythmias, Cardiac/etiology ; Cardiomyopathy, Dilated/etiology/*physiopathology ; Case-Control Studies ; Electrocardiography, Ambulatory ; Female ; Heart Rate/*physiology ; Humans ; Hypertension, Pulmonary/complications/*physiopathology ; Male ; Middle Aged ; Pulmonary Wedge Pressure/physiology ; Regression Analysis ; Stroke Volume/physiology ; }, abstract = {BACKGROUND: The decrease in heart rate variability (HRV) might be related to the hemodynamic status in heart failure. However, HRV in patients with severe isolated right heart failure has not been extensively studied.<br><br>AIMS: This study compared HRV in patients with congestive heart failure (CHF) and in patients with isolated right heart failure.<br><br>METHODS: Time and frequency domain analysis of HRV on 24-h ECG recording was assessed in 15 healthy subjects and in two groups of patients with severe heart failure awaiting heart or heart/lung transplantation. These were 15 patients with CHF due to idiopathic dilated cardiomyopathy (IDC) and 10 patients with isolated right heart failure due to primary pulmonary hypertension (PPH).<br><br>RESULTS: Measurement of HRV were significantly decreased in both groups of patients compared with the control group. Patients with IDC had higher pulmonary capillary wedge pressure than patients with PPH (P=0.04) but lower pulmonary artery pressure and lower pulmonary vascular resistance (PVR) (P<0.0001). However, all the measurements of HRV were significantly lower in patients with IDC than in patients with PPH (range 22-77%, P<0.05 to P<0.01). None of the HRV measurements correlated with filling pressure measurements.<br><br>CONCLUSIONS: The increase in pulmonary vascular resistance in heart failure is not the main causal factor behind a decrease in HRV.}, }
@article {pmid14764699, year = {2004}, author = {Jackson, SH and Yu, CR and Mahdi, RM and Ebong, S and Egwuagu, CE}, title = {Dendritic cell maturation requires STAT1 and is under feedback regulation by suppressors of cytokine signaling.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {172}, number = {4}, pages = {2307-2315}, doi = {10.4049/jimmunol.172.4.2307}, pmid = {14764699}, issn = {0022-1767}, mesh = {Animals ; Carrier Proteins/genetics/metabolism/*physiology ; Cell Differentiation/genetics/immunology ; Cells, Cultured ; DNA-Binding Proteins/deficiency/genetics/*physiology ; Dendritic Cells/*cytology/*immunology/metabolism ; Drug Synergism ; Feedback, Physiological/genetics/*immunology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Interleukin-4/pharmacology ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Progenitor Cells/cytology/immunology/metabolism ; Protein Biosynthesis ; Proteins/genetics/*physiology ; Repressor Proteins/biosynthesis/genetics/metabolism/*physiology ; STAT1 Transcription Factor ; Signal Transduction/genetics/*immunology ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; Trans-Activators/deficiency/genetics/*physiology ; Transcription Factors/biosynthesis/genetics/*physiology ; Transcriptional Activation/immunology ; Up-Regulation/genetics/immunology ; }, abstract = {In this study we show that activation of STAT pathways is developmentally regulated and plays a role in dendritic cell (DC) differentiation and maturation. The STAT6 signaling pathway is constitutively activated in immature DC (iDC) and declines as iDCs differentiate into mature DCs (mDCs). However, down-regulation of this pathway during DC differentiation is accompanied by dramatic induction of suppressors of cytokine signaling 1 (SOCS1), SOCS2, SOCS3, and cytokine-induced Src homology 2-containing protein expression, suggesting that inhibition of STAT6 signaling may be required for DC maturation. In contrast, STAT1 signaling is most robust in mDCs and is not inhibited by the up-regulated SOCS proteins, indicating that STAT1 and STAT6 pathways are distinctly regulated in maturing DC. Furthermore, optimal activation of STAT1 during DC maturation requires both IL-4 and GM-CSF, suggesting that synergistic effects of both cytokines may in part provide the requisite STAT1 signaling intensity for DC maturation. Analyses of STAT1(-/-) DCs reveal a role for STAT1 in repressing CD86 expression in precursor DCs and up-regulating CD40, CD11c, and SOCS1 expression in mDCs. We further show that SOCS proteins are differentially induced by IL-4 and GM-CSF in DCs. SOCS1 is primarily induced by IL-4 through a STAT1-dependent mechanism, whereas SOCS3 is induced mainly by GM-CSF. Taken together, these results suggest that cytokine-induced maturation of DCs is under feedback regulation by SOCS proteins and that the switch from constitutive activation of the STAT6 pathway in iDCs to predominant use of STAT1 signals in mDC is mediated in part by STAT1-induced SOCS expression.}, }
@article {pmid14764165, year = {2004}, author = {Steinbigler, P and Haberl, R and Steinbeck, G}, title = {T wave spectral variance for noninvasive identification of patients with idiopathic dilated cardiomyopathy prone to ventricular fibrillation even in the presence of bundle branch block or atrial fibrillation.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {27}, number = {2}, pages = {156-165}, doi = {10.1111/j.1540-8159.2004.00405.x}, pmid = {14764165}, issn = {0147-8389}, mesh = {Algorithms ; Atrial Fibrillation/*complications ; Bundle-Branch Block/*complications ; Cardiac Pacing, Artificial ; Cardiomyopathy, Dilated/*complications ; Electrocardiography, Ambulatory/*methods/statistics &amp; numerical data ; Fourier Analysis ; Heart Arrest/etiology ; Humans ; Middle Aged ; Myocardial Contraction/physiology ; Myocardial Ischemia/complications ; Reproducibility of Results ; Retrospective Studies ; Risk Factors ; Signal Processing, Computer-Assisted ; Statistics, Nonparametric ; Ventricular Fibrillation/*diagnosis/etiology ; }, abstract = {Conventional methods using Holter ECG recordings for noninvasive risk stratification are limited in patients with idiopathic dilated cardiomyopathy (IDC) prone to ventricular fibrillation (VF) having atrial fibrillation (AF) or bundle branch block (BBB). We therefore investigated, whether spectral assessment of beat-to-beat alternations of repolarization is associated with VF in these patients. Twenty-four-hour Holter ECG recordings in 462 patients with IDC were used. The VF group comprised of 64 consecutive patients who survived cardiac arrest, the no VF group consisted of 398 consecutive patients without a history of malignant ventricular arrhythmia. One hundred patients with ischemic cardiomyopathy (ICM) served as a control group. In each patient, 1,024 consecutive T waves were aligned using cross correlation methods. Two-dimensional Fourier transform (2D FFT) used the data matrix of 1,024 consecutive 200-ms segments centered to the T wave peak. Power spectra of the 2D FFT revealed the frequency content of the T wave in the first dimension and the periodicity of this frequency content in the second dimension. The ratio between periodic frequency contents and the sum of nonperiodic and periodic frequency contents between 0.5 and 50 Hz is equal to the T wave spectral variance (TWSV) index. Thus, TWSV index = 0 would mean that all 1,024 T waves are identical and TWSV index = 1 would mean that the 1,024 T waves are totally variable. The TWSV index was significantly higher in the VF group (0.93 +/- 0.14) than in the no VF group (0.53 +/- 0.13, P < 0.01). The best cutoff between the VF and the no VF group was achieved by using a TWSV index of 0.75 (sensitivity = 89%, specificity = 78%). No significant differences were observed between patients with and without AF or with and without BBB, and between patients with IDC and ICM. Even in the presence of BBB or AF spectral assessment of T wave alternations by TWSV index using 2D FFT in Holter ECG recordings, allows the identification of patients with IDC at risk for VF.}, }
@article {pmid14759716, year = {2004}, author = {Greenberg, R and Barnea, Y and Kaplan, O and Kashtan, H and Skornick, Y}, title = {Detection of cancer cells in the axillary drainage using RT-PCR after operations for breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {13}, number = {1}, pages = {49-55}, doi = {10.1016/j.breast.2003.10.006}, pmid = {14759716}, issn = {0960-9776}, mesh = {Axilla/pathology/surgery ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Case-Control Studies ; DNA Primers ; Exudates and Transudates/chemistry ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mucin-1/*biosynthesis/genetics ; Neoplastic Cells, Circulating/*metabolism ; Prognosis ; RNA, Messenger/analysis ; RNA, Neoplasm/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {The object of this study was to examine whether MUC-1 can be detected in the axillary lymphatic drainage of patients who have undergone conservative surgery for breast cancer and to assess the correlations between the presence of MUC-1 and prognostic factors in breast cancer. Sixty-eight women with invasive ductal carcinoma of the breast underwent wide local excision and axillary lymph node dissection. Axillary drains were inserted in all these cases, and the presence of MUC-1 and beta-actin was evaluated by RT-PCR in the lymphatic fluid collected after the operation. Prognostic factors included tumour size and grade, vascular and lymphatic invasion, clearance margins of the resected specimens and status of the axillary lymph nodes. RT-PCR assays for MUC-1 in the axillary fluid were positive in 17 patients (25%). The presence of MUC-1 was associated with increased tumour size and showed a positive correlation with axillary lymph node metastases and incomplete resection of the tumour. RT-PCR can disclose cancer cells in the axillary fluid after conservative surgery for breast cancer. The presence of MUC-1 in the axillary drainage may be associated with poor prognostic features, and its detection may have implications for therapy as it suggests that re-excision should be considered.}, }
@article {pmid14752511, year = {2004}, author = {Müller, FU and Loser, K and Kleideiter, U and Neumann, J and von Wallbrunn, C and Dobner, T and Scheld, HH and Bantel, H and Engels, IH and Schulze-Osthoff, K and Schmitz, W}, title = {Transcription factor AP-2alpha triggers apoptosis in cardiac myocytes.}, journal = {Cell death and differentiation}, volume = {11}, number = {5}, pages = {485-493}, doi = {10.1038/sj.cdd.4401383}, pmid = {14752511}, issn = {1350-9047}, mesh = {Adenoviridae/genetics ; Animals ; Apoptosis/*physiology ; Cardiomyopathy, Dilated/*metabolism ; Caspases/metabolism ; Cell Nucleus/*metabolism ; Cells, Cultured ; Cloning, Molecular ; DNA-Binding Proteins/genetics/*metabolism ; Genes, bcl-2/physiology ; Humans ; Myocardium ; Myocytes, Cardiac/*metabolism ; Poly(ADP-ribose) Polymerases/metabolism ; Rats ; Transcription Factor AP-2 ; Transcription Factors/genetics/*metabolism ; }, abstract = {Idiopathic-dilated cardiomyopathy (IDC) is a common primary myocardial disease of unknown etiology associated with apoptosis, cardiac dilatation, progressive heart failure and increased mortality. An elevation of the transcription factor activator protein 2alpha (AP-2alpha) is involved in vertebrate embryonic development and oncogenesis. Here, we show that AP-2alpha protein is expressed in the human heart and increased in human failing myocardium with IDC. Adenovirus-mediated overexpression of human AP-2alpha triggered apoptosis and increased mRNA levels of Bcl-2 family members Bax and Bcl-x in rat cardiomyocytes. Immunohistological analysis of human myocardium revealed an increased percentage of AP-2alpha-positive nuclei in IDC and, interestingly, a colocalization of AP-2alpha-positive but not -negative cells with a caspase-cleaved fragment of poly(ADP-ribose)polymerase. We suggest AP-2alpha as a novel cardiac regulator implicated in the activation of apoptosis in IDC.}, }
@article {pmid14746850, year = {2004}, author = {Ferlicot, S and Vincent-Salomon, A and Médioni, J and Genin, P and Rosty, C and Sigal-Zafrani, B and Fréneaux, P and Jouve, M and Thiery, JP and Sastre-Garau, X}, title = {Wide metastatic spreading in infiltrating lobular carcinoma of the breast.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {40}, number = {3}, pages = {336-341}, doi = {10.1016/j.ejca.2003.08.007}, pmid = {14746850}, issn = {0959-8049}, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*secondary ; Carcinoma, Lobular/genetics/*secondary ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; *Phenotype ; }, abstract = {The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin em leader) (P<0.001). In ILC, no significant link was found between the localisation(s) of metastases, the histological subtype and the EC status in the primary. In conclusion, in breast carcinomas, the frequency of multiple metastasis was found to be higher in ILC than IDC. This fact may be related to the phenotypic trait of discohesive small cells which characterises ILC. EC loss, observed in most cases of ILC, may result in alterations in cell-cell adhesion and a preferential growth at metastatic sites. A high rate of pleomorphic tumours was observed in the group of metastatic ILC, but the pattern of metastatic site(s) was not related to the histological subtype of the primary.}, }
@article {pmid14744536, year = {2004}, author = {Himmelfarb, M and Klopocki, E and Grube, S and Staub, E and Klaman, I and Hinzmann, B and Kristiansen, G and Rosenthal, A and Dürst, M and Dahl, E}, title = {ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy chain family is downregulated in breast cancer.}, journal = {Cancer letters}, volume = {204}, number = {1}, pages = {69-77}, doi = {10.1016/j.canlet.2003.09.011}, pmid = {14744536}, issn = {0304-3835}, mesh = {Amino Acid Sequence ; Blotting, Northern ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal/genetics/metabolism/pathology ; Carrier Proteins/*genetics/metabolism ; Cloning, Molecular ; DNA, Antisense/pharmacology ; Disease Progression ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization ; Molecular Sequence Data ; Neoplasms/genetics/metabolism/pathology ; Phylogeny ; Proteinase Inhibitory Proteins, Secretory ; RNA, Messenger/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {The inter-alpha-trypsin inhibitor (ITI) family constitutes a group of proteins built up from one light chain and a variable set of heavy chains. Originally identified as plasma protease inhibitors, recent data indicate that ITI plays a role in extracellular matrix (ECM) stabilization and in prevention of tumor metastasis. Here we describe cloning as well as phylogenetic and expression analysis of a novel member of the heavy chain gene family, ITIH5. ITIH5 contains the two domains conserved in all known ITIHs, the vault protein inter-alpha-trypsin (VIT) domain and a von Willebrand type A (vWA) domain. However, ITIH5 diverged early from a common ancestor of the other subfamilies. We found strong downregulation of ITIH5 expression in breast tumors by real-time PCR and RNA in situ hybridization. While normal breast epithelial cells clearly express ITIH5, expression is consistantly lost or strongly downregulated in invasive ductal carcinoma. ITIH5 mRNA was neither detectable in cancerous nor benign breast cell lines. We propose that loss of ITIH5 expression may be involved in breast cancer development.}, }
@article {pmid14720138, year = {2004}, author = {De la Cruz, C and Moriya, T and Endoh, M and Watanabe, M and Takeyama, J and Yang, M and Oguma, M and Sakamoto, K and Suzuki, T and Hirakawa, H and Orita, Y and Ohuchi, N and Sasano, H}, title = {Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study.}, journal = {Pathology international}, volume = {54}, number = {2}, pages = {90-96}, doi = {10.1111/j.1440-1827.2004.01590.x}, pmid = {14720138}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/blood supply/chemistry/*pathology ; Carcinoma, Ductal, Breast/blood supply/chemistry/*secondary ; Carcinoma, Papillary/blood supply/chemistry/*secondary ; Cell Nucleus/pathology ; Female ; Fluorescent Antibody Technique, Direct ; Humans ; Lymph Nodes/pathology ; Neoplasm Invasiveness ; }, abstract = {Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade (75.0%), as well as poorly differentiated histological grade (81.3%), was frequently seen. Lymph node metastases were evident in 92.9% of the examined cases, and about half of them showed more than 10 positive nodes. Comparison between serially experienced invasive ductal carcinoma, not otherwise specified (IDC-NOS), revealed that both high nuclear grade and poor histological grade were significantly more frequent (P < 0001), there was a lower frequency of positive estrogen receptor/progesterone receptor (P < 0.05, P < 0.01), a higher frequency of HER-2 overexpression (P < 0.025), and more frequent lymph node metastases (P < 0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show any statistically significant differences in frequency for positive p53, matrix metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or E-cadherin. However, IMPCa showed a significantly increased number of blood vessels counted by CD34 immunostains (P < 0.05). These results suggest that IMPCa is, at least, the same or more aggressive than lymph node positive cases of IDC-NOS. Hence, not only the high incidence of lymph node metastases but also distant, blood-borne metastases may be important.}, }
@article {pmid14717755, year = {2004}, author = {Son, BH and Ahn, SH and Ko, CD and Ka, IW and Gong, GY and Kim, JC}, title = {Significance of mismatch repair protein expression in the chemotherapeutic response of sporadic invasive ductal carcinoma of the breast.}, journal = {The breast journal}, volume = {10}, number = {1}, pages = {20-26}, doi = {10.1111/j.1524-4741.2004.09609.x}, pmid = {14717755}, issn = {1075-122X}, mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/genetics/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/genetics/*metabolism/pathology ; Carrier Proteins ; Cisplatin/administration &amp; dosage ; Cyclophosphamide/administration &amp; dosage ; *DNA-Binding Proteins ; Doxorubicin/administration &amp; dosage ; Drug Resistance, Neoplasm ; Female ; Fluorouracil/administration &amp; dosage ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Methotrexate/administration &amp; dosage ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Neoplasm Proteins/*metabolism ; Neoplasm Staging ; Nuclear Proteins ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Prognosis ; Proteins/*metabolism ; *Proto-Oncogene Proteins ; }, abstract = {The mismatch repair (MMR) gene plays a key role in the correction of DNA damage, and the loss of MMR has been implicated in resistance to a variety of chemotherapeutic drugs. The purpose of this study was to assess whether the reduced expression of hMLH1 and/or hMSH2 affects the chemotherapeutic responsiveness of sporadic invasive ductal carcinoma of the breast. Immunohistochemical studies were performed on 71 histologic specimens of breast cancer taken from the patients treated with surgery and subsequent cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide, Adriamycin, and 5-fluorouracil (CAF) chemotherapy for stage II or III primary breast cancer. Single-strand conformational polymorphism polymerase chain reaction (PCR-SSCP) and sequencing were carried out in 16 patients. A combined immunoreactivity score (hMLH1-IS and hMSH2-IS) was calculated by multiplying the staining grade by the intensity score. Positive expression (>4) of hMLH1-IS and hMSH2-IS were 57.7% and 60.6%, respectively, and complete losses of hMLH1 and hMSH2 were observed in 4.2% of patients. Of the patients with advanced cancer with lymph node metastasis, those having a low hMLH1-IS had a significantly higher failure rate with the CMF regimen than those having a high hMLH1-IS (p = 0.03). No significant difference was noted in chemotherapeutic response according to hMLH1 and hMSH2 expression in the CAF group. Both hMLH1-IS (p = 0.03) and progesterone receptor (PR) status (p = 0.03) were well correlated with CMF chemotherapy response in breast cancers with lymph node metastasis. Our study shows that a lack of hMLH1 expression may play a role in drug resistance, especially in the CMF group, and immunohistochemical assay for MMR protein can be used as a convenient tool for evaluating chemotherapeutic response in patients with breast cancer.}, }
@article {pmid14717664, year = {2004}, author = {Zekioglu, O and Erhan, Y and Ciris, M and Bayramoglu, H and Ozdemir, N}, title = {Invasive micropapillary carcinoma of the breast: high incidence of lymph node metastasis with extranodal extension and its immunohistochemical profile compared with invasive ductal carcinoma.}, journal = {Histopathology}, volume = {44}, number = {1}, pages = {18-23}, doi = {10.1111/j.1365-2559.2004.01757.x}, pmid = {14717664}, issn = {0309-0167}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*secondary/surgery ; Carcinoma, Papillary/chemistry/*secondary/surgery ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIMS: Invasive micropapillary carcinoma of the breast is an aggressive and distinctive variant of breast cancer. These tumours have a characteristic histological appearance and have been associated with a high incidence of axillary lymph node metastases and a poor clinical outcome. The aims of this study were to investigate the immunohistochemical profile of invasive micropapillary carcinoma of the breast, to compare it with invasive ductal carcinoma, and to identify the morphological parameters which predict its poor outcome.<br><br>METHODS AND RESULTS: Fifty-three (2.6%) invasive micropapillary carcinomas of the breast from 2022 cases of infiltrating breast carcinomas were identified by retrospective review. The patient age at presentation ranged from 33 to 78 years (mean 52.5 years). The tumour size ranged from 5 to 70 mm (mean 27 mm). Eighty-two percent (43 of 53) were of high histological grade; 69% (33 of 48) of cases with axillary lymph node dissections had positive lymph nodes; and 75.5% (40 of 53) had lymphatic invasion: 46% (22 of 48) of cases had extranodal extension. Of lymph node-positive cases, 61% had four or more metastatic lymph nodes. Of tumours with tumour size >10 mm, 77% had positive lymph nodes. The percentages of cases positive for oestrogen receptor (ER) and progesterone receptor (PR) were 68% and 61%, respectively. These values were significantly higher than the values for invasive ductal carcinomas. p53 and c-erbB-2 were detected in 48% and 54% of cases, respectively. The mean value of Ki67 was 26%. Follow-up was available in 36 patients. Eight patients had local recurrences, nine patients had distant metastases, and 10 patients died of disease within a follow-up period of 9 years.<br><br>CONCLUSION: Lymphotropism and an unfavourable prognosis are the hallmarks of this distinct entity. Prognostic markers such as ER, PR, p53, and c-erbB-2 failed to provide new criteria to allow discrimination of these tumours from other breast cancers.}, }
@article {pmid14711979, year = {2003}, author = {Amari, M and Moriya, T and Ishida, T and Harada, Y and Ohnuki, K and Takeda, M and Sasano, H and Horii, A and Ohuchi, N}, title = {Loss of heterozygosity analyses of asynchronous lesions of ductal carcinoma in situ and invasive ductal carcinoma of the human breast.}, journal = {Japanese journal of clinical oncology}, volume = {33}, number = {11}, pages = {556-562}, doi = {10.1093/jjco/hyg109}, pmid = {14711979}, issn = {0368-2811}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Female ; Genes, Tumor Suppressor ; Humans ; *Loss of Heterozygosity ; Microsatellite Repeats ; Paraffin Embedding ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is known to possess characteristics of the pre-invasive stage of breast cancer and is the precursor to invasive ductal carcinoma (IDC). However, the natural history of the progression from DCIS to IDC remains unknown at the molecular level.<br><br>METHODS: We investigated the loss of heterozygosities (LOHs) in tumors of seven patients with a history of breast biopsy. The seven specimens were diagnosed as DCIS on histopathological re-examination. These patients were diagnosed with ipsilateral breast cancer a few years after biopsy. We used thirteen selected microsatellite markers that were mapped to and/or very close to the tumor suppressor genes or regions with frequent LOHs in breast cancer. DNA isolated from microdissected formalin-fixed, paraffin-embedded tissues was subjected to a PCR-LOH analysis for these chromosome loci, and the pattern of LOHs was compared between the two asynchronous lesions for the seven cases.<br><br>RESULTS: In all patients except one, the LOHs were concordant at 91% as the informative chromosome loci in cases 1 to 6 were 56, and the concordance in LOH pattern between DCIS and IDC was detected at 50 loci. The LOHs had accumulated in accordance with the tumor progression from DCIS to IDC. The recurrent lesion occurred at or near the site of the primary biopsy and had similar or identical histopathologic features.<br><br>CONCLUSIONS: These recurrences observed were probably residual disease rather than true recurrences. Our results suggest the following: (i) genetic alternations accumulate during cancer progression from DCIS to IDC, (ii) DCIS is a lesion that has a high risk of developing invasive transformation and (iii) after approximately 5 years without treatment, DCIS may develop into IDC.}, }
@article {pmid14710238, year = {2004}, author = {Adamina, M and Bolli, M and Albo, F and Cavazza, A and Zajac, P and Padovan, E and Schumacher, R and Reschner, A and Feder, C and Marti, WR and Oertli, D and Heberer, M and Spagnoli, GC}, title = {Encapsulation into sterically stabilised liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes.}, journal = {British journal of cancer}, volume = {90}, number = {1}, pages = {263-269}, pmid = {14710238}, issn = {0007-0920}, mesh = {Antigens, Neoplasm/*immunology ; Epitopes ; Humans ; Immunotherapy/methods ; Liposomes ; Lymphocytes, Tumor-Infiltrating/immunology ; MART-1 Antigen ; Melanoma/*immunology ; Neoplasm Proteins/*immunology ; Skin Neoplasms/*immunology ; T-Lymphocytes, Cytotoxic/*immunology ; }, abstract = {Tumour-associated antigens (TAA)-specific vaccination requires highly immunogenic reagents capable of inducing cytotoxic T cells (CTL). Soluble peptides are currently used in clinical applications despite an acknowledged poor immunogenicity. Encapsulation into liposomes has been suggested to improve the immunogenicity of discrete antigen formulations. We comparatively evaluated the capacity of HLA-A2.1 restricted Melan-A/MART-1 epitopes in soluble form (S) or following inclusion into sterically stabilised liposomes (SSL) to be recognised by specific CTL, to stimulate their proliferation and to induce them in healthy donors' peripheral blood mononuclear cells (PBMC), as well as in melanoma-derived tumour-infiltrating lymphocytes (TIL). HLA-A2.1(+), Melan-A/MART-1-NA-8 melanoma cells served as targets of specific CTL in 51Cr release assays upon pulsing by untreated or human plasma-treated soluble or SSL-encapsulated Melan-A/MART-1 27-35 (M27-35) or 26-35 (M26-35) epitopes. These reagents were also used to stimulate CTL proliferation, measured as 3H-thymidine incorporation, in the presence of immature dendritic cells (iDC), as antigen-presenting cells (APC). Induction of specific CTL upon stimulation with soluble or SSL-encapsulated peptides was attempted in healthy donors' PBMC or melanoma-derived TIL, and monitored by 51Cr release assays and tetramer staining. Na-8 cells pulsing with SSL M27-35 resulted in a five-fold more effective killing by specific CTL as compared with equal amounts of S M27-35. Encapsulation into SSL also provided a partial (50%) protection of M27-35 from plasma hydrolysis. No specific advantages regarding M26-35 were detectable in these assays. However, at low epitope concentrations (</=100 ng ml(-1)), SSL M26-35 was significantly more effective in inducing CTL proliferation than S M26-35, in the presence of iDC, as APC. Preincubation with iDC for 6 h virtually abolished the capacity of S M26-35 to stimulate specific CTL proliferation, but only partially affected that of SSL M26-35. Most importantly, SSL M26-35 was able to enhance the induction of specific CTL in healthy donors PBMC and in melanoma-derived TIL as compared to S M26-35. Taken together, our data indicate that encapsulation of TAA epitopes into SSL results in effective immunogenic formulations suitable for clinical use in active specific tumour immunotherapy.}, }
@article {pmid14695466, year = {2004}, author = {Inoue, K and Hamada, M and Ohtsuka, T and Higaki, J}, title = {Relation of myocardial blood volume to left ventricular function and future cardiac events in patients with idiopathic dilated cardiomyopathy.}, journal = {Circulation journal : official journal of the Japanese Circulation Society}, volume = {68}, number = {1}, pages = {53-58}, doi = {10.1253/circj.68.53}, pmid = {14695466}, issn = {1346-9843}, mesh = {*Blood Volume ; Cardiomyopathy, Dilated/blood/complications/*physiopathology ; Coronary Angiography ; Coronary Circulation/*physiology ; Echocardiography ; Female ; Follow-Up Studies ; Heart Diseases/*epidemiology ; Humans ; Image Processing, Computer-Assisted ; Male ; Middle Aged ; Patient Selection ; Predictive Value of Tests ; Reference Values ; Regression Analysis ; Thallium Radioisotopes ; Time Factors ; Tomography, Emission-Computed, Single-Photon ; Ventricular Function, Left/*physiology ; }, abstract = {BACKGROUND: The hypothesis that myocardial blood volume is associated with left ventricular (LV) dysfunction and future cardiovascular events in patients with idiopathic dilated cardiomyopathy (IDC) was tested using intravenous myocardial contrast echocardiography (MCE).<br><br>METHODS AND RESULTS: Thirty-five patients with IDC and 10 age-matched healthy control subjects were enrolled. Using MCE, background-subtracted and peak myocardial contrast intensity (calibrated PMCI) were calculated as measures of myocardial blood volume. LV ejection fraction (LVEF) was calculated using the modified Simpson method. Patients with IDC were stratified into 2 groups according to the median value of the calibrated PMCI [high value group (n=17): calibrated PMCI > or = -22.7 dB, low value group (n=18): calibrated PMCI < -22.7 dB]. The calibrated PMCI was markedly reduced in patients with IDC compared with the control subjects (p=0.0025) and closely related to LVEF (r=0.688, p<0.0001). In the multivariate model, calibrated PMCI was the independent variable that predicted cardiac events in patients with IDC. According to the Kaplan-Meier analysis, cardiac event-free rates were significantly lower in the low-value group than in the high-value group (p<0.01).<br><br>CONCLUSIONS: Myocardial blood volume is closely related to LV dysfunction and future cardiac events in patients with IDC.}, }
@article {pmid14693746, year = {2003}, author = {Hoque, A and Carter, J and Xia, W and Hung, MC and Sahin, AA and Sen, S and Lippman, SM}, title = {Loss of aurora A/STK15/BTAK overexpression correlates with transition of in situ to invasive ductal carcinoma of the breast.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {12}, number = {12}, pages = {1518-1522}, pmid = {14693746}, issn = {1055-9965}, support = {N01-CN-65004/CN/NCI NIH HHS/United States ; R01 CA 61979/CA/NCI NIH HHS/United States ; R01 CA 89716/CA/NCI NIH HHS/United States ; }, mesh = {Aneuploidy ; Aurora Kinase A ; Aurora Kinases ; Biomarkers, Tumor/analysis ; Biopsy, Needle ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Transformation, Neoplastic/*pathology ; Culture Techniques ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Neoplasm Invasiveness/*pathology ; Protein Serine-Threonine Kinases/*genetics ; Sampling Studies ; Sensitivity and Specificity ; }, abstract = {The biological mechanisms involved in the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer are not fully understood. We previously have shown that the putative oncogene Aurora-A/STK15/BTAK, encoding a centrosome-associated kinase that regulates centrosomes and chromosome segregation, is amplified in human breast cancer. In this study, 37 archival breast tissue specimens of histologically confirmed DCIS lesions with adjacent invasive carcinoma and morphologically nonmalignant mammary ducts were analyzed immunohistochemically for expression of STK15. Statistically significant differences in overexpression of STK15 was found between invasive cancer and either nonmalignant mammary ducts (P < 0.0001) or DCIS lesions (P < 0.0005). Abnormalities in centrosome size and number was detected in the samples analyzed and 56% (14 of 25) of the cases also showed aneuploidy reflected in >2 signals of chromosome 3 and 17. Our data demonstrate that STK15 overexpression correlates with centrosome anomaly and aneuploidy in DCIS, and loss of STK15 overexpression is associated with progression of in situ to ductal invasive breast carcinoma.}, }
@article {pmid14692838, year = {2004}, author = {Susnik, B and Jordi Rowe, J and Redlich, PN and Chitambar, C and Chang, CC and Kampalath, B}, title = {A unique collision tumor in breast: invasive ductal carcinoma and mucosa-associated lymphoid tissue lymphoma.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {128}, number = {1}, pages = {99-101}, doi = {10.5858/2004-128-99-AUCTIB}, pmid = {14692838}, issn = {1543-2165}, mesh = {Aged ; Breast Neoplasms/complications/*pathology ; Carcinoma, Ductal, Breast/complications/*pathology ; Female ; Humans ; Lymphoma, B-Cell, Marginal Zone/complications/*pathology ; }, abstract = {We report an extraordinary case of a collision tumor consisting of invasive ductal carcinoma with adjacent malignant lymphoma presenting as a single mass in the breast. A 79-year-old woman presented with a breast mass. A core biopsy performed at an outside hospital was interpreted as medullary carcinoma. On review of the breast core biopsy, a diagnosis of a synchronous malignant lymphoma and invasive ductal carcinoma was rendered. The patient underwent lumpectomy and axillary dissection. The excised specimen revealed a 2.1-cm, moderately differentiated invasive ductal carcinoma, partially surrounded by malignant lymphoma with areas where both tumors were intermixed. All 27 axillary lymph nodes were extensively involved by lymphoma, and 1 lymph node demonstrated metastatic carcinoma. The morphology and results of immunohistochemistry, flow cytometry, and cytogenetic analysis were consistent with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.}, }
@article {pmid14691916, year = {2003}, author = {Diallo, R and Schaefer, KL and Bankfalvi, A and Decker, T and Ruhnke, M and Wülfing, P and Jackisch, C and Luttges, J and Sorensen, PH and Singh, M and Poremba, C}, title = {Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry.}, journal = {Human pathology}, volume = {34}, number = {12}, pages = {1299-1305}, doi = {10.1016/s0046-8177(03)00423-4}, pmid = {14691916}, issn = {0046-8177}, mesh = {Adult ; Aged ; Breast Neoplasms/*classification/genetics/*pathology ; Carcinoma, Ductal/genetics/*pathology ; Chromosome Aberrations ; DNA, Neoplasm/*analysis ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/metabolism ; Male ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Secretory carcinomas (SCA) are distinguished from infiltrating ductal carcinomas (IDC) of the breast by their characteristic histomorphology and more favorable prognosis and by the expression of a chimeric tyrosine kinase that is encoded by the ETV6-NTRK3 fusion gene. On this basis, we evaluated 13 SCAs (12 of them with ETV6-NTRK3 gene fusion) by molecular and immunohistochemical (IHC) methods. DNA was obtained from 8 of 13 microdissected SCAs and was analyzed for genetic alterations (GA) by comparative genomic hybridization (CGH). IHC staining was performed for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67 (MIB1) in all 13 cases. Molecular and immunohistochemical results in SCAs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. An average of 2.0 GAs (range: 0 to 6) were detected, including recurrent gains of chromosome 8q (37.5%) and 1q (25%) and losses of 22q (25%). Four of 13 (31%) SCAs were positive for ER, and 2 were positive for PR. The mean MIB1-labeling index was 11.4% (range: <1 to 34%). Her-2/neu protein overexpression was detected in 2 cases, including 1 with strong (score 3+) and 1 with weak HER2/neu expression (score 2+). Fluorescence in situ hybridization analysis of the latter case showed no evidence of HER-2/neu-gene amplification. Compared with previous findings in IDCs, SCAs are characterized by a relatively low number of GAs, a low proliferative rate, infrequent HER2/neu protein overexpression, decreased steroid hormone receptor expression, and expression of ETV6-NTRK3 fusion gene. These results support the hypothesis that SCAs have immunohistochemical and genetic features that distinguish them from IDCs of the usual type.}, }
@article {pmid14689308, year = {2004}, author = {Lotze, U and Egerer, R and Tresselt, C and Glück, B and Dannberg, G and Stelzner, A and Figulla, HR}, title = {Frequent detection of parvovirus B19 genome in the myocardium of adult patients with idiopathic dilated cardiomyopathy.}, journal = {Medical microbiology and immunology}, volume = {193}, number = {2-3}, pages = {75-82}, pmid = {14689308}, issn = {0300-8584}, mesh = {Adenoviridae/isolation &amp; purification ; Adult ; Aged ; Base Sequence ; Biopsy ; Cardiomyopathy, Dilated/*virology ; Endocardium/*virology ; Enterovirus/isolation &amp; purification ; Enterovirus Infections/virology ; Female ; *Genome, Viral ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Parvoviridae Infections/*virology ; Parvovirus B19, Human/*isolation &amp; purification ; Sequence Analysis, DNA ; }, abstract = {Aside from enteroviruses and other viruses, e.g., adenoviruses, which are known to be associated with idiopathic dilated cardiomyopathy (IDC), a cardiac tropism is also attributed to parvovirus B19 (PVB19). The purpose of the present study was to determine the prevalence of enterovirus, adenovirus and PVB19 genomes in the myocardium of adult patients with IDC and to analyze the significance of PVB19 with regard to the course of the disease, as compared to the other cardiotropic viruses. In 52 adult patients with IDC and 10 control patients with normal left ventricular ejection fraction (> or =55%) undergoing coronary artery bypass surgery, myocardial tissue samples were investigated for enteroviral RNA using polymerase chain reaction (PCR) and Southern blot hybridization of the PCR product. Specific nested PCR was used to assess the prevalence of adenovirus and PVB19 DNA, in addition to sequencing of the latter. The clinical and echocardiographic course of the disease was followed for a mean (+/- SD) period of 21.1+/-9.5 months. Fourteen of the 52 patients (27%) were enterovirus-positive, 2/52 (4%) patients were adenovirus-positive, 14/52 (27%) patients were PVB19-positive, 8/52 (15%) patients were enterovirus plus PVB19-positive, and in 14/52 (27%) patients no viral genomes were found. Six patients died during the follow-up period, without any significant difference between the patient groups: 1/14 (7%) in the enterovirus-positive, 0/2 (0%) in the adenovirus-positive, 2/14 (14%) in the PVB19-positive, 1/8 (12.5%) in the enterovirus plus PVB19-positive, and 2/14 (14%) in the virus-negative group. PVB19 genome was found in 4 of the 10 (40%) control patients, but no enterovirus or adenovirus genomes were detected in these patients. In conclusion, in the myocardium of patients with IDC, PVB19 is detectable as frequently as enteroviral genome. PVB19-positive patients with IDC have a rather favorable prognosis and do not differ significantly from the other virus-positive or virus-negative patient groups with respect to survival. Finally, the pathogenetic and prognostic significance of PVB19 in IDC still remains unclear.}, }
@article {pmid14689049, year = {2004}, author = {Ribeiro-Silva, A and Ramalho, LN and Garcia, SB and Zucoloto, S}, title = {Does the correlation between EBNA-1 and p63 expression in breast carcinomas provide a clue to tumorigenesis in Epstein-Barr virus-related breast malignancies?.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {37}, number = {1}, pages = {89-95}, doi = {10.1590/s0100-879x2004000100013}, pmid = {14689049}, issn = {0100-879X}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/metabolism/*virology ; Carcinoma, Ductal, Breast/genetics/metabolism/virology ; DNA-Binding Proteins ; Epstein-Barr Virus Nuclear Antigens/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Herpesvirus 4, Human/*isolation &amp; purification ; Humans ; Immunohistochemistry ; Middle Aged ; Phosphoproteins/*genetics ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Trans-Activators/*genetics ; Transcription Factors ; Tumor Suppressor Protein p53/*genetics ; Tumor Suppressor Proteins ; }, abstract = {Several investigators have identified Epstein-Barr virus (EBV) particles in breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis. The possible mechanism involved in this process is not clear. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and p53 and p63 expression in breast carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER) and anti-progesterone receptor (PR) antibodies. The cases were selected to represent each of the various histologic types: intraductal carcinoma (N=12), grade I invasive ductal carcinoma (N=15), grade II invasive ductal carcinoma (N=15), grade III invasive ductal carcinoma (N=15), tubular carcinoma (N=8), lobular carcinoma (N=10), and medullary carcinoma (N=10). The ductal breast carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson grading system modified by Elston and Ellis. One slide containing at least 1000 neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a correlation between EBNA-1 and p63 expression (P<0.001), but not between EBNA-1 and p53 (P=0.10). These data suggest a possible role for p63 in the mammary tumorigenesis associated with Epstein-Barr virus infection.}, }
@article {pmid14674989, year = {2004}, author = {Chung, MJ and Jung, SH and Lee, BJ and Kang, MJ and Lee, DG}, title = {Inactivation of the PTEN gene protein product is associated with the invasiveness and metastasis, but not angiogenesis, of breast cancer.}, journal = {Pathology international}, volume = {54}, number = {1}, pages = {10-15}, doi = {10.1111/j.1440-1827.2004.01576.x}, pmid = {14674989}, issn = {1440-1827}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/blood supply/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/blood supply/*genetics/metabolism/secondary ; Cell Nucleus/metabolism/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; *Gene Silencing ; Humans ; Immunoenzyme Techniques ; Microcirculation/metabolism/pathology ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/pathology ; Neoplasm Recurrence, Local ; *Neovascularization, Pathologic ; PTEN Phosphohydrolase/*genetics/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {PTEN is a novel tumor-suppressor gene located on chromosomal band 10q23. Loss of PTEN function has been implicated in the progression of several types of cancer, but the correlation between loss of PTEN expression and advanced carcinomas is not well established. The capacity for angiogenesis of a tumor is known to play a very important role in growth and metastasis, and there have been reports that PTEN relates to angiogenesis. In the present study, formalin-fixed and paraffin embedded tissues from 101 patients with breast carcinomas, including 88 cases of invasive ductal carcinomas and 13 cases of ductal carcinoma in situ (DCIS), were evaluated by immunohistochemical methods for the expression of PTEN and vascular endothelial growth factor (VEGF), as well as microvessel density (MVD). The results were compared with the clinicopathologic parameters. There was no loss of PTEN expression in any of the cases of DCIS, but 28 (32%) of the 88 invasive cases did not express PTEN. Loss of PTEN expression was associated with lymph node metastasis (P = 0.03), but did not correlate with tumor size, tumor grade, MVD or recurrence. VEGF expression significantly correlated with lymph node metastasis in invasive ductal carcinoma (P = 0.01). There was no correlation between the expression of PTEN and that of VEGF (P = 0.63). The present study suggests that loss of PTEN expression is common and correlates with tumor progression and lymph node metastasis in breast carcinoma. The relationship between loss of PTEN and progression of breast cancer may not be explained by modulation of angiogenesis.}, }
@article {pmid14640991, year = {2003}, author = {Segerlantz, M and Bramnert, M and Manhem, P and Laurila, E and Groop, LC}, title = {Inhibition of lipolysis during acute GH exposure increases insulin sensitivity in previously untreated GH-deficient adults.}, journal = {European journal of endocrinology}, volume = {149}, number = {6}, pages = {511-519}, doi = {10.1530/eje.0.1490511}, pmid = {14640991}, issn = {0804-4643}, mesh = {Adult ; Aged ; Analysis of Variance ; Blood Glucose/drug effects ; Double-Blind Method ; Energy Metabolism/drug effects ; Fatty Acids, Nonesterified/blood ; Female ; Hormone Replacement Therapy/adverse effects ; Human Growth Hormone/*deficiency/*therapeutic use ; Humans ; Hypolipidemic Agents/*pharmacology ; Insulin/*metabolism ; Lipolysis/*drug effects/physiology ; Male ; Middle Aged ; Pyrazines/*pharmacology ; }, abstract = {OBJECTIVE: Previous studies evaluating the lipolytic effect of GH have in general been performed in subjects on chronic GH therapy. In this study we assessed the lipolytic effect of GH in previously untreated patients and examined whether the negative effect of enhanced lipolysis on glucose metabolism could be counteracted by acute antilipolysis achieved with acipimox.<br><br>METHODS: Ten GH-deficient (GHD) adults participated in four experiments each, during which they received in a double-blind manner: placebo (A); GH (0.88+/-0.13 mg) (B); GH+acipimox 250 mg b.i.d. (C); and acipimox b.i.d. (no GH) (D), where GH was given the night before a 2 h euglycemic, hyperinsulinemic clamp combined with infusion of [3-(3)H]glucose and indirect calorimetry.<br><br>RESULTS: GH increased basal free fatty acid (FFA) levels by 74% (P=0.0051) and insulin levels by 93% (P=0.0051). This resulted in a non-significant decrease in insulin-stimulated glucose uptakes (16.61+/-8.03 vs 12.74+/-5.50 micromol/kg per min (s.d.), P=0.07 for A vs B). The rates of insulin-stimulated glucose uptake correlated negatively with the FFA concentrations (r=-0.638, P<0.0001). However, acipimox caused a significant improvement in insulin-stimulated glucose uptake in the GH-treated patients (17.35+/-5.65 vs 12.74+/-5.50 micromol/kg per min, P=0.012 for C vs B). The acipimox-induced enhancement of insulin-stimulated glucose uptake was mainly due to an enhanced rate of glucose oxidation (8.32+/-3.00 vs 5.88+/-2.39 micromol/kg per min, P=0.07 for C vs B). The enhanced rates of glucose oxidation induced by acipimox correlated negatively with the rate of lipid oxidation in GH-treated subjects both in basal (r=-0.867, P=0.0093) and during insulin-stimulated (r=-0.927, P=0.0054) conditions. GH did not significantly impair non-oxidative glucose metabolism (6.86+/-5.22 vs 8.67+/-6.65 micromol/kg per min, P=NS for B vs A). The fasting rate of endogenous glucose production was unaffected by GH and acipimox administration (10.99+/-1.98 vs 11.73+/-2.38 micromol/kg per min, P=NS for B vs A and 11.55+/-2.7 vs 10.99+/-1.98 micromol/kg per min, P=NS for C vs B). On the other hand, acipimox alone improved glucose uptake in the untreated GHD patients (24.14+/-8.74 vs 16.61+/-8.03 micromol/kg per min, P=0.0077 for D vs A) and this was again due to enhanced fasting (7.90+/-2.68 vs 5.16+/-2.28 micromol/kg per min, P=0.01 for D vs A) and insulin-stimulated (9.78+/-3.68 vs 7.95+/-2.64 micromol/kg per min, P=0.07 for D vs A) glucose oxidation.<br><br>CONCLUSION: The study of acute administration of GH to previously untreated GHD patients provides compelling evidence that (i) GH-induced insulin resistance is mainly due to induction of lipolysis by GH; and (ii) inhibition of lipolysis can prevent the deterioration of insulin sensitivity. The question remains whether GH replacement therapy should, at least at the beginning of therapy, be combined with means to prevent an excessive stimulation of lipolysis by GH.}, }
@article {pmid14635052, year = {2003}, author = {Pietra, G and Romagnani, C and Mazzarino, P and Millo, E and Moretta, L and Mingari, MC}, title = {Comparative analysis of NK- or NK-CTL-mediated lysis of immature or mature autologous dendritic cells.}, journal = {European journal of immunology}, volume = {33}, number = {12}, pages = {3427-3432}, doi = {10.1002/eji.200324515}, pmid = {14635052}, issn = {0014-2980}, mesh = {Cells, Cultured ; Cytomegalovirus/immunology ; *Cytotoxicity, Immunologic ; Dendritic Cells/*physiology ; HLA Antigens/metabolism ; Histocompatibility Antigens Class I/metabolism ; Humans ; Killer Cells, Natural/*immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Proteins/immunology ; }, abstract = {Natural killer (NK) cells have been shown to kill efficiently autologous immature dendritic cells (iDC), while sparing those undergone maturation. In this study we investigated the effect of the interaction between autologous DC and NK-cytolytic T lymphocytes (NK-CTL), a subset of HLA-E-restricted CD8(+) T cells that express HLA class I-specific inhibitory NK receptors. Although these cells share with NK cells various phenotypic and functional features (such as the capacity to lyse most allogeneic, NK-susceptible tumor cell lines), different from NK cells, NK-CTL failed to lyse autologous DC. However, after pulsing DC with a cytomegalovirus-derived, HLA-E-binding peptide recognized by NK-CTL, both iDC and mature DC became highly susceptible to lysis. On the other hand,the addition of the peptide resulted in the down-regulation of the NK-mediated lysis of the same autologous iDC. The capability of killing autologous DC, presenting a non-self, HLA-E-binding peptide, may represent a feedback mechanism by which NK-CTL down-regulate HLA-E-restricted responses to certain pathogens.}, }
@article {pmid14634509, year = {2003}, author = {Tsutsui, S and Kume, M and Era, S}, title = {Prognostic value of microvessel density in invasive ductal carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {10}, number = {4}, pages = {312-319}, doi = {10.1007/BF02967651}, pmid = {14634509}, issn = {1340-6868}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Breast Neoplasms/*blood supply/pathology/therapy ; Carcinoma, Ductal/*blood supply/secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Male ; Microcirculation ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Recurrence ; }, abstract = {BACKGROUND: Although the prognostic value of microvessel density (MVD) has been studied in breast cancer, the results still remain controversial.<br><br>PATIENTS AND METHODS: Paraffin embedded sections of invasive ductal carcinoma of the breast were immunohistochemically stained for factor VIII- related antigen in 252 patients with a median follow-up duration of 7.0 years. MVD quantification of the three most vascular areas at a magnification of x 200 was performed.<br><br>RESULTS: The 252 patients were stratified into high and low MVD groups according to a cut-off value that was the upper one-third MVD value of all patients. The patients with a high MVD had a significantly worse outcome in terms of both disease free survival (DFS) (p< 0.0001) and overall survival (OS) (p= 0.0012) compared with those with a low MVD. The same effects were seen in patients with lymph node negative as well as positive breast cancer. Multivariate analyses indicated the nodal status, nuclear grade and MVD (p= 0.0001) to be independent prognostic factors for the DFS, while the nodal status, estrogen receptor status, tumor size and MVD (p= 0.0006) were independent prognostic factors for the OS.<br><br>CONCLUSION: MVD was found to be an independent prognostic indicator of recurrence and death for breast cancer, and is therefore considered to be a useful factor for selecting high risk patients to receive adjuvant therapies.}, }
@article {pmid14634505, year = {2003}, author = {Yoo, KY and Kang, D}, title = {Current researches on breast cancer epidemiology in Korea.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {10}, number = {4}, pages = {289-293}, doi = {10.1007/BF02967647}, pmid = {14634505}, issn = {1340-6868}, mesh = {Biomedical Research/trends ; Breast Neoplasms/*epidemiology/*genetics/mortality ; Female ; Genetic Predisposition to Disease ; Humans ; Incidence ; Korea/epidemiology ; Mortality/trends ; *Polymorphism, Genetic ; Risk Factors ; }, abstract = {As a cause of death in women, breast cancer ranks second to stomach cancer in Korea. Age-standardized mortality rates for breast cancer steadily increased during the 1980s and 1990s. There are big differences in the incidence rates for breast cancer compared with Western countries. Epidemiological features, trends in morbidity and mortality, various age-specific incidence curves, migrant study results, and analysis of the risk factors, however, suggest that the incidence of breast cancer might be further increasing in Korea. The key epidemiological hormonal risk factors for breast cancer are all explicable in terms of the estrogen augmented by progesterone hypothesis. These include older age, family history of breast cancer, early menarche, late menopause, late full-term pregnancy, and never a breast feeding. Both the establishment of high-risk groups and the estimation of lifetime risk are essential to develop a control strategy against breast cancer. Invasive ductal carcinoma is the most common histologic type of breast cancer in Korea, and the five-year survival rate has been estimated as 80-83%. Recent studies on the identification of susceptibility factors such as genetic polymorphisms of GSTM1/T1/P1, COMT, CYP2E1, CYP19, CYP17, ER-alpha, XRCC1, XRCC3, RAD52, TGF-alpha, TNF-alpha, IL-1B, IL-1RN, CDK7 etc. that predispose individuals to breast cancer by gene-environment or gene-gene interactions may possibly give further insight into both the etiology and the prevention of this malignancy.}, }
@article {pmid14624360, year = {2004}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Prognostic significance of the intra-vessel tumor characteristics of invasive ductal carcinoma of the breast: a prospective study.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {444}, number = {1}, pages = {20-27}, pmid = {14624360}, issn = {0945-6317}, mesh = {Adult ; Aged ; Analysis of Variance ; Apoptosis ; Blood Vessels/*pathology ; Breast Neoplasms/*blood supply/mortality/*pathology ; Carcinoma, Ductal, Breast/*blood supply/mortality/*pathology ; Endothelium, Lymphatic/pathology ; Endothelium, Vascular/pathology ; Female ; Humans ; Lymphatic Metastasis/pathology ; Lymphatic Vessels/*pathology ; Middle Aged ; Mitosis ; Muscle, Smooth, Vascular/pathology ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prognosis ; Prospective Studies ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Risk Factors ; Survival Rate ; }, abstract = {Invasive ductal carcinomas (IDCs) of the breast are composed of stroma-invasive tumors and tumors in vessels. The purpose of this study was to prospectively investigate whether the histological characteristics of the tumors in vessels were more significantly associated with the outcome of 393 IDC patients than well-known histological parameters. Multivariate analyses showed greater than six apoptotic figures in tumor cells in lymph vessels to be significantly associated with increased hazard rates (HRs) of tumor recurrence and death in IDC patients without nodal metastasis (P<0.05). Among IDC patients with nodal metastasis whose tumors were positive for estrogen receptors (ERs) or progesterone receptors (PRs) or both, greater than six apoptotic figures in tumor cells in lymph vessels and greater than four mitotic figures in tumor cells in lymph vessels significantly increased the HR of tumor recurrence and the HR of death, respectively (P<0.05). Among IDC patients with nodal metastases whose tumors were negative for ERs and PRs, multivariate analyses showed that greater than two apoptotic figures in the blood vessel tumor emboli significantly increased the HRs of tumor recurrence and death (P<0.005). We conclude that apoptotic figures and mitotic figures in tumor cells in vessels are very important prognostic indicators for patients with IDC of the breast.}, }
@article {pmid14623812, year = {2003}, author = {Grimm, W and Christ, M and Bach, J and Müller, HH and Maisch, B}, title = {Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study.}, journal = {Circulation}, volume = {108}, number = {23}, pages = {2883-2891}, doi = {10.1161/01.CIR.0000100721.52503.85}, pmid = {14623812}, issn = {1524-4539}, mesh = {Adolescent ; Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Anti-Arrhythmia Agents/therapeutic use ; Arrhythmias, Cardiac/*epidemiology/etiology/prevention &amp; control ; Atrial Fibrillation/complications ; Baroreflex/drug effects ; Cardiomyopathy, Dilated/*complications/drug therapy ; Death, Sudden, Cardiac/epidemiology/etiology ; Defibrillators, Implantable ; Electric Countershock ; Electrocardiography, Ambulatory ; Female ; Germany/epidemiology ; Heart Rate ; Humans ; Life Tables ; Male ; Middle Aged ; Phenylephrine ; Proportional Hazards Models ; Prospective Studies ; Risk ; Stroke Volume ; Survival Analysis ; Tachycardia, Ventricular/epidemiology/etiology ; Ventricular Fibrillation/epidemiology/etiology ; }, abstract = {BACKGROUND: Arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator therapy is a completely unsolved issue in idiopathic dilated cardiomyopathy (IDC).<br><br>METHODS AND RESULTS: Arrhythmia risk stratification was performed prospectively in 343 patients with IDC, including analysis of left ventricular (LV) ejection fraction and size by echocardiography, signal-averaged ECG, arrhythmias on Holter ECG, QTc dispersion, heart rate variability, baroreflex sensitivity, and microvolt T-wave alternans. During 52+/-21 months of follow-up, major arrhythmic events, defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death, occurred in 46 patients (13%). On multivariate analysis, LV ejection fraction was the only significant arrhythmia risk predictor in patients with sinus rhythm, with a relative risk of 2.3 per 10% decrease of ejection fraction (95% CI, 1.5 to 3.3; P=0.0001). Nonsustained ventricular tachycardia on Holter was associated with a trend toward higher arrhythmia risk (RR, 1.7; 95% CI, 0.9 to 3.3; P=0.11), whereas beta-blocker therapy was associated with a trend toward lower arrhythmia risk (RR, 0.6; 95% CI, 0.3 to 1.2; P=0.13). In patients with atrial fibrillation, multivariate Cox analysis also identified LV ejection fraction and absence of beta-blocker therapy as the only significant arrhythmia risk predictors.<br><br>CONCLUSIONS: Reduced LV ejection fraction and lack of beta-blocker use are important arrhythmia risk predictors in IDC, whereas signal-averaged ECG, baroreflex sensitivity, heart rate variability, and T-wave alternans do not seem to be helpful for arrhythmia risk stratification. These findings have important implications for the design of future studies evaluating prophylactic implantable cardioverter-defibrillator therapy in IDC.}, }
@article {pmid14614327, year = {2003}, author = {Tisserand, P and Fouquet, C and Barrois, M and Gallou, C and Dendale, R and Stoppa-Lyonnet, D and Sastre-Garau, X and Fourquet, A and Soussi, T}, title = {Lack of HIN-1 methylation defines specific breast tumor subtypes including medullary carcinoma of the breast and BRCA1-linked tumors.}, journal = {Cancer biology &amp; therapy}, volume = {2}, number = {5}, pages = {559-563}, doi = {10.4161/cbt.2.5.511}, pmid = {14614327}, issn = {1538-4047}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Carcinoma, Medullary/*genetics/pathology ; Cytokines/*genetics ; *DNA Methylation ; DNA, Neoplasm/genetics/metabolism ; Female ; Genes, BRCA1/*physiology ; Genes, p53/physiology ; Genetic Predisposition to Disease ; Humans ; Mutation/genetics ; Promoter Regions, Genetic ; RNA, Neoplasm/genetics/metabolism ; Tumor Suppressor Proteins/*genetics ; }, abstract = {Medullary carcinoma is a poorly differentiated breast cancer with a high histologic grade and a paradoxically good prognosis. It accounts for only 3 percent of all breast cancers except in BRCA-1 families, in which it can account for as many as 13 percent of cancers. To date, only histologic criteria have been used to define this tumor type. In an attempt to more clearly define the genetic pathway leading to this subtype of cancer, we recently demonstrated that nearly 100 percent of these carcinomas display p53 mutations. In the present study, we extended our analysis to include HIN-1, a candidate tumor suppressor that has been shown to be silenced by methylation in the majority of breast tumors. In striking contrast to unselected sporadic invasive ductal carcinoma, we show that medullary carcinomas do not display a high frequency of HIN-1 methylation (p less than 0.001). This feature is also found in BRCA-1 associated tumors that shared several histologic characteristics with medullary carcinomas of the breast. Medullary carcinoma of the breast should therefore be considered to be a unique entity defined by specific histologic and molecular traits.}, }
@article {pmid14611905, year = {2003}, author = {Wang, Q and Zhang, M and Ding, G and Liu, Y and Sun, Y and Wang, J and Zhang, W and Fu, Z and Cao, X}, title = {Anti-ICAM-1 antibody and CTLA-4Ig synergistically enhance immature dendritic cells to induce donor-specific immune tolerance in vivo.}, journal = {Immunology letters}, volume = {90}, number = {1}, pages = {33-42}, doi = {10.1016/s0165-2478(03)00160-3}, pmid = {14611905}, issn = {0165-2478}, mesh = {Abatacept ; Animals ; Cell Differentiation ; Dendritic Cells/*immunology ; Drug Synergism ; Graft Survival ; Heart Transplantation ; *Immune Tolerance ; Immunoconjugates/*immunology ; Intercellular Adhesion Molecule-1/*immunology ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; T-Lymphocytes/*immunology ; Transplantation, Homologous ; }, abstract = {Immature dendritic cells (DC) have been demonstrated to induce T-cell hyporesponsiveness in vitro and immune tolerance in vivo. However, immature DC (iDC) may become mature once infused in vivo, thus limiting the prolongation of the allograft survival. Considering that mature DC express high level of B7, intercellular adhesion molecule-1 (ICAM-1), and T-cell activation needs costimulation signals provided by DC, we selected anti-ICAM-1 mAb and cytotoxic T lymphocyte antigen-4Ig fusion protein (CTLA-4Ig) for in vivo administration to block costimulation pathways in order to further improve the efficacy of iDC to induce immune tolerance. Seven days before allogeneic cardiac transplantations, the recipients were intravenously (i.v.) pretreated of donor-derived iDC with or without simultaneous injections of anti-ICAM-1 mAb and CTLA-4Ig. CTLA-4Ig or anti-ICAM-1 mAb administration alone resulted in significant prolongation of cardiac allograft survival induced by iDC. When used simultaneously, CTLA-4Ig and anti-ICAM-1 mAb induced permanent allografts acceptance even in 90% recipients. The recipients could keep the skin alive for a longer time in the donor-specific second transplantation, but no effect was observed on the skin from C3H third-party mice. The efficient induction of donor-specific tolerance observed above may be related to the more potent inhibition of donor-specific T-cell responses including cytotoxicity activity, Th1 cytokines production, and alloantibody production by the combined use of anti-ICAM-1 mAb and CTLA-4Ig. Our data suggest that anti-ICAM-1 antibody and CTLA-4Ig can synergistically enhance iDC to induce donor-specific immune tolerance in vivo.}, }
@article {pmid14601057, year = {2003}, author = {Fackler, MJ and McVeigh, M and Evron, E and Garrett, E and Mehrotra, J and Polyak, K and Sukumar, S and Argani, P}, title = {DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma.}, journal = {International journal of cancer}, volume = {107}, number = {6}, pages = {970-975}, doi = {10.1002/ijc.11508}, pmid = {14601057}, issn = {0020-7136}, support = {P50 CA 88843/CA/NCI NIH HHS/United States ; P50 CA 89393/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Base Sequence ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Cyclin D2 ; Cyclins/*genetics ; Cytokines/*genetics ; *DNA Methylation ; DNA Primers ; Female ; Genes, Tumor Suppressor ; Humans ; Middle Aged ; Multigene Family ; Neoplasm Invasiveness ; Neoplasm Proteins/*genetics ; *Nuclear Proteins ; Receptors, Retinoic Acid/*genetics ; Reference Values ; Transcription Factors/*genetics ; *Tumor Suppressor Proteins ; Twist-Related Protein 1 ; }, abstract = {Little is known about epigenetic silencing of genes by promoter hypermethylation in lobular breast cancers. The promoter methylation status of 5 cancer-related genes (RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist) was evaluated in 2 types of lobular cancers, in situ (LCIS) and invasive lobular carcinomas (ILC) (n = 32), and compared to ductal in situ (DCIS) and invasive (IDC) breast cancers (n = 71). By using methylation-specific PCR (MSP), 100% of ILC and 69% of LCIS cases were found to have 1 or more hypermethylated genes among the panel of 5 genes (compared to 100% IDC and 95% of DCIS). Two or more hypermethylated genes were detected per tumor in 79% of invasive and 61% of in situ lobular carcinomas compared to 81% of IDC and 77% of DCIS. By contrast, DNA from nearly all normal reduction mammoplasty tissues (n = 8) was unmethylated for the 5 genes. The methylation profiles of lobular vs. ductal carcinomas with respect to RASSF1A, Cyclin D2, RARbeta, and Hin-1 genes were similar, suggesting that gene silencing by promoter hypermethylation is likely to be important in both groups of diseases. Distinctly different, Twist was hyper- methylated less often in ILC (16%, 3/19 cases) than in IDC (56%, 15/27 cases) (p = 0.01). These results suggest that these 2 types of tumors share many common methylation patterns and some molecular differences. Additional studies might lend further understanding into the etiology and clinical behavior of this tumor type.}, }
@article {pmid14593298, year = {2003}, author = {Paumier, A and Sagan, C and Campion, L and Fiche, M and Andrieux, N and Dravet, F and Pioud, R and Classe, JM}, title = {[Accuracy of conservative treatment for infiltrating lobular breast cancer: a retrospective study of 217 infiltrating lobular carcinomas and 2155 infiltrating ductal carcinomas].}, journal = {Journal de gynecologie, obstetrique et biologie de la reproduction}, volume = {32}, number = {6}, pages = {529-534}, pmid = {14593298}, issn = {0368-2315}, mesh = {Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Female ; France/epidemiology ; Humans ; Lymphatic Metastasis ; Mastectomy/statistics &amp; numerical data ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology ; Prognosis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVES: Prognosis factors used for the management of infiltrative lobular carcinoma (ILC) are not different from those for infiltrative cuctal carcinoma (IDC). The aim of our work was to evaluate indications for conservative treatment for patients with ILC and to compare the results to those of patients with IDC. MATERIAL AND METHODS. Between 1985 and 1999 we retrospectively compared cases of 217 ILC with cases of 2155 IDC treated in Centre Rene Gauducheau, Nantes.<br><br>RESULTS: Clinical size of tumors was not different between ILC and IDC but pathological size>30 mm was more frequent for IDC. Good prognosis factors as pathological SBR classification I or II, positive hormone receptor, and the lack of axillary lymph node involvement, were more frequent for ILC. Clinical examination underestimated tumor size more frequently of ILC than IDC (p=0.02). Secondary mastectomy for involved margin was more frequent for ILC than IDC (p=0.001). For tumor with good prognosis factors, such as T<20mm, lack of lymph node involvement and SBR I or II with conservative treatment, 5 years local relapse were less frequent for ILC than IDC (p=0.025).<br><br>CONCLUSION: Parameters to validate conservative or radical treatment are the same for ILC and IDC. Diagnosis of ILC should not influence decisions regarding surgical treatment.}, }
@article {pmid14580261, year = {2003}, author = {Zhang, Z and Yamashita, H and Toyama, T and Omoto, Y and Sugiura, H and Hara, Y and Wu, X and Kobayashi, S and Iwase, H}, title = {Quantitative determination, by real-time reverse transcription polymerase chain reaction, of aromatase mRNA in invasive ductal carcinoma of the breast.}, journal = {Breast cancer research : BCR}, volume = {5}, number = {6}, pages = {R250-6}, pmid = {14580261}, issn = {1465-542X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Aromatase/*genetics ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Disease-Free Survival ; Estrogen Receptor alpha ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; RNA, Messenger/genetics/*metabolism ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction/methods ; }, abstract = {BACKGROUND: Estrogen is a mitogenic factor that is implicated in the genesis and progression of breast cancer via its binding to estrogen receptor (ER)-alpha. Synthesis of estrogen in situ is believed to be catalyzed mainly by aromatase. Previous studies comparing the relative contributions from tumor cells and stromal cells to local estrogen synthesis, as assessed by immunohistochemical analysis, were quite controversial and no consistent relationship was found between the presence of aromatase and any clinicopathologic factor. In addition, previous studies into aromatase gene expression and clinicopathologic factors are limited.<br><br>METHODS: We assessed the level of expression of aromatase mRNA, using quantitative real-time RT-PCR, in 162 cases of invasive ductal carcinoma of the breast. Associations between aromatase expression and different clinicopathologic factors were sought.<br><br>RESULTS: It was found that aromatase mRNA was expressed at significantly higher levels in patients older than 50 years, in those without axillary lymph node involvement, in those with tumor size less than 2 cm, and in ER-alpha positive tumors. However, no relationship was found between aromatase mRNA expression and any other clinicopathologic factor, including histologic grade and progesterone receptor status. Patients with high levels of expression of aromatase mRNA tended to have a better prognosis than did those patients with low expression.<br><br>CONCLUSION: These findings imply that ER-alpha and aromatase may be coexpressed in endocrine responsive patients. They may also indicate that aromatase expression could be a marker of endocrine responsiveness, and it may have prognostic implications for breast cancer progression.}, }
@article {pmid14575147, year = {2003}, author = {Pavlinkova, G and Yanagawa, Y and Kikuchi, K and Iwabuchi, K and Onoé, K}, title = {Effects of histamine on functional maturation of dendritic cells.}, journal = {Immunobiology}, volume = {207}, number = {5}, pages = {315-325}, doi = {10.1078/0171-2985-00247}, pmid = {14575147}, issn = {0171-2985}, mesh = {Animals ; Antigens, CD/metabolism ; B7-2 Antigen ; Cell Differentiation/*drug effects ; Cell Line ; Dendritic Cells/cytology/*drug effects/*immunology/metabolism ; Flow Cytometry ; Histamine/*pharmacology ; Histamine Antagonists/pharmacology ; Interleukin-12/genetics/metabolism ; Lipopolysaccharides/pharmacology ; Membrane Glycoproteins/metabolism ; Mice ; Phenotype ; Receptors, Histamine/genetics/metabolism ; Spleen/cytology/drug effects/immunology ; Tumor Necrosis Factor-alpha/pharmacology ; }, abstract = {There is increasing evidence that histamine affects dendritic cell (DC) activation, maturation, and preference for Th1/Th2 differentiation. In this paper we report that histamine affects interleukin (IL)-12 and IL-6 production in an immature DC (iDC) line derived from murine spleen. Histamine treatment of iDC significantly increased the IL-12 p40 mRNA and protein levels compared to histamine untreated iDC. In the presence of tumor necrosis factor (TNF)-alpha histamine also increased IL-12 p40 and IL-6 production. However, histamine significantly decreased IL-12 p40 production by lipopolysaccharide (LPS)-stimulated DC in a concentration dependent manner. When expressions of histamine H1 (H1R) and H2 (H2R) receptors in DC were analyzed by RT-PCR, both receptors were down-regulated after LPS or TNF-alpha stimulation compared to unstimulated iDC. Histamine treatment significantly increased the expression of H2R mRNA in iDC and H1R mRNA in LPS-activated DC. However, histamine treatment decreased the expression of both histamine receptors in TNF-alpha-stimulated DC. Similar results were obtained by flow cytometry with FITC-conjugated histamine. These results demonstrate that histamine can regulate the expression of its own receptors and activate iDC, which may influence subsequent functional states of mature DC in a maturation signal-dependent manner. Consequently, histamine may contribute to an immune response outcome.}, }
@article {pmid14571180, year = {2003}, author = {Tasca, S and Tambussi, G and Nozza, S and Capiluppi, B and Zocchi, MR and Soldini, L and Veglia, F and Poli, G and Lazzarin, A and Fortis, C}, title = {Escape of monocyte-derived dendritic cells of HIV-1 infected individuals from natural killer cell-mediated lysis.}, journal = {AIDS (London, England)}, volume = {17}, number = {16}, pages = {2291-2298}, doi = {10.1097/00002030-200311070-00003}, pmid = {14571180}, issn = {0269-9370}, mesh = {Adolescent ; Adult ; Antiretroviral Therapy, Highly Active ; CD4-Positive T-Lymphocytes/immunology ; Cytotoxicity, Immunologic/drug effects/*immunology ; Dendritic Cells/immunology/*virology ; Female ; Gene Products, tat/pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology ; HIV Infections/drug therapy/*immunology/virology ; *HIV-1 ; Humans ; Immune Tolerance ; Killer Cells, Natural/*immunology ; Male ; Middle Aged ; Monocytes/immunology ; Tumor Cells, Cultured ; Viral Load ; Viremia/immunology ; tat Gene Products, Human Immunodeficiency Virus ; }, abstract = {OBJECTIVE: To verify whether the in vitro sensitivity of immature dendritic cells (iDC) to lysis by autologous natural killer (NK) cells from HIV-infected individuals might be correlated with HIV disease progression.<br><br>DESIGN: Both dendritic cells (DC) and interlekin (IL)-2 activated NK cells were obtained from 13 HIV-infected individuals early after seroconversion and not receiving highly active antiretroviral therapy (HAART) and from 14 individuals with chronic HIV infection under HAART. The rate of NK cell-mediated killing of autologous iDC was correlated with classical parameters of HIV evolution.<br><br>METHODS: Peripheral blood monocytes obtained from the Ficoll-derived leukocyte fraction after adherence to plastic were stimulated with granulocyte-macrophage colony stimulating factor plus IL-4 to induce their differentiation into iDC to be used as target cells in a standard 4-h cytotoxicity assay. A fraction of autologous leukocytes was stimulated with IL-2 to induce activation of NK cells to be used as effector cells.<br><br>RESULTS: During early HIV infection the extent of ex vivo lysis of monocyte-derived DC by activated autologous NK cells was inversely and directly correlated with the levels of viraemia and with the percentage of circulating CD4 T cells, respectively. In contrast, the capacity of NK cells to kill iDC was lost independently of the levels of plasma viraemia or the concurrence of HAART in chronically infected individuals. Addition of exogenous HIV Tat during the cytotoxicity assay inhibited NK cell-mediated lysis of DC.<br><br>CONCLUSIONS: NK cell-mediated immune surveillance against infected DC may be effective only during early HIV infection and may not be restored by HAART.}, }
@article {pmid14567723, year = {2003}, author = {Xu, R and Feiner, H and Li, P and Yee, H and Inghirami, G and Delgado, Y and Perle, MA}, title = {Differential amplification and overexpression of HER-2/neu, p53, MIB1, and estrogen receptor/progesterone receptor among medullary carcinoma, atypical medullary carcinoma, and high-grade invasive ductal carcinoma of breast.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {127}, number = {11}, pages = {1458-1464}, doi = {10.5858/2003-127-1458-DAAOON}, pmid = {14567723}, issn = {1543-2165}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Medullary/*genetics ; Diagnosis, Differential ; Gene Amplification/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Genes, erbB-2 ; Genes, p53 ; Humans ; Ki-67 Antigen/biosynthesis/*genetics ; Lymphocytes, Tumor-Infiltrating/pathology ; Middle Aged ; Receptor, ErbB-2/biosynthesis/*genetics ; Receptors, Estrogen/biosynthesis/*genetics ; Receptors, Progesterone/biosynthesis/*genetics ; Tumor Suppressor Protein p53/biosynthesis/*genetics ; }, abstract = {CONTEXT: Medullary carcinoma (MC) is a special type of breast cancer that has a better prognosis than atypical medullary carcinoma (AMC) and high-grade invasive ductal carcinoma (HGIDC) with prominent lymphocytic infiltrates. What accounts for the different clinical courses of these carcinomas, despite their similar histology, is unknown. To address this issue, we performed a comparative study of amplification and overexpression of HER-2/neu and expression of several other important biochemical markers (p53, MIB1, and estrogen receptor [ER]/progesterone receptor [PR]) in these 3 cancer groups.<br><br>OBJECTIVE: To evaluate HER-2/neu, p53, MIB1, and ER/PR as markers in the differential diagnosis of MC, AMC, and HGIDC.Design.-Nine cases of MC, 13 cases of AMC, and 16 cases of HGIDC with prominent lymphocytic infiltrates were identified according to strict histologic criteria. All tests were performed on formalin-fixed, paraffin-embedded archival tissues. HER-2/neu gene amplification was examined by fluorescence in situ hybridization using PathVysion HER-2 DNA probes. Expression of HER-2/neu, p53, MIB1, and ER/PR was detected by immunohistochemistry. chi2 and Student t tests were applied for statistical analyses.<br><br>RESULTS: None of 9 cases of MC examined had either amplification or overexpression of HER-2/neu (0%). In contrast, HER-2/neu amplification was observed in AMC (46%, P <.025) and HGIDC (56%, P <.005). All 3 categories of tumors had similar percentages of expression of p53 (78% of MC, 77% of AMC, and 69% of HGIDC) and MIB1 (89% of MC, 92% of AMC, and 94% of HGIDC). Immunostaining for ER/PR was rarely positive in either MC or AMC, and there were no significant differences of expression of ER/PR between these 2 lesions (P >.05). However, the expression rate of ER/PR (31%/44%) in HGIDC is higher than in both MC (P =.05) and AMC (P =.01).<br><br>CONCLUSIONS: Medullary carcinoma of breast is distinct from AMC and HGIDC with prominent lymphocytic infiltrates in amplification and overexpression of HER-2/neu. This difference may account for its different clinical and biological behavior, and may potentially aid in diagnosis and management of these groups of patients.}, }
@article {pmid14557212, year = {2003}, author = {Li, CI and Moe, RE and Daling, JR}, title = {Risk of mortality by histologic type of breast cancer among women aged 50 to 79 years.}, journal = {Archives of internal medicine}, volume = {163}, number = {18}, pages = {2149-2153}, doi = {10.1001/archinte.163.18.2149}, pmid = {14557212}, issn = {0003-9926}, support = {R01 CA 85913/CA/NCI NIH HHS/United States ; T32 CA 09168/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/mortality ; Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality ; Carcinoma, Lobular/*mortality ; Female ; Humans ; Middle Aged ; Prognosis ; Proportional Hazards Models ; SEER Program ; United States/epidemiology ; }, abstract = {BACKGROUND: Recent studies suggest that the use of combined estrogen and progestin hormone replacement therapy is associated with an increased risk of invasive lobular carcinoma (ILC), but that it has little association with risk of invasive ductal carcinoma (IDC). Also, the incidence rates of ILC have risen over the past 10 years while those of IDC have remained constant. Differences in survival rates by histologic types of tumor have been reported, but few of the published studies were population based or had adequate power to address this issue.<br><br>METHODS: We conducted a retrospective cohort study spanning the years 1974 through 1998 using data from the 9 cancer registries that have participated in the Surveillance, Epidemiology, and End Results Program since 1974. The cohort consisted of 164 958 women aged 50 to 79 years who had been diagnosed as having 1 of 7 histologic types of invasive breast cancer. Risks of mortality due to any cause were estimated using the Cox proportional hazards model.<br><br>RESULTS: Women with ILC had a risk of mortality 11% lower than women with IDC. The magnitude of this difference has increased over the past 10 years and, from 1994 through 1998, the risk of mortality was 26% lower for women with ILC. Also, the risk of mortality was between 8% and 34% lower in women with mucinous carcinoma, comedocarcinoma, or medullary, tubular, and papillary carcinomas compared with women with IDC.<br><br>CONCLUSIONS: Differences in prognosis by histologic type of breast cancer were identified. The survival rate of women 50 to 79 years old who have ILC, the cancer whose histologic type is the most closely linked with the use of combined estrogen and progestin hormone replacement therapy, is more favorable than that of women with IDC and appears to be improving over time.}, }
@article {pmid14556972, year = {2003}, author = {Kikuchi, K and Yanagawa, Y and Iwabuchi, K and Onoé, K}, title = {Differential role of mitogen-activated protein kinases in CD40-mediated IL-12 production by immature and mature dendritic cells.}, journal = {Immunology letters}, volume = {89}, number = {2-3}, pages = {149-154}, doi = {10.1016/s0165-2478(03)00134-2}, pmid = {14556972}, issn = {0165-2478}, mesh = {Animals ; CD40 Antigens/*metabolism ; Dendritic Cells/*metabolism ; Interleukin-12/*biosynthesis/genetics ; Lipopolysaccharides/*metabolism ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinases/*metabolism ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Using a murine spleen-derived dendritic cell (DC) line (BC1) CD40-mediated interleukin (IL)-12 production was analyzed and compared between immature and mature DC. BC1 cells, immature DC (iDC), were maturated by treatment with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha. IL-12 production of LPS-treated DC (LPS/DC) was markedly enhanced by treatment with an anti-CD40 monoclonal antibody (mAb). Although the anti-CD40 mAb also enhanced IL-12 productions of iDC and TNF-alpha-treated DC (TNF/DC), these production levels were considerably low compared with that of LPS/DC. CD40-mediated IL-12-productions by iDC and TNF/DC were significantly enhanced by treatment with PD98059, a specific inhibitor of extracellular signal-related kinase (ERK) pathway. In contrast, PD98059 showed no significant effects on CD40-mediated IL-12-production by LPS/DC. These results demonstrated that ERK pathway was involved in negative regulation of the IL-12 productions by iDC and TNF/DC but not by LPS/DC. On the other hand, SB203580, a specific inhibitor of p38 mitogen activated protein kinase (MAPK) pathway, completely inhibited CD40-mediated IL-12-production by iDC, while not affecting those of TNF/DC and LPS/DC. Thus, p38 MAPK pathway appeared to positively regulate the IL-12 production in iDC but not in mature DC. It seems that roles of ERK and p38 MAPK for IL-12 production are developmentally changed in murine DC.}, }
@article {pmid14531536, year = {2003}, author = {Carlsson, E and Bosaeus, I and Nordgren, S}, title = {What concerns subjects with inflammatory bowel disease and an ileostomy?.}, journal = {Scandinavian journal of gastroenterology}, volume = {38}, number = {9}, pages = {978-984}, doi = {10.1080/00365520310004687}, pmid = {14531536}, issn = {0036-5521}, mesh = {Activities of Daily Living ; *Adaptation, Psychological ; Adult ; Aged ; Attitude to Health ; Female ; Humans ; Ileostomy/*psychology ; Inflammatory Bowel Diseases/complications/*psychology/surgery ; Male ; Middle Aged ; Quality of Life ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The greatest concern of patients with inflammatory bowel disease (IBD) is of having an ileostomy. The aim of this study was to describe worries and concerns in subjects with IBD and an ileostomy, and aspects of quality of life and coping strategies.<br><br>METHODS: 21 subjects with an ileostomy were included, mean age 51, range 36-65 (F/M = 12/9), Crohn disease (CD) n = 14, ulcerative colitis (UC) n = 6 and indeterminate colitis (IDC) n = 1. Worries and concerns were assessed using the rating form of IBD patient concerns (RFIPC). Health-related quality of life (HRQOL) was assessed using Short Form 36 (SF-36) and compared with a matched group for age and gender from the general population. Subjects' definition of quality of life, as well as perceived quality of life on a visual analogue scale, was evaluated. Coping strategies were investigated using the Jalowiec coping scale (JCS 40).<br><br>RESULTS: Greatest concerns were related to intimacy, access to quality medical care, energy level, loss of sexual drive, producing unpleasant odours, being a burden, ability to perform sexually, attractiveness and feelings about the body. Vitality was significantly reduced compared to controls. Subjects' definition of good quality of life mainly concerned social dimensions of life and health. Low values on perceived quality of life indicated greater concerns. Confrontational coping style was most frequently used.<br><br>CONCLUSION: The greatest concern for subjects with an ileostomy was intimacy. Vitality was reduced compared to controls. Integrating items of concern into counselling may result in greater coping ability and improved quality of life.}, }
@article {pmid14521261, year = {2003}, author = {Mrhalová, M and Kodet, R and Kalinová, M and Hilská, I}, title = {Relative quantification of ERBB2 mRNA in invasive duct carcinoma of the breast: correlation with ERBB-2 protein expression and ERBB2 gene copy number.}, journal = {Pathology, research and practice}, volume = {199}, number = {7}, pages = {453-461}, doi = {10.1078/0344-0338-00445}, pmid = {14521261}, issn = {0344-0338}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/secondary ; Female ; *Gene Dosage ; *Gene Expression Regulation, Neoplastic ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; RNA, Messenger/metabolism ; RNA, Neoplasm/chemistry ; *Receptor, ErbB-2/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {The option to treat patients suffering from ERBB-2 protein-positive invasive duct carcinomas of the breast (IDC) with Herceptin requires a precise determination of the ERBB2 status. The aim of the study was to evaluate the ERBB2 mRNA level, placing emphasis on cases with discordant findings between ERBB-2 protein expression (IHC) and a copy number of the ERBB2 gene (FISH). Thirty-nine IDCs (21 cases IHC and FISH concordant, 15 cases moderately discordant, 3 cases markedly discordant) were investigated. ERBB2 mRNA expression was determined using quantitative real-time RT-PCR (Q-RT-PCR). IDCs with negative ERBB-2 protein and without ERBB2 gene amplification had a low ERBB2 mRNA level. Cases with 3+ overexpression of the protein and with strong gene amplification (> 10 copies/tumor cell) had a significantly increased expression of ERBB2 mRNA. In 13 of 15 IDCs with moderate discrepancies (up to 10 copies of the gene per one tumor cell/negative ERBB-2 protein; without amplification/2+ protein) mRNA was low, comparable to that in cases with negative ERBB-2 protein and without ERBB2 gene amplification. In three cases with markedly discordant findings (the gene amplified/protein negative--one case; protein 3+/no amplification--2 cases), Q-RT-PCR results were within a "normal" limit. Ineffective gene amplification and protein accumulation are suggested explanations. Q-RT-PCR revealed two cases with highly expressed ERBB2 mRNA and discordant FISH and/or IHC findings. Increased effectiveness of transcription (protein 2+/high mRNA/without the gene amplification), and combined dysregulation (protein negative/high mRNA/no amplification) are possible causes of these findings. Q-RT-PCR appears useful in clarifying borderline or discrepant IHC and FISH findings.}, }
@article {pmid14520705, year = {2003}, author = {Li, CI and Malone, KE and Porter, PL and Weiss, NS and Tang, MT and Daling, JR}, title = {Reproductive and anthropometric factors in relation to the risk of lobular and ductal breast carcinoma among women 65-79 years of age.}, journal = {International journal of cancer}, volume = {107}, number = {4}, pages = {647-651}, doi = {10.1002/ijc.11465}, pmid = {14520705}, issn = {0020-7136}, support = {R01 CA072787/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; *Anthropometry ; Body Height ; Body Weight ; Breast Neoplasms/*epidemiology ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Lobular/*epidemiology ; Case-Control Studies ; Female ; Humans ; Neoplasm Invasiveness ; Odds Ratio ; Postmenopause ; *Reproductive History ; Risk Factors ; Washington/epidemiology ; }, abstract = {Use of combined estrogen-progestin hormone replacement therapy appears to be associated with an increased risk of invasive lobular breast carcinomas (ILC) and, to a lesser degree, with risk of invasive ductal carcinoma (IDC). Conceivably, ILCs are more hormonally responsive and so may be more strongly associated than IDCs with reproductive and anthropometric characteristics that can influence hormone levels. However, few epidemiologic studies of breast cancer have evaluated these factors by histologic type. We conducted a population-based case-control study of women aged 65-79 years in western Washington State. Responses from 975 women diagnosed with breast cancer during 1997-1999 were compared to those of 1,007 controls. Associations between various reproductive and anthropometric factors and risks of IDC (n = 656) and ILC (n = 196) were evaluated using polytomous logistic regression. Earlier age at menarche, later age at menopause and obesity were more strongly associated with elevated risks of IDC than ILC. Alternatively, oral contraceptive use was associated with an increased risk of ILC but not IDC. Thus, the pattern of results that we observed suggest that factors influencing endogenous hormones and duration of ovarian function may be more strongly associated with IDC risk, while exogenous hormones may be more strongly associated with ILC risk.}, }
@article {pmid14510128, year = {2001}, author = {Adegoke, BO and Badmos, KA}, title = {Acceleration of pressure ulcer healing in spinal cord injured patients using interrupted direct current.}, journal = {African journal of medicine and medical sciences}, volume = {30}, number = {3}, pages = {195-197}, pmid = {14510128}, issn = {0309-3913}, mesh = {Adult ; *Electric Stimulation Therapy/methods ; Humans ; Middle Aged ; Pressure Ulcer/etiology/nursing/*therapy ; Spinal Cord Injuries/*complications/physiopathology ; Time Factors ; *Wound Healing ; }, abstract = {This study was designed to investigate the efficacy of interrupted direct current (IDC) in augmenting routine nursing care in spinal cord injured (SCI) patients with pressure ulcers. Seven SCI patients aged 21 - 60 years (x = 43.8, S.D. = 13.9) with grade IV pressure ulcers were randomly assigned to either a group receiving routine nursing care plus IDC stimulations or a group receiving routine nursing care plus placebo IDC. Patients in both groups received 45 minutes treatment thrice weekly for 4 weeks, and had their pressure ulcers measured for surface area on day 0, at 2 weeks and at 4 weeks of the study using standard method. Percentage changes in surface area were calculated for the two groups at the different time frames. Ulcers in the IDC group had 22.2% reduction in surface area while those in the placebo IDC group had a 2.6% reduction in surface area. The reduction in size was most evident in the first two weeks of the study. The results indicate that IDC stimulation may be used in conjunction with routine nursing care to accelerate healing of grade IV pressure ulcers in SCI injured patients.}, }
@article {pmid14509156, year = {2003}, author = {Greenberg, R and Barnea, Y and Schneebaum, S and Kashtan, H and Kaplan, O and Skornik, Y}, title = {Detection of hepatocyte growth factor/scatter factor receptor (c-Met) and MUC1 from the axillary fluid drainage in patients after breast cancer surgery.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {5}, number = {9}, pages = {649-652}, pmid = {14509156}, issn = {1565-1088}, mesh = {Axilla ; Biomarkers, Tumor/*isolation &amp; purification ; Breast Neoplasms/classification/diagnosis/*surgery ; Carcinoma, Ductal, Breast/classification/diagnosis/secondary/*surgery ; Drainage/*methods ; Female ; Gene Expression Profiling ; Humans ; Lymph ; Lymph Nodes/*surgery ; Lymphatic Metastasis ; Middle Aged ; Mucin-1/*isolation &amp; purification ; Prognosis ; Proto-Oncogene Proteins c-met/*isolation &amp; purification ; RNA, Messenger ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Drains are inserted in the dissected axilla of most patients during surgery for breast cancer.<br><br>OBJECTIVE: To evaluate the presence and prognostic value of MUC1 and Met-hepatocyte growth factor/scatter factor in the axillary drainage of these patients.<br><br>METHODS: The study group included 40 consecutive patients with invasive ductal carcinoma of the breast who were suitable for breast-conserving treatment; 20 malignant melanoma patients found to have negative axillary sentinel lymph node served as the control group. The output of the drains, which had been placed in the axilla during operation, was collected, and the presence of MUC1, Met-HGF/SF and beta-actin were assessed in the lymphatic fluid by reverse transcription-polymerase chain reaction assays. The data were compared to the pathologic features of the tumor and the axillary lymph nodes, and to the estrogen and progesterone receptors status.<br><br>RESULTS: RT-PCR assays of the axillary lymphatic drainage were positive for MUC1 and Met-HGF/SF in 15 (37.5%) and 26 (65%) of the patients, respectively. Patients in whom MUC1 and Met-HGF/SF were not found in the axillary fluid had smaller tumors and less capillary and lymphatic invasion, compared to patients with positive assays (P < 0.0 for all these comparisons). The lymph nodes were negative for metastases in all patients with negative assays (P < 0.001). The presence of MUC1 and Met-HGF/SF showed negative correlations with the estrogen and progesterone receptors (P < 0.05).<br><br>CONCLUSION: MUC1 and Met-HGF/SF can be detected in the axillary fluids of patients with breast cancer. The expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor.}, }
@article {pmid14502779, year = {2003}, author = {Leidenius, MH and Krogerus, LA and Toivonen, TS and Von Smitten, KJ}, title = {The feasibility of intraoperative diagnosis of sentinel lymph node metastases in breast cancer.}, journal = {Journal of surgical oncology}, volume = {84}, number = {2}, pages = {68-73}, doi = {10.1002/jso.10296}, pmid = {14502779}, issn = {0022-4790}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/secondary/surgery ; Carcinoma, Lobular/*diagnosis/secondary/surgery ; Feasibility Studies ; Humans ; Intraoperative Period ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; Sensitivity and Specificity ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND AND OBJECTIVES: The aim of the study was to analyse in detail the feasibility of intraoperative assessment of sentinel lymph nodes in breast cancer.<br><br>METHODS: Altogether 139 consecutive breast cancer patients with metastases in axillary sentinel nodes were included in a prospective study. A combination of imprint cytology and frozen section was used as the method of intraoperative diagnosis of sentinel node metastases. The definite postoperative evaluation of the sentinel nodes was taken as the gold standard.<br><br>RESULTS: The overall sensitivity of intraoperative diagnosis was 83%, reaching 81% if the intraoperative assessment had been limited to the two first retrieved sentinel nodes. False negative (FN) findings were more common in connection with invasive lobular carcinoma (28%) than with invasive ductal carcinoma (8%) (P < 0.01) as well as in connection with micro-metastases, in 38% of the cases, compared to the larger metastases, 6% (P < 0.00005).<br><br>CONCLUSIONS: Intraoperative examination of sentinel lymph nodes enables breast surgery, axillary staging, and treatment in the same operation in a substantial proportion of breast cancer patients. Hospital costs as well as workload in the pathology laboratory may be reduced, limiting the intraoperative assessment to the two first retrieved nodes.}, }
@article {pmid12967783, year = {2003}, author = {Ichim, TE and Zhong, R and Min, WP}, title = {Prevention of allograft rejection by in vitro generated tolerogenic dendritic cells.}, journal = {Transplant immunology}, volume = {11}, number = {3-4}, pages = {295-306}, doi = {10.1016/S0966-3274(03)00048-0}, pmid = {12967783}, issn = {0966-3274}, mesh = {Animals ; Antigen Presentation ; Dendritic Cells/chemistry/immunology/*transplantation ; Fas Ligand Protein ; Graft Rejection/immunology/*prevention &amp; control ; Immune Tolerance ; Interleukin-12/genetics ; Killer Cells, Natural/immunology ; Lymphocyte Subsets/immunology ; Major Histocompatibility Complex ; Membrane Glycoproteins/genetics ; Mice ; NF-kappa B/antagonists &amp; inhibitors ; Transfection ; *Transplantation Tolerance ; }, abstract = {Achieving immunological tolerance in transplantation has been a long sought-after goal since the 1960s. It is, therefore, interesting that the dendritic cells (DC), which are classically known as the most potent stimulators of T cell activation, are now also considered putative tools for tolerance induction. In line with this, much work has been performed using DC for vaccination and immune stimulation. Recently, great interest has been generated regarding the ability of DC to act as immune regulatory cells. Specific subsets of DC or immature DC (iDC) appear to be responsible for maintaining self-tolerance. In this review we will highlight our efforts at elucidating the contribution of DC in transplant tolerant in mice. Specifically, four strategies will be outlined that are currently being used for the generation of DC that have tolerogenic properties in the prevention of allograft rejection. The present study demonstrates that modulated iDC with blunted T cell stimulatory or antigen presentation abilities can afford transplant tolerance by minimizing T cell activation and proinflammatory cytokine production. Moreover, in an alternate strategy, normally matured DC have also been modulated such that alloreactive T cells are specifically targeted for deletion.}, }
@article {pmid12939642, year = {2003}, author = {Nagorsen, D and Panelli, M and Dudley, ME and Finkelstein, SE and Rosenberg, SA and Marincola, FM}, title = {Biased epitope selection by recombinant vaccinia-virus (rVV)-infected mature or immature dendritic cells.}, journal = {Gene therapy}, volume = {10}, number = {20}, pages = {1754-1765}, pmid = {12939642}, issn = {0969-7128}, support = {Z01 SC003811-32//Intramural NIH HHS/United States ; }, mesh = {Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; Cancer Vaccines ; Cell Line ; Clone Cells ; Dendritic Cells/*immunology ; Epitopes/*immunology ; Flow Cytometry ; Genetic Therapy/*methods ; Genetic Vectors/*administration &amp; dosage ; HLA-A Antigens/*immunology ; HLA-A2 Antigen ; Humans ; Interferon-gamma/immunology ; Melanoma/immunology/therapy ; Membrane Glycoproteins/genetics ; Neoplasm Proteins/genetics ; Peptides ; Receptors, Antigen, T-Cell/immunology ; Vaccinia virus/*genetics ; gp100 Melanoma Antigen ; }, abstract = {Recombinant expression vectors represent a powerful way to deliver whole antigens (Ags) for immunization. Sustained Ag expression in vector-infected dendritic cells (DC) combines Ag-specific stimulation with powerful costimulation and, simultaneously, through 'self-selection' of ad hoc epitopes broadens the scope of immunization beyond restrictions posed by individual patients' human leukocyte antigen (HLA) phenotype. In this study, therefore, we evaluated the efficiency of a recombinant vaccinia virus encoding the gp100/PMel17 melanoma Ag (rVV-gp100) to infect immature (iDC) or mature dendritic cells (mDC) derived from circulating mononuclear cells and the effect of infection on their status of maturation. In addition, we tested the ability of rVV-gp100-infected iDC and mDC to present the HLA-A*0201-associated gp100:209-217 epitope (g209). Irrespective of status of maturation, rVV-gp100 infection induced gp100 expression while only partially reversing the expression of some maturation markers. However, endogenous presentation of the wild-type g209 epitope was inefficient. The low efficiency was epitope-specific since infection of DC with rVV encoding a gp100 construct containing the modified gp100:209-217 (210M) (g209-2M) epitope characterized by high binding affinity for HLA-A*0201 restored efficient Ag presentation. Presentation of an HLA-class II-associated epitope and cytokine release by DC was not altered by rVV infection. Thus, Ag expression driven by rVV may be an efficient strategy for whole Ag delivery. However, since the effectiveness of Ag processing and presentation is subject to stringent HLA/epitope pairing, and for other yet undefined rules, the assumption that whole Ag delivery may circumvent HLA restriction is incorrect and recombinant expression vectors encoding well-characterized polyepitopic constructs may prove more effective.}, }
@article {pmid12929205, year = {2003}, author = {Bozdech, Z and Llinás, M and Pulliam, BL and Wong, ED and Zhu, J and DeRisi, JL}, title = {The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum.}, journal = {PLoS biology}, volume = {1}, number = {1}, pages = {E5}, pmid = {12929205}, issn = {1545-7885}, support = {/WT_/Wellcome Trust/United Kingdom ; U01 AI053862/AI/NIAID NIH HHS/United States ; AI53862/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antimalarials/pharmacology ; Chromosome Mapping ; Chromosomes/ultrastructure ; Erythrocytes/*parasitology ; Gene Expression Regulation ; *Gene Expression Regulation, Developmental ; Genes, Protozoan ; Genome ; Genome, Protozoan ; Humans ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; Oligonucleotides/chemistry ; Open Reading Frames ; Plasmodium falciparum/*metabolism ; Plastids ; Protozoan Proteins ; RNA, Messenger/metabolism ; Time Factors ; *Transcription, Genetic ; }, abstract = {Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200-300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a "just-in-time" manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates.}, }
@article {pmid12927045, year = {2003}, author = {Kato, M and Kitayama, J and Kazama, S and Nagawa, H}, title = {Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {5}, number = {5}, pages = {R144-50}, pmid = {12927045}, issn = {1465-542X}, mesh = {Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/pathology/*secondary ; Chemokine CXCL12 ; Chemokines, CXC/biosynthesis/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Immunohistochemistry ; Lymph Nodes/*pathology ; Lymphatic Metastasis/pathology ; Receptors, CXCR4/*biosynthesis/genetics ; }, abstract = {BACKGROUND: The stromal cell-derived factor-1/CXC chemokine receptor-4 (SDF-1/CXCR4) signal has been shown to be important in various immunological reactions. Recent studies have suggested that CXCR4 is expressed in certain cancer cells and that they use this chemokine receptor efficiently for metastasis formation.<br><br>METHOD: The expression of CXCR4 was evaluated by immunohistochemical study in 79 surgically resected invasive ductal carcinomas, and the relation between the staining pattern and clinicopathological features was examined.<br><br>RESULTS: CXCR4 was diffusely and homogeneously expressed in 59 cancers, which were further divided into 28 high-expression and 31 low-expression cancers by their staining intensity. The other 20 cancers showed heterogeneous immunoreactivity in tumor tissue, which was defined as focal type. In comparison with the diffuse type, focal type tumors showed significantly more extensive lymph node metastasis, because the number and extent of metastatic nodes were larger in the focal than the diffuse type. In the diffuse type, the rate of node-positive cases did not show a difference in staining intensity. However, high-CXCR4 tumors showed more extensive nodal metastasis in comparison with low-expression tumors. In contrast, the expression pattern of CXCR4 did not have a significant correlation with hematogeneous metastasis. The overall survival of these patients tended to be better in the diffuse type than in the focal type, although the difference was not statistically significant.<br><br>CONCLUSION: The expression pattern of CXCR4 was significantly correlated with the degree of lymph node metastasis in breast cancers. Our data suggest that CXCR4 might be particularly important in facilitating metastasis through the lymphatic system.}, }
@article {pmid12894577, year = {2003}, author = {Seth, A and Kitching, R and Landberg, G and Xu, J and Zubovits, J and Burger, AM}, title = {Gene expression profiling of ductal carcinomas in situ and invasive breast tumors.}, journal = {Anticancer research}, volume = {23}, number = {3A}, pages = {2043-2051}, pmid = {12894577}, issn = {0250-7005}, mesh = {Biomarkers, Tumor/biosynthesis/genetics ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carrier Proteins/biosynthesis/genetics ; Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; *Insulin-Like Growth Factor Binding Proteins ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; Up-Regulation ; }, abstract = {UNLABELLED: Comparative and functional genomics are powerful tools to advance the understanding of the molecular basis of cancer. It is believed that genes are epigenetically regulated and, thus, each tumor type and stage will be characterized by a gene expression fingerprint. In this study we identified genes that are differentially expressed in ductal carcinoma in situ and invasive ductal carcinoma of the breast. To isolate genes that are associated with progression of breast cancer we performed differential display and subtractive cloning procedures using matched RNA from normal and tumor tissue. cDNA microarray analysis generated gene expression profiles typical of the transition from in situ to invasive breast cancer when we used mRNA extracted from a case of low- to intermediate-grade DCIS and a case of high-grade DCIS/IDC. cDNAs from these samples were the probes in a cDNA microarray hybridization to 9183 unique cDNAs representing 8507 genes. Signals from both transcriptomes were obtained for 8083 genes, and the balanced differential expression values between pure DCIS and DCIS/invasive tumors revealed 303 distinct cDNAs with a ratio of > 2. Interferon inducible genes were found to be expressed at the highest level in the pure DCIS sample. Genes most abundantly expressed in the invasive tumor were immunoglobulin heavy constant gamma 3 and calgranulin B. Further analysis of RNA and protein expression in breast tumor cell lines and patient tissue samples revealed that: IGFBP-rP1 is down-regulated in invasive tumors whereas cyclin I protein is regulated by ubiquitination and is associated with ER-negative breast cancers.<br><br>CONCLUSION: The known and novel genes discussed here represent targets for molecular characterization during breast cancer development as well as for designing novel strategies for diagnosis and treatment.}, }
@article {pmid12891210, year = {2003}, author = {Grimm, W and Rudolph, S and Christ, M and Pankuweit, S and Maisch, B}, title = {Prognostic significance of morphometric endomyocardial biopsy analysis in patients with idiopathic dilated cardiomyopathy.}, journal = {American heart journal}, volume = {146}, number = {2}, pages = {372-376}, doi = {10.1016/S0002-8703(03)00148-0}, pmid = {12891210}, issn = {1097-6744}, mesh = {Adolescent ; Adult ; Aged ; Biopsy ; Cardiomyopathy, Dilated/complications/mortality/*pathology ; Death, Sudden, Cardiac/etiology ; Female ; Follow-Up Studies ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Myocardium/*pathology ; Prognosis ; Tachycardia, Ventricular/etiology ; Ventricular Fibrillation/etiology ; }, abstract = {BACKGROUND: To date, considerable controversy exists on the prognostic significance of morphometric endomyocardial biopsy findings in patients with idiopathic dilated cardiomyopathy (IDC).<br><br>METHODS: Quantitative analyses of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters of left ventricular endomyocardial biopsy specimens were performed in 124 patients with IDC.<br><br>RESULTS: During 51 +/- 22 months follow-up after left ventricular endomyocardial biopsy, major arrhythmic events, defined as sustained ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden cardiac death, were observed in 24 patients (19%). Death from any cause or heart transplant was observed in 39 patients (31%). The amount of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters determined from left ventricular endomyocardial biopsy specimens did not differ significantly between patients with and patients without major arrhythmic events or between patients with and patients without transplant-free survival during follow-up.<br><br>CONCLUSIONS: Quantitative analysis of the amount of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters in left ventricular endomyocardial biopsy specimens does not appear to be useful for predicting arrhythmic events and transplant-free survival in IDC.}, }
@article {pmid12890042, year = {2003}, author = {Grimm, W and Schmidt, G and Maisch, B and Sharkova, J and Müller, HH and Christ, M}, title = {Prognostic significance of heart rate turbulence following ventricular premature beats in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiovascular electrophysiology}, volume = {14}, number = {8}, pages = {819-824}, doi = {10.1046/j.1540-8167.2003.03085.x}, pmid = {12890042}, issn = {1045-3873}, mesh = {Age Distribution ; Cardiomyopathy, Dilated/*diagnosis/*epidemiology/mortality/surgery ; Comorbidity ; Disease-Free Survival ; Electrocardiography, Ambulatory/*methods ; Germany/epidemiology ; Heart Transplantation/*mortality/statistics &amp; numerical data ; Humans ; Middle Aged ; Predictive Value of Tests ; Prevalence ; Prognosis ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Sex Distribution ; Single-Blind Method ; Survival Analysis ; Ventricular Premature Complexes/*diagnosis/*epidemiology/mortality/surgery ; }, abstract = {UNLABELLED: Heart Rate Turbulence in Dilated Cardiomyopathy.<br><br>INTRODUCTION: The aim of this study was to investigate the prognostic significance of heart rate turbulence (HRT) characterized by HRT onset and slope after ventricular premature beats in patients with idiopathic dilated cardiomyopathy (IDC).<br><br>METHODS AND RESULTS: Blinded HRT analysis was performed in 242 patients with IDC who were enrolled in the Marburg Cardiomyopathy database between 1992 and 2000. During 41 +/- 23 months of follow-up, 54 patients (22%) died or underwent heart transplant. On Cox univariate regression analysis, abnormal HRT onset, HRT slope, HRT onset combined with HRT slope, left ventricular (LV) ejection fraction, LV size, and New York Heart Association (NYHA) functional class III showed a significant association with total mortality or the need for heart transplant. On multivariate analysis, abnormal HRT onset identified patients without transplant-free survival, as did LV size and NYHA class III heart failure. Major arrhythmic events were observed in 42 patients (17%) during follow-up. On univariate analysis, abnormal HRT onset, HRT onset combined with HRT slope, male sex, NYHA class III, LV ejection fraction, and LV size were associated with a higher incidence of major arrhythmic events. On multivariate analysis, only LV ejection fraction remained as a significant arrhythmia risk predictor, with a relative risk of 2.2 per 10% decrease in ejection fraction (95% confidence interval 1.5-3.2).<br><br>CONCLUSION: In this selected patient population with IDC, HRT onset is a significant predictor of transplant-free survival, as are LV size and NYHA class. For arrhythmia risk stratification, however, only LV ejection fraction remained a significant risk predictor on multivariate analysis.}, }
@article {pmid12847261, year = {2003}, author = {Tinsley, KW and Grayson, MH and Swanson, PE and Drewry, AM and Chang, KC and Karl, IE and Hotchkiss, RS}, title = {Sepsis induces apoptosis and profound depletion of splenic interdigitating and follicular dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {171}, number = {2}, pages = {909-914}, doi = {10.4049/jimmunol.171.2.909}, pmid = {12847261}, issn = {0022-1767}, support = {GM44118/GM/NIGMS NIH HHS/United States ; GM55194/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*immunology ; B-Lymphocyte Subsets/chemistry/immunology ; Caspase 3 ; Caspases/physiology ; Cecum ; Cell Count ; Dendritic Cells, Follicular/enzymology/immunology/*pathology ; Disease Models, Animal ; Immunocompromised Host/immunology ; Immunohistochemistry ; Ligation ; Macrophages/chemistry/immunology ; Mice ; Mice, Inbred C57BL ; Punctures ; Sepsis/*immunology/*pathology ; Spleen/chemistry/enzymology/*immunology/*pathology ; Staining and Labeling ; T-Lymphocyte Subsets/chemistry/immunology ; }, abstract = {Dendritic cells are a phenotypically diverse group of APC that have unique capabilities to regulate the activity and survival of B and T cells. Although proper function of dendritic cells is essential to host control of invading pathogens, few studies have examined the impact of sepsis on dendritic cells. The purpose of this study was to determine the effect of sepsis on splenic interdigitating dendritic cells (IDCs) and follicular dendritic cells (FDCs) using a clinically relevant animal model. Immunohistochemical staining for FDCs showed that sepsis induced an initial marked expansion in FDCs that peaked at 36 h after onset. The FDCs expanded to fill the entire lymphoid zone otherwise occupied by B cells. Between 36 and 48 h after sepsis, there was a profound caspase 3 mediated apoptosis induced depletion of FDCs such that only a small contingent of cells remained. In contrast to the initial increase in FDCs, IDC numbers were decreased to approximately 50% of control by 12 h after onset of sepsis. IDC death occurred by caspase 3-mediated apoptosis. Such profound apoptosis induced loss of FDCs and IDCs may significantly compromise B and T cell function and impair the ability of the host to survive sepsis.}, }
@article {pmid12846864, year = {2003}, author = {Cabral, AH and Recine, M and Paramo, JC and McPhee, MM and Poppiti, R and Mesko, TW}, title = {Tubular carcinoma of the breast: an institutional experience and review of the literature.}, journal = {The breast journal}, volume = {9}, number = {4}, pages = {298-301}, doi = {10.1046/j.1524-4741.2003.09409.x}, pmid = {12846864}, issn = {1075-122X}, mesh = {Adenocarcinoma/*epidemiology/etiology/mortality/pathology/therapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/etiology/mortality/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/etiology/mortality/pathology/therapy ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Florida/epidemiology ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/etiology/mortality/pathology/therapy ; Neoplasm Staging ; Receptors, Estrogen ; Retrospective Studies ; Survival Analysis ; }, abstract = {Tubular carcinoma of the breast is a variant of invasive ductal carcinoma that is well differentiated and characterized by an orderly tubular formation. Although often perceived to have a better prognosis, there continues to be questions regarding the extent of treatment required. A retrospective review of 44 patients diagnosed with tubular carcinoma of the breast from 1987 to 1999 was performed. All documented data regarding patient and tumor characteristics plus the extent of treatment were analyzed and compared. Lymph node metastases were present in 4 of 32 patients (13%) who had nodes examined. Tumor size correlated with axillary status, with tumors less than 15 mm having no axillary nodal involvement. No other factor influenced nodal status. In breast conservation patients without adjuvant radiation, 5% (1 of 20) had local recurrence versus 0% (0 of 13) of patients who received postoperative radiation. Ductal carcinoma in situ (DCIS) was associated with 52% of tubular cancers. Second breast cancers developed in 16% of cases. There was no difference in presentation or outcome for pure versus mixed tubular carcinoma. Overall mortality was 2%. Overall survival for patients with tubular carcinoma is quite good. Breast conservation treatment results in low rates of local recurrence for tubular carcinoma with or without the use of adjuvant radiation therapy. Pure tubular carcinomas had the same behavior and overall prognosis as mixed tubular carcinomas and should be classified together. Lymph node status did not influence disease-free or overall survival.}, }
@article {pmid12845646, year = {2003}, author = {Buttiglieri, S and Galetto, A and Forno, S and De Andrea, M and Matera, L}, title = {Influence of drug-induced apoptotic death on processing and presentation of tumor antigens by dendritic cells.}, journal = {International journal of cancer}, volume = {106}, number = {4}, pages = {516-520}, doi = {10.1002/ijc.11243}, pmid = {12845646}, issn = {0020-7136}, mesh = {Annexin A5/metabolism ; Antigen Presentation/*physiology ; Antigens, Neoplasm/*immunology ; Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Cisplatin/pharmacology ; Cytokines/metabolism ; Dendritic Cells/*immunology ; Doxorubicin/pharmacology ; Epirubicin/pharmacology ; HSP70 Heat-Shock Proteins/metabolism ; Histocompatibility Antigens Class I/immunology ; Humans ; Necrosis ; Phagocytosis/drug effects ; Propidium/metabolism ; Stomach Neoplasms/*pathology ; T-Lymphocytes, Cytotoxic/immunology ; Tumor Cells, Cultured ; }, abstract = {Here we have studied the effects of apoptotic cell death induced by chemotherapic agents on tumor phagocytosis by dendritic cells (DC) and presentation of the relevant antigen to T lymphocytes. Annexin-V-FITC (Ann-V) and propidium iodide (PI) staining was used to assess early apoptotic (Ann-V(+)/PI(-)) vs. late apoptotic/secondary necrotic (Ann-V(+)/PI(+)) death after a 24 hr observation of untreated and drug-treated gastric carcinoma cells. After treatments, the HLA-A*0201(+) tumor cell line KATO III was exposed for 24 hr to allogeneic, HLA-related GM-CSF, IL-4-driven immature (i) DC. Tumor-loaded iDC were tested for IL-12 release in an ELISA assay, incubated with the DC-maturating factor TNF-alpha and used as stimulators for autologous T lymphocytes. Generation of antitumor T response against KATO cells was evaluated in an anti-MHC class I MAb-blocked Interferon-gamma ELISPOT assay. After treatment with Cis-platin (cis), all dying cells were in early apoptosis, whereas secondary necrosis was the prevalent death pattern observed after epirubicin (epi) and doxorubicin (doxo). Doxo and epi increased tumor expression of heat shock protein (hsp) 70 and uptake of tumor cell components by DC, whereas cis treatment had no effect on hsp70 and was associated with poor tumor uptake by DC. Significant upmodulation of IL-12 was observed by DC that had taken up the doxo- and epi-treated tumors (p< 0.005 and p< 0.01, respectively). Increased IFN-gamma release was also observed after stimulation of T lymphocytes with DC loaded with doxo- and epi-treated (p< 0.02 and p< 0.005, respectively) but not with cis-treated DC. These data show that the products of early apoptosis cannot efficiently cross-activate MHC class I-restricted anti-tumor lymphocytes even in the presence of DC maturating factors, whereas secondary necrosis is associated with robust T cell response.}, }
@article {pmid12841678, year = {2003}, author = {Dendale, R and Vincent-Salomon, A and Mouret-Fourme, E and Savignoni, A and Medioni, J and Campana, F and Vilcoq, JR and de la Rochefordière, A and Soussi, T and Asselain, B and de Cremoux, P and Fourquet, A}, title = {Medullary breast carcinoma: prognostic implications of p53 expression.}, journal = {The International journal of biological markers}, volume = {18}, number = {2}, pages = {99-105}, doi = {10.5301/jbm.2008.1279}, pmid = {12841678}, issn = {0393-6155}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/genetics/mortality ; Carcinoma, Medullary/*chemistry/genetics/mortality ; Female ; Genes, p53 ; Humans ; Immunohistochemistry ; Middle Aged ; Mutation ; Prognosis ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27-81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30-241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.}, }
@article {pmid12840971, year = {2003}, author = {Kanibolotskiĭ, AA and Lun'kova, LK and Makarova, OV and Solokhin, EV and Potemkin, AM and Mitkova, SV}, title = {[Prevalence and postmortem diagnosis of hemocontact infections in intravenous drug abusers based on forensic medical research data].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {46}, number = {3}, pages = {14-16}, pmid = {12840971}, issn = {0039-4521}, mesh = {Autopsy ; *Forensic Medicine ; HIV Infections/*complications/diagnosis ; Hepatitis B/*complications/diagnosis ; Hepatitis C/*complications/diagnosis ; Humans ; Immunoenzyme Techniques ; Prevalence ; Substance Abuse, Intravenous/*complications ; }, abstract = {The spread of viral hepatitis C and B and of HIV was studied among the intravenous drug consumers (IDC) on the basis of 42 forensic-medical autopsies. The enzyme immune-assay (EIA) of blood serum showed, in 95.2% of cases, antibodies to hepatitis C virus, antibodies to HbsAg and HIV were registered in 11.9% in both cases. The possibilities of using the autopsy-blood serum for EIA-diagnosis of viral hepatitis and HIV were demonstrated. Morphological examinations of IDC showed, in them, chronic hepatitis (CH) of minimal, weakly-pronounced and moderate activities. Viral CH in HIV infected IDCs is characterized by a minimal and small-pronounced activity of the process and it is not different, according to its activity, from viral CH in IDCs without HIV.}, }
@article {pmid12835955, year = {2003}, author = {Becker, R and Haass, M and Ick, D and Krueger, C and Bauer, A and Senges-Becker, JC and Voss, F and Hilbel, T and Niroomand, F and Katus, HA and Schoels, W}, title = {Role of nonsustained ventricular tachycardia and programmed ventricular stimulation for risk stratification in patients with idiopathic dilated cardiomyopathy.}, journal = {Basic research in cardiology}, volume = {98}, number = {4}, pages = {259-266}, doi = {10.1007/s00395-003-0398-7}, pmid = {12835955}, issn = {0300-8428}, mesh = {Adult ; Cardiomyopathy, Dilated/*mortality ; Disease-Free Survival ; Electrocardiography, Ambulatory ; Electrophysiologic Techniques, Cardiac ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; *Pacemaker, Artificial ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Risk Factors ; Tachycardia, Ventricular/*diagnosis/*mortality ; }, abstract = {BACKGROUND: The prognostic role of asymptomatic nonsustained ventricular tachycardia (NSVT) and programmed ventricular stimulation (PVS) in patients with idiopathic dilated cardiomyopathy (IDC) remains controversial.<br><br>METHODS: The prognostic significance of ventricular arrhythmias, ejection fraction, NYHA class, atrial fibrillation and age for overall and sudden death mortality was prospectively studied in 157 patients with IDC (group 1) free of documented sustained ventricular arrhythmia and syncope. In 99 patients with asymptomatic NSVT (group 2), PVS with 2 - 3 extrastimuli was performed. Non-inducible patients were discharged without specific antiarrhythmic therapy, whereas those with inducible monomorphic ventricular tachycardia were implanted with an ICD.<br><br>RESULTS: In group 1, 48% of patients had NSVT. Overall and sudden death mortality were significantly higher in patients with NSVT (34.2 vs. 9.8%, p = 0.0001 and 15.8 vs. 3.7%, p = 0.0037; follow-up 22 +/- 14 months). Multivariate analysis revealed that NSVT independently predicts both overall and sudden death mortality (p = 0.0021 and.0221, respectively; adjusted for EF, NYHA class and age). In group 2, inducibility of sustained ventricular tachyarrhythmia was 7%, but sustained monomorphic VT occurred in 3% only. Two of 7 inducible patients experienced arrhythmic events during a follow-up of 25 +/- 21 months (positive predictive value 29%). Overall and sudden death mortality were 29% and 0% in the inducible group vs. 17 and 4% in the non-inducible group. Both overall and sudden death mortality were significantly lower in non-inducible patients from group 2 as compared to patients from group 1 with NSVT (p = 0.0043 and 0.0048), most likely due to a more common use of betablockers and a higher EF in the former group (p < 0.001, respectively).<br><br>CONCLUSIONS: In patients with IDC, NSVT independently predicts both overall and sudden death mortality. Due to a low inducibility rate and a poor positive predictive value, PVS seems inappropriate for further arrhythmia risk assessment. However, in spite of documented NSVT, the incidence of SCD in patients on optimized medical treatment including betablockers seems to be very low, questioning the need for specific arrhythmia risk stratification.}, }
@article {pmid12835515, year = {2003}, author = {Tagawa, Y and Yasutake, T and Ikuta, Y and Oka, T and Terada, R}, title = {Chromosome 8 numerical aberrations in stage II invasive ductal carcinoma: correlation with patient outcome and poor prognosis.}, journal = {Medical oncology (Northwood, London, England)}, volume = {20}, number = {2}, pages = {127-136}, pmid = {12835515}, issn = {1357-0560}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; *Chromosome Aberrations ; *Chromosomes, Human, Pair 8 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Staging ; Prognosis ; Survival Analysis ; }, abstract = {Aberrations in chromosome 8 are common in breast cancer. However, the relationship between numerical aberrations of chromosome 8 and clinical behavior (especially prognosis) in breast cancer is not well understood. In this study, a total of 40 specimens of stage II invasive ductal carcinomas (IDCs) was analyzed by fluorescence in situ hybridization (FISH) with a chromosome 8 centromere-specific probe and DNA flow cytometry (stage IIA: 20 cases; stage IIB: 20 cases). All cases were followed for at least 5.7 yr (mean: 7.5 yr; median: 7.7 yr) after surgery or until death. Single (loss), double, and triple or more signals (gain) of chromosome 8 were found in 7.6 +/- 3.5% (range: 2-16%; median: 7%), 53.7 +/- 13.2% (range: 25-81%, median: 53%), and 38.7 +/- 13.2% (range: 17-65%, median: 38%), respectively, of tumors. The frequencies of chromosome 8 gain and disomy correlated with patient outcome (respectively p < 0.05 and p < 0.01). When median ratios of chromosome 8 loss, disomy, and gain were used as the cutoff values, the survival curves revealed that patients in the low-frequency group survived significantly longer than those in the high-frequency group for chromosome 8 gain (p < 0.05), and patients in the high-frequency group survived significantly longer than those in the low-frequency group for chromosome 8 disomy (p < 0.05). Poor prognosis was not associated with age, tumor size, lymph node metastasis, histologic type, TNM stage, estrogen-receptor status, progesterone- receptor status, or DNA ploidy. Our results suggest that the frequencies of chromosome 8 gain and disomy is a potentially useful parameter for predicting prognosis of stage II IDCs.}, }
@article {pmid12834769, year = {2003}, author = {Bakkali, H and Marchal, C and Lesur-Schwander, A and Verhaeghe, JL}, title = {[Breast cancer in women thirty years old or less].}, journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique}, volume = {7}, number = {3}, pages = {153-159}, doi = {10.1016/s1278-3218(03)00021-0}, pmid = {12834769}, issn = {1278-3218}, mesh = {Adult ; Age Distribution ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/diagnosis/*epidemiology/etiology/therapy ; Carcinoma, Ductal, Breast/epidemiology ; Combined Modality Therapy ; Female ; France/epidemiology ; Genetic Predisposition to Disease/genetics ; Humans ; Lymph Node Excision ; Mastectomy ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Staging ; Palpation ; Patient Selection ; Prognosis ; Receptors, Estrogen ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome ; }, abstract = {PURPOSE: Breast cancer rarely occurs in very young women, its diagnosis and management could sometimes be difficult. Our aim is to analyse the epidemiological and clinicopathological features of a group of very young women and especially to evaluate the results of therapeutic strategy.<br><br>METHODS: We report a retrospective study conducted at the department of radiotherapy in Alexis-Vautrin Centre, concerning 30 patients aged < or = 30 years in whom a diagnosis of invasive breast carcinoma was made between 1986 and 2001.<br><br>RESULTS: Six patients had familial history of breast cancer. Palpable tumor was found in 90% of cases, the average size was 3.5 cm. Eleven patients presented with stage I, 11 presented with stage II, 6 presented with stage III and 2 presented with stage IV. Five cancers were diagnosed after pregnancy (average tumor size = 5.8 cm). Eleven patients received neoadjuvant chemotherapy and 23 (82%) of 28 operable cases of invasive malignancy underwent breast conservative surgery (BCS). We found an invasive ductal carcinoma with grade III in 13/27 cases and a nodal involvement in a half of cases, 11 patients of 26 had no expression of oestrogen receptor. The average follow-up was 5 years: six patients (20%) recurred locally (all of them were initially treated by BCS), four patients developed a contralateral breast cancer and three developed a second malignancy. Ten patients died of their metastatic disease. The 5-year overall survival rate was 78%.<br><br>CONCLUSION: Our results are consistent with those of the published reports and suggest that very young women with breast cancer have a poorer prognosis compared with the older ones. They should receive, according to their prognostic factors, an appropriate regional, systemic and hormonal therapy.}, }
@article {pmid12824875, year = {2003}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Tumor cells in lymph vessels and lymph nodes closely associated with nodal metastasis by invasive ductal carcinoma of the breast.}, journal = {Cancer science}, volume = {94}, number = {6}, pages = {508-514}, doi = {10.1111/j.1349-7006.2003.tb01474.x}, pmid = {12824875}, issn = {1347-9032}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Disease Progression ; Female ; Humans ; Japan ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Lymphatic Vessel Tumors/*secondary ; Lymphatic Vessels/pathology ; Menopause ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; }, abstract = {No studies have ever precisely investigated the mechanism of nodal metastasis based on the histological characteristics of tumor cells in lymph vessels and lymph nodes. The purpose of this study was to investigate whether the histological characteristics of tumor cells in lymph vessels and lymph nodes of 393 patients with invasive ductal carcinoma (IDC) were significantly associated with increased nodal metastasis compared with well known histological characteristics of their primary-invasive tumor cells. Multivariate analyses showed that having a single nodal metastasis was closely dependent on primary-invasive tumor size or distance of lymph vessel tumor emboli from the margin of the primary-invasive tumor (P < 0.05) and that having 2 or more nodal metastases was significantly associated with the histological characteristics of the nodal metastatic tumors independently of the size of the primary-invasive tumor, and the number of nodes with extra-nodal invasion (ENI) significantly increased the relative risk (RR) of 4 or more nodal metastases in IDCs </= 20 mm and > 20 to </= 50 mm in size (P < 0.05). In IDCs > 50 mm in size, number of lymph vessels invaded, severe fibrosis of the stroma of extra-nodal invasive tumors, and distance of ENI from the node significantly increased the RR of 10 or more nodal metastases in the multivariate analysis (P < 0.05). The results of this study strongly suggest that the histological characteristics of tumor cells in lymph nodes and lymph vessels play an important role in nodal metastasis in IDCs of the breast.}, }
@article {pmid12817473, year = {2003}, author = {Wenzel, K and Felix, SB and Flachmeier, C and Heere, P and Schulze, W and Grunewald, I and Pankow, H and Hewelt, A and Scherneck, S and Bauer, D and Hoehe, MR}, title = {Identification and characterization of KAT, a novel gene preferentially expressed in several human cancer cell lines.}, journal = {Biological chemistry}, volume = {384}, number = {5}, pages = {763-775}, doi = {10.1515/BC.2003.085}, pmid = {12817473}, issn = {1431-6730}, mesh = {Alternative Splicing ; Amino Acid Sequence ; Base Sequence ; Carcinoma, Ductal, Breast/metabolism ; Cell Adhesion Molecules/genetics ; Cell Line, Tumor ; Chromosomes, Human, Pair 1/*genetics ; *DNA-Binding Proteins ; Gene Frequency ; Genes ; Humans ; Molecular Sequence Data ; Neoplasm Proteins/biosynthesis/*genetics ; Neoplasms/*genetics/metabolism ; Nuclear Envelope/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Cell Surface/genetics ; Recombinant Proteins/genetics/metabolism ; Sequence Homology, Amino Acid ; Transcription Factors/genetics ; Transcription Initiation Site ; Upstream Stimulatory Factors ; }, abstract = {We describe the molecular characterization of a novel human gene on chromosome 1q23.3, termed KAT, which is highly conserved among mammals. The KAT gene spans a genomic region of approximately 1.6 kilobases and consists of 4 exons encoding a 115 amino acid protein with a molecular mass of about 12.5 kDa. The gene is expressed in several human tissues, including kidney, liver, skeletal muscle, heart, colon, thymus, spleen, placenta and lung. We identified an alternatively spliced form, lacking exon 2, in human and mouse tissues. In silico analysis of expressed sequence tags, derived from different types of human tumors, revealed another splice variant. This transcript is characterized by retention of the third intron, leading to a truncated translation product. The KAT protein is localized around the nuclear membranes. It was found to be expressed in several breast, colon and lung carcinoma cell lines, but not in normal breast epithelial cell lines. In addition, KAT protein was detected in invasive ductal carcinoma, but not in adjacent tissues. This suggests a role of this gene in tumorigenesis.}, }
@article {pmid12795089, year = {2003}, author = {Kuroi, K and Toi, M}, title = {[Male breast cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {30}, number = {5}, pages = {599-605}, pmid = {12795089}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/therapeutic use ; *Breast Neoplasms, Male/diagnosis/drug therapy/genetics ; Combined Modality Therapy ; Cyclophosphamide/administration &amp; dosage ; Diagnosis, Differential ; Fluorouracil/administration &amp; dosage ; Gynecomastia/diagnostic imaging ; Humans ; Male ; Mammography ; Methotrexate/administration &amp; dosage ; Prognosis ; Ultrasonography, Mammary ; }, abstract = {As male breast cancer remains rare entity (less than 1% of cases of breast cancer), most of our current knowledge of it has been extrapolated from its female counterpart. The prevalence of male breast cancer increases with age, and the presentation occurs at an average age of approximately 60 years, 10 years older than in females with the disease. The majority of patients present with a painless, firm, subareolar mass, and the tumors are usually larger than 2 cm in diameter. There may be fixation to skin. Mammography and ultrasonography are useful to distinguish between breast cancer and gynecomastia. Pathologically, invasive ductal carcinoma is the predominant subtype, and lobular carcinoma is rare. Modified radical mastectomy is a principal surgical approach, and adjuvant therapy has been advocated in men based on the beneficial results of it in women. Hormonal manipulations constitute an essential part of adjuvant therapy, as male breast cancers have a high rate of hormone-receptor positivity. Although orchiectomy was practiced in the past, today, tamoxifen is the standard hormone therapy. With respect to systemic chemotherapy, the most common regimens are CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or other anthracyclin-based regimens. In cases of disease recurrence, hormonal manipulations, chemotherapy, or radiotherapy can be administered for palliative purposes. Several selective aromatase inhibitors are now available; however, there are limited data regarding their efficacy in men. The prognosis does not seem to be poor compared to that of females when age and stage are matched. Further studies are needed to characterize the biologic and molecular properties of male breast cancer and their prognostic significance, and to devise optimal treatment strategies. However, it is interesting to note that p53 and c-erbB-2, are expressed and angiogenesis occurs in male breast cancer. Moreover, male breast cancer patients can carry BRCA2 mutations.}, }
@article {pmid12794169, year = {2003}, author = {De, AK and Laudanski, K and Miller-Graziano, CL}, title = {Failure of monocytes of trauma patients to convert to immature dendritic cells is related to preferential macrophage-colony-stimulating factor-driven macrophage differentiation.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {170}, number = {12}, pages = {6355-6362}, doi = {10.4049/jimmunol.170.12.6355}, pmid = {12794169}, issn = {0022-1767}, support = {GM36214/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Antigen-Presenting Cells/immunology/metabolism/pathology ; Cell Differentiation/immunology ; Cells, Cultured ; Dendritic Cells/*immunology/metabolism/pathology ; Down-Regulation/immunology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-12/antagonists &amp; inhibitors/biosynthesis ; Interleukin-4/pharmacology ; Isoantigens/immunology ; Lymphocyte Culture Test, Mixed ; Macrophage Colony-Stimulating Factor/*physiology ; Macrophages/*immunology/metabolism/pathology ; Male ; Middle Aged ; Monocytes/*immunology/metabolism/pathology ; T-Lymphocyte Subsets/immunology/metabolism ; Wounds and Injuries/*immunology/*pathology ; }, abstract = {Following trauma, increased inflammatory monokine activation and depressed APC function can occur simultaneously. These contradictory monocyte (Mphi) dysfunctions could result if postinjury Mphi differentiation preferentially favored inflammatory macrophage (Mac) differentiation over development into the most potent APC, dendritic cells (DC). In this report, Mphi of trauma patients with a depressed MLR induction capacity are, for the first time, shown to be unable to differentiate in vitro to immature CD1a(+) DC under the influence of GM-CSF and IL-4. Trauma patient Mphi that retained MLR-inducing capacity had a nonsignificant reduction in DC differentiation capacity. Only patient Mphi populations with depressed differentiation to immature DC (iDC) demonstrated depressed IL-12 and IL-15 production and a continued reduced MLR induction capacity. Neither increased IL-10 production nor decreased CD11c(+) DC precursor numbers correlated with depressed Mphi-to-DC differentiation. Instead, these patients' APC-dysfunctional Mphi populations had increased expression of inflammatory Mac phenotypes (CD64(+), CD86(low), HLA-DR(low)) and up-regulated secretion of M-CSF. M-CSF combined with IL-6 inhibits Mphi-to-iDC differentiation and promotes Mphi-to-Mac differentiation by down-regulating GM-CSFR expression and increasing DC apoptosis. Both depressed GM-CSFR expression and increased Mphi iDC apoptosis, as well as increased expression of CD126 (IL-6R) and CD115 (M-CSFR), were detected in APC-defective patient Mphi. In vitro addition of anti-M-CSF enhanced the IL-4 plus GM-CSF-induced Mphi-to-DC differentiation of these patients. This suggests that, in trauma patients, enhanced Mphi-to-Mac differentiation with concomitant inhibited iDC development is partially due to increased circulating Mphi sensitivity to and production of M-CSF and contributes to postinjury immunoaberrations.}, }
@article {pmid12793903, year = {2003}, author = {Greenberg, R and Schwartz, I and Skornick, Y and Kaplan, O}, title = {Detection of hepatocyte growth factor/scatter factor receptor (c-Met) in axillary drainage after operations for breast cancer using reverse transcriptase-polymerase chain reaction.}, journal = {Breast cancer research : BCR}, volume = {5}, number = {3}, pages = {R71-6}, pmid = {12793903}, issn = {1465-542X}, mesh = {Axilla/*pathology/surgery ; Biomarkers, Tumor/biosynthesis/genetics ; Breast Neoplasms/genetics/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/secondary/surgery ; *Drainage ; Exudates and Transudates/chemistry ; Female ; Humans ; Lymph Nodes/pathology/surgery ; Lymphatic Metastasis/genetics/pathology ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Proto-Oncogene Proteins c-met/*biosynthesis/genetics ; RNA, Messenger/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; }, abstract = {BACKGROUND: The diverse biological effects of hepatocyte growth factor/scatter factor (HGF/SF) are mediated by c-Met, which is preferentially expressed on epithelial cells. Met signaling has a role in normal cellular activities, and may be associated with the development and progression of malignant processes. In this study we examined whether Met can be detected in the axillary drainage from patients who underwent conservative operations for breast cancer, and its prognostic significance.<br><br>METHODS: Thirty-one consecutive patients with invasive ductal carcinoma of the breast suitable for breast-conserving treatment were studied. The output of the drain that had been placed in the axilla during the operation was collected, and the presence of Met and beta-actin were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) assays. The data were compared with the pathological features of the tumor and the axillary lymph nodes, and with the estrogen receptor and progesterone receptor status.<br><br>RESULTS: RT-PCR of the axillary lymphatic drainage was positive for Met in 23 (74.2%) of the patients. Positive assays were correlated with increasing tumor size and grade, with capillary and lymphatic invasion, and with lymph node metastasis (P < 0.02, for all comparisons). All 12 patients with axillary lymph node metastases had positive assays for Met, compared with 57.9% of patients without lymph node metastases. All five patients with tumor involvement in the margins of the resection had positive assays for Met in their lymphatic fluid, compared with 18 of 26 positive assays (69.2%) for patients without involved margins (P < 0.04). Finally, Met showed negative correlations with positivity for estrogen receptor and progesterone receptor (P < 0.02).<br><br>CONCLUSION: Met can be detected in the axillary fluids of patients with breast cancer and its expression in the axillary drainage may have potential as a prognostic factor. This finding might be relevant to therapeutic considerations, because a positive assay for Met in histologically node-negative patients might point to the need to search for node microinvasion or involvement of the excision margins with tumor.}, }
@article {pmid12793894, year = {2003}, author = {Shirakawa, K and Kobayashi, H and Sobajima, J and Hashimoto, D and Shimizu, A and Wakasugi, H}, title = {Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model.}, journal = {Breast cancer research : BCR}, volume = {5}, number = {3}, pages = {136-139}, pmid = {12793894}, issn = {1465-542X}, mesh = {Animals ; Blood Vessels/pathology ; Breast Neoplasms/*blood supply/genetics/*pathology/ultrastructure ; Chromosome Aberrations ; Cytogenetic Analysis ; *Disease Models, Animal ; Endothelium, Vascular/*pathology/ultrastructure ; *Hemodynamics/genetics ; Humans ; Inflammation/genetics ; Magnetic Resonance Angiography ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Electron ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Paraffin Embedding ; Time Factors ; Transplantation, Heterologous/*methods ; Tumor Cells, Cultured ; }, abstract = {We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, vasculogenic mimicry, which showed an absence of endothelial cells, was observed. Comparison of WIBC-9 with an established non-IBC xenograft (MC-5), using time-course dynamic micro-magnetic resonance angiography analysis (with a newly developed intravascular macromolecular contrast agent for magnetic resonance imaging) demonstrated that the WIBC-9 tumor had blood flow and a vascular mimicry-angiogenesis junction.}, }
@article {pmid12792359, year = {2003}, author = {Woody, GE and Gallop, R and Luborsky, L and Blaine, J and Frank, A and Salloum, IM and Gastfriend, D and Crits-Christoph, P and , }, title = {HIV risk reduction in the National Institute on Drug Abuse Cocaine Collaborative Treatment Study.}, journal = {Journal of acquired immune deficiency syndromes (1999)}, volume = {33}, number = {1}, pages = {82-87}, doi = {10.1097/00126334-200305010-00012}, pmid = {12792359}, issn = {1525-4135}, support = {P30-MH-45178/MH/NIMH NIH HHS/United States ; U01-DA07693/DA/NIDA NIH HHS/United States ; DA05593/DA/NIDA NIH HHS/United States ; K05-DA 00168/DA/NIDA NIH HHS/United States ; U01-DA07673/DA/NIDA NIH HHS/United States ; U01DA07090/DA/NIDA NIH HHS/United States ; U01-DA07663/DA/NIDA NIH HHS/United States ; K02-DA 00326/DA/NIDA NIH HHS/United States ; U01-DA07085/DA/NIDA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Antisocial Personality Disorder ; Cocaine-Related Disorders/*complications/*therapy ; Female ; HIV Infections/*complications/etiology/*prevention &amp; control/transmission ; Humans ; Male ; Middle Aged ; *National Institutes of Health (U.S.) ; Patient Dropouts ; Psychotherapy ; Racial Groups ; Risk Factors ; *Risk Reduction Behavior ; Safe Sex ; Sex Factors ; Sexual Behavior ; Treatment Refusal ; United States ; }, abstract = {HIV risk was evaluated among 487 cocaine-dependent patients recruited from five treatment programs in a trial that examined the efficacy of four outpatient-based psychosocial treatments. Treatments were offered two to three times per week for 6 months and consisted of group drug counseling (GDC) or group counseling plus individual drug counseling (IDC), cognitive therapy (CT), or supportive-expressive therapy (SE). The average patient had used cocaine for 7 years, with 10 days of use in the last month. Crack smoking was the main route in 79%, and HIV risk was mainly due to multiple partners and unprotected sex. Treatment was associated with a decrease in cocaine use from an average of 10 days per month at baseline to 1 day per month at 6 months. Reduction in cocaine use was associated with an average 40% decrease in HIV risk across all treatment, gender, and ethnic groups, mainly as a result of fewer sexual partners and less unprotected sex. The combination of IDC and GDC was associated with an equal or even greater reduction in HIV risk than the other treatment conditions and thus shows promise as an effective HIV prevention strategy, at least for some patients.}, }
@article {pmid12786889, year = {2003}, author = {Umekita, Y and Yoshida, H}, title = {Expression of maspin is up-regulated during the progression of mammary ductal carcinoma.}, journal = {Histopathology}, volume = {42}, number = {6}, pages = {541-545}, doi = {10.1046/j.1365-2559.2003.01620.x}, pmid = {12786889}, issn = {0309-0167}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*metabolism/pathology ; Carcinoma, Ductal, Breast/chemistry/*metabolism/secondary ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*metabolism/secondary ; Disease Progression ; Female ; Fluorescent Antibody Technique, Indirect ; *Genes, Tumor Suppressor ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis ; Proteins/analysis/genetics/*metabolism ; Serpins/analysis/genetics/*metabolism ; Up-Regulation ; }, abstract = {AIMS: The tumour suppressor gene maspin is reported to inhibit the motility, invasiveness and metastasis of breast cancer cells. Maspin is expressed in normal mammary myoepithelial cells but is down-regulated during the progression of ductal carcinoma. However, we recently reported that maspin expression was frequently observed in invasive ductal carcinoma (IDC) with an aggressive phenotype, and it was a strong indicator of a poor prognosis. To our knowledge, to date, there has been no report investigating maspin expression in a large series of ductal carcinoma in situ (DCIS).<br><br>METHODS AND RESULTS: To clarify whether there is down-regulation during the progression of ductal carcinoma, we immunohistochemically investigated the expression of maspin in 145 DCIS, 92 invasive ductal carcinomas with a predominant intraductal component as well as 94 usual ductal hyperplasias and 27 atypical ductal hyperplasias. The expression of maspin in carcinoma cells was observed in 9.6% (14 of 145) of DCIS and 18.5% (17 of 92) of IDC with a predominant intraductal components. It significantly correlated with larger tumour size (P = 0.013; P = 0.042), higher histological grade (P = 0.015; P = 0.0003) and the presence of comedo-necrosis (P = 0.000005; P = 0.0074) in DCIS and IDC with a predominant intraductal components, respectively. In epithelial cells, the expression of maspin was observed in only one case of usual ductal hyperplasia, and all cases of atypical ductal hyperplasia were negative.<br><br>CONCLUSIONS: These results and our previous investigation in which 27.4% of IDC were positive for maspin suggest that the expression of maspin in epithelial cells could be up-regulated during the progression of ductal carcinoma, and that it could be correlated with the acquisition of an aggressive phenotype.}, }
@article {pmid12785176, year = {2002}, author = {Das, BR and Kundu, B and Khandapkar, R and Sahni, S}, title = {Geographical distribution of hepatitis C virus genotypes in India.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {45}, number = {3}, pages = {323-328}, pmid = {12785176}, issn = {0377-4929}, mesh = {*Genotype ; Hepacivirus/classification/*genetics/physiology ; Hepatitis C/diagnosis/epidemiology/*virology ; India/epidemiology ; RNA, Viral/genetics ; }, abstract = {HCV isolates from around the world show substantial nucleotide sequence variability throughout the viral genome. Based on the identification of these genome differences various genotypes and subtypes have been described from different geographical regions. They have been tentatively classified into six major genotypes and more than 30 subtypes, but new subtypes are continually being discovered. In recent years, substantial evidence has emerged indicating that typing and subtyping for HCV is clinically important. The present study aims at determining and comparing the prevalence of different genotypes from different parts of India (North, South, East and West). A total of 153 samples representing different regions have been genotyped in our lab. Our studies document a high prevalence of genotype 3 (> 76%) and very low prevalence of genotype 2 (< 2%), as a whole. However, genotype 3a has been found to be the highest (50%) with a decreased frequency of approximately 25% in the case of 3b, approximately 14% in 1b and approximately 10% in 1a, whereas a minimal number (approximately 4%) of genotype 4 has been found only in Southern and Western India.}, }
@article {pmid12779085, year = {2003}, author = {Tammen, H and Kreipe, H and Hess, R and Kellmann, M and Lehmann, U and Pich, A and Lamping, N and Schulz-Knappe, P and Zucht, HD and Lilischkis, R}, title = {Expression profiling of breast cancer cells by differential peptide display.}, journal = {Breast cancer research and treatment}, volume = {79}, number = {1}, pages = {83-93}, doi = {10.1023/a:1023309621042}, pmid = {12779085}, issn = {0167-6806}, mesh = {Biomarkers, Tumor/metabolism ; Breast/cytology ; Breast Neoplasms/genetics/*metabolism ; Cells, Cultured ; Epithelial Cells/*metabolism ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Humans ; Proteomics/*methods ; Tumor Cells, Cultured ; }, abstract = {Expression profiling of RNAs or proteins has become a promising means to investigate the heterogeneity of histopathologically defined classes of cancer. Peptides, representing degradation as well as processing products of proteins offer an even closer insight into cell physiology. Peptides are related to the turnover of cellular proteins and are capable to reflect disease-related changes in homoeostasis of the human body. Furthermore, peptides derived from tumor cells are potentially useful markers in the early detection of cancer. In this study, we introduced a method called differential peptide display (DPD) for separating, detecting, and identifying native peptides derived from whole cell extracts. This method is a highly standardized procedure, combining the power of reversed-phase chromatography with mass spectrometry. This technology is suitable to analyze cell lines, various tissue types and human body fluids. Peptide-based profiling of normal human mammary epithelial cells (HMEC) and the breast cancer cell line MCF-7 revealed complex peptide patterns comprising of up to 2300 peptides. Most of these peptides were common to both cell lines whereas about 8% differed in their abundance. Several of the differentially expressed peptides were identified as fragments of known proteins such as intermediate filament proteins, thymosins or Cathepsin D. Comparing cell lines with native tumors, overlapping peptide patterns were found between HMEC and a phylloides tumor (CP) on the one hand and MCF-7 cells and tissue from a invasive ductal carcinoma (DC) on the other hand.}, }
@article {pmid12778484, year = {2003}, author = {Della Chiesa, M and Vitale, M and Carlomagno, S and Ferlazzo, G and Moretta, L and Moretta, A}, title = {The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors.}, journal = {European journal of immunology}, volume = {33}, number = {6}, pages = {1657-1666}, doi = {10.1002/eji.200323986}, pmid = {12778484}, issn = {0014-2980}, mesh = {Antigens, CD/*analysis ; Cells, Cultured/immunology ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; HLA Antigens/immunology ; HLA-B Antigens/analysis ; HLA-C Antigens/analysis ; Histocompatibility Antigens Class I/immunology ; Humans ; Killer Cells, Natural/classification/*immunology ; Lectins, C-Type/*analysis ; NK Cell Lectin-Like Receptor Subfamily C ; NK Cell Lectin-Like Receptor Subfamily D ; Receptors, Immunologic/*analysis ; Receptors, KIR ; Receptors, KIR3DL1 ; Receptors, Natural Killer Cell ; }, abstract = {The cognate NK-DC interaction in inflamed tissues results in NK cell activation and acquisition of cytotoxicity against immature DC (iDC). This may represent a mechanism of DC selection required for the control of downstream adaptive immune responses. Here we show that killing of monocyte-derived iDC is confined to the NK cell subset that expresses CD94/NKG2A, but not killer Ig-like receptors (KIR). Consistent with these data, the expression of HLA-E (i.e. the cellular ligand of CD94/NKG2A) was down-regulated in iDC. On the other hand, HLA-B and HLA-C down-regulation in iDC was not sufficient to induce cytotoxicity in NK cells expressing KIR3DL1 or KIR2DL. Remarkably, CD94/NKG2A(+)KIR(-) NK cells were heterogeneous in their ability to kill iDC and an inverse correlation existed between their CD94/NKG2A surface density and the magnitude of their cytolytic activity. It is conceivable that the reduced CD94/NKG2A surface density enables these cells to efficiently sense the decrease of HLA-E surface expression in iDC. Finally, most NK cells that lysed iDC did not kill mature DC that express higher amounts of HLA class I molecules (including HLA-E)as compared with iDC. However, a small NK cell subset was capable of killing not only iDC but also mature DC.}, }
@article {pmid12774668, year = {2003}, author = {Karamian, NA and Kazanets, EG and Aĭvazova, DKh and Kovrigina, ES and Krasil'nikova, MV and Tokarev, IuN and Smetanina, NS}, title = {[Soluble transferrin receptors: significance and diagnostic value in anemia].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {}, number = {4}, pages = {40-42}, pmid = {12774668}, issn = {0869-2084}, mesh = {Anemia/blood/*diagnosis/etiology ; Anemia, Iron-Deficiency/blood/*diagnosis ; Child ; Child, Preschool ; Diagnosis, Differential ; Ferritins/blood ; Humans ; Iron/blood ; Receptors, Transferrin/*blood ; beta-Thalassemia/blood/diagnosis ; }, abstract = {The study was undertaken for the purpose of demonstrating a diagnostic importance of determining the level of soluble transferrin receptors not only in the diagnosis of iron-deficiency conditions (IDC) or in the differential diagnosis of anemia in a chronic disease (ACD) and of iron-deficiency anemia (IDA) but also in making a diagnosis in case of transfusion-dependent patients with Cooley's anemia. The iron metabolism (including determination of the serum iron (SI), of the total iron-binding ability (TIBA), of saturation of transferrin with iron (STFI), of serum transferrin (ST), and of soluble transferrin receptors (s-STR) was examined in 31 patients with different-genesis anemias, aged 3 to 7. Diagnoses were made for all children on the basis of the standard clinical-and-laboratory examinations and tests. A pattern of iron-metabolism parameters, typical of this pathology, was detected in all IDC patients; it is noteworthy, that the s-STR concentration amounted in this category to 9.4 +/- 1.35 mg/l, which essentially topped the normal values. It can be concluded on the basis of the obtained results that s-STR can be regarded as a key IDC marker. There was an increased SF (up to 324 +/- 64.5 mkg/L) alongside with hypoferremia in the ACD patients; the s-STR content was found to be within the reference values (3.21 +/- 0.55 mg/L), the determination of s-STR can be regarded as a test in the differential diagnosis of IDC and ACD. The results of s-STR research ranged, in patients with Cooley's anemia, drastically from 0.8 mg/L to 17 mg/L; it is noteworthy, that there was a reliable dependence on an adequacy of the conducted therapy in case of such patients. The highest sSTR values were found in children with the hereditary spherocytic hemolytic anemia (11.85 +/- 2.5 mg/L), which is, apparently, explained by a proliferative super-activity of the bone marrow observed in this pathology.}, }
@article {pmid12764685, year = {2003}, author = {Buch, RS and Schmidt, M and Reichert, TE}, title = {[Acute tongue necrosis provoked by epirubicin-cyclophosphamide treatment for invasive ductal breast cancer].}, journal = {Mund-, Kiefer- und Gesichtschirurgie : MKG}, volume = {7}, number = {3}, pages = {175-179}, pmid = {12764685}, issn = {1432-9417}, mesh = {Acute Disease ; Airway Obstruction/chemically induced/pathology ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration &amp; dosage/*adverse effects ; Epirubicin/administration &amp; dosage/*adverse effects ; Female ; Humans ; Middle Aged ; Necrosis ; Tongue/drug effects/*pathology ; Tongue Diseases/*chemically induced/pathology ; }, abstract = {CASE: Unilateral necrosis of the tongue is an uncommon symptom of different rare diseases. Previously, it had only been described as an infrequent complication of temporal arteritis or as a side effect of therapy with ergotamine. We present a case of unilateral necrosis of the tongue in a 62-year-old woman with invasive ductal carcinoma of the breast treated with epirubicin and cyclophosphamide.<br><br>RESULTS: The necrosis led to a rapid swelling of the tongue and consequently to an airway obstruction necessitating a tracheotomy. After excision of the necrosis, the swelling of the tongue and the airway obstruction subsided.<br><br>DISCUSSION: Because of the temporal connection between the occurrence of the necrosis and the administration of chemotherapy, an adverse effect of the administered drugs seems most likely. However, a paraneoplastic pathogenesis cannot be completely excluded. The occurrence of unilateral necrosis of the tongue is a rare complication of the above-mentioned conditions. However, it is important to be aware of the different causes leading to this rare disease in order to initiate the right therapy.}, }
@article {pmid12763681, year = {2003}, author = {Moretta, L and Ferlazzo, G and Mingari, MC and Melioli, G and Moretta, A}, title = {Human natural killer cell function and their interactions with dendritic cells.}, journal = {Vaccine}, volume = {21 Suppl 2}, number = {}, pages = {S38-42}, doi = {10.1016/s0264-410x(03)00197-x}, pmid = {12763681}, issn = {0264-410X}, mesh = {Bacterial Infections/immunology ; *Cell Communication ; Dendritic Cells/*physiology ; Histocompatibility Antigens Class I/physiology ; Humans ; Immunity, Innate ; Killer Cells, Natural/*physiology ; }, abstract = {Natural killer (NK) cells have long been considered as "primitive" and "non-specific" effector cells. However, the past 10 years have witnessed dramatic progress in our understanding of how NK cells function and their role in innate defenses. Thanks to specialized inhibitory receptors specific for MHC-class I molecules, they can sense the decrease or loss of these molecules, a typical condition of potentially dangerous cells such as tumor or virally-infected cells. NK cell triggering and lysis of these cells is mediated by several activating receptors and co-receptors that have recently been identified and cloned. While normal cells are usually resistant to the NK-mediated attack, a remarkable exception is represented by dendritic cells (DC). In their immature form (iDC), they are susceptible to NK-mediated lysis because of the expression of low levels of surface MHC-class I molecules. Since the process of DC maturation (mDC) is characterized by the surface expression of high levels of MHC-class I molecules, mDC become resistant to NK cells. Exposure to live bacteria induces rapid DC maturation and, thus, resistance to NK cells. The cross-talk between DC and NK cells is more complex and involves also a DC-dependent NK cell activation and proliferation. Thus, two important players of the innate immunity may be involved in a coordinated regulation of critical events occurring at the interface between innate and adaptive immunity.}, }
@article {pmid12759415, year = {2003}, author = {Hoves, S and Krause, SW and Halbritter, D and Zhang, HG and Mountz, JD and Schölmerich, J and Fleck, M}, title = {Mature but not immature Fas ligand (CD95L)-transduced human monocyte-derived dendritic cells are protected from Fas-mediated apoptosis and can be used as killer APC.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {170}, number = {11}, pages = {5406-5413}, doi = {10.4049/jimmunol.170.11.5406}, pmid = {12759415}, issn = {0022-1767}, mesh = {Adenoviridae/genetics ; Antigen-Presenting Cells/*immunology/metabolism ; Apoptosis/genetics/*immunology ; Cell Differentiation/genetics/immunology ; Cell Line ; Cells, Cultured ; Coculture Techniques ; Cytotoxicity Tests, Immunologic ; Dendritic Cells/*immunology/metabolism ; Fas Ligand Protein ; Genetic Vectors ; Green Fluorescent Proteins ; Humans ; Integrases/genetics ; Jurkat Cells ; Killer Cells, Natural/*immunology/metabolism ; Ligands ; Luminescent Proteins/genetics ; Lymphocyte Activation/genetics ; Lymphocyte Depletion ; Membrane Glycoproteins/biosynthesis/*genetics/physiology ; Monocytes/*immunology/metabolism ; Recombination, Genetic ; Solubility ; T-Lymphocyte Subsets/immunology/metabolism/pathology ; Transduction, Genetic ; Viral Proteins/genetics ; fas Receptor/biosynthesis/*physiology ; }, abstract = {Several in vitro and animal studies have been performed to modulate the interaction of APCs and T cells by Fas (CD95/Apo-1) signaling to delete activated T cells in an Ag-specific manner. However, due to the difficulties in vector generation and low transduction frequencies, similar studies with primary human APC are still lacking. To evaluate whether Fas ligand (FasL/CD95L) expressing killer APC could be generated from primary human APC, monocyte-derived dendritic cells (DC) were transduced using the inducible Cre/Loxp adenovirus vector system. Combined transduction of DC by AdLoxpFasL and AxCANCre, but not single transduction with these vectors, resulted in dose- and time-dependent expression of FasL in >70% of mature DC (mDC), whereas <20% of immature DC (iDC) expressed FasL. In addition, transduction by AdLoxpFasL and AxCANCre induced apoptosis in >80% of iDC, whereas FasL-expressing mDC were protected from FasL/Fas (CD95/Apo-1)-mediated apoptosis despite coexpression of Fas. FasL-expressing mDC eliminated Fas(+) Jurkat T cells as well as activated primary T cells by apoptosis, whereas nonactivated primary T cells were not deleted. Induction of apoptosis in Fas(+) target cells required expression of FasL in DC and cell-to-cell contact between effector and target cell, and was not dependent on soluble FasL. Induction of apoptosis in Fas(+) target cells required expression of FasL in DC, cell-to-cell contact between effector and target cell, and was not dependent on soluble FasL. The present results demonstrate that FasL-expressing killer APC can be generated from human monocyte-derived mDC using adenoviral gene transfer. Our results support the strategy to use killer APCs as immunomodulatory cells for the treatment of autoimmune disease and allograft rejection.}, }
@article {pmid12736568, year = {2003}, author = {Tsutsui, S and Ohno, S and Murakami, S and Kataoka, A and Kinoshita, J and Hachitanda, Y}, title = {Histological classification of invasive ductal carcinoma and the biological parameters in breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {10}, number = {2}, pages = {149-152}, doi = {10.1007/BF02967640}, pmid = {12736568}, issn = {1340-6868}, mesh = {Aneuploidy ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; ErbB Receptors/biosynthesis ; Female ; Humans ; Ploidies ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Tumor Suppressor Protein p53/biosynthesis ; }, abstract = {BACKGROUND: The histological classification of invasive ductal carcinoma proposed by the Japanese Breast Cancer Society is based on the appearance of breast cancer invasion. However, few studies have been done to clarify the relationship between the histological classification and other parameters that represent the biological characteristics of individual breast cancer cells.<br><br>MATERIALS AND METHODS: We analyzed 1,025 invasive ductal carcinomas, consisting of 424 papillotubular, 330 solid-tubular and 271 scirrhous cases, with regard to the status of estrogen receptor (ER), progesterone receptor (PgR), DNA ploidy, epidermal growth factor receptor (EGFR) and p53 protein.<br><br>RESULTS: Absence of ER and PgR, aneuploidy, EGFR positivity and p53 protein positivity were all observed significantly more frequently in solid-tubular tumors than in the other two types. In addition, the number of abnormal features with regard to these 5 biological parameters was also significantly higher in solid-tubular tumors than in the other two types.<br><br>CONCLUSION: Abnormalities in the biological parameters listed above were frequently found in the solid-tubular type of invasive ductal carcinoma.}, }
@article {pmid12732742, year = {2003}, author = {Snyder, RJ and Stillman, RM and Weiss, SD}, title = {Epidermoid cancers that masquerade as venous ulcer disease.}, journal = {Ostomy/wound management}, volume = {49}, number = {4}, pages = {63-4, 65-6}, pmid = {12732742}, issn = {0889-5899}, mesh = {Biopsy ; Cohort Studies ; *Diagnosis, Differential ; Female ; Florida ; Humans ; Male ; Neoplasms, Squamous Cell/*diagnosis/etiology ; Prevalence ; Skin Neoplasms/*diagnosis/etiology ; Ulcer/complications/*diagnosis/prevention &amp; control ; Ultraviolet Rays/adverse effects ; Vascular Diseases/complications/*diagnosis ; Wound Healing/physiology ; Wounds and Injuries/complications/diagnosis ; }, abstract = {Many lesions originally diagnosed as venous ulcers exhibit characteristics that are strikingly similar to skin cancers and might represent sites of primary carcinomas. To ascertain the frequency of malignancy in patients previously diagnosed with venous ulcer disease, a retrospective cohort review of patients evaluated at a Wound Healing Center in Florida was conducted. Charts of all patients with IDC-9 codes for varicose veins with stasis ulcer, varicose veins with ulcer and inflammation, and venous peripheral insufficiency were reviewed. Only charts of patients with one of these diagnoses and documented clinical varicosities, hemosiderosis, brawny edema, and lesions located at the medial or lateral lower leg were included. Sixty (60) patients were identified. Of these, 20 had lesions that were clinically suspicious for epidermoid skin cancers (ie, showing raised borders and chronic scaling). Biopsies confirmed malignancy in 15 of the 60 ulcers (25%). Of these, eight were squamous cell cancers. Given the high rate of malignancies in this cohort of patients, it is postulated that primary epidermoid cancers may mimic venous ulcers in appearance, location, and symptoms; that Marjolin's ulcers are rare despite their propensity to develop in many different types of wounds; and that patients with a history of venous ulcers and prolonged exposure to ultraviolet rays may benefit from lesion biopsies to test for epidermoid cancers.}, }
@article {pmid12715337, year = {2003}, author = {Ramalingam, P and Middleton, LP and Tamboli, P and Troncoso, P and Silva, EG and Ayala, AG}, title = {Invasive micropapillary carcinoma of the breast metastatic to the urinary bladder and endometrium: diagnostic pitfalls and review of the literature of tumors with micropapillary features.}, journal = {Annals of diagnostic pathology}, volume = {7}, number = {2}, pages = {112-119}, doi = {10.1053/adpa.2003.50015}, pmid = {12715337}, issn = {1092-9134}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Papillary/metabolism/pathology/*secondary ; Carcinoma, Transitional Cell/pathology ; Diagnosis, Differential ; Endometrial Neoplasms/metabolism/*secondary ; Female ; Humans ; Immunohistochemistry ; Keratin-7 ; Keratins/metabolism ; Lung Neoplasms/metabolism ; Middle Aged ; Receptors, Estrogen/metabolism ; Urinary Bladder Neoplasms/metabolism/*secondary ; }, abstract = {Carcinomas with micropapillary features have been described in the breast, urinary bladder, lung, and ovary. They are characterized by the presence of micropapillary tufts in clear spaces. Unequivocal vascular invasion is usually present at the periphery of the tumor. Consequently, these tumors have a high propensity for lymph node metastases and high-stage disease. The metastatic carcinoma can consist exclusively of the micropapillary component, which may elicit an erroneous diagnosis if located in the bladder or lung, as in the patient presented herein. We present a case of a 59-year-old woman with a history of bilateral breast carcinoma status post-bilateral mastectomy, chemotherapy, and tamoxifen therapy. She presented with urinary frequency, and a pelvic mass was noted. A biopsy of the endometrium revealed a poorly differentiated carcinoma. Urinary bladder biopsies showed a carcinoma with micropapillary features diagnosed as micropapillary transitional cell carcinoma. She presented to M.D. Anderson Cancer Center (Houston, TX) for further treatment recommendations. The urinary bladder and endometrial biopsies both contained carcinomas with micropapillary features. The mastectomy specimen showed an invasive ductal carcinoma with a significant micropapillary component. The tumor cells from the breast, endometrium, and urinary bladder were positive for cytokeratin (CK) 7 and estrogen receptor and negative for CK20. In view of the morphologic and immunohistochemical profile, the carcinoma in the endometrium and urinary bladder were interpreted as metastatic lesions from the breast primary. Carcinomas with a micropapillary component are morphologically identical in the breast, urinary bladder, and lung. However, micropapillary serous carcinoma has a different appearance more akin to borderline tumors of the ovary. Immunohistochemical stains are useful in distinguishing these lesions in that thyroid transcription factor-1 positivity suggests a lung primary, CK7 and estrogen receptor suggest a breast primary, and both CK7 and CK20 positivity suggest a urinary bladder primary. It is important to exclude metastatic carcinomas with micropapillary features before making a definite diagnosis of a primary tumor. Carcinomas with micropapillary features have a propensity for lymph node metastases and advanced stage disease. This article discusses the differential diagnosis of carcinomas with micropapillary features in different organs.}, }
@article {pmid12712492, year = {2003}, author = {Gupta, A and Deshpande, CG and Badve, S}, title = {Role of E-cadherins in development of lymphatic tumor emboli.}, journal = {Cancer}, volume = {97}, number = {9}, pages = {2341-2347}, doi = {10.1002/cncr.11332}, pmid = {12712492}, issn = {0008-543X}, support = {1P 50 CA89018-01/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma in Situ/metabolism/parasitology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/parasitology ; Carcinoma, Lobular/metabolism/pathology ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/*metabolism/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {BACKGROUND: E-cadherin (E-cad) is a cell adhesion molecule that is expressed in normal breast tissue. While loss of E-cad expression is a characteristic feature of lobular carcinoma, it also is observed in infiltrating ductal carcinoma (IDC). The presence of peritumoral intralymphatic emboli also is a poor prognostic feature in IDC. Invasive lobular carcinoma rarely is associated with intralymphatic emboli. In the current study, the authors assessed E-cad expression in cases of IDC with and without intralymphatic tumor emboli to examine the potential role played by these molecules in the development of lymphatic emboli.<br><br>METHODS: Fifty patients with high-grade invasive ductal carcinoma--25 with prominent lymphatic invasion (LVI) and intralymphatic tumor emboli and 25 without LVI--were tested for expression of E-cad. For both groups, the intensity and frequency of E-cad expression was evaluated in tumor cells and lymphatic emboli; normal lobules were used as internal controls.<br><br>RESULTS: Membranous expression of E-cad was observed in normal lobules and tumor cells in all patients, with the tumor cells exhibiting varying degrees of loss of expression. In the 25 LVI-positive patients, the majority of tumor cells (including intralymphatic emboli) expressed E-cad with an intensity and distribution similar to what was seen in normal lobules. In the LVI-negative patients, the intensity and the distribution of E-cad staining varied significantly. Tumor cells at the tumor-stroma interface showed a greater frequency and intensity of E-cad expression than did cells in the central region of the tumor.<br><br>CONCLUSIONS: Strong expression of E-cad was observed in LVI-positive patients with high-grade IDC but not in LVI-negative patients. Emboli also exhibited high-intensity expression. These findings, taken in conjunction with the knowledge that intralymphatic tumor emboli in lobular carcinoma (which is E-cad-negative) are rare, suggest that E-cad plays an important role in tumor development and growth within the lymphatics.}, }
@article {pmid12708494, year = {2003}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Significance of nodal metastatic tumor characteristics in nodal metastasis and prognosis of patients with invasive ductal carcinoma of the breast.}, journal = {Cancer science}, volume = {94}, number = {2}, pages = {181-187}, doi = {10.1111/j.1349-7006.2003.tb01416.x}, pmid = {12708494}, issn = {1347-9032}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Cell Nucleus/ultrastructure ; Combined Modality Therapy ; Disease Progression ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Japan ; Life Tables ; *Lymphatic Metastasis ; Menopause ; Middle Aged ; Mitotic Index ; Neoplasm Invasiveness ; Neoplastic Cells, Circulating ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Treatment Outcome ; }, abstract = {There is no study evaluating the significance of nodal metastatic tumor characteristics in tumor progression of invasive ductal carcinomas (IDCs) of the breast. The purpose of this study was to investigate whether nodal metastatic tumor characteristics play an important role in the tumor progression of IDCs. The subjects of this study were 205 IDC patients with nodal metastases. Significant associations with increased numbers of nodal metastases, and patient outcomes were evaluated by multivariate analyses, in comparison with well-known histological parameters. The numbers of lymph nodes with extra-nodal invasion and with extranodal blood vessel tumor emboli, the distance of extra-nodal blood vessel tumor emboli from the nodes, and the nodal tumor dimensions significantly increased the number of nodal metastases in the multivariate analysis (P<0.001). Cox multivariate analyses showed that the parameters which significantly increased hazard rates (HRs) of disease-free survival (DFS), distant organ metastasis (DOM) and overall survival were 6 or more mitotic figures of nodal metastatic tumors (P<0.05). Six or more lymph nodes with extra-nodal invasion, and an extra-nodal blood vessel tumor emboli dimension of >0.6 mm significantly increased the HRs of DFS and DOM in multivariate analyses (P<0.05). The present study demonstrated the important roles of nodal metastatic tumors in the tumor progression of IDCs.}, }
@article {pmid12692841, year = {2003}, author = {Roylance, R and Droufakou, S and Gorman, P and Gillett, C and Hart, IR and Hanby, A and Tomlinson, I}, title = {The role of E-cadherin in low-grade ductal breast tumourigenesis.}, journal = {The Journal of pathology}, volume = {200}, number = {1}, pages = {53-58}, doi = {10.1002/path.1326}, pmid = {12692841}, issn = {0022-3417}, mesh = {Alleles ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; Genes, Neoplasm/genetics ; Humans ; Immunohistochemistry/methods ; Mutation/genetics ; Neoplasm Invasiveness ; }, abstract = {Grade I invasive ductal breast carcinomas have a specific pattern of genetic aberrations, namely gain of 1q and loss of 16q. This pattern is very similar to the changes seen in invasive lobular breast carcinomas (ILCs). The gene on 16q involved in ILC is known to be E-cadherin (CDH1). This study has investigated whether the same gene is responsible for grade I invasive ductal carcinoma (IDC), using allele imbalance analysis, mutation screening, and immunohistochemistry (IHC). The data suggest that despite the shared pattern of genetic aberrations seen in grade I IDC and ILC, CDH1 is not the target gene in low-grade ductal tumourigenesis.}, }
@article {pmid12687856, year = {2003}, author = {Grimm, W and Herzum, I and Müller, HH and Christ, M}, title = {Value of heart rate variability to predict ventricular arrhythmias in recipients of prophylactic defibrillators with idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {26}, number = {1P2}, pages = {411-415}, doi = {10.1046/j.1460-9592.2003.00060.x}, pmid = {12687856}, issn = {0147-8389}, mesh = {Cardiomyopathy, Dilated/complications/mortality/*physiopathology/surgery ; *Defibrillators, Implantable ; Electrocardiography, Ambulatory ; Female ; *Heart Rate ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Risk Factors ; Stroke Volume ; Survival Analysis ; Survival Rate ; Tachycardia, Ventricular/diagnosis/etiology/*prevention &amp; control ; Ventricular Fibrillation/diagnosis/etiology/*prevention &amp; control ; }, abstract = {This study investigated the relation between heart rate variability (HRV) measured as standard deviation of normal to normal RR intervals (SDNN) on baseline 24-hour ambulatory electrocardiogram (ECG) and subsequent appropriate implantable cardioverter defibrillator (ICD) interventions in 70 patients with idiopathic dilated cardiomyopathy (IDC) in whom ICDs were implanted prophylactically in the presence of a low left ventricular ejection fraction (LVEF). During 43 +/- 26 months of follow-up, 26 of 70 (37%) study patients with IDC received one or more appropriate ICD interventions for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) documented by electrograms stored in the ICD. Mean SDNN at ICD implant was 94 +/- 33 ms. No difference was found between patients with (90 +/- 25 ms) versus without (96 +/- 37 ms) appropriate ICD interventions for VT or VF during follow-up. Multivariate Cox regression analysis of baseline clinical characteristics including age, gender, LVEF, NYHA functional class, nonsustained VT on Holter, history of syncope, left bundle branch block, baseline medication and HRV revealed LVEF as the only significant predictor of arrhythmia. These findings do not support the use of HRV measured as SDNN on 24-hour ambulatory ECG to select patients with IDC for prophylactic ICD therapy.}, }
@article {pmid12687844, year = {2003}, author = {Fauchier, L and Marie, O and Casset-Senon, D and Babuty, D and Cosnay, P and Fauchier, JP}, title = {Ventricular dyssynchrony and risk markers of ventricular arrhythmias in nonischemic dilated cardiomyopathy: a study with phase analysis of angioscintigraphy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {26}, number = {1P2}, pages = {352-356}, doi = {10.1046/j.1460-9592.2003.00048.x}, pmid = {12687844}, issn = {0147-8389}, mesh = {Cardiomyopathy, Dilated/*complications/*diagnostic imaging/physiopathology ; Death, Sudden, Cardiac/etiology ; Disease Progression ; Electrocardiography ; *Gated Blood-Pool Imaging ; Humans ; Middle Aged ; Prognosis ; Risk Factors ; Tachycardia, Ventricular/diagnosis/*etiology ; Ventricular Dysfunction/diagnosis/etiology ; Ventricular Fibrillation/diagnosis/*etiology ; }, abstract = {Biventricular pacing is a new form of treatment for patients with dilated cardiomyopathy and ventricular dyssynchrony. Limited information is available regarding the relationship between ventricular dyssynchrony and risk markers of ventricular arrhythmias in idiopathic dilated cardiomyopathy (IDC). In 103 patients with IDC, Fourier phase analysis of both ventricles was performed from equilibrium radionuclide angiography (ERNA). The difference between the mean phase of the LV and RV was a measure of interventricular dyssynchrony, and the standard deviations of the mean phases in each ventricle measured intraventricular dyssynchrony. There were no significant differences in inter- and intraventricular dyssynchrony between patients with versus without histories of sustained VT or VF, nonsustained VT, abnormal signal-averaged ECG, or induced sustained monomorphic VT. Dyssynchrony was not related to decreased heart rate variability (HRV). LV and interventricular dyssynchrony were weakly related to QT duration and QT dispersion. During a follow-up of 27 +/- 23 months, 21 patients had major adverse cardiac events (MACE), including 7 cardiac deaths, 11 progression of heart failure leading to cardiac transplantation, and 3 sustained VT/VF. The only independent predictors of MACE were an increased standard deviation of LV mean phase (P = 0.003), a decreased HRV (standard deviation of normal-to-normal intervals, P = 0.004), and histories of previous VT/VF (P = 0.03) or nonsustained VT (P = 0.04). In conclusion, left intraventricular dyssynchrony evaluated with ERNA was an independent predictor of MACE in IDC and was not related to usual risk markers of ventricular arrhythmias. This may have implications for resynchronization therapy and/or the use of implantable cardioverter defibrillators in IDC.}, }
@article {pmid12679975, year = {2002}, author = {Belicza, M and Lenicek, T and Glasnović, M and Elez, M and Gladić, V and Marton, I and Zuteković, S and Jurlina, H and Kusić, Z and Cvrtila, D and Strnad, M and Tomas, D and Cupić, H and Kruslin, B}, title = {[Change in the occurrence of breast cancer in hospital registries (1980-2000)].}, journal = {Lijecnicki vjesnik}, volume = {124}, number = {11-12}, pages = {347-353}, pmid = {12679975}, issn = {0024-3477}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology ; Breast Neoplasms, Male/epidemiology ; Croatia/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Radioactive Hazard Release ; Registries ; Ukraine ; Warfare ; }, abstract = {The aim of our retrospective study was to analyze distribution of histological types, age of patients and hormonal dependency of breast cancer cases in the period 1980-2000 using computer database "Thanatos". This period was divided with regard to the war into a pre-war (1980-1990), war (1991-1995) and post-war period (1996-2000). We also paid attention to the Chernobyl accident (pre-Chernobyl from 1980-1986 and post-Chernobyl from 1987-2000). Special attention was focused on the period during the war mainly due to the fact that very little data exist in literature dealing with the war as a stress factor that may have induced and promoted carcinogenesis. During this twenty-one year period 2296 patients were diagnosed with breast cancer. In the female population of 2274, 2228 (98%) of these were ductal and only 46 (2%) were invasive lobular carcinomas. In all of the male cases (22) the cancer was pathohistologically verified as the invasive ductal type. The male:female ratio was 1:103. Comparing the pre-war and war periods we found a more than double increase in the male:female ratio (from 1:131 to 1:66). We observed similar results when we looked at the period after the Chernobyl incident where the ratio increased from 1:139 to 1:79. When we analyzed the distribution of histological types we found a significant increase in lobular carcinomas during the post-war period, from 1.1% to 5.5%; this increase was less significant for the post-Chernobyl period (1.0% to 3.3%). The average age of the patients with invasive ductal carcinomas increased from 56.7 yrs during the pre-war period to 59.7 yrs during the war and finally to 61.1 yrs during the post-war period. The average age of males with breast cancer decreased from 63.6 and 63.5 during the pre-war and war periods to 58.8 yrs during the post-war period. These results suggest that the war could have influenced the shift in the age of occurrence of breast cancer in both sexes appearing in younger males and in females in their postmenopausal period. The most commonly diagnosed stage of invasive ductal carcinoma during the war and post-war periods was T1N0MX, but in the controlled pre-war period the most frequently diagnosed stage was T2N1MX. With this we see that the increase in the age of the patient is not due to a more advanced pTNM stage which suggests that the increased age of our patients seeking medical help is not due to the incapacitating effects that the war may have on people needing medical attention. Our results showed that most of the patients were ER positive (72% throughout the twenty-one year period) and their average rate and number increase with the age of the patient. We found a significant drop in hormone dependent tumors in the period from 1991-95, which could mean that tumors in a war environment manifest a more aggressive phenotype. Our results show that the war within our region most likely had an effect on some clinical parameters involving breast cancer patients. Possible effects caused by "Chernobyl" could not be proved due to the overwhelming effect that war had upon the patients within this region.}, }
@article {pmid12677894, year = {2002}, author = {Skálová, A and Stárek, I and Vanĕcek, T and Kucerová, V and Plank, L and Szépe, P}, title = {[Amplification and overexpression of HER-2/neu in parotid gland salivary duct carcinoma. Immunohistochemical study and fluorescence in situ hybridization].}, journal = {Ceskoslovenska patologie}, volume = {38 Suppl 1}, number = {}, pages = {27-34}, pmid = {12677894}, issn = {1210-7875}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma/*chemistry/genetics ; Female ; *Gene Amplification ; Genes, erbB-2/*genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Parotid Neoplasms/*chemistry/genetics ; Receptor, ErbB-2/*analysis ; Retrospective Studies ; *Salivary Ducts ; }, abstract = {Salivary duct carcinoma (SDC) is highly malignant salivary gland tumour with aggressive clinical behaviour, characterised by its histological resemblance to invasive ductal carcinoma of the breast. Amplification of gene HER-2/neu and overexpression of its gene product have been shown to have both prognostic and treatment implications in breast cancer. The reports concerning the expression of c-erbB2/HER-2/neu in salivary gland tumours are few and controversial. Thus, eleven cases of SDC were evaluated for HER-2/neu status using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first molecular genetic analysis of SDCs using FISH. HER-2/neu overexpression, identified as strong membrane staining, was observed in all but one case of SDC in majority of neoplastic cells while only four tumours, of nine cases analysed, revealed HER-2/neu gene amplification by means of FISH analysis. SDCs were associated with poor clinical outcome, 6 patients (55%) died of disseminated carcinoma within 4 to 44 months after therapy. There was no difference in outcome of patients with IHC positive-nonamplified and IHC positive-amplified tumours.}, }
@article {pmid12677891, year = {2002}, author = {Mrhalová, M and Kodet, R}, title = {[Indications for treatment in invasive ductal carcinoma of the breast with Herceptin from the aspect of laboratory diagnosis--study of the ERBB-2 protein and determination of the number of copies of the ERBB2 gene. Review].}, journal = {Ceskoslovenska patologie}, volume = {38 Suppl 1}, number = {}, pages = {4-14}, pmid = {12677891}, issn = {1210-7875}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/genetics ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/genetics ; Female ; Gene Amplification ; Genes, erbB-2/*genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2/*analysis ; Trastuzumab ; }, abstract = {Overexpression of the ERBB-2 protein has become a target of the anti-neoplastic treatment in patients with invasive duct carcinomas of the breast with a monoclonal antibody trastuzumab (Herceptin, Genentech). From this reason the immunohistochemical (IHC) evaluation of ERBB-2 protein expression is crucial. However, there are patients in whom the IHC investigation is biased by a subjective evaluation among cases considered negative (in the range of 1+) and positive (2+), and among cases considered positive 2+ and 3+. In such cases it is advisable to complement the IHC investigation by detection of copy numbers of the ERBB2 gene with fluorescence in situ hybridization (FISH). The overexpression of the protein is caused by the gene amplification in a majority of cases. The patients, whose carcinomas show overexpression of the ERBB-2 protein and the overexpression is caused by a significant gene amplification, profit from the Herceptin therapy. In this review we focus also on the methodology of FISH in paraffin sections and tissue imprints with respect to the detection of copy numbers of chromosome 17 and the ERBB2 gene.}, }
@article {pmid12673207, year = {2003}, author = {Kominsky, SL and Argani, P and Korz, D and Evron, E and Raman, V and Garrett, E and Rein, A and Sauter, G and Kallioniemi, OP and Sukumar, S}, title = {Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast.}, journal = {Oncogene}, volume = {22}, number = {13}, pages = {2021-2033}, doi = {10.1038/sj.onc.1206199}, pmid = {12673207}, issn = {0950-9232}, support = {P50 CA88843/CA/NCI NIH HHS/United States ; }, mesh = {Breast/cytology/*metabolism ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/pathology ; Carcinoma, Lobular/*chemistry/pathology ; Cell Adhesion/drug effects ; Cells, Cultured/chemistry/drug effects ; Claudins ; DNA Methylation ; Epithelial Cells/chemistry ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Hepatocyte Growth Factor/pharmacology ; Humans ; Membrane Proteins/biosynthesis/*deficiency/genetics/physiology ; Neoplasm Invasiveness/*genetics ; Neoplasm Proteins/biosynthesis/*deficiency/genetics/physiology ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; RNA, Messenger/analysis ; RNA, Neoplasm/analysis ; Sequence Analysis, DNA ; Severity of Illness Index ; Tight Junctions/*chemistry ; Tumor Cells, Cultured/chemistry/drug effects ; }, abstract = {Claudins are transmembrane proteins that seal tight junctions, and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Here, we report that Claudin-7 (CLDN-7) expression is lower in invasive ductal carcinomas (IDC) of the breast than in normal breast epithelium, as determined by both RT-PCR (9/10) and Western analysis (6/8). Immunohistochemical (IHC) analysis of ductal carcinoma in situ (DCIS) and IDC showed that the loss of CLDN-7 expression correlated with histological grade in both DCIS (P<0.001, n=38) and IDC (P=0.014, n=31), occurring predominantly in high-grade (Nuclear and Elston grade 3) lesions. Tissue array analysis of 355 IDC cases further confirmed the inverse correlation between CLDN-7 expression and histological grade (P=0.03). This pattern of expression is consistent with the biological function of CLDN-7, as greater discohesion is typically observed in high-grade lesions. In line with this observation, by IHC analysis, CLDN-7 expression was lost in the vast majority (13/17) of cases of lobular carcinoma in situ, which is defined by cellular discohesion. In fact, inducing disassociation of MCF-7 and T47D cells in culture by treating with HGF/scatter factor resulted in a loss of CLDN-7 expression within 24 h. Silencing of CLDN-7 expression correlated with promoter hypermethylation as determined by methylation-specific PCR (MSP) and nucleotide sequencing in breast cancer cell lines (3/3), but not in IDCs (0/5). In summary, these studies provide insight into the potential role of CLDN-7 in the progression and ability of breast cancer cells to disseminate.}, }
@article {pmid12653946, year = {2003}, author = {Skálová, A and Stárek, I and Vanecek, T and Kucerová, V and Plank, L and Szépe, P and Di Palma, S and Leivo, I}, title = {Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry.}, journal = {Histopathology}, volume = {42}, number = {4}, pages = {348-356}, doi = {10.1046/j.1365-2559.2003.01600.x}, pmid = {12653946}, issn = {0309-0167}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma/genetics/*metabolism/secondary ; Female ; Gene Amplification ; Gene Expression/*genetics ; *Genes, erbB-2 ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Parotid Neoplasms/genetics/*metabolism/pathology ; *Receptor, ErbB-2/genetics/metabolism ; *Salivary Ducts/pathology ; }, abstract = {AIMS: Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER-2/neu oncogene and over-expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER-2/neu using immunohistochemistry (IHC) has shown over-expression in most cases. However, correlation between IHC and molecular genetic analysis of HER-2/neu in salivary duct carcinoma has not yet been performed.<br><br>METHODS AND RESULTS: We have now evaluated 11 cases of salivary duct carcinomas for HER-2/neu status using IHC and fluorescent in-situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER-2/neu in salivary duct carcinoma.<br><br>CONCLUSIONS: In immunohistochemistry, over-expression of HER-2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER-2/neu gene by means of FISH analysis. Both amplified and non-amplified salivary duct carcinomas with strong immunohistochemical staining for HER-2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER-2/neu protein over-expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over-expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over-expression of HER-2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.}, }
@article {pmid12651069, year = {2003}, author = {Gansuvd, B and Hagihara, M and Higuchi, A and Ueda, Y and Tazume, K and Tsuchiya, T and Munkhtuvshin, N and Kato, S and Hotta, T}, title = {Umbilical cord blood dendritic cells are a rich source of soluble HLA-DR: synergistic effect of exosomes and dendritic cells on autologous or allogeneic T-Cell proliferation.}, journal = {Human immunology}, volume = {64}, number = {4}, pages = {427-439}, doi = {10.1016/s0198-8859(03)00016-8}, pmid = {12651069}, issn = {0198-8859}, mesh = {Adult ; *Antigen Presentation ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/cytology/*immunology ; Cell Differentiation ; Cells, Cultured ; Dendritic Cells/cytology/*immunology ; Female ; Fetal Blood/cytology/*immunology ; HLA-DR Antigens/*blood/metabolism ; Humans ; Lymphocyte Activation ; Monocytes/immunology ; Pregnancy ; T-Lymphocytes/immunology ; Transport Vesicles/*metabolism ; }, abstract = {In this study, we compared soluble HLA-DR (sHLA-DR) production in the culture supernatants of various cell sources [T and B cells, monocytes and dendritic cells (DCs) either from adult peripheral blood (PB) or umbilical cord blood (UCB)]. DCs produced the highest amount of sHLA-DR molecules as compared to other cell sources, with UCB DCs producing the highest amount. Different kinetics of sHLA-DR production were found between immature and mature UCB DCs (mDC, iDC) (derived either from CD34(+) or CD14(+) cells). Maximum production of sHLA-DR was observed in 72-hour culture supernatants of both CD34- and CD14-derived mDCs, whereas it peaked in the 24-hour culture supernatants from iDC. sHLA-DR molecules were pelleted after sequential centrifugation from UCB CD34(+) DCs and were found to contain both 36 kD alpha-chain and 29 kD beta-chain of HLA-DR, CD86, and Fas molecules. These sHLA-DR containing vesicles/exosomes alone evoked weak proliferative responses from autologous and allogeneic T cells, but the immune response was significantly increased when vesicles/exosomes were presented with DCs.}, }
@article {pmid12629061, year = {2003}, author = {Kitamura, N and Murata, S and Abe, H and Hanasawa, K and Tsukashita, S and Tani, T}, title = {Obstructive jaundice in a metastatic tumor of the pancreas from breast cancer: a case report.}, journal = {Japanese journal of clinical oncology}, volume = {33}, number = {2}, pages = {93-97}, doi = {10.1093/jjco/hyg018}, pmid = {12629061}, issn = {0368-2811}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*complications/*secondary ; Cholestasis/*etiology/pathology/therapy ; Fatal Outcome ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Pancreatic Neoplasms/*complications/*secondary ; }, abstract = {Metastatic pancreas tumors from breast cancer are comparatively uncommon and patients with this tumor usually remain asymptomatic during their life. A 55-year-old woman presented with obstructive jaundice following mastectomy for invasive ductal carcinoma. We diagnosed obstructive jaundice due to a pancreatic tumor demonstrated on computed tomography and performed percutaneous transhepatic cholangio-drainage. Although the patient recovered from the jaundice, she had exacerbation of pneumonia from which she died. At autopsy, invasive ductal carcinoma was found in the pancreas tumor. Immunohistochemical staining was performed to confirm whether the pancreatic tumor was primary or secondary. Human milk fat globules 1 and 2 and gross cystic disease fluid protein-15, which characteristically exist in normal breast tissue or breast carcinoma, were expressed both in the primary breast tumor and the pancreatic tumor. In contrast, both the anti-estrogen receptor and anti-progesterone receptor antibodies stained positively in the primary breast cancer; however, neither of them was positive in the metastatic pancreatic tumor. We report a rare case of a patient who presented with obstructive jaundice from a pancreatic tumor metastasizing from breast cancer and in whom immunohistochemical staining using the antibodies unique to the mammary gland was effective for the diagnosis of this secondary tumor.}, }
@article {pmid12607598, year = {2002}, author = {Lee, WY}, title = {Frequent loss of BRCA1 nuclear expression in young women with breast cancer: an immunohistochemical study from an area of low incidence but early onset.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {10}, number = {4}, pages = {310-315}, doi = {10.1097/00129039-200212000-00004}, pmid = {12607598}, issn = {1541-2016}, mesh = {Adult ; Age Factors ; Aged ; BRCA1 Protein/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Nucleus/metabolism ; Female ; Gene Expression ; Genes, BRCA1 ; Humans ; Immunohistochemistry ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Young women with breast cancer have a more unfavorable outcome and advanced disease than older women. This study was initiated to determine the difference in tumor biology between younger and older groups. One hundred fifty-five patients with invasive ductal carcinoma, not otherwise specified, comprised the study group, including 50 women aged less than 35 years, 50 aged 36 to 50 years, and 55 aged more than 50 years. Histopathologic parameters, including tumor size, combined histologic grade, and axillary lymph node status, were studied. Biomarkers, including estrogen receptor status, tumor proliferation rate as determined by Ki-67, and gene expressions of c-erbB-2, p53, bcl-2, and BRCA1, were determined by immunohistochemistry. Comparisons of the distribution of these parameters in three age groups were performed. Breast cancer occurring in women aged less than 35 years had a significantly higher incidence of large tumor, high proliferation rate, and loss of nuclear BRCA1 expression (44.0% versus 22.0% or 23.6%) than in the two older age groups. Breast cancer in women aged less than 35 years also had higher histologic grade and higher frequency of bcl-2-negative tumor than that found in the 36- to 50-year age group. No difference was found in lymph node status and c-erbB-2 and p53 gene expressions between the age groups. Loss of BRCA1 nuclear expression significantly correlated with higher histologic grade and high Ki-67 index (P < 0.05) in group A. These findings suggested that women aged less than 35 years have frequent loss of nuclear BRCA1 expression, which may be responsible for the specific tumor biology different from older women. However, c-erbB-2 and p53 gene expressions seem to have no important role in the adverse tumor behavior of breast cancer in young women.}, }
@article {pmid12601182, year = {2003}, author = {Lee, SG and Orel, SG and Woo, IJ and Cruz-Jove, E and Putt, ME and Solin, LJ and Czerniecki, BJ and Schnall, MD}, title = {MR imaging screening of the contralateral breast in patients with newly diagnosed breast cancer: preliminary results.}, journal = {Radiology}, volume = {226}, number = {3}, pages = {773-778}, doi = {10.1148/radiol.2263020041}, pmid = {12601182}, issn = {0033-8419}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology ; Chi-Square Distribution ; Contrast Media ; Feasibility Studies ; Female ; Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis ; Risk Factors ; Statistics, Nonparametric ; }, abstract = {PURPOSE: To investigate the role of screening magnetic resonance (MR) imaging in the detection of synchronous contralateral breast cancer in patients with newly diagnosed breast cancer.<br><br>MATERIALS AND METHODS: Between January 1999 and July 2001, 182 patients with newly diagnosed breast cancer (after either core or excisional biopsy with positive or close margins of resection) underwent bilateral contrast material-enhanced MR imaging at 1.5 T with a dedicated bilateral breast multicoil array. The contralateral breast was imaged for cancer screening. Family history of breast cancer, index cancer histology, breast density, and age at diagnosis of first breast cancer were assessed as potential risk factors for synchronous contralateral breast cancer.<br><br>RESULTS: Fifteen patients (8.2%) had a suspicious enhancing lesion depicted in the contralateral breast. Seven patients (3.8%) had malignant results: ductal carcinoma in situ (DCIS) in four, invasive ductal carcinoma with DCIS in two, and invasive ductal carcinoma in one. Eight patients (4.4%) had benign results: fibrocystic changes in four, atypical ductal hyperplasia in two, atypical lobular hyperplasia and focal lobular carcinoma in situ in one, and ductal hyperplasia in one. Six patients with negative MR findings underwent prophylactic mastectomy; no malignancy was found. No significant differences were noted among patients with true-positive (n = 7), false-positive (n = 8), or negative (n = 167) MR findings with regard to family history of breast cancer (P <.27), index cancer histology (P <.19), breast density (P <.34), or age at diagnosis of first breast cancer (P <.10).<br><br>CONCLUSION: The preliminary results demonstrate the feasibility of using MR imaging of the breast in a screening role, specifically to evaluate the contralateral breast in patients with newly diagnosed breast cancer to detect mammographically and clinically occult synchronous breast cancer.}, }
@article {pmid12570949, year = {2003}, author = {Arenal, A and Glez-Torrecilla, E and Ortiz, M and Villacastín, J and Fdez-Portales, J and Sousa, E and del Castillo, S and Perez de Isla, L and Jimenez, J and Almendral, J}, title = {Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease.}, journal = {Journal of the American College of Cardiology}, volume = {41}, number = {1}, pages = {81-92}, doi = {10.1016/s0735-1097(02)02623-2}, pmid = {12570949}, issn = {0735-1097}, mesh = {Adult ; Aged ; Body Surface Potential Mapping/methods ; Catheter Ablation/*methods ; Electrophysiologic Techniques, Cardiac/methods ; Feasibility Studies ; Female ; Heart Diseases/complications/surgery ; Humans ; Incidence ; Male ; Middle Aged ; Tachycardia, Ventricular/complications/epidemiology/*surgery ; Treatment Outcome ; }, abstract = {OBJECTIVES: We sought to evaluate the feasibility of identifying and ablating the substrate of unmappable ventricular tachycardia (VT).<br><br>BACKGROUND: Noninducible and nonstable VT cannot be ablated by the conventional approach.<br><br>METHODS: We studied 24 patients with documented monomorphic VT. Twenty-one patients had ischemic cardiomyopathy, two had nonischemic cardiomyopathy, and one had tetralogy of Fallot. Twelve patients had an implantable cardioverter-defibrillator. Conventional activation mapping was not possible in 18 patients: at least 1 of the clinical VTs or the clinical VT was not inducible in 12 patients, and VT was not tolerated in 6 patients. This group had experienced between 1 and 106 VT episodes in the month before the ablation procedure. Endocardial electroanatomic activation maps (Carto System) during sinus rhythm (SR) and right ventricular apex (RVA) pacing were obtained to define areas for which an electrogram displayed isolated, delayed components (E-IDC). These electrograms were characterized by double or multiple components separated by >/=50 ms.<br><br>RESULTS: One area of E-IDC was recorded in 20 patients, and 2 or more were recorded in 4 patients. In 23 patients, these areas were detected during RVA pacing; in only 14 during SR. An E-IDC area related to the clinical VT was identified in each patient. Ablation guided by E-IDC suppressed all but one clinical VT whose inducibility suppression was tested. During a follow-up period of 9 +/- 4 months, three patients had recurrences of the ablated VT and two of a different VT.<br><br>CONCLUSIONS: Electrograms with IDCs related to clinical VT can be identified in the majority of patients during RVA pacing. Radiofrequency ablation of E-IDC seems effective in controlling unmappable VT.}, }
@article {pmid12560691, year = {2003}, author = {Spiegel, AJ and Butler, CE}, title = {Recurrence following treatment of ductal carcinoma in situ with skin-sparing mastectomy and immediate breast reconstruction.}, journal = {Plastic and reconstructive surgery}, volume = {111}, number = {2}, pages = {706-711}, doi = {10.1097/01.PRS.0000041440.12442.05}, pmid = {12560691}, issn = {0032-1052}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/etiology/*surgery ; Carcinoma, Ductal, Breast/etiology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/etiology/*surgery ; Follow-Up Studies ; Humans ; *Mammaplasty ; *Mastectomy, Segmental ; *Mastectomy, Subcutaneous ; Middle Aged ; Neoplasm Recurrence, Local/*etiology ; Postoperative Complications/*etiology ; Reoperation ; Retrospective Studies ; Risk ; }, abstract = {Skin-sparing mastectomy with immediate breast reconstruction can provide an excellent cosmetic result. Despite its increasing popularity, few studies have assessed the risk of recurrence when the procedure is used for the treatment of ductal carcinoma in situ. To evaluate the oncologic safety of skin-sparing mastectomy used for the treatment of ductal carcinoma in situ, the recurrence rate was analyzed. Patients with ductal carcinoma in situ or invasive carcinoma or both who underwent skin-sparing mastectomy with immediate breast reconstruction between 1985 and 1994 and had a follow-up period of at least 6 years were included in this retrospective analysis. The recurrence rates were determined for invasive carcinoma (with or without foci of ductal carcinoma in situ) and ductal carcinoma in situ alone. A total of 221 patients were included, 177 patients with invasive carcinoma and 44 patients with ductal carcinoma in situ alone. The immediate breast reconstructions were performed with transverse rectus abdominis muscle (TRAM) flaps in 62 percent of patients, implants in 34 percent of patients, and latissimus dorsi myocutaneous flaps (with or without implants) in 4 percent of patients. The local recurrence rate was zero of 44 for patients with ductal carcinoma in situ and 5.6 percent (10 of 177) for patients with invasive carcinoma during a mean follow-up period of 9.8 years. There was a 6.8 percent (12 of 177) metastatic recurrence rate in the invasive carcinoma group. All recurrences were invasive ductal carcinoma. Of the patients with ductal carcinoma in situ alone, none developed metastatic disease. The combined metastatic and local recurrence rates for the invasive carcinoma group (n = 177) with each type of reconstruction were 13 percent (14 of 110), 12 percent (seven of 60), and 14 percent (one of seven) for TRAM flaps, implants, and latissimus dorsi flaps, respectively. The risk of recurrence following skin-sparing mastectomy and immediate breast reconstruction for ductal carcinoma in situ is low during this follow-up period. Therefore, skin-sparing mastectomy with immediate breast reconstruction seems to be a safe oncologic treatment option for ductal carcinoma in situ; however, a longer follow-up period is important to determine the long-term risk of recurrence.}, }
@article {pmid12560343, year = {2003}, author = {Königshoff, M and Wilhelm, J and Bohle, RM and Pingoud, A and Hahn, M}, title = {HER-2/neu gene copy number quantified by real-time PCR: comparison of gene amplification, heterozygosity, and immunohistochemical status in breast cancer tissue.}, journal = {Clinical chemistry}, volume = {49}, number = {2}, pages = {219-229}, doi = {10.1373/49.2.219}, pmid = {12560343}, issn = {0009-9147}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*genetics ; Female ; Gene Dosage ; Heterozygote ; Humans ; Immunohistochemistry ; Middle Aged ; Polymerase Chain Reaction ; Receptor, ErbB-2/*genetics ; }, abstract = {BACKGROUND: Amplification of the oncogene HER-2/neu influences breast cancer pathogenesis, and therapy and prognosis may be affected by the degree of amplification. The extent of amplification or protein overexpression typically is analyzed by fluorescence in situ hybridization or immunohistochemistry (IHC), but quantitative PCR techniques have been described that may provide alternatives to these methods.<br><br>METHODS: We developed a rapid-cycle, real-time PCR assay for quantification of HER-2/neu gene status. We compared results obtained with this assay with short tandem repeat findings by capillary electrophoresis (CE) and with protein overexpression assessments by IHC. Accuracy and linearity were tested on cell lines and with simulation experiments. We analyzed the amplification of HER-2/neu in 51 clinical tissue samples from patients with suspected breast cancer.<br><br>RESULTS: The intra- and interrun CVs for HER-2/neu quantification by real-time PCR were 12% and 18%, and the CV for different simulated amplification and deletion experiments was <7%. The results for HER-2/neu gene status in cell lines matched the values reported in literature. We detected HER-2/neu amplification by real-time PCR in 11 samples, all from patients with invasive ductal carcinoma. Allelic imbalances were found by CE analyses in three samples and by protein overexpression in six samples; five of these were also detected by real-time PCR. Comparison of the quantification results with known prognostic indices yielded results similar to those reported in several other published studies.<br><br>CONCLUSIONS: The assay is suitable for accurate and precise quantification of HER-2/neu copy numbers in tumor tissue samples obtained in routine clinical practice.}, }
@article {pmid12559622, year = {2003}, author = {Luppi, P and Rudert, W and Licata, A and Riboni, S and Betters, D and Cotrufo, M and Frati, G and Condorelli, G and Trucco, M}, title = {Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection.}, journal = {Human immunology}, volume = {64}, number = {2}, pages = {194-210}, doi = {10.1016/s0198-8859(02)00798-x}, pmid = {12559622}, issn = {0198-8859}, mesh = {Adolescent ; Adult ; Aged ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cardiomyopathy, Dilated/etiology/*immunology/virology ; Child ; Chlorocebus aethiops ; Complementarity Determining Regions/genetics ; Cytokines/biosynthesis/genetics ; DNA, Viral/isolation &amp; purification ; Diabetes Mellitus, Type 1/genetics ; Enterovirus B, Human/*pathogenicity ; Enterovirus Infections/complications/*immunology/virology ; Female ; Gene Expression Profiling ; Gene Frequency ; Gene Rearrangement, T-Lymphocyte ; Genes, T-Cell Receptor alpha ; Genes, T-Cell Receptor beta ; Genetic Predisposition to Disease ; HLA-DQ Antigens/genetics ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; HLA-DR Antigens/genetics ; HLA-DR4 Antigen/genetics ; HLA-DRB1 Chains ; Humans ; Lymphocyte Activation ; Macrophages/immunology ; Male ; Middle Aged ; Myocarditis/etiology/*immunology/virology ; Myocardium/*immunology/metabolism ; RNA, Messenger/analysis ; Receptors, Antigen, T-Cell, alpha-beta/*analysis ; T-Lymphocyte Subsets/*immunology ; Vero Cells/virology ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is one of the major causes of death in humans and has been linked to Coxsackievirus B (CVB) infection. The aim of this study was to analyze phenotypes of heart-infiltrating immune cells in patients suffering from myocarditis and IDC associated with CVB infections. We found that the myocardium of these patients was infiltrated by CD4(+) and CD8(+) T lymphocytes as well as macrophages. Evidence of CVB3/4 infections was also found. In the majority of patients, the T-cell receptor repertoire (TCR) of the infiltrating lymphocytes was restricted, with a polyclonal expansion of the Vbeta7 gene family. We also found that human leukocyte antigen (HLA) class II alleles associated with susceptibility to type 1 diabetes (HLA-DR4 and HLA-DQA1*04/05/06 alleles) were remarkably infrequent in IDC patients (p < 0.005), thus suggesting that they might confer protection against IDC. Finally, mRNA for interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha was detected in the cardiac specimens, although at a lower level compared with specimens from hearts without signs of viral infections. We conclude that CVB infection of the human myocardium is associated with a selective, yet polyclonal activation of different T-cell subsets in genetically susceptible individuals. This immune response may play a critical role in modulating disease progression after viral infections.}, }
@article {pmid12538684, year = {2003}, author = {Brown, JA and Dorfman, DM and Ma, FR and Sullivan, EL and Munoz, O and Wood, CR and Greenfield, EA and Freeman, GJ}, title = {Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {170}, number = {3}, pages = {1257-1266}, doi = {10.4049/jimmunol.170.3.1257}, pmid = {12538684}, issn = {0022-1767}, support = {AI39671/AI/NIAID NIH HHS/United States ; AI41584/AI/NIAID NIH HHS/United States ; CA84500/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD ; *Antigens, Surface ; Apoptosis/immunology ; Apoptosis Regulatory Proteins ; *B7-1 Antigen ; B7-H1 Antigen ; Binding, Competitive/immunology ; Blood Proteins/*antagonists &amp; inhibitors/biosynthesis/immunology/*metabolism ; Breast Neoplasms/immunology/metabolism ; CD4-Positive T-Lymphocytes/*immunology/metabolism ; Cell Membrane/immunology/metabolism ; Cells, Cultured ; Cytokines/*biosynthesis ; Dendritic Cells/cytology/*immunology ; Female ; Humans ; Immunoglobulin Fab Fragments/metabolism/pharmacology ; Intercellular Signaling Peptides and Proteins ; Ligands ; Lymphocyte Activation/*immunology ; Membrane Glycoproteins ; Mice ; Monocytes/immunology/metabolism ; Organ Specificity/immunology ; Peptides/*antagonists &amp; inhibitors/immunology/*metabolism ; Programmed Cell Death 1 Ligand 2 Protein ; Programmed Cell Death 1 Receptor ; Proteins/antagonists &amp; inhibitors/immunology/metabolism ; Tumor Cells, Cultured ; }, abstract = {Programmed death-1 ligand (PD-L)1 and PD-L2 are ligands for programmed death-1 (PD-1), a member of the CD28/CTLA4 family expressed on activated lymphoid cells. PD-1 contains an immunoreceptor tyrosine-based inhibitory motif and mice deficient in PD-1 develop autoimmune disorders suggesting a defect in peripheral tolerance. Human PD-L1 and PD-L2 are expressed on immature dendritic cells (iDC) and mature dendritic cells (mDC), IFN-gamma-treated monocytes, and follicular dendritic cells. Using mAbs, we show that blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-gamma and IL-10, while blockade of PD-L1 results in similar, more modest, effects. Blockade of both PD-L1 and PD-L2 showed an additive effect. Both whole mAb and Fab enhanced T cell activation, showing that PD-L1 and PD-L2 function to inhibit T cell activation. Enhancement of T cell activation was most pronounced with weak APC, such as iDCs and IL-10-pretreated mDCs, and less pronounced with strong APC such as mDCs. These data are consistent with the hypothesis that iDC have a balance of stimulatory vs inhibitory molecules that favors inhibition, and indicate that PD-L1 and PD-L2 contribute to the poor stimulatory capacity of iDC. PD-L1 expression differs from PD-L2 in that PD-L1 is expressed on activated T cells, placental trophoblasts, myocardial endothelium, and cortical thymic epithelial cells. In contrast, PD-L2 is expressed on placental endothelium and medullary thymic epithelial cells. PD-L1 is also highly expressed on most carcinomas but minimally expressed on adjacent normal tissue suggesting a role in attenuating antitumor immune responses.}, }
@article {pmid12532908, year = {2002}, author = {Mrhalová, M and Kodet, R and Strnad, P}, title = {[Invasive ductal carcinoma of the breast: study of the number of copies of the CCND1 gene and chromosome 11 using fluorescence in situ hybridization (FISH) in comparison with expression of cyclin D1 protein and estrogen receptors (ER alpha) with immunohistochemical detection].}, journal = {Casopis lekaru ceskych}, volume = {141}, number = {22}, pages = {708-714}, pmid = {12532908}, issn = {0008-7335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism ; Breast Neoplasms, Male/genetics ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Chromosomes, Human, Pair 11/*genetics ; Cyclin D1/*genetics/metabolism ; Estrogen Receptor alpha ; Female ; *Gene Amplification ; Humans ; *In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Receptors, Estrogen/*analysis ; }, abstract = {BACKGROUND: Overexpression of oncogenic proteins may be caused by gene amplifications. Cyclin D1 participates in regulation of the cell cycle. Relations between cyclin D1 expression and amplification of CCND1 gene encoding this protein in invasive duct breast carcinomas (IDC) are not fully elucidated. An increased interest is also focused on relations to the estrogen receptor (ER alpha).<br><br>METHODS AND RESULTS: We investigated copy numbers of the CCND1 gene, expression of cyclin D1 and expression of ER alpha in a group of 60 females and 1 male with IDC. The age range varied from 33 to 89 years (median 57 years). The number of CCND1 gene copies and the number of chromosome 11 was evaluated using FISH, the expression of cyclin D1 and ER alpha was investigated by IHC. We detected a strong amplification of CCND1 gene (> 10 copies per tumor cell nuclei) in 9 patients, weak amplification (< or = copies) in 16 patients. Amplification of the CCND1 gene correlated well with the overexpression of cyclin D1. We observed the overexpression of cyclin D1 also in 13 of 36 patients without the gene amplification; therefore, the mechanism of the protein overexpression is different than that caused by the gene amplification in a proportion of patients. Amplification of the CCND1 gene was associated with a high histologic grade of IDC, whereas cases with cyclin D1 overexpression only were not. 24 of 31 patients with overexpression of cyclin D1 coexpressed ER alpha. We did not find correlation between expression/amplification of cyclin D1/CCND1 gene and the size of carcinomas and with metastases to the axillary lymph nodes.<br><br>CONCLUSIONS: Amplification of the CCND1 gene is associated with overexpression of cyclin D1 in a majority of IDC. Overexpression of cyclin D1 is related to an increased expression of ER alpha. Interaction between cyclin D1 and ER alpha may explain low response to anti-estrogen therapy of some patients.}, }
@article {pmid12525766, year = {2003}, author = {Zhang, Z and Yamashita, H and Toyama, T and Omoto, Y and Sugiura, H and Hara, Y and Haruki, N and Kobayashi, S and Iwase, H}, title = {Estrogen receptor alpha mutation (A-to-G transition at nucleotide 908) is not found in different types of breast lesions from Japanese women.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {10}, number = {1}, pages = {70-73}, doi = {10.1007/BF02967628}, pmid = {12525766}, issn = {1340-6868}, mesh = {Adult ; Aged ; Asian People/*genetics ; Breast Diseases/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics ; Female ; Humans ; Japan ; Middle Aged ; *Mutation ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Precancerous Conditions/genetics ; Receptors, Estrogen/*genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: An estrogen receptor (ER) alpha variant with an A-to-G transition at nucleotide 908 (A908G) has been identified in typical hyperplastic mammary epithelium. This somatic mutation, which induces a Lys-to-Arg substitution at residue 303 within exon 4 at the border of the hinge and hormone-binding domains of the ER alpha, shows increased sensitivity to estrogen compared with wild-type ER alpha.<br><br>METHODS: To investigate whether this mutation was present in breast lesions, we performed mutation analyses using the PCR-restriction fragment length polymorphism (RFLP) method in 7 cases of hyperplasia, 18 cases of benign breast tumor, 26 cases of ductal carcinoma in situ (DCIS) and 215 cases of invasive ductal carcinoma (IDC). When we extracted DNA, the hyperplastic epithelium and cancer cells of DCIS were microdissected. We also performed direct sequencing analysis from 7 randomly-selected representative cases of hyperplasia, 9 cases of benign breast tumors, 11 cases of DCIS and 20 cases of IDC.<br><br>RESULTS: No A908G mutation was found in the ER alpha gene in these breast lesions.<br><br>CONCLUSION: This mutation might be absent or occur in so few cells as to be undetectable by PCR-RFLP or direct sequencing.}, }
@article {pmid12519301, year = {2003}, author = {Kikuchi, K and Yanagawa, Y and Aranami, T and Iwabuchi, C and Iwabuchi, K and Onoé, K}, title = {Tumour necrosis factor-alpha but not lipopolysaccharide enhances preference of murine dendritic cells for Th2 differentiation.}, journal = {Immunology}, volume = {108}, number = {1}, pages = {42-49}, pmid = {12519301}, issn = {0019-2805}, mesh = {Animals ; Cell Culture Techniques ; Cell Differentiation/immunology ; Cell Line ; Dendritic Cells/cytology/*immunology ; Dose-Response Relationship, Immunologic ; Immunophenotyping ; Interleukin-12/biosynthesis ; Lipopolysaccharides/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Th1 Cells/immunology ; Th2 Cells/*immunology ; Tumor Necrosis Factor-alpha/*immunology ; }, abstract = {Using murine spleen-derived dendritic cells (DC) and DO11.10 T cells specific for ovalbumin (OVA), the influences of maturational condition and antigen dose on the capability of DC to induce helper T-cell (Th) differentiation were analysed. Immature DC (iDC) with high- or low-dose OVA(323-339) predominantly induced Th1 or Th2 responses in DO11.10 T cells, respectively. DC matured by tumour necrosis factor-alpha (TNF/DC) induced a significantly higher Th2 response in the presence of low-dose OVA(323-339) than iDC and DC matured by lipopolysaccharide (LPS) (LPS/DC). In the presence of high-dose OVA(323-339), LPS/DC induced significantly lower levels of Th1 response than iDC. Under these conditions no difference in the Th1 response was noted between TNF/DC and iDC. The enhanced capability of TNF/DC with a low-dose antigen for Th2 polarization and the decreased preference of LPS/DC with a high-dose antigen to Th1 polarization were not related to the amount of IL-12 produced in these cultures. These results demonstrate for the first time that TNF/DC with a low-dose antigen are potent inducers of Th2 differentiation.}, }
@article {pmid12506168, year = {2003}, author = {Hoogerbrugge, N and Bult, P and de Widt-Levert, LM and Beex, LV and Kiemeney, LA and Ligtenberg, MJ and Massuger, LF and Boetes, C and Manders, P and Brunner, HG}, title = {High prevalence of premalignant lesions in prophylactically removed breasts from women at hereditary risk for breast cancer.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {21}, number = {1}, pages = {41-45}, doi = {10.1200/JCO.2003.02.137}, pmid = {12506168}, issn = {0732-183X}, mesh = {Adult ; Age Distribution ; Breast Neoplasms/*epidemiology/*genetics/pathology/prevention &amp; control ; Carcinoma in Situ/epidemiology/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/genetics/pathology ; Female ; *Genetic Predisposition to Disease ; Humans ; Hyperplasia/epidemiology/genetics/pathology ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Precancerous Conditions/*epidemiology/*genetics/pathology ; Prevalence ; Prospective Studies ; ROC Curve ; Risk ; }, abstract = {PURPOSE: Women with a hereditary predisposition for breast cancer have an extremely high risk of developing invasive breast carcinoma, and many women consider prophylactic mastectomy to avoid this risk. The use of prophylactic mastectomy is still debated. Identification of frequent premalignant lesions in mastectomy specimens would support the preventive concept of prophylactic mastectomy.<br><br>PATIENTS AND METHODS: We performed a prospective study of breast specimens from 67 women at extremely high genetic risk of breast cancer, with or without previous breast cancer, who were undergoing prophylactic mastectomy (66% were carriers of a BRCA1 or BRCA2 mutation). Breast specimens were studied by radiographic and macroscopic examination of 5-mm tissue slices, with subsequent histology of suspicious lesions and random samples from each quadrant of the breast and the nipple area.<br><br>RESULTS: In 57% of the women, one or more different types of high-risk histopathologic lesions were present: 37% atypical lobular hyperplasia, 39% atypical ductal hyperplasia, 25% lobular carcinoma-in-situ, and 15% ductal carcinoma-in-situ. A 4-mm invasive ductal carcinoma was found in one woman with ductal carcinoma-in-situ. None of these lesions was detected at palpation or mammography, which were performed before the mastectomy. The presence of high-risk lesions was independently related to age older than 40 years (odds ratio, 6.6; P =.01) and to bilateral oophorectomy before prophylactic mastectomy (odds ratio, 0.2; P = 0.02).<br><br>CONCLUSION: Many women at high risk of hereditary breast cancer develop high-risk histopathologic lesions, especially after the age of 40 years. Surveillance does not detect such high-risk histopathologic lesions.}, }
@article {pmid12486098, year = {2002}, author = {Verbovetski, I and Bychkov, H and Trahtemberg, U and Shapira, I and Hareuveni, M and Ben-Tal, O and Kutikov, I and Gill, O and Mevorach, D}, title = {Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7.}, journal = {The Journal of experimental medicine}, volume = {196}, number = {12}, pages = {1553-1561}, pmid = {12486098}, issn = {0022-1007}, mesh = {Antigens, CD/immunology/*metabolism ; *Apoptosis ; B7-2 Antigen ; Complement C3b/*immunology ; Complement System Proteins/immunology/metabolism ; Dendritic Cells/*immunology ; Down-Regulation ; Genes, MHC Class II ; HLA-DR Antigens/*metabolism ; Humans ; Integrin alphaXbeta2/metabolism ; Jurkat Cells ; Macrophage-1 Antigen/metabolism ; Membrane Glycoproteins/*metabolism ; Opsonin Proteins/*immunology ; Receptors, CCR7 ; Receptors, Chemokine/*metabolism ; Up-Regulation ; }, abstract = {Immature dendritic cells (iDCs) do not mature after uptake of apoptotic cells and may play a role in the induction of peripheral tolerance to self antigens derived from apoptotic material. The integrins, alphavbeta3, alphavbeta5, and the scavenger receptor, CD36, have been shown to mediate uptake of apoptotic cells by iDCs. However, it is not known whether the complement system, also takes part in this process. In this study we investigated the ability of iDCs to bind to apoptotic cells opsonized by iC3b. Monocyte-derived dendritic cells were offered apoptotic Jurkat cells opsonized by autologous iC3b and labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate. A significant increase (P < 0.001) in the amount of cleared apoptotic cells was seen at low ratios. Despite increased efficiency of uptake, interaction between iC3b-opsonized apoptotic cells and iDCs down-regulated the expression of major histocompatibility complex class II, CD86, CC chemokine receptor (CCR)2, CCR5, and beta2-integrins (P < 0.001), and up-regulated expression of CCR7 (P < 0.001). In addition, iDC maturation responses to CD40L and lipopolysaccharide were significantly inhibited. We conclude that opsonization of apoptotic cells by iC3b induces tolerant iDCs that are able to migrate to lymph nodes.}, }
@article {pmid12481013, year = {2002}, author = {Latta, EK and Tjan, S and Parkes, RK and O'Malley, FP}, title = {The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {15}, number = {12}, pages = {1318-1325}, doi = {10.1097/01.MP.0000038462.62634.B1}, pmid = {12481013}, issn = {0893-3952}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/biosynthesis/*genetics ; }, abstract = {HER2/neu overexpression/amplification is seen more frequently in ductal carcinoma in situ, particularly high-grade ductal carcinoma in situ (50-60%), than in invasive ductal carcinoma of the breast (25-30%). To date, however, the role of HER2/neu in the progression of in situ to invasive disease has not been clarified. Two hundred fifty-one breast tumors were retrieved from the pathology files at Mount Sinai Hospital. These included 91 cases of ductal carcinoma in situ, 136 cases of invasive ductal carcinomas with associated ductal carcinoma in situ, and 24 cases of pure invasive carcinomas. All cases were reviewed and stained with two monoclonal antibodies to HER2/neu (CB11 and TAB250). Immunohistochemical staining was recorded using a semiquantitative scoring system (1). Representative cases were also investigated using fluorescence in situ hybridization. HER2/neu protein overexpression (defined as immunohistochemical staining with score of >or=5) was seen in 34% of cases of pure ductal carcinoma in situ, 17% of invasive carcinomas with associated ductal carcinoma in situ, and 12.5% of pure invasive carcinomas (P =.01). Sixty percent of cases of high-grade ductal carcinoma in situ showed HER2/neu protein overexpression, versus 29% of high-grade invasive carcinomas with associated ductal carcinoma in situ and 22% of high-grade pure invasive ductal carcinomas (P =.02). The concordance between the immunohistochemical staining in the in situ and invasive components of individual tumors was 90%. Thirty-three cases were also evaluated by fluorescence in situ hybridization and showed concordance between the immunohistochemical results and the degree of gene amplification in 91% of cases, whereas 3 of 33 cases showed HER2/neu gene amplification (HER2/CEP17 = 2.3-3.7) by fluorescence in situ hybridization in the absence of positive immunohistochemical staining. One case showed HER2/neu gene amplification in the associated ductal carcinoma in situ (HER2/CEP17 ratio = 6.5), with no evidence of gene amplification in the invasive tumor (HER2/CEP17 ratio = 1.14). Multiple genetic events are required for the development of an invasive phenotype. The findings from this study suggest that the genetic event of HER2/neu gene amplification/protein overexpression may not play a key role in the progression of ductal carcinoma in situ to invasive carcinoma and that other molecular alterations may be more important in the initiation of invasion in ductal carcinoma of the breast.}, }
@article {pmid12475464, year = {2002}, author = {Fauchier, L and Marie, O and Casset-Senon, D and Babuty, D and Cosnay, P and Fauchier, JP}, title = {Interventricular and intraventricular dyssynchrony in idiopathic dilated cardiomyopathy: a prognostic study with fourier phase analysis of radionuclide angioscintigraphy.}, journal = {Journal of the American College of Cardiology}, volume = {40}, number = {11}, pages = {2022-2030}, doi = {10.1016/s0735-1097(02)02569-x}, pmid = {12475464}, issn = {0735-1097}, mesh = {Adult ; Cardiomyopathy, Dilated/diagnosis/*etiology/*physiopathology ; Electrocardiography ; Female ; Follow-Up Studies ; Gated Blood-Pool Imaging ; Heart Ventricles/diagnostic imaging/physiopathology ; Hemodynamics/physiology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Severity of Illness Index ; Statistics as Topic ; Time Factors ; Ventricular Dysfunction/diagnosis/*etiology/*physiopathology ; }, abstract = {OBJECTIVES: The study evaluated the prognostic value of interventricular and intraventricular dyssynchrony in idiopathic dilated cardiomyopathy (IDC).<br><br>BACKGROUND: Biventricular pacing is an emerging treatment for patients with dilated cardiomyopathy and ventricular dyssynchrony. The prognostic values of interventricular and intraventricular dyssynchrony have not been previously compared.<br><br>METHODS: A total of 103 patients with IDC were studied. Left bundle branch block was present in 25% of patients. Equilibrium radionuclide angiography was performed and Fourier phase analyses were examined in both ventricles. Difference between the mean phase of left ventricle (LV) and right ventricle (RV) assessed interventricular dyssynchrony, and standard deviations (SDs) of the mean phase in each ventricle assessed intraventricular dyssynchrony.<br><br>RESULTS: The QRS duration was related to both interventricular and intraventricular dyssynchrony. A degradation of the hemodynamic status was associated with an increase in intraventricular dyssynchrony but not in interventricular dyssynchrony. With a follow-up of 27 +/- 23 months, 18 patients had a major cardiac event (7 cardiac deaths; 11 worsening, leading to heart transplantation). The SDs of the LV and RV mean phase and QRS duration were predictors of cardiac event (all p < 0.0001), but interventricular dyssynchrony was not. Among 13 univariate predictors of cardiac event, the only independent predictors were an increased SD of LV mean phase (p = 0.0004) and an increased pulmonary capillary wedge pressure (p = 0.009).<br><br>CONCLUSIONS: Intraventricular dyssynchrony evaluated with phase analysis of radionuclide angiography is an independent predictor of cardiac event in IDC. The prognosis is related to intraventricular rather than to interventricular dyssynchrony in IDC.}, }
@article {pmid12461672, year = {2002}, author = {Livesey, G}, title = {Thermogenesis associated with fermentable carbohydrate in humans, validity of indirect calorimetry, and implications of dietary thermogenesis for energy requirements, food energy and body weight.}, journal = {International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity}, volume = {26}, number = {12}, pages = {1553-1569}, doi = {10.1038/sj.ijo.0802168}, pmid = {12461672}, mesh = {Body Weight/*physiology ; Calorimetry, Indirect/*standards ; Cross-Over Studies ; Dietary Carbohydrates/*metabolism ; Energy Intake/physiology ; Female ; Fermentation/physiology ; Humans ; Middle Aged ; Randomized Controlled Trials as Topic ; Terminology as Topic ; Thermogenesis/*physiology ; }, abstract = {BACKGROUND: Animal studies and theory show fermentable carbohydrate (FC) intake causes appreciably thermogenesis, but a similar occurrence in humans is controversial.<br><br>HYPOTHESES: (a) That indirect calorimetry (IDC) is a valid method to assess thermogenesis during fermentation. (b) That a consistent and rigorous approach to the analysis of published IDC data from human studies will establish a representative thermogenic response to FC. (c) That conventional estimates of food energy and energy requirements can mismatch appreciably, more especially when thermogenesis is ignored.<br><br>PURPOSE: To derive information and understanding of IDC, thermogenesis and energy balance in relation to food energy and energy requirement estimates.<br><br>METHODS: (a) The validities of IDC equations that estimate the heat of reaction and carbohydrate utilization were assessed for various types of FCs under various circumstances. (b) Pooled analysis of eight published randomized cross-over studies in humans with elevation of FC intake. Studies were analysed for the first time or reanalysed according to a consistent approach with appropriate corrections for confounders. (c) Some 1500 regular and 'special' diet compositions were examined to assess the extent to which Atwater general food energy factors and updated estimates of energy requirements mismatch due to variation in substrate-associated thermogenesis and substrate-associated faecal+urinary energy losses. Impact of such mismatches on BMI was assessed under conditions of all else being equal.<br><br>RESULTS: (a) Indirect calorimetry was valid, providing robust estimates of heat production during various types of fermentation; only small correction factors were necessary. By contrast, IDC equations for carbohydrate utilization sometimes applied poorly to FC. (b) A best estimate of thermogenesis in humans due to fermentation, above that due to oral glucose as a reference standard, was 0.39 (s.e.m. 0.14) kJ per kJ net metabolizable energy (NME; P<0.05, n=8 studies, total 72 humans) compared with 0.34 kJ/kJ from theory. Six sources of bias were identified; all had potential to underestimate FC thermogenesis. (c) Mismatches in energy availability and requirement estimates were often marked and translated into long-term differences in body mass index from approximately 20 to 33 kg/m(2) in average-height middle-aged initially obese women, and from approximately 22 to a non-survivable 13 kg/m(2) in initially slim women.<br><br>CONCLUSIONS: (a) Indirect calorimetry is valid for the present purpose. (b) Thermogenesis in response to FC is real in humans and is comparable to that in animals and in theory. (c) Mismatches between estimates of energy requirements and dietary energy as metabolizable energy means the two expressions are not directly comparable, which has implications for the expression of food energy, energy requirements and the conduct and interpretation of research related to body weight.}, }
@article {pmid12455059, year = {2003}, author = {Hamanaka, Y and Suehiro, Y and Fukui, M and Shikichi, K and Imai, K and Hinoda, Y}, title = {Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer.}, journal = {International journal of cancer}, volume = {103}, number = {1}, pages = {97-100}, doi = {10.1002/ijc.10801}, pmid = {12455059}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Neoplasm/*blood ; Autoantibodies/*blood ; Carcinoma, Ductal, Breast/*immunology/mortality/pathology ; Female ; Humans ; Immunoenzyme Techniques ; Immunoglobulin G/*blood ; Male ; Middle Aged ; Mucin-1/*immunology ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*immunology/mortality/pathology ; Prognosis ; Survival Rate ; Transfection ; }, abstract = {MUC1 is immunogenic in vivo and humoral and cellular immune responses against MUC1 have been detected in cancer patients. Our study explored the association of circulating anti-MUC1 antibodies with clinicopathological parameters or patients' survival of pancreatic cancer. Serum specimens from 36 patients with invasive ductal carcinoma of the pancreas were subjected to enzyme immunoassay for anti-MUC1 IgG or IgM antibodies. Serum levels of anti-MUC1 IgG antibodies were significantly correlated with survival time (p = 0.0004), whereas neither those of anti-MUC1 IgM nor anti-Galalpha(1,3)Gal IgG antibodies, the latter known as natural antibodies cross-reactive with MUC1, showed a given tendency. Some patients' sera with the higher antibody titer showed the reactivity with MUC1-transfectants of cultured pancreatic cancer cells, but not with MUC1-negative parental cells. When the samples were tentatively divided into 2 groups by the serum level of anti-MUC1 IgG antibodies, the survival of patients was significantly longer in the group with optical density >or=0.3 than in that with optical density <0.3 (p = 0.008). Circulating anti-MUC1 IgG antibody levels remained significant (HR, 0.03; 95% CI, 0.003-0.289; p = 0.0024) after multivariate analysis for pTNM stage, patient age and gender. These data suggest that circulating anti-MUC1-IgG antibody levels may be predictive for survival of pancreatic cancer patients.}, }
@article {pmid12437074, year = {2002}, author = {Hollender, P and Ittelett, D and Villard, F and Eymard, JC and Jeannesson, P and Bernard, J}, title = {Active matrix metalloprotease-9 in and migration pattern of dendritic cells matured in clinical grade culture conditions.}, journal = {Immunobiology}, volume = {206}, number = {4}, pages = {441-458}, doi = {10.1078/0171-2985-00193}, pmid = {12437074}, issn = {0171-2985}, mesh = {Cell Differentiation ; Cell Movement/drug effects ; Cells, Cultured ; Chemokine CCL20 ; Chemokines, CC/pharmacology ; Dendritic Cells/cytology/*enzymology/immunology/physiology ; Humans ; Macrophage Inflammatory Proteins/pharmacology ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/*metabolism ; Phenylalanine/*analogs &amp; derivatives/pharmacology ; Protease Inhibitors/pharmacology ; Receptors, CCR6 ; *Receptors, Chemokine ; Thiophenes/pharmacology ; Tissue Inhibitor of Metalloproteinases/metabolism ; }, abstract = {Dendritic cells (DC) represent potent antigen presenting cells (APC) that are capable of generating tumor-specific immunity. In DC-based vaccination the migration of the infused DC from the site of injection to the secondary lymphoid organs might be critical to induce an effective immune response. Therefore we analyzed the migrating properties of maturing DC generated from human blood monocytes under culture conditions in compliance with the good manufacturing practice (GMP) guidelines. Highly purified CD14+ monocytes were differentiated into immature DC (iDC), then optimally matured as evidenced by CD83 expression. Time-lapse videomicroscopy and Transwell migration assays performed with or without Matrigel, proved mature DC (mDC) to be highly migrating cells compared to iDC although mDC migratory response varied markedly according to individuals (n= 15). Moreover, as shown by gelatin zymography and ELISA, mDC predominantly expressed both the active form of the matrix metalloprotease-9 (MMP-9) and low amounts of its physiological inhibitor, the tissue inhibitor of metalloprotease-1 (TIMP-1) which may explain their high migrating capacity through Matrigel layers. Macrophage inflammatory protein-3beta (MIP-3beta), strongly increased mDC migration through Matrigel by up-regulating the membrane MMP-9 active form suggesting that injected mDC could be selectively guided to T-cell areas of lymph nodes by this chemokine. Taken together, we demonstrate for the first time that mDC, but not iDC, prepared in clinical grade conditions are both physiologically invasive cells expressing chemokine-active and -sensitive MMP-9, which may be critical for their trafficking through tissues after injection. Consequently, we argue that migration characteristics should be included into a gold standard for DC administrated to patients.}, }
@article {pmid12429029, year = {2002}, author = {Raccurt, M and Lobie, PE and Moudilou, E and Garcia-Caballero, T and Frappart, L and Morel, G and Mertani, HC}, title = {High stromal and epithelial human gh gene expression is associated with proliferative disorders of the mammary gland.}, journal = {The Journal of endocrinology}, volume = {175}, number = {2}, pages = {307-318}, doi = {10.1677/joe.0.1750307}, pmid = {12429029}, issn = {0022-0795}, mesh = {Breast/pathology/physiopathology ; Carcinoma in Situ/*genetics/pathology ; Epithelium/pathology/physiology ; Female ; Fibroadenoma/*genetics ; Gene Expression/*genetics ; Growth Hormone/*genetics ; Humans ; Lymphatic Metastasis/genetics ; Mammary Neoplasms, Animal/*genetics ; Neoplasm Invasiveness/genetics ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {We have demonstrated and localized human GH (hGH) gene expression in surgical specimens of normal human mammary gland and in proliferative disorders of the mammary gland of increasing severity using sensitive in situ RT-PCR methodology. hGH mRNA identical to pituitary hGH mRNA was first detected by RT-PCR of RNA derived from samples of normal human mammary gland. Cellular localization of hGH gene expression in the normal mammary gland exhibited restriction to luminal epithelial and myoepithelial cells of the ducts and to scattered stromal fibroblasts. We subsequently examined the expression of the hgh gene in three progressive proliferative disorders of the human mammary gland, i.e. A benign lesion (fibroadenoma), a pre-invasive stage (intraductal carcinoma) and an invasive ductal carcinoma. hGH mRNA was readily detected in the tumoral and non-tumoral epithelial components and also in cells of the reactive stroma including fibroblasts, myofibroblastic and myoepithelial cells, inflammatory infiltrate lymphocytes and endothelial cells in areas of neovascularization. In all three proliferative disorders examined, the intensity of the cellular labeling observed in both the epithelial and stromal compartments was always stronger compared with that in adjacent normal tissue. hGH protein was also present in significantly higher concentration in extracts derived from proliferative disorders of the mammary gland compared with extracts derived from normal mammary gland. We also examined hGH gene expression in axillary lymph nodes not containing and containing metastatic mammary carcinoma. hGH gene expression was evidenced in metastatic mammary carcinoma cells and in reactive stromal cells by both in situ hybridization and in situ RT-PCR. In contrast, in lymph nodes not containing metastatic mammary carcinoma, hGH mRNA was detected only by use of in situ RT-PCR. Thus, increased expression of the hGH gene in the epithelial component and the de novo stromal expression in proliferative disorders of the mammary gland are suggestive of a pivotal role for autocrine hGH in neoplastic progression of the mammary gland.}, }
@article {pmid12412200, year = {2002}, author = {Wang, ZY and Morinobu, A and Kawano, S and Saegusa, J and Wang, B and Kumagai, S}, title = {Gold sodium thiomalate suppresses the differentiation and function of human dendritic cells from peripheral blood monocytes.}, journal = {Clinical and experimental rheumatology}, volume = {20}, number = {5}, pages = {683-688}, pmid = {12412200}, issn = {0392-856X}, mesh = {Antirheumatic Agents/*pharmacology ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Dendritic Cells/cytology/*drug effects/immunology ; Flow Cytometry ; Gold Sodium Thiomalate/*pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology ; Humans ; Interleukin-12/*immunology ; T-Lymphocytes/drug effects/*immunology ; }, abstract = {OBJECTIVE: Gold sodium thiomalate (GST) is a drug commonly used for the treatment of rheumatoid arthritis (RA). To clarify the mechanism of therapeutic effects of GST on RA, we investigated if GST affects the differentiation of dendritic cells (DC), which are thought to play a pivotal role in RA pathogenesis.<br><br>METHODS: We generated immature DC (iDC) in vitro from PB monocytes during the 5 to 7-day culture in the presence of IL-4 and GM-CSF. Mature DC (mDC) were induced by adding TNF alpha on day 5 of the 7-day culture with GM-CSF and IL-4. DC capacity of stimulating T cells was examined in allogenic MLR using generated DC as stimulators. IL-12 production from DC was assayed with ELISA.<br><br>RESULTS: We found that: 1) mDC generated in the presence of GST showed lower expression of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR compared to control mDC on FACS analysis. 2) GST-treated mDC showed reduced capacity of stimulating allogenic T cells in mixed leukocyte reaction. 3) IL-12p70 production after stimulation with SAC or LPS plus IFN gamma was markedly reduced in GST-treated mDC.<br><br>CONCLUSION: GST suppresses the differentiation and function of DC generated from peripheral blood monocytes. This previously unknown action may explain the in vivo effects of GST in the treatment of RA.}, }
@article {pmid12404521, year = {2002}, author = {Cheung, YC and Lee, KF and Ng, SH and Chan, SC and Wong, AM}, title = {Sonographic features with histologic correlation in two cases of palpable breast cancer after breast augmentation by liquid silicone injection.}, journal = {Journal of clinical ultrasound : JCU}, volume = {30}, number = {9}, pages = {548-551}, doi = {10.1002/jcu.10110}, pmid = {12404521}, issn = {0091-2751}, mesh = {Biopsy, Needle ; Breast Implants/*adverse effects ; Breast Neoplasms/*diagnostic imaging/*etiology ; Carcinoma, Ductal, Breast/diagnostic imaging/etiology ; Carcinosarcoma/diagnostic imaging/etiology ; Female ; Humans ; Middle Aged ; Silicone Gels/*adverse effects ; Time Factors ; Ultrasonography, Mammary ; }, abstract = {Sonography is rarely used to evaluate the breasts in patients who have undergone liquid silicone injections for breast augmentation because strong acoustic shadowing from the resulting silicone granulomas hampers the examination. We report on 2 patients who underwent silicone injection 18 and 20 years earlier and in whom breast cancers (1 invasive ductal carcinoma and 1 carcinosarcoma) were diagnosed by sonographically guided core-needle biopsy. On sonograms, both cancers had a peripheral hypoechoic rim surrounding an echogenic center. The echogenic center corresponded histologically to a silicone granuloma in 1 patient and to a large area of necrosis in the other; the hypoechoic rims corresponded to areas of cancer in both patients.}, }
@article {pmid12390417, year = {2002}, author = {Mannweiler, S and Tsybrovskyy, O and Regauer, S}, title = {The flow cytometric DNA index can predict the presence of lymph node metastases in invasive ductal breast carcinoma.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {110}, number = {7-8}, pages = {580-586}, doi = {10.1034/j.1600-0463.2002.1007810.x}, pmid = {12390417}, issn = {0903-4641}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; DNA, Neoplasm/*metabolism ; Female ; Flow Cytometry ; Humans ; Lymph Nodes/metabolism/*pathology ; Lymphatic Metastasis ; Middle Aged ; Predictive Value of Tests ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Sensitivity and Specificity ; }, abstract = {Axillary lymph node (LN) dissection is an important staging procedure for invasive ductal breast carcinoma (IDC), but causes elevated morbidity. Reliable preoperative prediction of metastases is at present not possible. We investigated whether flow cytometric analysis of primary IDC can correctly predict the presence of LN metastases at the time of primary diagnosis. In 341 primary IDC, DNA index (DI) in absolute values, S-phase fraction (SPF), size of the primary tumor, tumor grade (G), estrogen/progesterone receptors (ER/PR) expression and age were analysed and correlated with the axillary LN status with the aim of correctly predicting the LN status. No predictive value was identified for S-phase fraction (SPF), tumor grade, or ER/PR expression. The DI correlated statistically with LN status in all patients. A practically useful association was, however, only observed in 37 women aged 45-58 years with an IDC >2 cm diameter: a DI >1.44 predicted the presence of LN metastases at the time of operation with a specificity of 100% and a sensitivity of 89%, a negative predictive value of 91% and a positive predictive value of 100%. Determination of the absolute values of the DI may be a useful adjunct to sentinel LN preparation when predicting the axillary LN status and may spare some women the morbidity associated with axillary LN dissection.}, }
@article {pmid12378597, year = {2002}, author = {Lu, D and Masood, S and Khalbuss, WE and Bui, M}, title = {A subset of breast invasive ductal carcinoma with distinctive cytomorphology, aggressive clinical behavior, and unique immunologic profiles.}, journal = {Cancer}, volume = {96}, number = {5}, pages = {294-300}, doi = {10.1002/cncr.10745}, pmid = {12378597}, issn = {0008-543X}, mesh = {Adult ; Age Distribution ; Aged ; Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/secondary ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tumor Suppressor Protein p53/analysis ; }, abstract = {BACKGROUND: Invasive ductal carcinoma of the breast is a heterogeneous collection of divergent types of carcinomas. Some subtypes have been characterized by histologic observations. This study describes a distinctive subset recognized through cytomorphologic examination of breast carcinoma specimens obtained by fine-needle aspiration biopsies (FNAB). Identification of this subset is established further by analyses of its clinical and immunologic characteristics.<br><br>METHODS: One hundred patients underwent FNAB and were diagnosed with breast ductal carcinoma. These diagnoses were followed by surgical resections and histologic evaluation of tumors. Immunohistochemical analyses of estrogen receptor, progesterone receptor, Her2/neu, p53 protein, and Ki-67 were performed. Patient's age, race, and family history of breast carcinoma were obtained. The objective of the study is to identify a cytomorphologically distinctive, clinically relevant, subset of breast carcinomas.<br><br>RESULTS: A subset carcinoma was recognized by cytomorphologic examination of Pap-stained FNAB slides. This subset consisted of seven patients with a median age of 37 years. At the time of surgical resection, all patients had axillary lymph node metastases. Six of seven patients had distant metastases. Immunohistochemical studies revealed that all tumors are positive for p53 protein and negative for estrogen and progesterone receptors.<br><br>CONCLUSION: This study presented a unique subset of breast ductal carcinomas that involved young patients and had aggressive growth behavior. These tumors expressed p53 protein but not estrogen and progesterone receptors.}, }
@article {pmid12354345, year = {2002}, author = {Madjar, S and Appell, RA}, title = {Impaired detrusor contractility: anything new?.}, journal = {Current urology reports}, volume = {3}, number = {5}, pages = {373-377}, pmid = {12354345}, issn = {1527-2737}, mesh = {Humans ; *Muscle Contraction ; Muscle, Smooth/physiopathology ; Nervous System/physiopathology ; Urinary Bladder Diseases/*physiopathology/therapy ; }, abstract = {Impaired detrusor contractility (IDC) is a poorly defined entity that represents a treatment challenge for the urologist. The etiology of IDC is variable and may include neurologic disorders, inflammatory conditions, and pharmacologic and psychogenic causes. The gold standard for the treatment of IDC is clean intermittent catheterization (CIC). Although well-established as efficacious and safe, CIC may be conceived as a major burden on a patient's quality of life and has been associated with urinary tract infections and urethral and/or bladder injury. Alternative treatment modalities for IDC can be divided into interventions at the nervous system supplying the bladder, the bladder itself, or the bladder outlet. We review and discuss novel and creative treatment options for patients with IDC that have been developed or tested over the past decade.}, }
@article {pmid12271427, year = {2002}, author = {Neglia, D and Sambuceti, G and Iozzo, P and L'Abbate, A and Strauss, HW}, title = {Myocardial metabolic and receptor imaging in idiopathic dilated cardiomyopathy.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {29}, number = {10}, pages = {1403-1413}, doi = {10.1007/s00259-002-0898-y}, pmid = {12271427}, issn = {1619-7070}, mesh = {Cardiomyopathy, Dilated/complications/*diagnostic imaging/*metabolism ; Cerebrovascular Circulation ; Energy Metabolism ; Fatty Acids/metabolism ; Fluorodeoxyglucose F18/pharmacokinetics ; Glucose/metabolism ; Heart/*diagnostic imaging/innervation ; Humans ; Myocardial Ischemia/complications/diagnostic imaging/metabolism ; Myocardium/*metabolism ; Parasympathetic Nervous System/diagnostic imaging/metabolism ; Radionuclide Imaging ; Radiopharmaceuticals/pharmacokinetics ; Receptors, Adrenergic/metabolism ; Receptors, Adrenergic, beta/metabolism ; Receptors, Cell Surface/*metabolism ; Receptors, Muscarinic/metabolism ; Sympathetic Nervous System/diagnostic imaging/metabolism ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is a distinct disease of the myocardium, of unknown etiology. The disease can occur acutely, or evolve in a subacute fashion. IDC is often associated with a substantial impairment of ventricular function, which may recover over time. Although spontaneous recovery of LV function occurs in 20%-45% of newly diagnosed patients, the majority of patients do not do well. IDC has an average 5-year mortality of 20%. Abnormalities of energetics, perfusion, and adrenergic control of the myocardium are markers of the status of LV dysfunction. As the heart fails, changes occur in the production and catabolism of high-energy substrates, the efficiency of mitochondrial oxidative processes, the distribution of resting perfusion and coronary vasodilating capacity and the adrenergic receptor density and function. This article reviews the information provided by metabolic and receptor imaging in patients with IDC, and the role the data may play in patient management.}, }
@article {pmid12270725, year = {2002}, author = {Murabayashi, N and Kurita-Taniguchi, M and Ayata, M and Matsumoto, M and Ogura, H and Seya, T}, title = {Susceptibility of human dendritic cells (DCs) to measles virus (MV) depends on their activation stages in conjunction with the level of CDw150: role of Toll stimulators in DC maturation and MV amplification.}, journal = {Microbes and infection}, volume = {4}, number = {8}, pages = {785-794}, doi = {10.1016/s1286-4579(02)01598-8}, pmid = {12270725}, issn = {1286-4579}, mesh = {Animals ; Antigens, CD/metabolism ; *Cell Differentiation ; Chlorocebus aethiops ; Dendritic Cells/cytology/*immunology/metabolism/*virology ; *Drosophila Proteins ; Flow Cytometry ; Glycoproteins/genetics/*metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunoglobulins/genetics/*metabolism ; Ligands ; Measles virus/genetics/*growth &amp; development/immunology ; Membrane Cofactor Protein ; Membrane Glycoproteins/*metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Cell Surface/*metabolism ; Signaling Lymphocytic Activation Molecule Family Member 1 ; Toll-Like Receptor 2 ; Toll-Like Receptors ; Vero Cells ; *Virus Replication ; }, abstract = {Human CD46 (membrane cofactor protein, or MCP) and CDw150 (signaling lymphocyte activation molecule, or SLAM) serve as receptors for measles virus (MV), which induces marked host immune suppression. Although monocytes express CD46, they are considerably resistant to MV. Once monocytes differentiate into immature myeloid dendritic cells (iDCs) (GM-CSF + IL-4-treated), the cells become susceptible to MV. Therefore, we have identified CD46-adapted and CDw150-adapted strains of MV, and the dynamics of CD46 and CDw150 during monocyte-iDC conversion were examined in conjunction with MV susceptibility. Strikingly, CDw150 was not detected in monocytes and moderately induced in iDCs, while CD46 was constantly expressed in monocyte-to-iDC differentiation. Thus, iDCs were found to become highly permissive to CDw150-adapted MV strains via expression of CDw150. In fact, polyclonal and monoclonal antibodies that specifically blocked the MV receptor function of CD46 or CDw150 cancelled MV replication in iDCs according to the preferential usage of either CD46 or CDw150 in each strain of MV. Next, we showed that DCs that matured via stimulation of their Toll-like receptors (TLRs) 2 and/or 4 exhibited an approximately fivefold increase in CDw150 at the protein level, and concomitantly, higher levels of MV amplification were observed in mixed culture of lymphocytes than in iDCs without TLR2/4 stimuli. Hence, amplification of CDw150-dependent MV strains was augmented in DCs parallel with the levels of CDw150 in the presence of lymphocytes possessing CDw150. TLR-mediated functional potential of DCs may affect the degree of MV amplification through distinct MV strain-specific receptor usage of CDw150 or CD46.}, }
@article {pmid12223529, year = {2002}, author = {Yang, D and Chen, Q and Gertz, B and He, R and Phulsuksombati, M and Ye, RD and Oppenheim, JJ}, title = {Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation.}, journal = {Journal of leukocyte biology}, volume = {72}, number = {3}, pages = {598-607}, pmid = {12223529}, issn = {0741-5400}, mesh = {Amino Acid Sequence ; Antigen Presentation ; Calcium Signaling/drug effects ; Chemotaxis, Leukocyte/drug effects ; Dendritic Cells/cytology/drug effects/*metabolism ; Endocytosis/drug effects ; Gene Expression Regulation/drug effects ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Ligands ; Lipopolysaccharides/pharmacology ; Microscopy, Confocal ; Molecular Sequence Data ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Oligopeptides/pharmacology ; Peptide Fragments/immunology/pharmacology ; Peptides/pharmacology ; RNA, Messenger/biosynthesis/genetics ; Receptors, Formyl Peptide ; Receptors, Immunologic/*biosynthesis/genetics/physiology ; Receptors, Peptide/*biosynthesis/genetics/physiology ; Recombinant Fusion Proteins/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology ; Virulence Factors, Bordetella/pharmacology ; }, abstract = {Immature and mature dendritic cells (iDC and mDC, respectively) migrate to different anatomical sites, e.g., sites of antigen (Ag) deposition and secondary lymphoid organs, respectively, to fulfill their roles in the induction of primary, Ag-specific immune responses. The trafficking pattern of iDC and mDC is based on their expression of functional chemotactic receptors and the in vivo sites expressing the corresponding ligands including chemokines and/or classical chemoattractants. In this study, we have evaluated the expression of the formyl peptide receptor like-2 (FPRL2) by human iDC and mDC. We show that iDC respond chemotactically and by Ca(2+) mobilization to N-formyl-Met-Leu-Phe and a recently identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), whereas mDC derived from the same donor only respond to WKYMVm. Furthermore, iDC and mDC express FPRL2 mRNA and protein. As mDC do not express any other members of the human FPR subfamily, FPRL2 expressed by DC must be functional and mediate the effect of WKYMVm on DC. Indeed, treatment of iDC and mDC with WKYMVm induces the internalization of FPRL2. Thus, human myeloid DC express functional FPRL2 and maintain its expression even after maturation, suggesting that the interaction of FPRL2 and its endogenous ligand(s) may be involved in regulating DC trafficking during Ag uptake and processing in the periphery as well as the T cell-stimulating phase of the immune responses.}, }
@article {pmid12218207, year = {2002}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Characteristics of tumors in lymph vessels play an important role in the tumor progression of invasive ductal carcinoma of the breast: a prospective study.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {15}, number = {9}, pages = {904-913}, doi = {10.1097/01.MP.0000024289.59262.CE}, pmid = {12218207}, issn = {0893-3952}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Cell Division ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; Lymphatic System/pathology ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating/*pathology ; Prospective Studies ; Risk Factors ; }, abstract = {It is unknown whether the characteristics of tumor cells in lymph vessels play an important role in the tumor progression of invasive ductal carcinoma (IDC) of the breast. The purpose of this study was to investigate the significance of the characteristics of tumor cells in the lymph vessels in relation to the tumor progression in 393 IDC patients in comparison with well-known histological parameters. The dimensions of lymph vessel tumor emboli were measured, and their structural features, nuclear atypia, and numbers of mitotic and apoptotic figures were also assessed. Multiple regression analysis showed the dimension, the distance, the number of mitotic figures, the number of apoptotic figures, and papillary features of lymph vessel tumor emboli to be significantly associated with the increased number of cells invading the lymph vessels (P < .05). The Cox proportional hazard multivariate analyses showed that more than six apoptotic figures in lymph vessel tumor emboli significantly increased the hazard rates (HRs) of tumor recurrence and death in IDCs without nodal metastasis and that more than four mitotic figures in lymph vessel tumor emboli significantly increased the HRs of tumor recurrence and death in IDCs with nodal metastasis (P < .05). The present study showed that the histological characteristics of tumor cells in lymph vessels play a very important role in the tumor progression of IDCs.}, }
@article {pmid12217024, year = {2002}, author = {Simon, U and Sanders, D and Jockel, J and Heppel, C and Brinz, T}, title = {Design strategies for multielectrode arrays applicable for high-throughput impedance spectroscopy on novel gas sensor materials.}, journal = {Journal of combinatorial chemistry}, volume = {4}, number = {5}, pages = {511-515}, doi = {10.1021/cc020025p}, pmid = {12217024}, issn = {1520-4766}, abstract = {This paper reports the first design and fabrication of a 64 multielectrode array for high-throughput impedance spectroscopy. The purpose of this work is the development of a measurement system for the discovery and improvement of sensor materials using combinatorial methods. An array of interdigital capacitors (IDC) screen-printed onto a high-temperature-resistant Al(2)O(3) substrate is determined to be the optimal test plate. The electrode layout, and therefore also the idle capacity, is determined by specific requirements. Calculation of the idle capacity of the IDC as a function of the electrode width and distance allows adjustment and thus optimization of the array. Parasitic effects caused by the leads and contacts are compensated by a software-aided calibration. Apart from the use of the substrates for discovery of new sensor materials, the presented electrode array is also suitable for electrocatalytic applications as well as impedance spectroscopic studies of semiconductors and dielectrics.}, }
@article {pmid12215297, year = {2002}, author = {Song, M and Mi, X and Li, B and Zhu, J and Gao, Y and Cui, S and Song, J}, title = {Expression of telomerase genes in cancer development in atypical hyperplasia of the mammary duct.}, journal = {Chinese medical journal}, volume = {115}, number = {8}, pages = {1221-1225}, pmid = {12215297}, issn = {0366-6999}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/*genetics/pathology ; DNA-Binding Proteins ; Female ; Gene Expression ; Humans ; Precancerous Conditions/*genetics/pathology ; RNA/*genetics/physiology ; RNA, Messenger/analysis ; Telomerase/*genetics/physiology ; }, abstract = {OBJECTIVE: To investigate telomerase gene expression in precancerous mammary lesion, such as atypical ductal hyperplasia and breast cancer and to study the relationship between expression and malignant transformation.<br><br>METHODS: Expression of human telomerase genes (hTR) and human reverse transcriptase gene (hTRT) in 76 cases of mammary tissue was evaluated using in situ hybridization and included 50 cases of mammary hyperplasia, 6 of which were benign hyperplasia, 9 were mild atypical hyperplasia, 12 were moderate atypical hyperplasia, 23 were severe atypical hyperplasia and 26 were mammary cancer.<br><br>RESULTS: The expressions of hTR and hTRT mRNA were much weaker or negative in benign hyperplasia (16.6%, 0), weak to mild moderate in atypical hyperplasia (22.2%, 11.1%, 33.3%, 25.0%), strong in severe atypical hyperplasia (60.9%, 52.1%), and significantly strong in mammary cancer (88.5%, 80.8%). The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P < 0.05) and the difference between severe atypical hyperplasia and intraductal carcinoma was not significant (P > 0.05).<br><br>CONCLUSION: Telomerase genes (hTR and hTRT) expressions are related to the transformation of atypical hyperplasia. Activated telomerase may play a role in mammary cancer development.}, }
@article {pmid12203362, year = {2002}, author = {Mercapide, J and Zhang, SY and Fan, X and Furió-Bacete, V and Schneider, J and López de la Osa, I and Patchefsky, AS and Klein-Szanto, AJ and Castresana, JS}, title = {CCND1- and ERBB2-gene deregulation and PTEN mutation analyses in invasive lobular carcinoma of the breast.}, journal = {Molecular carcinogenesis}, volume = {35}, number = {1}, pages = {6-12}, doi = {10.1002/mc.10069}, pmid = {12203362}, issn = {0899-1987}, support = {CA-06927/CA/NCI NIH HHS/United States ; CA-71539/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; *Cell Cycle Proteins ; Cyclin D1/*genetics ; DNA Mutational Analysis ; *DNA-Binding Proteins ; E2F Transcription Factors ; E2F1 Transcription Factor ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Ki-67 Antigen/metabolism ; Neoplasm Invasiveness/genetics ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases/*genetics ; Point Mutation ; Polymorphism, Single-Stranded Conformational ; Receptor, ErbB-2/*genetics ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/*genetics ; }, abstract = {Because of the relatively low incidence of lobular breast carcinoma, there are very few studies on the molecular characteristics of this breast cancer. In an attempt to improve its characterization, we investigated in a large collection of invasive lobular carcinomas (ILCs) the status of markers known to be involved in the better-studied invasive ductal carcinomas (IDC). In the current study we disposed of 80 well-characterized ILC cases. Gene amplification of cyclin D1 (CCND1) and c-erbB2-encoding gene (ERBB2) and expression of their gene products were studied by differential polymerase chain reaction (PCR) and immunohistochemistry, respectively. A comprehensive point mutation study of the phosphatase and tensin homolog tumor suppressor gene (PTEN) was pursued by single strand conformation polymorphism (SSCP)/sequencing analysis. The CCND1 gene was rarely amplified in ILC in spite of showing overexpression of the protein in 41% of tumors. Hence, unlike IDC, increase in gene dosage did not account for the protein excess. PTEN mutations were detected in ILC (truncating mutations) in around 2% of the tumors. Unlike IDC, ILC did not display ERBB2 overexpression and expression of the transcription factor E2F1 correlated inversely with tumor grade. The observed discrepancy in the pattern of the human oncogenes CCND1 and ERBB2, which are involved in the process of carcinogenesis of ductal tumors, appears to suggest a different molecular basis for development and progression of ILC.}, }
@article {pmid12185332, year = {2002}, author = {Wang, X and Mori, I and Tang, W and Nakamura, M and Nakamura, Y and Sato, M and Sakurai, T and Kakudo, K}, title = {p63 expression in normal, hyperplastic and malignant breast tissues.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {9}, number = {3}, pages = {216-219}, doi = {10.1007/BF02967592}, pmid = {12185332}, issn = {1340-6868}, mesh = {Biopsy, Needle ; Breast Diseases/genetics/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Culture Techniques ; Diagnosis, Differential ; Female ; Gene Expression Regulation ; Genes, Tumor Suppressor ; Genes, p53/*genetics ; *Genetic Predisposition to Disease ; Humans ; Hyperplasia/*genetics/pathology ; Immunohistochemistry ; Probability ; Reference Values ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: p63 is a homologue of the p53 tumor suppressor gene and its protein is selectively expressed in the basal cells of a variety of epithelial tissues. It has recently been confirmed that p63 is expressed in the basal cells of normal prostate glands but not in prostatic carcinomas. Whether expression of p63 in breast correlates with tumor progression is the focus of this study.<br><br>METHODS: Forty cases, which all contained normal breast tissue, ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma in the same patient were included in this investigation using an indirect immunohistochemical method and double staining.<br><br>RESULTS: p63 was exclusively expressed in the myoepithelial cells of normal breast, partially expressed in ductal hyperplasia, rarely expressed in carcinoma in situ and not expressed in invasive carcinomas.<br><br>CONCLUSION: The results suggest an association between loss of p63 expression and progression of breast ductal carcinoma. p63 immunostaining might be of assistance for distinguishing invasive ductal carcinoma from ductal carcinoma in situ or rare questionable ductal hyperplastic lesions, leading to correct therapy clinically.}, }
@article {pmid12182452, year = {2002}, author = {Ruwhof, C and Canning, MO and Grotenhuis, K and de Wit, HJ and Florencia, ZZ and de Haan-Meulman, M and Drexhage, HA}, title = {Accessory cells with a veiled morphology and movement pattern generated from monocytes after avoidance of plastic adherence and of NADPH oxidase activation. A comparison with GM-CSF/IL-4-induced monocyte-derived dendritic cells.}, journal = {Immunobiology}, volume = {205}, number = {3}, pages = {247-266}, doi = {10.1078/0171-2985-00129}, pmid = {12182452}, issn = {0171-2985}, mesh = {Antigen-Presenting Cells/cytology/immunology/*physiology ; Cell Adhesion/drug effects ; Cell Movement/drug effects/*physiology ; Dendritic Cells/cytology/immunology/*physiology ; Enzyme Activation/physiology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Monocytes/cytology/immunology/physiology ; NADPH Oxidases/*metabolism ; }, abstract = {Veiled cells (VC) present in afferent lymph transport antigen from the periphery to the draining lymph nodes. Although VC in lymph form a heterogeneous population, some of the cells clearly belong on morphological grounds to the Langerhans cell (LC)/ dendritic cell (DC) series. Here we show that culturing monocytes for 24 hrs while avoiding plastic adherence (polypropylene tubes) and avoiding the activation of NADPH oxidase (blocking agents) results in the generation of a population of veiled accessory cells. The generated VC were actively moving cells like lymph-borne VC in vivo. The monocyte (mo)-derived VC population existed of CD14(dim/-) and CD14(brighT) cells. Of these the CD14(dim/-) VC were as good in stimulating allogeneic T cell proliferation as immature DC (iDC) obtained after one week of adherent culture of monocytes in granulocyte-macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. This underscores the accessory cell function of the mo-derived CD14(dim/-) VC. Although the CD14(dim/-)VC had a modest expression of the DC-specific marker CD83 and were positive for S100, expression of the DC-specific markers CD1a, Langerin, DC-SIGN, and DC-LAMP were absent. This indicates that the here generated CD14(dim/-) VC can not be considered as classical LC/DC. It was also impossible to turn the CD14(dim/-) mo-derived VC population into typical DC by culture for one week in GM-CSF/IL-4 or LPS. In fact the cells died tinder such circumstances, gaining some macrophage characteristics before dying. The IL-12 production from mo-derived CD14(dim/-) VC was lower, whereas the production of IL-10 was higher as compared to iDC. Consequently the T cells that were stimulated by these mo-derived VC produced less IFN-gamma as compared with T cells stimulated by iDC. Our data indicate that it is possible to rapidly generate a population of CD14(dim/-) veiled accessory cells from monocytes. The marker pattern and cytokine production of these VC indicate that this population is not a classical DC population. The cells might earlier be related to the veiled macrophage-like cells also earlier described in afferent lymph.}, }
@article {pmid12177657, year = {2002}, author = {Adamopoulos, S and Parissis, JT and Georgiadis, M and Karatzas, D and Paraskevaidis, J and Kroupis, C and Karavolias, G and Koniavitou, K and Kremastinos, DT}, title = {Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy.}, journal = {American heart journal}, volume = {144}, number = {2}, pages = {359-364}, doi = {10.1067/mhj.2002.124052}, pmid = {12177657}, issn = {1097-6744}, mesh = {Adult ; Aged ; Apoptosis ; Cardiomyopathy, Dilated/*complications ; Cross-Over Studies ; Cytokines/blood ; Female ; Growth Hormone/*administration &amp; dosage ; Heart Failure/*blood/*drug therapy/etiology ; Humans ; Injections, Subcutaneous ; Interleukin-6/*blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha/*analysis ; }, abstract = {BACKGROUND: Recent studies have shown that an abnormal proinflammatory cytokine expression and apoptotic process contribute to adverse left ventricular remodeling and progress of chronic heart failure. This study investigates the effects of growth hormone (GH) administration on serum levels of representative proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy (IDC).<br><br>METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), its soluble receptors (sTNF-RI, sTNF-RII), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble Fas (sFas) and soluble Fas Ligand (sFasL) were determined (enzyme-linked immunosorbent assay method) in 10 patients with IDC (New York Heart Association class III, ejection fraction 24% +/- 2%) before and after a 3-month subcutaneous administration of 4 IU GH every other day (randomized crossover design). Peak oxygen consumption (Vo(2)max) was also used to evaluate the functional status of patients with IDC.<br><br>RESULTS: Treatment with GH produced a significant reduction in serum levels of TNF-alpha (8.2 +/- 1.2 vs 5.7 +/- 1.1 pg/mL, P <.05), sTNF-RI (3.9 +/- 0.4 vs 3.2 +/- 0.3 ng/mL, P <.05), sTNF-RII (2.6 +/- 0.3 vs 2.2 +/- 0.2 ng/mL, P <.05), IL-6 (5.5 +/- 0.6 vs 4.4 +/- 0.4 pg/mL, P =.05), sIL-6R (32.7 +/- 3.0 vs 28.2 +/- 3.0 ng/mL, P <.05), sFas (4.4 +/- 0.8 vs 3.1 +/- 0.6 ng/mL, P <.05), and sFasL (34.2 +/- 11.7 vs 18.8 +/- 7.3 pg/mL, P <.01). A significant improvement was also observed in VO2max after the completion of 3 months' treatment with GH (15.0 +/- 0.8 vs 17.2 +/- 1.0 mL/kg/min, P <.05). Good correlations were found between GH-induced reduction in TNF-alpha levels and increase in VO2max (r = -0.64, P <.05) as well as between GH-induced reduction in sFasL and increase in VO2max (r = -0.56, P =.08).<br><br>CONCLUSIONS: GH administration reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in patients with IDC. These immunomodulatory effects may be associated with improvement in clinical performance and exercise capacity of patients with IDC.}, }
@article {pmid12171884, year = {2002}, author = {Yamasawa, K and Nio, Y and Dong, M and Yamaguchi, K and Itakura, M}, title = {Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {8}, number = {8}, pages = {2563-2569}, pmid = {12171884}, issn = {1078-0432}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*genetics/*metabolism/mortality ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; DNA Repair ; Exons ; Female ; Genes, p53/*genetics ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; Male ; Middle Aged ; Multivariate Analysis ; Mutation ; Pancreatic Neoplasms/*genetics/*metabolism/mortality ; Point Mutation ; *Protein Biosynthesis ; Proteins/*genetics ; Sequence Analysis, DNA ; Sex Factors ; Time Factors ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {PURPOSE: The growth arrest and DNA damage-inducible 45 gene (GADD45a) is one of the downstream mediators of the p53 gene that stimulates DNA excision repair. The present study was designed to assess the clinicopathological significance of GADD45a and p53 in resectable invasive ductal carcinomas (IDCs) of the pancreas.<br><br>EXPERIMENTAL DESIGN: This study included 72 pancreatic IDC patients who received surgery between 1982 and 2001. Point mutations in exons 1 and 4 of GADD45a and the expression of the GADD45a gene product (Gadd45) and p53 protein were analyzed by direct DNA sequencing and immunohistochemistry.<br><br>RESULTS: Point mutations were found in exon 4 of GADD45a in eight cases (13.6%). Gadd45 and p53 were expressed in 54.2% (39 of 72) and 47.2% (34 of 72) of the patients. The expression of Gadd45 did not necessarily correlate with that of p53. However, Gadd45 expression correlated significantly with the grade of the pT factor of the tumors. Coexpression analysis of Gadd45 and p53 indicated that in patients with p53(+) IDC, the Gadd45(+) group had a significantly lower survival rate than the Gadd45(-) group. Furthermore, Gadd45 expression had no effect on the efficacy of the adjuvant chemotherapy. Multivariate analysis indicated that pTNM (tumor-node-metastasis) stage, grade, and adjuvant chemotherapy were significant variables for survival. Furthermore, in the p53(-) group, there were no significant variables. In contrast, in the p53(+) group, pTNM stage, histological grade, and Gadd45 expression were significant variables.<br><br>CONCLUSIONS: The frequency of GADD45a mutation is appreciable in human pancreatic IDC, and the expression of Gadd45, combined with that of p53, significantly affects the survival of patients with resectable IDCs of the pancreas.}, }
@article {pmid12165506, year = {2002}, author = {Coronella, JA and Spier, C and Welch, M and Trevor, KT and Stopeck, AT and Villar, H and Hersh, EM}, title = {Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {169}, number = {4}, pages = {1829-1836}, doi = {10.4049/jimmunol.169.4.1829}, pmid = {12165506}, issn = {0022-1767}, support = {1R03AG20314-01/AG/NIA NIH HHS/United States ; 5F32CA79115-04/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Antigens, Neoplasm/*metabolism ; B-Lymphocytes/*immunology/pathology ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Female ; Genes, Immunoglobulin ; Germinal Center/immunology/pathology ; Humans ; Immunoglobulin Fab Fragments/metabolism ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/*immunology/pathology ; Mutation ; Peptide Library ; Tumor Cells, Cultured ; }, abstract = {The objective of this study was to determine whether tumor-infiltrating B cells (TIL-B) of infiltrating ductal carcinoma (IDC) of the breast represent a tumor-specific humoral immune response. Immunohistochemical analysis of three Her-2/neu-negative IDC tumors from geriatric patients showed that TIL-B cluster in structures similar to germinal centers containing CD20(+) B lymphocyte and CD3(+) T lymphocyte zones with interdigitating CD21(+) follicular dendritic cells, suggesting an in situ immune response. A total of 29, 31, and 58 IgG1 H chain clones was sequenced from the three IDC tumors, respectively. Intratumoral oligoclonal expansion of TIL-B was demonstrated by a preponderance (45-68%) of clonal B cells. In contrast, only 7% of tumor-draining lymph node and 0% of healthy donor PBL IgG H chains were clonal, consistent with the larger repertoires of node and peripheral populations. Patterns and levels of TIL-B IgG H chain somatic hypermutation suggested affinity maturation in intratumoral germinal centers. To examine the specificity of TIL-B Ig, a phage-displayed Fab library was generated from the TIL-B of one IDC tumor. Panning with an allogeneic breast cancer cell line enriched Fab binding to breast cancer cells, but not nonmalignant cell lines tested. However, panning with autologous tumor tissue lysate increased binding of Fab to both tumor tissue lysate and healthy breast tissue lysate. These data suggest an in situ Ag-driven oligoclonal B cell response to a variety of tumor- and breast-associated Ags.}, }
@article {pmid12161228, year = {2002}, author = {Richartz, BM and Werner, GS and Ferrari, M and Figulla, HR}, title = {Comparison of left ventricular systolic and diastolic function in patients with idiopathic dilated cardiomyopathy and mild heart failure versus those with severe heart failure.}, journal = {The American journal of cardiology}, volume = {90}, number = {4}, pages = {390-394}, doi = {10.1016/s0002-9149(02)02495-5}, pmid = {12161228}, issn = {0002-9149}, mesh = {Analysis of Variance ; Cardiomyopathy, Dilated/*complications/diagnostic imaging/physiopathology ; Diastole ; Echocardiography, Doppler ; Female ; Heart Failure/complications/diagnostic imaging/physiopathology ; Humans ; Male ; Middle Aged ; Prospective Studies ; Pulmonary Edema/*etiology ; Regression Analysis ; Systole ; Ventricular Dysfunction, Left/complications/diagnostic imaging/physiopathology ; }, abstract = {The pathogenesis of acute pulmonary edema in idiopathic dilated cardiomyopathy (IDC) is not completely understood. Because pulse-wave tissue Doppler imaging (TDI) allows a direct comparison between systolic as well as diastolic wall motion velocities, we tested the hypothesis that acute pulmonary edema is caused by both systolic and diastolic failure. We prospectively studied 65 patients. Forty patients had IDC (group 1), 15 of whom had recent-onset pulmonary congestion (group 1a, New York Heart Association [NYHA] functional classes III and IV) and 25 of whom were in clinically stable condition without signs of pulmonary congestion (group 1b, NYHA I and II). All of these patients were restudied after 3, 7, and 45 days. Groups 1a and 1b were compared with 25 subjects without evidence of heart disease (group 2). Peak systolic wall motion velocity (Vs), peak wall motion velocity of the early (Ve), and late (Va) filling waves were measured by TDI; mitral inflow pattern was determined by pulse-wave Doppler and left ventricular (LV) ejection fraction (EF) by 2-dimensional echocardiography. In those patients without pulmonary edema (controls and group 1b, n = 50), we found a positive correlation between LVEF and Vs (r = 0.72, p <0.001) and between LVEF and Ve (r = 0.79, p <0.001). Early diastolic wall motion velocity always exceeded peak systolic wall motion velocity (Ve/Vs ratio >1). In patients with IDC with recent-onset pulmonary congestion (group 1a), Ve was significantly lower compared with group 1b (3.5 +/- 0.2 vs 4.9 +/- 0.4 cm/s, p <0.01, Ve/Vs ratio <1). Clinical improvement was paralled by a gradual increase in Ve (3.5 +/- 0.2 to 6.8 +/- 0.3 cm/s, p <0.01) but not in Vs or LVEF. Thus, in patients with IDC acute pulmonary edema is exclusively caused by diastolic rather than systolic failure.}, }
@article {pmid12152162, year = {2002}, author = {Thor, AD and Eng, C and Devries, S and Paterakos, M and Watkin, WG and Edgerton, S and Moore, DH and Etzell, J and Waldman, FM}, title = {Invasive micropapillary carcinoma of the breast is associated with chromosome 8 abnormalities detected by comparative genomic hybridization.}, journal = {Human pathology}, volume = {33}, number = {6}, pages = {628-631}, doi = {10.1053/hupa.2002.124034}, pmid = {12152162}, issn = {0046-8177}, support = {P01 CA44768/CA/NCI NIH HHS/United States ; P53 CA58207/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; *Chromosome Aberrations ; Chromosome Banding ; Chromosomes, Human, Pair 16 ; Chromosomes, Human, Pair 17 ; *Chromosomes, Human, Pair 8 ; Female ; Gene Deletion ; Genes, erbB-2/genetics ; Humans ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; }, abstract = {Invasive micropapillary carcinoma (IMC) of the breast is a rare variant of invasive ductal carcinoma (IDC) characterized by unique histology and an extremely high incidence of lymph node metastases (approximately 95%). Comparative genomic hybridization (CGH) was used to characterize DNA extracted from 16 archival IMC cases to identify clonal genetic changes associated with this unique and highly metastatic cancer subtype. The average number of chromosomal alterations per IMC tumor was 7.4 +/-2.9 (3.4 gains and 3.9 losses), fewer than the number that we have observed in IDCs not otherwise specified (9.5 +/-6.6), IDCs with erbB-2 gene amplification (12.6 +/-5.9), and invasive lobular carcinomas (8.2 +/-5.5). The mean number of changes in IMC was significantly higher than we have observed in the rarely metastasizing tubular subtype of IDC (3.9 +/-2.3, P = 0.001), but less than the more aggressive subset of erbB-2-amplified IDC (P = 0.02). Remarkably, 100% of IMCs demonstrated loss involving the short arm of chromosome 8 (8p). Six cases showed loss of the entire 8p arm, whereas in 10 cases the loss was limited to the distal portion (8p21-pter) with localized gain of proximal 8p (8p11-p12). A reciprocal gain of 8q was detected in 14 cases (88%). Other common alterations included loss of 17p in 50% of tumors and loss of 16q in 50% of IMC cases. Gains of 17q (38%), 1q (31%), and 16p (25%) were also commonly detected. In comparison, IDCs (not otherwise specified), IDCs of the tubular subtype, and invasive lobular carcinomas showed only modest 8p loss (33%, 28%, and 13%, respectively). This region of chromosome 8 may contain 1 or more genes whose loss leads to this particular histology and/or the lymphotrophic phenotype associated with this histopathologic pattern.}, }
@article {pmid12144821, year = {2002}, author = {Ellis, PE and Fong, LF and Rolfe, KJ and Crow, JC and Reid, WM and Davidson, T and MacLean, AB and Perrett, CW}, title = {The role of p53 and Ki67 in Paget's disease of the vulva and the breast.}, journal = {Gynecologic oncology}, volume = {86}, number = {2}, pages = {150-156}, doi = {10.1006/gyno.2002.6629}, pmid = {12144821}, issn = {0090-8258}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*analysis ; Middle Aged ; Paget Disease, Extramammary/*chemistry ; Paget's Disease, Mammary/*chemistry ; Prognosis ; Risk Factors ; Tumor Suppressor Protein p53/*analysis ; Vulvar Neoplasms/*chemistry ; }, abstract = {OBJECTIVE: Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon diseases, accounting for approximately 1% of all vulval neoplasms and 0.5-4% of all breast cancers, respectively. In 10-30% of vulval cases an invasive adenocarcinoma is present. In such cases the disease is often aggressive and recurrence rate is high. This is in contrast to PDB where the general consensus is that almost all cases are associated with an in situ or invasive ductal carcinoma. Our aim was to examine the presence of the tumor suppressor protein p53 and the proliferation marker Ki67 in PDV and PDB and correlate any differences in the expression of these two proteins with the presence of an underlying carcinoma.<br><br>METHODS: Immunohistochemistry was performed on 52 archival cases of PDV, which included 10 with associated invasive adenocarcinoma of the vulva, and on 37 archival cases of PDB, including 26 with available associated ductal carcinoma in situ (DCIS) or invasive carcinoma of the breast. All cases were formalin-fixed and paraffin wax-embedded. Monoclonal antibodies were used with microwave antigen retrieval. Streptavidin-biotin-horseradish peroxidase and 3,3'-diaminobenzidine detection methods were employed to visualize antibody binding and staining. A section was scored positive for p53 if more than 10% of cell nuclei were stained brown and Ki67 was expressed as a percentage of positive cells to the nearest 5% of cells showing nuclear positivity (Ki67 staining index).<br><br>RESULTS: p53 was expressed in 15 of 52 (29%) PDV cases and 5 of 37 (13%) cases of PDB. Four of the ten cases (40%) of PDV associated with invasive disease expressed p53 compared with 11 of 42 (26%) cases without invasive disease. The mean Ki67 staining index for PDV associated with invasion was 19%, and for that without invasion, 16%. In the breast cases, the mean staining index was 11%.<br><br>CONCLUSION: Our data suggest that p53 may have a role to play in PDV progression, and may be a late event in some cases, especially those associated with invasive disease. Ki67 has no apparent prognostic role in PDV as there was no significant difference between those cases associated with and those without invasive disease. Neither p53 nor Ki67 appears to have a prognostic role to play in PDB.}, }
@article {pmid12132871, year = {2001}, author = {Swede, H and Moysich, KB and Freudenheim, JL and Quirk, JT and Muti, PC and Hurd, TC and Edge, SB and Winston, JS and Michalek, AM}, title = {Breast cancer risk factors and HER2 over-expression in tumors.}, journal = {Cancer detection and prevention}, volume = {25}, number = {6}, pages = {511-519}, pmid = {12132871}, issn = {0361-090X}, support = {P30 CA16056/CA/NCI NIH HHS/United States ; R25 CA1820/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*etiology/*metabolism ; Contraceptives, Oral ; Female ; Humans ; Immunoenzyme Techniques ; Menarche ; Menopause ; Menstrual Cycle ; Parity ; Receptor, ErbB-2/*metabolism ; Risk Factors ; }, abstract = {Few epidemiologic studies have investigated the potential role of HER2 in the etiology of breast cancer. We conducted a case-case study of 156 women with incident, invasive ductal carcinoma. Multivariate unconditional logistic regression was used to estimate the odds ratios for a HER2 positive tumor in relation to known and putative risk factors of breast cancer. HER2 status was detected by immunohistochemistry on archival tissue. HER2 positive breast cancers tended to be larger and were less likely to express estrogen receptors, and the incidence rate was higher in patients less than 40 years old. We observed an association between a self-reported history of benign breast disease and the occurrence of HER2 positive breast cancer (OR, 2.1;95% CI, 1.1-4.1). We did not detect associations between HER2 over-expression and family history of breast cancer, parity, late age at first birth, ever having breast fed an infant, or oral contraceptive use. Our findings merit consideration in light of recent evidence of HER2 amplification or over-expression in benign breast disease. Should the link to breast cancer be established, HER2 positive benign breast disease could potentially serve as an early marker for preventive intervention.}, }
@article {pmid12118114, year = {2002}, author = {Kleer, CG and Tseng, MD and Gutsch, DE and Rochford, RA and Wu, Z and Joynt, LK and Helvie, MA and Chang, T and Van Golen, KL and Merajver, SD}, title = {Detection of Epstein-Barr virus in rapidly growing fibroadenomas of the breast in immunosuppressed hosts.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {15}, number = {7}, pages = {759-764}, doi = {10.1038/modpathol.3880602}, pmid = {12118114}, issn = {0893-3952}, support = {R01 CA77612/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*virology ; Carcinoma, Ductal, Breast/virology ; DNA, Viral/analysis ; Epstein-Barr Virus Infections/complications/*diagnosis ; Fibroadenoma/*virology ; Herpesvirus 4, Human/*isolation &amp; purification ; Humans ; Immunocompromised Host/*immunology ; Middle Aged ; Polymerase Chain Reaction ; Tumor Virus Infections/complications/*diagnosis ; }, abstract = {Fibroadenomas are the most common benign tumors of the female breast and are associated with a slight increase in the risk of subsequent breast cancer. Multiple fibroadenomas have been described in patients after renal transplantation and are thought to be secondary to drug-related growth stimulation. Epstein-Barr virus (EBV) has been detected in many neoplasms, including breast cancer. We set out to investigate whether EBV plays a role in the development of rapidly growing fibroadenomas in immunocompromised patients. We studied 19 fibroadenomas and one invasive ductal carcinoma that developed after organ transplantation or treatment for lupus erythematosus. As a control group we included 11 fibroadenomas from non-immunocompromised patients. DNA was amplified using polymerase chain reaction (PCR) of the EBV-encoded small RNA (EBER-2) DNA sequence. EBV latent membrane protein 1 (LMP-1) transcripts were amplified using reverse transcription (RT) PCR. Immunohistochemical (IHC) staining for LMP-1 protein was performed. A total of 9 out of 20 tumors (45%) were concordantly positive by PCR and IHC. IHC stained exclusively the epithelial cells. All the fibroadenomas in non-immunocompromised patients were negative for LMP-1 (Fisher's exact test P =.0006). These data suggest that EBV is associated with fibroadenomas in this immunosuppressed population and that the infection is specifically localized to epithelial cells. This is the first study suggesting a role for EBV in the pathogenesis of fibroadenomas.}, }
@article {pmid12113587, year = {2002}, author = {Giani, C and Campani, D and Rasmussen, A and Fierabracci, P and Miccoli, P and Bevilacqua, G and Pinchera, A and Cullen, KJ}, title = {Insulin-like growth factor II (IGF-II) immunohistochemistry in breast cancer: relationship with the most important morphological and biochemical prognostic parameters.}, journal = {The International journal of biological markers}, volume = {17}, number = {2}, pages = {90-95}, doi = {10.1177/172460080201700203}, pmid = {12113587}, issn = {0393-6155}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/pathology ; Female ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor II/*analysis/genetics ; Middle Aged ; Prognosis ; RNA, Messenger/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {Recent in situ hybridization experiments have shown a high content of IGF-II mRNA in breast cancer stroma. The aim of this study was to examine the relationship between IGF-II protein expression and several prognostic parameters in 75 infiltrating ductal carcinomas (IDC) of the breast. Tissue sections were evaluated for proliferative activity, IGF-II protein, ER, PgR, p53, and p21 expression using immunohistochemical procedures. The degree of stromal proliferation was assessed. Menopausal status, axillary lymph node involvement and nuclear grade were known. Thirty-five patients (44.3%) were premenopausal and 47 (62.6%) had lymph node metastases. Marked stromal proliferation was found in 34 (45.3%) specimens and high nuclear grade in 20 (26.5%). Eighteen tumors (24%) showed no IGF-II immunostaining. In the positive cases, IGF-II was detected both in the tumor stroma and in the cytoplasm of epithelial cancer cells: a high IGF-II content was found in 12 specimens (16.0%), a low content in 14 (18.7%) and a moderate content in 31 (41.3%). Twenty-four tumors (32.0%) showed high proliferative activity. Both ER and PgR were expressed in the nucleus of cancer cells: 49 tumors (65.3%) were ER positive (ER+) and 34 (45.3%) PgR positive (PgR+). p21 protein was detected in 37 tumors (49.6%) and p53 in 12 (16%). IGF-II protein was not correlated with menopausal status, lymph node metastases, nuclear grade, proliferative activity, ER or p53. In contrast, IGF-II correlated strongly with stromal proliferation (p=0.008), PgR (p=0.03) and p21 (p=0.01). This study demonstrates that in IDC of the breast IGF-II protein is expressed in the epithelium and stroma of the majority of tumors and is correlated with stromal amount, PgR and p21 expression. These preliminary results indicate that IGF-II expression in breast cancer is connected with two important regulators of breast cancer growth and differentiation.}, }
@article {pmid12103265, year = {2002}, author = {Kuoppala, A and Shiota, N and Kokkonen, JO and Liesmaa, I and Kostner, K and Mäyränpää, M and Kovanen, PT and Lindstedt, KA}, title = {Down-regulation of cardioprotective bradykinin type-2 receptors in the left ventricle of patients with end-stage heart failure.}, journal = {Journal of the American College of Cardiology}, volume = {40}, number = {1}, pages = {119-125}, doi = {10.1016/s0735-1097(02)01928-9}, pmid = {12103265}, issn = {0735-1097}, mesh = {Adult ; Blotting, Western ; Cardiomyopathy, Dilated/metabolism ; Coronary Disease/metabolism ; Down-Regulation ; Female ; Heart Failure/etiology/*metabolism ; Humans ; Male ; Middle Aged ; Myocardium/metabolism ; Nitric Oxide Synthase/biosynthesis ; Nitric Oxide Synthase Type III ; RNA, Messenger/genetics ; Receptor, Bradykinin B2 ; Receptors, Bradykinin/genetics/*metabolism/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Ventricular Function, Left/*physiology ; }, abstract = {OBJECTIVES: We sought to study the expression of bradykinin type-2 receptors (BK-2Rs) in patients with heart failure (HF).<br><br>BACKGROUND: Recent work in experimental animals has suggested that bradykinin (BK) exerts cardioprotective effects through specific BK-2Rs. However, nothing is known about the regulation of BK-2R expression in the pathogenesis of human HF.<br><br>METHODS: Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13) and from normal hearts (n = 6) unsuitable for donation. The patients had HF due to idiopathic dilated cardiomyopathy (IDC) (n = 7) or coronary heart disease (CHD) (n = 6). Tissue samples from the left ventricles were analyzed by competitive reverse-transcriptase-polymerase chain reaction and Western blotting for the expression of BK-2R messenger ribonucleic acid (mRNA) and protein.<br><br>RESULTS: In both the IDC and CHD hearts, the level of BK-2R mRNA expression was found to be significantly lower (30% and 38% of control values, respectively) than that in normal hearts. Correspondingly, the BK-2R protein level was significantly reduced in both the IDC and CHD hearts (45% and 62% of control values, respectively) and apparently involved all myocardial cell types. The down-regulation of BK-2R expression in failing hearts did not correlate with decreased cellularity or with the expression pattern of other members of the G-protein-coupled receptor superfamily. However, BK-2R down-regulation in the failing hearts was associated with a decrease in endothelial nitric oxide synthase in both IDC (53% of control value) and CHD (43% of control value) hearts.<br><br>CONCLUSIONS: These results are the first to suggest that a loss of BK-2Rs is involved in the pathogenesis of human HF.}, }
@article {pmid12101816, year = {2001}, author = {Bozkurt, A and Canataroğlu, A and Cetiner, S and Dönmez, Y and Usal, A and Demirtaş, M}, title = {Lymphocyte subsets in patients with idiopathic dilated cardiomyopathy.}, journal = {Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology}, volume = {1}, number = {2}, pages = {98-100}, pmid = {12101816}, issn = {1302-8723}, mesh = {Adult ; CD4-CD8 Ratio ; Cardiomyopathy, Dilated/blood/diagnostic imaging/*immunology ; Case-Control Studies ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural/*cytology ; Lymphocyte Subsets/*cytology ; Male ; Middle Aged ; Ultrasonography ; }, abstract = {OBJECTIVE: Although chronic myocardial inflammatory process mediated by viral and autoimmune factors has been postulated in the pathogenesis of idiopathic dilated cardiomyopathy (IDC), the role of autoimmune mechanisms still remains unclear. The aim of the present study was to investigate the rates of various T cell subsets and natural killer (NK) cells in peripheral blood in order to see whether they had a role in the immunoregulation of IDC.<br><br>METHODS: The surface markers of peripheral T and B lymphocytes were detected and percentages of pan T and B cells as well as helper (CD4+) and suppressor (CD8+) T lymphocytes subsets in the peripheral blood and their ratio (CD4+/CD8+) were determined in 27 patients with IDC and in 20 healthy controls. NK cell percentage was also studied.<br><br>RESULTS: There were no significant differences between IDC and control groups with respect to T and B cell percentages. The percentages of CD4+ T cell subsets were similar in both groups (48.7 +/- 8.7% vs. 43.5 +/- 9.7% respectively; p = 0.107). CD8+ T cell percentage was significantly decreased in patients with IDC than in controls (22.6 +/- 7.7% vs. 28.2 +/- 8.2%, respectively; p = 0.044). CD4+/CD8+ ratio was markedly higher in patients with IDC than controls (2.6 +/- 1.8 vs. 1.6 +/- 0.6, respectively; p = 0.006). There was no significant difference in the NK cell percentage between groups.<br><br>CONCLUSION: Decreased CD8+ T cell subset is the cause of increased CD4+/CD8+ ratio, which may imply decreased self-tolerance and an immunoregulatory defect in the pathogenesis of IDC.}, }
@article {pmid12099722, year = {2002}, author = {Asano, K and Bohlmeyer, TJ and Westcott, JY and Zisman, L and Kinugawa, K and Good, M and Minobe, WA and Roden, R and Wolfel, EE and Lindenfeld, J and David Port, J and Perryman, MB and Clevel, J and Lowes, BD and Bristow, MR}, title = {Altered expression of endothelin receptors in failing human left ventricles.}, journal = {Journal of molecular and cellular cardiology}, volume = {34}, number = {7}, pages = {833-846}, doi = {10.1006/jmcc.2002.2022}, pmid = {12099722}, issn = {0022-2828}, support = {HL 03404-03/HL/NHLBI NIH HHS/United States ; HL 48013/HL/NHLBI NIH HHS/United States ; HL616401/HL/NHLBI NIH HHS/United States ; }, mesh = {Cell Membrane/metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Iodine Radioisotopes ; Myocardium/*metabolism ; RNA, Messenger/metabolism ; Receptors, Endothelin/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Ventricular Dysfunction, Left/*metabolism ; }, abstract = {BACKGROUND: Endothelin signaling is activated in failing human hearts, and may contribute to progressive myocardial dysfunction and remodeling. However, the behavior of endothelin receptor systems (ET(A) and ET(B)) in failing human hearts is not well understood.<br><br>METHODS AND RESULTS: (125)[I]-endothelin-1 binding assays conducted in the presence of a non-hydrolyzable guanine nucleotide to uncouple agonist binding demonstrated that membranes prepared from nonfailing left ventricles (LVs) exhibit a mixed pattern of ET(A) (approximately 60%) and ET(B) (approximately 40%) receptor protein expression. Chronic LV failure from either idiopathic dilated (IDC) or ischemic (ISC) cardiomyopathy was accompanied by a significant (P<0.001) increase in ET(A) receptor density, to approximately 80% of the total population, and a significant (P<0.02) decrease in ET(B) receptor density. Ribonuclease protection assays demonstrated an increase in ET(A) mRNA abundance in IDC and ISC LVs, and a significant (P<0.04) increase in ET(B) mRNA abundance in ISC LVs. Enzyme-linked immunoabsorbent assays demonstrated a significant increase in tissue immunoreactive endothelin-1 concentration in IDC (P=0.01) and in IDC+ISC LVs (P=0.02), but receptor subtype protein or mRNA level was not significantly correlated with tissue ET-1 across all LVs. In situ reverse-transcription polymerase chain reaction in LV sections demonstrated that in both failing and nonfailing LVs the ET(A) gene is expressed in cardiac myocytes, vascular smooth muscle and endothelium; the ET(B) gene is expressed in cardiac myocytes, fibroblasts and endothelium; and the prepro-endothelin-1 gene is expressed in myocytes and interstitial cells.<br><br>CONCLUSIONS: In chronically failing human LVs, ET(A) receptor density is increased to become the dominant subtype while ET(B) receptor density is decreased. The ET(A), but not the ET(B) density change is accompanied by cognate regulation of mRNA abundance. Both receptor genes and prepro-endothelin-1 are expressed in cardiac myocytes. Finally, based on a lack of correlation with endothelin-1 tissue levels, it is unlikely that the failure-related changes in ET(A) and ET(B) receptor protein and mRNA expression result from homologous regulation by agonist exposure.}, }
@article {pmid12097593, year = {2002}, author = {Sanders, RW and de Jong, EC and Baldwin, CE and Schuitemaker, JH and Kapsenberg, ML and Berkhout, B}, title = {Differential transmission of human immunodeficiency virus type 1 by distinct subsets of effector dendritic cells.}, journal = {Journal of virology}, volume = {76}, number = {15}, pages = {7812-7821}, pmid = {12097593}, issn = {0022-538X}, mesh = {Cell Communication ; *Cell Differentiation ; Dendritic Cells/cytology/*virology ; HIV Infections/*transmission ; HIV-1/*physiology ; Humans ; Intercellular Adhesion Molecule-1/metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocyte Function-Associated Antigen-1/metabolism ; Phenotype ; T-Lymphocytes/*virology ; }, abstract = {Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4(+) Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission.}, }
@article {pmid12082640, year = {2002}, author = {Blanco, MJ and Moreno-Bueno, G and Sarrio, D and Locascio, A and Cano, A and Palacios, J and Nieto, MA}, title = {Correlation of Snail expression with histological grade and lymph node status in breast carcinomas.}, journal = {Oncogene}, volume = {21}, number = {20}, pages = {3241-3246}, doi = {10.1038/sj.onc.1205416}, pmid = {12082640}, issn = {0950-9232}, mesh = {Breast Neoplasms/chemistry/*genetics/pathology ; Cadherins/analysis ; Carcinoma, Ductal, Breast/chemistry/*genetics/pathology ; Carcinoma, Lobular/chemistry/genetics/pathology ; Cell Differentiation ; Cytoskeletal Proteins/analysis ; DNA-Binding Proteins/analysis/genetics/*physiology ; Desmoplakins ; Disease Progression ; Epithelial Cells/pathology ; Female ; Humans ; Lymphatic Metastasis/*genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/analysis/genetics/*physiology ; Phenotype ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Snail Family Transcription Factors ; *Trans-Activators ; Transcription Factors/analysis/genetics/*physiology ; beta Catenin ; }, abstract = {Snail is a zinc finger transcription factor that triggers the epithelial-mesenchymal transition (EMT) by directly repressing E-cadherin expression. Snail is required for mesoderm and neural crest formation during embryonic development and has recently been implicated in the EMT associated with tumour progression. In a series of human breast carcinomas, we have analysed the expression of Snail and that of molecules of the E-cadherin/catenin complexes. We have also correlated these data with the pathological features of the tumours. We show that Snail expression inversely correlates with the grade of differentiation of the tumours and that it is expressed in all the infiltrating ductal carcinomas (IDC) presenting lymph node metastases that were analysed. In addition, Snail is expressed in some dedifferentiated tumours with a negative nodal status. Considering that Snail is involved in the induction of the invasive and migratory phenotype in epithelial cells, these results indicate that it is also involved in the progression of breast ductal tumours, where it could additionally serve as a marker of the metastatic potential.}, }
@article {pmid12072425, year = {2002}, author = {Komori, T and Ishikawa, O and Ohigashi, H and Yamada, T and Sasaki, Y and Imaoka, S and Nakaizumi, A and Uehara, H and Tanaka, S and Mano, Y and Kasugai, T}, title = {Invasive ductal adenocarcinoma of the remnant pancreatic body 9 years after resection of an intraductal papillary-mucinous carcinoma of the pancreatic head: a case report and comparison of DNA sequence in K-ras gene mutation.}, journal = {Japanese journal of clinical oncology}, volume = {32}, number = {4}, pages = {146-151}, doi = {10.1093/jjco/hyf032}, pmid = {12072425}, issn = {0368-2811}, mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Aged ; Base Sequence ; Carcinoma, Pancreatic Ductal/*genetics/pathology ; Carcinoma, Papillary/*genetics/pathology ; Female ; Genes, ras/*genetics ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pancreatectomy ; Pancreatic Neoplasms/*genetics/pathology/surgery ; *Point Mutation ; }, abstract = {Recently, there have been a few case reports of invasive ductal adenocarcinoma (IDC) developed in the remnant pancreas after partial pancreatectomy for intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their histogenetic relationships among two sporadic tumors and their surrounding duct epithelium and it would be more reliable if genetic analysis is added to the conventional histology. We report a 76-year-old woman who received pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was transitional to the surrounding duct epithelium with papillary proliferation and a wide variety of dysplasia. Nine years after the operation, she died of IDC in the remnant pancreatic body and its surrounding duct epithelium consisted of hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction indicated that their transitioning patterns differed from each other: CGT in IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild dysplasia close to the IDC. This is the first report in which the DNA sequence of K-ras mutation was determined for the two sporadic pancreatic cancers and surrounding duct changes. The following two suggestions are made: (1) the cell-origin might have differed between the two types of cancer (IDC and IPMC); and (2) no precursor lesion toward IDC or IPMC was identified in their surrounding duct epithelium.}, }
@article {pmid12060456, year = {2002}, author = {Zehetleitner, G and Thiel, I and Petru, E}, title = {Long-term disease-free survival after breast cancer metastatic to the ovary.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {12}, number = {3}, pages = {317-318}, doi = {10.1046/j.1525-1438.2002.t01-2-01126.x}, pmid = {12060456}, issn = {1048-891X}, mesh = {Adult ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/radiotherapy/*secondary/surgery ; Disease-Free Survival ; Female ; Humans ; Laparotomy ; Mastectomy, Radical ; Ovarian Neoplasms/radiotherapy/*secondary/surgery ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {The prognosis of patients with breast cancer symptomatically metastatic to the ovary is almost uniformly poor. In this case report, we present a 33-year-old para-4 with a symptomatic metastasis to the ovary. Previously, a modified radical mastectomy with adjuvant radiotherapy had been performed for invasive ductal carcinoma of the left breast. Laparotomy showed a 13-cm tumor of the left ovary; frozen section histology showed malignancy consistent with the previous breast cancer. The patient received adjuvant combination chemotherapy. About 5 years later, a carcinoma of the right breast was treated with conservative surgery and adjuvant radiation and chemotherapy. After a further 4 years, a recurrence at the left chest wall was treated with radiation. At the last follow-up, more than 13 years after the first breast cancer and 12 years after the ovarian metastasis, the patient was alive and well without evidence of disease. Bilateral oophorectomy is a therapeutic option in premenopausal patients with localized or advanced breast cancer. Our patient experienced long-term disease-free survival following an isolated metastasis to one ovary. This represents the first report of long-term survival of such a patient in the literature.}, }
@article {pmid12037031, year = {2002}, author = {Megha, T and Ferrari, F and Benvenuto, A and Bellan, C and Lalinga, AV and Lazzi, S and Bartolommei, S and Cevenini, G and Leoncini, L and Tosi, P}, title = {p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin.}, journal = {Journal of clinical pathology}, volume = {55}, number = {6}, pages = {461-466}, pmid = {12037031}, issn = {0021-9746}, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Cell Division ; ErbB Receptors/metabolism ; Female ; *Genes, p53 ; Humans ; Keratins/metabolism ; Middle Aged ; Mitotic Index ; *Mutation ; Neoplasm Proteins/metabolism ; Neoplastic Stem Cells/pathology ; Phenotype ; Polymerase Chain Reaction/methods ; Polymorphism, Single-Stranded Conformational ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; Vimentin/metabolism ; }, abstract = {AIM: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information.<br><br>METHODS: The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast. In addition, p53 gene mutation was examined by polymerase chain reaction single strand conformation polymorphism analysis (SSCP).<br><br>RESULTS: Thirteen cases (eight DCIS and five IDC) showed expression of CK8, CK14, CK18, vimentin, and EGFR, consistent with a stem cell phenotype, whereas 44 cases (27 DCIS and 17 IDC) showed expression of CK8 and CK1, weak or negative expression of CK18, but were negative for vimentin and EGFR, consistent with a luminal cell phenotype. DCIS and IDC cases with a stem cell phenotype were ER/PgR negative and intermediately or poorly differentiated. In contrast, the cases with luminal cell phenotype were ER/PgR positive and well or intermediately differentiated. In addition, intermediately or poorly differentiated cases with a stem cell phenotype showed higher proliferative activity (per cent of MIB-l positive cells) than did intermediately or well differentiated cases with a luminal cell phenotype. Both DCIS and IDC cases with a stem cell phenotype were p53 positive and bcl-2 negative by immunohistochemistry. In IDC, p53 expression was associated with a reduction of both mitotic index and apoptotic index compared with DCIS. Most of the tumours showing a more differentiated phenotype (luminal) were p53 negative and bcl-2 positive. In these cases, cell kinetic parameters increased from DCIS to IDC. These data suggest the existence of subsets of DCIS and IDC that, because of their phenotypic characteristics, could be derived from subpopulations of normal breast cells having different control mechanisms of cell proliferation and neoplastic progression.<br><br>CONCLUSIONS: These results are compatible with the hypothesis that the phenotype of the cell of origin constrains both tumour phenotype and the choice of genetic events; however, the occurrence of p53 mutants by chance during neoplastic transformation cannot be excluded.}, }
@article {pmid12034524, year = {2002}, author = {Ojopi, EP and Cavalli, LR and Cavalieri, LM and Squire, JA and Rogatto, SR}, title = {Comparative genomic hybridization analysis of benign and invasive male breast neoplasms.}, journal = {Cancer genetics and cytogenetics}, volume = {134}, number = {2}, pages = {123-126}, doi = {10.1016/s0165-4608(01)00613-6}, pmid = {12034524}, issn = {0165-4608}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms, Male/*genetics/*pathology ; Chromosome Aberrations ; Chromosomes, Human, Pair 1/genetics ; Chromosomes, Human, Pair 11/genetics ; Chromosomes, Human, Pair 17/genetics ; Chromosomes, Human, Pair 4/genetics ; Chromosomes, Human, Pair 8/genetics ; Cytogenetic Analysis ; Humans ; Male ; Neoplasm Invasiveness/*genetics ; Nucleic Acid Hybridization ; }, abstract = {Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH analysis demonstrated overrepresentation of 8q in all three cases. One case of gynecomastia presented gain of 1p34.3 through pter, 11p14 through q12, and 17p11.2 through qter, and loss of 1q41 through qter and 4q33 through qter. The other gynecomastia presented del(1)(q41) as detected by both cytogenetic and CGH analysis. CGH analysis of the invasive ductal carcinoma confirmed a gain of 17p11.2 through qter previously detected by cytogenetic analysis. These regions showed some similarity in their pattern of imbalance to the chromosomal alterations described in female and male breast cancer.}, }
@article {pmid12031704, year = {2002}, author = {Tiago, AD and Badenhorst, D and Skudicky, D and Woodiwiss, AJ and Candy, GP and Brooksbank, R and Sliwa, K and Sareli, P and Norton, GR}, title = {An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated cardiomyopathy.}, journal = {Cardiovascular research}, volume = {54}, number = {3}, pages = {584-589}, doi = {10.1016/s0008-6363(02)00281-x}, pmid = {12031704}, issn = {0008-6363}, mesh = {Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Angiotensinogen/genetics ; Cardiomyopathy, Dilated/*enzymology/pathology/*physiopathology ; Case-Control Studies ; Cytochrome P-450 CYP11B2/*genetics ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Echocardiography ; Enzyme Inhibitors/therapeutic use ; Female ; Furosemide/therapeutic use ; Heart Ventricles/pathology ; Humans ; Logistic Models ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/genetics ; *Polymorphism, Genetic ; Radionuclide Ventriculography ; *Stroke Volume ; }, abstract = {OBJECTIVE: To assess whether renin-angiotensin-aldosterone (RAA) system gene polymorphisms shown to be associated with alterations in the activity of the system, may predict cardiac function changes subsequent to initiating medical therapy in heart failure.<br><br>METHODS: The impact of RAA system genotypes on left ventricular ejection fraction (LVEF) following therapy to patients with idiopathic dilated cardiomyopathy (IDC) and class II-III heart failure was assessed. In 107 patients LVEF and LV dimensions were determined using radionuclide ventriculography and echocardiography prior to and subsequent to receiving furosemide, digoxin and angiotensin-converting enzyme (ACE) inhibitor therapy. Patients and controls were genotyped for variants of the ACE (insertion-deletion polymorphism), angiotensinogen (AGT; M235T polymorphism) and the aldosterone synthase (CYP11B2, C-344T polymorphism) genes.<br><br>RESULTS: RAA system genotypes were not significantly associated with LVEF prior to initiating medical therapy. However, the CYP11B2 gene variant (P=0.0064 on covariate analysis [adjusted for multiple genotyping] with a 1-2% chance of false positive data), but neither the ACE, nor the AGT variants, predicted improvement in LV ejection fraction in patients on medical therapy.<br><br>CONCLUSION: A CYP11B2 gene variant predicts the variable improvement in LV ejection fraction that occurs subsequent to initiating medical therapy in IDC. These data suggest a role for the aldosterone synthase locus in regulating the progression of heart failure.}, }
@article {pmid12029439, year = {2002}, author = {Tsuura, Y and Suzuki, T and Honma, K and Sano, M}, title = {Expression of c-kit protein in proliferative lesions of human breast: sexual difference and close association with phosphotyrosine status.}, journal = {Journal of cancer research and clinical oncology}, volume = {128}, number = {5}, pages = {239-246}, doi = {10.1007/s00432-002-0329-2}, pmid = {12029439}, issn = {0171-5216}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/physiopathology ; Breast Neoplasms, Male/*genetics/metabolism/physiopathology ; Female ; Fibrocystic Breast Disease/*genetics/metabolism/physiopathology ; Humans ; Hyperplasia ; Male ; Proto-Oncogene Proteins c-kit/biosynthesis/*genetics ; Sex Factors ; }, abstract = {PURPOSE: The c-kit gene which codes transmembrane tyrosine kinase receptor protein plays an important role in several types of normal and/or neoplastic human tissues. We examined the expression patterns of c-kit protein in proliferative lesions of human breast tissues in both sexes.<br><br>METHODS: The localization of c-kit protein was examined immunohistochemically in human breast, consisting of 366 normal tissue, 156 benign lesions (fibroadenoma, fibrocystic change, intraductal papilloma, benign phyllodes tumor, and gynecomastia), 13 borderline diseases (atypical ductal hyperplasia, atypical lobular hyperplasia, and borderline malignant phyllodes tumor), and 197 malignant lesions (non-invasive and/or invasive ductal carcinoma and malignant phyllodes tumor).<br><br>RESULTS: In normal tissues and benign proliferative lesions, c-kit product was consistently detected on epithelial cell membranes and/or cytoplasms regardless of gender difference. In contrast, we failed to find c-kit product in female borderline epithelial lesions, including atypical lobular hyperplasia, or in female malignant lesions, except for two carcinomas. In situ hybridization analysis of c-kit mRNA in female tissues gave results comparable to those obtained by immunohistochemistry. On the other hand, c-kit product was consistently detected in male benign and malignant proliferative lesions. Apart from the female breast carcinomas which lacked c-kit, c-kit expression was almost always accompanied by positivity for phosphotyrosine in the breast tissues examined, suggesting possible phosphorylation of tyrosine residues of the c-kit receptor protein.<br><br>CONCLUSIONS: Loss of c-kit product was related to malignant transformation in female breast, but not in the case of male breast. We suggest that the oncogenesis pathway of breast epithelium is different between males and females in terms of c-kit expression.}, }
@article {pmid12021928, year = {2002}, author = {Röcken, C and Kronsbein, H and Sletten, K and Roessner, A and Bässler, R}, title = {Amyloidosis of the breast.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {440}, number = {5}, pages = {527-535}, doi = {10.1007/s00428-001-0555-z}, pmid = {12021928}, issn = {0945-6317}, mesh = {Aged ; Aged, 80 and over ; Amino Acid Sequence ; Amyloidosis/complications/*diagnosis/pathology ; Biopsy ; Breast Diseases/complications/*diagnosis/pathology ; Breast Neoplasms/complications/diagnosis/pathology ; Calcinosis/diagnosis/pathology ; Carcinoma, Ductal, Breast/complications/pathology ; Carcinoma, Lobular/complications/diagnosis/pathology ; Female ; Humans ; Immunoglobulin kappa-Chains/analysis/chemistry ; Lymphatic Metastasis ; Microscopy, Electron ; Middle Aged ; Peptide Fragments/chemistry ; }, abstract = {We report on three cases of amyloidosis of the breast, two of which coincided with breast cancer. Patient no. 1, a 60-year-old woman, presented with two mass lesions measuring 2 cm in diameter, one in each breast. Histologically, a tubulo-lobular carcinoma was found in the left breast accompanied by vascular, interstitial, and periductal amyloid deposits; the lesion in the right breast consisted of amyloid deposits only. Patient no. 2, an 86-year-old woman, presented with an ulcerated breast tumor measuring 5 cm in diameter on the left side. A poorly differentiated invasive ductal carcinoma was found in the mastectomy specimen, and it coincided with interstitial and vascular amyloid deposits. In both patients, tumor cells had invaded the amyloid deposits. Patient no. 3, a 73-year-old woman, presented with a mass measuring 5 x 3 x 3 cm in her left breast. Fibrocystic changes, as well as interstitial and periductal amyloid deposits, were found histologically. In each case electron microscopy showed rigid, non-branching fibrils of indefinite length and measuring 10-12 nm in diameter; these were consistent with amyloid fibrils. Clinical data, immunohistochemistry, and/or amino acid sequencing of the fibril proteins extracted from formalin-fixed and paraffin-embedded tissue specimens provided evidence that the amyloid deposits were of immunoglobulin light chain origin in all three cases. A review of the literature revealed that kappa-light chain has been described more frequently than lambda-light chain in the breast and that there are no specific clinical or radiological symptoms of amyloidosis affecting the breast; a diagnosis can be achieved only by histology.}, }
@article {pmid12020967, year = {2002}, author = {Kouwenhoven, M and Ozenci, V and Tjernlund, A and Pashenkov, M and Homman, M and Press, R and Link, H}, title = {Monocyte-derived dendritic cells express and secrete matrix-degrading metalloproteinases and their inhibitors and are imbalanced in multiple sclerosis.}, journal = {Journal of neuroimmunology}, volume = {126}, number = {1-2}, pages = {161-171}, doi = {10.1016/s0165-5728(02)00054-1}, pmid = {12020967}, issn = {0165-5728}, mesh = {Adult ; Cell Movement/immunology ; Dendritic Cells/cytology/*enzymology/metabolism ; Female ; Flow Cytometry ; Gene Expression Regulation, Enzymologic/immunology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Matrix Metalloproteinase 1/genetics/metabolism ; Matrix Metalloproteinase 2/genetics/metabolism ; Matrix Metalloproteinase 3/genetics/metabolism ; Matrix Metalloproteinase 9/genetics/metabolism ; Metalloendopeptidases/*genetics/metabolism ; Middle Aged ; Monocytes/*cytology ; Multiple Sclerosis/immunology/metabolism/*physiopathology ; RNA, Messenger/analysis ; Tissue Inhibitor of Metalloproteinase-1/*genetics/metabolism ; Tissue Inhibitor of Metalloproteinase-2/*genetics/metabolism ; }, abstract = {Dendritic cells (DC) are antigen-presenting cells (APC) that most efficiently initiate and control immune responses. Migration processes of blood DC are crucial to exert their professional antigen-presenting functions. Matrix-degrading metalloproteinases (MMP) are proteolytic enzymes, which are considered to be key enzymes in extracellular matrix (ECM) turnover and mediators of cell migration. Tissue inhibitors of metalloproteinases (TIMP) are important regulators of MMP activity. Here we investigate whether blood monocyte-derived immature DC (iDC) and mature DC (mDC) express, produce and secrete functionally active MMP-1, -2, -3 and -9 and their inhibitors TIMP-1 and -2, and examine their involvement in multiple sclerosis (MS). On mRNA level, we observed high numbers of MMP-2 and TIMP-2 mRNA expressing iDC in MS. On protein level, high percentages of MMP-1, -2 and -9 expressing iDC by flow cytometry, and high MMP-1 secretion by Western blot together with high MMP-2 and -9 activities in iDC supernatants as studied with zymography were observed. Similarly, MS is associated with high percentages of MMP-2 and -3 and of TIMP-1 expressing mDC by flow cytometry together with high MMP-3 secretion and high MMP-9 activity in culture supernatants. Spontaneous migratory capacity of both iDC and mDC over ECM-coated filters was higher in MS compared to healthy controls (HC). In conclusion, blood monocyte-derived iDC and mDC express, produce and secrete several MMP and TIMP. Alterations in these molecules as observed in MS may be functionally important for DC functioning.}, }
@article {pmid12014222, year = {2002}, author = {Patla, A and Rudnicka-Sosin, L and Pawlega, J and Stachura, J}, title = {Prognostic significance of selected immunohistochemical parameters in patients with invasive breast carcinoma concomitant with ductal carcinoma in situ.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {53}, number = {1}, pages = {25-27}, pmid = {12014222}, issn = {1233-9687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma in Situ/*metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Second Primary/metabolism/pathology ; Precancerous Conditions/*metabolism/pathology ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {The purpose of the present study was to carry out multivariate analysis of the effect of the expression of estrogen and progesterone receptors, p53, proliferative antigen (Ki67) and c-erbB-2 on 5-year survival in patients with invasive breast carcinoma concomitant with ductal carcinoma in situ. Material for study consisted of tissue specimens obtained from 48 patients undergoing modified Patey's mastectomy between 1991 and 1998. Univariate analysis revealed that the variables significantly affecting survival were tumour size on gross examination and the level of estrogen and progesterone receptors in the cells of invasive ductal carcinoma of the breast (for the level of significance p = 0.05). The Cox regression model revealed that the only independent variable having a significant effect on survival was the level of estrogen receptors in invasive cancer cells.}, }
@article {pmid12004646, year = {2002}, author = {Chlebovská, K and Chlebovskỳ, O and Ahlers, I and Ahlersová, E and Bacenková, D}, title = {Effect of K, MG aspartate on some biological parameters of aging rats.}, journal = {Archives italiennes de biologie}, volume = {140}, number = {2}, pages = {91-100}, pmid = {12004646}, issn = {0003-9829}, mesh = {Aging/*drug effects/metabolism/radiation effects ; Animals ; Aspartic Acid/*pharmacology ; Blood Proteins/*drug effects/metabolism/radiation effects ; Complement C3/drug effects/metabolism/radiation effects ; Gamma Rays/adverse effects ; Haptoglobins/drug effects/metabolism/radiation effects ; Hemopexin/drug effects/metabolism/radiation effects ; Immunity, Innate/drug effects/immunology/radiation effects ; Male ; Neutrophils/drug effects/metabolism/radiation effects ; Phagocytosis/drug effects/immunology/radiation effects ; Rats ; Rats, Wistar ; Serum Albumin/drug effects/metabolism/radiation effects ; Survival Rate ; Transferrin/drug effects/metabolism/radiation effects ; }, abstract = {The effect of K and Mg salts of aspartic acid (Cardilan) on the serum concentration of selected proteins and phagocytic activity in aging male Wistar rats was investigated. Cardilan was administered in tap water for 7 days a month for 3 months before the last observed interval (12, 18 and 24 month). In a part of animals, the aging process was accelerated by sublethally gamma-irradiation. The administration of Cardilan slowed down the changes in the concentration of prealbumin, albumin, haptoglobin, haemopexin, C3 complement in non-irradiated rats (DC). This effect was extended to the changes in transferrin level in irradiated rats (IDC). The phagocytic activity in both DC, IDC rats was lower compared with controls drinking water (DW, IDW), but not significantly. The effect of Cardilan administration appears to be the greatest in 24-month-old rats, when the treated animals survived better by 25% in IDC group and by 26% better in DC rats, compared with those of the same age controls. Potassium and magnesium salts of aspartates are suitable compounds for life prolongation in the experimental conditions.}, }
@article {pmid11994759, year = {2002}, author = {Park, SH and Kim, H and Song, BJ}, title = {Down regulation of bcl2 expression in invasive ductal carcinomas is both estrogen- and progesterone-receptor dependent and associated with poor prognostic factors.}, journal = {Pathology oncology research : POR}, volume = {8}, number = {1}, pages = {26-30}, pmid = {11994759}, issn = {1219-4956}, mesh = {Adult ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; *Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/*biosynthesis/genetics ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {In normal breast, Bcl2 is expressed in the non-pregnant and non-involuting mammary epithelium. The exact mechanism and the effect of the down regulation of the Bcl2 expression on breast cancer cells are not clearly defined. We compared down regulation as well as the persistent expression of Bcl2 with ER, PR, p53, and c-erb-B2 overexpression and clinicopathologic variables, and tumor stage in 11 cases of ductal carcinomas in situ (DCIS) and 44 cases of invasive ductal carcinomas (IDC) of Korean women by immunohistochemical studies. Bcl2 down regulation was found in 39% of IDC and in 18% of DCIS cases. In IDC, while persistent Bcl2 expression was displayed in 95% and 78.9% of ER and PR immunoreactive ones and 71.9 % of c-erb-B2 immunonegative ones. Seventeen cases of Bcl2 down regulated IDC had a significant correlation with ER negativity (94.1%), PR negativity, (76.5%), and high nuclear (61.1% is grade III) and histological grade (76% is grade III). However, in DCIS, no significant correlation between the Bcl2 expression and various parameters were obtained, probably due to small sample size. In conclusion, the Bcl2 expression was both ER and PR dependent and down regulation of Bcl2 in IDC was significantly correlated with poor prognostic factors.}, }
@article {pmid11991512, year = {2002}, author = {Okamo, H and Miura, K and Yamane, T and Fujii, H and Matsumoto, Y}, title = {Invasive ductal carcinoma of the breast associated with Poland's syndrome: report of a case.}, journal = {Surgery today}, volume = {32}, number = {3}, pages = {257-260}, doi = {10.1007/s005950200030}, pmid = {11991512}, issn = {0941-1291}, mesh = {Arm/abnormalities ; Breast Neoplasms/*complications/surgery ; Carcinoma, Ductal, Breast/*complications/surgery ; Female ; Humans ; Lymph Node Excision ; Mastectomy, Segmental ; Middle Aged ; Pectoralis Muscles/abnormalities/diagnostic imaging ; Poland Syndrome/*complications ; Tomography, X-Ray Computed ; }, abstract = {We report herein a rare case of invasive ductal carcinoma of the breast associated with Poland's syndrome. The patient was a 59-year-old woman who was referred to our department after a nodule had been found in the upper outer portion of the left breast by a breast cancer screening program. On physical examination, marked hypoplasia of the right breast and upper limb was noted. Preoperative computed tomography also revealed a defect in the right pectoralis muscles. A quadrantectomy of the left breast with lymphadenectomy was subsequently performed and pathological examination of the resected specimen showed invasive ductal carcinoma. Her medical history revealed that her mother had attempted to abort the pregnancy around the fifth week of her gestation. The present case suggests that such an event during gestational development may be associated with congenital anomalies predisposing to malignant disorders.}, }
@article {pmid11988637, year = {2002}, author = {Casademont, J and Miró, O}, title = {Electron transport chain defects in heart failure.}, journal = {Heart failure reviews}, volume = {7}, number = {2}, pages = {131-139}, pmid = {11988637}, issn = {1382-4147}, mesh = {DNA, Mitochondrial/genetics/metabolism ; Energy Metabolism/genetics/physiology ; Heart Failure/*etiology/*metabolism/physiopathology ; Humans ; Mitochondria, Heart/genetics/metabolism ; Mitochondrial Diseases/*etiology/*metabolism/physiopathology ; Myocardial Contraction/genetics/physiology ; }, abstract = {In recent years, the possibility that disorders of cardiac metabolism play a role in the mechanisms that lead to ventricular dilatation and dysfunction in heart failure has attracted much attention. Electron transport chain is constituted by a series of multimeric protein complexes, located in the inner mitochondrial membranes, whose genes are distributed over both nuclear and mitochondrial DNA. Its normal function is essential to provide the energy for cardiac function. Many studies have described abnormalities in mitochondrial DNA genes encoding for electron transport chain (ETC) in dilated cardiomyopathies. In some cases, heart failure is one more or less relevant symptom among other multisystem manifestations characteristic of mitochondrial encephalomyopathies, being heart failure imputable to a primary mitochondrial disease. In the case of idiopathic dilated cardiomyopathies (IDC), many mitochondrial abnormalities have also been described using hystological, biochemical or molecular studies. The importance of such findings is under debate. The great variability in the mitochondrial abnormalities described has prompted the proposal that mitochondrial dysfunction could be a secondary phenomenon in IDC, and not a primary one. Among other possible explanations for such findings, the presence of an increased oxidative damage due to a free radical excess has been postulated. In this setting, the dysfunction of ETC could be a consequence, but also a cause of the presence of an increased free radical damage. Independently of its origin, ETC dysfunction may contribute to the persistence and worsening of heart failure. If this hypothesis, still to be proven, was certain, the modulation of cardiac metabolism could be an interesting approach to treat IDC. The precise mechanisms that lead to ventricular dilatation and dysfunction in heart failure are still nowadays poorly understood. Circumstances such as cytotoxic insults, viral infections, immune abnormalities, contractile protein defects, ischemic factors and familial conditions have been thoroughly investigated [1]. It is possible that several mechanisms combine to produce the clinical syndrome of heart failure. In recent years the possibility that disorders of energy metabolism, either isolated or in combination with the other aforementioned factors, may play a role in the development of heart failure in susceptible patients has attracted much attention. The present paper reviews the current knowledge on mitochondrial function in the failing myocardium. We restrain our discussion to heart failure where an impaired inotropic state leads to a weakened systolic contraction (i.e. the so-called systolic heart failure). Idiopathic dilated cardiomyopathy (IDC) is the prototype of the conditions under discussion. Other circumstances where a defect in myocardial contraction is due to a chronic excessive work load (i.e., hypertension, valvular or congenital heart diseases), and states in which the principal abnormality involves impaired relaxation of the ventricle (i.e. diastolic heart failure), as well as mitochondrial defects outside the electron transport chain (i.e., defects in Krebs cycle or beta-oxidation of fatty acids) are only approached circumstantially.}, }
@article {pmid11985914, year = {2002}, author = {Crispell, KA and Hanson, EL and Coates, K and Toy, W and Hershberger, RE}, title = {Periodic rescreening is indicated for family members at risk of developing familial dilated cardiomyopathy.}, journal = {Journal of the American College of Cardiology}, volume = {39}, number = {9}, pages = {1503-1507}, doi = {10.1016/s0735-1097(02)01788-6}, pmid = {11985914}, issn = {0735-1097}, support = {1R01HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Cardiomyopathy, Dilated/*diagnosis/genetics/physiopathology ; Child ; Child, Preschool ; Echocardiography ; Electrocardiography ; Family ; Female ; Humans ; Infant ; Male ; Middle Aged ; Pedigree ; Phenotype ; Risk Factors ; Ventricular Dysfunction, Left/*diagnostic imaging ; }, abstract = {OBJECTIVES: This study evaluated the role of clinical rescreening of family members at risk for familial dilated cardiomyopathy (FDC).<br><br>BACKGROUND: Familial dilated cardiomyopathy is a genetic cardiomyopathy that usually is transmitted in an autosomal dominant pattern and may underlie from one-quarter to one-half of idiopathic dilated cardiomyopathy (IDC) diagnoses. Thus, FDC may present with advanced heart failure (HF) or sudden cardiac death (SCD). Because FDC may respond to medical intervention, we have previously recommended that screening of first-degree relatives (parents, siblings, children) of patients diagnosed with IDC be undertaken to rule out FDC, and that with a diagnosis of FDC in the kindred, unaffected but at-risk family members be rescreened every three to five years. METHODS; Follow-up screening (history, examination, electrocardiogram, echocardiography) of a large family with FDC was performed six years after initial screening. Of 68 family members who underwent rescreening, two (one with left ventricular enlargement only, one with a left bundle branch block) presented with advanced HF and SCD, respectively. Two additional subjects, asymptomatic at initial screening, were also affected with FDC at follow-up.<br><br>CONCLUSIONS: Considerable vigilance for disease presentation and progression is indicated in at-risk members of a kindred with FDC, especially those with incipient FDC.}, }
@article {pmid11967758, year = {2002}, author = {Emir, H and Eroğlu, E and Tekant, G and Büyükünal, C and Danişmend, N and Söylet, Y}, title = {Urodynamic findings of posterior urethral valve patients.}, journal = {European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie}, volume = {12}, number = {1}, pages = {38-41}, doi = {10.1055/s-2002-25093}, pmid = {11967758}, issn = {0939-7248}, mesh = {Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Urethra/*abnormalities/physiopathology ; Urinary Bladder/physiopathology ; Urinary Bladder Neck Obstruction/etiology/physiopathology ; *Urodynamics ; }, abstract = {The most frequently observed cause of obstructed bladder in children is the posterior urethral valve (PUV). In this report, we analysed the urodynamic findings of 26 patients whose valves were fulgurated 12.6 months previously (range: 2 days - 8 years,after the fulguration). The mean age of the patients at the time of the procedure was 4.5 years (range: 2 months -13 years). Bladder capacity was decreased in 15, increased in 6, and normal in 5 patients; hypo-compliance was observed in 13, hyper-compliance was observed in 4, and normo-compliance was observed in 9 children. Generally, hypo-compliance and decreased bladder capacity was more frequent in patients younger than 4 years of age. There were 10 patients with instable detrusor contractions(IDC) and high residual urine was present in 8 patients. Eight patients developed chronic renal failure and 6 of these patients had high residual urine. All the patients who required bladder augmentation during follow-up were the ones treated after 2.5 years of age; 4 of these 5 patients had hypo-compliance and low bladder capacity on urodynamic studies. In conclusion, all patients with PUV had pathological urodynamic findings that could change with age, and early relief of the infravesical obstruction could have an improving effect on bladder function. Urodynamic investigations may help us to design the proper treatment according to the bladder function.}, }
@article {pmid11956269, year = {2002}, author = {Diller, L and Medeiros Nancarrow, C and Shaffer, K and Matulonis, U and Mauch, P and Neuberg, D and Tarbell, NJ and Litman, H and Garber, J}, title = {Breast cancer screening in women previously treated for Hodgkin's disease: a prospective cohort study.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {20}, number = {8}, pages = {2085-2091}, doi = {10.1200/JCO.2002.08.031}, pmid = {11956269}, issn = {0732-183X}, mesh = {Adult ; Breast Neoplasms/epidemiology/*prevention &amp; control ; Female ; Hodgkin Disease/*radiotherapy ; Humans ; Mammography ; Middle Aged ; Neoplasms, Second Primary/*prevention &amp; control ; Prospective Studies ; Risk Factors ; Survivors ; }, abstract = {PURPOSE: Young women who are exposed to chest irradiation for Hodgkin's disease (HD) are at increased risk of breast cancer; this study investigated patient awareness of breast cancer risk and patient screening behavior and assessed the utility of mammographic screening in HD survivors.<br><br>PATIENTS AND METHODS: This is a prospective cohort study of 90 female long-term survivors of HD who had been treated > or = 8 years previously with mantle irradiation (current age, 24 to 51 years). Participants completed surveys of their perceptions of breast cancer risk and screening behaviors and received written recommendations for breast examinations and mammography. Annual follow-up was conducted through medical records, telephone, and/or mailed questionnaires.<br><br>RESULTS: At baseline, women were often unaware of their increased risk of breast cancer; 40% (35 of 87) reported themselves to be at equal or lower risk than women of the same age. Only 47% (41 of 87) reported having had a mammogram in the previous 24 months. Women who had received information from an oncologist were more likely to assess correctly their risk than women who received information from other sources (P <.001). Ten women developed 12 breast cancers (ductal carcinoma-in-situ [n = 2], invasive ductal carcinoma [n = 10]) during the study; two were diagnosed at study entry, and 10 during follow-up (median, 3.1 years). All cancers were evident on mammogram, and eight of 10 invasive cancers were node negative.<br><br>CONCLUSION: Practitioners who care for women after HD therapy need to educate patients regarding their risks and begin early screening. Screening by mammography can detect small, node-negative breast cancers in these patients.}, }
@article {pmid11955332, year = {2002}, author = {Song, M and Mi, X and Li, B and Zhu, J and Gao, Y and Cui, S and Song, J}, title = {[Expression of telomerase genes in mamary atypical ductal hyperplasia].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {31}, number = {1}, pages = {30-33}, pmid = {11955332}, issn = {0529-5807}, mesh = {Breast Neoplasms/*enzymology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/pathology ; DNA-Binding Proteins ; Female ; *Gene Expression ; Humans ; RNA, Messenger ; Telomerase/*genetics ; }, abstract = {OBJECTIVE: To investigate the relationship of telomerase genes and the malignant transformation of atypical mammary ductal hyperplasia.<br><br>METHODS: Telomerase genes hTR and hTRT in 50 cases of mammary hyperplasia (the cases included 6 benign hyperplasia, 9 mild atypical hyperplasia, 12 medium atypical hyperplasia, 23 severe atypical hyperplasia) and 26 cases of breast carcinoma were detected by in situ hybridization.<br><br>RESULTS: The expression of hTR and hTRT mRNA were weak or negative in benign hyperplasia (1/6, 0), weaker in mild-moderate atypical hyperplasia (2/9, 1/9, 4/12, and 3/12), strong in severe atypical hyperplasia (14/23, 60.9% and 12/23, 52.1%), while very strong expression (23/26, 88.5% and 21/25, 80.8%) in carcinoma of the breast. The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P < 0.05) and the difference between severe atypital hyperplasia and intraductal carcinoma was not significant (P > 0.05).<br><br>CONCLUSIONS: Telmerase genes (hTR, hTRT) expression is closely related to the malignant transformation of atypical hyperplasia. The reactivated telomerase may play a crucial role in the development of breast cancer.}, }
@article {pmid11929776, year = {2002}, author = {Zimmer, MI and Larregina, AT and Castillo, CM and Capuano, S and Falo, LD and Murphey-Corb, M and Reinhart, TA and Barratt-Boyes, SM}, title = {Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS.}, journal = {Blood}, volume = {99}, number = {8}, pages = {2859-2868}, doi = {10.1182/blood.v99.8.2859}, pmid = {11929776}, issn = {0006-4971}, support = {AI43664/AI/NIAID NIH HHS/United States ; AI43916/AI/NIAID NIH HHS/United States ; HL62056/HL/NHLBI NIH HHS/United States ; RR00119/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD/analysis ; Chemotaxis/immunology ; Dendritic Cells/immunology/*pathology/virology ; *Homeostasis ; Immunophenotyping ; Langerhans Cells/immunology/*pathology/virology ; Lymph Nodes/pathology/virology ; Macaca mulatta ; Models, Animal ; Simian Acquired Immunodeficiency Syndrome/*pathology ; }, abstract = {Langerhans cells (LCs) are immature dendritic cells (DCs) that capture antigen in peripheral tissues and migrate to draining lymph nodes, where they reside in the paracortex as interdigitating dendritic cells (IDCs). We studied the effects of simian immunodeficiency virus (SIV) on LCs and IDCs during different stages of infection in monkeys. LCs isolated from monkeys with acute SIV infection or acquired immunodeficiency syndrome (AIDS) underwent normal maturation in vitro, including a switch in chemokine receptor expression from CCR5 to CXCR4 and CCR7. LCs migrated normally from skin in response to contact sensitization in monkeys with acute SIV infection. In contrast, LC migration from skin was markedly impaired during AIDS, associated with a reduction in antigen-bearing DCs in draining lymph nodes. Lymph node IDCs were increased in proportion during acute SIV infection and had an activated phenotype, whereas during AIDS IDCs had significantly lower expression of CD40 and the activation marker CD83. IDCs from monkeys with AIDS were refractory to stimulation with CD40L, demonstrating a functional consequence of decreased CD40 expression. SIV-infected DCs were not identified in lymph nodes or skin of monkeys with AIDS, suggesting an indirect effect of infection on DC populations in vivo. These data indicate that DCs are mobilized to lymph nodes during acute SIV infection, but that during AIDS this process is suppressed, with LC migration and IDC activation being impaired. We conclude that disruption of DC homeostasis may play a role in immunopathology induced by human immunodeficiency virus and suggest that therapeutic strategies targeting DCs may have limited efficacy during AIDS.}, }
@article {pmid11921196, year = {2002}, author = {Russo, J and Tahin, Q and Lareef, MH and Hu, YF and Russo, IH}, title = {Neoplastic transformation of human breast epithelial cells by estrogens and chemical carcinogens.}, journal = {Environmental and molecular mutagenesis}, volume = {39}, number = {2-3}, pages = {254-263}, doi = {10.1002/em.10052}, pmid = {11921196}, issn = {0893-6692}, support = {CA87230/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast/*cytology ; Breast Neoplasms/etiology/genetics ; Carcinogens/*adverse effects ; Cell Transformation, Neoplastic/*chemically induced/pathology ; Epithelial Cells/*drug effects/pathology ; Estrogens/*adverse effects ; Female ; Humans ; Mice ; }, abstract = {Sporadic breast cancer, the most common cancer diagnosed in American and Northern European women, is gradually increasing in incidence in most Western countries. Prevention would be the most efficient way of eradicating this disease. This goal, however, cannot be accomplished until the specific agent(s) or mechanisms that initiate the neoplastic process are identified. Experimental studies have demonstrated that mammary cancer is a hormone-dependent multistep process that can be induced by a variety of compounds and mechanisms, that is, hormones, chemicals, radiation, and viruses, in addition to or in combination with genetic factors. Although estrogens have been shown to play a central role in breast cancer development, their carcinogenicity on human breast epithelial cells (HBECs) has not yet been clearly demonstrated. Breast cancer initiates in the undifferentiated lobules type 1, which are composed of three cell types: highly proliferating cells that are estrogen-receptor negative (ER-), nonproliferating cells that are ER positive (ER+), and very few (<1%) ER+ cells that proliferate. Interestingly, endogenous 17beta-estradiol (E(2)) is metabolized by the cytochrome P450 enzyme isoforms CYP1A1 and CYP1B1, which also activate benzo[a]pyrene (B[a]P), a carcinogen contained in cigarette smoke. We postulate that if estrogens are carcinogenic in HBECs, they should induce the same transformation phenotypes induced by chemical carcinogens and ultimately genomic changes observed in spontaneously developing primary breast cancers. To test this hypothesis we compared the transforming potential of E(2) on the HBEC MCF-10F with that of B[a]P. Both E(2) and B[a]P induced anchorage-independent growth, colony formation in agar methocel, and loss of ductulogenic capacity in collagen gel, all parameters indicative of cell transformation. In addition, the DNA of E(2)-transformed cells expressed LOH in chromosome 11 at 11q23.3, 11q24.2-q25, and LOH at 13q12-q13. B[a]P-induced cell transformation was also associated with LOH at 13q12-q13 and at 17p13.2. The relevance of these findings is highlighted by the observation that E(2)- and B[a]P-induced genomic alterations in the same loci found in ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma of the breast.}, }
@article {pmid11920633, year = {2002}, author = {Schnack Nielsen, B and Rank, F and Engelholm, LH and Holm, A and Danø, K and Behrendt, N}, title = {Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells.}, journal = {International journal of cancer}, volume = {98}, number = {5}, pages = {656-664}, doi = {10.1002/ijc.10227}, pmid = {11920633}, issn = {0020-7136}, mesh = {Animals ; Antibody Formation ; Blotting, Western ; Breast/*metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Cross-Linking Reagents ; Female ; Fluorescent Antibody Technique ; Humans ; In Situ Hybridization ; *Mannose-Binding Lectins ; Membrane Glycoproteins/*genetics/metabolism ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; RNA, Messenger/metabolism ; Rabbits ; Receptors, Cell Surface/*genetics/metabolism ; Stromal Cells/*metabolism/pathology ; Transcription, Genetic ; U937 Cells/metabolism/pathology ; }, abstract = {The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new uPAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically recognized uPARAP in Western blotting and gave a strong signal in immunohistochemistry. The immunohistochemic localization pattern was found to be identical to that of uPARAP mRNA as determined in parallel by in situ hybridization. uPARAP expression was then studied in both benign and malignant breast lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor-associated mesenchymal cells. Double immunofluorescence analysis of invasive ductal carcinoma using antibodies against specific cell markers showed that uPARAP was localized in myofibroblasts and macrophages. No malignant cells, no endothelial cells and no vascular smooth muscle cells showed uPARAP immunoreactivity. We conclude that expression of uPARAP is associated with the abnormal breast and that expression appears in myofibroblasts, macrophages and myoepithelium. We suggest that uPARAP is involved in the clearance of the uPA:uPAR complex as well as other possible ligands during benign and malignant tissue remodeling.}, }
@article {pmid11899244, year = {2001}, author = {Towbin, JA and Bowles, NE}, title = {Molecular genetics of left ventricular dysfunction.}, journal = {Current molecular medicine}, volume = {1}, number = {1}, pages = {81-90}, doi = {10.2174/1566524013364077}, pmid = {11899244}, issn = {1566-5240}, mesh = {Cardiomyopathies/*genetics/metabolism/physiopathology ; Dystrophin/genetics/*metabolism ; Echocardiography ; Humans ; Models, Biological ; Syndrome ; Ventricular Dysfunction, Left/*genetics/metabolism/physiopathology ; }, abstract = {The left ventricle (LV) plays a central role in the maintenance of health of children and adults due to its role as the major pump of the heart. In cases of LV dysfunction, a significant percentage of affected individuals develop signs and symptoms of congestive heart failure (CHF), leading to the need for therapeutic intervention. Therapy for these patients include anticongestive medications and, in some, placement of devices such as aortic balloon pump or left ventricular assist device (LVAD), or cardiac transplantation. In the majority of patients the etiology is unknown, leading to the term idiopathic dilated cardiomyopathy (IDC). During the past decade, the basis of LV dysfunction has begun to unravel. In approximately 30-40% of cases, the disorder is inherited; autosomal dominant inheritance is most common (although X-linked, autosomal recessive and mitochondrial inheritance occurs). In the remaining patients, the disorder is presumed to be acquired, with inflammatory heart disease playing an important role. In the case of familial dilated cardiomyopathy (FDCM), the genetic basis is beginning to unfold. To date, two genes for X-linked FDCM (dystrophin, G4.5) have been identified and four genes for the autosomal dominant form (actin, desmin, lamin A/C, delta-sarcoglycan) have been described. In one form of inflammatory heart disease, coxsackievirus myocarditis, inflammatory mediators and dystrophin cleavage play a role in the development of LV dysfunction. In this review, we will describe the molecular genetics of LV dysfunction and provide evidence for a "final common pathway" responsible for the phenotype.}, }
@article {pmid11893034, year = {2002}, author = {Rosenthal, SI and Depowski, PL and Sheehan, CE and Ross, JS}, title = {Comparison of HER-2/neu oncogene amplification detected by fluorescence in situ hybridization in lobular and ductal breast cancer.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {10}, number = {1}, pages = {40-46}, doi = {10.1097/00129039-200203000-00007}, pmid = {11893034}, issn = {1541-2016}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; *Gene Amplification ; *Genes, erbB-2 ; Humans ; In Situ Hybridization, Fluorescence ; *Oncogenes ; }, abstract = {BACKGROUND: Abnormal expression of the HER-2/neu oncogene, a tyrosine kinase-type transmembrane growth factor receptor localized to chromosome 17q, has been associated with poor prognosis and the prediction of therapy response in invasive breast cancer. The comparative incidence and significance of HER-2/neu gene amplification for lobular and ductal breast cancer have not been previously characterized.<br><br>DESIGN: Formalin-fixed, paraffin-embedded primary breast cancer tissue sections from 71 women diagnosed with invasive lobular carcinoma were tested for HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) method using the Ventana unique sequence probe (Ventana Medical Systems, Tucson, AZ). A series of 106 cases of invasive ductal carcinoma was similarly processed and tested. Lymph node status was available for 155 (88%) of the 177 cases and 82 (46%) were lymph node-negative (LN-) and 73 (41%) were lymph node-positive (LN+). Patients were treated for a mean of 65 months (range 1-169 months).<br><br>RESULTS: 9 of 71 (13%) cases of lobular cancer featured HER-2/neu gene amplification, whereas 51 (48%) of 106 cases of ductal cancer showed amplification (P < 0.0001). On univariate analysis of combined lobular and ductal cases, HER-2/neu gene amplification detected by FISH predicted disease-related death (P < 0.0001). HER-2/neu gene amplification also predicted disease-related death in lobular cases alone (P = 0.003), LN+ lobular cases separately (P = 0.019), and LN- and LN+ ductal cases separately and alone (P < 0.0001). Multivariate analysis of the lobular group alone revealed that LN+ status (P = 0.015) and stage (P = 0.01) were independent predictors of disease-related death, and HER-2/neu gene amplification reached near significance (P = 0.086). In the ductal carcinoma group alone, HER-2/neu gene amplification (P = 0.03), lymph node status (P = 0.0001), tumor stage (P = 0.0001), and tumor grade (P = 0.044) were independent predictors of overall disease survival.<br><br>CONCLUSIONS: HER-2/neu gene amplification detected by FISH was identified at a significantly lower rate in lobular compared with ductal breast cancer. HER-2/neu gene amplification when present in lobular breast cancer is a significant adverse prognostic factor.}, }
@article {pmid11887115, year = {2002}, author = {Groah, SL and Weitzenkamp, DA and Lammertse, DP and Whiteneck, GG and Lezotte, DC and Hamman, RF}, title = {Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer.}, journal = {Archives of physical medicine and rehabilitation}, volume = {83}, number = {3}, pages = {346-351}, doi = {10.1053/apmr.2002.29653}, pmid = {11887115}, issn = {0003-9993}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Catheters, Indwelling/*adverse effects ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Rehabilitation Centers ; Risk Factors ; Sex Distribution ; Spinal Cord Injuries/*rehabilitation ; Urinary Bladder Neoplasms/epidemiology/*etiology/mortality ; }, abstract = {OBJECTIVES: To evaluate whether the risk of bladder cancer is greater in individuals with spinal cord injury (SCI) than in the general population and whether indwelling catheter (IDC) use is a significant independent risk factor for bladder cancer.<br><br>DESIGN: Historical cohort study in which subjects with SCI were stratified according to bladder management method and followed for the development of bladder cancer.<br><br>SETTING: A large rehabilitation hospital in the Spinal Cord Injury Model Systems.<br><br>PARTICIPANTS: A total of 3670 patients with SCI who were evaluated for bladder cancer on at least 1 occasion by cystoscopy over a period of 1 to 47 years.<br><br>INTERVENTIONS: Not applicable.<br><br>MAIN OUTCOME MEASURES: Bladder cancer occurring after SCI determined by diagnosis at our facility, by subject report, or by report of next of kin.<br><br>RESULTS: Twenty-one cases of bladder cancer were found in the 3670 study participants. The risk of bladder cancer for subjects with SCI using IDC is 77 per 100,000 person-years, corresponding to an age- and gender-adjusted standardized morbidity ratio (SMR) of 25.4 (95% confidence interval [CI], 14.0--41.9) when compared with the general population. After controlling for age at injury, gender, level and completeness of SCI, history of bladder calculi, and smoking, those using solely IDC had a significantly greater risk of bladder cancer (relative risk [RR] = 4.9; 95% CI, 1.3--13.8) than those using nonindwelling methods. Mortality caused by bladder cancer in individuals with SCI was significantly greater than that of the US population (SMR = 70.6; 95% CI, 36.9--123.3).<br><br>CONCLUSIONS: Bladder cancer risk and mortality are heightened in SCI compared with the general population. IDC is a significant independent risk factor for the increased risk of and mortality caused by bladder cancer in the SCI population.}, }
@article {pmid11869841, year = {2002}, author = {Grimm, W and Hoffmann J, J&#xfc; and Müller, HH and Maisch, B}, title = {Implantable defibrillator event rates in patients with idiopathic dilated cardiomyopathy, nonsustained ventricular tachycardia on Holter and a left ventricular ejection fraction below 30%.}, journal = {Journal of the American College of Cardiology}, volume = {39}, number = {5}, pages = {780-787}, doi = {10.1016/s0735-1097(01)01822-8}, pmid = {11869841}, issn = {0735-1097}, mesh = {Adolescent ; Adult ; Aged ; Cardiac Output, Low/*complications/physiopathology ; Cardiomyopathy, Dilated/*complications/physiopathology ; *Defibrillators, Implantable ; Electrocardiography ; *Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Stroke Volume/*physiology ; Syncope/*etiology/physiopathology/*therapy ; Tachycardia, Ventricular/*etiology/physiopathology/*therapy ; Time Factors ; Ventricular Fibrillation/*etiology/physiopathology/*therapy ; }, abstract = {OBJECTIVES: This study investigated the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions for ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with idiopathic dilated cardiomyopathy (IDC) and nonsustained VT in the presence of a left ventricular ejection fraction below 30%, versus in patients with syncope and patients with a history of VT or VF.<br><br>BACKGROUND: To date, only limited information is available about the prophylactic use of ICDs in patients with IDC.<br><br>METHODS: From January 1993 to July 2000, 101 patients with IDC underwent implantation of ICDs with electrogram storage capability at our institution. Patients were placed into one of three groups according to their clinical presentation: asymptomatic or mildly symptomatic nonsustained VT in the presence of a left ventricular ejection fraction < or = 30% (49 patients, prophylactic group), unexplained syncope or near syncope (26 patients, syncope group) and a history of sustained VT or VF (26 patients, VT/VF group).<br><br>RESULTS: During 36 +/- 22 months follow-up, 18 of 49 patients (37%) in the prophylactic group received appropriate shocks for VT or VF, compared with 8 of 26 patients (31%) in the syncope group and with 9 of 26 patients (35%) of the VT/VF group. Multivariate Cox analysis of baseline clinical variables identified left ventricular ejection fraction, atrial fibrillation and a history of sustained VT or VF as predictors for appropriate ICD interventions during follow-up.<br><br>CONCLUSIONS: Patients with IDC and prophylactic ICD implantation for nonsustained VT in the presence of a left ventricular ejection fraction < or = 30% had an incidence of appropriate ICD interventions similar to that of patients with a history of syncope or sustained VT or VF. These findings indicate that ICDs may have a role in not only secondary but also primary prevention of sudden death in IDC.}, }
@article {pmid11866083, year = {2002}, author = {Mahlfeld, K and Kayser, R and Grasshoff, H}, title = {Permanent thoracic myelopathy resulting from herniation of a calcified intervertebral disc in a child.}, journal = {Journal of pediatric orthopedics. Part B}, volume = {11}, number = {1}, pages = {6-9}, doi = {10.1097/00009957-200201000-00002}, pmid = {11866083}, issn = {1060-152X}, mesh = {Calcinosis/*complications ; Child ; Female ; Humans ; Intervertebral Disc Displacement/complications/*diagnosis/surgery ; Laminectomy ; Magnetic Resonance Imaging ; Recovery of Function ; Retrospective Studies ; Spinal Cord Diseases/*etiology ; Thoracic Vertebrae/pathology ; }, abstract = {This retrospective study was made to illustrate the rare occurrence of neurologic deficits resulting from intervertebral disc calcification (IDC) in a child. Most authors agree that juvenile IDC is usually a benign, self-limiting disease with excellent prognosis. The symptoms subside spontaneously in 95% of patients. Conservative treatment is therefore usually sufficient. Reviewing the English-speaking literature, only two further cases of operated juvenile IDC with myelopathy have been published. In the current report, we describe a case of permanent thoracic myelopathy resulting from juvenile IDC treated by urgent decompressive thoracic laminectomy. At the 3-year follow-up examination, the patient had not recovered fully. Persisting deficits in motor and sensory function were observed.}, }
@article {pmid11862580, year = {2002}, author = {Hanson, EL and Jakobs, PM and Keegan, H and Coates, K and Bousman, S and Dienel, NH and Litt, M and Hershberger, RE}, title = {Cardiac troponin T lysine 210 deletion in a family with dilated cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {8}, number = {1}, pages = {28-32}, doi = {10.1054/jcaf.2002.31157}, pmid = {11862580}, issn = {1071-9164}, support = {1R01HL58626-01/HL/NHLBI NIH HHS/United States ; }, mesh = {Cardiomyopathy, Dilated/*genetics ; Cardiomyopathy, Hypertrophic, Familial/genetics ; Exons ; Female ; Gene Deletion ; Humans ; Lysine/genetics ; Male ; Middle Aged ; Mutation ; Pedigree ; Troponin T/*genetics ; }, abstract = {BACKGROUND: The gene for cardiac troponin T (TNNT2) is 1 of 7 autosomal disease genes implicated in familial dilated cardiomyopathy (FDC). Identical deletions in exon 13 of TNNT2 have been reported in 2 families with FDC, but little is known about the frequency of this deletion among patients with FDC and idiopathic dilated cardiomyopathy (IDC) and the associated phenotype.<br><br>METHODS AND RESULTS: Exon 13 of the cardiac troponin T gene was sequenced in 61 subjects with FDC and 53 subjects with IDC. A 3-base pair deletion (DeltaLys210), identified in 1 family with at least 7 clinically affected family members, is reported. Age of disease onset and disease severity varied widely among affected individuals; phenotypic findings included dilated cardiomyopathy, sudden cardiac death, conduction system disease including atrial fibrillation and atrioventricular block, and heart failure. Sudden-onset, rapidly progressive disease was observed in younger individuals.<br><br>CONCLUSIONS: Cardiac troponin T exon 13 lysine deletions can cause FDC of varying severity and are an important but uncommon cause of FDC.}, }
@article {pmid11857490, year = {2002}, author = {Farabegoli, F and Champeme, MH and Bieche, I and Santini, D and Ceccarelli, C and Derenzini, M and Lidereau, R}, title = {Genetic pathways in the evolution of breast ductal carcinoma in situ.}, journal = {The Journal of pathology}, volume = {196}, number = {3}, pages = {280-286}, doi = {10.1002/path.1048}, pmid = {11857490}, issn = {0022-3417}, mesh = {Breast Neoplasms/*genetics/mortality ; Carcinoma in Situ/*genetics/mortality ; Carcinoma, Ductal, Breast/*genetics/mortality ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; *Loss of Heterozygosity ; Neoplasms, Multiple Primary/*genetics/mortality ; Polymerase Chain Reaction ; }, abstract = {The patterns of allelic loss in 28 cases of pure ductal carcinoma in situ (DCIS) and 25 cases of DCIS associated with invasive ductal carcinoma (IDC) were compared, in order to define whether pure DCIS represented an earlier stage than DCIS associated with IDC in the progression of breast carcinoma. To this aim, the polymerase chain reaction (PCR) was performed on microdissected normal and neoplastic breast tissue, formalin-fixed and paraffin-embedded. Fifteen microsatellite markers were examined, on chromosomes 1p, 3p, 7q, 11q, 12p, 13q, 16q and 17q, mostly focused on regions altered in breast cancer. Loss of heterozygosity (LOH) was greater in pure DCIS than in the DCIS component associated with IDC for 11 out of 15 markers. The difference was statistically significant for D13S260 and D17S800 (p=0.008 and p=0.01, respectively). DCIS associated with IDC showed a lesser degree of alteration than the synchronous IDC component for ten out of 15 markers. In contrast, LOH at D11S1816 and D16S318 was lower in pure DCIS than in DCIS associated with IDC and even greater in the IDC component. These results confirm that DCIS is a possible but not an obligate precursor of invasive breast cancer and suggest that pure DCIS and DCIS associated with IDC may be genetically distinct. The evolution from DCIS to IDC may follow multiple pathways and not a linear model.}, }
@article {pmid11823735, year = {2002}, author = {Kelleher, MM}, title = {Removal of urinary catheters: midnight vs 0600 hours.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {11}, number = {2}, pages = {84-90}, doi = {10.12968/bjon.2002.11.2.9308}, pmid = {11823735}, issn = {0966-0461}, mesh = {Aged ; Catheters, Indwelling/*adverse effects ; Device Removal/*adverse effects ; Female ; Humans ; Male ; Prospective Studies ; Time Factors ; Urinary Catheterization/*adverse effects ; Urination Disorders/*etiology ; }, abstract = {In the fields of both nursing and medicine there is a dearth of published literature on the optimum time to remove indwelling urinary catheters (IDCs) following urological surgery. Tradition seems to be in favour of removing IDCs at 0600 hours despite a lack of evidence to support this practice. This study was undertaken to determine whether midnight removal of IDCs resulted in patients' resuming normal voiding patterns. A prospective clinical trial was conducted to determine the impact midnight removal of urinary catheters would have on the patients' voiding pattern, and subsequent discharge from hospital. One hundred and sixty patients were entered into the study. The patients were allocated at random to have their urinary catheter removed either at midnight or at 0600 hours. Patients who had their catheters removed at midnight passed a greater volume of urine with both their first (268 ml compared with 177 ml; P<0.0001) and second voids (322 ml compared with 195 ml; P<0.0001) than their counterparts in the 0600 group. This permitted earlier discharge from hospital. The results reported in this study support the findings of earlier research that midnight removal of IDC leads to an earlier resumption of normal voiding patterns, permits earlier discharge from hospital and appears to reduce patients' anxiety. The recommendation from this study is that there should be a change in hospital policy so that the majority of IDCs are removed at midnight.}, }
@article {pmid11808897, year = {2001}, author = {Venugopalan, P and Agarwal, AK and de Bono, D}, title = {Low proportion of familial dilated cardiomyopathy in an arab population with a high prevalence of consanguineous marriages.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {90}, number = {11}, pages = {1267-1270}, doi = {10.1080/080352501317130308}, pmid = {11808897}, issn = {0803-5253}, mesh = {Adolescent ; Adult ; Cardiomyopathy, Dilated/*ethnology/*genetics ; Child ; Child, Preschool ; *Consanguinity ; Female ; Humans ; Infant ; Male ; Middle Aged ; Oman/epidemiology ; Prospective Studies ; Statistics, Nonparametric ; }, abstract = {UNLABELLED: In this study, 770/890 (87%) first-degree relatives from 108 families of hospitalized patients with idiopathic dilated cardiomyopathy (IDC) were screened using clinical examination, electrocardiography and echocardiography. Thirty percent of the patients were born to consanguineous parents. Familial dilated cardiomyopathy (FDC) was found in 7 (6.5%) families, which is lower than the earlier published figures of 20-25%. Patients with IDC were younger at presentation (p = 0.002) and were more often associated with parental consanguinity (p = 0.04). but the survival rates of familial patients did not differ significantly.<br><br>CONCLUSION: Despite the high prevalence of consanguinity, there was a low proportion of FDC in the study population. With the prospects of treatment of asymptomatic IDC to slow the progression of the disease, all family members of newly identified IDC patients should receive screening and counselling, with appropriate therapy where indicated.}, }
@article {pmid11784211, year = {2001}, author = {Fujioka, S and Kitaura, Y}, title = {Coxsackie B virus infection in idiopathic dilated cardiomyopathy: clinical and pharmacological implications.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {15}, number = {12}, pages = {791-799}, doi = {10.2165/00063030-200115120-00002}, pmid = {11784211}, issn = {1173-8804}, mesh = {Antiviral Agents/*therapeutic use ; Cardiomyopathy, Dilated/*complications/drug therapy/*virology ; *Enterovirus B, Human/genetics ; Enterovirus Infections/*complications/*drug therapy/genetics/virology ; Heart/virology ; Humans ; Treatment Outcome ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is a myocardial disease characterised by ventricular dilatation, impaired contractility, and the symptoms of congestive heart failure. Although the causes of IDC remain uncertain, much interest has been focused on the enteroviral infection in the myocardium in the pathogenesis of this disease. Enteroviral RNA has been demonstrated in the myocardium at all stages of IDC. Recent studies using sequence analysis of enteroviral polymerase chain reaction (PCR) products have shown that the viruses detected in hearts of patients with IDC are coxsackie B. In addition, active coxsackieviral RNA replication in the myocardium has been demonstrated by strand-specific detection of viral RNA. Viral antigen has also been found in hearts with IDC by immunohistochemical techniques. In tissue culture experiments and transgenic mice, it has been shown that restricted coxsackieviral RNA replication, and not infectious virus progeny, in the myocardium can impair cardiac contractile function and lead to dilated cardiomyopathy. Coxsackieviral RNA in the myocardium can be a marker of a poor clinical outcome after partial left ventriculectomy, and might influence prognosis after heart transplantation. Therefore, there is a therapeutic need to detect replicating coxsackieviral RNA in the myocardium, and a specific therapy for coxsackie B viruses is indicated in the management of patients with virus-positive IDC.}, }
@article {pmid11773334, year = {2002}, author = {Voss, A and Baier, V and Schumann, A and Hasart, A and Reinsperger, F and Schirdewan, A and Osterziel, KJ and Leder, U}, title = {Postextrasystolic regulation patterns of blood pressure and heart rate in patients with idiopathic dilated cardiomyopathy.}, journal = {The Journal of physiology}, volume = {538}, number = {Pt 1}, pages = {271-278}, pmid = {11773334}, issn = {0022-3751}, mesh = {Adult ; *Blood Pressure ; Cardiac Complexes, Premature/*complications/*physiopathology ; Cardiomyopathy, Dilated/*complications/*physiopathology ; Electrocardiography ; Female ; *Heart Rate ; Humans ; Male ; Middle Aged ; Reference Values ; }, abstract = {Assessment of fluctuations in heart rate (HR) following a premature ventricular complex (PVC) is valuable for identifying patients at high risk of sudden cardiac death. We hypothesised that postextrasystolic potentiation is the main determinant of the regulation patterns of blood pressure (BP) and HR following a PVC. Twelve patients with idiopathic dilated cardiomyopathy (IDC) and 13 control subjects with single PVCs (comparable coupling intervals) were investigated. Non-invasive finger arterial BP and ECGs were analysed. Regulation patterns following a single PVC were quantified using the indices postextrasystolic amplitude potentiation (PEAP) and maximum turbulence slope of five consecutive mean BP values (MBP-TS), and compared with the HR turbulence parameters turbulence slope (HR-TS) and turbulence onset (HR-TO). PEAP was significantly higher in IDC patients compared to controls (48.7 +/- 32.6 vs. 9.8 +/- 5.4 %, P < 0.01), whereas MBP-TS was lower (0.97 +/- 0.60 vs. 2.07 +/- 1.04 mmHg BBI(-1) (BBI, beat-to-beat interval), P < 0.05), as was HR-TS (8.46 +/- 7.90 vs. 30.73 +/- 22.90 ms BBI(-1), P < 0.01). HR-TO was significantly higher in IDC patients (-0.56 +/- 2.19 vs. -5.52 +/- 4.13 %, P < 0.01). In addition, the regulation patterns of BP and HR following a single PVC differed significantly between IDC patients and controls. Specifically, we observed pronounced PEAPs in IDC patients. The baroreflex response initiated by the low pressure amplitude of the PVC was suppressed in IDC patients due to the augmented potentiation of the first postextrasystolic blood pressure. Furthermore, IDC patients displayed impressive postextrasystolic pulsus alternans phenomena, whereas healthy subjects exhibited a typical baroreflex pattern. The pulsus alternans phenomenon seems to be triggered by a PVC.}, }
@article {pmid11744991, year = {2002}, author = {Terasaki-Fukuzawa, Y and Kijima, H and Suto, A and Takeshita, T and Iezumi, K and Sato, S and Yoshida, H and Sato, T and Shimbori, M and Shiina, Y}, title = {Decreased nm23 expression, but not Ki-67 labeling index, is significantly correlated with lymph node metastasis of breast invasive ductal carcinoma.}, journal = {International journal of molecular medicine}, volume = {9}, number = {1}, pages = {25-29}, pmid = {11744991}, issn = {1107-3756}, mesh = {Antigens, Nuclear ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology/secondary ; Female ; Gene Expression ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/*metabolism ; Lymphatic Metastasis ; Monomeric GTP-Binding Proteins/genetics/*metabolism ; NM23 Nucleoside Diphosphate Kinases ; Nuclear Proteins ; *Nucleoside-Diphosphate Kinase ; Transcription Factors/genetics/*metabolism ; }, abstract = {The nm23 gene was originally identified by differential hybridization of metastatic murine melanoma cell lines. Some experimental studies demonstrated a significantly reduced metastatic potential of melanoma cell lines transfected with the nm23 gene. In this study, we clarified the relationship between lymph node status and nm23 immunoreactivity, as well as Ki-67 labeling index (LI), of human breast cancer. Of the 44 breast invasive ductal carcinomas, nm23-diffusely positive expression [nm23(+)] was detected in 17 (38.6%), and focally positive/negative expression [nm23(+/-/-)] in 27 (61.4%) cases. Lymph node metastasis was found at a significantly higher incidence in the nm23(+/-/-) cases (18/27, 66.7%) than in the nm23(+) cases (4/17, 23.5%) (p>0.001). In the lymph node metastasis-positive cases, mean LI of Ki-67 cells was 20.9% at the center of the tumors and 24.0% at the advanced margins. In the lymph node metastasis-negative cases, mean LI of Ki-67 cells was 12.4% at the center of the tumors and 27.2% at the advanced margins. Decrease of nm23 expression, but not Ki-67 LI, was significantly correlated with lymph node metastasis of breast invasive ductal carcinoma.}, }
@article {pmid11729483, year = {2001}, author = {Chino, Y and Suzuki, Y and Ubukata, N and Yoshihara, K and Tani, T and Ogata, M}, title = {[Hepatic infusion of docetaxel using PEIT for a patient with stage IV breast cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {28}, number = {12}, pages = {1897-1899}, pmid = {11729483}, issn = {0385-0684}, mesh = {Antineoplastic Agents, Phytogenic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*secondary ; Cyclophosphamide/administration &amp; dosage ; Docetaxel ; Drug Administration Schedule ; Ethanol/administration &amp; dosage ; Fadrozole/administration &amp; dosage ; Female ; Floxuridine/administration &amp; dosage ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Injections, Intralesional ; Liver Neoplasms/*drug therapy/*secondary ; Middle Aged ; Paclitaxel/*analogs &amp; derivatives/*therapeutic use ; *Taxoids ; }, abstract = {Hepatic infusion of docetaxel using PEIT was performed for a patient with stage IV breast cancer. Docetaxel was effective to a solitary liver metastatic lesion. A 64-year-old woman was admitted to our hospital because of a left breast mass that was bleeding. She was diagnosed with stage IV breast cancer. Surgery was performed on February 16th. The pathological diagnosis was invasive ductal carcinoma, and hormone receptors were negative. Two weeks after operation, monthly docetaxel injections were given together with doxifluidine 400 mg/day p.o., cyclophosphamide 50 mg/day p.o., and fadrozole hydrochloride hydrate 2 mg/day p.o. After two courses, hepatic infusion of docetaxel was performed using PEIT after informed consent. The patient's high serum CEA and CA15-3 level returned to the normal range. A metastatic lesion on CT changed to a cystic pattern. These results suggest that PEIT is worth trying in patients with solitary liver metastasis from breast cancer.}, }
@article {pmid11726136, year = {2001}, author = {Spisek, R and Bretaudeau, L and Barbieux, I and Meflah, K and Gregoire, M}, title = {Standardized generation of fully mature p70 IL-12 secreting monocyte-derived dendritic cells for clinical use.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {50}, number = {8}, pages = {417-427}, doi = {10.1007/s002620100215}, pmid = {11726136}, issn = {0340-7004}, mesh = {Apoptosis ; Cell Culture Techniques/*methods ; Cell Differentiation ; Cell Division ; Cell Survival ; Cells, Cultured/cytology/drug effects/metabolism ; Dendritic Cells/*cytology/drug effects/metabolism ; Dinoprostone/pharmacology ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Hemocyanins/immunology ; Humans ; Immunophenotyping ; Interleukin-1/pharmacology ; Interleukin-12/chemistry/*metabolism ; Interleukin-13/pharmacology ; Interleukin-6/pharmacology ; Lymphocyte Culture Test, Mixed ; Melanoma/pathology ; Phagocytosis ; Poly I-C/pharmacology ; Protein Structure, Tertiary ; Recombinant Proteins/pharmacology ; Reproducibility of Results ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/pharmacology ; }, abstract = {Dendritic cells (DC) have been shown to be efficient antigen-presenting cells (APC) and, as such, could be considered ideal candidates for cancer immunotherapy. Immature DC (iDC) efficiently capture surrounding antigens; however, only mature DC (mDC) prime naive T lymphocytes. Clinical trials using DC-based tumor vaccines have achieved encouraging, but limited, success, possibly due to the use of immature or incompletely mature DC. Thus, it was apparent that a method capable of generating large numbers of fully functional iDC, their pulsing with desired form of tumor antigens and the subsequent complete and reproducible maturation of iDC is needed. Therefore, we compared two different methods of producing large numbers of iDC. Both protocols yielded comparable numbers of cells with an iDC phenotype with phagocytic function. We next determined which of the clinically applicable activators could induce the complete and reproducible maturation of DC, in order to define the most suitable combination for future clinical trials. Only a combination of TNFalpha + Poly (I:C), or a previously described cytokine cocktail of TNFalpha + IL-1beta + IL-6 + prostaglandin E2, induced the complete activation of the whole DC population, as assessed by the cell surface expression of CD83 and costimulatory molecules. The matured DC were functionally superior to iDC in their ability to stimulate the proliferation of allogeneic lymphocytes and autologous keyhole limpet hemocyanin (KLH)-specific T lymphocytes. Furthermore, only the combination of TNFalpha + Poly (L:C) activated DC to produce large amounts of biologically active p70 IL-12. Thus DC maturation by TNFalpha + Poly (I:C) could efficiently bias T cell response towards Th1 response. Implementation of our results into clinical protocols used for DC generation could be beneficial for future immunotherapy trials.}, }
@article {pmid11721699, year = {2001}, author = {Matera, L and Mori, M and Galetto, A}, title = {Effect of prolactin on the antigen presenting function of monocyte-derived dendritic cells.}, journal = {Lupus}, volume = {10}, number = {10}, pages = {728-734}, doi = {10.1191/096120301717164967}, pmid = {11721699}, issn = {0961-2033}, mesh = {Animals ; *Antigen Presentation/drug effects ; Antigens, Surface/immunology ; Autoimmunity/immunology ; *Cell Differentiation ; Dendritic Cells/*cytology/drug effects/*immunology ; Humans ; Monocytes/*cytology ; Prolactin/*immunology/pharmacology ; Stem Cells/*cytology ; }, abstract = {Monocyte derived macrophages (Mphi) and dendritic cells (DC) play critical roles at the interface between innate and adaptive immunity. Both types of cells can effectively phagocytose exogenous antigens, whereas only DC can process and present them efficiently to antigen-specific T lymphocytes. The hormone PRL is also produced by immune cells and is regarded as a key component of the neuroendocrine--immune loop and a local regulator of lymphocyte response. Its main feature is cooperation with cytokines and hemopoietins. Triggering of monocyte PRL receptors with physiological-to-supraphysiological concentrations of PRL up-regulates the GM-CSF receptors, resulting in synergistic PRL-GM-CSF induced maturation of immature (i)DC. Further incubation induces increased antigen-presenting activity at the highest PRL concentrations studied (200 ng/ml). IFN-gamma, release by allogeneic lymphocytes is dependent on T cell-triggered IL-12 release by PRL-preincubated iDC. This, in turn, may be secondary to increased DC expression of CD40 or IFN-gamma. The permissive action of high PRL concentrations in the antigen presenting process may be of significance in initiation of the response against major histocompatibility complex (MHC)-presented self-antigens and may explain the association of hyperprolactinemia with autoimmune diseases.}, }
@article {pmid11706082, year = {2001}, author = {Wang, X and Mori, I and Tang, W and Yang, Q and Nakamura, M and Nakamura, Y and Sato, M and Sakurai, T and Kennichi, K}, title = {Metaplastic carcinoma of the breast: p53 analysis identified the same point mutation in the three histologic components.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {14}, number = {11}, pages = {1183-1186}, doi = {10.1038/modpathol.3880456}, pmid = {11706082}, issn = {0893-3952}, mesh = {Base Sequence ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Squamous Cell/genetics/metabolism/*pathology ; Chondrosarcoma/genetics/metabolism/pathology ; DNA Mutational Analysis ; DNA, Neoplasm/chemistry/genetics ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Metaplasia ; Middle Aged ; Point Mutation ; Tumor Suppressor Protein p53/analysis/genetics ; }, abstract = {A rare case of metaplastic carcinoma of the breast with both squamous metaplasia and cartilaginous metaplasia was reported. Histologically, the neoplasm revealed complex features, which were consisting of invasive ductal carcinoma, squamous carcinomatous component and chondrosarcomatoid component. Gradual transition of each component was recognized microscopically. p53 mutation analysis disclosed the same point mutation in three histologically different components, but not in the normal epithelium. Based on the morphologic findings, immunohistochemical findings and the p53 mutation analysis, we concluded that these three components in the tumor originated from the same duct progenitor cells.}, }
@article {pmid11706057, year = {2001}, author = {Nielsen, BS and Sehested, M and Duun, S and Rank, F and Timshel, S and Rygaard, J and Johnsen, M and Danø, K}, title = {Urokinase plasminogen activator is localized in stromal cells in ductal breast cancer.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {81}, number = {11}, pages = {1485-1501}, doi = {10.1038/labinvest.3780363}, pmid = {11706057}, issn = {0023-6837}, mesh = {Antibody Specificity ; Biomarkers, Tumor ; Breast Neoplasms/enzymology/*pathology ; Carcinoma, Ductal, Breast/enzymology/*pathology ; Detergents ; Enzyme-Linked Immunosorbent Assay ; Female ; Fixatives ; Fluorescent Antibody Technique ; Formaldehyde ; Humans ; In Situ Hybridization ; Octoxynol ; Paraffin Embedding ; RNA, Messenger/analysis ; Stromal Cells/*enzymology ; Trypsin ; Urokinase-Type Plasminogen Activator/*analysis/genetics/immunology ; }, abstract = {Urokinase plasminogen activator (uPA) regulates a proteolytic cascade that facilitates cancer invasion through degradation of the extracellular matrix, and high levels of uPA in human breast cancer tissue correlate with poor prognosis. We previously found that, in ductal breast cancer, uPA mRNA is highly expressed by myofibroblasts surrounding invasively growing cancer cells. However, the localization of uPA protein has not been settled in the published literature. Because uPA is a secreted molecule, it could conceivably be localized differently from its mRNA. We have studied the localization of uPA immunoreactivity in detail. Twenty-five cases of invasive ductal carcinoma were analyzed with three different uPA antibody preparations, all of which gave an essentially identical stromal staining pattern. Using double immunofluorescence, we identified uPA immunoreactivity in myofibroblasts and macrophages in all cases examined. Additionally, in approximately half of the tumors, we saw uPA staining of endothelial cells. In 3 of the 25 cases, a small subpopulation of the cancer cells was uPA-positive. We conclude that uPA immunoreactivity is almost exclusively associated with stromal cells, which thus play a major role in generation of proteolytic activity in ductal breast cancer.}, }
@article {pmid11694790, year = {2001}, author = {Ménard, S and Fortis, S and Castiglioni, F and Agresti, R and Balsari, A}, title = {HER2 as a prognostic factor in breast cancer.}, journal = {Oncology}, volume = {61 Suppl 2}, number = {}, pages = {67-72}, doi = {10.1159/000055404}, pmid = {11694790}, issn = {0030-2414}, mesh = {Adult ; Age of Onset ; Aged ; Biomarkers, Tumor/*analysis ; Breast/chemistry/pathology ; Breast Neoplasms/*chemistry/classification/genetics/mortality/pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/genetics/pathology ; Cell Transformation, Neoplastic/genetics ; Diagnostic Tests, Routine ; Disease Progression ; Estrogens ; Female ; Genes, bcl-2 ; Genes, erbB-2 ; Genes, p53 ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating ; Middle Aged ; Mitotic Index ; Models, Biological ; Necrosis ; Neoplasm Invasiveness ; Neoplasm Proteins/*analysis ; Neoplasms, Hormone-Dependent/chemistry/genetics/mortality/pathology ; Phenotype ; Precancerous Conditions/metabolism/pathology ; Prognosis ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Risk Factors ; }, abstract = {HER2 amplification/overexpression is a marker of poor prognosis in breast cancer. The prognostic impact of HER2 positivity is lower in node-negative compared with node-positive women. The only significant, independent prognostic factors in breast cancer are node status, HER2 status and menopausal status. HER2-positive tumors also contain p53 abnormalities, tend to be hormone receptor and bcl-2 negative, have lymphoid infiltration (LI) and a high mitotic index. Patients with LI who are HER2 positive have a better prognosis than those who are HER2 negative, whereas HER2-positive patients without LI have a significantly worse prognosis than HER2-negative patients. Morphological and biological alterations appear to identify two categories of breast tumor. Two hypotheses may explain the progression to two tumor types: (1) atypical ductal hyperplasia (ADH) is a precursor of ductal carcinoma in situ (DCIS), which is a precursor of invasive ductal carcinoma (IDC); or (2) ADH is a precursor of HER2-negative IDC whereas DCIS is a precursor of HER2-positive IDC. The second theory fits well with two breast cancer subsets and the characteristics of ADH and DCIS. The first type of IDC occurs in older patients, progresses slowly due to estrogen dependency but is aggressive long term. The other type progresses rapidly, is HER2 positive and is more likely to occur in young patients.}, }
@article {pmid11694076, year = {2001}, author = {Enomoto, M and Nagayama, H and Takahashi, TA}, title = {Enhancement of migratory and aggregate activities of human peripheral blood monocyte-derived dendritic cells by stimulation with RANTES.}, journal = {Microbiology and immunology}, volume = {45}, number = {9}, pages = {639-647}, doi = {10.1111/j.1348-0421.2001.tb01297.x}, pmid = {11694076}, issn = {0385-5600}, mesh = {Cell Movement ; Chemokine CCL5/analysis/genetics/*immunology ; Dendritic Cells/*immunology ; Dose-Response Relationship, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Humans ; Leukocytes, Mononuclear/*immunology ; Lymphocyte Activation ; Polymerase Chain Reaction ; RNA, Messenger/analysis ; Tumor Necrosis Factor-alpha/immunology ; }, abstract = {We examined the effects of various chemokines on the functional activation of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4)-generated human peripheral blood monocyte-derived immature dendritic cells (iDC). Stimulation of iDC with regulated on activation normal T cell expressed and secreted (RANTES) resulted in the promotion of their chemotactic migratory capacity in response to RANTES when compared with that of unstimulated cells. TNF-alpha induced a homotypic aggregated cluster formation of iDC in a dose-dependent manner, whereas the combination of TNF-alpha and RANTES exhibited more potent induction. IDC stimulated with RANTES were more efficient than unstimulated iDC in the production of endogenous RANTES. Treatment of iDC with the combination of TNF-alpha and RANTES was just little effective for the enhancement of allogeneic T-cell stimulatory capacity as compared with that of TNF-alpha treated iDC. These results suggest that endogenous secretions of RANTES from iDC stimulated with RANTES be potentially involved in RANTES-induced changes of properties with respect to morphology and function.}, }
@article {pmid11692213, year = {2001}, author = {de Leeuw, N and Ruiter, DJ and Balk, AH and de Jonge, N and Melchers, WJ and Galama, JM}, title = {Histopathologic findings in explanted heart tissue from patients with end-stage idiopathic dilated cardiomyopathy.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {14}, number = {5}, pages = {299-306}, doi = {10.1007/s001470100339}, pmid = {11692213}, issn = {0934-0874}, mesh = {Adult ; CD8-Positive T-Lymphocytes/immunology/pathology ; Cardiomyopathy, Dilated/*pathology ; Cell Nucleus/pathology/ultrastructure ; Female ; Heart Transplantation/*physiology ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Inflammation/immunology/pathology ; Myocardium/immunology/*pathology/ultrastructure ; Patient Selection ; T-Lymphocytes/immunology/pathology ; }, abstract = {Explanted hearts were examined to determine whether specific histopathologic features are present in the myocardium of patients with end-stage idiopathic dilated cardiomyopathy (IDC). Extensive histopathologic examination by light microscopy, electron microscopy and immunohistochemistry revealed marked fibrosis in the hearts of 21 of 37 IDC patients and in 26 of 35 patients with heart diseases of known causes. Reactive (interstitial and perivascular) fibrosis predominated in the IDC hearts, whereas both reparative (replacement) fibrosis and reactive fibrosis were found in the comparison group. Endocardial fibroelastosis was found in nine patients with IDC and in 14 patients from the comparison group. Distinct patterns of fibrosis were the sole significant histopathologic difference between myocardial samples from patients with IDC and from those with heart diseases of known causes. The diffuse presence of reactive fibrosis in IDC patients suggests a more generalised dysfunction that affects the composition of the myocardial extracellular matrix.}, }
@article {pmid11673063, year = {2001}, author = {Mehrabi, MR and Serbecic, N and Ekmekcioglu, C and Tamaddon, F and Ullrich, R and Sinzinger, H and Glogar, HD}, title = {The isoprostane 8-epi-PGF(2alpha) is a valuable indicator of oxidative injury in human heart valves.}, journal = {Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology}, volume = {10}, number = {5}, pages = {241-245}, doi = {10.1016/s1054-8807(01)00084-9}, pmid = {11673063}, issn = {1054-8807}, mesh = {Adult ; Aged ; Aortic Valve/*metabolism/*pathology ; Biomarkers ; Cardiomyopathies/*metabolism/*pathology ; Dinoprost/*analogs &amp; derivatives/*metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; *Oxidative Stress ; Pulmonary Valve/*metabolism/*pathology ; Radioimmunoassay ; Risk Factors ; }, abstract = {To date, little information is available concerning oxidative injury in human cardiac valves. Therefore, we sought to investigate whether the isoprostane, 8-epi-PGF(2alpha), a novel oxidative stress marker, is localized in aortic and pulmonary valves derived from explanted hearts of patients suffering from idiopathic dilative cardiomyopathy (IDC). By using semiquantitative immunohistochemistry, we demonstrated that 8-epi-PGF(2alpha) is localized in both valves with pulmonary valves accumulating more of this isoprostane compared to aortic valves (36.69+/-12.04% vs. 31.54+/-11.49%, P<.05). These results were confirmed by a radioimmunoassay (RIA) analysis showing a similar, but not significant, difference between the two valves (288.50+/-72.18 pg/mg protein in the pulmonary valves and 267.30+/-58.77 pg/mg protein in aortic valves, P=.09). Considering the data presented in this study, we suggest that 8-epi-PGF(2alpha) is a valuable indicator of oxidative injury in human semilunar valves.}, }
@article {pmid11665790, year = {2001}, author = {Baba, A and Yoshikawa, T and Chino, M and Murayama, A and Mitani, K and Nakagawa, S and Fujii, I and Shimada, M and Akaishi, M and Iwanaga, S and Asakura, Y and Fukuda, K and Mitamura, H and Ogawa, S and , }, title = {Characterization of anti-myocardial autoantibodies in Japanese patients with dilated cardiomyopathy.}, journal = {Japanese circulation journal}, volume = {65}, number = {10}, pages = {867-873}, doi = {10.1253/jcj.65.867}, pmid = {11665790}, issn = {0047-1828}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Autoantibodies/*analysis ; Cardiomyopathy, Dilated/etiology/*immunology ; Case-Control Studies ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Japan ; Male ; Middle Aged ; Myocardium/*immunology ; Odds Ratio ; Tachycardia, Ventricular/immunology ; }, abstract = {Few previous reports have comprehensively screened all the anti-myocardial autoantibodies (AMCA) in relation to other clinical profiles in patients with idiopathic dilated cardiomyopathy (IDC), so the present study used both immunohistochemistry (FITC) and immunoblotting (IB) for screening patients with IDC in order to characterize the clinical significance of AMCA. Sera were collected from 100 patients with IDC and age-matched 100 healthy control subjects (CTL). For FITC, an unfixed frozen section of human myocardium was used for the standard indirect immunofluorescence; for IB, total cardiac homogenates of the same myocardium were blotted to serum at 2 sets of dilution (1:200 and 1:10,000). The positive rates of AMCA detection for each method were as follows (IDC vs CTL); 39% vs 6% for FITC, 38% vs 4% for IB (1:200), and 10% vs 0% for IB (1:10,000). Fifty-nine patients with IDC and 8 CTL were positive for AMCA by either method, and 18 patients with IDC and 2 CTL were positive for AMCA by both methods. IB-positivity at 1:200 was an independent predictor by multiple logistic regression analysis of non-sustained ventricular tachycardias as well as left ventricular end-diastolic diameter and plasma norepinephrine concentration.}, }
@article {pmid11597324, year = {2001}, author = {Unger, MA and Rishi, M and Clemmer, VB and Hartman, JL and Keiper, EA and Greshock, JD and Chodosh, LA and Liebman, MN and Weber, BL}, title = {Characterization of adjacent breast tumors using oligonucleotide microarrays.}, journal = {Breast cancer research : BCR}, volume = {3}, number = {5}, pages = {336-341}, pmid = {11597324}, issn = {1465-5411}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Diagnosis, Differential ; Female ; Gene Expression Profiling ; Humans ; Neoplasms, Second Primary/genetics/*pathology ; Oligonucleotide Array Sequence Analysis ; RNA, Neoplasm/*genetics ; }, abstract = {BACKGROUND: Current methodology often cannot distinguish second primary breast cancers from multifocal disease, a potentially important distinction for clinical management. In the present study we evaluated the use of oligonucleotide-based microarray analysis in determining the clonality of tumors by comparing gene expression profiles.<br><br>METHOD: Total RNA was extracted from two tumors with no apparent physical connection that were located in the right breast of an 87-year-old woman diagnosed with invasive ductal carcinoma (IDC). The RNA was hybridized to the Affymetrix Human Genome U95A Gene Chip (12,500 known human genes) and analyzed using the Gene Chip Analysis Suite 3.3 (Affymetrix, Inc, Santa Clara, CA, USA) and JMPIN 3.2.6 (SAS Institute, Inc, Cary, NC, USA). Gene expression profiles of tumors from five additional patients were compared in order to evaluate the heterogeneity in gene expression between tumors with similar clinical characteristics.<br><br>RESULTS: The adjacent breast tumors had a pairwise correlation coefficient of 0.987, and were essentially indistinguishable by microarray analysis. Analysis of gene expression profiles from different individuals, however, generated a pairwise correlation coefficient of 0.710.<br><br>CONCLUSION: Transcriptional profiling may be a useful diagnostic tool for determining tumor clonality and heterogeneity, and may ultimately impact on therapeutic decision making.}, }
@article {pmid11562768, year = {2001}, author = {Hoang, MP and Callender, DL and Sola Gallego, JJ and Huang, Z and Sneige, N and Luna, MA and Batsakis, JG and El-Naggar, AK}, title = {Molecular and biomarker analyses of salivary duct carcinomas: comparison with mammary duct carcinoma.}, journal = {International journal of oncology}, volume = {19}, number = {4}, pages = {865-871}, doi = {10.3892/ijo.19.4.865}, pmid = {11562768}, issn = {1019-6439}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/genetics/pathology ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology ; Chromosome Aberrations ; DNA, Neoplasm/*analysis ; Female ; Flow Cytometry ; Humans ; Immunoenzyme Techniques ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Receptors, Androgen/analysis ; Salivary Gland Neoplasms/*chemistry/genetics/pathology ; Tumor Suppressor Protein p53/analysis ; }, abstract = {Salivary duct carcinoma (SDC) is a rare high-grade aggressive neoplasm that manifests close histologic features with invasive ductal carcinoma of the breast (IDC). In contrast to SDC, extensive molecular studies have been performed on IDC and led to the identification of certain biological markers. To investigate the underlying molecular and biologic characteristics of SDC, we performed molecular analyses using microsatellite markers on chromosomal arms 6q, 16q, 17p, and 17q, DNA flow cytometry and immunohistochemical staining for androgen receptor (AR) and p53 expression on 28 examples of these tumors in comparison to 24 IDC cases. Our results show that generally similar allelic alterations, elevated p53 and androgen receptor expressions, and high frequency of DNA aneuploidy are manifested in both SDCs and IDCs. Differences at certain markers on 6q, 17p and 17q chromosomal loci, however, were observed between the two entities. Certain loci on 6q were more frequently altered in SDC than IDC which loci on chromosomes 17p and q arms were more seen in IDCs than SDCs. The majority of SDCs had high AR expression while most of IDCs were AR negative. Our study indicates that: i) SDC may share some genetic alterations with IDC, ii) high AR expression in SDC may play a role in tumor progression, and iii) p53 overexpression and DNA aneuploidy in both entities reflect their aggressive behavior.}, }
@article {pmid11561770, year = {2001}, author = {Kollara, A and Kahn, HJ and Marks, A and Brown, TJ}, title = {Loss of androgen receptor associated protein 70 (ARA70) expression in a subset of HER2-positive breast cancers.}, journal = {Breast cancer research and treatment}, volume = {67}, number = {3}, pages = {245-253}, doi = {10.1023/a:1017938608460}, pmid = {11561770}, issn = {0167-6806}, mesh = {Biopsy ; Blotting, Western ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; *Cell Division ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Nuclear Receptor Coactivators ; *Oncogene Proteins ; Phosphorylation ; Receptors, Androgen/*biosynthesis/metabolism ; Signal Transduction ; Trans-Activators/*biosynthesis/metabolism ; *Transcription Factors ; Transfection ; Tumor Cells, Cultured ; }, abstract = {Co-transfection studies indicate that HER2 (erbB-2) overexpression results in the phosphorylation and enhanced transcriptional activity of the androgen receptor (AR). This amplification of AR action is further enhanced by the expression of ARA70, a putative co-activator with a predilection for the AR. Because androgens inhibit the growth of breast cancer cells whereas HER2 overexpression stimulates the growth of these cells, it seems possible that loss of expression of AR or ARA70 in some HER2 overexpressing tumors might confer a growth advantage to these cells. We examined ARA70 and AR expression in 20 HER2-positive (overexpressing) and 21 HER2-negative cases of breast invasive ductal carcinoma (IDC) to determine the relationship between loss of ARA70 and/or AR with HER2 overexpression. Strong ARA70 immunostaining was observed in all normal and breast epithelial cells in fibrocystic change and in in situ carcinoma present in the patient samples. Of the 41 cases of IDC, focal or complete loss of ARA70 protein expression was observed in 46% of the cases, with 60% of HER2-positive versus 33% of HER2-negative cases showing loss. Loss of AR expression was observed in 60% of HER2-positive versus 43% of HER2-negative cases. Remarkably, only 20% of HER2-positive tumors expressed both AR and ARA70, while 43% of HER2-negative tumors expressed both of these elements of the AR signaling pathway. This trend is consistent with a possible clinical relevance of the potential crosstalk between the HER2 and AR signaling pathways. Western blot analysis for ARA70 expression performed on frozen breast biopsies of normal or malignant breast tissue from four patients revealed a 70 kDa immunoreactive band in all four normal tissue samples, with an additional 35 kDa band in two of the breast cancer samples and in human breast cancer MCF-7 cells. This may reflect aberrant splicing in some breast cancers, leading to the emergence of the 35 kDa isoform.}, }
@article {pmid11523929, year = {2001}, author = {Zheng, WQ and Looi, LM and Cheah, PL}, title = {A comparison of the patterns of laminin expression in fibroadenoma, fibrocystic diseases, pre-invasive and invasive ductal breast carcinoma.}, journal = {Pathology}, volume = {33}, number = {3}, pages = {303-306}, pmid = {11523929}, issn = {0031-3025}, mesh = {Basement Membrane/chemistry/metabolism/pathology ; Breast Neoplasms/chemistry/*metabolism/pathology ; Carcinoma, Ductal, Breast/chemistry/*metabolism/secondary ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Fibroadenoma/chemistry/*metabolism/pathology ; Fibrocystic Breast Disease/chemistry/*metabolism/pathology ; Humans ; Immunoenzyme Techniques ; Laminin/analysis/*biosynthesis ; Middle Aged ; Neoplasm Staging ; }, abstract = {The basement membrane (BM), of which laminin is a major glycoprotein component, is an important barrier to tumour cells which must be breeched before metastatic spread can occur. We have compared the pattern of laminin expression in a range of benign and malignant breast lesions to better understand the process of tumour progression. A total of 162 cases of breast samples, comprising 18 fibroadenomas, 22 cases of fibrocystic disease, 96 cases of invasive ductal carcinoma and 26 carcinomas with intraductal components, were evaluated for laminin expression by a standard immunoperoxidase method on formalin-fixed, paraffin-embedded histological sections, using a commercial antibody against human laminin. The pattern of laminin expression was charted as follows: Type I, > 70% of BM complete/continuous; Type II, > 70% of BM moderately disrupted; Type III, > 70% of BM completely disrupted. The Type I pattern was observed in all cases of fibroadenoma and fibrocystic diseases, and in 77% of intraductal carcinoma components. Various patterns of BM disruption were observed in invasive ductal carcinoma. Severity of BM disruption correlated with histological grade of the carcinomas (P < 0.001). Small-sized tumours, those without lymphatic invasion and lymph node-negative tumours showed more complete patterns of laminin expression. The current study suggests that tumour cells with high histological grade possess an enhanced capacity to disrupt the basement membrane, an important step in the metastatic process. The detection of BM disruption by immunohistochemical staining for laminin is technically easy and may be usefully applied for the differentiation of in situ and microinvasive carcinoma.}, }
@article {pmid11479429, year = {2001}, author = {Lana, AM and Wen, DR and Cochran, AJ}, title = {The morphology, immunophenotype and distribution of paracortical dendritic leucocytes in lymph nodes regional to cutaneous melanoma.}, journal = {Melanoma research}, volume = {11}, number = {4}, pages = {401-410}, doi = {10.1097/00008390-200108000-00011}, pmid = {11479429}, issn = {0960-8931}, support = {CA29605/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Antigen Presentation ; Cell Size ; Dendritic Cells/*immunology/pathology ; Female ; HLA-DR Antigens/immunology ; Humans ; Immunohistochemistry ; *Immunophenotyping ; Leukocytes/immunology/pathology ; Lymph Nodes/*immunology/pathology ; Male ; Melanoma/*immunology/pathology ; Middle Aged ; Neoplasm Metastasis/immunology ; Neoplasm Staging ; Skin Neoplasms/*immunology/pathology ; }, abstract = {Our aim was to identify and delineate alterations in the distribution and immunophenotype of the lymphocytes and paracortical dendritic leucocytes (interdigitating dendritic cells; IDCs) in lymph nodes regional to tumours. Using immunocytochemistry and computer-assisted image analysis we examined 65 lymph nodes excised from 47 patients with malignant melanoma. Twenty-nine patients had American Joint Committee on Cancer (AJCC) stage II melanoma (no tumour spread beyond the primary site) and 18 had AJCC stage III disease (metastases in the regional nodes). There were significant differences in the frequency, morphology, immunophenotype and anatomical distribution of the IDCs and in the complexity of their dendritic processes in different areas within individual lymph nodes. We conclude that morphological and phenotypical variations in IDCs correlate with differing levels of antigen presentation. Downregulation of antigen presentation in lymph nodes regional to tumours is most probably mediated by tumour products. Differences in IDC distribution and characteristics in lymph nodes from different anatomical sites must be considered in interpreting studies of nodal morphology and function.}, }
@article {pmid11473487, year = {2001}, author = {Grassi, G and Seravalle, G and Bertinieri, G and Turri, C and Stella, ML and Scopelliti, F and Mancia, G}, title = {Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy.}, journal = {Clinical science (London, England : 1979)}, volume = {101}, number = {2}, pages = {141-146}, pmid = {11473487}, issn = {0143-5221}, mesh = {Adult ; Aged ; Analysis of Variance ; Baroreflex/drug effects/*physiology ; Blood Pressure/drug effects/physiology ; Cardiomyopathy, Dilated/blood/*complications/physiopathology ; Case-Control Studies ; Chromatography, High Pressure Liquid ; Female ; Heart Failure/blood/etiology/*physiopathology ; Heart Rate/drug effects/physiology ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/blood/*complications/physiopathology ; Nitroprusside/pharmacology ; Norepinephrine/blood ; Phenylephrine/pharmacology ; Renin/blood ; Stroke Volume/drug effects/physiology ; Sympathetic Nervous System/drug effects/*physiopathology ; Vasodilator Agents/pharmacology ; }, abstract = {Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n=22, age 60.3+/-2.4 years, means+/-S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n=20, age 58.9+/-2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3+/-4.2 and 67.8+/-3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.}, }
@article {pmid11446840, year = {2001}, author = {Patel, MI and Watts, W and Grant, A}, title = {The optimal form of urinary drainage after acute retention of urine.}, journal = {BJU international}, volume = {88}, number = {1}, pages = {26-29}, doi = {10.1046/j.1464-410x.2001.02253.x}, pmid = {11446840}, issn = {1464-4096}, mesh = {Acute Disease ; Aged ; Aged, 80 and over ; Catheters, Indwelling ; Drainage/*methods ; Feasibility Studies ; Humans ; Male ; Middle Aged ; Patient Satisfaction ; Prospective Studies ; Self Care/methods ; Treatment Outcome ; Urinary Catheterization/*methods ; Urinary Retention/complications/*therapy ; Urinary Tract Infections/complications ; }, abstract = {OBJECTIVE: To assess the outcome of different forms of urinary drainage, particularly for urinary tract infection (UTI), operative findings and patient preference, in patients treated for acute urinary retention (AUR).<br><br>PATIENTS AND METHODS: A feasibility trial was conducted of men presenting with AUR; after a short period of indwelling catheterization (IDC) patients were taught how to use clean intermittent self-catheterization (CISC). Patients who failed this were re-catheterized and taught to manage a valve, or failing this a leg bag, and then discharged home. The patients were followed to assess the occurrence of spontaneous voiding, UTI, findings at prostatectomy and patient satisfaction.<br><br>RESULTS: The CISC group (34 men) had a higher rate of spontaneous voiding than the IDC group (16 men; 56% vs 25%). The incidence of UTI was 32% in the CISC and 75% in the IDC group. At TURP, 20% in the CISC group had a UTI, compared with 69% in the IDC group. Patients using CISC preferred it and had fewer complications than the IDC group. The CISC group had a similar ability to manage and similar acceptance of their method of drainage as the IDC group.<br><br>CONCLUSION: CISC is managed and accepted well by patients who can use the technique and results in fewer UTIs. It should be considered in patients who present with AUR, and it may delay surgery.}, }
@article {pmid11439345, year = {2001}, author = {Cheng, CW and Wu, PE and Yu, JC and Huang, CS and Yue, CT and Wu, CW and Shen, CY}, title = {Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene.}, journal = {Oncogene}, volume = {20}, number = {29}, pages = {3814-3823}, doi = {10.1038/sj.onc.1204505}, pmid = {11439345}, issn = {0950-9232}, mesh = {Adaptor Proteins, Signal Transducing ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carrier Proteins ; CpG Islands ; DNA Methylation ; DNA-Binding Proteins/genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; MutL Protein Homolog 1 ; Neoplasm Proteins/genetics ; Nuclear Proteins ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Snail Family Transcription Factors ; Transcription Factors/genetics ; WT1 Proteins ; }, abstract = {Loss of heterozygosity (LOH) allows the expression of recessive mutation in tumor suppressor genes (TSG). Therefore, on the basis of Knudson's 'two-hit' hypothesis for TSG inactivation, the detection of a high LOH frequency in a chromosomal region is considered critical for TSG localization. One of these LOH regions in breast cancer is 16q22.1, which has been suggested to reflect the involvement of E-cadherin (E-cad), a cell-cell adhesion molecule. To confirm the tumorigenic role of E-cad, 81 sporadic invasive ductal carcinomas (IDCs) of the breast were tested for the 'two hits' required to inactivate this gene. A high frequency (37.3%) of LOH was detected in 67 informative tumors, but no mutation was found. To examine the possibility that transcriptional mechanisms serve as the second hit in tumors with LOH, specific pathways, including genetic variant and hypermethylation at the promoter region and abnormal expression of positive (WT1) and negative (Snail) transcription factors, were identified. Of these, promoter hypermethylation and increased expression of Snail were found to be common (>35%), and to be strongly associated with reduced/negative E-cad expression (P<0.05). However, unexpectedly, a significantly negative association was found between the existence of LOH and promoter hypermethylation (P<0.05), which contradicts the 'two-hit' model. Instead, since they coexisted in a high frequency of tumors, hypermethylation may work in concert with increased Snail to inactivate E-cad expression. Given that E-cad is involved in diverse mechanisms, loss of which is beneficial for tumors to invade but may also trigger apoptosis, this study suggests that maintaining a reversible mechanism, either by controlling the gene at the transcriptional level or by retaining an intact allele subsequent to LOH, might be important for E-cad in IDC and may also be common in TSGs possessing diverse functions. These findings provide clues to explain why certain TSGs identified by LOH cannot fulfil the two-hit hypothesis.}, }
@article {pmid11431676, year = {2001}, author = {La Vecchia, L and Zanolla, L and Varotto, L and Bonanno, C and Spadaro, GL and Ometto, R and Fontanelli, A}, title = {Reduced right ventricular ejection fraction as a marker for idiopathic dilated cardiomyopathy compared with ischemic left ventricular dysfunction.}, journal = {American heart journal}, volume = {142}, number = {1}, pages = {181-189}, doi = {10.1067/mhj.2001.116071}, pmid = {11431676}, issn = {0002-8703}, mesh = {Adult ; Cardiomyopathy, Dilated/*etiology/physiopathology ; Chi-Square Distribution ; Coronary Angiography ; Female ; Hemodynamics ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Ischemia/complications/physiopathology ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; Stroke Volume ; Systole ; Ventricular Dysfunction, Left/*complications/physiopathology ; Ventricular Dysfunction, Right/*complications/physiopathology ; }, abstract = {BACKGROUND: Evidence for the role of right ventricular (RV) function is emerging in patients with heart failure of different etiologies. Studies conducted in dilated cardiomyopathy (IDC) showed a high prevalence of RV dysfunction unrelated to the severity of pulmonary hypertension. The aim of the study was to investigate the role of RV dysfunction in ischemic versus nonischemic patients.<br><br>METHODS: A series of 153 patients with left ventricular (LV) dysfunction (defined as a LV ejection fraction <45%) of either ischemic (n = 61, coronary artery disease [CAD] group) or nonischemic (n = 92, IDC group) origin were studied invasively. Besides routine catheterization data, RV volumes and ejection fractions were obtained angiographically. Reference data were collected in a control group of healthy subjects. RV dysfunction was defined as a RV ejection fraction <35% and ventricular concordance as a <10% difference between RV and LV ejection fraction. The LV/RV end-diastolic volume ratio was calculated to assess the relative dilatation of the ventricular chambers. Hemodynamic and angiographic data were compared in the 2 groups by univariate and multivariate logistic regression analysis.<br><br>RESULTS: Patients with IDC and CAD had comparable LV ejection fractions (29% +/- 3% vs 31% +/- 8%, P not significant) and mean pulmonary pressures (27 +/- 12 mm Hg vs 26 +/- 11 mm Hg, P not significant); the LV/RV end-diastolic volume ratio was identical in the 2 groups (1.26 +/- 0.4 vs 1.24 +/- 0.4, P not significant). RV ejection fraction was significantly lower in IDC compared with CAD (33% +/- 10 % vs 46% +/- 11%, P <.0001), with a prevalence of RV dysfunction in the IDC group of 65% compared with 16% in the CAD group (P <.0001); similarly, the prevalence of ejection fraction concordance was 74% versus 33%, respectively (P <.0001). At multivariate analysis, a low RV ejection fraction was a powerful independent predictor of IDC compared with CAD (odds ratio 0.91, 95% confidence interval 0.87-0.94, P <.0001). RV dysfunction had a positive predictive value of 75% and a negative predictive value of 78% for the diagnosis of IDC; for ventricular concordance, these values were 81% and 69%, respectively. The correlation between mean pulmonary artery pressure and RV ejection fraction was weaker in the IDC group compared with the CAD group (R(2) = 0.032, P =.047 and R(2) = 0.172,P <.0001, respectively).<br><br>CONCLUSION: In the presence of LV dysfunction, a reduced RV ejection fraction is a powerful marker for IDC compared with CAD, independent of age, pulmonary hypertension, LV function, and ventricular dimensions. These findings support the concept that IDC is frequently characterized by a biventricular involvement and that the presence of RV dysfunction represents a distinguishing feature of this disease.}, }
@article {pmid11422790, year = {2001}, author = {Moriya, T and Suzuki, T and Pilichowska, M and Ariga, N and Kimura, N and Ouchi, N and Nagura, H and Sasano, H}, title = {Immunohistochemical expression of gonadotropin releasing hormone receptor in human breast carcinoma.}, journal = {Pathology international}, volume = {51}, number = {5}, pages = {333-337}, doi = {10.1046/j.1440-1827.2001.01210.x}, pmid = {11422790}, issn = {1320-5463}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/*metabolism/pathology ; Carcinoma, Ductal, Breast/chemistry/*metabolism/secondary ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/chemistry ; Lymph Nodes/pathology ; Menopause ; Middle Aged ; Neoplasm Staging ; Receptors, Estrogen/analysis/metabolism ; Receptors, LHRH/analysis/*metabolism ; Receptors, Progesterone/analysis/metabolism ; }, abstract = {Gonadotropin releasing hormone (GnRH) analogs can cause regression of hormone-dependent breast carcinomas via the specific GnRH receptor (GnRH-R). In an attempt to obtain a better understanding of GnRH actions in human breast carcinoma, the expression of GnRH-R was examined immunohistochemically in 58 invasive ductal carcinomas and correlated with various clinicopathological parameters. GnRH-R was immunolocalized in the cytoplasm of carcinoma cells in 37 of 58 invasive ductal carcinoma cases (64%). Immunoreactivity for GnRH-R was also detected focally in the cytoplasm of morphologically normal glandular epithelia adjacent to the carcinoma. A significant correlation was observed between the immunohistochemical expression of GnRH-R and estrogen receptor labeling index (LI; P = 0.030) or progesterone receptor LI (P = 0.0074). There was a significant inverse correlation between GnRH-R immunoreactivity and Ki-67 LI (P = 0.012). No significant correlations were detected between GnRH-R and other clinicopathological parameters, including patient age, menopausal status, stage, tumor size, lymph node status, histological grade and prognosis. This study indicates that GnRH-R is widely distributed in human breast carcinoma cells and regulates GnRH actions locally. Breast carcinomas positive for GnRH-R maintain some hormonal regulatory mechanisms, and GnRH actions may lead to a low proliferative rate in human breast carcinoma.}, }
@article {pmid11409797, year = {2001}, author = {Cox, CE and Nguyen, K and Gray, RJ and Salud, C and Ku, NN and Dupont, E and Hutson, L and Peltz, E and Whitehead, G and Reintgen, D and Cantor, A}, title = {Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS?.}, journal = {The American surgeon}, volume = {67}, number = {6}, pages = {513-9; discussion 519-21}, pmid = {11409797}, issn = {0003-1348}, support = {R21 CA66553-01/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Lymph Node Excision/economics ; Lymphatic Metastasis ; Mastectomy/economics ; Mastectomy, Segmental/economics ; Neoplasm Invasiveness/pathology ; Prospective Studies ; Risk Factors ; *Sentinel Lymph Node Biopsy/economics ; Staining and Labeling ; }, abstract = {The appropriateness of sentinel lymph node biopsy in the management of patients with biopsy diagnoses of ductal carcinoma in situ (DCIS) or DCIS with microinvasion (DCISM) has not been established. Three hundred forty-one patients presented with a biopsy diagnosis of DCIS or DCISM. Two hundred forty (70%) underwent sentinel node biopsy at their definitive procedure. All clinical and pathologic data were collected prospectively. Of 224 patients with a biopsy diagnosis of DCIS 23 (10%) were upstaged to infiltrating ductal carcinoma (IDC) at their definitive therapy and of 16 patients with a biopsy diagnosis of DCISM seven (44%) were upstaged to IDC. Excisional biopsies were no more sensitive for detecting IDC than was core biopsy. Lymph node metastases were detected in 26 of 195 (13%) patients with a definitive diagnosis of DCIS, in three of 15 (20%) with a definitive diagnosis of DCISM, and in eight of 30 (27%) with a definitive diagnosis of IDC. Sentinel lymph node biopsy is a valuable tool in the treatment of patients with DCIS and DCISM and is particularly needed in those undergoing mastectomy. No "high-risk" group of patients can be identified for selective sentinel lymph node biopsy.}, }
@article {pmid11400156, year = {2001}, author = {Sapino, A and Bongiovanni, M and Cassoni, P and Righi, L and Arisio, R and Deaglio, S and Malavasi, F}, title = {Expression of CD31 by cells of extensive ductal in situ and invasive carcinomas of the breast.}, journal = {The Journal of pathology}, volume = {194}, number = {2}, pages = {254-261}, doi = {10.1002/1096-9896(200106)194:2&lt;254::AID-PATH880&gt;3.0.CO;2-2}, pmid = {11400156}, issn = {0022-3417}, mesh = {Aged ; Aged, 80 and over ; Anus Neoplasms/immunology ; Biomarkers, Tumor/analysis ; Breast Neoplasms/blood supply/*immunology ; Carcinoma in Situ/blood supply/*immunology ; Carcinoma, Ductal, Breast/blood supply/*immunology ; Case-Control Studies ; Female ; Humans ; Hyaluronan Receptors/analysis ; Middle Aged ; *Neovascularization, Pathologic ; Paget Disease, Extramammary/immunology ; Paget's Disease, Mammary/immunology ; Platelet Endothelial Cell Adhesion Molecule-1/*analysis ; Vulvar Neoplasms/immunology ; }, abstract = {CD31, an adhesion molecule expressed by endothelial cells, leukocytes, and platelets, is used in surgical pathology as a marker of normal and neoplastic vascularization. During the assessment of angiogenesis in breast carcinomas, CD31 expression was observed in a single case of large (5.2 cm diameter) high nuclear grade ductal carcinoma in situ (HG-DCIS) associated with poorly differentiated invasive ductal carcinoma (G3-IDC). Expression was limited to the cell membrane. This study focused on 32 HG-DCIS> or = 2 cm, either pure or associated with IDC. Cancer cells wereCD31(+) in 11 cases. Double staining using anti-CD31 monoclonal antibody (MAb) and anti-CD44 MAb, the anti-hyaluronate receptor, showed that foci of CD31(+) and CD44(-) tumour cells could be traced throughout the glandular tree, marking the intraductal diffusion of tumour up to Paget's cells at the nipple. The associated G3-IDC and their lymph node metastases were instead CD31(+) and CD44(+). CD31(+) tumours were oestrogen receptor (ER)(-), frequently p53(+) and c-erb-B2(+), and infiltrated by CD4(+) T lymphocytes. Normal and hyperplastic epithelia were constantly CD31(-). Other endothelial markers (e.g Factor VIII-RA and CD34) were not expressed by carcinoma cells, as was CD38, the CD31 ligand. In conclusion, CD31 expression is a feature acquired by breast cancer cells in the DCIS model. CD31 expression mainly correlates with tumour cells spreading within the ductal system. Finally, the invasive phenotype requires the co-expression of CD31 and CD44.}, }
@article {pmid11391857, year = {2001}, author = {Minari, Y and Nio, Y and Hirahara, N and Dong, M}, title = {Heterogeneic distribution of thymidine phosphorylase between primary tumors and metastatic lesions of human pancreatic ductal carcinoma: implications for the efficacy of chemotherapy with 5-FU or its derivatives.}, journal = {Cancer chemotherapy and pharmacology}, volume = {47}, number = {5}, pages = {415-422}, doi = {10.1007/s002800000252}, pmid = {11391857}, issn = {0344-5704}, mesh = {Aged ; Antimetabolites, Antineoplastic/*pharmacokinetics/therapeutic use ; Carcinoma, Pancreatic Ductal/drug therapy/*enzymology/mortality/secondary ; Chemotherapy, Adjuvant ; Female ; Fluorouracil/*pharmacokinetics/therapeutic use ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/drug therapy/*enzymology/mortality/pathology ; Survival Rate ; Thymidine Phosphorylase/*metabolism ; Treatment Outcome ; }, abstract = {PURPOSE: It has been suggested that the expression of thymidine phosphorylase (TdRPase) correlates with the malignant potential of various cancers, but its involvement in human invasive ductal carcinoma (IDC) of the pancreas has not been reported. In the present study, the distribution and clinical significance of TdRPase in IDCs and benign diseases of the pancreas were assessed, especially in relation to the efficacy of chemotherapy with 5-FU or its derivatives.<br><br>METHOD: The expression of TdRPase in 148 specimens of pancreatic IDCs (66 primary lesions, 46 nodal lesions and 36 distant metastases from 126 patients) and in 24 specimens of benign diseases (4 cystadenomas, 3 hyperplasias, and 17 chronic pancreatitises) was examined by immunohistochemical staining with anti-TdRPase monoclonal antibody and evaluated in terms of three grades of immunoreactivity: negative 0, low 1, or high 2.<br><br>RESULTS: Positive TdRPase staining (low and high immunoreactivity) was detected in 71% (47/66) of the primary lesions, in 46% (21/46) of the involved nodes, in 53% (19/36) of various lesions of distant metastasis, and in 37% (9/24) of the benign diseases. The staining intensity was significantly higher in the IDC tissues than in the benign disease tissues, and significantly lower in the metastatic lesions than in the primary lesions. TdRPase reactivity did not correlate with the survival rate in both resectable and unresectable IDCs. In patients with both primary tumor and nodal involvement, however, high TdRPase activity in involved nodes was significantly associated with a poor prognosis. On the other hand, although adjuvant chemotherapy was found to improve the survival of patients, TdRPase activity in the tumor did not show any significant relationship with the efficacy of chemotherapy with 5-FU or its derivatives.<br><br>CONCLUSIONS: The present study suggested that in pancreatic IDC the activity of TdRPase in primary lesions is different from that in metastatic lesions, and that DNA is synthesized mainly through the salvage pathway in primary lesions and through a de novo pathway in metastatic lesions. This may be one of the reasons for the heterogeneity in chemosensitivity of human pancreatic IDC.}, }
@article {pmid11385691, year = {2001}, author = {Romanzi, LJ and Groutz, A and Heritz, DM and Blaivas, JG}, title = {Involuntary detrusor contractions: correlation of urodynamic data to clinical categories.}, journal = {Neurourology and urodynamics}, volume = {20}, number = {3}, pages = {249-257}, doi = {10.1002/nau.1002}, pmid = {11385691}, issn = {0733-2467}, mesh = {Female ; Humans ; Male ; Muscle Contraction ; Muscle Hypertonia/*classification/complications/*physiopathology ; Muscle, Smooth/physiopathology ; Urinary Bladder/*physiopathology ; Urinary Bladder Diseases/*classification/complications/*physiopathology ; Urinary Bladder, Neurogenic/etiology/physiopathology ; Urinary Incontinence/etiology/physiopathology ; Urinary Incontinence, Stress/etiology/physiopathology ; Urination Disorders/etiology/*physiopathology ; *Urodynamics ; }, abstract = {Data regarding the prevalence and urodynamic characteristics of involuntary detrusor contractions (IDC) in various clinical settings, as well as in neurologically intact vs. neurologically impaired patients, are scarce. The aim of our study was to evaluate whether the urodynamic characteristics of IDC differ in various clinical categories. One hundred eleven consecutive neurologically intact patients and 21 consecutive neurologically impaired patients, referred for evaluation of persistent irritative voiding symptoms, were prospectively enrolled. All patients were presumed by history to have IDC, and underwent detailed clinical and urodynamic evaluation. Based on clinical evaluation, patients were placed into one of four categories according to the main presenting symptoms and the existence of neurological insult: 1) frequency/urgency; 2) urge incontinence; 3) mixed stress incontinence and irritative symptoms; and 4) neurogenic bladder. IDC was defined by detrusor pressure of > or = 15 cm H2O whether or not the patient perceived the contraction; or < 15 cm H2O if perceived by the patient. Eight urodynamic characteristics of IDC were analyzed and compared between the four groups. IDC were observed in all of the neurologically impaired patients, compared with 76% of the neurologically intact patients (P < 0.001). No correlation was found between amplitude of IDC and subjective report of urgency. All clinical categories demonstrated IDC at approximately 80% of cystometric capacity. Eighty-one percent of the neurologically impaired patients, compared with 97% of the neurologically intact patients, were aware of the IDC at the time of urodynamics (P < 0.04). The ability to abort the IDC was significantly higher among continent patients with frequency/urgency (77%) compared with urge incontinent patients (46%) and neurologically impaired patients (38%). In conclusion, when evaluating detrusor overactivity, the characteristics of the IDC are not distinct enough to aid in differential diagnosis. However, the ability to abort IDC and stop incontinent flow may have prognostic implications, especially for the response to behavior modification, biofeedback, and pelvic floor exercise.}, }
@article {pmid11377350, year = {2001}, author = {Ortiz, M and Almendral, J and López-Palop, R and Villacastín, J and Arenal, A}, title = {Determinants of inducibility of ventricular tachycardia.}, journal = {The American journal of cardiology}, volume = {87}, number = {11}, pages = {1255-1259}, doi = {10.1016/s0002-9149(01)01545-4}, pmid = {11377350}, issn = {0002-9149}, mesh = {Adult ; Aged ; *Cardiac Pacing, Artificial ; *Electrocardiography ; Female ; Heart Conduction System/physiopathology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Risk Factors ; Stroke Volume/physiology ; Tachycardia, Ventricular/*diagnosis/etiology/physiopathology ; }, abstract = {We analyzed the incidence and predictive factors for induction of clinical ventricular tachycardia (VT) during an electrophysiologic study in 127 patients with structural heart disease and spontaneous VT documented by 12-lead electrocardiography. Eighty-five patients had coronary artery disease (CAD), 24 had idiopathic dilated cardiomyopathy (IDC), and 18 had right ventricular dysplasia (RVD). Clinical variables were age, gender, electrocardiographic patterns of spontaneous arrhythmia, cardiac diagnosis, left ventricular (LV) ejection fraction (EF), infarct location, and presence of LV aneurysm. Clinical VT was induced in 76 patients (60%, group 1) and was not induced in 51 patients (group 2). Clinical VT was induced in 83% of patients with RVD, 58% of patients with CAD, and 50% of patients with IDC (p = 0.07). LVEF tended to be significantly higher in group 1 than in group 2 (p = 0.06). The presence of left QRS axis in the frontal plane during spontaneous VT was significantly associated with a higher inducibility both in the general group (69% vs 46%, p <0.02) and in patients with CAD (70% vs 44%, p <0.02). In patients with CAD, only the presence of a left QRS axis was significantly associated with a higher inducibility. A multivariate analysis identified only the left QRS axis as a significant and independent predictor of induction of clinical VT. The association of a leftward axis with inducibility suggests that vectorial factors in the depolarization wavefronts may be related to inducibility since conventional stimulation is performed from the right ventricle, producing a leftward axis in most cases.}, }
@article {pmid11358433, year = {2001}, author = {Le, Y and Wetzel, MA and Shen, W and Gong, W and Rogers, TJ and Henderson, EE and Wang, JM}, title = {Desensitization of chemokine receptor CCR5 in dendritic cells at the early stage of differentiation by activation of formyl peptide receptors.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {99}, number = {3}, pages = {365-372}, doi = {10.1006/clim.2001.5021}, pmid = {11358433}, issn = {1521-6616}, support = {DA06650/DA/NIDA NIH HHS/United States ; DA11130/DA/NIDA NIH HHS/United States ; DA12113/DA/NIDA NIH HHS/United States ; F31DA05894/DA/NIDA NIH HHS/United States ; N01-CO-56000/CO/NCI NIH HHS/United States ; T32DA07237/DA/NIDA NIH HHS/United States ; }, mesh = {Cell Differentiation ; Chemokine CCL4 ; Chemokine CCL5/pharmacology ; Dendritic Cells/*physiology/virology ; Down-Regulation ; HIV-1/drug effects/physiology ; Humans ; Macrophage Inflammatory Proteins/pharmacology ; Phosphorylation ; Receptors, CCR5/*physiology ; Receptors, Formyl Peptide ; Receptors, Immunologic/*physiology ; *Receptors, Lipoxin ; Receptors, Peptide/*physiology ; }, abstract = {Chemokine receptors are subjected to heterologous desensitization by activation of formyl peptide receptors. We investigated the cross-talk between formyl peptide receptors and the chemokine receptor CCR5 in human monocyte-differentiated immature dendritic cells (iDC). Monocytes cultured with GM-CSF and IL-4 for 4 days exhibit markers characteristic of iDC and maintain the expression of both formyl peptide receptors FPR and FPRL1, as well as CCR5. Pretreatment of iDC with W peptide (WKYMVm), a potent agonist for FPR and FPRL1 but with preference for FPRL1, resulted in down-regulation of CCR5 from the cell surface and reduced cell response to the CCR5 ligands through a PKC-dependent pathway. Furthermore, W peptide induced a PKC-dependent phosphorylation of CCR5 and inhibited infection of iDC by R5 HIV-1. Our results indicate that the expression and functions of CCR5 in iDC can be attenuated by W peptide, which activates formyl peptide receptors, and suggest an approach to the design of novel anti-HIV-1 agents.}, }
@article {pmid11357998, year = {2000}, author = {Andrade, SG and Pimentel, AR and de Souza, MM and Andrade, ZA}, title = {Interstitial dendritic cells of the heart harbor Trypanosoma cruzi antigens in experimentally infected dogs: importance for the pathogenesis of chagasic myocarditis.}, journal = {The American journal of tropical medicine and hygiene}, volume = {63}, number = {1-2}, pages = {64-70}, doi = {10.4269/ajtmh.2000.63.64}, pmid = {11357998}, issn = {0002-9637}, mesh = {Animals ; Antibodies, Monoclonal ; Antigens, Protozoan/isolation &amp; purification ; Case-Control Studies ; Chagas Cardiomyopathy/immunology/*parasitology ; Dendritic Cells/*immunology/pathology ; Dogs ; Heart/parasitology ; Immunohistochemistry ; Myocarditis/immunology/*parasitology ; Myocardium/*cytology ; Trypanosoma cruzi/*pathogenicity ; }, abstract = {Heart sections from 16 mongrel dogs, two normal controls and 14 infected with Trypanosoma cruzi, were submitted to immunohistochemical staining with either rabbit anti-cow S100 Protein monoclonal antibody or rabbit anti-T. cruzi purified specific antibody, using the peroxidase technique to investigate the participation of the interstitial dendritic cells of the heart (IDCs) in myocarditis of Chagas disease. Trypanosoma cruzi antigens were revealed as granular and dense deposits in IDC membrane in the heart of infected dogs both during acute and chronic myocarditis, but not in normal controls. Anti-S100 Protein labeled the IDCs, both in normal and infected dogs and a significant increase in the numbers of IDCs occurred in the myocardium, proportionally to the intensity of the inflammatory infiltration. These findings suggest that IDCs, probably by presenting T. cruzi antigens to immune-competent cells, play an important role in the pathogenesis of Chagas disease.}, }
@article {pmid11353046, year = {2001}, author = {Tsuda, H and Takarabe, T and Akashi-Tanaka, S and Fukutomi, T and Hirohashi, S}, title = {Pattern of chromosome 16q loss differs between an atypical proliferative lesion and an intraductal or invasive ductal carcinoma occurring subsequently in the same area of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {14}, number = {5}, pages = {382-388}, doi = {10.1038/modpathol.3880322}, pmid = {11353046}, issn = {0893-3952}, mesh = {Adult ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics/pathology/surgery ; *Chromosomes, Human, Pair 16 ; DNA, Neoplasm/analysis ; Female ; Humans ; Loss of Heterozygosity ; Microsatellite Repeats ; Middle Aged ; Papilloma, Intraductal/genetics/pathology ; Polymerase Chain Reaction ; Precancerous Conditions/*genetics/pathology/surgery ; }, abstract = {Atypical proliferative lesions of the breast, such as atypical ductal hyperplasia and atypical papilloma, are considered to be precursors of breast carcinomas and have frequently been shown to have loss of heterozygosity (LOH) on chromosome 16q at the DNA level. We evaluated whether an atypical proliferative lesion and a carcinoma that subsequently occurred in the same area of the ipsilateral breast were of identical clonal origin in seven patients. Using DNA isolated from microdissected archival tissue of epithelial components of both the biopsy specimen of the atypical proliferative lesion and the mastectomy specimen of the carcinoma, the pattern of LOH on 16q was compared between these two lesions using polymerase chain reaction -microsatellite LOH analysis. As a control, LOH on 16q was examined in 13 cases of usual ductal hyperplasia, 10 usual papillomas, and 6 atypical ductal hyperplasias. In the seven cases, LOH on 16q was detected in three of the six atypical proliferative lesions and in five of the seven carcinomas, but the allele with LOH or a deleted region always differed between the two. LOH was detected in both atypical proliferative lesions and carcinomas in one case, only in the atypical proliferative lesion in two cases, and only in carcinomas in three cases. In the controls, LOH on 16q was absent in usual ductal hyperplasias or usual papillomas but was detected in two of six atypical ductal hyperplasias. Although atypical proliferative lesions were frequently confirmed to be of clonal nature with LOH on 16q, these lesions and carcinomas were considered to be clones, probably originated from a field with these clones.}, }
@article {pmid11348414, year = {2001}, author = {Diaz, LK and Wiley, EL and Morrow, M}, title = {Expression of epithelial mucins Muc1, Muc2, and Muc3 in ductal carcinoma in situ of the breast.}, journal = {The breast journal}, volume = {7}, number = {1}, pages = {40-45}, doi = {10.1046/j.1524-4741.2001.007001040.x}, pmid = {11348414}, issn = {1075-122X}, mesh = {Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Breast/chemistry ; Breast Neoplasms/*chemistry/pathology ; Carcinoma in Situ/*chemistry ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Culture Techniques ; Female ; Humans ; Immunohistochemistry ; Mucin-1/*analysis/*genetics ; Mucin-2 ; Mucin-3 ; Mucins/*analysis ; Prognosis ; Sensitivity and Specificity ; }, abstract = {Epithelial mucins are glycoproteins secreted by epithelial cells and their carcinomas. At least nine mucin genes have been identified, and their products (MUC1-MUC9) are expressed in various epithelia. MUC1 is a mucin expressed in breast epithelial cells, whereas MUC2 and MUC3 are primarily intestinal mucins. Although MUC1 and MUC2 expression has been documented in invasive ductal carcinoma of the breast, mucin expression in pure ductal carcinoma in situ (DCIS) has not been investigated. Sixty-one of 105 cases of DCIS without coexisting infiltrating carcinoma diagnosed during a 30-month period were selected as having sufficient tissue for study. Paraffin-embedded tissue sections were stained using immunohistochemical techniques with mouse monoclonal anti-MUC1, anti-MUC2, and rabbit-specific polyclonal anti-MUC3 antibodies. Immunoreactive epitopes of MUC1, MUC2, and MUC3 were expressed in DCIS in 61, 19, and 16 of 61 cases, respectively. MUC2 and MUC3 staining intensity in DCIS was markedly less than that observed for MUC1. Luminal and/or cytoplasmic patterns of staining were observed for MUC1. MUC2 and MUC3 showed only cytoplasmic staining. Cytoplasmic-only staining of MUC1 was associated with a higher grade of DCIS. Any MUC2 staining was also associated with a higher grade of DCIS. Coexpression of MUC2 and MUC3 was present in only 6 of 61 cases, and MUC3 staining was unrelated to the grade of DCIS. Cytoplasmic expression of MUC1 and MUC2 appears to be associated with a higher grade of DCIS. MUC3 expression appears to be independent of grade and expression of MUC1 and MUC2. The relationship of mucin expression and grade warrants further study.}, }
@article {pmid11348409, year = {2001}, author = {Kader, HA and Jackson, J and Mates, D and Andersen, S and Hayes, M and Olivotto, IA}, title = {Tubular carcinoma of the breast: a population-based study of nodal metastases at presentation and of patterns of relapse.}, journal = {The breast journal}, volume = {7}, number = {1}, pages = {8-13}, doi = {10.1046/j.1524-4741.2001.007001008.x}, pmid = {11348409}, issn = {1075-122X}, mesh = {Adenocarcinoma/epidemiology/*pathology ; Adolescent ; Adult ; Age Distribution ; Aged ; Axilla ; Breast Neoplasms/epidemiology/*pathology ; British Columbia/epidemiology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Case-Control Studies ; Disease-Free Survival ; Female ; Humans ; Incidence ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*pathology ; Neoplasm Staging ; Population Surveillance ; Probability ; Reference Values ; Retrospective Studies ; Risk Factors ; Survival Rate ; }, abstract = {Tubular carcinoma of the breast (TCB) is a recognized histologic variant of infiltrating ductal carcinoma (IDC) and has been considered to have a comparatively favorable prognosis. However, previous studies have been based on small numbers of cases, some pure TCB and some mixed histology, or have not employed an appropriate comparison group. In this study 171 pure TCB cases and a comparison group of 386 cases with grade I (well differentiated) IDC were identified in a population-based database maintained by the British Columbia Cancer Agency (BCCA). The proportion of cases with axillary nodal involvement at presentation was lower in TCB cases than in the grade I IDC comparison group (12.9% and 23.9%, respectively; p < 0.05). Low-risk tumors (T1 and without vascular lymphatic or perineural invasion) were more prevalent in the TCB patients than in the grade I IDC patients (66.7% and 60.0%; p < 0.05). Low-risk TCB cases had a significantly lower rate of nodal metastases at presentation than low-risk grade I IDC cases (7.0% and 13.2%; p < 0.05). Kaplan-Meier and log-rank analyses indicated a statistically significantly lower rate of local recurrence in TCB cases than among IDC cases (p < 0.05) and a trend toward a lower rate of systemic relapse in TCB cases (p = 0.07). However, no difference in disease-specific survival was observed between TCB cases and grade I IDC comparisons. We conclude that the biologic behavior of TCB was more favorable than that of a comparison group of IDC cases. In view of the low incidence of axillary node metastases at presentation in the low-risk TCB subset (7%), axillary dissection may be omitted as part of the initial surgical management in these patients.}, }
@article {pmid11346867, year = {2001}, author = {Sasson, AR and Fowble, B and Hanlon, AL and Torosian, MH and Freedman, G and Boraas, M and Sigurdson, ER and Hoffman, JP and Eisenberg, BL and Patchefsky, A}, title = {Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation.}, journal = {Cancer}, volume = {91}, number = {10}, pages = {1862-1869}, doi = {10.1002/1097-0142(20010515)91:10&lt;1862::aid-cncr1207&gt;3.0.co;2-#}, pmid = {11346867}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma in Situ/mortality/*pathology/therapy ; Carcinoma, Lobular/mortality/*pathology/therapy ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Factors ; Survival Rate ; }, abstract = {BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy.<br><br>METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years.<br><br>RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women.<br><br>CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.}, }
@article {pmid11345133, year = {2001}, author = {Hashimoto, K and Nio, Y and Sumi, S and Toga, T and Omori, H and Itakura, M and Yano, S}, title = {Correlation between TGF-beta1 and p21 (WAF1/CIP1) expression and prognosis in resectable invasive ductal carcinoma of the pancreas.}, journal = {Pancreas}, volume = {22}, number = {4}, pages = {341-347}, doi = {10.1097/00006676-200105000-00002}, pmid = {11345133}, issn = {0885-3177}, mesh = {Adult ; Aged ; Carcinoma, Pancreatic Ductal/*genetics/mortality/surgery ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/*genetics ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatectomy ; Pancreatic Neoplasms/*genetics/mortality/surgery ; Prognosis ; Survival Rate ; Transforming Growth Factor beta/*genetics ; }, abstract = {Transforming growth factor-beta1 (TGF-beta1) inhibits the growth of a variety of epithelial cells; however, in many types of tumors it loses its inhibitory effect. p21(WAF1/CIP1), one of the cyclin-dependent kinase (Cdk) inhibitors induced by TGF-beta1, is considered a downstream effector of the growth-inhibitory function of TGF-beta1. We assessed the clinicopathologic significance of TGF-beta1 and p21 expression in resectable invasive ductal carcinoma (IDC) of the pancreas. Immunohistochemical examination of the expression of TGF-beta1 and p21 in 62 patients revealed positive expression of TGF-beta1 in 28 (45%) and of p21 in 25 (40%) of the 62 patients, and a significant correlation between the two expressions. The survival curve of patients with TGF-beta1(+) tumors was significantly higher than that of patients with TGF-beta1(-) tumors; p21(+) patients showed a higher survival curve than did p21(-) patients, but the difference was not statistically significant. Simultaneous analysis of TGF-beta1 and p21 expression showed that the patients with TGF-beta1(+)/p21(+) tumors had a significantly better prognosis than the others. Multivariate analysis showed that TGF-beta1 was a significantly low risk factor for death due to IDC. The concurrent evaluation of TGF-beta1 and p21 expression would be an effective tool in the prediction of the prognosis of patients with pancreatic cancer.}, }
@article {pmid11343777, year = {2001}, author = {Chalmers, IJ and Aubele, M and Hartmann, E and Braungart, E and Werner, M and Höfler, H and Atkinson, MJ}, title = {Mapping the chromosome 16 cadherin gene cluster to a minimal deleted region in ductal breast cancer.}, journal = {Cancer genetics and cytogenetics}, volume = {126}, number = {1}, pages = {39-44}, doi = {10.1016/s0165-4608(00)00376-9}, pmid = {11343777}, issn = {0165-4608}, mesh = {Base Sequence ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosome Deletion ; Chromosome Mapping ; *Chromosomes, Human, Pair 16 ; DNA Primers ; Humans ; Loss of Heterozygosity ; Lymphatic Metastasis ; *Multigene Family ; Repetitive Sequences, Nucleic Acid ; }, abstract = {The cadherin family of cell adhesion molecules has been implicated in tumor metastasis and progression. Eight family members have been mapped to the long arm of chromosome 16. Using radiation hybrid mapping, we have located six of these genes within a cluster at 16q21-q22.1. In invasive lobular carcinoma of the breast frequent LOH and accompanying mutation affect the CDH1 gene, which is a member of this chromosome 16 gene cluster. CDH1 LOH also occurs in invasive ductal carcinoma, but in the absence of gene mutation. The proximity of other cadherin genes to 16q22.1 suggests that they may be affected by LOH in invasive ductal carcinomas. Using the mapping data, microsatellite markers were selected which span regions of chromosome 16 containing the cadherin genes. In breast cancer tissues, a high rate of allelic loss was found over the gene cluster region, with CDH1 being the most frequently lost marker. In invasive ductal carcinoma a minimal deleted region was identified within part of the chromosome 16 cadherin gene cluster. This provides strong evidence for the existence of a second 16q22 suppressor gene locus within the cadherin cluster.}, }
@article {pmid11342981, year = {2001}, author = {Iwase, H and Ando, Y and Ichihara, S and Toyoshima, S and Nakamura, T and Karamatsu, S and Ito, Y and Yamashita, H and Toyama, T and Omoto, Y and Fujii, Y and Mitsuyama, S and Kobayashi, S}, title = {Immunohistochemical analysis on biological markers in ductal carcinoma in situ of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {8}, number = {2}, pages = {98-104}, doi = {10.1007/BF02967487}, pmid = {11342981}, issn = {1340-6868}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/genetics/immunology ; Breast Neoplasms/*chemistry/classification/genetics ; Carcinoma, Ductal, Breast/*chemistry/classification/genetics ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/classification/genetics ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2/genetics/immunology ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis/immunology ; Middle Aged ; Receptors, Estrogen/analysis/immunology ; Tumor Suppressor Protein p53/analysis/immunology ; }, abstract = {BACKGROUND: The increasing use of mammographic screening has led to an increased detection of ductal carcinoma in situ (DCIS) of the breast. The detailed biological characteristics of DCIS and a new classification of DCIS based on these characteristics are needed.<br><br>METHODS: Immunohistochemical studies were performed to assess the expression of c-erbB-2 (ErbB-2), estrogen receptor (ER), p53 and proliferative activity (Ki-67) in 65 patients with pure DCIS and 60 with invasive ductal carcinoma (IDC). We classified pure DCIS tumors using three classifications, the architectural, Nottingham, and Van Nuys classifications.<br><br>RESULTS: ErbB-2, ER and p53 staining was positive in 34%, 66% and 21% of patients with DCIS, respectively, and 58%, 42% and 33% in patients with IDC, respectively. Ki-67 stained positively in 1.5% of patients with DCIS and 11.2% of patients with IDC. The comedo type showed a high rate of positive ErbB-2 and p53 staining. The cribriform and papillary types showed a high rate of positive ER staining. Under the Van Nuys classification, ErbB-2, p53 and Ki-67 expression were highest in the group with high nuclear grade and lowest in the group with non-high nuclear grade without necrosis.<br><br>CONCLUSION: Although the biological markers of IDC tended to suggest aggressive behavior more so than those of DCIS, these differences were based on the histological sub-type, comedo or non-comedo. The Van Nuys classification best defined the subgroups of DCIS with a distinct expression pattern of biological markers, and the best candidates for breast-conserving surgery.}, }
@article {pmid11341636, year = {1999}, author = {Wiley, MJ and Tran, TA}, title = {Perioperative urinary catheterisation in conjunction with epidural anaesthesia for hip and knee arthroplasty. Is it safe?.}, journal = {International journal of surgical investigation}, volume = {1}, number = {2}, pages = {157-160}, pmid = {11341636}, issn = {1028-5229}, mesh = {Aged ; Aged, 80 and over ; *Anesthesia, Epidural ; Anti-Bacterial Agents/therapeutic use ; *Arthroplasty ; Female ; Hip Joint/*surgery ; Humans ; Incidence ; Knee Joint/*surgery ; Male ; Middle Aged ; *Postoperative Care ; *Preoperative Care ; Prospective Studies ; Safety ; Urinary Catheterization/*adverse effects ; Urinary Tract Infections/epidemiology/etiology/prevention &amp; control ; }, abstract = {The place of indwelling urinary catheterisation following epidural anaesthesia to prevent acute retention of urine after hip and knee arthroplasty is controversial. Even with the use of aseptic techniques and closed sterile drainage, bacteriuria has been reported in 10-27% of catheterised patients. A prospective trial was carried out in 68 consecutive patients undergoing knee or hip joint arthroplasty with epidural anaesthesia to investigate the perioperative complications of short term urinary catheterisation. Following establishment of combined epidural and general anaesthesia, all patients underwent urinary catheterisation under aseptic technique by a member of the surgical team. Prophylactic antibiotics were given prior to insertion and continued for 24-48h postoperatively to minimise the risk of prosthetic infection. The mean indwelling urinary catheter (IDC) period was 3.6 days (range 2-14). There were three (4.4%) urinary tract infections (UTIs) all of which resolved with appropriate antibiotics. Two were detected upon removal of the urinary catheter and one was detected on the seventh postoperative day when symptoms were detected. No patient required recatheterisation. There was no other infective morbidity or wound infection. Our findings suggest the use of IDC for short periods combined with prophylactic antibiotics is safe in the perioperative phase of joint arthroplasty.}, }
@article {pmid11334657, year = {2001}, author = {Venugopalan, P and Houston, AB and Agarwal, AK}, title = {The outcome of idiopathic dilated cardiomyopathy and myocarditis in children from the west of Scotland.}, journal = {International journal of cardiology}, volume = {78}, number = {2}, pages = {135-141}, doi = {10.1016/s0167-5273(00)00480-0}, pmid = {11334657}, issn = {0167-5273}, mesh = {Adolescent ; Cardiomyopathy, Dilated/*mortality/physiopathology ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Multivariate Analysis ; Myocarditis/*mortality/physiopathology ; Retrospective Studies ; Risk Factors ; Scotland/epidemiology ; Survival Rate ; Time Factors ; }, abstract = {We analysed retrospectively all infants and children with idiopathic dilated cardiomyopathy (IDC) and myocarditis at the Regional Cardiac Centre of the Royal Hospital for Sick Children, Glasgow, during 1980-1997. Among the 39 patients with IDC, 25 (64%) were infants aged < 1 year, eight (20.5%) had wheezing as the presenting symptom, and only six (15%) had a significant cardiac murmur. Thirty-eight of thirty-nine patients diagnosed in life were followed-up for 1 day to 15 years (median 3 years). Twelve of the thirty-nine (31%) died, six deaths were within a week of presentation and the rest within a year. The survival at 1 year and at 12 years was 0.69 (95% CI 0.54 to 0.84). Fourteen patients had histologically proven myocarditis, and all 9/14 (64%) detected at post-mortem and one of the five diagnosed in life died. Patients with myocarditis exhibited an actuarial survival of 0.29 (95% CI 0.04 to 0.53) at 1 year and at 9 years, significantly lower than IDC patients (log rank 9.8, P < 0.01). There was no difference in the outcome for patients with positive or negative Coxsackie titres or who presented in the 1980s and in the 1990s. No risk factor that independently influenced the outcome or survival could be identified in either group. Thus our study from a relatively well-defined population of the west of Scotland showed that a significant proportion of children with IDC and myocarditis died in the first week of illness and that patients with myocarditis had shorter survival.}, }
@article {pmid11332083, year = {2001}, author = {Lee, JS and Kim, HS and Jung, JJ and Kim, YB and Park, CS and Lee, MC}, title = {Correlation between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior.}, journal = {Analytical and quantitative cytology and histology}, volume = {23}, number = {2}, pages = {161-168}, pmid = {11332083}, mesh = {Adult ; Aged ; Analysis of Variance ; Antigens, Neoplasm/analysis ; *Apoptosis ; Breast Neoplasms/*blood supply/pathology ; Carcinoma, Ductal, Breast/*blood supply/*pathology ; Cell Division ; DNA Fragmentation ; Endothelium, Vascular/*immunology ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted/methods ; In Situ Nick-End Labeling ; Middle Aged ; *Neovascularization, Pathologic ; Proliferating Cell Nuclear Antigen/metabolism ; }, abstract = {OBJECTIVE: To investigate the relationship between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior.<br><br>STUDY DESIGN: Microvessels were immunohistochemically labeled with antibody to CD34 in sections from 82 cases of invasive ductal carcinoma. Computerized image analysis was used to evaluate microvessel density (MVD). The authors measured the apoptotic index (AI) using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling technique and proliferating cell nuclear antigen labeling index (PCNA LI) by PCNA immunohistochemistry on serial sections.<br><br>RESULTS: Statistical analysis revealed a significant inverse correlation between MVD and AI (r = -.313, P = .004) and failed to find a significant correlation between MVD and PCNA LI. There was a significant positive correlation between AI and PCNA LI (r = .393, P = .000). Significant differences in AI between high MVD (> or = 59.9%) and low MVD (< 59.9%) were seen (P < .001), with no appreciable differences in PCNA LI between the two groups. Histologic grade and stage were the only independent prognostic factors in both disease-free and overall survival.<br><br>CONCLUSION: Angiogenesis in breast cancer may be related to the ability of tumor cells to survive rather than to their proliferative activity. Apoptosis is related to cell proliferation in breast cancer.}, }
@article {pmid11322170, year = {2001}, author = {Rieger-Christ, KM and Pezza, JA and Dugan, JM and Braasch, JW and Hughes, KS and Summerhayes, IC}, title = {Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas.}, journal = {Molecular pathology : MP}, volume = {54}, number = {2}, pages = {91-97}, pmid = {11322170}, issn = {1366-8714}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Cadherins/*genetics/metabolism ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; Cytoskeletal Proteins/metabolism ; Disease Progression ; Female ; Humans ; *Mutation ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Polymorphism, Single-Stranded Conformational ; *Trans-Activators ; beta Catenin ; }, abstract = {AIMS: The relation between lobular carcinoma in situ (LCIS) and invasive breast cancer is unresolved. In an attempt to establish whether LCIS is a precursor of invasive cancer the mutational status and the expression of E-cadherin was analysed in LCIS and associated invasive breast carcinoma in 23 patients.<br><br>METHODS: Foci of LCIS and associated invasive carcinoma were individually microdissected from tissue from 23 patients. Exons 4-16 of the E-cadherin gene were analysed using single strand conformation polymorphism (SSCP); protein expression and the localisation of E-cadherin and beta-catenin were assessed with the use of immunohistochemistry.<br><br>RESULTS: Immunohistochemistry revealed a lack of expression of E-cadherin and beta-catenin in most LCIS samples and invasive foci. In all but four cases, the staining pattern was identical in the LCIS and associated invasive areas. When E-cadherin was absent, beta-catenin was also undetected, suggesting a lack of expression of alternative classic cadherin members in these lesions. Coincident E-cadherin mutations in LCIS and associated invasive carcinoma were not identified in this series of patients. However, mutational analysis of E-cadherin in multiple foci of carcinoma in situ surrounding an invasive lesion provided evidence to support ductal carcinoma in situ as a precursor of invasive ductal carcinoma.<br><br>CONCLUSION: These data support the hypothesis that LCIS is not a precursor of invasive breast carcinoma but a marker of increased risk of developing invasive disease.}, }
@article {pmid11305533, year = {2001}, author = {Zecchin, M and Lenarda, AD and Bonin, M and Mazzone, C and Zanchi, C and Di Chiara, C and Davanzo, M and Scherl, G and Sabbadini, G and Sinagra, G}, title = {Incidence and predictors of sudden cardiac death during long-term follow-up in patients with dilated cardiomyopathy on optimal medical therapy.}, journal = {Italian heart journal : official journal of the Italian Federation of Cardiology}, volume = {2}, number = {3}, pages = {213-221}, pmid = {11305533}, issn = {1129-471X}, mesh = {Adult ; Age Distribution ; Aged ; Cardiomyopathy, Dilated/diagnosis/*mortality/*therapy ; *Cause of Death ; Cohort Studies ; Death, Sudden, Cardiac/*epidemiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Italy/epidemiology ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Probability ; Prospective Studies ; Registries ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; Sex Distribution ; Time Factors ; }, abstract = {BACKGROUND: In spite of a total mortality reduction in recent years, sudden cardiac death (SD) remains a major problem in patients with idiopathic dilated cardiomyopathy (IDC) and its occurrence is often unpredictable. Furthermore, the risk of SD may change during follow-up because of the natural history of the disease and the effects of therapeutic interventions. In our study, we evaluated the modifications of the risk of SD during follow-up in a cohort of patients with IDC and analyzed the variables predicting SD not only at enrolment but also at the last examination during optimal medical treatment.<br><br>METHODS: Since 1978, 343 consecutive patients with IDC were enrolled in the Heart Muscle Disease Registry of Trieste (Italy) and submitted to complete invasive and non-invasive study. Patients were re-evaluated usually at intervals of 12 months.<br><br>RESULTS: After a mean of 68+/-45 months, 125 events (death, heart transplantation or aborted SD) had occurred. The cumulative risk after 5 years was 30%, while after 10 years it almost doubled (54%). During the first 3 months after enrolment, the incidence of SD was high (3%). A plateau, lasting about 3.5 years, followed. A slow but progressive rise in the risk of mortality then occurred (6% at 5 years, 18% at 10 years). No variables evaluated at enrolment were associated with SD at multivariate analysis. On the other hand, the end-diastolic left ventricular diameter (> or = 38 mm/m2) and ejection fraction (< or = 0.30) were predictive of SD if evaluated within 1 year before the event. Beta-blocker treatment was associated with a non-significant reduction of risk.<br><br>CONCLUSIONS: In patients with IDC the incidence of SD progressively increased during long-term follow-up, especially in those with persistent severe left ventricular dilation and dysfunction who were not on beta-blocker treatment. Serial clinical evaluation may help to select patients at higher risk for SD.}, }
@article {pmid11304577, year = {2001}, author = {Kang, JH and Kim, SJ and Noh, DY and Park, IA and Choe, KJ and Yoo, OJ and Kang, HS}, title = {Methylation in the p53 promoter is a supplementary route to breast carcinogenesis: correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {81}, number = {4}, pages = {573-579}, doi = {10.1038/labinvest.3780266}, pmid = {11304577}, issn = {0023-6837}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; CpG Islands ; *DNA Methylation ; DNA, Neoplasm/chemistry ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; *Genes, p53 ; Humans ; Mutation ; Promoter Regions, Genetic ; }, abstract = {Aberrant methylation in the CpG sites located in the promoter region of several tumor suppressor genes has been reported in various types of cancers. However, the methylation status of the p53 promoter has not been clearly determined and no information is available on its role in breast cancer. The aim of the study was to determine the presence and timing of the methylation of CpG sites in the p53 promoter, in the progression from ductal carcinoma in situ to invasive cancer. We also explored the correlation between the CpG methylation of the p53 promoter and p53 mutation during the progression of breast cancer. The corresponding lesions of both the invasive and noninvasive types were microdissected in paraffin-embedded tissue of 26 breast carcinomas. Bisulfite-modified DNA sequencing for methylation status in the p53 promoter was carried out, and double-strand DNA sequencing was performed in the promoter region and exons 4 to 9 of the p53 gene. CpG site methylation in the p53 promoter was detected in three cases (11.5%). Two noninvasive and three invasive lesions harbored CpG methylation in the p53 promoter. Methylations in more than one site were observed in three lesions, all of which contained methylation in two sites. The methylated CpG sites were located near the AP1 and YY-1 binding sites and at the YY-1 binding site. The p53 mutation was not found in the lesions where methylation in p53 promoter region was evident. In 16 cases (61.5%), neither methylation nor p53 mutation was detected. We conclude that the methylation in the p53 promoter region is found in the breast cancer irrespective of the status of invasion, and that the hypermethylation in the p53 promoter region is an alternative pathway to tumorigenesis where there is no p53 gene mutation.}, }
@article {pmid11301349, year = {2001}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Highly proliferative fibroblasts forming fibrotic focus govern metastasis of invasive ductal carcinoma of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {14}, number = {4}, pages = {325-337}, doi = {10.1038/modpathol.3880310}, pmid = {11301349}, issn = {0893-3952}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Nuclear ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary ; Female ; Fibroblasts/chemistry/*pathology ; Fibrosis/pathology ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/analysis ; Lymph Nodes/pathology ; Lymphatic Metastasis/*pathology ; Menopause ; Middle Aged ; Mitotic Index ; Nuclear Proteins/analysis ; Premenopause ; Survival Rate ; }, abstract = {We have already reported that invasive ductal carcinomas (IDCs) with fibrotic focus (FF) have more aggressive characteristics than those without FF. FF is composed of a mixture of fibroblasts and various amounts of collagen fibers, suggesting that highly proliferative fibroblasts forming FF increase the malignant potential of IDCs with FF. The purpose of this study was to examine whether there is a difference of proliferative activity of fibroblasts forming and not forming FF, which plays an important role in the tumor progression of IDCS: Two hundred three consecutive cases of IDC of the breast surgically treated at the National Cancer Center Hospital East formed the basis for this study. The proliferative activity of the fibroblasts forming the FF was immunohistochemically evaluated by using mouse MIB-1 monoclonal antibody against Ki-67 antigen. The MIB-1 labeling index (LI) is the percentage of fibroblasts forming FF that have positively stained nuclei, and 300 fibroblasts were counted in each FF. The significance of the proliferative activity of fibroblasts forming FF with regard to lymph node metastasis (LNM) or distant-organ metastasis (DOM) was compared with well-known prognostic parameters. Multivariate analysis demonstrated that high MIB-1 LI of fibroblasts forming FF significantly increased the relative risk of LNM and the hazard rate of DOM (P < .001 and P = .009). The present study indicated that the metastatic ability of IDCs with FF is highly dependent on the proliferative activity of the fibroblasts forming FF.}, }
@article {pmid11288957, year = {2001}, author = {Ruibal, A and Arias, JI and Del Río, MC and Lapeña, G and Schneider, J and Tejerina, A}, title = {Histological grade in breast cancer: association with clinical and biological features in a series of 229 patients.}, journal = {The International journal of biological markers}, volume = {16}, number = {1}, pages = {56-61}, doi = {10.1177/172460080101600108}, pmid = {11288957}, issn = {0393-6155}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology/secondary ; Female ; Humans ; Hyaluronan Receptors/metabolism ; Hyaluronic Acid/metabolism ; Lymphatic Metastasis ; Ploidies ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; S Phase ; Tissue Plasminogen Activator/metabolism ; }, abstract = {In order to study the association of histological grade (HG) with specific clinical and biological parameters which may influence the clinical behavior of infiltrating ductal carcinomas of the breast (IDC), we analyzed in 229 tissue samples the cytosolic concentrations of estrogen receptor (ER), progesterone receptor (PR), pS2, cathepsin D, hyaluronic acid (HA) and tissue-type plasminogen activator (t-PA), as well as those of the erbB2 oncoprotein, epidermal growth factor receptor (EGFR), HA, CD44v5 and CD44v6 in the cell membrane fraction. Likewise, we considered size, ploidy, S-phase fraction and axillary node involvement as variables of the study. The transition from HG1 to HG2 and from HG2 to HG3 was accompanied by a number of common features: global increase in size, greater number of tumors >2.0 cm, decrease in membrane hyaluronic acid concentrations, increased cell proliferation (S-phase >7%) and greater aneuploidy. Other events observed during the transition from HG2 to HG3 were a decrease in ER, PR, t-PA and cytosolic hyaluronic acid. These results led us to consider that HG is associated with certain clinical-biological changes that may help explain its value as a prognostic factor in breast carcinomas.}, }
@article {pmid11267953, year = {2001}, author = {Solin, LJ and Fourquet, A and Vicini, FA and Haffty, B and Taylor, M and McCormick, B and McNeese, M and Pierce, LJ and Landmann, C and Olivotto, IA and Borger, J and de La Rochefordiere, A and Schultz, DJ}, title = {Salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ of the breast.}, journal = {Cancer}, volume = {91}, number = {6}, pages = {1090-1097}, pmid = {11267953}, issn = {0008-543X}, mesh = {Adult ; Aged ; Antineoplastic Agents, Hormonal/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/pathology/*surgery ; Databases, Factual ; Female ; Humans ; Mammography ; Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/*surgery ; Retrospective Studies ; Salvage Therapy ; Survival Analysis ; Tamoxifen/administration &amp; dosage ; Treatment Outcome ; }, abstract = {BACKGROUND: The purpose of the current study is to evaluate the outcome of salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast.<br><br>METHODS: An analysis was performed of 42 patients with local only first failure (n = 41) or local-regional only first failure (n = 1) after breast-conserving surgery and radiation treatment had been given for DCIS of the breast. Surgical treatment at the time of local recurrence included mastectomy (n = 37; 88%) or excision (n = 5; 12%). Adjuvant systemic therapy at the time of local recurrence was chemotherapy (n = 3; 7%), tamoxifen (n = 8; 19%), both (n = 1; 2%), none (n = 29; 69%), or unknown (n = 1; 2%). The median interval from the time of initial treatment to local recurrence was 4.8 years (range = 1.0-15.2 yrs). The median follow-up after salvage treatment was 4.5 years (range = 0.2-12.8 yrs).<br><br>RESULTS: At the time of the local recurrence, 22 patients (52%) had invasive ductal carcinoma, 18 patients (43%) had DCIS, 1 patient (2%) had invasive lobular carcinoma, and 1 patient (2%) had angiosarcoma. After salvage treatment, the rate of overall survival and the rate of cause specific survival for all 42 patients were 92% at both 5- and 8-years after treatment. The rate of freedom from distant metastases was 89% at 5 and 8 years. Favorable prognostic factors after salvage treatment were DCIS as the histology of the local recurrence and mammography only as the method of detection of the local recurrence.<br><br>CONCLUSIONS: The results of salvage treatment in the current study demonstrated that local recurrences were salvaged with high rates of survival and freedom from distant metastases. These results support the use of breast-conserving surgery and radiation for initial management of DCIS of the breast.}, }
@article {pmid11267940, year = {2001}, author = {Ariga, N and Suzuki, T and Moriya, T and Kimura, M and Inoue, T and Ohuchi, N and Sasano, H}, title = {Progesterone receptor A and B isoforms in the human breast and its disorders.}, journal = {Japanese journal of cancer research : Gann}, volume = {92}, number = {3}, pages = {302-308}, pmid = {11267940}, issn = {0910-5050}, mesh = {Breast/cytology/*pathology ; Breast Diseases/*pathology ; Breast Neoplasms/genetics/*pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Estrogen Receptor alpha ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Neoplasm Invasiveness ; Receptors, Estrogen/analysis ; Receptors, Progesterone/*analysis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Two different isoforms of progesterone receptor (PR), PRA and PRB, are expressed in target tissues at comparable levels. In this study, we first examined PRA and PRB immunoreactivity in human breast cancer and various intraductal proliferative epithelial lesions, and correlated these findings with clinicopathologic parameters. We then examined mRNA expression of PRA and PRB in six cases of invasive ductal carcinoma using RT-PCR. Immunoreactivity for both PRA and PRB was positive in the great majority of proliferative disease without atypia (PDWA) (85% for PRA and 96% for PRB) and atypical ductal hyperplasia (ADH) (100% for PRA and 100% for PRB), but the ratio of immunopositive cases and immunohistochemical (IHC) scores was significantly smaller in ductal carcinoma in situ (DCIS) (65% for PRA and 75% for PRB) and invasive ductal carcinoma (IDC) (66% for PRA and 55% for PRB) than in PDWA and ADH. There was a significant positive correlation between IHC scores for PRA and estrogen receptor alpha (ERalpha) in IDC, DCIS and ADH but not between PRB and ERalpha. In IDC, both PRA and PRB IHC scores were significantly associated with histological grade, but there was no association between PRA or PRB status and lymph node involvement, tumor size, or prognosis of the patients. The expression of mRNAs for both PRA and PRB was detected in all six cases of IDC examined. These results suggest that both PRA and PRB are strongly associated with ERalpha in human breast and this relation may be disturbed in breast cancer.}, }
@article {pmid11265127, year = {2001}, author = {Mizutani, Y and Yamashita, T and Sakamoto, G}, title = {[Radiation therapy for brain metastases from breast cancer by histological classification].}, journal = {Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica}, volume = {61}, number = {3}, pages = {89-95}, pmid = {11265127}, issn = {0048-0428}, mesh = {Adult ; Aged ; Brain Neoplasms/pathology/*radiotherapy/*secondary ; Breast Neoplasms/*classification/*pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Analysis ; }, abstract = {One hundred thirteen patients with metastatic brain tumor from breast cancer who were treated with external irradiation between 1989 and 1997 at Cancer Institute Hospital were studied. The patients were all histopathologically proven to have invasive ductal carcinoma (scirrhous type 54 cases, papillotubular type 18, solid-tubular type 41). The patients were evaluated for efficacy and histopathological subtypes. The time interval between the diagnosis of breast cancer and brain metastases was 53.6 months for the scirrhous type, 75.0 months for the papillotubular type, and 35.5 months for the solid-tubular type. The time interval between the diagnosis of initial distant metastases and brain metastases was 14.3 months for the scirrhous type, 22.5 months for the papillotubular type, and 12.5 months for the solid-tubular type. Efficacy rates (CR + PR) for external irradiation of the brain metastases were 40.0% for the scirrhous type, 66.7% for the papillotubular type, and 36.6% for the solid-tubular type. The papillotubular type had a favorable efficacy rate compared with the other two types. Median survival time (MST) from the start of treatment for brain metastases and one-year survival rate were 5 months and 11.1% for the scirrhous type, 7 months and 41.5% for the papillotubular type, and 4 months and 28.3% for the solid-tubular type, respectively. No statistically significant difference between survival rates was observed among the histopathological types. Univariate analysis showed performance status, number of metastatic tumors, and existence of extracranial metastases without bony metastasis to be significantly related to prognosis. Multivariate analysis showed only extracranial metastases without bony metastases to be related to prognosis.}, }
@article {pmid11249077, year = {2001}, author = {Furukawa, H and Iwata, R and Moriyama, N}, title = {Is CT during arterial portography useful for the preoperative evaluation of liver metastases from pancreatic carcinoma?.}, journal = {Pancreas}, volume = {22}, number = {2}, pages = {200-202}, doi = {10.1097/00006676-200103000-00015}, pmid = {11249077}, issn = {0885-3177}, mesh = {Humans ; Liver Neoplasms/*diagnostic imaging/*secondary/surgery ; Pancreatic Neoplasms/*diagnostic imaging/surgery ; Portography ; *Tomography, X-Ray Computed ; }, abstract = {We evaluated computed tomography during arterial portography (CTAP) for the preoperative evaluation of liver metastases from pancreatic carcinoma. Thirty-one patients with invasive ductal carcinoma of the pancreas underwent CTAP for evaluation of liver metastasis. Diagnostic accuracy of CTAP was compared with that of intravenous contrast-enhanced CT (IVCT). In this series, both CTAP and IVCT showed the same diagnostic accuracy for the patients. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of both CT examinations for detecting liver metastases were 60% (three of five), 100% (26 of 26), 100% (three of three), 93% (26 of 28), and 94% (29 of 31), respectively. CTAP did not confer any advantage over IVCT for the preoperative evaluation of liver metastases from pancreatic carcinoma.}, }
@article {pmid11238620, year = {2001}, author = {Bakri, Y and Schiffer, C and Zennou, V and Charneau, P and Kahn, E and Benjouad, A and Gluckman, JC and Canque, B}, title = {The maturation of dendritic cells results in postintegration inhibition of HIV-1 replication.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {166}, number = {6}, pages = {3780-3788}, doi = {10.4049/jimmunol.166.6.3780}, pmid = {11238620}, issn = {0022-1767}, mesh = {Active Transport, Cell Nucleus/immunology ; Antigens, CD34/biosynthesis ; Antiviral Agents/*immunology ; Cell Differentiation/immunology ; Cell Nucleus/immunology/metabolism/virology ; Cells, Cultured ; DNA, Viral/antagonists &amp; inhibitors/metabolism ; Dendritic Cells/*cytology/enzymology/immunology/*virology ; Down-Regulation/immunology ; HIV Long Terminal Repeat/immunology ; HIV-1/growth &amp; development/immunology/*physiology ; Hematopoietic Stem Cells/cytology/immunology/virology ; Humans ; Monocytes/cytology/immunology/virology ; Polymerase Chain Reaction ; Reverse Transcriptase Inhibitors/immunology ; Transcription, Genetic/immunology ; Virus Integration/*immunology ; Virus Replication/*immunology ; }, abstract = {Maturation of dendritic cells (DC) is known to result in decreased capacity to produce HIV due to postentry block of its replicative cycle. In this study, we compared the early phases of this cycle in immature DC (iDC) and mature DC (mDC) generated from monocytes cultured with GM-CSF and IL-4, trimeric CD40 ligand (DC(CD40LT)), or monocyte-conditioned medium (DC(MCM)) being added or not from day 5. Culture day 8 cells exposed to X4 HIV-1(LAI) or R5 HIV-1(Ba-L) were analyzed by semiquantitative R-U5 PCR, which detects total HIV DNA. CXC chemokine receptor 4(low) (CXCR4(low)) CCR5(+) iDC harbored similar viral DNA amounts when exposed to either strain. HIV-1(LAI) entered more efficiently into DC(CD40LT) or DC(MCM) with up-regulated CXCR4. CCR5(low) DC(CD40LT) still allowed entry of HIV-1(Ba-L), whereas CCR5(-) DC(MCM) displayed reduced permissivity to this virus. Comparing amounts of late (long terminal repeat (LTR)-gag PCR) and total (R-U5 PCR) viral DNA products showed that HIV-1(Ba-L) reverse transcription was more efficient than that of HIV-1(LAI), but was not affected by DC maturation. Southern blot detection of linear, circular, and integrated HIV DNA showed that maturation affected neither HIV-1 nuclear import nor integration. When assessing virus transcription by exposing iDC to pNL4-3.GFP or pNL4-3.Luc viruses pseudotyped with the G protein of vesicular stomatitis virus (VSV-G), followed by culture with or without CD40LT or MCM, GFP and luciferase activities decreased by 60-75% in mDC vs iDC. Thus, reduced HIV replication in mDC is primarily due to a postintegration block occurring mainly at the transcriptional level. We could not relate this block to altered expression and nuclear localization of NF-kappa B proteins and SP1 and SP3 transcription factors.}, }
@article {pmid11230710, year = {2001}, author = {Waldman, FM and Hwang, ES and Etzell, J and Eng, C and DeVries, S and Bennington, J and Thor, A}, title = {Genomic alterations in tubular breast carcinomas.}, journal = {Human pathology}, volume = {32}, number = {2}, pages = {222-226}, doi = {10.1053/hupa.2001.21564}, pmid = {11230710}, issn = {0046-8177}, support = {CA 44768/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/chemistry/*genetics/pathology ; Breast Neoplasms/chemistry/*genetics/pathology ; Cadherins/analysis ; DNA, Neoplasm/analysis ; Dissection ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Laser Therapy ; Micromanipulation ; Middle Aged ; *Nucleic Acid Hybridization ; Polymerase Chain Reaction ; }, abstract = {Tubular carcinoma of the breast is a well-differentiated variant of invasive ductal carcinoma and has been shown to have an exceptionally favorable prognosis, as manifested by a low incidence of lymph node metastases and an excellent overall survival. It is unknown whether this subtype represents an early step along the continuum of development to a more aggressive, poorly differentiated ductal cancer, or whether these cancers are destined to remain well differentiated with limited metastatic potential. We undertook an analysis of 18 pure tubular carcinomas of the breast using comparative genomic hybridization to evaluate the chromosomal changes in these tumors. An average of 3.6 chromosomal alterations of the genome were identified per case. The most frequent change involved loss of 16q (in 78% of tumors) and gain of 1q (in 50% of tumors). All but one case with 1q gain also exhibited a concomitant 16q loss. Other frequent changes involved 16p gain in 7 of 18 cases (39%) and distal 8p loss in 5 of 18 cases (28%). Comparison with known genomic alterations in a mixed group of invasive cancers shows tubular cancer to have fewer overall chromosomal changes per tumor (P <.01), higher frequency of 16q loss (P <.001), and lower frequency of 17p loss (P =.007). These results strongly suggest that tubular carcinomas are a genetically distinct group of breast cancers.}, }
@article {pmid11221991, year = {2001}, author = {Luppi, P and Licata, A and Haluszczak, C and Rudert, WA and Trucco, G and McGowan, FX and Finegold, D and Boyle, GJ and Trucco, M}, title = {Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of autoimmunity}, volume = {16}, number = {1}, pages = {3-13}, doi = {10.1006/jaut.2000.0462}, pmid = {11221991}, issn = {0896-8411}, mesh = {Antigens, Viral/analysis ; CD4 Antigens/biosynthesis ; CD8 Antigens/biosynthesis ; Cardiomyopathy, Dilated/*immunology/pathology/virology ; Cytokines/*genetics ; Enterovirus B, Human/genetics/immunology ; Gene Expression ; HLA-DQ Antigens/classification ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; Histocompatibility Testing ; Humans ; Immunoenzyme Techniques ; Interferon-gamma/genetics ; Interleukin-1/genetics ; Interleukin-2/genetics ; Interleukin-4/genetics ; Interleukin-6/genetics ; Leukocytes, Mononuclear/immunology ; Myocarditis/immunology ; Myocardium/immunology/pathology ; Picornaviridae/genetics/isolation &amp; purification ; RNA, Messenger ; Receptors, Antigen, T-Cell, alpha-beta/*analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3+-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoires, cytokine expression and presence of enterovirus-specific antigens. IDC patients who underwent heart transplantation at different times after the onset of heart failure were studied. A cardiac infiltrate of CD4+ and CD8+ T cells was present together with activated macrophages. Furthermore, the same Vbeta gene families, previously found to be skewed in hearts from fulminant cases of CVB3+-IDC, together with two additional Vbeta gene families, Vbeta1 and 5B, were increased. IL-1beta, IL-2, IL-6 and IFN-gamma were expressed in the myocardium while others, like IL-4 were not. In conclusion, an orchestrated complex of immune mechanisms seems to be the basis of IDC etiopathogenesis.}, }
@article {pmid11216956, year = {2001}, author = {Iwata, M and Yoshikawa, T and Baba, A and Anzai, T and Mitamura, H and Ogawa, S}, title = {Autoantibodies against the second extracellular loop of beta1-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of the American College of Cardiology}, volume = {37}, number = {2}, pages = {418-424}, doi = {10.1016/s0735-1097(00)01109-8}, pmid = {11216956}, issn = {0735-1097}, mesh = {Adult ; Aged ; Autoantibodies/*blood ; Cardiomyopathy, Dilated/epidemiology/*immunology ; Death, Sudden, Cardiac/epidemiology/*etiology ; Extracellular Matrix/immunology ; Female ; Heart Ventricles/immunology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Receptors, Adrenergic, beta-1/*immunology ; Tachycardia, Ventricular/*immunology/mortality ; }, abstract = {OBJECTIVES: We sought to define the clinical and long-term prognostic implications of autoantibodies that act against the second extracellular loop of beta1-adrenergic receptors (ARs) in patients with idiopathic dilated cardiomyopathy (IDC).<br><br>BACKGROUND: Although autoantibodies directed against various domains of beta-ARs are found in patients with IDC, only a subgroup against the second extracellular domain of beta1-ARs exerts intrinsic sympathomimetic-like actions on human beta-ARs. It is suggested that the autoantibodies take part in the pathophysiology of IDC and may affect long-term prognosis of patients with this disorder.<br><br>METHODS: Sera from 104 patients with IDC were screened for autoantibodies that act against the second extracellular loop of beta1-ARs by enzyme-linked immunosorbent assay, using a synthetic peptide corresponding to the domain. Relations of the autoantibodies to clinical variables and long-term prognosis were assessed by multivariate analysis.<br><br>RESULTS: Autoantibodies were detected in 40 patients (38%). Multifocal ventricular premature contractions (p < 0.01) and ventricular tachycardia (VT; p < 0.01) were more common in autoantibody-positive than in autoantibody-negative patients, although no differences in cardiac function or neurohormonal levels were demonstrated. The presence of autoantibodies (p = 0.001) and a low left ventricular ejection fraction (LVEF <30%; p = 0.02) were independent predictors of VT. Sudden death was independently predicted by the presence of autoantibodies (p = 0.03), as well as by LVEF <30% (p = 0.01), whereas total mortality was predicted only by LVEF <30% (p = 0.001).<br><br>CONCLUSIONS: Autoantibodies directed against the second extracellular loop of beta1-ARs were closely related to serious ventricular arrhythmias in patients with IDC, and the presence of autoantibodies independently predicted sudden death. These autoantibodies may contribute to electrical instability in patients with IDC.}, }
@article {pmid11212228, year = {2001}, author = {Shirakawa, K and Tsuda, H and Heike, Y and Kato, K and Asada, R and Inomata, M and Sasaki, H and Kasumi, F and Yoshimoto, M and Iwanaga, T and Konishi, F and Terada, M and Wakasugi, H}, title = {Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer.}, journal = {Cancer research}, volume = {61}, number = {2}, pages = {445-451}, pmid = {11212228}, issn = {0008-5472}, mesh = {Angiogenesis Inducing Agents/genetics/metabolism ; Animals ; Breast Neoplasms/genetics/metabolism/*pathology ; Cadherins/genetics/metabolism ; Cell Division ; Cytokines/genetics/metabolism ; Endothelium, Vascular/*pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrosis ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Integrins/genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Electron ; Middle Aged ; Necrosis ; Neoplasm Transplantation ; RNA, Messenger/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Receptor, TIE-2 ; Receptors, Growth Factor/genetics/metabolism ; Receptors, Vascular Endothelial Growth Factor ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous/pathology ; Tumor Cells, Cultured/metabolism/ultrastructure ; }, abstract = {We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.}, }
@article {pmid11197980, year = {2001}, author = {Lotze, U and Kaepplinger, S and Kober, A and Richartz, BM and Gottschild, D and Figulla, HR}, title = {Recovery of the cardiac adrenergic nervous system after long-term beta-blocker therapy in idiopathic dilated cardiomyopathy: assessment by increase in myocardial 123I-metaiodobenzylguanidine uptake.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {42}, number = {1}, pages = {49-54}, pmid = {11197980}, issn = {0161-5505}, mesh = {*3-Iodobenzylguanidine ; Adrenergic beta-Antagonists/*therapeutic use ; Cardiomyopathy, Dilated/*diagnostic imaging/*drug therapy ; Female ; Follow-Up Studies ; Heart/diagnostic imaging/*innervation ; Humans ; *Iodine Radioisotopes ; Male ; Middle Aged ; Myocardium/metabolism ; Prospective Studies ; Radiopharmaceuticals ; Sympathetic Nervous System/*physiopathology ; Technetium Tc 99m Sestamibi ; Time Factors ; Tomography, Emission-Computed, Single-Photon ; }, abstract = {UNLABELLED: In chronic heart failure, elevated plasma norepinephrine (NE) levels and a disparity between the neuronal release and the effective reuptake of NE lead to an increased concentration of NE in the presynaptic cleft, causing a downregulation of the myocardial beta-adrenoceptors. The clinical and prognostic effectiveness of beta-blocker therapy has been shown in patients with chronic heart failure in several large trials. The purpose of this study was to investigate the effect of long-term beta-blocker therapy on the cardiac adrenergic nervous system as assessed by the myocardial uptake of 123I-metaiodobenzylguanidine (MIBG), an analog of NE, in idiopathic dilated cardiomyopathy (IDC).<br><br>METHODS: In 10 patients with IDC and stable chronic heart failure the myocardial MIBG uptake was measured at baseline and at 1 y (median, 11.5 mo) after treatment with beta-blockers (metoprolol, n = 5; bisoprolol, n = 1; and carvedilol, n = 4) in addition to standard medication. In parallel with the changes in MIBG uptake, the New York Heart Association functional class, the left ventricular ejection fraction (LVEF), and the left ventricular end-diastolic diameter (LVEDD) were documented before and after 1 y of therapy with beta-blockers.<br><br>RESULTS: During the 1-y follow-up, a significant increase in myocardial 123I-MIBG uptake (P = 0.005) in parallel with an improved LVEF (P = 0.005) and a reduced LVEDD (P = 0.019) was found. A trend toward an improvement of the New York Heart Association functional class under the beta-blocker therapy (P = 0.139) was also found.<br><br>CONCLUSION: Assessment of the myocardial 123I-MIBG uptake is a useful noninvasive tool for evaluating changes in cardiac sympathetic nerve activity under medical therapy. Long-term treatment with beta-blockers in IDC causes a recovery of the cardiac adrenergic nervous system concomitantly with a clinical and hemodynamic improvement.}, }
@article {pmid11175617, year = {2001}, author = {Ferrini, FS and Rossi, MA and Neto, MM and Soares, FA}, title = {Schirrous invasive ductal carcinoma of the breast overexpress p53 oncoprotein.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {119}, number = {1}, pages = {4-6}, doi = {10.1590/s1516-31802001000100002}, pmid = {11175617}, issn = {1516-3180}, mesh = {Adult ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Female ; Humans ; Mutation ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Receptors, Steroid/genetics/*metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {CONTEXT: Breast cancer is the most important neoplasm in adult women, and its worldwide incidence is growing. The tumoral stroma is very important for modulating the growth and invasion of the tumor itself. The relationship between these two components is not completely understood. Schirrous carcinoma is a variant of ductal invasive carcinoma in which the stroma is very desmoplastic, and the importance of this finding still a motive for debate in the literature.<br><br>OBJECTIVE: To compare the desmoplastic reactions against biological markers, such as estrogen and progesterone receptors, oncoprotein c-erbB-2 and oncoprotein p53, with the objective of studying the relationship between the tumoral stroma and epithelial cancer cells.<br><br>TYPE OF STUDY: Retrospective study.<br><br>SETTING: Cancer Hospital A C Camargo and Faculty of Medicine of Ribeir&#xe3;o Preto, University of S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.<br><br>SAMPLE: 107 adult women operated because of ductal invasive carcinoma. The cases were separated into 4 groups according to the desmoplastic reaction - less than 15 per cent, between 15-50 per cent, 51-85 per cent, and more than 85 per cent fibrosis. The grade of fibrosis was determined by picrus-sirius staining and quantified by using a microscope with a stereo-imaging grid. Immunohistochemical methods were used to determine the expression of the hormonal receptors and c-erbB-2/p53 oncoprotein.<br><br>MAIN MEASUREMENTS: Extent of desmoplastic reaction versus expression of estrogen and progesterone receptors, oncoprotein c-erbB-2, and oncoprotein p53.<br><br>RESULTS: The results showed that schirrous carcinoma expresses oncoprotein p53 more frequently than other carcinomas with less extensive desmoplastic reaction. There were no differences between the grade of fibrosis and the other biological markers.<br><br>CONCLUSION: The intense stromal reaction in invasive ductal carcinoma may modulate the expression of p53. Further investigations should be made with the aim of understanding how this expression determines the proliferative activity in schirrous carcinoma, and whether this overexpression is secondary to mutation of the p53 gene or due to modulation of other molecules of the stroma.}, }
@article {pmid11157850, year = {2001}, author = {Sato, K and Kawasaki, H and Nagayama, H and Enomoto, M and Morimoto, C and Tadokoro, K and Juji, T and Takahashi, TA}, title = {Signaling events following chemokine receptor ligation in human dendritic cells at different developmental stages.}, journal = {International immunology}, volume = {13}, number = {2}, pages = {167-179}, doi = {10.1093/intimm/13.2.167}, pmid = {11157850}, issn = {0953-8178}, mesh = {Cell Differentiation/drug effects/immunology ; Cells, Cultured ; Chemokine CCL19 ; Chemokine CCL5/physiology ; Chemokines, CC/metabolism/physiology ; Chemotaxis, Leukocyte/drug effects ; Dendritic Cells/cytology/drug effects/*immunology/*metabolism ; Enzyme Activation/drug effects/immunology ; Focal Adhesion Kinase 1 ; Focal Adhesion Kinase 2 ; Focal Adhesion Protein-Tyrosine Kinases ; Genistein/pharmacology ; Humans ; Iodine Radioisotopes/metabolism ; JNK Mitogen-Activated Protein Kinases ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinases/immunology/metabolism ; Monocytes/immunology/metabolism ; Phosphorylation/drug effects ; Protein Binding/immunology ; Protein-Tyrosine Kinases/metabolism ; Receptors, Chemokine/biosynthesis/*immunology/*metabolism ; Signal Transduction/drug effects/*immunology ; Virulence Factors, Bordetella/pharmacology ; }, abstract = {Responsiveness of dendritic cells (DC) to inflammatory CC chemokines is down-regulated during their maturation. We analyzed the mechanism underlying these events. Cell-surface expression of CC chemokine receptor (CCR)-1, -3 and -5 was increased during differentiation of immature DC (iDC) from monocytes. In contrast, these expressions were decreased during development of iDC into mature DC (mDC) to levels similar to those of monocytes. Transcriptional expression of CCR-1, -3 and -5 was increased during differentiation of iDC from monocytes, while the expression was decreased during development of iDC into mDC. Expression of CCR-7 transcript was detected in mDC, but not in monocytes or iDC. Both monocytes and iDC, but not mDC, migrated in response to inflammatory CC chemokines such as regulated on activation normal T cell expressed and secreted (RANTES)/CCL5, whereas mDC, but not monocytes or iDC, migrated to macrophage inflammatory protein (MIP)-3ss/CCL19. Receptor engagement of monocytes or iDC by RANTES (for CCR-1, -3 and -5) resulted in protein tyrosine phosphorylation events including activation of focal adhesion kinase as well as mitogen-activated protein kinase, whereas this stimulation induced little activation of these molecular events in mDC when compared with monocytes or iDC. On the other hand, stimulation with MIP-3ss (for CCR-7) induced tyrosine phosphorylation events in mDC, but not in monocytes or iDC. These results suggest that the down-regulation of cell-surface expression of CCR and of their downstream signaling events may be involved in the reduced chemotaxis of DC to inflammatory CC chemokines during their maturation.}, }
@article {pmid11140941, year = {2000}, author = {Arimura, T and Nakamura, T and Hiroi, S and Satoh, M and Takahashi, M and Ohbuchi, N and Ueda, K and Nouchi, T and Yamaguchi, N and Akai, J and Matsumori, A and Sasayama, S and Kimura, A}, title = {Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy.}, journal = {Human genetics}, volume = {107}, number = {5}, pages = {440-451}, doi = {10.1007/s004390000389}, pmid = {11140941}, issn = {0340-6717}, mesh = {Adolescent ; Adult ; Aged ; Amino Acid Sequence ; Amino Acid Substitution ; Asian People/genetics ; Base Sequence ; Cardiomyopathy, Dilated/*genetics ; Carrier Proteins ; Cytoskeletal Proteins ; DNA Primers ; Exons ; Female ; Gene Frequency ; Gene Library ; *Genetic Variation ; Humans ; Japan ; LIM Domain Proteins ; Male ; Microfilament Proteins/genetics ; Middle Aged ; Molecular Sequence Data ; Muscle Proteins/*genetics ; Muscle, Skeletal/metabolism ; Mutation, Missense ; Myocardium/metabolism ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; RNA, Messenger/genetics ; Reference Values ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is characterized by a thin-walled heart with systolic dysfunction of unknown etiology. Because abnormalities in genes for cytoskeletal proteins related to Z-disc function have recently been reported to cause IDC, genomic organization of the gene for nebulette, a novel actin-binding Z-disc protein, was determined and its sequence variations were searched for in Japanese patients with IDC and healthy controls. The nebulette gene consists of 28 exons, and four sequence variations leading to amino acid replacement (Gln187His, Met351Val, Asn654Lys, and Thr728Ala) were identified in the patients. These variations were also found in the healthy controls and hence they were polymorphisms and not disease-specific mutations. Frequencies of Gln187His, Met351Val, and Thr728Ala variants were similar in the patients and controls. However, the frequency of homozygotes for Lys at codon 654, a variant at a relatively conserved residue in an actinbinding motif, was significantly increased in nonfamilial IDC patients (n=106) as compared with healthy control subjects (n=331) (7.54% vs 1.21%, OR=6.25, P=0.002, 95% CI=1.92-20.29), while this association was not found in familial IDC patients (n=24). These observations suggest that the nebulette polymorphism in the actin-binding motif was a novel genetic marker of susceptibility to nonfamilial IDC.}, }
@article {pmid11139967, year = {2000}, author = {Grimm, W and Hoffmann, J and Menz, V and Maisch, B}, title = {Relation between microvolt level T wave alternans and other potential noninvasive predictors of arrhythmic risk in the Marburg Cardiomyopathy Study.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {23}, number = {11 Pt 2}, pages = {1960-1964}, doi = {10.1111/j.1540-8159.2000.tb07062.x}, pmid = {11139967}, issn = {0147-8389}, mesh = {Adolescent ; Adult ; Aged ; Arrhythmias, Cardiac/complications/*diagnosis/physiopathology ; Baroreflex ; Bundle-Branch Block/complications/diagnosis ; Cardiac Volume ; Cardiomyopathy, Dilated/complications/*diagnosis/physiopathology ; *Electrocardiography ; Exercise Test ; Female ; Germany ; Heart Rate ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Risk Assessment ; Severity of Illness Index ; Stroke Volume ; Ventricular Function, Left ; }, abstract = {The relation between microvolt level T wave alternans (TWA) and other noninvasive arrhythmia risk predictors was analyzed in 221 consecutive patients with idiopathic dilated cardiomyopathy (IDC) and sinus rhythm enrolled in the Marburg Cardiomyopathy Study between March 1996 and May 2000. TWA analysis was also performed in 110 healthy controls of similar age and sex. TWA during symptom-limited exercise was positive, negative and indeterminate in, respectively, 108 (49%), 65 (29%) and 48 (22%) patients with IDC versus, respectively, 5 (5%), 98 (89%) and 7 (6%) healthy controls (P < 0.05). Patients with IDC and positive TWA had a lower left ventricular (LV) ejection fraction (29 +/- 9% vs 34 +/- 10%, P < 0.05) and greater LV end-diastolic diameter (69 +/- 8 mm versus 64 +/- 6 mm, P < 0.05) than patients with negative TWA. Other variables, including age, gender, New York Heart Association functional class, presence of bundle branch block, arrhythmias on 24-hour ambulatory electrocardiogram, heart rate variability and baroreflex sensitivity, were not significantly different between patients with positive vs negative TWA. The prognostic significance of TWA in IDC with regard to arrhythmic events and total mortality will be determined by multivariate Cox analysis at the end of a 5-year follow-up in this ongoing study.}, }
@article {pmid11128141, year = {2000}, author = {Kawatsu, K and Hamano, Y and Noguchi, T}, title = {Determination of domoic acid in Japanese mussels by enzyme immunoassay.}, journal = {Journal of AOAC International}, volume = {83}, number = {6}, pages = {1384-1386}, pmid = {11128141}, issn = {1060-3271}, mesh = {Animals ; Antibodies, Monoclonal ; Bivalvia/*chemistry ; Chromatography, High Pressure Liquid ; Immunoenzyme Techniques ; Indicators and Reagents ; Japan ; Kainic Acid/*analogs &amp; derivatives/*analysis ; Marine Toxins/*analysis ; }, abstract = {Ten samples of commercial blue mussels (Mytilus edulis) from Japan were analyzed for domoic acid by an indirect competitive enzyme immunoassay (idc-EIA) based on an anti-domoic acid monoclonal antibody. Domoic acid was found in all samples at low concentrations (0.11-1.81 ng/g mussel tissue). The presence of domoic acid was confirmed by liquid chromatography coupled with immunoaffinity chromatography using an anti-domoic acid monoclonal antibody as ligand. To our knowledge, this is the first reported detection of domoic acid, a causative agent of amnesic shellfish poisoning, in Japanese mussels.}, }
@article {pmid11123299, year = {2001}, author = {Visintin, A and Mazzoni, A and Spitzer, JH and Wyllie, DH and Dower, SK and Segal, DM}, title = {Regulation of Toll-like receptors in human monocytes and dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {166}, number = {1}, pages = {249-255}, doi = {10.4049/jimmunol.166.1.249}, pmid = {11123299}, issn = {0022-1767}, mesh = {Antigens, Surface/biosynthesis ; Blotting, Northern ; Cell Differentiation/immunology ; Cell Membrane/immunology/metabolism ; Cells, Cultured ; Dendritic Cells/cytology/enzymology/*metabolism ; *Drosophila Proteins ; Enzyme Activation/immunology ; Humans ; Interleukin-1 Receptor-Associated Kinases ; Lipopolysaccharides/pharmacology ; Lymphocyte Antigen 96 ; Membrane Glycoproteins/*biosynthesis/genetics/immunology ; Monocytes/cytology/enzymology/*metabolism ; Protein Kinases/metabolism ; RNA, Messenger/biosynthesis ; Receptors, Cell Surface/*biosynthesis/genetics/immunology ; Receptors, Interleukin-1/metabolism ; Toll-Like Receptor 3 ; Toll-Like Receptor 4 ; Toll-Like Receptors ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {A number of pathogens induce immature dendritic cells (iDC) to migrate to lymphoid organs where, as mature DC (mDC), they serve as efficient APC. We hypothesized that pathogen recognition by iDC is mediated by Toll-like receptors (TLRs), and asked which TLRs are expressed during the progression of monocytes to mDC. We first measured mRNA levels for TLRs 1-5 and MD2 (a protein required for TLR4 function) by Northern analysis. For most TLRs, message expression decreased severalfold as monocytes differentiated into iDC, but opposing this trend, TLR3 and MD2 showed marked increases during iDC formation. When iDC were induced to mature with LPS or TNF-alpha, expression of most TLRs transiently increased and then nearly disappeared. Stimulation of iDC, but not mDC, with LPS resulted in the activation of IL-1 receptor-associated kinase, an early component in the TLR signaling pathway, strongly suggesting that LPS signals through a TLR. Surface expression of TLRs 1 and 4, as measured by mAb binding, was very low, corresponding to a few thousand molecules per cell in monocytes, and a few hundred or less in iDC. We conclude that TLRs are expressed in iDC and are involved in responses to at least one pathogen-derived substance, LPS. If TLR4 is solely responsible for LPS signaling in humans, as it is in mice, then its extremely low surface expression implies that it is a very efficient signal transducer in iDC.}, }
@article {pmid11122455, year = {2000}, author = {Ciavarra, RP and Greene, AR and Horeth, DR and Buhrer, K and van Rooijen, N and Tedeschi, B}, title = {Antigen processing of vesicular stomatitis virus in situ. Interdigitating dendritic cells present viral antigens independent of marginal dendritic cells but fail to prime CD4(+) and CD8(+) T cells.}, journal = {Immunology}, volume = {101}, number = {4}, pages = {512-520}, pmid = {11122455}, issn = {0019-2805}, mesh = {Animals ; Antigen Presentation/*immunology ; Antigens, Viral/*immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Dendritic Cells/*immunology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Rhabdoviridae Infections/immunology ; Spleen/immunology ; T-Lymphocyte Subsets/*immunology ; Tumor Cells, Cultured ; Vesicular stomatitis Indiana virus/*immunology ; }, abstract = {Acute macrophage (M phi) depletion, using a liposome-mediated 'suicide technique', markedly suppressed priming of splenic CD4(+) and CD8(+) T-cell responses to vesicular stomatitis virus (VSV). However, phagocytic marginal dendritic cells (MDC), but not interdigitating dendritic cells (IDC), are now known to be also depleted by this technique. To clarify the role splenic dendritic cell (DC) subsets and M phi play in priming for a virus-specific T-cell-mediated immune response, DC and M phi were purified from VSV-infected mice and assayed for the presence of epitopes recognized by VSV helper T (Th) cells and cytotoxic T lymphocytes (CTL). Antigen pulse experiments performed in situ demonstrated that VSV Th cell and CTL epitopes became transiently associated only with DC, but not M phi or B cells, indicating that DC represent the critical antigen-presenting cell (APC) population in vivo for this virus. The failure of MDC/M phi-deficient mice to become primed was not due to the complete elimination of antigen-presenting DC because VSV peptide/class I and II complexes were detected on IDC following lipsome-mediated elimination of phagocytic cells. However, the VSV-induced chemokine response was dramatically suppressed in these mice. Thus, despite the expression of VSV peptide/class I and II complexes, IDC are not sufficient to prime VSV Th cells in the absence of MDC and/or splenic M phi.}, }
@article {pmid11114860, year = {2000}, author = {Komoike, Y and Motomura, K and Inaji, H and Koyama, H}, title = {Diagnosis of ductal carcinoma in situ (DCIS) and intraductal papilloma using fluorescence in situ hybridization (FISH) analysis.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {4}, pages = {332-336}, doi = {10.1007/BF02966400}, pmid = {11114860}, issn = {1340-6868}, mesh = {Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma in Situ/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/pathology ; Female ; Humans ; *In Situ Hybridization, Fluorescence ; Monosomy ; Papilloma/*diagnosis/genetics/pathology ; }, abstract = {BACKGROUND: It is often difficult to pre-operatively diagnose ductal carcinoma in situ (DCIS)or intraductal papilloma (IDP). Current reports show that breast cancer frequently has numerical aberrations of chromosomes 1, 11 and 17. We investigated whether fluorescence in situ hybridization (FISH) analysis using three centromere-specific probes for chromosomes 1, 11 and 17 was feasible for diagnosing intraductal breast lesions.<br><br>METHODS: Fine-needle aspiration specimens from 102 breast lesions including DCIS (10), invasive ductal carcinoma (IDC) (78), IDP (7), fibroadenoma (6) and mastopathy (1) were examined for numerical aberrations on chromosomes 1, 11, 17 using FISH. If over 15% of all cells showed one signal, the sample was judged monosomic. If over 20% of cells showed three or more signals, it was considered polysomic. If the specimen had an aberration of at least one chromosome, it was judged positive.<br><br>RESULTS: Nine of 10 DCISs showed numerical aberrations of at least one chromosome whereas 65 of 78 IDCs and 2 of 14 benign lesions (containing 7 IDPs of which one case was positive) showed numerical aberrations on these chromosomes. The proportion of positive results was highest with DCIS. Moreover 6 out of 7 DCISs showed an aberration of all three chromosomes simultaneously and one case showed an aberration of two chromosomes. All aberrations in case of DCIS were polysomic while two benign lesions and 15 IDCs showed a monosomic pattern.<br><br>CONCLUSION: FISH may enable more accurate diagnosis of intraductal breast lesions.}, }
@article {pmid11113011, year = {2000}, author = {Sharov, VG and Todor, AV and Silverman, N and Goldstein, S and Sabbah, HN}, title = {Abnormal mitochondrial respiration in failed human myocardium.}, journal = {Journal of molecular and cellular cardiology}, volume = {32}, number = {12}, pages = {2361-2367}, doi = {10.1006/jmcc.2000.1266}, pmid = {11113011}, issn = {0022-2828}, support = {HL-49090-06/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Atractyloside/pharmacology ; Endocardium/metabolism ; Enzyme Inhibitors/pharmacology ; Female ; Glutamic Acid/metabolism ; Heart Failure/metabolism/*physiopathology ; Heart Ventricles ; Humans ; Malates/metabolism ; Male ; Middle Aged ; Mitochondria/*metabolism/*physiology ; Myocardium/metabolism ; *Oxygen Consumption ; Phosphorylation ; }, abstract = {Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n=9) or idiopathic dilated (IDC, n=9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON). Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V(SUB)), state 3 respiration (after addition of ADP, V(ADP)) and respiration after the addition of atractyloside (V(AT)) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V(ADP)was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V(ADP)/V(AT), was also significantly decreased in HF compared to CON. In both ICM and IDC, V(ADP)was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance.}, }
@article {pmid11088049, year = {2000}, author = {Song, MM and Nio, Y and Dong, M and Tamura, K and Furuse, K and Tian, YL and He, SG and Shen, K}, title = {Comparison of K-ras point mutations at codon 12 and p21 expression in pancreatic cancer between Japanese and Chinese patients.}, journal = {Journal of surgical oncology}, volume = {75}, number = {3}, pages = {176-185}, doi = {10.1002/1096-9098(200011)75:3&lt;176::aid-jso5&gt;3.0.co;2-w}, pmid = {11088049}, issn = {0022-4790}, mesh = {Aged ; China ; Female ; Genes, ras/*genetics ; Humans ; Japan ; Male ; Middle Aged ; Pancreatic Neoplasms/ethnology/*genetics/pathology ; *Point Mutation ; Proto-Oncogene Proteins p21(ras)/*genetics ; Survival Analysis ; }, abstract = {BACKGROUND AND OBJECTIVES: K-ras (Kirsten-ras) point mutation (PM) in codon 12 are suggested to be significantly associated with the tumorigenesis of pancreatic cancer. The incidences of K-ras PMs in human pancreatic cancer are reported to be different between Europeans and Japanese. The present study was designed to compare the incidences and profile of K-ras PMs and ras-p21 expression in primary invasive ductal carcinoma (IDC) of the pancreas between Japanese and Chinese.<br><br>METHODS: The specimens included 51 Japanese and 34 Chinese patients with the primary IDC of the pancreas. K-ras PMs were tested by allele specific oligonucleotide dot blot hybridization methods and ras-p21 expression was stained by the immunohistochemical method.<br><br>RESULTS: K-ras PMs were detected in 48 Japanese IDCs (94%) and in 24 Chinese ones (71%). There was a significant difference between the two groups. The GAT mutation was more frequent both in Japanese (61%, 33/54) and in Chinese (60%, 18/30) IDCs. The transitions/transversions ratio in the Japanese group was 2.4 in this study. By contrast, that in the Chinese group was 1.5. The expression of p21 was detected in 24 Japanese IDCs (47%) and in 24 Chinese IDCs (71%). There was a significant difference between the two groups. The expression of p21 and the patterns of K-ras PMs did not show any significant influence on the survival of the patients both in Japanese and Chinese. In the present study, Chinese IDC had a lower frequency of K-ras PMs in codon 12 than Japanese IDC. The pattern of K-ras PMs in Chinese IDC was different from that in Japanese and European IDC, respectively.<br><br>CONCLUSIONS: Ki-ras PM and p21 expression were frequently seen both in Japanese and Chinese patients with pancreatic cancer. Factors such as lifestyle and environment may have influences on pancreatic carcinogenesis in various populations.}, }
@article {pmid11078277, year = {2000}, author = {Fauchier, L and Babuty, D and Cosnay, P and Poret, P and Rouesnel, P and Fauchier, JP}, title = {Long-term prognostic value of time domain analysis of signal-averaged electrocardiography in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {85}, number = {5}, pages = {618-623}, doi = {10.1016/s0002-9149(99)00821-8}, pmid = {11078277}, issn = {0002-9149}, mesh = {Arrhythmias, Cardiac/epidemiology ; Cardiomyopathy, Dilated/*diagnosis/mortality ; Death, Sudden, Cardiac/epidemiology ; Electrocardiography/*methods ; Electrocardiography, Ambulatory/methods ; Evaluation Studies as Topic ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Risk Assessment ; *Signal Processing, Computer-Assisted ; Survival Analysis ; Time Factors ; }, abstract = {The aim of this study was to evaluate the long-term prognostic value of signal-averaged electrocardiography (SAECG) in idiopathic dilated cardiomyopathy (IDC). Time domain analysis of SAECG was assessed in 131 patients with angiographically confirmed IDC (age 52+/-12 years; 108 men; left ventricular ejection fraction 33+/-12%) using specific criteria in 44 patients with bundle branch block. Late potentials (LP) on SAECG were present in 27% of the patients. Patients with LP had a similar left ventricular ejection fraction and a similar left ventricular end-diastolic diameter than patients with a normal SAECG. With a follow-up of 54+/-41 months, 24 patients suffered cardiac death and 19 had major arrhythmic events (sudden death, resuscitated ventricular fibrillation, or sustained ventricular tachycardia). Patients with LP had an increased risk of all-cause cardiac death (RR 3.3, 95% confidence interval 1.5 to 7.5, p = 0.004) and of arrhythmic events (RR 7.2, 95% confidence interval 2.6 to 19.4, p = 0.0001). Using multivariate analysis, only LP on SAECG (p = 0.001), reduced SD of all normal-to-normal intervals (SDNN) (p = 0.002), increased pulmonary capillary wedge pressure (p = 0.005), and history of sustained ventricular tachyarrhythmia (p = 0.02) predicted cardiac death. A history of previous sustained ventricular tachyarrhythmia (p = 0.0001), reduced SDNN (p = 0.003), and LP on SAECG (p = 0.006) were the only independent predictors of major arrhythmic events. Results were not altered when considering separately patients with or without bundle branch block, or after exclusion of patients with a history of sustained ventricular tachyarrhythmia. This study is one of the first to suggest that LP on SAECG is an independent predictor of all-cause cardiac death and is of high interest for arrhythmia risk stratification in IDC.}, }
@article {pmid11062111, year = {2000}, author = {Ruibal, A and Schneider, J and del Río, MC and Arias, J and Núñez, MI and Tejerina, A}, title = {[Expression of the adhesion molecule CD44v6 in infiltrating ductal carcinomas of the breast is associated with hormone dependence. Our experience with 168 cases].}, journal = {Revista espanola de medicina nuclear}, volume = {19}, number = {5}, pages = {350-355}, doi = {10.1016/s0212-6982(00)71889-1}, pmid = {11062111}, issn = {0212-6982}, mesh = {Adenocarcinoma, Mucinous/immunology ; Antigens, Neoplasm/*analysis ; Breast/immunology ; Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Carcinoma, Medullary/immunology ; Female ; Fibroadenoma/immunology ; Fibrocystic Breast Disease/immunology ; Glycoproteins/*analysis ; Humans ; Hyaluronan Receptors/*analysis ; Neoplasms, Hormone-Dependent/*immunology ; }, abstract = {In order to investigate the possible hormone-dependence of CD44v6 in human breast cancer, we assayed the concentrations of this isoform in the membrane fraction of 168 invasive ductal carcinomas (IDC) and in 26 normal breast tissue samples, 18 fibradenomas (FAD), 3 fibrocystic disease specimens (FD), 7 mucinous carcinomas and 4 medullary carcinomas using the ELISA method. The results were compared with those of the estrogen (ER) and progesterone (PR) receptors, pS2, tissue type plasminogen activator (t-PA), cathepsin D, epidermal growth factor receptor (EGFR) and c-erbB2/neu oncoprotein concentrations. Menopausal status, size of the tumor in the cases of cancers, axillary lymph node involvement, histologic grade, ploidy, cellular synthesis phase, multifocality and multicentricity were also considered as variables. The cut-off value for CD44v6-positivity was set at 5 ng/mg prt. membrane protein content. 64/138 (38.1%) infiltrating ductal carcinomas scored positive. This was significantly higher than for the normal breast tissue (0/26; p: 0.0001), similar to that seen in the FAD (3/18), fibrocystic disease (0/3), infiltrating mucinous carcinomas (4/7) and lobular (3/15) and significantly lower than for the infiltrating medullary carcinomas (4/4; p: 0.027). There were no significant differences with the other groups of tissues studied. Furthermore, CD44v6-positive IDC showed significantly higher concentrations of ER, PR and cathepsin D and lower (p: 0.051) concentrations of EGFR when compared to their CD44v6-negative counterparts. The significant coexpression of ER, PR and cathepsin D seems to indicate a possible role for hormonal regulation of CD44v6 expression while the role of pS2 and t-PA, estrogen related proteins, was very reduced.}, }
@article {pmid11060371, year = {2000}, author = {Hama, Y and Kaji, T and Iwasaki, Y and Hinokiyama, K and Shimizu, M and Kusano, S}, title = {Successful transcatheter embolization of penetrating aortic ulcer using interlocking detachable coils.}, journal = {Cardiovascular and interventional radiology}, volume = {23}, number = {5}, pages = {391-393}, doi = {10.1007/s002700010089}, pmid = {11060371}, issn = {0174-1551}, mesh = {Aortic Dissection/diagnostic imaging/etiology/*therapy ; Aortic Aneurysm, Thoracic/diagnostic imaging/etiology/*therapy ; Arteriosclerosis/complications ; Embolization, Therapeutic/*instrumentation ; Equipment Design ; Humans ; Male ; Middle Aged ; Tomography, X-Ray Computed ; }, abstract = {A 54-year-old man with persistent chest pain was hospitalized for hypertension and DeBakey type IIIb aortic dissection. The false lumen of the dissection was almost completely thrombosed; however, a penetrating atherosclerotic ulcer (PAU) was observed 5 weeks later. At that time, we successfully embolized the PAU with a microcatheter and interlocking detachable coils (IDCs). The patient is well with no episodes of relapse in 20 months of follow-up. This case suggests the utility of the microcatheter and IDC system as an alternative to surgery.}, }
@article {pmid11029808, year = {2000}, author = {Kanoh, T and Iino, Y and Horiguchi, J and Takei, H and Maemura, M and Yokoe, T and Morishita, Y}, title = {A case report of advanced male breast cancer with an objective response to tamoxifen treatment.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {3}, pages = {256-260}, doi = {10.1007/BF02967470}, pmid = {11029808}, issn = {1340-6868}, mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biopsy ; Brain Neoplasms/*secondary ; Breast Neoplasms, Male/*drug therapy/*pathology/psychology ; Carcinoma, Ductal, Breast/*secondary ; Fatal Outcome ; Humans ; Lung Neoplasms/*secondary ; Male ; Neoplasm Staging ; Quality of Life ; Tamoxifen/*therapeutic use ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {A 70-year-old man presented with a firm tumor in his right breast first noticed eight years ago. The tumor had enlarged gradually and had produced an ulcer with bleeding. On physical examination, a huge tumor entirely occupied the right breast and extensively had infiltrated the chest wall. Chest X-ray and CT showed massive pleural effusion and multiple small nodular lesions in the lung. Invasive ductal carcinoma of the breast was diagnosed by incisional biopsy,confirming advanced breast cancer with lung metastases and bilateral pleural effusion(T4cN2M1, Stage IV). Because ER and PgR levels were 110 fmol/mg and 190 fmol/mg, respectively, and because his general condition was poor, we selected medical treatment with tamoxifen(TAM). Thirty-two weeks later, the tumor had showed pronounced reduction with scarring. The patient underwent local excision of the scar tissue. The quality of life of the patient was favorably improved and no severe adverse events were observed. The tumor in the chest wall recurred two months after the end of TAM treatment, possibly because the patient did not accept continuous TAM therapy. The patient died from complications of brain metastasis 32 months after the start of TAM treatment. We report a rare case of advanced male breast cancer and on the effectiveness of continuous TAM treatment.}, }
@article {pmid11029799, year = {2000}, author = {Tsuda, H and Takarabe, T and Akashi-Tanaka, S and Fukutomi, T and Nanasawa, T and Watanabe, T}, title = {Evaluation of histopathological criteria for identifying node-negative breast cancer with high risk of early recurrence in the NSAS-BC protocol study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {3}, pages = {201-209}, doi = {10.1007/BF02967461}, pmid = {11029799}, issn = {1340-6868}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy/methods/*standards ; Breast Neoplasms/*pathology/surgery ; Clinical Protocols/standards ; Female ; Humans ; Japan ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*pathology/surgery ; Neoplasm Staging/methods/*standards ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: The histopathological criteria for high-risk node-negative primary breast cancer stated in the National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) protocol were used to grade a consecutive series of 488 cases at our hospital.<br><br>METHODS: To validate the criteria retrospectively, we examined the histological features of node-negative primary breast cancers which showed early relapse within 2 years after surgical therapy.<br><br>RESULTS: Early relapse occurred in 12 patients, distant metastases in 11, and local recurrence in one. Among 278 cases followed for up to 1.5 years or longer, early systemic relapse was detected in 10 (5.8%) of 172 higher-grade tumors (9 invasive ductal carcinomas of nuclear grade 3 and one invasive ductal carcinoma of nuclear grade 2) and one stromal cell sarcoma. Among the 115 low-risk tumors, only one case (0.9%) of invasive ductal carcinomas with nuclear grade 1 showed early local recurrence. Early relapse occurred in only one (1.5%) of 67 tumors with an invasive component of 1.0 cm but in 11 (5.2%) of 211 tumors with an invasive component of 1.1 cm. The recurrence rate increased to 9.3% (8/86) when tumor invasion was 2.1 cm. In 12 cancers showing recurrence, strand structure, large central acellular zones, and squamoid features were histologically observed in four, two, and three cases, respectively. The present results confirmed the reported tendency of correlation between strand pattern and bone metastasis, large central acellular zones and lung and brain metastasis, and squamoid features and lung metastasis. Synchronous bilateral and unilateral multiple cancers were characterized by lower nuclear grades.<br><br>CONCLUSIONS: At our hospital, the criteria used in the NSAS-BC protocol were demonstrated to identify node-negative cancers with high risk of early recurrence at a hospital level. To further identify groups prone to recurrence, longer follow-up would be necessary. In addition, the histological criteria could be improved to correlate with patient outcome more accurately.}, }
@article {pmid11029794, year = {2000}, author = {Nagasawa, M and Iino, Y and Horiguchi, J and Takei, H and Maemura, M and Horii, Y and Matsumoto, H and Nagaoka, H and Oyama, T and Nakajima, T and Morishita, Y}, title = {Sudden hemorrhage of the breast caused by breast cancer: a case report and review of the literature.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {2}, pages = {176-178}, doi = {10.1007/BF02967454}, pmid = {11029794}, issn = {1340-6868}, mesh = {Aged ; Breast Diseases/*etiology ; Breast Neoplasms/*complications ; Carcinoma, Ductal, Breast/*complications ; Female ; Hemorrhage/*etiology ; Humans ; }, abstract = {A rare case of sudden hemorrhage caused by breast cancer is reported. A 71-year-old woman noted bleeding from her left breast. Physical examination of the left breast showed a localized open cavity accompanied by bleeding and coagulation. The patient had no history of breast trauma or anticoagulation therapy. Incisional biopsy followed by histological examination resulted in a diagnosis of granulation tissue with no cancer cells present. Mammography and ultrasonography indicated probable breast cancer. As a result, a second incisional biopsy was performed, which suggested invasive ductal carcinoma without histological skin invasion. A modified radical mastectomy was performed under a diagnosis of stage II breast cancer. Breast cancer with sudden hemorrhage is rare. We review the literature and discuss the cause of this unusual manifestation.}, }
@article {pmid11029768, year = {2000}, author = {Yu, Y and Morimoto, T and Sasa, M and Okazaki, K and Harada, Y and Fujiwara, T and Irie, Y and Takahashi, E and Tanigami, A and Izumi, K}, title = {Human papillomavirus type 33 DNA in breast cancer in Chinese.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {1}, pages = {33-36}, doi = {10.1007/BF02967185}, pmid = {11029768}, issn = {1340-6868}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blotting, Southern ; Breast Neoplasms/epidemiology/ethnology/*virology ; Carcinoma, Ductal, Breast/epidemiology/ethnology/*virology ; China/epidemiology ; DNA Probes, HPV ; DNA, Neoplasm/genetics/*isolation &amp; purification ; DNA, Viral/genetics/*isolation &amp; purification ; Female ; Genes, Viral ; Humans ; Middle Aged ; Papillomaviridae/classification/genetics/*isolation &amp; purification/pathogenicity ; Papillomavirus Infections/epidemiology/ethnology/*virology ; Polymerase Chain Reaction ; Tumor Virus Infections/epidemiology/ethnology/*virology ; }, abstract = {BACKGROUND: The association between human papillomavirus (HPV) and anogenital tumors, especially cervical cancer, is well documented. However, it remains unclear whether there is also a correlation between HPV infection and human breast cancer.<br><br>METHODS: We used PCR and Southern blot hybridization to analyze HPV-related DNA specimens from 32 cases of invasive ductal carcinoma operated upon in the Shanghai region of China.<br><br>RESULTS: DNA derived from HPV33 was detected in 14 cases (43.8%). No HPV16 or HPV18 DNA was detected in any of the cases in this study. This is the first report demonstrating a correlation between HPV33 infection and breast cancer.<br><br>CONCLUSIONS: Our results suggest that HPV33 infection may be involved in the pathogenesis of breast cancer in Chinese.}, }
@article {pmid11026070, year = {2000}, author = {Hernández-Cadena, L and Téllez-Rojo, MM and Sanín-Aguirre, LH and Lacasaña-Navarro, M and Campos, A and Romieu, I}, title = {[Relationship between emergency consultations for respiratory diseases and air pollution in Juarez City, Chihuahua].}, journal = {Salud publica de Mexico}, volume = {42}, number = {4}, pages = {288-297}, pmid = {11026070}, issn = {0036-3634}, mesh = {Acute Disease ; Adolescent ; *Air Pollution ; Asthma/*epidemiology ; Child ; Child, Preschool ; Emergency Service, Hospital/*statistics &amp; numerical data ; Humans ; Infant ; Mexico ; Respiratory Tract Infections/*epidemiology ; *Urban Health ; }, abstract = {OBJECTIVE: To assess the relationship of < or = 10 microns particles (PM10) and atmospheric ozone concentrations, with the daily number of emergency visits due to asthma and acute respiratory diseases, among children aged under 15, living in Ciudad Juarez, Chihuahua, Mexico.<br><br>MATERIAL AND METHODS: Between 1998 and 1999, an ecologic study was conducted. Atmospheric data were obtained from the Environmental Protection Agency (EPA), from eight monitoring stations located in Ciudad Juarez, Chihuahua, and EI Paso, Texas. From July 1997 to December 1998, data from emergency room visits for respiratory illness were abstracted from existing medical records of two Mexican Institute of Social Security (IMSS) hospitals in Ciudad Juarez. Diagnoses were classified into two groups: a) asthma, and b) upper respiratory infections (URI), according to the International Classification of Diseases (ICD-9 and/or IDC-10). Statistical analysis was carried out using the Poisson regression time series method.<br><br>RESULTS: During the study period, the mean 24-hour PM10 level was 34.46 micrograms/m3 (SD = 17.99) and the mean ozone level was 51.60 ppb (SD = 20.70). The model shows that an increase of 20 micrograms/m3 in the mean 24-hour exposure to PM10 was related to an increase of 4.97% (95% CI 0.97-9.13) in emergency visits for asthma, with a 5-day lag, as well as to an increase of 9% (95% CI 1.8-16.8) when a cumulative 5-day exposure was considered. URI increased 2.95% as a cause of emergency room visits, for each 20 micrograms/m3 increase in the mean 24-hour exposure to PM10. The impact of PM10 on emergency visits for asthma was greater on days with ozone ambient levels exceeded 49 ppb (median value).<br><br>CONCLUSIONS: A positive association was found between environmental PM10 and ozone concentrations and the daily number of emergency room visits due to asthma and acute respiratory diseases, even with levels lower than the Mexican standard levels. Also, a synergic effect between PM10 and O3 was found.}, }
@article {pmid11007434, year = {2000}, author = {Aubele, M and Cummings, M and Walsch, A and Zitzelsberger, H and Nährig, J and Höfler, H and Werner, M}, title = {Heterogeneous chromosomal aberrations in intraductal breast lesions adjacent to invasive carcinoma.}, journal = {Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology}, volume = {20}, number = {1}, pages = {17-24}, doi = {10.1155/2000/930246}, pmid = {11007434}, issn = {0921-8912}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Chromosome Aberrations ; Chromosomes/ultrastructure ; Dissection ; Female ; Histocytochemistry/*methods ; Humans ; Hyperplasia/genetics/pathology ; Lasers ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; Precancerous Conditions/genetics/pathology ; }, abstract = {There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS). In this study we applied comparative genomic hybridization (CGH) to formalin-fixed, paraffin-embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC), to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser-microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and further processed for CGH analysis. Investigating multiple samples (n = 25) from four patients we found an average of 5.6 +/- 0.9 (mean +/- SEM) chromosomal imbalances already present in DH. In the twelve DCIS lesions an average of 10.8 (+/- 0.9) aberrations was identified with 14.8 (+/- 0.8) aberrations in the four adjacent IDC lesions. The increasing number of chromosomal changes in parallel with the histopathological sequence corroborate the hypothesis, that the carcinomas may have developed through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. However, heterogeneous results were identified in the multiple samples per entity from the same patient, demonstrated mainly in the DCIS samples in the chromosomal regions 6p, 9p, 11q, 16p and 17q, in the DH samples by 3p, 16p and 17q. This heterogeneous findings were most pronounced within the DH and was less in the DCIS and IDC samples. The only aberration consistently found in all samples-even in all DH sample-was amplification of the 20q13 region. Our results demonstrate, that the applied combination of laser-microdissection, DOP-PCR and CGH, may serve to analyse breast carcinogenesis pathways in suitable histological material. However, so far, it is unclear how to handle heterogeneous results and these make identification of relevant changes more difficult. Setting a threshold and evaluating only those chromosomal changes which are present in a majority of samples may be one possibility. This involves however, the risk that infrequent but possibly significant aberrations may be missed. Figures on http://www.esacp.org/acp/2000/20-1/aubele. htm.}, }
@article {pmid10988312, year = {2000}, author = {Broussas, M and Cornillet-Lefebvre, P and Bernard, J and Adjizian, JC and Potron, G and Nguyên, P}, title = {Separation of dendritic cells from highly purified human monocytes by counterflow centrifugation induces tissue factor expression.}, journal = {Transfusion}, volume = {40}, number = {9}, pages = {1088-1094}, doi = {10.1046/j.1537-2995.2000.40091088.x}, pmid = {10988312}, issn = {0041-1132}, mesh = {Animals ; Anions ; Antigens ; Cattle ; Cell Separation/*methods ; Cells, Cultured ; Centrifugation/methods ; Coagulants/metabolism ; Dendritic Cells/*cytology ; Fetal Blood/cytology ; Humans ; Monocytes/*cytology ; Phospholipids/biosynthesis ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Thromboplastin/*genetics/immunology ; }, abstract = {BACKGROUND: In vitro generation of dendritic cells (DCs) from human monocytes represents a promising tool in immunotherapy. However, it is not known whether the separation of DCs from monocytes induces tissue factor expression and therefore may trigger coagulation in patients receiving these DC preparations. The aim of this study is thus to analyze tissue factor expression on monocyte-derived DCs and to compare their ability to trigger thrombin generation to that of macrophages obtained from the same monocytes.<br><br>STUDY DESIGN AND METHODS: Human monocytes are separated by leukapheresis and washed by using counterflow centrifugation in sterile, endotoxin-free conditions. Macrophages are grown from human monocytes in the presence of GM-CSF alone and immature DCs are grown in the presence of GM-CSF plus IL-4 for 5 days with fetal calf serum (IDC-FCS). Immature DCs are also grown from human monocytes for 7 days in the presence of GM-CSF plus IL-4 with human group AB serum (IDC-HS). The addition of prostaglandin E(2) and TNFalpha in this culture medium at Day 5 leads to mature DCs (MDC-HS). Tissue factor mRNA expression is studied by RT-PCR analysis. Tissue factor antigen is measured by ELISA in cell lysates and by direct flow cytometry. The procoagulant activity of intact cells is assessed by using an amidolytic assay or a chronometric assay.<br><br>RESULTS: IDC-FCS express tissue factor mRNA and antigen and trigger thrombin generation. Procoagulant activity of IDC-FCS is dependent on both tissue factor expression and exposure to anionic phospholipid. Monocyte-derived macrophages cultured for 5 days with GM-CSF alone express lower levels of tissue factor mRNA, tissue factor antigen, and procoagulant activity than IDC-FCS. IDC-HS and MDC-HS also express high levels of tissue factor mRNA and antigen and support procoagulant activity.<br><br>CONCLUSION: Monocyte-derived DCs express a high level of functional tissue factor and support procoagulant activity. This finding should be taken into account in clinical trials.}, }
@article {pmid10973791, year = {2000}, author = {Dietz, AB and Bulur, PA and Knutson, GJ and Matasić, R and Vuk-Pavlović, S}, title = {Maturation of human monocyte-derived dendritic cells studied by microarray hybridization.}, journal = {Biochemical and biophysical research communications}, volume = {275}, number = {3}, pages = {731-738}, doi = {10.1006/bbrc.2000.3372}, pmid = {10973791}, issn = {0006-291X}, mesh = {Antigens, CD/genetics ; *Cell Differentiation ; Cytokines/genetics ; Dendritic Cells/*cytology/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Monocytes/*cytology/*metabolism ; Neuropeptides/genetics ; Nucleic Acid Hybridization ; *Oligonucleotide Array Sequence Analysis ; RNA, Messenger/analysis/genetics ; Receptors, Cytokine/genetics ; Transcription, Genetic ; }, abstract = {We compared the transcript profiles of human myeloid immature dendritic (IDC) cells and mature dendritic cells (MDC) by hybridization of cell-derived cDNA to DNA probes immobilized on microarrays. The microarrays contained probes for 4110 known genes. We report maturation-dependent changes in transcription of clusters of differentiation, cytokines, cytokine receptors, chemokines, chemokine receptors, neuropeptides, adhesion molecules, and other genes. We identified 1124 transcripts expressed in IDC and 1556 transcripts expressed in MDC. Maturation increased the levels of 291 transcripts twofold or more and reduced the levels of 78 transcripts to one-half or less than in IDC. We identified a concerted maturation-stage-dependent transcription of the variable chains of the members of the gamma-chain-cytokine receptor family IL-4R, IL-7R, and IL-15R. Also, we found the reversal of the ratio of transcripts for galectin-3 and galectin-9 upon maturation. We identified maturation-dependent changes in the levels of transcripts for numerous genes encoding proteins previously undetected in dendritic cells such as indoleamine 2,3-deoxygenase, Epstein-Barr virus induced protein 3 and kinesin-2. Moreover, MDC transcribed and translated insulin like growth factor-1 receptor, transforming growth factor alpha, and neuropeptide Y.}, }
@article {pmid10955735, year = {2000}, author = {Eriguchi, N and Aoyagi, S and Hara, M and Okuda, K and Tamae, T and Fukuda, S and Hashino, K and Sato, S and Fujiki, K and Furukawa, S and Jimi, A}, title = {Synchronous or metachronous double cancers of the pancreas and other organs: report on 12 cases.}, journal = {Surgery today}, volume = {30}, number = {8}, pages = {718-721}, pmid = {10955735}, issn = {0941-1291}, mesh = {Aged ; Carcinoma/*complications/pathology/surgery ; Colorectal Neoplasms/*pathology/surgery ; Female ; Gastrectomy ; Humans ; Lung Neoplasms/*pathology/surgery ; Male ; Middle Aged ; Neoplasms, Multiple Primary/*pathology/surgery ; Neoplasms, Second Primary/*pathology/surgery ; Pancreatectomy ; Pancreatic Neoplasms/*pathology/surgery ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/*pathology/surgery ; }, abstract = {Pancreatic carcinoma carries a poor prognosis, especially invasive ductal carcinoma of the pancreas. This retrospective study describes the results of the treatment and prognosis for double cancers in which cancer of the pancreas was associated with malignancies in other organs in 12 patients who were diagnosed and treated at Kurume University Hospital. The patients included 4 women and 8 men, with an average age of 67 years. Of the 12 tumors, 7 were metachronous pancreatic cancers which occurred after resections of other organ malignancies. Five patients had synchronous double cancers, one of whom was diagnosed to have gastric cancer on admission. Two other patients of this group were diagnosed to have lung cancer, while the remaining 2 patients suffered from colon cancer. By the time pancreatic cancer was diagnosed, gastrectomies had been performed in 7 patients for either gastric cancer or ulcers. In addition, one patient underwent a hysterectomy for uterine carcinoma and another received a low anterior resection for rectal carcinoma. Four of 5 patients in the synchronous group had nonresectable tumors and a palliative bypass operation was performed in 2 of these patients. Six patients who had metachronous double cancers died because of pancreatic cancer recurrence or metastases. We conclude that the prognosis of double cancers, where cancer of the pancreas is associated with other organ malignancies, primarily depends on the prognosis of the pancreatic carcinoma, and the present study suggests the necessity of long-term follow-up examinations for gastrectomy patients in order to make an early diagnosis of pancreatic cancer.}, }
@article {pmid10955380, year = {2000}, author = {Nanas, JN and Margari, ZJ and Lekakis, JP and Alexopoulos, GE and Prassopoulos, V and Agapitos, EV and Toumanidis, ST and Anastasiou-Nana, MI and Kostamis, P and Stamatelopoulos, SF}, title = {Indium-111 monoclonal antimyosin cardiac scintigraphy in men with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {85}, number = {2}, pages = {214-220}, doi = {10.1016/s0002-9149(99)00641-4}, pmid = {10955380}, issn = {0002-9149}, mesh = {Adult ; Antibodies, Monoclonal/blood ; Cardiomyopathy, Dilated/*diagnostic imaging/immunology/physiopathology ; Follow-Up Studies ; Humans ; *Indium Radioisotopes ; Male ; Middle Aged ; Myosins/immunology ; Prognosis ; Radionuclide Imaging ; Risk Factors ; Severity of Illness Index ; Ventricular Function, Left ; }, abstract = {This study examined the prognostic value and the evolution of the heart-to-lung ratio of monoclonal antimyosin antibody (MAA) uptake in patients with a diagnosis of idiopathic dilated cardiomyopathy (IDC). Uptake of indium-111-labeled MAA occurs when the myocytes become irreversibly damaged. The study included 29 men with IDC followed up for 3 years. The diagnosis was verified by endomyocardial biopsy in all patients. Patients who survived beyond 1 year were restudied. Baseline heart-to-lung ratio of MAA was 1.74+/-0.22. Multivariate Cox regression analysis revealed that MAA and New York Heart Association class were independent predictors of late mortality, with a hazard ratio of 4.4 (95% confidence interval 1.1 to 17.9, p = 0.036) and 7.5 (95% confidence interval 2.0 to 28.4, p = 0.003), respectively, when heart-to-lung ratio of MAA uptake was > 1.74 and New York Heart Association class was >11. When these patients were divided into those with chronic IDC (group I [n = 19]) and those with subacute IDC (group II [n = 10]), baseline heart-to-lung ratio was 1.7+/-0.2 and 1.86+/-0.25, respectively (p = NS). In the surviving patients, on restudy, the heart-to-lung ratio of MAA uptake was unchanged in group I (1.64+/-0.20, p = NS), but had decreased to the level of group I (1.66+/-0.21 [p = 0.008]) in group II. Thus, men with IDC and a high heart-to-lung ratio of MAA uptake have a worse long-term prognosis than patients with a lower ratio. The heart-to-lung ratio of MAA decreases comparably over time in subacute IDC and remains stable in chronic IDC.}, }
@article {pmid10951489, year = {2000}, author = {Dawkins, HJ and Sellner, LN and Turbett, GR and Thompson, CA and Redmond, SL and McNeal, JE and Cohen, RJ}, title = {Distinction between intraductal carcinoma of the prostate (IDC-P), high-grade dysplasia (PIN), and invasive prostatic adenocarcinoma, using molecular markers of cancer progression.}, journal = {The Prostate}, volume = {44}, number = {4}, pages = {265-270}, doi = {10.1002/1097-0045(20000901)44:4&lt;265::aid-pros1&gt;3.0.co;2-i}, pmid = {10951489}, issn = {0270-4137}, mesh = {Adenocarcinoma/*genetics/pathology/surgery ; Alleles ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology/surgery ; Disease Progression ; Genetic Markers/genetics ; Humans ; *Loss of Heterozygosity ; Male ; Microsatellite Repeats/genetics ; Neoplasm Invasiveness ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*genetics/pathology/surgery ; Prostatic Neoplasms/*genetics/pathology/surgery ; }, abstract = {BACKGROUND: Prostate ducts and acini whose lumens are filled with malignant cells represent a well-recognized histological pattern recently termed intraductal carcinoma of the prostate (IDC-P). These tumors are often associated with rapid disease progression, and most recur after radical surgery. Controversy exists as to whether IDC-P should be recognized as a separate entity, an extension of high-grade dysplasia (PIN) or invasive carcinoma as described by the Gleason grading system. This study investigates the use of molecular markers in defining the position of IDC-P in the evolutionary hierarchy of prostate cancer progression.<br><br>METHODS: IDC-P, high-grade dysplasia, and invasive cancers from a cohort of 20 selected radical prostatectomy specimens were screened for loss of heterozygosity (LOH), using 12 polymorphic microsatellite markers frequently lost in prostate cancer.<br><br>RESULTS: LOH was absent in Gleason grade 3 cancer, infrequent in high-grade dysplasia (9%) and Gleason grade 4 cancer (29%), but common in IDC-P (60%). In IDC-P, and to a lesser extent Gleason grade 4 cancers, multiple sites of allelic loss in individual cases were usual.<br><br>CONCLUSIONS: Allelic instability provides further evidence that IDC-P is not a simple extension of dysplasia, nor does it represent invasion of Gleason grade 3 cancers into the ductal/acinar system. IDC-P and Gleason grade 4 cancer represent late but possibly separate events in prostate cancer evolution.}, }
@article {pmid10944127, year = {2000}, author = {Pich, A and Margaria, E and Chiusa, L}, title = {Oncogenes and male breast carcinoma: c-erbB-2 and p53 coexpression predicts a poor survival.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {18}, number = {16}, pages = {2948-2956}, doi = {10.1200/JCO.2000.18.16.2948}, pmid = {10944127}, issn = {0732-183X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Antigens, Nuclear ; *Biomarkers, Tumor ; Breast Neoplasms, Male/*genetics/mortality ; Carcinoma, Ductal, Breast/*genetics/mortality ; Chi-Square Distribution ; Gene Expression ; Genes, erbB-2/*genetics ; Genes, p53/*genetics ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Male ; Middle Aged ; Nuclear Proteins/analysis ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-bcl-2/analysis ; Proto-Oncogene Proteins c-myc/analysis ; Receptor, ErbB-2/analysis ; Receptors, Androgen/analysis ; Receptors, Estrogen/analysis ; Retrospective Studies ; Risk Factors ; Statistics, Nonparametric ; Survival Analysis ; Survival Rate ; Tumor Suppressor Protein p53/analysis ; }, abstract = {PURPOSE: To investigate the prognostic value of biomarkers in male breast carcinoma (MBC).<br><br>PATIENTS AND METHODS: Fifty patients (mean age, 62.2 years) with invasive ductal carcinoma were retrospectively studied. All patients received surgery; 35 had adjuvant postoperative therapy. The median follow-up was 59 months (range, 1 to 230 months). c-myc, c-erbB-2, p53, and bcl-2 proteins were immunohistochemically detected on sections from formalin-fixed, paraffin-embedded tissues using 9E11, CB11, DO7, and bcl-2 124 monoclonal antibodies (mAbs). Estrogen, progesterone, and androgen receptors were detected using specific mAbs. Cell proliferation was assessed by MIB-1 mAb.<br><br>RESULTS: In univariate analysis, c-myc, c-erbB-2, and p53 protein overexpression was significantly correlated with prognosis. The median survival was 107 months for c-myc-negative and 52 months for c-myc-positive patients (P =.01), 96 months for c-erbB-2-negative and 39 months for c-erbB-2-positive patients (P =.02), and 100 months for p53-negative and 33 months for p53-positive patients (P =.0008). Tumor histologic grade (P =.01), tumor size (P =.02), patient age at diagnosis (P =.03), and MIB-1 scores (P =.0004) also had prognostic value. In multivariate analysis, only c-erbB-2 and p53 immunoreactivity retained independent prognostic significance. All nine patients who did not express c-erbB-2 and p53 proteins were alive after 58 months, whereas none of the 14 patients expressing both proteins survived at 61 months follow-up (P =.0002).<br><br>CONCLUSION: Overexpression of c-myc, c-erbB-2, and p53 proteins may be regarded as an additional prognostic factor in MBC. The combination of c-erbB-2 and p53 immunoreactivity can stratify patients into different risk groups.}, }
@article {pmid10939434, year = {2000}, author = {Rokutanda, N and Iino, Y and Yokoe, T and Maemura, M and Horiguchi, J and Takei, H and Koibuchi, Y and Iijima, K and Oyama, T and Morishita, Y}, title = {Primary squamous cell carcinoma of the breast during lactation: a case report.}, journal = {Japanese journal of clinical oncology}, volume = {30}, number = {6}, pages = {279-282}, doi = {10.1093/jjco/hyd069}, pmid = {10939434}, issn = {0368-2811}, mesh = {Adult ; Breast Neoplasms/*etiology/pathology/physiopathology ; Carcinoma, Squamous Cell/*etiology/physiopathology/secondary ; Female ; Humans ; *Lactation ; Lung Neoplasms/secondary ; }, abstract = {A case of primary squamous cell carcinoma of the breast during lactation is reported. The patient was a 32-year-old woman, in post-partum lactating 18 months after delivery, who was referred to our hospital following detection of a lump in her left breast during physical examination in mass screening for breast cancer. The tumor, palpated in the upper outer quadrant of the left breast, was firm, well-defined and 2.8 x 2.6 cm in size. Ultrasonograms identified an irregular-shaped hypoechoic lesion and mammograms revealed a well-defined, circumscribed tumor. Based on these findings, breast cancer was suspected and an excisional biopsy was performed. The resected specimen was a firm, solid and circumscribed tumor with central hemorrhage. Microscopic findings demonstrated that the tumor consisted of an invasive ductal carcinoma with marked squamous metaplasia, such as keratinization and squamo-columnar junction. Breast-conserving surgery was performed and no lymph node involvement was noted. Both estrogen and progesterone receptors of the tumor were negative. Generally, the size of both squamous cell carcinoma and carcinoma during the lactation period tends to be larger than ordinary carcinomas. In this case, the cancerous lesion was detected at a relatively early stage. Although the cancerous lesion was detected at a relatively early stage and no lymph node involvement was noted, lung metastases occurred within 12 months of the surgery. Malignant potential is generally considered to be high in cases of squamous cell carcinoma of the breast with lactation and thus intensive treatment potentially resulting in severe side effects was considered to be necessary for this patient.}, }
@article {pmid10935476, year = {1999}, author = {Rogers, MS and Foley, MA and Crotty, TB and Hartmann, LC and Ingle, JN and Roche, PC and Strehler, EE}, title = {Loss of immunoreactivity for human calmodulin-like protein is an early event in breast cancer development.}, journal = {Neoplasia (New York, N.Y.)}, volume = {1}, number = {3}, pages = {220-225}, pmid = {10935476}, issn = {1522-8002}, support = {T32 CA075926/CA/NCI NIH HHS/United States ; P20 CA 65800-01/CA/NCI NIH HHS/United States ; T32CA75926/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*chemistry ; Calmodulin/*analysis/genetics/physiology ; Down-Regulation ; Humans ; Immunohistochemistry ; Polymerase Chain Reaction ; Rabbits ; }, abstract = {Cell proliferation requires calmodulin, a protein that regulates calcium-dependent enzymes involved in signal transduction pathways in eukaryotic cells. Calmodulin-like protein (CLP) is found in certain epithelial cell types, including normal breast epithelium, and, although it closely resembles calmodulin in amino acid sequence, CLP interacts with different proteins than does calmodulin. The observation that CLP mRNA expression is dramatically reduced in transformed breast epithelial cells led to two hypotheses: (1) CLP helps to maintain the differentiated state in epithelial cells; and (2) downregulation of CLP accompanies malignant transformation of breast epithelial cells. The objective of this study was to determine if the expression of CLP in human breast cancer specimens is reduced in comparison to its expression in normal breast tissue. Eighty human breast cancer biopsy specimens were analyzed immunohistochemically for CLP expression by using a polyclonal rabbit antihuman CLP antibody. CLP expression was reduced in 79% to 88% of the invasive ductal carcinoma and lobular carcinoma specimens and in a similar fraction of the ductal carcinoma in-situ specimens, compared with normal breast specimens. None of the breast cancer specimens showed an increase in CLP expression. These findings support the hypotheses that CLP behaves as a functional tumor suppressor protein and is downregulated early in breast cancer progression.}, }
@article {pmid10930114, year = {2000}, author = {Lo, YF and Chen, TC and Chen, SC and Chao, CC}, title = {Aberrant expression of TSG101 in Taiwan Chinese breast cancer.}, journal = {Breast cancer research and treatment}, volume = {60}, number = {3}, pages = {259-266}, doi = {10.1023/a:1006426400524}, pmid = {10930114}, issn = {0167-6806}, mesh = {Blotting, Western ; Breast Neoplasms/ethnology/*genetics/metabolism ; China/ethnology ; DNA Primers/chemistry ; DNA-Binding Proteins/biosynthesis/*genetics ; Endosomal Sorting Complexes Required for Transport ; Female ; Gene Expression/genetics ; Humans ; Immunohistochemistry ; Leucine Zippers/*genetics ; Neoplasm Staging ; RNA, Messenger/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Deletion ; Taiwan/epidemiology ; Transcription Factors/biosynthesis/*genetics ; }, abstract = {Functional inactivation of the tsg101 gene in mouse fibroblasts results in cell transformation and the ability to form metastatic tumors in nude mice. The human tsg101 gene was mapped to chromosome 11q15.1-2 and found to mutate in some cancer patients. To test the expression pattern of the tsg 101 gene in Chinese breast cancer patients, we analyzed the mRNA by RT-PCR in 51 breast cancer patients. The full-length tsg101 and 7 truncated transcripts were detected in both normal and matched tumor tissues. A short transcript with a deletion of nucleotides 154-1054 is frequently presented in late-stage breast cancers. TSG101 protein expression was also detected by Western blot analysis in 30 breast cancer patients. A predicted full-length 46 kDa and three proteins with smaller molecular weight were detected. The full-length 46 kDa protein was less expressed in tumor specimens. Immunohistochemical stains from 10 patients of each stage 0-4 revealed that TSG101 protein was predominantly present in the cytoplasm. Cell nuclei were occasionally immunopositive and the chromosomes were deeply stained during cell division. The intracellular location and the expression of TSG101 protein were both not stage-dependent in primary breast cancers. In addition, normal mammary glands were more homogenously immunopositive than invasive ductal carcinoma. These results support the notion that the aberrant expression of TSG101 in breast cancer is associated with altered cell growth.}, }
@article {pmid10929825, year = {2000}, author = {Shahnavaz, H}, title = {Role of ergonomics in the transfer of technology to industrially developing countries.}, journal = {Ergonomics}, volume = {43}, number = {7}, pages = {903-907}, doi = {10.1080/001401300409099}, pmid = {10929825}, issn = {0014-0139}, mesh = {*Developing Countries ; *Ergonomics ; Humans ; Man-Machine Systems ; Risk Factors ; Technology Assessment, Biomedical ; *Technology Transfer ; }, abstract = {Technological development has contributed to economic growth and social progress as well as a reduction of many sources of occupational accidents, injuries and stresses. However, advanced technology has also brought new sources of work stress and injuries. Industrially developing countries (IDC) have tended to try to achieve economic growth and development by importing technology designed for IDC. However, because of several complex technical, cultural and socio-economic factors, this policy has not been always successful. Inappropriate technology transfer has led to many work environment and productivity problems. Consideration of ergonomics in the choice and utilization of the transferred technology can help to create a good fit between technology, technology users and the operating environment. Application of ergonomics is, however, not widely spread in most IDC. Ergonomics input will create the appropriate working environment in which people are safe and motivated to participate and can better utilize company resources for increasing system productivity, reliability and availability.}, }
@article {pmid10915850, year = {2000}, author = {Rouard, H and Léon, A and Klonjkowski, B and Marquet, J and Tennezé, L and Plonquet, A and Agrawal, SG and Abastado, JP and Eloit, M and Farcet, JP and Delfau-Larue, MH}, title = {Adenoviral transduction of human 'clinical grade' immature dendritic cells enhances costimulatory molecule expression and T-cell stimulatory capacity.}, journal = {Journal of immunological methods}, volume = {241}, number = {1-2}, pages = {69-81}, doi = {10.1016/s0022-1759(00)00214-3}, pmid = {10915850}, issn = {0022-1759}, mesh = {Adenoviridae ; Antigen Presentation ; Antigens, CD ; *Cancer Vaccines ; Cell Differentiation ; Cell Separation/methods ; Cells, Cultured ; Culture Techniques/*methods ; Dendritic Cells/*cytology/*immunology ; Gene Transfer Techniques ; Genetic Vectors ; HLA-DR Antigens/biosynthesis ; Humans ; Immunoglobulins/biosynthesis ; Leukapheresis ; Lymphocyte Culture Test, Mixed ; Membrane Glycoproteins/biosynthesis ; Recombinant Proteins/immunology ; T-Lymphocytes/immunology ; *Transgenes ; beta-Galactosidase/genetics/immunology ; }, abstract = {The therapeutic use of dendritic cells (DC) in antigen-specific anti-tumor vaccines, requires sufficient numbers of functional DC, the preparation of which should comply with the code of Good Manufacturing Practice. In addition, the expression of tumor specific antigen should be possible in these DC. As a preclinical step, the method reported here was developed in healthy volunteers. Monocytes (Mo) were isolated by leukapheresis from 12 donors, purified by elutriation and then cultured for 6 days in sealed bags in AIM-V serum free medium with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-13 (IL-13). Between 6x10(8) and 1x10(9) immature DC (iDC) could be differentiated from one leukapheresis. Cells displayed a characteristic iDC phenotype (CD1a(+), CD14(-), CD80(+), CD86(+), HLA DR(+), CD83(-)), and had potent allogeneic and antigen dependent autologous T cell-stimulatory capacity. Moreover, iDC could be further differentiated into mature DC by CD40 ligation as assessed by CD83 expression and the upregulation of HLA-DR and costimulatory molecules. After infection with a recombinant adenovirus encoding for beta-galactosidase (betaGal), 50% to 80% of iDC expressed betaGal without toxicity. Adenovirus infection increased the expression of both costimulatory molecules and CD83, and also increased allogeneic stimulatory capacity. Thus, the method developed here allows us to use large numbers of functional iDC as will be required for therapeutic uses in man. These DC can express a transgenic protein.}, }
@article {pmid10914818, year = {2000}, author = {Shen, KL and Yang, LS and Hsieh, HF and Chen, CJ and Yu, JC and Tsai, NM and Harn, HJ}, title = {Microsatellite alterations on human chromosome 11 in in situ and invasive breast cancer: a microdissection microsatellite analysis and correlation with p53, ER (estrogen receptor), and PR (progesterone receptor) protein immunoreactivity.}, journal = {Journal of surgical oncology}, volume = {74}, number = {2}, pages = {100-107}, doi = {10.1002/1096-9098(200006)74:2&lt;100::AID-JSO5&gt;3.0.CO;2-O}, pmid = {10914818}, issn = {0022-4790}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/*genetics ; Carcinoma in Situ/chemistry/*genetics ; Carcinoma, Ductal, Breast/chemistry/*genetics ; *Chromosomes, Human, Pair 11 ; Female ; Humans ; Immunohistochemistry ; Loss of Heterozygosity ; *Microsatellite Repeats ; Middle Aged ; Mutation ; Neoplasm Proteins/immunology ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) has been documented in a subset of sporadic tumors. Loss of heterozygosity (LOH) on chromosome 11 loci in breast cancer is a frequent event. The purpose of the present study is to examine the incidence of microsatellite alterations in in situ and invasive human breast carcinoma and to clarify their significance in regulating the dynamics of cancer progression.<br><br>METHODS: Four highly polymorphic (CA)n repeat microsatellites were used to determine microsatellite alterations in ten ductal carcinoma in situ (DCIS) and 19 invasive ductal carcinoma (IDC). To investigate the expression of p53, ER (estrogen receptor), and PR (progesterone receptor) association with MSI, immunohistochemistry staining was applied.<br><br>RESULTS: MSI were detected in 20% (2/10) of DCIS and in 47.4% (9/19) of IDC. The frequency of MSI in IDC was significantly higher than that in DCIS (P < 0.001). Also, the MSI seemed to correlate with clinical stage (P = 0.0001) and tumor size (P = 0.004) but not histological grade or age. In addition, we found that 27% of the tumors showed LOH at 11q23.3-24 region between loci D11S934 and D11S912. Seven of nine MSI cases demonstrated low or no expression of p53. However, there was significantly reduced expression of PR, but not ER in MSI cases.<br><br>CONCLUSIONS: Our results suggest that breast cancer acquires the RER phenotype (replication-error phenotype) in the relatively late stages, and that the RER phenotype is associated with aggressiveness of IDC (infiltrative duct carcinoma). The result also implicated that mismatch repair failure can alter the expression of PR but not ER and p53.}, }
@article {pmid10908085, year = {2000}, author = {Noori, A and Lindenfeld, J and Wolfel, E and Ferguson, D and Bristow, MR and Lowes, BD}, title = {Beta-blockade in adriamycin-induced cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {6}, number = {2}, pages = {115-119}, pmid = {10908085}, issn = {1071-9164}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Antineoplastic Agents/*adverse effects ; Carbazoles/therapeutic use ; Cardiomyopathies/chemically induced/*drug therapy/physiopathology ; Cardiomyopathy, Dilated/drug therapy/physiopathology ; Carvedilol ; Doxorubicin/*adverse effects ; Female ; Humans ; Male ; Metoprolol/therapeutic use ; Middle Aged ; Myocardial Contraction/drug effects ; Neoplasms/drug therapy ; Propanolamines/therapeutic use ; Propranolol/therapeutic use ; Retrospective Studies ; Stroke Volume/drug effects ; }, abstract = {Beta-blockade consistently improves myocardial systolic function in patients with both nonischemic and ischemic cardiomyopathy. The effects of beta-blockade on Adriamycin-induced cardiomyopathy (ACM), however, are unknown. We retrospectively evaluated the effects of beta-blockade on patients with ACM by using a case-controlled design. The control group consisted of 16 consecutively chosen age- and sex-matched patients with idiopathic dilated cardiomyopathy (IDC) who were treated with beta-blockers. Patients with ACM had a baseline mean left ventricular ejection fraction (LVEF) of 28%, which improved to 41% (P = .041) after treatment with beta-blockers. The control group had a baseline mean LVEF of 26%, which improved to 32% (P = .015) after treatment. The mean duration of beta-blocker therapy in the Adriamycin and control groups was 8 and 9 months, respectively. The degree of improvement between the 2 groups was not significantly different. Beta-blockers have a beneficial effect on cardiac function in patients with ACM, which is at least comparable with other forms of heart failure with systolic dysfunction.}, }
@article {pmid10907931, year = {2000}, author = {Kleer, CG and Michael, CW}, title = {Fine-needle aspiration of breast carcinomas with prominent lymphocytic infiltrate.}, journal = {Diagnostic cytopathology}, volume = {23}, number = {1}, pages = {39-42}, doi = {10.1002/1097-0339(200007)23:1&lt;39::aid-dc9&gt;3.0.co;2-#}, pmid = {10907931}, issn = {8755-1039}, mesh = {Adult ; Biopsy, Needle/methods ; Breast Neoplasms/classification/*pathology ; Carcinoma, Ductal, Breast/classification/*pathology ; Carcinoma, Medullary/classification/*pathology ; Female ; Follow-Up Studies ; Humans ; *Lymphocytes, Tumor-Infiltrating/immunology ; Middle Aged ; }, abstract = {Carcinomas of the breast with prominent lymphoplasmacytic background are commonly encountered in cytology. The aim of this study was to assess the prevalence of different types of carcinomas that share this common feature, identify possible distinguishing cytologic features, and evaluate the diagnostic pitfalls in this group of tumors. Eighteen fine-needle aspirations (FNAs) of breast carcinomas with heavy lymphoplasmacytic background were reviewed. Histologic follow-up was reviewed in all cases. Of 18 cases, there were 9 invasive ductal carcinomas (IDC), and 9 medullary carcinomas (6 typical and 3 atypical). FNAs from typical medullary carcinomas (TMC) showed more severe nuclear atypia and macronucleoli than the cases of IDC and atypical medullary carcinomas (AMC). Gland formation was absent in the TMC but was common in IDC and AMC. No cytologic differences were noted between IDC and AMC. Nucleoli were larger in TMC (mean 4, microm) than in AMC (mean, 2 microm) and IDC (mean, 1.5 microm). We conclude that lymphocytes and plasma cells may be seen in different types of breast carcinomas and should not be considered a diagnostic feature of TMC. Features potentially helpful in the cytologic differential diagnosis of a carcinoma with prominent lymphoplasmacytic background are nucleolar size (4 microm in MC, vs. 1.5 and 2 microm in IDC and AMC, respectively) and the degree of nuclear atypia. Lymphocytosis may be part of the carcinoma or may originate from a lymph node involved by metastases. In rare cases, a prominent neutrophilic infiltrate may also be present.}, }
@article {pmid10904838, year = {2000}, author = {Grimm, W and Hoffmann, J and Menz, V and Müller, HH and Maisch, B}, title = {Prediction of major arrhythmic events and sudden cardiac death in dilated cardiomyopathy. The Marburg Cardiomyopathy Study design and description of baseline clinical characteristics.}, journal = {Herz}, volume = {25}, number = {3}, pages = {189-199}, doi = {10.1007/s000590050006}, pmid = {10904838}, issn = {0340-9937}, mesh = {Adolescent ; Adult ; Aged ; Atrial Fibrillation/*diagnosis/physiopathology ; Bundle-Branch Block/*diagnosis/physiopathology ; Cardiomyopathy, Dilated/*diagnosis/physiopathology ; Death, Sudden, Cardiac/*etiology/prevention &amp; control ; Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Heart Failure/diagnosis/physiopathology ; Hemodynamics/physiology ; Humans ; Male ; Middle Aged ; Pressoreceptors/physiopathology ; Prospective Studies ; Risk Factors ; Signal Processing, Computer-Assisted ; Ventricular Fibrillation/*diagnosis/physiopathology ; }, abstract = {The Marburg Cardiomyopathy Study (MACAS) is a prospective observational study designed to determine the value of the following potential non-invasive arrhythmia risk predictors in more than 200 patients with idiopathic dilated cardiomyopathy (IDC) over a 5-year follow-up period: New York Heart Association functional class, left ventricular end-diastolic diameter and ejection fraction, left bundle branch block and atrial fibrillation on ECG, QTc and JTc-dispersion on 12-lead ECG, abnormal time-domain analysis and spectral turbulence analysis of the signal-averaged ECG, ventricular arrhythmias and heart-rate variability on 24-hour Holter ECG, baroreflex sensitivity, and microvolt T wave alternans during exercise. This report describes the rationale of MACAS as well as the clinical characteristics of the first 236 patients enrolled between March 1996 and October 1999. The prognostic significance of the potential arrhythmia risk predictors in MACAS will be determined by multivariate Cox analysis at the end of 5-year follow-up. Primary endpoints are total mortality and major arrhythmic events defined as sustained ventricular tachycardia, ventricular fibrillation or sudden cardiac death. The results of MACAS will have important implications for the design of future studies evaluating the role of prophylactic defibrillator therapy in idiopathic dilated cardiomyopathy.}, }
@article {pmid10903870, year = {2000}, author = {Mallorquí-Fernández, G and Pous, J and Peracaula, R and Aymamí, J and Maeda, T and Tada, H and Yamada, H and Seno, M and de Llorens, R and Gomis-Rüth, FX and Coll, M}, title = {Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 A resolution.}, journal = {Journal of molecular biology}, volume = {300}, number = {5}, pages = {1297-1307}, doi = {10.1006/jmbi.2000.3939}, pmid = {10903870}, issn = {0022-2836}, mesh = {Amino Acid Sequence ; Arginine/metabolism ; Binding Sites ; Blood Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Disulfides/metabolism ; *Eosinophil Cationic Protein ; Eosinophil Granule Proteins ; Eosinophils/*enzymology ; Escherichia coli ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/genetics/metabolism ; Ribonucleases/*chemistry/genetics/metabolism ; Sequence Alignment ; Static Electricity ; Structure-Activity Relationship ; }, abstract = {Eosinophil cationic protein (ECP; RNase 3) is a human ribonuclease found only in eosinophil leukocytes that belongs to the RNase A superfamily. This enzyme is bactericidal, helminthotoxic and cytotoxic to mammalian cells and tissues. The protein has been cloned, heterologously overexpressed, purified and crystallized. Its crystal structure has been determined and refined using data up to 1. 75 A resolution. The molecule displays the alpha+beta folding topology typical for members of the ribonuclease A superfamily. The catalytic active site residues are conserved with respect to other ribonucleases of the superfamily but some differences appear at substrate recognition subsites, which may account, in part, for the low catalytic activity. Most strikingly, 19 surface-located arginine residues confer a strong basic character to the protein. The high concentration of positive charges and the particular orientation of the side-chains of these residues may also be related to the low activity of ECP as a ribonuclease and provides an explanation for its unique cytotoxic role through cell membrane disruption.}, }
@article {pmid10892294, year = {2000}, author = {Nakano, S and Tsuruta, J and Iyama, K}, title = {[Remodeling of basement membrane in association with cancer invasion].}, journal = {Rinsho byori. The Japanese journal of clinical pathology}, volume = {48}, number = {5}, pages = {451-457}, pmid = {10892294}, issn = {0047-1860}, mesh = {Basement Membrane/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Collagen/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Neoplasm Invasiveness ; RNA, Messenger/metabolism ; }, abstract = {Type IV collagen the major component of basement membrane (BM), is composed of six genetically distinct alpha chains. In normal breast tissue, benign breast tumors, and in the intraductal components of invasive ductal carcinoma, alpha 1 (IV) and alpha 2 (IV) chains were stained in all BM, whereas alpha 5 (IV) and alpha 6 (IV) chains were restrictively localized in a linear pattern in the epithelial BM. However, in invasive ductal carcinoma, alpha 1 (IV) and alpha 2 (IV) chains were discontinuously or negatively stained in the cancer cell nest, and the assembly of alpha 5 (IV) and alpha 6 (IV) chains into the BM was completely inhibited. The results indicate that the mammary gland forms a second network of BM composed of alpha 5 (IV)/alpha 6 (IV) chains, in addition to the classic network of alpha 1 (IV)/alpha 2 (IV) chains. Remodeling of type IV collagen alpha chains during the development of invasive breast cancer seems to be differentially regulated, and to be associated with modification of histopathological findings.}, }
@article {pmid10886733, year = {2000}, author = {Umekita, Y and Yoshida, H}, title = {Cyclin D1 expression in ductal carcinoma in situ, atypical ductal hyperplasia and usual ductal hyperplasia: an immunohistochemical study.}, journal = {Pathology international}, volume = {50}, number = {7}, pages = {527-530}, doi = {10.1046/j.1440-1827.2000.01076.x}, pmid = {10886733}, issn = {1320-5463}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Cyclin D1/*metabolism ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Hyperplasia/metabolism/pathology ; Immunoenzyme Techniques ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis/pathology ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {The cell cycle regulatory gene, Cyclin D1, plays a critical role in the growth and progression of several types of human cancer, including breast cancer. Immunohistochemical study of Cyclin D1 expression has been extensively reported in invasive ductal carcinoma (IDC). In contrast, there have been few reports concerning Cyclin D1 expression in ductal carcinoma in situ (DCIS) and their positive rates are variable. The differences in the reported frequency may be largely due to the differences in antibodies used, immunohistochemical methods and the positive cut-off point. However, we speculated that the strictness of diagnosis of DCIS might be somewhat responsible for these differences in frequency. Therefore, we selected cases of DCIS by carefully eliminating cases of predominantly intraductal carcinoma (PIC). Moreover, to clarify whether Cyclin D1 expression is involved in multistep carcinogenesis or the progression of human breast cancer, we immunohistochemically investigated Cyclin D1 expression in 57 DCIS, 10 atypical ductal hyperplasia (ADH), 70 usual ductal hyperplasia (UDH), 44 PIC and 92 IDC. Cyclin D1 expression was detected in 41 DCIS cases (72%), 22 PIC cases (50%) and 40 IDC cases (43%). No expression of Cyclin D1 was observed in either ADH or UDH. There were no significant correlations between Cyclin D1 expression and histological grade or estrogen receptor expression in DCIS. These results suggest that Cyclin D1 expression may play an important role in the early stages of carcinogenesis, and that immunohistochemical detection of Cyclin D1 expression may be helpful in differentiating low-grade DCIS from ADH.}, }
@article {pmid10880771, year = {2000}, author = {Ando, Y and Iwase, H and Ichihara, S and Toyoshima, S and Nakamura, T and Yamashita, H and Toyama, T and Omoto, Y and Karamatsu, S and Mitsuyama, S and Fujii, Y and Kobayashi, S}, title = {Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast.}, journal = {Cancer letters}, volume = {156}, number = {2}, pages = {207-214}, doi = {10.1016/s0304-3835(00)00467-5}, pmid = {10880771}, issn = {0304-3835}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA, Neoplasm/genetics/isolation &amp; purification ; Female ; Humans ; *Loss of Heterozygosity ; *Microsatellite Repeats ; Middle Aged ; Paraffin Embedding ; Polymerase Chain Reaction ; Receptors, Estrogen/physiology ; }, abstract = {To investigate the alterations of genetic instabilities in carcinogenesis of the breast, we analyzed the allelotypic profile of 65 ductal carcinomas in situ (DCIS), compared with that of 207 invasive ductal carcinomas (IDC) of the breast. These studies were performed by means of examining microsatellite-length polymorphisms at seven loci (AluVpa, ESR, D11S988, D13S267, D16S398, D17S1159, and D17S855) from microdissected paraffin sections. Allelic loss or imbalance, considered a loss of heterozygosity (LOH), tended to be more frequently seen in IDC than in DCIS. In particular, the frequency of LOH at the 17p locus was significantly higher in IDC than in DCIS (42 vs. 23%, P=0.022). LOH in DCIS was most frequently seen at D16S398 (26%). LOH frequency at D16S398 in low- and intermediate-grade DCIS was higher than that in high-grade DCIS, while LOH frequencies at D11S988 and D17S1159 in low- and intermediate-grade DCIS was lower than those in high-grade DCIS. LOH frequency at D11S988 in non-comedo type DCIS was lower than that in comedo type DCIS. Furthermore, the frequency of microsatellite instability (MSI) at only one locus in DCIS (28%) was statistically higher than that in IDC (6%) (P<0.001), while there was no difference between the frequency of MSI at multiple loci in DCIS (6%) and that in IDC (3%). Together, these observations indicate that chromosomal losses of 16q may occur in low- and intermediate-grade DCIS and those of 11p and 17p may occur high-grade DCIS, and that MSI occurring at only one locus is not yet clear and MSI at multiple loci is uncommon in not only IDC but also DCIS of the breast.}, }
@article {pmid10879734, year = {2000}, author = {Jones, C and Foschini, MP and Chaggar, R and Lu, YJ and Wells, D and Shipley, JM and Eusebi, V and Lakhani, SR}, title = {Comparative genomic hybridization analysis of myoepithelial carcinoma of the breast.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {80}, number = {6}, pages = {831-836}, doi = {10.1038/labinvest.3780087}, pmid = {10879734}, issn = {0023-6837}, mesh = {Aged ; Breast Neoplasms/*genetics/pathology ; *Chromosome Aberrations ; Chromosome Mapping ; Female ; Humans ; Karyotyping ; *Loss of Heterozygosity ; Middle Aged ; Myoepithelioma/*genetics/pathology ; Nucleic Acid Hybridization/methods ; Polymerase Chain Reaction ; Retrospective Studies ; }, abstract = {Although there seems to be a common stem cell for the two epithelial cell types in the breast, the vast majority of breast cancers exhibit a luminal phenotype. Pure myoepithelial carcinomas are rare. We report our findings of genetic alterations in these tumors. We have analyzed 10 cases of pure myoepithelial cell carcinomas using laser capture microdissection and comparative genomic hybridization. The mean number of changes was 2.1 (range 0-4), compared with a mean of 8.6 (range 3.6-13.8) in unselected ductal carcinomas. Common alterations included loss at 16q (3/10 cases), 17p (3/10), 11q (2/10), and 16p (2/10), regions also commonly deleted in ductal carcinomas. The single case in which both pure myoepithelial carcinoma and invasive ductal carcinoma was present showed 2 alterations in the myoepithelial tumor (losses at 17p and 17q), whereas the invasive ductal component showed 15 alterations (5 gains and 9 losses), including loss at 17p. The sharing of 17p loss in myoepithelial and ductal carcinoma is consistent with a common stem cell model in the breast. The relatively few genetic alterations in otherwise aggressive neoplasms suggests that myoepithelial tumors may be a good model for the delineation of genes important in breast tumorigenesis.}, }
@article {pmid10874262, year = {2000}, author = {Grimm, W and Glaveris, C and Hoffmann, J and Menz, V and Müller, HH and Hufnagel, G and Maisch, B}, title = {Arrhythmia risk stratification in idiopathic dilated cardiomyopathy based on echocardiography and 12-lead, signal-averaged, and 24-hour holter electrocardiography.}, journal = {American heart journal}, volume = {140}, number = {1}, pages = {43-51}, doi = {10.1067/mhj.2000.107178}, pmid = {10874262}, issn = {0002-8703}, mesh = {Adolescent ; Adult ; Aged ; Analysis of Variance ; Cardiomyopathy, Dilated/*diagnosis/*mortality/physiopathology ; Death, Sudden, Cardiac/*epidemiology ; Echocardiography/*methods ; Electrocardiography, Ambulatory/*methods ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Multivariate Analysis ; Probability ; Proportional Hazards Models ; Prospective Studies ; Risk Assessment ; Risk Factors ; Survival Analysis ; Ventricular Fibrillation/*diagnosis/*epidemiology ; }, abstract = {BACKGROUND: To date, considerable controversy exists regarding noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy (IDC). Methods and Results Between 1992 and 1997, 202 patients with IDC without a history of sustained ventricular tachycardia (VT) underwent echocardiography, signal-averaged electrocardiogram (ECG), and 24-hour Holter ECG in the absence of antiarrhythmic drugs. During 32 +/- 15 months of prospective follow-up, major arrhythmic events, including sustained VT, ventricular fibrillation, or sudden death, occurred in 32 (16%) of 202 patients. After adjusting for baseline medical therapy and antiarrhythmic therapy during follow-up, multivariate Cox regression analysis identified a left ventricular (LV) end-diastolic diameter >/=70 mm and nonsustained VT on Holter as the only independent arrhythmia risk predictors. The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT was associated with a 14. 3-fold risk for future arrhythmic events (95% confidence interval 2. 3-90). To further elucidate the prognostic value of LV ejection fraction, multivariate Cox analysis was repeated with ejection fraction forced to remain in the model. In the latter model, an ejection fraction </=30% combined with nonsustained VT on Holter was found to be a significant arrhythmia risk predictor with a relative risk of 14.6 (95% confidence interval 2.2-97).<br><br>CONCLUSIONS: The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT on Holter, and the combination of LV ejection fraction </=30% and nonsustained VT on Holter, identify a subgroup of patients with IDC with a 14-fold risk for subsequent arrhythmic events. These findings have important implications for the design of future studies evaluating the role of prophylactic defibrillator therapy in patients with IDC.}, }
@article {pmid10866033, year = {1998}, author = {Burger, AM and Zhang, X and Seth, A}, title = {Detection of novel genes that are up-regulated (Di12) or down-regulated (T1A12) with disease progression in breast cancer.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {7 Suppl 1}, number = {}, pages = {S29-35}, doi = {10.1097/00008469-199802001-00007}, pmid = {10866033}, issn = {0959-8278}, mesh = {Breast Neoplasms/*genetics/pathology ; Carrier Proteins/*genetics ; Cloning, Molecular ; DNA, Neoplasm/analysis ; Disease Progression ; Down-Regulation/*genetics ; Gene Expression Regulation, Neoplastic ; Humans ; *Insulin-Like Growth Factor Binding Proteins ; *Neoplasm Proteins ; Neoplasm Staging ; Proteins/*genetics ; Sequence Analysis, DNA ; Tumor Cells, Cultured ; Up-Regulation/*genetics ; }, abstract = {Carcinogenesis is a multistep process and it is believed that seven to ten alterations are needed to convert a normal cell into a maligant one. Thus, identification of these specific genetic lesions and their role in the progression of cancer will lead to more effective methods for early diagnosis, as well as provide targets for treatment and therapeutic intervention. To isolate a number of genes that are differentially expressed in human breast carcinomas we used subtractive hybridization and differential display cloning techniques. By using these methods we obtained 952 clones, characterized 288 clones by restriction mapping, and 105 by Northern blotting and DNA sequencing. Twenty-four clones were found to be previously unidentified, unique genes. Full-length complementary (c)DNA was isolated from clone T1A12 and Di12, and further characterized by computer data search. Polyclonal antibodies were generated against N- and/or C-terminal peptides of the predicted T1A12 and Di12 amino acid sequences and immunohistochemistry was used to delineate gene function in breast cancers. We found that T1A12 is a novel member of the insulin-like growth factor binding protein family and that its expression decreases with disease progression. In 60 primary breast tissues examined, strong T1A12-specific immunoperoxidase staining was observed in luminal epithelial cells of normal lobules or ducts, and in blood vessels. Moderate protein expression was detected in hyperplastic and ductal carcinoma in situ (DCIS) cells, but no staining was found in invasive ductal carcinoma (IDC) cells. On the contrary, by using the same primary breast specimen Di12, a gene which shares no sequence homology with any protein, was found to be overexpressed in IDC cells but was not detectable in normal breast tissues. Specific strong Di12 staining was seen in the cytoplasm, with a slight increase in perinuclear regions of less well differentiated cells similar to those present in ductal carcinomas with poor prognosis. Both the T1A12 and Di12 genes, studied alone or in combination, could prove valuable for understanding the biology of breast cancer, detecting early and late stage disease, and for selecting appropriate treatments.}, }
@article {pmid10861509, year = {2000}, author = {Richard, F and Pacyna-Gengelbach, M and Schlüns, K and Fleige, B and Winzer, KJ and Szymas, J and Dietel, M and Petersen, I and Schwendel, A}, title = {Patterns of chromosomal imbalances in invasive breast cancer.}, journal = {International journal of cancer}, volume = {89}, number = {3}, pages = {305-310}, pmid = {10861509}, issn = {0020-7136}, mesh = {Adult ; Age Factors ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; *Chromosome Aberrations ; Female ; Humans ; In Situ Hybridization ; Middle Aged ; Neoplasm Invasiveness ; Nucleic Acid Hybridization ; Phenotype ; Receptors, Estrogen/biosynthesis ; }, abstract = {Invasive breast carcinomas are characterized by a complex pattern of chromosomal alterations. We applied comparative genomic hybridization (CGH) to analyze 105 primary breast carcinomas using histograms to indicate the incidence of DNA imbalances of tumor subgroups and difference histograms to compare invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive and -negative tumors (ER(+)/ER(-)). Only single imbalances showed a higher incidence in ILC compared with IDC, i.e., gains on chromosomes 4 and 5q13-q23 as well as deletions on chromosomes 6q, 11q14-qter, 12p12-pter, 16q, 17p, 18q, 19, and 22q. Of these, particularly gains of 4 and losses at 16q21-q23, and 18q12-q21 were statistically significant. For most loci, IDC showed more alterations providing a genetic correlate to the fact that ductal carcinoma overall is associated with a worse prognosis than ILC. Of these, many imbalances showing statistical significance were also observed in G3 and ER(-) tumors, i.e., deletions at 2q35-q37, 3p12-p14, 4p15-p16, 5q, 7p15, 8p22-p23, 10q, 11p, 14q21-q31, 15q, and gains at 2p, 3q21-qter, 6p, 8q21-qter, 10p, 18p11-q11, and 20q, suggesting that they contribute to a more aggressive tumor phenotype. By contrast, gains on chromosome 5q13-q23 as well as deletions at 6q, 16q and 22q were more prevalent in G1 and ER(+) tumors. The ratio profiles of all cases as well as histograms are accessible at our CGH online tumor database at http://amba.charite.de/cgh. Our results highlight distinct chromosomal subregions for cancer-associated genes. In addition, these imbalances may serve as markers for a genetic classification of invasive breast cancer.}, }
@article {pmid10854233, year = {2000}, author = {Yamano, M and Fujii, H and Takagaki, T and Kadowaki, N and Watanabe, H and Shirai, T}, title = {Genetic progression and divergence in pancreatic carcinoma.}, journal = {The American journal of pathology}, volume = {156}, number = {6}, pages = {2123-2133}, pmid = {10854233}, issn = {0002-9440}, mesh = {Aged ; Alleles ; Carcinoma, Ductal, Breast/*genetics/pathology ; Chromosome Mapping ; Female ; Genetic Variation ; Humans ; Hyperplasia/genetics ; Immunohistochemistry ; Loss of Heterozygosity ; Male ; Middle Aged ; Pancreas/abnormalities/pathology ; Pancreatic Neoplasms/*genetics/pathology ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Genetic alterations of pancreatic intraductal lesions adjacent to invasive ductal carcinoma were investigated. We submitted nine foci of ordinary epithelium, 12 foci of nonpapillary hyperplasia, 12 foci of papillary hyperplasia (pap HP), 66 foci of severe ductal dysplasia, and 27 invasive foci from a total of 10 pancreatic carcinomas for genetic analysis. All foci were individually microdissected and allelic losses of 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, and 18q were studied. All invasive and severely dysplastic intraductal foci exhibited loss of heterozygosity (LOH) at more than one chromosomal locus. For each case, allelic loss was frequently observed on 9p (severe ductal dysplasia 90%, invasion 100%), 17p (severe ductal dysplasia 80%, invasion 80%), and 18q (severe ductal dysplasia 88%, invasion 88%). Ninety-four percent of severe ductal dysplasia and 96% of invasive foci had multiple LOH. Seventeen percent of nonpapillary hyperplasia and 33% of pap HP showed LOH. Only one focus of pap HP showed multiple LOH. The patterns of allelic loss identified in severe ductal dysplasia were generally conserved in synchronous infiltrating tumors, supporting the paradigm that infiltrating tumors are clonally derived from severe ductal dysplasia. In eight of 10 cases, however, we found frequent genetic heterogeneity in the intraductal lesion, suggestive of genetic progression or diversion. These findings indicate that invasive pancreatic carcinoma evolves through successive and divergent genetic changes with selection of aggressive subclones in the intraductal component.}, }
@article {pmid10811140, year = {2000}, author = {Moinfar, F and Man, YG and Arnould, L and Bratthauer, GL and Ratschek, M and Tavassoli, FA}, title = {Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis.}, journal = {Cancer research}, volume = {60}, number = {9}, pages = {2562-2566}, pmid = {10811140}, issn = {0008-5472}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 3 ; Epithelial Cells/metabolism/pathology ; Epithelium/metabolism ; Female ; Humans ; *Loss of Heterozygosity ; Mesoderm/metabolism ; Polymerase Chain Reaction ; Stromal Cells/metabolism/*pathology ; }, abstract = {The high frequency of loss of heterozygosity (LOH) in epithelial cells of mammary ductal carcinoma in situ (DCIS) and IDC is a well known phenomenon, whereas the genetic abnormalities in the mammary stroma and its influence on the epithelial component have not been sufficiently studied. Using the PCR, we examined DNA extracts from microdissected stromal and epithelial tissues of 11 breast samples containing DCIS, including five cases associated with IDC. In each case, the mesenchymal tissue consisting of normal-appearing stroma at a distance from DCIS and IDC or stroma close to either DCIS or IDC was manually microdissected. Epithelial cells from morphologically clear-cut normal ducts and lobules, DCIS, and IDC were also microdissected. Twelve polymorphic DNA markers were tested to identify possible genetic alterations in the mesenchymal and epithelial cells on chromosomes 2p, 3p, 11q, 16q, and 17q. Samples from bilateral reduction mammoplasty from 10 women without any clinical, radiological, or pathological abnormalities were also selected as a control (reduction mammoplasty group). Whereas most cases (8/11, 73%) displayed at least one identical LOH in both epithelial and mesenchymal components, LOH at several loci was noted exclusively in stromal cells. The most frequent genetic alterations in the mesenchymal cells were at chromosomes 17q24, 16q23.1-24.2, 3p14.2, and 11q21-23.2, in 87.5, 62, 60, and 45% of informative cases, respectively. The LOH frequency in the stroma close to cancer ranged from 10 to 66.5% for DCIS and from 20 to 75% of informative cases for IDC. Furthermore, 10 of the 12 polymorphic markers revealed LOH in the stroma at a distance, ranging from 11 to 57% of informative cases. None of the control cases (women without any breast disease) revealed LOH either in the epithelial or in the stromal components. Our findings strongly support the concept of stromal-epithelial interaction in the development and progression of mammary neoplasia. Furthermore, this study suggests that genetic alterations in the stromal cells may precede genotypic changes in the epithelial cells. At least in some cases, the mammary stroma in DCIS or IDC apparently represents a neoplastic interactive component rather than a reactive response to the carcinoma. The frequent allelic loss (LOH) in the mammary stroma, identified in our study, may explain some of the fibroblastic abnormalities previously observed in patients with breast carcinoma or a variety of cancer-associated hereditary diseases. We conclude that the mammary stroma may play a key role in inducing neoplastic transformation of epithelial cells, recapitulating its role in normal mammary duct development.}, }
@article {pmid10811025, year = {2000}, author = {Abe, H and Kimura, W and Maema, A and Makuuchi, M}, title = {A case of pancreatic carcinoma with marked ductal dilatation: what contributed to the dilatation?.}, journal = {International journal of pancreatology : official journal of the International Association of Pancreatology}, volume = {27}, number = {1}, pages = {65-68}, pmid = {10811025}, issn = {0169-4197}, mesh = {Adenocarcinoma/complications/diagnostic imaging/*pathology ; Aged ; Aged, 80 and over ; Cholangiopancreatography, Endoscopic Retrograde ; Humans ; Hyperplasia ; Male ; Pancreatic Ducts/diagnostic imaging/*pathology ; Pancreatic Neoplasms/complications/diagnostic imaging/*pathology ; Pancreatitis/complications/diagnostic imaging/pathology ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: We report the case of an 82-yr-old man with invasive ductal carcinoma of the pancreatic head, in which the main pancreatic duct and duct of Santorini were markedly dilated, measuring 1.6 and 1.1 cm, respectively, in diameter on computed tomography.<br><br>METHODS: A preoperative diagnosis of ductal carcinoma of the pancreatic head was made, and Whipple's procedure was carried out.<br><br>RESULTS: Histopathologically, the tumor was diagnosed as moderately differentiated tubular adenocarcinoma, and the resected pancreatic parenchyma showed low papillary mucous cell hyperplasia and atypical hyperplasia in dilated ductular branches. Conclusion. Even among patients with tubular adenocarcinoma, the most common type of pancreatic ductal carcinoma, if the patient is aged and has chronic pancreatitis, the main pancreatic duct and duct of Santorini may dilate to the same degree as in mucin-hypersecreting neoplasm.}, }
@article {pmid10810803, year = {2000}, author = {Vester, EG and Dees, H and Dobran, I and Hennersdorf, M and Perings, C and Heydthausen, M and Winter, J and Strauer, BE}, title = {[14-year experience with implantable cardioverter/defibrillators: determination of prognosis and discharge behavior].}, journal = {Zeitschrift fur Kardiologie}, volume = {89 Suppl 3}, number = {}, pages = {194-205}, pmid = {10810803}, issn = {0300-5860}, mesh = {Adult ; Aged ; Arrhythmias, Cardiac/mortality/physiopathology/*therapy ; Cardiomyopathy, Dilated/complications ; Cardiomyopathy, Hypertrophic/complications ; Coronary Disease/complications ; Death, Sudden, Cardiac/prevention &amp; control ; *Defibrillators, Implantable ; Female ; Follow-Up Studies ; Hemodynamics ; Humans ; Male ; Middle Aged ; Prognosis ; Risk Factors ; Survival Analysis ; Time Factors ; Ventricular Function, Left/physiology ; }, abstract = {BACKGROUND: The treatment of life threatening ventricular arrhythmias with implantable cardioverter/defibrillators (ICD) has become the therapy of choice; the survival benefit of ICD treatment compared to drug therapy in patients with aborted sudden cardiac death (SCD) and hemodynamically unstable ventricular tachycardia has been proven. In addition for the primary prevention of SCD in high risk patients, ICD therapy is gaining growing acceptance.<br><br>PATIENTS AND METHODS: We analyzed the long-term follow-up of 274 consecutive patients (211 male, 63 female, age 59 +/- 12 years, left ventricular ejection fraction 39 +/- 15%) provided with an ICD between 1984 and 1998. The aim of the study was to ascertain the survival rate in different subgroups and to discover determining factors of ICD discharge and prognosis.<br><br>RESULTS: Long-term survival probability at 10 resp. 14 years was 84 resp. 65% for the total collective, and the freedom of event probability (neither shocks nor antitachycardiac pacing from the ICD) to 28% each. The risk to die from SCD was below 3% over time. The most pronounced differences regarding prognosis ensued from dividing the collective into heart insufficiency stages. Thus in NYHA class I and II versus III and IV, the cumulative event rate was 61% vs 82% at 5 years, and survival rate amounted to 94 vs 63% at 5 years and 87% vs 30% at 14 years (p < 0.001). Calculating the relative benefit of ICD therapy survival benefit provided by the ICD was shown to decrease significantly after 5 years for patients in NYHA class III/IV, while it increased progressively for patients in NYHA class I/II up to 10 years. Additional determinants of prognosis and ICD discharge rate were identified left ventricular ejection fraction, age and tendency for the basic cardiac disease, however neither the result of electrophysiological testing nor the results of non-invasive risk stratification. In patients with ischemic heart disease, revascularization procedures improved prognosis only in tendency, while the effect of ICD therapy was significant. In patients with the non-obstructive form of hypertrophic cardiomyopathy ICD, discharges occurred in about 50% of patients; in contrast patients with surgical myectomy for obstructive cardiomyopathy showed no events during follow-up. In patients with chronic inflammatory heart disease and normal left ventricular function (LVF), a very low event rate was expected if patients were treated by immunosuppressive drugs. Patients with dilated cardiomyopathy did not differ from patients with ischemic heart disease with respect to prognosis and ICD discharge rate.<br><br>CONCLUSION: Significant determinants of prognosis and ICD discharge rate are left ventricular function, age and with limitations the basic cardiac disease. In contrast to patients with better LVF relative survival benefit decreases significantly after 5 years in patients with a worse LVF. Patients with aborted SCD and preserved LVF experience half the ICD discharges compared to patients with poor LVF and gain at the same time a normalization of life expectancy. Causative treatment of the basic disease has an impact on the overall prognosis and event rate, but should in general not influence the decision for IDC implantation in high risk patients.}, }
@article {pmid10784614, year = {2000}, author = {Sleeman, MA and Fraser, JK and Murison, JG and Kelly, SL and Prestidge, RL and Palmer, DJ and Watson, JD and Kumble, KD}, title = {B cell- and monocyte-activating chemokine (BMAC), a novel non-ELR alpha-chemokine.}, journal = {International immunology}, volume = {12}, number = {5}, pages = {677-689}, doi = {10.1093/intimm/12.5.677}, pmid = {10784614}, issn = {0953-8178}, mesh = {Amino Acid Sequence ; Animals ; B-Lymphocytes/*immunology ; Base Sequence ; Blotting, Northern ; Cell Line ; Chemokines, CXC/analysis/*genetics/metabolism/pharmacology ; Chemotaxis/drug effects ; Flow Cytometry ; Gene Library ; Humans ; Keratinocytes/immunology ; Mice ; Mice, Inbred C3H ; Mice, Nude ; Molecular Sequence Data ; Monocytes/*immunology ; Odontogenic Cysts/immunology ; RNA, Messenger/analysis ; Skin/drug effects/immunology ; }, abstract = {A novel alpha-chemokine, designated KS1, was identified from an EST database of a murine immature keratinocyte cDNA library. The EST has 94% similarity to a recently cloned human gene, BRAK, that has no demonstrated function. Northern analysis of mouse and human genes showed detectable mRNA in brain, intestine, muscle and kidney. Tumour panel blots showed that BRAK was down-regulated in cervical adenocarcinoma and uterine leiomyoma, but was up-regulated in breast invasive ductal carcinoma. KS1 bound specifically to B cells and macrophages, as well as two B cell lines, CESS and A20, and a monocyte line, THP-1. KS1 showed no binding to naive or activated T cells. In addition, KS1 stimulated the chemotaxis of CESS and THP-1 cells but not T cells. The s.c. injection of KS1 creates a mixed inflammatory response in Nude and C3H/HeJ mice. The above data indicates that KS1 and its human homologue represents a novel non-ELR alpha-chemokine that may have important roles in trafficking of B cells and monocytes. We propose the name B cell- and monocyte-activating chemokine (BMAC) for this molecule to reflect the described biological functions.}, }
@article {pmid10782466, year = {2000}, author = {Marinho, AF and Botelho, M and Schmitt, FC}, title = {Evaluation of numerical abnormalities of chromosomes 1 and 17 in proliferative epithelial breast lesions using fluorescence in situ hybridization.}, journal = {Pathology, research and practice}, volume = {196}, number = {4}, pages = {227-233}, doi = {10.1016/S0344-0338(00)80071-0}, pmid = {10782466}, issn = {0344-0338}, mesh = {*Aneuploidy ; Breast/*metabolism/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 17/*genetics ; Female ; Humans ; Hyperplasia/genetics/pathology ; In Situ Hybridization, Fluorescence ; }, abstract = {Our aim was to investigate the putative role of chromosome abnormalities of chromosomes 1 and 17 in the process of breast carcinogenesis. Numerical abnormalities of chromosomes 1 and 17 were investigated using fluorescence in situ hybridisation (FISH) in a series of 16 primary invasive breast carcinomas associated with intraductal proliferative epithelial lesions. Chromosome 1 aneusomy was detected in 55.6% of ductal hyperplasia (DH), 81.8% of ductal carcinomas in situ (DCIS) and 87.5% of invasive ductal carcinomas (IDC). Chromosome 17 aneusomy was not detected in the cases of DH and was present in 90.9% of DCIS and in 87.5% of IDC. Simultaneous aneusomy of chromosome 1 and 17 was found in 81.8% of DCIS and in 75.0% of IDC. Our results showed that the number of chromosome 1 and 17 copies increases from normal epithelium to invasive cancer. The numerical abnormalities of chromosome 1 were already detected in DH, suggesting that a gain in the copy number of chromosome 1 may be involved early in breast carcinogenesis.}, }
@article {pmid10781762, year = {2000}, author = {Gavazzi, A and De Maria, R and Parolini, M and Porcu, M}, title = {Alcohol abuse and dilated cardiomyopathy in men.}, journal = {The American journal of cardiology}, volume = {85}, number = {9}, pages = {1114-1118}, doi = {10.1016/s0002-9149(00)00706-2}, pmid = {10781762}, issn = {0002-9149}, mesh = {Adult ; Alcoholism/*complications ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiomyopathy, Dilated/drug therapy/*etiology/physiopathology ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Ventricular Function, Left ; }, abstract = {Excessive ethanol intake is reported in 3% to 40% of patients with idiopathic dilated cardiomyopathy (IDC). In the prevasodilator era, the prognosis was reportedly better in alcoholic than in IDC patients, an advantage limited to abstinent patients. No large series of patients systematically treated with angiotensin-converting enzyme inhibitors has since been described. We analyzed long-term outcome according to alcohol abuse in male patients with IDC. Among 338 men who had been prospectively enrolled in a multicenter registry, 79 (23%) were defined as alcohol abusers and further classified at follow-up as having stopped (AAS) or continued (AAC) abuse. AAC subjects at enrollment reported a higher daily alcohol intake than AAS subjects (178 +/- 113 vs 127 +/- 54 g/day, p = 0.012). During a mean of 59 +/- 35 months, 102 patients died and 45 underwent transplantation. Seven-year transplant-free survival was significantly lower in alcohol abusers (41%) than in patients with IDC (53%, p = 0.026), and significantly lower in AAC subjects (27%) than in either patients with IDC or AAS (45%) (p = 0. 018). Although IDC patients had beneficial changes in left ventricular function at follow-up, only AAS patients had significant improvement in ejection fraction. In this large series of patients treated with angiotensin-converting enzyme inhibitors and prospectively followed up, excessive alcohol intake was found in about one fourth of cases and persistent alcohol abuse correlated with a worse prognosis and function at follow-up.}, }
@article {pmid10767354, year = {2000}, author = {Megha, T and Ferrari, F and Arcuri, F and Lalinga, AV and Lazzi, S and Cardone, C and Cevenini, G and Leoncini, L and Tosi, P}, title = {Cellular kinetics and expression of bcl-2 and p53 in ductal carcinoma of the breast.}, journal = {Oncology reports}, volume = {7}, number = {3}, pages = {473-478}, doi = {10.3892/or.7.3.473}, pmid = {10767354}, issn = {1021-335X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; *Genes, bcl-2 ; *Genes, p53 ; Humans ; Kinetics ; Middle Aged ; Mitotic Index ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Proto-Oncogene Proteins c-bcl-2/analysis/genetics ; Tumor Suppressor Protein p53/analysis/genetics ; }, abstract = {In this study, the expression of p53 (wild-type and mutated form) and bcl-2 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) of the breast was evaluated by immunohistochemistry and PCR-SSCP and correlated with cellular kinetic parameters, i.e., mitotic index (MI) and apoptotic index (AI). The results showed a significant inverse correlation between p53 and bcl-2 expression in all cases of DCIS and IDC. In the DCIS group, two subgroups with different kinetic characteristics were identified. The first group was characterized by p53 positivity, bcl-2 negativity and high values of MI and AI; the other group was characterized by p53 negativity, bcl-2 positivity and low values of MI and AI. Conversely, in IDC some cases were p53 negative, bcl-2 positive and with high values of AI and MI, other cases were p53 positive, bcl-2 negative and with low AI and MI. Molecular biological analysis showed that p53 was wild-type in DCIS, while it was in the mutated form in IDC. These results suggest that in IDC mutated p53 contributes to a change in cellular kinetics and the selection of genetically aberrant cells, thereby favouring neoplastic progression. The coexistence of bcl-2 positivity and high AI could be explained by the presence of of apoptosis that work independently of bcl-2.}, }
@article {pmid10748873, year = {1999}, author = {Kairouz, R and Clarke, RA and Marr, PJ and Watters, D and Lavin, MF and Kearsley, JH and Lee, CS}, title = {ATM protein synthesis patterns in sporadic breast cancer.}, journal = {Molecular pathology : MP}, volume = {52}, number = {5}, pages = {252-256}, pmid = {10748873}, issn = {1366-8714}, mesh = {Adult ; Aged ; Aged, 80 and over ; Ataxia Telangiectasia Mutated Proteins ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology/secondary ; Carcinoma, Intraductal, Noninfiltrating/*metabolism ; Cell Cycle Proteins ; DNA-Binding Proteins ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Proteins/*biosynthesis/genetics ; Protein Serine-Threonine Kinases/*biosynthesis/genetics ; Tumor Suppressor Proteins ; }, abstract = {AIMS: The gene mutated in ataxia-telangiectasia (A-T), designated ATM (for "A-T mutated"), is believed to be associated with an increased risk of developing breast cancer. Most patients with A-T have null mutations of the ATM gene that appear to give rise to a truncated nonfunctional ATM protein. Therefore, the increased risk of breast cancer reported in A-T heterozygotes appears to be the result of haplo-insufficiency of ATM in breast tissues. This study aimed to determine whether reduced synthesis of ATM was also an important factor in sporadic breast cancer.<br><br>METHODS: Paraffin wax embedded tissues from patients with breast invasive ductal carcinoma (IDC) (n = 42), patients with ductal carcinoma in situ (DCIS) (n = 17), and others with lymph node metastases (n = 14) were studied. A streptavidin-biotin-peroxidase system was used to stain tissue sections for the ATM protein using the ATM-4BA and CT-1 polyclonal and monoclonal antibodies, respectively. The protein truncation test was used to screen for mutations in the ATM gene in those patients who had greatly reduced ATM protein immunoreactivity in the primary carcinoma (n = 3).<br><br>RESULTS: Most metastatic breast carcinomas in lymph nodes (71%) had greatly reduced or absent ATM protein synthesis, which was significant when compared with that observed in non-metastatic invasive breast carcinomas (p = 0.029; chi 2 test). Although not significant (p = 0.045; chi 2 test), some sporadic breast carcinomas (14 of 42) also had reduced or absent ATM protein immunoreactivity. The protein truncation test did not reveal any gross ATM gene abnormality in the cases tested, indicating that the patients were not A-T heterozygotes, who are predisposed to breast cancer.<br><br>CONCLUSIONS: A reduction in immunohistochemically detectable ATM protein in sporadic breast carcinoma implicates ATM in the progression of the disease.}, }
@article {pmid10735507, year = {2000}, author = {Cummings, MC and Aubele, M and Mattis, A and Purdie, D and Hutzler, P and Höfler, H and Werner, M}, title = {Increasing chromosome 1 copy number parallels histological progression in breast carcinogenesis.}, journal = {British journal of cancer}, volume = {82}, number = {6}, pages = {1204-1210}, pmid = {10735507}, issn = {0007-0920}, mesh = {Breast Neoplasms/*genetics/physiopathology ; Carcinoma in Situ/*genetics/physiopathology ; Carcinoma, Ductal, Breast/*genetics/physiopathology ; *Cell Transformation, Neoplastic ; Chromosomes, Human, Pair 1/*genetics ; Disease Progression ; Female ; Gene Duplication ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Invasiveness/physiopathology ; Precancerous Conditions/*genetics/physiopathology ; }, abstract = {Chromosome 1 copy number in the benign breast lesions hyperplasia and atypical duct hyperplasia (ADH) was investigated using fluorescence in situ hybridization on paraffin sections. Progression of chromosome 1 changes occurring in parallel with histological progression from normal through hyperplasia and ADH to ductal carcinoma in situ (DCIS) and invasive carcinoma was also assessed, both overall and within individual patients. The mean signal number for normal cells was 1.14, while that for hyperplasia was 1.56 and ADH was 1.5, while values for DCIS of 1.95 and invasive duct carcinoma of 1.79, were higher (P < 0.001). Six of the seven cases also showed a significant trend towards an increasing proportion of cells with greater than 2 signals per nucleus occurring with histological progression (P < 0.001). These results support the concept that benign proliferative breast disease is a biological precursor of in-situ and invasive ductal carcinoma, the early histological changes possibly indicating a field effect with further genetic changes required for the development of a malignant phenotype.}, }
@article {pmid10728411, year = {2000}, author = {Jarreta, D and Orús, J and Barrientos, A and Miró, O and Roig, E and Heras, M and Moraes, CT and Cardellach, F and Casademont, J}, title = {Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy.}, journal = {Cardiovascular research}, volume = {45}, number = {4}, pages = {860-865}, doi = {10.1016/s0008-6363(99)00388-0}, pmid = {10728411}, issn = {0008-6363}, mesh = {Adult ; Analysis of Variance ; Cardiomyopathy, Dilated/etiology/*metabolism ; Case-Control Studies ; Citrate (si)-Synthase/analysis ; Cytochrome b Group/genetics ; Electron Transport ; Electron Transport Complex I ; Electron Transport Complex II ; Electron Transport Complex III/analysis ; Electron Transport Complex IV/analysis ; *Energy Metabolism ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Mitochondria, Heart/*enzymology ; Multienzyme Complexes/analysis ; Myocardial Ischemia/complications/metabolism ; NADH, NADPH Oxidoreductases/analysis ; Oxidative Phosphorylation ; Oxidoreductases/analysis ; Sequence Analysis, DNA ; Spectrophotometry ; Succinate Dehydrogenase/analysis ; }, abstract = {OBJECTIVE: To study the mitochondrial respiratory chain enzyme activities in patients with idiopathic dilated cardiomyopathy (IDC).<br><br>METHODS: Mitochondrial respiratory chain enzyme activities were assessed spectrophotometrically in left ventricular tissue of 17 patients with IDC undergoing cardiac transplantation, as well as in two groups of controls: a group of six patients suffering from ischemic dilated cardiomyopathy (IC) also undergoing cardiac transplantation, and a group of 17 organ donors considered normal from a cardiac point of view. Cytochrome b gene from three IDC patients whose complex III activity was particularly low and from three controls was also sequenced.<br><br>RESULTS: We found that complex III enzymatic activity was lower not only in IDC but also in IC patients when compared with normal controls. When analysing cytochrome b gene we only found neutral polymorphisms previously described.<br><br>CONCLUSIONS: In view of such results, we believe that the decrease of respiratory chain complex III activity found in some cases of IDC is a secondary phenomenon, and not due to a primary mitochondrial disease.}, }
@article {pmid10678582, year = {2000}, author = {Persons, DL and Bui, MM and Lowery, MC and Mark, HF and Yung, JF and Birkmeier, JM and Wong, EY and Yang, SJ and Masood, S}, title = {Fluorescence in situ hybridization (FISH) for detection of HER-2/neu amplification in breast cancer: a multicenter portability study.}, journal = {Annals of clinical and laboratory science}, volume = {30}, number = {1}, pages = {41-48}, pmid = {10678582}, issn = {0091-7370}, mesh = {Antimetabolites, Antineoplastic/administration &amp; dosage ; Antineoplastic Agents/administration &amp; dosage ; Antineoplastic Agents, Alkylating/administration &amp; dosage ; Breast Neoplasms/*diagnosis/drug therapy/*genetics ; Cell Nucleus/genetics ; Cyclophosphamide/administration &amp; dosage ; DNA, Neoplasm/analysis ; Double-Blind Method ; Doxorubicin/administration &amp; dosage ; Female ; Fluorouracil/administration &amp; dosage ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence/*standards ; Receptor, ErbB-2/*genetics ; Reproducibility of Results ; }, abstract = {Amplification and/or overexpression of HER-2/neu has been shown to be both a prognostic and predictive marker in breast cancer. Recent studies have also confirmed the efficacy of Herceptin (trastuzumab) as adjuvant therapy for patients with overexpression of HER-2/neu. Therefore, it is critical that precise and reproducible assays be used in the clinical laboratory setting for determination of the HER-2/neu status in patients with breast cancer. The objective of this study was to determine the portability (reproducibility between different institutions) of the PathVysion HER-2 fluorescence in situ hybridization (FISH) assay used for detection of amplification of the HER-2/neu gene in formalin-fixed, paraffin-embedded tissue sections of invasive ductal carcinoma of the breast. Study specimens consisted of one breast tumor with a normal HER-2/neu copy number, two tumors with a low level, and one tumor with a high level of HER-2/neu amplification. The PathVysion HER-2 assay was shown to be highly reproducible on different assay days (n = 3) and between different institutions (n = 5) in the detection of amplification of the HER-2/neu gene in routinely processed clinical specimens of breast carcinoma. In addition, this study examined the feasibility of enumerating FISH signals in 20 nuclei in contrast to 60 nuclei per specimen. Although a modest increase in variation was observed when analyzing 20 compared to 60 nuclei, the mean ratios were similar. Therefore, analysis of as few as 20 nuclei with this FISH HER-2/neu assay may be sufficient for determining the amplification level of the HER-2/neu gene.}, }
@article {pmid10718208, year = {2000}, author = {Aubele, MM and Cummings, MC and Mattis, AE and Zitzelsberger, HF and Walch, AK and Kremer, M and Höfler, H and Werner, M}, title = {Accumulation of chromosomal imbalances from intraductal proliferative lesions to adjacent in situ and invasive ductal breast cancer.}, journal = {Diagnostic molecular pathology : the American journal of surgical pathology, part B}, volume = {9}, number = {1}, pages = {14-19}, doi = {10.1097/00019606-200003000-00003}, pmid = {10718208}, issn = {1052-9551}, mesh = {Breast/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosome Aberrations ; *Chromosome Disorders ; Chromosomes, Human/genetics ; DNA, Neoplasm/analysis ; Dissection/methods ; Female ; Humans ; Hyperplasia/pathology ; Laser Therapy/methods ; Nucleic Acid Hybridization ; Oligonucleotide Probes/chemistry ; Polymerase Chain Reaction ; }, abstract = {Carcinoma of the breast is thought to evolve through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. Here lumpectomy specimens from five patients were studied, selected for the presence of ductal hyperplasia without atypia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Laser microdissection of tissue allowed precise sampling and direct correlation of phenotypic and genotypic changes. Analyses of the samples revealed an increasing mean number of chromosomal changes occurring with increasing histologic severity, and for the first time chromosomal abnormalities were demonstrated in ductal hyperplasia without atypia. Chromosomal changes found in each of the four histologic entities included gains on 10q, 12q, 16p, and 20q and loss on 13q. In ductal hyperplasia without atypia, gain on 20q as well as loss on 13q was detected with high frequency (four of five samples). Alterations identified in more than 50% of atypical ductal hyperplasia samples included gains on 3p, 8q, 15q, and 22q and loss on 16q. In ductal carcinoma in situ, gain of DNA on 1q and 17q and loss on 4q were additionally found, and in invasive ductal carcinoma, further gains on 6p, 10q, 11q13, and 17p were identified. The chromosomal alterations occurring in the different histopathologic lesions strongly suggest that these regions harbor tumor suppressor genes or oncogenes significant for the development of ductal carcinoma of the breast.}, }
@article {pmid10709098, year = {2000}, author = {Borg, A and Isola, J and Chen, J and Rubio, C and Johansson, U and Werelius, B and Lindblom, A}, title = {Germline BRCA1 and HMLH1 mutations in a family with male and female breast carcinoma.}, journal = {International journal of cancer}, volume = {85}, number = {6}, pages = {796-800}, doi = {10.1002/(sici)1097-0215(20000315)85:6&lt;796::aid-ijc10&gt;3.0.co;2-l}, pmid = {10709098}, issn = {0020-7136}, mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Aged ; BRCA2 Protein ; Breast Neoplasms/*genetics/metabolism/pathology ; Breast Neoplasms, Male/genetics/metabolism/pathology ; Carrier Proteins ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics ; Female ; *Genes, BRCA1 ; *Germ-Line Mutation ; Humans ; Immunohistochemistry ; Male ; Microsatellite Repeats ; MutL Protein Homolog 1 ; Neoplasm Proteins/*genetics ; Nuclear Proteins ; Pedigree ; Polymorphism, Single-Stranded Conformational ; Sister Chromatid Exchange ; Transcription Factors/genetics ; }, abstract = {Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease, predisposing to the development of colorectal cancer and other tumor types such as endometrial, small bowel, stomach, ovary and urinary tract carcinoma, while most investigators find no association between HNPCC and cancer of the breast. We have identified hMLH1 mutations in 2 Amsterdam-criteria HNPCC families where both male and female gene carriers were affected with breast cancer. To investigate whether these breast cancers were caused by other genetic factors, we analyzed the 2 breast cancer susceptibility genes BRCA1 and BRCA2. In one family we did not find any mutation in the breast cancer genes, while in the other, a BRCA1 mutation segregated in the breast cancer cases. Hereditary breast cancer, and in particular BRCA1 tumors, display discrete histo-pathological and immunohistological characteristics. The tumor from a woman with both hMLH1 mutations and a BRCA1 mutation exhibited typical BRCA1 histology, e.g., grade 3 invasive ductal carcinoma with dense lymphocytic infiltration, and immunohistology, estrogen receptor (ER) negative, progesterone receptor (PgR) negative, strongly p53 positive, c-erbB-2 negative and highly Ki67 positive (>50% stained cells). The histology of the breast tumor from the man with both one hMLH1 mutation and a BRCA1 mutation was a grade 2 invasive ductal carcinoma without any special BRCA1 features. Immunohistology was also different. This might merely reflect a true difference in male breast tumor progression vs. female. We cannot exclude that the combined effect of BRCA1 and hMLH1 dysfunction has a bearing on tumor progression.}, }
@article {pmid10697510, year = {1999}, author = {Yu, Y and Morimoto, T and Sasa, M and Okazaki, K and Harada, Y and Fujiwara, T and Irie, Y and Takahashi, E and Tanigami, A and Izumi, K}, title = {HPV33 DNA in premalignant and malignant breast lesions in Chinese and Japanese populations.}, journal = {Anticancer research}, volume = {19}, number = {6B}, pages = {5057-5061}, pmid = {10697510}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Breast Neoplasms/ethnology/*virology ; China ; DNA Primers ; DNA, Viral/*analysis ; Female ; Humans ; Japan ; Middle Aged ; Papillomaviridae/genetics/*isolation &amp; purification ; Polymerase Chain Reaction ; Precancerous Conditions/ethnology/*virology ; }, abstract = {The relationship between human papillomavirus (HPV) infection and breast cancer is controversial. In this study, paraffin-embedded tissue blocks prepared from 72 patients with benign, premalignant or malignant mammary lesions were randomly collected from the Shanghai region of China and Tokushima in Japan. DNA specimens extracted from all tissues were amplified by the polymerase chain reaction (PCR) using HPV16, 18 and 33 primers. Southern blot hybridization showed 19 cases to be positive for HPV33 DNA: The positive rate for HPV33 DNA in Chinese (41.7%) was significantly higher than in Japanese (11.1%) (P < 0.01): The positive rate for HPV33 DNA in invasive ductal carcinoma (34.1%) was higher than in benign or borderline mammary lesions (5%) (P < 0.02). There were no statistically significant difference among the relationship of the nuclear grade of breast cancers with HPV33 DNA-positivity. This is the first report of a positive correlation between HPV33 DNA and breast lesions in Chinese and Japanese populations. These results suggest that the infection by HPV33, but not HPV 16 or HPV 18, may be involved in breast hyperplastic lesions, especially breast cancer, in humans.}, }
@article {pmid10676601, year = {2000}, author = {Hoffmann, J and Grimm, W and Menz, V and Maisch, B}, title = {Cardiac autonomic tone and its relation to nonsustained ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy.}, journal = {Clinical cardiology}, volume = {23}, number = {2}, pages = {103-108}, pmid = {10676601}, issn = {0160-9289}, mesh = {Adolescent ; Adult ; Aged ; Baroreflex ; Cardiomyopathy, Dilated/complications/*physiopathology ; Electrocardiography, Ambulatory ; Female ; Heart/*innervation ; Heart Rate ; Humans ; Male ; Middle Aged ; Tachycardia, Ventricular/*diagnosis/etiology ; Vagus Nerve/*physiopathology ; }, abstract = {BACKGROUND: In contrast to postinfarct patients, little is known about cardiac autonomic tone and its relation to spontaneous ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy (IDC). Both heart rate variability (HRV) and baroreflex sensitivity (BRS) are indices of autonomic innervation of the heart.<br><br>HYPOTHESIS: The aim of the present study was to determine the relation between cardiac autonomic tone assessed by HRV and BRS and spontaneous nonsustained ventricular tachycardia (NSVT) on Holter in a large patient population with IDC.<br><br>METHODS: 24-h digital Holter recordings including HRV analysis and BRS testing were prospectively performed in 137 patients with IDC and preserved sinus rhythm. Mean age was 48 +/- 12 years, and mean left ventricular (LV) ejection fraction was 32 +/- 9%. The HRV analysis on Holter included the mean RR interval (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals differing more than 50 ms (pNN50). Testing for BRS was performed noninvasively using the phenylephrine method.<br><br>RESULTS: Of 137 study patients, 42 (31%) had spontaneous NSVT on 24-h Holter. Compared with patients without NSVT, patients with NSVT on Holter had a higher New York Heart Association (NYHA) functional class (NYHA III: 40 vs. 18%, p < 0.01), a lower ejection fraction (29 +/- 9 vs. 34 +/- 9%, p = 0.01), and an increased LV end-diastolic diameter (69 +/- 8 mm vs. 66 +/- 7 mm, p = 0.03). The HRV variables rMSSD, pNN50, RRm, and BRS did not differ significantly between patients with and without spontaneous NSVT. Only SDNN on Holter was slightly lower in patients with versus without NSVT (106 +/- 45 vs. 121 +/- 46 ms, p = 0.08).<br><br>CONCLUSIONS: Patients with IDC and spontaneous NSVT on Holter are characterized by a higher NYHA functional class, a lower LV ejection fraction, an increased LV end-diastolic diameter, and a tendency toward a lower SDNN value compared with patients without NSVT. The remaining measures of HRV including rMSSD and pNN50 reflecting primarily tonic vagal activity, as well as BRS reflecting predominantly reflex vagal activity, were similar in patients with and without NSVT. The prognostic significance of these findings in patients with IDC is currently under investigation in the Marburg Cardiomyopathy Study (MACAS) at our institution.}, }
@article {pmid10674030, year = {1999}, author = {de Leeuw, N and Melchers, WJ and Ruiter, DJ and Caforio, AL and Balk, AH and de Jonge, N and Galama, JM}, title = {Autoimmune markers are undetectable in end stage idiopathic dilated cardiomyopathy.}, journal = {Journal of clinical pathology}, volume = {52}, number = {10}, pages = {739-743}, pmid = {10674030}, issn = {0021-9746}, mesh = {Adolescent ; Adult ; Autoantibodies/*analysis/blood ; Biomarkers/analysis/blood ; Cardiomyopathy, Dilated/*immunology/surgery ; Female ; Fluorescent Antibody Technique, Indirect ; Heart Transplantation ; Histocompatibility Testing ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Myocardium/*immunology ; }, abstract = {BACKGROUND: Autoreactive humoral and cellular immune responses may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Certain human leucocyte antigens (HLA) could also be linked to the development of IDC.<br><br>AIM: To determine whether various markers of autoimmunity are present in the final phase of the disease, to substantiate the role of an autoimmune process in IDC.<br><br>METHODS: 37 patients with end stage IDC were studied, together with 39 patients with end stage heart disease of known aetiology who were included for comparison. Multiple myocardial tissue samples from the explanted heart of each patient were evaluated (immuno)histologically. An indirect immunofluorescence assay was used to screen patient serum samples for the presence of heart specific autoantibodies. HLA class I and II frequencies were determined in each group and compared with HLA frequencies from healthy blood donors.<br><br>RESULTS: Only scanty small mononuclear cell infiltrates were present in myocardial tissue of seven patients with IDC and of 11 patients with heart disease of known cause. The majority of these inflammatory cells were negative for T cell markers. All blood specimens were negative for heart specific autoantibodies and there was no apparent association of IDC with particular HLA phenotypes.<br><br>CONCLUSIONS: These findings suggest that an active autoimmune process is not involved in the end stage of IDC.}, }
@article {pmid10657633, year = {2000}, author = {Johansson, B and Ingvarsson, S and Björck, P and Borrebaeck, CA}, title = {Human interdigitating dendritic cells induce isotype switching and IL-13-dependent IgM production in CD40-activated naive B cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {164}, number = {4}, pages = {1847-1854}, doi = {10.4049/jimmunol.164.4.1847}, pmid = {10657633}, issn = {0022-1767}, mesh = {Antibodies, Monoclonal/pharmacology ; B-Lymphocyte Subsets/immunology/*metabolism ; CD40 Antigens/biosynthesis/*pharmacology ; Cell Separation ; Coculture Techniques ; Cytokines/biosynthesis ; Dendritic Cells/*immunology/metabolism ; Humans ; Immunoglobulin Class Switching/*immunology ; Immunoglobulin Isotypes/*biosynthesis ; Immunoglobulin M/*biosynthesis ; Immunosuppressive Agents/pharmacology ; Interleukin-13/immunology/*physiology ; Interphase/immunology ; Lymphocyte Activation/*immunology ; Solubility ; }, abstract = {Interdigitating dendritic cells (IDC) represent a mature progeny of dendritic cells (DC) in vivo and are exhibiting a strong lymphocyte stimulatory potential. Because of the restricted localization to secondary lymphoid organs where decisive cellular interactions take place in the initial events of immunity, IDC regulatory function was addressed in relation to naive B cells. In this study, we demonstrate that human tonsillar IDC induce a dual response from CD40-activated IgD+/CD38- naive B lymphocytes. IDC direct naive B cells toward either isotype switching or an IL-13-dependent IgM secretion. IDC-dependent proliferation, isotype switching, and Ig production are all strictly mediated by soluble factors, suggesting that such skewing in B cell activation is the result of differential cytokine expression. Moreover, IDC-expressed IL-13 represents a novel source of a cytokine with recently established effects in Th2 induction as well as in immunological disorders resulting in allergic reactions.}, }
@article {pmid10653829, year = {2000}, author = {Müller, J and Wallukat, G and Dandel, M and Bieda, H and Brandes, K and Spiegelsberger, S and Nissen, E and Kunze, R and Hetzer, R}, title = {Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy.}, journal = {Circulation}, volume = {101}, number = {4}, pages = {385-391}, doi = {10.1161/01.cir.101.4.385}, pmid = {10653829}, issn = {1524-4539}, mesh = {Autoantibodies/*blood/isolation &amp; purification ; Cardiomyopathy, Dilated/*immunology/physiopathology/*therapy ; Case-Control Studies ; Echocardiography ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin A/blood ; Immunoglobulin E/blood ; Immunoglobulin G/*blood/isolation &amp; purification ; Immunoglobulin M/blood ; Immunosorbent Techniques ; Male ; Middle Aged ; Prospective Studies ; Receptors, Adrenergic, beta-1/*immunology ; Ventricular Function, Left ; }, abstract = {BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) frequently is a progressive disease without causative therapy options. Following the hypothesis that in certain patients autoantibodies against cardiac structures may induce, maintain, or promote the progression of the disease, we investigated whether the elimination of these autoantibodies through immunoadsorption would improve cardiac function.<br><br>METHODS AND RESULTS: This prospective case-control study included 34 patients with IDC. Each patient presented with moderate to severe heart failure and evidence of autoantibodies directed against beta(1)-adrenoceptors (beta(1)-AABs). Seventeen patients received standard medical therapy (control group), whereas 17 were also treated with immunoadsorption (treatment group) to eliminate beta(1)-AABs. A 1-year follow-up included echocardiographic assessment of left ventricular ejection fraction and internal diameters, beta(1)-AAB levels, and clinical status every 3 months. Within 1 year, the mean+/-SD left ventricular ejection fraction rose from 22.3+/-3.3% to 37.9+/-7.9% (P=0.0001) in the treatment group, with a relative increase of 69.9%. However, in the control group, no overall increase was seen (from 23.8+/-3.0% to 25.2+/-5.9%, P=0. 3154). Left ventricular diameter in diastole decreased by 14.5% from 74.5+/-7.1 to 63.7+/-6.0 mm in the treatment group (P=0.0001) and by 3.8% (P=0.2342) in the control group. In the treatment group, the NYHA functional rating improved after immunoadsorption (P=0.0001). beta(1)-AABs did not increase anew.<br><br>CONCLUSIONS: In IDC, the use of immunoadsorption is superior to the use of standard medical therapy. It significantly improves cardiac performance and clinical status.}, }
@article {pmid10641149, year = {1999}, author = {Sharma, BK and Ray, A and Kaur, S and Gupta, S}, title = {Immunohistochemical co-expression of c-erbb-2/Neu oncoprotein, altered tumour suppressor (p53) protein, EGF-R and EMA in histological subtypes of infiltrating duct carcinoma of the breast.}, journal = {Indian journal of experimental biology}, volume = {37}, number = {3}, pages = {223-227}, pmid = {10641149}, issn = {0019-5189}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; ErbB Receptors/metabolism ; Female ; Humans ; Immunohistochemistry ; Mucin-1/metabolism ; Mutation ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Carcinoma of the breast has an unpredictable biological behaviour. Several oncogenes have been implicated in the progression of breast cancer. Immunohistochemical staining of c-erbB-2 (Neu) oncoprotein and mutant p53 protein on 45 cases of infiltrating duct carcinoma (IDC) of the breast revealed 33% membrane positivity of c-erbB-2 oncoprotein, 46% nuclear positivity of mutated p53 protein, 33% and 84% membrane positivity of EGF-R and EMA respectively. Staining profile of c-erb-B2 oncoprotein in various histological subtypes of IDC of the breast indicated a high positivity rate in comedo followed by NOS and cibriform subtype. Similarly, high incidence of immunopositivity of mutated p53 protein was observed in comedo and cibriform subtypes while papillary carcinoma were found exclusively positive for mutated p53 protein. Interestingly, tubular subtype of IDC was not positive for c-erbB-2 oncoprotein as well as p53 mutant protein. Further, comedo and cibriform subtypes of IDC revealed 'high grade' histological features of tumour of the breast with high mitotic count, presence of marked pleomorphism and multinucleation thus, reflecting a positive relationship with overexpression of c-erbB-2 (Neu) oncoprotein as well as mutant p53 protein. The results on immunoexpression of c-erbB-2 oncoprotein and mutated p53 protein in various histological subtypes of IDC of the breast demonstrated c-erbB-2 status as an important predictor and also indicated that oncogene product may be involved in growth factor response pathway.}, }
@article {pmid10639814, year = {1999}, author = {Kurokawa, R and Saito, R and Nakamura, Y and Kagami, H and Ichikizaki, K}, title = {Ruptured vertebral artery-posterior inferior cerebellar artery aneurysm associated with facial nerve paresis successfully treated with interlocking detachable coils--case report.}, journal = {Neurologia medico-chirurgica}, volume = {39}, number = {12}, pages = {863-866}, doi = {10.2176/nmc.39.863}, pmid = {10639814}, issn = {0470-8105}, mesh = {Aged ; Aged, 80 and over ; Aneurysm, Ruptured/complications/diagnosis/*therapy ; Cerebellum/*blood supply ; Diagnostic Imaging ; *Embolization, Therapeutic ; Facial Paralysis/diagnosis/etiology/*therapy ; Female ; Humans ; Intracranial Aneurysm/complications/diagnosis/*therapy ; Treatment Outcome ; *Vertebral Artery/pathology ; }, abstract = {An 81-year-old female presented with severe headache. Computed tomography revealed subarachnoid hemorrhage. She developed right facial nerve paresis on the next day. Angiography revealed a right vertebral artery-posterior inferior cerebellar artery aneurysm. The aneurysm was successfully occluded with interlocking detachable coils (IDCs) on the 7th day. Magnetic resonance (MR) imaging 1 month after IDC placement showed partially thrombosed aneurysm near the internal acoustic meatus. Ten months after the ictus, MR imaging revealed marked resolution of the intra-aneurysmal thrombus and reduction of the aneurysm size. Her facial nerve function gradually recovered during this period. Her facial nerve paresis was probably caused by acute stretching of the facial nerve by the ruptured aneurysm that was in direct contact with the nerve. Intra-aneurysmal thrombosis using coils can reduce aneurysm size and alleviate cranial nerve symptoms.}, }
@article {pmid10636255, year = {2000}, author = {Tiret, L and Mallet, C and Poirier, O and Nicaud, V and Millaire, A and Bouhour, JB and Roizès, G and Desnos, M and Dorent, R and Schwartz, K and Cambien, F and Komajda, M}, title = {Lack of association between polymorphisms of eight candidate genes and idiopathic dilated cardiomyopathy: the CARDIGENE study.}, journal = {Journal of the American College of Cardiology}, volume = {35}, number = {1}, pages = {29-35}, doi = {10.1016/s0735-1097(99)00522-7}, pmid = {10636255}, issn = {0735-1097}, mesh = {Adolescent ; Adult ; Aged ; Alleles ; Cardiomyopathy, Dilated/*genetics ; Female ; Gene Frequency/genetics ; Genetic Predisposition to Disease/*genetics ; *Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic/*genetics ; Risk Factors ; }, abstract = {OBJECTIVES: The study investigated the potential role of eight candidate genes in the susceptibility to idiopathic dilated cardiomyopathy (IDC).<br><br>BACKGROUND: Idiopathic dilated cardiomyopathy has a familial origin in 20% to 25% of cases, and several genetic loci have been identified in rare monogenic forms of the disease. These findings led to the hypothesis that genetic factors might also be involved in sporadic forms of the disease. In complex diseases that do not exhibit a clear pattern of familial aggregation, the candidate gene approach is a strategy widely used to identify susceptibility genes. All genes coding for proteins involved in biochemical or physiological abnormalities of cardiac function are potential candidates for IDC.<br><br>METHODS: We studied 433 patients with IDC and 401 gender- and age-matched controls. Polymorphisms investigated were the I/D polymorphism of the angiotensin I-converting enzyme (ACE) gene, the T174M and M235T polymorphisms of the angiotensinogen (AGT) gene, the A-153G and A+39C polymorphisms of the angiotensin-II type 1 receptor (AGTR1) gene, the T-344C polymorphism of the aldosterone synthase (CYP11B2) gene, the G-308A polymorphism of the tumor necrosis factor-alpha (TNF) gene, the R25P polymorphism of the transforming growth factor beta1 (TGFB1) gene, the G+11/in23T polymorphism of the endothelial nitric oxide synthase (NOS3) gene and the C-1563T polymorphism of the brain natriuretic peptide (BNP) gene.<br><br>RESULTS: None of the polymorphisms were significantly associated with the risk or the severity of the disease.<br><br>CONCLUSIONS: We did not find evidence for an involvement of any of the 10 investigated polymorphisms in the susceptibility to IDC.}, }
@article {pmid10628933, year = {1999}, author = {Wakasugi, H and Funakoshi, A and Iguchi, H and Takase, M and Inoue, M and Ohshima, A and Seo, Y}, title = {Pancreatic carcinoma associated with chronic pancreatitis.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {38}, number = {12}, pages = {951-956}, doi = {10.2169/internalmedicine.38.951}, pmid = {10628933}, issn = {0918-2918}, mesh = {Adenocarcinoma/*etiology ; Adult ; Aged ; Chronic Disease ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/*etiology ; Pancreatitis/*complications ; }, abstract = {The incidence of invasive ductal carcinoma of the pancreas was 3.1% (6 cases) in 196 patients with definite chronic pancreatitis. Five patients (3 men and 2 women) had calcific pancreatitis and 1 patient (man) had non-calcific pancreatitis. Large pancreatic stones were recognized in 2 women. Most of the patients complained of continuous intractable abdominal pain and/or back pain together with weight loss and appetite loss. Serum CA19-9 levels and exacerbation of glucose intolerance were retrospectively noted to have been elevated in 1 patient. However, it was difficult to obtain a definitive diagnosis by imaging examinations earlier, due to the presence of chronic pancreatitis. Median survival of the 6 patients was 6.5 months from admission.}, }
@article {pmid10619809, year = {2000}, author = {Mehta, S and Liu, PP and Fitzgerald, FS and Allidina, YK and Douglas Bradley, T}, title = {Effects of continuous positive airway pressure on cardiac volumes in patients with ischemic and dilated cardiomyopathy.}, journal = {American journal of respiratory and critical care medicine}, volume = {161}, number = {1}, pages = {128-134}, doi = {10.1164/ajrccm.161.1.9903055}, pmid = {10619809}, issn = {1073-449X}, mesh = {Aged ; Cardiac Volume/*physiology ; Cardiomyopathy, Dilated/diagnostic imaging/*physiopathology/therapy ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Contraction ; Myocardial Ischemia/diagnostic imaging/*physiopathology/therapy ; *Positive-Pressure Respiration ; Prognosis ; Radionuclide Angiography ; Stroke Volume ; }, abstract = {The effects of continuous positive airway pressure (CPAP) on left (LV) and right ventricular (RV) volumes in patients with congestive heart failure (CHF) have not been studied. We hypothesized that CPAP would cause greater reductions in cardiac volumes in CHF patients with idiopathic dilated cardiomyopathy (IDC) than in those with ischemic cardiomyopathy (IsC), because their ventricles are more compliant. The effects of a 30-min CPAP application at 10 cm H(2)O on RV and LV end-diastolic (EDV) and end-systolic volumes (ESV), determined by radionuclide angiography, were therefore tested in 22 patients with CHF due to IsC (n = 13) or IDC (n = 9). CPAP-induced reductions in LVEDV, LVESV, RVEDV, and RVESV were significantly greater (p < 0.05) in the IDC than in the IsC group. Whereas in the IsC group CPAP caused no significant changes in LV or RV volumes, in the IDC group it induced significant reductions in RVEDV (527 +/- 77 ml to 354 +/- 50 ml, p = 0.03) and RVESV (400 +/- 78 ml to 272 +/- 54 ml, p = 0.04) that were greater than any reductions in LVEDV and LVESV. We conclude that CPAP causes greater short-term reductions in RV and LV volumes in CHF patients with IDC than in those with IsC, and that among patients with IDC, CPAP causes greater reductions in RV than in LV volumes.}, }
@article {pmid10598049, year = {1999}, author = {Varga, Z and Caduff, R}, title = {Glycogen-rich carcinomas of the breast display unique characteristics with respect to proliferation and the frequency of oligonucleosomal fragments.}, journal = {Breast cancer research and treatment}, volume = {57}, number = {2}, pages = {215-219}, doi = {10.1023/a:1006285819701}, pmid = {10598049}, issn = {0167-6806}, mesh = {Adenocarcinoma, Clear Cell/*metabolism/secondary ; Aged ; Aged, 80 and over ; Apoptosis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/secondary ; Case-Control Studies ; Cohort Studies ; *DNA Fragmentation ; Female ; Gene Expression Regulation, Neoplastic ; Glycogen/*metabolism ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Lymphatic Metastasis ; Middle Aged ; Oligonucleotides/*metabolism ; Random Allocation ; Retrospective Studies ; }, abstract = {We determined the proliferation rate and apoptotic activity of glycogen-rich carcinomas of the breast as opposed to non-clear cell tumors by means of MIB-1 immunohistochemistry and in situ detection of oligonucleosomal fragments (TUNEL reaction). The retrospective biopsy series included six invasive clear cell carcinomas of the glycogen-rich type as well as 15 randomly selected cases of invasive ductal carcinoma without evidence of glycogen storage. Three patients in the clear cell group and seven patients in the control cohort developed lymph-node metastasis. The MIB-1 labeling index of glycogen-rich carcinomas averaged 9.05%, while that of the controls was 30.03%. Apoptotic nuclei were present in a mean of 1.26% of glycogen-rich carcinoma cells. The control tumors exhibited an average apoptotic frequency of 5.85%. Tumor size, hormone receptor status, and presence or absence of lymph node involvement were found not to correlate with either proliferation or apoptosis. We conclude that glycogen-rich breast carcinomas are characterized by a peculiar 'low proliferation-low apoptosis' cell kinetic profile. The aggressive clinical behavior of these neoplasms may possibly be accounted for by an ineffective apoptotic elimination of otherwise slowly proliferating tumor cells.}, }
@article {pmid10552895, year = {1999}, author = {Yu, FY and Chu, FS}, title = {Production and characterization of a monoclonal anti-anti-idiotype antibody against fumonisin B(1).}, journal = {Journal of agricultural and food chemistry}, volume = {47}, number = {11}, pages = {4815-4820}, doi = {10.1021/jf990185x}, pmid = {10552895}, issn = {0021-8561}, mesh = {Animals ; *Antibodies, Monoclonal ; Carboxylic Acids/*immunology ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; *Fumonisins ; Hybridomas ; Mice ; Mice, Inbred BALB C ; }, abstract = {A monoclonal anti-anti-idiotype antibody (mAb3) against fumonisin B(1) (FmB1) was produced from the hybridoma cell line 7C7F4, which was generated by the fusion of P3/NS-1/1-AG4-1 myeloma cells with spleen cells isolated from a Balb/c mouse that had been immunized with the Fab fragments of affinity-purified anti-idiotype antibodies. The mAb3 belongs to the immunoglobulin M, kappa light chain. A direct competitive enzyme-linked immunosorbent assay (dc-ELISA) and an indirect competitive ELISA (idc-ELISA) were established for antibody characterization and toxin analysis. In an idc-ELISA using FmB1-ovalbumin (OVA) as the coating antigen, the concentrations causing 50% inhibition of binding (IC(50)) of mAb3 to the solid-phase FmB1-OVA by free FmB1, FmB2, and FmB3 were found to be 75, 95, and 450 ng/mL, respectively. In the dc-ELISA, the concentration causing IC(50) of FmB1-horseradish peroxidase to the solid-phase mAb3 by free FmB1 was found to be 233 ng/mL. Analysis of 12 samples naturally contaminated with fumonisins with mAb3-based idc-ELISA and polyclonal-based dc-ELISA showed a good correlation between these two methods with a correlation coefficient of 0.76 at p < 0.02. The linear regression slope was found to be y[polyclonal ELISA] = 0.87x[mAb3 ELISA] - 52 ppb.}, }
@article {pmid10594477, year = {1999}, author = {Padrini, R and Panfili, M and Magnolfi, G and Piovan, D and Casarotto, D and Ferrari, M}, title = {Myocardial region (right or left ventricle) and aetiology of heart failure can influence the inotropic effect of ouabain in failing human myocardium.}, journal = {British journal of clinical pharmacology}, volume = {48}, number = {5}, pages = {743-749}, pmid = {10594477}, issn = {0306-5251}, mesh = {Aging/physiology ; Cardiomyopathy, Dilated/complications/physiopathology ; Cardiotonic Agents/*pharmacology ; Female ; Heart Failure/drug therapy/etiology/*pathology ; Hemodynamics/drug effects ; Humans ; In Vitro Techniques ; Male ; Middle Aged ; Myocardial Contraction/drug effects ; Myocardial Ischemia/complications/pathology ; Myocardium/*pathology ; Ouabain/*pharmacology ; Ventricular Dysfunction, Left/drug therapy/pathology/physiopathology ; Ventricular Dysfunction, Right/drug therapy/pathology/physiopathology ; }, abstract = {AIMS: To investigate whether the inotropic effect of ouabain in failing human myocardium varies according to the heart chamber tested (right or left ventricle) or the aetiology of the heart disease, i.e. ischaemic or idiopathic.<br><br>METHODS: The inotropic effect of ouabain was measured, as the percentage change in baseline tension, in myocardial strips isolated from right (RV; n=21) and left ventricles (LV; n=21) of hearts explanted from patients with idiopathic (IDC; n=11) and ischaemic cardiomyopathy (CAD; n=10). Concentration-effect curves obtained with ouabain (0.05-1.6 micromol l-1) were analysed using the Emax sigmoidal model, and the following parameters were calculated: Emax, EC50, n and EC10 (threshold concentration). The influence of ventricular chamber and heart failure aetiology on these parameters was evaluated by means of a two-way anova.<br><br>RESULTS: Age and baseline haemodynamic parameters did not differ between IDC and CAD patients. Baseline strip contractility was highly variable (range: 0.48-10.0 mN), but neither ventricular chamber nor aetiology could explain such variability. A two-way anova showed that EC10 was greater in CAD than in IDC preparations (0.097+/-0.013 micromol l-1 vs 0.059+/-0. 009 micromol l-1; 95% C.I. for difference 0.043, 0.071) and Emax was lower in RV than in LV (121+/-21% vs 250+/-38%; 95% C.I. -221, -36), while EC50 and n were not significantly different between groups.<br><br>CONCLUSIONS: The inotropic effect of ouabain in human myocardium may vary according to aetiology of heart failure and the ventricle being tested. Although our results do not support the hypothesis of increased sensitivity to cardiac glycosides in CAD patients, they may explain the diminished effect observed in patients with RV failure.}, }
@article {pmid10592049, year = {1999}, author = {Werner, M and Mattis, A and Aubele, M and Cummings, M and Zitzelsberger, H and Hutzler, P and Höfler, H}, title = {20q13.2 amplification in intraductal hyperplasia adjacent to in situ and invasive ductal carcinoma of the breast.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {435}, number = {5}, pages = {469-472}, doi = {10.1007/s004280050429}, pmid = {10592049}, issn = {0945-6317}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Centromere/genetics ; Chromosomes, Human, Pair 20/*genetics ; Female ; *Gene Amplification ; Gene Dosage ; Humans ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis/genetics ; Nucleic Acid Hybridization ; }, abstract = {The 20q13 region harboring recently described putative oncogenes is frequently amplified in invasive ductal carcinoma (IDC). The aim of this study was to examine the 20q13 copy number in intraduct hyperplasia (IH), atypical duct hyperplasia (ADH), and ductal carcinoma in situ (DCIS) adjacent to IDC. In 5 patients, comparative genomic hybridization (CGH) after laser microdissection revealed 20q13 amplification in four of five cases of IH, in all of three cases of IH with atypia, all five of DCIS, and all five of IDC. Fluorescence in situ hybridization (FISH) confirmed the amplification at 20q13.2 in IH in the two specimens analyzed. The amplification rate, however, was higher in DCIS and IDC. In phenotypically normal ductal epithelium normal values were found for 20q13 copy number by FISH (n=2) and CGH (n=5). Although the number of cases presented here is small, our results suggest that mutations in the 20q13.2 region in IH may be associated with accelerated proliferation and hyperplasia of the ductal epithelium. Progression to DCIS and ICD is accompanied by a further increase in the 20q13.2 copy number.}, }
@article {pmid10590366, year = {1999}, author = {Camp, RL and Rimm, EB and Rimm, DL}, title = {Met expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma.}, journal = {Cancer}, volume = {86}, number = {11}, pages = {2259-2265}, doi = {10.1002/(sici)1097-0142(19991201)86:11&lt;2259::aid-cncr13&gt;3.0.co;2-2}, pmid = {10590366}, issn = {0008-543X}, support = {R0-1 GM57604/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/pathology ; Carcinoma/*genetics/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Hepatocyte Growth Factor/biosynthesis ; Humans ; Immunohistochemistry ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins c-met/*biosynthesis ; }, abstract = {BACKGROUND: Activation of Met, the receptor for scatter factor/hepatocyte growth factor, is associated with mitogenesis, motogenesis, and decreased cell adhesion. Elevated expression of Met has been shown in advanced cases of carcinoma of the prostate, stomach, pancreas, and thyroid. The authors previously demonstrated that Met expression is an independent prognostic marker associated with decreased survival in patients with breast carcinoma.<br><br>METHODS: Expression of Met in 113 archival breast carcinoma specimens from patients with axillary lymph node negative invasive ductal carcinoma was evaluated using a standard immunoperoxidase technique. Cases were scored by two pathologists using an H-score algorithm and then analyzed for correlation with known prognostic factors and survival.<br><br>RESULTS: Expression of Met showed a bimodal distribution with 25% of cases showing high levels of expression. In contrast to previous studies, the results of the current study showed a significant association between Met expression and nuclear and histologic grade. The 5-year survival rate for Met negative patients with tumors with low Met expression was 95% in this cohort, compared with 80% for patients with tumors showing high Met expression. Patients whose tumors had a high level of Met expression were found to have a 5-year relative risk (RR) of dying of metastatic disease of 5.05 (P = 0.03) independent of patient age and tumor size. Combined analysis of Met and nuclear grade resulted in a marked increase in independent predictive value (RR = 33.4; P < 0.01).<br><br>CONCLUSIONS: The results of the current study found that high levels of Met expression were associated with death due to metastatic disease in patients with axillary lymph node negative breast carcinoma. Expression of Met may be a useful prognostic indicator of more aggressive disease in patients whose prognosis is not easily stratified by current histopathologic markers.}, }
@article {pmid10585588, year = {2000}, author = {Aubele, M and Mattis, A and Zitzelsberger, H and Walch, A and Kremer, M and Welzl, G and Höfler, H and Werner, M}, title = {Extensive ductal carcinoma In situ with small foci of invasive ductal carcinoma: evidence of genetic resemblance by CGH.}, journal = {International journal of cancer}, volume = {85}, number = {1}, pages = {82-86}, doi = {10.1002/(sici)1097-0215(20000101)85:1&lt;82::aid-ijc15&gt;3.0.co;2-s}, pmid = {10585588}, issn = {0020-7136}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Chromosome Aberrations ; Chromosomes, Human/genetics ; Female ; Gene Dosage ; Humans ; In Situ Hybridization, Fluorescence ; Lasers ; Lymphatic Metastasis/genetics/pathology ; Microsatellite Repeats/genetics ; Neoplasms, Multiple Primary/*genetics/pathology ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; Reproducibility of Results ; }, abstract = {Although ductal carcinoma in situ (DCIS) of the breast is accepted as a potential precursor lesion for invasive ductal cancer (IDC), the critical genetic events associated with the tumor progression remain unknown. Since some extensive DCIS may show a small focus of IDC, these cases seem to be particularly suitable to investigate the primary abnormalities that determine the progression from in situ to early invasive cancer. We combined laser-microdissection with degenerative oligonucleotide-primed PCR (DOP-PCR) and comparative genomic hybridization (CGH) to detect copy number changes in 7 cases of extensive (>4 cm) DCIS with 1 small adjacent invasive focus. In 3 of the cases, single lymph node metastases (LN) were already present and were also investigated. Analysis of DCIS, IDC and LN components in the same patients revealed several consistent chromosomal changes present at all 3 sites: 1q, 7q, 8q, 16, 17, 19, 20q, 21q and 22q, the most frequent losses on 4q, 11q and 13q. DNA gain on 3p and 12q were more frequently found in IDC than in DCIS, suggesting the presence of proto-oncogenes activated during the progression to invasive cancer on these regions. Using paired analysis, resemblence of alterations found in DCIS and IDC could be quantified (odds ratio 7.0, p< or = 0.01). Gains on 6p, 10q, 14q and 15q and losses on 9p were identified in DCIS and IDC but not in LN, which may, therefore, represent early events in the carcinogenic process. Additional losses were found in the LNs on 2q, 3q, 5q, 6q, 12q and 16q. CGH results on chromosome 1 and 20 were confirmed by FISH and on chromosomal region 9p by microsatellite analyses. Our findings strongly underline the precursor status of high-grade DCIS, in which most of the chromosomal changes identified in IDC are already present. However, although the early stages of breast cancer, i.e., DCIS and the small foci of IDC were mainly characterized by DNA gains, the progression to metastatic tumor (LN) must have involved additional DNA losses on several regions.}, }
@article {pmid10582399, year = {1999}, author = {Rodríguez-Moguel, L and Bega-Ramos, B}, title = {[Risk of breast cancer of low differentiation in tumors with estrogen-negative receptors].}, journal = {Ginecologia y obstetricia de Mexico}, volume = {67}, number = {}, pages = {503-507}, pmid = {10582399}, issn = {0300-9041}, mesh = {Adult ; Breast Neoplasms/*etiology/pathology ; Carcinoma, Ductal, Breast/*etiology/pathology ; Cell Differentiation ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; *Receptors, Estrogen ; }, abstract = {The risk for poorly differentiated invasive ductal carcinoma was evaluated in negative estrogen receptor tumors determined by immunohistochemical method. The results were correlated with the histological grade. The poorly differentiated tumors had a major risk (OR = 17.8) to be negative. A high risk of correlation was found between the estrogen receptor positivity and the well differentiated tumors (grade I), p = .0001. Our results are similar to other previous reports. The usefulness of this findings and its occasional role when it was not possible the determination of this receptor for lacking economical or technological resources is discussed.}, }
@article {pmid10530439, year = {1999}, author = {de Leeuw, N and Melchers, WJ and Balk, AH and de Jonge, N and Galama, JM}, title = {Study on microbial persistence in end-stage idiopathic dilated cardiomyopathy.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {29}, number = {3}, pages = {522-525}, doi = {10.1086/598625}, pmid = {10530439}, issn = {1058-4838}, mesh = {Adolescent ; Adult ; Aged ; Bacteremia/complications/*diagnosis/epidemiology ; Biopsy, Needle ; Cardiomyopathy, Dilated/*microbiology/pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Myocarditis/complications/*diagnosis/epidemiology ; RNA, Bacterial/analysis ; RNA, Viral/analysis ; Reference Values ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; Seroepidemiologic Studies ; Serologic Tests ; Severity of Illness Index ; Viremia/complications/*diagnosis/epidemiology ; }, abstract = {Microbial persistence may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Therefore, we evaluated the role of various cardiopathogenic microorganisms in patients with end-stage IDC. In a previous study, we did not find evidence for the persistence of enterovirus RNA in end-stage IDC. In the present study, we looked for other microorganisms that are frequently associated with heart disease, including cytomegalovirus, hepatitis B virus, hepatitis C virus, Borrelia burgdorferi, Chlamydia species, mycoplasmata, and Toxoplasma gondii. Serology, polymerase chain reaction (PCR) analysis specific for detection of microbial genomic sequences, or both investigations were performed on myocardial samples from 37 patients with end-stage IDC. PCR analysis was performed on multiple myocardial samples per patient. Thirty-nine patients with end-stage heart disease of known cause were included as controls. On the basis of our serological data and PCR analyses, we did not find any evidence that microbial persistence in the heart is involved in the end-stage disease process of IDC.}, }
@article {pmid10523696, year = {1999}, author = {Amari, M and Suzuki, A and Moriya, T and Yoshinaga, K and Amano, G and Sasano, H and Ohuchi, N and Satomi, S and Horii, A}, title = {LOH analyses of premalignant and malignant lesions of human breast: frequent LOH in 8p, 16q, and 17q in atypical ductal hyperplasia.}, journal = {Oncology reports}, volume = {6}, number = {6}, pages = {1277-1280}, doi = {10.3892/or.6.6.1277}, pmid = {10523696}, issn = {1021-335X}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; *Chromosomes, Human, Pair 16 ; *Chromosomes, Human, Pair 17 ; *Chromosomes, Human, Pair 8 ; Female ; Humans ; Hyperplasia ; *Loss of Heterozygosity ; Middle Aged ; Precancerous Conditions/*genetics/pathology ; }, abstract = {The number of breast cancer patients is increasing yearly, and it is important to establish effective methods for clinical management. We investigated loss of heterozygosity (LOH) in tumors derived from 23 patients that harbored synchronous lesions of atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). Fourteen selected microsatellite markers that were mapped to and/or very close to the tumor suppressor genes or regions with frequent LOH in breast cancer. Our results suggested that i) losses of chromosomal regions 8p, 16q, and 17q are early genetic changes, and ii) ADH is a premalignant lesion for the development of breast cancer.}, }
@article {pmid10520424, year = {1999}, author = {Volchenko, NN}, title = {[Multiple primary breast cancer].}, journal = {Arkhiv patologii}, volume = {61}, number = {4}, pages = {21-25}, pmid = {10520424}, issn = {0004-1955}, mesh = {Breast/pathology ; Breast Neoplasms/*pathology/secondary ; Diagnosis, Differential ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/pathology ; Neoplasms, Multiple Primary/*pathology/secondary ; Neoplasms, Second Primary/pathology ; Prognosis ; Risk Factors ; }, abstract = {Primary multiplicity (PM) of mammary carcinoma is found in 669 (39%) cases of 1690 invasive tumors. PM is more typical for invasive ductal carcinoma with predominance of the intraductal component (67%), Paget cancer (61%), invasive lobular carcinoma (55.5%) and tubular carcinoma (52%). Invasive PM develops in the presence of the corresponding background with areas of grave dysplasia and intraepithelial carcinoma. True PM does not influence the disease prognosis.}, }
@article {pmid10503903, year = {1999}, author = {Mori, H and Sugie, S and Rahman, W and Suzui, N}, title = {Chemoprevention of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine-induced mammary carcinogenesis in rats.}, journal = {Cancer letters}, volume = {143}, number = {2}, pages = {195-198}, doi = {10.1016/s0304-3835(99)00124-x}, pmid = {10503903}, issn = {0304-3835}, mesh = {Allyl Compounds/pharmacology/therapeutic use ; Animals ; Anticarcinogenic Agents/*pharmacology/therapeutic use ; Aspirin/pharmacology/therapeutic use ; Benzoflavones/pharmacology/therapeutic use ; Carcinogens/administration &amp; dosage/*toxicity ; Disulfides/pharmacology/therapeutic use ; Drug Antagonism ; Eflornithine/pharmacology/therapeutic use ; Female ; Hydroxybenzoates/pharmacology/therapeutic use ; Imidazoles/administration &amp; dosage/*toxicity ; Indoles/pharmacology/therapeutic use ; Mammary Neoplasms, Experimental/*chemically induced/*prevention &amp; control ; Rats ; Rats, Sprague-Dawley ; beta-Naphthoflavone/pharmacology/therapeutic use ; }, abstract = {Modifying effects of dietary exposure of diallyl disulfide (DAD), aspirin, DL-alpha-difluoromethylomithine (DFMO), beta-naphthoflavone (beta-NF), alpha-naphthoflavone (alpha-NF), indole-3-carbinol (I3C) and protocatechuic acid (PCA) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were examined in two experiments with female rats. For both experiments, PhIP in corn oil at a concentration of 85 mg/kg was given to animals via an intragastric tube for eight doses for an initial 4 weeks, and test chemicals were given in the diet (Experiment 1: DAD, 200 ppm; aspirin, 400 ppm; DFMO, 400 ppm; beta-NF, 1000 ppm; Experiment 2: alpha-NF, 1000 ppm; I3C, 1000 ppm; PCA, 2000 ppm) for an initial 4 weeks. The experiments were terminated after 25 weeks. In Experiment 1, exposure of beta-NF decreased the incidence and multiplicity of total mammary tumors (fibroadenoma, intraductal carcinoma and invasive ductal carcinoma) (P < 0.001 and P < 0.0001), and lowered the incidence of ductal carcinoma (P < 0.0001). DAD lowered the incidence of ductal carcinoma and decreased the multiplicity of the total tumors (P < 0.01 and P < 0.005). Furthermore, aspirin decreased the total tumors (P < 0.05). In Experiment 2, alpha-NF decreased the multiplicity of ductal carcinoma (P < 0.05). These results suggest that alpha-NF, beta-NF, DAD or aspirin could be chemopreventing agents for mammary neoplasia.}, }
@article {pmid10483968, year = {1999}, author = {Crispell, KA and Wray, A and Ni, H and Nauman, DJ and Hershberger, RE}, title = {Clinical profiles of four large pedigrees with familial dilated cardiomyopathy: preliminary recommendations for clinical practice.}, journal = {Journal of the American College of Cardiology}, volume = {34}, number = {3}, pages = {837-847}, doi = {10.1016/s0735-1097(99)00276-4}, pmid = {10483968}, issn = {0735-1097}, support = {R01 HL-58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Cardiomyopathy, Dilated/diagnosis/*genetics ; Child ; Child, Preschool ; Echocardiography ; Female ; Genetic Testing ; Humans ; Infant ; Male ; Middle Aged ; Oregon ; Pedigree ; Phenotype ; Physical Examination ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: This study aimed to characterize the clinical profile of familial dilated cardiomyopathy (FDC) in the families of four index patients initially diagnosed with idiopathic dilated cardiomyopathy (IDC) and to provide clinical practice recommendations for physicians dealing with these diseases.<br><br>BACKGROUND: Recent evidence indicates that approximately one-half of patients diagnosed with IDC will have FDC, a genetically transmissible disease, but the clinical profile of families screened for FDC in the U.S. has not been well documented. Additionally, recent ethical guidelines suggest increased responsibilities in caring for patients with newly found genetic cardiovascular disease.<br><br>METHODS: After identification of four families with FDC, we undertook clinical screening including medical history, physical examination, electrocardiogram and echocardiogram. Diagnostic criteria for FDC-affected status of asymptomatic family members was based on left ventricular enlargement (LVE). Subjects with confounding cardiovascular diagnoses or body mass indices >35 were excluded.<br><br>RESULTS: We identified 798 living members from the four FDC pedigrees, and screened 216 adults and 129 children (age <16 years). Twenty percent of family members were found to be affected with FDC; 82.8% of those affected were asymptomatic. All four pedigrees demonstrated autosomal dominant patterns of inheritance. The average left ventricular end-diastolic dimension was 61.4 mm for affected and 48.4 mm for unaffected subjects, with an average age of 38.3 years (+/- 14.6 years) for affected and 32.1 years for unaffected subjects. The age of onset for FDC varied considerably between and within families. Presenting symptoms when present were decompensated heart failure or sudden death.<br><br>CONCLUSIONS: We propose that with a new diagnosis of IDC, a thorough family history for FDC should be obtained, followed by echocardiographic-based screening of first-degree relatives for LVE, assuming their voluntary participation. If a diagnosis of FDC is established, we suggest further screening of first-degree relatives, and all subjects with FDC undergo medical treatment following established guidelines. Counseling of family members should emphasize the heritable nature of the disease, the age-dependent penetrance and the unpredictable clinical course.}, }
@article {pmid10483138, year = {1999}, author = {Uno, H and Fujita, M and Hino, N and Nakagawa, H and Miyagawa, H and Aoki, J and Taniyama, K and Sasaki, N}, title = {[High-dose chemotherapy with autologous peripheral blood stem cell transplantation support in a patient with breast cancer metastasis to bone marrow: immunocytochemical monitoring of cancer-cell contamination].}, journal = {[Rinsho ketsueki] The Japanese journal of clinical hematology}, volume = {40}, number = {7}, pages = {556-562}, pmid = {10483138}, issn = {0485-1439}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*administration &amp; dosage ; Bone Marrow Neoplasms/*secondary/*therapy ; Breast Neoplasms/*pathology/*therapy ; Carcinoma, Ductal, Breast/*secondary/*therapy ; Cisplatin/administration &amp; dosage ; Combined Modality Therapy ; Doxorubicin/administration &amp; dosage ; Drug Administration Schedule ; Female ; *Hematopoietic Stem Cell Transplantation ; Humans ; Immunohistochemistry ; Methotrexate/administration &amp; dosage ; *Transplantation, Autologous ; Vinblastine/administration &amp; dosage ; }, abstract = {A 32-year-old woman who 1 year earlier underwent a right mastectomy for stage II breast cancer with the histology of invasive ductal carcinoma (scirrhus type) was admitted due to recurrent, metastatic breast cancer in January 1997. She presented multiple metastatic lesions in the skin, lymph nodes, bone, lungs, liver, and spleen, and her bone marrow was replaced almost entirely by tumor cells. The patient was sequentially treated with 5 courses of cyclophosphamide (CPA) and adriamycin (ADM) (CA); 2 courses of CPA, ADM, and 5-fluorouracil; 5 caurses of docetaxel hydrate; and 1 course of CA. After recovery of the normal bone marrow by standard-dose chemotherapies, peripheral blood stem cells (PBSC) were then collected after mobilization with G-CSF. The number of breast cancer cells in bone marrow and PBSC samples was determined by immunocytochemical staining with an anti-cytokeratin monoclonal antibody. The number of tumor cells in PBSC sample was within the level for non-metastatic breast cancer. Complete remission was obtained with high-dose chemotherapy consisting of CPA and Thio-TEPA, and supported by autologous PBSC transplantation.}, }
@article {pmid10482392, year = {1999}, author = {Kawatsu, K and Hamano, Y and Noguchi, T}, title = {Production and characterization of a monoclonal antibody against domoic acid and its application to enzyme immunoassay.}, journal = {Toxicon : official journal of the International Society on Toxinology}, volume = {37}, number = {11}, pages = {1579-1589}, doi = {10.1016/s0041-0101(99)00106-3}, pmid = {10482392}, issn = {0041-0101}, mesh = {Animals ; Antibodies, Monoclonal/*biosynthesis/*chemistry ; Antibody Specificity ; Bivalvia/chemistry ; Brachyura/chemistry ; Cattle ; Cross Reactions ; Foodborne Diseases ; Humans ; Immunoenzyme Techniques ; Isomerism ; Kainic Acid/*analogs &amp; derivatives/analysis/immunology ; Marine Toxins/*analysis/*immunology ; Mice ; Mice, Inbred BALB C ; Ostreidae/chemistry ; Ovalbumin/chemistry ; Serum Albumin, Bovine/chemistry ; Shellfish/analysis ; gamma-Globulins/chemistry ; }, abstract = {For production of monoclonal antibodies against domoic acid, a causative agent of amnesic shellfish poisoning, three immunogens, domoic acid conjugated with bovine serum albumin (BSA), ovalbumin (OVA) and human gamma globulin (HGG), were prepared. The antiserum obtained from BALB/c mice immunized with domoic acid-BSA showed the highest affinity for domoic acid. The monoclonal antibody, DA-3, obtained from the mice was highly specific for domoic acid and showed a minor cross-reactivity with the isomers of domoic acid (isodomoic acids B, E, F, G and H), except for isodomoic acid A. Using DA-3 antibody, an indirect competitive enzyme immunoassay (idc-EIA) was developed for measurement of domoic acid. The working range for quantitative measurement of domoic acid and the quantification limit for domoic acid in shellfish were estimated to be 0.15-10 ng/ml and less than 0.04 microg/g, respectively. The mean recovery of domoic acid added to extracts of shellfish at toxin levels of 0.02 to 0.2 microg/ml was 103% with a coefficient of variation of 4.5%. The newly developed idc-EIA seems to be a useful method for monitoring domoic acid in shellfish.}, }
@article {pmid10449154, year = {1999}, author = {de Jong, EC and Vieira, PL and Kalinski, P and Kapsenberg, ML}, title = {Corticosteroids inhibit the production of inflammatory mediators in immature monocyte-derived DC and induce the development of tolerogenic DC3.}, journal = {Journal of leukocyte biology}, volume = {66}, number = {2}, pages = {201-204}, doi = {10.1002/jlb.66.2.201}, pmid = {10449154}, issn = {0741-5400}, mesh = {Cell Differentiation ; Clobetasol/*analogs &amp; derivatives/pharmacology ; Dendritic Cells/cytology/*drug effects/immunology ; Glucocorticoids/*pharmacology ; Humans ; Hydrocortisone/*pharmacology ; Immune Tolerance ; Interleukin-12/biosynthesis ; Interleukin-6/biosynthesis ; Monocytes/cytology/drug effects/immunology ; Tumor Necrosis Factor-alpha/biosynthesis ; }, abstract = {Corticosteroids (CS) are potent immunosuppressive agents that are known to affect T cell-mediated inflammation by the inhibition of proliferation and cytokine production, as well as the immunostimulatory function of monocytes and macrophages. Not much is known of the effect of corticosteroids on dendritic cells (DC), the professional T cell stimulatory antigen-presenting cells. We report that the endogenous CS hydrocortisone and the synthetic CS clobetasol-17-propionate strongly inhibited the production of the inflammatory mediators interleukin (IL)-12 p70, tumor necrosis factor alpha (TNF-alpha), and IL-6 by lipopolysaccharide (LPS)-stimulated monocyte-derived immature DC (iDC) in vitro. In contrast, the stimulatory capacity, antigen uptake, and the expression of costimulatory molecules were not affected. In accordance with the decreased production of IL-12 p70, CS-treated iDC induced less production of the inflammatory Th1 cytokine interferon-y and enhanced levels of the Th2 cytokines IL-10 and IL-5 in staphylococcal enterotoxin B-stimulated CD4+ Th cells. Furthermore, CS inhibited the maturation of iDC as assessed by the lack of expression of CD83 as well as by the prevention of the loss of antigen uptake capacities. These type 3 DC (DC3) matured in the presence of CS produce less IL-12 p70 and have a decreased T cell stimulatory capacity. Moreover, uncommitted T cells that encounter the CS-induced DC3 develop into Th2-biased cells, which may additionally decrease the Th1-mediated tissue damage but, on the other hand, Th2 cytokines may promote undesirable elevation of IgE and eosinophilia. These findings indicate that suppression of T cell-mediated inflammation by CS not only relies on direct effects on T cells, but also on various effects on DC, their professional antigen-presenting cells.}, }
@article {pmid10432437, year = {1999}, author = {Luppi, P and Alexander, A and Bertera, S and Noonan, K and Trucco, M}, title = {The same HLA-DQ alleles determine either susceptibility or resistance to different coxsackievirus-mediated autoimmune diseases.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {13}, number = {1}, pages = {14-26}, pmid = {10432437}, issn = {0393-974X}, mesh = {Adolescent ; Adult ; Animals ; Autoimmune Diseases/genetics/*immunology/virology ; Cardiomyopathy, Dilated/genetics/*immunology/virology ; Child ; Child, Preschool ; Chlorocebus aethiops ; Coxsackievirus Infections/genetics/*immunology ; Diabetes Mellitus, Type 1/genetics/*immunology/virology ; Disease Susceptibility ; Enterovirus B, Human/*immunology ; Female ; Genes, T-Cell Receptor alpha ; Genes, T-Cell Receptor beta ; HLA-DQ Antigens/*genetics ; HeLa Cells ; Heart/virology ; Humans ; Immunohistochemistry ; Infant ; Male ; Monocytes/immunology/virology ; Pancreas/virology ; Superantigens ; Vero Cells ; }, abstract = {An important characteristic of autoimmune diseases is their association with major histocompatibility complex class I and class II alleles. In this study, we compared insulin-dependent diabetes mellitus (IDDM) with idiopathic dilated cardiomyopathy (IDC) from a strictly immunologic perspective. Although the target organs are different, being in one case the insulin-producing beta cells of the pancreas and in the other case the myocytes of the heart, many aspects of the tissue-specific immune destruction are common. Similar yet different Coxsackievirus B strains with either pancreotropic or cardiotropic specificity are able to perpetrate the first injury of the respective target tissue. Their shared capacity of inducing a superantigenic reaction further enhances the damage. Once previously secluded autoantigens are then exposed to the immune system, the tissue injury is completed via a more conventional type of immune response. On the basis of the compounded results we obtained, it is possible to propose that the same HLA-DQ molecules which are able to protect the individuals from IDDM (e.g., HLA-DQA1*0102, DQB1*0602) seem to favour the enteroviral attack to the myocardium, while alleles which confer the strongest susceptibility to IDDM (e.g., DQA1*0301, DQB1*0302), seem unable to sustain the immune attack against the heart.}, }
@article {pmid10429716, year = {1999}, author = {Orel, SG and Weinstein, SP and Schnall, MD and Reynolds, CA and Schuchter, LM and Fraker, DL and Solin, LJ}, title = {Breast MR imaging in patients with axillary node metastases and unknown primary malignancy.}, journal = {Radiology}, volume = {212}, number = {2}, pages = {543-549}, doi = {10.1148/radiology.212.2.r99au40543}, pmid = {10429716}, issn = {0033-8419}, mesh = {Axilla ; Breast/*pathology ; Breast Neoplasms/diagnosis/*secondary ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Lymphatic Metastasis ; *Magnetic Resonance Imaging ; Middle Aged ; Neoplasms, Unknown Primary/*diagnosis ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To assess the usefulness of magnetic resonance (MR) imaging of the breast in patients with malignant axillary adenopathy and unknown primary malignancy.<br><br>MATERIALS AND METHODS: Between October 1993 and December 1997, 38 women with malignant axillary adenopathy and negative mammographic and physical examination findings underwent contrast material-enhanced MR imaging. Sixteen patients were excluded due to axillary tail cancer (n = 7), lack of follow-up (n = 4), second primary malignancy (n = 3), or chemotherapy before MR imaging (n = 2). The study population comprised the remaining 22 patients. Histopathologic findings were available in 20 patients; follow-up MR imaging findings were available in two patients.<br><br>RESULTS: MR imaging depicted a primary breast cancer in 19 patients (86%; identified at excisional biopsy or mastectomy in 17, resolved on follow-up MR images during treatment in two). MR imaging depicted 4-30-mm cancers (mean, 17 mm), which correlated closely with histopathologic size. Two patients (9%) had false-negative findings: (a) One had a 2-mm invasive ductal carcinoma, and (b) one had 17- and 20-mm invasive ductal carcinomas. Of the 19 patients, 11 underwent mastectomy, seven underwent breast-conservation therapy, and one did not undergo a surgical procedure.<br><br>CONCLUSION: MR imaging is very sensitive for the detection of mammographically and clinically occult breast cancer in patients with malignant axillary adenopathy. In these patients, MR imaging offers potential not only for cancer detection but also for staging the cancer within the breast, which may be useful for treatment planning.}, }
@article {pmid10425186, year = {1999}, author = {Hiroi, S and Harada, H and Nishi, H and Satoh, M and Nagai, R and Kimura, A}, title = {Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese.}, journal = {Biochemical and biophysical research communications}, volume = {261}, number = {2}, pages = {332-339}, doi = {10.1006/bbrc.1999.1036}, pmid = {10425186}, issn = {0006-291X}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Base Sequence ; Cardiomyopathy, Dilated/enzymology/*genetics/immunology ; Case-Control Studies ; DNA Primers/genetics ; Female ; Genetic Markers ; Genotype ; HLA-DR Antigens/*genetics ; HLA-DRB1 Chains ; Humans ; Japan ; Male ; Mice ; Middle Aged ; Mitochondria/metabolism ; Odds Ratio ; Oligonucleotide Probes/genetics ; *Polymorphism, Genetic ; Protein Processing, Post-Translational ; Protein Sorting Signals/genetics/metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Risk Factors ; Superoxide Dismutase/*genetics/metabolism ; }, abstract = {To reveal genetic risk factors of nonfamilial idiopathic cardiomyopathy (IDC) in Japanese, polymorphisms in the SOD2 and HLA-DRB1 genes were investigated in 86 patients and 380 healthy controls. There was a significant excess of homozygotes for the V allele [Val versus Ala (A allele), a polymorphism in the leader peptide of manganese superoxide dismutase at position 16] of the SOD2 gene in the patients compared with the controls (87.2% versus 74.7%, odds ratio = 2.30, p = 0.013, pc < 0.03), and a significant increase in the frequency of HLA-DRB1*1401 in the patients was confirmed (14.0% vs 4.5%, odds ratio = 3.46, p = 0.001, pc < 0.03). A two-locus analysis suggested that these two genetic markers (SOD2-VV genotype and DRB1*1401) may play a synergistic role in controlling the susceptibility to nonfamilial IDC. In addition, processing efficiency of Val-type SOD2 leader peptide in the presence of mitochondria was siginificantly lower than that of the Ala-type by 11 +/- 4%, suggesting that this lower processing efficiency was in part an underlying mechanism of the association between the SOD2-VV genotype and nonfamilial IDC.}, }
@article {pmid10424149, year = {1999}, author = {Kikuchi, A and Chida, K and Misu, T and Okita, N and Takase, S and Nagata, T and Sakai, K and Itoyama, Y}, title = {[A case of limbic encephalitis associated with breast cancer developed in an HTLV-1 carrier].}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {39}, number = {5}, pages = {555-559}, pmid = {10424149}, issn = {0009-918X}, mesh = {Adult ; Atrophy ; Breast Neoplasms/*complications ; Carcinoma, Ductal, Breast/*complications ; *Carrier State ; Encephalitis/*etiology/pathology ; Female ; HTLV-I Infections/*complications ; Humans ; *Limbic System/pathology ; Magnetic Resonance Imaging ; Paraneoplastic Syndromes/*etiology/pathology ; }, abstract = {We here present a case of 44-year-old woman, a carrier of human T-lymphotrophic virus type-1 (HTLV-1), who suffered from limbic encephalitis and breast cancer. In December 1997, the patient's behavior became abnormal. Three weeks later, she became markedly forgetful. At that time neurological examinations revealed that she had anterograde and retrograde amnesia, disorientation, and confabulation, although her consciousness was clear. Anti-Hu and anti-Yo antibodies and antinuclear antibodies in the serum were negative. Flow cytometric study of the peripheral blood lymphocytes showed an increased percentage of CD3+CD25+ cells, although the percentages of CD4+CD45RA+ and CD4+CD45RO+ cells were normal. Lymphocytic responses to phytohemagglutinin or concanavalin A were normal. Anti-HTLV-1 antibody was positive both in the serum and in the cerebrospinal fluid (CSF). The level of immunoglobulin G was high and two oligoclonal immunoglobulin G bands were positive in the CSF. Cytological study of the CSF showed no atypical cells. Findings for herpes simplex virus type I and II DNAs were negative with polymerase chain reaction in the CSF. There was no elevation of antibody titers against viruses including herpes simplex virus, cytomegalovirus, and measles virus, either in the serum or the CSF. Magnetic resonance imaging showed signal abnormalities in the medial portions of both temporal lobes, in particular, in the bilateral hippocampus. Six weeks after the onset, a cancerous tumor in her right breast was detected and removed by open surgery. The pathological diagnosis was invasive ductal carcinoma with neuroendocrine features. After mastectomy, anterograde and retrograde amnesia and disorientation mildly improved. The follow-up magnetic resonance imaging showed that signal abnormalities in the medial portions of both temporal lobes decreased and that the bilateral hippocampus became atrophic. We diagnosed the present case as paraneoplastic limbic encephalitis. There has been only one case report of limbic encephalitis associated with breast cancer.}, }
@article {pmid10397273, year = {1999}, author = {Silva, JM and Dominguez, G and Garcia, JM and Gonzalez, R and Villanueva, MJ and Navarro, F and Provencio, M and San Martin, S and España, P and Bonilla, F}, title = {Presence of tumor DNA in plasma of breast cancer patients: clinicopathological correlations.}, journal = {Cancer research}, volume = {59}, number = {13}, pages = {3251-3256}, pmid = {10397273}, issn = {0008-5472}, mesh = {Breast/pathology ; Breast Neoplasms/blood/*genetics/*pathology/surgery ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; DNA Methylation ; DNA, Neoplasm/*blood ; Exons ; Female ; *Genes, p53 ; Genetic Markers ; Humans ; Loss of Heterozygosity ; *Microsatellite Repeats ; Neoplasm Staging ; *Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; }, abstract = {Using different molecular techniques, DNA has been detected in the plasma of cancer patients with various types of tumors. We undertook the present study to investigate the presence of plasma DNA, before mastectomy, in patients with breast cancer at diagnosis and to analyze the clinicopathological spectrum of this subgroup of patients with respect to patients without DNA with tumor characteristics. We studied 62 patients with breast cancer, who were selected sequentially after mastectomy and diagnosis of breast carcinomas. Genomic DNA extracted from tumor and normal tissues, normal blood cells, and plasma was used for molecular studies. Alterations in polymorphic markers selected because they had been found to show a high rate of alterations in breast cancer in previous studies (D17S855, D17S654, D16S421, TH2, D10S197, and D9S161), as well as mutations in the p53 gene and aberrant methylation at the first exon of p16INK4a, were used to identify and characterize tumor and plasma DNA. Thirteen clinicopathological parameters were analyzed in each patient. We identified 56 cases (90%) with at least one molecular event in tumor DNA, and 41 cases (66%) with a similar alteration in plasma DNA. Comparison of the clinicopathological parameters between patients with and without plasma DNA revealed significant differences in the axillary involvement, rate of invasive ductal carcinoma, high proliferative index, and the parameter comprised of lymph node metastases, histological grade II, and peritumoral vessel involvement. A high proportion of breast cancer patients exhibited plasma DNA at diagnosis similar to tumor DNA, and its presence correlated significantly with pathological parameters associated with a poor prognosis.}, }
@article {pmid10395063, year = {1999}, author = {Levine, RJ and Caulfield, JB and Norton, P and Chantler, PD and Deziel, MR and Slayter, HS and Margossian, SS}, title = {Myofibrillar protein structure and assembly during idiopathic dilated cardiomyopathy.}, journal = {Molecular and cellular biochemistry}, volume = {195}, number = {1-2}, pages = {1-10}, pmid = {10395063}, issn = {0300-8177}, support = {HL49597/HL/NHLBI NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Actin Cytoskeleton/chemistry/metabolism/ultrastructure ; Cardiomyopathy, Dilated/enzymology/*metabolism ; Fluorescent Antibody Technique, Direct ; Humans ; Microscopy, Electron ; Muscle Proteins/*chemistry/*metabolism/ultrastructure ; Myocardium/chemistry/metabolism/ultrastructure ; Myofibrils/*chemistry/metabolism/ultrastructure ; Protein Conformation ; Staining and Labeling ; }, abstract = {A neutral protease, mekratin, active in human hearts at end stage idiopathic dilated cardiomyopathy (IDC), mediates the breakdown of cardiac myosin LC2. Myosin purified from IDC heart tissue forms unusually short synthetic thick filaments. Therefore, determination of filament length and mekratin distribution in IDC heart muscle were initiated. Native thick filaments were prepared directly from control and IDC tissues and analyzed. Also, paraffin-embedded tissue sections were stained with a fluorescently-labeled anti-protease antibody to establish its distribution in myocardial tissues. Control sections had only very weak, background levels of fluorescence whereas IDC sections stained intensely throughout, indicating a wide ranging distribution of the protease within the myocyte cytoplasm. SDS-PAGE revealed LC2 to be present in stoichiometric amounts in control but greatly reduced in IDC heart muscle. Native thick filaments from control myocardium were structurally stable. They had a median length of 1.65 microm with well-defined bare zones and displayed the 43 nm helical periodicity typical of the relaxed arrangement of myosin heads close to the filaments' shafts. In contrast, native IDC filaments were less stable, and had a median length of 0.9 microm. These filaments were highly disordered: they had no surface periodicity and myosin heads were positioned away from the filaments' shafts. The shorter, less stable, aperiodic thick filaments from IDC hearts appear to result from depletion of LC2 caused by increased activity of mekratin in the IDC myocardium.}, }
@article {pmid10391153, year = {1999}, author = {Margossian, SS and Anderson, PA and Chantler, PD and Deziel, M and Umeda, PK and Patel, H and Stafford, WF and Norton, P and Malhotra, A and Yang, F and Caulfield, JB and Slayter, HS}, title = {Calcium regulation in the human myocardium affected by dilated cardiomyopathy: a structural basis for impaired Ca2+-sensitivity.}, journal = {Molecular and cellular biochemistry}, volume = {194}, number = {1-2}, pages = {301-313}, pmid = {10391153}, issn = {0300-8177}, support = {HL20749/HL/NHLBI NIH HHS/United States ; HL44094/HL/NHLBI NIH HHS/United States ; HL49597/HL/NHLBI NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Adenosine Triphosphatases/metabolism ; Adolescent ; Adult ; Base Sequence ; Calcium/*metabolism ; Cardiomyopathy, Dilated/enzymology/*metabolism ; DNA Primers ; DNA, Complementary ; Female ; Humans ; Hydrolysis ; Male ; Middle Aged ; Myocardium/enzymology/*metabolism ; Myosin Light Chains/metabolism ; Protein Isoforms/metabolism ; Serine Endopeptidases/metabolism ; Troponin/genetics/metabolism ; }, abstract = {Calcium regulation in the human heart is impaired during idiopathic dilated cardiomyopathy (IDC). Here, we analyze the structural basis for impairment in the regulatory mechanism. Regulation of contractility was monitored by MgATPase and Ca2+-binding assays as a function of calcium. Myofibrillar proteolysis and expression of troponin T isoforms were established by gel electrophoresis and by Western blots. Myofibrillar ATPase assays in low salt however, revealed a drastic lowering of calcium sensitivity in IDC myofibrils as indicated by reductions in both activation by high calcium and in EGTA-mediated inhibition of MgATPase. Structural changes in myofilament proteins were found in most IDC hearts, specifically proteolysis of myosin light chain 2 (LC2), troponin T and I (TnT and TnI), and sometimes a large isoform shift in TnT. IDC did not induce mutations in LC2 and troponin C (TnC), as established by cDNA sequence data from IDC cases, thus, calcium binding to IDC myofibrils was unaffected. Reassociation of IDC myofibrils with native LC2 raised MgATPase activation at high Ca2+ to control levels, while repletion with intact, canine TnI/TnT restored inhibition at low Ca2+. A model, identifying possible steps in the steric blocking mechanism of regulation, is proposed to explain IDC-induced changes in Ca2+-regulation. Moreover, shifts in TnT isoforms may imply either a genetic or a compensatory factor in the development and pathogenesis of some forms of IDC.}, }
@article {pmid10359044, year = {1999}, author = {Koyama, T and Hasebe, T and Tsuda, H and Hirohashi, S and Sasaki, S and Fukutomi, T and Imoto, S and Umeda, T and Mukai, K}, title = {Histological factors associated with initial bone metastasis of invasive ductal carcinoma of the breast.}, journal = {Japanese journal of cancer research : Gann}, volume = {90}, number = {3}, pages = {294-300}, pmid = {10359044}, issn = {0910-5050}, mesh = {Analysis of Variance ; Bone Neoplasms/pathology/*secondary ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Cell Division ; Female ; Humans ; Lymphatic Metastasis ; Mitotic Index ; Neoplasm Recurrence, Local ; Osteoblasts/pathology ; Prognosis ; }, abstract = {Bone is one of the most common sites of recurrence of breast cancer. Therefore, it would be clinically very useful if breast cancers with a high probability of bone metastasis (BM) could be identified by histopathological examination of the primary lesions. To elucidate histological characteristics associated with predisposition to initial BM, we examined nine histopathological parameters in the primary lesions of 110 invasive ductal carcinomas (IDCs) of the breast with 0 to 3 regional node metastases. These cases had recurrence between 4 months and 10.1 years after the initial radical surgery. The first metastatic site was bone in 24 cases, whereas other sites were involved in 86 cases. IDCs growing in a strand growth pattern or with fibrotic focus (FF) had a significantly higher frequency of initial BM than those growing in a non-strand growth pattern or without FF, respectively. Strand growth pattern was a significant predictor of the initial BM in multivariate analysis. In all 54 IDCs that developed BM during the follow-up period, osteolytic metastasis was significantly more frequent in the group with FF than in that without FF. This study demonstrated that strand growth pattern and the presence of FF are significant histopathological factors associated with initial BM. The combination of those predictive factors along with prognostic factors may provide a useful approach to identify patients at high risk for initial BM, enabling early treatment for the recurrent cancer.}, }
@article {pmid10352319, year = {1999}, author = {Ruibal, A and Núñez, MI and del Río, Mf and Arias, J and Martínez, MI and Rabadán, J and Tejerina, A}, title = {[Clinical-biological differences between invasive ductal carcinomas and breast lobular carcinomas. Preliminary results].}, journal = {Revista espanola de medicina nuclear}, volume = {18}, number = {2}, pages = {84-87}, pmid = {10352319}, issn = {0212-6982}, mesh = {Adult ; Aneuploidy ; Breast Neoplasms/*chemistry/diagnosis/genetics ; Carcinoma, Ductal, Breast/*chemistry/diagnosis/genetics ; Carcinoma, Lobular/*chemistry/diagnosis/genetics ; Cathepsin D/analysis ; Diploidy ; ErbB Receptors/analysis ; Estrogens/analysis ; Female ; Growth Inhibitors/analysis ; Growth Substances/analysis ; Humans ; Immunoenzyme Techniques ; Immunoradiometric Assay ; Lymphatic Metastasis ; Middle Aged ; Oncogene Proteins/analysis ; Polyploidy ; Proteins/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tissue Plasminogen Activator/analysis ; Trefoil Factor-1 ; Tumor Suppressor Proteins ; }, abstract = {In order to know the biological differences between both histological types, we have analyzed some clinical and biological parameters in tissues of women having infiltrating carcinomas (247 ductal (IDCs) 17 and lobular (ILCs) of the breast. Our preliminary results led us to suggest the following. 1) In negative axillary lymph node involvement (N-) patients, ILCs were more frequently associated with diploidy and the existence of multiple foci; likewise, they had higher pS2 cytosolic levels than IDC; 2) in N+ patients, ILC were associated with multicentricity and had higher concentrations of progesterone receptors and 3) these findings could help to explain us the clinical and biological peculiarities, as well as, the clinical outcome of both histological types.}, }
@article {pmid10330430, year = {1999}, author = {Mogensen, J and Klausen, IC and Pedersen, AK and Egeblad, H and Bross, P and Kruse, TA and Gregersen, N and Hansen, PS and Baandrup, U and Borglum, AD}, title = {Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.}, journal = {The Journal of clinical investigation}, volume = {103}, number = {10}, pages = {R39-43}, pmid = {10330430}, issn = {0021-9738}, mesh = {Actins/chemistry/*genetics/physiology ; Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Hypertrophic/*genetics/pathology/physiopathology ; DNA Primers/genetics ; Exons ; Female ; Genetic Linkage ; Humans ; Lod Score ; Male ; Middle Aged ; Models, Molecular ; Myocardial Contraction/genetics ; Pedigree ; Point Mutation ; Protein Conformation ; }, abstract = {We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.}, }
@article {pmid10232583, year = {1999}, author = {Tanaka, T and Kimura, M and Matsunaga, K and Fukada, D and Mori, H and Okano, Y}, title = {Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast.}, journal = {Cancer research}, volume = {59}, number = {9}, pages = {2041-2044}, pmid = {10232583}, issn = {0008-5472}, mesh = {Anaphase ; Aneuploidy ; Aurora Kinases ; Breast/enzymology ; Breast Diseases/enzymology ; Breast Neoplasms/*enzymology/genetics ; Carcinoma, Ductal, Breast/*enzymology/genetics ; Cell Division ; Centrosome/*enzymology ; Chromosomes, Human, Pair 20/genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/*biosynthesis/genetics ; *Oncogenes ; Proliferating Cell Nuclear Antigen/analysis ; Protein Kinases/*biosynthesis/genetics ; *Protein Serine-Threonine Kinases ; }, abstract = {A centrosomal serine/threonine kinase, AIK1(3)/breast tumor amplified kinase/aurora2, which was recently identified as an oncogene, shows high amino acid identity with chromosome segregation kinases, fly Aurora, and yeast Ipl1. Immunohistochemical analyses of invasive ductal adenocarcinomas of the breast revealed that overexpression of AIK1 was observed in 94% of the cases, irrespective of the histopathological type, whereas the protein was not detected in normal ductal and lobular cells. Benign breast lesions including fibrocystic disease and fibroadenoma (epithelial components) displayed weakly detectable AIK1 expression in part of the lesions. This is the first immunohistochemical report of AIK1 expression in primary human breast carcinomas. Although the physiological function(s) of AIK1 kinase during cell division remains to be determined, the markedly high positivity of AIK1 staining in the cancer lesions suggested a possible involvement of its overexpression in the tumorigenesis of some of breast cancer cells.}, }
@article {pmid10229542, year = {1999}, author = {Mueller-Premru, M and Gubina, M and Kaufmann, ME and Primozic, J and Cookson, BD}, title = {Use of semi-quantitative and quantitative culture methods and typing for studying the epidemiology of central venous catheter-related infections in neonates on parenteral nutrition.}, journal = {Journal of medical microbiology}, volume = {48}, number = {5}, pages = {451-460}, doi = {10.1099/00222615-48-5-451}, pmid = {10229542}, issn = {0022-2615}, mesh = {Bacteremia/*epidemiology ; Bacterial Typing Techniques ; Biofilms ; Catheters, Indwelling/*adverse effects/microbiology ; Coagulase/deficiency ; Electrophoresis, Gel, Pulsed-Field ; Humans ; Infant, Newborn ; Intensive Care Units ; Parenteral Nutrition/*adverse effects ; Plasmids ; Slovenia/epidemiology ; Staphylococcal Infections/*epidemiology ; Staphylococcus/*classification/genetics ; Staphylococcus epidermidis/genetics ; *Veins ; }, abstract = {To study the epidemiology - especially the impact of contaminated stopcocks - on central venous catheter (CVC) infection and catheter-related sepsis (CRS), semi-quantitative (SQ) and quantitative (Q) culture methods and typing of coagulase-negative staphylococci (CNS) were employed in 49 neonates with clinical signs of sepsis while receiving parenteral nutrition in the paediatric intensive care unit. The patients were divided into two groups according to stopcock contamination: group A consisted of 18 patients (36%) with contaminated stopcocks and group B consisted of 31 patients (64%) with sterile stopcocks. Five specimens were obtained from each patient, in addition to that from the stopcock: a swab taken from the skin surrounding the catheter puncture site; the CVC tip; the intradermal segment (IDC); and samples of parenteral fluid and blood. A total of 294 specimens (392 sites) was cultured and micro-organisms were identified. All CNS isolated were typed by biotyping, antibiogram, plasmid analysis and pulsed-field gel electrophoresis (PFGE), and the discriminatory power of the typing methods was compared. The CVC tips were infected in 25 patients (51%); 15 (83%) in group A and 10 (32%) in group B. Sepsis was detected in 24 neonates (49%), 13 in group A and 11 in group B. This was catheter-related in 15 patients (63%), 12 in group A and 3 in group B. CNS were recovered from 13 (52%) of 25 infected CVCs, nine in group A and four in group B. Sixty-five CNS isolates were recovered from these patients and belonged to 14 biotypes, 22 antibiograms, 22 plasmid profiles and 26 PFGE types. Typing showed that in six of nine patients in group A, CNS of the same type were recovered from the catheter tip and the stopcock, in one patient the catheter tip and skin isolates were the same and in two others the catheter tip isolates were different from stopcock and skin isolates. In all four patients in group B, different CNS types were recovered from CVC tips and skin. Bacteraemia was caused by CNS in 14 patients (58%), six in group A and eight in group B. Typing confirmed that nine cases (six in group A and three in group B) were catheter-related but five were not. SQ and Q culture methods and typing, especially by PFGE, allowed the study to determine that bacteria from contaminated stopcocks were frequently the source of CVC infection and CRS.}, }
@article {pmid10227724, year = {1999}, author = {Yonezawa, S and Horinouchi, M and Osako, M and Kubo, M and Takao, S and Arimura, Y and Nagata, K and Tanaka, S and Sakoda, K and Aikou, T and Sato, E}, title = {Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor.}, journal = {Pathology international}, volume = {49}, number = {1}, pages = {45-54}, doi = {10.1046/j.1440-1827.1999.00823.x}, pmid = {10227724}, issn = {1320-5463}, mesh = {Adenocarcinoma, Mucinous/metabolism/pathology ; Adenocarcinoma, Papillary/metabolism/pathology ; Adult ; Aged ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization ; Male ; Middle Aged ; Mucin 5AC ; Mucin-2 ; Mucins/*genetics ; Pancreas/chemistry/pathology ; Pancreatic Neoplasms/metabolism/*pathology ; RNA, Messenger/genetics ; Survival Analysis ; }, abstract = {Previously it has been found that the MUC2 gene for intestinal type secretory mucin is highly expressed in intraductal papillary mucinous tumors (IPMT), which are characterized by non-invasive growth and a favorable outcome. In contrast, MUC2 mRNA is rarely expressed in invasive ductal carcinomas (IDC), which have poor outcomes. The gastric type secretory mucin, MUC5AC, is strongly expressed in the surface mucous cells of gastric mucosa. As both MUC2 and MUC5AC mucins share the characteristics of forming highly viscous gels, it is expected that not only MUC2 mucin expression but also MUC5AC mucin expression may be associated with a favorable prognosis in patients with pancreatic tumors. MUC5AC mucin gene expression was examined in 24 cases of IPMT and 38 cases of IDC by in situ hybridization using a digoxigenin-labeled oligonucleotide. The results were compared with MUC2 mucin gene expression. Neither MUC5AC mRNA nor MUC2 mRNA was detected in normal pancreatic tissues. MUC5AC mRNA was expressed in 20 of 24 cases of IPMT (83%) and in five of 38 cases of IDC (13%). In contrast, MUC2 mRNA was expressed in 14 of 24 cases of IPMT (58%) and in none of the 38 cases of IDC (0%). The expression rates of MUC5AC mRNA and MUC2 mRNA in IPMT were significantly higher than those in IDC (P< 0.001, respectively). Intraductal papillary mucinous tumors are characterized by three histological types: (i) villous dark cell type; (ii) papillary clear cell type; and (iii) compact cell type. The villous dark cell type generally expressed both MUC5AC+ and MUC2+ genes. Alternatively, the papillary clear cell type and the compact cell type usually showed MUC5AC+ and MUC2- expression. Patients with MUC5AC mRNA expression had a significantly better survival prognosis than those with no MUC5AC mRNA expression (P< 0.005). In conclusion, MUC5AC gene expression occurs in a majority of IPMT cases, even in those with no MUC2 production. MUC5AC expression can be}, }
@article {pmid10226540, year = {1999}, author = {Tökés, AM and Hortoványi, E and Csordás, G and Kulka, J and Mózes, G and Hatalyák, A and Kádár, A}, title = {Immunohistochemical localisation of tenascin in invasive ductal carcinoma of the breast.}, journal = {Anticancer research}, volume = {19}, number = {1A}, pages = {175-179}, pmid = {10226540}, issn = {0250-7005}, mesh = {Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Receptors, Estrogen/analysis ; Tenascin/*analysis/immunology ; Tumor Suppressor Protein p53/analysis ; }, abstract = {BACKGROUND: The association of TN expression, tumour grading and expression of commonly used histopathologic prognostic factors (p53 and estrogen receptor) was examined in 62 cases of invasive ductal carcinoma of the breast.<br><br>MATERIAL AND METHODS: Following histological grading immunohistochemical reactions were undertaken on routine histopathologic samples and the results semiquantitatively evaluated.<br><br>RESULTS: Strong TN expression was found in close proximity of the neoplastic epithelial cells in each case, but not in other areas of the stroma. In 10 (16%) cases TN expression was detected to the neoplastic epithelial cells as well. There was no statistically significant difference in the extent of stromal TN immunoreaction between tumours of different grades. A significant difference was found in p53 and estrogen receptor immunoreactions by tumour grade (p = 0.05). TN immunoreaction in the stroma did not correlate with the nuclear expression of p53, Ki-67 and estrogen receptor in the tumour cells.<br><br>CONCLUSIONS: TN immunoreactivity does not seem to correlate with currently used prognostic factors. The increased expression of stromal TN in invasive breast ductal carcinomas is an other indicator of possible role played by the extracelular matrix components in cancer development.}, }
@article {pmid10220795, year = {1999}, author = {Tanimoto, K and Akbar, SM and Michitaka, K and Onji, M}, title = {Immunohistochemical localization of antigen presenting cells in liver from patients with primary biliary cirrhosis; highly restricted distribution of CD83-positive activated dendritic cells.}, journal = {Pathology, research and practice}, volume = {195}, number = {3}, pages = {157-162}, doi = {10.1016/S0344-0338(99)80028-4}, pmid = {10220795}, issn = {0344-0338}, mesh = {Adult ; Aged ; Antigen-Presenting Cells/*chemistry ; Antigens, CD/*analysis ; Cholestasis/immunology/pathology ; Dendritic Cells/*immunology ; Female ; HLA-DR Antigens/analysis ; Hepatitis C, Chronic/immunology/pathology ; Humans ; Immunoglobulins/*analysis ; Immunohistochemistry ; Liver/*immunology/pathology ; Liver Cirrhosis, Biliary/*immunology/pathology ; Male ; Membrane Glycoproteins/*analysis ; Middle Aged ; }, abstract = {In order to have insights into the abnormal immune regulation in primary biliary cirrhosis (PBC), different types of antigen presenting cells (APC) were localized immunohistochemically in liver specimens from 26 patients with PBC and compared with the distributions of APC from 11 and 10 patients with chronic hepatitis C (CH-C) and large bile duct obstruction, respectively. In all diagnostic conditions, 30-90% of the infiltrating cells were positive for HLA DR. In PBC, the numbers of interdigitating cells (IDC) were significantly higher than the numbers of CD83-positive dendritic cells (DC) (34.0 +/- 38.8 vs. 5.5 +/- 7.1/specimen, mean +/- SD, p < 0.05). On the other hand, the numbers of IDC (14.2 +/- 20.0/specimen) and CD83-positive DC (7.9 +/- 8.7/specimen) were almost similar in CH-C (p > 0.05). Positive stainings for IDC and CD83-positive DC were rarely seen in large bile duct obstruction. This is the first report on the existence of activated CD83-positive DC in PBC. The significantly increased numbers of IDC and the highly restricted distributions of CD83-positive DC in PBC indicate that activated DC may play a role in the abnormal immune pathogenesis of PBC.}, }
@article {pmid10204104, year = {1999}, author = {Gherardi, G and Marveggio, C}, title = {Cytologic score and DNA-image analysis in the classification of borderline breast lesions: a prospective study on 47 fine-needle aspirates.}, journal = {Diagnostic cytopathology}, volume = {20}, number = {4}, pages = {212-218}, doi = {10.1002/(sici)1097-0339(199904)20:4&lt;212::aid-dc6&gt;3.0.co;2-n}, pmid = {10204104}, issn = {8755-1039}, mesh = {Biopsy, Needle ; Breast Neoplasms/classification/*pathology ; DNA, Neoplasm/analysis/genetics ; Humans ; Image Cytometry/*methods ; Ploidies ; }, abstract = {We prospectively evaluated the accuracy of the cytologic score system developed by Masood et al. combined with DNA-image analysis in the subclassification of 47 fine-needle aspiration samples with cytologic features of borderline breast lesions. Cytologic scores ranged between 12-18. All cases underwent surgical excision of the lesion, and histology revealed 24 cases of florid hyperplasia, 8 of atypical hyperplasia, and 11 noninvasive and 4 invasive ductal carcinomas. DNA-image analysis demonstrated 33 diploid and 14 aneuploid cases. Diploid samples were divided into slowly proliferating (S + G2/M < or = 13%) and rapidly proliferating (S + G2/M > 13%) cases. By considering florid hyperplasia a "low-risk" lesion and by amalgamating atypical hyperplasia, and in situ and invasive ductal carcinoma in the category of "high-risk" lesions, the positive predictive value of a score value > 16 was 100%. In cases scoring < or = 16, the slowly proliferating pattern had a negative predictive value of 95%, while the aneuploid and rapidly proliferating patterns had a positive predictive value of 100% and 63%, respectively. We conclude that a combination of cytologic score evaluation and DNA-image analysis is very useful in differentiating "low-risk" from "high-risk" cases in the field of breast borderline lesions, thus improving the impact of fine-needle aspiration diagnosis on patient management.}, }
@article {pmid10193332, year = {1998}, author = {Shousha, S and Costello, C and Luqmani, YA and Sinnett, HD}, title = {CD5 positive breast carcinoma in a patient with untreated chronic lymphocytic leukaemia: molecular studies of chromosome 13q.}, journal = {Journal of clinical pathology}, volume = {51}, number = {11}, pages = {862-864}, pmid = {10193332}, issn = {0021-9746}, mesh = {Aged ; Antigens, Neoplasm/*analysis ; Breast Neoplasms/chemistry/*genetics ; CD5 Antigens/*analysis ; *Chromosomes, Human, Pair 13 ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/metabolism ; Neoplasms, Second Primary/chemistry/*genetics ; }, abstract = {A 67 year old woman presented with a right breast lump which proved to be a grade 2 invasive ductal carcinoma with axillary lymph node metastasis. She had a five year history of CD5 positive chronic lymphocytic leukaemia, which never required treatment. Immunoperoxidase stains for CD5, using the monoclonal antibody NCL-CD-54C7, showed that there was extensive infiltration of axillary lymph nodes with CD5 positive B lymphocytes. Strong staining for CD5 was also seen in the carcinoma cells within the breast and lymph node metastases. It has recently been suggested that there is a tumour suppresser locus in chronic lymphocytic leukaemia at 13q12.3 near or at the BRCA2 locus. Deletion of regions on chromosome 13q containing the BRCA2 and RB1 genes has also been reported in sporadic breast cancers. These observations suggest that there may be a link between these two diseases acting through chromosome 13, but amplification of several microsatellite repeat markers failed to show any loss of heterozygosity or repeat instability at either these or several other loci on chromosome 13. Examination of additional such cases is needed to perform a more comprehensive study of the significance of positive CD5 staining of breast carcinoma.}, }
@article {pmid10192865, year = {1999}, author = {Knez, I and Cerwenka, H and Moinfar, F and Hoff, M and Mächler, H and Anelli-Monti, M and Radner, H and Rigler, B}, title = {Invasive ductal carcinoma of the male breast expanding from pacemaker pocket decubitus.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {22}, number = {3}, pages = {531-533}, doi = {10.1111/j.1540-8159.1999.tb00484.x}, pmid = {10192865}, issn = {0147-8389}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*etiology/pathology/surgery ; Carcinoma, Ductal, Breast/*etiology/pathology/surgery ; Humans ; Male ; Mastectomy, Radical ; Pacemaker, Artificial/*adverse effects ; Ulcer/*etiology ; }, abstract = {After twenty-five years of therapy with different unifocal pacemaking systems, an 84-year old male patient developed a nonseptic pacemaker decubitus. A rare incidental finding of invasive ductal carcinoma of the right mammary gland was surgically treated by a generous excision of the tumor and by consecutive modified radical mastectomy. According to published literature, the association of invasive ductal carcinoma arising from a pacemaker pocket decubitus and followed by curative treatment has not been previously reported. We do conclude that pacemaker generators in close relationship to the mammary gland should be considered with suspicion.}, }
@article {pmid10094898, year = {1999}, author = {Irvin, WP and Cathro, HP and Grosh, WW and Rice, LW and Andersen, WA}, title = {Primary breast carcinoma of the vulva: a case report and literature review.}, journal = {Gynecologic oncology}, volume = {73}, number = {1}, pages = {155-159}, doi = {10.1006/gyno.1998.5269}, pmid = {10094898}, issn = {0090-8258}, mesh = {Adenocarcinoma/complications/*pathology ; *Breast ; Choristoma/complications/*pathology ; Female ; Humans ; Middle Aged ; Vulvar Diseases/complications/*pathology ; Vulvar Neoplasms/complications/*pathology ; }, abstract = {BACKGROUND: In 1872, Hartung was the first to describe the case of a fully formed mammary gland arising in the left labium majora of a 30-year-old woman. Since Hartung's initial report, 38 additional cases of ectopic vulvar breast tissue have been described. This case report describes the rare occurrence of primary mammary adenocarcinoma arising within the vulva.<br><br>CASE: A 64-year-old G4P4 white female presented with a 4-year history of a 2 x 1 cm firm, indurated, raised lesion of the left lateral mons. A wide local excision with ipsilateral inguinofemoral lymphadenectomy was performed. Given histological findings characteristic of both invasive ductal carcinoma and invasive lobular carcinoma, in conjunction with the presence of estrogen and progesterone receptors within the tumor, a diagnosis of infiltrating adenocarcinoma arising within ectopic breast tissue was made.<br><br>CONCLUSIONS: Thirty-nine reported cases of ectopic breast tissue arising within the vulva have been reported in the world literature. Though the diagnosis of primary breast carcinoma arising within the vulva is based primarily upon histologic pattern, estrogen and progesterone receptor positivity provide supporting evidence. Given the rarity of this condition, guidelines for therapy are unavailable; we therefore suggest looking to the current management of breast cancer in order to establish a sensible approach.}, }
@article {pmid10092064, year = {1999}, author = {Nakano, S and Iyama, K and Ogawa, M and Yoshioka, H and Sado, Y and Oohashi, T and Ninomiya, Y}, title = {Differential tissular expression and localization of type IV collagen alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) chains and their mRNA in normal breast and in benign and malignant breast tumors.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {79}, number = {3}, pages = {281-292}, pmid = {10092064}, issn = {0023-6837}, mesh = {Breast/*metabolism ; Breast Neoplasms/*metabolism ; Collagen/chemistry/*genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Isomerism ; RNA, Messenger/*metabolism ; Reference Values ; Tissue Distribution/physiology ; }, abstract = {Type IV collagen, the major component of basement membrane (BM), is composed of six genetically distinct alpha chains. We investigated the cellular regulation and origin of these alpha(IV) chains in normal and neoplastic breast tissues by immunohistochemistry by using alpha(IV) chain-specific antibodies and by in situ hybridization. In normal breast, alpha1(IV) and alpha2(IV) chains were stained in all BM, whereas alpha5(IV) and alpha6(IV) chains were restrictively localized in a linear pattern in the BM of the mammary gland. Similar immunostaining profiles were observed in benign breast tumors and in the intraductal components of invasive ductal carcinoma. However, in invasive ductal carcinoma, alpha1(IV) and alpha2(1V) chains were discontinuously or negatively stained in the cancer cell nests, and the assembly of alpha5(IV) and alpha6(IV) chains into the BM was completely inhibited. Coexpression of alpha5(IV) and alpha6(IV) chains was related to the localization of alpha-smooth muscle actin (alpha-SMA)-positive myoepithelial cells. By in situ hybridization, in fibroadenoma and invasive ductal carcinoma, the signals for alpha1(IV) and alpha2(IV) mRNA were abundant in stromal cells. However, the signals for alpha5(IV) and alpha6(IV) mRNA were not seen in any of these cells. In contrast, in intraductal papilloma, coexpression of alpha1 (IV)/alpha2(IV) mRNA and alpha5(IV)/alpha6(IV) mRNA was identified in epithelial cells. The results indicate that the mammary gland forms a second network of BM composed of alpha5(IV)/alpha6(IV) chains, in addition to the classic network of alpha1(IV)/alpha2(IV) chains. The expression of type IV collagen alpha chains seems to be differentially regulated by the epithelial-myoepithelial interaction and to be associated with the invasive potential of breast cancer.}, }
@article {pmid10091731, year = {1999}, author = {Kayahara, M and Nagakawa, T and Ohta, T and Kitagawa, H and Ueno, K and Tajima, H and Elnemr, A and Miwa, K}, title = {Analysis of paraaortic lymph node involvement in pancreatic carcinoma: a significant indication for surgery?.}, journal = {Cancer}, volume = {85}, number = {3}, pages = {583-590}, doi = {10.1002/(sici)1097-0142(19990201)85:3&lt;583::aid-cncr8&gt;3.0.co;2-j}, pmid = {10091731}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aorta ; Carcinoma/mortality/*secondary/surgery ; Female ; Humans ; Lymphatic Metastasis/*pathology ; Male ; Middle Aged ; Pancreatic Neoplasms/mortality/*pathology/surgery ; Statistics as Topic ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: Lymph node status is a key prognostic factor for pancreatic carcinoma. The paraaortic lymph nodes are the highest level of lymph nodes that can be resected safely in the abdomen for pancreatic and other gastrointestinal tumors. The pattern of paraaortic lymph node involvement and its relation with other lymph node groups were analyzed and the significance of this information relative to surgical therapy examined.<br><br>METHODS: Between 1974-1996, 99 patients with invasive ductal carcinoma of the pancreas underwent pancreatectomy at the study institution. The pattern of lymph node involvement, particularly paraaortic, was evaluated by careful pathologic review of extended lymphadenectomy specimens. RESULTS. Fifty-eight of 76 patients (76%) with carcinoma in the pancreatic head (Ph) and 19 of 23 patients (83%) with carcinoma of the pancreatic body and tail (Pbt) had lymph node involvement. Fourteen patients with Ph disease (18%) and 4 with Pbt disease (17%) had paraaortic lymph node involvement. Tumor size did not correlate with paraaortic lymph node involvement. A correlation was found between Group 13 (posterior pancreaticoduodenal lymph nodes), Group 14 (lymph nodes surrounding the superior mesenteric artery), and the paraaortic lymph nodes for Ph disease. All paraaortic lymph node metastases were located in the 16M region (the region between the celiac trunk and the inferior mesenteric artery). For patients with Pbt disease, the distribution of paraaortic lymph node metastases was the same as for those with Ph disease. Only 33% of cases of paraaortic lymph node metastases were suspected preoperatively or perioperatively. The longest survival for a patient with paraaortic lymph node metastases was 36 months and 17 months, respectively, for patients with Ph and Pbt disease.<br><br>CONCLUSIONS: The paraaortic lymph nodes are frequent sites of metastasis from pancreatic carcinoma, and are difficult to evaluate preoperatively or perioperatively. This situation mandates paraaortic lymph node dissection, at least in the 16M region.}, }
@article {pmid10081498, year = {1998}, author = {Hasebe, T and Imoto, S and Sasaki, S and Mukai, K}, title = {A proposal for a new histological classification scheme for predicting short-term tumor recurrence and death in patients with invasive ductal carcinoma of the breast.}, journal = {Japanese journal of cancer research : Gann}, volume = {89}, number = {12}, pages = {1358-1373}, pmid = {10081498}, issn = {0910-5050}, mesh = {Adipose Tissue/pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood supply/*classification/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/blood supply/*classification/mortality/pathology/therapy ; Cell Nucleus/ultrastructure ; Disease Progression ; Disease-Free Survival ; Female ; Fibrosis ; Humans ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Mitotic Index ; Multivariate Analysis ; Muscles/pathology ; Necrosis ; Neoplasm Proteins/analysis ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Predictive Value of Tests ; Prognosis ; Receptors, Estrogen/analysis ; Risk Factors ; Sensitivity and Specificity ; *Severity of Illness Index ; Skin/pathology ; Survival Analysis ; Treatment Outcome ; }, abstract = {Tumor recurrence rate (TRR) and mortality rate (MR) of invasive ductal carcinoma (IDC) of the breast in short-term follow-up are relatively low. Nevertheless, it is extremely important to identify patients at risk of early recurrence or death after surgery. The aim of this study was to establish a new histological prognostic classification scheme for IDC in order accurately to predict the short-term outcome. The following histological parameters were analyzed in 201 IDCs: 1) tumor size, 2) structural atypia, 3) nuclear atypia, 4) number of mitotic figures, 5) fibrotic focus (FF), 6) vascular invasion, 7) tumor necrosis, 8) skin invasion, 9) muscle invasion, 10) nodal status and 11) extramammary fat invasion. Multivariate analysis showed that nuclear atypia, presence of FF, and the invasive length of fat invasion (ILFI) were the most important histological parameters correlated with TRR or MR of IDCs. Accordingly, a new histological classification based on nuclear atypia, FF and ILFI (Nucleus-Fibrotic focus-Fat invasion, NFF) was devised. Comparative studies were performed with the following existing prognostic classifications: 1) histological grade, 2) modified Scarff-Bloom-Richardson histological grade, 3) prognostic index and 4) pathological TNM (pTNM) stage classifications. Patient grouping defined by NFF classification significantly correlated with tumor recurrence or death of IDCs in all cases, cases at stages I and II, those without lymph node metastasis and those who were estrogen receptor (ER)-positive after adjustment for the other four classifications, using multivariate analysis. NFF classification appeared superior to existing prognostic classifications for the accurate prediction of the short-term outcome for patients with IDCs in low risk groups.}, }
@article {pmid10080429, year = {1999}, author = {Candy, GP and Skudicky, D and Mueller, UK and Woodiwiss, AJ and Sliwa, K and Luker, F and Esser, J and Sareli, P and Norton, GR}, title = {Association of left ventricular systolic performance and cavity size with angiotensin-converting enzyme genotype in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {83}, number = {5}, pages = {740-744}, doi = {10.1016/s0002-9149(98)00981-3}, pmid = {10080429}, issn = {0002-9149}, mesh = {Aged ; Alleles ; Cardiac Output, Low/enzymology/genetics/physiopathology ; Cardiomyopathy, Dilated/*enzymology/genetics/physiopathology ; Case-Control Studies ; Cohort Studies ; Diastole ; Echocardiography ; Female ; Forecasting ; Gated Blood-Pool Imaging ; Gene Deletion ; Genetic Markers ; Genotype ; Heart Ventricles/*pathology ; Humans ; Male ; Middle Aged ; Mutagenesis, Insertional/genetics ; Myocardium/enzymology ; Odds Ratio ; Peptidyl-Dipeptidase A/blood/*genetics/metabolism ; Polymorphism, Genetic/genetics ; Regression Analysis ; Risk Factors ; Stroke Volume/physiology ; Survival Rate ; Systole/*physiology ; Ventricular Function, Left/*physiology ; }, abstract = {The insertion-deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is a marker linked to differences in plasma and cardiac ACE activity as well as to an increased mortality in patients with idiopathic heart failure. We examined the possibility that ACE gene ID variants are associated with differences in left ventricular (LV) systolic performance or internal LV dimensions in a high-risk cohort of patients with idiopathic dilated cardiomyopathy (IDC). The ACE genotype was determined in 171 patients selected with IDC in New York Heart Association functional class II to III heart failure and with a LV ejection fraction of < or = 40%. Left ventricular performance and dimensions were assessed using echocardiography (n = 161) and radionuclide ventriculography (n = 169). The frequency of ACE gene ID alleles was not different in the study versus non-age-matched (n = 171; odds ratio 0.94) and age-matched (n = 106, odds ratio 0.88) control groups. Ejection fraction was found to be worse in patients with the DD genotype (echocardiography, DD = 23.5 +/- 0.70, ID + II = 26.8 +/- 0.8, p = 0.009; ventriculography, DD = 21.7 +/- 0.9, ID + II = 25.3 +/- 0.8, p = 0.003). LV end-systolic and end-diastolic diameters were increased in patients with the DD genotype. Multifactor regression analysis showed the ACE genotype to be an independent predictor of both ejection fraction (echocardiography, p <0.02; ventriculography, p <0.03) and end-diastolic diameter (p <0.02). In conclusion, the results of this study indicate that the DD genotype of the ACE gene is independently associated with both a reduced LV systolic performance and an increased LV cavity size in patients with IDC.}, }
@article {pmid10077011, year = {1999}, author = {Su, MY and Wang, Z and Carpenter, PM and Lao, X and Mühler, A and Nalcioglu, O}, title = {Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {9}, number = {2}, pages = {177-186}, doi = {10.1002/(sici)1522-2586(199902)9:2&lt;177::aid-jmri5&gt;3.0.co;2-8}, pmid = {10077011}, issn = {1053-1807}, mesh = {Albumins ; Animals ; Carcinogens ; Contrast Media ; Diagnosis, Differential ; Ethylnitrosourea ; Female ; Gadolinium ; Gadolinium DTPA ; Mammary Neoplasms, Experimental/chemically induced/*pathology ; Rats ; Rats, Sprague-Dawley ; Time Factors ; }, abstract = {A carcinogen (N-ethyl-N-nitrosourea)-induced animal tumor model was established to grow malignant and benign breast tumors. In each tumor the pharmacokinetic characteristics were measured by using three contrast agents, gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA; <1 kD), Gadomer-17 (35 kD), and albumin-Gd-DTPA (70-90 kD). Infiltrating ductal carcinomas (IDC) with low, medium, and high Scarf-Bloom-Richardson grades and fibroadenomas (FA) were analyzed. We found that Gd-DTPA could differentiate between FA and malignant tumors, but not between malignant tumors of low and high grades. In contrast, the intermediate size agent Gadomer-17 could differentiate between high-grade and low-grade IDC, but not between low-grade IDC and FA due to their similar enhancement patterns (despite their different origins). The largest agent, albumin-Gd-DTPA, was capable of differentiating both, but the low contrast-to-noise ratio was its major technical concern. The results in this breast tumor model suggest that macromolecular agents provide useful information for differential diagnosis among IDCs of various grades, but they do not provide superior information than Gd-DTPA for differential diagnosis between IDC and FA.}, }
@article {pmid10026446, year = {1999}, author = {Imamura, M and Hosotani, R and Kogire, M}, title = {Rationale of the so-called extended resection for pancreatic invasive ductal carcinoma.}, journal = {Digestion}, volume = {60 Suppl 1}, number = {}, pages = {126-129}, doi = {10.1159/000051468}, pmid = {10026446}, issn = {0012-2823}, mesh = {Adenocarcinoma/pathology/*surgery/therapy ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Chemotherapy, Adjuvant ; Female ; Fluorouracil/therapeutic use ; Humans ; Liver Neoplasms/drug therapy/secondary ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; *Pancreatectomy ; Pancreatic Ducts/pathology/*surgery ; Pancreatic Neoplasms/pathology/*surgery/therapy ; Prognosis ; Radiotherapy, Adjuvant ; Survival Analysis ; }, abstract = {It has generally been recognized that for adenocarcinoma of the pancreas, surgical resection provides the only chance for cure. In this study, we have analyzed the long-term survival of 141 patients with invasive ductal adenocarcinoma of the pancreas who received macroscopically curative resection. Multivariate analysis demonstrated that comprehensive stage of the tumor, curability of the resection, and adjuvant radiation therapy were independent prognostic factors. Pancreatectomy in this study was done with an extensive retroperitoneal clearance of para-aortic lymph node and nerve tissues, so-called extended resection. Survival curves of these patients revealed that the R0 resection is essentially necessary for long-term survival. Survival curve without microscopic lymph node metastasis was significantly better than that with node metastasis; however, 3 patients with node metastasis have been alive for more than 3 years. The survival curve of the patients who received adjuvant radiation therapy was better than of those who underwent surgery alone, and postoperative regional chemotherapy with continuous 5-FU infusion decreased hepatic metastases within 6 months. The results suggest that local recurrence of pancreatic cancer might possibly be controlled by extended resection and adjuvant irradiation, and early development of hepatic metastases might be controlled with regional chemotherapy.}, }
@article {pmid10024984, year = {1999}, author = {Fujimura, N and Hirohata, M and Abe, T and Tokutomi, T and Shigemori, M}, title = {[A case of aneurysmal neck clipping following incomplete neck clipping and coil embolization].}, journal = {No shinkei geka. Neurological surgery}, volume = {27}, number = {1}, pages = {49-54}, pmid = {10024984}, issn = {0301-2603}, mesh = {Adult ; Aneurysm/*therapy ; Carotid Artery Diseases/*therapy ; Carotid Artery, Internal ; Embolization, Therapeutic/*methods ; Female ; Humans ; Subarachnoid Hemorrhage/etiology ; Surgical Instruments ; }, abstract = {We report a case with radical neck clipping following incomplete embolization with coils and imperfect neck clipping. A 43-year-old woman suffered from a subarachnoid hemorrhage (Hunt &amp; Hess Grade IV) due to the rupture of a left paraclinoid internal carotid aneurysm on 28 October, 1996. Neck clipping of the aneurysm was performed at day 1. Follow-up angiogram at 2 weeks after surgery showed however a small residual aneurysm. The second angiogram 1.5 months later showed the growth of the residual aneurysm. The residual part of the aneurysm was then treated with endovascular embolization using interlocking detachable coils (IDC), resulting in incomplete occlusion of the aneurysm. The direct surgical clipping of the residual aneurysm was performed via Dolenc approach. A fenestrated clip was applied to the partial embolized aneurysm, when the aneurysmal wall was ruptured between the occluded part of the aneurysm and the residual dome. The fenestrated clip was then reapplied successfully under temporary occlusion of the parent artery. Because of the stenosis of the parent artery, STA-MCA anastomosis was then performed. Postoperative recovery of the patient was uneventful and postoperative angiogram showed stenosis of the parent artery with patent bypass flow. The patient was discharged without complications. Technical problems in neck clipping following incomplete embolization with coils are discussed.}, }
@article {pmid10022453, year = {1999}, author = {Sasano, H and Suzuki, T and Matsuzaki, Y and Fukaya, T and Endoh, M and Nagura, H and Kimura, M}, title = {Messenger ribonucleic acid in situ hybridization analysis of estrogen receptors alpha and beta in human breast carcinoma.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {84}, number = {2}, pages = {781-785}, doi = {10.1210/jcem.84.2.5435}, pmid = {10022453}, issn = {0021-972X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry ; Carcinoma, Ductal, Breast/*chemistry ; Female ; Humans ; *In Situ Hybridization ; Middle Aged ; Oligonucleotide Probes ; RNA, Messenger/*analysis ; Receptors, Estrogen/*genetics ; }, abstract = {We examined the expression of a recently characterized novel estrogen receptor (ER) beta in 25 cases of invasive ductal carcinoma of the breast, using messenger RNA (mRNA) in situ hybridization, and compared the findings with those of ERalpha, to study its localization and its possible biological significance in human breast cancer. ERalpha and ERbeta hybridization signals were both detected, predominantly in carcinoma cells and in some stromal cells, in 18 of 25 (72%) and 11 of 25 (44%) cases, respectively. The cases in which more than 25% of carcinoma cells demonstrated mRNA hybridization signals were 13 of 25 (52%) and 2 of 25 (8%) cases for ERalpha and ERbeta, respectively. Among the cases expressing ERbeta, 10 of 11 (91%) also expressed ERalpha mRNA; and in these 10 cases, coexpressing both ERalpha and beta, the number of carcinoma cells expressing ERalpha was greater than that expressing ERbeta in 9 cases. Eight cases demonstrated only ERalpha mRNA hybridization signals in carcinoma cells. These results indicate that ERbeta is coexpressed with ERalpha in most ERbeta-positive breast carcinoma cells, which suggests that the expression of ERbeta depends on the presence of ERalpha in the great majority of human breast cancer. In addition, the number of carcinoma cases and/or the ratio of carcinoma cells expressing ERalpha was much greater than those expressing ERbeta. The relative ratio of ERalpha and ERbeta expression in carcinoma cells may be related to various estrogen-dependent biological features of human breast cancer.}, }
@article {pmid9892111, year = {1999}, author = {Tsuda, H and Takarabe, T and Fukutomi, T and Hirohashi, S}, title = {der(16)t(1;16)/der(1;16) in breast cancer detected by fluorescence in situ hybridization is an indicator of better patient prognosis.}, journal = {Genes, chromosomes &amp; cancer}, volume = {24}, number = {1}, pages = {72-77}, doi = {10.1002/(sici)1098-2264(199901)24:1&lt;72::aid-gcc10&gt;3.0.co;2-m}, pmid = {9892111}, issn = {1045-2257}, mesh = {Breast Neoplasms/*diagnosis/*genetics ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 16/*genetics ; DNA Probes ; DNA, Neoplasm ; Female ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence/methods ; Prognosis ; *Translocation, Genetic ; }, abstract = {By two-color fluorescence in situ hybridization (FISH), der(16)t(1;16) or der(1;16) was frequently detected in low-grade papillary carcinoma but not in benign intraductal papilloma of the breast. In order to clarify the incidence and clinicopathological significance of der(16)t(1;16)/der(1;16) in common breast cancers, der(16)t(1;16)/der(1;16) was examined by two-color FISH in breast cancers resected from 51 patients by using DNA probes for 16cen, 16q11.2, and 1q12 labeled with biotin or digoxigenin. der(16)t(1;16)/der(1;16) was clonally detected in 16 cancers (31%), being more frequent in ductal carcinomas of lower grade and invasive lobular carcinoma than in high-grade invasive ductal carcinoma (P<0.001). der(16)t(1;16)/der(1;16) was also correlated with a higher amount of hormone receptors in the tumor (P<0.05). Disease-free and overall survival rates of the patient group with der(16)t(1;16)/der(1;16)-positive cancer were higher (88% and 94%) than those of the group with der(16)t(1;16)/der(1; 16)-negative cancer (39% and 68%) (P<0.05). Among the 16 patients with lymph node metastasis who received one of two similar forms of postsurgical adjuvant chemo-endocrine therapy, the prognosis of those with der(16)t(1;16)/der(1;16)-positive cancer was better than that of those with der(16)t(1;16)/der(1;16)-negative cancer (P<0.05). der(16)t(1;16)/der(1;16) detected by FISH is considered helpful in identifying patients with a better prognosis and for stratification of patients in randomized clinical trials of adjuvant chemo-endocrine therapies.}, }
@article {pmid9854494, year = {1998}, author = {Nio, Y and Dong, M and Uegaki, K and Hirahara, N and Minari, Y and Sasaki, S and Takamura, M and Iguchi, C and Tamura, K}, title = {p53 expression affects the efficacy of adjuvant chemotherapy after resection of invasive ductal carcinoma of the pancreas.}, journal = {Anticancer research}, volume = {18}, number = {5B}, pages = {3773-3779}, pmid = {9854494}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Carcinoma/*drug therapy/metabolism/pathology/secondary ; Chemotherapy, Adjuvant ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Pancreatectomy ; Pancreatic Neoplasms/*drug therapy/*metabolism/pathology/surgery ; Prognosis ; Survival Rate ; Treatment Outcome ; Tumor Suppressor Protein p53/*biosynthesis/metabolism ; }, abstract = {p53 tumor suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair, suggesting its involvement in the mechanisms of drug resistance or chemosensitivity. The present study assessed the implication of p53 expression in the prognosis of patients and the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma (IDC) of the pancreas. A total of 58 patients with primary IDC of the pancreas underwent pancreatectomy between 1982 and 1996: 28 patients received surgery alone and 30 patients received postsurgical adjuvant chemotherapy. p53 protein was stained immunohistochemically with anti-p53 monoclonal antibody. p53 was positively expressed in 29 out of 58 primary lesions (50%), and the survival curve of the patients with p53 (+) pancreatic cancer is lower than that of those with p53 (-) cancer. On the other hand, the survival curve of adjuvant chemotherapy group was also higher than that of surgery alone group, and furthermore, in patients with p53 (+) cancer, the survival curve of adjuvant chemotherapy group was significantly better than that of the surgery alone group. A multivariate analysis showed that p53 expression or adjuvant chemotherapy is not a significant risk-factor for prognosis, but that adjuvant chemotherapy is a significant risk factor for the patients with p53 (+) pancreatic cancer, which suggests that p53 expression affects the efficacy of chemotherapy. p53 expression may be beneficial as an indicator for introduction of adjuvant chemotherapy in pancreatic cancer patients.}, }
@article {pmid9831206, year = {1998}, author = {Zhu, XL and Hartwick, W and Rohan, T and Kandel, R}, title = {Cyclin D1 gene amplification and protein expression in benign breast disease and breast carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {11}, number = {11}, pages = {1082-1088}, pmid = {9831206}, issn = {0893-3952}, mesh = {Breast/chemistry/metabolism/pathology ; Breast Diseases/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism ; Carcinoma in Situ/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism ; Cyclin D1/*genetics/metabolism ; DNA, Neoplasm/analysis/genetics ; Gene Amplification ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Tumor Cells, Cultured/cytology/metabolism ; }, abstract = {Cyclin D1 plays a critical role in regulating cell-cycle progression. Gene amplification and protein overexpression of cyclin D1 have been detected in breast cancer but little is known concerning whether these changes occur in normal breast tissue and in breast lesions associated with increased risk of development of invasive breast cancer. We looked for cyclin D1 gene amplification and protein overexpression in 30 cases of benign breast disease (16 epithelial hyperplasias without atypia and 14 atypical ductal hyperplasias) and 18 ductal carcinomas in situ by use of differential PCR and immunohistochemical staining. We compared the resulting frequencies to those in 15 cases of normal breast tissue and 17 invasive ductal carcinomas. We found cyclin D1 gene amplification in 15% of those with normal breast tissue, 19% of those with epithelial hyperplasia without atypia, 27% of those with atypical ductal hyperplasia, 35% of those with ductal carcinoma in situ, and 25% of those with invasive ductal carcinoma; corresponding figures for protein overexpression were 13, 13, 57, 50, and 64%. These results suggest that cyclin D1 amplification and protein overexpression can occur before histologic alterations are seen but that the frequencies of these changes are higher in histologic lesions with cellular atypia (atypical hyperplasia and ductal carcinoma in situ), reaching frequencies similar to those observed in invasive carcinoma.}, }
@article {pmid9831188, year = {1998}, author = {Sher, A and Reis e Sousa, C}, title = {Ignition of the type 1 response to intracellular infection by dendritic cell-derived interleukin-12.}, journal = {European cytokine network}, volume = {9}, number = {3 Suppl}, pages = {65-68}, pmid = {9831188}, issn = {1148-5493}, mesh = {Animals ; Dendritic Cells/*immunology/*metabolism/parasitology ; Immunity, Cellular ; Interleukin-12/*biosynthesis/*physiology ; Intracellular Fluid/immunology/metabolism/parasitology ; Th1 Cells/*immunology/*metabolism ; Toxoplasma/immunology ; Toxoplasmosis, Animal/immunology ; }, abstract = {Host resistance to many intracellular pathogens is dependent on the induction of host IFN-gamma. This response in turn is triggered by the critical initiation cytokine, IL-12. Activated macrophages provide a major source of IL-12 during infection yet are unlikely to be the initial cell to produce the cytokine because of their need for IFN-gamma priming and/or other co-stimulatory signals. We have utilized an in vivo approach to identify the primary IL-12 producing cells which respond to the intracellular protozoan Toxoplasma gondii. Our results indicate that in spleen interdigitating dendritic cells (IDC) but not macrophages rapidly synthesize IL-12 after injection of parasite products or live tachyzoites. This response is both IFN-gamma and T lymphocyte independent. The same microbial stimulus results in the migration of IDC precursors into T cell areas and the upregulation of co-stimulatory cell-surface molecules. We postulate that these early dendritic cell activation events represent the "ignition switch" for the subsequent Type 1 cytokine response which leads to control of infection.}, }
@article {pmid9828838, year = {1998}, author = {Lee, AH and Dublin, EA and Bobrow, LG and Poulsom, R}, title = {Invasive lobular and invasive ductal carcinoma of the breast show distinct patterns of vascular endothelial growth factor expression and angiogenesis.}, journal = {The Journal of pathology}, volume = {185}, number = {4}, pages = {394-401}, doi = {10.1002/(SICI)1096-9896(199808)185:4&lt;394::AID-PATH117&gt;3.0.CO;2-S}, pmid = {9828838}, issn = {0022-3417}, mesh = {Breast/metabolism ; Breast Neoplasms/blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/*metabolism/pathology ; Carcinoma, Lobular/blood supply/*metabolism/pathology ; Endothelial Growth Factors/genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization ; Lymphokines/genetics/*metabolism ; Neoplasm Invasiveness ; Neovascularization, Pathologic/*metabolism ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; }, abstract = {Angiogenesis is essential for tumour growth and important in tumour metastasis and prognosis. Vascular endothelial growth factor (VEGF) stimulates endothelial proliferation in vitro and angiogenesis in vivo. VEGF expression has been correlated with high vascularity in tumours, including carcinoma of the breast. This study investigated VEGF expression and vascularity of invasive lobular (n = 10) and invasive ductal carcinoma (n = 28), and pure ductal carcinoma in situ of the breast (n = 33). VEGF protein expression was studied with immunohistochemistry and VEGF mRNA with in situ hybridization. Vascular density was assessed on sections stained for von Willebrand factor. There was more expression of both VEGF protein (P = 0.006) and mRNA (P = 0.002) in invasive ductal than in invasive lobular carcinoma. VEGF protein (rs = 0.32, P = 0.047) and mRNA (rs = 0.56, P = 0.04) correlated with vascular density in invasive ductal carcinoma. In invasive lobular carcinoma, vascular density did not correlate with VEGF mRNA (rs = 0.15, P = 0.35) and was inversely related to VEGF protein (rs = -0.57, P = 0.04). There were no significant differences in vascular density between the two types of invasive carcinoma, suggesting that VEGF is important in angiogenesis in invasive ductal carcinoma, but that other angiogenic factors are important in invasive lobular carcinoma. Although VEGF protein was frequently expressed in ductal carcinoma in situ, no relationship was found between VEGF and the two patterns of angiogenesis previously described.}, }
@article {pmid9825383, year = {1998}, author = {Grimm, W and Glaveris, C and Hoffmann, J and Menz, V and Mey, N and Born, S and Maisch, B}, title = {Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: design and first results of the Marburg Cardiomyopathy Study.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {21}, number = {11 Pt 2}, pages = {2551-2556}, doi = {10.1111/j.1540-8159.1998.tb01217.x}, pmid = {9825383}, issn = {0147-8389}, mesh = {Arrhythmias, Cardiac/*epidemiology ; Cardiomyopathy, Dilated/*complications/epidemiology ; Death, Sudden, Cardiac/prevention &amp; control ; Defibrillators, Implantable ; Electrocardiography/methods ; Electrocardiography, Ambulatory/methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Research Design ; Risk Assessment ; Signal Processing, Computer-Assisted ; Time Factors ; }, abstract = {The Marburg Cardiomyopathy Study (MACAS) is a prospective, observational study designed to determine the value of the following potential noninvasive arrhythmia risk predictors in at least 200 patients with idiopathic dilated cardiomyopathy (IDC) over a 5-year follow-up period: NYHA-class, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, left bundle branch block and atrial fibrillation on ECG, QT/JT dispersion on 12-lead ECG, signal-averaged ECG, ventricular arrhythmias and heart rate variability (HRV) on 24-hour Holter ECG, baroreflex sensitivity, and microvolt T wave alternans during exercise. This article describes the findings among the first 159 patients with IDCs enrolled in MACAS until May 1998 (40 women, 119 men; age: 49 +/- 12 years; LVEF: 32 +/- 10%). Twenty-nine patients (18%) had atrial fibrillation and 130 patients (82%) were in sinus rhythm. Patients with sinus rhythm were further stratified according to LVEF < 30% (n = 54) versus LVEF > or = 30% (n = 76). Compared to patients with LVEF > or = 30%, patients with LVEF < 30% more often had left bundle branch block (43% vs 25%, P < 0.05), nonsustained VT (44% vs 22%, P < 0.05), decreased HRV (SDNN: 95 +/- 39 vs 128 +/- 42 ms, P < 0.01), decreased baroreflex sensitivity (5.6 +/- 4 vs 8.3 +/- 6 ms/mmHg, P < 0.01), and T wave alternans (59% vs 37%, P < 0.05). The prognostic significance of these findings will be determined by multivariate Cox analysis at the end of a 5-year follow-up. Primary endpoints in MACAS are overall mortality and arrhythmic events (i.e., sustained VT or VF, or sudden cardiac death).}, }
@article {pmid9816548, year = {1998}, author = {Okamura, K and Hayakawa, H and Kusagawa, M and Takahashi, H and Kosaka, A and Katsuta, K and Mizumoto, R}, title = {Treatment of pancreas head carcinoma in a 91-yr-old man. Report of a case successfully treated with pylorus-preserving pancreatoduodenectomy.}, journal = {International journal of pancreatology : official journal of the International Association of Pancreatology}, volume = {24}, number = {2}, pages = {133-138}, pmid = {9816548}, issn = {0169-4197}, mesh = {Aged ; Aged, 80 and over ; Angiography ; Carcinoma/*diagnostic imaging/pathology/*surgery ; Cholangiography ; Humans ; Lymph Node Excision ; Male ; Pancreatic Neoplasms/*diagnostic imaging/pathology/*surgery ; Pancreaticoduodenectomy/*methods ; Radiography, Abdominal ; Tomography, X-Ray Computed ; }, abstract = {The case of a 91-yr-old man who had a tumor of the pancreas head successfully resected is reported. He was admitted to our hospital because of obstructive jaundice, and then percutaneous transhepatic biliary drainage (PTBD) was performed. Cholangiography via PTBD tube showed marked stenosis of the bile duct in the head of the pancreas. Endoscopic retrograde pancreatography (ERP) showed obstruction of the main pancreatic duct in the head of the pancreas, and carcinoma in the head of the pancreas was diagnosed. Abdominal angiography showed stenosis of the celiac trunk caused by compression from the median arcuate ligament, but no tumor stain or encasement in the pancreas was detected. Because the patient had lived an extremely healthy life and had no serious concurrent disease before admission, laparotomy was performed. The tumor in the head of the pancreas was about 2 cm in diameter and restricted inside the pancreas. Pylorus-preserving pancreatoduodenectomy (PpPD) with regional lymph node dissection was performed. The tumor was 1.5 cm in its maximal diameter, and histopathologically was diagnosed as an invasive ductal carcinoma of the pancreas with moderately differentiated tubular adenocarcinoma. The patient had an uneventful postoperative course and now, 3 yr after surgery, he is doing very well and leading a normal daily life.}, }
@article {pmid9815608, year = {1997}, author = {Tamagawa, E and Ueda, M and Takahashi, S and Sugano, K and Uematsu, S and Mukai, M and Ogata, Y and Kitajima, M}, title = {Pancreatic lymph nodal and plexus micrometastases detected by enriched polymerase chain reaction and nonradioisotopic single-strand conformation polymorphism analysis: a new predictive factor for recurrent pancreatic carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {3}, number = {11}, pages = {2143-2149}, pmid = {9815608}, issn = {1078-0432}, mesh = {Adult ; Aged ; Carcinoma, Intraductal, Noninfiltrating/*genetics/mortality/*pathology/surgery ; Codon ; DNA, Neoplasm/genetics/isolation &amp; purification ; Disease-Free Survival ; Female ; *Genes, ras ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Pancreatic Neoplasms/*genetics/mortality/*pathology/surgery ; *Point Mutation ; Polymerase Chain Reaction/methods ; *Polymorphism, Single-Stranded Conformational ; Predictive Value of Tests ; Recurrence ; Survival Analysis ; Treatment Outcome ; }, abstract = {K-ras point mutations have been observed in approximately 90% of pancreatic carcinomas. We genetically analyzed cases of pancreatic regional lymph nodal and plexus micrometastases in invasive ductal carcinoma of the pancreas who were node negative or had metastases limited histopathologically to pancreaticoduodenal lymph nodes. These cases underwent curative resection in our institute. The utility of genetic analysis was compared with that of histopathological study, in terms of postoperative clinical outcome, as a predictive factor for recurrent pancreatic carcinoma. Samples for DNA extraction were obtained from formalin-fixed, paraffin-embedded specimens. A 0.5-microg quantity of DNA was subjected to enriched PCR and nonradioisotopic single-strand conformation polymorphism analysis. K-ras codon 12 mutations were detected in 83% (10 of 12) of invasive ductal carcinomas. In four cases, the genetic analysis of regional lymph nodal metastases and pancreatic plexus invasion of the pancreatic carcinoma yielded results concordant with those of histopathological analysis. In six cases, however, the metastases detected by genetic analysis were more advanced than was indicated by the histopathological examination. The survival rate of cases with metastases beyond the pancreaticoduodenal lymph nodes was significantly lower than that of cases with metastases limited to the pancreaticoduodenal lymph nodes or with no nodal involvement based on genetic analysis (P < 0.05). Intraoperative analysis of point mutations at K-ras codon 12 in the regional lymph nodes and the pancreatic plexus by enriched PCR/nonradioisotopic single-strand conformation polymorphism analysis is a highly accurate predictive factor for recurrent pancreatic carcinoma.}, }
@article {pmid9769473, year = {1998}, author = {Tsuda, H and Takarabe, T and Shimamura, K and Hirohashi, S}, title = {Detection of alterations in chromosomes 16 and 1 by fluorescence in situ hybridization in breast tumors cytologically or histologically equivocal for malignancy.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {66}, number = {6}, pages = {268-273}, doi = {10.1159/000028033}, pmid = {9769473}, issn = {1015-2008}, mesh = {Biopsy, Needle ; Breast Neoplasms/diagnosis/*genetics/*pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Case-Control Studies ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 16/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Phyllodes Tumor/diagnosis/genetics/pathology ; }, abstract = {Structural and numerical alterations, and fusion of chromosomes 16 and 1 have been shown to occur frequently in low-grade breast carcinoma, but not in benign papilloma by fluorescence in situ hybridization (FISH). We carried out FISH analysis of 11 benign tumors and 3 breast tumors for which the preoperative diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode tumor which was cytologically equivocal for malignancy, alteration of the chromosome 16 or 1 signal was not detected as a predominant cell clone. On the other hand, in 1 grade 1 invasive ductal carcinoma which was judged as equivocal for malignancy and 1 marked adenosis with atypia which was judged as malignant by fine-needle aspiration cytology, the majority of constituent tumor cells showed fusion of chromosomes 16 and 1. Detection of alterations in chromosomes 16 and 1 as a predominant clone was suggested to be an indicator of lesion malignancy even though the grade of malignancy may not be high. As a supportive diagnostic procedure, FISH analysis may give information about the nature of lesions, when the lesions are clinically or pathologically equivocal for cancer.}, }
@article {pmid9767470, year = {1998}, author = {Downing, JE and Virag, L and Jones, IW}, title = {NADPH diaphorase-positive dendritic profiles in rat thymus are discrete from autofluorescent cells, immunoreactive for inducible nitric oxide synthase, and show strain-specific abundance differences.}, journal = {Immunology}, volume = {95}, number = {1}, pages = {148-155}, pmid = {9767470}, issn = {0019-2805}, mesh = {Animals ; Autoimmune Diseases/*immunology ; Dendritic Cells/*enzymology ; Female ; Genetic Predisposition to Disease/immunology ; Histocytochemistry ; Male ; NADPH Dehydrogenase/analysis/*metabolism ; Nitric Oxide Synthase/analysis/antagonists &amp; inhibitors/*metabolism ; Nitric Oxide Synthase Type II ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Thymus Gland/immunology ; }, abstract = {Predisposition to autoimmune disorder in Lewis rats has been associated with abnormal hypothalamic regulation of circulating steroids, leading to inadequate suppression of T helper 1 (Th1) cell-mediated inflammatory reactions. In addition, autoimmune syndromes can be triggered within formerly resistant animals, following damage to the negative selection process of the thymus. A contribution to the autoimmune-susceptible phenotype may therefore derive from the status of thymic tolerance. One mechanism of intrathymic negative selection may involve nitric oxide. Because inducible nitric oxide synthase (iNOS) is known to be inhibitable by steroids, its expression might be different within strains having neuroendocrine disturbance. We report on a study to compare intrathymic iNOS expression in autoimmune-prone Lewis rats with other resistant strains. Interdigitating cells (IDC), darkly stained for diaphorase, were confirmed as immunoreactive for iNOS. They were located towards the medullary side of an accumulation of unstained, but autofluorescent cells (presumed to be macrophages) that circumscribes the corticomedullary zone. The role of iNOS+ IDC in the apoptotic deletion of T cells has been suggested by other studies. Despite the blunted steroidal condition reported for Lewis, nitrergic cell abundance was shown, by quantitative analysis of histochemical stain, to be on average approximately twofold lower compared with resistant strains (Fischer and Sprague-Dawley). This trend was evident in males and females, and confirmed by independent observers. We hypothesize that an intrathymic, iNOS-dependent mechanism may be important for the suppression of potentially autoreactive T-cell clones.}, }
@article {pmid9758360, year = {1998}, author = {Bentz, JS and Yassa, N and Clayton, F}, title = {Pleomorphic lobular carcinoma of the breast: clinicopathologic features of 12 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {11}, number = {9}, pages = {814-822}, pmid = {9758360}, issn = {0893-3952}, mesh = {Adult ; Aneuploidy ; *Apolipoproteins ; Apolipoproteins D ; Breast Neoplasms/genetics/mortality/*pathology ; Carcinoma, Lobular/genetics/mortality/*pathology ; Carrier Proteins/metabolism ; *Glycoproteins ; Humans ; Immunohistochemistry ; *Membrane Transport Proteins ; Middle Aged ; Neoplasm Proteins/metabolism ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {Pleomorphic lobular carcinoma (PLC) of the breast was recently identified as a histologic variant of infiltrating lobular carcinoma (ILC) with a poor prognosis. Twelve cases identified from a large series of breast carcinomas were studied retrospectively. Of 11 cases with adequate follow up, 9 were fatal. This was significantly worse than either infiltrating ductal carcinoma (IDC) or classical ILC (P < or = .002), even when stratified by axillary lymph node status. Among the fatal cases, the median survival time was 2.1 years, significantly shorter than that for classical lobular, but not ductal, carcinoma A distinctive pattern of in situ carcinoma, which has been described as PLC in situ, was identified in 7 of the 12 patients. This in situ component was composed of tumor cells with nuclear atypia, cytologically similar to the invasive tumor. Most PLCs lacked estrogen and progesterone receptors and stained with BRST-2, an antibody to gross cystic disease fluid protein-15, suggesting the presence of apocrine differentiation. In summary, PLC has many of the histologic features of ILC but has anaplastic nuclei, abundant cytoplasm, and apocrine differentiation. PLC is often aneuploid, usually lacks steroid receptors, and has a significantly poorer prognosis than does classical ILC.}, }
@article {pmid9741521, year = {1998}, author = {Grimm, W and Hoffmann, J and Menz, V and Luck, K and Maisch, B}, title = {Programmed ventricular stimulation for arrhythmia risk prediction in patients with idiopathic dilated cardiomyopathy and nonsustained ventricular tachycardia.}, journal = {Journal of the American College of Cardiology}, volume = {32}, number = {3}, pages = {739-745}, doi = {10.1016/s0735-1097(98)00306-4}, pmid = {9741521}, issn = {0735-1097}, mesh = {Adolescent ; Adult ; Aged ; *Cardiac Pacing, Artificial ; Cardiomyopathy, Dilated/*diagnosis/physiopathology/therapy ; Death, Sudden, Cardiac/etiology ; Defibrillators, Implantable ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk ; Tachycardia, Paroxysmal/*diagnosis/physiopathology/therapy ; Tachycardia, Ventricular/*diagnosis/physiopathology/therapy ; Ventricular Function, Left/physiology ; }, abstract = {OBJECTIVES: This study investigated the role of programmed ventricular stimulation (PVS) for arrhythmia risk prediction in patients with idiopathic dilated cardiomyopathy (IDC) and spontaneous nonsustained ventricular tachycardia (VT).<br><br>BACKGROUND: Nonsustained VT in patients with IDC has been associated with a high incidence of sudden cardiac death.<br><br>METHODS: Over the course of 4 years, 34 patients with IDC, a left ventricular (LV) ejection fraction < or = 35%, and spontaneous nonsustained VT underwent PVS. All patients were prospectively followed for 24+/-13 months.<br><br>RESULTS: Sustained ventricular arrhythmias were induced in 13 patients (38%). Sustained monomorphic VT was induced in three patients (9%), and polymorphic VT or ventricular fibrillation (VF) in another 10 patients (29%). No sustained ventricular arrhythmia could be induced in 21 study patients (62%). Prophylactic implantation of third-generation defibrillators (ICDs) with electrogram storage capability was performed in all 13 patients with inducible sustained VT or VF, and in nine of 21 patients (43%) without inducible sustained VT or VF. There were no significant differences between the additional use of amiodarone, d,I-sotalol, and beta-blocker therapy during follow-up in patients with and without inducible VT or VF. During 24+/-13 months of follow-up, arrhythmic events were observed in nine patients (26%) including sudden cardiac deaths in two patients and ICD shocks for rapid VT or VF in seven patients. Arrhythmic events during follow-up occurred in four of 13 patients with inducible ventricular arrhythmias compared with five of 21 patients without inducible ventricular arrhythmias at PVS (31% vs. 24%, p=NS).<br><br>CONCLUSION: PVS does not appear to be helpful for arrhythmia risk stratification in patients with IDC, a left ventricular ejection fraction < or =35%, and spontaneous nonsustained VT. Due to the limited number of patients, however, the power of this study is too small to exclude moderately large differences in outcome between patients with IDC with and without inducible VT or VF.}, }
@article {pmid9735416, year = {1998}, author = {Rio, PG and Pernin, D and Bay, JO and Albuisson, E and Kwiatkowski, F and De Latour, M and Bernard-Gallon, DJ and Bignon, YJ}, title = {Loss of heterozygosity of BRCA1, BRCA2 and ATM genes in sporadic invasive ductal breast carcinoma.}, journal = {International journal of oncology}, volume = {13}, number = {4}, pages = {849-853}, doi = {10.3892/ijo.13.4.849}, pmid = {9735416}, issn = {1019-6439}, mesh = {Adult ; Aged ; Aged, 80 and over ; Ataxia Telangiectasia Mutated Proteins ; BRCA1 Protein/*genetics ; BRCA2 Protein ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Cycle Proteins ; DNA-Binding Proteins ; Data Interpretation, Statistical ; Female ; Genes/*genetics ; Humans ; Loss of Heterozygosity/genetics ; Microsatellite Repeats/genetics ; Middle Aged ; Neoplasm Proteins/*genetics ; *Protein Serine-Threonine Kinases ; Proteins/*genetics ; Transcription Factors/*genetics ; Tumor Suppressor Proteins ; }, abstract = {The present study was undertaken to analyse the loss of heterozygosity (LOH) of the three genes, BRCA1, BRCA2 and ATM, and their correlation to clinicopathological parameters in sporadic breast cancer. We studied 59 sets of invasive ductal carcinoma, compared to matched normal control DNA. Microsatellite markers intragenic to BRCA1 (D17S1323, D17S1322, D17S855), BRCA2 (D13S1699, D13S1701, D13S1695) and ATM (D11S2179) were simultaneously used. In addition, one marker telomeric to BRCA2 (D13S1694) and four markers flanking ATM were analysed (D11S1816, D11S1819, D11S1294, D11S1818). Thirty-one per cent of the informative cases showed loss of heterozygosity for the BRCA1 gene, 22.8% for BRCA2 gene and 40% for ATM. LOH of BRCA1 correlated with high grade tumors (p=0.0005) and negative hormone receptors (p=0.01). LOH of ATM correlated with higher grade (p=0.03) and a younger age at diagnosis (p=0.03) in our set of tumors. No correlations were detected between BRCA2 LOH and any of the analysed clinicopathological parameters. However, a correlation was detected between allelic loss of the D13S1694 marker, telomeric to BRCA2, and larger tumor sizes and negative estrogen receptors, favoring the hypothesis of the presence of another putative tumor suppressor gene, telomeric to BRCA2, in the 13q12-q14 region. Only 11 tumors had LOH at more than one of the three genes, most of them (6/11) associated LOH of BRCA1 and ATM. One tumor only combined loss of the three genes BRCA1, BRCA2 and ATM.}, }
@article {pmid9727548, year = {1998}, author = {Luppi, P and Rudert, WA and Zanone, MM and Stassi, G and Trucco, G and Finegold, D and Boyle, GJ and Del Nido, P and McGowan, FX and Trucco, M}, title = {Idiopathic dilated cardiomyopathy: a superantigen-driven autoimmune disease.}, journal = {Circulation}, volume = {98}, number = {8}, pages = {777-785}, doi = {10.1161/01.cir.98.8.777}, pmid = {9727548}, issn = {0009-7322}, support = {DK-46864/DK/NIDDK NIH HHS/United States ; HL-46207/HL/NHLBI NIH HHS/United States ; HL-52589/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Antibody Formation ; Autoimmune Diseases/*blood ; Cardiomyopathy, Dilated/*etiology/immunology ; Child, Preschool ; Chlorocebus aethiops ; Female ; Genome, Human ; Humans ; Immunohistochemistry ; Infant ; Lymph Nodes/immunology ; Lymphocyte Activation ; Male ; Myocardium/immunology ; Receptors, Antigen, T-Cell/analysis ; Superantigens/*blood ; T-Lymphocytes/immunology ; Thymus Gland/immunology ; Vero Cells ; }, abstract = {BACKGROUND: Many cases of idiopathic dilated cardiomyopathy (IDC) result from an inflammatory myocarditis. The specific immunological mechanisms are not yet defined. Various autoimmune diseases are associated with superantigen-triggered immune responses, resulting in massive T-cell activation and tissue damage. We studied 3 cases in a search for evidence that such a phenomenon is also implicated in IDC.<br><br>METHODS AND RESULTS: Myocardial, lymph node, and thymic tissue samples were obtained from IDC patients who were undergoing heart transplantation. Infiltrating immune-cell phenotypes and gene expression of T-cell receptor (TCR) alpha- and beta-chain variable (Valpha and Vbeta) regions were analyzed by immunostaining and polymerase chain reaction. Similar technical approaches were used to assay the tissues for the presence of coxsackievirus B (CVB). In all the specimens analyzed, an overexpression of the TCR Vbeta3, Vbeta7, and Vbeta13.1 gene families was detected among the infiltrating T cells. These tissues were also found to be CVB3-positive. In vitro exposure of peripheral blood mononuclear cells to lysates of cells infected with CVB3 was capable of stimulating expansion of the same TCR Vbeta families. The TCR Valpha repertoire was never found to be skewed.<br><br>CONCLUSIONS: A superantigen-mediated immune response is involved in human heart disease. CVB3 may directly or indirectly trigger this response, suggesting a possible mechanistic link between CVB infection and myocarditis development progressing to IDC.}, }
@article {pmid9718175, year = {1998}, author = {Avisar, E and Khan, MA and Axelrod, D and Oza, K}, title = {Pure mucinous carcinoma of the breast: a clinicopathologic correlation study.}, journal = {Annals of surgical oncology}, volume = {5}, number = {5}, pages = {447-451}, doi = {10.1007/BF02303864}, pmid = {9718175}, issn = {1068-9265}, mesh = {Adenocarcinoma, Mucinous/*pathology/secondary/surgery ; Adult ; Age Factors ; Aged ; Breast Neoplasms/*pathology/surgery ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Ploidies ; Prognosis ; Receptors, Estrogen/analysis ; Retrospective Studies ; }, abstract = {BACKGROUND: Pure mucinous carcinoma (PMC) of the breast has a better prognosis than does invasive ductal carcinoma not otherwise specified and is more prevalent in older patients. We investigated the correlation between prognostic indices and clinical outcome in this histologic subset.<br><br>METHODS: A retrospective review was done of patients with PMC treated between 1989 and 1996. Demographic data, pathologic indices of prognosis, axillary nodal status, and outcome were assessed.<br><br>RESULTS: Out of 6083 cases of breast carcinoma, 30 were PMC. Only 3 of 25 (12%) axillary dissections were positive. The average age of the group with positive nodes was 57 years, as compared to 69.5 years (95% CI; 63.24-75.76) in the group with negative nodes. All the tumors with positive nodes were aneuploid and had a high nuclear grade, compared to a 31.25% aneuploidy rate in the group without nodal disease (P = .058). Negative ER receptors were found in only 2 of 20 (10%) of the patients tested. Both had axillary disease (P = .016). Tumor size did not correlate with axillary metastasis. Two of the 29 patients died from unrelated diseases. The other 27 patients are alive with no evidence of disease.<br><br>CONCLUSIONS: Axillary nodal disease is rare in PMC and correlates with a younger age, aneuploidy, high nuclear grade, or a negative ER receptor status. Sentinel lymph node biopsy may help identify the need for axillary dissection.}, }
@article {pmid9703774, year = {1998}, author = {Schenck, U}, title = {Fine needle aspiration and mammary secretion, cytology and core biopsy.}, journal = {Anticancer research}, volume = {18}, number = {3C}, pages = {2151-2153}, pmid = {9703774}, issn = {0250-7005}, mesh = {Biopsy/*methods ; Biopsy, Needle/*methods ; Breast/*cytology/*metabolism ; Breast Neoplasms/diagnosis/pathology ; Carcinoma in Situ/diagnosis/pathology ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Female ; Humans ; }, abstract = {Cytology of breast secretions, fine needle aspiration cytology (FNA) of the breast and core biopsy of the breast have been used for a long time. However, the application of the different approaches and their benefit for patients is still discussed. While FNA has challenged surgical biopsy since many years, additionally, core biopsy gets more important due to simplification of handling and decreasing tissue trauma. In conjunction with imaging techniques the number of necessary surgical biopsies has dramatically decreased in many places. Characteristics of the two approaches are tabulated in this contribution, which focuses on symptomatic patients presenting with either lumps of the breast or mammary secretions. Cytologic examination of breast secretions allows early diagnosis of intraductal carcinoma in situ and invasive ductal carcinoma in about 1% of all breast secretions. Careful localisation of the lesions is necessary. Most cases of breast cancer do not cause secretions, so, breast secretion cytology will contribute only in a minority of cases. In cases showing both, breast secretion and lumps, these should be considered as possibly caused by different lesions.}, }
@article {pmid9685946, year = {1998}, author = {de la Maza, A and Coderch, L and Gonzalez, P and Parra, JL}, title = {Subsolubilizing alterations caused by alkyl glucosides in phosphatidylcholine liposomes.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {52}, number = {1-2}, pages = {159-168}, doi = {10.1016/s0168-3659(97)00205-8}, pmid = {9685946}, issn = {0168-3659}, mesh = {Glucosides/*pharmacology ; Liposomes/*chemistry ; Micelles ; Phosphatidylcholines/*chemistry ; Solubility ; Structure-Activity Relationship ; Surface-Active Agents/*pharmacology ; }, abstract = {The subsolubilizing alterations caused by a series of alkyl glucosides (alkyl chain lengths ranging from C8 to C12) in unilamellar phosphatidylcholine (PC) liposomes were investigated. The surfactant to phospholipid molar ratios (RE) and the normalized bilayer/aqueous phase partition coefficients (K) were determined by monitoring the increase of the fluorescence intensity of liposome suspensions due to the 5(6)-carboxyfluorescein (CF) released from the interior of vesicles to the bulk aqueous phase. Given that the free surfactant concentrations was always lower than the critical micelle concentration (CMC) of the surfactant tested we may assume that the surfactant-liposome interactions were mainly ruled by the action of surfactant monomers. In general terms, the decrease in the surfactant alkyl chain length (or the rise in the surfactant CMC) resulted in an increase in the ability of these surfactants to alter the permeability of liposomes and, inversely, in an abrupt decrease in their affinity with these bilayers structures. The overall balance of these opposite tendencies shows that at the two interaction levels studied (50 and 100% of CF release) the nonyl and the octyl glucoside showed, respectively, the highest ability to alter the release of the CF trapped in bilayers (lowest RE values), whereas the dodecyl glucoside showed the highest degree of partitioning into liposomes or affinity with these bilayer structures (highest K values).}, }
@article {pmid9681624, year = {1998}, author = {Ozlük, A and Yildirim, E and Oral, S and Celen, O and Berberoğlu, U}, title = {Carcinomas of the thyroid and breast associated with Pendred's syndrome: report of a case.}, journal = {Surgery today}, volume = {28}, number = {6}, pages = {673-674}, pmid = {9681624}, issn = {0941-1291}, mesh = {Adenocarcinoma, Follicular/*complications ; Breast Neoplasms/*complications ; Carcinoma, Ductal, Breast/*complications ; Deafness/*complications/congenital ; Female ; Goiter/*complications ; Humans ; Middle Aged ; Neoplasms, Multiple Primary/*complications ; Syndrome ; Thyroid Neoplasms/*complications ; }, abstract = {We report herein the case of a 49-year-old woman with Pendred's syndrome who developed follicular carcinoma of the thyroid and invasive ductal carcinoma of the breast. To the best of our knowledge, this is the first case of different primary neoplasms developing in a patient with Pendred's syndrome.}, }
@article {pmid9665177, year = {1998}, author = {Campbell, ID and Downing, AK}, title = {NMR of modular proteins.}, journal = {Nature structural biology}, volume = {5 Suppl}, number = {}, pages = {496-499}, doi = {10.1038/733}, pmid = {9665177}, issn = {1072-8368}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Fibrillin-1 ; Fibrillins ; Fibronectins/chemistry ; Humans ; Magnetic Resonance Spectroscopy/*methods ; Microfilament Proteins/chemistry/genetics ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Proteins/*chemistry ; Sequence Homology, Amino Acid ; }, abstract = {NMR studies of domains, dissected from large modular proteins, are described. Particular emphasis is placed on modules from the extracellular proteins fibrillin-1 and fibronectin.}, }
@article {pmid9635530, year = {1998}, author = {Shen, KL and Harn, HJ and Ho, LI and Yu, CP and Chiu, SC and Lee, WH}, title = {The extent of proliferative and apoptotic activity in intraductal and invasive ductal breast carcinomas detected by Ki-67 labeling and terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling.}, journal = {Cancer}, volume = {82}, number = {12}, pages = {2373-2381}, doi = {10.1002/(sici)1097-0142(19980615)82:12&lt;2373::aid-cncr11&gt;3.0.co;2-m}, pmid = {9635530}, issn = {0008-543X}, mesh = {*Apoptosis ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma in Situ/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Cell Division ; Cell Survival ; DNA Fragmentation ; DNA Nucleotidylexotransferase/physiology ; DNA, Neoplasm/analysis ; Deoxyuracil Nucleotides ; Digoxigenin/analogs &amp; derivatives ; Female ; Genes, bcl-2/*genetics ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Middle Aged ; Neoplasm Invasiveness ; Receptors, Estrogen/*genetics ; Receptors, Progesterone/*genetics ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {BACKGROUND: The balance among cell proliferation, cell differentiation, and cell death determines the cell number in a population as well as the size or even the stage of a tumor. Thus, to improve our understanding of the pathogenesis of neoplasms, it is important to investigate the regulation of both cell proliferation and cell death.<br><br>METHODS: This study examined the occurrence of apoptosis and proliferative capacity in 46 breast carcinomas: 20 intraductal carcinomas (ductal carcinomas in situ [DCIS]) and 26 infiltrative ductal carcinomas (IDC). Terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling (TUNEL) and immunostaining with the Ki-67 antibody were used in the examination. A ladder of DNA fragments induced by apoptosis was demonstrated by means of DNA agarose gel electrophoresis in 10 of the available TUNEL positive and negative samples.<br><br>RESULTS: The results were correlated with p53, bcl-2, estrogen receptor (ER), and progesterone receptor (PR) protein expression, which would suggest association with apoptosis by immunohistochemistry. The apoptosis and proliferation of each cancer were expressed as the number of tumor cells undergoing apoptosis and proliferation per 1000 tumor cells. The extent of apoptosis was more frequently observed in DCIS than in IDC (21.9+/-6.8 vs. 4.0+/-0.9, P < 0.001), and the proliferation activity was significantly higher in IDC than in DCIS (16.8+/-6.5 vs. 3.5+/-0.8, P < 0.006). Apoptosis associated with MIB-1 positive cells and TUNEL labeling was significantly higher in IDC than in DCIS (3.26 vs. 0.42, P=0.001). In DCIS, apoptosis was correlated with p53 (r=0.663, P=0.005), and p53 had a reverse correlation with bcl-2 (r=0.620, P= 0.018). Moreover, bcl-2 expression was associated with ER (P=0.028) and PR (P= 0.005) expression in both DCIS and IDC.<br><br>CONCLUSIONS: The results of this study show that a higher degree of apoptosis and lower proliferation activity in intraductal carcinoma result in a steady-state, self-renewing condition in which net growth of the tumor is rare. The results also indicate that apoptosis was altered by the expression of p53, bcl-2, ER, and PR.}, }
@article {pmid9652759, year = {1998}, author = {Marsh, KL and Varley, JM}, title = {Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive carcinoma of the breast.}, journal = {British journal of cancer}, volume = {77}, number = {9}, pages = {1439-1447}, pmid = {9652759}, issn = {0007-0920}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/secondary ; Carcinoma, Ductal, Breast/*genetics/secondary ; Chromosomes, Human, Pair 9/*genetics ; DNA, Neoplasm/*genetics ; Female ; Genetic Markers/*genetics ; Humans ; Loss of Heterozygosity/*genetics ; Neoplasm Invasiveness/genetics ; }, abstract = {Twenty-three cases of ductal carcinoma in situ (DCIS), ten of which had an associated invasive component, were studied for loss of heterozygosity (LOH) of microsatellite markers on chromosome 9p and the results compared with a panel of 20 invasive breast carcinomas. In addition to the gene encoding p16, chromosome 9p is also thought to contain other putative tumour-suppressor genes. If the three panels of breast tumours showed LOH of markers in this region this would suggest that such putative genes were important in breast carcinogenesis. By studying both preinvasive and invasive breast tumours, it should also be possible to gain further information about the relationship between lesions of a different stage and to determine whether DCIS is indeed a precursor of invasive ductal carcinoma. Levels of LOH were low in the invasive-only set of tumours. Surprisingly, considerably higher levels of loss were observed in the tumours with an in situ component. Also, much heterogeneity was observed between different DCIS ducts or invasive tumour and DCIS from the same case.}, }
@article {pmid9652450, year = {1998}, author = {de Leeuw, N and Melchers, WJ and Balk, AH and de Jonge, N and Galama, JM}, title = {No evidence for persistent enterovirus infection in patients with end-stage idiopathic dilated cardiomyopathy.}, journal = {The Journal of infectious diseases}, volume = {178}, number = {1}, pages = {256-259}, doi = {10.1086/517448}, pmid = {9652450}, issn = {0022-1899}, mesh = {Adolescent ; Adult ; Cardiomyopathy, Dilated/*virology ; Enterovirus/genetics/*isolation &amp; purification/physiology ; Enterovirus Infections/*virology ; Female ; Heart/*virology ; Humans ; Male ; Middle Aged ; RNA, Viral/analysis ; }, abstract = {Persistence of enteroviruses in heart tissue has been implicated in the etiology of idiopathic dilated cardiomyopathy (IDC). Therefore, we determined the prevalence of enterovirus RNA in heart tissue from patients with end-stage IDC. During heart transplantation, 287 transmural biopsy specimens were aseptically collected from the explanted hearts of 38 patients with IDC and of 39 patients with cardiac failure of known cause. A nested polymerase chain reaction with general specificity for enteroviruses was used to screen for the presence of enterovirus RNA in the heart tissue samples. No enterovirus RNA was detected in any of the 287 heart biopsy specimens. These findings lead to a conclusion that enteroviruses do not persist in heart tissue from patients with end-stage IDC, nor with other heart diseases of known cause.}, }
@article {pmid9646066, year = {1998}, author = {La Vecchia, L and Bedogni, F and Castellani, A and Martini, M and Paccanaro, M and Sartori, M and Bozzola, L and Bevilacqua, P and Vincenzi, M}, title = {Assessment of right ventricular function and interstitial fibrosis in idiopathic dilated cardiomyopathy: hemodynamic correlates and prognostic value.}, journal = {Giornale italiano di cardiologia}, volume = {28}, number = {5}, pages = {513-523}, pmid = {9646066}, issn = {0046-5968}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*physiopathology ; Confounding Factors, Epidemiologic ; Endomyocardial Fibrosis/etiology/*physiopathology ; Female ; *Hemodynamics ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; *Ventricular Function, Right ; }, abstract = {BACKGROUND: Right ventricular (RV) function and morphometric quantitation of interstitial fibrosis in idiopathic dilated cardiomyopathy (IDC) have not been the subject of specifically designed clinical observations. In particular, their role in routine assessment and prognostic evaluation of patients (pts) with IDC remains to be settled.<br><br>METHODS: Eighty-one consecutive IDC patients (63 M, 18 F; mean age 52 +/- 11 yrs) with left ventricular (LV) systolic dysfunction (angiographic ejection fraction - EF - < 55%), normal coronary arteries and no histologic evidence of myocarditis were studied. Cardiac catheterization and endomyocardial biopsy (EMB) were routinely performed in all cases. RV volumes and EF were obtained by angiography according to Ferlinz' method and interstitial fibrosis was quantitated by computer-assisted morphometric analysis. These data were analyzed in order to study correlations with hemodynamic parameters and to assess their prognostic value in a long-term follow-up.<br><br>RESULTS: In the study population, right ventricular EF was significantly lower than in normal controls (35 +/- 11% vs 53 +/- 6%, p < 0.0001) and showed a significant positive correlation with LV EF (r = 0.54; p < 0.0001), and a weak but significant negative correlation with fibrosis (r = -0.29; p = 0.03). RV volumes, but not EF, were significantly related to mean pulmonary pressure. At multivariate analysis, RV end-diastolic volume (EDV) and EF were the two independent predictors of severe heart failure (NYHA class III-IV). After a mean follow-up of 64 +/- 36 months, 20 pts died and 9 had heart transplantation, for a 63% transplant-free survival rate (TFS). Multivariate analysis identified three independent predictors of TFS: LV stroke work index (p < 0.0001), RV stroke work index (p = 0.02) and RV EDV (p = 0.03). Fibrosis was predictive of survival only in the subgroup with LV EF < 20%.<br><br>CONCLUSIONS: Assessment of RV function provides useful information in the evaluation of hemodynamic profile and prognosis of pts with IDC. Quantitation of interstitial fibrosis by morphometry provides little additional data.}, }
@article {pmid9616213, year = {1998}, author = {Fentzke, RC and Korcarz, CE and Lang, RM and Lin, H and Leiden, JM}, title = {Dilated cardiomyopathy in transgenic mice expressing a dominant-negative CREB transcription factor in the heart.}, journal = {The Journal of clinical investigation}, volume = {101}, number = {11}, pages = {2415-2426}, pmid = {9616213}, issn = {0021-9738}, support = {HL54592/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Cardiomyopathy, Dilated/*etiology/metabolism/pathology ; Cyclic AMP Response Element-Binding Protein/*physiology ; Echocardiography ; Gene Expression Regulation ; Heart Failure/etiology ; Male ; Mice ; Mice, Transgenic ; Myocardium/*metabolism ; Myosin Heavy Chains/genetics ; Ventricular Function, Left ; }, abstract = {Idiopathic-dilated cardiomyopathy (IDC) is a common primary myocardial disease of unknown etiology characterized by progressive biventricular failure, cardiac dilatation, and premature mortality. Here we show that transgenic mice expressing a dominant-negative form of the CREB transcription factor (CREBA133) under the control of the cardiac myocyte-specific alpha-MHC promoter develop dilated cardiomyopathy that closely resembles many of the anatomical, physiological, and clinical features of human IDC. Between 2 and 20 wk of age, these mice develop four chamber cardiac dilatation, decreased systolic and diastolic left ventricular function, and attenuated contractile responses to the beta-adrenergic agonist, isoproterenol. Histologically, the CREBA133 hearts demonstrated both atrophic and hypertrophied fibers as well as significant interstitial fibrosis. These anatomical and hemodynamic changes were associated with hepatic congestion and peripheral edema, intracardiac thrombi, and premature mortality. Taken together, these results implicate CREB as an important regulator of cardiac myocyte function and provide a genetic model of dilated cardiomyopathy which should facilitate studies of both the pathogenesis and therapy of this clinically important disorder.}, }
@article {pmid9617588, year = {1998}, author = {Gunnes, G and Press, CM and Tverdal, A and Landsverk, T}, title = {Compartments within the lymph node cortex of calves and adult cattle differ in the distribution of leukocyte populations: an immunohistochemical study using computer-assisted morphometric analysis.}, journal = {Developmental and comparative immunology}, volume = {22}, number = {1}, pages = {111-123}, doi = {10.1016/s0145-305x(97)00038-4}, pmid = {9617588}, issn = {0145-305X}, mesh = {Age Factors ; Analysis of Variance ; Animals ; Antigens, CD/analysis ; B-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/cytology ; Cattle ; Histocompatibility Antigens Class II/analysis ; Image Processing, Computer-Assisted ; Immunohistochemistry ; *Jejunum ; Lymph Nodes/*anatomy &amp; histology/*immunology ; *Lymphocyte Subsets ; Receptors, Antigen, T-Cell, gamma-delta/analysis ; }, abstract = {The combination of an immunohistochemical technique and a panel of monoclonal antibodies was used to investigate the presence of leukocyte populations in the distal jejunal lymph node of 3-4 week old calves and adult cattle. The application of computer-assisted morphometric analysis enabled information to be obtained on the distribution of leukocyte populations in lymphoid compartments of the lymph node cortex. Semi-quantitative estimates of the areas of staining in histological sections showed that calves possessed significantly fewer B-cells and CD4+ cells in the outer cortex and significantly fewer T-cells (CD4+, CD8+ and gamma delta T-cells) in the deep cortex. These findings were interpreted to be a possible consequence of immunosuppression resulting from the passive transfer of maternal immunity in colostrum. The presence of some B-cell follicles in the region defined as the deep cortex suggested the on-going differentiation of this predominantly T-cell compartment. The larger presence of interdigitating cells (IDC) in the deep cortex of calves than adults was suggested by significantly larger CD1+ populations and it was argued that this could be the result of the confrontation with exogenous antigen faced by calves in early postnatal life. Antigen presenting populations, pan MHC II+ and MHC II DQ+ populations, were increased in all compartments of calf lymph nodes but were not significantly different from the populations in adult lymph nodes. Variance component analysis of the data generated in the present study showed that the image analysis technique was an effective and statistically powerful approach to investigate leukocyte populations within the specific microenvironments of the lymph node.}, }
@article {pmid9563954, year = {1998}, author = {Olson, TM and Michels, VV and Thibodeau, SN and Tai, YS and Keating, MT}, title = {Actin mutations in dilated cardiomyopathy, a heritable form of heart failure.}, journal = {Science (New York, N.Y.)}, volume = {280}, number = {5364}, pages = {750-752}, doi = {10.1126/science.280.5364.750}, pmid = {9563954}, issn = {0036-8075}, support = {5-P50-HL-53773/HL/NHLBI NIH HHS/United States ; M01-RR00064/RR/NCRR NIH HHS/United States ; }, mesh = {Actins/chemistry/*genetics/physiology ; Adolescent ; Adult ; Cardiomyopathy, Dilated/*genetics/metabolism/pathology ; Child ; Child, Preschool ; Chromosomes, Human, Pair 15 ; Exons ; Female ; Heart/physiopathology ; Humans ; Male ; *Mutation ; Myocardium/chemistry/pathology ; Pedigree ; Phenotype ; Polymorphism, Single-Stranded Conformational ; Protein Conformation ; Sarcomeres/physiology ; }, abstract = {To test the hypothesis that actin dysfunction leads to heart failure, patients with hereditary idiopathic dilated cardiomyopathy (IDC) were examined for mutations in the cardiac actin gene (ACTC). Missense mutations in ACTC that cosegregate with IDC were identified in two unrelated families. Both mutations affect universally conserved amino acids in domains of actin that attach to Z bands and intercalated discs. Coupled with previous data showing that dystrophin mutations also cause dilated cardiomyopathy, these results raise the possibility that defective transmission of force in cardiac myocytes is a mechanism underlying heart failure.}, }
@article {pmid9591734, year = {1998}, author = {Simpson, RH and Cope, N and Skálová, A and Michal, M}, title = {Malignant adenomyoepithelioma of the breast with mixed osteogenic, spindle cell, and carcinomatous differentiation.}, journal = {The American journal of surgical pathology}, volume = {22}, number = {5}, pages = {631-636}, doi = {10.1097/00000478-199805000-00015}, pmid = {9591734}, issn = {0147-5185}, mesh = {Actins/analysis ; Adenomyoma/*pathology/ultrastructure ; Breast Neoplasms/*pathology/ultrastructure ; Carcinoma/*pathology ; Fatal Outcome ; Female ; Humans ; Immunohistochemistry ; Microscopy, Electron ; Middle Aged ; Myoepithelioma/*pathology/ultrastructure ; Neoplasm Recurrence, Local/pathology ; Ossification, Heterotopic/*pathology ; Sarcoma/pathology ; }, abstract = {A 50-year-old woman had a malignant tumor of the left breast, which recurred twice, metastasized, and caused death after 39 months. Histologically, the original neoplasm and the first recurrence comprised an adenomyoepithelioma, in addition to a sarcoma composed of trabeculae of mature and immature bone, osteoid, and partly calcified, dense collagenous tissue. The trabeculae were lined by alpha-smooth muscle actin-positive mononuclear tumor cells, which also extended into the stroma. Similarly, scattered osteoclastlike, multinucleate giant cells were present in the stroma and in the region of the trabeculae. This same pattern of adenomyoepithelioma and osteosarcoma also was seen in the last recurrence, together with a proliferation of undifferentiated malignant spindle-shaped cells. The last biopsy also contained a separate small focus of invasive ductal carcinoma of usual type. It was concluded that this, apparently unique, tumor probably represented an adenomyoepithelioma in which a metaplastic sarcoma of osteogenic and undifferentiated types developed from the myoepithelial element, and in which a carcinoma developed from the epithelial component.}, }
@article {pmid9589904, year = {1998}, author = {Imai, Y and Yamakawa, M and Kasajima, T}, title = {The lymphocyte-dendritic cell system.}, journal = {Histology and histopathology}, volume = {13}, number = {2}, pages = {469-510}, doi = {10.14670/HH-13.469}, pmid = {9589904}, issn = {0213-3911}, mesh = {Animals ; Dendritic Cells/*immunology ; Humans ; Lymphocytes/*immunology ; Mice ; }, abstract = {Antigens provoke immune responses. The group of immunocompetent cells related directly to this response includes T and B cells, macrophages (M phi) and dendritic cells (DCs). DCs acting as antigen-presenting cells have been recently recognized to be important in initiating the immune response. B cells and follicular dendritic cells (FDCs), the major immunocompetent cells in the B-cell dependent area, play an important role in humoral immunity, while T cells and interdigitating cells (IDCs), which are the major immunocompetent cells in the T-cell dependent (TD)-area, play an important role in cellular immunity. The B cell-IDC interaction in the TD-area is also essential for the B-cell response against TD-antigen. Consequently, the lymphocyte-DC interaction is essential in the response to antigenic stimulation and in inducing the potent effector cells. B cell-DC, T cell-DC and DC-B cell-T cell interactions are regulated in predetermined sites by complex and varied mechanisms. Much recent evidence demonstrates that DCs modulate lymphocyte biology in its broadest aspects, including generation, differentiation, proliferation, and activation. In this review, we outline recent studies on the generation, structure, and function of lymphatic tissues, propose the concept of the "Lymphocyte-Dendritic Cell System (LDS)", and finally describe the significance and functions of this system in health and disease.}, }
@article {pmid9562249, year = {1998}, author = {Holt, JC and Hatcher, VB and Caulfield, JB and Norton, P and Umeda, PK and Melendez, JA and Martino, L and Mudzinsky, SP and Blumenstock, F and Slayter, HS and Margossian, SS}, title = {Cloning of the cDNA and nucleotide sequence of a skeletal muscle protease from myopathic hamsters.}, journal = {Molecular and cellular biochemistry}, volume = {181}, number = {1-2}, pages = {125-135}, pmid = {9562249}, issn = {0300-8177}, support = {HL44094/HL/NHLBI NIH HHS/United States ; HL49597/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *Cardiac Myosins ; Cardiomyopathy, Dilated/*enzymology ; Cloning, Molecular ; Cricetinae ; DNA, Complementary/*genetics ; Dogs ; Humans ; Molecular Sequence Data ; Molecular Weight ; Muscle, Skeletal/*enzymology ; Muscular Diseases/enzymology ; Myocardium/enzymology ; Myofibrils/enzymology ; Myosin Light Chains/metabolism ; Rats ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Serine Endopeptidases/chemistry/*genetics/isolation &amp; purification/metabolism ; Species Specificity ; }, abstract = {A neutral protease with an estimated Mr of about 26 kD and responsible for cleavage ofmyosin LC2 was isolated from hamster skeletal muscle. Complementary DNAs were generated by RT-PCR using total hamster muscle RNA and degenerate oligonucleotide primers based on the sequences of two internal peptides. The nucleotide sequences of the resultant cDNAs were subsequently determined and the complete amino acid sequence of the protease deduced. Although the hamster protein shared 63-85% identity in nucleotide and amino acid sequences with rat and mouse mast cell proteases, it had a higher degree of specificity for myosin LC2 than mast cell proteases which also digested myosin LC1 and myosin heavy chains. As a result, the hamster protease was designated mekratin because of its unique enzymatic specificities to distinguish it from other mast cell proteases. A polyclonal antibody was raised specific to the hamster muscle and human cardiac muscle mekratins without apparent cross-reaction with rat mast cell proteases. We have earlier demonstrated the presence in excess of a neutral protease that specifically cleaves LC2 in human hearts obtained at end stage idiopathic dilated cardiomyopathy (IDC). Western analyses revealed that heart tissue from patients with IDC contained 5-10 fold more mekratin than control samples. Furthermore, the level of the protease in human IDC tissues was similar to that seen in myopathic hamster skeletal muscle. No bands were recognized by the antibody when IDC myofibrils were probed due to the removal of soluble proteins during sample preparation. Thus, these results strongly suggest that the anti-mekratin antibody will provide positive identification of IDC in many cases and diagnosis by exclusion may be replaced.}, }
@article {pmid9554529, year = {1998}, author = {Ghoussoub, RA and Dillon, DA and D'Aquila, T and Rimm, EB and Fearon, ER and Rimm, DL}, title = {Expression of c-met is a strong independent prognostic factor in breast carcinoma.}, journal = {Cancer}, volume = {82}, number = {8}, pages = {1513-1520}, doi = {10.1002/(sici)1097-0142(19980415)82:8&lt;1513::aid-cncr13&gt;3.0.co;2-7}, pmid = {9554529}, issn = {0008-543X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Proteins/genetics/*metabolism ; Prognosis ; Proto-Oncogene Proteins c-met/genetics/*metabolism ; Receptors, Estrogen/metabolism ; Survival Rate ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: The c-met protooncogene encodes the met protein, the receptor for scatter factor/hepatocyte growth factor, a growth factor that modulates the motility and stable interaction of the epithelial cells. This study assesses the expression of met receptor in breast carcinoma and its prognostic value with respect to survival.<br><br>METHODS: Immunofluorescence was used to evaluate 91 archival breast carcinoma specimens using a polyclonal antibody to the cytoplasmic domain of the receptor. Cases were scored by two pathologists on a percentage basis and then converted to binary scores (positive or negative) on the basis of a bimodal distribution.<br><br>RESULTS: Strong expression of met was found in 20 invasive ductal breast tumor specimens (22%). The 5-year survival of patients whose tumors showed decreased met expression was 89%, in contrast to a 52% 5-year survival rate in patients whose tumors expressed met (P = 0.008). This trend also was observed in patients without lymph node metastases at presentation, in whom met negative patients had a 95% 5-year survival compared with only 62% for met positive patients (P = 0.006) Multivariate analysis using the Cox proportional hazards model showed met expression to be an independent predictor of survival, with a predictive value nearly equivalent to that associated with lymph node status.<br><br>CONCLUSIONS: The authors conclude that expression of met in patients with invasive ductal carcinoma of the breast is a strong, independent predictor of decreased survival and may be a useful prognostic marker with which to identify a subset of patients with more aggressive disease.}, }
@article {pmid9541473, year = {1998}, author = {Berndt, A and Borsi, L and Luo, X and Zardi, L and Katenkamp, D and Kosmehl, H}, title = {Evidence of ED-B+ fibronectin synthesis in human tissues by non-radioactive RNA in situ hybridization. Investigations on carcinoma (oral squamous cell and breast carcinoma), chronic inflammation (rheumatoid synovitis) and fibromatosis (Morbus Dupuytren).}, journal = {Histochemistry and cell biology}, volume = {109}, number = {3}, pages = {249-255}, doi = {10.1007/s004180050224}, pmid = {9541473}, issn = {0948-6143}, mesh = {Arthritis, Rheumatoid/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Squamous Cell/*metabolism/pathology ; Chronic Disease ; Dupuytren Contracture/*metabolism/pathology ; Female ; Fibronectins/*biosynthesis/genetics ; Humans ; In Situ Hybridization/*methods ; Inflammation ; Mouth Neoplasms/*metabolism/pathology ; Neoplasm Invasiveness ; RNA ; Synovial Fluid ; Synovitis/metabolism/pathology ; }, abstract = {The splicing variant of fibronectin containing the ED-B domain (oncofoetal fibronectin) occurs in foetal tissues, reparative processes, organ fibrosis and in tumour tissues. Consequently, a supportive effect of ED-B+ fibronectin for tissue remodelling and tumour progression is assumed. A non-radioactive RNA-RNA in situ hybridization protocol for the investigation of ED-B+ fibronectin synthesis applicable in human tissues is introduced. The ED-B+ fibronectin synthesis was investigated in human disease processes, for which the occurrence of ED-B+ fibronectin is well demonstrated by immunohistochemistry (rheumatoid arthritis, oral squamous cell carcinoma, invasive ductal carcinoma of the breast and nodular palmar fibromatosis). The ED-B+ fibronectin synthesis could be shown in lining cells and in endothelial cells of synovial villi in rheumatoid arthritis, in stromal cells of oral squamous cell carcinoma and invasive ductal carcinoma and in fibro-/myofibroblasts in the proliferative and early involutional phase of nodular palmar fibromatosis. By means of double labelling (alpha-smooth muscle actin immunostaining - ED-B+ fibronectin in situ hybridization), the ED-B+ fibronectin synthesis could be shown to be a typical feature of myofibroblasts. In contrast to the often diffuse ED-B+ fibronectin immunostaining, only a few synthetically active stromal cells were observed focally accentuated within the tumour, which were interpreted as hot spots of tumour-stroma interaction.}, }
@article {pmid9521061, year = {1998}, author = {Gerloni, M and Lo, D and Zanetti, M}, title = {DNA immunization in relB-deficient mice discloses a role for dendritic cells in IgM--&gt;IgG1 switch in vivo.}, journal = {European journal of immunology}, volume = {28}, number = {2}, pages = {516-524}, doi = {10.1002/(SICI)1521-4141(199802)28:02&lt;516::AID-IMMU516&gt;3.0.CO;2-M}, pmid = {9521061}, issn = {0014-2980}, support = {AI31583/AI/NIAID NIH HHS/United States ; AI36467/AI/NIAID NIH HHS/United States ; AI38375/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; DNA/*administration &amp; dosage/*immunology ; Dendritic Cells/*immunology ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Humans ; Immunoglobulin Class Switching/*genetics ; Immunoglobulin Constant Regions/genetics ; Immunoglobulin G/*biosynthesis/genetics ; Immunoglobulin M/*biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Proto-Oncogene Proteins ; Radiation Chimera ; Recombinant Fusion Proteins/genetics ; Spleen ; Transcription Factor RelB ; Transcription Factors/*deficiency/genetics ; Transgenes/immunology ; }, abstract = {A single intraspleen inoculation of plasmid DNA coding for an immunoglobulin heavy chain gene initiates immunity and establishes immunologic memory against the antigenic determinants of transgenic immunoglobulins, somatic transgene immunization. During priming mice produce IgM but not IgG1 antibodies. Since IgM --> IgG1 class switch occurs spontaneously during the primary immune response to protein antigens we investigated possible mechanisms for failure of spontaneous isotype switch in vivo in this model of immunity. We found that inoculation of plasmid DNA in the form of a chimeric gene coding for granulocyte-macrophage colony-stimulating factor (GM-CSF) was able to drive IgG1 class switch readily after priming. Since GM-CSF activates cells of the dendritic lineage we tested the possibility that dendritic cells (DC) may be involved in regulating IgM --> IgG1 switch. To this end we used bone marrow chimeras constructed from mice carrying the null mutation for the relB member of the NF-kappaB/Rel family as these mice lack bone marrow-derived mature DC. RelB (-/-) mice and (-/-) bone marrow chimeras inoculated with DNA/GM-CSF did not produce IgG1 antibodies during the primary immune response. Since relB (-/-) bone marrow chimeras lack DC of donor origin but possess resident follicular dendritic cells we conclude that Ig class switch in vivo is regulated by the function of interdigitating dendritic cells (IDC). Thus, IDC may contribute to the qualitative aspects of the emerging immune response.}, }
@article {pmid9502414, year = {1998}, author = {Ahmad, A and Hanby, A and Dublin, E and Poulsom, R and Smith, P and Barnes, D and Rubens, R and Anglard, P and Hart, I}, title = {Stromelysin 3: an independent prognostic factor for relapse-free survival in node-positive breast cancer and demonstration of novel breast carcinoma cell expression.}, journal = {The American journal of pathology}, volume = {152}, number = {3}, pages = {721-728}, pmid = {9502414}, issn = {0002-9440}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*enzymology/pathology ; Carcinoma in Situ/*enzymology/pathology/secondary ; Carcinoma, Ductal, Breast/*enzymology/pathology/secondary ; Carcinoma, Lobular/*enzymology/pathology/secondary ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lymph Nodes/enzymology ; Lymphatic Metastasis ; Matrix Metalloproteinase 11 ; Metalloendopeptidases/genetics/*metabolism ; Middle Aged ; Prognosis ; RNA, Messenger/biosynthesis ; Retrospective Studies ; }, abstract = {Stromelysin 3 (ST3) is a matrix metalloproteinase implicated in mammary carcinoma progression. To date, localization of ST3 expression in breast cancer by in situ hybridization and immunocytochemistry has shown that the expression of the enzyme is limited to only the stromal fibroblasts surrounding the cancer cells. We have immunostained a large group of ductal carcinoma in situ and invasive breast carcinomas using a monoclonal antibody (5ST-4A9) raised against the hemopexin-like domain of human ST3. We show that invasive lobular carcinomas express significantly less ST3 than invasive ductal carcinomas (IDCs) (P = 0.002). We also show, for the first time, that certain breast carcinoma cells that have undergone a degree of epithelial-to-mesenchymal transition, the so-called metaplastic carcinomas, can express ST3 mRNA and protein, which may in part explain the increased metastatic propensity seen in a number of these tumors. In addition, patients with IDC who had moderate to strong ST3 levels had significantly shorter disease-free survival than those with negative or weak ST3 levels (P = 0.02). Furthermore, in node-positive IDC patients, multivariate analysis revealed that ST3 level was a strong, independent prognostic parameter for disease-free survival (P = 0.005).}, }
@article {pmid9498754, year = {1998}, author = {Leenen, PJ and Radosević, K and Voerman, JS and Salomon, B and van Rooijen, N and Klatzmann, D and van Ewijk, W}, title = {Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {160}, number = {5}, pages = {2166-2173}, pmid = {9498754}, issn = {0022-1767}, mesh = {Animals ; Biomarkers/analysis ; CD13 Antigens/analysis/biosynthesis ; Clodronic Acid ; Dendritic Cells/classification/drug effects/*immunology/metabolism ; Ganciclovir/administration &amp; dosage ; HIV Long Terminal Repeat/genetics ; Herpesvirus 1, Human/enzymology/genetics ; Infusion Pumps, Implantable ; Liposomes/immunology ; Macrophages/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Phagocytosis/*immunology ; Radiation Chimera/immunology ; Spleen/anatomy &amp; histology/cytology/*immunology ; Thymidine Kinase/genetics ; }, abstract = {In the normal mouse spleen, two distinct populations of dendritic cells (DC) are present that differ in microanatomical location. The major population of marginal DC is found in the "marginal zone bridging channels" and extends into the red pulp. The interdigitating cells (IDC) are localized in the T cell areas in the white pulp. The aim of the present study was to characterize these two splenic DC populations with regard to their phenotype, in vivo phagocytic function, and turnover. Both marginal DC and IDC are CD11c+ and CD13+, but only IDC are NLDC-145+ and CD8alpha+. Notably, both populations, when freshly isolated, express the macrophage markers F4/80, BM8, and Mac-1. To study the phagocytic capacity of these cells, we employed the macrophage "suicide" technique by injecting liposomes loaded with clodronate i.v. Marginal DC, but not IDC, were eliminated by this treatment. Phagocytosis of DiI-labeled liposomes by DC confirmed this finding. The two DC populations differed significantly with regard to their turnover rates, as studied in a transgenic mouse model of conditional depletion of DC populations with high turnover. In these mice, marginal DC were completely eliminated, but the IDC population remained virtually intact. From these data we conclude that the marginal DC population has a high turnover, in contrast to the IDC population. Taken together, the present results indicate that marginal DC and IDC represent two essentially distinct populations of DC in the mouse spleen. They differ not only in location, but also in phenotype, phagocytic ability, and turnover.}, }
@article {pmid9491141, year = {1998}, author = {Tsubosa, Y and Fukutomi, T and Tsuda, H and Kanai, Y and Akashi-Tanaka, S and Nanasawa, T and Linuma, G and Ushio, K}, title = {Breast cancer in Cowden's disease: a case report with review of the literature.}, journal = {Japanese journal of clinical oncology}, volume = {28}, number = {1}, pages = {42-46}, doi = {10.1093/jjco/28.1.42}, pmid = {9491141}, issn = {0368-2811}, mesh = {Breast Neoplasms/*etiology/surgery ; Carcinoma, Ductal, Breast/*etiology/surgery ; Endometrial Neoplasms/pathology ; Female ; Hamartoma Syndrome, Multiple/diagnostic imaging/*pathology ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Radiography ; }, abstract = {We report a case of invasive breast cancer in a 62-year-old female patient with Cowden's disease. A left modified radical mastectomy was performed and histopathology of the tumor showed invasive ductal carcinoma, histological grade 3, without lymph node metastasis. The patient had a past history of endometrial cancer at 55 but did not have a family history of malignant disease. Goiter was palpable but aspiration cytology revealed no malignancy. There were several papillomas on the oral mucosa and multiple papillomatous lesions on the right femur. Barium X-ray and endoscopic examination revealed multiple, small, hyperplastic polypoid lesions on the esophagus, stomach and rectum. Histopathology of the biopsy specimens from the esophagus and stomach showed acanthotic squamous epithelium and foveolar hyperplastic polyps. The patient was followed up closely to monitor the thyroid lesions and polyposis of the digestive tract. A total of 12 breast cancer patients who also had Cowden's disease have been reported in Japan and these cases are reviewed in this report.}, }
@article {pmid9467958, year = {1998}, author = {Burger, A and Li, H and Zhang, XK and Pienkowska, M and Venanzoni, M and Vournakis, J and Papas, T and Seth, A}, title = {Breast cancer genome anatomy: correlation of morphological changes in breast carcinomas with expression of the novel gene product Di12.}, journal = {Oncogene}, volume = {16}, number = {3}, pages = {327-333}, doi = {10.1038/sj.onc.1201517}, pmid = {9467958}, issn = {0950-9232}, mesh = {Amino Acid Sequence ; Animals ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cloning, Molecular ; DNA, Complementary ; DNA, Neoplasm ; Female ; Gene Expression ; Humans ; Molecular Sequence Data ; Neoplasm Proteins/biosynthesis/chemistry/*genetics ; Protein Biosynthesis ; Proteins/chemistry/*genetics ; RNA, Messenger ; RNA, Neoplasm ; Rabbits ; Sequence Analysis ; Tumor Cells, Cultured ; }, abstract = {To determine which genes may be activated or inactivated during breast cancer development, we employed two cloning strategies (subtractive hybridization and differential display) using RNA samples from a human breast tumor and its matching normal breast cell line. Of 950 clones isolated, 102 cDNA inserts were analysed by DNA sequencing and database searching. We found 30 clones that were obviously unidentified, with no significant homology to any listed human gene. We focused upon one of the novel genes, Di12, that is differentially expressed as a 1.35 kb RNA in breast cancer tissues and cell-lines, and in several normal tissues. A full length cDNA of this gene was cloned, and its DNA sequence revealed an open reading frame of 339 amino acids. Antibodies to the ten N-terminal amino acids were developed to investigate the expression of Di12 in breast cancer cell-lines and tumors. The Di12 protein was found in tissue sections of infiltrating ductal carcinomas (IDCs), but not in benign or normal breast specimens. RT-PCR analysis confirmed expression of Di12 in 80% of infiltrating ductal carcinomas (IDCs). As IDC constitutes approximately 70% of breast cancers seen clinically, the level of Di12 expression may be predictive of disease progression.}, }
@article {pmid9441154, year = {1997}, author = {Müller, J and Wallukat, G and Weng, YG and Dandel, M and Spiegelsberger, S and Semrau, S and Brandes, K and Bieda, H and Hummel, M and Loebe, M and Meyer, R and Hetzer, R}, title = {[Temporary mechanical left heart support. Recovery of heart function in patients with end-stage idiopathic dilated cardiomyopathy].}, journal = {Herz}, volume = {22}, number = {5}, pages = {227-236}, pmid = {9441154}, issn = {0340-9937}, mesh = {Adult ; Autoantibodies/blood ; Cardiomyopathy, Dilated/physiopathology/*therapy ; Echocardiography ; Endomyocardial Fibrosis/physiopathology/therapy ; Female ; Follow-Up Studies ; Heart Failure/physiopathology/*therapy ; *Heart-Assist Devices ; Hemodynamics/*physiology ; Humans ; Male ; Middle Aged ; Receptors, Adrenergic, beta-1/immunology ; Shock, Cardiogenic/physiopathology/therapy ; Ventricular Function, Left/*physiology ; }, abstract = {BACKGROUND: Implantation of a mechanical cardiac support system (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. Our experience now includes 13 patients who have been "weaned" from MCSS and we report about the overall results of this treatment as well as the effects of ventricular unloading on cardiac function, anti-beta 1-adrenoceptor-autoantibody (A-beta 1-AAB) level and the degree of myocardial fibrosis.<br><br>METHODS: 13 patients with non-ischemic IDC who had been admitted here in cardiogenic shock (CI < 1.61.min-1.m2, left ventricular ejection fraction [LVEF] < 16% and left ventricular internal diameter in diastole [LVIDd] > 68 mm) and who all tested positive for A-beta 1-AABs were implanted with an uni-(12 patients) or a biventricular (1 patient) mechanical assist device. Echocardiographic evaluation and A-beta 1-AAB-level-monitoring was routinely performed after implantation and explantation of the MCSS and the degree of myocardial fibrosis was assessed at the time of implantation and after explantation.<br><br>RESULTS: During a mean duration of mechanical support of 236 +/- 201 days (range: 30 to 794 days), LV-EF improved to a mean of 46% and LVIDd decreased to a mean value of 56 mm in these 13 patients. A-beta 1-AABs decreased and disappeared 11.7 weeks after implantation of the device and did not reincrease thereafter. The highly pathologic degree of fibrosis at the time of implantation diminished to normal values about 1 year after explantation. One patient died of anesthesiologic complications and another patient shortly presented with a new episode of cardiac insufficiency 6 months after explantation. He was implanted again with an univentricular assist device was successfully transplanted 3 weeks later. Mean observation period of the remaining 11 patients now amounts to 12.6 +/- 9.77 (range: 3 to 26) months after explantation of the device--as of May, 31, 1997--with a cumulative observation period of 139 patient months.<br><br>CONCLUSION: Temporary implantation of a MCSS may normalize cardiac function in selected patients with IDC. The striking degree of myocardial fibrosis can reduce to normal values after explantation of the device. A-beta 1-AABs disappear during ventricular unloading and do not increase thereafter. "Weaning" from mechanical device may constitute an alternative treatment to cardiac transplantation in selected patients.}, }
@article {pmid9416940, year = {1997}, author = {Sun, JP and James, KB and Yang, XS and Solankhi, N and Shah, MS and Arheart, KL and Thomas, JD and Stewart, WJ}, title = {Comparison of mortality rates and progression of left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy and dilated versus nondilated right ventricular cavities.}, journal = {The American journal of cardiology}, volume = {80}, number = {12}, pages = {1583-1587}, doi = {10.1016/s0002-9149(97)00780-7}, pmid = {9416940}, issn = {0002-9149}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cardiomyopathy, Dilated/complications/diagnostic imaging/*mortality/pathology ; Dilatation, Pathologic ; Disease Progression ; Echocardiography ; Female ; Heart Ventricles/diagnostic imaging/*pathology ; Humans ; Male ; Middle Aged ; Risk Factors ; Survival Rate ; Ventricular Dysfunction, Left/*complications/diagnostic imaging/pathology ; }, abstract = {This study assesses the influence of right ventricular (RV) dilation on the progression of left ventricular (LV) dysfunction and survival in patients with idiopathic dilated cardiomyopathy (IDC). Using transthoracic echocardiography, we studied 100 patients with IDC aged 20 to 80 years (mean 55 +/- 14); 67% were men. In the apical 4-chamber view, diastolic LV and RV chamber area measurements classified patients into 2 groups: group RV enlargement+ (RV area/LV area > 0.5) included 54 patients; group RV enlargement- (no RV enlargement) had RV area/LV area < or = 0.5. Echocardiographic studies were repeated in all patients after a mean of 33 +/- 16 months. At the time of the initial study, the 2 groups did not differ in age, gender, incidence of atrial fibrillation and diabetes, left ventricular mass, and LV ejection fraction, but the RV enlargement+ group had more severe tricuspid regurgitation and less LV enlargement. After 47 +/- 22 months (range 12 to 96), patients in group RV enlargement+ had lower LV ejection fraction (29% vs 34%, p = 0.006) than patients with initial RV enlargement-. At clinical follow-up, mortality was higher (43%) in patients with initial RV enlargement+ than the RV enlargement- patients (15%), p = 0.002. For survivors, the mitral deceleration time averaged 157 +/- 36 ms; for nonsurvivors or patients who required transplant, the mitral deceleration time averaged 97 +/- 12 ms (p < 0.0001). With use of a multivariate Cox model adjusting for LV ejection fraction, LV size, and age, the relative risk ratio of mortality from initial RV enlargement+ was 4.4 (95% confidence limits 1.7 to 11.1) (p = 0.002). Thus, patients with significant RV dilation had nearly triple the mortality over 4 years and more rapidly deteriorating LV function than patients with less initial RV dilation. In IDC, RV enlargement is a strong marker for adverse prognosis that may represent a different morphologic subset.}, }
@article {pmid9410910, year = {1997}, author = {Lowes, BD and Minobe, W and Abraham, WT and Rizeq, MN and Bohlmeyer, TJ and Quaife, RA and Roden, RL and Dutcher, DL and Robertson, AD and Voelkel, NF and Badesch, DB and Groves, BM and Gilbert, EM and Bristow, MR}, title = {Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.}, journal = {The Journal of clinical investigation}, volume = {100}, number = {9}, pages = {2315-2324}, pmid = {9410910}, issn = {0021-9738}, support = {5MO 1 RR00051/RR/NCRR NIH HHS/United States ; HL-48013/HL/NHLBI NIH HHS/United States ; }, mesh = {Atrial Natriuretic Factor/metabolism ; Calcium-Transporting ATPases/genetics ; Cardiomegaly/genetics ; Gene Expression Regulation ; Heart Failure/genetics ; Humans ; Hypertension, Pulmonary/genetics ; Myocardium/*metabolism ; Myosin Heavy Chains/*genetics ; RNA, Messenger/genetics ; Receptors, Adrenergic, beta/genetics ; Tissue Distribution ; }, abstract = {Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of beta1-receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of beta2-receptor gene expression in PPH but not IDC. The major new findings were that (a) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of alpha-myosin heavy chain mRNA (alpha-MHC, 23-34% of total), and (b) in heart failure alpha-MHC was downregulated (by 67-84%) and beta-MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial alpha-MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction.}, }
@article {pmid9387168, year = {1997}, author = {Koizumi, T and Kawano, T and Kazekawa, K and Kawaguchi, T and Honma, T and Kaneko, Y and Dosaka, A and Tabuchi, K}, title = {[Histological findings in aneurysm treated with IDC: scanning electron microscopical study].}, journal = {No shinkei geka. Neurological surgery}, volume = {25}, number = {11}, pages = {1027-1031}, pmid = {9387168}, issn = {0301-2603}, mesh = {Aged ; Embolization, Therapeutic/*instrumentation/methods ; Endothelium, Vascular/ultrastructure ; Humans ; Intracranial Aneurysm/*pathology/*therapy ; Male ; Microscopy, Electron, Scanning ; }, abstract = {We reported the scanning electron microscopic findings of an aneurysm embolized with interlocking detachable coils (IDC). A 78-year-old man was referred to our hospital because of left hemiparesis and dysphagia. CT scan showed multiple lacunar infarction in the bilateral corona radiata. Angiography demonstrated a small incidental aneurysm of the right internal carotid artery (IC-PC junction). The left hemiparesis gradually improved and 2 weeks after admission the aneurysm was treated with IDC. Three coils were placed in the aneurysm and post-operative angiography demonstrated complete embolization. Dysphagia caused by the pseudobulbar pulse did not improve and, 4 weeks after endovascular surgery, the patient died of aspiration pneumonia. An autopsy was performed and the scanning electron microscopical findings of the aneurysm showed development of endothelial cells on the coil surface. Many clinical reports supported the usefulness of Guglielmi detachable coils (GDC) and several experimental reports demonstrated the intimal proliferation in aneurysms embolized with coils. However, pathological changes of the aneurysms treated with coils have been reported in only four clinical cases. There was no evidence of endothelialization in any of these cases. To our knowledge, our case is the first report describing the endothelial proliferation over the coils. It is necessary to accumulate histopathological data and long-term follow-up in humans treated with coils.}, }
@article {pmid9370944, year = {1997}, author = {Poulsom, R and Hanby, AM and Lalani, EN and Hauser, F and Hoffmann, W and Stamp, GW}, title = {Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium.}, journal = {The Journal of pathology}, volume = {183}, number = {1}, pages = {30-38}, doi = {10.1002/(SICI)1096-9896(199709)183:1&lt;30::AID-PATH1085&gt;3.0.CO;2-K}, pmid = {9370944}, issn = {0022-3417}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Blotting, Northern ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Lobular/metabolism ; Female ; Growth Substances/genetics/*metabolism ; Humans ; Hyperplasia/metabolism ; Immunoenzyme Techniques ; In Situ Hybridization ; *Mucins ; *Muscle Proteins ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; *Neuropeptides ; Peptides/genetics/*metabolism ; Precancerous Conditions/*metabolism ; Proteins/genetics/*metabolism ; RNA, Messenger/genetics ; Trefoil Factor-1 ; Trefoil Factor-2 ; Trefoil Factor-3 ; Tumor Suppressor Proteins ; }, abstract = {pS2-TFF 1 is expressed in breast cancers and has been investigated as a potential prognostic factor reflecting oestrogen dependence. The relationship to the expression of other trefoil peptides, human spasmolytic polypeptide (hSP-TFF 2) and intestinal trefoil factor (hITF/hPI.B-TFF 3) is documented here. Fifty-seven breast specimens were selected from surgical pathology archives and included five normal breasts (two lactating), seven benign proliferative lesions, 11 ductal carcinomas in situ (DCIS), three lobular carcinomas in situ (LCIS), 24 invasive ductal carcinomas (IDC), and seven invasive lobular carcinomas (ILC). The comparative distribution of trefoil mRNAs was assessed by in situ hybridization using 35S-labelled riboprobes and immunohistochemical staining for pS2-TFF 1 and hSP-TFF 2. pS2-TFF 1 and hITF/hPI.B-TFF 3 mRNA were focally present at low signal intensity in normal and benign breast. Both pS2-TFF 1 and hITF/hPI.B-TFF 3 were expressed in all DCIS, LCIS and ILC, and 21/24 IDC. Overall, expression patterns of pS2-TFF 1 and hITF/hPI.B-TFF 3 coincided, but hITF/hPI.B-TFF 3 mRNA was usually found in a greater proportion of cells. Expression of hSP-TFF 2 peptide or mRNA was not detected in any of these cases. MCF 7 breast carcinoma cells also expressed hITF/hPI.B-TFF 3 and pS2-TFF 1 mRNAs but not hSP-TFF 2. hITF/hPI.B-TFF 3 co-expression with pS2-TFF 1 may act as a prognostic factor, but also raises questions about the regulatory pathway for pS2-TFF 1 hITF/hPI.B-TFF 3. Trefoil factors have effects on cell motility and spreading in vitro, and co-expression of hITF/hPI.B-TFF 3 with pS2-TFF 1 could be functionally significant if they form a heterodimer or compete for receptor binding. Absence of hSP-TFF 2 expression may be of equal relevance to tumour cell biology.}, }
@article {pmid9359548, year = {1997}, author = {Arbustini, E and Grasso, M and Porcu, E and Bellini, O and Diegoli, M and Fasani, R and Banchieri, N and Pilotto, A and Morbini, P and Dal Bello, B and Campana, C and Gavazzi, A and Viganò, M}, title = {Enteroviral RNA and virus-like particles in the skeletal muscle of patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {80}, number = {9}, pages = {1188-1193}, doi = {10.1016/s0002-9149(97)00638-3}, pmid = {9359548}, issn = {0002-9149}, mesh = {Adult ; Autoimmune Diseases/immunology/virology ; Cardiomyopathy, Dilated/immunology/*virology ; Case-Control Studies ; Enterovirus Infections/*complications/diagnosis/immunology ; Female ; Heart/virology ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*virology ; Polymerase Chain Reaction ; RNA, Viral/*analysis ; Recurrence ; Virion/*isolation &amp; purification ; }, abstract = {The role of chronic viral infection in the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) has generated considerable research. Enteroviruses were the favorite candidates as etiologic agents of IDC. However, enteroviruses were rarely demonstrated in affected hearts. We investigated whether enteroviral infection persists in the heart and in extracardiac sites, particularly in skeletal muscle, in patients with IDC. Blood and myocardial and skeletal muscle samples were collected at cardiac transplantation from 31 IDC patients, 24 non-IDC heart disease patients, and 3 heart donors. Samples underwent ultrastructural studies and ribonucleic acid (RNA) extraction. RNA was reverse-transcribed, and 2 nested fragments (bps 179 and 126) were amplified in the highly conserved 5' noncoding region of enteroviral genomic RNA. Enteroviral RNA was found in the skeletal muscle of 12 cases, whereas only 4 hearts (2 of which with positive skeletal muscle) were positive. Of the 24 controls, 2 were positive (1 muscle and heart, 1 muscle only). Automated sequencing confirmed the enteroviral nature of the amplified products. Ultrastructural study showed enterovirus-like particles in 4 of the enterovirus-positive muscles, and myopathic changes in all enterovirus-positive cases. Skeletal muscle hosts chronic enteroviral infection in more than one third of patients with sporadic IDC. Two hypotheses may explain this link. Myocardial damage may derive directly from recurrent subclinical heart infections caused by enteroviruses harbored in skeletal muscle. Alternatively, enterovirus-related myopathy may trigger an autoimmune response to antigens shared by muscle and myocardium. Further studies are needed to assess the importance of these, non-mutually exclusive mechanisms in IDC pathogenesis.}, }
@article {pmid9355973, year = {1997}, author = {Nishizaki, T and Chew, K and Chu, L and Isola, J and Kallioniemi, A and Weidner, N and Waldman, FM}, title = {Genetic alterations in lobular breast cancer by comparative genomic hybridization.}, journal = {International journal of cancer}, volume = {74}, number = {5}, pages = {513-517}, doi = {10.1002/(sici)1097-0215(19971021)74:5&lt;513::aid-ijc6&gt;3.0.co;2-6}, pmid = {9355973}, issn = {0020-7136}, support = {CA44768/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism ; Bromodeoxyuridine/metabolism ; Cadherins/analysis ; Carcinoma, Ductal, Breast/genetics/metabolism ; Carcinoma, Lobular/*genetics/metabolism ; Chromosome Aberrations ; DNA, Neoplasm/*genetics/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Nucleic Acid Hybridization ; }, abstract = {Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are distinguished by their histopathological appearance. However, little is known about the differences in genetic changes between lobular cancers and ductal cancers. We used comparative genomic hybridization (CGH) and compared aberrations in 19 ILCs and 46 IDCs. The total number of aberrations was lower in ILC than in IDC. While the average number of DNA copy number losses did not reach significance between them, copy number gains were significantly lower in ILCs. Fifteen of 19 ILCs (79%) showed increased copy number of 1q, and 12 cases (63%) revealed loss of 16q. The presence of these aberrations was independent of nodal status, histologic subtypes (pleomorphic or classic ILC), or BrdUrd-labeling index. ILCs had a higher frequency of 16q loss than did ductal cancers, and a lower frequency of 8q and 20q gains. Our data suggest that the altered growth pattern and clinical presentation which characterize infiltrating lobular cancers are correlated with distinct genetic alterations.}, }
@article {pmid9352975, year = {1997}, author = {Pohlner, K and Portig, I and Pankuweit, S and Lottspeich, F and Maisch, B}, title = {Identification of mitochondrial antigens recognized by antibodies in sera of patients with idiopathic dilated cardiomyopathy by two-dimensional gel electrophoresis and protein sequencing.}, journal = {The American journal of cardiology}, volume = {80}, number = {8}, pages = {1040-1045}, doi = {10.1016/s0002-9149(97)00600-0}, pmid = {9352975}, issn = {0002-9149}, mesh = {Adult ; Amino Acid Sequence ; Autoantigens/*blood ; Cardiomyopathy, Dilated/*immunology ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Male ; Middle Aged ; Mitochondria/*immunology ; Molecular Sequence Data ; }, abstract = {Antimitochondrial antibodies in sera of patients with idiopathic dilated cardiomyopathy (IDC) have been described previously, but the corresponding antigens have not been analyzed systematically. We therefore used both 1-dimensional and high-resolution 2-dimensional gel electrophoresis followed by immunoblotting and N-terminal amino acid sequencing to identify the relevant mitochondrial antigens, which are recognized by serum antibodies. Sera were obtained from patients with IDC (n = 75) and healthy controls (n = 182). For detection of antimitochondrial antibodies the mitochondrial antigen fraction, consisting of submitochondrial particles isolated from a bovine heart, was separated on SDS-PAGE and all sera were examined by immunoblot analysis. For further characterization of the mitochondrial epitopes the antigen fraction was separated in the first dimension according to isoelectric points using isoelectric focusing followed by gel electrophoresis. Proteins recognized by serum antibodies in 2-dimensional immunoblots were analyzed by N-terminal amino acid sequencing. In 1-dimensional immunoblot analysis, 51% of patients with IDC and 34% of controls contained serum antibodies reacting with mitochondrial protein bands with molecular weights of about 30, 43, 60, and preferentially 50 to 55 and 70 to 75 kD (p <0.01). We identified a 75-kD subunit of nicotinamide-adenine dinucleotide dehydrogenase (17% in IDC patients vs 5% in controls, p <0.05) and 2 core proteins of ubiquinol-cytochrome-c reductase (core P1: 39% in IDC patients vs 15% in controls, p <0.05; core P2: 20% in IDC patients vs 10% in controls, p <0.1), both enzymes of the respiratory chain, as are most relevant mitochondrial antigens. Furthermore, serum antibodies of patients with IDC were directed against lipoamide-dehydrogenase (15% vs 10% in controls) and a subunit of pyruvate-dehydrogenase (9% vs 3% in controls). Because these antigens play an important role in energy metabolism, the respective antibodies can be more than merely diagnostic markers of cell damage. To attribute them also to pathogenetic relevance appears to be a most attractive but still speculative hypothesis.}, }
@article {pmid9339958, year = {1997}, author = {Hjalmarson, A and Kneider, M and Waagstein, F}, title = {The role of beta-blockers in left ventricular dysfunction and heart failure.}, journal = {Drugs}, volume = {54}, number = {4}, pages = {501-510}, pmid = {9339958}, issn = {0012-6667}, mesh = {Adrenergic beta-Antagonists/administration &amp; dosage/*therapeutic use ; Blood Pressure/drug effects ; Cardiac Output/drug effects ; Cardiomyopathy, Dilated/*drug therapy/etiology/mortality ; Dose-Response Relationship, Drug ; Exercise Test/drug effects ; Humans ; Length of Stay ; Myocardial Infarction/complications/drug therapy ; Myocardial Ischemia/drug therapy/mortality ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Ventricular Dysfunction, Left/*drug therapy ; }, abstract = {It was first reported by our group in 1975 that heart failure due to idiopathic dilated cardiomyopathy (IDC) could be improved by long term treatment with a beta-blocker, starting at a low dose and continuing with a stepwise up-titration. Since then, many studies have been performed in patients with heart failure of various aetiologies and the beneficial effects of long term beta-blockade have been confirmed. About 3000 patients have been included in randomised studies in which beta-blockade, given for more than 2 months, mostly elicited significant improvements in functional class, exercise capacity, cardiac function, quality of life and/or morbidity. When started at a very low dose (one-tenth to one-twentieth of the doses generally used in angina or hypertension), the treatment is well tolerated in most patients. In these studies, various types of beta-blockers were used, including beta1-selective blockers and nonselective blockers with additional properties (vasodilator and antioxidative) such as metoprolol, bisoprolol, bucindolol and carvedilol. Several large studies have also reported benefits on mortality and morbidity. In the Metoprolol in Dilated Cardiomyopathy (MDC) trial, metoprolol treatment in patients with IDC resulted in a 34% reduction of the primary combined endpoint, total number of deaths and need for cardiac transplantation. In the Cardiac Insufficiency Bisoprolol Study (CIBIS), in patients with idiopathic as well as ischaemic cardiomyopathy, there was a nonsignificant 20% reduction in mortality. In the US carvedilol studies (n = 1094), also in patients with ischaemic and idiopathic cardiomyopathy, carvedilol reduced mortality by 65%, which was highly significant. A nonsignificant reduction in mortality was observed in the Australia-New Zealand (ANZ) Heart Failure Study with carvedilol. In all these studies there was a reduction in hospitalisations, with all drugs being generally well tolerated. It can thus be concluded that the beneficial effects of beta-blockers on cardiac function and morbidity have been documented in a large number of studies in selected groups of patients. The treatment has been accepted in some countries by the regulatory authorities. Larger, placebo-controlled studies are needed to convincingly demonstrate a reduction in total mortality as observed in the pooling of the 4 US carvedilol studies. Such studies are in progress for various beta-blockers, which may lead to acceptance of their routine clinical use in patients with congestive heart failure.}, }
@article {pmid9378970, year = {1997}, author = {Czerniecki, BJ and Carter, C and Rivoltini, L and Koski, GK and Kim, HI and Weng, DE and Roros, JG and Hijazi, YM and Xu, S and Rosenberg, SA and Cohen, PA}, title = {Calcium ionophore-treated peripheral blood monocytes and dendritic cells rapidly display characteristics of activated dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {159}, number = {8}, pages = {3823-3837}, pmid = {9378970}, issn = {0022-1767}, mesh = {Bone Marrow Cells/classification/cytology/immunology ; CD4-Positive T-Lymphocytes/classification/drug effects/immunology ; CD8-Positive T-Lymphocytes/drug effects/immunology ; Calcimycin/*pharmacology ; Cells, Cultured ; Centrifugation ; Culture Media ; Dendritic Cells/cytology/*drug effects/*immunology ; Drug Combinations ; Endotoxins/pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Immunophenotyping ; Interleukin-4/pharmacology ; Ionomycin/*pharmacology ; Isoantigens/genetics ; Leukapheresis ; Leukocytes, Mononuclear/classification/cytology/immunology ; Macrophage Activation/drug effects ; Monocytes/*drug effects/*immunology ; Recombinant Proteins/pharmacology ; }, abstract = {Human peripheral blood contains a small subpopulation of immature dendritic cells (iDC) distinguished from circulating monocytes by their low expression of CD14. We utilized leukapheresis and countercurrent centrifugal elutriation to obtain myeloid origin mononuclear cell (MOMC) fractions of monocytes and iDC for study. These subpopulations were ultrastructurally and immunophenotypically similar before culture. After a 20- to 96-h culture either alone, with recombinant human granulocyte-monocyte CSF, or with endotoxin, greater up-regulation of costimulatory molecule expression was observed among iDC than among monocytes, and only iDC expressed the activation molecule CD83. Treatment with rhIL-4 caused many MOMC to develop morphologic properties of dendritic cells within 96 h, but costimulatory molecule up-regulation and CD14 down-regulation were heterogeneous, and CD83 expression was infrequent. In contrast, calcium ionophore (CI) treatment induced rapid and consistent effects in MOMC from both healthy volunteers and cancer patients, including down-regulated CD14 expression, acquisition of dendritic cell morphologic properties, up-regulated MHC and costimulatory molecule expression, and de novo CD83 expression. Many such effects occurred within 20 h of treatment. CI treatment activated purified CD14+ monocytes and also enhanced the spontaneous activation of purified CD14-/dim iDC in culture. Unfractionated MOMC, purified monocytes, and purified iDC displayed equivalently enhanced T cell-sensitizing efficiency following CI treatment. CD4+ T cell sensitization to keyhole limpet hemocyanin and CD8+ T cell sensitization to MART-1 melanoma-associated peptide were achieved in a single culture stimulation. Therefore, circulating monocytes and iDC can be induced by CI to manifest properties of activated DC, providing large numbers of efficient, nontransformed autologous APC for T cell sensitization strategies.}, }
@article {pmid9316532, year = {1997}, author = {Fauchier, L and Babuty, D and Cosnay, P and Autret, ML and Fauchier, JP}, title = {Heart rate variability in idiopathic dilated cardiomyopathy: characteristics and prognostic value.}, journal = {Journal of the American College of Cardiology}, volume = {30}, number = {4}, pages = {1009-1014}, doi = {10.1016/s0735-1097(97)00265-9}, pmid = {9316532}, issn = {0735-1097}, mesh = {Adult ; Aged ; Arrhythmias, Cardiac/*etiology ; Cardiomyopathy, Dilated/*complications/mortality/*physiopathology ; Case-Control Studies ; Electrocardiography, Ambulatory ; Female ; Heart Failure/*etiology ; *Heart Rate ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Oxygen Consumption ; Predictive Value of Tests ; Prognosis ; Pulmonary Wedge Pressure ; Stroke Volume ; Survival Analysis ; Ventricular Dysfunction, Left/*etiology ; }, abstract = {OBJECTIVES: This study was designed to evaluate heart rate variability (HRV) in patients with idiopathic dilated cardiomyopathy (IDC), to determine its correlation with hemodynamic variables and ventricular arrhythmias and to evaluate its prognostic value in IDC.<br><br>BACKGROUND: Previous studies have shown that HRV could predict arrhythmic events in patients after infarction, but the characteristics of HRV in IDC have not been fully established.<br><br>METHODS: Time domain analysis of HRV on 24-h electrocardiographic (ECG) recording was performed in 93 patients with IDC, and results were compared with those in 63 control subjects.<br><br>RESULTS: Patients with IDC, even those without congestive heart failure, had significantly lower values for HRV than those of control subjects. HRV was related to left ventricular shortening fraction (R = 0.5, p = 0.0001) and to peak oxygen uptake (R = 0.53, p = 0.01). HRV was not different in patients with runs of ventricular tachycardia or in patients with late potentials on the signal-averaged ECG. During a mean follow-up period (+/-SD) of 49.5 +/- 35.6 months, patients with reduced HRV had an increased risk of cardiac death or heart transplantation (p = 0.006). On multivariate analysis, cardiac events were predicted by increased left ventricular end-diastolic diameter (p = 0.0001), reduced standard deviation of all normal to normal RR intervals (p = 0.02) and increased pulmonary capillary wedge pressure (p = 0.04).<br><br>CONCLUSIONS: Decreased HRV in patients with IDC is related to left ventricular dysfunction and not to ventricular arrhythmias. Analysis of HRV can identify patients with IDC who have an increased risk of cardiac death or heart transplantation.}, }
@article {pmid9271010, year = {1997}, author = {Mourad, WA}, title = {Aneuploidy in sclerosing adenosis may predict an increased risk of malignancy. A study using the AgNOR silver stain.}, journal = {Pathology}, volume = {29}, number = {3}, pages = {255-259}, doi = {10.1080/00313029700169015}, pmid = {9271010}, issn = {0031-3025}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Aneuploidy ; Breast Neoplasms/genetics/*pathology ; Diploidy ; Female ; Fibrocystic Breast Disease/genetics/*pathology ; Follow-Up Studies ; Humans ; Middle Aged ; Nucleolus Organizer Region/*chemistry ; Predictive Value of Tests ; Risk Factors ; Sclerosis/genetics/pathology ; Silver Staining ; }, abstract = {Sclerosing adenosis (SA) of the breast if a disease associated with an increase relative risk of malignancy. The exact incidence and factors influencing malignant transformation in association with SA are not well established. Two counts of the AgNOR silver staining technique have been correlated with ploidy and proliferative activity. The first count which is the mean number of AgNOR granules (mAgNOR), correlates with ploidy. The second count is the percentage of nuclei exhibiting > or = 5 AgNORs/nucleus (pAgNOR) and reflects proliferative activity. The hypothesis in the current study was that aneuploidy, as determined by the AgNOR silver staining technique, may potentially identify lesions of SA with an increased association with malignant breast disease. The AgNOR silver staining technique was performed on 69 cases of SA with the application of the two counts. Of these cases 53 were not associated with malignancy and 16 were associated with synchronous or metachronous carcinoma of the breast, these being 11 cases of invasive ductal carcinoma (IDC), four cases of ductal carcinoma in situ (DCIS) and one case of lobular carcinoma in situ (LCIS). The patient ages ranged from 27 to 84 years (median 53 years) with a median follow up of 28 months. Six of the 53 cases of SA no associated with malignancy (11%) had aneuploid mAgNOR counts of > or = 2.4 whereas 12 of the 16 cases associated with carcinoma (80%) had such counts (p < 0.0005). This included nine cases of IDC, two cases of DCIS and the case of LCIS. Of the six aneuploid cases not associated with malignancy, two cases showed cytological atypia, one case was associated with atypical ductal hyperplasia and one case was seen in a leukemic patient who had received chemotherapy and radiation therapy. The pAgNOR counts showed a statistically less significant correlation with malignancy (p < 0.03). These findings suggest that aneuploidy, measured by the AgNOR silver stein, seen in SA may help identify lesions with a higher relative risk of being associated with breast carcinoma and hence that may require more aggressive management than diploid ones.}, }
@article {pmid9244223, year = {1997}, author = {Müller, J and Wallukat, G and Weng, YG and Dandel, M and Spiegelsberger, S and Semrau, S and Brandes, K and Theodoridis, V and Loebe, M and Meyer, R and Hetzer, R}, title = {Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy.}, journal = {Circulation}, volume = {96}, number = {2}, pages = {542-549}, doi = {10.1161/01.cir.96.2.542}, pmid = {9244223}, issn = {0009-7322}, mesh = {Adult ; Aged ; Autoantibodies/blood ; Cardiomyopathy, Dilated/blood/immunology/physiopathology/*therapy ; Follow-Up Studies ; *Heart-Assist Devices ; Humans ; Male ; Middle Aged ; Receptors, Adrenergic, beta-1/blood ; Time Factors ; Ventricular Function, Left ; }, abstract = {BACKGROUND: Implantation of mechanical cardiac support systems (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. We report of long-term effects of ventricular unloading on cardiac function, humoral anti-beta1-adrenoceptor autoantibodies (A-beta1-AABs), and myocardial fibrosis.<br><br>METHODS AND RESULTS: Seventeen patients in New York Heart Association functional class IV with nonischemic IDC received MCSS. All had a cardiac index of < 1.6 L x min(-1) x m(-2) of body surface area, a left ventricular ejection fraction (LVEF) of <16%, and a left ventricular internal diameter in diastole (LVIDd) of >68 mm and tested positive for A-beta1-AABs. Echocardiographic evaluation, serum tests for A-beta1-AABs, and histological assessment of myocardial fibrosis were performed before and after MCSS implantation. The mean support duration was 230+/-201 days. Six patients died, four were transplanted, and two are still on MCSS. Five patients with significant cardiac recovery (mean LVIDd, 54+/-2.3 mm; LVEF, 47+/-3.7%) were weaned after 160 to 794 days and are now device free for 51 to 592 days. A-beta1-AABs disappeared gradually during MCSS without increase after weaning; cardiac function and volume density of fibrosis remained normal. Nine patients' cardiac function hardly improved during ventricular unloading.<br><br>CONCLUSIONS: Cardiac function can be normalized in selected patients with end-stage IDC by MCSS. The degree of preoperative myocardial fibrosis may be an indicator for outcome; A-beta1-AABs can be used to monitor myocyte recovery. Weaning from MCSS offers an alternative to cardiac transplantation in certain patients.}, }
@article {pmid9327609, year = {1997}, author = {Sparacino, G and Vicini, P and Bonadonna, R and Marraccini, P and Lehtovirta, M and Ferrannini, E and Cobelli, C}, title = {Removal of catheter distortion in multiple indicator dilution studies: a deconvolution-based method and case studies on glucose blood-tissue exchange.}, journal = {Medical &amp; biological engineering &amp; computing}, volume = {35}, number = {4}, pages = {337-342}, pmid = {9327609}, issn = {0140-0118}, support = {RR-02176/RR/NCRR NIH HHS/United States ; RR-11095/RR/NCRR NIH HHS/United States ; }, mesh = {Blood Glucose/*metabolism ; *Blood Specimen Collection ; *Catheterization ; Forearm ; Humans ; Models, Biological ; Myocardium/metabolism ; *Radioisotope Dilution Technique ; }, abstract = {The study of blood-tissue exchange by the multiple indicator dilution technique often needs frequent sampling in the blood of the indicator dilution curves (IDC). Usually, this requires the use of a catheter supported by a pump. This causes a distortion in the IDC, which must be removed for proper interpretation of the data. A deconvolution-based methodology to remove IDC distortion is presented. First, the catheter impulse response is modelled by means of data obtained from a suitable experiment. Then the reconstruction of the blood IDC is tackled by a new nonparametric deconvolution algorithm, which provides (quasi) time-continuous signals and exploits statistically based criteria for the choice of the regularisation parameter. The methodology is applied to the removal of catheter distortion in studies of glucose blood-tissue exchange in the human forearm and myocardium.}, }
@article {pmid9226257, year = {1997}, author = {Kikuchi, Y and Kojima, H and Tanaka, T and Takatsuka, Y and Kamio, Y}, title = {Characterization of a second lysine decarboxylase isolated from Escherichia coli.}, journal = {Journal of bacteriology}, volume = {179}, number = {14}, pages = {4486-4492}, pmid = {9226257}, issn = {0021-9193}, mesh = {Amino Acid Sequence ; Base Sequence ; Blotting, Southern ; Carboxy-Lyases/chemistry/*genetics/isolation &amp; purification/metabolism ; Chromosomes, Bacterial ; Cloning, Molecular ; DNA, Bacterial/genetics ; Escherichia coli/*enzymology/genetics ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; }, abstract = {We report here on the existence of a new gene for lysine decarboxylase in Escherichia coli K-12. The hybridization experiments with a cadA probe at low stringency showed that the homologous region of cadA was located in lambda Kohara phage clone 6F5 at 4.7 min on the E. coli chromosome. We cloned the 5.0-kb HindIII fragment of this phage clone and sequenced the homologous region of cadA. This region contained a 2,139-nucleotide open reading frame encoding a 713-amino-acid protein with a calculated molecular weight of 80,589. Overexpression of the protein and determination of its N-terminal amino acid sequence defined the translational start site of this gene. The deduced amino acid sequence showed 69.4% identity to that of lysine decarboxylase encoded by cadA at 93.7 min on the E. coli chromosome. In addition, the level of lysine decarboxylase activity increased in strains carrying multiple copies of the gene. Therefore, the gene encoding this lysine decarboxylase was designated Idc. Analysis of the lysine decarboxylase activity of strains containing cadA, ldc, or cadA ldc mutations indicated that ldc was weakly expressed under various conditions but is a functional gene in E. coli.}, }
@article {pmid9205235, year = {1997}, author = {Huynh, PT and Parellada, JA and de Paredes, ES and Harvey, J and Smith, D and Holley, L and Maxin, M}, title = {Dilated duct pattern at mammography.}, journal = {Radiology}, volume = {204}, number = {1}, pages = {137-141}, doi = {10.1148/radiology.204.1.9205235}, pmid = {9205235}, issn = {0033-8419}, mesh = {Adult ; Aged ; Biopsy ; Breast Diseases/*etiology ; Breast Neoplasms/complications/*diagnostic imaging/*pathology ; Calcinosis/*etiology ; Carcinoma, Ductal, Breast/complications/*diagnostic imaging/*pathology ; Dilatation, Pathologic ; Female ; Humans ; Mammography/*standards ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {PURPOSE: To determine the importance of a dilated duct pattern at mammography.<br><br>MATERIALS AND METHODS: Mammograms obtained in 46 women with histopathologically proved, asymmetrically dilated ducts were retrospectively studied. The laterality and location of the asymmetrically dilated duct, the presence of branching, and associated findings such as microcalcifications, nipple discharge, and interval change were evaluated.<br><br>RESULTS: Eleven patients (24%) had malignant results (ductal carcinoma in situ or invasive ductal carcinoma). Among these, six (54%) had suspicious microcalcifications. Nonsubareolar location and interval change are significant (P = .04) variables associated with malignancy.<br><br>CONCLUSION: Mammographic asymmetrically dilated ducts in a nonsubareolar area that are associated with interval change, suspicious microcalcifications, or both warrant biopsy.}, }
@article {pmid9220309, year = {1997}, author = {Lozano, MD and Rubocki, RJ and Wilson, JE and McManus, BM and Wisecarver, JL}, title = {Human leukocyte antigen class II associations in patients with idiopathic dilated cardiomyopathy. Myocarditis Treatment Trial Investigators.}, journal = {Journal of cardiac failure}, volume = {3}, number = {2}, pages = {97-103}, doi = {10.1016/s1071-9164(97)90041-5}, pmid = {9220309}, issn = {1071-9164}, support = {R01-HL34744/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Alleles ; Cardiomyopathy, Dilated/genetics/*immunology ; Female ; *HLA-D Antigens/genetics ; HLA-DQ Antigens/genetics ; HLA-DR Antigens/genetics ; Histocompatibility Testing ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; }, abstract = {BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) is a disease of unknown etiology for which immune abnormalities, possibly related to viral infections, are suspected but unproven. Previous serologic studies have reported associations between human leukocyte antigen DR4 and IDC. A molecular study of human leukocyte antigen associations was undertaken in patients with IDC to further explore the possibility of susceptibility markers of genetically determined disease.<br><br>METHODS AND RESULTS: In this study, 36 patients from the Myocarditis Treatment Trial (32 IDC and 4 myocarditis patients) were examined using restriction fragment length polymorphism analysis and polymerase chain reaction amplification with sequence-specific primers to perform class II typing. All 4 myocarditis patients were DQ5 positive and 3 possessed the allele DQB1*0501. In the IDC group, the frequency of human leukocyte antigen DR4 was similar to that reported in the normal population. In addition, there was no excess prevalence of any molecularly defined DR4 alleles (0401-0419). There was an increase in the frequency of DR12 in IDC patients. The frequencies of the alleles DQB1 *0503 and DQB1*0301 and/or *0304 were also increased in IDC patients versus the normal population.<br><br>CONCLUSION: The molecular studies point to a relationship between the DQ locus and IDC.}, }
@article {pmid9167459, year = {1997}, author = {}, title = {Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Breast Cancer Linkage Consortium.}, journal = {Lancet (London, England)}, volume = {349}, number = {9064}, pages = {1505-1510}, pmid = {9167459}, issn = {0140-6736}, support = {CA61231/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/genetics/pathology ; Adenocarcinoma, Mucinous/genetics/pathology ; Adult ; Aged ; BRCA2 Protein ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Lobular/genetics/pathology ; Carcinoma, Medullary/genetics/pathology ; Case-Control Studies ; Female ; *Genes, BRCA1 ; *Genes, Tumor Suppressor ; Genetic Markers/*genetics ; Genetic Predisposition to Disease ; *Heterozygote ; Humans ; Middle Aged ; Mitosis ; Mutation/*genetics ; Neoplasm Proteins/*genetics ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: A few breast cancer cases are attributable to a hereditary predisposition to the disease. We aimed to compare the histological features of breast cancer in women carrying mutations in the susceptibility genes BRCA1 and BRCA2 with controls unselected for family history.<br><br>METHODS: The morphological characteristics of specimens from 440 patients with familial breast cancer, including 118 in carriers of BRCA1 mutations and 78 in carriers of BRCA2 mutations, were compared with those from 547 age-matched controls, unselected for family history, by seven pathologists.<br><br>FINDINGS: Cancers in carriers of BRCA1 (p < 0.0001) and BRCA2 mutations (p = 0.04) were, on average, of a higher overall grade than in controls. For example, the proportions in grade 3 were 66% of 139, 41% of 58 and 36% of 368 specimens, respectively. However, when the three grade indices were considered independently, breast cancers in BRCA1-mutation carriers showed more pleomorphism (p = 0.006), a higher mitotic count (p < 0.0001), and less tubule formation than controls (p = 0.006), whereas cancers in BRCA2-mutation carriers showed less tubule formation (p = 0.003), but no difference in pleomorphism or mitotic count. The occurrence of invasive lobular carcinoma and invasive ductal carcinoma was not significantly different between carriers of BRCA1 or BRCA2 mutations and controls. Medullary or atypical medullary carcinoma was, however, found more often in BRCA1 (13%, p < 0.0001) than in BRCA2-mutation carriers (3%) or controls (2%). Tubular carcinoma was less common in BRCA2-mutation carriers. The few mucoid carcinomas were all in familial cases. Carriers of BRCA1 mutations showed less ductal carcinoma in situ around the invasive lesion than controls (41 vs 56%, p = 0.001). Lobular carcinoma in situ was less common in familial cancers (p = 0.013), but differences were not significant for BRCA1-mutations or BRCA2-mutation carriers, separately.<br><br>INTERPRETATION: The histology of breast cancers in predisposed women differs from that in sporadic cases, and there are differences between breast cancers in carriers of BRCA1 and BRCA2 mutations. The findings suggest that breast cancer due to BRCA1, has a different natural history to BRCA2 or apparently sporadic disease, which may have implications for screening and management.}, }
@article {pmid9174626, year = {1997}, author = {Coene, ED and Schelfhout, V and Winkler, RA and Schelfhout, AM and Van Roy, N and Grooteclaes, M and Speleman, F and De Potter, CR}, title = {Amplification units and translocation at chromosome 17q and c-erbB-2 overexpression in the pathogenesis of breast cancer.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {430}, number = {5}, pages = {365-372}, doi = {10.1007/s004280050045}, pmid = {9174626}, issn = {0945-6317}, mesh = {Breast/chemistry/metabolism/pathology ; Breast Neoplasms/chemistry/*etiology/genetics ; Carcinoma, Ductal, Breast/chemistry/*etiology/genetics ; Cell Transformation, Neoplastic/pathology ; *Chromosomes, Human, Pair 17 ; Female ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, erbA/genetics ; Genes, erbB-2/genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Karyotyping ; Oncogene Proteins v-erbA/analysis/genetics/metabolism ; Peroxidase/analysis/genetics/metabolism ; Receptor, ErbB-2/analysis/*genetics/metabolism ; *Translocation, Genetic ; }, abstract = {Hyperplasia without and with atypia is considered to be a precursor lesion for certain breast carcinomas. The cytogenetic events and the molecular pathology involved in the multistep process from normal to invasive carcinoma are unknown. To characterise the sequence of early genetic abnormalities of chromosome 17q and their biological consequences in the pathogenesis of breast cancer, we performed immunohistochemistry on 451 breast tissues including 180 normal breast specimens, 28 hyperplastic lesions without atypia and 44 with atypia, 100 cases of ductal carcinoma in situ (DCIS) and 99 cases of invasive ductal carcinoma. We correlated the overexpression of the c-ErbB-2 protein, the histological and the recently proposed differentiation classification of DCIS with the extent of DCIS. For fluorescence in situ hybridisation (FISH) analysis, different probes spanning the 17q region including the c-erbB-2 gene locus and those which are found adjacent, were used. Reverse painting and comparative genomic hybridisation (CGH) were performed on several breast cancer cell lines. c-ErbB-2 overexpression was observed in only 29% of DCIS and 23% of invasive carcinomas, but not in hyperplastic and normal tissue. c-ErbB-2 overexpression is correlated with poor differentiation in DCIS but not in invasive carcinoma. In DCIS, there was no correlation with the histological subtype classification. The average extent of DCIS is significantly increased from 13.81 mm in c-ErbB-2 negative cases to 29.37 mm in c-ErbB-2 positive cases. The increase was considered to be a possible consequence of the overexpression and is probably due to the previously described motility enhancing effect of the c-ErbB-2 protein. The histological and differentiation classification of DCIS did not correlate with the extent of disease. Using FISH, amplified genes at 17q12, always including the c-erbB-2 gene, were detected in all cases of DCIS and invasive carcinoma with c-ErbB-2 overexpression. The centromeric region and the NF1 locus, which is located between the centromere and c-erbB-2, were not amplified in any of the DCIS and invasive breast carcinomas, but co-amplification of the myeloperoxidase gene was detected in 3/5 DCIS and 1/5 invasive carcinomas with c-ErbB-2 overexpression. In contrast to c-erbB-2, immunohistochemical overexpression of their respective gene products was not observed. FISH, reverse painting and CGH show similar amplified genes with amplified c-erbB-2 in c-ErbB-2 overexpressing SK-BR-3 and BT474 human breast cancer cells. The amplified genes are part of two different amplicons. Extensive modifications of the 17q chromosomal region, caused by translocation, were also observed in these cell lines. It is concluded that the modifications of chromosome 17q, inducing overexpression of c-ErbB-2 protein, occur at the level of transition from hyperplasia to DCIS. They are preserved in invasive carcinoma with overexpression of c-ErbB-2 protein. This had led to the hypothesis that these modifications at 17q may lead to a larger extent of DCIS.}, }
@article {pmid9174620, year = {1997}, author = {Björck, P and Flores-Romo, L and Liu, YJ}, title = {Human interdigitating dendritic cells directly stimulate CD40-activated naive B cells.}, journal = {European journal of immunology}, volume = {27}, number = {5}, pages = {1266-1274}, doi = {10.1002/eji.1830270531}, pmid = {9174620}, issn = {0014-2980}, mesh = {B-Lymphocytes/*immunology ; CD40 Antigens/*physiology ; Cell Communication/immunology ; Cell Differentiation/immunology ; Cell Separation ; Dendritic Cells/classification/*immunology ; Humans ; *Lymphocyte Activation ; Lymphoid Tissue/immunology ; Palatine Tonsil/cytology ; Spleen/immunology ; T-Lymphocytes/immunology ; }, abstract = {Human interdigitating dendritic cells (IDC) were isolated from tonsils based on their CD40+ lineage-negative expression in situ. Isolated IDC displayed a phenotypic profile similar to that of IDC in tonsils and spleen in situ, characterized by high-level expression of major histocompatibility complex class II, the co-stimulatory molecules B7.1 (CD80) and B7.2 (CD86), expression of the late DC maturation marker CD83, and no expression of CD1a, CD13, or CD33. IDC also showed weak nonspecific esterase staining and had the ability to induce an allogeneic mixed lymphocyte reaction. In this study, we further show that in the presence of surrogate activated T cells in the form of CD40 ligation and IL-2, IDC enhance the proliferation of naive B cells and induce their differentiation into plasma cells producing IgM. Evidence for the anatomical co-localization of naive B cells and IDC in the T cell area together with the data obtained in vitro implies a role for IDC in the initiation of the extrafollicular reaction.}, }
@article {pmid9095001, year = {1997}, author = {Kuukasjärvi, T and Tanner, M and Pennanen, S and Karhu, R and Kallioniemi, OP and Isola, J}, title = {Genetic changes in intraductal breast cancer detected by comparative genomic hybridization.}, journal = {The American journal of pathology}, volume = {150}, number = {4}, pages = {1465-1471}, pmid = {9095001}, issn = {0002-9440}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Chromosome Mapping ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; }, abstract = {Ductal carcinoma in situ (DCIS) is considered a direct precursor of invasive ductal breast cancer (IDC). We combined tissue microdissection and comparative genomic hybridization to identify genetic changes in five DCIS lesions with no invasion and in two that were adjacent to IDC. Extensive genetic changes characterized pure DCIS cases with gains of 1q, 6q, 8q, and Xq as well as losses of 17p and chromosome 22 being most often involved. Except for the Xq gain, these changes are also common to IDC. Separate analysis of DCIS and IDC components in the same tumor revealed an almost identical pattern of genetic changes in one case, whereas substantial differences were found in another. We conclude that many of the common genetic changes in IDC may take place before development of invasive growth. However, a simple linear progression model may not always account for the DCIS-IDC transition.}, }
@article {pmid9137366, year = {1997}, author = {Le Bouëdec, G and de Latour, M and Levrel, O and Dauplat, J}, title = {[Krükenberg tumors of breast origin. 10 cases].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {26}, number = {10}, pages = {454-457}, pmid = {9137366}, issn = {0755-4982}, mesh = {Adult ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Krukenberg Tumor/diagnosis/pathology/*secondary ; Middle Aged ; Ovarian Neoplasms/diagnosis/pathology/*secondary ; Retrospective Studies ; }, abstract = {OBJECTIVE: To assess the characteristic features of ovarian carcinoma mucocellular secondary to breast cancer.<br><br>METHODS: A retrospective pathology evaluation of ovariectomy specimens was conducted to compare the histological types with the original pathology diagnosis of breast cancer.<br><br>RESULTS: Ten cases of ovarian carcinoma mucocellular were observed. Histologically, the ovarian stroma presented voluminous mucin-containing vacuoles in epitheliomatous cells with peripheralized nuclei. In 7 out of 10 cases, the primary breast cancer was invasive lobular carcinoma.<br><br>DISCUSSION: These pathology findings are in agreement with comparative studies on the metastatic behavior of different histological types of breast cancer: invasive lobular carcinoma differs from invasive ductal carcinoma by its tropism for gastrointestinal and internal genital organs.}, }
@article {pmid9148862, year = {1997}, author = {Cardillo, MR and Yap, E and Castagna, G}, title = {Molecular genetic analysis of TGF beta1 in breast cancer.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {16}, number = {1}, pages = {57-63}, pmid = {9148862}, issn = {0392-9078}, mesh = {Breast Neoplasms/*genetics/pathology ; Exons/genetics ; Female ; Humans ; Mutation ; Neoplasm Proteins/analysis/*genetics ; Polymerase Chain Reaction/methods ; Polymorphism, Single-Stranded Conformational ; RNA, Messenger/analysis ; Transforming Growth Factor beta/analysis/*genetics ; }, abstract = {Conflicting data suggest that TGF-beta1 can either inhibit or promote the progression of breast cancer. To determine the biological role of TGF beta1 in mammary carcinoma, in this study we examined the gene structure, expression and localization of TGF-beta1 using paraffin-embedded samples from 32 (27 IDC, 1 ILC, 1 DCIS, 1 ADH) breast lesions. Gene mutations in the region coding for the active protein were investigated by PCR-SSCP of exons 5, 6, and 7. mRNA -TGF-beta1 expression and distribution was examined by NISH using cDNA probes generated by RT-PCR and immunohistochemistry. We detected two mutations in exon 6 TGF-beta1 from IDC; and TGF beta1 mRNA and proteins in 28 (87%) of the tumors. Invasive breast carcinomas had more intense TGF-beta1 activity than CIS and than normal tissue adjacent to tumor. TGF beta1 mRNA and proteins were higher at the edge of the tumor than in the center and were also higher in less differentiated breast neoplasms. TGF-beta1 mRNA transcription and protein levels did not correlate either with TGF-beta1 exon 6 mutation or type and grade of differentiation of breast tumors. These observations suggest that TGF beta1 mutations in breast neoplasms might cause loss or inactivation of the growth inhibitory effects of TGF-beta1. They also support the proposed role of TGF-beta1 in the pathogenesis of breast cancer.}, }
@article {pmid9096916, year = {1997}, author = {Fruhwald, FM and Ramschak-Schwarzer, S and Pichler, B and Watzinger, N and Schumacher, M and Zweiker, R and Klein, W and Eber, B}, title = {Subclinical thyroid disorders in patients with dilated cardiomyopathy.}, journal = {Cardiology}, volume = {88}, number = {2}, pages = {156-159}, doi = {10.1159/000177323}, pmid = {9096916}, issn = {0008-6312}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/blood/diagnosis/*etiology ; Death, Sudden, Cardiac/etiology ; Euthyroid Sick Syndromes/blood/*complications/diagnosis ; Female ; Humans ; Hypothyroidism/blood/complications/diagnosis ; Male ; Middle Aged ; Risk Factors ; *Thyroid Function Tests ; Thyroid Hormones/blood ; Thyrotoxicosis/blood/complications/diagnosis ; Ultrasonography ; }, abstract = {UNLABELLED: Severe thyrotoxicosis can cause irreversible congestive heart failure. To investigate the coincidence of subclinical thyroid disorders and idiopathic dilated cardiomyopathy (IDC) we investigated these patients with respect to their morphological and functional thyroid status. Thyroid sonography as well as thyroid hormone levels were measured in all patients.<br><br>RESULTS: Sixty-one patients (50 male, 11 female) with chronic stable IDC were included. Two out of 61 patients showed completely normal thyroid morphology and function. The other 59 patients showed either morphological or functional abnormalities or both. Of the 53 patients with morphological abnormalities 23 patients (all male) showed diffuse goiter as opposed to 29 nodular enlarged organs (24 male, 5 female). No clinically significant hypothyroidism or thyrotoxicosis was seen. A good correlation was found between the duration of IDC and thyroid volume (r = 0.44; p < 0.001). Two patients died during the study period, 1 from sudden death and 1 from progressive heart failure.<br><br>CONCLUSION: Subclinical thyroid disorders are frequently seen in patients with long-standing IDC when they live in an area of chronic iodine deficiency. This can be explained by chronic salt restriction as basic treatment for congestive heart failure. Therefore we conclude that examination of the thyroid gland should be done routinely in patients with IDC, especially when restriction of salt intake is recommended by the treating physician.}, }
@article {pmid9088975, year = {1997}, author = {Björck, P and Banchereau, J and Flores-Romo, L}, title = {CD40 ligation counteracts Fas-induced apoptosis of human dendritic cells.}, journal = {International immunology}, volume = {9}, number = {3}, pages = {365-372}, doi = {10.1093/intimm/9.3.365}, pmid = {9088975}, issn = {0953-8178}, mesh = {Antibodies, Monoclonal/pharmacology ; Apoptosis/*drug effects ; CD40 Antigens/*drug effects/physiology ; CD40 Ligand ; Cell Differentiation/drug effects ; Cell Separation ; Cells, Cultured ; Coculture Techniques ; DNA Fragmentation ; Dendritic Cells/*cytology/immunology ; Fibroblasts ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Hematopoietic Stem Cells/drug effects ; Humans ; Membrane Glycoproteins/genetics/*pharmacology ; Palatine Tonsil/cytology ; Proto-Oncogene Proteins c-bcl-2/physiology ; Recombinant Fusion Proteins/pharmacology ; Signal Transduction/physiology ; Transfection ; Tumor Necrosis Factor-alpha/pharmacology ; fas Receptor/*immunology ; }, abstract = {Dendritic cells (DC) are cells of the hematopoletic system specialized in capturing antigens and initiating T cell-mediated immune responses. We show here that human DC generated in vitro by culturing CD34+ cord blood progenitor cells in granulocyte macrophage colony stimulating factor plus tumor necrosis factor-alpha express the Fas antigen (APO-1, CD95) and undergo apoptosis upon triggering of Fas by mAb. However, only a proportion of the cells die in response to Fas ligation, an observation that may be related to the virtual absence of the bcl-2 protein in about half of the cells. Ligation of DC CD40 by culture on CD40L-transfected fibroblastic cells up-regulates the expression of bcl-2 and, concomitantly, renders DC virtually resistant to Fas-induced apoptosis. Parallel experiments with mature, interdigitating dendritic cells (IDC) isolated from tonsils revealed that IDC express Fas but do not enter into apoptosis following Fas ligation, a finding that may be explained by their high levels of bcl-2. Thus, upon encountering antigen-specific T cells, DC become resistant to Fas-induced apoptosis, as a consequence of CD40 ligation and possibly by mechanisms associated to the up-regulation of bcl-2 protein expression.}, }
@article {pmid9042800, year = {1997}, author = {Yonezawa, S and Sueyoshi, K and Nomoto, M and Kitamura, H and Nagata, K and Arimura, Y and Tanaka, S and Hollingsworth, MA and Siddiki, B and Kim, YS and Sato, E}, title = {MUC2 gene expression is found in noninvasive tumors but not in invasive tumors of the pancreas and liver: its close relationship with prognosis of the patients.}, journal = {Human pathology}, volume = {28}, number = {3}, pages = {344-352}, doi = {10.1016/s0046-8177(97)90134-9}, pmid = {9042800}, issn = {0046-8177}, support = {CA24321/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Bile Duct Neoplasms/*genetics/metabolism/pathology ; Cystadenocarcinoma/*genetics/metabolism/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Middle Aged ; Mucin-2 ; Mucins/*genetics/metabolism ; *Neoplasm Invasiveness ; Pancreatic Neoplasms/*genetics/metabolism/pathology ; Polymerase Chain Reaction ; Prognosis ; RNA, Messenger/analysis ; }, abstract = {We have previously reported that MUC2 apomucin was highly expressed in noninvasive tumors of the pancreas (intraductal papillary tumor [IdPT]) and liver (bile duct cystadenocarcinoma [BdCC]), which show more favorable outcomes than invasive carcinomas. In contrast, MUC2 was rarely expressed in invasive carcinomas of the pancreas (invasive ductal carcinoma [IDC]) and the liver (invasive cholangiocarcinoma [ICC]). In the present study, we examined localization of MUC2 messenger RNA (MUC2 mRNA) by using a complementary DNA (cDNA) probe for the MUC2 tandem repeat for in situ hybridization (pHAM1). Localization of MUC2 apomucin was determined by using an antibody directed against MUC2 apomucin (anti-MRP) for immunohistochemistry study. Eleven IdPTs and 10 IDCs of the pancreas, and 8 BdCC and 8 ICCs of the liver were examined. Nine (82%) of 11 IdPTs showed positive expression of MUC2 mRNA in the neoplastic cells, whereas none (0%) of the IDCs showed expression of MUC2 mRNA. Six (75%) of the 8 BdCCs showed positive expression of MUC2 mRNA in the neoplastic cells, whereas none (0%) of the 8 ICCs showed expression of MUC2 mRNA. The localization of MUC2 mRNA and that of MUC2 apomucin usually coincided, although a few cases (1 IDC, 1 BdCC, and 1 ICC) showed focal expression of MUC2 apomucin despite the absence of detectable MUC2 mRNA. These results indicate that the expression of MUC2 apomucin in IdPTs and BdCCs correlates with expression of MUC2 mRNA. In both patient groups with pancreatic tumors and hepatic tumors, patients with positive MUC2 mRNA expression in the tumors showed significantly better survival than those with negative MUC2 mRNA expression in the tumors. The production of MUC2, an abundant extracellular mucin, by most IdPTs and BdCCs may be correlated with tumors that display lower levels of invasion and metastasis.}, }
@article {pmid9042790, year = {1997}, author = {Nayar, R and Zhuang, Z and Merino, MJ and Silverberg, SG}, title = {Loss of heterozygosity on chromosome 11q13 in lobular lesions of the breast using tissue microdissection and polymerase chain reaction.}, journal = {Human pathology}, volume = {28}, number = {3}, pages = {277-282}, doi = {10.1016/s0046-8177(97)90124-6}, pmid = {9042790}, issn = {0046-8177}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; *Chromosome Deletion ; Chromosomes, Human, Pair 11/*genetics ; Female ; Heterozygote ; Humans ; Hyperplasia/genetics/pathology ; Polymerase Chain Reaction ; }, abstract = {Demonstration of identical allelic loss on chromosome 11q13 in synchronous in situ (DCIS) and invasive ductal (IDC) breast carcinoma has provided molecular evidence of the progression of DCIS to IDC. We investigated loss of heterozygosity (LOH) at chromosome 11q13 in the spectrum of "marker/premalignant" and "malignant" lobular lesions of the breast, including atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and infiltrating lobular carcinoma (ILC). Thirty-eight cases with various combinations of ALH, LCIS, and ILC were studied. Synchronous ductal lesions were present in 9 of 38 cases. Areas of interest were specifically isolated by tissue microdissection. The extracted DNA was amplified by polymerase chain reaction (PCR) and analyzed with two polymorphic markers for chromosome 11q13 (INT2 and PYGM). LOH at 11q13 was identified in ILC and LCIS in approximately one third of informative cases. LCIS in association with ILC showed a loss in 50% of cases, whereas pure LCIS in the absence of ILC had a much lower frequency of LOH, which was comparable to that of pure ALH. These results suggest that LOH on chromosome 11q13 may play an important role in development of ILC, similar to that of IDC from DCIS/ADH. Additionally, frequent LOH in ILC and LCIS associated with ILC and a significantly lower and comparable frequency of LOH in LCIS without ILC and ALH implies that genetic alteration(s) on chromosome 11q13 may be important in the transition of LCIS to ILC. LOH was detected in three of nine synchronous ductal lesions (one IDC and two DCIS), confirming our earlier findings and indicating that lobular and ductal neoplasia in the breast show some similar genetic changes. We hypothesize that LOH may help in separating morphologically similar yet genetically different subgroups of ALH and LCIS into one group with genetic changes and an increased potential to progress to invasive cancer and another group, the "marker" lesions of LCIS/ALH, that remain stable or possibly regress.}, }
@article {pmid9012470, year = {1997}, author = {Siegfried, JM and Weissfeld, LA and Singh-Kaw, P and Weyant, RJ and Testa, JR and Landreneau, RJ}, title = {Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer.}, journal = {Cancer research}, volume = {57}, number = {3}, pages = {433-439}, pmid = {9012470}, issn = {0008-5472}, support = {P20 CA58235/CA/NCI NIH HHS/United States ; R01 CA45745/CA/NCI NIH HHS/United States ; R01 CA50694/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/chemistry/*mortality/pathology ; Female ; Hepatocyte Growth Factor/*analysis/immunology ; Humans ; Lung Neoplasms/chemistry/*mortality/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Mas ; Survival Rate ; }, abstract = {We have shown previously that hepatocyte growth factor (HGF), which is produced by lung fibroblasts, is a potent mitogen and motogen for both normal and neoplastic bronchial epithelium, and that expression of the HGF receptor, the c-met proto-oncogene protein, is uniformly found in the human bronchial epithelium and in non-small cell lung carcinomas (NSCLCs; P. Singh-Kaw et al., Am. J. Physiol., 268: L1012-L1020, 1995). Yamashita et al. have reported an association of HGF with poor survival in invasive ductal carcinoma of the breast (Cancer Res., 54: 1630-1633, 1994). There are few prognostic markers for lung cancer, and the high recurrence rate for stage I lung cancer suggests the frequent presence of undetectable tumor burden in such patients. Criteria are needed to evaluate these patients for risk of recurrence. We have now evaluated whether HGF present in resectable lung tumors has prognostic significance. In this study, 56 primary NSCLCs, mainly adenocarcinomas, were examined for presence of HGF by quantitative Western blot. These tumors consisted of tissue from 34 stage I patients, 9 stage II patients, and 13 stage IIIa patients who underwent curative resection for primary NSCLC. Extracts of whole tumor tissue were analyzed after separation of proteins by electrophoresis and transfer of proteins to nitrocellulose membranes. Immunoreactive (ir)-HGF was visualized by reaction with a polyclonal anti-HGF antiserum and quantitated by densitometry. Lung tumor content of ir-HGF varied widely among individuals. Median ir-HGF content in tumor extracts was 15.3 ng/40 microg of tumor protein; mean ir-HGF was 27.2 ng/40 microg of tumor protein. The median and mean ir-HGF were both significantly higher in tumor tissue from patients who suffered a recurrence during the follow-up period compared with those with no evidence or residual disease; this was true of all patients (P = 0.0001) and stage I patients analyzed separately (P = 0.002). Analysis of survival curves indicated that ir-HGF levels higher than the median were associated with poor overall survival (P < 0.03). Univariate analysis showed three factors related to poor overall survival in this set of patients: ir-HGF, tumor (T) status (a measure of primary tumor size and extent), and age. Nodal (N) status and stage were only marginally related to overall survival, most likely because the majority of the patients in the study were stage I. N status, stage, and T status were related to disease-free survival, however. Multivariate Cox analysis showed that ir-HGF, T status, and age independently had a negative impact on overall survival. ir-HGF was a strong independent negative prognostic indicator (P = 0.0001) with a relative risk of 1.022 per unit of ir-HGF (ng/40 microg of protein). This demonstrates that, in this group of patients, the relative risk of ir-HGF content increased continuously as ir-HGF increased, and exceeded 10 at units of ir-HGF of 100 or more. In comparison, in this group of patients, the relative risk of a T status greater than 1 was 4.75 and that of age greater than 65 was 3.95. The combined negative effect of a T status greater than 1 and elevated ir-HGF on survival was also highly pronounced (P < 0.005). In addition, elevated ir-HGF had a negative impact on survival when patients were stratified by stage or N status. Stage I patients with high ir-HGF values had a worse outcome than stage II or stage IIIa patients with low ir-HGF values. Elevated ir-HGF was strongly associated with poor outcome for resectable NSCLC patients as a group, and also identified stage I patients with poor outcome, indicating that it could be a useful indicator of risk of relapse and death in patients who have early lung cancer. The impact of elevated ir-HGF was especially prominent in patients whose T status was greater than 1, suggesting that patients with both risk factors who are stag}, }
@article {pmid9066738, year = {1997}, author = {Sogawa, K and Masaki, T and Miyauchi, A and Sugita, A and Kito, K and Ueda, N and Miyamoto, K and Okazaki, K and Okutani, K and Matsumoto, K}, title = {Enhanced expression of PP1 gamma 1, a catalytic subunit isoform of protein phosphatase type 1, in invasive ductal carcinoma of the breast.}, journal = {Cancer letters}, volume = {112}, number = {2}, pages = {263-268}, doi = {10.1016/s0304-3835(96)04589-2}, pmid = {9066738}, issn = {0304-3835}, mesh = {Adult ; Antigens, Neoplasm/*analysis ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics ; Catalysis ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Isoenzymes/*analysis ; Macromolecular Substances ; Middle Aged ; Phosphoprotein Phosphatases/*analysis ; S Phase/physiology ; }, abstract = {Breast cancer is one of the most common malignancies of women. Assessing the biological parameters of malignant tumors may facilitate predictions of clinical outcome. The expression of the three catalytic subunits of protein phosphatase (PP) type 1, PP1 alpha, PP1 gamma 1 and PP1 delta, as well as the one catalytic subunit of PP type 2, PP2AC, were examined in ten cases of mammary dysplasia, ten cases of fibroadenoma and 12 cases of invasive ductal carcinoma, using immunohistochemical analysis. Moreover, we measured the S-phase fraction of the cell cycle for use as a marker value of cell growth, using flow cytometric analysis. The percentage of proliferating cells that stained positive with antisera against PP1 gamma 1 was significantly higher in invasive ductal carcinoma than in mammary dysplasia and fibroadenoma. Furthermore, invasive ductal carcinoma showed a markedly high number of tumor cells in the S-phase of the cell cycle, as compared to mammary dysplasia and fibroadenoma. Our results indicate that PP1 gamma 1 may be involved in the accelerated growth of malignant cells in breast tumors.}, }
@article {pmid8994410, year = {1997}, author = {Maeda, M and Holder, E and Lowes, B and Valent, S and Bies, RD}, title = {Dilated cardiomyopathy associated with deficiency of the cytoskeletal protein metavinculin.}, journal = {Circulation}, volume = {95}, number = {1}, pages = {17-20}, doi = {10.1161/01.cir.95.1.17}, pmid = {8994410}, issn = {0009-7322}, mesh = {Blotting, Western ; Cardiomyopathy, Dilated/*pathology ; Humans ; Immunohistochemistry ; Myocardium/*chemistry ; Polymerase Chain Reaction ; Vinculin/*analogs &amp; derivatives/analysis/*deficiency ; }, abstract = {BACKGROUND: The cytoskeleton plays an important role in maintaining cell structure and integrity. Defects in cytoskeletal proteins can cripple cell strength and may cause cardiomyopathy. We analyzed heart tissues from subjects with dilated cardiomyopathy for abnormalities in the cardiac cytoskeleton. Metavinculin, a cardiac isoform of the cytoskeletal protein vinculin, connects actin microfilaments to the intercalated disk and membrane costameres of the heart.<br><br>METHODS AND RESULTS: Metavinculin and vinculin transcripts and protein were analyzed by polymerase chain reaction (PCR) and Western blotting. Thirty-three human heart specimens were studied, including 5 normal controls, 4 subjects with ischemic cardiomyopathy, 1 with X-linked cardiomyopathy, and 23 with idiopathic dilated cardiomyopathy (IDC). PCR of cardiac cDNA detected absence of the metavinculin transcript in cardiac tissue from a subject with IDC. PCR of genomic DNA showed that the metavinculin exon was present but not utilized in the cardiac transcript. Western blot analysis demonstrated absence of metavinculin protein in the heart from this subject. Immunostaining of cardiac vinculin in this heart showed disorganized intercalated disk structures. Metavinculin deficiency was associated with normal cardiac expression of the cytoskeletal proteins vinculin, alpha-actinin, and dystrophin. Normal metavinculin expression in the other heart specimens suggests that the defect is specific in the IDC subject identified.<br><br>CONCLUSIONS: These results demonstrate an association between metavinculin deficiency and dilated cardiomyopathy due to a defect in alternative mRNA splicing.}, }
@article {pmid10868038, year = {1997}, author = {Peng, J and Dubreuil, A and Raverdy, N and Ganry, O and Lorriaux, A}, title = {[Epidemiology of breast cancers in the Somme department (1990-1993)].}, journal = {Annales de chirurgie}, volume = {51}, number = {9}, pages = {974-980}, pmid = {10868038}, issn = {0003-3944}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/pathology ; Carcinoma, Ductal, Breast/epidemiology ; Carcinoma, Lobular/epidemiology ; Female ; France/epidemiology ; Humans ; Incidence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Rural Population ; Survival Rate ; Urban Population ; }, abstract = {Breast cancer is the commonest female cancer in the Somme region and represents the leading cause of cancer mortality in women. It therefore constitutes an important public health problem. From 1990 to 1993, 1,106 new cases of breast cancer were recorded by the Somme Cancer Registry. The incidence continued to increase over this period in the Somme region. The mortality rate for this period was 35.1/100,000 women, while the standardized mortality rate for the world population was 20.9/100,000 women. The most frequent histological types were invasive ductal carcinoma (64.3%) and invasive lobular carcinoma (5%). Carcinoma in situ represented 2.9% cases; 4% of patients presented metastases at the time of diagnosis. For the period 1990-1993, 44.3% cases were classified as T1, 37.9% as T2 and 11.5% as T3-T4. The lymph node extension rate was less than 15% for tumours less than 10 mm (on the resection specimen). The 5-year survival rate was 73%. It is important to increase the rate of early diagnosis in order to improve the overall survival of this disease.}, }
@article {pmid9365176, year = {1997}, author = {Toikkanen, S and Pylkkänen, L and Joensuu, H}, title = {Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma.}, journal = {British journal of cancer}, volume = {76}, number = {9}, pages = {1234-1240}, pmid = {9365176}, issn = {0007-0920}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/epidemiology/genetics/*mortality/pathology ; Carcinoma, Lobular/epidemiology/genetics/*mortality/pathology ; Female ; Flow Cytometry ; Follow-Up Studies ; Humans ; Lymphatic Metastasis/diagnosis ; Middle Aged ; Multivariate Analysis ; Prognosis ; S Phase ; Survival Rate ; }, abstract = {The outcome and prognostic factors of 217 women with invasive lobular carcinoma (ILC) and those of 1121 women with invasive ductal carcinoma (IDC) of the breast were compared. The patients were followed up for 10-43 years. Women with ILC had axillary nodal metastases less frequently than those with IDC (43% vs 53%, P = 0.02), although there was no difference in the primary tumour size between the groups. ILCs were more frequently of low grade, had lower mitotic counts and had less tumour necrosis. Furthermore, ILCs had lower S-phase fractions and were more often DNA diploid in flow cytometric analysis than IDCs (P < 0.0001 for all comparisons). The 5- and 30-year corrected survival rates of women with ILC were 78% and 50%, respectively, compared with 63% and 37% for women with IDC (P = 0.001). Small pT1NOMO ILCs (n = 41) had 100% 10-year and 83% 20-year corrected survival rates. In a multivariate analysis, a large primary tumour size, the presence of axillary nodal metastases, a high mitotic count and the presence of tumour necrosis all had an independent prognostic value in ILC. We conclude that ILC is associated with better survival than IDC.}, }
@article {pmid9365159, year = {1997}, author = {Vos, CB and Cleton-Jansen, AM and Berx, G and de Leeuw, WJ and ter Haar, NT and van Roy, F and Cornelisse, CJ and Peterse, JL and van de Vijver, MJ}, title = {E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis.}, journal = {British journal of cancer}, volume = {76}, number = {9}, pages = {1131-1133}, pmid = {9365159}, issn = {0007-0920}, mesh = {Breast Neoplasms/*genetics/*metabolism ; Cadherins/*genetics/*metabolism ; Carcinoma in Situ/genetics/*metabolism ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Lobular/genetics/*metabolism ; Chromosome Deletion ; DNA/analysis ; Heterozygote ; Humans ; Immunohistochemistry ; }, abstract = {In breast cancer, inactivating point mutations in the E-cadherin gene are frequently found in invasive lobular carcinoma (ILC) but never in invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) adjacent to ILC has previously been shown to lack E-cadherin expression, but whether LCIS without adjacent invasive carcinoma also lacks E-cadherin expression and whether the gene mutations present in ILC are already present in LCIS is not known. We report here that E-cadherin expression is absent in six cases of LCIS and present in 150 cases of ductal carcinoma in situ (DCIS), both without an adjacent invasive component. Furthermore, using mutation analysis, we could demonstrate the presence of the same truncating mutations and loss of heterozygosity (LOH) of the wild-type E-cadherin in the LCIS component and in the adjacent ILC. Our results indicate that E-cadherin is a very early target gene in lobular breast carcinogenesis and plays a tumour-suppressive role, additional to the previously suggested invasion-suppressive role.}, }
@article {pmid9214117, year = {1997}, author = {Bychkova, NV and Pozharisskiĭ, KM}, title = {[Aneuploidy and proliferative activity in breast cancer (flow-cytometric investigation)].}, journal = {Voprosy onkologii}, volume = {43}, number = {2}, pages = {171-175}, pmid = {9214117}, issn = {0507-3758}, mesh = {Adult ; Aged ; *Aneuploidy ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cell Division ; DNA, Neoplasm/genetics ; Female ; Flow Cytometry ; Humans ; Middle Aged ; }, abstract = {Flow-cytometric assay of DNA levels and proliferative activity of cell in 43 cancers of the breast was carried out. The cytometric data were evaluated versus age, histological malignancy and regional metastasis incidence. The study pointed to a direct correlation between malignancy and aneuploidy (increased fraction of cells featuring unbalanced levels of DNA as well as enhanced DNA index) involved in invasive ductal carcinoma. Aneuploidy and proliferative activity frequency is relatively higher in cases of regionally disseminated tumors. Aneuploidy tumor incidence is higher in age groups under 50 than in older patients.}, }
@article {pmid9043471, year = {1997}, author = {Salvadori, B and Biganzoli, E and Veronesi, P and Saccozzi, R and Rilke, F}, title = {Conservative surgery for infiltrating lobular breast carcinoma.}, journal = {The British journal of surgery}, volume = {84}, number = {1}, pages = {106-109}, pmid = {9043471}, issn = {0007-1323}, mesh = {Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Carcinoma, Lobular/*surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy/*methods ; Middle Aged ; Neoplasm Recurrence, Local/*etiology ; Proportional Hazards Models ; Risk Factors ; Survival Analysis ; }, abstract = {BACKGROUND: Some reports state that infiltrating lobular breast carcinoma (ILC) should not be treated by conservative methods because of a high risk of local recurrence. The aim of this study was to determine whether patients with conservatively treated ILC have a higher risk of intrabreast relapse than those with infiltrating ductal carcinoma (IDC).<br><br>METHODS: Some 286 consecutive patients with ILC of the breast were compared with 1903 women with IDC treated at the Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, over the same interval (1973-1989). Patients in both series received the same treatment: quadrantectomy, complete axillary dissection and radiotherapy to the breast. Adjuvant treatment was administered according to nodal and menopausal status (chemotherapy or tamoxifen). Follow-up lasted until December 1994, with a median of 137 months for patients with ILC and 133 for those with IDC. Histology slides were reviewed to assess the presence of multifocality (ILC 4.5 per cent versus IDC 3.6 per cent and extensive intraduct component (ILC 0.3) per cent versus IDC 6.4 per cent).<br><br>RESULTS: No difference in cumulative local recurrence rate was found between the two groups at 10 years (approximately 7 per cent).<br><br>CONCLUSION: Conservative surgery is equally safe for patients with infiltrating lobular or ductal carcinoma of the breast.}, }
@article {pmid8945070, year = {1996}, author = {Grimm, W and Hoffmann, J and Knop, U and Winzenburg, J and Menz, V and Maisch, B}, title = {Value of time- and frequency-domain analysis of signal-averaged electrocardiography for arrhythmia risk prediction in idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {19}, number = {11 Pt 2}, pages = {1923-1927}, doi = {10.1111/j.1540-8159.1996.tb03254.x}, pmid = {8945070}, issn = {0147-8389}, mesh = {Action Potentials ; Adolescent ; Adult ; Aged ; Arrhythmias, Cardiac/diagnosis/*etiology ; Cardiomyopathy, Dilated/*complications ; Death, Sudden, Cardiac/etiology ; Electrocardiography/*methods ; Female ; Follow-Up Studies ; Forecasting ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; *Risk Assessment ; Sensitivity and Specificity ; *Signal Processing, Computer-Assisted ; Tachycardia, Ventricular/etiology ; Time Factors ; Ventricular Fibrillation/etiology ; Ventricular Function ; }, abstract = {Signal-averaged electrocardiography (SAECG) was performed in 120 consecutive patients with idiopathic dilated cardiomyopathy (IDC), and in 60 healthy controls. Time-domain analysis of SAECGs revealed ventricular late potentials in 27 of 120 patients with IDC (23%) compared to 2 of 60 controls (3%; P < 0.05). Frequency-domain analysis of SAECGs showed ventricular late potentials in 9 of 120 patients with IDC (8%) compared to none of the 60 controls (0%, P < 0.05). During a prospective follow-up of 15 +/- 7 months, serious arrhythmic events, defined as sustained ventricular tachyarrhythmias or sudden death, occurred in 17 of 120 patients with IDC (14%). The sensitivity, specificity, and positive and negative predictive values of ventricular late potentials for serious arrhythmic events were 35%, 80%, 22%, and 88% for the time-domain analysis, and 18%, 94%, 33%, and 87% for the frequency-domain analysis of SAECG, respectively. Thus, neither the time-nor the frequency-domain analysis of SAECG appears to be useful for risk stratification in the setting of IDC in view of their low sensitivity and low positive predictive value for serious arrhythmic events during follow-up.}, }
@article {pmid8945062, year = {1996}, author = {Grimm, W and Steder, U and Menz, V and Hoffmann, J and Grote, F and Maisch, B}, title = {Clinical significance of increased OT dispersion in the 12-lead standard ECG for arrhythmia risk prediction in dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {19}, number = {11 Pt 2}, pages = {1886-1889}, doi = {10.1111/j.1540-8159.1996.tb03246.x}, pmid = {8945062}, issn = {0147-8389}, mesh = {Arrhythmias, Cardiac/*diagnosis/etiology ; Cardiac Output, Low/etiology ; Cardiomyopathy, Dilated/*complications ; Case-Control Studies ; Death, Sudden, Cardiac/etiology ; Defibrillators, Implantable ; Electrocardiography/*methods ; Female ; Follow-Up Studies ; Forecasting ; Humans ; Male ; Middle Aged ; Prospective Studies ; *Risk Assessment ; Risk Factors ; Stroke Volume ; Tachycardia, Ventricular/etiology ; Ventricular Dysfunction, Left/etiology ; Ventricular Fibrillation/etiology ; }, abstract = {QT dispersion was determined from the 12-lead standard ECGs from 107 patients with idiopathic dilated cardiomyopathy (IDG) and compared to QT dispersion measurements in 100 healthy age and sex matched controls. QT dispersion, rate corrected QT dispersion and adjusted QTc dispersion were significantly greater in patients with IDC compared to controls. During a prospective follow-up of 13 +/- 7 months, arrhythmic events, defined as sustained VT, VF, or sudden death, occurred in 12 (11%) of 107 study patients with IDC. QT dispersion was increased in patients with arrhythmic events compared to patients without arrhythmic events during follow-up (76 +/- 17 vs 60 +/- 26 ms; P = 0.03). Differences in QTc dispersion and adjusted QTc dispersion between patients with and without arrhythmic events, however, failed to reach statistical significance. Thus, although QT dispersion was increased in patients with IDC and arrhythmic events during follow-up, its clinical usefulness for risk stratification appears to be very limited due to the large overlap of QT dispersion among patients with and without arrhythmic events.}, }
@article {pmid8945053, year = {1996}, author = {Hoffmann, J and Grimm, W and Menz, V and Knop, U and Maisch, B}, title = {Heart rate variability and major arrhythmic events in patients with idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {19}, number = {11 Pt 2}, pages = {1841-1844}, doi = {10.1111/j.1540-8159.1996.tb03237.x}, pmid = {8945053}, issn = {0147-8389}, mesh = {Adolescent ; Adult ; Aged ; Arrhythmias, Cardiac/*etiology/therapy ; Cardiomyopathy, Dilated/*complications/physiopathology ; Death, Sudden, Cardiac/etiology ; Defibrillators, Implantable ; Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Forecasting ; *Heart Rate ; Humans ; Male ; Middle Aged ; Parasympathetic Nervous System/physiopathology ; Prospective Studies ; Risk Factors ; Sinoatrial Node/physiopathology ; Tachycardia, Ventricular/etiology/therapy ; Ventricular Dysfunction, Left/etiology/therapy ; Ventricular Fibrillation/etiology/therapy ; }, abstract = {This prospective study of 71 patients with idiopathic dilated cardiomyopathy (IDC) and preserved sinus rhythm was designed to evaluate the relation between heart rate variability (HRV) and subsequent major arrhythmic events. Standard time- and frequency-domain HRV parameters were obtained from analysis of 24-hour Holter ECG recordings. During a mean follow-up of 15 +/- 5 months, major arrhythmic events including sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death occurred in 10 of the 71 study patients (14%). Neither time- nor frequency-domain indices of HRV differed significantly between patients with and patients without subsequent major arrhythmic events. However, there was a trend toward a lower standard deviation of the average normal RR interval for all 5-minute segments of the 24-hour recording (68 +/- 17 ms vs 80 +/- 31 ms; P = 0.06) in patients with major arrhythmic events. In addition, the percentage of adjacent normal RR intervals differing > 50 ms over the recording period tended to be lower in patients with major arrhythmic events (6% +/- 3% vs 9% +/- 6%; P = 0.08). Our results indicate a tendency toward attenuated parasympathetic activity in IDC patients with subsequent major arrhythmic events compared to arrhythmia-free patients. Larger studies with longer follow-up periods are necessary to clarify the role of HRV measurements for arrhythmia risk prediction in patients with IDC.}, }
@article {pmid8942552, year = {1996}, author = {Warneke, J and Berger, R and Johnson, C and Stea, D and Villar, H}, title = {Lumpectomy and radiation treatment for invasive lobular carcinoma of the breast.}, journal = {American journal of surgery}, volume = {172}, number = {5}, pages = {496-500}, doi = {10.1016/S0002-9610(96)00227-9}, pmid = {8942552}, issn = {0002-9610}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/pathology/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*radiotherapy/secondary/*surgery ; Carcinoma, Lobular/mortality/pathology/*radiotherapy/secondary/*surgery ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/epidemiology ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Large studies have shown a similar outcome when comparing mastectomy with lumpectomy and external beam radiation therapy in the treatment of infiltrating ductal carcinoma. However, this has not been studied extensively for invasive lobular carcinoma. We studied the pattern of recurrence and overall survival of patients treated with lumpectomy and radiation for either invasive lobular carcinoma (ILC) or combined invasive lobular carcinoma/invasive ductal carcinoma (ILC/IDC) of the breast.<br><br>DESIGN: A retrospective chart review was performed for 111 patients with ILC or ILC/IDC who were diagnosed and/or treated at the university hospital between 1984 and 1994.<br><br>RESULTS: Of the 111 patients, 93 had stage I or II tumors. Thirty-four patients (37%) were treated with lumpectomy and adjuvant postoperative radiotherapy with one (3%) local recurrence and a mean overall survival of 83.6 months. Fifty-nine patients (63%) were treated by modified radical mastectomy with two local recurrences (3%) and a mean overall survival of 71.7 months.<br><br>CONCLUSIONS: Patients with ILC or ILC/IDC can be effectively treated with lumpectomy and radiation for stage I and II tumors while maintaining a low risk of local recurrence and equivalent overall survival.}, }
@article {pmid8923858, year = {1996}, author = {Sasano, H and Frost, AR and Saitoh, R and Harada, N and Poutanen, M and Vihko, R and Bulun, SE and Silverberg, SG and Nagura, H}, title = {Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {81}, number = {11}, pages = {4042-4046}, doi = {10.1210/jcem.81.11.8923858}, pmid = {8923858}, issn = {0021-972X}, mesh = {17-Hydroxysteroid Dehydrogenases/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Aromatase/*metabolism ; Breast Neoplasms/*enzymology/immunology/metabolism ; Carcinoma, Ductal, Breast/enzymology/immunology/metabolism ; Carcinoma, Lobular/enzymology/immunology/metabolism ; Estradiol/biosynthesis ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Middle Aged ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {The in situ formation of estradiol plays an important role in the development and biological behavior of human breast cancer Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD type 1) are two principal enzymes involved in in situ estradiol production. We evaluated the expression of aromatase and 17 beta-HSD type 1 by immunohistochemistry in 41 cases of invasive breast carcinoma (19 lobular and 22 ductal). We then examined the correlation among the expression of these enzymes, estrogen (ER) and progesterone (PR) receptor status, Ki67 labeling index of carcinoma cells, age, and the clinical stage of the patients. Marked aromatase immunoreactivity was observed in stromal cells around carcinomatous glands in 32 of 41 cases (78%), and 17 beta-HSD type 1 immunoreactivity was detected in carcinoma cells in 23 of 41 cases (56%). There was a significant correlation observed between expression of 17 beta-HSD type 1 and aromatase in invasive lobular carcinoma (P = 0.0119), but not in invasive ductal carcinoma. There was an inverse correlation between aromatase and ER status in invasive ductal carcinoma (P = 0.0213), but not in invasive lobular carcinoma. No other correlations were observed among 17 beta-HSD type 1, aromatase, PR, ER, clinical stage, age, and Ki67 labeling indexes. Aromatase and 17 beta-HSD are not always expressed simultaneously in human breast carcinoma, but their simultaneous expression is more frequent in invasive lobular carcinoma than invasive ductal carcinoma. Consequently, different mechanisms may be involved in the regulation of expression of these two enzymes in human breast carcinoma.}, }
@article {pmid8971351, year = {1996}, author = {Centeno, JA and Pestaner, JP and Mullick, FG and Virmani, R}, title = {An analytical comparison of cobalt cardiomyopathy and idiopathic dilated cardiomyopathy.}, journal = {Biological trace element research}, volume = {55}, number = {1-2}, pages = {21-30}, pmid = {8971351}, issn = {0163-4984}, mesh = {Adult ; Beer ; Cardiomyopathies/chemically induced/*pathology ; Cardiomyopathy, Dilated/*pathology ; Cobalt/analysis/*toxicity ; Female ; *Food Additives ; Humans ; Male ; Middle Aged ; Myocardium/*pathology ; Myofibrils/pathology ; Necrosis ; Retrospective Studies ; }, abstract = {Toxic cardiomyopathy (TC) has a rapid clinical course and morphologically resembles idiopathic dilated cardiomyopathy (IDC). To further characterize TC, we used light microscopy to compare lesions caused by cobalt (Co) to those of IDC. Cobalt levels were also measured as a chemical marker to differentiate TC from IDC. We reviewed cases with TC and IDC and excluded all cases with chemotherapy-induced myopathy and catecholamine toxicity as well as cases with possible infectious, ischemic, or hypersensitivity-induced myopathies. We compared the light microscopic findings of 12 TC cases of 12 cases of IDC, and measured trace Co levels on digested heart tissue samples. The TC cases had prominent myofibrillar loss and atrophy; no cases had neutrophil infiltration or frank myocyte necrosis. In contrast, IDC had minimal myofibril loss and atrophy. Cobalt levels in the range of 0.6 to 5.45 micrograms/g of dry tissue were obtained for the TC cases, while IDC demonstrated Co levels of 0.01-0.2 micrograms/g. Distinction between TC and IDC is predominantly a function of myocyte change, with TC showing myofibrillar loss and atrophy in the absence of inflammatory infiltrates and fibrosis; IDC is predominantly associated with myocyte hypertrophy, atrophy, and fibrosis.}, }
@article {pmid8962875, year = {1996}, author = {Iordănescu, C}, title = {[Current trends in herpetic keratitis].}, journal = {Oftalmologia (Bucharest, Romania : 1990)}, volume = {40}, number = {4}, pages = {402-409}, pmid = {8962875}, issn = {1220-0875}, mesh = {Antiviral Agents/therapeutic use ; Combined Modality Therapy ; Cornea/surgery ; Humans ; Interferons/therapeutic use ; Keratitis, Herpetic/diagnosis/*epidemiology/therapy ; Morbidity/trends ; }, abstract = {The virus simplex herpes (VSH) differs from other viruses in that it frequently affects the eyes and because of the gravity of lesions. It belongs to the herpes-virus family which also includes the varicella virus, the cytomegalovirus, zone and the Epstein-Barr virus. The main feature consists of the fact that after the first infection in latent form, the virus remains inside the body and may cause recidives. The type I determines oculofacial lesions. While the type II determines genital lesions. Seldom it may affects the eye in a severe form. In fact there is inside every type a great antigenic variability, with many intermediate forms. The antiviral drugs from the 1 generation, like IDU (iodoxuridine), IDC (iododezoxiuridine), vidarabine and TFT (trifluoro-thymidine) are rather toxic because of the lack in their action selectivity. The antiviral drugs from the second generation, like the acyclovir, have a more selective action. The corticotherapy, locally administrated, is useful in the immunopathological lesions in the recidivated profound forms. The corticotherapy must be reduced at the minimal doses, which should be taken before an antiviral prophylactic chemotherapy.}, }
@article {pmid8992375, year = {1996}, author = {Laubichler, W and Kühberger, A and Sedlmeier, P}, title = {["Pyromania" and arson. A psychiatric and criminologic data analysis].}, journal = {Der Nervenarzt}, volume = {67}, number = {9}, pages = {774-780}, doi = {10.1007/s001150050052}, pmid = {8992375}, issn = {0028-2804}, mesh = {Adult ; Comorbidity ; Expert Testimony/legislation &amp; jurisprudence ; Female ; Firesetting Behavior/*diagnosis/psychology/rehabilitation ; Humans ; Male ; Motivation ; Paraphilic Disorders/diagnosis/psychology/rehabilitation ; Personality Disorders/diagnosis/psychology ; Psychiatric Status Rating Scales ; Recurrence ; }, abstract = {We analyzed psychiatric and criminological data from 103 arsonists. The following criticisms of the definition of pyromania according to DSM-III-R and IDC-10 seem appropriate. First, the categoric exclusion of aggressive motives does not seem very promising, since approximately one fourth of arsonists whose firesetting is based on motives quoted in DSM-III-R may also have an aggressive motive. Second, ICD-10 gives being drunk and alcoholism as a criterion for the exclusion of pyromania. This seems untenable, since the behavior classed as pyromania is largely a product of alcohol misuse. Repeated firesetting, resulting from being fascinated by fire etc., may be less a disturbance of impulse control but rather the manifestation of a psychoinfantilism, which, supported by alcohol abuse, extends into older age. The mean age of such arsonists is slightly above 20 years. The tendency for relapses after imprisonment seems to be low; this tendency probably decreases spontaneously in older age. The mean age of arsonists with aggressive motives is a little below 30 years, those setting fire with suicidal motives have a mean age of 35, deluded arsonists have a mean age of 40 years. Concrete sexual motives are relatively rare. Approximately 50% of arsonists have a purely aggressive motive. Retaliation is a rare cause, however, since most of them do not even know the victims. One third of these persons set the fire in their own homes. Most arsonists show a personality disorder, with insecurity and narcissism predominating. Data on firesetting are to be treated with caution, since two thirds of all cases are newer resolved; one fourth of cases concern minors, and in Central Europe arsonists with rational motives are hardly ever referred to psychiatrists.}, }
@article {pmid8752193, year = {1996}, author = {Grimm, W and Steder, U and Menz, V and Hoffman, J and Maisch, B}, title = {QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {78}, number = {4}, pages = {458-461}, doi = {10.1016/s0002-9149(96)00337-2}, pmid = {8752193}, issn = {0002-9149}, mesh = {Anti-Arrhythmia Agents/therapeutic use ; Arrhythmias, Cardiac/drug therapy/*etiology/physiopathology/therapy ; Bundle-Branch Block/complications/physiopathology ; Cardiomyopathy, Dilated/*complications/drug therapy/physiopathology/therapy ; Case-Control Studies ; Cohort Studies ; Death, Sudden, Cardiac/etiology ; Defibrillators, Implantable ; *Electrocardiography ; Female ; Follow-Up Studies ; Humans ; Hypertrophy, Left Ventricular/complications/physiopathology ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Stroke Volume ; Tachycardia, Ventricular/etiology/physiopathology ; Ventricular Dysfunction, Left/etiology/physiopathology ; Ventricular Fibrillation/etiology/physiopathology ; }, abstract = {QT dispersion was measured in the 12-lead standard electrocardiogram in 107 patients with idiopathic dilated cardiomyopathy (IDC) and 100 age- and sex- matched controls without structural heart disease. All 107 study patients with IDC were prospectively followed in order to determine possible associations between QT dispersion and arrhythmic events, i.e., sustained ventricular tachycardia, ventricular fibrillation, or sudden death. QT dispersion, rate-corrected QT dispersion, and adjusted QTc dispersion, which takes account of the number of leads measured, were significantly greater in patients with IDC than in controls. During 13 +/- 7 months follow-up, arrhythmic events occurred in 12 of 107 study patients with IDC (11%). QT dispersion was increased in patients with versus without arrhythmic events during follow-up (76 +/- 17 vs 60 +/- 26 ms; p=0.03). QTc dispersion and adjusted QTc dispersion were not significantly different between patients with and without arrhythmic events (80 +/- 21 vs 75 +/- 35 ms, and 27 +/- 6 vs 24 +/- 10 ms, respectively). Thus, although QT dispersion was increased in patients with IDC and arrhythmic events during follow-up, its usefulness for arrhythmia risk prediction was limited by the large overlap of QT dispersion between patients with and without arrhythmic events.}, }
@article {pmid8924674, year = {1996}, author = {Friedrich, M and Krauth, M and Lange, K}, title = {[Angiosarcoma of the breast after breast-preserving therapy of invasive ductal carcinoma].}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {165}, number = {2}, pages = {195-197}, doi = {10.1055/s-2007-1015739}, pmid = {8924674}, issn = {1438-9029}, mesh = {Breast Neoplasms/radiotherapy/surgery/*therapy ; Carcinoma, Ductal, Breast/radiotherapy/surgery/*therapy ; Combined Modality Therapy ; Female ; Hemangiosarcoma/diagnosis/diagnostic imaging/*etiology ; Humans ; Magnetic Resonance Imaging ; *Mastectomy, Segmental ; Middle Aged ; Neoplasms, Second Primary/diagnosis/diagnostic imaging/*etiology ; Prognosis ; Radiotherapy Dosage ; Ultrasonography ; }, }
@article {pmid8881501, year = {1996}, author = {Mestroni, L and Milasin, J and Vatta, M and Pinamonti, B and Sinagra, G and Rocco, C and Matulic, M and Falaschi, A and Giacca, M and Camerini, F}, title = {Genetic factors in dilated cardiomyopathy.}, journal = {Archives des maladies du coeur et des vaisseaux}, volume = {89 Spec No 2}, number = {}, pages = {15-20}, pmid = {8881501}, issn = {0003-9683}, support = {E.0291/TI_/Telethon/Italy ; }, mesh = {Cardiomyopathy, Dilated/diagnosis/*genetics ; Chromosome Mapping ; Chromosomes, Human, Pair 1/genetics ; Chromosomes, Human, Pair 14/genetics ; Chromosomes, Human, Pair 3/genetics ; Chromosomes, Human, Pair 9/genetics ; Dystrophin/genetics ; Genes, Dominant ; Humans ; *Molecular Biology ; Pedigree ; X Chromosome/genetics ; }, abstract = {Recent studies have demonstrated that genetic factors are likely to play a major role in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). In clinical surveys, a familial trait has been demonstrated in 20 to 30% of idiopathic dilated cardiomyopathy patients (familial dilated cardiomyopathy). Molecular genetic studies have confirmed the clinical hypothesis of genetic heterogeneity in familial dilated cardiomyopathy, and are currently producing relevant advances in the understanding of this disease. The autosomal dominant form is considered to be the most frequent form of inherited idiopathic dilated cardiomyopathy. After the exclusion of a large series of candidate genes, the first familial dilated cardiomyopathy gene has been mapped to the long arm of chromosome 9. A second locus has been found on chromosome 1. Moreover, in two large families, characterized by a peculiar form of conduction delays and later development of myocardial dysfunction, the disease loci have been mapped to chromosome 1 and 3, respectively. The identification of the disease genes is in progress. In families with X-linked dilated cardiomyopathy, the disease gene has been identified as the dystrophin gene. The 5' end of the gene appears to be the critical region for the development of dilated cardiomyopathy without clinical evidence of muscle dystrophy. Furthermore, other cytoskeletal proteins, such as adhalin, could be involved in the pathogenesis of familial dilated cardiomyopathy. In familial right ventricular cardiomyopathy (or arrhythmogenic right ventricular dysplasia) characterized by isolated or prevalent right ventricular involvement, three different disease loci have been identified so far: two localized on the long arm of chromosome 14 and one on chromosome 1. The disease genes are still unknown and are currently under investigation. The study of the genetic factors at the molecular level is starting to elucidate the pathogenetic mechanisms of idiopathic dilated cardiomyopathy. These findings will also have relevant clinical and therapeutic implications.}, }
@article {pmid8877079, year = {1996}, author = {Gasser, R and Fruhwald, F and Schumacher, M and Seinost, G and Reisinger, E and Eber, B and Keplinger, A and Horvath, R and Sedaj, B and Klein, W and Pierer, K}, title = {Reversal of Borrelia burgdorferi associated dilated cardiomyopathy by antibiotic treatment?.}, journal = {Cardiovascular drugs and therapy}, volume = {10}, number = {3}, pages = {351-360}, pmid = {8877079}, issn = {0920-3206}, mesh = {Adolescent ; Adult ; Aged ; Angiotensin-Converting Enzyme Inhibitors/administration &amp; dosage/therapeutic use ; Borrelia Infections/diagnosis/*drug therapy/physiopathology ; Borrelia burgdorferi Group/*drug effects ; Cardiomyopathy, Dilated/diagnosis/*drug therapy/epidemiology/microbiology ; Ceftriaxone/administration &amp; dosage/adverse effects/pharmacology/*therapeutic use ; Cephalosporins/administration &amp; dosage/pharmacology/*therapeutic use ; Chi-Square Distribution ; Culture Media ; Digitalis ; Diuretics/administration &amp; dosage/therapeutic use ; Electrocardiography ; Female ; Heart/microbiology ; Humans ; Immunoglobulin G/blood ; Injections, Intravenous ; Male ; Middle Aged ; Plants, Medicinal ; Plants, Toxic ; Stroke Volume/*drug effects ; }, abstract = {It is suggested that Borrelia burgdorferi infection could be associated with dilated cardiomyopathy (IDC). Stanek et al. were able to cultivate Borrelia burgdorferi from myocardial biopsy tissue of a patient with longstanding dilated cardiomyopathy. Here we present a study in which we examined the effect of standard antibiotic treatment on the left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy associated with Borrelia burgdorferi infection. In this study we assessed the serum (IgG, IgM Elisa) and history of 46 IDC patients with specific regard to Borrelia burgdorferi infection (mean LVEF 30.4 +/- 1.3%, measured by cardiac catheterization and echocardiography with the length-area-volume method). All 46 patients received standard treatment for dilated cardiomyopathy: ACE inhibitors, digitalis, and diuretics. Eleven (24%) patients showed positive serology and a history of Borrelia burgdorferi infection; nine of these also had a typical history of tick bite and erythema chronicum migrans (ECM) and/or other organ involvement, and two had no recollection of tick bite or ECM but showed other Borrelia burgdorferi-associated disorders (neuropathy, oligoarthritis). These 11 patients with Borrelia burgdorferi infection received standard antibiotic treatment with intravenous ceftriaxone 2 g bid for 14 days. Six (55%) recovered completely and showed a normal LVEF after 6 months, three (27%) improved their LVEF, and two (18%) did not improve at all. This amounts to nine (82%) patients with recovery/improvement in the Borrelia burgdorferi group. The 35 patients who did not show positive serology or a history of Borrelia burgdorferi infection did not receive antibiotic treatment. In this group without Borrelia burgdorferi infection 12 (26%), showed recovery/improvement following the standard treatment of dilated cardiomyopathy (see earlier). Our results indicate that Borrelia burgdorferi infection could play a decisive role in the development of dilated cardiomyopathy, especially in a geographical region such as Graz, where Borrelia burgdorferi is endemic. While we are aware of the small number of Borrelia burgdorferi patients in this study, we nevertheless conclude that in a remarkable number of patients with signs of Borrelia burgdorferi infection, dilated cardiomyopathy could be reversed and LVEF improved.}, }
@article {pmid8814452, year = {1996}, author = {Yaremko, ML and Kutza, C and Lyzak, J and Mick, R and Recant, WM and Westbrook, CA}, title = {Loss of heterozygosity from the short arm of chromosome 8 is associated with invasive behavior in breast cancer.}, journal = {Genes, chromosomes &amp; cancer}, volume = {16}, number = {3}, pages = {189-195}, doi = {10.1002/(SICI)1098-2264(199607)16:3&lt;189::AID-GCC6&gt;3.0.CO;2-V}, pmid = {8814452}, issn = {1045-2257}, support = {CA14559/CA/NCI NIH HHS/United States ; P20CA66132/CA/NCI NIH HHS/United States ; R55CA5607/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosome Deletion ; *Chromosomes, Human, Pair 8 ; DNA, Neoplasm ; Female ; Genetic Markers ; Humans ; Microsatellite Repeats ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Polymorphism, Genetic ; }, abstract = {Loss of heterozygosity (LOH) from the short arm of chromosome 8 (8p) is frequent in many human cancers, including breast, colon, prostate, and bladder cancers. LOH occurs in two regions of 8p, 8p21 and 8p22, and suggests the presence of two separate tumor suppressor genes. In breast cancers, 8p LOH occurs in both early and late clinical stage tumors, while in colon, prostate, and bladder cancers, there is an association between 8p LOH and advanced clinical stage. We investigated this discrepancy by comparing 8p LOH in infiltrating ductal carcinomas (IDC) to breast cancers of earlier clinical stage, i.e., tumors with no invasion [ductal carcinoma in situ (DCIS)-only tumors]. We used three markers which sample several reported loci of 8p LOH. We microdissected tumor from paraffin blocks of 39 IDC and 23 DCIS-only breast cancers and amplified tumor/normal DNA pairs for the microsatellite markers D8S254 (8p22), D8S133 (8p21.3), and NEFL (8p21). All cases of IDC were informative with at least one marker, with a combined rate of LOH of 46%. The results for each marker were [no. LOH/no. informative (%)]: D8S254, 8/26 (31%); D8S133 12/31 (39%), and NEFL, 9/25 (36%). In the DCIS-only group, all 23 were informative for at least one marker, but 8p LOH was absent. We conclude that 8p LOH from 8p21-22 is frequent in IDC of the breast, but absent in DCIS-only cases, and may play a role in breast cancer progression by conferring invasive ability.}, }
@article {pmid8711701, year = {1996}, author = {Kolbenstvedt, A and Smevik, B and Vatne, K and Kolmannskog, F and Naalsund, A}, title = {[Embolization of congenital pulmonary arteriovenous malformations].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {116}, number = {16}, pages = {1883-1885}, pmid = {8711701}, issn = {0029-2001}, mesh = {Adult ; Arteriovenous Malformations/complications/diagnostic imaging/*therapy ; Brain Abscess/diagnostic imaging/etiology ; *Embolization, Therapeutic/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Artery/*abnormalities/diagnostic imaging ; Pulmonary Veins/*abnormalities/diagnostic imaging ; Radiography ; Radionuclide Imaging ; }, abstract = {Patients with arteriovenous pulmonary malformations are at risk of developing secondary brain disease such as transient ischemic attacks, strokes or abscesses. Lethal haemothorax and haemoptysis also occur. 12 of 14 malformations in five patients were treated using a total of eight procedures. One patient experienced a transient unilateral hemiparesis, otherwise no complications occurred. None of the 43 deployed occlusion coils was lost through the fistulas. Complete occlusion was achieved in all lesions where coils could be placed in a stable position. One patient suffered a minor recurrence. The use of interlocking detachable coils (IDC) which can be retracted or repositioned prior to full deployment is recommended.}, }
@article {pmid8806958, year = {1996}, author = {Wallace, ML and Smoller, BR}, title = {Differential sensitivity of estrogen/progesterone receptors and BRST-2 markers in metastatic ductal and lobular breast carcinoma to the skin.}, journal = {The American Journal of dermatopathology}, volume = {18}, number = {3}, pages = {241-247}, doi = {10.1097/00000372-199606000-00003}, pmid = {8806958}, issn = {0193-1091}, mesh = {Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; *Apolipoproteins ; Apolipoproteins D ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology/*secondary ; Carcinoma, Lobular/pathology/*secondary ; Carrier Proteins/*analysis ; Cell Differentiation ; Coloring Agents ; Female ; Glycoproteins/*analysis ; Humans ; Immunohistochemistry ; *Membrane Transport Proteins ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Skin Neoplasms/pathology/*secondary ; }, abstract = {Cutaneous metastases arising from breast carcinoma are quite common. A standard panel of immunohistochemical markers including estrogen receptor (ER), progesterone receptor (PR), and BRST-2 are frequently used in surgical pathology to identify neoplasms with breast differentiation. It is well known that as the grade of a tumor increases, and as tumors lose their differentiation, immunohistochemistry results become more unpredictable in determining possible primary sites of origin. Although previous studies have identified a decrease of ER sensitivity in breast metastases, a possible sensitivity differential of cutaneous metastases of invasive lobular versus invasive ductal carcinoma by using the standard immunohistochemical panel has not been previously reported. With the standard panel, we compared the staining sensitivity of metastatic invasive ductal carcinoma (10 cases) to metastatic invasive lobular carcinoma (four cases) to the skin. ER positivity was identified in one case of metastatic ductal carcinoma and none of the four lobular carcinomas. PR positivity was noted in all cases of metastatic ductal and lobular carcinoma. BRST-2 positivity was found in only two of 10 cases of metastatic ductal carcinoma and all four of four cases of metastatic lobular carcinoma. These results indicate that a differential sensitivity exists for the BRST-2 marker when comparing cutaneous metastases of invasive lobular with invasive ductal carcinoma.}, }
@article {pmid8758255, year = {1996}, author = {Musarrat, J and Arezina-Wilson, J and Wani, AA}, title = {Prognostic and aetiological relevance of 8-hydroxyguanosine in human breast carcinogenesis.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {32A}, number = {7}, pages = {1209-1214}, doi = {10.1016/0959-8049(96)00031-7}, pmid = {8758255}, issn = {0959-8049}, support = {ES02388/ES/NIEHS NIH HHS/United States ; ES6074/ES/NIEHS NIH HHS/United States ; }, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis/biosynthesis ; Breast/chemistry ; Breast Neoplasms/*chemistry/etiology/genetics ; DNA Damage ; DNA, Neoplasm/genetics ; Deoxyguanosine/*analogs &amp; derivatives/analysis/biosynthesis ; Female ; Humans ; Immunoblotting ; Middle Aged ; Oxidative Stress/*physiology ; Prognosis ; Receptors, Estrogen/analysis ; Smoking/metabolism ; Tumor Cells, Cultured ; }, abstract = {In order to estimate the level of oxidative damage and its role in breast cancer, the promutagenic oxidative lesion, 8-hydroxy-2'-deoxyguanosine (8-OHdG), was determined in DNA isolated from 75 human breast tissue specimens and from normal and transformed human breast cell lines, utilising a newly developed solid-phase immunoslot blot assay. The amount of 8-OHdG was found to be 0.25 +/- 0.03 pmol/microgram in normal breast tissue from reduction mammoplasty, 0.98 +/- 0.174 pmol/microgram in benign tumours and 2.44 +/- 0.49 pmol/microgram DNA in malignant breast tissue with invasive ductal carcinoma. The malignant tissue had a statistically significant 9.76-fold higher level of 8-OHdG than normal tissue (P < 0.001, Mann-Whitney). A statistically significant 12.9-fold (P = 0.004) higher endogenous formation of 8-OHdG was also observed in cultured breast cancer cells compared with normal breast epithelial cells. In addition, a significantly elevated level (3.35-fold higher, P < 0.05) of 8-OHdG observed in oestrogen receptor-positive compared with oestrogen-negative malignant tissues, and in breast cancer cell lines (9.3-fold higher, P = 0.007) suggests a positive relationship between 8-OHdG formation and oestrogen responsiveness. The extent of 8-OHdG adducts did not show a discernible correlation with either the age or the smoking status of the patients. These results indicate that the accumulation of 8-OHdG in DNA has a predictive significance for breast cancer risk assessment and is conceivably a major contributor in the development of breast neoplasia.}, }
@article {pmid8690464, year = {1996}, author = {Van Den Berg, TK and Hasbold, J and Renardel De Lavalette, C and Döpp, EA and Dijkstra, CD and Klaus, GG}, title = {Properties of mouse CD40: differential expression of CD40 epitopes on dendritic cells and epithelial cells.}, journal = {Immunology}, volume = {88}, number = {2}, pages = {294-300}, pmid = {8690464}, issn = {0019-2805}, mesh = {Animals ; Antibodies, Monoclonal ; B-Lymphocytes/*immunology ; CD40 Antigens/*immunology ; Dendritic Cells/*immunology ; Epithelium/*immunology ; Epitopes/immunology ; Female ; Lymph Nodes/immunology ; Mice ; Mice, Inbred BALB C ; Species Specificity ; Spleen/immunology ; Thymus Gland/immunology ; Tissue Distribution ; }, abstract = {In this study we describe the tissue distribution of mouse CD40 using two monoclonal antibodies (mAb) against different epitopes of the molecule. In lymphoid tissues CD40 was expressed by B lymphocytes. Most B cells in typical B-cell compartments were CD40-positive, including germinal centre B cells. Interestingly, the two CD40 epitopes were differentially distributed on subpopulations of dendritic cells and epithelial cells. The 3/23 mAb, but not 3/3, recognized interdigitating dendritic cells (IDC) in lymph nodes, spleen and thymus. Langerhans cells were CD40 negative. In contrast, epithelial cells in the thymus and some other tissues (e.g. skin) were stained with the 3/3 mAb, but not with the 3/23 mAb. The expression of CD40 on dendritic cells and epithelial cells is in agreement with earlier findings in humans. Our data also demonstrate that different epitopes of CD40 are differentially expressed on dendritic cells and epithelial cells. This suggests the existence of different forms of CD40, that are expressed in a cell-type-specific fashion.}, }
@article {pmid8658057, year = {1996}, author = {Ribeiro-Rodrigues, R and Colley, DG and Correa-Oliveira, R and Carter, CE}, title = {Antibodies reactive to Trypanosoma cruzi epimastigotes or amastigotes express different idiotypic patterns if from patients with different clinical forms of Chagas' disease.}, journal = {Scandinavian journal of immunology}, volume = {43}, number = {6}, pages = {671-679}, doi = {10.1046/j.1365-3083.1996.d01-262.x}, pmid = {8658057}, issn = {0300-9475}, support = {5 PO1 AI 26505/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Protozoan/*immunology ; Chagas Cardiomyopathy/immunology ; Chagas Disease/classification/*immunology ; Humans ; Immunoglobulin Idiotypes/*immunology ; Trypanosoma cruzi/*immunology ; }, abstract = {Antibodies (Abs) were purified from pooled sera of patients with either indeterminate (IND or I) or cardiac (CARD or C) Chagas' disease, on either epimastigote (EPI or E) or amastigote-enriched (AMAST or A) antigen (Ag) columns and their idiotypic (Id) expression examined. Anti-Id rabbit Abs were raised to the different preparations (E-IdI, E-IdC, A-IdI and A-IdC). Competitive ELISAs using anti-Ids were able to discriminate between IdI and IdC, disregarding Ag reactivity. E-IdI and A-IdI present different inhibitory abilities, as do E-IdC and A-IdC, but IdC always competes with IdI for anti-IdI comparably. In contrast, a 4-8-fold increase of IdI is required to compete in parallel with IdC for anti-IdC. Therefore, Ids from IND patients share only low levels of the Ids that are most characteristic of CARD patients. While some CARD Abs also express Ids in common with IND patients, these studies reveal that CARD Abs express some Ids that are characteristic to only CARD patients, and these Ids are present on Abs purified with either EPI or AMAST.}, }
@article {pmid9166516, year = {1996}, author = {Solin, LJ and McCormick, B and Recht, A and Haffty, BG and Taylor, ME and Kuske, RR and Bornstein, BA and McNeese, M and Schultz, DJ and Fowble, BL and Barrett, W and Yeh, IT and Kurtz, JM and Amalric, R and Fourquet, A}, title = {Mammographically detected, clinically occult ductal carcinoma in situ treated with breast-conserving surgery and definitive breast irradiation.}, journal = {The cancer journal from Scientific American}, volume = {2}, number = {3}, pages = {158-165}, pmid = {9166516}, issn = {1081-4442}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Humans ; *Mammography ; Mass Screening ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Radiotherapy ; Survival Analysis ; Survival Rate ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is increasingly detected as a nonpalpable lesion on mammographic screening performed for the early detection of breast cancer. Because of the growing incidence of mammographically detected DCIS, the present study was undertaken to determine the outcome of treatment of nonpalpable, mammographically detected intraductal carcinoma of the breast using breast-conserving surgery and definitive breast irradiation.<br><br>MATERIALS AND METHODS: An analysis was performed of 110 women who presented with unilateral, nonpalpable, mammographically detected intraductal carcinoma of the breast and who were treated with breast-conserving surgery and definitive breast irradiation at 10 institutions in Europe and the United States. In all patients, complete gross excision of the primary tumor was performed, and breast irradiation was delivered with definitive intent. When performed, pathologic axillary lymph node staging was node negative (n=29). The median follow-up time was 9.3 years.<br><br>RESULTS: The 10-year actuarial overall survival rate was 93%, and the 10-year actuarial cause-specific survival rate was 96%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 15 local recurrences in the treated breast. The actuarial rate of local failure was 7% at 5 years and 14% at 10 years. The histology of the local recurrence was intraductal carcinoma in 9 cases and invasive ductal carcinoma (with or without associated intraductal carcinoma) in 6 cases. The median time to local recurrence was 5.0 years (mean, 5.4; range, 2.1-15.2). With a median follow-up time of 4.4 years after salvage treatment, 14 of the 15 patients with local recurrence were alive without evidence of disease at the time of last follow-up examination. The crude incidence of local recurrence was 7% (3/42) when the final pathology margin of tumor excision was negative, 29% (5/17) when the margin was close or positive, and 14% (7/51) when the margin was unknown. There was no difference in the rate of local recurrence based on pathologic characteristics of the primary tumor.<br><br>DISCUSSION: Results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases at 10 years following the treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Local recurrences within the treated breast were detected early and were treated with salvage for cure. These results support the initial treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Improvements in patient selection have the potential to reduce the risk of local recurrence.}, }
@article {pmid8809881, year = {1996}, author = {Shamoto, M and Osada, A and Shinzato, M and Kaneko, C and Yoshida, A}, title = {Do epidermal Langerhans cells, migrating from skin lesions, induce the paracortical hyperplasia of dermatopathic lymphadenopathy?.}, journal = {Pathology international}, volume = {46}, number = {5}, pages = {348-354}, doi = {10.1111/j.1440-1827.1996.tb03620.x}, pmid = {8809881}, issn = {1320-5463}, mesh = {Antibodies, Monoclonal ; Cell Division/immunology ; Cell Movement ; Epidermis/immunology/*pathology ; Humans ; Hyperplasia/pathology ; Immunohistochemistry ; Langerhans Cells/immunology/*pathology ; Lymph Nodes/immunology/*pathology ; Lymphatic Diseases/immunology/*pathology ; Microscopy, Immunoelectron ; Proliferating Cell Nuclear Antigen/analysis ; }, abstract = {In the present study, immunohistochemical and immuno-electron microscopic techniques were used to differentiate Langerhans cells (LC) from interdigitating cells (IDC) in the lymph nodes (LN) of dermatopathic lymphadenopathy. The majority of the dendritic cells that existed in the LN of dermatopathic lymphadenopathy were positive for OKT-6 (CD 1a) antibody. It was concluded that these dendritic cells were not IDC, but LC. Electron microscopically, LC in these LN contained a few Birbeck granules (BG). In order to prove the fact that these dendritic cells were LC, the existence of BG was investigated ultrastructurally by examining serial sections, and immunoelectron microscopically for CD 1a positive cells. Most of the LC in the lymph nodes we examined were negative for the anti-proliferating nuclear antigen (PCNA) antibody. This finding may mean that LC in the LN are fully developed cells and do not divide in the LN. Langerhans cells may migrate from the skin lesions to the paracortical areas in the LN, which then may become enlarged.}, }
@article {pmid8738420, year = {1996}, author = {Castro, A and Bono, MR and Simon, V and Rosemblatt, M}, title = {Lymphocyte adhesion to endothelium derived from human lymphoid tissue.}, journal = {European journal of cell biology}, volume = {70}, number = {1}, pages = {61-68}, pmid = {8738420}, issn = {0171-9335}, mesh = {Antibodies/pharmacology ; Cell Adhesion ; Child ; Endothelium, Lymphatic/*cytology ; Fibronectins/immunology ; Flow Cytometry/methods ; Humans ; Integrins/immunology ; Intercellular Adhesion Molecule-1/biosynthesis ; Lymphocytes/*cytology ; Palatine Tonsil/cytology ; Vascular Cell Adhesion Molecule-1/biosynthesis ; }, abstract = {The development of an efficient immune response depends on the capacity of antigen-specific lymphocytes to migrate into secondary lymphoid organs. The first step in the process of lymphocyte extravasation involves lymphocyte binding to the vascular endothelium. Although several adhesion receptors have been implicated in the migration of lymphocytes to inflamed tissue, their role in the extravasation of these cells to normal lymphoid organs is not yet clearly established. The involvement of adhesion molecules in lymphocyte entrance to secondary lymphoid organs can be better assessed in an in vitro system using endothelial cells in culture. Here we report on the isolation and culture of a homogeneous population of adherent cells of endothelial origin derived from human tonsils (TEC) and on adhesion studies performed with these cells. Beginning from primary cultures of human tonsils, we isolated a population of cells that we show by FACScan analysis to present the intracellular endothelial cell marker Von Willebrand factor and LVAP-2, a surface molecule present in venules from lymphoid organs. The cells are negative for FDC, IDC and macrophage markers. They express ICAM-1, VCAM-1 and CD40 both constitutively and in inducible forms and are induced by IFN-gamma to express major histocompatibility complex class II antigens. As opposed to endothelial cells from human umbilical cord (HUVEC), they do not need to be activated by cytokines to bind lymphoid cells via VLA-4. The mAb HP2/1 directed to the integrin VLA-4 blocks adhesion of Ramos and Daudi cells to tumor necrosis factor alpha (TNF-alpha)-treated HUVEC and to untreated TEC but not of tonsil-derived MNC. On the other hand, an anti-VCAM-1 antibody that blocks adhesion of Ramos and Daudi cells to TNF-alpha-treated HUVEC, does not block adhesion of these cells to TEC, suggesting the presence on the tonsillar endothelial cells of a ligand for VLA-4 different from VCAM-1. We show here that this ligand is not fibronectin.}, }
@article {pmid8732665, year = {1996}, author = {Ram, TG and Ethier, SP}, title = {Phosphatidylinositol 3-kinase recruitment by p185erbB-2 and erbB-3 is potently induced by neu differentiation factor/heregulin during mitogenesis and is constitutively elevated in growth factor-independent breast carcinoma cells with c-erbB-2 gene amplification.}, journal = {Cell growth &amp; differentiation : the molecular biology journal of the American Association for Cancer Research}, volume = {7}, number = {5}, pages = {551-561}, pmid = {8732665}, issn = {1044-9523}, support = {CA40064/CA/NCI NIH HHS/United States ; T32CA09676/CA/NCI NIH HHS/United States ; }, mesh = {Androstadienes/pharmacology ; Antineoplastic Agents/*metabolism ; Blotting, Northern ; Blotting, Southern ; Blotting, Western ; Breast Neoplasms ; Cell Division/drug effects/physiology ; DNA, Neoplasm/analysis ; Enzyme Inhibitors/pharmacology ; Epidermal Growth Factor/pharmacology ; Epithelial Cells ; Epithelium/physiology ; ErbB Receptors/*physiology ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic/physiology ; Genes, erbB-2/genetics ; Glycoproteins/*physiology ; Humans ; Insulin-Like Growth Factor I/pharmacology ; Mitogens/physiology ; Neuregulins ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/*metabolism ; Proto-Oncogene Proteins/*physiology ; RNA, Messenger/analysis ; Receptor, ErbB-2/*genetics/metabolism ; Receptor, ErbB-3 ; Signal Transduction/genetics ; Tumor Cells, Cultured/cytology/enzymology ; Tyrosine/metabolism ; Wortmannin ; }, abstract = {Amplification and overexpression of the c-erbB-2 gene in 21MT-2 and 21MT-1 human breast carcinoma cells results in progressively elevated levels of constitutively tyrosine-phosphorylated p185erbB-2 and is associated with progressive insulin-like growth factor (IGF) and combined IGF/epidermal growth factor (EGF) independence in culture. In addition, the neu differentiation factor/heregulins (HRGs), a family of ligands that activate p185erbB-2 through direct binding to erbB-3 or erbB-4, are potent mitogens for various nonneoplastic mammary epithelial cells and carcinoma cell lines in the absence of both IGF and EGF in culture. We have investigated the ability of ligand induction with HRGs or the constitutive activation of p185erbB-2 in the 21MT breast carcinoma cells to induced the recruitment of phosphatidylinositol 3-kinase (PI3K) by p185erbB-2 and erbB-3. HRG was found to potently induce the recruitment of the M(r) 85,000 regulatory subunit of PI3K by phosphotyrosine proteins in both nonneoplastic H16N-2 mammary epithelial cells (which express normal c-erbB-2 levels) and in the 21MT-2 and 21MT-1 cell lines, which were all isolated from a single patient with intraductal and invasive ductal carcinoma of the breast and express c-erbB-3 but not c-erbB-4 in culture. The activation of PI3K in these cells was also associated with high-level mitogenic responsiveness to HRG, as well as the IGF/EGF-independent proliferation of the 21MT cell lines in culture. The recruitment of PI3K by phosphotyrosine protein during ligand-induced activation, or that seen constitutively in the 21MT tumor cells, did not involve detectable tyrosine phosphorylation of p85. The HRG-induced recruitment of p85 and the constitutive recruitment of p85 in the 21MT cell lines involved direct association with both p185erbB-2 and erbB-3, although greater levels were recruited directly by erbB-3. Wortmannin, a potent inhibitor of PI3K enzymatic activity, also blocked the autonomous proliferation of the 21MT cells, and this effect was reversible in long-term cultures. These data indicate that PI3K may be an especially important mediator of HRG-induced proliferation in mammary epithelial cells and is involved in the autonomous proliferation of growth factor-independent breast carcinoma cells with c-erbB-2 gene amplification.}, }
@article {pmid8691344, year = {1996}, author = {Castronovo, V and Van Den Brûle, FA and Jackers, P and Clausse, N and Liu, FT and Gillet, C and Sobel, ME}, title = {Decreased expression of galectin-3 is associated with progression of human breast cancer.}, journal = {The Journal of pathology}, volume = {179}, number = {1}, pages = {43-48}, doi = {10.1002/(SICI)1096-9896(199605)179:1&lt;43::AID-PATH541&gt;3.0.CO;2-N}, pmid = {8691344}, issn = {0022-3417}, mesh = {Antibody Specificity ; Antigens, Differentiation/immunology/*metabolism ; Antigens, Neoplasm/immunology/*metabolism ; Biomarkers, Tumor/*metabolism ; Blotting, Northern ; Blotting, Western ; Breast/metabolism ; Breast Neoplasms/immunology/*metabolism/pathology ; Disease Progression ; *Down-Regulation ; Epithelium/metabolism ; Female ; Galectin 3 ; Humans ; Immunoenzyme Techniques ; Neoplasm Invasiveness ; }, abstract = {Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of galectin-3 during the interactions between cells and laminin is not yet known, it has recently been observed that its expression is down-regulated at both the protein and the mRNA level in colon cancer tissues in correlation with progression of the disease. This study investigated the possibility that breast cancer cells might also exhibit decreased galectin-3 expression in association with their aggressiveness. The expression of galectin-3 was examined by immunoperoxidase staining, using a polyclonal antibody raised against recombinant galectin-3, in a collection of 98 human breast lesions including 12 fibroadenomas, 15 fibrocystic disease lesions, 22 in situ carcinomas, and 49 infiltrating ductal carcinomas, 19 of which had positive axillary lymph nodes. Normal breast tissue adjacent to the lesions was present in 59 biopsies. Normal breast tissue expressed high levels (3+) of galectin-3. High expression (2+ to 3+) was also found in most benign lesions examined. The expression of galectin-3 was significantly decreased in in situ carcinoma and this down-regulation was more pronounced in invasive ductal carcinoma, particularly when associated with infiltration of axillary lymph nodes. These data constitute the first observation that galectin-3 is down-regulated in breast cancer and suggest the decreased expression of this galactoside-binding lectin is associated with the acquisition of the invasive and metastatic phenotype.}, }
@article {pmid8630282, year = {1996}, author = {Beckmann, MW and Picard, F and An, HX and van Roeyen, CR and Dominik, SI and Mosny, DS and Schnürch, HG and Bender, HG and Niederacher, D}, title = {Clinical impact of detection of loss of heterozygosity of BRCA1 and BRCA2 markers in sporadic breast cancer.}, journal = {British journal of cancer}, volume = {73}, number = {10}, pages = {1220-1226}, pmid = {8630282}, issn = {0007-0920}, mesh = {Age Factors ; BRCA1 Protein ; BRCA2 Protein ; Base Sequence ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; Chromosomes, Human, Pair 17 ; DNA Primers/chemistry ; Genetic Markers ; Heterozygote ; Humans ; Lymphatic Metastasis ; Microsatellite Repeats ; Middle Aged ; Molecular Sequence Data ; Neoplasm Proteins/*genetics ; Sequence Deletion ; Transcription Factors/*genetics ; }, abstract = {The development of familial and sporadic breast cancer is based on genetic alterations of tumour-suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation. To investigate LOH of BRCA1 (17q21) and BRCA2 (13-q12-13) in sporadic breast cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for detection of microsatellite polymorphisms was applied. A total of 137 breast cancer and 15 benign breast specimens with matched normal tissue were examined. Fluorescent-labelled PCR products were analysed in an automated DNA sequencer (ALFTM Pharmacia). Losses at both loci were correlated with different histological types, age, tumour size, lymph node status, grading and steroid hormone receptor expression, [SHR: oestrogen receptor (ER), progesterone receptor (PgR)]. For BRCA1 (D17S855, THRA1, D17S579) losses could be detected in invasive ductal carcinoma (IDC; n = 108) in 32-38%, invasive lobular carcinoma (ILC; n = 19) in 21-42% depending on the marker applied, but not in benign breast tumours (n = 15). Losses of BRCA1 markers correlated with larger tumour size, higher grade, and PgR expression. For BRCA2 (D13S260, D13S267, D13S171) losses could be detected in 108 IDCs in 30-38%, in 19 ILCs in 17-39% depending on the marker applied, but not in benign breast tumours. Losses of BRCA2 markers correlated only with higher grade. Microsatellite analyses combined with detection of fluorescent-labelled PCR products by an automated laser DNA sequencer can be used for routine determination of LOH. In sporadic breast cancer, LOH of BRCA1 of BRCA2 does not add decisive prognostic value as stated for familial breast cancer.}, }
@article {pmid8689655, year = {1996}, author = {Linck, B and Bokník, P and Eschenhagen, T and Müller, FU and Neumann, J and Nose, M and Jones, LR and Schmitz, W and Scholz, H}, title = {Messenger RNA expression and immunological quantification of phospholamban and SR-Ca(2+)-ATPase in failing and nonfailing human hearts.}, journal = {Cardiovascular research}, volume = {31}, number = {4}, pages = {625-632}, pmid = {8689655}, issn = {0008-6363}, mesh = {*Adenosine Triphosphate ; Adult ; Autoradiography ; Base Sequence ; Blotting, Northern ; Calcium-Binding Proteins/analysis/*genetics ; Calcium-Transporting ATPases/analysis/*genetics ; Cardiomyopathy, Dilated/metabolism ; DNA Primers/genetics ; Electrophoresis, Polyacrylamide Gel ; Female ; Heart Failure/*metabolism ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Myocardium/chemistry/*metabolism ; RNA, Messenger/analysis/*metabolism ; }, abstract = {OBJECTIVES: Human heart failure is associated with prolonged relaxation and prolonged Ca2+ transients which indicates an impaired function of the sarcoplasmic reticulum (SR) and may be detrimental for cardiac function. Controversy exists whether the altered SR function is accompanied by changes in the expression of phospholamban (PLB) and cardiac SR-Ca(2+)-ATPase (SERCA2) on mRNA and/or protein levels.<br><br>METHODS: We determined mRNA and/or protein levels for PLB and SERCA2 in the same left ventricular tissue of patients undergoing heart transplantation due to idiopathic dilated cardiomyopathy (IDC) or ischemic cardiomyopathy (ICM) in comparison to left ventricular tissue from nonfailing human hearts (NF). Total protein extracts were prepared and subjected to SDS gel electrophoresis. PLB and SERCA2 were identified with specific antibodies. Total RNA was isolated and hybridized with 32P-labeled cDNAs for human PLB and rat SERCA2.<br><br>RESULTS: Hybridization revealed the three expected mRNAs with the PLB probe (3.3 kb, 1.9 kb and 0.6 kb) and a single band with the SERCA2 probe (4.5 kb). Determination of respective proteins by immunoblotting revealed unchanged protein levels for PLB and SERCA2, whereas the mRNA levels for PLB and SERCA2 were reduced by about 30% and 50%, respectively.<br><br>CONCLUSIONS: These data show the level of SERCA2 and PLB protein and mRNA in the same hearts. The reduced mRNA level of SERCA2 and PLB is in accordance with previous data. However, the unchanged protein levels may indicate that the diminished RNA expression is not accompanied by a corresponding decrease for these proteins in human heart failure. These data also show that the altered SR function in human heart failure cannot be explained by altered protein levels of PLB and SERCA2. Furthermore, it is suggested that extrapolations from cardiac mRNA levels to protein expression may be misleading.}, }
@article {pmid8597535, year = {1996}, author = {Ram, TG and Dilts, CA and Dziubinski, ML and Pierce, LJ and Ethier, SP}, title = {Insulin-like growth factor and epidermal growth factor independence in human mammary carcinoma cells with c-erbB-2 gene amplification and progressively elevated levels of tyrosine-phosphorylated p185erbB-2.}, journal = {Molecular carcinogenesis}, volume = {15}, number = {3}, pages = {227-238}, doi = {10.1002/(SICI)1098-2744(199603)15:3&lt;227::AID-MC8&gt;3.0.CO;2-E}, pmid = {8597535}, issn = {0899-1987}, mesh = {Base Sequence ; Breast/metabolism/physiology ; Breast Neoplasms/*genetics/*metabolism ; Cell Division/physiology ; Epidermal Growth Factor/*physiology ; Female ; *Gene Amplification ; *Genes, erbB-2 ; Glycoproteins/pharmacology ; Humans ; Insulin-Like Growth Factor I/*physiology ; Molecular Sequence Data ; Neuregulins ; Phosphorylation ; Receptor, ErbB-2/*metabolism ; Tumor Cells, Cultured ; Tyrosine/metabolism ; }, abstract = {Growth factor-independent proliferation is an essential aspect of the transformation process. To study the influence of c-erbB-2 overexpression on the autonomous growth of human mammary cancer cells, we used a series of non-neoplastic and neoplastic human mammary epithelial cell lines isolated from a patient with intraductal and invasive ductal carcinoma of the breast. The non-neoplastic cell line, H16N-2, which expresses a normal level (single gene copy) of c-erbB-2, was used for comparison with the neoplastic cell lines. Both the metastatic tumor cell lines, 21MT-1 and 21 MT-2, showed equivalent amplification of the c-erbB-2 gene; however, 21MT-1 cells showed a higher level of c-erbB-2 overexpression. Therefore, the H16N-2, 21MT-2, and 21MT-1 cell series forms a distinct gradient of progressively increasing c-erbB-2 gene expression. Furthermore, the overexpression of c-erbB-2 in the 21MT cell lines was concordant with increases in the constitutive tyrosine kinase activity of p185erb-2 measured in the absence of exogenous growth factors in culture. Normal mammary epithelial cells require both insulin-like growth factor (IGF)-l (or supraphysiological concentrations of insulin) and epidermal growth factor (EGF) to proliferate under serum-free conditions in culture. By contrast, 21MT-2 cells showed a reduced requirement for IGF but still required EGF to proliferate. 21MT-1 cells did not require either insulin or EGF to proliferate. Therefore, the progressive increases in constitutive p185erbB-2, tyrosine kinase activity in the 21MT-2 and 21MT-1 cell lines was directly correlated with IGF independence and combined IGF and EGF independence under defined conditions in culture. Experiments using conditioned media and anti-IGF-1 receptor and anti-EGF receptor neutralizing antibodies showed that the growth-factor independence of the tumor cells did not involve detectable IGF- or EGF-like autocrine activity expressed by the 21MT cells. Furthermore, neu differentiation factor/heregulin, a ligand that indirectly activates p185erbB-2 by direct binding to erbB-3 receptors, potently stimulated the proliferation of the growth factor-dependent H16N-2 cells (which expressed c-erbB-2 and c-erbB-3 but not c-erbB-4) in the absence of both IGF and EGF. Thus, HRG-induced mitogenesis mimicked the autonomous growth seen in the 21MT cells that have the highest level of constitutive p185erbB-2 activation. These data support the hypothesis that the constitutive activation of p185erbB-2 in human mammary carcinoma cells causes growth-factor independence by directly activating multiple signal-transduction pathways that substitute for both IGF and EGF during proliferation.}, }
@article {pmid8868021, year = {1996}, author = {Kiatchoosakun, S and Mahanonda, N and Phankingthongkum, R and Wansanit, K and Kangkagate, C and Sahasakul, Y and Jootar, P and Chaithiraphan, S}, title = {Left ventricular hypertrophy: relationship of echocardiographic and electrocardiographic findings in idiopathic dilated cardiomyopathy.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {79}, number = {2}, pages = {103-107}, pmid = {8868021}, issn = {0125-2208}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/complications/*diagnosis/physiopathology ; Diagnosis, Differential ; Echocardiography/methods ; Electrocardiography/methods ; Female ; Humans ; Hypertrophy, Left Ventricular/complications/*diagnosis/physiopathology ; Male ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {Diagnosis of left ventricular hypertrophy is important in patients with cardiac disease. To test the correlation of echocardiographic and electrocardiographic findings for diagnosis of left ventricular hypertrophy in Idiopathic Dilated Cardiomyopathy (IDC), 18 patients with proven IDC were examined. There were 15 males and 3 females, ages ranged from 22-60 years (mean 43 +/- 10.7). LV mass index ranged from 134.4-421.2 g/m2 (mean 187.8 +/- 68.6). All 18 patients had LVH by echocardiography but only 10 patients (55.6%) had LVH by using ECG Romhilt-Estes scoring system. The correlation between echocardiographic and electrocardiographic findings for diagnosis LVH was not significant (r = 0.026; p = 0.935) and echocardiography was better than electrocardiography for diagnosis of LVH in IDC.}, }
@article {pmid9216816, year = {1996}, author = {Usmani, K and Khanum, A and Afzal, H and Ahmad, N}, title = {Breast carcinoma in Pakistani women.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {15}, number = {2-4}, pages = {251-253}, pmid = {9216816}, issn = {0731-8898}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma/epidemiology/*pathology/secondary ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Pakistan/epidemiology ; }, abstract = {In many developed and developing countries including Pakistan, breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. Among 4575 women presenting to the Cancer Research Foundation of Pakistan between 1987 and 1994 with breast lumps, 1201 (26%) were found to have breast cancer. Their ages ranged from 19 to 79 years. The peak incidence was in the 30 to 39 age group. Most patients were multiparous with an average of five children. The size of the tumor was greater than 5 cm in 66% of the cases. Invasive ductal carcinoma was the most common morphological type. According to the Bloom and Richardson grading system, 58% of cases were grade III. Lymph node metastases were present in 73% of the cases.}, }
@article {pmid9060066, year = {1996}, author = {Stotzer, PO and Blomberg, L and Conway, PL and Henriksson, A and Abrahamsson, H}, title = {Probiotic treatment of small intestinal bacterial overgrowth by Lactobacillus fermentum KLD.}, journal = {Scandinavian journal of infectious diseases}, volume = {28}, number = {6}, pages = {615-619}, doi = {10.3109/00365549609037970}, pmid = {9060066}, issn = {0036-5548}, mesh = {Aged ; Breath Tests ; Chronic Disease ; Cross-Over Studies ; Double-Blind Method ; Feces/microbiology ; Humans ; Hydrogen/analysis ; Intestinal Diseases/*microbiology/*therapy ; *Lactobacillus ; }, abstract = {The principle of using harmless bacteria for conquering pathogens has been used for many years. It has been used prophylactically against travellers' diarrhoea and for protection of recurrent pseudomembranous colitis. The aim of this study was to treat a chronic infectious condition, small intestinal bacterial overgrowth, by oral administration of a certain strain of Lactobacillus. 17 patients with long-standing bacterial overgrowth of the small intestine were included. The study was designed as a double-blind cross-over, where the patients were their own controls. The study was divided into 4 parts. (A) For the first 2 weeks placebo was given b.i.d. (B) For the next 4 weeks patients received either placebo or 10(10) Lactobacillus fermentum KLD b.i.d. (C) A wash-out period of 4 weeks followed. (D) Finally, for the second 4 week treatment period patients were crossed over to receive either lactobacilli or placebo. A hydrogen breath test with 50 g glucose was performed at the start and at the end of each period. Symptom scores were recorded on the last week of each period. The study was completed by 14 patients. Lactobacillus treatment showed no significant difference compared to placebo with respect to the results of the hydrogen breath test: 29 (3-95) vs 14 (3-129) ppm, (median and 10th and 90th percentiles), stool frequency: 14 (8-40) vs 12 (7-31) defecations/week. or symptom score: 12 (5-46) vs 17 (6-42) scores/week). High numbers of L. fermentum KLD in faecal samples were only seen in 2 patients. In conclusion, dosage with L. fermentum KLD in this study did not significantly alter the parameters investigated.}, }
@article {pmid8973769, year = {1996}, author = {Zhang, WG and Ma, AQ and Wei, J and Feng, QM and Liu, ZQ}, title = {Study of autoantibodies against the adenine nucleotide translocator in idiopathic dilated cardiomyopathy.}, journal = {Blood pressure. Supplement}, volume = {3}, number = {}, pages = {45-48}, pmid = {8973769}, issn = {0803-8023}, mesh = {Adenosine Diphosphate/metabolism ; Animals ; Autoantibodies/*immunology/pharmacology ; Cardiomyopathy, Dilated/*immunology ; Cattle ; Humans ; Mitochondria, Heart/drug effects/metabolism ; Mitochondrial ADP, ATP Translocases/*immunology ; }, abstract = {The frequency, dynamical change and effects of autoantibodies against the adenine nucleotide translocator (ANT) in idiopathic dilated cardiomyopathy (IDC) were studied. Sera of 16 patients with IDC showed significant binding capacity to the ANT protein (33.3%). Anti-ANT antibody titre was gradually tapered in approx. 2-3 months duration. However, anti-ANT antibody can inhibit the ADP/ATP exchange of heart mitochondria and be organ-specific. Short-term (6 weeks) treatment of 15 anti-ANT antibody-positive IDC patients with prednisone was of beneficial effect. Our results show that autoimmunity to the ANT can contribute to the pathogenesis and/or progression of IDC to a certain extent. But we must pay more attention to the fact that anti-ANT antibody characteristically exists short-term. Therefore, a short-term immunosuppressive treatment should be given to those IDC patients whose anti-ANT antibody is positive.}, }
@article {pmid8803708, year = {1996}, author = {Awad, AT and el-Husseini, G and Anwar, M and Abu-Nasr, A and Anwar, AA and Sakr, M}, title = {Bilateral primary breast cancers: a clinicopathological study of the second primary.}, journal = {International surgery}, volume = {81}, number = {1}, pages = {57-60}, pmid = {8803708}, issn = {0020-8868}, mesh = {Breast/parasitology ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Multiple Primary/mortality/*pathology ; Neoplasms, Second Primary/mortality/*pathology ; Risk Factors ; Survival Rate ; Time Factors ; }, abstract = {Out of 2238 patients with breast cancer 35 developed carcinoma of the contralateral breast. Thirty-three developed metachronous tumours while two developed synchronous tumours. The thirty-five patients were followed up for periods between 4-8 years. The majority of patients belonged to the fourth decade and the peak incidence of developing a metachronous tumour occurred three to five years after diagnosis of the first primary. T2 lesions were the most frequent initial primaries and N1 lesions were commoner than N2. IDC was the commonest histopathological subtype. The overall two-year survival rate was 57.1% (20/35).}, }
@article {pmid8778952, year = {1996}, author = {Krenn, V and Schalhorn, N and Greiner, A and Molitoris, R and König, A and Gohlke, F and Müller-Hermelink, HK}, title = {Immunohistochemical analysis of proliferating and antigen-presenting cells in rheumatoid synovial tissue.}, journal = {Rheumatology international}, volume = {15}, number = {6}, pages = {239-247}, pmid = {8778952}, issn = {0172-8172}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Antigen-Presenting Cells/immunology/*pathology ; Antigens, CD/analysis ; Antigens, Differentiation, B-Lymphocyte/analysis ; Arthritis, Rheumatoid/immunology/*pathology ; B-Lymphocytes/immunology ; CD3 Complex/analysis ; Cell Adhesion Molecules/analysis ; Cell Count ; Female ; Humans ; Immunohistochemistry/methods ; Ki-67 Antigen ; *Lectins ; Male ; Middle Aged ; Mitosis/physiology ; Neoplasm Proteins/*analysis ; Nuclear Proteins/*analysis ; Sialic Acid Binding Ig-like Lectin 2 ; Synovial Membrane/immunology/*pathology ; T-Lymphocytes/immunology ; }, abstract = {We analysed the proliferative activity of synovial lining cells (SLCs), the distribution of proliferating B and T lymphocytes and the relationship of proliferating B and T lymphocytes to the pattern of antigen-presenting cells (APCs) within the rheumatoid synovial tissue (n = 21). The immunohistochemical detection of the proliferation-associated antigen Ki67 revealed low proliferative activity of SCL with and without expression of the Kim 8 (CD68) antigen. Ki67-positive B lymphocytes could be observed within secondary follicles (2/21), in small follicular dendritic reticulum cell (FDC)-containing follicle-like aggregates (7/21) and near the enlarged synovial intima (6/21). Ki67-positive T lymphocytes could be detected in T-lymphocyte aggregates (8/21), in the vicinity of blood vessels (18/21) and within the enlarged synovial intima (15/21). Semiquantitative analysis showed a strong correlation between the numbers of Ki67-positive B lymphocytes and FDCs and between the numbers of Ki67-positive T lymphocytes and interdigitating dendritic reticulum cells (IDC). There were significant differences in the number of Ki 67-positive B and T lymphocytes, IDCs and FDCs between the two groups of rheumatoid arthritis (RA) patients with different local clinical activity. These findings demonstrate a low proliferation of SLCs with and without expression of the monocyte-specific antigen Kim 8 and imply that B and T lymphocyte proliferation occurs in the presence of FDCs and IDCs. These results indicate that the RA synovial tissue is a site for antigen-dependent proliferation and maturation of B and T lymphocytes. The atypical pattern of FDC distribution within the rheumatoid synovial tissue "dysmorphic follicle" may be regarded as morphological substrate for a dysmaturation compartment of B lymphocytes leading to pathogenetic autoimmune phenomena in RA patients.}, }
@article {pmid8745224, year = {1996}, author = {Thoenes, M and Förstermann, U and Tracey, WR and Bleese, NM and Nüssler, AK and Scholz, H and Stein, B}, title = {Expression of inducible nitric oxide synthase in failing and non-failing human heart.}, journal = {Journal of molecular and cellular cardiology}, volume = {28}, number = {1}, pages = {165-169}, doi = {10.1006/jmcc.1996.0016}, pmid = {8745224}, issn = {0022-2828}, mesh = {Animals ; Cardiomyopathies/chemically induced/*enzymology/metabolism ; Cardiomyopathy, Dilated/enzymology ; Cell Line ; Cyclic GMP/metabolism ; *Gene Expression ; Heart Failure/*enzymology/etiology ; Heart Ventricles ; Humans ; Isoenzymes/biosynthesis ; Macrophages/enzymology ; Mice ; Mitoxantrone/adverse effects ; Muscular Dystrophies/enzymology ; Myocardial Ischemia/enzymology ; Myocardium/*enzymology/metabolism ; Nitric Oxide Synthase/*biosynthesis ; Reference Values ; Sepsis/enzymology/metabolism ; }, abstract = {Recently, a significant activity of inducible nitric oxide synthase (iNOS) has been reported in biopsies from failing hearts due to idiopathic dilated cardiomyopathy (IDC). Thus, a potential pathophysiological role of iNOS in IDC has been stated. In order to investigate, whether iNOS expression is of pathophysiological relevance in human heart failure, we measured iNOS protein expression and cGMP content in left ventricular myocardium from non-failing and failing human hearts. Immunoblot analysis revealed iNOS protein expression in four out of six failing hearts from septic patients, whereas no iNOS-protein expression was detected in either non-failing human hearts (n = 6) or failing hearts due to IDC (n = 9), ischemic heart disease (IHD, n = 7), Becker muscular dystrophy (BMD, n = 2) and mitoxantrone-induced toxic cardiomyopathy TCM, n = 1). cGMP content was increased by 130% in septic hearts, whereas there was no cGMP increase in hearts with IDC. IHD and BMD compared to non-failing hearts. We conclude, that the induction of iNOS may play a role in contractile dysfunction observed in septic shock, but is unlikely to be of major pathophysiological importance in end-stage heart failure due to IDC, IHD, BMD and TCM.}, }
@article {pmid8686330, year = {1996}, author = {Fruhwald, FM and Watzinger, N and Schumacher, M and Zweiker, R and Pokan, R and Eber, B and Klein, W}, title = {[Serum digoxin level in patients with dilated cardiomyopathy].}, journal = {Wiener medizinische Wochenschrift (1946)}, volume = {146}, number = {5}, pages = {98-101}, pmid = {8686330}, issn = {0043-5341}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/*blood/diagnostic imaging/drug therapy ; Digoxin/administration &amp; dosage/*pharmacokinetics ; Dose-Response Relationship, Drug ; Echocardiography/drug effects ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Stroke Volume/drug effects ; }, abstract = {To investigate whether measuring levels of digoxin in patients with idiopathic dilated cardiomyopathy (IDC) is helpful in dose adjustment of digoxin we did the following study. In 77 patients (63 male, 14 female) with invasively verified IDC serum-digoxin levels were measured after a treatment period with beta-acetyldigoxin of at least 6 months. All patients received digoxin, 76 had ACE-inhibitors and 69 used diuretics. Mean serum-levels of digoxin were 0.96 ng/ml while using a mean daily dose of digoxin of 0.24 mg. Those who showed a serum level of digoxin within the recommended range took a slightly higher daily dose of digoxin when compared to those with low levels of digoxin (0.26 vs. 0.23 mg/day, p < 0.05). Therefore, we conclude that low serum-levels of digoxin are mainly caused by low intake of digoxin and it is justified to measure digoxin-levels in IDC-patients even if it increases costs.}, }
@article {pmid8554451, year = {1996}, author = {Bose, S and Lesser, ML and Norton, L and Rosen, PP}, title = {Immunophenotype of intraductal carcinoma.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {120}, number = {1}, pages = {81-85}, pmid = {8554451}, issn = {0003-9985}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Antigens, CD/analysis ; Breast Neoplasms/chemistry/*classification/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*classification/pathology ; Female ; Humans ; Immunoenzyme Techniques ; *Immunophenotyping ; Ki-67 Antigen ; Macrophages/immunology ; Middle Aged ; Neoplasm Proteins/analysis ; Nuclear Proteins/analysis ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; T-Lymphocytes/immunology ; Tumor Suppressor Protein p53/analysis ; }, abstract = {OBJECTIVE: Mammography and breast-conserving therapy have focused attention on the classification of intraductal carcinoma (IDC) and emphasized the prognostic importance of comedo versus noncomedo variants. We used histochemical markers to define the immunophenotype of 43 IDCs with respect to comedo versus noncomedo status and patterns of angiogenesis.<br><br>RESULTS: Reactions in comedo carcinomas were significantly negative for estrogen receptor and progesterone receptor, and positive for p53 and HER-2/neu more often than the noncomedo variant. All seven IDCs associated with Paget's disease showed positive reactions for HER-2/neu. Basement membrane immunoreactivity for type IV collagen and laminin was discontinuous in most examples of IDC regardless of type, with a trend toward more intense staining in comedo than in noncomedo carcinomas. Periductal angiogenesis was not significantly related to the type of IDC but was more pronounced with comedo carcinomas.<br><br>CONCLUSIONS: These observations indicate that there are immunophenotypic correlates to the current structural classification of IDC. The immunophenotype of IDC is helpful in subclassifying an IDC and could prove useful as a prognostic indicator for local control in patients treated by breast-conserving therapy.}, }
@article {pmid8553586, year = {1996}, author = {Ludewig, B and Gelderblom, HR and Becker, Y and Schäfer, A and Pauli, G}, title = {Transmission of HIV-1 from productively infected mature Langerhans cells to primary CD4+ T lymphocytes results in altered T cell responses with enhanced production of IFN-gamma and IL-10.}, journal = {Virology}, volume = {215}, number = {1}, pages = {51-60}, doi = {10.1006/viro.1996.0006}, pmid = {8553586}, issn = {0042-6822}, mesh = {CD4-Positive T-Lymphocytes/immunology/ultrastructure/*virology ; Cell Communication ; Cell Line ; Cells, Cultured ; Giant Cells/virology ; HIV-1/drug effects/*physiology ; Humans ; Interferon-gamma/*biosynthesis ; Interleukin-10/*biosynthesis ; Langerhans Cells/metabolism/ultrastructure/*virology ; Tumor Cells, Cultured ; Virus Replication/drug effects ; Zidovudine/pharmacology ; }, abstract = {Mature Langerhans cells (mLC), the ex vivo correlates of interdigitating dendritic cells (IDC), are susceptible to infection with HIV-1. As IDC are important activators of T helper (Th) cells in vivo, we examined the interaction of HIV-1-infected mLC with CD4+ T lymphocytes. HIV-1-infected mLC readily formed clusters with the T cells and efficiently transmitted HIV-1 to the CD4+ Th cells. Formation of syncytia between mLC and T cells was initiated by HIV-1-infected mLC. In the clusters of HIV-1-infected mLC and activated T cells a massive HIV-1 production was observed leading to the subsequent elimination of the activated and infected T helper cells. Examination of the cytokine pattern produced during interaction of infected mLC with CD4+ T cells revealed an enhanced production of IFN-gamma and IL-10 in the cocultures. These results suggest that during antigen presentation-driven T cell activation by IDC in the lymphoid tissues, HIV-1-infected IDC might efficiently transmit the virus to Th cells, leading to altered Th cell responses.}, }
@article {pmid7501973, year = {1996}, author = {Haines, GK and Cajulis, R and Hayden, R and Duda, R and Talamonti, M and Radosevich, JA}, title = {Expression of the double-stranded RNA-dependent protein kinase (p68) in human breast tissues.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {17}, number = {1}, pages = {5-12}, doi = {10.1159/000217961}, pmid = {7501973}, issn = {1010-4283}, mesh = {Breast/*enzymology/pathology ; Breast Neoplasms/*enzymology ; DEAD-box RNA Helicases ; Female ; Gene Expression ; *Genes, Tumor Suppressor ; Humans ; Hyperplasia/enzymology ; Immunohistochemistry ; Nuclear Proteins/*genetics ; Precancerous Conditions/enzymology ; *Protein Kinases ; *RNA Helicases ; RNA, Double-Stranded/metabolism ; }, abstract = {P68 is a potent inhibitor of protein synthesis in virally infected cells and has been suggested to function in noninfected cells as a tumor suppressor gene. We have previously demonstrated that p68 expression correlates directly with cellular differentiation and inversely with proliferative activity in normal epithelium and in several human tumor systems. In order to determine the role of p68 in human breast cancer, we utilized immunohistochemistry and mapped the expression of p68 in tissue from 200 breast biopsy specimens. A total of 434 foci, ranging from normal breast tissue to infiltrating carcinoma were examined. We found that p68 was present at basal levels in normal lobular and luminal ductal epithelial cells, with higher levels present in myoepithelial cells. Nonproliferative fibrocystic lesions showed variable expression of p68, with high levels seen within foci of apocrine metaplasia and low levels in cystically dilated terminal duct units. Low levels of p68 were seen in typical ductal proliferations, lobular neoplasia (atypical lobular hyperplasia and lobular carcinoma in situ), and in fibroadenomas. Foci of atypical ductal hyperplasia in situ and invasive ductal carcinoma generally showed higher levels of p68 expression. Among the infiltrating carcinomas, p68 expression correlated with nuclear grade. This suggests that the ability of p68 to inhibit cellular proliferation may be impaired in breast cancer and that its expression, although modestly paralleling cellular differentiation, is not a predictive indicator of improved survival.}, }
@article {pmid8682101, year = {1995}, author = {Mestroni, L and Krajinovic, M and Severini, GM and Milasin, J and Pinamonti, B and Rocco, C and Vatta, M and Falaschi, A and Giacca, M and Camerini, F}, title = {Molecular genetics of dilated cardiomyopathies.}, journal = {European heart journal}, volume = {16 Suppl O}, number = {}, pages = {5-9}, doi = {10.1093/eurheartj/16.suppl_o.5}, pmid = {8682101}, issn = {0195-668X}, mesh = {Cardiomyopathy, Dilated/diagnosis/*genetics ; Chromosome Aberrations/genetics ; Chromosome Disorders ; Chromosomes, Human, Pair 14 ; DNA, Mitochondrial/genetics ; Dystrophin/genetics ; Female ; Genes, Dominant/genetics ; Genes, Recessive/genetics ; Genetic Linkage/genetics ; Humans ; Hypertrophy, Right Ventricular/diagnosis/genetics ; Male ; Molecular Biology ; Myosin Heavy Chains/genetics ; Pedigree ; Prospective Studies ; Sex Chromosome Aberrations/genetics ; X Chromosome ; }, abstract = {The application of molecular genetics in cardiology is currently producing important results in the study of the pathogenetic mechanisms underlying cardiomyopathies. Recent clinical surveys have indicated that genetic factors play a major pathogenetic role in idiopathic dilated cardiomyopathy (IDC). Familial IDC is frequent (20-30%) and is probably a heterogeneous entity, as suggested by the clinical variability and the different pattern of inheritance in the affected families. Molecular genetic studies have demonstrated the existence of heterogeneity also at the genetic level. In a series of families with X-linked IDC, the disease gene has been identified as the dystrophin gene. In familial right ventricular cardiomyopathy (or right ventricular dysplasia), a new nosological entity characterized by isolated right ventricular involvement that can mimic IDC, the disease gene has been localized in the long arm of chromosome 14. In families with matrilineal transmission, the cardiomyopathy could be linked to mitochondrial DNA alterations. Autosomal dominant familial IDC, considered to be the most frequent form, is currently under active investigation. Our preliminary data have excluded a large series of candidate genes, among which are the cardiac beta-myosin heavy chain and several other genes encoding for cardiac contractile proteins, genes of the HLA region, and about 60 genes involved in the immune regulation.}, }
@article {pmid8682086, year = {1995}, author = {Mirić, M and Misković, A and Vasiljević, JD and Keserović, N and Pesić, M}, title = {Interferon and thymic hormones in the therapy of human myocarditis and idiopathic dilated cardiomyopathy.}, journal = {European heart journal}, volume = {16 Suppl O}, number = {}, pages = {150-152}, doi = {10.1093/eurheartj/16.suppl_o.150}, pmid = {8682086}, issn = {0195-668X}, mesh = {Adolescent ; Adult ; Biopsy ; Cardiomyopathy, Dilated/pathology/physiopathology/*therapy ; Child ; Combined Modality Therapy ; Electrocardiography, Ambulatory/drug effects ; Endocardium/pathology ; Female ; Hemodynamics/drug effects/physiology ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Male ; Middle Aged ; Myocarditis/pathology/physiopathology/*therapy ; Myocardium/pathology ; Prospective Studies ; Thymus Extracts/adverse effects/*therapeutic use ; Treatment Outcome ; Ventricular Function, Left/drug effects/physiology ; Virus Diseases/*therapy ; }, abstract = {It is becoming increasingly apparent that idiopathic dilated cardiomyopathy (IDC) probably results from an acute viral myocarditis. One reasonable hypothesis is that persistent viral infection causes myocardial destruction leading to left ventricular dilatation and heart failure. The aim of this study was to evaluate the efficacy of interferon-alpha (IFN) and thymomodulin in the treatment of idiopathic myocarditis and IDC. Clinical, immunological, haemodynamic and histological evaluation was performed in 40 patients before inclusion in the study. Patients were randomized into three treatment groups: (a) conventional therapy plus IFN, (b) conventional therapy plus thymomodulin and (c) conventional therapy alone. Two-year follow-up included repeated endomyocardial biopsy, echocardiographic evaluation, treadmill exercise test, Holter monitoring study and radionuclide assessment of left ventricular function during exercise. Left ventricular ejection fraction increased during follow-up in most of the IFN-and thymomodulin-treated patients, and only in a few of conventionally treated patients. Left ventricular reserve was significantly higher at 2-year follow-up in patients treated with immunomodulators. No serious adverse effects were noticed during treatment. Our results suggest that treatment of myocarditis and/or IDC with IFN or thymomodulin induces an earlier and significantly superior clinical improvement than conventional therapy alone.}, }
@article {pmid8652258, year = {1995}, author = {Pedersen, L and Zedeler, K and Holck, S and Schiødt, T and Mouridsen, HT}, title = {Medullary carcinoma of the breast. Prevalence and prognostic importance of classical risk factors in breast cancer.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {31A}, number = {13-14}, pages = {2289-2295}, doi = {10.1016/0959-8049(95)00408-4}, pmid = {8652258}, issn = {0959-8049}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Medullary/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Prognosis ; Regression Analysis ; Risk Factors ; Survival Analysis ; }, abstract = {In an earlier study of 235 breast cancers with medullary features, we concluded from a multivariate Cox regression analysis that only four histopathological features contained significantly positive prognostic information. In the present study, continuing our work on the same population base, we used these histological characteristics (predominantly syncytial growth pattern, no tubular component, diffuse stromal infiltration with mononuclear cells and sparse necrosis (< 25%), as diagnostic criteria for medullary carcinoma of the breast (MC). We found a significantly better prognosis for patients with MC than those with non-medullary carcinoma (NMC) or infiltrating ductal carcinoma (IDC). All tumours in the MC group were grade II or III (96% grade III). A significantly different distribution of general risk factors such as lymph node status, invasion, steroid receptor status, and menopausal status, was found between the group of MC and the control group of IDC grades II + III. Further, general risk factors, which are found to be of major prognostic importance in IDC, had little prognostic impact in MC. We found MC to be biologically unique, and patients with MC have a better than average prognosis compared to that of IDC. We propose a new histological definition of MC, but stress that prospective studies have to be performed.}, }
@article {pmid7586255, year = {1995}, author = {Holzinger, C and Schöllhammer, A and Imhof, M and Reinwald, C and Kramer, G and Zuckermann, A and Wolner, E and Steiner, G}, title = {Phenotypic patterns of mononuclear cells in dilated cardiomyopathy.}, journal = {Circulation}, volume = {92}, number = {10}, pages = {2876-2885}, doi = {10.1161/01.cir.92.10.2876}, pmid = {7586255}, issn = {0009-7322}, mesh = {Cardiomyopathy, Dilated/blood/*immunology/pathology ; Case-Control Studies ; Female ; Flow Cytometry ; Heart Failure/blood/immunology/pathology ; Humans ; Immunity, Cellular/immunology ; Immunoenzyme Techniques ; Immunophenotyping ; Lymphocyte Activation ; Male ; Middle Aged ; Myocardium/pathology ; T-Lymphocyte Subsets/*immunology/pathology ; T-Lymphocytes/*classification/immunology ; }, abstract = {BACKGROUND: Immunological factors in the pathogenesis of idiopathic dilated cardiomyopathy (IDC) were suggested previously on the basis of the demonstration of mononuclear cell infiltrates and autoantibodies against the myocardium. The present study investigated whether tissue leukocyte subpopulations isolated from hearts with IDC (n = 6) differ in phenotype from those of tissues without IDC (n = 7).<br><br>METHODS AND RESULTS: Leukocytes were quantified as reactive cells per square millimeter in perivascular, interstitial, and parenchymal tissue sections. Freshly isolated heart-tissue T cells and peripheral-blood T cells from the same patients were analyzed by triple staining and flow cytometry to identify T-cell subpopulations as well as their states of differentiation (expression of CD45RA and Leu-8 versus CD45RO) and activation (IL-2R, IL-7R, very late antigen-1, HLA-DR). All types of infiltrating cells (T cells, B cells, macrophages, granulocytes) are increased in hearts with IDC compared with normal hearts, but only CD8+ T cells and macrophages are increased relative to the other leukocyte subpopulations. CD45RO+/CD45RA-/Leu-8- cells constitute the majority of heart-tissue T cells in both normal hearts and hearts with IDC. Strikingly, hearts with IDC are infiltrated by eightfold greater numbers of perivascularly located IL-2R(+)- (26% of all T cells) and CD45RO(+)-activated memory T cells; moreover, in contrast to normal heart, approximately 40% of both CD4+ and CD8+ heart-tissue T cells express activation markers.<br><br>CONCLUSIONS: Both normal hearts and hearts with IDC are populated by leukocytes. The quantitative increase in IDC, associated with a dramatically altered activation status of heart-tissue T cells, suggests a direct role of infiltrating leukocytes in the pathogenesis of IDC.}, }
@article {pmid8529848, year = {1995}, author = {Gavazzi, A and De Maria, R and Porcu, M and Beretta, L and Casazza, F and Castelli, G and Luvini, M and Parodi, O and Recalcati, F and Renosto, G}, title = {[Dilated cardiomyopathy: a new natural history? The experience of the Italian Multicenter Cardiomyopathy Study (SPIC)].}, journal = {Giornale italiano di cardiologia}, volume = {25}, number = {9}, pages = {1109-1125}, pmid = {8529848}, issn = {0046-5968}, mesh = {Adolescent ; Adult ; Aged ; Cardiomyopathy, Dilated/*diagnosis/drug therapy/mortality ; Child ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Prospective Studies ; Survival Analysis ; }, abstract = {BACKGROUND: The natural history of idiopathic dilated cardiomyopathy (IDC), once a disease with a dire prognosis, is thought to be changing. Aim of this study was to describe the clinical characteristics, long term course and prognostic factors of IDC patients followed up prospectively since the late eighties.<br><br>METHODS: Patients with a diagnosis of IDC confirmed by normal coronary angiography, non specific endomyocardial biopsy findings and a left ventricular ejection fraction below 50% were consecutively enrolled in a multicenter registry and followed up at 6-months intervals.<br><br>RESULTS: From January 1986 till January 1994, 441 IDC patients with a mean age of 43 +/- 13 years (range 8-68) entered the registry. Thirty per cent of patients were women and 8% had familial dilated cardiomyopathy. NYHA class was I-II in 77% and 35% of patients were asymptomatic at the time of diagnosis. Treatment included digitalis in 235 patients (53%), diuretics in 239 (54%), angiotensin converting enzyme inhibitors in 269 (61%), betablockers in 108 (24%). Chronic atrial fibrillation was detected in 10% of patients and left bundle branch block in 24%. Mean cardiothoracic ratio was 0.54 +/- 0.06. Mean left ventricular end diastolic dimension was 38 +/- 6 mm/m2; 48% of patients had minimal or mild left ventricular dilatation. Mean left ventricular ejection fraction was 30 +/- 10%. At Holter monitoring 67% of cases had complex ventricular arrhythmias, 37% had ventricular tachycardia and 4% had advanced atrioventricular block. Mean exercise stress test duration was 9 +/- 4 minutes. After a mean follow up of 31 +/- 24 months, 337 patients were alive without transplantation and 5 were lost to follow up; 60 patients (14%) had died of cardiac causes, namely heart failure (6%), sudden death (7%) and pulmonary embolism (< 1%) and 30 had been transplanted (7%), while 4 had died of unclear causes. Survival and transplant-free survival were 94% and 90% at 2 years and 82 and 76% at 5 years, respectively. At multivariate analysis pulmonary capillary wedge pressure (p = 0.0001, odds ratio, for values > 15 mm Hg, 2.05) and betablocker treatment (p = 0.002, odds ratio 0.26) were independent predictors of survival.<br><br>CONCLUSIONS: In this large, multicenter prospective study, prognosis of IDC in the eighties appears to be improved. Early diagnosis, together with improved medical treatment, probably bears a causal relation to these changes.}, }
@article {pmid7653492, year = {1995}, author = {Brown, CA and O'Connell, JB}, title = {Myocarditis and idiopathic dilated cardiomyopathy.}, journal = {The American journal of medicine}, volume = {99}, number = {3}, pages = {309-314}, pmid = {7653492}, issn = {0002-9343}, mesh = {Cardiomyopathy, Hypertrophic/diagnosis/*etiology/physiopathology/therapy ; Humans ; Myocarditis/chemically induced/*complications/microbiology ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) accounts for 25% of cases of heart failure in the United States. Understanding the relationship between an inciting event or agent and the development of IDC has progressed only recently. Once IDC has developed, treatment is palliative and little can be done to alter the natural course of the disease. Active myocarditis, a suspected precursor of IDC, is myocardial inflammation and injury without ischemia. The disease ranges from a self-limited flulike illness to one of serious consequence with arrhythmias, heart failure, or death. Many agents have been associated with myocarditis, and the clinical manifestations depend on an interplay between the inciting agent and the host response. The development of a murine model and the expanded use of endomyocardial biopsy using the Dallas criteria have increased our understanding of myocarditis and its sequelae. Therapy consists of managing symptoms using conventional medical regimens for heart failure. Immunosuppressive therapy should be reserved for patients with biopsy-proven disease who have failed conventional therapy. Continued deterioration warrants ventricular assistance and consideration of cardiac transplantation.}, }
@article {pmid7500542, year = {1995}, author = {Honda, Y and Yokota, Y and Yokoyama, M}, title = {Familial aggregation of dilated cardiomyopathy--evaluation of clinical characteristics and prognosis.}, journal = {Japanese circulation journal}, volume = {59}, number = {9}, pages = {589-598}, doi = {10.1253/jcj.59.589}, pmid = {7500542}, issn = {0047-1828}, mesh = {Adolescent ; Adult ; Aged ; Bias ; Cardiomyopathy, Dilated/*epidemiology/*genetics/mortality ; Cause of Death ; Death, Sudden, Cardiac ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Prognosis ; Survival Rate ; }, abstract = {To investigate the prevalence, clinical characteristics, and prognosis of familial cases of idiopathic dilated cardiomyopathy (IDC), family screenings were carried out in 117 IDC patients and their relatives. Familial occurrence was suspected in 29 families (25%). Ten families (9%) with 24 patients were confirmed to be familial, but the other 19 families (16%) remained suspected. The age at the time of diagnosis was lower and the cardiac symptoms tended to be milder in the familial group than in the non-familial group, but there were no differences in other clinical parameters. There was also no difference in the survival rate. However, when only NYHA class III and IV patients were selected, the 1-year and 5-year survival rates were lower in the familial group than in the non-familial group. Congestive heart failure was the most common cause of death in the non-familial group, while sudden death was the most common cause of death in the familial group. Among familial IDC patients who were deceased, the left ventricular end-diastolic pressure was higher and the cardiac index was lower at the time of diagnosis than those in patients who were still alive. We conclude that, since the prognosis of familial IDC patients is poor once their cardiac symptoms become severe, early diagnosis and treatment are extremely important.}, }
@article {pmid7666587, year = {1995}, author = {Horiguchi, J and Iino, Y and Takei, H and Morishita, Y}, title = {Prognostic significance of c-erbB-2 expression in invasive ductal carcinoma of the breast.}, journal = {Japanese journal of clinical oncology}, volume = {25}, number = {4}, pages = {119-123}, pmid = {7666587}, issn = {0368-2811}, mesh = {Adenocarcinoma, Scirrhous/chemistry/mortality/secondary ; Adult ; Breast Neoplasms/*chemistry/mortality/pathology ; Carcinoma, Ductal, Breast/*chemistry/mortality/secondary ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; Survival Rate ; }, abstract = {The expression of c-erbB-2 oncoprotein was studied in relation to the histological type of invasive ductal carcinoma. The expression of c-erbB-2 was found in 26 (17.6%) of 148 cases, and was a significant prognostic indicator in patients with lymph node metastasis, but not in those without. The patients were divided into a scirrhous group and a non-scirrhous group on the basis of histological type. There was no significant difference between the two groups in age, clinical stage, lymph node status, estrogen receptor status, operation method or c-erbB-2 expression. The expression of c-erbB-2 was a significant prognostic indicator in the scirrhous group, irrespective of lymph node metastasis, but not in the non-scirrhous group. We conclude that the prognostic significance of c-erbB-2 expression differs among histological types of invasive ductal carcinoma, and that c-erbB-2 expression is a prognostic indicator in patients with scirrhous carcinoma.}, }
@article {pmid7621870, year = {1995}, author = {Ludewig, B and Graf, D and Gelderblom, HR and Becker, Y and Kroczek, RA and Pauli, G}, title = {Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40-ligand) and TNF-alpha, but strongly enhanced by interleukin-10.}, journal = {European journal of immunology}, volume = {25}, number = {7}, pages = {1943-1950}, doi = {10.1002/eji.1830250722}, pmid = {7621870}, issn = {0014-2980}, mesh = {Apoptosis/*drug effects ; CD40 Ligand ; Cell Membrane/ultrastructure ; Cells, Cultured ; Chromatin/ultrastructure ; Cytoplasm/ultrastructure ; Dendritic Cells/*cytology/immunology ; Endoplasmic Reticulum/ultrastructure ; Humans ; Immunophenotyping ; In Vitro Techniques ; Interleukin-10/*pharmacology ; Langerhans Cells/cytology/immunology ; Membrane Glycoproteins/*pharmacology ; Tumor Necrosis Factor-alpha/*pharmacology ; }, abstract = {In the lymphoid tissues, adaptive immune responses are initiated by the interaction of interdigitating dendritic cells (IDC) with naive T cells. To understand this interplay better, we used mature Langerhans cells (mLC), migrating from human epidermis, as the correlate of IDC ex vivo to evaluate the different effects of tumor necrosis factor (TNF)-alpha. TNF-related activation protein (TRAP; CD40-ligand) and interleukin-10 (IL-10) on induction or prevention of apoptotic cell death in these cells. Spontaneous decrease of mLC viability in culture was due to apoptosis, as determined by the appearance of typical morphological changes such as dilatation of the endoplasmic reticulum (ER), chromatin condensation and membrane blebbing. IL-10 strongly reduced mLC viability, whereas TRAP and TNF-alpha facilitated the survival of mLC. Spontaneous DNA fragmentation was detectable after 24 h in culture. IL-10 led to an earlier onset of DNA fragmentation, whereas TRAP and TNF-alpha delayed internucleosomal DNA cleavage. We found that IL-10-treated mLC were readily ingested and removed by macrophages. TNF-alpha and TRAP, in contrast, reduced engulfment of mLC by macrophages. Interestingly, IL-10, even at low concentrations, reverted the effects of TNF-alpha and TRAP in inhibiting mLC apoptosis. Furthermore, IL-10 led to the down-regulation of various surface antigens, especially of CD86 and CD54, whereas TNF-alpha and TRAP enhanced the expression of MHC class I and II antigens and of the accessory molecules CD40, CD54, CD80 and CD86. Taken together, these results show that mLC spontaneously undergo apoptosis in culture and that the progression of mLC to apoptosis is inhibited by TRAP and TNF-alpha, but accelerated by IL-10.}, }
@article {pmid7611175, year = {1995}, author = {Cook, DL and Weaver, DL}, title = {Comparison of DNA content, S-phase fraction, and survival between medullary and ductal carcinoma of the breast.}, journal = {American journal of clinical pathology}, volume = {104}, number = {1}, pages = {17-22}, doi = {10.1093/ajcp/104.1.17}, pmid = {7611175}, issn = {0002-9173}, mesh = {Adult ; Aged ; Aneuploidy ; *Breast Neoplasms/genetics/mortality/pathology ; *Carcinoma, Ductal, Breast/genetics/mortality/pathology ; *Carcinoma, Medullary/genetics/mortality/pathology ; DNA, Neoplasm/*analysis/genetics ; Flow Cytometry ; Humans ; Middle Aged ; Mitotic Index ; Prognosis ; S Phase ; Survival Rate ; }, abstract = {Medullary carcinoma (MC) of the breast has been regarded as a subtype of breast carcinoma with a relatively favorable prognosis despite its high nuclear grade and high mitotic index. High nuclear grade and high mitotic index have been correlated with DNA aneuploidy and high S-phase fraction (SPF) by flow cytometry. Generally in breast cancer, these histologic and DNA content features predict a less favorable prognosis. To address this paradox, all cases of MC of the breast (20 of 1,365 carcinomas [1.5%]) diagnosed between 1968 and 1982 were compared to age- and stage-matched cases of infiltrating ductal carcinoma (IDC) diagnosed during the same time period. All of the MC and 80% of the IDC had one or more DNA aneuploid stem lines. Average total SPF was 8.1% for MC and 4.8% for IDC. DNA analysis was performed from paraffin blocks (average CV: 4.5% DNA diploid; 4.1% DNA aneuploid), and subjected to computer modeled analysis. Statistically significant differences between presence or absence of DNA aneuploidy (P = .035) and total SPF (P = .029) were demonstrated between the two groups. Thirteen of 20 patients (65%) with MC (average followup 130 months) were alive at the end of the study period compared to 12 of 20 patients (60%) with IDC (average follow-up 160 months). The difference in crude survival was not statistically significant (P = .867). However, there was a tendency toward early death in MC and late death in IDC. Within the TNM stage-matched patients, no significant difference was demonstrated for tumor size or nodal status when these variables were examined separately. In conclusion, statistically significant differences in DNA content and proliferative fraction exist between medullary carcinoma of the breast and ductal carcinoma. The biologic and clinical differences demonstrated in this analysis warrant careful consideration before including cases of medullary carcinoma in studies evaluating newer prognostic variables in breast cancer.}, }
@article {pmid7577324, year = {1995}, author = {Eskin, BA and Grotkowski, CE and Connolly, CP and Ghent, WR}, title = {Different tissue responses for iodine and iodide in rat thyroid and mammary glands.}, journal = {Biological trace element research}, volume = {49}, number = {1}, pages = {9-19}, pmid = {7577324}, issn = {0163-4984}, mesh = {Animals ; Body Weight/drug effects ; Female ; Iodides/*pharmacology ; Iodine/*pharmacology ; Mammary Glands, Animal/cytology/*drug effects/physiology ; Organ Size/drug effects ; Rats ; Rats, Sprague-Dawley ; Thyroid Gland/anatomy &amp; histology/*drug effects/physiology ; }, abstract = {This research describes the effects of short-term elemental iodine (I2) and iodide (I-) replacement on thyroid glands and mammary glands of iodine-deficient (ID) Sprague-Dawley female rats. Iodine deficiency causes atypical tissue and physiologic changes in both glands. Tissue histopathology and the endocrine metabolic parameters, such as serum TT4, tissue and body weights, and vaginal smears, are compared. A moderate reduction in thyroid size from the ID control (IDC) was noted with both I- and I2, whereas serum total thyroxine approached the normal control with both I- and I2, but was lower in IDC. Thyroid gland IDC hyperplasia was reduced modestly with I2, but eliminated with I-. Lobular hyperplasia of the mammary glands decreased with I2 and increased with I- when compared with the IDC; extraductal secretions remained the same as IDC with I2, but increased with I-; and periductal fibrosis was markedly reduced with I2, but remained severe with I-. Thus, orally administered I2 or I- in trace doses with similar iodine availability caused different histopathological and endocrine patterns in thyroid and mammary glands of ID rats. The significance of this is that replacement therapy with various forms of iodine are tissue-specific.}, }
@article {pmid7560165, year = {1995}, author = {Lakhani, SR and Collins, N and Stratton, MR and Sloane, JP}, title = {Atypical ductal hyperplasia of the breast: clonal proliferation with loss of heterozygosity on chromosomes 16q and 17p.}, journal = {Journal of clinical pathology}, volume = {48}, number = {7}, pages = {611-615}, pmid = {7560165}, issn = {0021-9746}, mesh = {Aged ; Aged, 80 and over ; Breast/*pathology ; Breast Neoplasms/*genetics ; Carcinoma in Situ/genetics ; Carcinoma, Ductal, Breast/genetics ; Cell Division ; *Chromosome Deletion ; Chromosomes, Human, Pair 16/*genetics ; Chromosomes, Human, Pair 17/*genetics ; Clone Cells/pathology ; Female ; Humans ; Hyperplasia/genetics ; Middle Aged ; Polymerase Chain Reaction ; }, abstract = {AIMS: To determine if allelic loss on chromosomes 16q and 17p, commonly encountered in in situ and invasive ductal carcinomas, is present in atypical ductal hyperplasia (ADH); to determine whether ADH is a neoplastic (clonal) or hyperplastic (polyclonal) proliferation.<br><br>METHODS: Fourteen cases of ADH were examined for allele loss at loci on chromosome 16q and 17p using a microdissection technique, polymorphic DNA markers and the polymerase chain reaction (PCR).<br><br>RESULTS: Loss of heterozygosity (LOH) was detected in five of nine informative cases on chromosome 16q at the microsatellite D16S413 and two of eight informative cases on chromosome 17p at D17S796.<br><br>CONCLUSIONS: The incidence of LOH at these loci is similar to that previously observed in ductal carcinoma in situ and in invasive ductal carcinoma. Because of the nature of the technique used, our findings also demonstrate that ADH is a monoclonal, and hence, neoplastic proliferation rather than a hyperplastic (polyclonal) condition as its name suggests. There is thus a case for including ADH, as presently defined, within the spectrum of ductal carcinoma in situ.}, }
@article {pmid7782762, year = {1995}, author = {Ludewig, B and Holzmeister, J and Gentile, M and Gelderblom, HR and Rokos, K and Becker, Y and Pauli, G}, title = {Replication pattern of human immunodeficiency virus type 1 in mature Langerhans cells.}, journal = {The Journal of general virology}, volume = {76 (Pt 6)}, number = {}, pages = {1317-1325}, doi = {10.1099/0022-1317-76-6-1317}, pmid = {7782762}, issn = {0022-1317}, mesh = {Antibodies, Monoclonal ; Antigens, CD/analysis ; Cells, Cultured ; Cytokines/*pharmacology ; HIV Core Protein p24/analysis ; HIV-1/drug effects/*physiology/ultrastructure ; Humans ; Immunohistochemistry ; Kinetics ; Langerhans Cells/*immunology/ultrastructure/*virology ; Microscopy, Electron ; *Virus Replication/drug effects ; }, abstract = {Langerhans cells (LC), the dendritic antigen presenting cells of the skin, mature into potent immunostimulatory cells during migration to regional lymph nodes, where they are identified as interdigitating cells (IDC). Since mature Langerhans cells (mLC) resemble IDC in phenotype and immunostimulatory capacity, we examined whether these cells were susceptible to infection with macrophagetropic and lymphotropic strains of human immunodeficiency virus type 1 (HIV-1). Highly purified cell preparations of mLC migrating from human epidermis expressed high amounts of major histocompatibility complex (MHC) class I and II antigens and of the accessory molecules CD40, CD80 and CD86, indicative of the phenotype of potent immunostimulatory cells. CD4 expression was upregulated on mLC during cultivation, independent of the presence of tumour necrosis factor alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the culture medium. The macrophagetropic HIV-1 strain SF162 replicated to higher titres in mLC than the lymphotropic strain IIIB. Both strains induced syncytia, with SF162 showing a more rapid cytopathic effect. Addition of TNF-alpha enhanced virus production, due to better cell viability under TNF-alpha treatment, whereas GM-CSF did not significantly influence viability of cells and replication pattern of the virus. These findings suggest that in the infected individual IDC in lymph nodes may function as target cells for HIV-1.}, }
@article {pmid7774895, year = {1995}, author = {Sneige, N and McNeese, MD and Atkinson, EN and Ames, FC and Kemp, B and Sahin, A and Ayala, AG}, title = {Ductal carcinoma in situ treated with lumpectomy and irradiation: histopathological analysis of 49 specimens with emphasis on risk factors and long term results.}, journal = {Human pathology}, volume = {26}, number = {6}, pages = {642-649}, doi = {10.1016/0046-8177(95)90170-1}, pmid = {7774895}, issn = {0046-8177}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma in Situ/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*pathology/radiotherapy/surgery ; Combined Modality Therapy ; Female ; Fibrosis ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Middle Aged ; Necrosis ; Neoplasm Recurrence, Local/*pathology/radiotherapy/surgery ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; }, abstract = {Forty-nine women with ductal carcinoma in situ (DCIS) treated with lumpectomy and irradiation were studied retrospectively. The median age was 50 years (range, 29 to 73 years) and the median follow-up time from initiation of therapy was 86 months (range, 17 to 230 months). Twelve patients presented with palpable masses (0.4 to 4 cm), three with breast thickening, and three with nipple discharge. In 31 patients the tumors were detected by mammography. Intraoperatively, excision of lesions was confirmed by specimen x-ray (38 specimens) or gross inspection (five specimens) and was recorded to be complete. No record was available in the other six patients. Margins of excision free of DCIS were microscopically confirmed in 25 specimens. The size of impalpable DCIS lesions recorded in 25 patients ranged from 0.4 to 5.0 cm (mean, 1.5 cm). Using Lagios' classification system, there were 18 classic comedocarcinomas, high nuclear grade (NG) with necrosis; seven cribriform/papillary, high NG with necrosis; 17 cribriform/micropapillary, intermediate NG with or without necrosis; and seven cribriform/micropapillary, low NG without necrosis. In two patients residual malignant calcifications were present on the postoperative mammogram. Disease recurred in the treated breast at the site of incision in five patients at 18 months and 8, 11, and 12 (two patients) years from initial therapy. The rate of local disease recurrence was 2% at 5 years and 6% at 10 years; three recurrences showed invasive ductal carcinoma and two were DCIS. To evaluate risk factors the following characteristics were considered: necrosis, NG, histological type, periductal fibrosis, periductal lymphoid infiltrate, margin status, age, and method of tumor detection. The end points chosen were recurrence and death from any cause (because only one patient died of disease). Although the recurrences were attributed to residual disease in two patients, of the clinical and pathological parameters evaluated, only periductal fibrosis showed a significant relationship with outcome, with a P value < or = .05 by the Wilcoxon test. On the other hand, using the proportional hazards model, necrosis was a significant predictor for recurrence (P = .02), as was the pair fibrosis and tumor detection when taken together (P = .05). Fibrosis significantly associated with high NG, Lagios' histological subtypes I and II, periductal lymphoid infiltrate, and necrosis (P < or = .0006).(ABSTRACT TRUNCATED AT 400 WORDS)}, }
@article {pmid7591715, year = {1995}, author = {Snyman, JR and Sommers, DK and van Wyk, M and Gregorowski, MD}, title = {The influence of betahistine on the dynamics of the cutaneous hypersensitivity reaction in patients with grass pollen allergy.}, journal = {Immunopharmacology}, volume = {30}, number = {1}, pages = {71-78}, doi = {10.1016/0162-3109(95)00007-g}, pmid = {7591715}, issn = {0162-3109}, mesh = {Adult ; *Betahistine ; Cross-Over Studies ; Dermatitis, Allergic Contact/complications/*diagnosis/pathology ; Female ; *Histamine Agonists/administration &amp; dosage ; Humans ; Hypersensitivity, Delayed/diagnosis/pathology ; Hypersensitivity, Immediate/diagnosis/pathology ; Intradermal Tests ; Leukocyte Count/drug effects ; Male ; Poaceae/immunology ; Pollen/*immunology ; Rhinitis, Allergic, Seasonal/*complications ; }, abstract = {Histamine has been well documented as an immune modulator, but the dynamics of a number of histamine receptor agonists and antagonists have not been similarly established. The aim of this study was to determine the effect of betahistine (an H3-receptor blocker with partial H1- and H2-agonism) on the dynamics of the cutaneous hypersensitivity reaction. The skin blister technique was used to collect inflammatory cells after intradermal (i.d.) administration of grass pollen antigen, histamine and betahistine to 11 atopic volunteers. In this open, cross-over study, volunteers were randomly allocated to five treatment protocols i.e. (a) histamine 1 microgram i.d.; (b) betahistine 57, 114 and 285 micrograms i.d.; (c) i.d. grass pollen antigen; (d) (c) plus oral betahistine; (e) (c) plus oral betahistine, cetirizine, (H1-blocker) and cimetidine (H2-blocker). Blister fluid containing cells were collected on microscope slides at 6 and 24 h after i.d. injections. The areas of the wheal and flare and of induration were measured, respectively, at 0.25, and, 1, 6 and 24 h. Combined oral therapy with cetirizine, cimetidine and betahistine reduced the area of grass pollen-induced induration significantly at all time periods, but caused a significant increase in eosinophil and neutrophil vacuolisation during the late phase reaction. This did not occur with orally administered betahistine alone. Intradermal betahistine induced significantly more neutrophil and eosinophil vacuolization than histamine and, in contrast to the latter, also mediated a concentration-dependent late phase induration. The results of this study suggest that the H3-receptor regulates a feedback system in conjunction with that previously proven for the H2-receptor.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid7543649, year = {1995}, author = {Barrón, S and Tusell, JM and Serratosa, J}, title = {Effect of hexachlorocyclohexane isomers on calmodulin mRNA expression in the central nervous system.}, journal = {Brain research. Molecular brain research}, volume = {30}, number = {2}, pages = {279-286}, doi = {10.1016/0169-328x(95)00015-k}, pmid = {7543649}, issn = {0169-328X}, mesh = {Animals ; Blotting, Northern ; Calmodulin/*biosynthesis/genetics ; Central Nervous System/drug effects/*metabolism ; Gene Expression ; Hexachlorocyclohexane/*pharmacology ; In Situ Hybridization ; Male ; RNA, Messenger/metabolism ; Rats ; Rats, Wistar ; Time Factors ; }, abstract = {Three different calmodulin genes that encode the same protein have been found in the brain of all mammalian species so far examined. Little is known about the factors involved in regulating the expression of this gene family in the central nervous system. We have investigated the possibility of differential expression of two calmodulin genes, CaM I and CaM II, which are expressed strongly in neuronal cells in the adult rat brain, after treatment with the gamma (lindane) and the delta isomers of the hexachlorocyclohexane (HCH). In this study a decrease of CaM I mRNA (mainly in the 4.0 kb transcript) was found in the cortex of the rats after 24 h of isomer administration. CaM I expression seemed to be more sensitive to delta isomer action, whereas the gamma isomer acted mainly at CaM II level. The levels of mRNA of calmodulin CaM II gene were also found to decrease after lindane administration; delta-HCH produced an increase of this transcript. These results were obtained by Northern blot analysis and confirmed by means of in situ hybridization. Our results suggest that levels of neuronal calmodulin mRNA species are modified in response to changes in neuronal activity.}, }
@article {pmid7492954, year = {1995}, author = {Harn, HJ and Chang, CY and Ho, LI and Liu, CA and Jeng, JR and Lin, FG and Jent-Wei, }, title = {Evidence that polymorphism of the angiotensin I converting enzyme gene may be related to idiopathic dilated cardiomyopathy in the Chinese population.}, journal = {Biochemistry and molecular biology international}, volume = {35}, number = {6}, pages = {1175-1181}, pmid = {7492954}, issn = {1039-9712}, mesh = {Adult ; Alleles ; Base Sequence ; Cardiomyopathy, Dilated/etiology/*genetics ; China ; *DNA Transposable Elements ; *Gene Deletion ; Genotype ; Humans ; Introns ; Molecular Sequence Data ; Peptidyl-Dipeptidase A/*genetics ; *Polymorphism, Genetic ; }, abstract = {Angiotensin I-converting enzyme (ACE) is responsible for the production of angiotension II and the breakdown of kinins, leading to increased blood pressure (BP), induction of vascular smooth muscle cell proliferation, and the stimulation of myocardial-cell hypertrophy. A 287 bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction in a cross-sectional study of 35 patients with idiopathic dilated cardiomyopathy (IDC) and 35 patients with normally functioning hearts (NT). Compared with the deletion/deletion (D/D) frequency in the control population, the frequency of the deletion allele was 0.757 in IDC patients and 0.600 in NTs; the difference between observed alleles in all subjects in each group was significant (x2 = 3.96; P < 0.05). The data thus provide evidence in favor of an association between idiopathic dilated cardiomyopathy and a polymorphism at the ACE locus (17q23), thus implicating this locus, and possibly a genetic variant of ACE, itself, in human idiopathic dilated cardiomyopathy.}, }
@article {pmid7659082, year = {1995}, author = {Holt, JC and Caulfield, JB and Norton, P and Chantler, PD and Slayter, HS and Margossian, SS}, title = {Human cardiac myosin light chains: sequence comparisons between myosin LC1 and LC2 from normal and idiopathic dilated cardiomyopathic hearts.}, journal = {Molecular and cellular biochemistry}, volume = {145}, number = {1}, pages = {89-96}, pmid = {7659082}, issn = {0300-8177}, support = {HL-33014/HL/NHLBI NIH HHS/United States ; HL-35358/HL/NHLBI NIH HHS/United States ; HL-49597/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cardiomyopathy, Dilated/*metabolism ; Chickens ; Chromatography, High Pressure Liquid ; Conserved Sequence ; Female ; Humans ; Male ; Molecular Sequence Data ; Mollusca ; Myocardium/*chemistry ; *Myosin Light Chains ; Myosins/*chemistry/isolation &amp; purification ; Peptide Mapping ; Rats ; Sequence Analysis ; Sequence Homology, Amino Acid ; }, abstract = {The primary structures of light chains isolated from the human myocardium with idiopathic dilated cardiomyopathy (IDC) were determined and compared with the sequence structures of myosin light chains obtained from control human heart myosin. Sequences were determined by chemical analysis and the identity of N-terminal residues established by mass spectrometry. The N-terminal residues in essential (ELC) and regulatory (RLC) light chains were blocked and were identified to be trimethyl alanine. The amino acid sequences of ELC and RLC from control human myosin revealed a high degree of homology with those purified from rat and chicken cardiac myosin. Comparison with a published partial chemical sequence of the human heart myosin light chains revealed significant variations. However, there was very good agreement with published sequences obtained by molecular biological techniques. Sequences of the light chains from cardiomyopathic myosin revealed no difference in the primary structures when compared with control human heart myosin light chains indicating IDC had no influence on, nor was caused by, altered myosin light chain gene expression.}, }
@article {pmid7705825, year = {1995}, author = {Ni, K and Dehner, LP}, title = {Schwannoma with metastatic carcinoma of the breast: an unconventional form of glandular peripheral sheath tumor.}, journal = {Human pathology}, volume = {26}, number = {4}, pages = {457-459}, doi = {10.1016/0046-8177(95)90149-3}, pmid = {7705825}, issn = {0046-8177}, mesh = {Aged ; Arm ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/secondary ; Cysts/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Multiple Primary/*pathology ; Neurilemmoma/*pathology/secondary ; Soft Tissue Neoplasms/*pathology ; }, abstract = {We report a schwannoma of the left arm harboring metastatic adenocarcinoma in a 68-year-old woman who had a history of invasive ductal carcinoma of the left breast with widespread metastases. The soft tissue tumor of the left arm had the morphological features of a typical schwannoma except for the presence of multiple foci of moderately to poorly differentiated adenocarcinoma and a grossly visible cyst that was lined by benign appearing cuboidal to low columnar epithelium. The immunohistochemical studies showed that the spindle cells were diffusely and strongly positive for vimentin, S-100 protein, and collagen type IV, and focally reactive for Leu 7. The cyst and the foci of adenocarcinoma were both stained for cytokeratin, but the adenocarcinomatous foci also were immunoreactive for estrogen receptor, gross cystic disease fluid protein, and focally for S-100 protein, in contrast to the lack of positivity for these three markers in the epithelium of the cyst. To the best of our knowledge this case is a unique one of a schwannoma with metastatic mammary carcinoma producing yet another variation on the theme of a glandular peripheral nerve sheath tumor.}, }
@article {pmid7560351, year = {1995}, author = {Rosso, R and Gianelli, U and Carnevali, L}, title = {Acquired progressive lymphangioma of the skin following radiotherapy for breast carcinoma.}, journal = {Journal of cutaneous pathology}, volume = {22}, number = {2}, pages = {164-167}, doi = {10.1111/j.1600-0560.1995.tb01401.x}, pmid = {7560351}, issn = {0303-6987}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma/*pathology/therapy ; Female ; Humans ; Lymphangioma/*pathology ; Middle Aged ; Radiotherapy/*adverse effects ; Skin Neoplasms/pathology/*secondary ; }, abstract = {A case of a vascular tumor clinically and pathologically consistent with acquired progressive lymphangioma (benign lymphangioendothelioma) in a 48-year-old woman is reported. The lesion appeared in the skin close to a mastectomy scar 3 years after surgery and radiotherapy for invasive ductal carcinoma. On histologic examination, it mimicked an aggressive vascular neoplasm because of its infiltrative pattern. However, follow-up studies confirmed the benign nature of the lesion, clinically and histologically. This case indicates that acquired progressive lymphangioma may follow radiotherapy and must be considered in the differential diagnosis of other vascular proliferations occurring in the skin of the breast, especially of low-grade postradiation angiosarcoma, a recently described neoplastic entity.}, }
@article {pmid7550995, year = {1995}, author = {Nagasaki, M and Harada, T and Morikawa, S}, title = {A new monoclonal antibody (IE8) reactive with dendritically shaped cells in the human tonsil.}, journal = {Pathology international}, volume = {45}, number = {4}, pages = {266-274}, doi = {10.1111/j.1440-1827.1995.tb03455.x}, pmid = {7550995}, issn = {1320-5463}, mesh = {Animals ; *Antibodies, Monoclonal ; *Antibodies, Neoplasm ; Antigen-Antibody Reactions ; Antigens, Neoplasm/immunology ; Biomarkers ; Cell Line, Transformed ; Dendritic Cells/*immunology/pathology ; Humans ; Interphase/immunology ; Leukocytes, Mononuclear/immunology ; Lymphoma/pathology ; Mice ; Mice, Inbred BALB C ; Molecular Weight ; Palatine Tonsil/*immunology/pathology ; Precipitin Tests ; Tumor Cells, Cultured ; }, abstract = {A new monoclonal antibody (mAb), 1E8 (IgG1, kappa), was obtained from a hybridoma prepared by fusion of mouse myeloma cells (NS-1) with splenic cells of mice immunized with a human B blastic malignant lymphoma cell line, HPE-Ret-3 (Ret-3). The mAb showed a reactivity unrestricted to a specific cell lineage on flow cytometrical analysis of the reactivity with human lympho-hematopoietic cell lines. In peripheral blood, 1E8 reacted with the cells of all lineage, that is, lymphocytes, monocytes, granulocytes and platelets, even though its intensity was very low by immunohistochemistry. Immunohistochemical examination of human tonsil with 1E8 showed a characteristic staining pattern. Positive cells scattered in follicular (mantle zone and germinal center), parafollicular (T-dependent area), subepithelial and interstitial connective tissue areas. These positive cells seemed to be categorized into dendritically shaped cells (DSC), including dendritic cells (DC) and a subpopulation of macrophages in follicles, interdigitating cells (IDC) and irregularly shaped mononuclear cells. The localization of 1E8 antigen staining was similar to that of integrin CD11c, although its distribution on hematopoietic cell lines did not coincide with that of 1E8 antigen. Immunobiochemical studies showed that 1E8 bound two cell surface proteins with molecular size of 70,000-90,000 and 35,000 Da each. Consequently, 1E8 antigen might be a novel marker of DSC.}, }
@article {pmid7878527, year = {1995}, author = {Gaffney, EV and Halpin, DP and Blakemore, WS}, title = {Relationship between low estrogen receptor values and other prognostic factors in primary breast tumors.}, journal = {Surgery}, volume = {117}, number = {3}, pages = {241-246}, doi = {10.1016/s0039-6060(05)80196-5}, pmid = {7878527}, issn = {0039-6060}, mesh = {Adult ; Aneuploidy ; Breast Neoplasms/*chemistry/genetics/pathology ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology ; DNA, Neoplasm/genetics ; Diploidy ; Female ; Humans ; Immunohistochemistry ; Prognosis ; Radioligand Assay ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; S Phase ; }, abstract = {BACKGROUND: The current study compared the immunocytochemical expression of estrogen (ER) and progesterone (PgR) receptors by malignant breast cells to the hormone receptor concentrations reported from radioligand assays. These values were examined in relation to DNA ploidy and the fraction of cells in S phase.<br><br>METHODS: ER and PgR concentrations, DNA ploidy, and S-phase fractions were measured by standard techniques with 124 samples of invasive ductal carcinoma. Suspensions of tumor cells were examined by immunocytochemical assay (ICA) for the percentages of ER and PgR positive cells.<br><br>RESULTS: Twenty-six of the 38 tumors from patients 50 years of age or younger were classified as high S-phase fraction, and 28 tumors had aneuploid levels of DNA. The 20 ER positive tumors each contained less than 100 fmol/mg. Thirty-nine of the 86 tumors from patients older than 50 years were classified as high S phase, and 41 were aneuploid. Sixty-five samples were considered ER positive by radioligand assay. ICA showed that tumors in either age group with less than 40 fmol/mg did not contain ER positive cells. The proportion of samples with PgR levels between 10 and 100 fmol/mg was small, and fewer PgR positive tumors were categorized as negative when examined by ICA for receptor containing cells. The reclassification of the hormone receptor status of a tumor based on ICA appeared to be independent of S-phase and ploidy values.<br><br>CONCLUSIONS: Tumors that are classified as ER or PgR positive based on accepted cutoff values for radioligand assays may actually be receptor negative because the tumors do not appear to contain receptor positive cells.}, }
@article {pmid7787994, year = {1995}, author = {Nomoto, M and Yonezawa, S and Tokunaga, M and Kim, YS and Sato, E}, title = {Mucin antigens expression and Ki-67 labeling in breast cancer: the peculiarity in scirrhous carcinoma.}, journal = {Pathology international}, volume = {45}, number = {3}, pages = {233-239}, doi = {10.1111/j.1440-1827.1995.tb03447.x}, pmid = {7787994}, issn = {1320-5463}, support = {CA24321/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Scirrhous/*immunology/pathology ; Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/*analysis ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/*immunology/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Lymphatic Metastasis ; Middle Aged ; Mucins/*immunology ; Neoplasm Proteins/*analysis ; Nuclear Proteins/*analysis ; Prognosis ; }, abstract = {The expression of mucin-related antigens (Tn, T, Sialosyl-Tn [STn], DF3 [mammary-type apomucin related antigen], and intestinal-MRP [intestinal-type apomucin related antigen]) as well as Ki-67 labeling was examined in 58 mammary invasive ductal carcinomas (IDC) divided into 26 scirrhous subtype (SC) and 32 non-scirrhous subtype comprising papillotubular carcinoma and solid-tubular carcinoma (PT-ST). These data were analyzed in connection with the various pathological prognostic factors such as nodal status, tumor size, estrogen receptor status and histological grading of carcinomas. The results were as follows: (a) in SC, the expression rate of Tn was significantly higher in the cases with positive lymph node metastasis or with large tumor size (> 2 cm) than in those with negative lymph node metastasis or with small tumor size (< or = 2 cm); (b) in PT-ST, the expression rate of STn was higher in the cases with positive lymph node metastasis or with large tumor size than in those with negative lymph node metastasis or with small tumor size; (c) in SC, Ki-67 labeling was significantly higher in the cases with positive lymph node metastasis than in those with negative lymph node metastasis; and (d) in PT-ST, Ki-67 labeling was lower in the cases with positive lymph node metastasis than in those with negative lymph node metastasis. In conclusion, Tn antigen expression was correlated with pathological prognostic factors in SC but not in PT-ST, whereas STn antigen expression was correlated with pathological prognostic factors in PT-ST but not in SC.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid7665243, year = {1995}, author = {Murphy, DS and McHardy, P and Coutts, J and Mallon, EA and George, WD and Kaye, SB and Brown, R and Keith, WN}, title = {Interphase cytogenetic analysis of erbB2 and topoII alpha co-amplification in invasive breast cancer and polysomy of chromosome 17 in ductal carcinoma in situ.}, journal = {International journal of cancer}, volume = {64}, number = {1}, pages = {18-26}, doi = {10.1002/ijc.2910640106}, pmid = {7665243}, issn = {0020-7136}, mesh = {Aneuploidy ; Breast Neoplasms/*genetics ; Carcinoma in Situ/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Chromosome Aberrations/*genetics ; Chromosome Disorders ; *Chromosomes, Human, Pair 17 ; DNA Topoisomerases, Type II/*genetics ; Gene Amplification ; *Genes, erbB-2 ; Humans ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2/*genetics ; }, abstract = {Breast cancer is a genetically complex disease. Fluorescence in situ hybridisation can be used to analyse the genetics of breast-cancer progression in interphase cytogenetics. We have analysed the histological distribution of erbB2 and topoll alpha co-amplification in paraffin sections of invasive breast cancer and show that the co-amplified loci share the same histological distribution in the tumour and have a similar nuclear distribution within individual nuclei. Regions of the tumours without amplification are easily recognized and tumours with erbB2 and topoll alpha co-amplification can be distinguished from those with erbB2 amplification alone. In addition, FISH was used to show polysomy of chromosome 17 in non-invasive ductal carcinoma in situ of the breast and erbB2 amplification in both the invasive and non-invasive components of a breast cancer biopsy. This report of an interphase cytogenetic analysis of non-invasive breast carcinoma in situ demonstrates the usefulness of FISH for the genetic study of breast cancer progression.}, }
@article {pmid7567169, year = {1995}, author = {Bisceglia, M and Castelvetere, M and Dimitri, L and Monte, V and D'Angelo, V}, title = {[Cerebral amyloid angiopathy (congophilic angiopathy): a rare cause of massive cerebral hemorrhage. Report of an "age-related" sporadic case].}, journal = {Pathologica}, volume = {87}, number = {1}, pages = {65-70}, pmid = {7567169}, issn = {0031-2983}, mesh = {Age Factors ; Aged ; Cerebral Amyloid Angiopathy/*complications/pathology ; Cerebral Hemorrhage/*etiology ; Female ; Humans ; }, abstract = {Cerebral amyloidosis is a form of organ-limited amyloidosis, which doesn't involve any organ other than brain and which comprises several subtypes, including "congophilic angiopathy" (CA), "senile plaques" (SP), "neurofibrillary degeneration" (ND), "stellate amyloid cores" of spongiform encephalopathies. It is found in 5 to around 20% of human population in people aged 60 to 90 years, the increasing being strictly related to ageing. Usually it is associated to SP and occasionally to ND, being distinguished into familial and non-familial (age-related) variants. It affects intracortical and leptomeningeal variously sized vessels of the brain and is a leading pathogenetic factor in determining a rare but possibly even recurrent form of a massive intraparenchymal cerebral hemorrhage, constituting a 0.2 per cent of brain vascular accidents of any origin and a 5-10 per cent if only primary non traumatic brain hemorrhages are considered. A case of non-familial CA in a previously non-demented nor hypertensive female patient aged 65 years is reported on, who was admitted due to an almost abrupt onset of neurologic symptoms mainly dominated by a sudden loss of consciousness together with a left sensory-motor deficiency syndrome. The patient who had been operated on of unilateral mastectomy eight years earlier due to an invasive ductal carcinoma of the breast was found affected by a devastating brain hemorrhage in the right temporo-occipital lobes with subsequent deflection of the brainstem axis toward the opposite side detected by means of CT/MRI and angiographic investigations.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid7812921, year = {1995}, author = {Malins, DC and Polissar, NL and Nishikida, K and Holmes, EH and Gardner, HS and Gunselman, SJ}, title = {The etiology and prediction of breast cancer. Fourier transform-infrared spectroscopy reveals progressive alterations in breast DNA leading to a cancer-like phenotype in a high proportion of normal women.}, journal = {Cancer}, volume = {75}, number = {2}, pages = {503-517}, doi = {10.1002/1097-0142(19950115)75:2&lt;503::aid-cncr2820750213&gt;3.0.co;2-0}, pmid = {7812921}, issn = {0008-543X}, mesh = {Breast/chemistry ; Breast Neoplasms/etiology/*genetics ; Carcinoma, Ductal, Breast/etiology/*genetics ; DNA, Neoplasm/*chemistry ; Factor Analysis, Statistical ; Female ; Humans ; Models, Biological ; Precancerous Conditions ; Spectroscopy, Fourier Transform Infrared ; }, abstract = {BACKGROUND: The authors previously have shown by gas chromatography-mass spectrometry that the hydroxyl radical (.OH) induces alterations in the DNA base structure of the female breast, which are premalignant markers of breast cancer. Fourier transform-infrared (FT-IR)-spectroscopy also has a high potential for revealing a broad array of structural changes in DNA that may provide important new insight into breast cancer etiology and prediction.<br><br>METHODS: DNA from normal reduction mammoplasty tissue, invasive ductal carcinoma, and nearby microscopically normal tissue was analyzed by FT-IR spectroscopy. Statistical models based on DNA spectral properties were developed and compared with a statistical model previously used with base modifications.<br><br>RESULTS: Substantial differences were found in the spectral properties of DNA from women with normal and cancerous breast tissue, indicating an ability to discriminate cancerous tissue from noncancerous tissue with a sensitivity and specificity of 83%. Most importantly, the normal population was divided into subgroups in which a nonrandom progression was identified and a cancer-like DNA phenotype that was highly correlated (r > or = 0.90) with that of the patients with cancer was exhibited in 59% of the women. The spectral data, which also were highly correlated with the base-model data, were used to establish a model for predicting the probability of breast cancer. Consistent with the high cancer reoccurrence rate in the ipsilateral breast, 8 of 10 of the microscopically normal tissue specimens remaining after tumor excision were classified as cancerous using this model.<br><br>CONCLUSIONS: Progressive structural changes in the DNA of the normal female breast, leading to a premalignant cancer-like phenotype in a high proportion of women, are the basis for a new paradigm for understanding the etiology of breast cancer and predicting its occurrence at early stages of oncogenesis. The results also suggest therapeutic strategies for potentially reversing the extent of DNA damage, which may be useful in disease prevention and treatment.}, }
@article {pmid9700362, year = {1995}, author = {Beijleveld, LJ and Damoiseaux, JG and Van Breda Vriesman, PJ}, title = {Differential effects of X-irradiation and cyclosporin-A administration on the thymus with respect to the generation of cyclosporin-A-induced autoimmunity.}, journal = {Developmental immunology}, volume = {4}, number = {2}, pages = {127-138}, doi = {10.1155/1995/18495}, pmid = {9700362}, issn = {1044-6672}, mesh = {Animals ; Antibodies, Monoclonal ; *Autoimmunity/drug effects/radiation effects ; Cyclosporine/*administration &amp; dosage ; Dendritic Cells/drug effects/immunology/radiation effects ; Epithelial Cells/drug effects/immunology/radiation effects ; Female ; Injections, Subcutaneous ; Lymphocyte Count/drug effects/radiation effects ; Macrophages/drug effects/immunology/radiation effects ; Rats ; Rats, Inbred Lew ; T-Lymphocytes/drug effects/immunology/radiation effects ; Thymectomy ; Thymus Gland/cytology/*drug effects/*radiation effects ; Time Factors ; X-Rays ; }, abstract = {Cyclosporin A (CsA), a potent inhibitor of T-cell activation, has been shown to have several effects on thymocyte maturation, thymic stromal cells, and the generation of autoreactive T cells. In Lewis rats, the combination of lethal irradiation, syngeneic bone marrow transplantation, and a 4-week course of CsA administration causes the development of an autoimmune disease (CsA-AI) resembling allogeneic graft-versus-host disease. This occurs upon withdrawal of CsA, provided the thymus receives irradiation and is present during CsA treatment. In this study, the separate effects of irradiation or CsA treatment on thymic stromal cells and thymocytes, compared to the combinatory effects, were examined using immunohistochemistry and tricolor flow cytometric analysis. CsA treatment causes an involution of the thymic medulla and a strong reduction of the cell number of thymocytes and stromal cells residing in the medulla. However, within the remaining medullary area, changes in cell distribution and antigen density on these cells were not observed. Irradiation on the other hand causes a strong depletion of thymocytes. The thymocyte population is recovered within 2 weeks and a cortical and medullary region can be distinguished. CsA treatment in combination with irradiation results in a strongly inhibited recovery of the medulla during CsA treatment, whereas the cortex recovers to normal size and morphology. The presence of the medullary IDC and epithelial cells is reduced proportionally to the small size of the medulla. However, the distribution of these stromal cells is normal. During the CsA administration, the thymuses from irradiated and CsA-treated rats are very similar to thymuses from CsA-treated rats. In conclusion, no changes specific for irradiation plus CsA treatment have been observed. Regarding the distribution and size of medullary stromal cells and residing thymocytes, thymuses from irradiated and CsA-treated rats hardly differ from the thymuses from rats treated only with CsA. Therefore, irradiation seems essential in the generation of CsA-AI by eliminating suppressor-cell circuits in the periphery.}, }
@article {pmid8651043, year = {1995}, author = {Fruhwald, FM and Watzinger, N and Schumacher, M and Zweiker, R and Eber, B and Klein, W}, title = {[Dilated cardiomyopathy--diagnosis and conservative therapy].}, journal = {Acta medica Austriaca}, volume = {22}, number = {5}, pages = {90-93}, pmid = {8651043}, issn = {0303-8173}, mesh = {Angiotensin-Converting Enzyme Inhibitors/adverse effects/therapeutic use ; Cardiomyopathy, Dilated/diagnosis/*drug therapy/etiology ; Cardiovascular Agents/adverse effects/*therapeutic use ; Digitalis Glycosides/adverse effects/therapeutic use ; Diuretics/adverse effects/therapeutic use ; Hemodynamics/drug effects ; Humans ; Prognosis ; }, abstract = {Diagnosis of dilated cardiomyopathy (IDC) is a diagnosis of exclusion. Physical examination of the patient, non-invasive tests and invasive tests have to be done to exclude secondary dilated cardiomyopathies. Treatment can be divided into baseline therapy, established treatment, e.g. ACE-inhibitors, digitalis and diuretics and optional treatment including betablocker, anticoagulation and an natural course of IDC for an individual patient is not clear although there are several prognostic parameters for this disease.}, }
@article {pmid8574061, year = {1995}, author = {Tokizawa, N and Iino, Y and Yokoe, T and Izumi, M and Kawate, S and Anzai, T and Morishita, Y and Honma, M}, title = {Sudden hemorrhage of the breast caused by breast cancer without skin invasion: report of a case.}, journal = {Surgery today}, volume = {25}, number = {10}, pages = {920-922}, pmid = {8574061}, issn = {0941-1291}, mesh = {Aged ; Breast Neoplasms/*complications/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*complications/diagnostic imaging/pathology ; Female ; Hemorrhage/*etiology ; Humans ; Mammography ; Neoplasm Invasiveness ; Skin/*pathology ; }, abstract = {A rare case of sudden hemorrhage caused by breast cancer is herein presented. A 65-year-old woman was admitted to our hospital because of bleeding from her left breast. On physical examination, a continuous hemorrhage accompanied by an open cavity formation was observed in her left breast. She had no history of breast trauma. Her bleeding profile studies and liver function were both normal. In addition, no anticoagulation medication had been administered. The histological findings of the cavity wall indicated invasive ductal carcinoma without skin invasion. After carrying out chemotherapy, a standard radical mastectomy was performed.}, }
@article {pmid7895264, year = {1995}, author = {Maeda, K and Kosco-Vilbois, MH and Burton, GF and Szakal, AK and Tew, JG}, title = {Expression of the intercellular adhesion molecule-1 on high endothelial venules and on non-lymphoid antigen handling cells: interdigitating cells, antigen transporting cells and follicular dendritic cells.}, journal = {Cell and tissue research}, volume = {279}, number = {1}, pages = {47-54}, pmid = {7895264}, issn = {0302-766X}, support = {AI-17412/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/immunology ; Antigen-Presenting Cells/*metabolism ; Dendritic Cells/*metabolism ; Endothelium, Vascular/cytology/*metabolism ; Female ; Immunoenzyme Techniques ; Intercellular Adhesion Molecule-1/*biosynthesis/genetics ; Lymph Nodes/cytology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Microscopy, Immunoelectron ; }, abstract = {Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the development of germinal center reactions in vitro, and the present study was undertaken to determine the distribution of ICAM-1 in active germinal centers in vivo and in murine secondary lymphoid tissues in general. Anti-ICAM-1-specific monoclonal antibodies were used in conjunction with immunohistochemistry at both the light and ultrastructural levels of resolution. Examination of cryostat sections of lymph nodes, spleens, and Peyer's patches revealed that anti-ICAM-1 distinctly labeled cells in the light zones of germinal centers, a few cells in the T cell zones (e.g. paracortex of lymph nodes), cells in the sinus floor of the subcapsular sinuses of lymph nodes, and high endothelial venules (HEV). Ultrastructural studies revealed that the cells labeling with anti-ICAM-1 in germinal centers were follicular dendritic cells (FDC) which appeared to have more ICAM-1 than any other cell type. The surfaces of well-developed, intricate, convoluted FDC processes were intensely labeled even under conditions where B cells appeared negative. Interdigitating cells (IDC) were also labeled as were certain endothelial cells in the HEV. The cells in the subcapsular sinus floor labeling with anti-ICAM-1 were the "antigen transporting cells" (ATC) that carry antigen-antibody complexes into lymph node follicles. We suspect ATC are FDC precursors which mature into FDC in the follicles. Interestingly, FDC, IDC, and ATC are 3 important accessory cells known to handle antigens in specific compartments of lymphoid tissues.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid7706519, year = {1995}, author = {Schmitt, FC and Andrade, L}, title = {Spectrum of carcinoembryonic antigen immunoreactivity from isolated ductal hyperplasias to atypical hyperplasias associated with infiltrating ductal breast cancer.}, journal = {Journal of clinical pathology}, volume = {48}, number = {1}, pages = {53-56}, pmid = {7706519}, issn = {0021-9746}, mesh = {Adolescent ; Adult ; Antigens, Neoplasm/*analysis ; Breast/immunology/*pathology ; Breast Diseases/immunology ; Breast Neoplasms/*immunology ; Carcinoembryonic Antigen/*analysis ; Carcinoma, Ductal, Breast/*immunology ; Female ; Humans ; Hyperplasia/immunology ; Immunoenzyme Techniques ; Middle Aged ; Precancerous Conditions/immunology ; }, abstract = {AIMS: To study the immunohistochemical expression of carcinoembryonic antigen (CEA) in ductal hyperplasia of the breast and to investigate its putative relation with atypia and co-existing infiltrating ductal carcinoma.<br><br>METHODS: Paraffin wax embedded tissue from 37 cases of isolated ductal hyperplasia (five with atypia and 32 without atypia) and 25 cases of ductal hyperplasia associated infiltrating ductal carcinoma (IDC) (seven with atypia and 18 without atypia) was stained with a monoclonal anti-CEA antibody using a standard avidin biotin immunoperoxidase method.<br><br>RESULTS: CEA immunoreactivity was observed in eight (12.8%) ductal hyperplasia cases. The percentage of CEA positivity in ductal hyperplasia cases with atypia (33.3%) was substantially higher than that observed in cases of ductal hyperplasia without atypia (8.0%). Six cases of ductal hyperplasia associated IDC reacted with CEA; in these six cases the neoplastic cells of the co-existing carcinoma were also CEA positive. The percentage of CEA immunoreactivity in ductal hyperplasia associated IDC was higher than that observed in isolated ductal hyperplasia (24.0 v 5.4%). The percentage of CEA immunoreactivity in atypical ductal hyperplasia associated IDC was similar to that observed in IDC alone (42.9 v 40.0%).<br><br>CONCLUSIONS: The presence of CEA immunoreactivity has been confirmed in benign proliferative breast lesions. The prevalence of such immunoreactivity increases from 3.1% in isolated, nonatypical ductal hyperplasia to 42.9% in atypical ductal hyperplasia associated IDC. This finding and the similarity of the frequency of CEA positivity in atypical ductal hyperplasia associated IDC and in IDC alone suggests that there is a pathogenetic link between ductal hyperplasia and some types of breast cancer.}, }
@article {pmid7633124, year = {1995}, author = {Haga, S and Makita, M and Shimizu, T and Watanabe, O and Imamura, H and Kajiwara, T and Fujibayashi, M}, title = {Histopathological study of local residual carcinoma after simulated lumpectomy.}, journal = {Surgery today}, volume = {25}, number = {4}, pages = {329-333}, pmid = {7633124}, issn = {0941-1291}, mesh = {Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Female ; Humans ; Mastectomy ; *Mastectomy, Segmental ; Neoplasm Recurrence, Local ; Neoplasm, Residual ; }, abstract = {From 1989 to 1991, 24 patients with invasive ductal carcinoma underwent simulated lumpectomy at Tokyo Women's Medical College Daini Hospital. The mastectomy specimens were then examined histopathologically in serial sections for the presence of residual tumors or multicentricity. Lumpectomy specimens from cancer foci at resected margins were also examined. In this study, 23 of 24 patients demonstrated positive resection margins (95.8%). Residual tumors were found in mastectomy specimens from 16 patients (66.7%); unilateral multifocal carcinomas were found in 2 of these patients (8.3%). The incidence and severity of residual tumors did not correlate with primary tumor size or the distance between the nipple and the primary tumor but directly correlated with the severity of intraductal spread of the primary tumor. Tumors with central necrosis were associated with a higher incidence of residual tumors. Our study thus indicates that there is a high risk that some residual tumor will be left in the conserved breast when lumpectomy is performed. Multifocal carcinoma and tumors showing severe intraductal spread and central necrosis are thus associated with extensive residual tumors and are likely to cause local recurrence.}, }
@article {pmid7530588, year = {1995}, author = {Storm, FK and Gilchrist, KW and Warner, TF and Mahvi, DM}, title = {Distribution of Hsp-27 and HER-2/neu in in situ and invasive ductal breast carcinomas.}, journal = {Annals of surgical oncology}, volume = {2}, number = {1}, pages = {43-48}, pmid = {7530588}, issn = {1068-9265}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism ; Carcinoma in Situ/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Heat-Shock Proteins/genetics/*metabolism ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Staining and Labeling ; }, abstract = {BACKGROUND: The overexpression of heat shock protein 27 (hsp-27) in early-stage breast cancer is associated with histopathologic features of poor prognosis and clinically with an increased probability of disease recurrence. Hsp-27 is overexpressed in 25% of invasive ductal carcinomas (IDC); however, its distribution in ductal carcinoma in situ (DCIS) and DCIS associated with IDC has not been investigated. We postulated that hsp-27 might be detected and variably expressed in DCIS and, like HER-2/neu oncoprotein expression, might be a tumor-specific marker worthy of future clinical investigation.<br><br>METHODS: To test these hypotheses, the distribution of hsp-27 in noncomedo and comedo DCIS, and DCIS associated with IDC, was evaluated by immunohistochemistry and compared with HER-2/neu expression within the same cancers.<br><br>RESULTS: Hsp-27 was overexpressed in 28 of 47 (approximately 60%) cases of DCIS; expression in pure DCIS was 16 of 24 (67%), and 12 of 23 (approximately 50%) in DCIS associated with IDC. Hsp-27 expression by in situ and invasive components of the same neoplasm were concordant in 22 of 23 (approximately 95%) cases tested. Comedo variants appeared to have somewhat higher hsp-27 expression than noncomedo DCIS, whether or not there was an associated IDC. These results are reminiscent of HER-2/neu oncoprotein expression in DCIS and DCIS associated with IDC observed by others. However, although 4 of 22 (18%) cancers containing DCIS + IDC expressed HER-2/neu, no relationship with hsp-27 expression in the same cancers was observed.<br><br>CONCLUSIONS: We found a high incidence of hsp-27 overexpression in DCIS and in DCIS associated with IDC. This rate is twice that previously observed in IDC alone. Hsp-27 expression is independent of HER-2/neu expression.}, }
@article {pmid7954261, year = {1994}, author = {Moriya, T and Silverberg, SG}, title = {Intraductal carcinoma (ductal carcinoma in situ) of the breast. A comparison of pure noninvasive tumors with those including different proportions of infiltrating carcinoma.}, journal = {Cancer}, volume = {74}, number = {11}, pages = {2972-2978}, doi = {10.1002/1097-0142(19941201)74:11&lt;2972::aid-cncr2820741113&gt;3.0.co;2-z}, pmid = {7954261}, issn = {0008-543X}, mesh = {Adult ; Breast Neoplasms/*pathology ; Carcinoma in Situ/*pathology/secondary ; Carcinoma, Ductal, Breast/*pathology/secondary ; Carcinoma, Intraductal, Noninfiltrating/*pathology/secondary ; Cell Nucleus/ultrastructure ; Female ; Humans ; Lymphatic Metastasis/pathology ; Middle Aged ; Mitosis ; Necrosis ; Neoplasm Invasiveness ; }, abstract = {BACKGROUND: Several studies have suggested that ductal carcinoma in situ (DCIS) of the comedo type (variably defined) is biologically more aggressive than other patterns of DCIS and more likely to progress rapidly to invasive carcinoma.<br><br>METHODS: Eighty-five pure DCISs were compared histopathologically with 64 carcinomas containing both intraductal and infiltrating ductal components (mixed DCIS/IDC).<br><br>RESULTS: Solid DCIS with and without necrosis was seen more frequently seen in the mixed DCIS/IDC series, especially in cases with less than 50% DCIS. Periductal stromal inflammation and multifocality also were seen more frequently in mixed DCIS/IDC than in pure DCIS. High nuclear grade and high mitotic activity were also more common in the DCIS component of the mixed cases and were well correlated with the intraductal and infiltrating components of the same tumors in most of the cases. The frequency of axillary lymph node metastases was correlated with the proportions of stromal invasion but not with the DCIS subtypes. When the criteria (solid growth pattern, high nuclear grade, and central necrosis) for the diagnosis of intraductal comedocarcinoma were analyzed separately, the first of these correlated most strongly with mixed DCIS/IDC compared with pure DCIS, the second less strongly, and the third not at all, although central necrosis has been considered the main or only diagnostic criterion for comedocarcinoma in several previous reports.<br><br>CONCLUSIONS: Solid growth pattern and high nuclear grade are the most important histopathologic features of DCIS used to predict progression to invasive carcinoma. No major changes between the intraductal and invasive elements of the same tumors were noted, but other studies have suggested that markers of aggressiveness either increase or decrease in the progression to invasion. These conflicting data require further investigation.}, }
@article {pmid7800489, year = {1994}, author = {Panyutin, IG and Neumann, RD}, title = {Sequence-specific DNA double-strand breaks induced by triplex forming 125I labeled oligonucleotides.}, journal = {Nucleic acids research}, volume = {22}, number = {23}, pages = {4979-4982}, pmid = {7800489}, issn = {0305-1048}, mesh = {Base Sequence ; DNA/*chemistry/radiation effects ; *DNA Damage ; Deoxycytosine Nucleotides/chemistry ; Genes, nef/genetics ; Iodine Radioisotopes/chemistry ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Phosphorus Radioisotopes/chemistry ; }, abstract = {A triplex-forming oligonucleotide (TFO) complementary to the polypurine-polypyrimidine region of the nef gene of the Human Immunodeficiency Virus (HIV) was labeled with 125I at the C5 position of a single deoxycytosine residue. Labeled TFO was incubated with a plasmid containing a fragment of the nef gene. Decay of 125I was found to cause double-strand breaks (DSB) within the nef gene upon triplex formation in a sequence specific manner. No DSB were detected after incubation at ionic conditions preventing triplex formation or when TFO was labeled with 32P instead of 125I. Mapping DSB sites with single base resolution showed that they are distributed within 10 bp of a maximum located exactly opposite the position of the [125I] IdC in the TFO. We estimate that on average the amount of DSB produced per decay is close to one.}, }
@article {pmid7977122, year = {1994}, author = {Bortman, G and Sellanes, M and Odell, DS and Ring, WS and Olivari, MT}, title = {Discrepancy between pre- and post-transplant diagnosis of end-stage dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {74}, number = {9}, pages = {921-924}, doi = {10.1016/0002-9149(94)90587-8}, pmid = {7977122}, issn = {0002-9149}, mesh = {Biopsy ; Cardiomyopathy, Dilated/*diagnosis/pathology/*surgery ; Coronary Angiography ; Coronary Disease/pathology ; Echocardiography ; Endocardium/pathology ; Female ; *Heart Transplantation ; Humans ; Hypertrophy, Left Ventricular/pathology ; Male ; Middle Aged ; Myocarditis/pathology ; Myocardium/pathology ; Retrospective Studies ; }, abstract = {A pretransplant diagnosis was compared with the diagnosis made after macroscopic and microscopic examination of the explanted hearts in 112 cardiac transplant recipients. A coronary angiogram was recorded in 87.5% and endomyocardial biopsy was performed in 12.5% of patients within 1 year of the transplant. Echocardiograms were obtained in all patients. Before transplantation, 57.1% of patients were classified as having ischemic cardiomyopathy and 33.9% were classified as having idiopathic dilated cardiomyopathy (IDC). At explantation, severe coronary artery disease was found in all patients with a pretransplant diagnosis of ischemic cardiomyopathy, in 9 patients with a pretransplant diagnosis of IDC (6 of them had a "normal" pretransplant angiograms), and in 3 of the 4 patients with presumptive alcoholic cardiomyopathy. Left ventricular hypertrophy, undetected on echocardiography, was found at autopsy in 11 patients with presumed IDC, and acute myocarditis was found in 3 patients with a pretransplant diagnosis of IDC. A correct pretransplant diagnosis can lead to different management (e.g., bypass surgery rather than transplant), and may also portend different pre- and post-transplant prognoses. The results of this study suggest that an "in-depth" search for a cause should be conducted in all patients with heart failure, regardless of their clinical presentation. Our study also emphasizes the limitations of coronary angiography and echocardiography in patients with IDC and the need for improving current diagnostic techniques in these patients.}, }
@article {pmid7977121, year = {1994}, author = {Carlquist, JF and Ward, RH and Husebye, D and Feolo, M and Anderson, JL}, title = {Major histocompatibility complex class II gene frequencies by serologic and deoxyribonucleic acid genomic typing in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {74}, number = {9}, pages = {918-920}, doi = {10.1016/0002-9149(94)90586-x}, pmid = {7977121}, issn = {0002-9149}, support = {S07 RR-05804-09/RR/NCRR NIH HHS/United States ; }, mesh = {Alleles ; Cardiomyopathy, Dilated/epidemiology/*genetics ; Gene Frequency ; *Genes, MHC Class II ; Genotype ; HLA-DP Antigens/genetics ; HLA-DQ Antigens/genetics ; HLA-DR Antigens/genetics ; Humans ; Polymerase Chain Reaction ; }, abstract = {Certain immunologic features associated with idiopathic dilated cardiomyopathy (IDC) suggest an infectious and/or autoimmune etiology. In this regard, an association between the major histocompatibility complex class II allele, DR4, and increased risk for IDC was previously identified. In the present report, 43 additional patients with IDC and 236 control subjects were studied for major histocompatibility class II allele associations. DR alleles were identified by microcytotoxicity. No significant differences between control subjects and patients with IDC were seen, although the frequency of DR4 was increased among patients. DR4 subtyping (n = 9) was performed by "dot blot" hybridization of allele-specific oligonucleotide probes to PCR-amplified genomic deoxyribonucleic acid. The DRB1*0401 and DRB1*0404 alleles were each found in 44% (n = 4) of patients with IDC, and DRB1*0407 was identified in 1 patient (11%). DQ and DP alleles were identified by restriction endonuclease codigestion of polymerase chain reaction-amplified deoxyribonucleic acid. The digested fragments were separated and identified by polyacrylamide gel electrophoresis. Differences between patients and control subjects were observed for DQA1*0501 (11% of patients vs 28% of control subjects, p < 0.05) and DQB1*0201 (13% patients vs 25% control subjects, p < 0.05). A modest difference was noted for DQA1*0301 (35% patients vs 23% control subjects, p = 0.08). These findings suggest a complex immune-related etiology for IDC that cannot be explained solely by the presence or absence of a single class II allele. However, this and other studies continue to implicate genes within the class II region in determining the risk for IDC.}, }
@article {pmid7927891, year = {1994}, author = {Kaczmarek, J and Castellani, P and Nicolo, G and Spina, B and Allemanni, G and Zardi, L}, title = {Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues.}, journal = {International journal of cancer}, volume = {59}, number = {1}, pages = {11-16}, doi = {10.1002/ijc.2910590104}, pmid = {7927891}, issn = {0020-7136}, mesh = {Adenocarcinoma, Mucinous/chemistry ; Antibodies, Monoclonal ; Breast/*chemistry/pathology ; Breast Neoplasms/*chemistry ; Carcinoma, Ductal, Breast/chemistry ; Carcinoma, Lobular/chemistry ; Female ; Fibroadenoma/chemistry ; Fibrocystic Breast Disease/metabolism ; Fibronectins/*analysis/genetics ; Glycosylation ; Humans ; Hyperplasia ; Immunohistochemistry ; RNA Splicing ; Tissue Distribution ; }, abstract = {Two different oncofetal fibronectins (FN) have been reported: one, generated by O-glycosylation in the splicing region IIICS that is recognized by monoclonal antibody (MAb) FDC-6, and another, recognized by MAb BC-I, generated by the alternative splicing of the FN pre-mRNA which includes an extra type-III repeat called ED-B. Using these and 2 other MAbs (IST-4 which recognizes all different FN isoforms and IST-6 which recognizes only the FN molecules that do not include the ED-B sequence) we have immunohistochemically studied 171 normal, hyperplastic and neoplastic breast-tissue specimens. Although all normal specimens reacted strongly with MAbs IST-4 and IST-6, they did not show the presence of oncofetal FNs as established by the use of BC-I and FDC-6. In contrast, out of the 97 cases of invasive ductal carcinomas studied, 90 (93%) and 96 (99%) reacted positively with BC-I and FDC-6, respectively, the reaction being observed in the tumoral stroma connective tissue and in tumoral vessels. Furthermore, invasive lobular carcinoma showed less intense and less frequent staining with BC-1 and FDC-6 (10 and 11 out of 14, respectively). We found differences in the distribution of the 2 oncofetal fibronectin isoforms within the same specimens. The most remarkable difference was observed in the tumoral vessels: in invasive ductal carcinoma MAb BC-1 revealed a positive reaction with vessels in 78% of cases while FDC-6 showed such a reaction in only 59% of cases.}, }
@article {pmid7837253, year = {1994}, author = {Krajinovic, M and Mestroni, L and Severini, GM and Pinamonti, B and Camerini, F and Falaschi, A and Giacca, M}, title = {Absence of linkage between idiopathic dilated cardiomyopathy and candidate genes involved in the immune function in a large Italian pedigree.}, journal = {Journal of medical genetics}, volume = {31}, number = {10}, pages = {766-771}, pmid = {7837253}, issn = {0022-2593}, mesh = {Adult ; Antigens, CD/*genetics ; Autoantigens/genetics ; Cardiomyopathy, Dilated/*genetics/*immunology ; Chromosome Mapping ; Complement System Proteins/genetics ; Female ; Genes, Dominant ; *Genes, Immunoglobulin ; Genetic Linkage ; Genetic Markers ; Humans ; Interleukins/genetics ; Italy ; *Major Histocompatibility Complex ; Male ; Pedigree ; Receptors, Antigen, T-Cell/genetics ; Receptors, Fc/genetics ; Receptors, Immunologic/*genetics ; Receptors, Interleukin/genetics ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is a heart disease of unknown aetiology characterised by impaired ventricular function usually associated with dilatation of the cardiac chambers. In order to test the hypothesis of an immunological cause for the disease at the genetic level, we performed linkage analysis between the putative disease locus and some of the potential candidate genes involved in the immune response or coding for the targets for autoantibodies in a large multigeneration family (63 members) from southern Italy with autosomal dominant transmission of the disease. Twenty-nine polymorphic markers on 18 different chromosomal locations were investigated, including markers linked to the genes coding for the HLA antigens, the immunoglobulin heavy and light chains, the receptors for the immunoglobulin Fc fragments, the subunits of the T cell receptor and the associated CD3, CD4, CD8, and CD45 antigens, interleukins 1, 3, 4, 5, 6, 9, and 11, the interleukin 1 and 2 receptors, and the genes coding for the beta 1 adrenoreceptor, the adenine nucleotide translocator-1, and the cardiac alpha and beta myosin heavy chains. No evidence for genetic linkage to IDC was found at any of these candidate loci. These results indicate that the still unidentified IDC gene maps outside several loci involved in the regulation of immune reactivity.}, }
@article {pmid8082076, year = {1994}, author = {Mourad, WA and Setrakian, S and Hales, ML and Abdulla, M and Trucco, G}, title = {The argyrophilic nucleolar organizer regions in ductal carcinoma in situ of the breast. The significance of ploidy and proliferative activity analysis using this silver staining technique.}, journal = {Cancer}, volume = {74}, number = {6}, pages = {1739-1745}, doi = {10.1002/1097-0142(19940915)74:6&lt;1739::aid-cncr2820740616&gt;3.0.co;2-t}, pmid = {8082076}, issn = {0008-543X}, mesh = {Breast Neoplasms/*genetics/ultrastructure ; Carcinoma in Situ/*genetics/ultrastructure ; Carcinoma, Ductal, Breast/*genetics/ultrastructure ; Female ; Humans ; Nucleolus Organizer Region/*pathology ; Ploidies ; }, abstract = {BACKGROUND: Two interphase argyrophilic nucleolar organizer region (AgNOR) counts have been correlated with ploidy and proliferative activity in patients with ductal carcinoma in situ (DCIS) of the breast. The first is the mean number of AgNORs (mAgNOR); it reflects ploidy. The second is the percentage of nuclei with greater than or equal to five AgNORs/nucleus (pAgNOR); it correlates with proliferative activity. DCIS of the breast is a heterogeneous group of lesions that is not associated uniformly with invasive ductal carcinoma. A significant number of patients with DCIS will, however, progress to invasive ductal carcinoma. Factors identifying the invasive potential of DCIS in these patients have not been defined clearly. The authors postulated that pAgNOR in DCIS may predict the invasive potential of these lesions.<br><br>METHODS: The authors studied 86 cases of DCIS of the breast by the AgNOR silver stain using the two above-mentioned counts.<br><br>RESULTS: There were 54 comedo and 32 noncomedo DCIS cases. Forty-one cases (47%) were associated with invasive ductal carcinoma. Thirty cases of comedo DCIS (55%) showed mAgNOR counts suggestive of aneuploidy (> or = 2.4/nucleus), whereas only seven cases of noncomedo DCIS (22%) showed such counts (P = 0.001). Cases associated with invasion had higher incidence of aneuploid mAgNOR counts (P = 0.0003). The pAgNOR counts in comedo DCIS ranged from 1% to 36% (median, 11%), whereas in noncomedo DCIS pAgNOR counts ranged from 0% to 22% (median, 7%) (P = 0.007). The 41 cases associated with invasion had pAgNOR counts ranging from 3% to 36% (median, 12%), whereas those not associated with invasion had pAgNOR counts ranging from 0% to 24% (median, 5%) (P = 0.000001). This difference was irrespective of the type of DCIS or mAgNOR counts.<br><br>CONCLUSIONS: Comedo DCIS of the breast may show a higher incidence of aneuploidy and increased proliferative activity and invasive ductal carcinoma than does noncomedo DCIS. Ploidy and proliferative activity, measured by AgNOR staining in DCIS, may have a significant predictive value in identifying the invasive potential of these lesions.}, }
@article {pmid8059728, year = {1994}, author = {Rizeq, MN and Rickenbacher, PR and Fowler, MB and Billingham, ME}, title = {Incidence of myocarditis in peripartum cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {74}, number = {5}, pages = {474-477}, doi = {10.1016/0002-9149(94)90906-7}, pmid = {8059728}, issn = {0002-9149}, mesh = {Adult ; Biopsy ; Cardiomyopathy, Dilated/*complications/pathology ; Female ; Humans ; Incidence ; Middle Aged ; Myocarditis/epidemiology/*etiology/pathology ; Pregnancy ; *Pregnancy Complications, Cardiovascular/pathology ; Puerperal Disorders/*complications/pathology ; Retrospective Studies ; }, abstract = {Peripartum cardiomyopathy (PC), an uncommon cause of peripartum heart failure, is defined as a cardiomyopathy presenting in the last trimester of pregnancy or the first 6 months postpartum, without evidence of preexisting cardiovascular disease. The etiology of PC and idiopathic dilated cardiomyopathy (IDC) remains uncertain. Several reports have addressed possible differences in clinical presentation and prognosis between these groups. A relatively high incidence of myocarditis has been recently reported in patients with PC, raising the possibility that this may represent a distinct difference between this condition and IDC. A retrospective review of endomyocardial biopsy specimens from 34 patients fulfilling the criteria for a diagnosis of PC was therefore performed to further evaluate this finding. Results indicate a lower incidence of myocarditis (8.8%, 3 of 34) than that reported in other studies. This incidence was comparable to that found in an age- and sex-matched control population undergoing transplantation for IDC (9.1%, 2 of 22). Factors that may influence the diverse range in the reported incidence of myocarditis are discussed.}, }
@article {pmid8083125, year = {1994}, author = {Solin, LJ and Fourquet, A and McCormick, B and Haffty, B and Recht, A and Schultz, DJ and Barrett, W and Fowble, BL and Kuske, R and Taylor, M}, title = {Salvage treatment for local recurrence following breast-conserving surgery and definitive irradiation for ductal carcinoma in situ (intraductal carcinoma) of the breast.}, journal = {International journal of radiation oncology, biology, physics}, volume = {30}, number = {1}, pages = {3-9}, doi = {10.1016/0360-3016(94)90512-6}, pmid = {8083125}, issn = {0360-3016}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*radiotherapy/*surgery ; Carcinoma in Situ/drug therapy/*radiotherapy/*surgery ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/*radiotherapy/*surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Humans ; Lymph Nodes/surgery ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/*surgery ; Ovariectomy ; Prognosis ; Salvage Therapy ; Tamoxifen/therapeutic use ; }, abstract = {PURPOSE: The purpose of the present study is to evaluate the outcome of salvage treatment for local recurrence in the breast following the initial treatment of ductal carcinoma in situ (intraductal carcinoma) with breast-conserving surgery and definitive breast irradiation.<br><br>METHODS AND MATERIALS: An analysis was performed of 42 local failures in the breast that occurred following the initial treatment of ductal carcinoma in situ (intraductal carcinoma) with breast-conserving surgery and definitive breast irradiation. At the time of the local recurrence, 23 cases (55%) showed invasive ductal carcinoma, and 19 cases (45%) showed intraductal carcinoma, one with associated Paget's disease. The surgical treatment at the time of local recurrence included mastectomy (n = 39), excision (n = 2), or other (n = 1). Adjuvant systemic therapy at the time of local recurrence included chemotherapy (n = 2), hormonal treatment (n = 7), both (n = 1), or none (n = 32). The median follow-up after salvage treatment was 3.7 years (mean = 4.0 years; range = 0.1-9.5 years).<br><br>RESULTS: The 5-year actuarial outcome following salvage treatment for the 42 local recurrences showed an overall survival rate of 78% and a cause-specific survival rate of 84%. The 5-year actuarial rate of freedom from distant metastases was 86%. None of the patients with histology of the local recurrence of intraductal carcinoma or with detection of the local recurrence with mammographic findings only developed distant metastatic disease after salvage treatment. The 5-year actuarial rate of freedom from chest wall recurrence following salvage mastectomy was 92%. All three of the patients who developed chest wall recurrence following salvage mastectomy also developed distant metastatic disease.<br><br>CONCLUSIONS: These results demonstrate that local recurrences following the initial treatment of ductal carcinoma in situ with breast-conserving surgery and definitive breast irradiation can be salvaged with high rates of survival, freedom from distant metastases, and freedom from chest wall recurrence. The results of salvage treatment support the use of breast-conserving surgery and definitive breast irradiation for the initial management of ductal carcinoma in situ of the breast.}, }
@article {pmid8181129, year = {1994}, author = {Obrador, D and Ballester, M and Carrió, I and Moya, C and Bosch, I and Martí, V and Bernà, L and Estorch, M and Udina, C and Marrugat, J}, title = {Presence, evolving changes, and prognostic implications of myocardial damage detected in idiopathic and alcoholic dilated cardiomyopathy by 111In monoclonal antimyosin antibodies.}, journal = {Circulation}, volume = {89}, number = {5}, pages = {2054-2061}, doi = {10.1161/01.cir.89.5.2054}, pmid = {8181129}, issn = {0009-7322}, mesh = {Adult ; *Antibodies, Monoclonal ; Cardiomyopathy, Alcoholic/*diagnostic imaging/epidemiology ; Cardiomyopathy, Dilated/*diagnostic imaging/epidemiology ; Female ; Follow-Up Studies ; Heart Transplantation ; Humans ; *Indium Radioisotopes ; Logistic Models ; Male ; *Organometallic Compounds ; Prognosis ; *Radioimmunodetection ; Risk Factors ; }, abstract = {BACKGROUND: The clinical relevance of myocardial cell damage in dilated cardiomyopathy is uncertain. Myocardial uptake of 111In monoclonal antimyosin antibodies (MAA) was used to study myocardial damage in patients with idiopathic (IDC) and alcoholic (ADC) dilated cardiomyopathy and to assess its prognostic implications.<br><br>METHODS AND RESULTS: MAA and echocardiographic studies were performed in 117 patients. Intensity of antibody uptake was measured by heart-to-lung ratio (HLR) (normal < 1.55). Studies were repeated in survivors and patients who did not receive a cardiac transplant. Follow-up extended up to 62 months (mean, 23 +/- 16 months). Eighty-eight patients with IDC showed a 77% prevalence of abnormal MAA. After acute-onset IDC, reduction of HLR (1.81 +/- 0.2 to 1.56 +/- 0.1) (P = .007) with improvement in ejection fraction (EF) (35 +/- 10% to 46 +/- 14%) (P = .018) was observed. No changes in HLR or EF were detected in patients with chronic stable IDC. Twenty-nine patients with ADC showed a lower prevalence (48%) of abnormal MAA studies than those with IDC (P = .003). HLR was higher in 13 active (1.78 +/- 0.3) than in 16 past consumers (1.49 +/- 0.2) (P = .019); in the former, HLR decreased to 1.44 +/- 0.2 (P = .012), and EF improved (35 +/- 14% to 53 +/- 18%) (P = .05) after abstention. Intensities of uptake HLR of > 1.87 were associated with increased risk of death or transplantation.<br><br>CONCLUSIONS: In patients with IDC, variations of MAA uptake are detected in patients who present acutely but not in those with chronic stable disease. In patients with ADC, MAA uptake mainly depends on alcohol consumption. In both situations, reduction of uptake correlates with improvement of ventricular function. Higher intensities of MAA uptake are associated with a worse outcome. The intensity of antibody uptake, along with other clinical and functional variables, may be helpful in risk stratification of patients with dilated cardiomyopathy.}, }
@article {pmid8180021, year = {1994}, author = {Qi, CF and Liscia, DS and Normanno, N and Merlo, G and Johnson, GR and Gullick, WJ and Ciardiello, F and Saeki, T and Brandt, R and Kim, N}, title = {Expression of transforming growth factor alpha, amphiregulin and cripto-1 in human breast carcinomas.}, journal = {British journal of cancer}, volume = {69}, number = {5}, pages = {903-910}, pmid = {8180021}, issn = {0007-0920}, mesh = {Amphiregulin ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry ; EGF Family of Proteins ; *Epidermal Growth Factor ; Female ; GPI-Linked Proteins ; Genes, p53/genetics ; Glycoproteins/*analysis ; Growth Substances/*analysis ; Humans ; *Intercellular Signaling Peptides and Proteins ; *Membrane Glycoproteins ; Neoplasm Proteins/*analysis ; Point Mutation/genetics ; RNA, Messenger/analysis ; RNA, Neoplasm/analysis ; Transforming Growth Factor alpha/*analysis ; }, abstract = {The expression of three epidermal growth factor (EGF)-related peptides, transforming growth factor alpha (TGF-alpha), amphiregulin (AR) and cripto-1 (CR-1), was examined by immunocytochemistry (ICC) in 68 primary infiltrating ductal (IDCs) and infiltrating lobular breast carcinomas (ILCs), and in 23 adjacent non-involved human mammary tissue samples. Within the 68 IDC and ILC specimens, 54 (79%) expressed immunoreactive TGF-alpha, 52 (77%) expressed AR and 56 (82%) expressed CR-1. Cytoplasmic staining was observed with all of the antibodies, and this staining could be eliminated by preabsorption of the antibodies with the appropriate peptide immunogen. Cytoplasmic staining with all of the antibodies was confined to the carcinoma cells, since no specific immunoreactivity could be detected in the surrounding stromal or endothelial cells. In addition to cytoplasmic reactivity, the AR antibody also exhibited nuclear staining in a number of the carcinoma specimens. No significant correlations were found between the percentage of carcinoma cells that were positive for TGF-alpha, AR or CR-1 and oestrogen receptor status, axillary lymph node involvement, histological grade, tumour size, proliferative index, loss of heterozygosity on chromosome 17p or overall patient survival. However, a highly significant inverse correlation was observed between the average percentage of carcinoma cells that expressed AR in individual tumours and the presence of a point-mutated p53 gene. Likewise, a significantly higher percentage of tumour cells in the ILC group expressed AR as compared with the average percentage of tumour cells that expressed AR in the IDC group. Of the 23 adjacent, non-involved breast tissue samples, CR-1 could be detected by ICC in only three (13%), while TGF-alpha was found in six (26%) and AR in ten (43%) of the non-involved breast tissues. These data demonstrate that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epithelial cells may serve as a potential tumour marker for breast cancer.}, }
@article {pmid8176940, year = {1994}, author = {Sasa, M and Kondo, K and Komaki, K and Morimoto, T and Monden, Y}, title = {p53 alteration correlates with negative ER, negative PgR, and high histologic grade in breast cancer.}, journal = {Journal of surgical oncology}, volume = {56}, number = {1}, pages = {46-50}, doi = {10.1002/jso.2930560110}, pmid = {8176940}, issn = {0022-4790}, mesh = {Adult ; Aged ; Base Sequence ; Breast Neoplasms/*genetics/metabolism/*pathology ; Female ; Genes, p53/*genetics ; Humans ; Middle Aged ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction/methods ; Polymorphism, Genetic ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; }, abstract = {Seventy tumors of invasive ductal carcinoma of the breast were examined for p53 alteration by the RT-PCR-SSCP method. Sixty-five samples (92.9%) were investigated in the regions of codons 101-200 and 201-300. In total, 16 samples (24.6%) showed p53 gene alteration. We found that p53 gene alteration showed a correlation with (1) a negative ER status, (2) a negative PgR status, and (3) a high histologic grade (especially numerous mitotic figures) of the tumor. However, we found no correlation between p53 gene alteration and the lymph node status or clinical stage. Thus, p53 gene alteration in breast cancer may occur in highly malignant breast cancer other than advanced clinical stage cancer or node-positive cancer.}, }
@article {pmid7913915, year = {1994}, author = {Vicente, A and Varas, A and Alonso, L and Gómez de Moral, M and Zapata, AG}, title = {Ontogeny of rat thymic dendritic cells.}, journal = {Immunology}, volume = {82}, number = {1}, pages = {75-81}, pmid = {7913915}, issn = {0019-2805}, mesh = {Animals ; Antigens, CD/analysis ; Antigens, Differentiation, T-Lymphocyte/analysis ; CD2 Antigens ; Cells, Cultured ; Dendritic Cells/*cytology/immunology ; Histocompatibility Antigens Class II/analysis ; Immunophenotyping ; Rats ; Rats, Wistar/*anatomy &amp; histology/embryology ; Receptors, Immunologic/analysis ; Thymus Gland/*cytology/embryology/immunology ; }, abstract = {In the present study we have combined various in vivo and in vitro approaches to analyse the appearance and development throughout ontogeny and postnatal life of the dendritic cell (DC) populations of rat thymus. The in situ ultrastructural study demonstrated immature interdigitating cells (IDC)/DC in the thymus of 17-day-old embryonic rats, but thymic stromal cell cultures from 16-day-old fetal rats seemed to contain DC precursors which, after several days in culture, produced strongly class II major histocompatibility complex (MHC)-positive, mature DC. According to morphology and class II MHC expression we also defined three different DC populations in the late embryonic rat thymus; two of them, which remained in the adult rat thymus, could represent distinct developmental stages within the IDC/DC lineage. The third cell subset might be involved in a massive process of negative selection, presumably occurring at the end of fetal life in the rat thymus. In supporting the existence of thymic DC subpopulations, we also demonstrated a differential expression of various cell markers, including CD4, CD8, CD25, adhesion molecules and the antigen recognized by OX44 monoclonal antibody (mAb), on thymic DC during both embryonic and adult life. Their possible significance for the attributed functions to thymic DC are discussed extensively.}, }
@article {pmid7800951, year = {1994}, author = {Müller, JG and Czub, S and Marx, A and Brinkmann, R and Plesker, R and Müller-Hermelink, HK}, title = {Detection of SIV in rhesus monkey thymus stroma cell cultures.}, journal = {Research in virology}, volume = {145}, number = {3-4}, pages = {239-244}, doi = {10.1016/s0923-2516(07)80028-8}, pmid = {7800951}, issn = {0923-2516}, mesh = {Animals ; Atrophy ; Cell Death ; Cell Line ; Cells, Cultured ; Macaca mulatta ; Proviruses/isolation &amp; purification ; Simian Acquired Immunodeficiency Syndrome/etiology/pathology/*virology ; Simian Immunodeficiency Virus/*isolation &amp; purification/pathogenicity ; T-Lymphocytes/pathology/virology ; Thymus Gland/pathology/*virology ; }, abstract = {To clarify the pathogenesis of SIV-induced thymus atrophy, the presence of SIV within thymus stromal cell cultures (epithelial cells, IDC, macrophages or fibroblasts) was investigated. The material studied consisted of 15 thymus specimens of rhesus macaques infected with SIVmac251 (2-4 months postinoculation). No viral antigen was detected, either in the cultures, by immunohistochemistry, or in cell culture supernatants, by ELISA (p17 antigen), and no viral RNA was detected by in situ hybridization. Only after coculture with the C8166 cell line, was virus detected in 2 out of 15 stroma cultures. The fact that the virus could only be detected after several passages of coculture with the C8166 cell line indicates that the virus exists in the thymus stroma cells in the form of proviral DNA. The infection of thymus stromal cells may contribute to the destruction of the thymus microenvironment and to the SIV-induced thymus atrophy.}, }
@article {pmid8194838, year = {1994}, author = {Mestroni, L and Krajinovic, M and Severini, GM and Falaschi, A and Giacca, M and Camerini, F}, title = {Molecular genetics of dilated cardiomyopathy.}, journal = {Herz}, volume = {19}, number = {2}, pages = {97-104}, pmid = {8194838}, issn = {0340-9937}, mesh = {Cardiomyopathy, Dilated/diagnosis/*genetics ; Chromosome Aberrations/genetics ; Chromosome Disorders ; Enterovirus/genetics ; Enterovirus Infections/genetics ; Gene Expression Regulation, Viral/physiology ; Genes, Dominant/genetics ; Genetic Linkage/genetics ; Humans ; *Molecular Biology ; Pedigree ; Polymerase Chain Reaction ; Sex Chromosome Aberrations/genetics ; X Chromosome ; }, abstract = {The recent advances in molecular biology and genetic engineering are producing relevant results in cardiology, in particular in the field of cardiomyopathies. Molecular genetics has been used for the detection of viral genomes persisting in myocardial tissue of patients with idiopathic dilated cardiomyopathy (IDC). Very recent data, based on highly sensitive and specific technologies, suggest, however, that enterovirus persistence is not a major cause of the disease. Another application of molecular genetics is the study of the familial form of IDC, using linkage analysis as a tool for the identification of the disease gene. According to this method, the X-linked form of familial IDC has been mapped within the dystrophin gene in a series of families, and preliminary reports suggest that the mutation (or mutations) concerns the muscle-promoter region. Linkage studies on the autosomal dominant form of IDC are in progress. A possible approach is the identification of linkage between the disease and an array of "candidate genes". Preliminary data have ruled out the involvement of a series of relevant candidates genes, among which the cardiac beta-myosin heavy chain gene. An alternative approach for linkage studies is to perform a random screening of the genome, in which a large number of anonymous markers are selected and tested. In conclusion, molecular genetics is starting to provide fundamental data about the pathogenetic mechanisms of IDC. The relevance of these findings is also crucial for clinical and therapeutic implications.}, }
@article {pmid7908995, year = {1994}, author = {Horiguchi, J and Iino, Y and Takei, H and Morishita, Y and Nakajima, T}, title = {Expression of proliferating cell nuclear antigen in invasive ductal carcinoma of the breast.}, journal = {Japanese journal of clinical oncology}, volume = {24}, number = {2}, pages = {79-84}, pmid = {7908995}, issn = {0368-2811}, mesh = {Adenocarcinoma/genetics/pathology/secondary ; Adenocarcinoma, Scirrhous/genetics/pathology/secondary ; Adult ; Age Factors ; Antigens, Neoplasm/*analysis/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology/secondary ; Carcinoma, Papillary/genetics/pathology/secondary ; Cell Nucleus/ultrastructure ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Nuclear Proteins/*analysis/genetics ; Prognosis ; Proliferating Cell Nuclear Antigen ; Receptors, Estrogen/analysis ; Survival Rate ; }, abstract = {Formalin-fixed, paraffin-embedded sections from 92 breast cancers (invasive ductal carcinomas) were immunostained with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The labeling index of PCNA ranged widely from 2 to 76 (mean 24.8)%. The labeling index was classified into three groups: low (< 25%), intermediate (25-50%), high proliferation (> 50%). Younger patients seemed to have a higher labeling index than older ones. The labeling index for tumors < or = 2 cm was lower than that of tumors larger than 2 cm. The labeling index in patients with high estrogen receptor (ER) levels (> 100 fmol/mg cytosol protein) was significantly lower than that in patients with low ER levels (< 10 fmol/mg cytosol protein). In relation to histological type, the labeling index of scirrhous carcinoma was significantly lower than that of papillotubular carcinoma or solid-tubular carcinoma. The high proliferating group had a significantly worse overall survival rate than the low proliferating group. Labeling index was shown to be a possible prognostic indicator.}, }
@article {pmid7908610, year = {1994}, author = {Bristow, MR and O'Connell, JB and Gilbert, EM and French, WJ and Leatherman, G and Kantrowitz, NE and Orie, J and Smucker, ML and Marshall, G and Kelly, P}, title = {Dose-response of chronic beta-blocker treatment in heart failure from either idiopathic dilated or ischemic cardiomyopathy. Bucindolol Investigators.}, journal = {Circulation}, volume = {89}, number = {4}, pages = {1632-1642}, doi = {10.1161/01.cir.89.4.1632}, pmid = {7908610}, issn = {0009-7322}, mesh = {Adrenergic beta-Antagonists/*administration &amp; dosage/therapeutic use ; Cardiomyopathy, Dilated/*complications ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Heart Failure/*drug therapy/epidemiology/etiology ; Humans ; Male ; Middle Aged ; Propanolamines/*administration &amp; dosage/therapeutic use ; Prospective Studies ; Ventricular Function, Left/drug effects ; }, abstract = {BACKGROUND: Small-scale clinical investigations have demonstrated that single doses of beta-blocking agents can improve left ventricular function in heart failure from idiopathic dilated cardiomyopathy (IDC). The purpose of this multicenter clinical trial was to determine the dose-effect characteristics of beta-blockade in a heart failure population that includes ischemic dilated cardiomyopathy (ISCD).<br><br>METHODS AND RESULTS: Bucindolol is a nonselective beta-blocking agent with mild vasodilatory properties. One hundred forty-one subjects with class II or III heart failure, left ventricular ejection fraction (LVEF) < or = 0.40, and background therapy of angiotensin-converting enzyme inhibitors, digoxin, and diuretics were given an initial challenge dose of bucindolol 12.5 mg. One hundred thirty-nine subjects (99 with IDC, 40 with ISCDC) tolerated challenge and were randomized to treatment with placebo or bucindolol 12.5 mg/d (low dose), 50 mg/d (medium dose), or 200 mg/d (high dose). At the end of 12 weeks, left ventricular function and other parameters were measured and compared with baseline values. There was a dose-related improvement in left ventricular function in bucindolol-treated subjects. In the high-dose bucindolol group, radionuclide-measured LVEF improved by 7.8 EF units (%) compared with 1.8 units in the placebo group (P < .05), and compared with the placebo group, a greater percentage of subjects had an increase in LVEF by > or = 5 units. In contrast, all three bucindolol doses prevented deterioration of myocardial function as defined by an LVEF decline of > or = 5 units.<br><br>CONCLUSIONS: In heart failure from systolic dysfunction, beta-blockade with bucindolol produces a dose-related improvement in and prevents deterioration of left ventricular function.}, }
@article {pmid8147306, year = {1994}, author = {Juillière, Y and Buffet, P and Marie, PY and Berder, V and Danchin, N and Cherrier, F}, title = {Comparison of right ventricular systolic function in idiopathic dilated cardiomyopathy and healed anterior wall myocardial infarction associated with atherosclerotic coronary artery disease.}, journal = {The American journal of cardiology}, volume = {73}, number = {8}, pages = {588-590}, doi = {10.1016/0002-9149(94)90339-5}, pmid = {8147306}, issn = {0002-9149}, mesh = {Cardiomyopathy, Dilated/epidemiology/*physiopathology ; Case-Control Studies ; Coronary Artery Disease/complications/epidemiology/*physiopathology ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction/complications/epidemiology/*physiopathology ; Prospective Studies ; Pulmonary Wedge Pressure/physiology ; Stroke Volume/physiology ; Systole/*physiology ; Thermodilution ; Ventricular Function, Right/*physiology ; }, abstract = {A case-controlled study assessed right ventricular (RV) systolic function in 10 patients with idiopathic dilated cardiomyopathy (IDC) and in 10 with healed anterior wall myocardial infarction associated with atherosclerotic coronary artery disease (CAD). Each patient was matched for sex, left ventricular ejection fraction +/- 5% and pulmonary artery mean pressure +/- 5 mm Hg. All patients had sinus rhythm and a left ventricular ejection fraction < 45%. A new, well-validated thermodilution technique was used to assess RV ejection fraction and volumes. RV ejection fraction was lower in the IDC than in the CAD group (25 +/- 14% vs 36 +/- 11%; p < 0.02). Linear correlations between RV parameters and pulmonary artery pressure were significantly present in both groups. However, the slopes of the equations were not statistically different. In comparison with healed anterior wall myocardial infarction with CAD and for similar levels of left ventricular dysfunction, RV systolic function appeared to be more altered in IDC.}, }
@article {pmid8120761, year = {1994}, author = {Rogers, DA and Lobe, TE and Rao, BN and Fleming, ID and Schropp, KP and Pratt, AS and Pappo, AS}, title = {Breast malignancy in children.}, journal = {Journal of pediatric surgery}, volume = {29}, number = {1}, pages = {48-51}, doi = {10.1016/0022-3468(94)90521-5}, pmid = {8120761}, issn = {0022-3468}, mesh = {Adolescent ; Adult ; Breast Neoplasms/mortality/*pathology/secondary/therapy ; Carcinoma, Ductal, Breast/pathology ; Child ; Female ; Humans ; Lymphoma, Follicular/pathology ; Male ; Neoplasms, Second Primary/pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Rhabdomyosarcoma/pathology/secondary ; }, abstract = {In 25 years, 18 patients with breast cancer were treated at St Jude Children's Research Hospital, 16 were female and 2 were male. The patients presented with primary malignancy (2), metastatic disease (13), or secondary malignancy (3). One of the females with primary breast malignancy had alveolar rhabdomyosarcoma. She was treated with wide excision and is currently receiving chemotherapy. The other patient presented with non-Hodgkin's lymphoma of the right breast. After biopsy, she was treated with chemotherapy. Of 13 patients with metastatic disease, the primary lesion was rhabdomyosarcoma in nine. One patient each had non-Hodgkin's lymphoma, Hodgkin's lymphoma, neuroblastoma, and signet-cell adenocarcinoma. All patients with metastatic disease to the breast died of the disease. Three females presented with invasive ductal carcinoma of the breast after treatment for Hodgkin's disease. Two underwent mastectomy and are alive without evidence of disease. One patient refused therapy and died of the second malignancy. We conclude that (1) breast malignancies had three distinctly different presentations in our patients, (2) the breasts of pediatric oncology patients should be carefully and routinely examined for metastatic disease, and (3) metastatic disease in the breast of a child is a manifestation of disseminated disease and is associated with an extremely poor prognosis.}, }
@article {pmid7981441, year = {1994}, author = {Bier, B and Douglas-Jones, A and Tötsch, M and Dockhorn-Dworniczak, B and Böcker, W and Jasani, B and Schmid, KW}, title = {Immunohistochemical demonstration of metallothionein in normal human breast tissue and benign and malignant breast lesions.}, journal = {Breast cancer research and treatment}, volume = {30}, number = {3}, pages = {213-221}, pmid = {7981441}, issn = {0167-6806}, mesh = {Breast/*cytology/pathology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoid Tumor/pathology ; Carcinoma/*pathology ; Carcinoma, Ductal, Breast/pathology ; Epithelial Cells ; Epithelium/pathology ; Female ; Fibrocystic Breast Disease/*pathology ; Humans ; Immunohistochemistry ; Metallothionein/*analysis ; Papilloma, Intraductal/pathology ; Reference Values ; Risk Factors ; }, abstract = {Metallothioneins (MTs) are a set of low molecular weight proteins with a high binding affinity to metal ions. MT over-expression has been recently demonstrated in invasive ductal carcinoma of the breast with poor clinical prognosis. In the present study, MTs have been immunohistochemically investigated in normal human breast tissue and a variety of benign, pre-invasive, and malignant breast lesions. In normal breast tissue, MTs were present in myoepithelial cells whereas the vast majority of luminal cells were MT negative. In lesions without increased cancer risk (adenosis and scleradenosis), MT was only immunolocalized in myoepithelial cells. In papillomas, MT was also found exclusively in myoepithelial cells. In most cases of epitheliosis, both the luminal and myoepithelial cells expressed MT. Atypical lobular hyperplasia, lobular carcinoma in situ, and 13/15 invasive lobular carcinomas showed no MT over-expression. The two invasive lobular carcinomas with MT over-expression were classified as pleomorphic lobular carcinomas with apocrine differentiation. In contrast to lobular cancerization, 12/24 ductal in situ carcinomas and 9/20 invasive ductal carcinomas showed MT over-expression. In situ components found within invasive ductal carcinomas usually reflected the MT status of their invasive counterpart. It is concluded from our immunohistochemical results that breast carcinoma cases with MT overexpression arise from lesions which also show MT overexpression. Thus MT expression in carcinomas may be regarded as a genuine feature of the tumour cells and seems not to be related to endogenous or exogenous factors known to induce MT synthesis.}, }
@article {pmid7913368, year = {1994}, author = {Umekita, Y and Takasaki, T and Yoshida, H}, title = {Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, non-invasive and invasive mammary carcinoma: an immunohistochemical study.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {424}, number = {5}, pages = {491-494}, pmid = {7913368}, issn = {0945-6317}, mesh = {Breast/*pathology ; Breast Neoplasms/chemistry/*genetics/pathology ; Carcinoma, Ductal, Breast/chemistry/*genetics/pathology ; ErbB Receptors/analysis/genetics ; Female ; *Gene Expression ; Humans ; Hyperplasia ; Immunohistochemistry ; Proto-Oncogene Proteins/analysis/genetics ; Receptor, ErbB-2 ; Tumor Suppressor Protein p53/analysis/*genetics ; }, abstract = {To clarify whether p53 protein expression is involved in multistep carcinogenesis or the progression of mammary ductal carcinoma, we investigated p53 protein expression in 83 invasive ductal carcinomas (IDC), 10 IDC with a predominant intraductal component, 13 non-invasive ductal carcinoma (NIDC), 16 atypical ductal hyperplasia (ADH) and 39 benign epithelial hyperplasia (EH), using immunohistochemistry. Expression of p53 protein was detected in 24 (28.9%) cases of IDC, 5 (50%) cases of IDC with a predominant intraductal component and 1 (7.6%) case of NIDC. No expression was observed in either ADH or EH. In IDC, including cases with a predominant intraductal component, p53 protein expression was associated with a higher histological grade (P < 0.0001) or mitotic index (P < 0.0005). Although overexpression of c-erbB-2 protein has also shown a similar association with these prognostic indicators, expression of p53 protein correlated regardless of the status of c-erbB-2 overexpression. Completely coordinated expression of p53 protein was seen in both intraductal and invasive components. The intraductal component in IDC including cases with a predominant intraductal component which expresses p53 protein had significantly higher histological grade (P < 0.0005) or more comedo-subtypes (P < 0.0001). These results suggested that p53 protein expression occurs at a stage of NIDC with high histological grade or in comedo-subtypes. Its expression is maintained throughout invasion.}, }
@article {pmid7904475, year = {1994}, author = {Bellamy, CO and Harrison, DJ}, title = {Evaluation of glutathione S-transferase Pi in non-invasive ductal carcinoma of breast.}, journal = {British journal of cancer}, volume = {69}, number = {1}, pages = {183-185}, pmid = {7904475}, issn = {0007-0920}, mesh = {Adult ; Aged ; Breast Neoplasms/*enzymology/pathology ; Carcinoma in Situ/*enzymology/pathology/secondary ; Carcinoma, Ductal, Breast/*enzymology/pathology/secondary ; ErbB Receptors/analysis/genetics ; Evaluation Studies as Topic ; Female ; Follow-Up Studies ; Gene Expression/genetics ; Glutathione Transferase/*analysis ; Humans ; Immunohistochemistry ; Isoenzymes/*analysis ; Middle Aged ; Proto-Oncogene Proteins/analysis/genetics ; Receptor, ErbB-2 ; }, abstract = {Glutathione S-transferase Pi (GST P) has been reported to be a marker of dysplastic lesions. For this reason expression of GST P by intraduct breast carcinoma was evaluated by immunohistochemistry. Thirty-seven of 92 carcinomas (40%) were GST P positive. GST P staining did not correlate with histological variables, c-erbB-2 overexpression or with clinical outcome. The GST P status of recurrences did not correlate with that of the index lesion. There is little evidence that GST P is a useful marker of the potential of intraduct breast carcinoma to become invasive.}, }
@article {pmid7870220, year = {1994}, author = {Engin, K}, title = {Prognostic factors in bilateral breast cancer.}, journal = {Neoplasma}, volume = {41}, number = {6}, pages = {353-357}, pmid = {7870220}, issn = {0028-2685}, mesh = {Actuarial Analysis ; Adult ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplasms, Multiple Primary/*pathology ; Prognosis ; Risk Factors ; Survival Analysis ; }, abstract = {Twenty-nine bilateral breast carcinoma patients were analyzed retrospectively. The incidence of bilateral carcinoma of the breast among unilateral breast cancer patients was approximately 2.4%. Median age was 46 years at the time of first cancer diagnosis (range 26-69 years). The majority of the lesions were invasive ductal carcinoma (86%). Of 58 tumors, 10 were staged as Stage I (17%), 30 as Stage II (52%), 8 as Stage III (14%) and 10 as Stage IV (17%). Patients were treated with various combinations of surgery, radiation treatment and chemotherapy. Of 29 patients with bilateral breast cancer, 5 presented with simultaneous bilateral disease (17%), 7 (24%) with synchronous tumors whereas 17 (59%) developed asynchronous tumors. The mean interval between two cancers was 2.6 +/- 0.6 years. Overall survival was 4.8 +/- 0.7 years and overall 5-year actuarial survival was calculated to be 51%. Age, menopausal status and tumor size at the time of initial cancer correlated with the time interval between two cancers. Age, tumor size and nodal status at the time of initial cancer and the time interval between two cancers correlated with the overall survival.}, }
@article {pmid7812508, year = {1994}, author = {Sinn, HP and Oelmann, A and Anton, HW and Diel, IJ}, title = {Metastatic potential of small and minimally invasive breast carcinomas.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {425}, number = {3}, pages = {237-241}, pmid = {7812508}, issn = {0945-6317}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*pathology ; Neoplasm Invasiveness/pathology ; }, abstract = {Invasive ductal mammary carcinomas (IDC) of 1 cm in tumour size or less account for less than 20% of all IDC. We have observed 167 such cases at our Institution between 1985 and 1989. These were divided into carcinomas with an extensive or predominant intraductal component (EIC or PIC, being least 2x or 4x larger than the invasive component; 90) and compared statistically with the control group (no EIC or PIC; 77) for known prognostic factors and for their metastatic behaviour. Lymph nodes were step sectioned in order to detect occult micrometastases. The median follow up time was 62.6 months. Lymph node metastases were seen in 10% of pT1a and 19% of pT1b cases. Significant differences were found when comparing the EIC/PIC group with the control group (pT1a: 11% vs. 0%, pT1b: 37% vs. 11% lymph node metastases). Also, axillary and infraclavicular recurrence rates were higher for EIC/PIC carcinomas compared with other IDC of < or = 1 cm (9.3% vs. 4.2%). This significantly adverse metastatic behaviour of the EIC/PIC tumours may be in part due to the more frequent occurrence of multifocal tumours in this group (in 43% vs. 6%), resulting in a greater tumour burden. We conclude that the overall risk of lymph node metastasis is not negligible in carcinomas of 1 cm or less in diameter with the risk being more than doubled for carcinomas with an intraductal component exceeding the invasive tumour by a factor of two. These differences were relevant only to regional metastases; the risk for distant metastasis and survival was identical after 5 years.}, }
@article {pmid7531829, year = {1994}, author = {Tusell, JM and Barron, S and Serratosa, J}, title = {Anticonvulsant activity of calmodulin antagonist W-7 in convulsions induced by lindane and BayK-8644: effects in c-fos expression.}, journal = {Neurotoxicology}, volume = {15}, number = {3}, pages = {751-756}, pmid = {7531829}, issn = {0161-813X}, mesh = {3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/*toxicity ; Animals ; Anticonvulsants/*pharmacology ; Calcium Channels/drug effects ; Gene Expression/drug effects ; Genes, fos/*drug effects ; Hexachlorocyclohexane/*toxicity ; In Situ Hybridization ; Male ; Mice ; RNA, Messenger/analysis ; Seizures/chemically induced ; Sulfonamides/*pharmacology ; }, abstract = {The anticonvulsant activity of calmodulin antagonist W-7, was investigated on convulsions induced in mice by the insecticide lindane and by the calcium channel agonist BayK-8644. We also studied the inhibitory effect of W-7 on on c-fos mRNA expression induced by both convulsants. We observed a good correlation between doses and the acute convulsive effects of lindane and BayK-8644. The incidence rate and time to onset were clearly dose-dependent. W-7 antagonized the convulsive effects of lindane and BayK-8644 in all the parameters studied. A significant decrease in the incidence rate and time to onset were observed when they are compared with the values obtained with the ED100 of lindane- and BayK-8644 induced seizures. Both were able to activate the mRNA expression of the proto-oncogene. The pattern of this expression displayed by in situ hybridization was very similar. A dramatic increase was found in dentate gyrus and high levels of mRNA expression also occurring in hippocampal fields and cortical regions. In accordance with the behavioural results, W-7 antagonized also the c-fos expression induced by lindane and BayK-8644. Our results suggest that lindane as BayK-8644 may activate voltage-dependent calcium channels leading to calmodulin activation.}, }
@article {pmid7902887, year = {1993}, author = {Sasa, M and Komaki, K and Tsuzuki, H and Kamamura, Y and Mori, T and Miki, H and Uyama, T and Morimoto, T and Monden, Y}, title = {Tumor progression accompanied by increase in proliferation rate in breast cancer: a preliminary report.}, journal = {Journal of surgical oncology}, volume = {54}, number = {4}, pages = {255-259}, doi = {10.1002/jso.2930540415}, pmid = {7902887}, issn = {0022-4790}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/secondary ; Cell Division ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Nuclear Proteins/*analysis ; Proliferating Cell Nuclear Antigen ; }, abstract = {Forty consecutive cases with invasive ductal carcinoma of the breast (samples of both the primary invasive area and the involved node were available for 19 cases, multiple sections of breast tissue including both the primary invasive area and forefront intraductal cancerous area were available for 15 cases; and multiple sections of breast cancerous tissue and the involved node were available for six cases) were examined by immunohistochemical analysis for evaluation of their proliferation rate. In this study, we selected the PCNA index as a marker of the proliferation rate of the tumor cells. We demonstrated that the PCNA index of the primary invasive area was significantly higher than that of the forefront intraductal area (P = 0.0017), and the PCNA index of the involved nodes was significantly higher than that of the primary invasive area (P = 0.0004). These preliminary findings suggest that the progression from the tumor cells of the intraductal cancerous area to the metastatic tumor cells must be accompanied by two phases of increase in the proliferation rate.}, }
@article {pmid8302815, year = {1993}, author = {Gaffey, MJ and Frierson, HF and Mills, SE and Boyd, JC and Zarbo, RJ and Simpson, JF and Gross, LK and Weiss, LM}, title = {Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {6}, number = {6}, pages = {721-728}, pmid = {8302815}, issn = {0893-3952}, mesh = {Adult ; Breast Neoplasms/microbiology/*pathology ; Carcinoma, Ductal, Breast/microbiology/pathology ; Carcinoma, Medullary/microbiology/*pathology ; DNA, Viral/analysis ; Female ; Herpesvirus 4, Human/genetics ; Humans ; Immunohistochemistry ; Lymphocyte Subsets/*pathology ; Middle Aged ; Polymerase Chain Reaction ; }, abstract = {Fifty-two infiltrating breast carcinomas with medullary features (BCMF) were studied immunohistochemically to determine the immunophenotype of the mononuclear tumor inflammatory cells (MTIC) in formalin-fixed, paraffin-embedded material. The neoplasms were also examined for Epstein-Barr virus (EBV) DNA by the polymerase chain reaction (PCR). BCMF were independently classified as medullary carcinoma (MC) or infiltrating ductal carcinoma (IDC) by six observers according to the criteria of Pedersen et al. DNA from 35 BCMF was successfully amplified using PCR, but all were negative for EBV DNA. These included, by 4/6 consensus diagnosis, 16 MC, 18 IDC, and one BCMF which failed to achieve consensus diagnosis. MTIC were present to a mild degree in 19 BCMF (37%) and to moderate to severe degrees in 33 (63%). MTIC were predominantly (> or = 75%) lymphocytic in 31 BCMF (13 MC, 16 IDC, two without consensus diagnostic agreement), and plasmacytic in 10 (six MC, four IDC); equal proportions of lymphocytes and plasma cells occurred in 11 (six MC, five IDC). Lymphocytic MTIC were mostly CD45RO+/CD3+ T-cells in nearly all cases, and showed a predominant CD3+/CD4+ and CD3+/CD4- immunophenotype in 36% and 64% of cases, respectively. Natural killer cells (CD57+) and histiocytes (MAC 387+) were virtually absent. The number, cell type, and T-cell subsets of the MTIC were unrelated to consensus diagnosis, axillary lymph node status, or overall survival. EBV is unassociated with MC, despite the histologic similarities of MC to EBV-associated lymphoepithelial lesions of other organs.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid8213548, year = {1993}, author = {Lessmeier, TJ and Lehmann, MH and Steinman, RT and Fromm, BS and Akhtar, M and Calkins, H and DiMarco, JP and Epstein, AE and Estes, NA and Fogoros, RN}, title = {Outcome with implantable cardioverter-defibrillator therapy for survivors of ventricular fibrillation secondary to idiopathic dilated cardiomyopathy or coronary artery disease without myocardial infarction.}, journal = {The American journal of cardiology}, volume = {72}, number = {12}, pages = {911-915}, doi = {10.1016/0002-9149(93)91106-r}, pmid = {8213548}, issn = {0002-9149}, mesh = {Cardiomyopathy, Dilated/*complications/physiopathology ; Coronary Disease/*complications/physiopathology ; Death, Sudden, Cardiac ; *Defibrillators, Implantable ; Female ; Follow-Up Studies ; Forecasting ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; Retrospective Studies ; Stroke Volume/physiology ; Survival Rate ; Tachycardia, Ventricular/etiology/physiopathology/therapy ; Treatment Outcome ; Ventricular Fibrillation/*etiology/physiopathology/*therapy ; Ventricular Function, Left/physiology ; }, abstract = {Patients with idiopathic dilated cardiomyopathy (IDC) constitute a minority among implantable cardioverter-defibrillator (ICD) recipients; how these patients fare versus those with coronary artery disease (CAD) is not well defined, nor is the mechanism of cardiac arrest recurrence, which may involve a more significant role of bradyarrhythmias. A retrospective multicenter study regarding outcome of ICD therapy was conducted in 224 patients with either IDC (n = 69; 31%) or CAD (n = 155; 69%) presenting exclusively with ventricular fibrillation (VF) unassociated with acute myocardial infarction. Patients with IDC were significantly younger (mean age 57 vs 61 years in patients with CAD, p < 0.04) and less male predominant (64 vs 79% in patients with CAD, p < 0.02). There was no significant difference in mean left ventricular ejection fraction (0.27 in IDC patients vs 0.29 in CAD patients), but sustained ventricular tachycardia was induced less often in patients with IDC (21 vs 58% in CAD patients, p < 0.001). Bradycardia pacing, either by an ICD with bradycardia pacing ability or a separate bradycardia pacemaker, was available in only 15% of ICD implantees. During a median follow-up duration of 1.7 years for patients with IDC and 1.9 years for patients with CAD, estimated cumulative event rates were similar for any type shock (2-year incidence of 74% in IDC patients, 69% in CAD patients) as well as for appropriate shock (2-year incidence of 46% in IDC patients, 40% in CAD patients).(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid8211676, year = {1993}, author = {Borst, MJ and Ingold, JA}, title = {Metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast.}, journal = {Surgery}, volume = {114}, number = {4}, pages = {637-41; discussion 641-2}, pmid = {8211676}, issn = {0039-6060}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology/*secondary ; Carcinoma, Lobular/mortality/*pathology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Survival Analysis ; }, abstract = {BACKGROUND: Many studies have analyzed the metastatic patterns of breast carcinoma. However, very few studies have analyzed the differences in metastatic patterns of lobular versus ductal carcinoma.<br><br>METHODS: By use of our tumor registry, the metastatic sites of all invasive lobular and invasive ductal breast carcinoma cases during an 18-year period (January 1973 to December 1990) were analyzed.<br><br>RESULTS: There were 2605 cases of invasive lobular and invasive ductal breast carcinoma. Lobular carcinoma accounted for 359 (14%) and ductal carcinoma for 2246 (86%) of the cases. The percentage of patients with regional lymph node metastasis at diagnosis was not significantly different between the two groups. The rates of metastasis to all lymph nodes, liver, and central nervous system were not significantly different. However, the rates of metastasis to the gastrointestinal system (4.5% vs 0.2%), gynecologic organs (4.5% vs 0.8%), peritoneum-retroperitoneum (3.1% vs 0.6%), adrenal glands (0.6% vs 0%), bone-marrow (21.2% vs 14.4%), and lung-pleura (2.5% vs 10.2%) were significantly different (p < 0.05).<br><br>CONCLUSIONS: The metastatic patterns of lobular and ductal carcinoma of the breast are different, with gastrointestinal system, gynecologic organ, and peritoneum-retroperitoneum metastases markedly more prevalent in lobular carcinoma. Physicians should be aware of these different metastatic patterns of lobular and ductal carcinoma of the breast.}, }
@article {pmid8312582, year = {1993}, author = {Sasa, M and Kondo, K and Komaki, K and Uyama, T and Morimoto, T and Monden, Y}, title = {Frequency of spontaneous p53 mutations (CpG site) in breast cancer in Japan.}, journal = {Breast cancer research and treatment}, volume = {27}, number = {3}, pages = {247-252}, pmid = {8312582}, issn = {0167-6806}, mesh = {Adult ; Aged ; Base Sequence ; Breast Neoplasms/*genetics ; Female ; *Genes, p53 ; Humans ; Middle Aged ; Molecular Sequence Data ; *Mutation ; Polymerase Chain Reaction ; }, abstract = {Sixty-five tumors of invasive ductal carcinoma of the breast were examined for p53 alteration by the reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) method and sequencing analysis. In total, 16 samples (24.6%) showed p53 gene alteration. Sixteen of these alterations were evaluated by sequencing analysis, and 15 showed missense point mutations while one showed a 9-base pair deletion. In the 15 point mutations, G:C to A:T transitions constituted the majority (53%), and five tumors (33%) had a transition at the CpG site, which are mutational patterns not commonly found in breast tumors from Europe and America. On the other hand, there were no G:C to T:A transversions in our cases, which were frequently observed transversions in Europe and America. These p53 mutation patterns in breast cancer in Japan are not similar to those in Europe and America reported by Hollstein et al. and Coles et al.. These findings suggest that there are some differences between mechanisms of breast cancer in Japan and in Europe and America.}, }
@article {pmid8517433, year = {1993}, author = {Keeling, PJ and Kulakowski, P and Yi, G and Slade, AK and Bent, SE and McKenna, WJ}, title = {Usefulness of signal-averaged electrocardiogram in idiopathic dilated cardiomyopathy for identifying patients with ventricular arrhythmias.}, journal = {The American journal of cardiology}, volume = {72}, number = {1}, pages = {78-84}, doi = {10.1016/0002-9149(93)90223-y}, pmid = {8517433}, issn = {0002-9149}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/complications/*physiopathology ; Electrocardiography/*methods ; Female ; Humans ; Male ; Middle Aged ; Signal Processing, Computer-Assisted ; Tachycardia, Ventricular/*diagnosis/etiology ; Time Factors ; }, abstract = {In idiopathic dilated cardiomyopathy (IDC), the relation between the signal-averaged electrocardiogram and ventricular tachycardia (VT) remains unclear. In this study, conventional time domain and frequency domain analyses (2-dimensional, spectral temporal mapping and spectral turbulence analysis) of the signal-averaged electrocardiogram were performed in 64 patients with IDC. Eight patients had a history of symptomatic sustained VT and an additional 24 had nonsustained VT recorded during ambulatory electrocardiography. Conventional time domain analysis, using the 25 and 40 Hz filter, and spectral temporal mapping, detected late potentials within the terminal QRS in 8 (13%), 14 (22%) and 18 (28%) patients, respectively. Late potentials were seen more often in patients with than without VT, and in patients with sustained versus nonsustained VT, but these differences were not significant. The predictive accuracy of these techniques in detecting either form of VT were: sensitivity, 22, 25 and 31%; specificity, 97, 81 and 75%; and overall predictive value, 59, 53 and 50%, respectively. Two-dimensional frequency domain analysis of the signal-averaged electrocardiogram revealed a higher energy and area ratio in patients with than without VT (entire QRS), and in patients with sustained versus nonsustained VT (entire QRS and terminal QRS). Spectral turbulence analysis was abnormal in 24 patients (39%), but no differences were observed between patients with and without VT. During follow-up (mean duration 18 +/- 14 months), 5 patients had arrhythmic events (3 died suddenly, 1 had aborted sudden death and 1 developed sustained VT).(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid8500519, year = {1993}, author = {Faas, SJ and Rothstein, JL and Kreider, BL and Rovera, G and Knowles, BB}, title = {Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells.}, journal = {European journal of immunology}, volume = {23}, number = {6}, pages = {1201-1214}, doi = {10.1002/eji.1830230602}, pmid = {8500519}, issn = {0014-2980}, support = {CA-10815/CA/NCI NIH HHS/United States ; CA-18470/CA/NCI NIH HHS/United States ; CA-21124/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, Polyomavirus Transforming/genetics ; Cell Differentiation ; Cell Division ; Cell Line ; Cytokines/genetics ; Female ; Gene Expression ; Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology ; Histocompatibility Antigens Class I/metabolism ; Histocompatibility Antigens Class II/metabolism ; Immunophenotyping ; Liver/embryology ; Male ; Mice ; Mice, Nude ; Mice, Transgenic ; RNA, Messenger/genetics ; Thymus Gland/*cytology/immunology ; }, abstract = {The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development.}, }
@article {pmid8387875, year = {1993}, author = {Malins, DC and Holmes, EH and Polissar, NL and Gunselman, SJ}, title = {The etiology of breast cancer. Characteristic alteration in hydroxyl radical-induced DNA base lesions during oncogenesis with potential for evaluating incidence risk.}, journal = {Cancer}, volume = {71}, number = {10}, pages = {3036-3043}, doi = {10.1002/1097-0142(19930515)71:10&lt;3036::aid-cncr2820711025&gt;3.0.co;2-p}, pmid = {8387875}, issn = {0008-543X}, mesh = {Breast/metabolism ; Breast Neoplasms/*etiology/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*etiology/metabolism ; *DNA Damage ; Female ; Humans ; Hydroxides/*chemistry ; Mammaplasty ; *Reactive Oxygen Species ; Regression Analysis ; Risk Factors ; }, abstract = {BACKGROUND: Substantial hydroxyl radical (.OH)-induced base lesions, recently found in the DNA of invasive ductal carcinoma of the female breast, are likely to be intimately related to oncogenesis. However, virtually no information was available regarding relationships between the different base lesions in the normal and cancerous breast. Such information is essential in understanding initial stages in the development of breast cancer and the potential of the base lesions as early predictors of cancer risk.<br><br>METHODS: The .OH-induced DNA base lesions in normal reduction mammoplasty tissue (RMT) were compared with those from invasive ductal carcinoma (IDC) and nearby microscopically normal tissue (MNT). Comparisons were then undertaken on relationships between the base lesion profiles in the normal and cancerous breast using 22 statistical models.<br><br>RESULTS: DNA from the RMT was characterized by a high ratio of ring-opening products (e.g., 4,6-diamino-5-formamidopyrimidine) to hydroxy-adducts of adenine and guanine. A dramatic shift in this relationship in favor of carcinogenic hydroxy-adducts (e.g., 8-hydroxyguanine) was found in the cancerous breast. Statistical models with a high sensitivity (91%) and specificity (97%) provided a consistent means of classifying tissues (e.g., 96% correct).<br><br>CONCLUSIONS: The dramatic shift in the DNA base lesion relationships in oncogenesis is attributed to alterations in the redox potential of the breast favoring oxidative conditions and cancer formation. These findings suggest that base lesion profiles are potential sentinels for cancer risk assessment. Further, intervention in controlling the tissue redox potential may provide benefit in delaying or preventing early oncogenic changes and the ultimate manifestation of cancer.}, }
@article {pmid7680285, year = {1993}, author = {Clezardin, P and Frappart, L and Clerget, M and Pechoux, C and Delmas, PD}, title = {Expression of thrombospondin (TSP1) and its receptors (CD36 and CD51) in normal, hyperplastic, and neoplastic human breast.}, journal = {Cancer research}, volume = {53}, number = {6}, pages = {1421-1430}, pmid = {7680285}, issn = {0008-5472}, mesh = {Amino Acid Sequence ; Animals ; Antigens, CD/*analysis ; Breast/*chemistry/pathology ; Breast Neoplasms/*chemistry ; CD36 Antigens ; Carcinoma/*chemistry ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; In Situ Hybridization ; Integrins/*analysis ; Mice ; Molecular Sequence Data ; Platelet Membrane Glycoproteins/*analysis/immunology ; Receptors, Cytoadhesin/*analysis ; Thrombospondins ; }, abstract = {We have previously shown that thrombospondin (TSP) is present in normal breast secretions, and high levels of TSP are observed in malignant breast secretions and cytosols. Three genes encoding for three distinct TSPs (TSP1, TSP2, TSP3) have recently been described. In this study, using both immunohistochemistry and in situ hybridization, we report on the distribution of TSP1 in normal, hyperplastic, and neoplastic human breast. Its immunolocalization was also compared with that of two known cell surface receptors for TSP1: CD36 and CD51. In nonlactating ducts of normal and hyperplastic breast, TSP1 and CD51 are expressed in the basement membrane and in the basal surface of myoepithelial cells, respectively. In lactating adenomas, both TSP1 and CD51 disappear from the myoepithelial-stromal junction of ducts. However, TSP1 becomes selectively expressed at the apices of secretory epithelial cells of lactating ducts together with CD36, suggesting that the distribution of TSP1 and the appearance of its receptors are dependent on the secretory activity of human mammary ducts. In neoplastic human breast, a strong immunostaining for TSP1 is observed in the basement membrane surrounding in situ carcinomas (preinvasive cancer), and excessive TSP1 deposits are also observed in desmoplasia of invasive ductal carcinomas. TSP1 mRNA is localized in myoepithelial cells surrounding in situ carcinomas and in fibroblasts present in desmoplastic areas. On the other hand, few invasive ductal carcinoma cells (10%) express TSP1, while CD51 is moderately expressed by some neoplastic clusters, and no immunoreactivity is observed for CD36. By contrast, TSP1 is codistributed with CD51 in most of the invasive lobular carcinoma cells (40 to 80%) and with CD36 in a subpopulation (30 to 40%) of these invasive tumor cells. As previously observed with lactating adenomas, it is likely that the coexpression of TSP1 and CD36 is related to the secretory activity of invasive lobular carcinoma cells. The different distribution of TSP1 in invasive ductal versus lobular carcinomas may well reflect biological differences between these two main types of breast carcinoma. In this regard, the coexpression of TSP1 and CD36 may, in part at least, account for the variably invasive behavior of lobular carcinoma cells.}, }
@article {pmid8381208, year = {1993}, author = {Folli, F and Solimena, M and Cofiell, R and Austoni, M and Tallini, G and Fassetta, G and Bates, D and Cartlidge, N and Bottazzo, GF and Piccolo, G and De Camilli, P}, title = {Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer.}, journal = {The New England journal of medicine}, volume = {328}, number = {8}, pages = {546-551}, doi = {10.1056/NEJM199302253280805}, pmid = {8381208}, issn = {0028-4793}, support = {AI 30248-01/AI/NIAID NIH HHS/United States ; DK 43078-01/DK/NIDDK NIH HHS/United States ; MH 45191-01/MH/NIMH NIH HHS/United States ; }, mesh = {Aged ; Animals ; Autoantibodies/*analysis/blood ; Autoantigens/immunology ; Blotting, Western ; Brain/immunology ; Breast Neoplasms/*complications ; Carcinoma, Intraductal, Noninfiltrating/*complications ; Cerebrospinal Fluid/immunology ; Female ; Glutamate Decarboxylase/immunology ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Nerve Tissue Proteins/*immunology ; Paraneoplastic Syndromes ; Precipitin Tests ; Rats ; Stiff-Person Syndrome/etiology/*immunology ; Synapses/*immunology ; }, abstract = {BACKGROUND: The stiff-man syndrome is a rare disease of the central nervous system characterized by progressive rigidity of the body musculature. Autoantibodies directed against glutamic acid decarboxylase are present in about 60 percent of patients with the syndrome. In this group, there is a striking association of the stiff-man syndrome with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus.<br><br>METHODS: We studied three women with the stiff-man syndrome and breast cancer, seeking autoantibodies directed against nervous system antigens in serum and cerebrospinal fluid by immunocytochemical techniques, Western blotting, and immunoprecipitation.<br><br>RESULTS: Autoantibodies directed against a 128-kd brain protein were found in two of the women with the stiff-man syndrome and breast cancer. These results led to a search for breast cancer in the third patient with the stiff-man syndrome, who also had autoantibodies. A small invasive ductal carcinoma was detected by ultrasonography and removed. Serum samples from all three patients were negative for autoantibodies directed against glutamic acid decarboxylase. Autoantibodies against the 128-kd antigen were not detected in control patients with the stiff-man syndrome without breast cancer or in patients with cancer who did not have the syndrome. Within the nervous system, the 128-kd autoantigen was localized in neurons and concentrated at synapses.<br><br>CONCLUSIONS: In a subgroup of patients with the stiff-man syndrome, the condition is likely to have an autoimmune paraneoplastic origin. The detection of autoantibodies against the 128-kd antigen in patients with this syndrome should be considered an indication to search for an occult breast cancer.}, }
@article {pmid8449193, year = {1993}, author = {Werner, GS and Figulla, HR and Munz, DL and Klingel, K and Kandolf, R and Emrich, D and Kreuzer, H}, title = {Myocardial indium-111 antimyosin uptake in patients with idiopathic dilated cardiomyopathy: its relation to haemodynamics, histomorphometry, myocardial enteroviral infection, and clinical course.}, journal = {European heart journal}, volume = {14}, number = {2}, pages = {175-184}, doi = {10.1093/eurheartj/14.2.175}, pmid = {8449193}, issn = {0195-668X}, mesh = {Actuarial Analysis ; Adult ; Aged ; Antibodies, Monoclonal/*metabolism ; Biopsy ; Cardiomyopathy, Dilated/complications/*metabolism/pathology/physiopathology ; Endocardium/pathology ; Enterovirus Infections/complications ; Female ; Follow-Up Studies ; Heart Diseases/mortality ; Hemodynamics/physiology ; Humans ; Indium Radioisotopes ; Male ; Middle Aged ; Myocardium/*metabolism ; Myosins/*immunology ; Survival Analysis ; Tomography, Emission-Computed, Single-Photon ; }, abstract = {The myocardial uptake of indium-111 antimyosin indicates the presence of ongoing myocyte damage. To evaluate the role of this finding in patients with idiopathic dilated cardiomyopathy (IDC), 36 patients were studied by planar and SPECT antimyosin imaging. The diagnosis of IDC was based on coronary angiography and left ventricular endomyocardial biopsy. The antimyosin scan was evaluated qualitatively from SPECT images and assessed quantitatively by a count density index (CDI) which measured the tracer activity over the heart relative to the lung and sternal region (normal value less than 1.20). Group 1 consisted of 13 patients (36%) with an increased myocardial antimyosin uptake, while 23 patients had a normal antimyosin scan (group 2). Clinical data, pulmonary artery pressures, gated blood pool ejection fraction and histomorphometry of endomyocardial biopsies were similar in both groups. During a follow-up of 21 +/- 12 months there were two cardiac deaths in group 1 and 10 deaths in group 2 (P = 0.12). The 2-year survival rate was 81% and 59%, respectively. During follow-up, there was no significant change in haemodynamic parameters in either group, but there was a slight improvement in functional NYHA class in group 1 (P < 0.05). No association was found between the presence of myocardial enterovirus infection, determined in 17 patients by in situ hybridization and the antimyosin scan (P = 0.5 g). Myocardial antimyosin uptake was found in a high percentage of patients with IDC, indicating ongoing myocyte damage. This finding was not related to any clinical, haemodynamic, morphological parameter, or enterovirus infection. Myocyte damage is a distinct feature in a subgroup of patients with IDC unrelated to any known causes of myocellular destruction. This subgroup showed a trend towards a more favourable clinical outcome.}, }
@article {pmid8419551, year = {1993}, author = {Cortés, R and Mengod, G and Celada, P and Artigas, F}, title = {p-chlorophenylalanine increases tryptophan-5-hydroxylase mRNA levels in the rat dorsal raphe: a time course study using in situ hybridization.}, journal = {Journal of neurochemistry}, volume = {60}, number = {2}, pages = {761-764}, doi = {10.1111/j.1471-4159.1993.tb03213.x}, pmid = {8419551}, issn = {0022-3042}, mesh = {Animals ; Blotting, Northern ; Fenclonine/*pharmacology ; In Situ Hybridization ; Kinetics ; Male ; Oligonucleotide Probes ; RNA, Messenger/*metabolism ; Raphe Nuclei/drug effects/*enzymology ; Rats ; Time Factors ; Tryptophan Hydroxylase/*genetics ; }, abstract = {The effects of a single dose of p-chlorophenylalanine on the mRNA encoding tryptophan-5-hydroxylase (EC 1.14.16.4) in the rat dorsal raphe nucleus were analyzed using in situ hybridization. The levels of tryptophan-5-hydroxylase mRNA were markedly increased in cell bodies located in the ventromedial part of the dorsal raphe 1-2 days after p-chlorophenylalanine (300 mg/kg, i.p.) administration. This was followed by a decrease in the amount of tryptophan-5-hydroxylase mRNA, which returned to basal values by 5 days after treatment. An almost symmetric time course was observed for the midbrain serotonin concentration. Our results on the temporal pattern of changes in tryptophan-5-hydroxylase mRNA levels in the ventromedial part of the dorsal raphe are opposite to those reported for the enzyme activity and serotonin concentration after p-chlorophenylalanine treatment. These changes may result from modifications in enzyme mRNA expression, suggesting that tryptophan-5-hydroxylase gene transcription is involved in feedback mechanisms regulating serotonin synthesis.}, }
@article {pmid8381766, year = {1993}, author = {Raju, U and Zarbo, RJ and Kubus, J and Schultz, DS}, title = {The histologic spectrum of apocrine breast proliferations: a comparative study of morphology and DNA content by image analysis.}, journal = {Human pathology}, volume = {24}, number = {2}, pages = {173-181}, doi = {10.1016/0046-8177(93)90297-t}, pmid = {8381766}, issn = {0046-8177}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; DNA, Neoplasm/*analysis ; Female ; Humans ; Ploidies ; }, abstract = {Apocrine features occurring in sclerosing adenosis (apocrine adenosis), atypical ductal hyperplasia (ADH), and non-comedo ductal carcinoma in situ (DCIS) often add to diagnostic difficulty. We have evaluated the usefulness of DNA content determined by image analysis in apocrine metaplasia and hyperplasia, apocrine adenosis, ADH, DCIS, lobular carcinoma in situ, invasive ductal carcinoma, and infiltrating lobular carcinoma as a potential diagnostic aid in some of these problematic breast lesions with apocrine features. Infiltrating ductal carcinoma and DCIS were further subdivided into high- or low-grade category based on nuclear features. Microscopic fields containing 63 lesions were identified in slides from breast excisions. From each selected area 100 cells in corresponding fields in paired Feulgen-stained sections were digitized for computerized ploidy analysis with lymphocyte nuclei in the same slides serving as internal diploid controls. Aneuploidy was assessed using combined DNA index and modified Auer histogram criteria for DNA content abnormalities. There was strong association between the assessment of nuclear grade and ploidy (Fisher's exact test, P < .00001). All but one of the benign and low-grade malignant lesions (97%) were in the diploid range (six of seven apocrine metaplasia cases, three of three apocrine adenosis cases, 14 of 14 ADH cases, 10 of 10 low-grade DCIS cases, two of two lobular carcinoma in situ cases, and two of two infiltrating lobular carcinoma cases). In contrast, 24 of 25 (96%) of the high-grade malignant lesions were aneuploid (10 of 10 DCIS cases and 14 of 15 infiltrating ductal carcinoma cases). We conclude that DNA ploidy status does not offer additional diagnostic information to light microscopy in distinguishing among benign apocrine proliferations, ADH, and low-grade DCIS since these proliferations share a diploid range DNA content.}, }
@article {pmid8096256, year = {1993}, author = {Narita, T and Funahashi, H and Satoh, Y and Takagi, H}, title = {Proliferating cell nuclear antigen immunostaining in breast cancer and its relation to prognosis.}, journal = {Japanese journal of clinical oncology}, volume = {23}, number = {1}, pages = {20-25}, pmid = {8096256}, issn = {0368-2811}, mesh = {Antigens, Neoplasm/analysis ; Breast Neoplasms/*immunology/mortality/pathology ; Carcinoma/immunology/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/immunology/mortality/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Neoplasm Proteins/analysis ; Nuclear Proteins/*analysis ; Prognosis ; Proliferating Cell Nuclear Antigen ; Survival Rate ; }, abstract = {Proliferating cell nuclear antigen (PCNA) appears in the cell nuclei during the late G1 to S phases of the cell cycle and is thought to be closely related to cellular proliferation. The authors have conducted an immunohistochemical study in order to investigate the tissue expression of PCNA and its clinical significance in breast cancer. Excluding cases with absolutely no positive cells on the section specimen, the mean value (%) for the PCNA labeling index (LI) was 30.4 in 187 cases of invasive ductal carcinoma. No correlations between PCNA LI and any clinicopathological factors such as tumor diameter and tumor stage were observed. Also, no significant correlation was observed with Ki-67 LI. A positive correlation was, however, observed with the tissue expression of c-erbB-2 protein. We divided 82 patients with stage II invasive ductal carcinoma into PCNA LI of < 10, PCNA LI of 10-50 and PCNA of > 50, and analyzed the specimens for any correlation with prognosis. The group with PCNA LI of > 50 had significantly poorer prognoses than the other groups. From the above, we concluded immunostaining for PCNA to be useful as a prognostic factor and as an indicator of the degree of malignancy in breast cancer.}, }
@article {pmid8505699, year = {1993}, author = {Wisecarver, JL and Synovec, MS and Pirrucello, S and Linder, J}, title = {Marking characteristics of anti-nuclear matrix protein NM200.4 in human breast carcinomas and normal human tissues.}, journal = {Journal of clinical laboratory analysis}, volume = {7}, number = {2}, pages = {134-138}, doi = {10.1002/jcla.1860070213}, pmid = {8505699}, issn = {0887-8013}, mesh = {Antibodies, Antinuclear/*analysis ; Antibodies, Monoclonal/*immunology ; Antigens, Nuclear ; Autoantigens/immunology ; Breast Neoplasms/*immunology ; Female ; Humans ; Male ; Nuclear Matrix/*immunology ; Nuclear Proteins/*immunology ; }, abstract = {Nuclear matrix proteins are a group of recently described proteins that are thought to be cell-type specific. Using a monoclonal antibody (NM 200.4; Matritech, Cambridge, MA) generated against nuclear matrix proteins isolated from a human breast carcinoma cell line, we examined frozen tissue sections from 30 breast carcinomas, and a variety of normal tissues to determine the antibody specificity, and to assess the relationship with the staining pattern and tumor type and hormone receptor status. Most breast carcinomas marked with the antibody, but stromal and vascular endothelial cells in the tissues surrounding these lesions also marked focally. Marking of vascular endothelium in a variety of benign tissues, renal tubular epithelium, and occasionally uterine smooth muscle cells was also observed. Normal breast tissue from 4 patients without breast cancer did not react. Studies on breast tumors revealed that 15/20 invasive ductal, 3/4 in situ ductal, 3/3 medullary, 2/2 invasive lobular, and 1/1 colloid carcinomas marked with this antibody. Image analysis revealed that the staining intensity of medullary carcinoma was twice that found in invasive ductal carcinoma (avg pixel density 76.6 vs. 30.1; P < 0.05). Invasive lobular and in situ ductal carcinoma also expressed higher staining intensities than invasive ductal carcinoma, but these differences were not significant. Invasive ductal carcinomas had heterogeneity in staining intensity (avg. pixel intensity range: 0-94 units). Tumors with multiple aneuploid populations had significantly higher stain intensity values than either diploid lesions or lesions containing a single aneuploid population (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid8465654, year = {1993}, author = {Iijima, T and Doi, M and Kamma, H and Horiguchi, H and Yazawa, T and Ogata, T}, title = {Pulmonary vasculature in idiopathic dilated cardiomyopathy: a morphometric study.}, journal = {Acta pathologica japonica}, volume = {43}, number = {1-2}, pages = {28-35}, doi = {10.1111/j.1440-1827.1993.tb02911.x}, pmid = {8465654}, issn = {0001-6632}, mesh = {Adult ; Aged ; Arteries/pathology ; Cardiomyopathy, Dilated/*pathology ; Female ; Fibrosis/pathology ; Humans ; Hypertrophy, Left Ventricular/*pathology ; Lung/*blood supply/pathology ; Male ; Middle Aged ; Myocardium/*pathology ; Veins/pathology ; }, abstract = {The pulmonary vascular alterations of seven patients with idiopathic dilated cardiomyopathy (IDC) were morphometrically examined, and the relation between the vascular alterations and morphological status of the hearts was studied. Most patients with IDC showed not only fibrous thickening of small pulmonary veins but also intimal circumferential fibrosis and medial hypertrophy of small pulmonary muscular arteries to various degrees. The histological features of the pulmonary vessels were compatible with hypertensive vascular changes observed in patients with mitral stenosis. There was a significant correlation between medial hypertrophy of the pulmonary muscular arteries and right ventricular hypertrophy. The pulmonary vascular changes in IDC were always associated with left atrioventricular dilatation, but were only found in patients with prominent hypertrophy of the left ventricles. Medial hypertrophy of the pulmonary muscular arteries was related more to left ventricular hypertrophy than to left ventricular dilatation. These findings suggest that the pulmonary vascular changes in IDC are caused by venous pulmonary hypertension, which may be developed at the late stage when left ventricular hypertrophy predominates.}, }
@article {pmid8384543, year = {1993}, author = {Fardeau, C and Langlois, M and Nugier, F and Asselot, C and Aymard, M and Denis, J}, title = {Cross-resistances to antiviral drugs of IUdR-resistant HSV1 in rabbit keratitis and in vitro.}, journal = {Cornea}, volume = {12}, number = {1}, pages = {19-24}, doi = {10.1097/00003226-199301000-00004}, pmid = {8384543}, issn = {0277-3740}, mesh = {Animals ; Antiviral Agents/*therapeutic use ; Drug Resistance, Microbial ; Female ; Idoxuridine/*therapeutic use ; Keratitis, Herpetic/*drug therapy/microbiology ; Microbial Sensitivity Tests ; Phenotype ; Rabbits ; Random Allocation ; Simplexvirus/drug effects/metabolism ; Thymidine Kinase/metabolism ; }, abstract = {The emergence of cross-resistance to various antiviral drugs was investigated both in vivo and in vitro for herpes simplex virus type 1 (HSV1) resistant to idoxuridine (IUdR 0.24%) obtained by seven successive passages (from P0 to P7) in rabbit keratitis treated by IUdR. The viral population obtained at the seventh IUdR passage (P7) showed an activity of the thymidine kinase (TK) reduced to 5.6% of the parental strain (PO); moreover, most of the clones of P7 showed an altered TK phenotype determined by the [125I]iododeoxycytidine (IDC) procedure. In rabbit keratitis, IUdR-resistant viral population P7 showed cross-resistance to bromovinyl desoxyuridine (BVDU) (0.5%) and to acyclovir (ACV) (3%). Under trifluorothymidine (1%) treatment, P7 showed an intermediate sensitivity. HSV1 at P7 remained sensitive to adenine arabinoside (Ara A) (3%) and to dihydroxy-propoxymethylguanine used at high concentration (3%). The in vitro sensitivity determination to various antiviral drugs was investigated by dye-uptake assay for the initial viral population PO and for HSV1 collected under IUdR treatment at the third (P3) and the seventh (P7) passages. Cross-resistance to TK-dependent drugs, such as IDC, BVDU, and ACV were found at P7. P7 remained sensitive to Ara A and to phosphonoformic acids antiviral drugs known not to be dependent on viral TK.}, }
@article {pmid8297656, year = {1993}, author = {Jain, S and Fisher, C and Smith, P and Millis, RR and Rubens, RD}, title = {Patterns of metastatic breast cancer in relation to histological type.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {29A}, number = {15}, pages = {2155-2157}, doi = {10.1016/0959-8049(93)90053-i}, pmid = {8297656}, issn = {0959-8049}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/secondary ; Brain Neoplasms/secondary ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Carcinoma, Lobular/*secondary ; Female ; Humans ; Lung Neoplasms/secondary ; Middle Aged ; Peritoneal Neoplasms/secondary ; Pleural Neoplasms/secondary ; }, abstract = {We have examined the clinical records fo 1238 patients with operable breast cancer to identify the sites of metastatic disease. Infiltrating ductal carcinoma (IDC) recurred more commonly in lung (P < 0.05), pleura (P < 0.05) and brain (P < 0.05), while infiltrating lobular carcinoma (ILC) more commonly metastasised to the bone marrow (P < 0.01) and peritoneum (P < 0.01). Bone involvement as the initial presentation of distant metastatic disease occurred in over 50% of women with ILC, significantly more commonly than in those with IDC (34%, P < 0.01). Survival was similar for the two groups, both from time of diagnosis and from time of development of distant metastases.}, }
@article {pmid1359968, year = {1992}, author = {McKeever, DJ and Awino, E and Morrison, WI}, title = {Afferent lymph veiled cells prime CD4+ T cell responses in vivo.}, journal = {European journal of immunology}, volume = {22}, number = {12}, pages = {3057-3061}, doi = {10.1002/eji.1830221205}, pmid = {1359968}, issn = {0014-2980}, mesh = {Animals ; Antigen-Presenting Cells/physiology ; Antigens/metabolism ; CD4-Positive T-Lymphocytes/*immunology ; Cattle ; Dendritic Cells/*immunology ; Lymph Nodes/cytology/*immunology ; Receptors, Fc/physiology ; }, abstract = {The interdigitating cell (IDC) population of the lymph node paracortex is believed to be responsible for the induction of CD4+ T cell responses to soluble antigens. We have examined the role of afferent lymph veiled cells (ALVC), the putative precursors of IDC, in the induction of primary bovine CD4+ T cell responses in vivo. ALVC prepared from lymph draining an antigen inoculation site stimulated maximal responses in antigen-specific T cell clones as soon as 30 min after inoculation. In addition, antigen-pulsed ALVC were shown to induce primary antigen-specific T cell responses when administered in vivo. Observed influences of fixation and the addition of chloroquine or class II major histocompatibility complex-specific monoclonal antibodies on presenting function confirmed that ALVC process and present antigens using the endosomal pathway. We conclude that ALVC rapidly internalize antigens deposited in the periphery, and process them for presentation to naive T cells in the draining lymph node. Their function is, therefore, likely to be an important factor in the induction of primary T cell responses to soluble antigens in vivo.}, }
@article {pmid1462362, year = {1992}, author = {de Waal, EJ and Rademakers, LH and Schuurman, HJ and van Loveren, H}, title = {Interdigitating cells in the rat thymus during cyclosporin A treatment: ultrastructural observations.}, journal = {Thymus}, volume = {20}, number = {3}, pages = {163-170}, pmid = {1462362}, issn = {0165-6090}, mesh = {Animals ; Autoimmunity ; Biomarkers ; Cyclosporine/*pharmacology ; Dendritic Cells/*drug effects/immunology/ultrastructure ; Histocompatibility Antigens/*analysis ; Histocompatibility Antigens Class II/analysis ; Male ; Rats ; Thymus Gland/*drug effects/ultrastructure ; Time Factors ; }, abstract = {Major Histocompatibility Complex (MHC) class II-positive cells are almost completely absent in the rat thymic medulla after cyclosporin A (CsA) exposure. This phenomenon has been related to alterations in the medullary interdigitating cells (IDCs), representing either down-modulation of RT1 class II antigen on persistent IDCs, or actual disappearance of IDCs. To resolve this issue, we performed an ultrastructural study of the rat thymic medulla during CsA treatment (15 mg/kg body weight/day CsA subcutaneously for 7 to 14 days). At day 7 after exposure, only very few IDCs could be identified. They showed an abnormal ultrastructural morphology as judged by inconspicuous membrane interdigitations and lack of Birbeck granules. At day 14, the number of IDCs was larger. At this time, the IDCs had a normal ultrastructure, except for the almost complete absence of Birbeck granules. We conclude that CsA causes an initial depletion of IDCs from the thymic medulla. The ultrastructural morphology of the few IDCs present suggests an immature character. New IDC immigrants appear in the medullary area already during CsA treatment, indicating early recovery.}, }
@article {pmid1450384, year = {1992}, author = {Kawaguchi, H and Fukuda, I and Shiina, T and Toyoshima, Y}, title = {Dynamical behavior of psb gene transcripts in greening wheat seedlings. I. Time course of accumulation of the pshA through psbN gene transcripts during light-induced greening.}, journal = {Plant molecular biology}, volume = {20}, number = {4}, pages = {695-704}, pmid = {1450384}, issn = {0167-4412}, mesh = {Blotting, Northern ; *Genes, Plant ; Kinetics ; Light ; Multigene Family ; Operon ; Photosynthetic Reaction Center Complex Proteins/*genetics ; Photosystem II Protein Complex ; Seeds ; *Transcription, Genetic ; Triticum/embryology/*genetics/physiology ; }, abstract = {The time course of the accumulation of the transcripts from 13 psb genes encoding a major part of the proteins composing photosystem II during light-induced greening of dark-grown wheat seedlings was examined focusing on early stages of plastid development (0.5 h through 72 h). The 13 genes can be divided into three groups. (1) The psbA gene is transcribed as a single transcript of 1.3 kb in the dark-grown seedlings, but its level increases 5- to 7-fold in response to light due to selective increase in RNA stability as well as in transcription activity. (2) The psbE-F-L-J operon, psbM and psbN genes are transcribed as a single transcript of 1.1 kb, two transcripts of 0.5 and 0.7 kb and a single transcript of 0.3 kb, respectively, in the dark-grown seedlings. The levels of accumulation of every transcript remain unchanged or rather decrease during plastid development under illumination. (3) The psbK-I-D-C gene cluster and psbB-H operon exhibit fairly complicated northern hybridization patterns during the greening process. When a psbC or psbD gene probe was used for northern hybridization, five transcripts differing in length were detected in the etioplasts from 5-day old dark-grown seedlings. After 2 h illumination, two new transcripts of different length appeared. Light induction of new transcripts was also observed in the psbB-H operon.}, }
@article {pmid1444792, year = {1992}, author = {Berend, ME and Sullivan, DC and Kornguth, PJ and Skinner, CS and Ost, A and Iglehart, JD and Skinner, MA}, title = {The natural history of mammographic calcifications subjected to interval follow-up.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {127}, number = {11}, pages = {1309-1313}, doi = {10.1001/archsurg.1992.01420110055012}, pmid = {1444792}, issn = {0004-0010}, mesh = {Aged ; Biopsy, Needle/standards ; Breast Diseases/*complications/diagnostic imaging/pathology ; Breast Neoplasms/*epidemiology/etiology/pathology ; Calcinosis/*complications/diagnostic imaging/pathology ; Decision Trees ; Female ; Follow-Up Studies ; Humans ; Incidence ; Mammography/standards ; Middle Aged ; Neoplasm Staging ; Predictive Value of Tests ; Risk Factors ; }, abstract = {The purpose of this investigation was to determine the natural history and risk of malignancy associated with isolated indeterminate microcalcifications subjected to interval follow-up. During a 2-year study, 91 patients were identified with indeterminate microcalcifications alone. Specific roentgenographic features of the calcifications were evaluated on initial and follow-up mammograms. During a mean follow-up of 36 months, 19 (21%) of the women exhibited mammographic changes. Ten patients (11%) with suspicious changes underwent a needle-directed biopsy 6 to 30 months after the initial mammographic screening. Five women (5.5%) were diagnosed as having breast carcinoma; three had invasive ductal carcinoma and two had purely intraductal lesions. Four patients had axillary lymph node dissections and no metastatic disease was found. We found no significant differences in the roentgenographic features associated with malignant vs benign lesions apart from an increased overall estimation of the probability of malignancy rating in the five patients with breast carcinoma. We recommend that patients be followed up with mammography at regular intervals for at least 18 months following recognition of indeterminate microcalcifications.}, }
@article {pmid1335210, year = {1992}, author = {Rayne, SC and Santa Cruz, DJ}, title = {Anaplastic Paget's disease.}, journal = {The American journal of surgical pathology}, volume = {16}, number = {11}, pages = {1085-1091}, doi = {10.1097/00000478-199211000-00007}, pmid = {1335210}, issn = {0147-5185}, mesh = {Adult ; Aged ; Bowen's Disease/pathology ; Diagnosis, Differential ; Female ; Histocytochemistry ; Humans ; Immunohistochemistry ; Middle Aged ; Paget's Disease, Mammary/classification/metabolism/*pathology ; Prognosis ; Risk Factors ; }, abstract = {Six cases of a distinct, histologically anaplastic variant of mammary Paget's disease are described. Patients ranged in age from 40 to 85 years. All patients had scaling erythematous lesions confined to the nipple; none had palpable breast masses. Histologically, the lesions had features resembling Bowen's disease, including full-thickness epidermal atypia, loss of nuclear polarity, and marked cytologic anaplasia. Intraepidermal acantholysis was a distinctive feature in all cases. In some biopsies, small groups and single typical Pagetoid cells were seen within the areas of confluent Bowen-like change. Immunohistochemically, carcinoembryonic antigen (CEA) was positive in three of six patients; epithelial membrane antigen (EMA) in five of six patients, and cytokeratin AE1/AE3 in three of six patients. Mucicarmine stains were uniformly negative. In our series, anaplastic Paget's disease was associated with concomitant invasive ductal carcinoma in three of six patients (50%). This percentage is significantly higher than that previously reported for patients with Paget's disease and without palpable breast mass. Histologic features that are helpful in distinguishing between anaplastic Paget's disease and Bowen's include cleft-like acantholysis, absence of dyskeratotic cells, and persistence of basal cell layer. More rarely, but very helpful when present, are underlying ductal carcinoma, intracellular lumina, and associated conventional Paget's disease. Immunohistochemistry results were variable and of relative value. Our study suggests that a nipple lesion histologically resembling Bowen's disease is likely to represent anaplastic Paget's disease.}, }
@article {pmid1387298, year = {1992}, author = {Ramos, JA and Ramis, AJ and Marco, A and Domingo, M and Rabanal, R and Ferrer, L}, title = {Histochemical and immunohistochemical study of the mucosal lymphoid system in swine.}, journal = {American journal of veterinary research}, volume = {53}, number = {8}, pages = {1418-1426}, pmid = {1387298}, issn = {0002-9645}, mesh = {Acid Phosphatase/analysis ; Adenosine Triphosphatases/analysis ; Animals ; Carboxylic Ester Hydrolases/analysis ; Dendritic Cells/chemistry/enzymology ; Eosinophils/chemistry/enzymology ; Female ; Fibroblasts/chemistry/enzymology ; Glucuronidase/analysis ; Histocytochemistry ; Immunoglobulins/analysis ; Immunohistochemistry ; Lymphocytes/chemistry/enzymology ; Macrophages/chemistry/enzymology ; Male ; Naphthol AS D Esterase/analysis ; Palatine Tonsil/*cytology/enzymology ; Peyer's Patches/*cytology/enzymology ; S100 Proteins/analysis ; Specific Pathogen-Free Organisms ; Swine/anatomy &amp; histology/*immunology ; }, abstract = {Enzyme histochemical and immunohistochemical techniques were used to examine palatine tonsils and aggregated lymphoid follicles (Peyer's patches) of the ileum in 6- to 9-day-old and in 6-month-old pigs. Histochemical techniques were used to detect alpha-naphthyl-acetate esterase (ANAE), alpha-naphthyl-butyrate esterase (ANBE), beta-glucuronidase, adenosine triphosphatase (ATPase), and acid phosphatase (AcP). Nonspecific esterases (ANAE, ANBE) were detected in macrophages, T-cell area lymphocytes, eosinophils, fibroblastic reticular cells (FRC), follicular dendritic cells (FDC), and interdigitating cells (IDC). beta-Glucuronidase reactivity was strong in macrophages, eosinophils, FDC, and IDC, and weaker in FRC. Adenosine triphosphatase reactivity was detected in B-cell area lymphocytes, FDC, FRC, and IDC. Cell types with acid phosphatase reactivity were macrophages, FDC, FRC, and IDC. Nonepithelial cells of tonsils and aggregated lymphoid follicles of the ileum had similar enzymatic reactions. In Peyer's patches, however, epithelial cells were positive for all enzymes studied; in tonsils, only nonspecific esterases were detected. Immunoperoxidase techniques were used to detect S-100 protein and cytoplasmic immunoglobulins (IgG, IgM, and IgA). The S-100 protein was detected in lymphocytes, FDC, and FRC of tonsils and Peyer's patches; in tonsillar epithelial and endothelial cells; and in IDC of Peyer's patches.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid1382176, year = {1992}, author = {Vendrell, M and Pujol, MJ and Tusell, JM and Serratosa, J}, title = {Effect of different convulsants on calmodulin levels and proto-oncogene c-fos expression in the central nervous system.}, journal = {Brain research. Molecular brain research}, volume = {14}, number = {4}, pages = {285-292}, doi = {10.1016/0169-328x(92)90095-s}, pmid = {1382176}, issn = {0169-328X}, mesh = {Animals ; Brain/drug effects ; Calcium Channel Blockers/pharmacology ; Calcium Channels/drug effects/physiology ; Calmodulin/*metabolism ; Cell Nucleus/ultrastructure ; Convulsants/*pharmacology ; Gene Expression Regulation/*drug effects ; Genes, fos/*genetics ; Hexachlorocyclohexane/*pharmacology ; Male ; Nerve Tissue Proteins/*metabolism ; Neurons/drug effects/ultrastructure ; Rats ; Rats, Inbred Strains ; Stereoisomerism ; Synaptosomes/ultrastructure ; }, abstract = {In the present study, a relationship between convulsant activity and two cellular events, changes in calmodulin (CaM) concentration and proto-oncogene c-fos expression has been considered. c-fos has been found activated after the administration of the organochlorine insecticide lindane, the Ca2+ channel agonist Bay K, and N-methyl-D-aspartate (NMDA). The administration of the voltage-dependent Ca2+ channel antagonist nifedipine was able to block the expression elicited by lindane. The effect of lindane on c-fos expression could not be blocked by prior administration of MK-801, a non-competitive antagonist of the NMDA receptor. These results suggest a possible role for the voltage-dependent Ca2+ channels in the mechanism of action of lindane. By means of in situ hybridization, the different patterns of c-fos expression after the administration of the mentioned compounds have been described. A possible modification of the levels of CaM has also been investigated. Among all the subcellular fractions considered, only levels of nuclear CaM appeared to be affected after the different treatments. The changes observed seemed to follow a similar pattern to that described for c-fos induction. Calcium entry through these voltage-dependent calcium channels would be the link between membrane depolarizing events and expression of c-fos and/or increase in nuclear CaM.}, }
@article {pmid1618839, year = {1992}, author = {Carr, DW and Hausken, ZE and Fraser, ID and Stofko-Hahn, RE and Scott, JD}, title = {Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain.}, journal = {The Journal of biological chemistry}, volume = {267}, number = {19}, pages = {13376-13382}, pmid = {1618839}, issn = {0021-9258}, support = {DK 08767/DK/NIDDK NIH HHS/United States ; DK 44239/DK/NIDDK NIH HHS/United States ; GM 44427/GM/NIGMS NIH HHS/United States ; }, mesh = {A Kinase Anchor Proteins ; *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Autoradiography ; Base Sequence ; Carrier Proteins/genetics/*metabolism ; Circular Dichroism ; Cloning, Molecular ; DNA ; Electrophoresis, Polyacrylamide Gel ; Humans ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Phosphorylation ; Protein Conformation ; Protein Kinases/*metabolism ; Thyroid Gland/*metabolism ; }, abstract = {The type II cAMP-dependent protein kinase (PKA) is localized to specific subcellular environments through binding of the dimeric regulatory subunit (RII) to anchoring proteins. Subcellular localization is likely to influence which substrates are most accessible to the catalytic subunit upon activation. We have previously shown that the RII-binding domains of four anchoring proteins contain sequences which exhibit a high probability of amphipathic helix formation (Carr, D. W., Stofko-Hahn, R. E., Fraser, I. D. C., Bishop, S. M., Acott, T. E., Brennan, R. G., and Scott J. D. (1991) J. Biol. Chem. 266, 14188-14192). In the present study we describe the cloning of a cDNA which encodes a 1015-amino acid segment of Ht 31. A synthetic peptide (Asp-Leu-Ile-Glu-Glu-Ala-Ala-Ser-Arg-Ile-Val-Asp-Ala-Val-Ile-Glu-Gln-Val -Lys-Ala-Ala-Tyr) representing residues 493-515 encompasses the minimum region of Ht 31 required for RII binding and blocks anchoring protein interaction with RII as detected by band-shift analysis. Structural analysis by circular dichroism suggests that this peptide can adopt an alpha-helical conformation. Both Ht 31 (493-515) peptide and its parent protein bind RII alpha or the type II PKA holoenzyme with high affinity. Equilibrium dialysis was used to calculate dissociation constants of 4.0 and 3.8 nM for Ht 31 peptide interaction with RII alpha and the type II PKA, respectively. A survey of nine different bovine tissues was conducted to identify RII binding proteins. Several bands were detected in each tissues using a 32P-RII overlay method. Addition of 0.4 microM Ht 31 (493-515) peptide to the reaction mixture blocked all RII binding. These data suggest that all anchoring proteins bind RII alpha at the same site as the Ht 31 peptide. The nanomolar affinity constant and the different patterns of RII-anchoring proteins in each tissue suggest that the type II alpha PKA holoenzyme may be specifically targeted to different locations in each type of cell.}, }
@article {pmid1601043, year = {1992}, author = {Leenen, PJ and Melis, M and Kraal, G and Hoogeveen, AT and Van Ewijk, W}, title = {The monoclonal antibody ER-BMDM1 recognizes a macrophage and dendritic cell differentiation antigen with aminopeptidase activity.}, journal = {European journal of immunology}, volume = {22}, number = {6}, pages = {1567-1572}, doi = {10.1002/eji.1830220633}, pmid = {1601043}, issn = {0014-2980}, mesh = {Aminopeptidases/*immunology ; Animals ; Antibodies, Monoclonal/*immunology ; Antibody Specificity ; Antigens, Differentiation/*immunology ; Dendritic Cells/*enzymology ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Gene Expression ; Hybridomas ; In Vitro Techniques ; Intestine, Small/immunology ; Liver/immunology ; Lung/immunology ; Lymph Nodes/immunology ; Macrophages/*enzymology ; Male ; Mice ; Mice, Inbred BALB C ; Rats ; Spleen/immunology ; Thymus Gland/immunology ; }, abstract = {Here we describe the reactivity of monoclonal antibody (mAb) ER-BMDM1, directed against a 160-kDa cell membrane-associated antigen (Ag) with amino-peptidase activity. The aminopeptidase recognized by ER-BMDM1 is present on various mouse macrophage (M phi) and dendritic cell (DC) subpopulations as well as on microvillous epithelia. Analysis of ER-BMDM1 Ag expression in in vitro models of M phi maturation revealed that the Ag is expressed at increasing levels upon maturation of M phi. In vivo, high level expression of the ER-BMDM1 Ag occurs after the monocytic stage of maturation, since bone marrow cells and peripheral blood monocytes are essentially ER-BMDM1 negative. Analysis of isolated-resident and elicited M phi populations showed that ER-BMDM1 recognizes a specific subpopulation of mature M phi: only some resident peritoneal and alveolar M phi are ER-BMDM1 positive, whereas virtually all thioglycollate-elicited peritoneal exudate M phi bind the mAb. In lymphoid organs, a subpopulation of M phi is recognized as well as interdigitating cells (IDC) located in T cell areas. Phenotypic analysis of isolated DC--the in vitro equivalents of IDC--from spleen and lymph nodes confirmed that the majority of this important antigen-presenting cell population expresses the ER-BMDM1 aminopeptidase. The molecular characteristics of the ER-BMDM1 Ag suggest that it may represent the mouse homolog of human CD13.}, }
@article {pmid1590237, year = {1992}, author = {Manolio, TA and Baughman, KL and Rodeheffer, R and Pearson, TA and Bristow, JD and Michels, VV and Abelmann, WH and Harlan, WR}, title = {Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop.}, journal = {The American journal of cardiology}, volume = {69}, number = {17}, pages = {1458-1466}, doi = {10.1016/0002-9149(92)90901-a}, pmid = {1590237}, issn = {0002-9149}, mesh = {*Cardiomyopathy, Dilated/diagnosis/epidemiology/etiology/therapy ; Humans ; Incidence ; Prevalence ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.}, }
@article {pmid1590235, year = {1992}, author = {Dusleag, J and Klein, W and Eber, B and Gasser, R and Brussee, H and Rotman, B and Grisold, M}, title = {Frequency of magnetic resonance signal abnormalities of the brain in patients aged less than 50 years with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {69}, number = {17}, pages = {1446-1450}, doi = {10.1016/0002-9149(92)90899-a}, pmid = {1590235}, issn = {0002-9149}, mesh = {Adolescent ; Adult ; Age Factors ; Brain/pathology ; Brain Diseases/complications/*diagnosis ; Cardiomyopathy, Dilated/*complications/diagnostic imaging/physiopathology ; Echocardiography ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; }, abstract = {Twenty patients with idiopathic dilated cardiomyopathy (IDC) aged less than 50 years (mean 41) and an age-matched group of 20 healthy volunteers were studied. All subjects were free of cerebrovascular symptoms and risk factors for stroke. Magnetic resonance imaging of the brain, extracranial Doppler ultrasonography, heart catheterization and echocardiography were performed. In patients with IDC, a higher frequency of ventricular enlargement (p less than 0.02), cortical atrophy (p less than 0.01) and white matter lesions (p less than 0.05) was observed. Cerebral infarcts were found in 4 patients (p less than 0.05) who showed clinically severe limitation of functional capacity (New York Heart Association class III or IV). The extent of cortical atrophy, and the duration of clinical evidence of IDC showed a significant correlation (p less than 0.04). The data indicate a high incidence of parenchymal abnormalities of the brain in young, neurologically asymptomatic patients with IDC.}, }
@article {pmid1335439, year = {1992}, author = {Bhave, S and Saxena, R and Jambhekar, N}, title = {Paget's disease of the breast: a study of 43 cases.}, journal = {Indian journal of cancer}, volume = {29}, number = {2}, pages = {90-95}, pmid = {1335439}, issn = {0019-509X}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Paget's Disease, Mammary/*pathology ; }, abstract = {Paget's Disease of the breast is caused by spread of duct carcinoma cells along the mammary ducts to the epidermis of the nipple and areola. This is a study of 43 cases of Paget's Disease of the breast. Though only few patients presented with a lump; a carcinoma, either DCIS or IDC or both were found in all cases. The presence of an underlying breast carcinoma in Paget's Disease of the breast suggests that radical mastectomy is the treatment of choice in this condition.}, }
@article {pmid1320141, year = {1992}, author = {Enjoji, M and Matsukuma, A and Sakamoto, G and Toyoshima, S and Hirota, T and Wada, A and Ishida, T and Enomoto, K and Koyama, H and Yamamoto, H}, title = {Invasive ductal carcinoma of the breast with a predominant intraductal component: cooperative clinicopathologic study in seven Japanese centers.}, journal = {Japanese journal of clinical oncology}, volume = {22}, number = {2}, pages = {84-91}, pmid = {1320141}, issn = {0368-2811}, mesh = {Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology/secondary ; Female ; Follow-Up Studies ; Histocytological Preparation Techniques ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Mastectomy, Radical ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Prognosis ; Survival Rate ; }, abstract = {A nationwide multicenter joint study was undertaken to investigate the clinicopathologic characteristics of invasive ductal carcinoma of the breast with a predominant intraductal component, a diagnostic entity proposed in the histologic typing of breast tumors by the World Health Organization in 1981. A total of 368 tumors, of which 218 were studied pathologically between 1983 and 1987 and 150 between 1971 and 1977, were accumulated for the present study from seven medical institutes in Japan. The incidence of such types of tumor was higher in the latter period than in the former, as was that of pure intraductal carcinomas. Seventy of the 368 tumors displayed metastatic nodal involvement and nine tumor deaths were observed from 150 tumors followed up for over 10 years following radical mastectomy, the overall quantity of the extraductal stromal invasion clearly acting on lymph node metastases and patients' outcome. We consider a total stromal invasion of greater than 5 mm to be critical in the prognosis of patients with tumor of this type.}, }
@article {pmid1311717, year = {1992}, author = {Bristow, MR and Minobe, W and Rasmussen, R and Larrabee, P and Skerl, L and Klein, JW and Anderson, FL and Murray, J and Mestroni, L and Karwande, SV}, title = {Beta-adrenergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms.}, journal = {The Journal of clinical investigation}, volume = {89}, number = {3}, pages = {803-815}, pmid = {1311717}, issn = {0021-9738}, mesh = {Adenylyl Cyclases/analysis ; Adult ; Cardiomyopathy, Dilated/physiopathology ; Catecholamines/analysis ; Female ; Heart/*physiopathology ; Heart Failure/*physiopathology ; Humans ; Hypertension, Pulmonary/*physiopathology ; Iodocyanopindolol ; Isoproterenol/metabolism ; Male ; Myocardial Contraction ; Neuropeptide Y/analysis ; Pindolol/analogs &amp; derivatives/metabolism ; Receptors, Adrenergic, alpha/analysis/physiology ; Receptors, Adrenergic, beta/analysis/*physiology ; }, abstract = {In order to investigate the general cause of beta-adrenergic receptor neuroeffector abnormalities in the failing human heart, we measured ventricular myocardial adrenergic receptors, adrenergic neurotransmitters, and beta-adrenergic receptor-effector responses in nonfailing and failing hearts taken from nonfailing organ donors, subjects with endstage biventricular failure due to idiopathic dilated cardiomyopathy (IDC), and subjects with primary pulmonary hypertension (PPH) who exhibited isolated right ventricular failure. Relative to nonfailing PPH left ventricles, failing PPH right ventricles exhibited (a) markedly decreased beta 1-adrenergic receptor density, (b) marked depletion of tissue norepinephrine and neuropeptide Y, (c) decreased adenylate cyclase stimulation in response to the beta agonists isoproterenol and zinterol, and (d) decreased adenylate cyclase stimulation in response to Gpp(NH)p and forskolin. These abnormalities were directionally similar to, but generally more pronounced than, corresponding findings in failing IDC right ventricles, whereas values for these parameters in nonfailing left ventricles of PPH subjects were similar to values in the nonfailing left ventricles of organ donors. Additionally, relative to paired nonfailing PPH left ventricles and nonfailing right ventricles from organ donors, failing right ventricles from PPH subjects exhibited decreased adenylate cyclase stimulation by MnCl2. These data indicate that: (a) Adrenergic neuroeffector abnormalities present in the failing human heart are due to local mechanisms; systemic processes do not produce beta-adrenergic neuroeffector abnormalities. (b) Pressure-overloaded failing right ventricles of PPH subjects exhibit decreased activity of the catalytic subunit of adenylate cyclase, an abnormality not previously described in the failing human heart.}, }
@article {pmid1373548, year = {1992}, author = {Shamoto, M and Shinzato, M and Hosokawa, S and Kaneko, C and Hakuno, T and Nomoto, K}, title = {Langerhans cells in the lymph node: mirror section and immunoelectron microscopic studies.}, journal = {Virchows Archiv. B, Cell pathology including molecular pathology}, volume = {61}, number = {5}, pages = {337-341}, doi = {10.1007/BF02890436}, pmid = {1373548}, issn = {0340-6075}, mesh = {Aged ; Antigens, CD/*analysis ; Antigens, CD1 ; Female ; Humans ; Langerhans Cells/*immunology/ultrastructure ; Lymph Nodes/*immunology/ultrastructure ; Male ; Microscopy, Immunoelectron ; Middle Aged ; S100 Proteins/analysis ; Spleen/immunology/ultrastructure ; }, abstract = {Cells immunostained with antibodies against both OKT-6 and S-100 protein were observed only in superficial and hilar lymph nodes draining tissues with predominantly squamous epithelia. In contrast, in mesenteric lymph nodes and the spleen, only S-100 protein-positive, but OKT-6-negative cells were found. We suspect that the S-100 and OKT-6-positive cells might be Langerhans cells (LC) and the S-100-positive, OKT-6-negative cells, interdigitating reticulum cells (IDC). We further postulate that the LC in superficial and hilar lymph nodes might migrate from squamous epithelia, with which contact is required for the formation of Birbeck granules.}, }
@article {pmid1323259, year = {1992}, author = {Bristow, MR and Feldman, AM}, title = {Changes in the receptor-G protein-adenylyl cyclase system in heart failure from various types of heart muscle disease.}, journal = {Basic research in cardiology}, volume = {87 Suppl 1}, number = {}, pages = {15-35}, doi = {10.1007/978-3-642-72474-9_2}, pmid = {1323259}, issn = {0300-8428}, mesh = {Adenylyl Cyclases/*metabolism ; Cardiomyopathies/*physiopathology ; Cardiomyopathy, Dilated/physiopathology ; Down-Regulation ; GTP-Binding Proteins/*metabolism ; Heart/*physiopathology ; Humans ; Hypertension, Pulmonary/physiopathology ; Receptors, Adrenergic, beta/*metabolism ; }, abstract = {The abnormalities of the receptor-G protein-adenylyl cyclase (RCG) system in failing human myocardium as the result of 1) idiopathic dilated cardiomyopathy (IDC), 2) ischemic dilated cardiomyopathy (ISCDC), and 3) primary pulmonary hypertension (PPH) were investigated. Depending on the etiology of heart failure, abnormalities of the RCG system result from a reduced number of beta 1 receptors, uncoupling of beta 1 or beta 2 receptors, alteration of G protein function, or decreased catalytic subunit activity of adenylyl cyclase. Compared to IDC, beta 1 receptor down-regulation is less pronounced in ISCDC, and slightly more pronounced in PPH. Preliminary data suggest that beta 1 receptor down-regulation results from alteration in steady-state receptor mRNA levels. Increased functional activity of Gi protein, which seems to result from posttranslational modification, is observed in IDC and ISCDC. Altered Gi protein function may be the basis for beta-receptor uncoupling in IDC and ISCDC, whereas in PPH, this phenomenon may result from altered adenylyl cyclase function. Catalytic subunit activity of adenylyl cyclase is decreased in order of increasing pulmonary hypertension in right-ventricular preparations from PPH greater than IDC greater than ISCDC. However, catalytic subunit activity is similar in LV preparations from all three groups. The decrease in adenylyl cyclase catalytic subunit activity may be the result of the marked cellular injury produced by pressure overload. In summary, numerous desensitization phenomena occur in the failing human heart that are etiology- or model-dependent. To a certain extent, these changes are teleologically beneficial, as they are able to partially protect the failing heart from potentially toxic adrenergic stimuli.}, }
@article {pmid1322388, year = {1992}, author = {Solin, LJ and Fowble, BL and Yeh, IT and Kowalyshyn, MJ and Schultz, DJ and Weiss, MC and Goodman, RL}, title = {Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation.}, journal = {International journal of radiation oncology, biology, physics}, volume = {23}, number = {5}, pages = {961-968}, doi = {10.1016/0360-3016(92)90900-3}, pmid = {1322388}, issn = {0360-3016}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/radiotherapy/*surgery ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Retrospective Studies ; Survival Analysis ; Survival Rate ; }, abstract = {An analysis was performed of 39 consecutive women with microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation during the period 1977 to 1988. Microinvasive ductal carcinoma was defined as predominantly intraductal carcinoma with microscopic or early invasion. Surgical treatment of the primary tumor included excisional biopsy or wide resection. Axillary lymph node staging showed that 37 patients were pathologically node negative and two patients were pathologically node positive, each with only one positive lymph node. The median follow-up was 55 months (mean = 65 months; range = 25-135 months). The 5-year actuarial rate of overall and cause-specific survival were both 97%. The 5-year actuarial rate of freedom from distant metastases was 93%. Nine patients developed a recurrence in the breast; eight of the nine patients had isolated local only first failures, and one of the nine patients had a local recurrence simultaneously with distant metastases. The median time to local failure was 42 months (mean = 53 months; range = 20-116 months). Of the eight patients with local only first failure, seven patients have been salvaged with further treatment and remain free of disease at the time of last follow-up, and one patient has died of subsequent distant metastatic disease. Median follow-up after salvage treatment was 29 months (mean = 27 months; range = 0-54 months). Comparison of the patients with microinvasive ductal carcinoma with two control groups of intraductal carcinoma and invasive ductal carcinoma was performed. Although the rate of local failure was significantly higher for patients with microinvasive ductal carcinoma as compared to the two control groups, the rates of survival and freedom from distant metastases for patients with microinvasive ductal carcinoma were intermediate to the two control groups. Because of the high rates of survival and freedom from distant metastases and because of the ability to salvage patients with local recurrence, breast-conserving surgery and definitive irradiation should continue to be considered as an alternative to mastectomy for appropriately selected and staged patients with microinvasive ductal carcinoma of the breast.}, }
@article {pmid1283028, year = {1992}, author = {Wolfersdorf, M and Faust, V and Hölzer, R}, title = {[Suicide in the Ravensburg/Oberschwaben area. Results of a study of 508 suicides based on criminal police records].}, journal = {Schweizer Archiv fur Neurologie und Psychiatrie (Zurich, Switzerland : 1985)}, volume = {143}, number = {6}, pages = {485-495}, pmid = {1283028}, issn = {0258-7661}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Cause of Death ; Cross-Sectional Studies ; Female ; Germany/epidemiology ; Humans ; Incidence ; Male ; Mental Disorders/mortality ; Middle Aged ; Motivation ; Suicide/*legislation &amp; jurisprudence/psychology/statistics &amp; numerical data ; }, abstract = {On the basis of criminal police files we studied 508 suicides which happened between 1970 up to 1981 in the Ravensburg area in southern Germany. The police files also included medical records about in- or outpatient psychiatric treatment and also data about former violent behaviour. Mental disease as follows were most frequent: Depression 66% (diagnoses were made according to IDC-0 by two doctors under supervision of two senior psychiatrists; ICD-9: 300.4, 309.0 and 309.1 22%, ICD-9 296.1, 296.3 7.1% of the entire suicide group); neuroses and personality disorders 19%, addition, especially alcoholism, 28%. No psychiatric diagnosis could be made retrospectively in 10.6% (54 suicides). Sign in the presuicidal development like depressive symptoms, hopelessness and feelings of having no future, sleeping disturbances, feelings of guilt and anxiety, inner restlessness, but also changes in the direction of serenity and relaxation, treats of suicidal behaviour and reactions of the family and environment were reported showing a broad span of reactions from lack of perception to wrong interpretation. 15% of the suicides had also criminal activities in their former history. From a psychiatric point of view, improved diagnostic and therapeutic procedures in the treatment of the mentally ill, especially in the field of outpatient medical care of depressive and addictive patients, and better information of the relatives is to be demanded in order to prevent suicides.}, }
@article {pmid1764031, year = {1991}, author = {Jaeger, JL and Shimizu, N and Gitlin, JD}, title = {Tissue-specific ceruloplasmin gene expression in the mammary gland.}, journal = {The Biochemical journal}, volume = {280 (Pt 3)}, number = {Pt 3}, pages = {671-677}, pmid = {1764031}, issn = {0264-6021}, support = {HL41536/HL/NHLBI NIH HHS/United States ; }, mesh = {Aging/metabolism ; Animals ; Blotting, Northern ; Blotting, Western ; Cell Differentiation ; Ceruloplasmin/genetics/immunology/isolation &amp; purification/*metabolism ; Female ; Frozen Sections ; Gene Expression ; Liver/metabolism ; Male ; Mammary Glands, Animal/*metabolism ; Nucleic Acid Hybridization ; Organ Specificity ; RNA, Antisense ; RNA, Messenger ; Rats ; Transferrin/isolation &amp; purification ; }, abstract = {Using a ceruloplasmin cDNA clone in RNA blot analysis, a single 3.7 kb ceruloplasmin-specific transcript was detected in rat mammary gland tissue from pregnant and lactating animals. Ceruloplasmin gene expression in the mammary gland was tissue-specific, with no evidence of expression in brain, heart or other extrahepatic tissues. Ceruloplasmin mRNA was also detected in mammary gland tissue from male, virgin female and non-pregnant/multiparous animals, and the abundance of ceruloplasmin-specific transcripts in virgin female rats was independent of their stage of oestrus. In virgin female mammary gland the content of ceruloplasmin mRNA was 20% of that in hepatic tissue from these animals and approx. 2-3-fold greater than that found in mammary gland tissue of pregnant or lactating animals. Development studies revealed ceruloplasmin gene expression in male and female mammary gland by only 2 weeks of age, prior to the onset of puberty. Biosynthetic studies indicated that the ceruloplasmin mRNA in mammary gland tissue was translated into a 132 kDa protein qualitatively similar to that synthesized in liver. By in situ hybridization, ceruloplasmin gene expression was localized to the epithelium lining the mammary gland alveolar ducts, without evidence of expression in the surrounding mesenchyme. Ceruloplasmin gene expression was also detected in a human breast adenocarcinoma cell line and in biopsy tissue from women with invasive ductal carcinoma. Taken together, these data indicate that the mammary gland is a prominent site of extrahepatic ceruloplasmin gene expression and add to the evidence that ceruloplasmin biosynthesis is associated with growth and differentiation in non-hepatic tissues.}, }
@article {pmid1777424, year = {1991}, author = {Mjaaland, S and Fossum, S}, title = {Antigen targetting with monoclonal antibodies as vectors--II. Further evidence that conjugation of antigen to specific monoclonal antibodies enhances uptake by antigen presenting cells.}, journal = {International immunology}, volume = {3}, number = {12}, pages = {1315-1321}, doi = {10.1093/intimm/3.12.1315}, pmid = {1777424}, issn = {0953-8178}, mesh = {Adjuvants, Immunologic ; Animals ; Antibodies, Monoclonal/*immunology/metabolism ; Antigen-Presenting Cells/*immunology ; Antigens/*administration &amp; dosage ; Blotting, Western ; Fluorescein-5-isothiocyanate ; Haptens ; Histocompatibility Antigens Class II/immunology ; Lymph Nodes/cytology/immunology ; Rats ; Rats, Inbred Strains ; }, abstract = {Immunization of rats with haptenized monoclonal antibodies (mAbs) against accessory cells enhances anti-hapten antibody responses. To see whether the mAb-conjugates really targetted the antigen (hapten) to the antigen presenting cells, we have investigated the lymph node distribution of locally injected radiolabelled conjugates. Compared with control conjugates, i.e. haptenized non-binding mAbs, a much larger proportion of the specific conjugates were retained in the draining lymph nodes. Whereas control conjugates were rapidly phagocytosed and degraded by macrophages, the specific conjugates were associated with the targetted accessory cells, which were radiolabelled for extended periods. Haptenated MRC OX6 (anti-MHC class II) gave strong labelling of interdigitating cells (IDC) in the paracortex with 70% of IDC still labelled by 4 days and 15% by 16 days following injection. By Western blots intact OX6 conjugates were still detected in the draining lymph node as long as 3 days after injections, whereas control conjugates were hardly detectable even by 24 h. The findings substantiate the idea that mAbs can be exploited for vectorial transport of antigens to accessory cells.}, }
@article {pmid1683602, year = {1991}, author = {Woodley, SL and Gilbert, EM and Anderson, JL and O'Connell, JB and Deitchman, D and Yanowitz, FG and Mealey, PC and Volkman, K and Renlund, DG and Menlove, R}, title = {Beta-blockade with bucindolol in heart failure caused by ischemic versus idiopathic dilated cardiomyopathy.}, journal = {Circulation}, volume = {84}, number = {6}, pages = {2426-2441}, doi = {10.1161/01.cir.84.6.2426}, pmid = {1683602}, issn = {0009-7322}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Age Factors ; Cardiomyopathy, Dilated/*complications ; Double-Blind Method ; Exercise ; Female ; Heart Failure/*drug therapy/etiology/physiopathology ; Hemodynamics/drug effects ; Humans ; Male ; Middle Aged ; Norepinephrine/blood ; Propanolamines/*therapeutic use ; Ventricular Function, Left/drug effects ; }, abstract = {BACKGROUND: We investigated the effects of bucindolol, a nonselective, non-ISA beta-blocker with mild-vasodilatory properties, in patients with congestive heart failure from ischemic dilated cardiomyopathy (ISCDC, n = 27) and compared the results with those in subjects with heart failure from idiopathic dilated cardiomyopathy (IDC, n = 22).<br><br>METHODS AND RESULTS: Patients were randomized in a double-blind fashion to receive 12 weeks' treatment with either bucindolol or placebo, with randomization stratified for IDC or ISCDC: Invasive (right heart catheterization) and noninvasive (echo, MUGA, central venous norepinephrine, exercise treadmill studies, and symptom scores) tests of heart failure severity were determined at baseline and end of the study. For all subjects (ISCDC plus IDC), relative to placebo treatment, bucindolol-treated patients had significant improvement in ejection fraction, left ventricular size and filling pressure, stroke work index, symptom score, and central venous norepinephrine. However, most of these differences could be attributed to improvement in the IDC subgroup, as the only parameter with a statistically significant degree of improvement in the bucindolol-treated ISCDC subgroup was left ventricular size.<br><br>CONCLUSIONS: We conclude that beta-blockade may produce quantitatively different degrees of response in different kinds of heart muscle disease.}, }
@article {pmid1666557, year = {1991}, author = {Schmitz, W and Eschenhagen, T and Mende, U and Müller, FU and Scholz, H}, title = {The role of alpha 1-adrenergic and muscarinic receptors in cardiac function.}, journal = {European heart journal}, volume = {12 Suppl F}, number = {}, pages = {83-87}, doi = {10.1093/eurheartj/12.suppl_f.83}, pmid = {1666557}, issn = {0195-668X}, mesh = {Animals ; Carbachol/pharmacology ; Depression, Chemical ; Humans ; Myocardial Contraction/drug effects/*physiology ; Phenylephrine/pharmacology ; Receptors, Adrenergic, alpha/drug effects/*physiology ; Receptors, Muscarinic/drug effects/*physiology ; Stimulation, Chemical ; }, abstract = {The positive inotropic effect of an alpha 1-adrenoceptor agonist, such as phenylephrine, is accompanied by an increase in the presumed second messenger, inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4), which may release calcium from the sarcoplasmic reticulum (SR) and/or facilitate calcium entry from the extracellular space. In addition, phenylephrine sensitizes the contractile proteins for calcium. Alpha 1-adrenergic positive inotropic effects are enhanced in heart muscle preparations from cardiomyopathic hamsters and are reduced in heart muscle preparations from human failing myocardium. How the negative inotropic effects of M-cholinoceptor agonists work in the presence of cAMP-increasing agents in ventricular heart muscle preparations is discussed. It involves cAMP-reduction, an increase in cGMP and activation of phosphatase activity. In a rat model, chronic beta-adrenergic stimulation leads to increased sensitivity of rat ventricular tissue for the negative inotropic effect of the M-cholinoceptor agonist, carbachol. This might be due to facilitated signal transduction via increased Gi proteins. In human ventricular tissue from hearts with end-stage heart failure, due to idiopathic dilated cardiomyopathy (IDC), an increased Gi protein has also been found. However, the negative inotropic effects of carbachol were unchanged. The data indicate that changes in alpha-adrenergic and M-cholinergic responses in the heart may depend on underlying causes that induce changes.}, }
@article {pmid1657351, year = {1991}, author = {Solin, LJ and Recht, A and Fourquet, A and Kurtz, J and Kuske, R and McNeese, M and McCormick, B and Cross, MA and Schultz, DJ and Bornstein, BA}, title = {Ten-year results of breast-conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ) of the breast.}, journal = {Cancer}, volume = {68}, number = {11}, pages = {2337-2344}, doi = {10.1002/1097-0142(19911201)68:11&lt;2337::aid-cncr2820681102&gt;3.0.co;2-r}, pmid = {1657351}, issn = {0008-543X}, mesh = {Actuarial Analysis ; Adult ; Aged ; Breast Neoplasms/*radiotherapy/*surgery ; Carcinoma in Situ/*radiotherapy/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*radiotherapy/secondary/*surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Survival Analysis ; }, abstract = {An analysis of 259 women with 261 treated breasts from nine institutions in Europe and the United States was performed to determine the 10-year results of the treatment of intraductal carcinoma of the breast with definitive irradiation. All patients had undergone complete gross excision of the primary intraductal carcinoma, and definitive breast irradiation was delivered in all cases. The median follow-up time was 78 months (range, 11 to 197 months). The 10-year actuarial overall survival rate was 94%, and the 10-year actuarial cause-specific survival rate (including deaths only from carcinoma of the breast) was 97%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 28 failures in the breast, and the 10-year actuarial rate of local failure was 16%. The pathologic type of local recurrences showed invasive ductal carcinoma in 14 of 28 recurrences (50%) and noninvasive ductal carcinoma in 14 of 28 recurrences (50%). The median time to local failure was 50 months (range, 17 to 129 months). Twenty-four of 28 patients with local failure were salvaged with additional treatment, generally mastectomy, and 4 of 28 patients with local failure subsequently had distant metastases. Median follow-up time after salvage treatment of breast recurrence was 29 months (range, 3 to 90 months). Two patients without local failure subsequently had distant metastases, one of which occurred after a node-positive, contralateral breast carcinoma. These results demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases for the treatment of patients with intraductal carcinoma of the breast. The local recurrences within the treated breast were generally salvaged with additional treatment, although with limited follow-up. Because of the long natural history of intraductal carcinoma of the breast, prolonged and careful follow-up of patients after breast-conservation and definitive irradiation is required.}, }
@article {pmid1655233, year = {1991}, author = {Pienta, KJ and Coffey, DS}, title = {Correlation of nuclear morphometry with progression of breast cancer.}, journal = {Cancer}, volume = {68}, number = {9}, pages = {2012-2016}, doi = {10.1002/1097-0142(19911101)68:9&lt;2012::aid-cncr2820680928&gt;3.0.co;2-c}, pmid = {1655233}, issn = {0008-543X}, support = {CA15416/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/secondary/surgery ; Cell Nucleus/*ultrastructure ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies ; }, abstract = {Alterations in nuclear structure are the morphologic hallmark of cancer diagnosis. Nuclear size, shape, chromatin pattern, and nucleolar size and number have all been reported to change in breast cancer. Attempts to quantify nuclear alterations to establish grading systems, predict prognosis, and/or set guidelines for therapy have met with varied success. Therefore, the authors quantified the changes that occur with breast cancer with nuclear morphology in several different groups of patients: normal controls, intraductal carcinoma, invasive ductal carcinoma with negative nodes at mastectomy, and invasive ductal carcinoma with positive lymph nodes. Pleomorphism as measured by both nuclear area and intrasample variation increased with invasive histology and metastatic breast cancer. It is still unclear whether node-negative Stage II breast cancer requires adjuvant therapy. This issue would be less complicated if it were possible to identify those women at high risk of recurrence. Therefore, the authors retrospectively identified 30 women with node-negative Stage II infiltrating ductal carcinoma with a long follow-up period of 6 to 12 years. Computer-assisted morphometry of nuclei in routine hematoxylin and eosin-stained pathologic slides was done using the DynaCell Analysis System in a blinded fashion. DynaCell measures 15 nuclear parameters, including perimeter, area volume, roundness, and ellipticity. Although nuclear area and variance were related to breast cancer progression, nuclear morphometry did not predict successfully which patients would have recurrent disease in the women with Stage II, node-negative lesions at the time of mastectomy.}, }
@article {pmid1724633, year = {1991}, author = {Chen, ZL and Wen, DR and Coulson, WF and Giuliano, AE and Cochran, AJ}, title = {Occult metastases in the axillary lymph nodes of patients with breast cancer node negative by clinical and histologic examination and conventional histology.}, journal = {Disease markers}, volume = {9}, number = {5}, pages = {239-248}, pmid = {1724633}, issn = {0278-0240}, support = {CA 29605/CA/NCI NIH HHS/United States ; CA 43658/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies ; Breast Neoplasms/*pathology ; Carcinoma/diagnosis/*secondary ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*secondary ; False Negative Reactions ; Female ; Humans ; Immunohistochemistry ; Keratins/analysis ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; }, abstract = {We examined axillary lymph nodes from 80 women with node-negative breast cancer, by immunohistochemistry, utilizing polyclonal antibodies to cytokeratins and carcino-embryonic antigen and monoclonal antibodies to cytokeratins and milk fat globulin. Occult metastatic tumor, undetectable in hematoxylin and eosin stained slides, but visible by immunohistochemistry, was detected in 23 of 80 patients (29 per cent). Occult tumor was observed in patients with invasive ductal carcinoma (21/76-28 per cent) and in individuals with invasive lobular carcinoma (2/4-50 per cent). In patients with occult metastases the primary tumors were slightly larger (mean 2.39 cm, range 1.00-5.00 cm) than those of patients whose nodes were negative for tumor cells (mean, 2.03 cm, range, 0.60-4.50 cm). Information concerning clinical outcome is available for 61 patients followed for between 1 and 7 years (mean 3.2 years). Three of 17 patients (18 per cent) who had occult tumor in the nodes developed distant metastases, all less than 3 years after initial surgery. One of the 44 patients (2 per cent) whose nodes were free of occult tumor developed distant metastases 5 years following surgery. Local recurrences in the area of the mastectomy occurred in one of 17 patients with occult nodal tumor (6 per cent), less than 1 year after surgery. Local recurrences were seen in three of 44 patients without occult metastases (7 per cent), in two patients 5 years after mastectomy and in one patient 7 years after mastectomy.}, }
@article {pmid1661623, year = {1991}, author = {Noguchi, M and Taniya, T and Ohta, N and Koyasaki, N and Miyazaki, I and Mizukami, Y}, title = {Lymph node metastases versus DNA ploidy as prognostic factors for invasive ductal carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {19}, number = {1}, pages = {23-31}, pmid = {1661623}, issn = {0167-6806}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/mortality/pathology/secondary ; DNA, Neoplasm/*genetics ; Data Interpretation, Statistical ; Female ; Flow Cytometry ; Humans ; *Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; *Ploidies ; Prognosis ; Survival Rate ; }, abstract = {We evaluated the relationship between the DNA ploidy status and other variable prognostic factors, especially regional lymph node metastases, in 121 patients with invasive ductal carcinoma of breast, together with the value of these factors in estimating the prognostic of breast cancer. The ploidy status was diploid in 40% of the patients, and aneuploid in 60%. A significantly higher incidence of aneuploidy was found in patients with more than 4 positive axillary lymph nodes, positive internal mammary lymph nodes, or clinical stage 3 of malignancy. In a univariate study, overall survival and disease-free survival were significantly correlated with axillary and internal mammary lymph node metastases, tumor size, and clinical stage of malignancy. The disease-free survival rates for the diploid group tended to be somewhat higher than those for the aneuploid group of patients without axillary lymph node metastases. In the multivariate analysis, however, only axillary lymph node metastasis was significantly correlated with overall survival and disease-free survival. There was also a trend for the internal mammary lymph node metastases to be correlated with survival. As the DNA ploidy status was closely correlated with the axillary and internal mammary lymph node metastases, it did not appear to be an independent prognostic factor in this small series.}, }
@article {pmid1653879, year = {1991}, author = {Lamovec, J and Bracko, M}, title = {Metastatic pattern of infiltrating lobular carcinoma of the breast: an autopsy study.}, journal = {Journal of surgical oncology}, volume = {48}, number = {1}, pages = {28-33}, doi = {10.1002/jso.2930480106}, pmid = {1653879}, issn = {0022-4790}, mesh = {Autopsy ; Breast Neoplasms/*pathology ; Carcinoma/*secondary ; Carcinoma, Intraductal, Noninfiltrating/secondary ; Chi-Square Distribution ; Female ; Humans ; }, abstract = {We analyzed the autopsy records and autopsy histological slides of 261 patients with breast carcinoma who died at the Institute of Oncology, Ljubljana, from January 1972 to October 1989, with particular attention to the metastatic pattern of infiltrating lobular carcinoma (ILC) which we compared with infiltrating ductal carcinoma (IDC). In 226 of 261 patients who died with metastatic disease there were 25 cases of ILC, 195 cases of IDC, 4 cases of mixed IDC-ILC, and 2 cases of mucinous carcinoma. There was no statistically significant difference in frequency of metastases to common metastatic sites, such as the liver, bone, and pleura, with the exception of the lungs, in which IDC metastases prevailed (P less than 0.006). By contrast, a statistically highly significant prevalence of ILC metastases to the peritoneum/retroperitoneum, hollow viscera, internal genital organs, leptomeninges, and myocardium was found (P values of less than 0.006- less than 10(-6). The metastases to these sites were characterized by diffuse growth of neoplastic cells that infiltrated in a lymphoma or leukemia-like fashion. Such metastases may remain clinically silent for a long time, in spite of their extensiveness. The difference of metastatic pattern between ILC and IDC is insufficiently appreciated in most of the published studies on ILC.}, }
@article {pmid1866769, year = {1991}, author = {Hsiao, L and Takahashi, K and Takeya, M and Arao, T}, title = {Differentiation and maturation of macrophages into interdigitating cells and their multicellular complex formation in the fetal and postnatal rat thymus.}, journal = {Thymus}, volume = {17}, number = {4}, pages = {219-235}, pmid = {1866769}, issn = {0165-6090}, mesh = {Animals ; Antibodies, Monoclonal ; Antigens, Differentiation/analysis ; Biomarkers ; Cell Differentiation ; Dendritic Cells/*cytology ; Female ; Gestational Age ; Histocompatibility Antigens Class II/analysis ; Langerhans Cells/cytology ; Macrophages/*cytology ; Male ; Microscopy, Immunoelectron ; Rats ; Rats, Inbred Strains ; Rosette Formation ; Thymus Gland/*cytology/embryology/growth &amp; development ; }, abstract = {Three mouse anti-rat macrophage monoclonal antibodies, TRPM-1, TRPM-2, and TRPM-3, as well as anti-rat Ia monoclonal antibody, were used to study the emergence, differentiation, and maturation of macrophages in the fetal and postnatal rat thymus immunohistochemically and immunoelectron microscopically. At 14 days of gestation, primitive/fetal macrophages entered the thymic primordium and showed Ia expression, where afterwards the epithelial cells also expressed Ia antigens prominently at 15 days of gestation. After 16 days of gestation, differentiation of a subpopulation of primitive/fetal macrophages into interdigitating cells (IDCs) is suggested. From 19 days of gestation, TRPM-1-positive dendritic cells including IDCs started forming multicellular complexes with thymocytes and the epithelial cells also formed similar complexes with thymocytes. One day after birth, TRPM-1 positive IDC-thymocyte complexes distributed throughout the thymic medulla. The number of TRPM-1- and Ia-positive IDCs increased by day, and Langerhans cells (LCs) appeared in the thymic medulla within a few days after birth. By two weeks after birth, the distribution pattern of Ia- and TRPM-1-positive cells became similar to that of adult rats. In ontogeny, intimate cell membrane appositions were frequently observed between thymocytes and Ia-positive epithelial cells or IDCs in the thymic multicellular complexes. These complexes were discriminated into two types; epithelial cell-thymocyte complexes and IDC- or LC-thymocyte ones. In vitro, two types of the thymic nurse cells (TNCs) were identified: epithelial cells and IDCs or LCs. Besides epithelial cells, IDCs or macrophages formed rosettes with thymocytes. These TNCs and rosettes in vitro seem to correspond to the thymic multicellular complexes in vivo.}, }
@article {pmid1851336, year = {1991}, author = {Kurtz, JM and Jacquemier, J and Brandone, H and Ayme, Y and Hans, D and Bressac, C and Spitalier, JM}, title = {Inoperable recurrence after breast-conserving surgical treatment and radiotherapy.}, journal = {Surgery, gynecology &amp; obstetrics}, volume = {172}, number = {5}, pages = {357-361}, pmid = {1851336}, issn = {0039-6087}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/mortality/*pathology/surgery ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; }, abstract = {Factors associated with inoperable local recurrence were investigated by a clinical and pathologic review of 596 patients with Stages I and II carcinoma of the breast treated by breast-conserving operations and megavoltage radiotherapy. After a median follow-up period of 71 months, 13 of 70 local recurrences observed were anatomically unsuitable for salvage surgical treatment, affecting 2.2 per cent of patients initially treated. In most, inoperable recurrences clinically resembled primary inflammatory carcinoma of the breast. All inoperable failures occurred in patients with invasive ductal carcinoma and were associated with the presence of unfavorable prognostic features (positive nodes, histologic grade 3, negative estrogen receptor, vascular invasion and lymphocytic stromal reaction). Despite doxorubicin-based chemotherapy, prognosis after inoperable recurrence was quite poor, although survival time in excess of two years was seen in receptor positive, lower grade recurrent tumors in which treatment included hormone therapy.}, }
@article {pmid1849988, year = {1991}, author = {Cochrane, HR and May, FE and Ashcroft, T and Dark, JH}, title = {Enteroviruses and idiopathic dilated cardiomyopathy.}, journal = {The Journal of pathology}, volume = {163}, number = {2}, pages = {129-131}, doi = {10.1002/path.1711630208}, pmid = {1849988}, issn = {0022-3417}, mesh = {Adult ; Animals ; Biopsy ; Cardiomyopathy, Dilated/etiology/*microbiology ; Child ; Coxsackievirus Infections ; Enterovirus/*isolation &amp; purification ; Enterovirus B, Human ; Enterovirus Infections/*complications ; Female ; Humans ; Male ; Mice ; Middle Aged ; Myocarditis/microbiology ; Myocardium/pathology ; Nucleic Acid Hybridization ; RNA Probes ; RNA, Viral/*analysis ; }, abstract = {Previous studies have suggested that some cases of idiopathic dilated cardiomyopathy (IDC) are due to persistent viral infection following an episode of viral myocarditis. Viral RNA sequences have recently been detected in material from patients with IDC using molecular biological techniques. We tested 40 samples from recipients' hearts explanted at cardiac transplantation for the presence of enteroviral RNA sequences, using a Northern blotting technique. Material from 19 cases of IDC and 21 cases of non-cardiomyopathic cardiac failure was examined together with Coxsackie-virus-infected neonatal mouse heart as a positive control and non-infected adult mouse heart as a negative control. A sharp band of viral RNA was detected in the positive control sample. No hybridization signal attributable to viral RNA was obtained for the negative control or for any of the test samples. We conclude that the role of enteroviruses in the pathogenesis of cardiomyopathy is not fully established and that further study is warranted.}, }
@article {pmid1825038, year = {1991}, author = {Carlquist, JF and Menlove, RL and Murray, MB and O'Connell, JB and Anderson, JL}, title = {HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies.}, journal = {Circulation}, volume = {83}, number = {2}, pages = {515-522}, doi = {10.1161/01.cir.83.2.515}, pmid = {1825038}, issn = {0009-7322}, support = {S07 RR-05804-09/RR/NCRR NIH HHS/United States ; }, mesh = {Cardiomyopathy, Dilated/epidemiology/*genetics ; Gene Frequency ; HLA-DQ Antigens/*genetics ; HLA-DR Antigens/*genetics ; Histocompatibility Testing ; Humans ; Meta-Analysis as Topic ; Reproducibility of Results ; Risk Factors ; }, abstract = {We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study. To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles. Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p less than 0.005). A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls). HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p less than 0.005; relative risk, 6.1; etiologic fraction, 0.22). We identified the combined DR4-DQw4 haplotype in five of 41 Caucasian IDC patients (12%) and none of 53 controls (p less than 0.007). A comparison of specific antigen frequencies between the preliminary and validation studies did not reveal significant differences; therefore, the data from the two studies were examined in combination. For the combined studies, DR4 was elevated (51% versus 27% in controls, p less than 0.001), and DRw6 was decreased (9% versus 24% in controls, p less than 0.01). The relative risk for DR4 was 2.8, and the etiologic fraction was 0.33.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid1868494, year = {1991}, author = {Rönnblom, LE and Forsberg, H and Evrin, PE}, title = {Increased level of HLA-DR-expressing T lymphocytes in peripheral blood from patients with idiopathic dilated cardiomyopathy.}, journal = {Cardiology}, volume = {78}, number = {3}, pages = {161-167}, doi = {10.1159/000174781}, pmid = {1868494}, issn = {0008-6312}, mesh = {Aged ; Cardiomyopathy, Dilated/blood/*immunology ; Female ; Fluorescent Antibody Technique ; HLA-DR Antigens/*immunology ; Heart Failure/blood/immunology ; Humans ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; T-Lymphocyte Subsets/*immunology ; }, abstract = {Peripheral blood leukocytes from 14 patients with idiopathic dilated cardiomyopathy (IDC), 13 patients with ischemic congestive heart failure, and 12 controls were characterized using different antibodies. The proportions of B lymphocytes, T lymphocytes, and the different T lymphocyte subsets were estimated. No difference between the three groups could be found in the various T and B cells subpopulations. Using a two-color direct immunofluorescence technique, the occurrence of circulating T helper/inducer (Leu-3a) and T cytotoxic/suppressor cells (Leu-2a) expressing HLA-DR antigens was examined. Only IDC patients demonstrated increased levels of HLA-DR-positive T helper/inducer cells (2.8 +/- 2.4%) and T cytotoxic/suppressor cells (2.8 +/- 2.3%) as compared with patients with ischemic congestive heart failure (0.8 +/- 0.7 and 1.0 +/- 1.0%, respectively) and controls (0.6 +/- 0.5 and 0.9 +/- 0.6%, respectively). When individual IDC patients were studied, 4 out of 12 patients had an increased level of HLA-DR-expressing T helper/inducer cells, and 7 out of 12 patients had elevated HLA-DR-positive T cytotoxic/suppressor cells. The findings suggest that activation of the T lymphocytes may be of importance in the pathogenesis of IDC.}, }
@article {pmid1789052, year = {1991}, author = {De Paepe, A and Kluyskens, Y and Van Durme, JP and Naudts, K and Claeys, R and De Wagter, X}, title = {Familial idiopathic dilated cardiomyopathy (IDC).}, journal = {Acta cardiologica}, volume = {46}, number = {5}, pages = {577-582}, pmid = {1789052}, issn = {0001-5385}, mesh = {Adult ; Cardiomyopathy, Dilated/*genetics ; Humans ; Male ; Pedigree ; }, abstract = {A three-generation family is presented in which several relatives died from or are affected by idiopathic dilated cardiomyopathy (IDC). The transmission pattern is autosomal dominant. Although familial instances of IDC have been reported the proportion of familial cases tends to be underestimated. Moreover, different transmission patterns have been associated with IDC. This report adds further evidence to the fact that an autosomal dominant form of IDC clearly exists and that early screening of asymptomatic first degree relatives is mandatory for accurate genetic counselling of patients and their family members.}, }
@article {pmid1705064, year = {1991}, author = {Wakabayashi, T and Onoda, H}, title = {Interdigitating reticulum cells in human renal grafts.}, journal = {Virchows Archiv. A, Pathological anatomy and histopathology}, volume = {418}, number = {2}, pages = {105-110}, pmid = {1705064}, issn = {0174-7398}, mesh = {Adolescent ; Adult ; Antibodies/immunology ; Antigens, CD1 ; Antigens, Differentiation/analysis ; Antigens, Differentiation, T-Lymphocyte/analysis ; CD3 Complex ; Dendritic Cells/*cytology/immunology/ultrastructure ; Female ; Fluorescent Antibody Technique ; HLA-DR Antigens/analysis ; Humans ; Kidney/*cytology/immunology/ultrastructure ; Kidney Transplantation/immunology/*pathology ; Male ; Microscopy, Immunoelectron/methods ; Receptors, Antigen, T-Cell/analysis ; S100 Proteins/analysis ; }, abstract = {Seventeen human renal graft biopsies taken 1 h to 50 days after transplantation and 3 human renal non-graft biopsies (2 minimal change and 1 non-tumour portion of angiomyolipoma) were investigated with immunoelectron microscopy in order to identify interdigitating reticulum cells (IDC) or dendritic cells (DC) in renal tissues. The antibodies used consisted of a rabbit polyclonal antibody of antihuman S100 beta protein, mouse monoclonal antibodies of antihuman HLA-DR, anti-CD3, and anti-CD1a. IDC or DC were identified in 11 renal grafts. They were found both in the glomerular and interstitial (peritubular) capillary lumens but not in the interstitium of 1 case: both were present in the interstitial capillary lumens and interstitium of another case, and in the interstitium only of 9 cases. In the remaining 6 grafts and 3 non-grafts they were not detected. These 6 grafts and 3 non-grafts did not show any pathological change except for foot process fusion of the glomerular epithelia in 2 cases of minimal change. These findings suggest that IDC or DC are not normally present in human renal tissues. The presence of the cell in the glomerular and peritubular capillary lumens of a biopsy taken after 1 h and their presence in the interstitial capillary lumens of another graft biopsy, suggest that the IDC or DC in human renal grafts are derived from recipients, not donors, and that they migrate from the circulating blood toward the interstitium.}, }
@article {pmid1665479, year = {1991}, author = {Mohanty, I and Nayak, M and Nanda, BK}, title = {Cell mediated immune status in carcinoma breast.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {34}, number = {1}, pages = {1-6}, pmid = {1665479}, issn = {0377-4929}, mesh = {Adenocarcinoma, Mucinous/*immunology ; Breast Neoplasms/*immunology ; Carcinoma/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*immunology ; Female ; Humans ; Immunity, Cellular ; Leukocyte Count ; *T-Lymphocytes ; }, abstract = {Thirty six cases of carcinoma breast were subjected to the assessment of CMI status by estimating different T lymphocyte parameters. The mean TPLC, T% and TTC in case of carcinoma were 1955/mm3 blood, 41% and 825/mm3 blood respectively which are evidently depressed than that of controls. This depression is progressive and clinical stage related, the least being in stage I and the most being in stage IV. The infiltrating varieties revealed a significant depression of T lymphocyte values than the non-infiltrating ones. Among the infiltrating types, IDC (T-38.9%) and Muc. Ca (T-29.1%) revealed most significant depression, thereby indicating worst prognosis. Six cases of IDCS, 2 cases of Medullary Ca and a solitary case of comedo Ca revealed a significant lymphocyte infiltration into the tumour cell mass proper. There was a depressed lymphocyte values but of lesser magnitude indicating a better prognosis. 6 cases without metastasis (clinical St. I) showed a lesser degree of depressed CMI than the cases with metastasis.}, }
@article {pmid1711920, year = {1990}, author = {Gould, VE and Koukoulis, GK and Virtanen, I}, title = {Extracellular matrix proteins and their receptors in the normal, hyperplastic and neoplastic breast.}, journal = {Cell differentiation and development : the official journal of the International Society of Developmental Biologists}, volume = {32}, number = {3}, pages = {409-416}, doi = {10.1016/0922-3371(90)90057-4}, pmid = {1711920}, issn = {0922-3371}, mesh = {Adenofibroma/chemistry ; Biomarkers ; Breast/*chemistry/embryology/pathology ; Breast Neoplasms/*chemistry ; Carcinoma/chemistry ; Carcinoma, Intraductal, Noninfiltrating/chemistry ; Cell Adhesion Molecules, Neuronal/analysis ; Extracellular Matrix Proteins/*analysis ; Female ; Fibrocystic Breast Disease/*metabolism ; Fibronectins/analysis ; Humans ; Hyperplasia ; Integrins/*analysis ; Laminin/analysis ; Phenotype ; Phyllodes Tumor/chemistry ; Tenascin ; }, abstract = {We studied by immunohistochemistry, the distribution of tenascin (Ten), cellular fibronectin (cFn), laminin and certain pertinent extracellular matrix protein receptors in normal human female breast, variants of fibrocystic disease (FCD), benign tumors, and ductal and lobular carcinomas. Monoclonal antibodies (mAb) to Ten, extradomain A containing cFn (EDAcFn), A and B chains of laminin, and beta-1 (beta-1) and different alpha subunits of intergrins were used. In in-situ ductal and lobular carcinomas, laminin staining had focal gaps, Ten-immunoreactivity displayed periductal or periacinar bands, and cFn showed broad and intense periductal staining; strong reactions for beta-1 and alpha-6 were noted in the basal cytoplasm of non-neoplastic myoepithelial cells while few tumor cells stained weakly. In infiltrating ductal and lobular carcinomas (IDC, ILC), laminin reactivity was weak, uneven or absent around neoplastic clusters whereas stromal staining for Ten and cFn was extensive and strong. In most IDC, moderate beta-1 and alpha-6 staining involved variable subpopulations; one mucinous carcinoma stained strongly and diffusely. In 20-40% of cells in ILC, beta-1 and alpha-6 were localized in delicate, ramified cytoplasmic processes. Indirect immunofluorescence studies with mAbs to other alpha-integrin subunits suggest that in various breast carcinomas only alpha-3 is expressed in tumor cells and that the vessels contained alpha-1 integrin. As compared with the normal breast, FCD and benign tumors, reactivity for Ten and cFn is increased in breast carcinomas while laminin is attenuated and decreased or absent; yet, Ten cannot be regarded as a carcinoma marker since it can be detected in benign tumors, FCD, and even in the normal breast.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid2252996, year = {1990}, author = {Welch, M and Durrans, D and Gonzalez, J and Daya, H and Owen, AM}, title = {Microdochectomy for discharge from a single lactiferous duct.}, journal = {The British journal of surgery}, volume = {77}, number = {11}, pages = {1213-1214}, doi = {10.1002/bjs.1800771106}, pmid = {2252996}, issn = {0007-1323}, mesh = {Adolescent ; Adult ; Aged ; Breast/*surgery ; Breast Diseases/diagnosis/pathology/*surgery ; Breast Neoplasms/diagnosis/pathology/surgery ; *Exudates and Transudates ; Female ; Humans ; Mammography ; Methods ; Middle Aged ; Nipples/*pathology ; }, abstract = {Microdochectomy for persistent discharge from a single lactiferous duct was performed in 162 women. Invasive or in situ ductal carcinoma was diagnosed in 16 patients (10 per cent), none of whom had a palpable lump. The discharge was blood-stained in 14 of these women and in two it was clear. Mammography was performed in 15 of these 16 patients and was abnormal in only five. Three patients had atypical ductal hyperplasia, one of whom subsequently developed an invasive ductal carcinoma. Microdochectomy for persistent discharge from a single lactiferous duct is curative and gives a diagnosis of the cause. It remains the treatment of choice whether the discharge is blood-stained or clear.}, }
@article {pmid2250366, year = {1990}, author = {Ohsumi, S and Urakami, J and Matsumori, H and Sasaki, S and Murakami, M and Nose, S}, title = {[A case of two primary carcinomas: thyroid papillary carcinoma with anaplastic transformation of metastatic cervical lymph node and breast cancer].}, journal = {Gan no rinsho. Japan journal of cancer clinics}, volume = {36}, number = {14}, pages = {2439-2444}, pmid = {2250366}, issn = {0021-4949}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Carcinoma, Papillary/*pathology ; Cell Transformation, Neoplastic/pathology ; Female ; Humans ; Lymphatic Metastasis ; Neck ; *Neoplasms, Multiple Primary ; Thyroid Neoplasms/*pathology ; }, abstract = {Reported is the case of a 70-year-old woman who, on diagnosis, was found to have a papillary carcinoma of the thyroid gland that showed an anaplastic transformation of a metastatic lesion of the right cervical lymph node. The primary lesion, however, contained no anaplastic areas. Simultaneously, she also was found to have a primary carcinoma of the left breast, an invasive ductal carcinoma. She thus received a total thyroidectomy with a right cervical node dissection, a modified radical mastectomy, and irradiation of the right cervical area, but no intensive chemotherapy was performed. Six months after the thyroidectomy, the anaplastic carcinoma caused her death. On autopsy, it was found to have involved the right cervical area, the lungs, the mediastinum, the right axilla, and the right kidney.}, }
@article {pmid2076634, year = {1990}, author = {Xie, X}, title = {[Assay of S-100+ Langerhans cells in cervical carcinoma].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {12}, number = {6}, pages = {406-409}, pmid = {2076634}, issn = {0253-3766}, mesh = {Antibodies/analysis ; Carcinoma in Situ/*pathology ; Carcinoma, Squamous Cell/*pathology ; Dendritic Cells/immunology ; Female ; Humans ; Immunohistochemistry ; Langerhans Cells/*immunology ; Neoplasm Invasiveness ; S100 Proteins/*immunology ; Uterine Cervical Neoplasms/*pathology ; }, abstract = {Langerhans cells (LC) in the normal cervix (control, 19 cases) and cervical carcinoma in situ (CIS, 19 cases), interdigitating cells (IDC) and follicular dendritic cells (FDC) in obturator lymph node draining infiltrating cervical carcinoma (30 cases) were quantitatively assayed by ABC immunohistochemical method using anti-S-100 protein antibody. The results indicated that S-100+ LC in situ, S-100+ IDC and S-100+ FDC in obturator lymph node showed dendritic features with a specific distribution. The number of LC in situ in infiltrating carcinoma increased significantly as compared with CIS and control groups. There was no change in LC number between Grades II and III of squamous cell carcinoma. The number of IDC was significantly less in Stage II than in Stage I lesion. FDC number in different depths of invasion and clinical stages showed no obvious change. The results suggest that progression of cervical carcinoma is closely related to decrease in LC in situ and IDC in regional lymph node. Predominant immune response of the host to cervical carcinoma should be cellular immune.}, }
@article {pmid2258536, year = {1990}, author = {Perticone, F and Borelli, D and Ceravolo, R and Mattioli, PL}, title = {Antiarrhythmic short-term protective magnesium treatment in ischemic dilated cardiomyopathy.}, journal = {Journal of the American College of Nutrition}, volume = {9}, number = {5}, pages = {492-499}, doi = {10.1080/07315724.1990.10720406}, pmid = {2258536}, issn = {0731-5724}, mesh = {Aged ; Cardiomyopathy, Dilated/*complications ; Electrocardiography, Ambulatory ; Female ; Heart Ventricles ; Humans ; Magnesium Sulfate/*therapeutic use ; Male ; Middle Aged ; Tachycardia/*drug therapy/physiopathology ; Time Factors ; }, abstract = {The efficacy of magnesium sulfate (MgSO4) infusion in the treatment of ventricular arrhythmias was evaluated in 10 normomagnesemic patients: seven men and three women, aged 56-78 years (mean +/- SD, 63.8 +/- 9.3). All of the patients had ischemic dilated cardiomyopathy (IDC) and severe ventricular arrhythmias: multiform ventricular premature contractions (VPCs), couplets, runs of ventricular tachycardia (VT), and R-on-T phenomenon. Four had evidence of old myocardial infarction (MI), four had chronic ischemic cardiomyopathy, and two had effort angina pectoris. Dilated cardiomyopathy was diagnosed by chest X-ray (cardiothoracic ratio greater than 0.5) and echocardiogram (end-diastolic left-ventricular diameter greater than 56 mm). All of the patients underwent two successive 24-hr Holter monitoring at the time of admission and after 3, 5, and 10 days from the beginning of therapy. Ventricular arrhythmias were classified according to modified Lown criteria. Renal function was normal. Magnesium sulfate in 0.9% sodium chloride was given by slow infusions (50 mg/min/60 min) twice daily for 7 days. They were antiarrhythmic in all of the patients: VPCs and couplets mean values decreased from 7971 +/- 2612 to 321 +/- 141 (p less than 0.001) and from 405 +/- 113 to 7 +/- 4 (p less than 0.001), respectively; VT runs (33.8 +/- 5.8) disappeared by the fifth day of treatment. Both the heart rate and the QTc interval remained unchanged from baseline values. The slow magnesium infusion did not notably raise serum Mg when evaluated immediately after stopping the infusion, as compared with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid2128549, year = {1990}, author = {Gazzinelli, RT and Gazzinelli, G and Cançado, JR and Cardoso, JE and Brener, Z and Colley, DG}, title = {Two modes of idiotypic stimulation of T lymphocytes from patients with Chagas' disease: correlations with clinical forms of infection.}, journal = {Research in immunology}, volume = {141}, number = {8}, pages = {757-770}, doi = {10.1016/0923-2494(90)90006-k}, pmid = {2128549}, issn = {0923-2494}, support = {AI 26505/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Animals ; Antibodies, Anti-Idiotypic/*immunology ; Antibodies, Protozoan/immunology ; Antigen-Presenting Cells/immunology ; Antigens, Protozoan/pharmacology ; Chagas Cardiomyopathy/*immunology ; Chagas Disease/*immunology ; Chloroquine/pharmacology ; Humans ; Interleukin-2/pharmacology ; Leukocytes, Mononuclear/drug effects ; Lymphocyte Activation/*immunology ; T-Lymphocytes/*immunology ; Trypanosoma cruzi/immunology ; }, abstract = {Patients with chronic Trypanosoma cruzi infections have peripheral auto-anti-idiotype (Id) T cells that proliferate on exposure to immunoaffinity-purified antibodies against T. cruzi epimastigote antigens (EPI). The responses of some patients' (group 1) peripheral blood mononuclear cells (PBMC) to anti-EPI antibodies from sera of patients with the cardiac form of Chagas' disease (Id-C) were inhibited by chloroquine, but responses of other patients' (group 2) PBMC to Id-C were not inhibited. PBMC responses of both group-1 and -2 patients to anti-EPI antibodies from asymptomatic (indeterminate) patients (Id-I) were inhibited by chloroquine, as were their responses to the antigens in EPI. Most patients (69%) in group 1 had indeterminate Chagas' disease, and 100% of the patients in group 2 had severe, cardiac or digestive Chagas' disease. Both the direct (chloroquine-insensitive) and indirect (processed) modes of stimulation by anti-EPI antibodies required adherent cells. In group 2 (direct stimulation), this requirement was met by exogenous IL-1, and neither anti-HLA-DR,DP(DQ) monoclonal antibody (mAb) nor sodium azide inhibited T-cell proliferation. Indirect Id stimulation of group-1 cells by Id-I or Id-C, and group-2 cells by Id-I or EPI, was inhibited by anti-HLA-DR,DP(DQ) mAb or sodium azide, and exogenous IL-1 alone did not support this processed, MHC-mediated T-cell stimulation, but live adherent cells did. The mode of activation of auto-anti-Id T cells from patients with Chagas' disease depends on the clinical form of infection of both the cell donor and the donor of the stimulating anti-EPI antibodies.}, }
@article {pmid2203677, year = {1990}, author = {Shimokawa, Y and Takeya, M and Miyauchi, Y and Takahashi, K}, title = {A monoclonal antibody, RbM2, specific for a lysosomal membrane antigen of rabbit monocyte/macrophages.}, journal = {Immunology}, volume = {70}, number = {4}, pages = {513-519}, pmid = {2203677}, issn = {0019-2805}, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; Antibody Specificity/immunology ; Antigens/analysis ; Ascitic Fluid/immunology ; Endocytosis/immunology ; Immunoenzyme Techniques ; Lysosomes/*immunology ; Macrophages/*immunology ; Mice ; Mice, Inbred BALB C ; Molecular Weight ; Monocytes/*immunology ; Rabbits ; }, abstract = {An anti-macrophage monoclonal antibody (mAb), RbM2, was produced using thioglycolate-elicited rabbit peritoneal macrophages as immunogen. The immunohistochemical approach revealed an intense reactivity of this mAb to macrophages, particularly those engaged in phagocytosis, in different organs and tissues, and to peripheral blood monocytes. Immunoelectron microscopy demonstrated reaction products of RbM2 in the lysosomes of macrophages and monocytes. This selective reactivity with the mAb was further confirmed in various experiments by endocytosis of Latex particles with different diameters or IgG-coated sheep erythrocytes. The results indicate that RbM2 recognizes a lysosomal membrane antigen of 50,000 molecular weight (MW). In contrast, dendritic cells, such as follicular dendritic cells (FDC) of lymphoid follicles, interdigitating cells (IDC) of lymphoid T zones, or epidermal Langerhans' cells, were not reactive with the antibody. Thus, RbM2 is useful not only in differentiating the phagocytic macrophages from the immunologically accessory dendritic cell populations but also in identifying lysosomes and their related structures in macrophages.}, }
@article {pmid1973597, year = {1990}, author = {Bacus, SS and Ruby, SG and Weinberg, DS and Chin, D and Ortiz, R and Bacus, JW}, title = {HER-2/neu oncogene expression and proliferation in breast cancers.}, journal = {The American journal of pathology}, volume = {137}, number = {1}, pages = {103-111}, pmid = {1973597}, issn = {0002-9440}, mesh = {Breast Neoplasms/*genetics/pathology ; Cell Division ; DNA, Neoplasm/analysis ; ErbB Receptors/analysis ; Female ; Humans ; Proto-Oncogene Mas ; Proto-Oncogene Proteins/*genetics ; *Proto-Oncogenes ; Receptor, ErbB-2 ; }, abstract = {Amplification of the HER-2/neu proto-oncogene in breast cancer has been reported to correlate with poor patient prognosis. The proliferation, or growth fraction, of cells has also been shown to be of prognostic importance in breast cancer. A study was conducted to evaluate the correlation between HER-2/neu gene expression and proliferation in breast cancer. Quantitative immunohistochemical methods for the detection of the HER-2/neu protein expression and for assessing the proliferation fraction on frozen sections of tumor cells were used. The detection of epidermal growth factor receptor (EGFR) along with quantitative DNA ploidy analysis, also was performed on the same breast cancers. The results indicated two subgroups of invasive ductal carcinoma; 1) HER-2/neu overexpressing cases that were negative for EGFR expression and had low proliferation fraction, and a tetraploid DNA pattern (22 cases), and 2) other combinations of HER-2/neu expression and EGFR expression, with a high proliferation fraction and an aneuploid DNA pattern (38 cases). Eight cases of carcinoma in situ were positive for HER-2/neu overexpression and negative for EGFR expression, and had a high proliferation fraction and a tetraploid DNA pattern. Twenty-six cases of low-grade carcinoma exhibited low proliferation and a diploid DNA pattern.}, }
@article {pmid2340493, year = {1990}, author = {Geleick, D and Müller, H and Matter, A and Torhorst, J and Regenass, U}, title = {Cytogenetics of breast cancer.}, journal = {Cancer genetics and cytogenetics}, volume = {46}, number = {2}, pages = {217-229}, doi = {10.1016/0165-4608(90)90107-l}, pmid = {2340493}, issn = {0165-4608}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics ; *Chromosome Aberrations ; Female ; Genetic Markers ; Humans ; Karyotyping ; Middle Aged ; Ploidies ; }, abstract = {Chromosome counts were performed on 1,100 cells from 17 malignant breast carcinomas and on 168 cells of four normal tissue samples after amethopterin treatment and G-banding. Karyotypes were established from 216 cells of 11 tumor-derived cultures and from 47 cells of four nonmalignant tissue-derived cultures. Karyotypes of cells from nonmalignant samples showed a normal diploid chromosomal constitution with no consistent loss or gain of a specific chromosome. Structural chromosomal abnormalities were not observed. Tumor-derived cultures could be distinguished from normal cultures on the basis of a significantly increased incidence of numerical changes and structural chromosomal aberrations. In nine of 11 tumor-derived cultures, numerically normal cells were shown to be pseudodiploid, with frequencies ranging to 43% (mean, 13.2%) of the diploid cells. In agreement with previous reports, cytogenetic analyses showed predominantly diploid cells. Clonal numerical changes of chromosomes 17, 18, 20, and 21 could be detected in three tumor samples. Clonal structural abnormalities could be observed in two of 11 analyzed tumours. A t(6;12)(p21;p13) and an enlarged chromosome 7 (7q+) were found in a patient with invasive ductal carcinoma. An inversion of chromosome 7 [inv(7)(q11.2q32)] was observed in one case, also diagnosed as invasive ductal carcinoma. The significance of these findings in relation to clinical data is discussed.}, }
@article {pmid2311124, year = {1990}, author = {Darden, AG and Forbes, RD and Darden, PM and Guttmann, RD}, title = {The effects of genetics and age on expression of MHC class II and CD4 antigens on rat cardiac interstitial dendritic cells.}, journal = {Cellular immunology}, volume = {126}, number = {2}, pages = {322-330}, doi = {10.1016/0008-8749(90)90324-k}, pmid = {2311124}, issn = {0008-8749}, mesh = {Age Factors ; Animals ; CD4 Antigens/*analysis ; Dendritic Cells/*immunology ; Female ; Histocompatibility Antigens Class II/*analysis ; Major Histocompatibility Complex ; Male ; Myocardium/*immunology ; Rats ; Rats, Inbred Strains ; Species Specificity ; }, abstract = {Interstitial dendritic cells (IDC) in normal hearts of inbred rat strains and congenic and congenic recombinant lines were identified and quantitated by immunohistologic methods, on the basis of cellular reactivity with MRC-OX6, a monoclonal antibody (MAb) directed against MHC class II determinants, and with W3/25, a MAb directed against a CD4 epitope. In all strains and lines examined, the W3/25+ IDC frequency was uniformly high with little interstrain variation. In contrast, all rat strains and lines examined showed either high or low OX6+ IDC frequency. Double staining by two color immunofluorescence indicated that strains with a low OX6+ IDC frequency were characterized by a high frequency of W3/25+ OX6- IDC and a low frequency of W3/25+ OX6+ IDC. In strains with high OX6+ IDC frequency, the majority of IDC coexpressed both markers. Comparative analysis of (i) MHC identical background disparate strains and lines, (ii) MHC disparate background identical strains and lines, and (iii) F2 segregation analysis of intercrosses and backcrosses derived from an original cross between high and low frequency OX6+ IDC strains, all indicated that OX6+ IDC frequency is dependent upon both MHC- and non-MHC-linked genetic factors. It is suggested that rat cardiac OX6+ IDC frequency is influenced by a minimum of two autosomal genes, one of which is MHC linked. The frequencies of both W3/25+ IDC frequency reached adult levels by 10 days of age; adult levels of OX6+ IDC were not attained until Day 21. It is postulated that in the rat heart, W3/25+ OX6- IDC are potential precursors of W3/25+ OX6+ IDC, and that the cellular frequency of coexpression in the adult is under genetic influence. Whether these genetic factors modify constitutive or physiologic levels of class II-inducing lymphokine activity, or influence cellular susceptibility of IDC to induced class II expression is unclear.}, }
@article {pmid2165559, year = {1990}, author = {Nakazawa, T and Yamamoto, K and Kohno, N and Saitoh, Y}, title = {[Immunohistochemical study on HLA expression of human breast cancer].}, journal = {Nihon Geka Gakkai zasshi}, volume = {91}, number = {4}, pages = {508-514}, pmid = {2165559}, issn = {0301-4894}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Intraductal, Noninfiltrating/immunology/pathology ; Female ; Frozen Sections ; HLA Antigens/*metabolism ; Humans ; Immunoenzyme Techniques ; Lymphocytes/pathology ; Middle Aged ; Prognosis ; }, abstract = {One hundred and nine cases of breast cancer were examined by immunoperoxidase staining of frozen section for their HLA expression. Sixty one cases (56%) were negative or very weak for HLA class I expression, while normal mammary ductal epithelia showed intense positivity in both class I and class II antigens. The extent of expression correlated well with the histopathological subtyping of invasive ductal carcinoma in Japan, which reflects the prognosis quite well. Degree of lymphoid cell infiltration was also proportional to HLA expression by tumor cells. It may be that lack of HLA antigen expression leads to failure of induction of cytotoxic T cells, thus modulating the immunological response and influencing prognosis.}, }
@article {pmid2157608, year = {1990}, author = {Clavien, PA and Laffer, U and Torhost, J and Harder, F}, title = {Gastro-intestinal metastases as first clinical manifestation of the dissemination of a breast cancer.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {16}, number = {2}, pages = {121-126}, pmid = {2157608}, issn = {0748-7983}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; Carcinoma/diagnosis/secondary/therapy ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/secondary/therapy ; Combined Modality Therapy ; Diagnosis, Differential ; Female ; Gastrointestinal Neoplasms/diagnosis/*secondary/therapy ; Humans ; Linitis Plastica/diagnosis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptors, Estrogen/metabolism ; Stomach Neoplasms/diagnosis ; }, abstract = {Of 1192 patients treated for breast cancer, four had extrahepatic gastro-intestinal metastases as first clinical manifestation of the tumour dissemination. One woman presented with gastric metastases mimicking a linitis plastica. Another had metastases localized to the rectum also mimicking a linitis plastica. Two women had peritoneal and retroperitoneal metastases that caused, in one case, a right hydronephrosis. Histology of the four primary tumours showed invasive lobular carcinoma (ILC) mixed with invasive ductal carcinoma in two. However, ILC exclusively was found at the site of the gastro-intestinal metastases involving the serosal layer (two cases) and extending to the submucosa (one case) or to the mucosal stroma (one case). Thus, when a women with previous history of invasive lobular breast cancer experiences gastro-intestinal symptoms, particular attention should be paid to the large and deep biopsy of lesions to ascertain the histological type and whether oestrogen or progesterone receptors differ from those of the primary breast lesion. Since survival is extremely variable (one woman is alive 7 years after the discovery of gastro-intestinal metastases), treatment including surgery, hormonal manipulation and chemotherapy with the expectation of a cure is often justifiable, particularly if no other extensive metastases are present.}, }
@article {pmid2157083, year = {1990}, author = {Tamura, G and Masuda, T and Satoh, T and Satodate, R and Ishida, M and Saitoh, K}, title = {Karyometric and DNA content analyses of cancer cells in stage III breast cancer with reference to prognosis.}, journal = {Japanese journal of clinical oncology}, volume = {20}, number = {1}, pages = {78-82}, pmid = {2157083}, issn = {0368-2811}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/mortality/pathology ; Cell Nucleus/ultrastructure ; DNA, Neoplasm/*analysis ; Female ; Genetic Markers ; Humans ; Karyometry ; Middle Aged ; Prognosis ; }, abstract = {Karyometric and DNA content analyses were simultaneously performed on 32 cases of stage III invasive ductal breast cancer using an image analysis system. From the karyometric analysis, the nuclear areas (NAs; microns 2) were (mean +/- SD) 36.27 +/- 9.40 in five-year survivors (n 17) and 57.14 +/- 13.26 in non-survivors (n 15). The nuclear shape factors (NSFs; NSF = 4 pi X NA/NP2; NP, nuclear perimeter) were 0.756 +/- 0.037 in survivors and 0.716 +/- 0.040 in non-survivors. The NA was significantly larger (P less than 0.01) and the NSF significantly lower (P less than 0.01) in non-survivors than in survivors. From the DNA content analysis, the DNA content values (c; see Measurements section) were +/- 2.59 +/- 0.70 in survivors and 3.72 +/- 1.08 in non-survivors. The percentages of aneuploid cells over 4c were 7.10 +/- 9.89 in survivors and 23.07 +/- 20.19 in non-survivors. The DNA content and the percentage of aneuploid cells over 4c were significantly higher (P less than 0.01) in non-survivors than in survivors. This method may be valuable for estimating the prognosis of patients with invasive ductal carcinoma of the breast.}, }
@article {pmid2162505, year = {1990}, author = {Turi, V and Lucev, M and D'Abrosca, F and Gerosa, E}, title = {[Cancer of the male breast with atypical ductal hyperplasia and contralateral gynecomastia].}, journal = {Minerva chirurgica}, volume = {45}, number = {3-4}, pages = {203-205}, pmid = {2162505}, issn = {0026-4733}, mesh = {Adult ; Breast Diseases/*complications/pathology ; Breast Neoplasms/*complications/pathology ; Carcinoma, Intraductal, Noninfiltrating/*complications/pathology ; Gynecomastia/*complications/pathology ; Humans ; Hyperplasia/complications ; Male ; }, abstract = {A case of right mammary invasive ductal carcinoma in young man with atypical ductal hyperplasia and gynecomastia of the second breast is described. The review of the existing literature stress the rarity of this observation. Nevertheless, in all cases of male mammary carcinoma the accurate examination must always include the contralateral breast to search the possible precancerous lesions or etiologic factors.}, }
@article {pmid2229899, year = {1990}, author = {Denis, J and Chouraqui, P and Karpouzas, I and Hoang-Xuan, T and Pouliquen, Y}, title = {[Treatment of superficial herpes simplex keratitis with vidarabine (Vira A): multicenter study of 100 cases].}, journal = {Journal francais d'ophtalmologie}, volume = {13}, number = {3}, pages = {143-150}, pmid = {2229899}, issn = {0181-5512}, mesh = {Adult ; Antiviral Agents ; Bromodeoxycytidine/analogs &amp; derivatives ; Corneal Ulcer/drug therapy/etiology ; Deoxycytidine/analogs &amp; derivatives ; Drug Resistance ; Female ; Humans ; Idoxuridine ; Keratitis, Dendritic/complications/*drug therapy ; Male ; Middle Aged ; Ointments ; Recurrence ; Vidarabine/*therapeutic use ; }, abstract = {The efficacy of 3% Ara-A ophthalmic ointment (Vira A) has been evaluated on 100 epithelial herpetic keratitis; the poor intra-ocular penetration of Ara-A explains the exclusion of stromal keratitis and kerato-unveitis. Patients were treated 5 times a day until complete epithelial healing of ulcers, then twice a day during 7 days. Healing was obtained within 10.6 days for 87% of the patients, who have been treated by Ara-A at first (n = 77) or after failure of IDU or of IDC (n = 23). The healing rate was higher for the 52 first ocular episodes (92%) than for the 48 recurrences (81%); it decreases to 77% for recurrences after failure of IDU or IDC. Geographic ulcers heal in 76% of cases only. Their length has no influence on their healing. The longest healing time, 10.6 days, can be explained by the long period of time before beginning to apply Ara-A, 12.8 days: significative correlation between both periods of time is highlighted and shows the advantage of an early treatment. The need for a local corticotherapy (n = 8) does not hinder healing in 15.5 days. Two weeks after discontinuation of the treatment, 3 patients presented a relapse, sensitive to a 2nd Ara-A course; a maintenance treatment, superior to 7 days, is necessary. Tolerance to Vira A ointment is good. Indications of Ara-A during ocular herpes are superficial keratitis, especially those resistant to IDU or, from experimental data, to ACV, and their prevention by a possible long term treatment.}, }
@article {pmid2177615, year = {1990}, author = {Aasmundstad, TA and Haugen, OA}, title = {DNA ploidy in intraductal breast carcinomas.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {26}, number = {9}, pages = {956-959}, doi = {10.1016/0277-5379(90)90619-5}, pmid = {2177615}, issn = {0959-8049}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; DNA, Neoplasm/*analysis ; Female ; Flow Cytometry ; Humans ; *Ploidies ; Prognosis ; Recurrence ; Time Factors ; }, abstract = {Cellular DNA-ploidy in 74 clinically detected intraductal breast carcinomas (IDCs) was analysed by flow cytometry. The histograms were classified as either diploid or aneuploid, and the DNA ploidy pattern compared with that of invasive breast carcinomas and normal breast tissue. All normal breast tissues were diploid while 28 (38%) of the IDCs were aneuploid, the DNA indices ranging from 1.32 to 2.00. The frequency of aneuploidy in invasive ductal carcinomas (73%) was significantly higher (P = 0.003), DNA index ranging from 1.34 to 2.92, compared with that in IDCs. Retrospectively, 14.5% of the patients had invasive breast cancer 16-166 months after the diagnosis of IDC. Neither DNA ploidy nor histopathological classification alone predicted clinical outcome, but patients with DNA diploid non-comedo IDC had a more favourable course.}, }
@article {pmid2152504, year = {1990}, author = {Agger, R and Crowley, MT and Witmer-Pack, MD}, title = {The surface of dendritic cells in the mouse as studied with monoclonal antibodies.}, journal = {International reviews of immunology}, volume = {6}, number = {2-3}, pages = {89-101}, doi = {10.3109/08830189009056621}, pmid = {2152504}, issn = {0883-0185}, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; Antigens, CD/analysis ; Antigens, Differentiation/analysis ; Biomarkers/analysis ; Dendritic Cells/*chemistry/immunology ; Histocompatibility Antigens Class II/analysis ; Integrins/analysis ; Langerhans Cells/chemistry ; Lymphoid Tissue/cytology ; Mice ; }, abstract = {A family of dendritic cells has been identified in situ and in vitro by microscopy and immunolabeling. The members of this family include the dendritic cells isolated from lymphoid organs, Langerhans cells [LC] of the epidermis, veiled cells in afferent lymph, and interdigitating cells [IDC] in the T-cell areas. Some common features to all members of the family are high levels of MHC class II antigens, a lack of most B and T cell markers, and an absence or low levels of macrophage/granulocyte antigens. This review summarizes the markers of mouse dendritic cells as assessed by a panel of monoclonal antibodies, and stresses a few recent findings. 1) In spleen, there are two populations of dendritic cells. More than 75% of isolated cells are 33D1+, NLDC145-, and J11d-, while the remainder have the reciprocal phenotype and thus share the NLDC145 antigen of IDC. Thymic dendritic cells, released by collagenase digestion, and epidermal LC also are 33D1-, NLDC145+, J11d+. 2) When epidermal LC are placed in culture, there are changes in cell function and phenotype. There is a decrease in Fc gamma receptors and the F4/80 macrophage antigen, an increase in class I and II MHC products and p55 IL-2 receptors, and persistence of the NLDC145 IDC antigen. The cultured LC thereby resembles the IDC. 3) A new antibody N418 shows that dendritic cells express the p150/90 member of the leukocyte beta 2 integrin family. Immunolabeling of tissue sections of spleen indicates that N418+ dendritic cells not only are present in the periarterial sheaths, the location of IDC, but also in "nests" at the periphery of the T area where 33D1 has been found. The peripheral collections interrupt the marginal zone of macrophages that separates white and red pulp, and places the dendritic cells in the path of T cells as they move through the white pulp. Therefore the members of the dendritic cell family have important markers in common, as well as differences that are associated with state of immunologic function and location.}, }
@article {pmid2152502, year = {1990}, author = {Fairchild, PJ and Austyn, JM}, title = {Thymic dendritic cells: phenotype and function.}, journal = {International reviews of immunology}, volume = {6}, number = {2-3}, pages = {187-196}, doi = {10.3109/08830189009056629}, pmid = {2152502}, issn = {0883-0185}, mesh = {Animals ; Antigens/*immunology/metabolism ; Biomarkers ; Birds/immunology ; Cell Differentiation ; Cell Movement ; Dendritic Cells/chemistry/*immunology/transplantation/ultrastructure ; Histocompatibility Antigens Class I/chemistry ; Histocompatibility Antigens Class II/chemistry ; Immunophenotyping ; Lymphocyte Activation ; Mammals/immunology ; Spleen/cytology ; T-Lymphocytes/immunology ; Thymus Gland/*cytology/immunology ; Transplantation, Heterotopic ; }, abstract = {Interdigitating (IDC) cells of the thymus have been characterized in situ by their ultrastructure and phenotype. Thymic dendritic cells (DC), thought to represent their in vitro correlate, resemble splenic DC in their ability to initiate peripheral T cell responses. In vivo, however, DC of the thymus have been implicated in tolerance induction, although at one time they were thought to impart MHC-restriction on developing T cells. Our present understanding of these areas is reviewed here. An in vitro model has been developed to address directly the function of DC in the thymus. Mature DC and immature thymocytes migrate into deoxyguanosine-treated thymus lobes where they adopt a reciprocal distribution, DC homing primarily to the medulla while the thymocytes remain in the cortex. These observations support the close relationship between thymic DC and IDC and provide a powerful tool to examine the role of DC in thymocyte ontogeny.}, }
@article {pmid2152498, year = {1990}, author = {Hart, DN and McKenzie, JL}, title = {Interstitial dendritic cells.}, journal = {International reviews of immunology}, volume = {6}, number = {2-3}, pages = {127-138}, doi = {10.3109/08830189009056624}, pmid = {2152498}, issn = {0883-0185}, mesh = {Animals ; Biomarkers/analysis ; Bone Marrow Cells ; Cell Movement ; *Dendritic Cells/cytology/immunology ; Graft Rejection ; Histocompatibility Antigens Class II/analysis ; Humans ; Immunophenotyping ; Inflammation ; Langerhans Cells ; Leukocytes ; Macrophages ; Organ Specificity ; Rats ; Rats, Nude ; Receptors, Complement/analysis ; Receptors, Fc/analysis ; }, abstract = {Interstitial dendritic cells (IDC) were first identified in the interstitium of non-lymphoid organs as leucocytes which stained intensely with anti-MHC class II antibodies. These cells have been identified in several species including man, and can be distinguished from tissue macrophages by their immunological phenotype and cytochemical and functional characteristics. IDC appear to be closely related to lymphoid dendritic cells (DC), and have the capacity to bind antigen and stimulate T lymphocyte responses. It seems probable that they represent a stage of nonlymphoid dendritic cell differentiation necessary for antigen surveillance, similar to the Langerhans cell of the skin. Exposure to antigen appears to induce migration of these cells into adjacent lymphatics and subsequent localization in the interfollicular areas of lymph node, where the DC present processed antigen to activate a primary T cell response. The IDC has been identified as the passenger leucocyte within organ allografts which contributes substantially to graft immunogenicity, so that eradication of donor organ IDC improves organ graft survival.}, }
@article {pmid2801117, year = {1989}, author = {Okamoto, T}, title = {Glycogen-rich clear cell carcinoma of the breast. An autopsy case.}, journal = {Acta pathologica japonica}, volume = {39}, number = {7}, pages = {469-472}, doi = {10.1111/j.1440-1827.1989.tb02464.x}, pmid = {2801117}, issn = {0001-6632}, mesh = {Adenocarcinoma/analysis/*pathology/ultrastructure ; Adrenal Gland Neoplasms/secondary ; Aged ; Breast Neoplasms/analysis/*pathology/ultrastructure ; Female ; Glycogen/*analysis ; Humans ; Immunohistochemistry ; Liver Neoplasms/secondary ; Lung Neoplasms/secondary ; }, abstract = {An autopsy case of glycogen-rich clear cell carcinoma (GRCCC) which arose in the right breast of a 72-year-old woman is reported. Light microscopic examination of the small finger-tip-sized tumor revealed solid alveolar proliferation of clear cells containing abundant glycogen. Immunohistochemically, most of the clear tumor cells were stained for epithelial membrane antigen (EMA) and alpha-lactalbumin, whereas a few eosinophilic tumor cells were positive for S-100 protein, EMA and actin. Electron microscopically, aggregates of glycogen particles, numerous empty glycogen lakes, microvilli, tight junctions and basal lamina were identified. Autopsy disclosed marked metastases to the liver, lung, adrenal, skin and lymph nodes. Primary breast cancer was confirmed by exclusion of a primary at any other site. It is suggested that although rare, GRCCC of the breast is as aggressive as usual invasive ductal carcinoma, and is associated with severe nodal and blood-borne metastases, followed by death.}, }
@article {pmid2473279, year = {1989}, author = {Maruyama, T and Tanaka, S and Bozóky, B and Kobayashi, F and Uda, H}, title = {New monoclonal antibody that specifically recognizes murine interdigitating and Langerhans cells.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {61}, number = {1}, pages = {98-106}, pmid = {2473279}, issn = {0023-6837}, mesh = {Animals ; *Antibodies, Monoclonal ; Antibody Specificity ; Dendritic Cells/immunology/ultrastructure ; Immunohistochemistry ; Langerhans Cells/*immunology/ultrastructure ; Mice ; Mice, Nude ; Microscopy, Electron ; Staining and Labeling ; }, abstract = {A new monoclonal antibody, M1-8, that recognizes murine interdigitating cells (IDC) and Langerhans cells was obtained from a hybridoma prepared by fusion of SP2/0 mouse myeloma cells with splenic cells of rats immunized with IDC-rich cell suspension obtained from lymph nodes of athymic nude mice (BALB/c nu/nu). The specificity was assessed immunohistochemically on frozen sections of lymph nodes and epidermal sheets from both nude and normal mice. M1-8 reacted with paracortical IDC, veiled cells of the marginal sinus, and epidermal Langerhans cells in both normal and nude mice. In simultaneous staining by M1-8 and nonspecific esterase or anti-Ia or anti-Thy-1,2 antibody, the same epidermal dendritic cells were positive for all these antigens except Thy-1,2. Immunoelectron microscopy of the lymph node suspension using gold colloid particles revealed the attachment of gold particles to the cell membrane of IDC. Analysis by flow cytometry of the lymph node cell suspension showed 14 or 6% of M1-8-positive cells in nude or normal mouse, respectively. Immunohistochemical analysis showed that M1-8 also reacted with dendritic cells in the thymus and spleen and had a different distribution from F4/80. M1-8 also reacted with monocytes in bone marrow and peripheral blood, alveolar macrophages, and thioglycollate-stimulated peritoneal exudate macrophages. The antibody belongs to the immunoglobulin M class, reacts immunochemically with a glycoprotein in the cell membrane, and has a molecular mass of approximately 15 kDa.}, }
@article {pmid2546902, year = {1989}, author = {Chapuis, L and Hessler, C}, title = {[Breast cancer before 36 years of age].}, journal = {Helvetica chirurgica acta}, volume = {55}, number = {6}, pages = {895-902}, pmid = {2546902}, issn = {0018-0181}, mesh = {Adult ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Diagnosis, Differential ; Female ; Humans ; Neoplasm Staging ; Prognosis ; }, abstract = {Breast cancer in young women is a dreaded disease of bad prognosis, classically worse than for older women. A local study was undertaken in Lausanne to evaluate this notion. 94 cases aged less than 36 years were collected over 15 years, the incidence being 9 new cases per years per 100,000 under-36 women. 76% of the tumors were discovered accidentally by the patient, 24% by a physician during a routine breast examination. Delays from first symptom to histologic diagnosis were short, averaging 19 weeks. 80 mammographies were performed on the 94 cases, of whom 50 positives for a cancer, and 29 negative or doubtful. 22 of these negative 29 were reevaluated, 7 being positive for a tumor and 15 negative, showing either a benign mass or no lesion at all. 6 of the 7 positives were misdiagnosed in easy-to-read breasts, the false interpretation being chiefly caused by the young age of the patients. Pathologically, the rate of invasive ductal carcinoma was very high at 91.4%, which is the highest in the literature, and much higher than for older women in Lausanne (68%). Survival was 84% at two years, 63% at five years and 46% at 10 years, all deaths due to breast cancer. Those rates are better, globally and stage by stage, than for older women or than other reports on young women. We conclude that breast cancer in young women has a better prognosis than formerly thought.}, }
@article {pmid2525436, year = {1989}, author = {Wiley, KN and Clark, A and Fox, M}, title = {The in-vitro inhibition of rat alloantigen presentation by immunotoxins--implications for allografting.}, journal = {Clinical and experimental immunology}, volume = {76}, number = {1}, pages = {132-137}, pmid = {2525436}, issn = {0009-9104}, mesh = {Animals ; Antibodies, Monoclonal/pharmacology ; Dendritic Cells/*drug effects/immunology ; *Graft Rejection ; Immunotoxins/*pharmacology ; Isoantigens/*immunology ; Lymphocyte Culture Test, Mixed ; Mice ; Rats ; Ricin/*pharmacology ; Transplantation, Homologous ; }, abstract = {The removal of graft interstitial dendritic cells (IDC) prior to transplantation into a recipient has been shown to improve graft survival in a number of experimental studies. We report the in-vitro properties of two immunotoxins (IT) which could be used to deplete graft IDC when administered ex vivo by hypothermic perfusion in an experimental rat transplantation model. Ricin A chain (RAC) IT targeted at either class II major histocompatibility complex (MHC) molecules or leukocyte common antigens (LCA) were prepared. These IT had similar equilibrium constants, binding kinetics and inhibiting activity of cell-free protein synthesis. IT cytotoxicity was assessed by inhibition of alloantigen presentation by targeted low density spleen cells (LDSC) in a one way mixed lymphocyte culture (MLC). When LDSC were hypothermically incubated for 2 h with IT only the anti class II MHC IT inhibited the MLC and the maximum inhibition depended on the cell allotypes. The inhibition was increased to almost 100% when chloroquine was incorporated throughout the culture period.}, }
@article {pmid2537237, year = {1989}, author = {Watt-Boolsen, S and Ottesen, G and Andersen, JA and Bayer, T and Jespersen, NC and Keiding, N and Mouridsen, HT and Dombernowsky, P and Blichert-Toft, M}, title = {Significance of incisional biopsy in breast carcinoma: results from a clinical trial with intended excisional biopsy.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {15}, number = {1}, pages = {33-37}, pmid = {2537237}, issn = {0748-7983}, mesh = {Axilla ; Biopsy/*methods ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; *Lymph Node Excision ; Mastectomy/*methods ; Menopause ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Risk Factors ; }, abstract = {The recurrence-free survival rates (RFS) after one-stage mastectomy and partial axillary dissection in 1242 low risk breast cancer patients with invasive ductal carcinoma with or without residual cancer tissue (RCT) in the wall of the biopsy cavity were compared. RFS was significantly lower in patients with RCT (RCT-positive) whether premenopausal (n = 416) or postmenopausal (n = 826). By applying the Cox multivariate analysis on RCT and various known prognostic criteria, the incidence rates for RCT-positive patients relative to RCT-negative patients were estimated. The relative risk by RCT-positivity was in the order of 1.45, indicating that RCT is an independent risk factor contributing an increased risk of recurrence of about 45%.}, }
@article {pmid2720711, year = {1989}, author = {Romeo, F and Pelliccia, F and Cianfrocca, C and Ferraironi, A and Nigri, A and Reale, A}, title = {[Idiopathic dilated cardiomyopathy: clinical and prognostic significance of the morpho-functional involvement of the right heart].}, journal = {Cardiologia (Rome, Italy)}, volume = {34}, number = {1}, pages = {27-32}, pmid = {2720711}, issn = {0393-1978}, mesh = {Adult ; Atrial Fibrillation/etiology ; Cardiomyopathy, Dilated/*complications ; Female ; Heart/*physiopathology ; Heart Ventricles/physiopathology ; Humans ; Male ; Middle Aged ; Prognosis ; }, abstract = {Aim of this study was to evaluate whether different severity of clinical and functional impairment of right heart in patients with idiopathic dilated cardiomyopathy (IDC) might condition distinct clinical features and prognosis. From 104 consecutive patients with hemodynamically assessed diagnosis of IDC studied between 1977 and 1987 in our Institute, 39 patients (28 males and 11 females, mean age 41 +/- 14 years) were selected on the basis of ejection fraction ranging from 35 to 50%, left ventricular end-diastolic pressure ranging from 13 to 20 mmHg and left ventricular end diastolic volume less than or equal to 150 ml/m2. A significant involvement of right heart (diagnosed according to a mean right atrial pressure greater than or equal to 9 mmHg, a right ventricular end-diastolic pressure greater than or equal to 9 mmHg and a right ventricular end-diastolic diameter greater than or equal to 30 mm) was assessed in 16 patients (41%), 11 males and 5 females, aged 40 +/- 15 years (Group A). On the contrary the remaining 23 patients (59%), 17 males and 6 females, aged 42 +/- 12 years, had a normal right heart (Group B). At entry into the study, clinical features appeared similar in the 2 groups of patients whereas patients of Group A had significantly higher incidence of atrial fibrillation (25% vs 4%, p less than 0.01) and complex ventricular arrhythmia (greater than or equal to 4 Lown class) (25% vs 4%, p less than 0.01) compared with patients of Group B. With respect to conduction defects no difference was found between Group A and Group B.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid2554853, year = {1989}, author = {Sprecher, E and Becker, Y}, title = {Langerhans cell density and activity in mouse skin and lymph nodes affect herpes simplex type 1 (HSV-1) pathogenicity.}, journal = {Archives of virology}, volume = {107}, number = {3-4}, pages = {191-205}, pmid = {2554853}, issn = {0304-8608}, mesh = {Adenosine Triphosphatases ; Animals ; Cell Count ; Dendritic Cells/drug effects/immunology ; Fluorescent Antibody Technique ; Herpes Simplex/*immunology ; Langerhans Cells/microbiology/*physiology ; Lymph Nodes/cytology/immunology/microbiology ; Lymphocyte Activation ; Mice ; Mice, Inbred A ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Picibanil ; Simplexvirus/isolation &amp; purification/*pathogenicity ; Skin/cytology/immunology/microbiology ; Skin Diseases, Infectious/*immunology/microbiology ; }, abstract = {Langerhans cells are epidermal antigen-presenting cells that function by taking up antigens in the skin, migrating to the lymph nodes, where they are designated interdigitating cells, and triggering the immune response. The role of interdigitating cells (IDC) was investigated in a murine model of herpes simplex virus-1 infection in the skin. The number of IDC in the lymph nodes began to increase on the first day following infection and reached a peak three days p.i. Low titers of infectious virus were recovered from the fraction of lymph node cells that consisted of 60-80% IDC at one day p.i. Lymph node cells that were obtained from mice immunized with HSV-1 proliferated in vitro in response to viral antigens but did not respond to mock antigens. When mice were immunized with HSV-1 inoculated into skin that had been depleted of Langerhans cells, this in vitro proliferative response was abolished. Thus, the present results suggest that Langerhans cells function in the immune defense of the skin against HSV-1 infection by transporting the virus to the peripheral lymph nodes where an immune response is initiated. Injection of the immunomodulator OK-432 into the footpad skin caused a local increase in the number of Langerhans cells in the epidermis and led to an increased migration of dendritic cells to the lymph nodes. Under these conditions, a decrease in HSV-1 pathogenicity was noted. These observations indicate that the pathogenicity of herpes simplex virus type 1 in the skin is affected by Langerhans cell density and activity in the epidermis and the lymph nodes.}, }
@article {pmid2535949, year = {1989}, author = {Hardman, PD and Worth, A and Lee, U and Baird, RM}, title = {The risk of occult invasive breast cancer after excisional biopsy showing in-situ ductal carcinoma of comedo pattern.}, journal = {Canadian journal of surgery. Journal canadien de chirurgie}, volume = {32}, number = {1}, pages = {56-60}, pmid = {2535949}, issn = {0008-428X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Biopsy/methods ; Breast Neoplasms/*pathology/surgery ; Carcinoma in Situ/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Reoperation ; Risk Factors ; }, abstract = {Between Jan. 1, 1985 and Aug. 31, 1987, 62 in-situ ductal carcinomas with a predominantly comedo pattern were identified in 61 patients in British Columbia from excisional biopsy of a palpable or mammographically demonstrable lesion of a breast. The biopsies were intended to remove the lesion completely. Fifty-seven (92%) of the 61 patients required wide re-excision or total mastectomy, usually within a month of the initial biopsy. Occult invasive disease was demonstrated in 14 of the re-excision specimens (24.5%) and residual in-situ carcinoma was present in a further 24 (42.1%), giving an overall rate of residual disease of 66.6%. Axillary lymph nodes were sampled in 54 cases. Metastases were found in two cases (3.7%) and each was associated with occult infiltrating ductal carcinoma in the breast. This suggests that in-situ ductal carcinoma having a predominant comedo pattern may be more widespread and associated with a higher incidence of invasive ductal carcinoma than is generally believed.}, }
@article {pmid2518347, year = {1989}, author = {Szekeres, G and Audouin, J and Diebold, J}, title = {Immunohistological demonstration of lymph node reticulum cells in the acquired immunodeficiency syndrome related complex. A study in Bouin-fixed tissues.}, journal = {Acta morphologica Hungarica}, volume = {37}, number = {1-2}, pages = {47-53}, pmid = {2518347}, issn = {0236-5391}, mesh = {AIDS-Related Complex/immunology/*pathology ; Acetates ; *Acetic Acid ; Animals ; Dendritic Cells/immunology/*pathology ; Fixatives ; Formaldehyde ; Humans ; Immunohistochemistry ; Lymph Nodes/immunology/*pathology ; Picrates ; }, abstract = {The results of an immunohistochemical study on paraffin sections of the lymph nodes from 5 patients with the acquired immunodeficiency syndrome (AIDS) related complex (ARC) are presented. The distribution and frequency of follicular dendritic cells (FDC) and of interdigitating cells (IDC) were examined with the monoclonal antibodies J3D3 (directed against the C3b complement receptor, CD 35) and IOB1a (specific for the C3D, CD21) as well as with the polyclonal anti-S-100 protein antiserum in Bouin-fixed, paraffin-embedded sections using a Streptavidin-biotin-peroxidase technique. Disruption of the follicular FDC network was demonstrated. No major alteration of the IDC was noted. The immunomorphological patterns observed in this study were comparable with the previously reported lymph node alterations studied in frozen section.}, }
@article {pmid2503440, year = {1989}, author = {Inagi, R and Yoshida, T and Isobe, K and Nakashima, I}, title = {Donor Igh-linked genetic control of allotype-specific antibody response.}, journal = {Immunogenetics}, volume = {30}, number = {2}, pages = {70-75}, pmid = {2503440}, issn = {0093-7711}, mesh = {Animals ; Antibodies, Anti-Idiotypic/*immunology ; *Antibody Formation ; Antibody Specificity ; Dose-Response Relationship, Immunologic ; Immunoglobulin Allotypes/*immunology ; Immunoglobulin G/*immunology ; Immunoglobulin Heavy Chains/*immunology ; Immunoglobulin Variable Region/*immunology ; Mice ; Mice, Inbred Strains/*immunology ; Solubility ; }, abstract = {Immunogenicity of allogeneic immunoglobulins in mice were studied, measuring the allotype-specific antibody activity by agglutination of allogeneic antibody-coated red blood cells. It was found that the serum from C.B-20 mice (Ighb, BALB/c-congenic) was uniquely immunogenic in BALB/c mice for allotype antibody response. Whereas the C57BL/6 (Ighb) serum was immunogenic only when heat aggregated and/or combined with adjuvant, the ultracentrifugation-deaggregated C.B-20 serum was definitely immunogenic when administered in a moderate dose (100 microliters/mouse). Even more surprising was the fast that very low doses (0.01-0.1 microliter) of soluble C.B-20 serum, but not C57BL/6 serum, down regulated the allotype-specific response effectively. Genetic analysis on congenic mice suggested that the immunogenicity is controlled by donor Igh or Igh-V (Id-C.B) inasmuch as the serum from BALB/c-congenic C.B-20 (Igh-VbCb), but not BALB/c-congenic BAB/14 (Igh-VaCb), mice was active in BALB/c mice in soluble form. Further studies showed that the Id-C.B was dominantly expressed on the immunoglobulins of (BALB/c x C.B-20)F1 and (C56BL/6 X C.B-20)F1 strains, and was originally derived from the C57BL/Ka strain. The major determinant for the antibody production was encoded in Igh-C, but not in Igh-V. It is suggested that Id-C.B controls the allotype-specific antibody response in an unusual manner, possibly acting as a unique determinant activating helper T cells.}, }
@article {pmid3072958, year = {1988}, author = {Marquardt, H and Westendorf, J and Schaefer, A and Boldt, J and De Clercq, E and Marquardt, H}, title = {Mutagenic and antimutagenic effects of 5-substituted 2'-deoxyuridines depending on the nature of the 5-substituent.}, journal = {Arzneimittel-Forschung}, volume = {38}, number = {12}, pages = {1820-1824}, pmid = {3072958}, issn = {0004-4172}, mesh = {Animals ; Cricetinae ; Cricetulus ; DNA/biosynthesis ; DNA Repair/drug effects ; Deoxyuridine/analogs &amp; derivatives/*pharmacology/toxicity ; In Vitro Techniques ; Male ; Microsomes, Liver/metabolism ; Mutagenicity Tests ; *Mutagens ; Rats ; Rats, Inbred Strains ; Salmonella typhimurium/drug effects/genetics ; Tumor Cells, Cultured/drug effects ; }, abstract = {Various 5-substituted pyrimidine 2'-deoxyribosides with anti-herpes activity were investigated for their genotoxic activity. 5-Iodo-2'-deoxycytidine (IDC), 5-(2-chloroethyl)-2'-deoxycytidine (CEDC), 5-(3-chloropropyl)-2'-deoxyuridine (CPDU), (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 5-ethyl-2'-deoxyuridine (EDU), 2'-deoxyuridine (DU) and 2'-deoxythymidine (DT) were non-mutagenic in Salmonella typh. as well as in V79 Chinese hamster cells, 5-Iodo-2'-deoxyuridine (IDU) was moderately mutagenic and 5-(2-chloroethyl)-2'deoxyuridine (CEDU) was highly mutagenic in V79 cells; neither IDU nor CEDU were mutagenic in the bacterial assay. None of the compounds induced unscheduled DNA synthesis in primary rat hepatocytes. In addition, antimutagenic effects of 2'-deoxyuridines were discovered: in V79 cells, BVDU, EDU, DU and DT prevented the mutagenicity induced by CEDU; in these cells EDU also inhibited the mutagenicity induced by MNNG. In primary rat hepatocytes, IDU and EDU inhibited the induction of unscheduled DNA synthesis induced by MNNG, DMBA or UV-light. The compounds were inactive at inducing differentiation in hematopoietic cells. The significance of these data, particularly with regard to the use of 5-substituted 2'-deoxyuridines in anti-herpes therapy, is discussed.}, }
@article {pmid2846422, year = {1988}, author = {Wargotz, ES and Silverberg, SG}, title = {Medullary carcinoma of the breast: a clinicopathologic study with appraisal of current diagnostic criteria.}, journal = {Human pathology}, volume = {19}, number = {11}, pages = {1340-1346}, doi = {10.1016/s0046-8177(88)80290-9}, pmid = {2846422}, issn = {0046-8177}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; }, abstract = {Fifty-three cases of mammary carcinoma originally diagnosed as medullary carcinoma (MC) or infiltrating duct carcinoma (IDC) with medullary features were reviewed and reclassified using the strictly defined histologic criteria applied a decade ago by Ridolfi et al. Our study interval (1961 to 1982) allowed for a minimum follow-up of 5 years for each patient, with a mean follow-up period of 7.2 years. When reclassified, 24 tumors fulfilled the criteria for MC, 16 tumors were determined to be atypical MC, and ten tumors were found to be IDC; the observed 5-year survival rates were 95%, 80%, and 70%, respectively. These findings confirmed those of other investigators, that when specific criteria are applied, MC proves to be a form of mammary carcinoma with a favorable prognosis. However, we also found that when tumors were excluded from the MC category solely on the basis of in situ carcinoma, focal marginal infiltration, or a sparse mononuclear infiltrate, the survival rate of these patients was similar to that of patients in the medullary category. Thus, we propose that one of these criteria alone should not suffice to exclude the diagnosis of MC. On the other hand, tumors with two or more of these atypical features, or with extensive marginal infiltration, no mononuclear cellular infiltrate, and/or less than 75% syncytial growth, should be classified as IDC with medullary features. Typical MC with bland nuclei or a focal microglandular growth pattern only were not observed in this series; however, these findings should probably also cause a tumor to be classified in the IDC category. By dividing our cases into two rather than three groups, we found a statistically significant difference between the survival rates of 94% and 64% for MC (34 tumors) and IDC (14 tumors), respectively. Although the latter figure probably exceeds the survival rate for IDC without medullary features, the difference does not appear great enough to warrant a separate diagnostic category.}, }
@article {pmid2459860, year = {1988}, author = {Schmidt, G and Barthel, P and Goedel-Meinen, L and Baedeker, W and Ulm, K}, title = {[Spontaneous variability of ventricular arrhythmias in relation to the kind and extent of underlying heart disease].}, journal = {Zeitschrift fur Kardiologie}, volume = {77}, number = {8}, pages = {523-526}, pmid = {2459860}, issn = {0300-5860}, mesh = {Adult ; Aged ; Cardiac Complexes, Premature/physiopathology ; Cardiomyopathy, Dilated/*physiopathology ; Coronary Disease/*physiopathology ; *Electrocardiography ; Female ; Heart Ventricles/*physiopathology ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; Signal Processing, Computer-Assisted ; Tachycardia/*physiopathology ; }, abstract = {The influence of the underlying heart disease on the spontaneous variability of ventricular arrhythmias was investigated prospectively in 53 patients (25 CHD, 28 IDC) with frequent and complex ventricular arrhythmias. In each patient, two consecutive ambulatory 24-h Holter ECGs were prepared and in each tape the mean hourly arrhythmia count (AC) was determined separately for singular VPCs, couplets, and salvos. The spontaneous variability between the two long-term ECGs was defined as the logarithm of the ratio (ACday 2 + 0.01)/(ACday 1 + 0.01). The 95% confidence intervals of the stated types of arrhythmias were calculated as +/- 2 SD. The results were analyzed as a function of the underlying etiology, NYHA class, and left ventricular ejection fraction. There were no differences between patients with CHD and IDC. The extent of left ventricular dysfunction did not have any influence either. In patients of NYHA class 3 there was a higher spontaneous variability of VPCs, couplets and salvos than in patients of NYHA class 2, but the differences could not be ensured statistically. We conclude from the results that the validation of an antiarrhythmic treatment can be performed independently from the nature of the underlying heart disease and the left ventricular ejection fraction. However, it remains unclear whether a greater variability must be expected in patients of NYHA class 3 than in patients of NYHA class 2.}, }
@article {pmid3285097, year = {1988}, author = {Nabarra, B and Papiernik, M}, title = {Phenotype of thymic stromal cells. An immunoelectron microscopic study with anti-IA, anti-MAC-1, and anti-MAC-2 antibodies.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {58}, number = {5}, pages = {524-531}, pmid = {3285097}, issn = {0023-6837}, mesh = {Animals ; Antibodies, Monoclonal ; Antigens, Differentiation/analysis ; Antigens, Surface/analysis ; Dendritic Cells/immunology/ultrastructure ; Epithelial Cells ; Epithelium/immunology/ultrastructure ; Female ; Galectin 3 ; Histocompatibility Antigens Class II/analysis ; Immunohistochemistry ; Macrophage-1 Antigen ; Macrophages/immunology/ultrastructure ; Mice ; Mice, Inbred DBA ; Microscopy, Electron/methods ; Phenotype ; Thymus Gland/*cytology/immunology/ultrastructure ; }, abstract = {To better comprehend the thymic microenvironment, it is necessary to identify the antigenic profile of cells forming the thymic reticulum which are involved in intrathymic T cell differentiation. These cells are of three types: epithelial cells, macrophages, and interdigitating cells (IDC). Although several studies have been done on thymus section in light microscopy, identification of the positive cells, and mainly the antigenic equipment of the macrophages and IDC has not been clearly analyzed. Morphology, in electron microscopy is so far the best method to identify the different types of cells, and immunoelectron microscopy on thymic sections may be the best method to define clearly stromal cell phenotypes. In the present paper, we analyzed two antigens which classically define the macrophage family, Mac-1 and Mac-2, as well as major histocompatibility complex class II antigen which is present on epithelial cells and on bone marrow derived stromal cells. We show that epithelial cells are Ia+ Mac-1-, Mac-2-; macrophages are all Mac-1+, Mac-2+ but only half are Ia+; IDC are Ia+, Mac-1+, Mac-2+. These results show that IDC and macrophages both express antigens which were originally described as macrophage-specific.}, }
@article {pmid2456534, year = {1988}, author = {Milner, PG and Dimarco, JP and Lerman, BB}, title = {Electrophysiological evaluation of sustained ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {11}, number = {5}, pages = {562-568}, doi = {10.1111/j.1540-8159.1988.tb04551.x}, pmid = {2456534}, issn = {0147-8389}, support = {HL-35860/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Anti-Arrhythmia Agents/therapeutic use ; Cardiomyopathy, Dilated/complications/*physiopathology ; Electric Stimulation ; Electrocardiography ; *Electrophysiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Recurrence ; Tachycardia/drug therapy/etiology/*physiopathology ; Ventricular Fibrillation/drug therapy/etiology/*physiopathology ; }, abstract = {Sustained ventricular tachyarrhythmias and sudden death are particularly prevalent in patients with idiopathic dilated cardiomyopathy (IDC). In contrast to patients with ischemic heart disease, the value of electrophysiological stimulation (EPS) in patients with IDC has not yet been established. To clarify the role of EPS in these patients, we studied 19 patients (58 +/- 11 years) with IDC who had symptomatic ventricular tachycardia (VT) or ventricular fibrillation (VF). The mean left ventricular ejection fraction was 26 +/- 9%. Ten patients had survived out-of-hospital cardiac arrest, eight had documented sustained monomorphic VT and one patient had non-sustained VT associated with syncope. Thirteen of the 19 patients (68%) had their clinical ventricular tachyarrhythmias induced at EPS (12 VT, 1 VF). In nine of 13 patients (69%), the arrhythmias were subsequently suppressed during serial electrophysiological drug testing. During 17 +/- 11 months of follow-up, 10/19 (53%) patients experienced recurrence of their arrhythmias and nine out of 19 (47%) patients died; six died suddenly and three secondary to heart failure. There was no difference in arrhythmia recurrence between patients with and without inducible ventricular tachyarrhythmias at initial study. Furthermore, suppression of arrhythmia during serial testing did not predict outcome; recurrences were observed in five out of nine patients whose arrhythmias were suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid2895542, year = {1988}, author = {Kirchner, T and Hoppe, F and Schalke, B and Müller-Hermelink, HK}, title = {Microenvironment of thymic myoid cells in myasthenia gravis.}, journal = {Virchows Archiv. B, Cell pathology including molecular pathology}, volume = {54}, number = {5}, pages = {295-302}, doi = {10.1007/BF02899226}, pmid = {2895542}, issn = {0340-6075}, mesh = {Adolescent ; Adult ; Antigen-Presenting Cells/pathology ; Child ; Child, Preschool ; Humans ; Immunohistochemistry ; Infant ; Middle Aged ; Muscles/*cytology/immunology ; Myasthenia Gravis/*pathology ; Thymus Gland/*cytology/immunology ; }, abstract = {The microenvironment of myoid cells (MyCs) was studied in myasthenia gravis (MG) thymitis with lymphoid follicular hyperplasia (LFH) (nine cases) and with diffuse B cell infiltration (one case), and compared with findings in the thymuses of non-myasthenic control subjects (ten cases). Double immunostaining was used to demonstrate MyCs labelled by anti-desmin together with other thymic components such as keratin-positive epithelial cells, Ki-M 1-positive interdigitating reticulum cells (IDCs), Ki-M 4-positive follicular dendritic reticulum cells, Ki-M 6-positive macrophages, CD22-positive B-cells, CD1-positive cells, CD3-positive T-cells or HLA-DR-positive cells. Round or elongated MyCs were confined to the thymic medulla and were surrounded by CD3-positive T-cells and CD22-positive B-cells. In MG thymitis MyCs were localized in the vicinity of, but not inside germinal centres (GCs). MyCs were always HLA-DR-negative, but were invariably embedded in a cellular micromilieu with strong HLA-DR expression. A remarkable feature of MG thymitis was that the great majority of MyCs were in intimate contact with intramedullary IDCs. Morphometric studies confirmed that such contacts were significantly less frequent in thymuses from non-myasthenic subjects. This indicates that an IDC-dependent antigen-presenting process for T-cells may actively involve MyCs in MG thymitis.}, }
@article {pmid2852696, year = {1988}, author = {Weber, J and Tournemaine, N and Audoin, AF and Digabel-Chabay, C}, title = {[An unusual clinical form of intraductal breast carcinoma: an inflammatory syndrome. Apropos of 5 cases].}, journal = {Journal de gynecologie, obstetrique et biologie de la reproduction}, volume = {17}, number = {5}, pages = {635-640}, pmid = {2852696}, issn = {0368-2315}, mesh = {Adult ; Biopsy, Needle ; Calcinosis/pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Histiocytes/pathology ; Humans ; Mammography ; Mastitis/pathology ; Middle Aged ; Syndrome ; Thermography ; }, abstract = {The authors report 5 cases of in situ intraductal breast carcinoma (IDC) revealed or complicated by a clinical inflammatory syndrome. These cases showed some common features with other IDCs, such as mammographic signs and histologic forms of epitheliamatous proliferation, but were also characterized by clinical inflammatory signs different from those of rapidly developing "inflammatory" cancer, frequent nipple discharge, frequent positive results in bacteriologic examinations of nipple discharge and the role of cytologic studies of discharge in determining a definite diagnosis of carcinoma. Some hypotheses as to etiology are also discussed.}, }
@article {pmid3326293, year = {1987}, author = {Smetana, R and Glogar, D and Weidinger, F and Meisinger, V}, title = {[Heavy metal and trace element deviations. A comparison of idiopathic dilated cardiomyopathy and coronary heart disease].}, journal = {Wiener medizinische Wochenschrift (1946)}, volume = {137}, number = {23}, pages = {553-557}, pmid = {3326293}, issn = {0043-5341}, mesh = {Aged ; Cadmium/metabolism ; Cadmium Poisoning/metabolism ; Cardiomyopathy, Dilated/*metabolism ; Coronary Disease/*metabolism ; Female ; Hemodynamics ; Humans ; Male ; Metals/*metabolism ; Middle Aged ; Risk Factors ; Trace Elements/*metabolism ; }, abstract = {Blood, serum and urine (24-hour-samples) concentrations of cadmium, zinc, calcium and magnesium were determined by means of atomic absorption spectrophotometry in 60 patients, therefrom 30 patients with idiopathic dilated cardiomyopathy (IDC) and 30 patients with coronary heart disease (CHD). The data of heavy metal and trace element concentrations of IDC and CHD patients were compared with each other and furthermore, for each group separately, correlated with patients history data, laboratory evaluations and data from heart catherization protocol. IDC patients showed higher blood cadmium concentrations (p less than 0.001) and lower serum zinc concentrations (p less than 0.001) compared to CHD patients. Serum levels of calcium and magnesium were not different in both groups. In urine samples IDC patients had lower concentrations of calcium (p less than 0.01) and magnesium (p less than 0.01) compared to CHD patients. Urine concentrations of cadmium and zinc were in the same range in both groups. The comparison of heavy metal and trace element concentrations with clinical data did not reveal definite correlations, however, data from experimental studies pointing out interactions of heavy metals and trace elements, could serve as useful interpretations. Hypomagnesemia in both patient groups (IDC, CHD) requires clinical follow up and substitution treatment.}, }
@article {pmid2831624, year = {1987}, author = {McAlpine, LG and Williams, DJ and Dagg, JH}, title = {Breast cancer, chronic lymphocytic leukaemia and mucormycosis.}, journal = {Scottish medical journal}, volume = {32}, number = {5}, pages = {150-151}, doi = {10.1177/003693308703200511}, pmid = {2831624}, issn = {0036-9330}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*complications ; Carcinoma/*complications ; Carcinoma, Intraductal, Noninfiltrating/*complications ; Female ; Humans ; Leukemia, Lymphoid/*complications ; Mucormycosis/*complications ; *Neoplasms, Multiple Primary ; }, abstract = {Prolonged survival following diagnosis of lipid-rich carcinoma of breast is unusual. We report on a patient in whom lipid-rich carcinoma of one breast, invasive ductal carcinoma of the other breast and chronic lymphocytic leukaemia were diagnosed simultaneously; she survived 14 years without breast tumour recurrence and died with atypical mucormycosis.}, }
@article {pmid2438920, year = {1987}, author = {Yamazoe, M}, title = {Response of the left ventricle in idiopathic dilated cardiomyopathy to postextrasystolic potentiation.}, journal = {American heart journal}, volume = {113}, number = {6}, pages = {1449-1456}, doi = {10.1016/0002-8703(87)90661-2}, pmid = {2438920}, issn = {0002-8703}, mesh = {Adult ; Blood Pressure ; Cardiac Catheterization ; Cardiac Complexes, Premature/*physiopathology ; Cardiomyopathy, Dilated/*etiology/physiopathology ; Female ; Heart/*physiopathology ; Heart Ventricles ; Humans ; Male ; Middle Aged ; Movement ; *Myocardial Contraction ; }, abstract = {The effectiveness of postextrasystolic potentiation (PESP) was assessed to detect residual function of the left ventricle in seven patients with idiopathic dilated cardiomyopathy (IDC). The postextrasystolic changes in the aortic pressure pulse, global left ventricular function, and quantitative regional left ventricular wall motion were investigated. PESP caused an increase in the peak systolic aortic pressure (116 +/- 17 to 130 +/- 25 mm Hg, p less than 0.01), a decrease in the peak diastolic aortic pressure (74 +/- 12 to 61 +/- 11 mm Hg, p less than 0.001), a decrease in preejection period/left ventricular ejection time (PEP/LVET) ratio (0.637 +/- 0.136 to 0.457 +/- 0.097, p less than 0.001), and an increase in the global left ventricular ejection fraction (LVEF) (0.26 +/- 0.09 to 0.40 +/- 0.12, p less than 0.01). Postextrasystolic changes in LVEF were inversely related to changes in PEP/LVET (r = -0.76, p less than 0.05). The postextrasystolic patterns of the regional wall motion of the left ventricle were different in each patient. The results of this study suggest that residual left ventricular function can be detected in patients with IDC by their response to PESP.}, }
@article {pmid2441534, year = {1987}, author = {Schmidt, G and Goedel-Meinen, L and Ulm, K and Jahns, G and Barthel, P and Stief, P and Schaudig, UH and Klein, G and Baedeker, W and Blömer, H}, title = {[Spontaneous variability of ventricular extrasystoles: criteria for validating anti-arrhythmia therapy in relation to the length of the control interval].}, journal = {Zeitschrift fur Kardiologie}, volume = {76}, number = {5}, pages = {292-295}, pmid = {2441534}, issn = {0300-5860}, mesh = {Anti-Arrhythmia Agents/*therapeutic use ; Cardiac Complexes, Premature/*drug therapy ; Cardiomyopathy, Dilated/complications ; Coronary Disease/complications ; *Electrocardiography ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; }, abstract = {Calculations about the variability of PVCs are usually based upon the results of two Holter ECGs, either successive ones or separated by a short interval. No studies are available indicating whether the criteria calculated for short control intervals also holds true when evaluating chronic antiarrhythmic treatment over longer control periods. This study was performed to investigate the influence of the length of the control interval on the spontaneous variability and thus on the reduction of PVCs required to secure an antiarrhythmic effect. In a prospective study, 444 ambulatory ECGs were obtained in 90 patients with CAD or IDC and untreated ventricular arrhythmia of Lown grade IV. Patient follow-up was carried out over an average of 181 +/- 297 days. The degree of arrhythmia was expressed as the mean hourly PVC rate. The variability of PVC counts between two Holter ECGs was defined as the logarithm of the quotient PVCday 2(n + 1)/PVCday 1(n + 1). The spontaneous distribution of variability quotients was defined separately (mean +/- 2 SD) for each of four ranges of control intervals (0-6 days, 7-89 days, 90-364 days, greater than or equal to 365 days). The per cent reduction (R) in PVC frequency necessary to establish drug efficacy, was calculated according to the formula R (%) = 10(0)-10(-2SD) X 100, whereas the percentage change necessary to prove aggravation of arrhythmia (A) was assessed by the formula A (%) = 10(0)+10(+2SD X 100. R increased from 63% (0-6 days), 81% (7-89 days), 93% (90-364 days) to 98% (greater than or equal to 365 days).(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid3531383, year = {1986}, author = {Forbes, RD and Parfrey, NA and Gomersall, M and Darden, AG and Guttmann, RD}, title = {Dendritic cell-lymphoid cell aggregation and major histocompatibility antigen expression during rat cardiac allograft rejection.}, journal = {The Journal of experimental medicine}, volume = {164}, number = {4}, pages = {1239-1258}, pmid = {3531383}, issn = {0022-1007}, mesh = {Animals ; Blood Vessels/immunology ; Cell Aggregation ; Dendritic Cells/*pathology ; Endothelium/immunology ; *Graft Rejection ; *Heart Transplantation ; Histocompatibility Antigens/*analysis ; Lymphocytes/*pathology ; Microscopy, Electron ; Myocardium/immunology/pathology/ultrastructure ; Rats ; Rats, Inbred ACI ; Rats, Inbred BN ; Transplantation, Homologous ; }, abstract = {To determine the pattern of cellular expression of donor MHC class I and class II antigens during the course of rat cardiac allograft rejection, ACI cardiac allografts transplanted to BN recipients were examined from day 2 to day 6 using immunohistologic and immunoelectron microscopic methods. We used both monomorphic and donor-specific mouse anti-rat MHC class I and class II mAbs in this study. In normal ACI hearts, MHC class I reactivity was confined to the vascular endothelium and to interstitial cells. Ongoing rejection was characterized by an increased donor MHC class I staining intensity of microvascular endothelium and induction of donor class I surface reactivity on cardiac myofibers. Donor MHC class II reactivity was exclusively confined to interstitial dendritic cells (IDC) in both normal ACI hearts and in rejecting allografts, although rejection was associated with marked fluctuations in class II IDC frequency. An early numerical depression in class II IDC present in both allografts and syngeneic heart grafts was attributed to a direct effect of the transplantation procedure. By days 3-4, allografts showed an absolute overall increase in donor class II IDC frequency, which was associated with the presence of multiple localized high-density IDC-lymphocyte aggregates. The lymphocytes present in the focal areas were predominantly of the class II-reactive Th cell subpopulation. These aggregates may thus represent the in vivo homologue of dendritic cell-lymphocyte clustering, which has been shown to be required for primary class II allosensitization in the rat and mouse in vitro. During the late phase of rejection, there was a marked numerical fall in donor class II IDC, which correlated with extensive overall graft destruction. This study has shown that acute rat cardiac allograft rejection can occur in the absence of donor MHC class II expression by allograft vascular endothelium and cardiac myofibers. The IDC, which are believed to represent the principal class II alloantigen presenting cells in the rat heart, remain the sole class II-expressing cellular constituents of the graft throughout the course of rejection.}, }
@article {pmid3738591, year = {1986}, author = {Ferrari, HA and Renner, GJ and Luebrecht, SM and Love, GA}, title = {High-frequency jet ventilation: applications for endoscopy and surgery of the airway.}, journal = {Southern medical journal}, volume = {79}, number = {8}, pages = {941-943}, doi = {10.1097/00007611-198608000-00006}, pmid = {3738591}, issn = {0038-4348}, mesh = {Adult ; Airway Obstruction/etiology/surgery/*therapy ; Carcinoma, Squamous Cell/complications ; Evaluation Studies as Topic ; Female ; Humans ; Laryngeal Neoplasms/complications ; Laryngoscopy ; Lung Diseases, Obstructive/complications ; Male ; Middle Aged ; Oxygen Inhalation Therapy ; Premedication ; Respiration, Artificial/adverse effects/*methods ; }, abstract = {Twenty-four patients underwent endoscopic procedures under general anesthesia and mechanical ventilation by high-frequency jet ventilation, provided by a catheter inserted through the cricothyroid membrane and connected to an IDC-VS600 ventilator. The arterial blood gas values, arterial blood pressures, and heart rates observed were within acceptable clinical levels. In some patients, blockage of the airway by the surgeon required shutting off the ventilator to prevent a pneumothorax. With the rapid rate jet ventilation, we found that laryngeal bleeding after biopsy passed outward from the larynx into the hypopharynx. It was necessary for the surgeon to wear protective eye and face shielding when performing endoscopies to avoid getting blood and secretions on his face. The unobstructed surgical field is an advantage of the jet ventilation, which can be continued in the postoperative period until the patient is fully recovered.}, }
@article {pmid3020058, year = {1986}, author = {Langlois, M and Allard, JP and Nugier, F and Aymard, M}, title = {A rapid and automated colorimetric assay for evaluating the sensitivity of herpes simplex strains to antiviral drugs.}, journal = {Journal of biological standardization}, volume = {14}, number = {3}, pages = {201-211}, doi = {10.1016/0092-1157(86)90004-1}, pmid = {3020058}, issn = {0092-1157}, mesh = {Antiviral Agents/*pharmacology ; Colorimetry/*methods ; Microbial Sensitivity Tests/*methods ; Mutation ; Simplexvirus/*drug effects/enzymology/genetics ; Thymidine Kinase/metabolism ; }, abstract = {A rapid and sensitive colorimetric assay has been developed to evaluate the sensitivity of herpes simplex viruses (HSV) to antiviral agents. The chessboard titration of viruses and antiviral drugs and the automatic reading and analysis of the data allows objective and accurate results to be rapidly obtained. Virus sensitivity was expressed as an ED50 value which was the concentration of drug (micrograms/ml) reducing viral cpe by 50%. The ED50 values of antiviral drugs [acetylguanosine (ACV), idoxuridine (IDU), deoxycytidine (IDC) and bromovinyl deoxyuridine] for several HSV reference strains were determined and the method was then applied to clinical specimens. The selection of ACV and IDU resistant mutants was performed on a cloned sensitive HSV 1 ocular strain. We observed cross-resistance between ACV and IDU for the mutants isolated. The resistance to thymidine-kinase-dependent antiviral agents varied in inverse ratio to the thymidine kinase activity induced by HSV strains.}, }
@article {pmid3519443, year = {1986}, author = {Groeneveld, PH and Erich, T and Kraal, G}, title = {The differential effects of bacterial lipopolysaccharide (LPS) on splenic non-lymphoid cells demonstrated by monoclonal antibodies.}, journal = {Immunology}, volume = {58}, number = {2}, pages = {285-290}, pmid = {3519443}, issn = {0019-2805}, mesh = {Acid Phosphatase/metabolism ; Animals ; Antibodies, Monoclonal/immunology ; Carboxylesterase ; Carboxylic Ester Hydrolases/metabolism ; Cell Movement ; Immunoenzyme Techniques ; Leukocyte Count ; Lipopolysaccharides/*pharmacology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Spleen/cytology/*drug effects/enzymology ; }, abstract = {In the present study, the effect of LPS on different splenic non-lymphoid cells was investigated. Marginal zone (MZ) macrophages, marginal metallophils and interdigitating cells (IDC) were demonstrated using specific monoclonal antibodies in a two-step immunoperoxidase procedure in combination with enzyme histochemistry. The results indicate that the number of marginal zone macrophages decreases markedly after LPS treatment, but is followed by a rapid repopulation as observed by monoclonal antibody staining and selective uptake of FITC-Ficoll. Marginal metallophils are normally located at the inner border of the marginal sinus and can specifically be identified by the monoclonal antibody MOMA-1. Following LPS stimulation, many MOMA-1-positive cells were present in the corona and central parts of the follicles, with decreasing numbers near the marginal sinus. These findings strongly suggest that LPS induces a migration of marginal metallophils towards the follicle centres. Most of the tangible body macrophages in the follicle centres appeared to be slightly MOMA-1-positive, which indicates that marginal metallophils may, at least under certain circumstances, differentiate into tangible body macrophages. In the inner PALS, many interdigitating cells, NLDC-145-positive cells, can be found. The number of NLDC-145-positive cells was shown to be severely decreased at later time-intervals after LPS administration, resulting in an almost unstained inner PALS at 2 days. In contrast to the above-mentioned splenic non-lymphoid cells, the red pulp macrophages are only minimally affected by LPS.}, }
@article {pmid2424458, year = {1986}, author = {Iguchi, T and Kurosaka, M and Ziff, M}, title = {Electron microscopic study of HLA-DR and monocyte/macrophage staining cells in the rheumatoid synovial membrane.}, journal = {Arthritis and rheumatism}, volume = {29}, number = {5}, pages = {600-613}, doi = {10.1002/art.1780290504}, pmid = {2424458}, issn = {0004-3591}, support = {AM-09989/AM/NIADDK NIH HHS/United States ; AM-14155/AM/NIADDK NIH HHS/United States ; }, mesh = {Arthritis, Rheumatoid/*immunology/pathology ; HLA-DR Antigens ; Histocompatibility Antigens Class II/*analysis ; Humans ; In Vitro Techniques ; Macrophages/*ultrastructure ; Microscopy, Electron ; Monocytes/*ultrastructure ; Staining and Labeling ; Synovial Membrane/*immunology/ultrastructure ; }, abstract = {We examined synovial membrane samples from 6 rheumatoid arthritis (RA) and 3 osteoarthritis patients and from 1 normal subject, by an immunoelectron microscopic technique using anti-HLA-DR (anti-Ia) and anti-monocyte/macrophage (63D3) monoclonal antibodies. In the lining layer, the type A macrophage-like cells were strongly DR+ and 63D3+, whereas the type B fibroblast-like cells were almost completely negative. Lymphocyte-rich areas (containing more than 90% densely packed lymphocytes) showed weak and patchy DR staining of the lymphocytes. In these areas, 3-5% of the cells were macrophage-like cells which were 63D3-, a type of staining compatible with that of the interdigitating cell (IDC). In the plasma cell-containing (transitional) areas, many strongly DR+ macrophage-like cells were observed in close contact with lymphocytes and plasma cells. Ten to twenty percent of these cells were 63D3-, which suggests that they were IDC. Cells with the structural appearance of IDC were most frequently seen in those transitional areas which contained elevated concentrations (50-70%) of lymphocytes. In uninfiltrated interstitial areas, approximately 50% of the cells stained strongly with both anti-DR and 63D3 antibody, indicating that they were cells of monocyte/macrophage lineage, presumably histiocytes. This investigation has demonstrated the presence of the DR antigen in the RA synovial membrane on 1) phagocytic cells of the lining area, 2) lymphocytes and small numbers of IDC-like cells in dense, lymphocyte-rich areas, 3) large numbers of macrophage-like cells, of which some had the morphologic appearance of IDC, in transitional or plasma cell-containing areas, and 4) histiocytic cells in uninfiltrated interstitial areas. The observation of large numbers of DR+ macrophages and IDC-like cells in close contact with lymphocytes and plasma cells in the RA synovial membrane emphasizes their role in an active immune response. The observation of substantial numbers of potentially immunocompetent, DR+ histiocytic cells in uninfiltrated regions of the synovial membrane suggests that such cells may play a role in the progression of the synovial inflammatory reaction.}, }
@article {pmid3950549, year = {1986}, author = {Kraal, G and Breel, M and Janse, M and Bruin, G}, title = {Langerhans' cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody.}, journal = {The Journal of experimental medicine}, volume = {163}, number = {4}, pages = {981-997}, pmid = {3950549}, issn = {0022-1007}, mesh = {Animals ; *Antibodies, Monoclonal ; *Bone Marrow Cells ; Langerhans Cells/*immunology ; Lymphoid Tissue/*cytology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Molecular Weight ; Peritoneal Cavity/cytology ; Rats ; Skin/cytology ; }, abstract = {An mAb, NLDC-145, is described that specifically reacts with a group of nonlymphoid dendritic cells including Langerhans cells (LC), veiled cells (VC), and interdigitating cells (IDC). The antibody does not react with precursor cells in bone marrow and blood. Macrophages are not stained by the antibody, but a subpopulation of Ia+ peritoneal exudate cells is recognized. Possible relationships of the various nonlymphoid dendritic cell (NLDC) types are discussed.}, }
@article {pmid3457707, year = {1986}, author = {Fossum, S and Rolstad, B}, title = {The roles of interdigitating cells and natural killer cells in the rapid rejection of allogeneic lymphocytes.}, journal = {European journal of immunology}, volume = {16}, number = {4}, pages = {440-450}, doi = {10.1002/eji.1830160422}, pmid = {3457707}, issn = {0014-2980}, mesh = {Animals ; Antibodies, Monoclonal ; Antigen-Presenting Cells/*immunology ; Antigens, Surface/analysis ; *Cytotoxicity, Immunologic ; Histocompatibility Antigens Class II/analysis ; Killer Cells, Natural/*immunology ; Lymph/*immunology ; Microscopy, Electron ; Phagocytes/*immunology/ultrastructure ; Phagocytosis ; Rats ; }, abstract = {The fate of radiolabeled allogeneic thoracic duct lymphocytes injected into congenitally athymic, nude rats was followed by autoradiography and electron microscopy. The allogeneic cells entered the host lymphoid organs at a normal rate, but once inside the lymphoid tissue they were rapidly phagocytozed by interdigitating cells (IDC) situated in the lymph node paracortex and the splenic periarteriolar lymphoid sheaths. Neither host nor donor T cells were required to initiate phagocytosis, as purified donor B cells were also avidly ingested by the athymic host IDC. Compared with fully allogeneic cells phagocytosis of semiallogeneic donor cells was much less efficient. When natural killer cell activity was blocked by preinjecting the recipients with antibodies against natural killer cells (anti-asialo GM1 or MRC OX-8) phagocytosis of the allogeneic cells was strongly reduced. As IDC did not bind these antibodies, the finding indicates that natural killer cells were needed to discriminate between own and foreign lymphocytes and to kill the allogeneic cells, which were then ingested by surrounding IDC. This was further supported by the observation that dendritic, constitutively Ia+ cells from peripheral lymph, phenotypically identical to IDC, did not lyse or phagocytoze allogeneic lymphocytes in vitro.}, }
@article {pmid3510968, year = {1986}, author = {Namikawa, R and Mizuno, T and Matsuoka, H and Fukami, H and Ueda, R and Itoh, G and Matsuyama, M and Takahashi, T}, title = {Ontogenic development of T and B cells and non-lymphoid cells in the white pulp of human spleen.}, journal = {Immunology}, volume = {57}, number = {1}, pages = {61-69}, pmid = {3510968}, issn = {0019-2805}, mesh = {B-Lymphocytes/immunology/*ultrastructure ; Bone Marrow/embryology ; Humans ; Immunoenzyme Techniques ; Immunoglobulin D/analysis ; Immunoglobulin M/analysis ; Liver/embryology ; Microscopy, Electron ; Morphogenesis ; Receptors, Antigen, B-Cell/analysis ; S100 Proteins/analysis ; Spleen/*embryology/immunology ; T-Lymphocytes/immunology/*ultrastructure ; Thymus Gland/embryology ; }, abstract = {The ontogenic development of lymphoid and non-lymphoid cells in human splenic white pulp was studied histologically with immunoperoxidase technique, together with that of lymphoid cells from fetal liver, bone marrow and thymus by membrane immunofluorescence assay. The primitive white pulp, which appeared as small accumulations of lymphocytes around arterioles at 14 weeks of gestation (g.w.), was mainly composed of B1 antigen-positive B cells. After the appearance of follicular structure accompanied by follicular dendritic cells (FDC) stained with anti-DRC1 antibody at 26 g.w., these perivascular structures of B cells were located in the periphery of the white pulp areas. A large number of B cells composing the perivascular structure had surface IgM (sIgM) and IgD (sIgD) from the earliest stage (14 g.w.), although this type of B cell with mature phenotype was seldom observed in fetal liver or bone marrow at this stage. It was suggested that the spleen is an important site for B-cell maturation from sIg-negative B cells observed in 10-14 g.w. fetal liver, and that FDC are not involved in this development of B cells. The organization of 9.6 antigen-positive T cells around arterioles developed 4 weeks later than that of B cells, at 18 g.w., although 11 g.w. fetal thymocytes already showed a phenotype very similar to that of infants. Interdigitating reticulum cells (IDC) stained with anti-S-100 protein serum appeared from 14 g.w. before the T-cell organization, suggesting that IDC may play an essential role in the homing of T cells.}, }
@article {pmid2999258, year = {1985}, author = {Van Dyke, RB and Connor, JD}, title = {Uptake of [125I]iododeoxycytidine by cells infected with herpes simplex virus: a rapid screening test for resistance to acyclovir.}, journal = {The Journal of infectious diseases}, volume = {152}, number = {6}, pages = {1206-1211}, doi = {10.1093/infdis/152.6.1206}, pmid = {2999258}, issn = {0022-1899}, mesh = {Acyclovir/*pharmacology ; Animals ; Bromodeoxycytidine/analogs &amp; derivatives ; Cell Line ; Chlorocebus aethiops ; Deoxycytidine/*analogs &amp; derivatives/metabolism ; Drug Resistance, Microbial ; Herpes Simplex/drug therapy/*metabolism/microbiology ; Humans ; Kidney ; Microbial Sensitivity Tests/methods ; Simplexvirus/drug effects/enzymology ; Thymidine Kinase/metabolism ; }, abstract = {A rapid screening test for resistance to acyclovir, mediated by a lack of thymidine kinase (TK) activity in herpes simplex virus (HSV), was developed by utilizing the uptake of [125I]iododeoxycytidine (IdC) by infected Vero cells. Cells infected with TK+ virus demonstrate uptake of IdC within 3 hr of infection. The assay can detect as few as 690 pfu of virus. Cells infected with TK virus have an uptake of IdC similar to that of uninfected cells, whereas cells infected with TK+ generally have an uptake greater than 10 times that of uninfected cells if tested when obvious viral cytopathic effect is present. All 19 clinical HSV isolates tested were correctly identified as TK+. Of 17 blinded HSV isolates tested, all six TK- isolates were correctly identified. A single strain with an ID50 of 3.4 micrograms/ml and an altered TK substrate specificity was incorrectly classified as TK+. The assay is a useful, rapid screening test for viral TK activity.}, }
@article {pmid4027536, year = {1985}, author = {Wilkinson, MJ and Howell, A and Harris, M and Adam, NM and Lupton, E and Johnson, RJ and Sellwood, RA}, title = {Retroperitoneal tumour infiltration detected by bone scanning in patients with infiltrating lobular carcinoma of the breast.}, journal = {The British journal of surgery}, volume = {72}, number = {8}, pages = {626-628}, doi = {10.1002/bjs.1800720814}, pmid = {4027536}, issn = {0007-1323}, mesh = {Bone Neoplasms/diagnostic imaging/*secondary ; Bone and Bones/*diagnostic imaging ; Breast Neoplasms/*pathology ; Humans ; Kidney Pelvis/diagnostic imaging ; Radionuclide Imaging ; Retroperitoneal Neoplasms/diagnostic imaging/*secondary ; Ureteral Neoplasms/diagnostic imaging/secondary ; }, abstract = {Radionuclide bone scans performed in some patients with carcinoma of the breast showed abnormal retention of isotope in the renal pelvis which developed and progressed during the period of follow-up after mastectomy. This phenomenon was seen in 15 of 30 patients with infiltrating carcinoma of the breast (ILC) but in none of 29 with infiltrating duct carcinoma (IDC). Autopsies were performed in eight of the patients with ILC and three of those with IDC. Diffuse retroperitoneal and ureteric infiltration was seen in seven (88 per cent), with ILC and none with IDC. These data suggest that this scan abnormality is an indicator of retroperitoneal spread by ILC.}, }
@article {pmid3159251, year = {1985}, author = {Anderson, JL and Carlquist, JF and Higashikubo, R}, title = {Quantitation of lymphocyte subsets by immunofluorescence flow cytometry in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {55}, number = {13 Pt 1}, pages = {1550-1554}, doi = {10.1016/0002-9149(85)90971-3}, pmid = {3159251}, issn = {0002-9149}, mesh = {Adult ; Aged ; B-Lymphocytes/immunology ; Cardiomyopathies/*immunology/pathology ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Killer Cells, Natural/immunology ; Lymphocytes/*classification/immunology/pathology ; Male ; Middle Aged ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is a disease in which immune aberration has been postulated but not confirmed. The frequency of lymphocyte subsets was evaluated in 22 patients with IDC and in 22 blood bank control subjects, using monoclonal antibodies to cell surface markers to allow cell sorting by immunofluorescence flow cytometry. Eighteen patients with heart failure from other causes were also studied. Functional correlations were also made for the natural killer cell subset. Total T-cell frequency, determined with antihuman T (Hybritech), was similar in IDC and control groups: mean 73 +/- 12% in IDC patients and 70 +/- 9% in control subjects. B-cell frequency, determined with antihuman Ia (Hybritech), was also similar: 36 +/- 11% in IDC patients and 31 +/- 10% in control subjects. Helper T-cell frequency, identified by OKT4 (Ortho), averaged 47 +/- 11% in IDC and 44 +/- 8% in control subjects (difference not significant). Suppressor/cytotoxic T-cell frequency, established by OKT8, was the same: 28 +/- 8% in IDC and 30 +/- 7% in control subjects, although relative deficiency in suppressor functional activity has been reported in IDC. Helper to suppressor (OKT4/8) ratios, aberrant in many autoimmune diseases, did not differ significantly (IDC 1.9 +/- 0.8, control 1.5 +/- 0.6). Lymphocyte subsets and OKT4/8 ratio were also similar between IDC and heart failure patients. Natural killer cell frequencies, estimated using 2 antibodies (antihuman Leu-7 and Leu-11, Becton-Dickinson) were the same (9.3 +/- 4.9% in IDC patients, 9.0 +/- 4.5% in control subjects, Leu-7).(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid3881522, year = {1985}, author = {Szakal, AK and Gieringer, RL and Kosco, MH and Tew, JG}, title = {Isolated follicular dendritic cells: cytochemical antigen localization, Nomarski, SEM, and TEM morphology.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {134}, number = {3}, pages = {1349-1359}, pmid = {3881522}, issn = {0022-1767}, support = {2S07RR05430/RR/NCRR NIH HHS/United States ; 2S07RR05697/RR/NCRR NIH HHS/United States ; AI 17142/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigen-Presenting Cells/immunology/*ultrastructure ; Antigens/*analysis ; Cell Separation/methods ; Histocytochemistry ; Horseradish Peroxidase/*immunology ; Immunoenzyme Techniques ; Lymph Nodes/*ultrastructure ; Mice ; Mice, Inbred C3H ; Microscopy, Electron, Scanning ; Microscopy, Interference ; Microscopy, Phase-Contrast ; Peroxidases/*immunology ; }, abstract = {The objectives of the present study were to determine the cytological features of isolated follicular dendritic cells (FDC), which distinguish them from other leukocytes or dendritic cell types. Consequently, we have developed methods for the fixation, peroxidase cytochemistry, and visualization of FDC, which are applicable to cytological evaluations by Nomarski optics, scanning, and transmission electron microscopy. A functionally supported identification of FDC in vitro was made possible by utilizing, in conjunction with the dendritic morphology, the cytochemically identifiable antigen, horseradish peroxidase (HRP), and the known capacity of FDC to sequester immune complexes (i.e. HRP-anti-HRP) on their plasma membranes. The observations showed that FDC constitute a relatively pleomorphic, nonphagocytic group, distinct from other dendritic type cells such as lymphoid dendritic cells, Langerhans cells, and interdigitating cells (LDC, LC, and IDC), as well as typical leukocytes. Morphologically distinct FDC were identified as cells either with filiform dendrites or with "beaded" dendrites. FDC possessed a single or sometimes a double, lymphocyte-size cell body, which contained an irregular, lobated nucleus, Golgi apparatus, numerous small vesicles, and some mitochondria. Mitochondria were not abundant in the dendritic processes. Filiform dendrites tended to branch and anastomose near the cell body and form a radiating "sunburst"-like pattern. On the average, dendrites measured 15-20 microns in length and 0.1-0.3 micron in diameter. Occasional dendrites were extremely elongated, reached several hundred microns in length, and terminated in an enlargement measuring nearly a micron in diameter. Other filiform dendrites usually had a club-shaped terminal enlargement. The microspheres of "beaded" dendrites ranged between 0.3 and 0.6 micron in diameter. The dendritic processes were also shown to have a highly ordered pattern of immune complex attachment on their surface, suggestive of a periodic arrangement of receptor sites.}, }
@article {pmid4038571, year = {1985}, author = {Greenberg, JM and Murphy, JH and Okada, RD and Pohost, GM and Strauss, HW and Boucher, CA}, title = {Value and limitations of radionuclide angiography in determining the cause of reduced left ventricular ejection fraction: comparison of idiopathic dilated cardiomyopathy and coronary artery disease.}, journal = {The American journal of cardiology}, volume = {55}, number = {5}, pages = {541-544}, doi = {10.1016/0002-9149(85)90243-7}, pmid = {4038571}, issn = {0002-9149}, support = {HL 07416/HL/NHLBI NIH HHS/United States ; HL 21751/HL/NHLBI NIH HHS/United States ; HL 26215/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Cardiac Output ; Cardiomyopathy, Hypertrophic/*diagnostic imaging/physiopathology ; Coronary Disease/*diagnostic imaging/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Myocardial Contraction ; Radionuclide Imaging ; *Stroke Volume ; }, abstract = {The radionuclide angiograms of 59 patients with a left ventricular (LV) ejection fraction (EF) less than 0.40, 23 with idiopathic dilated cardiomyopathy (IDC) and 36 with coronary artery disease (CAD) were analyzed to assess the usefulness of radionuclide angiography in distinguishing these conditions. Mean right ventricular EF was lower in the IDC group than in the CAD group, 0.31 vs 0.45 (p less than 0.01). LV wall motion was scored from 3 (normal) to -1 (dyskinesia). The incidence of akinesia was similar in IDC and CAD groups, 70% and 83%, respectively. Dyskinesia was more common in the CAD group (42% vs 17%), but the difference was not statistically significant. Segmental wall motion analysis showed similar patterns of wall motion in both groups, with contraction best preserved in the anterobasal, posterobasal and superolateral segments. Patients in the CAD group had worse apical motion (p less than 0.01) and better wall motion in the anterobasal (p less than 0.05) and superolateral walls (p less than 0.01), compared with patients in the IDC group. To assess symmetry of contraction, a maximum difference score was derived for each patient. Symmetry (a score less than 1) was present in 5 IDC and no CAD patients, whereas asymmetry (a score of 2 or more) was present in 27 CAD and 7 IDC patients (p less than 0.01). Wall motion became more symmetric in both groups when LVEF was less than 0.20. Logistic regression analysis revealed that the maximum difference score was the best predictor of the diagnosis, but only because of better separation at the extremes of maximum difference score values.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid3975356, year = {1985}, author = {Linz, U and Stöcklin, G}, title = {Chemical and biological consequences of the radioactive decay of iodine-125 in plasmid DNA.}, journal = {Radiation research}, volume = {101}, number = {2}, pages = {262-278}, pmid = {3975356}, issn = {0033-7587}, mesh = {Bromodeoxycytidine/analogs &amp; derivatives ; DNA/*radiation effects ; Deoxycytidine/analogs &amp; derivatives ; *Iodine Radioisotopes ; Microscopy, Electron ; Plasmids/*radiation effects ; Radiation Genetics ; Radioactivity ; }, abstract = {Doubly labeled [U-14C, 5-125I]iododeoxycytidine (IdC) triphosphate was synthesized and incorporated enzymatically into defined positions of the plasmid pBR322. After storage under various conditions, the stable end products were analyzed using radio-GC, radio-HPLC, and electron microscopy. In addition, solutions of 14C-IdC-labeled DNA containing Na125I as an internal radiation source were studied to investigate the influence of internal radiolysis. Transmutation of the covalently bound 125I leads to complete destruction of the labeled nucleotide, giving rise to 14CO2 and 14CO as major products. Fragmentation of the pyrimidine base is independent of solvent and DNA configuration. Internal radiolysis caused by Na125I leads to only minor damage. Electron microscopy studies reveal that decay-induced double strand breaks (dsb) occur both at the site of decay and in areas as far as hundreds of base pairs apart from that site. Number and distribution of the breaks is strongly dependent on solvent and DNA configuration. A direct correlation exists between the extent of fragmentation of the nucleotide and the mean number of dsb.}, }
@article {pmid4075378, year = {1985}, author = {Vellguth, S and von Gaudecker, B and Müller-Hermelink, HK}, title = {The development of the human spleen. Ultrastructural studies in fetuses from the 14th to 24th week of gestation.}, journal = {Cell and tissue research}, volume = {242}, number = {3}, pages = {579-592}, pmid = {4075378}, issn = {0302-766X}, mesh = {Female ; Fetus/physiology ; Gestational Age ; Humans ; Lymphocytes/cytology/ultrastructure ; Microscopy, Electron ; Pregnancy ; Spleen/*embryology/ultrastructure ; }, abstract = {Splenic tissue of human fetuses from the 14th to the 24th week of gestation (menstrual age) were investigated by light- and electron microscopy to describe the development of the red and white pulp in close relationship to the differentiation of the vascular tree. Special interest is focussed on the differentiation of the T-cell- and the B-cell regions and their specific stationary cells. The preliminary stage, here called the "primary vascular reticulum," lasts up to the 14th gestational week (gw). Numerous erythrocytes, normoblasts and macrophages are seen among a network of mesenchymal cells and argyrophilic fibers. Hematopoiesis, especially erythropoiesis, can be recognized. The characteristic organ structure becomes established during the subsequent transformation stage of the fetal spleen, beginning with the 15th gw. Splenic lobules begin to form during the 15th to 17th gw. They consist of a central artery, surrounded by a sheath of lightly stained stationary cells which resemble myofibroblasts. At the periphery of these lobules the red pulp forms. Initially mobile cells are distributed throughout the reticulum. Soon they begin to accumulate in the venous sinuses, which develop from lacunae among the reticular network and come into contact with the venous system. The endothelial wall of these sinuses remains discontinuous, confirming the theory of the "open" vascularization of the spleen. The development of the larger veins is correlated with the differentiation of the splenic trabeculae. The development of the white pulp is correlated with the stage of lymphoid colonization within the spleen, beginning around the 18th gw. An accumulation of lymphocytes around the central arteries can be recognized during the 19th and 20th gw. These lymphoid cells show morphological and immunohistochemical characteristics of T-precursor cells. Within the now assembling periarterial lymphoid sheath (PALS) a few precursors of interdigitating cells (IDC) are recognizable, giving evidence for the differentiation of the T-cell region. Around the 23rd gw the assemblage of primary follicles is discernible at the periphery of the PALS. Precursors of the follicular dendritic reticulum cell (FDRC), the specific stationary cell of the B-cell region, have been recognized. This observation leads to the conclusion that the small primary follicles represent the beginning formation of the B-cell region. The significance of the vascular system for the differentiation of the specific splenic organization is discussed.}, }
@article {pmid3970586, year = {1985}, author = {Sonoda, Y and Asano, S and Miyazaki, T and Sagami, S}, title = {Electron microscopic study on Langerhans cells and related cells in lymph nodes of DNCB-sensitive mice.}, journal = {Archives of dermatological research}, volume = {277}, number = {1}, pages = {44-54}, pmid = {3970586}, issn = {0340-3696}, mesh = {Animals ; Cytoplasmic Granules/ultrastructure ; Dermatitis, Contact/etiology/*pathology ; Dinitrochlorobenzene/*immunology ; Langerhans Cells/*ultrastructure ; Lymph Nodes/*ultrastructure ; Mice ; Mice, Inbred C3H ; Microscopy, Electron ; Nitrobenzenes/*immunology ; }, abstract = {To understand contact hypersensitivity, it is important to know the kinetics of Langerhans cells (LC) and related cells in the lymph node (LN), as well as in the skin. For this purpose, we tried experimentally to induce increased numbers of LCs, Birbeck granule-like structure (BgS)-containing cells, and interdigitating reticulum cells (IDC) in DNCB-sensitive mice and studied them by means of electron microscopy with the following results: (1) cytologically, LC, BgS-containing cells and IDC were closely related; (2) BgS seemed to arise from rough-surfaced endoplasmic reticulum (r-ER), and BgS-containing cells were midway in nature between LC and IDC from the morphological view point. From these findings, it appears that IDC, BgS-containing cells, and LCs were simultaneously involved in the contact hypersensitivity reactions of LNs.}, }
@article {pmid3967278, year = {1985}, author = {van der Brugge-Gamelkoorn, GJ and van de Ende, MB and Sminia, T}, title = {Non-lymphoid cells of bronchus-associated lymphoid tissue of the rat in situ and in suspension. With special reference to interdigitating and follicular dendritic cells.}, journal = {Cell and tissue research}, volume = {239}, number = {1}, pages = {177-182}, pmid = {3967278}, issn = {0302-766X}, mesh = {Animals ; Antibodies, Monoclonal ; Bronchi/enzymology/immunology/*ultrastructure ; Histocytochemistry ; Immunochemistry ; Lymphoid Tissue/enzymology/immunology/*ultrastructure ; Male ; Rats ; Rats, Inbred Strains ; }, abstract = {Immunohistochemical, enzyme-histochemical and electron-microscopical methods were used to study non-lymphoid cells of control and stimulated rat bronchus associated lymphoid tissue (BALT) in situ and in suspensions. Particular attention was paid to the so-called antigen-handling cells, i.e., the interdigitating cells (IDC), which are situated in the T-cell areas, the follicular dendritic cells (FDC), which appear to be restricted to germinal centers, and macrophages, present both in T-cell and B-cell areas. The interdigitating cells were distinguished by being Ia-positive and by the presence of acid phosphatase and non-specific esterase activity in an area near the nucleus. Follicular dendritic cells could be observed in situ by using a monoclonal antibody and by the in vitro trapping of HRP-anti-HRP complexes. Several types of macrophages were found. At the electron-microscopical level no well-developed IDC and FDC could be detected in control BALT. However, in BALT of lipopolysaccharide-stimulated and mycoplasma-infected rats, well-developed IDC and FDC were found. It can be concluded that IDC's and FDC's can be found in BALT.}, }
@article {pmid2988675, year = {1985}, author = {Hulet, A and Michel, P and Cornut, F and Hustin, J}, title = {[Development of aggressive cystosarcoma phyllodes after conservative treatment of breast adenocarcinoma].}, journal = {Bulletin du cancer}, volume = {72}, number = {2}, pages = {80-86}, pmid = {2988675}, issn = {0007-4551}, mesh = {Breast Neoplasms/*etiology/pathology/radiotherapy/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*radiotherapy/surgery ; Cobalt Radioisotopes/adverse effects ; Combined Modality Therapy ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/etiology ; Neoplasms, Multiple Primary/*pathology ; Neoplasms, Radiation-Induced/*etiology ; Phyllodes Tumor/*etiology/pathology/surgery ; }, abstract = {The case report is that of patient who underwent tumorectomy plus X-ray therapy for mammary invasive ductal carcinoma. Eight years later a large cystosarcoma phyllodes, developed and quickly recurred after conservative surgery. Reviewing previous mammograms, the authors discovered that at the time of irradiation, there was a small lump which had the appearance of fibroadenoma. It may be that heavy X-ray therapy on a benign epithelial and stromal tumour of the breast, played a major role in the later development of cystosarcoma phyllodes.}, }
@article {pmid2861687, year = {1985}, author = {Mignot, MH and Lens, JW and Mullink, H and Stolk, JG and Oort, J and Drexhage, HA}, title = {The involvement of dendritic cells in the handling of the immune stimulant C. parvum. A morphological investigation using immunoperoxidase techniques.}, journal = {Virchows Archiv. B, Cell pathology including molecular pathology}, volume = {48}, number = {4}, pages = {317-324}, doi = {10.1007/BF02890138}, pmid = {2861687}, issn = {0340-6075}, mesh = {Animals ; Dendrites/*immunology ; Guinea Pigs ; Immunoenzyme Techniques ; Lymph Nodes/cytology/immunology ; Propionibacterium acnes/*immunology ; }, abstract = {In earlier experiments we showed that locally administered Corynebacterium parvum (C. parvum) stimulated the T-cell system and had a beneficial effect on the recurrence rate of surgically resected cancers of the uterine cervix. In this paper we report the use of an immunoperoxidase technique to trace C. parvum antigen in the draining lymph nodes. In a guinea pig model the popliteal lymph node was studied after the injection of 70 micrograms of C. parvum in the hind footpad. At 6 h, intact bacteria were detected in sinus histiocytes. A transient granuloma formation was apparent between days 2 and 6, originating in the subcapsular and interfollicular areas. Three antigen-positive cell types were observed in these granulomas: a) cytophagocytic macrophages which were weakly positive, the antigen being distributed in clumps; b) dendritic cells with a strong, fine-granular positivity and c) some epithelioid cells with a small positive cytoplasmic rim. The majority of epithelioid cells was negative. Antigen-positive dendritic cells were also observed just beyond the granulomas in the T-dependent paracortical area. These cells are known as interdigitating cells (IDC) and present antigen to T-cells. Ten days following C. parvum injection the lymph node follicles became positive and the antigen could be detected in the long cellular protrusions of the dendritic reticulum cells (DRC). DRC probably play a part in immunological memory by trapping antigen in the form of immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid6536115, year = {1984}, author = {de Siqueira, AA and Tanaka, AC and Santana, RM and de Almeida, PA}, title = {[Maternal mortality in Brazil, 1980].}, journal = {Revista de saude publica}, volume = {18}, number = {6}, pages = {448-465}, doi = {10.1590/s0034-89101984000600004}, pmid = {6536115}, issn = {0034-8910}, mesh = {Adolescent ; Adult ; Brazil ; Child ; Female ; Humans ; Hypertension/mortality ; *Maternal Mortality ; Middle Aged ; Obstetric Labor Complications/mortality ; Pre-Eclampsia/mortality ; Pregnancy ; Pregnancy Complications/mortality ; Pregnancy Complications, Cardiovascular/mortality ; }, }
@article {pmid6391190, year = {1984}, author = {Radzun, HJ and Parwaresch, MR and Feller, AC and Hansmann, ML}, title = {Monocyte/macrophage-specific monoclonal antibody Ki-M1 recognizes interdigitating reticulum cells.}, journal = {The American journal of pathology}, volume = {117}, number = {3}, pages = {441-450}, pmid = {6391190}, issn = {0002-9440}, mesh = {Animals ; *Antibodies, Monoclonal ; Antibody Specificity ; Antigen-Presenting Cells/enzymology/*immunology ; Antigens, Surface/analysis/immunology ; Cell Line ; Female ; Histocytochemistry ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/ultrastructure ; Macrophages/*immunology ; Mice ; Mice, Inbred BALB C ; Monocytes/enzymology/*immunology/ultrastructure ; Palatine Tonsil/ultrastructure ; }, abstract = {A monoclonal antibody, Ki-M1, was produced, and its immunoreactivity was tested by light and electron-microscopic immunohistochemistry. Ki-M1 was found to react with monocytes, cells of the mononuclear phagocyte system (MPS), interdigitating reticulum cells (IDC), and the so-called indeterminate dendritic cells of lymphoid tissue. No reactivity was seen in other human tissues or other hematopoietic cells, including granulocytes and cells of the unstimulated promyelocyte cell line HL-60. Thus, Ki-M1 is the first of the monoclonal antibodies to MPS cells to react with both human IDC and MPS cells. This suggests that IDC and MPS cells may have a common cytogenesis.}, }
@article {pmid6241603, year = {1984}, author = {Thorbecke, GJ and Belsito, DV and Bienenstock, AN and Possick, LE and Baer, RL}, title = {The Langerhans cell, as a representative of the accessory cell system, in health and disease.}, journal = {Immunobiology}, volume = {168}, number = {3-5}, pages = {313-324}, doi = {10.1016/S0171-2985(84)80119-9}, pmid = {6241603}, issn = {0171-2985}, support = {AG-04980/AG/NIA NIH HHS/United States ; AM-07190/AM/NIADDK NIH HHS/United States ; }, mesh = {Acquired Immunodeficiency Syndrome/*immunology ; Adenosine Triphosphatases/metabolism ; Animals ; Antigen-Presenting Cells/enzymology/*immunology ; Antigens, Surface ; Histocompatibility Antigens Class II ; Humans ; Langerhans Cells/enzymology/*immunology ; Lymphocyte Culture Test, Mixed ; Macrophage-1 Antigen ; Macrophages/immunology ; Mice ; Rats ; Receptors, Complement ; Receptors, Fc ; Receptors, IgG ; Skin/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; }, abstract = {Cell surface receptors and antigens present on Langerhans' cells (LC) suggest a close relationship between LC and interdigitating cells (IDC) in lymph node sections or lymphoid dendritic cells (LDC) in cell suspensions. One of the reported differences is that Fc receptors (FcR) which are present on LC, are absent on LDC. This difference can at least partly be explained by a laboratory artefact: FcR on murine LC are irreversibly modulated by the Ig that contaminates the bovine albumin commonly used for gradients. Furthermore, the demonstration of FcR on murine LC requires prolonged exposure to EA at 4 degrees C. A significant percentage of nonadherent, low density, Ig- lymph node cells also express such FcR. These cells can stimulate syngeneic mixed lymphocyte reactions as can LC isolated from epidermis. Consideration of LC as cutaneous representatives of the accessory cell system led to an investigation of their numbers in epidermal sheets of patients with acquired immunodeficiency syndrome (AIDS). A marked reduction in Ia+, ATPase+, OKT6+ LC was found as compared to controls, suggesting that accessory cell deficiency may play a role in the extreme immunodeficiency seen in AIDS patients.}, }
@article {pmid6548366, year = {1984}, author = {Shousha, S and James, AH and Fernandez, MD and Bull, TB}, title = {Squamous cell carcinoma of the breast.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {108}, number = {11}, pages = {893-896}, pmid = {6548366}, issn = {0003-9985}, mesh = {Adult ; Breast Neoplasms/immunology/metabolism/pathology/*ultrastructure ; Carcinoembryonic Antigen/analysis ; Carcinoma, Squamous Cell/metabolism/pathology/*ultrastructure ; Female ; Humans ; Middle Aged ; Mucins/metabolism ; }, abstract = {We saw two cases of pure squamous cell carcinoma of the breast, one of which is associated with dermatomyositis. Electron microscopy of appropriately fixed tissue obtained from one tumor confirmed the squamous nature of the polyhedral and spindle-shaped tumor cells. One tumor was assayed for estrogen and progesterone receptor proteins and was found to be lacking both. Test results for mucin and carcinoembryonic antigen (CEA) were negative in both tumors. In contrast, a similarly examined case of invasive ductal carcinoma with areas of squamous metaplasia had slightly elevated concentrations of estrogen and progesterone receptor proteins, and test results for mucin and CEA were positive.}, }
@article {pmid6388063, year = {1984}, author = {McKenzie, JL and Beard, ME and Hart, DN}, title = {The effect of donor pretreatment on interstitial dendritic cell content and rat cardiac allograft survival.}, journal = {Transplantation}, volume = {38}, number = {4}, pages = {371-376}, doi = {10.1097/00007890-198410000-00011}, pmid = {6388063}, issn = {0041-1337}, mesh = {Animals ; Antilymphocyte Serum/pharmacology ; Bone Marrow Cells ; Bone Marrow Transplantation ; Connective Tissue/drug effects ; *Connective Tissue Cells ; Cyclophosphamide/pharmacology ; Graft Survival/*drug effects ; *Heart Transplantation ; Hydrocortisone/pharmacology ; Leukocyte Count ; Models, Biological ; *Preoperative Care/methods ; Rats ; Rats, Inbred Strains ; Species Specificity ; Whole-Body Irradiation ; }, abstract = {Different pretreatment schedules were applied to rat heart donors and their effect on heart interstitial dendritic cell content was observed using monoclonal antibodies and immunofluorescence techniques. Interstitial dendritic cell (IDC) numbers were correlated with the histology and survival of hearts transplanted into untreated allogeneic recipients. Hearts from AS donors pretreated with cyclophosphamide and total-body irradiation showed prolonged survival in DA recipients only when more than 95% of the graft interstitial dendritic cells were depleted. Reconstitution studies established that prolonged graft survival following donor pretreatment depended on the removal of bone-marrow-derived cells and that these were IDCs. These results suggest that the IDC is the most significant "passenger leucocyte", and that very small numbers of residual IDCs were still sufficient to cause rapid rejection. DA rat heart contained three times as many IDCs as the AS strain and DA hearts were much more difficult to deplete of IDCs. Pretreated DA hearts were rejected by AS recipients, although grafts with a lower IDC content resulted in an attenuated histological rejection response and a markedly decreased recipient lymphocytotoxin response. To be effective, donor pretreatment schedules had to be initiated 5 days prior to transplantation. Pretreatment 6 hr prior to transplantation failed to deplete IDC or prolong graft survival even in he weak (ASxDA)F1 to DA model. Pretreatment protocols used clinically have probably not removed IDCs adequately and the development of methods that deplete IDCs effectively could improve graft survival at no risk to the recipient.}, }
@article {pmid6331484, year = {1984}, author = {Harris, M and Howell, A and Chrissohou, M and Swindell, RI and Hudson, M and Sellwood, RA}, title = {A comparison of the metastatic pattern of infiltrating lobular carcinoma and infiltrating duct carcinoma of the breast.}, journal = {British journal of cancer}, volume = {50}, number = {1}, pages = {23-30}, pmid = {6331484}, issn = {0007-0920}, mesh = {Adult ; Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/*pathology ; Carcinoma/pathology/*secondary ; Carcinoma, Intraductal, Noninfiltrating/pathology/*secondary ; Female ; Humans ; Lung Neoplasms/secondary ; Meningeal Neoplasms/secondary ; Middle Aged ; Neoplasm Metastasis/*pathology ; Peritoneal Neoplasms/secondary ; Retroperitoneal Neoplasms/secondary ; }, abstract = {The metastatic sites of infiltrating duct (IDC) and infiltrating lobular carcinoma (ILC) have been compared using both clinical and autopsy data. The following statistically significant differences were found: Lung parenchymal metastases were more common in IDC. Bone trephine biopsies were more likely to be positive in ILC. Carcinomatous meningitis was associated almost exclusively with ILC. Peritoneal/retroperitoneal metastases of distinctive pattern occurred in ILC. There was often associated linitis plastica-like involvement of the stomach wall and diffuse infiltration of the uterus. Hydronephrosis was a common secondary phenomenon.}, }
@article {pmid6585136, year = {1984}, author = {Anderson, JL and Carlquist, JF and Lutz, JR and DeWitt, CW and Hammond, EH}, title = {HLA A, B and DR typing in idiopathic dilated cardiomyopathy: a search for immune response factors.}, journal = {The American journal of cardiology}, volume = {53}, number = {9}, pages = {1326-1330}, doi = {10.1016/0002-9149(84)90088-2}, pmid = {6585136}, issn = {0002-9149}, mesh = {ABO Blood-Group System/immunology ; Adult ; Aged ; Cardiomyopathy, Dilated/*immunology ; Female ; HLA Antigens/*immunology ; HLA-A Antigens ; HLA-B Antigens ; HLA-DR Antigens ; Haploidy ; Heart Failure/*immunology ; Histocompatibility Antigens Class II/*immunology ; Histocompatibility Testing/*methods ; Humans ; Male ; Middle Aged ; }, abstract = {Several autoimmune diseases have been associated with increased frequencies of various histocompatibility antigen (HLA) types that may be linked to immune response genes. Idiopathic dilated cardiomyopathy (IDC) has been proposed as a disease with autoimmune features, but HLA associations have not been evaluated. We performed HLA typing in 37 consecutive patients with IDC. Patients with habitual alcoholism were excluded. Results showed that no single HLA type could account for most cases; IDC is a genetically heterogeneous disease. However, uneven distributions were noted for certain types. Haplotype frequency of B27 was 0.145 in patients vs 0.033 in 5,726 local control subjects (p less than 0.001). Other A and B frequencies (except A2) were evenly distributed. HLA DR typing also revealed differences. The DR4 locus was present in 54% (19 of 35) of patients, vs 32% (26 of 82) of blood bank control subjects (p less than 0.02). The associated relative risk of DR4 was 2.2 and the etiologic fraction 0.29. Sex, disease chronicity, functional class, ejection fraction and biopsy evidence of myocarditis did not distinguish DR4-positive from DR4-negative patients, but they were older (54 +/- 12 vs 42 +/- 14 years, p less than 0.02). Of note, 68% were positive for DR4 or B27, or both. HLA DR6Y was underrepresented; it was present in 9% (3 of 35) of patients, vs 26% (21 of 82) of control subjects (p less than 0.04). The relative risk of DR6Y was 0.27 and the preventive fraction 0.19. These associations will require independent confirmation. However, they suggest that genetically determined immune response factors associated with HLA loci may play a role in pathogenesis in certain patients with IDC.}, }
@article {pmid6421928, year = {1984}, author = {Kazdin, DS and Gilman-Sachs, A and Dray, S and Horng, WJ}, title = {Induction of "latent a2" allotype in a1a1 homozygous rabbits as the major part of a bidirectional immune response to immunization with anti-a2 antibody.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {132}, number = {4}, pages = {1909-1916}, pmid = {6421928}, issn = {0022-1767}, support = {A1-07043//PHS HHS/United States ; A1-15228//PHS HHS/United States ; }, mesh = {Animals ; Antibodies, Anti-Idiotypic/*administration &amp; dosage/biosynthesis/physiology ; Antibody Specificity ; Binding Sites, Antibody ; Binding, Competitive ; Genotype ; Homozygote ; *Immunization ; Immunoglobulin Allotypes/*biosynthesis/genetics/immunology ; Immunoglobulin G/metabolism/physiology ; Immunoglobulin Heavy Chains/biosynthesis/genetics/immunology ; Immunoglobulin Idiotypes/genetics/*immunology ; Immunoglobulin Variable Region/biosynthesis/genetics/immunology ; Rabbits ; }, abstract = {Previously, we induced Ab to a common idiotypic specificity (IdC) of rabbit anti-a2 VH Ab. We observed then that some of the putative anti-IdC Ab molecules induced by immunizing a1a1 rabbits with anti-a2 Ab did not have the expected nominal allotypic markers (a1, x32, or y33) characteristic of the genotype of the immunized rabbits. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab induced population of molecules that reacted with anti-a2 Ab but bore an unidentified (unknown) VH region marker. The following observations indicate that these molecules bear a "latent a2" allotypic marker: (a) when the unknown VH molecules were used to immunize a1 a1 and a3 a3 rabbits, anti-a2 Ab was produced; (b) when an a2 a2 rabbit was immunized with the same preparation of unknown VH molecules, an anti-idiotypic Ab was produced; and (c) when the unknown VH molecules were used to inhibit the binding of labeled a2 IgG to anti-a2 Ab, the inhibition curve obtained was essentially the same as that obtained by using normal a2 IgG. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab provided a bidirectional stimulus to produce both nominal "a1" anti-IdC Ab and a "latent a2" allotype. The distribution of nominal to latent allotypes induced ranged from 3% nominal/92% latent to 57% nominal/23% latent. In absolute terms, the maximum amount of "latent a2" molecules was 1.18 mg/ml of serum, which far exceeds the amount of latent allotype described by others (0.3 mg/ml of serum). The effective induction of large amounts of "latent a2" allotype may have resulted from a simultaneous stimulation of an idiotope and a paratope on the surface of the "latent a2"-producing cells.}, }
@article {pmid6702645, year = {1984}, author = {Meinertz, T and Hofmann, T and Kasper, W and Treese, N and Bechtold, H and Stienen, U and Pop, T and Leitner, ER and Andresen, D and Meyer, J}, title = {Significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {53}, number = {7}, pages = {902-907}, doi = {10.1016/0002-9149(84)90522-8}, pmid = {6702645}, issn = {0002-9149}, mesh = {Arrhythmias, Cardiac/*complications/diagnosis/drug therapy ; Cardiomyopathy, Dilated/*complications ; Digitalis Glycosides/therapeutic use ; Diuretics/therapeutic use ; Electrocardiography ; Follow-Up Studies ; Heart Failure/*complications ; Heart Ventricles ; Hemodynamics ; Humans ; Monitoring, Physiologic ; Prospective Studies ; }, abstract = {The incidence and prognostic significance of ventricular arrhythmias identified by 24-hour ambulatory electrocardiography (Holter) was prospectively assessed in 74 patients with idiopathic dilated cardiomyopathy (IDC). The criteria for diagnosis of IDC were based on clinical and cardiac catheterization findings. Holter monitoring was performed at the time of entry into the study. Patients were followed for 2 to 21 months (mean 11 +/- 3). Frequent ventricular premature complexes (VPCs) (greater than 1,000/24 hours) were seen in 35%, and complex VPCs (Lown grade III and IV) in 87% of the patients. Forty-nine percent of the patients had nonsustained ventricular tachycardia (VT) consisting of 3 to 32 beats with rates from 110 to 230 beats/min, and 20% had ventricular pairs. No correlation was found between clinical symptoms or the degree of left ventricular (LV) impairment and the number of ventricular pairs or episodes of VT. During follow-up, 19 patients died, 7 from congestive heart failure (CHF) and 12 suddenly. Patients who died suddenly had significantly more episodes of VT, ventricular pairs or total VPCs (p less than 0.01 each) compared with survivors and those who died from CHF. No significant differences were found between patients who died from CHF or suddenly with respect to LV end-diastolic pressure, LV end-diastolic volume index, LV ejection fraction (EF) and cardiac index. A linear stepwise discriminant function analysis using hemodynamic (LVEF and cardiac index) and arrhythmic (number of VT episodes and ventricular pairs) variables resulted in a meaningful separation between survivors and patients who died from CHF or suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid6588009, year = {1984}, author = {Duijvestijn, AM and Sminia, T and Köhler, YG and Janse, EM and Hoefsmit, EC}, title = {Ontogeny of the rat thymus micro-environment: development of the interdigitating cell and macrophage populations.}, journal = {Developmental and comparative immunology}, volume = {8}, number = {2}, pages = {451-460}, doi = {10.1016/0145-305x(84)90052-1}, pmid = {6588009}, issn = {0145-305X}, mesh = {Acid Phosphatase/analysis ; Animals ; Epithelial Cells ; Esterases/analysis ; Female ; Histocompatibility Antigens Class II/analysis ; Macrophages/*cytology/enzymology ; Male ; Pregnancy ; Rats ; Rats, Inbred Strains ; Thymus Gland/cytology/embryology/*growth &amp; development ; }, abstract = {The ontogeny of the rat thymus micro-environment and in particular the development of the interdigitating cell (IDC) and macrophage (M phi) populations has been studied. At day 15 of fetal life the thymus consisted of an epithelial primordium in which some Thy-1 positive thymocytes were present around local capillaries in a central area. At day 16 some Ia positive cells, which could not be further identified, and some monocyte-like M phi were observed in the central area. From day 17 the thymus became lobulated by ingrowth of small blood vessels with perivascular connective tissue from the surrounding capsule. An Ia positive epithelial reticulum developed which became populated by increasing numbers of thymocytes. Some strongly acid phosphatase positive M phi were present from this stage of development. From day 19 cortical and medullary areas could be distinguished in the thymus. The cortex consisted of an Ia positive epithelial reticulum in which closely packed thymocytes and scattered M phi were present. The medulla demonstrated a confluent Ia staining and consisted of an epithelial reticulum in which thymocytes, strongly non-specific esterase positive IDC and an occasional M phi were present. Also highly phagocytic IDC-like cells were observed in the medulla, most likely they comprise the population of differentiating IDC. Thymocyte proliferation areas, which were strongly pyroninophilic, were observed from day 21 in the cortex, just beneath the surrounding connective tissue capsule. A distinct cortico-medullary region with many M phi was present one week after birth. From this stage the IDC and M phi distribution was comparable with older thymi.}, }
@article {pmid6194427, year = {1983}, author = {Kazdin, DS and Horng, WJ}, title = {A bi-directional immune network mechanism: simultaneous induction of idiotype and anti-anti-idiotype in rabbits immunized with antibody to a common idiotypic specificity of anti-VHa2-allotype antibodies.}, journal = {Molecular immunology}, volume = {20}, number = {8}, pages = {819-826}, doi = {10.1016/0161-5890(83)90078-0}, pmid = {6194427}, issn = {0161-5890}, support = {AI-07043/AI/NIAID NIH HHS/United States ; AI-15228/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Anti-Idiotypic/*immunology ; Antibody Specificity ; Epitopes/*immunology ; Immunodiffusion ; Immunoglobulin Allotypes/*immunology ; Immunoglobulin Heavy Chains/immunology ; Immunoglobulin Idiotypes/*immunology ; Immunoglobulin Variable Region/immunology ; Immunosuppression Therapy ; Rabbits ; }, abstract = {Recently, we identified a common idiotypic specificity (IdC) present on all of the allo and auto anti-VHa2-allotype antibodies tested. In this report, we immunized allotype-matched rabbits with anti-IdC Ab. When an a1a1 homozygote was immunized with anti-IdC Ab (also from an a1a1 rabbit), two distinct Ab populations were induced which were isolated through the use of immunoadsorbent column chromatography. One of these Ab populations, adsorbed to and eluted from an insolubilized a2 IgG column, was anti-VHa2-allotype Ab (Ab 1), which reacted with a2 Ig and inhibited the reaction between the a2 allotype and anti-VHa2-allotype Ab. The other Ab population, adsorbed to and eluted from an insolubilized immunogen anti-IdC column, was anti-anti-IdC Ab (Ab 3), which was specific for the immunogen anti-IdC Ab. In another experiment, when an a1a2 heterozygous rabbit was immunized with anti-IdC Ab, only the Ab 3 was induced, which appeared to be identical to the Ab 3 induced in the a1a1 rabbit. However, when the expression of the a2 allotype in an a1a2 heterozygous rabbit was suppressed and then this rabbit was immunized with anti-IdC Ab, both Ab 1 and Ab 3 were induced. These data indicate the occurrence of a bi-directional immune response within our immune network system. According to Jerne's network theory, Ab 3 appeared to be induced through a stimulation by the idiotope of the immunogen Ab 2, whereas Ab 1 appeared to be induced through a reverse stimulation by the paratope of the immunogen Ab 2. Furthermore, the production of Ab 1 in these rabbits exhibiting the bi-directional immune response was at least 3-5 times greater than that of Ab 3 production indicating that the response through the reverse stimulation appeared to be dominant. The importance of this bi-directional immune response is discussed in this paper.}, }
@article {pmid6345663, year = {1983}, author = {Ward, JM and Argilan, F and Reynolds, CW}, title = {Immunoperoxidase localization of large granular lymphocytes in normal tissues and lesions of athymic nude rats.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {131}, number = {1}, pages = {132-139}, pmid = {6345663}, issn = {0022-1767}, support = {N01-CO-75380/CO/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/immunology ; Bronchopneumonia/immunology/pathology ; Enteritis/immunology/pathology ; Epithelial Cells ; Epithelium/analysis/immunology ; Female ; Hyperplasia/immunology/pathology ; Immunoenzyme Techniques ; Killer Cells, Natural/analysis/*immunology ; Lymph Nodes/immunology/pathology/ultrastructure ; Male ; Peyer's Patches/analysis/cytology/immunology ; Rats ; Rats, Inbred F344 ; Rats, Mutant Strains/*immunology ; }, abstract = {The immunocytochemical localization of cells reacting with the OX-8 monoclonal antibody was studied in athymic nude rats by the avidin-biotin-peroxidase complex (ABC) immunoperoxidase technique. By a number of criteria, including morphology and tissue distribution of OX-8-positive cells, it is postulated that the majority of lymphocytes reacting with OX-8 antibody in nude rats are LGL. The cell surface of large lymphocytes reacted with the OX-8 antibody in fixed tissue sections. The tissues with the greatest density and percentages of these reactive cells included the paracortex of lymph nodes in association with interdigitating cell (IDC) hyperplasia, bronchial-associated lymphoid tissue (BALT), the medullary cords and sinuses of lymph nodes, and intestinal epithelium. Ultrastructure of the paracortical areas of IDC hyperplasia revealed granular lymphocytes in close association with IDC. Tissues with the fewest positive cells included bone marrow, B cell areas of lymphoid tissues, and parenchymal epithelial organs. In healthy and cachectic nude rats, various incidental and pathologic lesions contained a significant number of OX-8-positive cells. Large numbers of positive lymphocytes were seen in suppurative pneumonic lesions, enteritis, focal ulcerative epithelial lesions, and papovaviral sialoadenitis. The observation of a large number of OX-8-positive lymphocytes in nonlymphoid organs supports the hypothesis that these cells play a major role in the first line of defense against not only tumors but also infectious agents.}, }
@article {pmid6218746, year = {1983}, author = {Huang, SK and Messer, JV and Denes, P}, title = {Significance of ventricular tachycardia in idiopathic dilated cardiomyopathy: observations in 35 patients.}, journal = {The American journal of cardiology}, volume = {51}, number = {3}, pages = {507-512}, doi = {10.1016/s0002-9149(83)80089-7}, pmid = {6218746}, issn = {0002-9149}, mesh = {Adult ; Aged ; Anti-Arrhythmia Agents/therapeutic use ; Cardiomegaly/*complications ; Cardiomyopathies/*complications ; Electrocardiography ; Female ; Follow-Up Studies ; Heart Failure/*complications ; Hemodynamics ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; Tachycardia/*complications/diagnosis/drug therapy ; }, abstract = {To evaluate the significance of ventricular tachycardia (VT) in idiopathic dilated cardiomyopathy (IDC), 35 consecutive patients seen between 1976 and 1980 were studied. The criteria for diagnosis of IDC were based on clinical, laboratory, and cardiac catheterization findings. All patients had right and left heart catheterization, left ventriculography, and coronary cineangiography. Long-term ambulatory electrocardiograms (Holter) were obtained in all patients at the time of diagnosis. There were 24 male and 11 female patients aged 22 to 72 years (mean +/- standard deviation [SD]51 +/- 12). Frequent ventricular premature beats (VPB) (30/h) were observed in 29 patients (83%): complex VPB (Lown grades 3, 4, and 5) in 93% and simple VPB in 7%. Twenty-one patients (60%) had nonsustained VT consisting of 3 to 46 beats (8 +/- 5) with rates from 75 to 210/min. No difference between patients with and those without VT was observed in regard to the presenting symptoms, functional classification, electrocardiographic findings, heart size on chest X-ray, and the hemodynamic measurements including cardiac index, left ventricular end-diastolic pressure, and ejection fraction. Patients with VT were older (p less than 0.05). Follow-up observation from 4 to 74 months (34 +/- 17) showed that 2 patients died suddenly (1 with and 1 without previous VT), a third patient died from intractable congestive heart failure, and the fourth from sepsis. It is concluded that (1) the incidence of ventricular arrhythmias in IDC is high, (2) VT is frequent and tends to occur in the nonsustained form, and (3) there is no correlation between VT and the clinical and hemodynamic findings. VT does not appear to predict prognosis during a relatively short follow-up period in patients with IDC.}, }
@article {pmid6419454, year = {1983}, author = {Füllbrandt, U and Meissner, K and Löning, T and Jänner, M}, title = {A second look at intraepithelial Langerhans cells in mycosis fungoides and related disorders. Ultrastructural study with special reference to Langerhans granules and virus-like particles.}, journal = {Virchows Archiv. A, Pathological anatomy and histopathology}, volume = {402}, number = {1}, pages = {47-60}, pmid = {6419454}, issn = {0174-7398}, mesh = {Adult ; Aged ; Cell Membrane/ultrastructure ; Female ; Humans ; Inclusion Bodies, Viral/*ultrastructure ; Langerhans Cells/*ultrastructure ; Lymphocytes/ultrastructure ; Lysosomes/ultrastructure ; Male ; Microscopy, Electron ; Middle Aged ; Mycosis Fungoides/*ultrastructure ; Skin Neoplasms/*ultrastructure ; }, abstract = {Skin biopsies of patients with small and large plaque parapsoriasis, premycotic lesions and mycosis fungoides in different stages were examined. Special attention was paid to the relationships between Langerhans cells (LC) and the neighbouring keratinocytes and lymphocytes. At the contact areas of LC and keratinocytes as well as LC and lymphocytes, particular cell membrane phenomena were observed. Aggregations of Langerhans granules and fusions of granules with LC plasma membranes were found exclusively at LC-keratinocyte interfaces. At LC-lymphocyte contact zones cell membrane appositions were seen. In all cases investigated, virus-like particles were mainly found in LC and indeterminate cells (IDC). In 3 cases lymphocytes also contained these particles. It was of particular interest that virus-like particles were observed in skin specimens of all diseases investigated. Discrimination of these particles from other cellular organelles - especially lysosomes - was difficult, however. The significance of our findings, particularly regarding to the supposed virus aetiology of cutaneous T cell lymphomas, is discussed.}, }
@article {pmid6133389, year = {1983}, author = {Gerdes, J and Stein, H and Mason, DY and Ziegler, A}, title = {Human dendritic reticulum cells of lymphoid follicles: their antigenic profile and their identification as multinucleated giant cells.}, journal = {Virchows Archiv. B, Cell pathology including molecular pathology}, volume = {42}, number = {2}, pages = {161-172}, doi = {10.1007/BF02890379}, pmid = {6133389}, issn = {0340-6075}, mesh = {Antigens/immunology ; Child ; Humans ; Immunoenzyme Techniques ; Lymphoma/pathology ; Macrophages ; Mononuclear Phagocyte System/*immunology ; Palatine Tonsil/cytology/immunology ; Phenotype ; }, abstract = {The B-dependent areas of human lymphoid tissue contain non-lymphoid, non-phagocytic cells known as dendritic reticulum cells (DRC). These cells can be detected only very occasionally in routinely stained histologic sections. Recently we were able to overcome this limitation by preparing a monoclonal antibody, termed R 4/23, that reacts selectively with DRC. Thus by using an optimized immunoperoxidase method applied to frozen sections, it is possible to detect DRC in situ. To determine the antigenic profile of DRC, serial frozen sections of human tonsils were immunostained with R 4/23 and a large panel of other monoclonal antibodies or conventional antisera. In addition, touch imprints of tonsils and cytocentrifuge slides of cell suspensions with increased concentrations of DRC were immunostained with these reagents. DRC proved to be positive for mu, gamma, alpha, kappa and lambda chains, complement component C3b, C3b receptors, C3d receptors, HLA-A,B,C antigens, human Ia-like antigens, common ALL antigen (cALLa), and antigens that are characteristic of the monocyte/macrophage lineages. DRC did not express delta chains, T cell antigens, or antigens that are expressed on interdigitating reticulum cells (IDC) and Langerhans cells. DRC in touch imprints and suspensions prepared from hyperplastic tonsils were found to be giant cells often with 10 or more nuclei. In certain cases of follicular hyperplasia and of centroblastic-centrocytic lymphoma, DRC with several nuclei were also detectable in situ. These results show that (1) the phenotype of DRC differs from that of all other cell types in lymphoid tissue, (2) this phenotype most nearly resembles that of cells of the monocyte/macrophage series, thus suggesting that DRC are related to these cell lineages, and (3) DRC are multinucleated giant cells.}, }
@article {pmid7047373, year = {1982}, author = {Hoefsmit, EC and Duijvestijn, AM and Kamperdijk, EW}, title = {Relation between langerhans cells, veiled cells, and interdigitating cells.}, journal = {Immunobiology}, volume = {161}, number = {3-4}, pages = {255-265}, doi = {10.1016/S0171-2985(82)80081-8}, pmid = {7047373}, issn = {0171-2985}, mesh = {Animals ; Antigens ; *Cell Communication ; Cell Differentiation ; Cytoplasmic Granules/ultrastructure ; Histocompatibility Antigens Class II ; Humans ; Langerhans Cells/cytology/immunology/*ultrastructure ; Lymph/cytology/immunology/*ultrastructure ; Macrophages/cytology/immunology/ultrastructure ; Monocytes/cytology/immunology ; Phagocytes/cytology/immunology/*ultrastructure ; Rats ; Thymus Gland/cytology ; }, abstract = {Tissue macrophages are bone marrow derived mononuclear cells which play an important role in the immune response, especially as antigen presenting cells. They comprise a heterogeneous population of cells with phagocytic activity. On morphological functional and cytochemical criteria it is likely that the Langerhans cell (LC) in the epidermis, the veiled cell (VC) in the afferent lymph and the interdigitating cell (IDC) in the thymus dependent area of peripheral lymphoid organs and the thymus medulla belong to a subpopulation of the macrophages. They are low phagocytic, Ia positive and are highly immunogenic. VC and IDC may contain Birbeck granules, the characteristic organelles of the LC, suggesting a relationship between these cell types. An epithelial micro-environment as present in the skin epidermis and the thymus is necessary for the induction of these granules, which appear to have no immunological significance. In a scheme the development from monocyte into LC or into VC and subsequently IDC is postulated. Probably VC transport antigen from the skin area via the afferent lymphatics into the draining lymph node. In the thymus dependent area of this organ they present this antigen to T cells and mature into IDC. IDC in the medullary area of the thymus may also be involved in antigen presentation to immunocompetent T cells. However, in this central lymphoid organ a function in instruction of helper T cells may not be excluded.}, }
@article {pmid6951633, year = {1982}, author = {Kadin, ME}, title = {Possible origin of the Reed-Sternberg cell from an interdigitating reticulum cell.}, journal = {Cancer treatment reports}, volume = {66}, number = {4}, pages = {601-608}, pmid = {6951633}, issn = {0361-5960}, mesh = {Antigens, Neoplasm/analysis ; Antigens, Surface/analysis ; Histocompatibility Antigens Class II/analysis ; Hodgkin Disease/immunology/*ultrastructure ; Humans ; Lymph Nodes/immunology/*ultrastructure ; Lymphatic Diseases/pathology/ultrastructure ; Lymphocytes/immunology/*ultrastructure ; Macrophages/ultrastructure ; }, abstract = {In a comparative immunologic and cytochemical analysis, Reed-Sternberg (RS) cells from seven patients with Hodgkin's disease were found to more closely resemble interdigitating reticulum cells (IDC) than normal or malignant histiocytic reticulum cells (macrophages); malignant macrophages were established as a cell line from a patient with malignant histiocytosis. RS cells and IDC both showed strong expression of human Ia-like antigens, a close physical association with helper/inducer T cells, and a lack of at least two common macrophage antigens. Supportive evidence of the identity of RS cells and IDC was their lack of lymphoid and myeloid characteristics smaller content of nonspecific esterase and acid phosphatase than that in histiocytes, similar cytology, and location in thymic-dependent regions of lymphoid tissues. Malignant transformation of the IDC to an RS cell could result in diminished antigen-presenting capacity and contribute to the defect in T-cell-mediated immunity that commonly occurs in Hodgkin's disease.}, }
@article {pmid6277459, year = {1982}, author = {Nevin, JE and Baggerly, JT and Laird, TK}, title = {Radiotherapy as an adjuvant in the treatment of carcinoma of the breast.}, journal = {Cancer}, volume = {49}, number = {6}, pages = {1194-1200}, doi = {10.1002/1097-0142(19820315)49:6&lt;1194::aid-cncr2820490621&gt;3.0.co;2-d}, pmid = {6277459}, issn = {0008-543X}, mesh = {Breast Neoplasms/*radiotherapy/surgery ; Carcinoma, Intraductal, Noninfiltrating/*radiotherapy/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Postoperative Period ; Prognosis ; Radiotherapy, High-Energy ; Retrospective Studies ; }, abstract = {During the period from 1950-1974, 510 patients with a diagnosis of invasive ductal carcinoma treated with the standard Halsted radical mastectomy were reviewed retrospectively from the records of the Tumor Clinic of The Memorial Hospital, Danville, Virginia. The primary aim of the study was to determine whether postoperative adjuvant radiation therapy (POART) as delivered in a community hospital setting contributed to better cancer control and effectively influenced five and ten year survival rates. The results of the review indicated that the use of POART whether from an orthovoltage or cobalt source did not differentially influence the patient's disease outcome. The use of POART did not improve the five- and ten-year survival rates regardless of lesion location in patients with Stages I, II, and III disease with positive lymph nodes. POART did cause a significant decline in five- and ten-year survival rates of patients with Stage II and III disease with negative nodes when compared to the survival of patients with the same stage of disease that did not receive POART, i.e., 75% versus 94% five-year difference, and a 65% versus 85% ten-year difference. These results suggest that radiotherapy may have a detrimental effect on immunocompetence and thus alter survival rates in certain circumstances. Therefore, any clinical investigation measuring the results of various therapeutic modalities singularly or in combination should be based on pathologic staging rather than clinical staging so that these factors can be adequately evaluated.}, }
@article {pmid7151125, year = {1982}, author = {Kamperdijk, EW and de Leeuw, JH and Hoefsmit, EC}, title = {Lymph node macrophages and reticulum cells in the immune response. The secondary response to paratyphoid vaccine.}, journal = {Cell and tissue research}, volume = {227}, number = {2}, pages = {277-290}, pmid = {7151125}, issn = {0302-766X}, mesh = {Animals ; Antibody Formation ; *Immunization, Secondary ; *Immunologic Memory ; Lymph Nodes/cytology/*immunology ; Lymphocytes/cytology/immunology ; Lysosomes/ultrastructure ; Macrophages/*immunology/ultrastructure ; Male ; Organoids/ultrastructure ; Phagocytosis ; Plasma Cells/immunology ; Rats ; Rats, Inbred Strains ; Typhoid-Paratyphoid Vaccines/*immunology ; }, abstract = {The morphology and kinetics of macrophages and reticulum cells of rat lymph nodes have been studied in relation to the immune response to a second exposure to antigen. During the first 24 h after stimulation monocyte-like exudate macrophages, including some scattered interdigitating cells (IDC), contain granules similar to those present in epidermal Langerhans cells and lymph-borne veiled cells. In this induction phase these macrophages migrate from the marginal sinus into the paracortex and during the migration they gradually transform into IDC. In the proliferation phase the paracortex is mainly populated by transitional macrophages and there are almost no typical IDC present between the lymphoblasts. In the memory phase the relative number of IDC again rapidly increases. During this period in the paracortex there are often typical IDC which contain partially digested necrotic lymphocytes, thus resembling tingible body macrophages (TBM) of the germinal centre in this respect. It is suggested that the newly arrived macrophages induce the lymphoblast reaction, while mature IDC may have an inhibitory function in the memory phase of the immune response. In this phase the phagocytic potential of IDC is clearly shown.}, }
@article {pmid6981458, year = {1982}, author = {von Gaudecker, B and Müller-Hermelink, HK}, title = {The development of the human tonsilla palatina.}, journal = {Cell and tissue research}, volume = {224}, number = {3}, pages = {579-600}, pmid = {6981458}, issn = {0302-766X}, mesh = {B-Lymphocytes/cytology ; Cell Differentiation ; Cell Nucleus/ultrastructure ; Connective Tissue/embryology ; Cytoplasm/ultrastructure ; Epithelium/ultrastructure ; Gestational Age ; Humans ; Macrophages/ultrastructure ; Microscopy, Electron ; Monocytes/ultrastructure ; Organoids/ultrastructure ; Palatine Tonsil/*embryology/ultrastructure ; T-Lymphocytes/cytology ; }, abstract = {Tonsils of human fetuses at the 8th to the 28th gestational week (g.w.) were investigated by electron microscopy, enzyme histochemistry, and immunohistochemistry on cryostat sections. The development of the tonsilla palatina starts during the 14th g.w. when the mesenchyme underlying the mucous membrane of the tonsillar cavity becomes invaded by mononuclear wandering cells. In fetuses of about the 16th g.w. epithelial crypts grow down into the connective tissue and are infiltrated by T-lymphocytes. At the same time, precursors of interdigitating cells (IDC) can be identified among the epithelial cells. Frequently, lymphocytes and IDC-like cells are in close contact. From these findings it is concluded that the infiltrated crypt epithelium in the human tonsilla palatina represents a T-cell region. Primary follicles develop in earlier fetal stages than in all other secondary lymphoid organs. They contain precursors of dendritic reticulum cells and lymphoid cells that belong to the B-cell line. These primary follicles may be considered as the first assemblage of B-cell regions in human fetal lymphoid tissue. The present findings indicate that the formation of different stationary elements during the development of B-cell regions and T-cell regions is an important factor for the homing and antigen-dependent maturation of different subpopulations of immunocompetent lymphoid cells.}, }
@article {pmid7388920, year = {1980}, author = {von Gaudecker, B and Müller-Hermelink, HK}, title = {Ontogeny and organization of the stationary non-lymphoid cells in the human thymus.}, journal = {Cell and tissue research}, volume = {207}, number = {2}, pages = {287-306}, pmid = {7388920}, issn = {0302-766X}, mesh = {Cell Differentiation ; Cell Nucleus/ultrastructure ; Epithelial Cells ; Gestational Age ; Hematopoiesis ; Hematopoietic Stem Cells/cytology ; Humans ; Lymphocytes/cytology ; Organoids/ultrastructure ; Thymus Gland/cytology/*embryology ; }, abstract = {Ontogenetic differentiation of the human thymus was investigated in 50 embryos by means of light and electron microscopic methods in an attempt to clarify the morphogenesis of the complicated microecology of thymic tissue. At the 8th gestational week (g.w.), the primordium of the thymus contains almost exclusively undifferentiated epithelial cells. At the 10th g.w., the epithelial cells in the central part are spindle-shaped. During the subsequent weeks the cortical region of the thymus becomes separated into lobes by mesenchymal septa containing hemopoietic precursor cells and large electronlucent cells with irregularly shaped nuclei. The latter cells are also found in the deeper presumptive medullary regions of the thymus; they differentiate into interdigitating reticulum cells (IDC). The permeation of the medulla of the thymus by non-epithelial IDC occurs concurrently with the formation of cortical and medullary epithelial cells. Between the 12th and 14th g.w. the cortical and medullary differentiation is completed. At this time-stage cortical small lymphocytes differ in morphological shape from medullary lymphocytes, the latter acquiring the appearance of immunocompetent T cells and establishing intimate contact with the IDC. These findings indicate that the thymic cortex and medulla contain different epithelial cells. In addition, the thymic medulla displays cells characterized by the morphology of typical interdigitating reticulum cells of peripheral lymphoid tissue. The structural pattern of the thymus is correlated to morphologically differing lymphoid cell populations in the cortical and medullary regions.}, }
@article {pmid94035, year = {1979}, author = {Lasfargues, EY and Coutinho, WG and Dion, AS}, title = {A human breast tumor cell line (BT-474) that supports mouse mammary tumor virus replication.}, journal = {In vitro}, volume = {15}, number = {9}, pages = {723-729}, pmid = {94035}, issn = {0073-5655}, mesh = {Antigens, Viral/analysis ; Breast Neoplasms/*microbiology ; Carcinoma, Intraductal, Noninfiltrating/*microbiology ; Cell Line ; Fluorescent Antibody Technique ; Humans ; Mammary Tumor Virus, Mouse/enzymology/*growth &amp; development/immunology ; RNA-Directed DNA Polymerase/metabolism ; Virus Replication ; }, abstract = {A human breast tumor cell line BT-474 derived from an invasive ductal carcinoma was experimentally infected in vitro with a mouse mammary tumor virus from the TIII strain (RIII-MuMTV). The virus that replicated in the human cells was characterized as a mouse virus by immunofluorescence, electron microscopy and the presence of a specific RNA-directed DNA polymerase. The cells themselves were human as per the karyotype and isoenzyme migration patterns. It is concluded that human cells are susceptible to the mouse mammary tumor virus and can, eventually, support its replication.}, }
@article {pmid384701, year = {1979}, author = {Bässler, R}, title = {[Pathomorphology and indications in plastic surgery of the breast].}, journal = {Zeitschrift fur plastische Chirurgie}, volume = {3}, number = {2}, pages = {65-87}, pmid = {384701}, issn = {0342-7978}, mesh = {Breast/pathology/*surgery ; Breast Diseases/*surgery ; Breast Neoplasms/*surgery ; Female ; Fibrocystic Breast Disease/*surgery ; Foreign-Body Reaction/etiology ; Humans ; Mastectomy/methods ; Middle Aged ; Polyurethanes ; *Prostheses and Implants/adverse effects ; Silicones ; *Surgery, Plastic ; }, abstract = {The pathohistological features of two breasts with implants coated with polyurethane are described.--The first case with an implant of 4 months shows a capsule with cellular collagen tissue and triangular and rectangular polyurethane particles with foreign body reactions. The second case, an autopsy of a female artist, revealed a mammary augmentation in both breasts in situ. The prothesis were surrounded by a regular capsule tissue without inflammation.--The different reactions in the connective tissue of the breasts surrounding the implants are described: Silicone implants by Cronin and polyurethane coated implants by Ashley. Complications of breast prothesis are discussed. The constrictive fibrosis is initiated by local chronic inflammation and foreign body reactions. The subcutaneous mastectomy with implantation of prothesis is performed today in cases of fibrocystic diseases with atypical epithelial proliferations, in cases with recurrend fibrocystic disease, with non-invasive ductal carcinoma and lobular carcinoma in situ. The subcutaneous mastectomy is therefore a prophylactic and a therapeutic method.}, }
@article {pmid469223, year = {1979}, author = {McGibbon, WH}, title = {Green shanks and adult mortality in chickens.}, journal = {The Journal of heredity}, volume = {70}, number = {1}, pages = {44-46}, doi = {10.1093/oxfordjournals.jhered.a109186}, pmid = {469223}, issn = {0022-1503}, mesh = {Animals ; Chickens/*genetics ; Female ; *Genes, Lethal ; *Genes, Recessive ; Hemangioma/*genetics ; Male ; Phenotype ; *Skin Pigmentation ; }, abstract = {A mutation of recent origin in Cornell randombred Leghorn chickens causes the shanks to be colored green due to melanin-like deposition in the dermis, in contrast to normal yellow. Some pigment is often present in the mandibles and the mature feathers display an ashen cast. This mutant is determined by an allele, idc, on the sex chromosome. Excessive adult mortality with a high incidence of tumors, mainly hemangiomas, is associated with this gene--at least extending over a two-generation observation interval. Pullets receiving this mutant allele (idc) from their sire die at 2 to 3 times the rate of sisters, with yellow shanks, that carry the Id allele.}, }
@article {pmid219301, year = {1979}, author = {Richters, A and Paller, M}, title = {The relationship between sIgM positive lymph-node lymphocytes and breast cancer metastasis.}, journal = {Journal of surgical oncology}, volume = {11}, number = {1}, pages = {79-84}, doi = {10.1002/jso.2930110114}, pmid = {219301}, issn = {0022-4790}, mesh = {Axilla ; Breast Neoplasms/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*immunology ; Female ; Humans ; *Immunoglobulin M ; Lymph Nodes/immunology ; Lymphatic Metastasis/*immunology ; Lymphocytes/*immunology ; Prognosis ; *Receptors, Antigen, B-Cell ; }, abstract = {The relative frequency of lymphocytes with surface immunoglobulins (sIgM, sIgG, sIgA) was studied in breast-cancer patients' axillary lymph nodes by the immunofluorescence technique. The study encompassed a total of 105 patients, most of whom had infiltrating ductal carcinoma (IDC). The results have indicated a significantly higher (p less than 0.005) average percentage of sIgM positive lymphocytes in lymph nodes in the group of IDC patients with lymph-node metastasis. Short-term followup was available for a limited number of patients, but no conclusions were reached with respect to sIgM positive lymphocytes. It is suggested that evaluation of axillary lymph-node and peripheral blood lymphocyte subpopulations for each cancer patient would provide new information which could aid in determining the extent of the disease process. Moreover, such information may be of assistance in decisions of therapeutic modalities, detection of occult metastasis, and prediction of prognosis.}, }
@article {pmid688370, year = {1978}, author = {Kamperdijk, EW and Raaymakers, EM and de Leeuw, JH and Hoefsmit, EC}, title = {Lymph node macrophages and reticulum cells in the immune response. I. The primary response to paratyphoid vaccine.}, journal = {Cell and tissue research}, volume = {192}, number = {1}, pages = {1-23}, pmid = {688370}, issn = {0302-766X}, mesh = {Animals ; Antibodies, Bacterial/*biosynthesis ; *Bone Marrow Cells ; Lymph Nodes/*cytology/immunology/ultrastructure ; Macrophages/*immunology/ultrastructure ; Male ; Organoids/ultrastructure ; Rats ; *Typhoid-Paratyphoid Vaccines ; }, abstract = {The reactivity of rat lymph node macrophages and reticulum cells has been studied in relation to the course of the immune response. Special attention was paid to the interdigitating cells (IDC) in the paracortex and the dendritic reticulum cells (DRC) in the germinal centre. Different types of macrophage predominate in the three different phases of the immune response. In the induction phase exudate macrophages predominate. They transform their morphology depending on the micro-environment in which they settle. These cells may contain Birbeck granules. Our experiments suggest, that these granules are immunologically specific organelles, associated with the induction of a primary humoral response. In the proliferation phase transitional cells between newly arrived macrophages and IDC predominate in the paracortex and the number of IDC decreases. In the memory phase IDC repopulate this thymus dependent area, indicating that the characteristic morphology of these cells results from the immune response in the T cell environment. The DRC are specifically related to the germinal centre, the morphological transformation of this peculiar reticulum cell occurs under the influence of the germinal centre reaction. The germinal centre reaction originates by tingible body macrophages (TBM).}, }
@article {pmid644282, year = {1978}, author = {Gloor, E}, title = {[A case of Peutz-Jeghers syndrome combined with bilateral breast cancer, an adenocarcinoma of the cervix and ovarian genital cord neoplasms with annular tubules].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {108}, number = {19}, pages = {717-721}, pmid = {644282}, issn = {0036-7672}, mesh = {Adenocarcinoma/*complications ; Bone Neoplasms/etiology ; Breast Neoplasms/*complications ; Female ; Humans ; Hysterectomy ; Intestinal Polyps/complications ; Mastectomy ; Middle Aged ; Neoplasm Metastasis ; Ovarian Neoplasms/*complications ; Peutz-Jeghers Syndrome/*complications/genetics ; Uterine Cervical Neoplasms/*complications ; }, abstract = {The clinico-pathological findings are presented in a case of Peutz-Jeghers syndrome associated with a bilateral mammary invasive ductal carcinoma, a well-differentiated mucinous adenocarcinoma of the cervix and microscopic, bilateral ovarian sex cord tumors with annular tubules. The sex cord tumor with annular tubules was described in 1970 by SCULLY, who recognized its striking association with the Peutz-Jeghers syndrome. Two cases of adenocarcinoma of the cervix and another case of uterine adenocarcinoma of unspecified localization associated with Peutz-Jeghers syndrome were found in the literature. It is possible that women with Peutz-Jeghers syndrome run an increased risk of developing adenocarcinoma of the uterine cervix.}, }
@article {pmid929037, year = {1977}, author = {Lhermitte, F and Agid, Y and Feuerstein, C and Serre, F and Signoret, JL and Studler, JM and Bonnet, AM}, title = {[Abnormal movements caused by L-DOPA in patients with Parkinson's disease: correlation with the plasma concentrations of DOPA and O-methyl-DOPA].}, journal = {Revue neurologique}, volume = {133}, number = {8-9}, pages = {445-454}, pmid = {929037}, issn = {0035-3787}, mesh = {Dihydroxyphenylalanine/*blood ; Dose-Response Relationship, Drug ; Dyskinesia, Drug-Induced/*blood ; Humans ; Levodopa/*adverse effects ; Methyldopa/*blood ; Middle Aged ; Parkinson Disease/*drug therapy ; }, abstract = {This study involved twleve parkinsonian patients exposed to abnormal movements provoked by L-DOPA. Including six patients with "mid-dose" dyskinesias and six others with "onset and end of dose" dyskinesias, Correlation between the circumstances of onset of abnormal movements and plasma concentrations of DOPA and O-methyl-DOPA, after administration of a dose of L-DOPA + IDC, gave the following results: 1) mid-dose dyskinesias appeared with the highest plasma concentrations of DOPA, at the maximum therapeutic effect; 2) onset and end of dose occurred during rise and fall in plasma levels of DOPA, coinciding with the relief and the reappearance of parkinsonian symptoms respectively; 3) no correlation could be established between plasma concentrations of O-methyl-DOPA and the duration of the period of clinical remission or of abnormal movements. These biochemical data, completed by the neuropharmacological study of one patient with onset and end of dose abnormal movements suggest the predominant role of a disturbance in central dopaminergic mechanisms in the genesis of abnormal movements, whatever their nature.}, }
@article {pmid897439, year = {1977}, author = {Lhermitte, F and Agid, Y and Signoret, JL and Studler, JM}, title = {["Beginning and end of dose" dyskinesias caused by L-DOPA].}, journal = {Revue neurologique}, volume = {133}, number = {5}, pages = {297-308}, pmid = {897439}, issn = {0035-3787}, mesh = {Benserazide/*therapeutic use ; Drug Therapy, Combination ; Dyskinesia, Drug-Induced/*etiology ; Female ; Humans ; Hydrazines/*therapeutic use ; Levodopa/administration &amp; dosage/*adverse effects/therapeutic use ; Male ; Middle Aged ; Parkinson Disease/*drug therapy ; }, abstract = {The four cases of dyskinesia at the "beginning and end of dose" caused by L-Dopa presented in this series were characterized by four essential features: 1) their onset at the beginning and end of the period of effectiveness of a dose of L-Dopa + IDC (benserazide); 2) their ballic and dystonic appearance associated with a reinforcement of Parkinsonian signs; 3) the possibility of their reduction by an increase and fractionning of the daily dose of L-Dopa; 4) the particular nature of the underlying Parkinsonian problem in which they were seen, i.e. the young age at onset of the disease, the severity of akinesia, and the quality of the clinical response to L-Dopa. Thus on the basis of the circumstances of their development, their appearance, and their treatment, such forms of dyskinesia at the "beginning and end of dose" appear to be different from classical "mid-dose" dyskinesia. In addition, they pose a new physiolopathological problem.}, }
@article {pmid168957, year = {1975}, author = {Hunter, RL and Ferguson, DJ and Coppleson, LW}, title = {Survival with mammary cancer related to the interaction of germinal center hyperplasia and sinus histiocytosis in axillary and internal mammary lymph nodes.}, journal = {Cancer}, volume = {36}, number = {2}, pages = {528-539}, doi = {10.1002/1097-0142(197508)36:2&lt;528::aid-cncr2820360232&gt;3.0.co;2-u}, pmid = {168957}, issn = {0008-543X}, mesh = {Axilla ; Breast/pathology ; Breast Neoplasms/immunology/*mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/immunology/*mortality/pathology ; Female ; Humans ; Hyperplasia ; Lymph Nodes/immunology/pathology ; *Lymphatic Metastasis ; Mastectomy ; Prognosis ; }, abstract = {In a review of the histologic sections of axillary and internal mammary lymph nodes removed during surgery for invasive ductal carcinoma of the breast, we found that 16 of 17 patients in whom sinus histiocytosis was the dominant lymphoid proliferative reaction are alive with no evidence of cancer 5 or more years after operation. In contrast, 5 of 6 patients in whom germinal center hyperplasia was the only significant reaction found died of cancer in less than 5 years. Patients with both sinus histiocytosis and germinal center hyperplasia in significant amounts had survival that was intermediate; 17 of 25 of these patients are currently alive and apparently free of cancer. In addition, 5 of 6 patients in whom no evidence was found of any lymphoid proliferative reaction and 3 of 3 patients with diffuse cortical hyperplasia in their axillary lymph nodes died of cancer in less than 5 years. Germinal center hyperplasia was associated with nodal metastases anatomically in individual lymph nodes and statistically in the series of cases. The internal mammary lymph nodes of most cases showed less proliferative reaction to tumor than the axillary lymph nodes. The pattern of proliferative reactions in lymph nodes and its correlation with survival after surgery suggest that different immune reactions may either suppress or enhance the growth of carcinoma of the breast.}, }